Chlorhexidine oral rinse

CHLORHEXIDINE oral rinse (Peridex, Periogard) is used to treat gingivitis. Bacteri

a that grow on your teeth between brushings cause gingivitis. Chlorhexidine dest
roys this bacteria. Chlorhexidine oral rinse will help to decrease gum bleeding
and redness and swelling of your gums. Chlorhexidine oral rinse will not prevent
plaque or tartar from forming on your teeth. Proper toothbrushing and flossing
are still needed. Treatment with chlorhexidine oral rinse usually begins immedia
tely after a dental cleaning.
Prior to prescribing this medication, your dentist will need to know if you have
any of the following conditions:
an unusual or allergic reaction to chlorhexidine, especially skin antiseptics
other gum or dental problems
front tooth fillings, dentures or other mouth appliances, especially those having
rough surfaces
Chlorhexidine oral rinse should be used immediately after brushing and flossing.
Rinse all toothpaste completely from your mouth. The cap on the original contai
ner may be used to measure the 15ml (1 tablespoonful) dose. Fill the cap to the
"fill line." If you do not have the cap, ask your pharmacist or other healthcare
professional for a device to measure the dose. Swish 15 ml chlorhexidine oral r
inse in your mouth for 30 seconds. Do not swallow the medicine. Use the medicine
full strength; do not mix with water before using. Do not eat or drink for seve
ral hours after using the oral rinse as this may decrease the effect of the medi
cine. Your dose and daily use may be different from these directions. Follow the
directions from your dentist or other healthcare professional.
Contact your pediatrician or health care professional regarding the use of this
medicine in children. Special care may be needed. If you miss a dose of this med
icine, use it as soon as possible. If it is almost time for your next dose, skip
the missed dose and start back on your regular schedule. Do not use double dose
s. Very little chlorhexidine is taken-up by your body. The oral rinse should not
interact with any other medications you are taking.
Tell your dentist all other medicines you are taking including non-prescription
medicines, nutritional supplements, or herbal products. Also tell your dentistl
if you are a frequent user of drinks with caffiene or alcohol, if you smoke or i
f you use illegal drugs. These may effect the way your medicine works. Check bef
ore stopping or starting any of your medications.
Side effects that you should report to your dentist as soon as possible include:
shortness of breath
rash
hives
itching
swelling of tongue or throat
Side effects that usually do not require medical attention (report to your presc
riber or other health care professional if they continue or are bothersome). Vis
it your dentist every 3 months for gum diease maintenance and to check on your p
rogress. Chlorhexidine oral rinse may have a bitter aftertaste. Do not rinse you
r mouth after using chlorhexidine oral rinse because that will increase the bitt
er taste. Also, rinsing will decrease the effect of the chlorhexidine.
Chlorhexidine oral rinse may change the way food tastes to you. This effect may
last up to 4 hours after using the rinse. Usually this effect becomes less notic
eable as you continue using the rinse. Your taste should return to normal after

stopping the use of chlorhexidine.

Chlorhexidine oral rinse may increase tartar build-up and stain your teeth, dent
ures or fillings. Brush with a tartar control toothpaste and floss daily to help
decrease the amount of tartar build-up and staining. It is important to visit y
our dentist at least every 6 months to have your teeth cleaned.
PerioChip
More than 75 percent of Americans over the age of 35 suffer from periodontal dis
ease, a bacterial infection of the gums, teeth, and bone that surrounds the teet
h. As the disease progresses, your immune system produces white blood cells to f
ight the infection. Unfortunately, the white blood cells release enzymes that de
stroy the soft tissue and bone that hold your teeth in place, and as a result, y
our teeth may become loose. If left untreated, this destruction of supporting bo
ne will eventually lead to tooth loss.
Fortunately, we now have an effective treatment called PerioChip that we apply d
irectly to the infected area. PerioChip fights periodontal disease and its tissu
e-destroying effects by reducing the number of harmful bacteria in your gums.
A PerioChip is a biodegradable gelatin chip that's about the size of a baby's fi
ngernail. It contains the antiseptic chlorhexidine, a medication that's placed d
irectly on the infected gum tissue. As the chip disintegrates, it releases the m
edication into the periodontal pocket, first at a high concentration, then at a
controlled rate for the duration of the treatment. The antiseptic greatly reduce
s the number of bacteria in the infected pocket and speeds the healing process.
Unlike antibiotics, PerioChip does not produce bacterial resistance; it works by
destroying the bacteria's cell walls.
Depending on your needs, we can place up to 8 PerioChips in a single visit. We t
ypically recommend PerioChip treatment after we perform a procedure called scali
ng and root planing, and then again about every 3 to 6 months for as long as per
iodontal pockets are 5 millimeters deep or more. Unlike some other treatments th
at contain antibiotics, PerioChip can be administered every 3 months for up to 2
4 months.
PerioChip is not a cure for periodontal disease and cannot replace supportive bo
ne that may have been lost if the disease was left untreated. You'll still need
to be meticulous about your daily oral hygiene and come to see us every 3 to 4 m
onths for exams and professional cleanings. However, when it's used as part of y
our comprehensive periodontal therapy, PerioChip can help prevent further destru
ction of bone and connective tissue.
Periostat
Periodontal disease is an infection of the teeth, gums, and the bone that surrou
nds the teeth. It's caused by specific bacteria that live in the spaces between
the teeth and gums, called pockets. The bacteria that cause periodontal disease
trigger the body's immune system to produce enzymes, and these enzymes are what
actually cause bone loss.
If left untreated, the destruction of supporting bone eventually leads to tooth
loss. In fact, periodontal disease is the number-one cause of adult tooth loss.
The traditional treatment for periodontal disease has always included a series o
f steps, beginning with the removal of plaque and tartar from the root surfaces.
This procedure is called root planing. After healing, the areas are re-evaluate
d, homecare techniques are modified, and in severe cases, surgery is recommended
. Fortunately, recent breakthroughs have led to the development of another effec
tive tool in the ongoing fight against periodontal disease -- a new systemic med

ication called Periostat.

Periostat is taken not for its antibiotic effect, but for its inhibiting effect
on the bone-destroying enzymes that are released by the body in response to peri
odontal disease. It's taken twice daily, one capsule in the morning and one in t
he evening, about an hour before meals. When used in combination with scaling, r
oot planing, and improved homecare techniques, Periostat suppresses the level of
destructive enzymes that cause bone loss, which will in turn help to reduce poc
ket depth and promote healthy gum-tooth attachment. We won't prescribe Periostat
if you're allergic to tetracyclines, or are pregnant or nursing; we also don't
prescribe it for infants or children under eight years of age.
Periostat is an important advance in the treatment of adult periodontitis that,
when combined with scaling, root planing and improved homecare techniques, can h
elp stop the ongoing damage caused by periodontal disease.

2324434
Title: Use of gellable pharmaceutical compositions in periodontology
United States Patent: 6,818,224
Issued: November 16, 2004
Inventors: Fanara; Domenico (Wanze, BE); Vranckx; Henri (Brussels, BE); Deleers
; Michel (Linkebeek, BE); Grognet; Pierre (Brussels, BE)
Assignee: UCB, S.A. (Brussels, BE)
Appl. No.: 259366
Filed: September 17, 2002
Abstract
A method is described for preparing a fluid pharmaceutical composition which all
ows the controlled release of at least one active substance. The method involves
mixing a therapeutically effective amount of at least one active substance, fro
m 3 to 55% by weight of phospholipid, from 16 to 72% by weight of pharmaceutical
ly acceptable solvent, and from 4 to 52% by weight of fatty acid. The compositio
n has a property of gelling instantaneously in the presence of an aqueous phase.
Description of the Invention
The present invention relates to pharmaceutical compositions which allow the sus
tained release of at least one active substance, to methods for preparing these
compositions, as well as to their use for treating periodontitis, gingivitis, de
ntal abscesses, mouth ulcers and mycoses.
Periodontitis is a disease which is revealed by the destruction of the supportin
g tissues of teeth subsequent to an inflammation which is caused by the anaerobi
c microorganisms of dental plaque. Without treatment, the disease inevitably dev
elops and increasing numbers of bacterial populations continuously maintain the
immune reaction which triggers the phenomena of periodontal disease and periodon
toclasia. As soon as it reaches a depth greater than 3 mm, the gingivo-dental cr

evice is considered to be a periodontal pocket. Periodontitis is also accompanie

d by the resorption of the alveolar bone. Its development finally leads to tooth
loss.
Periodontitis is a disease which more greatly affects the adult population over
forty years old. Periodontitis is not, however, a disease of elderly people; it
quite frequently affects even the young.
It is possible to distinguish acute infections (superficial gingivitis or deep p
eriodontal abscesses); "rapidly evolving" infections (adolescent and young-adult
periodontitis); and finally, chronic infections which evolve in stages (chronic
periodontal disease).
The methods for treating periodontitis comprise in particular daily hygiene and
mechanical means (cleaning, descaling, surfacing of roots, etc.), as well as loc
al and systemic antiseptic and antibiotic means.
Antiseptics can be administered locally in the form of mouthwashes, toothpastes
or creams. However, this mode of local administration does not allow the antisep
tics to diffuse all the way to the bottom of the periodontal pockets. The functi
on of this mode of administration cannot go beyond the stage of prophylaxis.
With regard to antibiotics, they are no more active by topical administration fo
r the same reason, since they do not manage to reach the depth of the bacterial
biofilms (or plaque). When the severity of the case makes it necessary, antibiot
ics are thus generally administered systemically, relying on their diffusion as
far as the periodontal pockets through the gingival fluid which continually flow
s into them.
Another method consists in using pharmaceutical compositions which allow the con
trolled release of antiseptic or antibiotic agents, and which are inserted direc
tly at the bottom of the periodontal pocket. Sustained-release compositions exis
t which are deposited on solid devices such as soaked threads, gelatin chips, et
c. Such devices can leave insoluble frameworks in place which must, of course, b
e removed at the end of treatment.
The literature also mentions fluid pharmaceutical compositions, such as more or
less viscous emulsions or suspensions, which are administered into the periodont
al pocket generally with the aid of syringes.
International patent application WO 95/34287 describes biodegradable lipid compo
sitions in the form of L2 crystalline phases which allow the controlled release
of active substances and which comprise, besides the active substance, at least
one unsaturated fatty acid diacylglycerol which has 16 to 22 carbon atoms or sat
urated fatty acid diacylglycerol which has 14 to 22 carbon atoms, at least one p
hospholipid chosen from glycerophosphatides and sphingophosphatides, and, option
ally, at least one polar liquid chosen from water, glycerol, ethylene glycol and
propylene glycol. These compositions have the characteristic of transforming in
to cubic liquid crystal phases upon contact with water, which makes it possible
to "mould" the active substance in the site where it is desired for the action t
o take place. The said document mentions, among other uses, the possibility of u
sing such compositions for treating periodontitis. However, the effectiveness of
such compositions in the treatment of periodontitis is not illustrated in that
document.
European patent 429224 describes compositions which are in the form of gels cont
aining from 1 to 99% by weight of monoolein and from 1 to 90% by weight of activ
e substance, which are placed in the periodontal cavity. In the presence of the
surrounding water, these compositions become more viscous and keep the active su
bstance close to its site of action. The active substance is released slowly in

controlled fashion.
U.S. Pat. No. 5,230,895 describes the use of compositions which are in the form
of solutions or pastes which are capable of transforming into gel when they have
been placed in the periodontal pocket. These compositions are biodegradable and
allow the controlled release of the active substance in the site of action. The
y contain a mixture of glycerides and of an active substance chosen such that it
is capable of forming a gel in the environment of the periodontal pocket. The c
ompositions illustrated in the said document contain at least 70% of Myverol.TM.
18-92, which is a composition of sunflower monoglycerides which has a monoglyce
ride content of at least 90%.
U.S. Pat. No. 5,143,934 describes compositions which allow the administration, b
y controlled release, of an active substance in a periodontal pocket, and which
comprise at least one monoglyceride and at least one plant oil in proportions wh
ich are sufficient to form a liquid crystal phase upon contact with the water pr
esent in the periodontal pocket. These compositions are solid at room temperatur
e, but they have a melting point which is lower than body temperature.
In that document, the results obtained for several compositions of this type are
compared with the results obtained with a conventional mechanical treatment. It
is noted that the compositions which are described therein make it possible to
obtain a reduction in the size of the periodontal pockets and a decrease in blee
ding during three months of treatment. However, the effect obtained by applying
the compositions is no better, and is even slightly worse, than the result which
may be obtained with the reference mechanical treatment.
In addition, since the compositions described in U.S. Pat. No. 5,143,934 are sol
id at room temperature, they must be liquefied at the moment of insertion into t
he periodontal pocket.
The applicant has now just discovered novel pharmaceutical compositions which ca
n be easily applied into the periodontal pocket and which allow the sustained re
lease of active substances in this pocket. The applicant has in particular just
discovered that these novel compositions are very well suited to the treatment o
f periodontitis, due to both their effectiveness and their ease of use. In addit
ion, these compositions are obtained by an extremely simple preparation method.
Consequently, the present invention relates to fluid pharmaceutical compositions
which allow the controlled release of at least one active substance and which c
omprise
a) a therapeutically effective amount of at least one active substance,
b) from 3 to 55% by weight of phospholipid,
c) from 16 to 72% by weight of pharmaceutically acceptable solvent, and
d) from 4 to 52% by weight of fatty acid, these compositions having the property
of gelling instantaneously in the presence of an aqueous phase.
According to another aspect, the invention relates to methods for preparing thes
e compositions.
According to a third aspect, the invention relates to the use of these compositi
ons for treating periodontitis, gingivitis, dental abscesses, mouth ulcers and m
ycoses.
The compositions according to the present invention comprise a therapeutically e
ffective amount of at least one active substance. The latter can be lipid-solubl

e or water-soluble. By way of example, mention will be made of antibiotics, in p

articular antibiotics which are active against anaerobic bacteria, such as doxyc
ycline or minocycline, and the pharmaceutically acceptable salts thereof, anti-i
nfectious agents such as metronidazole, chlorhexidine, benzalkonium chloride, pchloro-m-cresol, 2,4-dichlorobenzyl alcohol, hexamidine or chlorofen, and the ph
armaceutically acceptable salts thereof, local anesthetics such as lidocaine, pr
ocaine, tetracaine, articaine, bupivacaine, mepivacaine or prilocaine, and the p
harmaceutically acceptable salts thereof, steroidal or other anti-inflammatory a
gents such as hydrocortisone, cortisone, prednisone, prednisolone, methylprednis
olone, triamcinolone, betamethasone or dexamethasone, and the pharmaceutically a
cceptable salts thereof, as well as aceclofenac, diclofenac, ibuprofen and pirox
icam, and the pharmaceutically acceptable salts thereof, anti-mycotic agents suc
h as griseofialvin, amphotericin B, natamycin or nystatin, and the pharmaceutica
lly acceptable salts thereof, or alternatively peptide active substances such as
calcitonin, somatostatin, bone growth hormone and other growth or repair factor
s.
The compositions according to the present invention contain from 3 to 55% of pho
spholipid. The phospholipids which can be used according to the present inventio
n are phosphoric esters of polyols and of fatty acids. They may originate from v
ery varied sources, both natural and via a synthetic pathway. The phospholipids
may be hydrogenated or nonhydrogenated. By way of examples, mention will be made
of phosphatidylchloine, hydrogenated phosphatidylcholine, phosphatidylglycerol
salts, dicaproylphosphatidylcholine or distearoylphosphatidylglycerol salts. The
se phospholipids can also be used as a mixture. Preferably, the phospholipid whi
ch is present in the compositions according to the present invention is phosphat
idylcholine.
When the phospholipid is chosen from phosphatidylcholine, phosphatidylglycerol s
alts, dicaproylphosphatidylcholine or distearoylphosphatidylglycerol salts, the
preferred compositions according to the present invention contain from 15 to 55%
by weight of phospholipid. When the phospholipid is a hydrogenated phosphatidyl
choline, the compositions according to the present invention contain from 3 to 1
1%, preferably from 3 to 10%, by weight of phospholipid.
The compositions according to the present invention contain one or more pharmace
utically acceptable solvents. The expression "pharmaceutically acceptable solven
t" is intended to mean a solvent such as propylene glycol, polyethylene glycols,
mineral oils, such as liquid paraffin or silicone oils, or any other solvent in
which the phospholipid used is soluble. Mixtures of several pharmaceutically ac
ceptable solvents can also be used. Propylene glycol is preferably used. The sol
vent used is pharmaceutically acceptable, which means that the solvent will not
produce any biological reaction reflected by infections, inflammations or other
phenomena of rejection.
The compositions according to the present invention also contain from 4 to 52% o
f at least one fatty acid. The fatty acids which can be used according to the pr
esent invention are saturated or unsaturated organic carboxylic acids containing
from 4 to 22 carbon atoms, preferably from 8 to 18 carbon atoms. By way of exam
ple, mention will be made of oleic acid, caprylic acid, capric acid, caproic aci
d, myristic acid, butyric acid, etc. Mixtures of fatty acids can also be used. T
he preferred fatty acid according to the present invention is oleic acid.
Optionally, the compositions according to the present invention can also contain
up to 15% by weight of water. It will be noted that the amount of water which i
s present in the compositions according to the invention is chosen such that the
composition has the desired consistency for the use envisaged.
The applicant has also discovered that phospholipids which are in the form of co
mmercially available mixtures are suitable for the compositions according to the

present invention. As examples of such commercially available compositions, men

tion will be made of Phosal 50 PG.TM. (55.8% of phosphatidylcholine, 1.9% of soy
bean fatty acids, 2.9% of sunflower monoglycerides, 1.9% of ethanol, 37.3% of pr
opylene glycol and 0.2% of ascorbyl palmitate) and Phosal 53 MCT.TM. (60.8% of p
hosphatidylcholine, 2% oleic acid, 3% of sunflower monoglycerides, 5% of ethanol
, 29% of triglycerides and 0.2% of ascorbyl palmitate), which are available from
Nattermann Phospholipid GmbH.
The compositions according to the present invention can also contain the followi
ng optional components: up to 5% by weight of monoglyceride or of diglyceride or
of a mixture of mono- and of diglyceride, and/or up to 15% by weight of triglyc
erides.
The compositions according to the present invention can also contain one or more
preservatives (such as ethanol), one or more antioxidants (such as ascorbyl pal
mitate) or one or more complexing agents (such as EDTA (ethylenediaminetetraacet
ate)).
The compositions according to the present invention allow the controlled release
of at least one active substance. The term "controlled release" is intended to
mean an active substance release profile which is desirable for the treatment en
visaged. The release of the active substance can thus be more or less held back
or slowed down as a function of the active substance used and of the desired the
rapeutic effect. It will be noted that the release of the active substance can b
e easily controlled by simple variations in the proportions of the components of
the compositions according to the present invention. The compositions are thus
very well suited to diverse therapeutic applications in which the controlled rel
ease of an active substance is sought in a very precise biological site.
The compositions according to the present invention are fluid pharmaceutical com
positions which are in the form of emulsions, suspensions or oily preparations.
They have the property of gelling instantaneously in the presence of an aqueous
phase. Specifically, when the compositions according to the present invention ar
e placed in the presence of an excess of aqueous phase, they go from a fluid sta
te to the state of a gel which is immiscible with the surrounding aqueous phase.
This makes the compositions of the invention particularly suitable for treating
diverse conditions requiring a local treatment in the medium which is permanentl
y irritated with an aqueous phase. Such uses include in particular the treatment
of periodontitis, gingivitis or dental abscesses, or alternatively the treatmen
t of mouth ulcers and mycoses.
The preparations according to the invention can also be judiciously used to obta
in, via the subcutaneous and intramuscular routes, sustained and programmed rele
ase of certain medicinal products. Upon contact with water, a gel forms under sk
in or in the muscle, and the medicinal product may diffuse and be released slowl
y from this gel.
Consequently, the present invention also relates to the use of compositions acco
rding to the present invention for treating a person or an animal suffering from
periodontitis, gingivitis or dental abscesses, mouth ulcers or mycoses, charact
erized in that a composition according to the present invention is applied to th
e site requiring the treatment.
In the case of a patient suffering from periodontitis, the treatment method cons
ists in applying the composition of the invention into one or more periodontal p
ockets by means of a dental instrument which is suitable for this purpose. Appli
cation by means of syringes is particularly easy and makes it possible to obtain
an extremely satisfactory result.

In the case of a patient suffering from gingivitis, dental abscesses, mouth ulce
rs or mycoses, the treatment consists of a simple application of the composition
to the site requiring treatment. Optionally, this application can be carried ou
t by the patient himself.
According to another aspect, the present invention relates to methods for prepar
ing compositions according to the present invention. The compositions according
to the present invention are obtained by a method comprising the following succe
ssive steps:
i) the phospholipid(s) is(are) dissolved in the pharmaceutically acceptable solv
ent(s);
ii) the fatty acid(s) is(are) added to the phospholipid solution with stirring;
iii) the active substance(s) is(are) incorporated into the mixture obtained at t
he end of step ii), and
iv) water is optionally added to the composition obtained in step iii).
When the active substance is water-soluble, it is dissolved in a minimal amount
of water before the incorporation in step iii). When the active substance is not
soluble in water, it is incorporated in step iii) in the mixture of phospholipi
d, pharmaceutically acceptable solvent and fatty acid. In the case of substance
which is both insoluble in water and insoluble or relatively insoluble in lipid,
it is also incorporated in step iii), optionally in micronized form.