Tp ch Ha hc, T. 45 (2), Tr.

147 - 151, 2007

Tng hp bt hiroxyapatit kch th c nano

bng ph ng php kt ta ha hc
n Ta son 10-4-2006
o Quc H ng, Phan Th Ngc Bch
Vin Ha hc, Vin Khoa hc v$ Cng ngh Vit Nam
Summary
Hydroxyapatite (HA) powder was synthesized by simple precipitation method using H3PO4
and Ca(OH)2 at the different temperatures. The obtained HA samples were examined using
methods of XRD, SEM, FTIR and TGA. The investigations indicated that precipitating at ambient
temperature can create the single phase HA powder with the particle size under 100 nm.

I - M u
Hydroxyapatit Ca10(PO4)6(OH)2 l mt loi
gm sinh hc, c nhiu ng dng trong y sinh
hc do cc c tnh qu gi ca chng: c hot
tnh v t3ng thch sinh hc cao vi cc t
b o v cc m, khng b c th o thi, tn ti
nhiu trng thi tp hp,... [1 - 3].
Hydroxyapatit (HA) l khong cht chnh
trong khung x3ng ng3i v ng vt, cc
dng xp v dng mn (kch th3c 20 - 100 nm).
Do vy, HA 3c dng cung cp canxi v
photphat ngn nga chng loMng x3ng ng3i.
Mt lp HA mn, mng ph trn x3ng nhn to
c tc dng tng c3ng kh nng lin kt vi m
v x3ng t nhin hoc to th nh lp men rng
mi cng chc, ho n to n ging men rng t
nhin [4]. Mi y, ng3i ta cn pht hin HA
dng xp c kh nng vn chuyn v phn tn
insulin trong rut [5, 6].
Trn th gii, vic nghin cu ch to HA
bng cc ph3ng php khc nhau v kho st
cc c tnh ca chng ang rt pht trin [1, 2].
Trong n3c, cc hp cht v c c kh nng ng
dng l m vt liu sinh hc ni chung v HA ni
ring cn ch3a 3c ch nhiu. B i bo n y
trnh b y qu trnh tng hp HA bng con
3ng kt ta n gin, t cc ha cht c bn

Ca(OH)2, H3PO4, v kho st sn phm thu 3c

bng cc ph3ng php: nhiu x tia X (XRD),
hin vi in t qut (SEM), hp th hng ngoi
(FTIR) v phn tch s thay i khi l3ng theo
nhit (TGA). Cc c tr3ng M xc nh cng
3c so snh vi s liu ca mu HA chun ca
Vin tiu chun v cng ngh quc gia M
(NIST) [7, 8].
II - Thc nghim
Chun b mu: Bt HA 3c iu ch bng
ph3ng php kt ta ha hc t dung dch
H3PO4 v huyn ph Ca(OH)2 trong n3c. Cc
ha cht s dng u l loi tinh khit phn tch
ca Trung Quc.
Ca(OH)2 v H3PO4 3c chun b trong n3c
ct vi nng 0,05M v 0,03 M t3ng ng.
L3ng dung dch s dng ng vi t l Ca/P =
1,70.
Dung dch H3PO4 3c nh t t tng git
v o cc ng huyn ph Ca(OH)2 trn my
khuy t. Kt thc qu trnh thm H3PO4, tip
tc khuy hn hp trong khong 2h ti nhit
M nh. Sau , gn bt phn dung dch trong,
thm n3c ct v o khuy tip khong 2h na
loi Ca(OH)2 d3. Kt ta to th nh sau phn ng
3c lc, ra nhiu ln bng n3c ct, cui cng
147

ra bng dung dch H3PO4 0,001 M n pH

trung tnh v sy kh 75 - 80oC.
Qu trnh tng hp 3c thc hin ti ba
nhit : 30oC, 60oC v 90oC.
Mt phn mu sau 3c nung n 600o
v 1100oC.
Th nh phn pha 3c xc nh bng ph3ng
php nhiu x tia X (XRD), trn my Siemens
D5000 (CHLB c).
Hnh dng v kch th3c ht 3c xc nh
t nh hin vi in t qut (SEM) trn thit b
Hitachi S4800 (Nht Bn). ng thi, kch
th3c bn trong ca ht cng 3c tnh t gin
XRD.
Kho st tnh cht nhit bng ph3ng php
TGA trong mi tr3ng kh N2, thit b phn tch
Shimadzu TGA-50H (Nht Bn).
Mu cng 3c c tr3ng bng ph3ng php
ph hng ngoi (FTIR), trn my IMPACT 410Nicolet (CHLB c).
III - Kt qu v tho lun
1. Tng hp HA
Bng ph3ng php iu ch M chn, qu
trnh din ra theo phn ng [9]:
10Ca(OH)2 + 6H3PO4 =
Ca10(PO4)6(OH)2 + 18 H2O
(1)
Trong qu trnh iu ch, yu t pH ng
vai tr quan trng. pH 9 - 10 3c iu
chnh bng cch thm t t H3PO4 v o Ca(OH)2.
H3PO4 l mt axit c mnh trung bnh, phn
ly th nh 3 giai on [9]:
H3PO4
-

H2PO4

2-

H2PO4- + H+
2-

HPO4 + H
3-

pKa1 = 2,2 (2)

pKa2 = 7,2 (3)

PO4 + H
pKa3 = 12,3 (4)
HPO4
Nh3 vy, nu thm H3PO4 vi tc cao,
pH ca dung dch s gim t ngt, dn n s
phn ly axit khng ho n to n, to ra cc ion
HPO42- v H2PO4-. iu c th dn n vic
ln mt phn kt ta cha cc ion n y (chng
hn Ca10-x(HPO4)x(PO4)6-x(OH)2-x) trong th nh
phn HA tng hp 3c.
T l Ca/P ban u 3c ly d3 (1,70) so vi
148

th nh phn t l3ng trong cng thc ca HA

(1,67) cng l m bo mi tr3ng pH 9 - 10
cho qu trnh phn ng.
2. Th nh phn pha
Trn gin XRD, vch nhiu x c3ng
100% ca Ca(OH)2 v tr 2 = 34o (JCPDS #40733), trng vi vch c3ng 24% ca HA
(2 = 34,05o, JCPDS #24-0033). Do vy, c
th khng nh trong sn phm HA to th nh c
cn tn ti cht u Ca(OH)2 hay khng, tr3c
khi o XRD, mu 3c nung n 600oC. n
nhit n y, Ca(OH)2 chuyn th nh CaO theo
phn ng [9]:
Ca(OH)2

600o C

CaO + H2O

(5)

Cc vch nhiu x mnh ca CaO (JCPDS

#37-1497) u v tr tch bit so vi HA.
Gin XRD ca mu HA tng hp 30oC
(mu ngay sau tng hp v mu nung) 3c 3a
ra trn hnh 1. Cc mu tng hp cc nhit
khc cng cho kt qu XRD t3ng t. Trn gin
XRD ca tt c cc mu nung n 600oC ch
xut hin cc vch nhiu x c tr3ng cho HA,
khng thy s c mt ca cc cht u hay tp
cht chng hn nh3 cc mui canxi photphat
khc. C th ni rng, HA n pha M 3c to
th nh.
So vi gin XRD ca mu HA khng
nung, trn gin ca cc mu HA nung n
600o v 1100oC, cc vch nhiu x tr nn hp
hn, mt s vch (2 = 32,19, 32,87, 34,05o,...)
th hin r hn vi c3ng t3ng 3ng trong
gin ca mu chun. iu n y cho thy
tinh th ca mu ngay sau tng hp ch3a cao v
qu trnh tinh th ha tip tc xy ra khi nung
mu n nhit cao.
So vi mu chun NIST, c tr3ng XRD ca
mu tng hp l ho n to n trng khp.
3. nh h ng ca nhit phn ng n
hnh dng v kch th c ht
nh SEM ca mu HA tng hp cc nhit
khc nhau 3c ch ra trn hnh 2.
Mu tng hp 90oC: ht kh ng u vi
dng hnh tr, d i khong 200 - 300 nm, 3ng
knh d3i 50 nm.

Mu tng hp 60oC: so vi mu tng hp

90oC, kch th3c ht ni chung gim, cc ht
co ngn hn, nhiu ht c chiu d i d3i 100
nm, 3ng knh trung bnh khong 30 - 40 nm.
Mu tng hp 30oC: kch th3c ht gim
ng k, ht tr nn cn i hn, chiu d i cn
khong 50 nm, 3ng knh khong 20 nm.
Nh3 vy, khi tng hp nhit thp, xung
quanh nhit phng c th thu 3c bt HA
kh mn vi kch th3c trung bnh d3i 50 nm.
i vi mu 3c to ra 30oC, kch th3c
ht bn trong (hiu theo ngha l cc domen tinh

th, mi ht thng th3ng bao gm nhiu

domen tinh th nh) cng 3c xc nh t gin
nhiu x tia X. Bng ph3ng php WarrenAverbach [10], t rng vch nhiu x 2 =
25,88o, ng vi phn x (002), gi tr kch th3c
ht theo khi nim trn 3c xc nh nm trong
khong 11-13 nm. Gi tr n y nh3 vy cng ph
hp vi kch th3c ht xc nh bng ph3ng
php SEM.
Mu HA chun cng c dng hnh tr, d i
khong 100 - 300 nm v 3ng knh 50 - 150
nm.

a
b
c
Hnh 1: Gin XRD mu HA khng nung (a), nung 600oC (b) v nung 1100oC (c)

a
a
b
c
Hnh 2: nh SEM ca cc mu HA 3c tng hp (a) 90oC, (b) 60oC v (c) 30oC
4. c tr ng nhm phn t bng ph hng
ngoi
Ph hng ngoi ca mu HA (hnh 3) th
hin cc vn hp th c tr3ng cho nhm PO43- (
vng 1030 - 1100, 960, 560 - 600, 470 cm-1),
nhm OH- (630, 3570 cm-1) ca HA v mt vn
hp th ca H2O t do vng 3430 v 1630 cm-1.
Ngo i ra, trn ph cn xut hin vn hp th c
tr3ng cho nhm CO32- 1410 - 1470 cm-1 v
khong 870 cm-1. iu n y chng t trong qu
trnh tng hp, Ca(OH)2 M b cacbonat ha mt
phn, to th nh nhm CO32-, thay th cho nhm
PO43- hoc nhm OH- trong th nh phn ca HA

(khi l3ng nhm CO32- chim khong 0,032%

khi l3ng to n b mu HA tiu chun [7]).
Ph IR ca mu tng hp v c bn cng
ph hp vi ph ca mu chun NIST.
5. c tr ng nhit ca cc mu HA
Gin TGA t3ng t nhau i vi tt c
cc mu HA (mt mu i din 3c th hin
trn hnh 4). S thay i khi l3ng th hin rt
r qua hai giai on, t nhit phng n
khong 400oC v trn 700o n 1000oC. Giai
on gim khi l3ng th nht c th xem l
ng vi s mt n3c t do (n3c m) v mt
149

tc v ph IR ca mu HA nung n 600oC vn
th hin mt vn hp th rng ca n3c
khong 3430 cm-1, trong khi vn ph n y
khng cn xut hin trn ph IR ca mu nung
n 1100oC.

S sng, cm-1

%T

%T

%T

phn ca n3c hp th trong tinh th. Giai on

th hai l s tip tc mt n3c kt tinh v c th
lin quan n qu trnh decacbonat ho, phn
hu phn nhm CO32- c mt trong mu. C th
cho rng, sau 600oC qu trnh mt n3c vn tip

S sng, cm-1

S sng, cm-1

c
o

Hnh 3: Ph IR ca mu HA khng nung (a), nung 600 C (b) v nung 1100oC (c)
Cng trn ph IR ca mu nung n 1100oC
(hnh 3c), vn hp th c tr3ng cho nhm CO32M bin mt. iu n y kt hp vi s xut hin
ca CaO trn gin XRD ca chnh mu HA
n y (cc vch c tr3ng vi 2 = 37,35, 53,85o)
M chng minh cho s decacbonat ha mu nh3
M th hin trn 3ng TGA.

na, trn gin TGA, phn gim khi l3ng

trong khong 700oC n 1000oC, va do mt
n3c va lin quan n qu trnh phn hu n y,
ch chim khong 1,4% tng khi l3ng mu.
Nh3 vy, c th xem mu HA tng hp bn n
nhit M nung l 1100oC.
IV - Kt lun
Bng ph3ng php kt ta n gin t
Ca(OH)2 v H3PO4 M tng hp 3c
hydroxyapatite Ca10(PO4)6(OH)2 n pha, t3ng
i mn vi kch th3c ht d3i 100 nm v bn
nhit n 1100oC. Cc kt qu nghin cu M
khng nh nhit v pH trong qu trnh
tng hp l nhng thng s quan trng, c nh
h3ng quyt nh n cht l3ng v kch th3c
ht HA.

Nhit , oC
Hnh 4. Gin TGA ca mu HA1
V trn gin XRD ca mu HA nung n
1100oC (hnh 1c), ch c mt pha HA v pha
CaO, khng c tricanxi photphat Ca3(PO4)2, nn
c th cho rng, phn CaO to th nh ch lin
quan n s decacbonat ha nhm CO32- c mt
trong mu, ch khng lin quan n s phn
hu HA to th nh CaO v Ca3(PO4)2 [11]. Thm
150

Cc c tr3ng ca mu HA tng hp v c
bn l ph hp vi mu chun NIST.
Cc ph3ng php ha hc tng hp HA t
cc cht ban u khc nhau ang 3c tin h nh
nghin cu.
Cc tc gi cm n Gio sF ng V Minh
(ChFng trnh nghin cu c bn 2005-2006) v$
Vin Ha hc ( t$i c s chn lc 2005) N
h tr kinh ph thc hin cng trnh n$y.

T i liu tham kho

nanoparticles in ultrasonic precipitation,

Ceramics Inter. (2005) (in press).

1. M. P. Ferraz, F. J. Monteiro, C. M. Manuel.

6. W. Paul, Ch. Sharma. Porous hydroxyapatite

Journal of Applied Biomaterials &

Biomechanics 2, P. 74 - 80 (2004).
2. H. S. Liu,T. S. Chin, L. S. Lai, S. Y. Chiu,
K. H. Chung, C. S. Chang & M. T. Lui.
Ceramics International 23, P. 19 - 25
(1997).

nanoparticles for instestinal delivery of

insulin, Trends in Biomaterials & Artificial
Organs., Vol. 14, P. 37 - 38 (2001).

3. M. Sinha, S. B. Qadri, et al. 10th Foresight

Conference on Molecular Nanotechnology
(2002), www.foresight.org

4. Kazue Yamagishi, Kazuo Onuma, Takashi

Suzuki, Fumio Okada, Junji Tagami,
Masayuki Otsuki, Pisol Senawangse.
Nature, Vol. 433, P. 819 (2005).
5. Li-yun Cao, Chuan-bo Zhang, Jian-feng
Huang, Synthesis of hydroxyapatite

7. M. Markovic, B. O. Fowler, Ming S. Tung.

J. Research of the National Ins. of Standards
and Technology, Vol. 109, No. 6, P. 553 568 (2004).

8. E. Bouyer, F. Gitzhofer, M. I. Boulose.

Materials in Medicine 11, P. 523 - 531
(2000).

9. L Th Ct T3ng. Lun n tin s, H Ni

(2005).

10. Zhengwen Yanga, Yinshan Jianga, YuJie

Wang, Liyan Ma, Fangfei Li. Materials
Letters 58, P. 3586 - 3590 (2004).

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