1、| =0 4Za 1, S18 $2 ,n(1.SD S/SxD Sv9 3 , 100730;2.SE g9 3 S/ , 100081)K1:随着药用高分子材料的发展,阴道给药凝胶制剂将会成为一种具有发展前景的腔道给药制剂。本文通过对近年来有代表性的文献进行分析和归纳,介绍了阴道用凝胶剂的研究进展,为其深入研究提供参考。随着阴道系统给药吸收机制研究的深入及药用高分子材料的发展,相信不久的将来会有稳定的、更方便的、生物利用度更高的凝胶制剂问世。1oM:阴道给药;凝胶剂ms |:R94 DS M :A cI|:1001-0971(2005)05-0346-04l :2005-03-06| %5
2、 %5, O| * ,0 H.eOl,+%h0 r0 db。 VYV|0| =,YV|T l (2)YV -T ( V 7;(3) Fvs0。 T“ AFM %,VFV l PV ,i PV , B“ T V ,V7 0 T HW。| “ “。1 E Fh Ti OT , V ? f Jh(HIV) |346 Foreign Medical SciencesSection on Pharmacy 2005Oct;32(5)DOI:10.13220/ki.jipr.2005.05.017E0。El-Gizawy4Jb:T 00,! i5%|E 4。8V Kl 0 i0.2%, 4 T%Ti O?
3、C030 s = 。 “5 k,r Bh o01 h|s 0 i,TV , 80 i1r B 8(P 0.05)。 8,|01h,0 i vKl 0 i。 -| =pH,TV ,pH1BA/(P 0.05)。9,! V0T HW,i O P|pHS =。Lee5 P 5 934P!| 00NP-9T T0“d(AmDDS), AmDDS 4。9F 5 V4AmDDSlT - MT,V79FT ,0 db HW;9F spH, VT T ;AmDDSEDTAiY0 db;yN, VYV0 NP-9 e dAmDDS。DCruz6 7?B | 0# F.l%h ? 4 (30 80 nm) 0 4
4、GM-144,c0 dY=?, Captex 300, Cremophor EL, Phospholipon 90G,Rhodigel, Pluronic F-68P )。GM-14430 s = V% Et0。 ,1 GM-144NP-9SEt8 =Er 。84 x vt,s3F, F28, s,|GM-1442%NP-9i 。TA U,GM-144AE。vFM1 ,GM-1442%NP-9F qsY75%70.8%。yN,GM-144 g rNP-9 B“, Br|E0。Et|O L,6Et 010d,B? 3 、 、% ?+5 “。 ,GM-144 V ?B “5r、 |E0,i O V
5、h .l%h。Owen7 ( 0 db , =c3%NP-9。 dTApH(3.55.9) Xs0 1i i(300 900 mOsm)v v 3 T。 pH( -NP-9“d rT AY。 pH/, T9 ,NP-9 i H( -TAV ),Kv v t_ pH/7h ; iH,v v t_ Xs0 1i i9F7/,#K Xs0 1i i pH9F7/, iWs NP-9s0v7 。 X t e d d“d 1i,Jain8! d8, d | d“d。E!x、%?、 (dicetylphospholipid,DCP) |8, ( (6.70.85)m, q98%。80 1i L,|T ,1
6、%08 8 db 0)。TV ,8 4db HWr60 h,7d8 420 h。8= L NTV ,8 08 (v 8 =8), A 。 P8 v ,8 ( (8.50.6)/(4.60.4), q46%;88 ( 5/(1.20.8), qr85%。Ficicioglu9 8 |00 nVr。32 o, sF s。 o Pi I=?(50 mgd-1, BL), 2, s|8 8450mg,K b8 0 = F8 。TF b |0F。 |0F0 = F8 F。N V,8 |00 = F 3 r,7 b0 i 7 0 3T 5o974P980PT88; 0。TV , 8,8pH 4.5 A24
7、 h, v80%0 =8。h| 9 14 ,cM PRO2000| 4 V )4i ? HIV .l%h。TV ,N z 0 s, ? 3 Q。Stafford159 c ; | ,9 Br、 、 0 sz h4。Coggins16 B| PC-503 # 0 s, 1sB ; 2%0。T?C,34 o4 ? 3n, 3# /e,iOB C 0 , o|PC-503 H? 3AQ。Kieweg17V , F 3 FHIV04r | %0$s f | = ? 。“ s)ZF#V V AY。8 E L,6 g r| 3 d (PAA)38 4,T?C,PAA 4$ ? 8 4, -1 s w Y,
8、 w 1T E VM,78 1G V V A ? 。PAA q w Q1,78 $ q (consistency index)1, g M d(shear-thin-ning)Q11“。4 、 #s 0M。 H 8A , P =$h,V7 Pz 、 n , P 8 ?YV|7s ,5% (, ? ,10%s 1 -A0 SZ T?, 0 、 v - (PEG2) - ?(PEG1)。Shetty181 - F E2| (1348 Foreign Medical SciencesSection on Pharmacy 2005Oct;32(5)2mg)| 4(3mg) “5r。TV , F0 f
9、 4FAY,T4 cm(SD2.5cm)3.3 cm(SD 2 cm)。Grig-naffini19“1 |B dPGE20PGE2 r。 gCervidil 4c10mg v ( )。|0b| H,| A/, l n,0.3mgh-1 q db0 V12h。Crinone ,4 x8PCs0 F/ 4, s0 | nT |C ,8 VYV|T l, l HW25 50 h。4 V 。5 8 ,|0 4 V “, E、 F )、 Fh、 f、 、 。 “ -, 4 + M 4? , !e、 4、p P、 b!、 I、 z+,C ? 4 1 v。 SE J 0 S5 (SFDA)K # h “5
10、 k| 、 X 、 ma、9b:、b , B:| 4。 “0s0 ?Z,|0 4?Z ,|B ?Z-|04。 |0Z T ZL,1 a 0+ y ,M“|“d0 l #0s0 ?Z,#0T m ,| 、0ZL、 3 4 W。 ID1 Justin-Temu M, Damian F, Kinget R, et al.Intravaginal gels asdrug delivery systems J .J Womens Health(Larchmt), 2004, 13(7):834-844.2 GagneN, CormierH, Omar RF, et al.Protective effec
11、t of a ther-moreversible gelagainst the toxicity of nonoxynol-9 J .Sex TransmDis, 1999, 26(3):177-183.3 DCruz OJ, Uckun FM.Gel-microemulsions as vaginal spermicidesandintravaginal drug delivery vehicles J .Contraception , 2001, 64(2):113-123.4 El-Gizawy SA, Aglan NI.Formulationand evaluationof metro
12、nida-zole acid gel for vaginal contraception J .J Pharm Pharmacol,2003, 55(7):903-909. 5 LeeCH, Chien YW.Development andevaluationof a mucoadhesivedrug delivery system for dual-controlled delivery of nonoxynol-9 J .J ControlRelease, 1996, 39:93-103. 6 DCruzOJ, Yiv SH, UckunFM.GM-144, anovellipophili
13、c vaginalcontraceptivegel-microemulsion J .AAPS PharmSciTech, 2001, 2(2):E5. 7 Owen DH, Dunmire EN, PlanysAM, etal.Factors influencingnonoxynol-9permeationandbioactivity incervicalmucus J .J Con-trolRelease, 1999, 60(1):23-24. 8 JainSK, Singh R, SahuB.Development ofa liposome-basedcontra-ceptive sys
14、tem for intravaginal administration of progesterone J .Drug Dev Ind Pharm, 1997, 23:827-830. 9 Ficicioglu C, Gurbuz B, TasdemirS, et al.High local endometrialeffect of vaginal progesterone gel J .Gynecol Endocrinol, 2004, 18(5):240-243. 10 Wassen L, SchonK, HolmgrenJ, etal.Localintravaginal vaccina-
15、tionof the femalegenitaltract J .Scand J Immunol, 1996, 44(4):408-414. 11 Paternoster DM, Tudor L, Milani M, et al.Efficacy of an acidicvaginal gelonvaginalpHandinterleukin-6levelsinlow-riskpregnantwomen:a double-blind, randomized placebo-controlled trial J .JMatern FetalNeonatal Med , 2004, 15(3):1
16、98-201. 12 Chang JY, OhYK, Kong HS, etal.Prolonged antifungal effects ofclotrimazole-containing mucoadhesive thermosensitive gelsonvaginitis J .J Control Release, 2002, 82:39-50. 13 Paveli , kalko-BasnetN, chubert RI.Liposomalgels forvaginaldrug deliveryJ .IntJ Pharm , 2001, 219(1/2):139-149. 14 May
17、er KH, Karim SA, Kelly C, et al.Safety and tolerability ofvaginal PRO2000gel insexually activeHIV-uninfectedandabstinentHIV-infectedwomen J .AIDS, 2003, 17(3):321-329. 15 StaffordMK, Cain D, Rosenstein I, et al.A placebo-controlled,double-blindprospective study inhealthy female volunteersofdextrinsu
18、lphate gel:anovelpotentialintravaginalvirucide J .J Acquir Im-muneDeficSyndr Hum Retrivirol, 1997, 14(3):213-218. 16 Coggins C, Blanchard K, Alvarez F, et al.Preliminary safety andacceptability of a carrageenangel forpossible use asa vaginalmicro-bicideJ .Sex Transm Infect, 2000, 76(6):480-483. 17 K
19、iewegSL, GeonnottiAR, KatzDF.Gravity-inducedcoatingflowsofvaginal gelformulations:in vitro experimentalanalysis J .J PharmSci, 2004, 93(12):2941-2952. 18 Shetty A, Livingston I, Acharya S, et al.Vaginal prostaglandin E2gel versus tablet in the induction of labourat term -a retrospectiveanalysis J .J Obstet Gynaecol, 2004, 24(3):243-246. 19 Grignaffini A, Soncini E, Anfuso S, et al.Dinoprostone:slow re-lease vaginal insert(Propess)andintracervicalgel(Prepidil)fortheinduction of labourwith unriped cervix J .Minerva Ginecol(Ita-lian), 2004, 56(5):413-418.349SD0s 2005 M10 32 5
