Research Topic task started on Mon Dec 27, 2010 at 12:12 PM

2 Research Topic candidates were identified in CAPLUS and MEDLINE. using the phrase "naproxen"

Selected 2 of 2 candidate topics. 12792 references were found containing "naproxen" as entered. 13491 references were found containing the concept "naproxen".

Research Topic Refine started

4258 references were found when refined using the phrase "synthesis"

Copyrights:

CAPLUS: Copyright 2009 American Chemical Society. All Rights Reserved. (The UK patent material in this product/service is UK Crown copyright and is made available with permission. Crown Copyright. The French (FR) patent material in this product/service is made available from Institut National de la Propriete Industrielle (INPI).) MEDLINE: Produced by the U.S. National Library of Medicine REGISTRY: Copyright 2009 American Chemical Society. All Rights Reserved. (Some records contain information from GenBank(R). See also: Benson D.A., Karsch-Mizrachi I., Lipman D.J., Ostell J., Rapp B.A., Wheeler D.L. Genbank. Nucl. Acids Res. 28(1):15-18 (2000). Property values tagged with IC are from the ZIC/VINITI data file provided by InfoChem.) CAS Registry is a service mark of the American Chemical Society. CASREACT: Copyright 2009 American Chemical Society. All Rights Reserved. CASREACT contains reactions from CAS and from: ZIC/VINITI database (1974-1999) provided by InfoChem; INPI data prior to 1986; Biotransformations database compiled under the direction of Professor Dr. Klaus Kieslich; organic reactions, portions copyright 1996-2006 John Wiley & Sons, Ltd., John Wiley and Sons, Inc., Organic Reactions Inc., and Organic Syntheses Inc. Reproduced under license. All Rights Reserved. CHEMLIST, CHEMCATS: Copyright 2009 American Chemical Society. All Rights Reserved.

Bibliographic Information

Naproxen-eudragit RS100 nanoparticles: Preparation and physicochemical characterization. Adibkia, Khosro; Javadzadeh, Yousef; Dastmalchi, Siavoush; Mohammadi, Ghobad; Niri, Fatemeh Kari; Alaei-Beirami, Mahmood. Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. Colloids and Surfaces, B: Biointerfaces (2011), 83(1), 155-159. Publisher: Elsevier B.V., CODEN: CSBBEQ ISSN: 0927-7765. Journal written in English. AN 2010:1595651 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract The objective of the present study was to formulate naproxen-eudragit RS100 nanoparticles and investigate the physicochem. characteristics of the prepd. nanoparticles. The nanoparticles of naproxen with eudragit RS100 were formulated using the solvent evapn./extn. technique (the single emulsion technique). The effect of several process parameters, i.e., drug/polymer ratio, aq. phase vol. and speed of homogenization were considered on the size of the nanoformulations. The physicochem. characteristics of nanoparticles were studied applying particle size anal., differential scanning calorimetry, X-ray crystallog., Fourier transform IR spectroscopy and SEM. The release rate of naproxen from various drug/polymer nanoparticles was investigated as well. All the prepd. formulations using eudragit RS100 resulted in nanorange size particles with relative spherical smooth morphol. The nanoparticles of naproxen-eudragit RS100 displayed lower crystallinity. The intermol. interaction between naproxen and eudragit RS100 was detected in the FT-IR spectrum of the nanoparticles. All the nanoparticles displayed a slowed release pattern with the reduced burst release in comparison with the intact drug powder and phys. mixts. of drug and polymer. According of these findings, formulation of the naproxen-eudragit RS100 nanoparticles was able to improve the physicochem. characteristics of the drug and possibly will increase the anti-inflammatory effects of drug following its ocular or intra-joint administration. Bibliographic Information Effect of cytochrome P450 and aldo-keto reductase inhibitors on progesterone inactivation in primary bovine hepatic cell cultures. Lemley, C. O.; Wilson, M. E. Division of Animal and Nutritional Sciences, Davis College of Agriculture, Natural Resources and Design, West Virginia University, Morgantown, USA. Journal of Dairy Science (2010), 93(10), 4613-4624. Publisher: Elsevier, CODEN: JDSCAE ISSN: 0022-0302. Journal written in English. AN 2010:1565274 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract Progesterone is required for maintenance of pregnancy, and peripheral concns. of progesterone are affected by both prodn. and inactivation. Hepatic cytochrome P 450 (EC 1.14.14.1) and aldo-keto reductase (EC 1.1.1.145-151) enzymes play a pivotal role in the first step of steroid inactivation, which involves the addn. of hydroxyl groups to various sites of the cyclopentanoperhydrophenanthrene nucleus. The current objective was to discern the proportional involvement of hepatic progesterone inactivating enzymes on progesterone decay using specific enzyme inhibitors. Ticlopidine, diltiazem, curcumin, dicumarol, and naproxen were used because of their selective inhibition of cytochrome P450s, aldo-keto reductases, and glucuronosyltransferases. Liver biopsies were collected from 6 lactating Holstein dairy cows, and cells were dissocd. using a nonperfusion technique. Confluent wells were preincubated for 4 h with enzyme inhibitor and then challenged with progesterone for 1 h. Cell viability was unaffected by inhibitor treatment and averaged 84 1%. In control wells, 50% of the progesterone had been inactivated after a 1-h challenge with 5 ng/mL of progesterone. Preincubation with curcumin, ticlopidine, or naproxen caused the greatest redn. in progesterone inactivation compared with controls and averaged 77, 39, or 37%, resp. Hydroxylation of 4-nitrophenol to 4-nitrocatechol in intact cells was inhibited by approx. 65% after treatment with curcumin or ticlopidine. Glucuronidation of phenol red or 4-nitrocatechol in intact cells was inhibited by treatment with curcumin, dicumarol, or naproxen. In cytoplasmic prepns., aldo-keto reductase 1C activity was inhibited by curcumin, dicumarol, or naproxen treatment. Microsomal cytochrome P 450 2C activity was inhibited by treatment with curcumin or ticlopidine, whereas cytochrome P 450 3A activity

was inhibited by treatment with curcumin or diltiazem. The contribution of cytochrome P 450 2C and cytochrome P 450 3A enzymes to progesterone inactivation in bovine hepatic cell cultures was 40 and 15%, resp. Depending on the inhibitor used, it would appear that the aldoketo reductase enzymes contribute approx. 40% to the obsd. progesterone inactivation, although a portion of this inactivation may be attributed to the loss of glucuronosyltransferase activity. Future work focusing on decreasing the activity of these enzymes in vivo could lead to an increase in the bioavailability of progesterone. Bibliographic Information Study on DMA-LiCl-cellulose chiral stationary phases in HPLC. Ma, Chao; Ai, Ping; Zhang, Mei; Peng, Ya; Yuan, Liming. School of Chemistry and Chemical Engineering, Yunan Normal University, Kunming, Peop. Rep. China. Huaxue Yanjiu Yu Yingyong (2010), 22(7), 907-910. Publisher: Huaxue Yanjiu Yu Yingyong Bianjibu, CODEN: HYYIFM ISSN: 1004-1656. Journal written in Chinese. AN 2010:1534516 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract DMA-LiCl-cellulose is coated on 3-aminopropyl silica gel as chiral stationary phases for high performance liq. chromatog. (HPLC), and its chiral column(250 mm*2.0mm, i.d.)was prepd. under the pressure of 40 MPa. In the normal phase of high performance liq. chromatog., 21 chiral compds., including alcs., acids, amines, amino acids and drugs, were resolved on this column, 13 kinds of chiral compds. have been sepd. The results indicate that the chiral stationary phase possesses a good chiral sepn. ability. Bibliographic Information Structural evaluation of crystalline ternary -cyclodextrin complex. Higashi, Kenjirou; Ideura, Saori; Waraya, Haruka; Moribe, Kunikazu; Yamamoto, Keiji. Graduate School of Pharmaceutical Sciences, 1-8-1, Inohana, Chiba University, chuo-ku, Chiba-8675, Japan. Journal of Pharmaceutical Sciences (2011), 100(1), 325-333. Publisher: Wiley-Liss, Inc., CODEN: JPMSAE ISSN: 0022-3549. Journal written in English. AN 2010:1533402 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract The structure of a cryst. -cyclodextrin ( -CD) ternary complex contg. salicylic acid (SA) and flurbiprofen (FBP) prepd. by sealed heating was investigated. FBP/ -CD inclusion complex was prepd. by copptn.; its molar ratio was detd. as 1/1. Powder X-ray diffraction measurements showed that the mol. packing of CD changed from hexagonal to monoclinic columnar form by sealed heating of SA with dried FBP/ -CD inclusion complex, indicating ternary complex formation. The stoichiometry of SA/FBP/ -CD was estd. as 2/1/1. Solid-state transformation of -CD mol. packing upon water vapor adsorption and desorption was irreversible for this ternary complex, in contrast to the reversible transition for the FBP/ -CD inclusion complex. The ternary complex contained one FBP mol. in the cavity of -CD and two SA mols. in the intermol. space between neighboring -CD column stacks. IR and 13C solid-state NMR spectroscopies revealed that the mol. states of SA and FBP changed upon ternary complex formation. In the complex, dimer FBP mols. were sandwiched between two -CD mols. whereas each monomer SA mol. was present in the intermol. space of -CD. Ternary complex formation was also obsd. for other drug-guest systems using naproxen and ketoprofen. Thus, the complex can be used to formulate variety of drugs. 2010 Wiley-Liss, Inc. and the American Pharmacists Assocn. J Pharm Sci 100:325-333, 2011. Bibliographic Information Application of ion-type cyclodextrin derivative in preparing medicinal preparation based on ion-

introduction transdermal drug delivery system. Liang, Wenquan; Hu, Ying; Xu, Donghang; Liang, Yi. (Zhejiang University, Peop. Rep. China). Faming Zhuanli Shenqing (2010), 11pp. CODEN: CNXXEV CN 101897977 A 20101201 Patent written in Chinese. Application: CN 2010-10239927 20100729. Priority: CN 2010-10239927 20100729. AN 2010:1518057 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. CN 101897977 Priority Application CN 2010-10239927 Kind A Date 20101201 Application No. CN 2010-10239927 Date 20100729

20100729

Abstract The title ion-type cyclodextrin deriv. is from cation-type cyclodextrin deriv. (such as quaternary ammonium salt cation-type -cyclodextrin), and/or anion-type cyclodextrin deriv. (such as carboxymethyl- cyclodextrin, thio- -cyclodextrin, and/or sulfobutyl- -cyclodextrin). The medicine is mol.-type medicine, charged medicine (its soly. < 1 mg/mL), weakly acidic charged medicine (its dissocn. const. pKa > 4), and/or weakly alk. charged medicine (its dissocn. const. pKa < 4). The medicine in the medical prepn. can be included into inclusion compd. with the ion-type cyclodextrin deriv., with improved soly. and transdermal penetration rate. Bibliographic Information Molecular recognition material of D-naproxen imprinted polymers' preparation and their microstructure and properties. Zhang, Zhi-liang; Wang, Bing. College of Environmental Science and Chemical Engineering, Tianjin Polytechnic University, Tianjin, Peop. Rep. China. Gaofenzi Cailiao Kexue Yu Gongcheng (2010), 26(9), 112-116. Publisher: Gaofenzi Cailiao Kexue Yu Gongcheng Bianjibu, CODEN: GCKGEI ISSN: 1000-7555. Journal written in Chinese. AN 2010:1504272 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract A template mol. of D-naproxen was selected as the target. A differential UV absorption spectrum anal. method was designed to verify the nature of mol. interaction between naproxen and functional monomer. The facts proved that supra-mol. complex is formed by self-assembly through the non-covalent, including: hydrogen bonding and ionic bond. A group of mol. imprinted polymers (MIP), synthesized in different amt. of solvent, were analyzed by IR spectra. It shows that these products have the necessary characteristics of the structure. The transmission electron microscopy was firstly used to observe the morphol. of MIP, by which the pore-forming mechanism and the effect of the solvent were investigated. And those MIP were also tested in the adsorption kinetics expts. to testify the influence of morphol. factors on the materials' adsorption properties. According to the calcn. results of the selectivity assay for the synthetic MIP, the specific absorption capacity index and the imprint factor were obtained. It was up to 3.756. Bibliographic Information Pharmaceutical formulations comprising NSAID and proton pump inhibitor drugs. Yedurkar, Pramod Dattatray; Kharwade, Pramod; Vishwanathan, Narayanan Badri; Mhetre, Sandeep; Chiluka, Vinay Kumar; Pechetti, Siva Satya Krishna Babu. (Dr. Reddy's Laboratories Limited, India; Dr. Reddy's

Laboratories, Inc.). U.S. Pat. Appl. Publ. (2010), 15pp. CODEN: USXXCO US 20100305163 A1 20101202 Patent written in English. Application: US 2010-782964 20100519. Priority: IN 2009CH1158 20090520; US 2009-291233P 20091230; IN 2010-CH806 20100325. CAN 154:18823 AN 2010:1499851 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. US 20100305163 Priority Application IN 2009-CH1158 US 2009-291233P IN 2010-CH806 Kind A1 Date 20101202 Application No. US 2010-782964 Date 20100519

A P A

20090520 20091230 20100325

Abstract Aspects of the invention relate to pharmaceutical formulations comprising an NSAID and acid reducer drug for therapeutic purposes, and methods of prepg. the same. Further aspects of the invention relate to fixed dose pharmaceutical formulations comprising naproxen, or pharmaceutically acceptable salts thereof, and esomeprazole, or pharmaceutically acceptable salts thereof. Bibliographic Information Synthesis of Hollow CaCO3 Nanospheres Templated by Micelles of Poly(styrene-b-acrylic acid-bethylene glycol) in Aqueous Solutions. Bastakoti, Bishnu Prasad; Guragain, Sudhina; Yokoyama, YuuIchi; Yusa, Shin-Ichi; Nakashima, Ken-Ichi. Department of Chemistry, Faculty of Science and Engineering, Saga University, 1 Honjo-machi, Saga, Japan. Langmuir (2011), 27(1), 379-384. Publisher: American Chemical Society, CODEN: LANGD5 ISSN: 0743-7463. Journal; Online Computer File written in English. AN 2010:1497441 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract An asym. triblock copolymer, poly(styrene-b-acrylic acid-b-ethylene glycol) (PS-b-PAA-b-PEG), was synthesized via reversible addn.-fragmentation chain transfer controlled radical polymn. Micelles of PS-bPAA-b-PEG with PS core, PAA shell, and PEG corona were then prepd. in aq. solns., followed by extensive characterization based on dynamic light scattering, zeta-potential, and transmission electron microscopy (TEM) measurements. The well-characterized micelles were used to fabricate hollow nanospheres of CaCO3 as a template. It was elucidated from TEM measurements that the hollow nanospheres have a uniform size with cavity diams. of ca. 20 nm. The X-ray diffraction anal. revealed a high purity and crystallinity of the hollow nanospheres. The hollow CaCO3 nanospheres thus obtained have been used for the controlled release of an anti-inflammatory drug, naproxen. The significance of this study is that we have overcome a previous difficulty in the synthesis of hollow CaCO3 nanospheres. After mixing of Ca2+ and CO32- ions, the growth of CaCO3 is generally quite rapid to induce large crystal, which prevented us from obtaining hollow CaCO3 nanospheres with controlled structure. However, we could solve this issue by using micelles of PS-b-PAA-b-PEG as a template. The PS core acts as a template that can be removed to form a cavity of hollow CaCO3 nanospheres, the PAA shell is beneficial for arresting Ca2+ ions to produce CaCO3, and the PEG corona stabilizes the CaCO3/micelle nanocomposite to prevent secondary aggregate formation. Bibliographic Information

P(4-vinylpyridine) based smart nanoparticles with tunable characteristics and functions. Sahner, Nurettin; Ozay, Ozgur; Butun, Sultan. Department of Chemistry, Canakkale Onsekiz Mart University, Canakkale, Turk. Abstracts, Joint 66th Southwest and 62nd Southeast Regional Meeting of the American Chemical Society, New Orleans, LA, United States, December 1-4 (2010), SESW-297. Publisher: American Chemical Society, Washington, D. C CODEN: 69NMZR Conference; Meeting Abstract written in English. AN 2010:1486464 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract Polymeric particles based on 4-vinylpyridine (4-VP) with N-isopropylacrylamide (NIPAM), 2hydroxyethyl methacrylate (HEMA), acrylic acid (AAc), and methacrylic acid (MAc) were synthesized as stimuli-responsive (pH, temp. and magnetic field) materials in copolymeric formulation and composites with core-shell morphol. By varying the parameters such as keeping the 4-VP ratio const. and changing the comonomer amts. particles with variant shell and core thickness were preapred. This flexible p(4-VP)based nanoparticles were further modified by reacting with different functional groups contg. alkyhalides for quaternization to generate pos. charge and desired hydrophobiciy (different alkyl chain length). Furthermore, the synthesized polymeric functional particles were used to embed magnetic ferrites to induce magnetic responsive behaviormaterials by encapsulating sep. prepd. magnetic ferrites metal nanoparticles. It was demonstrated that the synthesized particles and their modified forms can be used as drug delivery devices utilizing some model drugs such as naproxen and trimethroprim. Addnl. p(4-VP) based particle are also very useful for environmental application to remove some org. pollutant from aq. environment. The potential applications of these versatile particle systems will be discussed. Bibliographic Information Preparation of heterocycle substituted benzene or naphthalene derivatives for modulation of uric acid level. De la Rosa, Martha; Girardet, Jean-Luc; Watson, Karen. (Ardea Biosciences, Inc., USA). PCT Int. Appl. (2010), 122pp. CODEN: PIXXD2 WO 2010135536 A2 20101125 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in English. Application: WO 2010-US35580 20100520. Priority: US 2009180100P 20090520. CAN 153:643496 AN 2010:1468143 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010135536 Kind A2 Date Application No. Date 20101125 WO 2010-US35580 20100520 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA,

GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM Priority Application US 2009-180100P

20090520

Abstract The title compds. with general formula I or Ar1-X1-W-Ar2 [wherein Ar = optionally substituted 5membered arom. heterocycle contg. 1 to 4 heteroatoms each independently selected from N, O, or S, and where the groups X and R1 are attached to positions on the Ar ring which are immediately adjacent to each other; X = O or S; R1 = substituted benzene; R2 = halo, nitro, or (C1-4)alkyl; R3 = H or halo; R4 = substituted benzene, substituted (C2-4)alkenyl, optionally substituted heterocycle , substituted -SONH2, etc.; Ar1 = optionally substituted 5- or 6-membered arom. heterocycle contg. 1 to 4 heteroatoms selected from N, O, or S, optionally substituted 5- or 6-membered carbocycle, or optionally substituted benzimidazole; X1 = a valence bond, O, S, SO, etc.; W = a divalent radical; Ar2 = substituted benzene, substituted pyridine, optionally substituted fused phenyl-carbocyclic ring, optionally substituted 5- or 6membered arom. heterocycle, etc.] or metabolites, pharmaceutically acceptable salts, solvates, polymorphs, esters, tautomers, or prodrugs thereof were prepd. for the redn. of blood uric acid levels. For example, compd. II was prepd. in a multi-step synthesis. Compd. II showed uric acid level modulating ability in Uric Acid Uptake Assay with EC50 value of < 5 M.
Me R2 R1 Ar X CH 2 CO H N R3 N N S Me CO 2 H

R4

II

Bibliographic Information Preparation of naphthalene azole derivatives for modulating uric acid levels. De la Rosa, Martha; Girardet, Jean-Luc. (Ardea Biosciences, Inc., USA). PCT Int. Appl. (2010), 84pp. CODEN: PIXXD2 WO 2010135530 A2 20101125 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in English. Application: WO 2010US35573 20100520. Priority: US 2009-180102P 20090520. CAN 154:10894 AN 2010:1468142 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information

Patent No. WO 2010135530

Kind A2

Date Application No. Date 20101125 WO 2010-US35573 20100520 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM

Priority Application US 2009-180102P

20090520

Abstract Title compds. I [R1 = electron lone pair, H, Br, etc; R2 = (un)substituted phenyl; R3 = -X-CR5aR5b(CR6aR6b)n-C(O)-O-Rm; X = S or O; R5a, R5b, R6a and R6b independently = H, F, Cl , etc; n = 0-1; Rm = H, (un)substituted alkyl, aryl, etc; Ar = 5-membered arom. heterocycle; R1, R2 and R3 are immediately adjacent to each other], and their pharmaceutically acceptable salts, solvates, polymorphs, esters, tautomers or prodrugs are prepd. Thus, e.g., II was prepd. by reacting 1-(naphthalen-1-yl)-1H-pyrazole-5-thiol (prepn. given) with Et bromoisobutyrate followed by hydrolysis. Compds. of the invention were tested for their uric acid uptake activity in vitro, e.g., II exhibited EC50 < 5 M. The invention compds. are useful for the treatment or prevention of disorders related to aberrant levels of uric acid such as hyperuricemia and gout.
Me N N Ar R1 R2 R3 I II S O Me OH

Bibliographic Information Encapsulated particles for amorphous stability enhancement. Timmons, Richard B.; Susut, Ceren; Owens, Donald E., III; Windsor, J. Brian; Khorzad, Rachel Kennedy. (University of Texas, USA; AeonClad Coatings, LLC). U.S. Pat. Appl. Publ. (2010), 44pp., Cont.-in-part of U. S. Ser. No. 931,480. CODEN: USXXCO US 20100297248 A1 20101125 Patent written in English. Application: US 2010-785162 20100521. Priority: US 2004-931480 20040901. CAN 153:651508 AN 2010:1466281 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R))

Patent Family Information Patent No. US 20100297248 US 20060045822 Priority Application US 2004-931480 Kind A1 A1 Date 20101125 20060302 Application No. US 2010-785162 US 2004-931480 Date 20100521 20040901

A2

20040901

Abstract The present invention provides compns. and methods of making and encapsulating one or more active agents in a chem. vapor deposition layer to enhance the stability. Thus, a plasma-enhanced chem. vapor deposition process was employed using both methacrylic acid (MAA) and Me methacrylate (MMA) monomers to deposit a thin coating layer on the surface of an amorphous itraconazole (ITZ) particles prepd. by hot melt extrusion of a blend of cryst. ITZ and Eudragit L100-55 excipient (1:2). The potency of the particles after coating was 28.62%, compared to 28.73% for hot melt extrusion amorphous particles. Bibliographic Information Synthesis and characterization of soft polymeric nanoparticles and composites with tunable properties. Sahiner, Nurettin; Ilgin, Pinar. Chemistry Department, Faculty of Sciences and Arts, Canakkale Onsekiz Mart University, Canakkale, Turk. Journal of Polymer Science, Part A: Polymer Chemistry (2010), 48(22), 5239-5246. Publisher: John Wiley & Sons, Inc., CODEN: JPACEC ISSN: 0887-624X. Journal written in English. AN 2010:1460114 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract Polymeric particles comprising acrylonitrile (AN)-based core and acrylamide deriv.-based shell in the submicron range with pos. and neg. charges were synthesized via microemulsion polymn. 2-Acrylamido-2methylpropane sulfonic acid (AMPS) and 3-(acrylamidopropyl)-trimethyl ammonium chloride (APTMACI) were used as shell-forming charged monomers onto AN core for the synthesis of p(AN-coAMPS) and p(AN-co-APTMACI), resp., using an oil-in-water emulsion system. To tune the characteristics of the core-shell particles, AN moieties in the core were amidoxi-mated to change the nature of the core from hydrophobic (nitrile) to hydrophilic (amidoxime) nature. Addnl., colloidal magnetite particles (Fe3O4) produced by chem. copptn. technique under alk. and inert conditions were also included inside p(AN-co-AMPS) and p(AN-co-APTMACI) particles as dual-responsive nanocomposites against pH and magnetic field. With the magnetic properties, AN-based core with modifiable characteristics and acrylamide-based polyelectrolyte shells with variable charges and sizes were further used as drug carriers. For potential targeted drug delivery application of the synthesized soft particles and their composites Naproxen and Trimethoprim were used as model drugs, and he release studies were carried in phosphate buffer saline (pH = 7.4) at ambient temp. Bibliographic Information Solid pharmaceutical preparations containing copolymers based on polyethers combined with poorly water-soluble polymers. Kolter, Karl; Djuric, Dejan; Fischer, Stefan. (Basf SE, Germany). PCT Int. Appl. (2010), 31pp. CODEN: PIXXD2 WO 2010130728 A2 20101118 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL,

IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in German. Application: WO 2010-EP56447 20100511. Priority: EP 2009-160129 20090513. CAN 153:651438 AN 2010:1437170 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010130728 Kind A2 Date Application No. Date 20101118 WO 2010-EP56447 20100511 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM

Priority Application EP 2009-160129

20090513

Abstract The invention relates to dosage forms which contain prepns. of poorly water-sol. substances in a polymer matrix of polyether copolymers, said polyether copolymers being obtained by the radically initiated polymn. of a mixt. from 30 to 80% by wt. of N-vinyl lactam, 10 to 50% by wt. of vinyl acetate and 10 to 50% by wt. of a polyether, and at least one poorly water-sol. polymer, the poorly water-sol. substance being present in the polymer matrix as an amorphous substance. Bibliographic Information Discovery of PF-04457845: A Highly Potent, Orally Bioavailable, and Selective Urea FAAH Inhibitor. Johnson, Douglas S.; Stiff, Cory; Lazerwith, Scott E.; Kesten, Suzanne R.; Fay, Lorraine K.; Morris, Mark; Beidler, David; Liimatta, Marya B.; Smith, Sarah E.; Dudley, David T.; Sadagopan, Nalini; Bhattachar, Shobha N.; Kesten, Stephen J.; Nomanbhoy, Tyzoon K.; Cravatt, Benjamin F.; Ahn, Kay. Pfizer Worldwide Research and Development, Groton, CT, USA. ACS Medicinal Chemistry Letters ACS ASAP. Publisher: American Chemical Society, CODEN: AMCLCT ISSN: 1948-5875. Journal written in English. AN 2010:1421092 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract Fatty acid amide hydrolase (FAAH) is an integral membrane serine hydrolase that degrades the fatty acid amide family of signaling lipids, including the endocannabinoid anandamide. Genetic or pharmacol.

inactivation of FAAH leads to analgesic and anti-inflammatory phenotypes in rodents without showing the undesirable side effects obsd. with direct cannabinoid receptor agonists, indicating that FAAH may represent an attractive therapeutic target for the treatment of inflammatory pain and other nervous system disorders. Herein, we report the discovery and characterization of a highly efficacious and selective FAAH inhibitor PF-04457845 (23, I). Compd. 23 inhibits FAAH by a covalent, irreversible mechanism involving carbamylation of the active-site serine nucleophile of FAAH with high in vitro potency (kinact/Ki and IC50 values of 40300 M-1 s-1 and 7.2 nM, resp., for human FAAH). Compd. 23 has exquisite selectivity for FAAH relative to other members of the serine hydrolase superfamily as demonstrated by competitive activity-based protein profiling. Oral administration of 23 at 0.1 mg/kg results in efficacy comparable to that of naproxen at 10 mg/kg in a rat model of inflammatory pain. Compd. 23 is being evaluated in human clin. trials.

N HN F3 C N

Bibliographic Information Preparation and Characterization of Novel Amphiphilic Hydrogels with Covalently Attached Drugs and Fluorescent Markers. Lin, Caiping; Gitsov, Ivan. Department of Chemistry, College of Environmental Science and Forestry, State University of New York, Syracuse, NY, USA. Macromolecules (Washington, DC, United States) (2010), 43(23), 10017-10030. Publisher: American Chemical Society, CODEN: MAMOBX ISSN: 0024-9297. Journal written in English. AN 2010:1420986 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract This paper describes the synthesis of styrene-based macromonomers with covalently attached model drugs (ibuprofen and naproxen) or fluorescent markers (pyrene) and their incorporation into linear or hyperbranched p-(chloromethyl)styrene copolymers. Alternatively the copolymers were produced by postpolymn. modification of linear or hyperbranched poly[p-(chloromethyl)styrene], PPCMSt, with the same compds. The incorporation of these copolymers into amphiphilic conetworks was achieved by two methods: Williamson ether synthesis between PPCMSt and poly(ethylene glycol), PEG, with hydroxyl end groups or by nucleophilic substitution between the chloromethyl moieties in PPCMSt and the amine end groups in poly(oxyalkylenediamine), Jeffamine. The dynamic and equil. swelling properties were studied on representative Jeffamine hydrogels. The swelling studies showed that the conetworks absorb water quickly and reach equil. in 1-2 h, the equil. swelling ratio of gels based on linear or hyperbranched copolymer being 181-358% and 244-480%, resp. Preliminary drug release studies in different aq. media

showed that the release kinetics and the amt. of drugs released from hydrogels depend on the phys. properties of drugs, the microstructure of polymer network, and the drug-polymer interaction and more particularly on the hydrolysis dynamics of ester linkage between the drug and the polymer matrix. Bibliographic Information Enhanced stability of inverse thermal gelling composite hydrogels. Shoichet, Molly S.; Baumann, M. Douglas; Kang, Catherine Elizabeth. (Can.). U.S. Pat. Appl. Publ. (2010), 26pp., Cont.-in-part of U.S. Ser. No. 410,831. CODEN: USXXCO US 20100285113 A1 20101111 Patent written in English. Application: US 2010-778879 20100512. Priority: US 2005-674299P 20050425; US 2006-410831 20060425. CAN 153:627175 AN 2010:1408465 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. US 20100285113 US 20060280797 US 7767656 Priority Application US 2005-674299P US 2006-410831 Kind A1 A1 B2 Date 20101111 20061214 20100803 Application No. US 2010-778879 US 2006-410831 Date 20100512 20060425

P A2

20050425 20060425

Abstract The present invention relates to a composite hydrogel comprising a blend of an aq. soln. of an anionic polysaccharide or a deriv. thereof, such as hyaluronan (also commonly referred to as hyaluronic acid) or a deriv. thereof and an aq. soln. of methylcellulose or another water sol. cellulose deriv. thereof, having dispersed polymeric particles, such as polymeric hydrophobic particles therein selected from micro particles and nanoparticles, and wherein the stability of the hydrogel is enhanced relative to the stability of the hydrogel alone. The polymeric particles may contain at least one therapeutic agent, in which case each therapeutic agent exhibits a linear sustained release rate that can be tuned or altered by selecting the appropriate polymer formulation of the micro particles and/or nanoparticles. The composite may be injectable, and in the absence of a therapeutic agent may be used as a bulking agent for reconstructive and cosmetic surgery or may act as a platform for subsequent delivery of therapeutic agents. A hyaluronic acidMe cellulose gelling composite was prepd. and release of EGF from this composite was studied. Bibliographic Information Preparation of naphthalene derivatives for use as cyclooxygenase inhibitors. Rao, Tadimeti; Zhang, Chengzhi; Gant, Thomas G.; Sarshar, Sepehr. (Auspex Pharmaceuticals, Inc., USA). PCT Int. Appl. (2010), 58pp. CODEN: PIXXD2 WO 2010129505 A2 20101111 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in English. Application: WO 2010-US33480 20100504. Priority: US 2009-175678P 20090505. CAN 153:618571 AN 2010:1405890 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information

Patent No. WO 2010129505

Kind A2

Date Application No. Date 20101111 WO 2010-US33480 20100504 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM

Priority Application US 2009-175678P

20090505

Abstract Title compds. I [each R independently = H or deuterium; and at least one of R = deuterium], and their pharmaceutically acceptable salts, are prepd. and disclosed as cyclooxygenase inhibitors. Thus, e.g., II was prepd. by esterification of (S)-2-(6-methoxy-2-naphthyl)propanoic acid with 1,4-dibromobutane followed by nitration. Select I were evaluated for their cyclooxygenase inhibitory activity (data given).
R R R R O R R R R O R R R R I R R R R O NO 2

R R

O R R

Me O O O NO 2

Me O

II

Bibliographic Information Novel pH-sensitive Carriers Containing Naproxen Pendant Groups for Colon-Specific Drug Delivery. Mahkam, Mehrdad; Poorgholy, Nahid. Chemistry Department, Azarbaijan University of

Tarbiat Moallem, Tabriz, Iran. International Journal of Polymeric Materials (2011), 60(1), 1-10. Publisher: Taylor & Francis, Inc., CODEN: IJPMCS ISSN: 0091-4037. Journal written in English. AN 2010:1396510 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract The carboxyl group of naproxen was converted into a vinyl ester group by reacting naproxen with vinyl acetate in the presence of mercuric acetate as a catalyst. Cubane-1, 4-dicarboxylic acid (CDA) was covalently linked with 2-hydroxyethyl methacrylate (HEMA) as the crosslinking agent (CA). Methacrylictype polymeric prodrugs were synthesized by free radical copolymn. of methacrylic acid, vinyl ester deriv. of naproxen (VIN) and polyethylene glycol monomethacrylate (PEGMA) in the presence of a cubane crosslinking agent. In vitro release profiles were established sep. in enzyme-free simulated gastric and intestinal fluids (SGF, pH 1 and SIF, pH 7.4). Bibliographic Information HPLC-MS/MS detection of relieve pain drugs and glucocorticosteroid in traditional Chinese preparations. Ling, Xiao; Xu, Zhizhou; Niu, Chong. Shandong Provincial Institute for Drug Control, Jinan, Shandong Province, Peop. Rep. China. Yaowu Fenxi Zazhi (2010), 30(7), 1311-1314. Publisher: Yaowu Fenxi Zazhi Bianji Weiyuanhui, CODEN: YFZADL ISSN: 0254-1793. Journal written in Chinese. AN 2010:1382073 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract A specific, sensitive and rapid HPLC-MS-MS assay was developed for diclofenac, naproxen, indometacin, amidopyrine, prednisone and prednisone acetate, and a detection method for identification of the above chem. drugs illegally adulterated in traditional Chinese medicine (TCM) prepns. was provided. HPLCMS/MS was used to sep. and identify the above chem. drugs. The sepn. was performed on a Agilent C18 (150 mm 4.6 mm, 5 m) and consisted of 0.01 mol L-1 ammonium formate (with 0.1% formic acid)methanol. The mass spectrometer (Agilent Trap Mass) was operated in the pos. ion mode and in two scan modes including full scan MS and full scan MS-MS. The obtained mass spectra were analyzed for their fragmentation pathways. The obtained mother ions, fragment ions and retention time were used to identify the above drugs. It was found that naproxen, diclofenac and indometacin were illegally adulterated in the pure TCM prepns. The method was selective and sensitive, and it could be used to detect the illegally added components in traditional Chinese prepns. and control the quality. Bibliographic Information Synthesis and characterizations of naproxen intercalated Mg-Al layered double hydroxides. Du, Bao-Zhong; Wang, Ru-Min. Department of Applied Chemistry, Northwestern Polytechnical University, Xi'an, Peop. Rep. China. Journal of Chinese Pharmaceutical Sciences (2010), 19(5), 371-378. Publisher: Editorial Office of Journal of Chinese Pharmaceutical Sciences, CODEN: JCHSE4 ISSN: 1003-1057. Journal written in English. AN 2010:1379223 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract Naproxen (Nap), a non-steroidal anti-inflammatory drug (NSAIDs), was intercalated into the gallery of Mg-Al layered double hydroxides (LDHs) by ion exchange and co-pptn. with different location of magnesium ion and aluminum ion solns., resp. The product was characterized with powder X-ray diffraction (XRD), Fourier Transform IR spectral (FT-IR) and Thermogravimetry (TG). The results showed an expanded LDH structure, indicating that the drug was successfully intercalated into LDH with the monolayer perpendicular to (along the short axis orientation in proper angle) Nap anion. As compared to the pure form of Nap, the thermal stability of the intercalated Nap was significantly enhanced due to the

host-guest interaction involving hydrogen bond and electrostatic attraction. We further investigated the drug release characteristics of the pillared LDH materials by a dissoln. test in simulation gastrointestinal and intestinal fluids under different pH values. The results indicated that the release percentages decrease upon increasing pH from 4.60 to 7.43, likely due to the dependence of release mechanism on pH. We have carried out a kinetic simulation to the release data and found that the dissoln. mechanism was mainly responsible for the release behavior of Nap-LDHs at pH 4.60, while the ion-exchange mechanism was responsible for that at pH 7.43. In addn., the initial release rates and equil. percent releases of the nanohybrids depended significantly on the synthesis methods, from which we have proposed a schematic model. The current study clearly showed that this drug-inorg. layered material has prospective applications in drug delivery system. Bibliographic Information Foamable vehicle and pharmaceutical compositions comprising aprotic polar solvents and uses thereof. Tamarkin, Dov; Schuz, David; Berman, Tal; Hazot, Yohan. (Foamix Ltd., Israel). PCT Int. Appl. (2010), 103pp. CODEN: PIXXD2 WO 2010125470 A2 20101104 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in English. Application: WO 2010-IB1126 20100428. Priority: US 2009-173378P 20090428. CAN 153:589499 AN 2010:1374638 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010125470 Kind A2 Date Application No. Date 20101104 WO 2010-IB1126 20100428 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM

Priority Application US 2009-173378P

20090428

Abstract The present invention relates to a foamable pharmaceutical and cosmetic compns. and foams comprising an aprotic polar solvent and uses thereof. Thus, a waterless foamable compns. comprising DMSO, glycerol monostearate and AP-70 propellant was prepd. having excellent foam quality and colapse time of > 180 s.

The addn. of various drugs (diclofenac, minocycline HCl or terbinafine) gave good quality breakable foams which did not collapse after 180 s of incubation at 36 . Microscopic observation of foam samples revealed the drugs were dissolved in these formulations. The drug bioavailability should be improved if dissolved since the DMSO can then aid penetration. Bibliographic Information Deuterated cizolirtine derivatives as modulators of substance P release, CGRP activity, adrenoceptor activity and 5HT receptor activity and their preparation and use for the treatment of diseases. Gant, Thomas G.; Sarshar, Sepehr. (Auspex Pharmaceuticals, Inc., USA). PCT Int. Appl. (2010), 81pp. CODEN: PIXXD2 WO 2010123999 A2 20101028 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in English. Application: WO 2010-US31906 20100421. Priority: US 2009-171140P 20090421. CAN 153:580300 AN 2010:1346463 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010123999 Kind A2 Date Application No. Date 20101028 WO 2010-US31906 20100421 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM 20101118 US 2010-764494 20100421

US 20100291151 Priority Application US 2009-171140P

A1

20090421

Abstract The invention relates to deuterated cizolirtine derivs. of formula I, which are modulators of substance P release, CGRP activity, adrenoceptor activity and 5HT receptor activity and which are useful in treatment of diseases. Compds. of formula I wherein each R is independently H and D; each A is independently CR2; provided that at least one R is D; and pharmaceutically acceptable salts thereof, are claimed. Example compd. II citric acid was prepd. by a multistep procedure (procedure given). All the invention compds. were evaluated for their modulatory activity (data given).

R R R O CH 3

R R R O N R N

R A A

CR 3 N CR 3 N I

N CD 3

CH 3 II

CR 3

Bibliographic Information Process for preparation of sitagliptin and intermediates thereof. Satyanarayana Reddy, Manne; Eswaraiah, Sajja; Satyanarayana, Revu; Kondal Reddy, Bairy; Srinivas, Aluru. (MSN Laboratories Limited, India). PCT Int. Appl. (2010), 96pp. CODEN: PIXXD2 WO 2010122578 A2 20101028 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in English. Application: WO 2010-IN249 20100420. Priority: IN 2009-CH901 20090420; IN 2009-CH2652 20091103; IN 2010-CH1084 20100419. CAN 153:555207 AN 2010:1342878 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010122578 Kind A2 Date Application No. Date 20101028 WO 2010-IN249 20100420 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM

Priority Application IN 2009-CH901 IN 2009-CH2652 IN 2010-CH1084

A A A

20090420 20091103 20100419

Abstract The present invention pertains to novel and improved processes for the prepn. of sitagliptin and intermediates thereof. For example, a mixt. of 7-[(3R)-3-amino-1-oxo-4-(2,4,5-trifluorophenyl)butyl]5,6,7,8-tetrahydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazine mandelate salt (prepn. given), water, and dichloromethane was stirred for 5 min at 20-30 C, then basified with sodium carbonate soln. and stirred for 20 min at 20-30 C. The aq. and org. layers were sepd., and the aq. layer was extd. with dichloromethane. Combined org. layers was condensed under reduced pressure to remove solvent, then suspended in iso-Pr alc. and water at 20-30 C and stirred for 15 min to obtain a solid, filtered through hiflow bed and washed with aq. iso-Pr alc. Orthophosphoric acid was added to the filtrate at 20-35 C and stirred for 30 min, heated to reflux, and then cooled to 55-60 C. The reaction mixt. was seeded with sitagliptin phosphate monohydrate and then stirred for 3 h at 55-60 C, cooled to 20-25 C slowly, added iso-Pr alc., stirred for 2 h at same temp. to afford a solid, filtered, washed with aq. iso-Pr alc. and dried to get sitagliptin phosphate monohydrate as the final product. Bibliographic Information A novel formulation of naproxen particles. Dodd, Aaron; Meiser, Felix; Norret, Marck; Russell, Adrian; Bosch, H. William. (Iceutica Pty Ltd, Australia). PCT Int. Appl. (2010), 144pp. CODEN: PIXXD2 WO 2010121326 A1 20101028 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in English. Application: WO 2010-AU470 20100423. Priority: AU 2009-901746 20090424; US 2009-172289P 20090424. CAN 153:589439 AN 2010:1342520 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010121326 Kind A1 Date Application No. Date 20101028 WO 2010-AU470 20100423 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM

Priority Application AU 2009-901746

20090424

US 2009-172289P

20090424

Abstract The present invention relates to methods for producing particles of naproxen using dry milling processes with a grinding matrix, as well as compns. comprising naproxen, medicaments produced using naproxen in particulate form and/or compns., and to methods of treatment of an animal, including man, using a therapeutically effective amt. of naproxen administered by way of said medicaments. Thus, naproxen was milled with a mixt. of two matrixes, 50% of a primary matrix (lactose monohydrate) plus 20% of a sec. matrix (trisodium citrate dihydrate or calcium carbonate). The particle size of these millings was smaller than the same milling with just lactose monohydrate or the secondary matrix, showing the synergy of mixed matrixes. Bibliographic Information A novel formulation of meloxicam particles prepared by milling. Dodd, Aaron; Meiser, Felix; Norret, Marck; Russell, Adrian; Bosch, H. William. (Iceutica Pty Ltd, Australia). PCT Int. Appl. (2010), 132pp. CODEN: PIXXD2 WO 2010121325 A1 20101028 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in English. Application: WO 2010-AU469 20100423. Priority: AU 2009-901742 20090424; US 2009-172284P 20090424. CAN 153:589438 AN 2010:1342518 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010121325 Kind A1 Date Application No. Date 20101028 WO 2010-AU469 20100423 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM

Priority Application AU 2009-901742 US 2009-172284P

A P

20090424 20090424

Abstract The present invention relates to methods for producing particles of meloxicam using dry milling processes as well as compns. comprising meloxicam, medicaments produced using meloxicam in particulate form and/or compns., and to methods of treatment of an animal, including man, using a therapeutically effective amt. of meloxicam administered by way of said medicaments. Thus, meloxicam was milled in lactose monohydrate with or without surfactant (sodium dodecyl sulfate). The addn. of surfactant improved the milling performance and ability to mill the powder. Milled meloxicam powder was then encapsulated into hard-gelatin capsules. The meloxicam capsules were bioequivalent to in terms of the amt. of meloxicam absorbed under both fasted and fed conditions to the ref. com. product Mobic. However, under fasted conditions, the rate of absorption from the inventive product was greater than that from the ref. product. There appeared to be no substantive differences between the adverse effects experienced with the two formulations. Bibliographic Information Deuterated tasocitinib derivatives as Janus kinase 3 inhibitors and their preparation and use for the treatment and prevention of Janus kinase 3-mediated diseases. Rao, Tadimeti S.; Zhang, Chengzhi. (Auspex Pharmaceuticals, LLC, USA). PCT Int. Appl. (2010), 138pp. CODEN: PIXXD2 WO 2010123919 A2 20101028 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in English. Application: WO 2010US31773 20100420. Priority: US 2009-170858P 20090420; US 2010-300887P 20100203. CAN 153:555186 AN 2010:1342515 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010123919 Kind A2 Date Application No. Date 20101028 WO 2010-US31773 20100420 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM 20101118 US 2010-763858 20100420

US 20100291026 Priority Application US 2009-170858P US 2010-300887P

A1

P P

20090420 20100203

Abstract The invention relates to deuterated tasocitinib derivs. of formula I, which are Janus kinase 3 inhibitors and which are useful in the treatment and prevention of Janus kinase 3-mediated diseases. Compds. of formula I wherein each R is independently H and D; each A is independently CR2; with provision; and pharmaceutically acceptable salts thereof, are claimed. Example compd. II citric acid was prepd. by a multistep procedure (procedure given). All the invention compds. were evaluated for their Janus kinase 3 inhibitory activity (data given).
A CR 3 R R N CR 3 NC R O N CH 3 CD 3

R NC

A N O R

A N

N N D N

N N R R I

N H

II

Bibliographic Information Shellac and paclitaxel coated catheter balloons. Orlowski, Michael. (Eurocor GmbH, Germany). Eur. Pat. Appl. (2010), 26pp. CODEN: EPXXDW EP 2243501 A1 20101027 Designated States R: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LI, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, TR, AL, BA, RS. Patent written in English. Application: EP 2009-75191 20090424. Priority: EP 2009-75191 20090424. CAN 153:564499 AN 2010:1336584 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. EP 2243501 Kind A1 Date Application No. Date 20101027 EP 2009-75191 20090424 R: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LI, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, TR, AL, BA, RS 20101028 WO 2010-EP2824 20100426 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT,

WO 2010121840

A2

RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM Priority Application EP 2009-75191

20090424

Abstract The present invention relates to a method for coating catheter balloons preferably textured catheter balloons with the pharmacol. agent paclitaxel and the biol. and biodegradable polymer compn. shellac and optionally further components. Moreover the present invention relates to paclitaxel and shellac coated catheter balloons obtained according to the coating methods disclosed herein as well as the use of such coated catheter balloons for the short time release of the pharmaceutically active agent paclitaxel for prophylaxis and treatment of restenosis esp. restenosis caused by angioplasty. The coated catheter balloons can be used alone or in combination with a coated or uncoated stent crimped on the catheter balloon before or after the coating with shellac and paclitaxel. A soln. of 70 g of paclitaxel and 50 g of shellac in 1.0 mL of ethanol having a water content of about 3 percent by vol. is prepd. and applied onto the horizontal area of the surface of the catheter balloon by brushing or spattering. Subsequently, the catheter balloon is thoroughly dried and sterilized with ethylene oxide. After sterilization, the balloon is provided with a protective sheath intended to protect the active agent on the coated dilatable catheter balloonduring transport and storage which sheath is removed prior to the insertion of the catheter by the cardiologist. Bibliographic Information Preparation of creatine salts with nonsteroidal antiinflammatory acids. Redaelli, Vincenzo. (Chorisis S.r.l., Italy). Ital. Appl. (2005), 20pp. CODEN: ITXXCZ IT 2004MI2385 A1 20050315 Patent written in Italian. Application: IT 2004-MI2385 20041215. Priority: IT 2004-MI2385 20041215. CAN 153:530844 AN 2010:1333754 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. IT 2004MI2385 IT 1357984 Priority Application IT 2004-MI2385 Kind A1 B1 Date 20050315 20090320 Application No. IT 2004-MI2385 Date 20041215

20041215

Abstract The invention relates to the synthesis of salts of creatine [H2NC(:NH)NMeCH2CO2H] with nonsteroidal anti-inflammatory drugs (NSAIDs) and alkali or alk.-earth metals. Examples describe the synthesis of claimed salts ibuprofen-creatine-potassium, naproxen-creatine-potassium, and diclofenac-creatinepotassium. Bibliographic Information Resolution without resolving agents by use of preferential enrichment and attrition induced

grinding. Slagt, Vincent; Kellogg, Richard M. Neth. Chimica Oggi (2010), 28(4), 44-46. Publisher: Tekno Scienze, CODEN: CHOGDS ISSN: 0392-839X. Journal written in English. AN 2010:1303366 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract Two techniques for sepn. of racemates without aid of external chiral sources are discussed. The techniques are based on the natural occurrence of conglomerates. The first is very well known, namely preferential crystn. We suggest methods to make conglomerates more accessible in order to improve the attractiveness of this method. The second method is entirely new and involves attrition induced grinding of racemizable conglomerates as solids in contact with soln. wherein racemization occurs, with a theor. 100 percent yield and 100 percent enantiomeric excess. This technique has recently been applied to the synthesis of two popular drugs, Clopidogrel and Naproxen. The sepn. of racemates into the individual enantiomers requires chiral recognition in some form. This may be accomplished, for example, by means of sepn. of diastereomeric salts, chiral chromatog. or kinetic resoln. with enzymes. A special case is formed by conglomerates in which the symmetry breaking, essential to any sepn. of the enantiomers, has already been carried out by Nature. Textbooks report that some 5-10 percent of chiral org. compds. crystallize as conglomerates. How can optimal use be made of this advantage provided by Nature in an as inexpensive way as possible to sep. the enantiomers, namely without resolving agents We discuss briefly here two techniques to do this together with considerations of a) how to identify conglomerates, b) how to increase the chance of finding a suitable conglomerate, c) how the chem. of the compds. can be employed in their resoln. and d) the role of previously under appreciated phys. phenomena such as Ostwald ripening. Bibliographic Information Method for determining drugs with hepatotoxicity. Choi, Seon Ok; Ko, Mun Jeong; Jung, Ho Sang; Ahn, Jun Ik; Shin, Hui Jeong; Kim, Hye Su; Jung, Hye Ju. (Korea Food & Drug Administration, S. Korea). Repub. Korean Kongkae Taeho Kongbo (2010), 12pp. CODEN: KRXXA7 KR 2010110679 A 20101013 Patent written in Korean. Application: KR 2009-29143 20090403. Priority: KR 200929143 20090403. CAN 153:571724 AN 2010:1296512 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. KR 2010110679 Priority Application KR 2009-29143 Kind A Date 20101013 Application No. KR 2009-29143 Date 20090403

20090403

Abstract The title method comprises the steps of: (1) treating hepatic cell with a test drug and culturing the cell, (2) extg. total cell RNA and synthesizing cRNA, and (3) measuring the expression of a gene, which can judge hepatotoxicity induction, comparing with a control, and judging hepatotoxicity induction. The method can effectively det. the hepatotoxicity of specific pharmaceuticals, and can be widely used in development of hepatotoxicity-free pharmaceuticals. Bibliographic Information Phthalimide derivatives of non-steroidal anti-inflammatory compounds and/or TNF- modulators, method for preparation thereof, pharmaceutical compositions containing the same and uses thereof

for the treatment of inflammatory diseases. Santos, Jean Leandro dos Santos; Vizioli, Ednir de Oliveira; Chin, Chung Man; Menegon, Renato Farina; Blau, Lorena. (EMS S.A., Brazil). PCT Int. Appl. (2010), 113pp. CODEN: PIXXD2 WO 2010115252 A1 20101014 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in Portuguese. Application: WO 2010-BR99 20100407. Priority: BR 2009-1298 20090406. CAN 153:530258 AN 2010:1281326 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010115252 Kind A1 Date Application No. Date 20101014 WO 2010-BR99 20100407 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM

Priority Application BR 2009-1298

20090406

Abstract The invention relates to phthalimide derivs. of non-steroidal anti-inflammatory compds. of formula I and/or TNF- modulators, to a method for producing these derivs., to pharmaceutical compns. contg. these derivs., and to uses thereof, including the use for the treatment of inflammatory diseases, in particular those assocd. with chronic inflammatory conditions, such as rheumatoid arthritis, and inflammatory intestinal diseases (such as Crohn's disease), and to the use of these compns. as antipyretics, analgesics and platelet aggregation inhibitors. Compds. of formula I wherein NSAID is a non-steroidal anti-inflammatory drug contg. at least one carboxylic acid subunit; W is F, Cl, Br, NO2, NH2, OH, OCH3, OCF3, CF3; CH3; X is (CH2)n-, 2-OH-Ph, 3-OH-Ph, etc, as specified in the disclosure, n = 0-6, are claimed. Methods for prepn. of compds. of formula I are claimed. In an example, Me salicylate (com. or prepd. from salicylic acid) was condensed with hydrazine hydrate (MeOH, 16 h reflux) followed by imidation with phthalic anhydride (3h reflux at 130 in glacial AcOH) to afford N-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-2-hydroxybenzamide (II) as a white solid in 85% yield (last step). The invention compds. were evaluated for their antiinflammatory activity and gastric toxicity on std. models in vivo.

O NSAID

N W

N HO

II

Bibliographic Information Topical and external tilorone pharmaceutical composition for treatment of purulent-destructive mucosal and skin diseases, systemic diseases in immunodeficiency states. Mezhburd, E. V.; Kosyakova, N. I.; Murashev, A. N. (ZAO "Biologicheskie Issledovaniya Sistemi", Russia). Russ. (2010), 75pp. CODEN: RUXXE7 RU 2401104 C2 20101010 Patent written in Russian. Application: RU 2008-147790 20081204. Priority: RU 2008-147790 20081204. CAN 153:465448 AN 2010:1270642 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. RU 2401104 Priority Application RU 2008-147790 Kind C2 Date 20101010 Application No. RU 2008-147790 Date 20081204

20081204

Abstract Tje invention comprises a topical and external pharmaceutical compn. for treatment of purulent-destructive mucosal and skin diseases, and also systemic diseases in immunodeficiency states characterized by the fact that it contains tilorone, a base and at least one target additive in a certain component relation, wt %. The target additive is specified from: immunomodulator, analgesic, cytostatic or their mixt. This reduces the latent period of action of the compn., extends applications of tilorone, and gives higher effectiveness of prepns. based on the offered pharmaceutical compn. Bibliographic Information Application of compound 20(S)-ginsenoside Rh2 in preparing the medicine for treating benign proliferative diseases of gynecologic reproductive system. Zhu, Yan; Cao, Lin; Zhou, Jieyun; Xie,

Shuwu; Gui, Youlun. (Shanghai Institute of Planned Parenthood Research, Peop. Rep. China). Faming Zhuanli Shenqing (2010), 13pp. CODEN: CNXXEV CN 101849954 A 20101006 Patent written in Chinese. Application: CN 2010-10194603 20100607. Priority: CN 2010-10194603 20100607. CAN 153:497664 AN 2010:1267738 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. CN 101849954 Priority Application CN 2010-10194603 Kind A Date 20101006 Application No. CN 2010-10194603 Date 20100607

20100607

Abstract This invention relates to the application of compd. 20(S)-ginsenoside Rh2 with the formula I in prepg. the medicine for treating benign proliferative diseases of gynecol. reproductive system such as endometriosis and/or hysteromyoma by inhibiting endometrium growth of endometriosis and/or myoma growth of hysteromyoma. The medicine (oral prepn., suppository or injection) comprises above compd. and pharmaceutically acceptable carrier. Bibliographic Information Method for producing bicyclic -amino acid derivative. Kitagawa, Yutaka; Imai, Makoto. (Daiichi Sankyo Company, Limited, Japan). PCT Int. Appl. (2010), 40pp. CODEN: PIXXD2 WO 2010110361 A1 20100930 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in Japanese. Application: WO 2010JP55202 20100325. Priority: JP 2009-75792 20090326. CAN 153:456954 AN 2010:1222184 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010110361 Kind A1 Date Application No. Date 20100930 WO 2010-JP55202 20100325 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ,

BY, KG, KZ, MD, RU, TJ, TM Priority Application JP 2009-75792

20090326

Abstract There is disclosed a method for producing a compd. which has an excellent activity as an voltage-gated potassium channel 2 subunit ligand. There is specifically disclosed a method for producing a [6(aminomethyl)bicyclo[3.2.0]hept-3-en-6-yl]acetic acid compd. represented by general formula [I; R1 = H, C1-6 alkyl; R2 = H or carboxy-protecting group] or a salt thereof through optical resoln. which comprises dissolving a mixt. of compds. contg. I and its stereoisomers (II, III, and IV) and an optically active org. acid in solvent and crystg. the I acid salt crystal. Thus, 627.0 g [6-aminomethyl-3-ethylbicyclo[3.2.0]hept-3-en6-yl]acetic acid tert-Bu ester p-toluenesulfonate (85:15 = (1R*,5S*,6S*):(1S*,5R*,6S*)-diastereomer mixt.) was stirred with 4.7 L MeCN at 40 , treated with 116.3 g D-mandelic acid, stirred at 40 , gradually cooled to 3 , and stirred at 3 for 1 h. The pptd. crystals were filtered off and dried at 40 under reduced pressure to give, 251.2 g [(1R,5S,6S)-6-aminomethyl-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid tertBu ester D-mandelate (V) (29.4% yield, 97.6% ee).
H R1 H H R1 H NH 2 H O t-Bu O H V Me CO 2 H NH 2 CO 2 R 2 III R1 H NH 2 CO 2 R 2 I R1 H H NH 2 CO 2 R 2 IV H NH 2 CO 2 R 2 II

OH

Bibliographic Information Topical Delivery of a Naproxen-Dithranol Co-drug: In Vitro Skin Penetration, Permeation, and Staining. Lau, Wing Man; White, Alex W.; Heard, Charles M. Welsh School of Pharmacy, Cardiff University, Cardiff, UK. Pharmaceutical Research (2010), 27(12), 2734-2742. Publisher: Springer, CODEN: PHREEB ISSN: 0724-8741. Journal; Online Computer File written in English. CAN 154:18152 AN 2010:1205213 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R))

Abstract This work probed the topical delivery and skin-staining properties of a novel co-drug, naproxyl-dithranol (Nap-DTH), which comprises anti-inflammatory (naproxen) and anti-proliferative (dithranol) moieties. Freshly excised, full-thickness porcine ear skin was dosed with satd. solns. of the compds. After 24 h, the skin was recovered and used to prep. comparative depth profiles by the tape-stripping technique and to examine the extent of skin staining. Depth profiles showed that Nap-DTH led to a 5-fold increase in drug retention in the skin compared to dithranol. The application of Nap-DTH also demonstrated improved stability, resulting in lower levels of dithranol degrdn. products in the skin. Furthermore, significantly less naproxen from hydrolyzed Nap-DTH permeated into the receptor phase compared to naproxen when applied alone (0.08 0.03 nmol cm-2 and 180 60 nmol cm-2, resp.). Moreover, the reduced staining of the skin was very apparent for Nap-DTH compared to dithranol. Topical delivery of Nap-DTH not only improves the delivery of naproxen and dithranol, but also reduces unwanted effects of the parent moieties, in particular the skin staining, which is a major issue concerning the use of dithranol. Bibliographic Information Preparation and characterization of amphiphilic polyethyleneglycol-graft-poly(lactic acid) (PPLA) copolymer micelles. Zhang, Xiaoxi; Pan, Jun; Yan, Hao; Mi, Li; Jiang, Weimin; Ren, Huiqing; Wang, Runguang. Research Center of Bioinspired Material Science and Engineering, College, Chongqing University, Chongqing, Peop. Rep. China. Jingxi Huagong (2010), 27(6), 584-588. Publisher: Jingxi Huagong Bianjibu, CODEN: JIHUFJ ISSN: 1003-5214. Journal written in Chinese. AN 2010:1203222 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract A new polymer namely polyethyleneglycol-graft-poly (lactic acid) (PPLA) polymeric micelle was prepd. and explore for its potential application to drug delivery. The rotary evapn. method was applied for the prepn. graft copolymer micelle, which was characterized. With naproxen as the model drug, the effect of several factors including acetone vol., naproxen feed amt. and the addnl. sequence of material were investigated on the entrapment efficiency by single-factorial expts. The crit. micelle concn. was 3 10-4 g/L. Distributing in a narrow range, the spherical-shaped micelle's av. particle diam. was under 200 nm. The micelle also presented a certain stability when dild., standing and alk. change to basic condition at room temp. The optimum prepn. procedure was as follows: after simultaneously dissolved in acetone, naproxen and PPLA were dropped into water, while vol. ratio between acetone and water and the wt. ratio between naproxen and PPLA were 1:10 and 0.8:10 resp., and PPLA micelle concn. 1.0 g/L. In PBS duration release could be up to 5 days at 37 degree C. Thus, PPLA could be considered as a novel applied polymer carriers in the promising drug delivery system for hydrophobic drugs. Bibliographic Information Enantioselective Synthesis of -Methyl Carboxylic Acids from Readily Available Starting Materials via Chemoenzymatic Dynamic Kinetic Resolution. Thalen, Lisa K.; Sumic, Anna; Bogar, Krisztian; Norinder, Jakob; Persson, Andreas K. A.; Baeckvall, Jan-E. Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, Stockholm, Swed. Journal of Organic Chemistry (2010), 75(20), 6842-6847. Publisher: American Chemical Society, CODEN: JOCEAH ISSN: 0022-3263. Journal written in English. CAN 153:505361 AN 2010:1186313 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract An enantioselective method for the synthesis of -Me carboxylic acids starting from trans-cinnamaldehyde,

a readily available and inexpensive compd., has been developed. Allylic alc. (E)-PhCH:CHCH(Me)OH (I) was obtained via a std. Grignard addn. to trans-cinnamaldehyde. Dynamic kinetic resoln. was applied to allylic alc. I utilizing a ruthenium catalyst and either an (R)-selective lipase or an (S)-selective protease to provide the corresponding allylic esters in high yield and high ee. A copper-catalyzed allylic substitution was then applied to provide the corresponding alkenes with inversion of stereochem. Subsequent C-C double bond cleavage afforded pharmaceutically important -Me substituted carboxylic acids in high ee and overall yields of up to 76%. Bibliographic Information Preparation and physicochemical characterization of naproxen-PLGA nanoparticles. Javadzadeh, Yousef; Ahadi, Fatemeh; Davaran, Soodabeh; Mohammadi, Ghobad; Sabzevari, Araz; Adibkia, Khosro. Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. Colloids and Surfaces, B: Biointerfaces (2010), 81(2), 498-502. Publisher: Elsevier B.V., CODEN: CSBBEQ ISSN: 0927-7765. Journal written in English. AN 2010:1184291 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract Naproxen is a non-steroidal anti-inflammatory drug which can be used for the treatment of inflammatory disorders like uveitis and arthirit rheumatoid. The aim of the present study was to investigate the physicochem. characteristics of naproxen-PLGA nanoparticles. The nanoparticles of naproxen with PLGA were formulated using the solvent evapn./extn. technique (the single emulsion technique). Several process parameters i.e., drug/polymer ratio, aq. phase vol. and speed of homogenization were considered with the aim of achieve optimal prepn. conditions. The physicochem. characteristics of nanoparticles were studied applying particle size anal., differential scanning calorimetry, X-ray crystallog., Fourier transform IR spectroscopy and SEM. The release rate of naproxen from various drug/polymer nanoparticles was investigated as well. All the prepd. formulations using PLGA resulted in nano-range size particles (352571 nm) with spherical smooth morphol. The nanoparticles of naproxen-PLGA displayed lower crystallinity with no chem. interactions between the drug and polymer mols. The nanoparticles exhibited the slower release of drug in comparison with the intact drug and the phys. mixts. According of these findings, formulation of the naproxen-PLGA nanoparticles was able to improve the physicochem. characteristics of the drug and possibly will increase the anti-inflammatory effects of drug following its ocular or intra-joint administration. Bibliographic Information Celecoxib, but not rofecoxib or naproxen, attenuates cardiac hypertrophy and fibrosis induced in vitro by angiotensin and aldosterone. Wang, Bing H.; Bertuci, Micka; Ma, Jian Yang; Adrahtas, Anastasia; Cheung, Raymond Y.; Krum, Henry. Centre for Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. Clinical and Experimental Pharmacology and Physiology (2010), 37(9), 912-918. Publisher: Wiley-Blackwell, CODEN: CEXPB9 ISSN: 0305-1870. Journal written in English. CAN 153:571117 AN 2010:1166880 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract Cyclooxygenase (COX)-2 inhibitors and other non-steroidal anti-inflammatory drugs (NSAIDs) were implicated in increased cardiovascular events. However, the direct effects of these drugs on cardiac function were not explored extensively. Given the important role of the renin-angiotensin-aldosterone system (RAAS) in cardiac remodeling, we sought to det. the effect of COX-2 inhibitors and non-specific (NS-) NSAIDs on RAAS-induced cardiac hypertrophy and fibrosis in neonatal rat cardiac myocytes (NCM) and fibroblasts (NCF) isolated from 1-2-day-old Sprague-Dawley rat pups. The NCM were pretreated for 2 h with COX-2 inhibitors (celecoxib or rofecoxib) or NS-NSAIDs (naproxen; all at 0.1-10 mol/L) before being stimulated with 10 mol/L aldosterone for 72 h or with 0.1 mol/L angiotensin

(Ang) II for 60 h. Hypertrophy of NCM was assessed by [3H]-leucine incorporation. The NCF were pretreated with COX-2 inhibitors or naproxen as described for NCM before being stimulated with 0.1 mol/L AngII for 48 h. Collagen synthesis was subsequently assayed by [3H]-proline incorporation. Pooled cryopreserved male and female rat hepatocytes were treated with or without COX-2 inhibitors for 1 h before 1 nmol/L aldosterone (.apprx.540 pg/mL) was added to all wells. Cells were incubated for a further 60 min and culture media harvested by centrifugation. Human hepatic HepG2 cells were treated with compds. with or without serum starvation for 48 h. All cells were pretreated with COX-2 inhibitors for 2 h before the addn. of aldosterone. Cell culture media were harvested after a further 3, 18, 24, or 48 h incubation. Aldosterone concns. in the culture media were detd. by enzyme immunoassay. Aldosteroneand AngII-stimulated NCM hypertrophy was inhibited by celecoxib, but not by rofecoxib or naproxen. In NCF, AngII-stimulated collagen synthesis was inhibited by celecoxib and, to a lesser extent, by rofecoxib, whereas naproxen had no effect. The COX-2 inhibitors inhibited aldosterone uptake and/or metab. by rat hepatocytes, but had no effect in human hepatic HepG2 cells. These results demonstrate a potential antiremodeling effect of selective COX-2 inhibitors in the setting of RAAS stimulation in cardiac cells, whereas naproxen has no effect. Bibliographic Information Synthesis, characterization and anti-inflammatory activity of 5-{[((5-substituted-aryl)-1,3,4thiadiazol-2-yl)thio]-n-alkyl}-1,3,4-oxadiazole-2-thiol. Shirote, Pramodkumar Jaykumar; Bhatia, Manish Sudesh. Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur, India. Chinese Journal of Chemistry (2010), 28(8), 1429-1436. Publisher: Shanghai Institute of Organic Chemistry, CODEN: CJOCEV ISSN: 1001-604X. Journal written in English. CAN 154:10804 AN 2010:1166410 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract A series of potent and less toxic, 5-{[((5-substituted aryl)-1,3,4-thiadiazol-2-yl)thio]-n-alkyl}-1,3,4oxadiazole-2-thiol3, e. g. I, was synthesized. Each compd. was evaluated for anti-inflammatory activity by carrageenan-induced rat paw edema method. Four compds., including I, showed comparatively potent antiinflammatory activity as compared to control as well as other test compds. These potent compds. were also tested for acute ulcerogenic activity. Results of both studies were found statistically significant.
N CH Me I S N S CH 2 3 CO N O N SH

Bibliographic Information External preparation containing analgesic/anti-inflammatory agent. Miura, Seiji; Awamura, Tsutomu; Yamazaki, Yuhiro; Fujii, Hironari. (Kowa Co., Ltd., Japan; Kyukyu Pharmaceutical Co., Ltd.). PCT Int. Appl. (2010), 34pp. CODEN: PIXXD2 WO 2010103845 A1 20100916 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD,

TG. Patent written in Japanese. Application: WO 2010-JP1762 20100311. Priority: JP 2009-57974 20090311. CAN 153:416029 AN 2010:1161750 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010103845 Kind A1 Date Application No. Date 20100916 WO 2010-JP1762 20100311 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM

Priority Application JP 2009-57974

20090311

Abstract Disclosed is an external prepn. which contains (A) a nonsteroidal analgesic/anti-inflammatory agent (B) a polyhydric alc. (C) a polyoxyalkylene alkyl ether and/or a polyoxyalkylene alkenyl ether The nonsteroidal analgesic/anti-inflammatory agent contained in the external prepn. has improved medicinal effects, and thus the external prepn. can be effective at a low concn. In addn., the external prepn. has excellent appearance. The external prepn. may further contain (D) terpene and/or terpene-contg. essential oil, and/or (E) a higher alc. For example, amfenac sodium 1, polyoxyethylene (2) lauryl ether (Nikkol BL-2) 2, diisopropanolamine 0.15, di-Bu hydroxytoluene 0.5, propylene glycol 3, oleyl alc. (Novol J) 2, and lmenthol 1 g were added to an adhesive base material prepd. from SIS 5505P, terpene resin (YS Resin PX 1150N), polybutene 3SH, and liq. paraffin (Hicol M72), and applied on a PET film followed by covering with a substrate sheet to give an adhesive patch, which showed excellent analgesic effect in rats. Bibliographic Information External preparation containing analgesic/anti-inflammatory agent. Miura, Seiji; Awamura, Tsutomu; Yamazaki, Yuhiro; Fujii, Hironari. (Kowa Co., Ltd., Japan; Kyukyu Pharmaceutical Co., Ltd.). PCT Int. Appl. (2010), 34pp. CODEN: PIXXD2 WO 2010103844 A1 20100916 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in Japanese. Application: WO 2010-JP1761 20100311. Priority: JP 2009-57973 20090311. CAN 153:416028 AN 2010:1161737 CAPLUS (Copyright (C) 2010 ACS on SciFinder

(R)) Patent Family Information Patent No. WO 2010103844 Kind A1 Date Application No. Date 20100916 WO 2010-JP1761 20100311 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM

Priority Application JP 2009-57973

20090311

Abstract Disclosed is an external prepn. which contains (A) a nonsteroidal analgesic/anti-inflammatory agent (B) an org. amine. The external prepn. has improved skin permeation, and the nonsteroidal analgesic/antiinflammatory agent contained in the external prepn. has excellent stability. In addn., the external prepn. has excellent appearance. The external prepn. may further contain (C) a polyoxyalkylene alkyl ether and/or polyoxyalkylene alkenyl ether, (D) a terpene and/or terpene-contg. essential oil, and/or (E) a higher alc. For example, amfenac sodium 1, polyoxyethylene (2) lauryl ether (Nikkol BL-2) 5, diisopropanolamine 0.5, oleyl alc. (Novol J) 5, and l-menthol 4 g were added to an adhesive base material prepd. from SIS 5505P, terpene resin (YS Resin PX 1150N), polybutene 3SH, and liq. paraffin (Hicol M72), and applied on a PET film followed by covering with a substrate sheet to give an adhesive patch, which showed good storage stability and skin permeability of amfenac. Bibliographic Information External preparation containing analgesic/anti-inflammatory agent. Miura, Seiji; Kanebako, Makoto. (Kowa Co., Ltd., Japan). PCT Int. Appl. (2010), 43pp. CODEN: PIXXD2 WO 2010103843 A1 20100916 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in Japanese. Application: WO 2010JP1760 20100311. Priority: JP 2009-57972 20090311. CAN 153:416027 AN 2010:1161734 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information

Patent No. WO 2010103843

Kind A1

Date Application No. Date 20100916 WO 2010-JP1760 20100311 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM

Priority Application JP 2009-57972

20090311

Abstract Disclosed is an external prepn. which contains the following components (A), (B), (C) and (D). (A) a nonsteroidal analgesic/anti-inflammatory agent (B) a terpene and/or an essential oil contg. a terpene (C) a higher alc. (D) a polyoxyalkylene alkyl ether and/or a polyoxyalkylene alkenyl ether. The external prepn. has improved skin permeation, and is thus effective at a low concn. In addn., the external prepn. has excellent appearance. For example, amfenac sodium 1 g was dissolved in polyoxyethylene (2) lauryl ether (Nikkol BL-2) 10 g, and further mixed with oleyl alc. (Novol J) 5, and l-menthol 4 g. The mixt. soln. was combined with an adhesive compn. prepd. from SIS (Kraton D-1161JP), terpene resin (YS resin PX1150N), polybutene (HV-300F), and liq. apraffin (Carnation J72), and applied on a PET film followed by covering a substrate sheet to give an adhesive patch. Bibliographic Information Sustained release composition of therapeutic agent comprising graft copolymers. Muthusamy, Ramesh; Kulkarni, Mohan Gopalkrishna. (Council of Scientific & Industrial Research, India). PCT Int. Appl. (2010), 49 pp. CODEN: PIXXD2 WO 2010103365 A2 20100916 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in English. Application: WO 2010-IB459 20100305. Priority: IN 2009-DE453 20090309. CAN 153:440639 AN 2010:1161501 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010103365 WO 2010103365 Kind A2 A3 Date 20100916 20101118 Application No. WO 2010-IB459 Date 20100305

W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM, AP, EA, EP, OA Priority Application IN 2009-DE453

20090309

Abstract A pH-dependent drug delivery system for oral administration is described, comprising a pH-sensitive graft copolymer, a therapeutically active agent and other pharmaceutically acceptable ingredients. More specifically, a compn. is capable of suppressing the drug release in the acidic pH prevalent in the stomach and releasing the drug over an extended period of time at pH prevalent in the intestinal region. Thus, a sustained release tablet of diclofenac sodium (100 mg) comprising the pH-sensitive adipic acid-1,4cyclohexanedimethanol-glycidyl methacrylate-methacrylic acid graft copolymer was prepd. Bibliographic Information Medical composition and injection containing sulfamonomethoxine, sulfamethoxazole, trimethoprim, pyrimethamine and non-steroidal anti-inflammatory drugs for treating livestock toxoplasmosis, and preparation method thereof. Zhang, Yaoqi; Zhang, Xinlei; Sun, Xuefeng; Zhu, Jingjing. (Henan Huitong Tianxia Animal Pharmaceutical Co., Ltd., Peop. Rep. China). Faming Zhuanli Shenqing (2010), 19pp. CODEN: CNXXEV CN 101816663 A 20100901 Patent written in Chinese. Application: CN 2009-10064270 20090226. Priority: CN 2009-10064270 20090226. CAN 153:391867 AN 2010:1115847 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. CN 101816663 Priority Application CN 2009-10064270 Kind A Date 20100901 Application No. CN 2009-10064270 Date 20090226

20090226

Abstract The title medical compn. contains (by%) sulfamonomethoxine 18-36, sulfamethoxazole 16-65, trimethoprim 7-18, pyrimethamine 4-14, and non-steroidal anti-inflammatory drugs 6-16. The title injection contains (by%) sulfamonomethoxine 5-10, sulfamethoxazole 4-20, trimethoprim 2-5, pyrimethamine 1-3, non-steroidal anti-inflammatory drugs 1.5-4, PEG-400 5-10, propylene glycol 10-30,

 -pyrrolidone 30-60, antioxidant 0.1-0.2, metal complexing agent 0.01-0.02, and water for injection as balance. The prepn. method comprises: (1) heating mixed soln. of PEG-400, propylene glycol, and pyrrolidone to 40-50, adding sulfamonomethoxine, sulfamethoxazole, trimethoprim, pyrimethamine and non-steroidal anti-inflammatory drugs in sequence, stirring and dissolving to obtain soln., (2) dissolving antioxidant and metal complexing agent with water to obtain soln., and (3) combining solns. obtained in steps 1 and 2, adjusting pH to 10.5 with NaOH, adding water for injection to full amt., stirring for 30 min, filtering, filling and sealing, and sterilizing at 100 for 30 min. The invention can repel and kill Toxoplasma gondii, prevent secondary infection of other pathogens, and release symptoms and complications caused by Toxoplasma gondii. Bibliographic Information Preparation of naproxen by catalysis with a symmetry C2 chiral system supported on mesoporous silica. Perez, G. Cuauhtemoc; Perez, G. Salud; Zavala, S. Miguel; Arias, G. Lucina; Fuentes, Z. Gustavo. Departamento de Sistemas Biologicos, Universidad Autonoma Metropolitana Unidad Xochimilco, Mexico City, Mex. Revista Mexicana de Ciencias Farmaceuticas (2010), 41(2), 25-29. Publisher: Asociacion Farmaceutica Mexicana, A.C., CODEN: RMCFDT ISSN: 1027-3956. Journal written in Spanish. CAN 153:600561 AN 2010:1105810 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract (S)-Naproxen was prepd. by hydrogenation of naphthylacrylic acid under mild reaction conditions using as catalyst (R)-2,2'-diamino-6,6'-dimethylbiphenyl supported on MCM-41 ruthenium [(R)-MAB-Ru-MCM41]. This catalyst system is very stable, recyclable, and cheaper than BINAP and the wastes generated are less hazardous to the environment. Quant. conversion was obtained in only 90 min and the enantiomeric excess was very close to 100%. The turn over frequency (TOF) value for MAB-Ru-MCM-41 was smaller than that for the MeDuPHOS-Rh system. Bibliographic Information Preparation of pyrimidinylpiperazines as PDE4 inhibitors. Nickolaus, Peter; Goeggel, Rolf; Peter, Daniel. (Boehringer Ingelheim International GmbH, Germany). PCT Int. Appl. (2010), 107pp. CODEN: PIXXD2 WO 2010097332 A1 20100902 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in German. Application: WO 2010-EP52077 20100218. Priority: EP 2009-153853 20090227; EP 2009-166127 20090722. CAN 153:382977 AN 2010:1101848 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010097332 Kind A1 Date Application No. Date 20100902 WO 2010-EP52077 20100218 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG,

PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM Priority Application EP 2009-153853 EP 2009-166127

A A

20090227 20090722

Abstract Title compds. I [X = SO, SO2; R1 = H,l; alkyl; R2 = H, alkyl; R3 = heteroaryl with provisos] and their pharmaceutically acceptable salts and formulations were prepd. Pyrimidinylpiperazine II is an example from the disclosed process. Compds. I exhibited activity with NSAID formulations.
S N N N N H I F II N N

N N N N R1 N

R3

S X O

R2

Bibliographic Information Preparation of pyrimidinylpiperidines as PDE4 inhibitors. Nickolaus, Peter; Goeggel, Rolf; Peter, Daniel. (Boehringer Ingelheim International GmbH, Germany). PCT Int. Appl. (2010), 134pp. CODEN: PIXXD2 WO 2010097334 A1 20100902 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in German. Application: WO 2010-EP52079 20100218. Priority: EP 2009-153855 20090227; EP 2009-166131 20090722. CAN 153:382976 AN 2010:1101846 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information

Patent No. WO 2010097334

Kind A1

Date Application No. Date 20100902 WO 2010-EP52079 20100218 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM

Priority Application EP 2009-153855 EP 2009-166131

A A

20090227 20090722

Abstract Title compds. I [X = SO, SO2; R1 = H,alkyl; R2 = H, alkyl; R3 = aryl with provisos; R4 = H, CN, OH, etc.] and their pharmaceutically acceptable salts and formulations were prepd. Pyrimidinylpiperidines II is an example from the disclosed process. Compds. I exhibited activity with NSAID formulations.
Cl

R3 R4 S X N N R1 I O H N N N CH 2 -OH N

R2

Me

Me

II

Bibliographic Information Formulation based on micronized zeolite, green tea extract, and genistein as a therapeutic agent for reduction of body weight and cellulite. Lelas, Antonio; Cepanec, Ivica. (Novatech Istrazivanje D.O.O., Croatia). PCT Int. Appl. (2010), 32pp. CODEN: PIXXD2 WO 2010097643 A1 20100902 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME,

MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in English. Application: WO 2009-HR5 20090224. Priority: WO 2009-HR5 20090224. CAN 153:343678 AN 2010:1100573 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010097643 Kind A1 Date Application No. Date 20100902 WO 2009-HR5 20090224 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM

Priority Application WO 2009-HR5

20090224

Abstract The invention relates to a pharmaceutical formulation based on variable portions of: (i) micronized zeolite (MZ) of general formula: (Men+)x/n[(AlO)x(SiO2)y].mH20 (Me = Na, K, Mg, Ca; whereas ratio of Si to Al y:x is 6:1 to 1:1; no. of cryst. water m = 0-20), which is characterized by particles size < 5 m; in concns. from 1-50%, most preferably from 3-30%; (ii) green tea ext. contg. at least 30% of epigallocatechin gallate (EGCG) and 5% of caffeine; in concns. from 0.1-90%, most preferably from 20-90%; (iii) genistein; in concns. from 0.05-20%, most preferably from 1-10%; and (iv) one or more excipients which yield in desired pharmaceutical or cosmetic form: tablets, capsules, ointments, creams, gels, lotions, shampoos, powders, liq. powders, syrups, suspensions, and therapeutic patches; in concns. from 1-98.85%, most preferably from 10-75%; which is useful for highly effective redn. of body wt. and cellulite. Thus, women using a hydrophilic (O/W) cream contg. 2% of micronized zeolite clinoptilolite (MZ), 2% of green tea ext. and 0.25% genistein reported significant redn. of intensity of cellulite appearance in comparison to women which used a control cream of the same compn. but without MZ. Bibliographic Information Process for microwave irradiation-mediated single step green synthesis of 2-aryl aldehydes and their analogues. Sinha, Arun Kumar; Sharma, Abhishek; Kumar, Rakesh; Sharma, Naina. (Council of Scientific & Industrial Research, India). PCT Int. Appl. (2010), 31pp. CODEN: PIXXD2 WO 2010097811 A1 20100902 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG,

PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in English. Application: WO 2010-IN110 20100225. Priority: IN 2009-DE348 20090225. CAN 153:382665 AN 2010:1100402 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010097811 Kind A1 Date Application No. Date 20100902 WO 2010-IN110 20100225 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM

Priority Application IN 2009-DE348

20090225

Abstract The invention provides a process for the prepn. of a series of 2-aryl and 2,2-diaryl aldehydes and analogs of formula I which are privileged intermediates for com. important nonsteroidal anti-inflammatory drugs including naproxen, flurbiprofen and potent anticancer drug candidates, including phenstatin (no biol. data shown) through a unique single step synthetic methodol. utilizing easily available substrates in the form of aryl alkenes as well as environmentally benign aq. reaction conditions in the form of solvents such as mixts. of water and DMSO or dioxane and reagents N-bromosuccinimide, N-iodosuccinimide, Ncholorosuccinimide and phase transfer catalyst such as cetyltrimethyl ammonium bromide, N-hexyl ammonium chloride for a reaction time varying from 1 min - 30 min, depending upon microwave or conventional heating, without using expensive transition metal catalysts or Lewis acids/bases with yield varying from 35-55 %, depending upon the solvent and substrate used. Compds. of formula I wherein, R' is Me, Et, Ph or C6H4-(4'-OMe); X is O or N-NH-SO2-C6H4-CH3; R1 to R5 are H, OH, MeO, Ph, halogen atom or R2+R3 together represent (CH=CH-CH=CH) group or (O-CH2-O) group and R1, R4, R5 are H, OH, MeO, Ph halogen atom, are claimed. Thus, in an example, a water-DMSO soln. of 2,4,5trimethoxyphenylpropene was treated with N-bromosuccinimide under microwave irradn. (220 W, 12 min. at 200 C) in the presence of cetyltrimethylAmmonium bromide (as PTC) followed by workup to afford the example compd. 2-(2,4,5-trimethoxyphenyl)propionaldehyde (II) as a white viscous liq. in 60% yield. The structure of II was further confirmed by transforming it into the corresponding tosylhydrazone (white solid, m.p. = 150-151 C, 60% yield). The developed method provides a clean and convenient alternative to access a diverse range of medicinally important 2-aryl and 2,2-diaryl aldehydes based scaffolds in lieu of the conventional multistep protocols employing expensive and hazardous transition metal catalysts and Lewis acids/bases.

R1 R2

HC

R' R5 R4 I

R3

OMe

CHO Me

Me O OMe II

Bibliographic Information Study on preparation of naproxen microemulsion with high drug-loading rate and its antiinflammatory and analgesic effect. Li, Jing; Wang, Yingli; Li, Peng; Xu, Zhen; Xie, Yin; Tian, Qingping. School of Pharmacy, Shanxi Medical University, Taiyuan, Peop. Rep. China. Zhongguo Yaofang (2010), 21(5), 406-408. Publisher: Zhongguo Yaofang Zazhishe, CODEN: ZYHAA4 ISSN: 1001-0408. Journal written in Chinese. AN 2010:1098200 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract The aim of this paper is to prep. naproxen microemulsion with high drug-loading rate and study its antiinflammatory and analgesic effect. Naproxen microemulsion was prepd. by phase transfer temp. (PIT) method with polysorbate-80 as surfactants, alc. as cosurfactant and iso-Pr myristate as oil phase. 1% dichlofenac sodium gel was used as pos. control. High-dose group, medium-dose group and low-dose group were treated with naproxen microemulsion. Then xylene and carrageenan were used to induce ear edema in mice and pedal swelling in rats resp. in order to study anti-inflammatory effect of Naproxen microemulsion. The hot-plate test and writhing test were adopted to study the analgesic effect. Drugloading rate of prepn. reached 4.2%. Xylene-induced ear edema in mice and carrageen-induced pedal swelling in rats were relieved significantly by treating with middle dose and high dose Naproxen microemulsion. The threshold of pain in mice was also increased and writhing times caused by acetic acid decreased (P<0.01 or P<0.05). Medium dose and high dose Naproxen microemulsion was equal or superior to pos. control in anti-inflammatory and analgesic effect. Naproxen microemulsion prepd. by PIT method shows obvious anti-inflammatory and analgesic effect in mice and rats, which may be a new type of naproxen prepn. Bibliographic Information Preparation of a new 1,3-alternate-calix[4]arene-bonded HPLC stationary phase for the separation of phenols, aromatic amines and drugs. Erdemir, Serkan; Yilmaz, Mustafa. Department of Chemistry, Selcuk University, Konya, Turk. Talanta (2010), 82(4), 1240-1246. Publisher: Elsevier

B.V., CODEN: TLNTA2 ISSN: 0039-9140. Journal written in English. 2010:1093044 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract

CAN 153:570091 AN

The authors synthesized the 1,3-alternate 25,27-dioctyloxy-26,28-bis-[3-aminopropyloxy]-calix[4]arene and then immobilized onto -chloropropylsilica gel (CPS). The HPLC behavior of some arom. hydrocarbons, phenolic compds., arom. amines and drug compds. was studied on this 1,3-alternatecalix[4]arene-bonded silica gel stationary phase (CIMS). The effect of org. modifier content and pH of the mobile phase on retention and selectivity of these compds. were studied. According to chromatog. data, the selectivity of CIMS for analytes ascribes to various interactions between CIMS and the analytes, such as hydrophobic interaction, hydrogen bonding interaction, - interaction and inclusion interaction. Bibliographic Information Research of synthesis and structure of optical pure acylhydrazone. Zhou, Xia; Wu, Yi; Zhao, Bin. Zhongshan Torch Polytechnic, Zhongshan, Guangdong Province, Peop. Rep. China. Huaxue Yu Shengwu Gongcheng (2010), 27(2), 38-41. Publisher: Huaxue Yu Shengwu Gongcheng Bianjibu, CODEN: HYSGAF ISSN: 1672-5425. Journal written in Chinese. CAN 153:529835 AN 2010:1049654 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract A method for the prepn. of a Naproxen-derived Schiff base was designed and the synthesis of the target compds. was achieved by a condensation reaction of ( S)-6-methoxy- -methyl-2-naphthaleneacetic acid hydrazide with 2-hydroxybenzaldehyde. The Schiff base presented two different sets of signals in the 1HNMR spectrum either in chloroform solvent or in dimethylsulfoxide solvent, thus indicating the presence of both (E)-isomer and (Z)-isomer. In chloroform at room temp., the (E/Z)-ratio was 49:51 and in DMSO the (E/Z)-ratio was 70:30. Bibliographic Information Quality-by-Design (QbD): process trajectory development for a pharmaceutical co-precipitation process based on an integrated real-time process monitoring strategy. Wu, Huiquan; Khan, Mansoor A. Division of Product Quality Research, Silver Spring, MD, USA. AIChE Annual Meeting, Conference Proceedings, Nashville, TN, United States, Nov. 8-13, 2009 (2009), wu2/1-wu2/17. Publisher: American Institute of Chemical Engineers, New York, N. Y CODEN: 69NCB7 Conference; Computer Optical Disk written in English. AN 2010:1046164 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract Pharmaceutical co-pptn. as an important technique to improve the dissoln. and absorption of poorly sol. drugs has been modified to prep. extended release prepns. However, no much attention has been paid to demonstrate the process understanding of this important process. Process knowledge is an essential part of the Quality-by-Design (QbD) design space establishment. In this work, an integrated PAT approach was developed for real-time monitoring of a pharmaceutical (naproxen) and a polymer(eudragit) co-pptn. process. Process trajectory was constructed based on principal component anal. (PCA) of the real-time PAT data, including process NIR spectra and process turbidity data. The process trajectory clearly reveals various distinguishable process events and process signatures, such as incubation, nucleation, and crystal growth. The practical implication of the process knowledge gained for process control and the establishment of operational process space will be discussed.

Bibliographic Information Fate and removal of Pharmaceuticals and Personal Care Products (PPCPs) in a conventional activated sludge treatment process. Suarez, S.; Omil, F.; Lema, J. M. School of Engineering, University of Santiago de Compostela, Spain. WIT Transactions on Ecology and the Environment (2010), 135(Water Pollution X), 255-265. Publisher: WIT Press, CODEN: WTEEAZ ISSN: 1746-448X. Journal written in English. AN 2010:1045517 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract The fate and behavior of 16 Pharmaceutical and Personal Care Products (PPCPs), including fragrances, hormones and medicines with different physico-chem. properties, was assessed during a conventional biol. wastewater treatment process in a denitrifying/nitrifying pilot plant. The reactor was fed with a synthetic mixt. that reproduced the chem. characteristics of a medium charged urban wastewater with an av. compn. of 500 mg/L of COD, 40 mg/L of N-NH4+ and 8 mg/L of P-PO4-3. Selected PPCPs were spiked to this feed at concns. between 10 and 40 g/L. The pilot plant has been operated continuously for three years under stable conditions. The occurrence of PPCPs along the different compartments of the pilot plant was detd. in a first step by measuring their concns. in the liq. phase. This was further complemented with detailed mass balances in which the most relevant removal mechanisms during biol. treatment have been included (volatilisation, sorption and degrdn.). The lowest removal efficiencies were obtained for carbamazepine, diazepam and diclofenac, whereas the highest transformations (>80%) were achieved for fragrances, fluoxetine, ibuprofen, naproxen and natural estrogens. Sorption has shown to play an important role in the biotransformation of musk compds., which had previously shown not to be easily biodegraded, probably by enhancing their retention inside the pilot plant. The removal of the fragrance celestolide was addnl. influenced by volatilisation in the aerobic, which supposed up to 45% of its overall elimination. The SRT of the plant had only an effect on the transformation degree of compds. with a significant sorption potential. The pos. effect of operating at warmer temps. was only significant for two antibiotics, for which an increase in their transformation degree of around 30% was detd. Bibliographic Information Method for manufacturing porous sustained-release preparation film for preventing tissue adhesion. Moon, Hyeong Sun. (S. Korea). Repub. Korean Kongkae Taeho Kongbo (2010), 8pp. CODEN: KRXXA7 KR 2010090409 A 20100816 Patent written in Korean. Application: KR 2009-9661 20090206. Priority: KR 2009-9661 20090206. CAN 153:343588 AN 2010:1042519 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. KR 2010090409 Priority Application KR 2009-9661 Kind A Date 20100816 Application No. KR 2009-9661 Date 20090206

20090206

Abstract The title method comprises: (1) mixing first org. solvent 100 wt. parts with polylactide 1-20 wt. parts to obtain a mixt. soln., (2) adding second org. solvent 10-100 wt. parts in the mixt. soln. obtained in step 1, (3) feeding the mixt. soln. obtained in step 2 into a mold, and drying to manuf. a porous film, (4) coating antibiotics or anti-inflammatory agents on the porous film, and (5) removing the org. solvent from the porous film. Owing to biodegradable polymer material, the manufd. porous film can be biodegraded in vivo.

Bibliographic Information NO-NSAIDs: Nitric oxide-releasing prodrugs of non-steroidal anti-inflammatory drugs with gastricsparing properties. Nemmani, Kumar V.; Borhade, Namdev; Pathan, Asif R.; Mali, Sunil V.; Karwa, Manoj; Senthilkumar, S. P.; Pamidiboina, Venu; Gund, Machhindra; Deshmukh, Nitin J.; Gaikwad, Parikshit; Jain, Arun K.; Deshattiwar, Jagannath J.; Halder, Somnath; Desai, Dattatraya C.; Mudgal, Jayesh; Dhiman, Mini; Burhan, Aslam U.; Sharma, Ankur; Dubash, Nauzer P.; Mangu, Naveen K.; Dutta, Milan; Thakre, Gajanan; Goud, Santosh; Pacharne, Dnyaneshwar; Babu, Lokesh; Deshpande, Shubhada; Nadar, Vijaya; Sharma, Somesh; Satyam, Apparao. Pharmacology Department, PIRAMAL LIFE SCIENCES LIMITED, Nirlon Complex, Goregaon East, Mumbai, India. Abstracts of Papers, 240th ACS National Meeting, Boston, MA, United States, August 22-26, 2010 (2010), MEDI-156. Publisher: American Chemical Society, Washington, D. C CODEN: 69NAQG Conference; Meeting Abstract; Computer Optical Disk written in English. AN 2010:1011765 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract Lately, a new class of gastric-sparing nitric-oxide-releasable non-steroidal anti-inflammatory drugs (NONSAIDs) is being studied as "Safe NSAIDs". As an extension of our novel disulfide linker technol., we have designed, synthesized and evaluated 25+ novel NO-NSAID prodrugs of aspirin, diclofenac, naproxen, flurbiprofen, ketoprofen, indomethacin, sulindac and ibuprofen. Although amide-contg. prodrugs did not show any bioavailability or antiinflammatory activity, the remaining types of prodrugs exhibited fair to excellent pharmacokinetic, anti-inflammatory and gastric-sparing properties. Among them, however, imide-contg. NO-Aspirin, NO-Flurbiprofen and NO-Ketoprofen, ester-contg. NO-Diclofenac, NONaproxen, NO-Sulindac and NO-Ibuprofen, and double ester-contg. NO-Ketoprofen have shown promising pharmacokinetic, anti-inflammatory and NO-releasing properties and protected rats from NSAID-induced gastric damage which could be attributable to the beneficial effects of NO released from these prodrugs. Bibliographic Information Greening up the Grignard reaction in the pharmaceutical industry: Development of continuous stirred tank reactor (CSTR) processes. Kopach, Michael E.; Groh McClary, Jennifer; Johnson, Martin D. Chemical Product Research & Development, Eli Lilly and Company, Indianapolis, IN, USA. Abstracts of Papers, 240th ACS National Meeting, Boston, MA, United States, August 22-26, 2010 (2010), IEC-12. Publisher: American Chemical Society, Washington, D. C CODEN: 69NAQG Conference; Meeting Abstract; Computer Optical Disk written in English. AN 2010:1010760 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract Since its inception at the start of the 20th century, the Grignard reaction has been broadly studied and applied to the synthesis of numerous complex substances in the prepn. of food additives, industrial chems., and in the prepn. of pharmaceutical intermediates. For example, Pfizer and Astra Zeneca utilized Grignard chem. for key steps in the manuf. of Droloxifene and Tamoxifen, resp.; both of which are non-steroidal estrogen antagonists used for the treatment of breast cancer. Perhaps the most well known application of Grignard chem. in the pharmaceutical industry is Roche's manufg. process for analgesic Naproxen. In addn., Eli Lilly has successfully commercialized a Grignard process for the manuf. of Darvon in the 1970's. Despite these successes the Grignard reaction remains one of the more challenging reactions to bring to com. scale due to acute hazards which include: 1) Strongly exothermic activation an reaction steps; 2) heterogeneous reactions with potential suspension and mixing issues; 3) magnesium handling and waste disposal issues. An attractive and practical processing option is to perform the Grignard reaction in a CSTR (continuous stirred tank reactor) setup. Process hazards are minimized by operating at a small net vol. at any point in time, and it is possible to only activate the magnesium metal once for an entire

campaign. The CSTR system also affords more stable reaction control by operating under steady state. Bibliographic Information Method for manufacturing silica capillary column having molecularly imprinted polymer. Jung, Won Jo; Shabi, Abas Jaidy. (Inha Industry Partnership Institute, S. Korea). Repub. Korean Kongkae Taeho Kongbo (2010), 19pp. CODEN: KRXXA7 KR 2010088008 A 20100806 Patent written in Korean. Application: KR 2009-7128 20090129. Priority: KR 2009-7128 20090129. CAN 153:349383 AN 2010:1005068 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. KR 2010088008 Priority Application KR 2009-7128 Kind A Date 20100806 Application No. KR 2009-7128 Date 20090129

20090129

Abstract The title method comprises attaching double-bond ligand to the inner wall of a SiO2 capillary tube; dissolving monomer mixt. contg. functional monomer, strongly acidic monomer, crosslinking monomer, imprinted mol. and polymn. initiator in mixed solvent contg. hydrogen-bond solvent and nonhydrogenbond solvent to prep. polymn. mixt.; filling the polymn. mixt. in the SiO2 capillary tube; sealing both ends of the SiO2 capillary tube filled with the polymn. mixt.; heating to polymerize; and washing the prepd. SiO2 capillary column. The imprinted mol., esp. acidic template mol. or template mol. contg. carboxyl group, is used to form a porous thin film of molecularly imprinted polymer. The manuf. process is simple, and the manuf. repeatability is good. The prodn. cost is reduced. Through forming a film with uneven surface and porous structure, the template mol. is easy to wash off, and the template mol. residue and persistent bleeding problem are avoided. The mol. recognition ability is good, and the chromatog. mass movement resistance is largely reduced. Both chiral sepn. and achiral sepn. are good. The SiO2 capillary column can be used as a capillary electrochromatog. column. Bibliographic Information Chronotherapeutic pharmaceutical composition including a hydrophilic agent and a pHindependent coating. Boldhane, Sanjay; Jathar, Shripad; Nerurkar, Maneeshp. (Piramal Healthcare Ltd., India). PCT Int. Appl. (2010), 19pp. CODEN: PIXXD2 WO 2010089772 A2 20100812 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in English. Application: WO 2010-IN35 20100121. Priority: IN 2009-MU140 20090122. CAN 153:296015 AN 2010:1003638 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010089772 Kind A2 Date 20100812 Application No. WO 2010-IN35 Date 20100121

WO 2010089772

A3

IN 2009MU00140 Priority Application IN 2009-MU140

20101014 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM, AP, EA, EP, OA 20100827 IN 2009-MU140 20090122

20090122

Abstract The present invention relates to chronotherapeutic pharmaceutical compns. and a method of prepg. the same. The compn. comprises of at least one active ingredient, a pH independent agent and a hydrophilic agent. The active ingredient in the compn. is coated with the pH independent agent. The compn. provides a dual controlled release system, which aids in an initial lag time of 4-6 h and controlled release of the active ingredient up to 24 h. Thus tablet cores contained (mg/tablet): naproxen 500.0; dibasic calcium phosphate dihydrate 126.5; silica 3.5; polyvinylpyrrolidone K30 70.0. water q.s. The coating included (mg/tablet): Eudragit NE 30D 116.7; talc 17.5; water q.s. Bibliographic Information Process for the preparation of chiral -arylpropionates via mechanical processing. Kaptein, Bernardus; Vlieg, Elias; Noorduin, Willem Lieuwe. (DSM IP Assets B.V., Neth.). PCT Int. Appl. (2010), 22pp. CODEN: PIXXD2 WO 2010089343 A1 20100812 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in English. Application: WO 2010-EP51347 20100204. Priority: EP 2009-152244 20090206. CAN 153:310978 AN 2010:1000793 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010089343 Kind A1 Date Application No. Date 20100812 WO 2010-EP51347 20100204 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ,

LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM Priority Application EP 2009-152244

20090206

Abstract R1CHMeCOR2 [I; R1 = (substituted) biphenyl, naphthyl, Ph, thienyl; R2 = amide, OR3; R3 = protecting group, (substituted) amine cation, metal cation] having an enantiomeric excess of 50-99.99% were prepd. by mech. processing of I having an enantiomeric excess of 0-50% and which is present in both the solid state and in soln.; said mech. processing comprises high shear forces or impact forces, i.e. grinding. Thus, Me (RS)-2-(6-methoxynaphthalen-2-yl)propionate (prepn. given) contg. a 1.5% enantiomeric excess of Me (S)-2-(6-methoxynaphthalen-2-yl)propionate was slurried in MeOH contg. NaOMe and subjected to ultrasound at 23 in the presence of glass beads to give a solid phase of enantiopure Me (S)-2-(6methoxynaphthalen-2-yl)propionate. Bibliographic Information Preparation of benzoic acid phenylpyridinyl ethyl ester derivatives for use as phosphodiesterase inhibitors. Amari, Gabriele; Armani, Elisabetta; Delcanale, Maurizio. (Chiesi Farmaceutici S.p.A., Italy). PCT Int. Appl. (2010), 49pp. CODEN: PIXXD2 WO 2010089107 A1 20100812 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in English. Application: WO 2010-EP676 20100204. Priority: EP 2009-1660 20090206. CAN 153:311116 AN 2010:1000666 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010089107 Kind A1 Date Application No. Date 20100812 WO 2010-EP676 20100204 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC,

EP 2216327

A1

VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM 20100811 EP 2009-1660 20090206 R: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LI, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, TR, AL, BA, RS

Priority Application EP 2009-1660

20090206

Abstract Title compds. (-)-I [R1 and R2 independently = (un)substituted alkyl, oxyalkyl, or NHSO2(alkyl), provided at least one is NHSO2(alkyl); n = 0 or 1], and their pharmaceutically acceptable salts, are prepd. and disclosed as phosphodiesterase inhibitors. Thus, e.g., (-)-II was prepd. by condensation of 3cyclopropylmethoxy-4-difluoromethoxybenzaldehyde with 3,5-dichloro-4-methylpyridine followed by condensation with (S)-2-(6-methoxynaphthalen-2-yl)propionic acid, hydrolysis, condensation with 3cyclopropylmethoxy-4-(N-tert-butoxycarbonyl-N-methanesulfonyl)aminobenzoic acid, and deprotection. Select (-)-I were evaluated in PDE4 inhibitory activity ih the blood mononuclear cells (PBMCs) assays, e.g., (-)-II demonstrated 50% inhibition off LPS-induced TNF-a release IC50 value between 0.06 and 4.4 nM.

R1 R2

O O F 2C

Cl

(O) n

Cl

SO 2 Me NH

O O O F 2C O * Cl II Cl N

Bibliographic Information Preparation of nitrate cellulose stationary phase and its application in separation of chiral compounds. Jiang, Yundong; Zhang, Mei; Xie, Shengming; Song, Qing; Yuan, Liming. School of Chemistry and Chemical Engineering, Yunnan Normal University, Kunming, Peop. Rep. China. Huaxue Yanjiu (2010), 21(2), 77-79. Publisher: Huaxue Yanjiu Bianjibu, CODEN: HUYAF4 ISSN: 1008-1011. Journal written in Chinese. CAN 153:633136 AN 2010:999850 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract Nitrate cellulose was coated on silylated silica gel to prep. a novel coating-type stationary phase of highperformance liq. chromatog. (HPLC). The resulting stationary phase was packed into an HPLC column of 250 mm*4.6 mm and used for the sepn. of chiral compds. under a pressure of 40 MPa. It was found that the coated stationary phase could be well used to sep. chiral compds. with a satisfactory efficiency. Bibliographic Information

Copper (II) complexes of the anti-inflammatory drug naproxen and 3-pyridylmethanol as auxiliary ligand. Characterization, superoxide dismutase and catecholase - mimetic activities. Abuhijleh, A. Latif; Khalaf, Juhienah. Chemistry Department, Birzeit University, West Bank, Palestinian Territory, Occupied. European Journal of Medicinal Chemistry (2010), 45(9), 3811-3817. Publisher: Elsevier Masson SAS, CODEN: EJMCA5 ISSN: 0223-5234. Journal written in English. CAN 153:520576 AN 2010:996207 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract The synthesis and spectral characterization of binary copper(II) complex of the non-steroidal antiinflammatory drug naproxen (Nap) with formula [Cu2(Nap)4]n (1) and its ternary complex with 3pyridylmethanol (3-pym) of formula [Cu(Nap)2(3-pym)2]n (2) were studied. Complex 1 is polymeric consisting of units of the known paddle-wheel dicopper(II) tetracarboxylates of four naproxenate ions bridging the two copper atoms. The units are axially connected through the neighboring carboxylate oxygen atoms. The x-ray mol. structure measurements of 2 showed that it is polymeric consisting of mononuclear units having trans-CuN2O2 + O2 chromophores which are bridged by 3-pyridylmethanol ligands through their methanolic oxygen atoms. The measured superoxide dismutase (SOD) mimetic activities of the complexes indicated that complexes 1 and 2 are excellent SOD mimics with an IC50 of 0.30 M for 1 and 0.39 M for 2. The catecholase activities of the complexes toward the aerobic oxidn. of 3,5-di-tert-butylcatechol (DTBC) to 3,5-di-tert-butylquinone (DTBQ) showed that both complexes have moderate catalytic oxidase activities. Bibliographic Information Preparation of benzoic acid phenylpyridinyl ethyl ester derivatives for use as phosphodiesterase inhibitors. Amari, Gabriele; Armani, Elisabetta; Delcanale, Maurizio. (Chiesi Farmaceutici S.p.A., Italy). Eur. Pat. Appl. (2010), 23pp. CODEN: EPXXDW EP 2216327 A1 20100811 Designated States R: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LI, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, TR, AL, BA, RS. Patent written in English. Application: EP 2009-1660 20090206. Priority: EP 2009-1660 20090206. CAN 153:311115 AN 2010:992689 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. EP 2216327 Kind A1 Date Application No. Date 20100811 EP 2009-1660 20090206 R: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LI, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, TR, AL, BA, RS 20100812 WO 2010-EP676 20100204 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY,

WO 2010089107

A1

US 20100204256 Priority Application EP 2009-1660

A1

KG, KZ, MD, RU, TJ, TM 20100812 US 2010-700926

20100205

20090206

Abstract Title compds. I [R1 and R2 independently = (un)substituted alkyl, oxyalkyl, or NHSO2(alkyl), provided at least one is NHSO2(alkyl); n = 0 or 1], and their pharmaceutically acceptable salts, are prepd. and disclosed as phosphodiesterase inhibitors. Thus, e.g., II was prepd. by condensation of 3-cyclopropylmethoxy-4difluoromethoxybenzaldehyde with 3,5-dichloro-4-methylpyridine followed by condensation with (S)-2-(6methoxynaphthalen-2-yl)propionic acid, hydrolysis, condensation with 3-cyclopropylmethoxy-4-(N-tertbutoxycarbonyl-N-methanesulfonyl)aminobenzoic acid, and deprotection. Select I were evaluated in PDE4 inhibitory activity ih the blood mononuclear cells (PBMCs) assays, e.g., II demonstrated 50% inhibition off LPS-induced TNF-a release IC50 value between 0.06 and 4.4 nM.
R1 R2

O O F2 HC

Cl

(O) n

Cl

SO 2 Me NH O

O O F 2HC

Cl

Cl

II

Bibliographic Information

Ester prodrug-loaded electrospun cellulose acetate fiber mats as transdermal drug delivery systems. Wu, Xiao-mei; Branford-White, Christopher J.; Zhu, Li-min; Chatterton, Nichoals P.; Yu, Deng-guang. College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, Peop. Rep. China. Journal of Materials Science: Materials in Medicine (2010), 21(8), 2403-2411. Publisher: Springer, CODEN: JSMMEL ISSN: 0957-4530. Journal written in English. AN 2010:991054 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract Cellulose acetate (CA) fibers loaded with the ester prodrugs of naproxen, including Me ester, Et ester and iso-Pr ester, were prepd. through electrospinning using acetone/N,N-dimethylacetamide(DMAc)/ethanol (4:1:1, vol./vol./v) as solvent. The chem. and morphol. characterizations of the medicated fibers were investigated by means of SEM, DSC, XRD and FTIR, as well as the studies of the drug release properties. The results indicated that the morphol. and diam. of the fibers were influenced by the concn. of spinning soln., applied voltage, electrospun solvent and the surfactants. The av. diams. of the fibers ranged between 100 and 500 nm for three prodrugs. There was good compatibility between CA and three prodrugs in the blended fibers, resp. In vitro release indicated that const. drug release from the fiber was obsd. over 6 days. The prodrugs were successfully encapsulated into the fibers, and this system was stable in terms of effectiveness in release. Bibliographic Information Laccase-catalyzed degradation of anti-inflammatories and estrogens. Lloret, L.; Eibes, G.; LuChau, T. A.; Moreira, M. T.; Feijoo, G.; Lema, J. M. Dept. of Chemical Engineering, School of Engineering, University of Santiago de Compostela, Santiago de Compostela, Spain. Biochemical Engineering Journal (2010), 51(3), 124-131. Publisher: Elsevier B.V., CODEN: BEJOFV ISSN: 1369703X. Journal written in English. AN 2010:982947 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract Pharmaceuticals are regarded as emerging environmental pollutants since many of them are ubiquitous, recalcitrant and biol. active. In this paper, the degrdn. of several pharmaceuticals such as anti-inflammatory drugs (diclofenac and naproxen) and estrogen hormones (estrone, 17 -estradiol, 17 -ethinylestradiol) was assessed by means of the com. laccase (Lac) from Myceliophthora thermophila. The influence of different mediators (synthetic and natural) and their concn. on the Lac-based oxidn. system were evaluated. Estrogens were completely degraded after only 15 min while the other types of pharmaceuticals presented higher persistence since 1 h of incubation was required for total removal of diclofenac and 8 h to attain up to 60% of naproxen degrdn. Among the different natural mediators, syringaldehyde greatly enhanced the action of the Lac, similarly to the synthetic mediator 1-hydroxibenzotriazole (HBT) in the case of estrogens and diclofenac. The other natural mediators presented significantly high efficiency, obtaining removal percentages ranging from 80% to 100% after 24 h of enzymic reaction. Bibliographic Information Iodine-coated expandable medical device especially stents and balloon catheters for the prevention of restenosis. Benjamin Daniel, Orlowski. (Germany). Eur. Pat. Appl. (2010), 14pp. CODEN: EPXXDW EP 2213316 A1 20100804 Designated States R: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LI, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, AL, BA, RS. Patent written in German. Application: EP 2010-75050 20100202. Priority: DE 2009-102009007579 20090202. CAN 153:269975 AN 2010:969626 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R))

Patent Family Information Patent No. EP 2213316 Kind A1 Date Application No. Date 20100804 EP 2010-75050 20100202 R: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LI, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, AL, BA, RS 20100805 DE 2009-102009007579 20090202

DE 102009007579

A1

Priority Application DE 2009-102009007579 A

20090202

Abstract The invention concerns medical device for the dilation of vessel lumens; the device are coated with iodine or an iodine complex contained in a carrier that can further include drugs. Typical combinations are iodine with paclitaxel and iodine with rapamycin. Iodine complexes with polymers can be used. Carrier materials are selected from the group of natural and synthetic polymers; drug selections include cytostatics, antiinflammatory agents, fungicides, antineoplastic agents. Stents, catheters also with porous carbon surface are coated in various procedures. In one example a com. available dilation catheter with expandable balloon is coated in vacuum with a iodine-contg. Parylene C soln. Bibliographic Information Kinetic Resolution of Racemic -Arylalkanoic Acids with Achiral Alcohols via the Asymmetric Esterification Using Carboxylic Anhydrides and Acyl-Transfer Catalysts. Shiina, Isamu; Nakata, Kenya; Ono, Keisuke; Onda, Yu-suke; Itagaki, Makoto. Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo, Japan. Journal of the American Chemical Society (2010), 132(33), 11629-11641. Publisher: American Chemical Society, CODEN: JACSAT ISSN: 0002-7863. Journal written in English. CAN 153:286671 AN 2010:961210 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract A variety of optically active carboxylic esters are produced by the kinetic resoln. of racemic -substituted carboxylic acids using achiral alcs., arom. or aliph. carboxylic anhydrides, and chiral acyl-transfer catalysts. The combination of 4-methoxybenzoic anhydride (PMBA) or pivalic anhydride with the modified benzotetramisole-type catalyst, I, is the most effective for promotion of the enantioselective coupling reaction between racemic carboxylic acids and a novel nucleophile, bis( -naphthyl)methanol, to give the corresponding esters, e.g. II, with high ee's. This protocol was successfully applied to the prodn. of nonracemic nonsteroidal anti-inflammatory drugs from racemic compds. utilizing the transacylation process to generate the mixed anhydrides from the acid components with the suitable carboxylic anhydrides.

S N

Cl

O O Me

II

Bibliographic Information Self-assembled drug-loading chitosan nanoparticle and preparation method thereof. Zhu, Limin; Yu, Dengguang; Shen, Xiaxia; Wu, Chengyao; Nie, Wei. (Donghua University, Peop. Rep. China). Faming Zhuanli Shenqing (2010), 7pp. CODEN: CNXXEV CN 101785760 A 20100728 Patent written in Chinese. Application: CN 2010-10132541 20100325. Priority: CN 2010-10132541 20100325. CAN 153:295940 AN 2010:948548 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. CN 101785760 Priority Application CN 2010-10132541 Kind A Date 20100728 Application No. CN 2010-10132541 Date 20100325

20100325

Abstract The title self-assembled drug-loading chitosan nanoparticle is prepd. by self-assembling core/shell type composite fiber electrospun felt in water, and has a core/shell structure with chitosan as shell and drug as core, where the ratio of chitosan to drug is 1:1. The said drug is tamoxifen, diclofenac, ibuprofen, meloxican, triptolide, alkannin, insulin, growth factor, Sarcandra glabra, Zanthoxylum nitidum, etc. The prepn. method comprises prepg. core soln. and chitosan-contg. shell soln., resp.; electrospinning using coaxial electrospinning nozzle for 5-10 s; and adding dropwise high-pure water in the fiber. The said core soln. comprises tamoxifen 5% (wt./vol.), PVP k30 5% (wt./vol.), and formic acid in balance. The said shell soln. comprises PVP k60 10% (wt./vol.), chitosan 1% (wt./vol.), Triton X-100 0.5% (vol./vol.), and formic acid-ethanol (1:1, vol./vol.) in balance. The said coaxial electrospinning nozzle comprises an L type spinning nozzle mantle, and a spinning axis being coaxial with the tube of the mantle. The inventive method is simple, can manuf. the core/shell type fiber by one step, and is suitable for industrial prodn.

Bibliographic Information Controlled release pharmaceutical or food formulation and process for its preparation. Selva, Stefano; Marchitto, Leonardo; Ciottoli, Giovanni Battista; Ragni, Lorella; Russo, Vincenzo; Liberati, Elisa. (Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.p.A., Italy). PCT Int. Appl. (2010), 46pp. CODEN: PIXXD2 WO 2010084038 A1 20100729 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in English. Application: WO 2010-EP50137 20100108. Priority: EP 2009-425014 20090123. CAN 153:269819 AN 2010:937355 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010084038 Kind A1 Date Application No. Date 20100729 WO 2010-EP50137 20100108 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM

Priority Application EP 2009-425014

20090123

Abstract The present invention relates to a controlled release pharmaceutical or food formulation comprising at least one active pharmaceutical or food ingredient dispersed in a mixt. of a glycogen with a polysaccharide, and the process for its prepn. The invention also relates to a slow release system represented by a mixt. of a glycogen with a polysaccharide, and its use for the prepn. of slow release pharmaceutical or food formulations. Tablets were prepd. and tested contg. paracetamol (active ingredient) 257, Methocel K100M 85.7, Polglumyt 257, Aerosil (glidant) 3, and Pruv (lubricant) 9. The tablets released almost 100 % of the active ingredient over a 24-h period and had a nearly linear release curve. Bibliographic Information Abuse resistant melt extruded formulation having reduced alcohol interaction. Roth, Wolfgang; Burst, Alexander; Zietsch, Martina. (Abbott G.m.b.H. & Co. K.-G., Germany). PCT Int. Appl. (2010),

130pp. CODEN: PIXXD2 WO 2010083894 A1 20100729 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in English. Application: WO 2009-EP56362 20090526. Priority: US 2009-359788 20090126; US 2006-760707P 20060121; US 2007-625705 20070122; US 2007-780625 20070720; US 2008-23288P 20080124. CAN 153:242349 AN 2010:936705 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010083894 Kind A1 Date Application No. Date 20100729 WO 2009-EP56362 20090526 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM 20091224 US 2009-359788 20090126

US 20090317355 Priority Application US 2009-359788 US 2006-760707P US 2007-625705 US 2007-780625 US 2008-23288P

A1

A P A1 A2 P

20090126 20060121 20070122 20070720 20080124

Abstract The present invention relates to compns. for oral administration. The invention preferably comprises at least one abuse-resistant drug delivery compn. for delivering a drug having potential for dose dumping in alc., related methods of prepg. these dosage forms, and methods of treating a patient in need thereof comprising administering the inventive compns. to the patient. Most preferably, the dosage form includes verapamil. These formulations have reduced potential for abuse. In another formulation, preferably the abuse relevant drug is an opioid and the non-abuse relevant drug is acetaminophen or ibuprofen. More preferably, the opioid is hydrocodone, and the non-abuse relevant analgesic is acetaminophen. In certain preferred embodiments, the dosage forms are characterized by resistance to solvent extn.; tampering, crushing or grinding. Certain embodiments of the inventions provide dosage forms that provide an initial burst of release of drug followed by a prolonged period of controllable drug release. Thus, the dissoln. profile of verapamil release from a melt extruded formulation contg. verapamil hydrochloride in a hydroxypropyl cellulose and hypromellose matrix, was tested in 5% and 40% ethanol medium over 8 h. For both extreme conditions of 0% and 40% ethanol, the mean dissoln. percentage was identical at 1 h (19%) and at 8 h was only slightly higher in the 40% ethanol medium (81%) compared to the 0% ethanol

medium (77%). Release profiles under all conditions were characterized by an initial rapid release rate which progressively decreased over time, suggesting a sustained release mechanism with a near zero-order release. Bibliographic Information Synthesis, characterization and pharmacological activity of ester prodrugs of Naproxen. Kumar, Surender; Tyagi, D. K.; Gupta, Arun. Postgraduate Department of Chemistry, DAV (P.G.) College, Dehra Dun, India. Asian Journal of Pharmaceutical and Clinical Research (2010), 3(3), 208-211. Publisher: Asian Journal of Pharmaceutical and Clinical Research, CODEN: AJPCBB ISSN: 0974-2441. http://www.ajpcr.com/Vol3Issue3/17.pdf Journal; Online Computer File written in English. AN 2010:935953 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract Seven ester derivs. of Naproxen have been synthesized via acid alc. coupling of Naproxen and alc. derivs. in dichloromethane medium. These newly synthesized prodrugs were analyzed by NMR and IR spectroscopy. All the compds. were evaluated for anti-inflammatory activity by carrageenan induced rat hind paw edema method and analgesic activity by acetic acid induced writhing. Bibliographic Information Hydrophilic and hydrophobic polymer based naproxen buccal mucoadhesive film: design and in vitro evaluation. Haque, Tasnuva; Talukder, Mesbah U.; Hossan, Md. S. Department of Pharmacy, Stamford University Bangladesh, Dhaka, Bangladesh. Latin American Journal of Pharmacy (2010), 29(2), 232-239. Publisher: Colegio de Farmaceuticos de la Provincia de Buenos Aires, CODEN: LAJPA9 ISSN: 0326-2383. Journal written in English. AN 2010:932398 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract The aim of the present study was to develop a sustained release mucoadhesive buccal film of naproxen, which can be used to treat the inflammation in the oral cavity. The mucoadhesive buccal films were prepd. by solvent casting method. The prepd. films were evaluated for their physicochem. parameters and in vitro release pattern. All the formulations showed uniform wt., thickness, content uniformity and folding endurance. Surface pH was found to be compatible with salivary pH. Na-CMC and HPMC based films (F3 and F-1) showed highest water uptake (80 and 72% at 4 h) and wt. loss (33.40 and 38.48%) as well as ex vivo residence time (270 and 230 min, resp.). Mucoadhesive strength was found to be decreased with the incorporation of hydrophilic polymers. Highest sustained release up to 4 h was found for F-3 (4356%, MDT 3.941 h) and then for F-1 (69.26%, MDT 3342 h). Bibliographic Information Drugs associated with hepatotoxicity and their reporting frequency of liver adverse events in VigiBase: unified list based on international collaborative work. Suzuki, Ayako; Andrade, Raul J.; Bjornsson, Einar; Lucena, M. Isabel; Lee, William M.; Yuen, Nancy A.; Hunt, Christine M.; Freston, James W. Division of Gastroenterology, Duke University, Durham, NC, USA. Drug Safety (2010), 33(6), 503-522. Publisher: Wolters Kluwer Health, CODEN: DRSAEA ISSN: 0114-5916. Journal written in English. AN 2010:931620 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract Background: Challenges exist in the clin. diagnosis of drug-induced liver injury (DILI) and in obtaining

information on hepatotoxicity in humans. Objective: (i) To develop a unified list that combines drugs incriminated in well vetted or adjudicated DILI cases from many recognized sources and drugs that have been subjected to serious regulatory actions due to hepatotoxicity; and (ii) to supplement the drug list with data on reporting frequencies of liver events in the WHO individual case safety report database (VigiBase). Data Sources and Extn.: (i) Drugs identified as causes of DILI at three major DILI registries; (ii) drugs identified as causes of drug-induced acute liver failure (ALF) in six different data sources, including major ALF registries and previously published ALF studies; and (iii) drugs identified as being subjected to serious governmental regulatory actions due to their hepatotoxicity in Europe or the US were collected. The reporting frequency of adverse events was detd. using VigiBase, computed as Empirical Bayes Geometric Mean (EBGM) with 90% confidence interval for two customized terms, 'overall liver injury' and 'ALF'. EBGM of 2 was considered a disproportional increase in reporting frequency. The identified drugs were then characterized in terms of regional divergence, published case reports, serious regulatory actions, and reporting frequency of 'overall liver injury' and 'ALF' calcd. from VigiBase. Data Synthesis: After excluding herbs, supplements and alternative medicines, a total of 385 individual drugs were identified; 319 drugs were identified in the three DILI registries, 107 from the six ALF registries (or studies) and 47 drugs that were subjected to suspension or withdrawal in the US or Europe due to their hepatotoxicity. The identified drugs varied significantly between Spain, the US and Sweden. Of the 319 drugs identified in the DILI registries of adjudicated cases, 93.4% were found in published case reports, 1.9% were suspended or withdrawn due to hepatotoxicity and 25.7% were also identified in the ALF registries/studies. In VigiBase, 30.4% of the 319 drugs were assocd. with disproportionally higher reporting frequency of 'overall liver injury' and 83.1% were assocd. with at least one reported case of ALF. Conclusions: This newly developed list of drugs assocd. with hepatotoxicity and the multifaceted anal. on hepatotoxicity will aid in causality assessment and clin. diagnosis of DILI and will provide a basis for further characterization of hepatotoxicity. Bibliographic Information Preparation of capsaicin derivative as for treating pain. Huang, Wenlong; Zhang, Huibin; Qian, Hai; Zhou, Jinpei; Fu, Zhixian; Zhang, Xiaoyan; Dai, Dongyan. (China Pharmaceutical University, Peop. Rep. China). Faming Zhuanli Shenqing (2010), 33pp. CODEN: CNXXEV CN 101774938 A 20100714 Patent written in Chinese. Application: CN 2010-10018167 20100120. Priority: CN 2010-10018167 20100120. CAN 153:260018 AN 2010:891669 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. CN 101774938 Priority Application CN 2010-10018167 Kind A Date 20100714 Application No. CN 2010-10018167 Date 20100120

20100120

Abstract Title compds. I [R1 = 2-methyloctene or 2-methyloctane; R2 = ONO2, phenylalkylcarbonyl, naphthalenylethylcarbonyl, etc.; X = NHCO, alkyl, alkoxy, etc.; n = 0-2], and their pharmaceutically acceptable salts, are prepd. and disclosed for treating pain. Thus, e.g., II was prepd. by reacting diclofenac with capsaicin in the presence of DCC/DMAP. II demonstrated inhibition of 47.58% in mouse auricle swelling test caused by dimethylbenzene. The title compds. can be used as analgesics.

O MeO ( X) n N H R1 I

R2

O MeO O Cl NH O N H Me Me

Cl

II

Bibliographic Information Simultaneous dissolution of naproxen and flurbiprofen from a novel ternary -cyclodextrin complex. Higashi, Kenjirou; Ideura, Saori; Waraya, Haruka; Limwikrant, Waree; Moribe, Kunikazu; Yamamoto, Keiji. Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba, Japan. Chemical & Pharmaceutical Bulletin (2010), 58(5), 769-772. Publisher: Pharmaceutical Society of Japan, CODEN: CPBTAL ISSN: 0009-2363. Journal written in English. AN 2010:881802 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract A cryst. ternary complex was prepd. by sealed-heating of naproxen (NPX) with a flurbiprofen (FBP)/ cyclodextrin ( -CD) inclusion complex. The dissoln. rates of NPX and FBP in the ternary complex were almost the same, indicating that FBP and NPX from the complex dissolved simultaneously. The ternary CD complex showing a fascinating dissoln. property could be a new formulation for combination therapies. Bibliographic Information Preparation of spherical crystal agglomerates of naproxen containing disintegrant for direct tablet making by spherical crystallization technique. Nokhodchi, A.; Maghsoodi, M. School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. AAPS PharmSciTech (2008), 9(1), 54-59. Publisher: Springer, CODEN: AAPHFZ ISSN: 1530-9932. http://springerlink.com/content/c15112x182179517/fulltext.pdf Journal; Online Computer File written in English. AN 2010:855437 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract The purpose of this research was to obtain directly compressible agglomerates of naproxen contg. disintegrant by spherical crystn. technique. Acetone-water contg. hydroxypropyl celloluse (HPC) and

disintegrant was used as the crystn. system. In this study croscarmellose sodium (Ac-Di-Sol) was employed as disintegrant. The agglomerates were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD), and SEM and were evaluated for flow, packing and tableting properties and drug release. The growth of particle size and the spherical form of the agglomerates resulted in formation of products with good flow and packing properties. The improved compaction properties of the agglomerated crystals were due to their fragmentation occurred during compression. DSC and XRPD studies showed that naproxen particles, crystd. in the presence of HPC and Ac-Di-Sol did not undergo structural modifications. The dissoln. rate of naproxen from tablets made of naproxen-(Ac-Di-Sol) agglomerates was enhanced significantly because of including the disintegrant in to the particles. This was attributed to an increase in the surface area of the practically water insol. drug is exposed to the dissoln. medium. In conclusion the spherical crystn. technique developed in this study is suitable for obtaining agglomerates of drug with disintegrant. Bibliographic Information Effect of drying methods on swelling, erosion and drug release from chitosan-naproxen sodium complexes. Bhise, Kiran S.; Dhumal, Ravindra S.; Paradkar, Anant R.; Kadam, Shivajirao S. Department of Pharmaceutics, Poona College of Pharmacy, Bharati Vidyapeeth University, Pune, Maharashtra, India. AAPS PharmSciTech (2008), 9(1), 1-12. Publisher: Springer, CODEN: AAPHFZ ISSN: 1530-9932. http://springerlink.com/content/u02pt4g4422pj607/fulltext.pdf Journal; Online Computer File written in English. AN 2010:855431 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract The purpose of this research was to explore theapplication of ionic interactions between naproxen sodium (NS) and chitosan (CH) in complexes (NSC) prepd. by tray drying (TD) and spray drying (SD) methods. Drug-polymer ratio (1:1) in the NSC was optimized on the basis of dialysis studies. The particulate systems of NSC were prepd. by tray drying (TD) and spray drying (SD) methods. Release retarding polymers were added to the NSC and to the phys. mixts. contg. NS-CH and their effects on water uptake, matrix erosion and drug release at different pH were compared. Spray dried complexes (SDC) were spherical, free flowing, light and fine amorphous particles in contrast to the cryst., hard, tenacious, irregularly shaped, denser tray dried complexes (TDC) with poor flowability. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform IR (FTIR) patterns confirm the conversion of cryst. to high energy amorphous phase suitable for ionic interactions in NSC. Presence of release retarding polymers, kappa carrageenan and hydroxypropylmethylcellulose (HPMC) in the NSC compacts retarded the drug release and improved the matrix integrity. Carrageenan matrixes exhibited more retardation than HPMC tablets. FTIR patterns, erosion, swelling and drug release from matrixes support ionic interactions between NS and CH in NSC. The reasons for retarded drug release from the chitosan matrixes at acidic pH include poor soly. of drug at acidic pH, formation of a rate limiting polymer gel barrier along the periphery of matrixes and the ionic interactions between oppositely charged moieties. Bibliographic Information Abuse resistant melt extruded formulation having reduced alcohol interaction. Roth, Wolfgang; Burst, Alexander; Zietsch, Martina; Liu, Wei; Dutta, Sandeep. (Abbott Laboratories, USA; Abbott GmbH & Co. K.-G.). U.S. Pat. Appl. Publ. (2010), 65pp., Cont.-in-part of Ser. No. US 2009-359788, filed on 26 Jan 2009 whichCont.-in-pa. CODEN: USXXCO US 20100172989 A1 20100708 Patent written in English. Application: US 2009-631010 20091204. Priority: US 2006-760707P 20060121; US 2007625705 20070122; US 2007-780625 20070720; US 2008-23288P 20080124; US 2009-359788 20090126. CAN 153:184711 AN 2010:850807 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information

Patent No. US 20100172989 US 20070190142 US 20090022798 US 20090317355 Priority Application US 2006-760707P US 2007-625705 US 2007-780625 US 2008-23288P US 2009-359788

Kind A1 A1 A1 A1

Date 20100708 20070816 20090122 20091224

Application No. US 2009-631010 US 2007-625705 US 2007-780625 US 2009-359788

Date 20091204 20070122 20070720 20090126

P A2 A2 P A2

20060121 20070122 20070720 20080124 20090126

Abstract The present invention relates to compns. for oral administration. The invention preferably comprises at least one abuse-resistant drug delivery compn. for delivering a drug having potential for dose dumping in alc., related methods of prepg. these dosage forms, and methods of treating a patient in need thereof comprising administering the inventive compns. to the patient. Most preferably, the dosage form includes verapamil. These formulations have reduced potential for abuse. In another formulation, preferably the abuse relevant drug is an opioid and the non-abuse relevant drug is acetaminophen or ibuprofen. The opioid is hydrocodone, and the non-abuse relevant analgesic is acetaminophen. The dosage forms are characterized by resistance to solvent extn.; tampering, crushing or grinding. The dosage forms provide an initial burst of release of drug followed by a prolonged period of controllable drug release. Bibliographic Information Opioid- and NSAID-containing oral pharmaceuticals. Evenstad, Kenneth L.; Wertz, Christian F.; Jensen, James S.; O'Neill, Victoria Ann; Berge, Stephen M. (Upsher-Smith Laboratories, Inc., USA). PCT Int. Appl. (2010), 51pp. CODEN: PIXXD2 WO 2010078486 A2 20100708 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in English. Application: WO 2009-US69902 20091231. Priority: US 2008141765P 20081231. CAN 153:155592 AN 2010:847789 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010078486 WO 2010078486 Kind A2 A3 Date Application No. Date 20100708 WO 2009-US69902 20091231 20100826 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC,

VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM, AP, EA, EP, OA Priority Application US 2008-141765P

20081231

Abstract Sustained-release oral pharmaceutical compns. include an opioid (including salts) and a salt of a nonsteroidal anti-inflammatory drug (NSAID). Sustained release hydrophilic matrix tablets are prepd. contg. tramadol-HCl, Naproxen Na and docusate Na. Bibliographic Information Chiral bis(amino amides) as chiral solvating agents for enantiomeric excess determination of -hydroxy and arylpropionic acids. Altava, Belen; Burguete, M. Isabel; Carbo, Noelia; Escorihuela, Jorge; Luis, Santiago V. Departamento de Quimica Inorganica y Organica, Universitat Jaume I, Castellon, Spain. Tetrahedron: Asymmetry (2010), 21(8), 982-989. Publisher: Elsevier Ltd., CODEN: TASYE3 ISSN: 0957-4166. Journal written in English. CAN 153:447170 AN 2010:845769 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract A family of bis(amino amides) derived from natural amino acids was synthesized and tested for the NMR enantiodiscrimination, as chiral solvating agents, for enantiomeric excess detn. of some carboxylic acids. Those bis(amino amide) receptors contain different structural modifications and the splitting of the signals of the acids, after addn. of the corresponding CSAs, depends on those structural variables. The influence of amino acid side chain and the nature of the aliph. spacer are important parameters to obtain good chiral discriminations. The results obtained clearly show the chiral recognition abilities of these bis(amino amide) ligands and suggest their advantageous use as chiral solvating agents for carboxylic acids. The binding between bis(amino amides) and carboxylic acids was studied by ESI-MS, NMR, DSC, and mol. modeling. Probably enantiodiscrimination involves the formation of an ionic pair after proton transfer from the carboxylic substrate to the bis(amino amides). Bibliographic Information Study of analgesic effect of naproxen solid dispersions in crospovidone and Elaeagnus Angustifolia fruit powder by using formalin test. Mohajjel Nayebi, A.; Barzegar Jalali, M.; Pourmohammad, S. Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. Ulum-i Daroei (2009), 15(2), 125-132. Publisher: Tabriz University of Medical Sciences, CODEN: UDTIAM ISSN: 1735403X. Journal written in Persian. AN 2010:828620 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract Objectives: Naproxen is a poor water sol. non-steroidal analgesic and anti-inflammatory drug. Oral absorption and effectiveness of a drug can be improved by prepg. solid dispersions and subsequent increase

of dissoln. rate. The aim of this study was to evaluate analgesic effect of solid dispersions of naproxen (1:1) in crospovidone and Elaeagnus Angustifolia fruit powder by using co-grinding technique and formalin test. Methods: Study was carried out in male wistar rats weighing 180-200 g (n = 8 rats per each group). Formalin test was performed one hour after oral administration of drugs by intraplantar injection of formalin 2.5%. Results: Solid dispersions of naproxen in crosspovidone and Elaeagnus Angustifolia produced more (P < 0.001) analgesic effect when compared with phys. mixts. of naproxen with crosspovidone and Elaeagnus Angustifolia and pure naproxen powder. The analgesic effect of phys. mixts. of naproxen with crosspovidone and Elaeagnus Angustifolia were not significantly different from pure naproxen powder. The analgesic effect of solid dispersion of naproxen-crosspovidone was markedly (P < 0.01) more than of solid dispersion of naproxen - Elaeagnus Angustifolia. Conclusion: We suggest that the analgesic effect of naproxen may be increased by prepg. its solid dispersions in crosspovidone and Elaeagnus Angustifolia fruit powder. Bibliographic Information Physicomechanical properties of naproxen-loaded microparticles prepared from Eudragit L100. Maghsoodi, M. Drug Applied Research Center and School of Pharmacy, University of Medical Sciences, Tabriz, Iran. AAPS PharmSciTech (2009), 10(1), 120-128. Publisher: Springer, CODEN: AAPHFZ ISSN: 1530-9932. http://springerlink.com/content/a7476v08427xw440/fulltext.pdf Journal; Online Computer File written in English. AN 2010:809570 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract Microparticles of naproxen with Eudragit L100 and Aerosil were prepd. by the emulsion solvent diffusion method in order to avoid local gastrointestinal irritation, one of the major side effects of nonsteroidal antiinflammatory drugs after oral ingestion. The process of prepn. involved the use of ethanol as good solvent, dichloromethane as a bridging liq., water as poor solvent, Aerosil as anti-adhesion agent, and sodium dodecyl sulfate to aid in the dispersion of the drug and excipients into the poor solvent. The obtained microparticles were evaluated for micromeritic properties, yield, encapsulation efficiency, drug phys. state, and drug release properties. The influence of formulation factors and prepn. condition (polymer/naproxen ratio, Aerosil/polymer ratio, and the initial difference of temp. between the solvent and nonsolvent) on the properties of the microparticles were also examd. The resultant microparticles were finely spherical and uniform with high incorporation efficiency (>79%) and yield (>71%). The incorporation efficiency was enhanced with increasing the ratio of excipients to drug and the initial difference of temp. between the solvent and nonsolvent. The mean diam. of the microparticles was influenced by all of the manufg. parameters. Studies carried out to characterize the micromeritic properties of formulations, such as flowability and packability, showed that microparticles were suitable for further pharmaceutical manipulation (e.g., capsule filling). Drug release studies of the microparticles confirmed the gastroresistance, and math. studies showed that the drug released followed a Hixon and Crowell kinetic. These microparticles represent a simple method for the prepn. of drug-loaded enteric microparticles with desired micromeritic properties and gastroresistance release. Bibliographic Information Downscaling drug nanosuspension production: processing aspects and physicochemical characterization. Van Eerdenbrugh, Bernard; Stuyven, Bernard; Froyen, Ludo; Van Humbeeck, Jan; Martens, Johan A.; Augustijns, Patrick; Van den Mooter, Guy. Laboratory for Pharmacotechnology and Biopharmacy, K. U. Leuven, Louvain, Belg. AAPS PharmSciTech (2009), 10(1), 44-53. Publisher: Springer, CODEN: AAPHFZ ISSN: 1530-9932. http://springerlink.com/content/f2u04m55vqg6235h/fulltext.pdf Journal; Online Computer File written in English. AN 2010:809560 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract

In this study, scaling down nanosuspension prodn. to 10 mg of drug compd. and evaluation of the nanosuspensions to 1 mg of drug compd. per test were investigated. Media milling of seven model drug compds. (cinnarizine-indomethacin-itraconazole-loviride-mebendazole-naproxen-phenytoin) was evaluated in a 96-well plate setup (10, 20, and 30 mg) and a glass-vial-based system in a planetary mill (10, 100, and 1,000 mg). Physicochem. properties evaluated on 1 mg of drug compd. were drug content (highperformance liq. chromatog.), size [dynamic light scattering (DLS)], morphol. (SEM), thermal characteristics (differential scanning calorimetry), and X-ray powder diffraction (XRPD). Scaling down nanosuspension prodn. to 10 mg of drug compd. was feasible for the seven model compds. using both designs, the planetary mill design being more robust. Similar results were obtained for both designs upon milling 10 mg of drug compd. Drug content detn. was precise and accurate. DLS was the method of choice for size measurements. Morphol. evaluation and thermal anal. were feasible, although sample prepn. had a big influence on the results. XRPD in capillary mode was successfully performed, both in the suspended state and after freeze-drying in the capillary. Results obtained for the latter were superior. Both the prodn. and the physicochem. evaluation of nanosuspensions can be successfully downscaled, enabling nanosuspension screening applications in preclin. development settings. Bibliographic Information Synthesis and pharmacological evaluation of condensed heterocyclic 6-substituted-1,2,4-triazolo[3,4b]-1,3,4-thiadiazole derivatives of naproxen. [Erratum to document cited in CA147:385911]. Amir, Mohammad; Kumar, Harish; Javed, Sadique A. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, New Delhi, India. Bioorganic & Medicinal Chemistry Letters (2010), 20(14), 4282. Publisher: Elsevier B.V., CODEN: BMCLE8 ISSN: 0960-894X. Journal written in English. CAN 153:145409 AN 2010:806520 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract On page 4505, in Scheme 1, structure 2 was incorrectly given; the correct version of the structure is given. Bibliographic Information Carboxylic acid medicine-polysaccharide conjugate, its preparation method and application. Zhou, Jianping; Yao, Jing; Hou, Lin. (China Pharmaceutical University, Peop. Rep. China). Faming Zhuanli Shenqing Gongkai Shuomingshu (2010), 11pp. CODEN: CNXXEV CN 101745119 A 20100623 Patent written in Chinese. Application: CN 2010-10100332 20100125. Priority: CN 201010100332 20100125. CAN 153:213528 AN 2010:794206 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. CN 101745119 Priority Application CN 2010-10100332 Kind A Date 20100623 Application No. CN 2010-10100332 Date 20100125

20100125

Abstract The invention relates to a carboxylic acid medicine-polysaccharide conjugate with amphiphilic property, its prepn. by condensation reaction of carboxylic acid medicine and polysaccharide, and application as carrier or macromol. prodrug. The polysaccharide contains carboxy or structure which can be derived into

carboxy, such as low-mol. wt. heparin, desulfated heparin, hyaluronic acid, chondrin, poly-sulfated chondrin, alginic acid, chitosan, carboxymethyl chitosan, hydroxyethyl chitosan, succinyl chitosan, glucan, fungal polysaccharide. The carboxylic acid medicine is lyophobic carboxy-contained anti-tumor medicine, anti-inflammation agent, anti-infection medicine, lipid-regulating agent and antithrombotics. The process for prepg. the conjugate comprises: dissolving carboxyl acid medicine in org. solvent, condensationreacting with alkylenediamine (as link with C no.= 2-12) in presence of dicyclohexyl carbodiimide (DCC) and hydroxysuccinimide (NHS) as activating agent to obtain active intermediate with a free amino group; dissolving polysaccharide in solvent, condensation-reacting with the active intermediate in presence of 1ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) as activating agent to obtain the product. The conjugate can be used as carrier of active mols. (such as taxanes, camptothecins, flavones, vincristines, anthraquinones, podophyllotoxins) in kinds of dosage forms for injection, oral medication, external use or mucosal administration. The conjugate can self-assemble into nano micelles and the process for prepg. medicine-carried nano micelles comprises: dissolving the conjugate in water (with a wt. ratio of 3-50: 1000) to obtain polysaccharide conjugate nano micelles; dissolving org. medicine with ED in pharmaceutically acceptable solvent, mixing with the nano micelles, homogenizing by ultrasonic sound or high pressure, removing org. solvent and small mol. by dialysis, ultra-filtration or column chromatog., and freeze-drying to obtain medicine-carried nano micelles with particle size of 10-1000 nm. The carboxylic acid medicine-polysaccharide conjugate has better potency, lower untoward effect and higher security than the raw medicine. Bibliographic Information Determination of non-steroidal anti-inflammatory drugs residues in animal muscles by liquid chromatography-tandem mass spectrometry. Jedziniak, Piotr; Szprengier-Juszkiewicz, Teresa; Olejnik, Malgorzata; Zmudzki, Jan. Department of Pharmacology and Toxicology, National Veterinary Research Institute, Pulawy, Pol. Analytica Chimica Acta (2010), 672(1-2), 85-92. Publisher: Elsevier B.V., CODEN: ACACAM ISSN: 0003-2670. Journal written in English. CAN 153:86095 AN 2010:791507 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract A confirmatory method for the detn. of residues of nine non-steroidal anti-inflammatory drugs and one metabolite in animal muscles has been developed. After enzymic hydrolysis samples were extd. with acetonitrile and cleaned up using alumina and C18 SPE cartridges. Liq. chromatog.-tandem mass spectrometry was used for the sepn. and detn. of analytes. The method was validated in bovine muscles, according to the Commission Decision 2002/657/EC criteria. Applicability of the method in the anal. of swine, horse and chicken muscles was checked by precision and recovery expt. The influence of matrix effect on the quantification of non-steroidal anti-inflammatory drugs residues was investigated. The method was used for the confirmation of phenylbutazone and oxyphenbutazone in horse muscle sample. Bibliographic Information Multiresponsive polymeric particles with tunable morphology and properties based on acrylonitrile (AN) and 4-vinylpyridine (4-VP). Sahiner, Nurettin; Ilgin, Pinar. Faculty of Sciences and Arts, Chemistry Department, Canakkale Onsekiz Mart University, Canakkale, Turk. Polymer (2010), 51(14), 3156-3163. Publisher: Elsevier Ltd., CODEN: POLMAG ISSN: 0032-3861. Journal written in English. CAN 153:241612 AN 2010:791336 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract We report the synthesis of amphiphilic, pH and magnetic field sensitive polymeric particles obtained from the modification of poly(acrylonitrile-co-4-vinylpyridine) (p(AN-c-4-VP)) core-shell nanoparticles. The magnetic metal nanoparticles were encapsulated in the microemulsion during the polymn. to achieve magnetic-p(AN-c-4-VP)-composites with various morphol. We further chem. modified each component of

p(AN-c-4-VP) particles and its composite to tune the hydrophilicity of the particles. Modification of nitrile (hydrophobic) groups to amidoxime (hydrophilic) groups by amidoximation reaction on AN, and quaternization of nitrogen on pyridine ring of 4-VP were carried out to tune the hydrophilicity and the charge of the particles. The modification also performed on magnetic responsive composites after inclusion of sep. prepd. magnetic Fe3O4 nanoparticles. It was further demonstrated that these multiresponsive particles can be used as drug carrier. A nonsteroidal and anti-inflammatory drug Naproxen was used as a model active agent for drug loading and the release studies from p(AN-c-4-VP) based particles in phosphate buffer soln. (pH = 7.4) at ambient temp. Bibliographic Information Dendrimer based modular platforms for therapeutic and diagnostic applications. Baker, James R., Jr.; Banaszak Holl, Mark M.; Cheng, Xue-Min; Huang, Baohua; McNemy, Daniel; Mullen, Douglas G.; Thomas, Thommey. (The Regents of the University of Michigan, USA). U.S. Pat. Appl. Publ. (2010), 56pp. CODEN: USXXCO US 20100158850 A1 20100624 Patent written in English. Application: US 2009-645081 20091222. Priority: US 2008-140480P 20081223. CAN 153:126470 AN 2010:786377 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. US 20100158850 WO 2010075423 WO 2010075423 Kind A1 A2 A3 Date Application No. Date 20100624 US 2009-645081 20091222 20100701 WO 2009-US69257 20091222 20101118 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM, AP, EA, EP, OA

Priority Application US 2008-140480P

20081223

Abstract The dendrimer based modular platforms are configured such that two or more dendrimers (e.g., PAMAM dendrimers) are coupled together (e.g., via a cycloaddn. reaction), wherein each of the coupled dendrimers is functionalized (e.g., functionalized for targeting, imaging, sensing, and/or providing a therapeutic or diagnostic material and/or monitoring response to therapy). In some embodiments, the invention provides dendrimer based modular platforms having coupled dendrimers (e.g., two or more coupled dendrimers), wherein each dendrimer is conjugated to one or more functional groups (e.g., therapeutic agent, imaging agent, targeting agent, triggering agent) (e.g., for specific targeting and/or therapeutic use of the dendrimer based modular platform). In some embodiments, the functional groups are conjugated to the dendrimers

via a linker and/or a triggering agent. In addn., the invention is directed to methods of synthesizing dendrimer based modular platforms, compns. comprising the dendrimer based modular platforms, as well as systems and methods utilizing the dendrimer based modular platforms [e.g., in diagnostic and/or therapeutic settings [e.g., for the delivery of therapeutics, imaging, and/or targeting agents (e.g., in disease (e.g., cancer) diagnosis and/or therapy, etc.)]]. Bibliographic Information Determination of chemical components illegally mixed in antirheumatic traditional Chinese medicine by LC-MS. Lai, Guofang; Cheng, Bin; Lu, Jing. Yunnan Institute for Food and Drug Control, Kunming, Peop. Rep. China. Zhongguo Yaoshi (Wuhan, China) (2010), 13(4), 453-455. Publisher: Yaowu Liuxingbingxue Zazhishe, CODEN: ZYWCAH ISSN: 1008-049X. Journal written in Chinese. AN 2010:780480 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract Objective: To establish a quick, accurate, sensitive method for anal. of 4-acetamidophenol, trimethoprim, piroxicam, naproxen and phenylbutazone illegally mixed in Antirheumatic traditional Chinese medicine (TCM). Method: Five Chem. components in TCM prepn. were sepd., identified and detd. by HPLC-DAD and UPLC/MS/MS. Result: 4-Acetamidophenol, piroxicam and naproxen were found in formulations. Conclusion: The method is sensitive and accurate, and can be used to detect the 4-acetamidophenol, trimethoprim, piroxicam, naproxen and phenylbutazone illegally mixed in Antirheumatic traditional Chinese medicine. Bibliographic Information Naproxen drug delivery using periodic mesoporous silica SBA-15. Halamova, Dasa; Badanicova, Maria; Zelenak, Vladimir; Gondova, Tatana; Vainio, Ulla. Department of Inorganic Chemistry Faculty of Science, P.J. Safarik University, Kosice, Slovakia. Applied Surface Science (2010), 256(22), 64896494. Publisher: Elsevier B.V., CODEN: ASUSEE ISSN: 0169-4332. Journal written in English. CAN 153:241600 AN 2010:779883 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract In this paper, the authors present the release of naproxen from hexagonal periodic mesoporous silica SBA15, which serves as a drug delivery system. Naproxen, the well-known nonsteroidal anti-inflammatory drug (NSAID), was loaded into the pores of SBA-15 silica modified with aminopropyl groups. The physicochem. properties of the modified sample (A-SBA-15/napro) were compared with the unmodified SBA-15 mesoporous silica loaded with the drug (SBA-15/napro). The kinetic of the naproxen release into the physiol. soln. was studied. The released amt. of naproxen represented 90.7% from the unmodified SBA-15 in 72 h, while from the sample A-SBA-15/napro the released amt. represented about 80.9%. The prepd. materials were characterized by nitrogen adsorption/desorption, Small angle x-ray scattering (SAXS), Fourier-transform IR spectroscopy (FT-IR) and the thermoanal. methods (TG/DTA). Thin layer chromatog. (TLC) was used for quant. detn. of the released naproxen. Bibliographic Information Pharmaceutical composition and injection for treating porcine eperythrozoonosis and preparation method thereof. Zhang, Yaoqi; Zhang, Xinlei. (Henan Huitong Tianxia Animal Pharmaceutical Co., Ltd., Peop. Rep. China). Faming Zhuanli Shenqing (2010), 14pp. CODEN: CNXXEV CN 101732328 A 20100616 Patent written in Chinese. Application: CN 2008-10231017 20081124. Priority: CN 2008-10231017 20081124. CAN 153:155491 AN 2010:769486 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R))

Patent Family Information Patent No. CN 101732328 Priority Application CN 2008-10231017 Kind A Date 20100616 Application No. CN 2008-10231017 Date 20081124

20081124

Abstract The title pharmaceutical compn. contains (by wt.%): imidocarb hydrochloride 17-52, doxycycline hydrochloride 17-35, nonsteroidal antiinflammatory agent 13-65, and glucocorticosteroid or its salt 0.2-2. The title injection comprises (by wt.%): imidocarb hydrochloride 5-15, doxycycline hydrochloride 5-10, nonsteroidal antiinflammatory agent 2-20, glucocorticosteroid or its salt 0.05-0.5, MgCl2 0.5-5, metal complexing agent 0.01-0.05, antioxidant 0.1-0.2, propylene glycol 5-20, and injection water as balance. The pharmaceutical compn. has advantages of reasonable formula, stable phys. and chem. properties, rapid action, long effective time, high bioavailability, safe usage, and good curative effect. Bibliographic Information Theoretical and Experimental Investigation on the Solid Solubility and Miscibility of Naproxen in Poly(vinylpyrrolidone). Paudel, Amrit; Van Humbeeck, Jan; Van den Mooter, Guy. Laboratory of Pharmacotechnology and Biopharmacy, K.U.Leuven, Louvain, Belg. Molecular Pharmaceutics (2010), 7(4), 1133-1148. Publisher: American Chemical Society, CODEN: MPOHBP ISSN: 1543-8384. Journal written in English. CAN 153:184096 AN 2010:768390 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Abstract The objective of the present study was to det. the solid state soly. and miscibility of naproxen in poly(vinylpyrrolidone) (PVP) and the mutual interaction using the std. thermodn. models and thermal anal. Solid dispersions were prepd. by spray drying several compns. of naproxen and PVP with different mol. wts., viz., PVP K 12, PVP K 25 and PVP K 90, and analyzed using modulated differential scanning calorimetry (mDSC). The kinetic miscibility limit in terms of a single mixed phase glass transition temp. was found to be relatively similar for the dispersions contg. PVP with different chain lengths ( 50% wt./wt. drug in PVP). But the systems with different PVP followed diverse patterns of compn. dependent mixed phase glass transition temp. as well as the degree of plasticization by water. The cryst. solid soly. values of naproxen in PVP estd. by using its soly. data in n-methylpyrrolidone, a low mol. wt. analog of PVP, were 6.42, 5.85 and 5.81% wt./wt. of drug in PVP K 12, PVP K 25 and PVP K 90 resp. The values estd. for corresponding amorphous soly. showed no marked difference. The remarkable difference between thermodn. soly./miscibility and kinetic miscibility implied that naproxen was highly supersatd. in the PVP solid dispersions and only stabilized kinetically. The neg. value of the drug-polymer interaction parameter (-0.36) signified the systems to be favorably mixing. The m.p. depression data of naproxen in PVP pointed to the compn. dependence and chain length effect on the interaction. The moisture sorption by the phys. mixts. not only provided the compn. dependent interaction parameter but also conferred an est. of compn. dependent miscibility of naproxen in PVP in the presence of water. Bibliographic Information Manufacture and application of pharmaceutical composition containing antiinflammatory drugpolysaccharide conjugate. Zhou, Jianping; Yao, Jing; Hou, Lin. (China Pharmaceutical University,

Peop. Rep. China). Faming Zhuanli Shenqing Gongkai Shuomingshu (2010), 11pp. CODEN: CNXXEV CN 101732728 A 20100616 Patent written in Chinese. Application: CN 2010-10100280 20100125. Priority: CN 2010-10100280 20100125. CAN 153:155482 AN 2010:768348 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. CN 101732728 Priority Application CN 2010-10100280 Kind A Date 20100616 Application No. CN 2010-10100280 Date 20100125

20100125

Abstract The title antiinflammatory drug-polysaccharide conjugate is manufd. through introducing a hydrophobic carboxylic acid-series nonsteroidal anti-inflammatory agent to the carboxyl group of a polysaccharide mol. with alkylenediamine as a connecting arm, is amphiphilic, and can form nanometer micelles through selfassembly in an aq. medium. The polysaccharide mol. is selected from carboxyl-contg. un-fractioned heparin, low-mol.-wt. heparin, desulfated heparin, hyaluronic acid, chondroitin, polysulfated chondroitin, and alginic acid, and from chitosan polysaccharide, carboxymethyl chitosan, hydroxyethyl chitosan, succinyl chitosan, glucan, and fungal polysaccharide with introduced carboxyl. The antiinflammatory drug is selected from hydrophobic carboxyl-contg. salicylic acid-, phenylpropionic acid-, phenylacetic acid-, indole-, fenamic acid-, and enoic acid-series nonsteroidal anti-inflammatory agents. The conjugate can enwrap antirheumatic agents so as to treat rheumatoid arthritis together with an antiinflammatory agent to generate synergistic effects. The invention also discloses a pharmaceutical compn. contg. the conjugate and a slow-effect antirheumatic agent. The conjugate and the pharmaceutical compn. have the advantages of high safety and good treatment effect, and can be used through injection, oral administration or external application. Bibliographic Information Compositions comprising azelastine and methods of use thereof. Fuge, Dennis; Higson, John; Roecklein, Bryan A.; Balwani, Gul; D'Addio, Alexander D. (Meda Pharmaceuticals Inc., USA). U.S. Pat. Appl. Publ. (2010), 148pp., Cont.-in-part of U.S. Ser. No. 486,454. CODEN: USXXCO US 20100152147 A1 20100617 Patent written in English. Application: US 2009-569548 20090929. Priority: US 2004-630274P 20041124; US 2005-284109 20051122; US 2006-486454 20060714; WO 2005-US42362 20051122. CAN 153:97764 AN 2010:756977 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. US 20100152147 US 20060110331 AU 2005309657 CA 2588338 EP 1827499 Kind A1 A1 A1 A1 A1 Date Application No. Date 20100617 US 2009-569548 20090929 20060525 US 2005-284109 20051122 20060601 AU 2005-309657 20051122 20060601 CA 2005-2588338 20051122 20070905 EP 2005-824835 20051122 R: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HU, IE, IS, IT, LI, LT, LU, LV, MC, NL, PL, PT, RO, SE, SI, SK, TR, AL, BA, HR, MK, YU 20080102 CN 2005-80046487 20051122 20080626 JP 2007-543411 20051122

CN 101098714 JP 2008521812

A T

BR NZ US MX IN KR

2005017891 555501 20070020330 2007006233 2007KN02092 2007104884

A A A1 A A A

20081021 20100129 20070125 20071123 20070810 20071029

BR NZ US MX IN KR

2005-17891 2005-555501 2006-486454 2007-6233 2007-KN2092 2007-7014388

20051122 20051122 20060714 20070524 20070608 20070622

Priority Application US 2004-630274P US 2005-284109 US 2006-486454 WO 2005-US42362

P A2 A2 W

20041124 20051122 20060714 20051122

Abstract The present invention provides pharmaceutical compns. comprising azelastine, or a pharmaceutically acceptable salt or ester thereof including azelastine hydrochloride, and optionally one or more addnl. active agents. Preferred compns. further comprise one or more pharmaceutically acceptable carriers or excipients that reduce the amt. of post-nasal drip, and/or that minimize or mask the unpleasant bitter taste assocd. with post-nasal drip of the compns. into the oral cavity, upon intranasal or ocular administration of the compns. Esp. effective excipients used in the compns. of the present invention are hypromellose as a viscosity modifier and sucralose as a taste-masking agent. The invention also generally relates to pharmaceutical compns. comprising one or more active pharmaceutical ingredients, such as azelastine or pharmaceutically acceptable salts or esters thereof including azelastine hydrochloride, particularly wherein the compns. are provided in unit dosage form. In certain embodiments, the invention provides such unit dosage pharmaceutical compns. comprising azelastine hydrochloride formulated for use as nasal sprays and/or ocular solns. or drops. The invention also provides methods of treating or preventing certain disorders, or symptomatic relief therefrom, by administering the compns. of the invention to a patient, e.g., for the symptomatic relief of a variety of allergic and non-allergic conditions, particularly conjunctivitis, sinusitis, rhinitis and rhinosinusitis. The compns. and methods of the present invention provide significant value in terms of patient acceptability, convenience, and compliance. A nasal spray formulation contg. 0.05-0.150% azelastine hydrochloride prepd. using hypromellose as a thickener, 0.01-2.0% a steroid (fluticasone, mometasone, dexamethasone beloxil, loteprednol, budesonide, or triamcinolone), and sucralose as both a sweetener and a taste-masking agent was exemplified. Bibliographic Information Cosmetic composition containing acetylated oligoglucuronans. Fournial, Arnaud; Grizaud, Claire Marie; Le Moigne, Caroline; Mondon, Philippe. (Sederma, Fr.). Fr. Demande (2010), 101pp. CODEN: FRXXBL FR 2939799 A1 20100618 Patent written in French. Application: FR 2008-58501 20081211. Priority: FR 2008-58501 20081211. CAN 153:96659 AN 2010:752478 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. FR 2939799 WO 2010067327 Kind A1 A1 Date Application No. Date 20100618 FR 2008-58501 20081211 20100617 WO 2009-IB55663 20091210 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK,

MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM Priority Application FR 2008-58501

20081211

Abstract The present invention relates to the field of cosmetic and dermopharmaceutical compns. It concerns oligomer compds. of D-glucuronic acid or D-glucuronate with a (1-4) sequence (or oligoglucuronans) contg. a degree of acetylation specifically between 8.7 0.5 and 9.2 0.5 % by wt. of O-CO-CH3 group compared to the wt. of glucuronic acid and with a degree of polymn. (DP) of 18-19 2. The oligomer compds. according to the present invention are intended to stimulate the elasticity of the dermis and epidermis although they also act to increase dermo-epidermal cohesion in order to combat skin aging, lines, wrinkles, visible and/or tactile skin discontinuities, loss of firmness, elasticity and tone and to combat skin tissue deformability. The invention also concerns a cosmetic compn. contg. at least one compd. as recited according to the present invention. A cosmetic body fluid included 9.1 % acetylated oligoglucuronan as a soln. in liposomes. Bibliographic Information Cosmetic composition containing acetylated oligoglucuronans. Fournial, Arnaud; Grizaud, ClaireMarie; Le Moigne, Caroline; Mondon, Philippe. (Sederma, Fr.). PCT Int. Appl. (2010), 86pp. CODEN: PIXXD2 WO 2010067327 A1 20100617 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in English. Application: WO 2009-IB55663 20091210. Priority: FR 2008-58501 20081211. CAN 153:96644 AN 2010:750007 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010067327 Kind A1 Date Application No. Date 20100617 WO 2009-IB55663 20091210 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN,

FR 2939799 Priority Application FR 2008-58501

A1

ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM 20100618 FR 2008-58501 20081211

20081211

Abstract The present invention relates to the field of cosmetic and dermopharmaceutical compns. It concerns oligomer compds. of D-glucuronic acid or D-glucuronate with a (1-4) sequence (or oligoglucuronans) contg. a degree of acetylation specifically between 8.7 0.5 and 9.2 0.5 % by wt. of O-CO-CH3 group compared to the wt. of glucuronic acid and with a degree of polymn. (DP) of 18-19 2. The oligomer compds. according to the present invention are intended to stimulate the elasticity of the dermis and epidermis although they also act to increase dermo-epidermal cohesion in order to combat skin aging, lines, wrinkles, visible and/or tactile skin discontinuities, loss of firmness, elasticity and tone and to combat skin tissue deformability. The invention also concerns a cosmetic compn. contg. at least one compd. as recited according to the present invention. A cosmetic body fluid included 9.1 % acetylated oligoglucuronan as a soln. in liposomes. Bibliographic Information Preparation of heteroaryl-substituted urea modulators of fatty acid amide hydrolase. Breitenbucher, J. Guy; Keith, John M.; Tichenor, Mark S.; Chambers, Alison L.; Jones, William M.; Hawryluk, Natalie A.; Timmons, Amy K.; Merit, Jeffrey E.; Seierstad, Mark J. (Janssen Pharmaceutica NV, Belg.). PCT Int. Appl. (2010), 102pp. CODEN: PIXXD2 WO 2010068453 A1 20100617 Designated States W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM. Designated States RW: AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, MC, MT, NL, NO, PT, SE, SM, TR, BF, BJ, CF, CG, CI, CM, GA, ML, MR, NE, SN, TD, TG. Patent written in English. Application: WO 2009-US65757 20091124. Priority: US 2008-117884P 20081125. CAN 153:87828 AN 2010:746207 CAPLUS (Copyright (C) 2010 ACS on SciFinder (R)) Patent Family Information Patent No. WO 2010068453 Kind A1 Date Application No. Date 20100617 WO 2009-US65757 20091124 W: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN,

ZA, ZM, ZW RW: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR, BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG, BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM Priority Application US 2008-117884P

20081125

Abstract The title compds. I [Ar1 = (un)substituted isoxazolo[5,4-c]pyridin-3-yl, isoxazolo[4,5-c]pyridin-3-yl, isoxazolo[4,5-b]pyridin-3-yl, etc.; Z = N, or CH; Ar2 = (un)substituted Ph, 9-10 membered fused bicyclic heteroaryl], useful as FAAH inhibitors, were prepd. E.g., a multi-step synthesis of II, starting from tert-Bu piperazine-1-carboxylate and 3-(4-chlorophenoxy)benzaldehyde, was given. Exemplified compds. I were tested against human FAAH (data given). Compds. I may be used in pharmaceutical compns. and methods for the treatment of disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity, such as anxiety, pain, inflammation, sleep disorders, eating disorders, insulin resistance, diabetes, osteoporosis, and movement disorders (e.g., multiple sclerosis). Pharmaceutical compn. comprising compd. I in combination with other active ingredient, was disclosed.
O Ar 1 N H N Z Ar 2 I

N N N

O N H N N O Cl

II