经皮给药新型高分子基质及乳酸酯促透作用的研究
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摘要
压敏胶作为经皮给药系统中较为理想的经皮释放用胶粘剂基质,往往既要起到药物及促透剂等的载体或储库作用,还要兼具使经皮给药系统紧密地粘附于皮肤表面的压敏粘附作用,是经皮给药系统中最为关键的组成部分。高分子压敏胶的多层次性结构,比如结构单元组成、分子链长短和形态、侧链、聚集态结构、交联网络结构等,对粘附性以及药物的负载、释放和稳定性有很大的影响,其结构的调控非常重要。近年来发展起来的可逆加成-断裂链转移活性自由基聚合(RAFT)为合成具有特定多层次性结构和功能的高分子压敏胶提供了技术手段。
通过RAFT设计和调控聚合物压敏胶多层次性结构、研究压敏胶多层次性结构对药物释放的影响和对药物释放调控作用是本论文的研究工作之一。本文首先以咔唑为原料,通过简单的水相法合成了一系列咔唑基RAFT试剂N-咔唑二硫代甲酸苄基酯、N-咔唑二硫代甲酸α-甲基苄基酯、N-咔唑二硫代甲酸异丙苯酯、N-咔唑二硫代甲酸异丁基酯以及二硫化双(N-咔唑硫代甲酰)中间体,并以此中间体为基础进一步合成了N-咔唑二硫代甲酸异丁腈酯和N-咔唑二硫代甲酸腈基戊酸两种RAFT试剂,研究了它们对自由基聚合的调控作用,并选定性能比较好的N-咔唑二硫代甲酸异丁腈酯为RAFT试剂,分别以丙烯酸乙酯、丙烯酸丁酯、丙烯酸异辛酯为软单体,以丙烯酸甲酯、甲基丙烯酸甲酯以及苯乙烯为硬单体,以甲基丙烯酸β-羟乙酯为改性单体,合成了不同结构的两嵌段或三嵌段丙烯酸酯类嵌段共聚物压敏胶。并通过高效凝胶渗透色谱、核磁等手段对嵌段聚合物进行了表征,还考察了上述压敏胶的初粘力、180°剥离、持粘力等力学性能。以布洛芬、烟酸甲酯和5-氟尿嘧啶为模型药物,考察了这些压敏胶的结构对药物释放的影响和调控作用。研究结果表明RAFT聚合合成的嵌段聚合物压敏胶具有良好的力学性能,而且压敏胶的结构变化对药物释放具有显著的影响,因此,可以利用RAFT聚合调控压敏胶的结构实现对药物释放的调控。
本文还以γ-缩水甘油氧丙基三甲氧基硅烷(GPTMS)为偶联剂,通过溶胶-凝胶法,对聚乙烯醇进行化学交联改性,制备了一系列有机-无机杂化凝胶涂膜基质,采用粘度计、红外、光散射、扫描电镜、差热量热等方法研究了杂化凝胶涂膜基质的结构性能,并进行了拉力测试、水蒸汽渗透以及溶胀性能测试,在体考察了杂化膜的使用舒适度和刺激反应;还以布洛芬和5-氟尿嘧啶为模型药物,考察了该涂膜基质对药物释放的影响,结果表明该有机-无机杂化凝胶涂膜基质是一种性能优异的新型经皮给药基质材料。
使用化学促透剂是促进药物经皮渗透的有效手段,寻找性能优良的促透剂仍是经皮给药发展的重要方向之一。本文通过酯化反应合成了一系列乳酸酯,并以布洛芬、水杨酸、地塞米松和5-氟尿嘧啶为模型药物,在丙二醇的药物饱和溶液以及亲水性和疏水性压敏胶基质中,考察了该系列乳酸酯对上述药物经皮渗透的促进效率,结果表明乳酸酯的促透效果与乳酸酯的脂肪醇半族碳原子数以及药物的物理化学性质有关,其中乳酸癸酯和乳酸十二酯具有较好的经皮给药促透作用。
Pressure sensitive adhesives (PSAs) in transdermal drug delivery system (TDDS) not only are used to bond transdermal drug delivery devices to the outermost layer of the skin, but also are applied to act as a reservoir of drugs or penetration enhancers. As for pressure sensitive adhesives, the multilayer-molecular structures, such as constitutional unit, structure and configuration of the polymer chains, aggregation and crosslinking structure et al., have significant impact on drug release, stability, loading amount and so on. Therefore, the structure control of PSAs is important for TDDS. Fortunately, the reversible addition-fragmentation chain transfer (RAFT) polymerization method has recently been developed to prepare polymers with well-defined structure and low polydispersity.
In this paper, RAFT polymerization had been used to prepare a series of PSAs with well-defined structure. First, several carbazyl dithiocarbamates as RAFT agents were prepared by an improved aqueous phase method based on a nucleophilic substitution reaction between sodium carbazole-carbodithioate and alkyl halides at room temperature, including N-carbazole-carbodithioate (BCBD), 1-phenylethyl N-carbazole-carbodithioate (PCBD), cumyl N-carbazolylcarbodithioate (CCBD), tert-butyl N-carbazolecarbodithioate (TBBD), as well as di(thiocarbazolyl) disulfide (DTCD). Then, 2-cyanoprop-2-yl N-carbazolylcarbodithioate (CYCBD) and 4-cyanovalericacid N-carbazolylcarbodithioate (CVCBD) were synthesized based on a substitution reaction between DTCD and azobisisobutyronitrile or azobis(cyanovaleric acid). After the studies on the relative effectiveness of these carbazyl RAFT agents in the RAFT polymerizations, CYCBD with the best control ability was selected as RAFT reagent to initiate copolymerization of acrylate monomers. Ethyl acrylate、butyl acrylate and 2-ethylhexyl acrylate were chosen as the soft monomers, methyl acrylate, methyl methacrylate and styrolene as the hard monomers andβ-hydroxyethyl methacrylate as the crosslink monomers. The structure of the prepared block copolymers were characterized by GPC and 1HNMR. The mechanical properties such as initial bonding strength, cohesion and adhesion were measured according to the related Chinese Standard. At last, ibuprofen, methyl nicotinate and 5-fluorouracil were chosen as drug model to estimate the drug release behavior in the obtained PSAs in vitro and the results show that these PSAs can be used to control drug release.
Another objective of this thesis was to develop a novel organic-inorganic hybrid polymeric gel that is suitable for the bioadhesive film applied on skin as TDDS. The film-forming gels were prepared by using poly(vinyl alcohol) as base material,γ-(glycidyloxypropyl) trimethoxysilane (GPTMS) as cross-linker, glycerol as plasticizer and (N-vinyl pyrrolidone) as a tackifier. The mechanical properties, skin adhesion properties, swelling properties and water vapor permeability of the films prepared from different formulations of hybrid gels were studied. The miscibility and the thermal properties of films were investigated by using FT-IR, DSC, SEM and XRD. In addition, release and permeation characteristics of drugs form the resultant films were studied by using hydrophilic 5-fluorouracil and hydrophobic ibuprofen as the model drugs. All results show that the incorporation of GPTMS into the PVA can significantly enhance film mechanical strength and improve film skin adhesion properties of the film, decrease the crystalline regions of PVA and enhance the drug release. Moreover, skin irritation of the hybrid films was investigated in vivo in human subjects, and the results show that the films cause non-irritation to skin after topical application for 120 hours. The organic-inorganic hybrid polymer gel possesses very good properties for application in the skin and may provide a novel and promising formulation for transdermal drug delivery system.
Finally, a series of lactate esters was synthesized and their enhancement on the skin permeation of four kinds of drugs with different physicochemical properties in propylene glycol or PSAs was also studied, including ibuprofen, salicylic acid, dexamethasone and 5-fluorouracil. All results indicated that lactate esters can exert a significant influence on the transdermal delivery of the model drugs and there is a structure-activity relationship between the tested lactate esters and their enhancement effects. The results also suggested that the lactate esters with the chain length of fatty alcohol moieties of 10-12 are more effective enhancers.
通过RAFT设计和调控聚合物压敏胶多层次性结构、研究压敏胶多层次性结构对药物释放的影响和对药物释放调控作用是本论文的研究工作之一。本文首先以咔唑为原料,通过简单的水相法合成了一系列咔唑基RAFT试剂N-咔唑二硫代甲酸苄基酯、N-咔唑二硫代甲酸α-甲基苄基酯、N-咔唑二硫代甲酸异丙苯酯、N-咔唑二硫代甲酸异丁基酯以及二硫化双(N-咔唑硫代甲酰)中间体,并以此中间体为基础进一步合成了N-咔唑二硫代甲酸异丁腈酯和N-咔唑二硫代甲酸腈基戊酸两种RAFT试剂,研究了它们对自由基聚合的调控作用,并选定性能比较好的N-咔唑二硫代甲酸异丁腈酯为RAFT试剂,分别以丙烯酸乙酯、丙烯酸丁酯、丙烯酸异辛酯为软单体,以丙烯酸甲酯、甲基丙烯酸甲酯以及苯乙烯为硬单体,以甲基丙烯酸β-羟乙酯为改性单体,合成了不同结构的两嵌段或三嵌段丙烯酸酯类嵌段共聚物压敏胶。并通过高效凝胶渗透色谱、核磁等手段对嵌段聚合物进行了表征,还考察了上述压敏胶的初粘力、180°剥离、持粘力等力学性能。以布洛芬、烟酸甲酯和5-氟尿嘧啶为模型药物,考察了这些压敏胶的结构对药物释放的影响和调控作用。研究结果表明RAFT聚合合成的嵌段聚合物压敏胶具有良好的力学性能,而且压敏胶的结构变化对药物释放具有显著的影响,因此,可以利用RAFT聚合调控压敏胶的结构实现对药物释放的调控。
本文还以γ-缩水甘油氧丙基三甲氧基硅烷(GPTMS)为偶联剂,通过溶胶-凝胶法,对聚乙烯醇进行化学交联改性,制备了一系列有机-无机杂化凝胶涂膜基质,采用粘度计、红外、光散射、扫描电镜、差热量热等方法研究了杂化凝胶涂膜基质的结构性能,并进行了拉力测试、水蒸汽渗透以及溶胀性能测试,在体考察了杂化膜的使用舒适度和刺激反应;还以布洛芬和5-氟尿嘧啶为模型药物,考察了该涂膜基质对药物释放的影响,结果表明该有机-无机杂化凝胶涂膜基质是一种性能优异的新型经皮给药基质材料。
使用化学促透剂是促进药物经皮渗透的有效手段,寻找性能优良的促透剂仍是经皮给药发展的重要方向之一。本文通过酯化反应合成了一系列乳酸酯,并以布洛芬、水杨酸、地塞米松和5-氟尿嘧啶为模型药物,在丙二醇的药物饱和溶液以及亲水性和疏水性压敏胶基质中,考察了该系列乳酸酯对上述药物经皮渗透的促进效率,结果表明乳酸酯的促透效果与乳酸酯的脂肪醇半族碳原子数以及药物的物理化学性质有关,其中乳酸癸酯和乳酸十二酯具有较好的经皮给药促透作用。
Pressure sensitive adhesives (PSAs) in transdermal drug delivery system (TDDS) not only are used to bond transdermal drug delivery devices to the outermost layer of the skin, but also are applied to act as a reservoir of drugs or penetration enhancers. As for pressure sensitive adhesives, the multilayer-molecular structures, such as constitutional unit, structure and configuration of the polymer chains, aggregation and crosslinking structure et al., have significant impact on drug release, stability, loading amount and so on. Therefore, the structure control of PSAs is important for TDDS. Fortunately, the reversible addition-fragmentation chain transfer (RAFT) polymerization method has recently been developed to prepare polymers with well-defined structure and low polydispersity.
In this paper, RAFT polymerization had been used to prepare a series of PSAs with well-defined structure. First, several carbazyl dithiocarbamates as RAFT agents were prepared by an improved aqueous phase method based on a nucleophilic substitution reaction between sodium carbazole-carbodithioate and alkyl halides at room temperature, including N-carbazole-carbodithioate (BCBD), 1-phenylethyl N-carbazole-carbodithioate (PCBD), cumyl N-carbazolylcarbodithioate (CCBD), tert-butyl N-carbazolecarbodithioate (TBBD), as well as di(thiocarbazolyl) disulfide (DTCD). Then, 2-cyanoprop-2-yl N-carbazolylcarbodithioate (CYCBD) and 4-cyanovalericacid N-carbazolylcarbodithioate (CVCBD) were synthesized based on a substitution reaction between DTCD and azobisisobutyronitrile or azobis(cyanovaleric acid). After the studies on the relative effectiveness of these carbazyl RAFT agents in the RAFT polymerizations, CYCBD with the best control ability was selected as RAFT reagent to initiate copolymerization of acrylate monomers. Ethyl acrylate、butyl acrylate and 2-ethylhexyl acrylate were chosen as the soft monomers, methyl acrylate, methyl methacrylate and styrolene as the hard monomers andβ-hydroxyethyl methacrylate as the crosslink monomers. The structure of the prepared block copolymers were characterized by GPC and 1HNMR. The mechanical properties such as initial bonding strength, cohesion and adhesion were measured according to the related Chinese Standard. At last, ibuprofen, methyl nicotinate and 5-fluorouracil were chosen as drug model to estimate the drug release behavior in the obtained PSAs in vitro and the results show that these PSAs can be used to control drug release.
Another objective of this thesis was to develop a novel organic-inorganic hybrid polymeric gel that is suitable for the bioadhesive film applied on skin as TDDS. The film-forming gels were prepared by using poly(vinyl alcohol) as base material,γ-(glycidyloxypropyl) trimethoxysilane (GPTMS) as cross-linker, glycerol as plasticizer and (N-vinyl pyrrolidone) as a tackifier. The mechanical properties, skin adhesion properties, swelling properties and water vapor permeability of the films prepared from different formulations of hybrid gels were studied. The miscibility and the thermal properties of films were investigated by using FT-IR, DSC, SEM and XRD. In addition, release and permeation characteristics of drugs form the resultant films were studied by using hydrophilic 5-fluorouracil and hydrophobic ibuprofen as the model drugs. All results show that the incorporation of GPTMS into the PVA can significantly enhance film mechanical strength and improve film skin adhesion properties of the film, decrease the crystalline regions of PVA and enhance the drug release. Moreover, skin irritation of the hybrid films was investigated in vivo in human subjects, and the results show that the films cause non-irritation to skin after topical application for 120 hours. The organic-inorganic hybrid polymer gel possesses very good properties for application in the skin and may provide a novel and promising formulation for transdermal drug delivery system.
Finally, a series of lactate esters was synthesized and their enhancement on the skin permeation of four kinds of drugs with different physicochemical properties in propylene glycol or PSAs was also studied, including ibuprofen, salicylic acid, dexamethasone and 5-fluorouracil. All results indicated that lactate esters can exert a significant influence on the transdermal delivery of the model drugs and there is a structure-activity relationship between the tested lactate esters and their enhancement effects. The results also suggested that the lactate esters with the chain length of fatty alcohol moieties of 10-12 are more effective enhancers.
引文
[1]. Hunt J.A., Shoichet M.S., Biomaterials: drug delivery systems, Curr. Opin. Solid State Mater. Sci., 2002, 6(4):281~283
[2].郁正艳,金明飞,左翼,等,药物传输系统(DDS)的研究现状与发展前景,生命的化学,2004,24(5):428~431
[3]. Chen H., Langer R., Oral particulate delivery:status and future trends, Adv. Drug Delivery Rev.,1998,34(2-3):339~350
[4]. Kermode M., Unsafe injections in low-income country health settings: need for injection safety promotion to prevent the spread of blood-borne viruses, Health Promot. Int., 2004, 19:95~103
[5]. Nir Y., Paz A., Sabo E., et al, Fear of injections in young adults:prevalence and associations, Am. J. Trop. Med. Hyg., 2003, 68:341~344
[6]. Kane A., Lloyd J., Zaffran M., et al, Transmission of hepatitis B, hepatitis C and human immunodeficiency viruses through unsafe injections in the developing world: model-based regional estimates, Bull, World Health Organ., 1999, 77: 801~807
[7].梁秉文,中药经皮给药制剂技术,北京:化学工业出版社,2006:1~2
[8]. Prausnitz1 M R., Langer R., Transdermal drug delivery, Nat. Biotechnol., 2008, 26(11):1261~1268
[9]. Prausnitz M R., Mitragotri S., Langer R., Current status and future potential of transdermal drug delivery, Nat. Rev. Drug Discovery, 2004,3:115~124
[10].胡晋红,张立超,朱全刚,我国透皮给药的研究进展,解放军药学学报,2002,18(1):38~41
[11].杨华生,朱庆文,梁秉文,药用辅料在中药经皮给药制剂中的应用,中医外治杂志,2007,16(3):3~5
[12].梁秉文,中药经皮给药制剂技术,北京:化学工业出版社,2006:7~9
[13]. Barry B.W., Is transdermal drug delivery research still important today? Drug Discovery Today, 2001, 60:967~97l
[14].梁秉文,中药经皮给药制剂技术,北京:化学工业出版社,2006:4~5
[15].刘强,吕治平,中药经皮给药制剂的进展及发展趋势,中医外治杂志,2004,13(1):31~33
[16].马卓,沈雄,陈前锋,中药透皮吸收制剂的研究进展,中药材,2005, 28(12):1136~1138
[17]. Kretsos K., Transport phenomena in the human skin:[博士学位论文], New York: University of New York, 2003
[18].梁秉文,中药经皮给药制剂技术,北京:化学工业出版社,2006:10~16
[19].陈勇平,通过噬菌体文库鉴定透皮输运蛋白质肽:[博士学位论文],合肥:中国科学技术大学,2007
[20]. Moser K., Kriwet K., Naik A., et al, Passive skin penetration enhancement and its quantification in vitro, Eur. J. Pharm. Biopharm., 2001, 52:103~112
[21].梁文权,经皮给药新剂型,北京:人民卫生出版社,1998:253~256
[22].陆彬,药物剂型与新技术,北京:人民卫生出版社,1998:356~361
[23].梁秉文,中药经皮给药制剂技术,北京:化学工业出版社,2006: 19~33
[24]. Hadgraft J., Dermal and transdermal drug design, Int. J. Pharm. Med., 1999, 13: 155~158
[25]. Yano T., Noda K., Skin permeability of various non-steroids anti-inflammatory drugs in man, Life Sci., 1986, 39:1043~1050
[26]. Wuster R.C., Kramer S.F., Research of drug transdermal through skin, J. Pham. Sci., 1961, 50:288~291
[27]. Walke R.B., Smith E.W., The role of percutaneous penetration enhancers, Adv. Drug Delivery Rev., 1996, 18:295~301
[28]. Wester R.C., Maibach H.L., Effects of diffcrellt drug permeation, J. Invest. Dermatol., 1976, 67:518~521
[29]. Noonan P.K, Wester R.C., Enhanced transdermal delivery of drugs, J. Pharm. Sci., 1980, 69:365~372
[30].梁秉文,中药经皮给药制剂技术,北京:化学工业出版社,2006: 19~33
[31].梁秉文,中药经皮给药制剂技术,北京:化学工业出版社,2006: 34~35
[32]. Simon, G.A., Maibach, H.I., The pig as an experimental animal model of percutaneous permeation in man: qualitative and quantitative observations-an overview, Skin Pharmacol. Appl. Skin Physiol., 2000, 13: 229~234
[33]. Howes D, Guy R, Hadrgft J, et al, Methods for assessing percutaneous absorption. ECVAM workshop report 13. Altern. Lab. Anim., 1996, 24:81-106
[34]. Prausnitz M. R., Mitragotri S., Langer R., Current status and future potential of transdermal drug delivery, Nat. Rev. Drug Discov., 2004, 3:115~124
[35]. Bando H., Yamashita F., Takakura Y., et al, Theoretical design of skinpenetration enhancement via prodrug enhancer combination based on a diffusion model, Proceed. Intern. Symp. Control. Rel. Bioact. Mater., 1995, 22:668~671
[36]. Williams A.C., Barry B.W., Penetration enhancers, Adv. Drug Delivery Rev., 2004, 56:603~618
[37]. Kirjavainen M., Urtti A., Valjakka K.R., et al, Liposome-skin interactions and their effects on the skin permeation of drugs, Eur. J. Pharm. Sci., 1999, 7(4):279~286
[38]. Lawrence M.J., Rees G.D., Microemulsion-based media as novel drug delivery systems, Adv. Drug Delivery Rev., 2000, 45 (1):89~121
[39].朱振峰,杨菁,药物纳米控释系统的最新研究进展,国外医学生物医学工程分册,1998,21(6):327~333
[40]. Kreuter J., Alyautdin R.N., Kharkewich D.A., et al, Passage of peptides through the blood-brain barrier with colloidal polymer particles(nanoparticles), Brain Res., 1995, 674:171~174
[41]. Megrab N.A., Williams A.C., Barry B.W., Oestradiol permeation through human skin and silastic membrane: effects of propylene glycol and supersaturation, J. Control. Release, 1995, 36 :277~294
[42]. Barry B.W., Novel mechanisms and devices to enable successful transdermal drug delivery, Eur. J. Pharm. Sci., 2001, 14:101~114
[43].昝佳,蒋国强,陈军,等,经皮给药系统的研究进展和发展趋势,精细化工,2002,19(6):367~371
[44]. Kattan A.E., Asbill C.S., Haidar S., Transdermal testing aspects and methods, PSTT, 2000, (3):426~430
[45]. Higuehi W.I., Li S.K., Ghanem A.H., et a1, Mechanistic aspects of iontophoresis in human epidermal membrane, J. Control. Release, 1999, 62:13~23
[46]. Weaver J.C., Vaughan T.E., Chizmadzhev Y., Theory of electrical creation of aqueous pathways across skin transport barrier, Adv. Drug Delivery Rev., 1999, 35: 21~39
[47]. Mitracotri S., Ray D., Farrell J., et a1, Synergistic effect of ultrasound and sodium lauryl sulfate on transdermal drug delivery, J. Pharm. Sci., 2000, 89(7): 892~900
[48]. Mitracotri S., Ray D., Farrell J., et al, Enhancement of transdermal transportusing ultrasound and surfactants, Proceed. Intern. Symp. Control. Rel. Bioact. Mater., 1999, 6(2):176~177
[49]. Mark R.P., Microneedles for Transdermal drug delivery, Adv. Drug Delivery Rev., 2004, 56(5):581~587
[50].崔黎丽,江键,夏钟福,等,驻极体对皮肤角质层结构修饰作用的研究,功能材料,1998,29:892~895
[51].金一,内田昌希,超高速氮气系统经皮微球给药研究,药学学报,2001,36(2):140~144
[52]. Lee S., Meauliffe J., Flotte T.J., et a1, Photomeehaniea1 transderma1 delivery of maromolecules, J. Invest. Dermatol., 1998, 111:925~929
[53]. Doukas A.G., Transdermal drug delivery with a pressure wave, Adv. Drug Delivery Rev., 2004, 56, (5):559~579
[54]. Samir D., Elizabeth M., Permeability of ketorolac acid and its esteranglogs through human cadaver skin, J. Pharm. Sci., 1994, 83 (11):1548~1552
[55].朱全刚,胡晋红,范国荣,酮洛芬异丙脂在皮肤细胞中的代谢,中国医院药学杂志,2002, 22(4):195~198
[56].姜忠义,高蓉,许松伟,药物蛋白的聚乙二醇修饰,中国药学杂志,2002, 37(6 ): 409~412
[57]. Hudziak R.M., Barofsky D., Barofsky D.F., et al, Resistance of morpholino phosphorodiamidate oligomers to enzymatic degradation, Antisense Nucleic Acid Drug Dev., 1996, 6:267~271
[58]. Stein D., Foster E., Huang S.B., et al, A specificity comparison of four antisense types: Morpholino, 2'-O-methyl RNA, DNA and phosphorodiamidate DNA, Antisense Nucleic Acid Drug Dev., 1997, 7:15~21
[59]. Langer R., Transdermal drug delivery: past progress, current status, and future prospects, Adv. Drug Delivery Rev., 2004, 56:557~558
[60]. Finnin B.C., Morgan T.M., Transdermal Penetration Enhancers:Applications, Limitations,and Potential, J. Pharm. Sci., 1999, 88(10):955~958
[61]. Barry B.W., Lipid-protein-partitioning theory of skin penetration enhancement, J. Control. Release, 1991, 15:237~248
[62]. Pfister W., Dean S., Hsieh S., Permeation enhancers compatible with transdermal drug delivery systems. I. Selection and formulation considerations, Pharm. Tech., 1990, 8:132~140
[63]. Kanikkannan N., Kandimalla K., Lamba S., et al, Structure-activityrelationship of chemical penetration enhancers in transdermal drug delivery, Curr. Med. Chem., 2000, 7(6):593~608
[64]. Szente L., Szejtli J., Hightly soluble cyclodextrin derivatives: chemistry,properties, and trends in development, Adv. Drug Delivevry Rev., 1999, 36(1): 17~28
[65]. Lopez R.F., CollettOt J.H., Bentley M.V., Influenee of cyclodextrin complexation on the in vitro permeatian and skin metabolismof dexamethasone, Int. J. Pharm., 2000, 200(1): 127~132
[66]. Godwin D.A., Wiley C.J., Felton L.A., Using cyclodextrin complexation to enhance secondary photoprotection of topically applied ibuprofen, Eur. J. Pharm. Biopharm., 2006, 62:85~93
[67]. Vaddi H.K., Ho P.C., Chan Y.W., et a1, Terpenes in ethanol: haloperidol permeation and partition through human skin and stratum corneum changes, J. Control. Release, 2002, 81:121~133
[68]. Krishnaiah Y.S.R., Satyanarayana V., Bhaskar P., Influence of menthol and pressure-sensitive adhesives on the in vivo performance of membrane-moderated transdermal therapeutic system of nicardipine hydroehloride in human volunteers, Eur. J. Pharm. Biopharm., 2003, 55(3): 329~337
[69]. Higaki K., Amnuaikit C., Kimura T., Strategies for overcoming the stratum corneum; chemical and physical approaches, Am. J. Drug Deliv., 2003, 1(3): 187~214
[70]. Jain A.K., Narishetty S.T.K., Panchagnual R., Transdermal drug delivery of imipramine hydrochloride, I. Effect of terpenes, J. Control. Release, 2002, 79(1): 93~101
[71]. Amnuaikit C., Ikeuchi I., Ogawara K., et a1, Skin permeation of propranolol from polymeric film containing terpene enhancers for transdermal use, Int. J. Pharm., 2005, 289: 167~178
[72]. Williams A.C., Edwards H.G.M., Lawson E.E., Molecular interactions between the penetration enhancer 1,8-cineole and human skin, J. Raman Spectrosc., 2006, 37: 361~366
[73]. KlimentováJ., Hrabálek A., VávrováK., et al, Synthesis and transdermal penetration-enhancing activity of carbonic and carbamic acid esters-Comparison with transkarbam 12, Bioorg. Med. Chem. Lett., 2006, 16:1981~1984
[74]. Holas T., VávrováK., ?íma M., et al, Synthesis and transdermal permeation-enhancing activity of carbonate and carbamate analogs of Transkarbam 12, Bioorg. Med. Chem. Lett., 2006, 14: 2896~2903
[75]. Akimoto T., Nagase Y., Novel transdermal drug penetration enhancer: synthesis and enhancing effect of a1ky1disiloxane cornpounds containing g1ucopyranosy1 group, J. Control. Release, 2003, 88(2):243~252
[76]. Akimoto T., Kawahara K., Nagase Y., et al, Polymeric transdermal drug penetration enhancer the enhancing effect of oligodimethylsiloxane containing a g1ucopyranosy1 end group, J. Control. Release, 2001, 77: 49~57
[77]. Sim Y.C., Nam Y.S., Shin Y.H., et al, Proteolytic enzyme conjugated to SC-glucan as an enzymatic transdermal drug penetration enhancer. Pharmazie, 2003, 58(4):252~256
[78]. ChenY.P., Shen Y.Y., Guo X., et al, Transdermal protein delivery by a co-administered pcptide identified via phage display, Nat. Biatechnol., 2006, 24: 455~50
[79]. Bangham A.D., Liposomes: realizing their promise, Hospita1 Practice, 1992, 27:51~59
[80]. Mezei M., Gulasekharam V., Liposomes: a selective drug delivery system for the topical route of administration:Ι. Lotion dosage form, Life sci., 1980, 26:473~489
[81]. Chung S.J., Future drug delivery research in South Korea, J. Control. Release, 1999, 62:73~79
[82].赵会英,郑俊民,生物大分子药物的经皮给药,沈阳药科大学学报,2001, (2):68~72
[83]. Betz G., Imboden R., Imanidis G., Interaction of liposome formulations with human skin in vitro, Int. J. Pharm., 2001, 229:117~129
[84]. Cevc G., Gebauer D., Stieber J., et al, Ultraflexible vesicles, Transfersomes, have an extremely low pore penetration resistance and transport therapeutic amours of insulin across the intact nammalian skin, Biochim. Biophys. Acta., 1998, 1368: 2011~2023
[85]. Jain S., Jain P., Umamaheshwari R.B., et al, Transfersomes: a novel vesivular carrier for enhanced transdermal delivery: development, characterization, and performance evaluation, Drug Dev. Ind. Pharm., 2003,29(9):1013~1016
[86]. Hofer C., Lehemer A., Hartung R., A transdermal approach for IL-2 therapy by new untraderformable carriers-transfersomes, J. Urol., 2000, 163(4):114~119
[87]. Paul A., Cevc G., Noninvasive administration of protein antigens, transdermal immunization with the bovine serum albumin in transfersomes, Vaccine Res., 1995, 4:145~163
[88]. Touitou E., Dayan N., Bergelson L., et al, Ethosomes- novel vesicularcarriers for enhancer delivery:characterization and skin penetration properties, J. Control. Release, 2000, 65:401~403
[89]. Dayan N., Touitou E., Carriers for skin delivery of trihexyphenidyl HCl: ehosomes vs liposomes, Biomaterials, 2000, 21: 1879~1881
[90]. Schhreier H., Bouwstra J., Liposomes and niosomes as topical drug carriers: dermal and transdermal drug delivery, J. Control. Release, 1994, 30:1~5
[91]. Peltola S., Saarinen-Savolainen P., Kiesvaara J., et al, Microemulsion for topical delivery of estradio1, Int. J. Pharm., 2003, 254:99~107
[92]. Nistico S., Puglisi G., Fresta M., et al, Lecithin microemulsions for the topical administration of ketoprofen: percutaneous adsorption through human skin and in vivo human skin tolerability, Int. J. Pharm., 2002, 244:21~31
[93]. Kreilgaard M., Pedersen E.J, Jaroszewski J.W., NMR characterisation and transdermal drug delivery potential of microemulsion systems, J. Control. Release, 2000, 69:421~433
[94]. Chen H., Chang X., Weng T., et al, A study of microemulsion systems for transdermal delivery of triptolide, J. Control. Release, 2004, 98:427~436
[95]. Uhrich K.E., Cannizzaro S.M., Langer R.S., et al, Polymeric systems for controlled drug release, Chem. Rev., 1999, 99: 3181~3198
[96].黄际薇,张永明,黄凤爱,等,促进药物透皮吸收的方法,中国医院药学杂志,2000,20(11):680~682
[97]. Jenning V., Gysler A., Schafer-Korting M., et al, Vitamin A loaded solid lipid nanoparticles for topic use: occlusive properties and drug targeting to the upper skin, Eur. J. Pharm. Biopharm., 2000, 49(3): 211~218
[98].瞿文,陈庆华,朱宝泉,固体脂质纳米粒的研究进展,中国医药工业杂志,2001,32(9):424~429
[99]. Muller B., Kreuter J., Enhanced transport of nanoparticle associated drugsthrough natural and artificial membranes-a general phenomenon, Int. J. Pharm., 1999, 178:23~32
[100]. Moser K.K., Kriwet C., Froehlich Y.N., et al, Supersaturation: Enhancement of skin penetration and permeation of a lipophilic drug, Pharm. Res., 2001, 18(7): 1006-1011
[101]. Shibaji T., Yasuhara Y., Oda N., et a1, A mechanism of the high frequency AC iontophoresis, J. Control. Release, 2001, 73:37~ 47
[102]. Bao J.L., Ping Q.N., Enhanced transdermal delivery of tetracaine by electroporation, Int. J. Pharm., 2000, 202: 121~124
[103]. Hashmi S., Ling P., Hashmi G., et al, Genetic transformation of nematodes using arrays of micromechanical piercing structures, Biotechniques, 1995, 19: 766~770
[104]. Henry S., Mcallisiter D., Allen M.G., et al, Microfabricated microneedles: a novel method to increase transdermal drug delivery, J. Pharm. Sci., 1998, 87: 922~925
[105]. Matriano J.A., Cormier M., Johnson J., et al, Macroflux microprojection array patch technology: a new and efficient approach for intracutaneous immunization, Pharm. Res., 2002, 19:63~70
[106]. Lee S., Kollias N., Daniel J., et a1, Topical drug delivery in human with a single photomechanica1 wave, Pharm. Res., 1999, 16:1717~1721
[107].元英进,刘明言,董岸杰,中药现代化生产关键技术,北京:化学工业出版社,2002:231~232
[108]. Hurkmans M., Bodde H.E., Van Driel M.J., Skin irritation caused by transdermal drug delivery systems during long-term (5 days) application, Br. J. Dermatol., 1985, 112:461~476
[109]. Chien Y.W., Development of transdermal controlled release drug delivery system: An overview. In:Kydonieus AF and Berner B, eds, Transdermal Delivery of drugs, Raton B, CRC press , 1987: 81~100
[110]. Chien, Y.M., Microsealed drug delivery systems: Theoretical aspects and biomedical assessments, in Int. Symp. on recent advances in drug delivery systems, Anderson, J M and Kim S W, Eds., Plenum Press, New York, 1984:367
[111]. Tan H.S., Pfister W.R., Pressure-sensitive adhesives for transdermal drug delivery systems, PSTT, 1999, 2: 60~69
[112]. Higuchi T., Rates of release of medicaments from the ointment bases containing drugs in suspension, J. Pharm. Sci., 1961, 50:874~875
[113]. Baker R.W., Londsdale H.K., Controlled release: Mechanism and rates. In controlled release of biologically active agents, Tanquary, AC and Lacey Eds., Plenum press, New York, 1974:15~71
[114]. John H.R., Role of polymer permeability in the control of drug release, in polymer permeability, J. Comyn. Eds., Elsevier applied science publishers, 1986:242~244
[115]. Wolff M., Cordes G., Luckow V., In vitro and in vivo release of nitroglycerin from a new transdermal therapeutic system, Pharm, Res., 1985, 1:23~29
[116].梁秉文,中药经皮给药制剂技术,北京:化学工业出版社,2006: 49~53
[117]. Webster I., Recent developments in pressure-sensitive adhesives for medical applications, Int. J. Adhes. Adhes., 1997, 17:69~73
[118]. Venkatraman S., Gale R., Skin adhesives and skin adhesion: 1. Transdermal drug delivery systems, Biomaterials, 1998, 19 (13):1119~1136
[119]. Arrowsmith D.J., Adhesion of electroformed copper and nickel to plastic laminates, Trans. Inst. Met. Finsh., 1970, 48:88~97
[120]. Packham D.E., Adhesive aspects of polymeric coating, New York, Plenum Press, 1983
[121].陈子达,李玲,邹翰,医用胶粘剂的研究进展,化学与粘合,2001,1:21~28
[122].梁秉文,经皮给药制剂,北京:中国医药科技出版社,1992:223~226
[123]. Langer R.S., Medical applications of controlled release, CRC press, 1984, 1: 230~231
[124].阿方萨斯,V.波丘斯,粘接与胶黏剂技术导论,北京:化学工业出版社,2005,209~237
[125]. Temin S.C., In:Skeist I., Handbook of Adhesives, New York, NY NSA: Marcel Dekker, 1990:133~135
[126]. Royx S.D., Gutierrez M., Flynn G.L., Controlled transdermal delivery of fentanyl: characterizations of pressure-sensitive adhesives for matrix patch design, J. Pharm. Sci., 1996, 85:491~495
[127]. Satas D., Handbook of pressure sensitive adhesive technology, New York:Van Nostrand Reinhold,1989:71~74
[128]. Qinglin S., Qiang G., Shuqing Z., et al, Study on the composition design ofthe water emulsion acrylates pressure-sensitive adhesive, Chemical Engineering, 1996, 24(2):65~67
[129]. Christensen S.F., Mckinley G.H., Rheological modeling of the peeling of pressure-sensitive adhesives and other elastomers, Int. J. Adhes. Adhes., 1998, 18:333~343
[130]. Kinning D.J., Bulk, surface and interfacial characterization of silicone-polyurea segmented copolymers, J. Adhesion, 2001, 75(1): 1~26
[131]. Gordon G.V., Schmidt R.G., PSA release force profiles from silicone liners: probing viscoelastic contributions from release system components, J Adhes., 2000, 72(2): 133~156
[132]. Bunker S., Staller C., Miniemulsion polymerization of acrylated methyl oleate for pressure sensitive adhesives, Int. J. Adhes. Adhes., 2003, 23:29~38
[133]. Ozawa T., Ishiwata S., KanoY., Acrylate copolymer/ultraviolet curable oligomer blends as pressure-sensitive adhesives, J. Adhes., 2000, 72(1):1~16
[134]. Chiriac A.P., The improvement of adhesive character of an acrylovinylic macromolecular compound, Polym. Test., 2001, 20:873~877
[135]. Yamamoto M., Nakano F., Doi T., et al, Synthesis and PSA performance study for novel acrylic and butyl acrylate block copolymers, Int. J. Adhes. Adhes., 2002, 22:37~40
[136]. Francis E.G., Christian W.J., George E.S., Thermally reversible polyurethane hydrogels and cosmetic,biological and medical uses, US 5000955,1991-03-19
[137]. Minghetti Y., Cilurzo F., Tosi L., et al, Design of a new water-soluble pressure- sensitive adhesive for patch preparation, AAPS PharmSciTech., 2003, 4:8~14
[138]. Mukherjee B., Mahapatra S., Gupta R., et al, A comparison between povidone-ethylcellulose and povidone-eudragit transdermal dexamethasone matrix patches based on in vitro skin permeation, Eur. J. Pharm. Biopharm., 2005, 59:475~483
[139]. Zhang J.H., Liu Z.P., Deng L.D., et.al., A novel hydrophilic adhesive matrix with self-enhancement for transdermal drug delivery, Pharm. Res., 2009, 26(6):1398~1406
[140].翟茂林,哈鸿飞,水凝胶的合成、性质及应用,大学化学,2001,5:22~27
[141].吉井文男,有粘性的PVA水凝胶的制备方法,JP 9263671,1997-10-07
[142]. Razzak M.T., Irradiation of polyvinyl alcohol and polyvinyl pyrrolidoneblended hydrogel for wound dressing, Radiat. Phys. Chem., 2001, 62:107~113
[143].贾伟,高文远,王涛,中药巴布剂的研究现状,中国中药杂志,2003,28(1):7~11
[144].范碧亭,张兆旺,施顺清,中药药剂学[M],上海:上海科学技术出版社出版,1997:320~323
[145]. Lee J.W., Robinson J.H., Bioadhesive-based dosage forms: the next generation, J. Pharm. Sci., 2000, 89:850~ 866
[146].秦东梅,王恒,李海瑛,羟丙甲基纤维素在药剂学中的应用,安徽医药,2004, 8(3): 173~175
[147].庄越,曹宝成,萧瑞祥,实用药物制剂技术,北京:人民卫生出版社,1999:399~400
[148]. Gholap S.G., Jog J.P., Badiger M.V., Synthesis and characterization of hydrophobically modified poly (vinyl alcohol) hydrogel membrane, Polymer, 2004, 45:5863~5873
[149].虞绍铸,张曩玲,复方喜树碱涂膜剂的制备和疗效观察,中国药业,2001,10(6):19~23
[150].刘建平,虞宣,崔丽,酮基布洛芬涂膜剂的制备及控释机理研究,中国药科大学学报,1996,27 (11) :652~654
[151]. Schroeder I.Z., Franke P., Schaefer U.F., et al, Development and characterization of film forming polymeric solutions for skin drug delivery, Eur. J. Pharm. Biopharm.,2007,65: 111~121
[152]. Chiefari J., Chong Y.K., Rizzardo E., et al, Living free-radical polymerization by reversible addition-fragmentation chain transfer: the RAFT process, Macromolecules, 1998, 31:5559~5562
[153]. Jancova K., Kops J., Chem X., et al, The RAFT Polymerization, Macromole Rapid Commun, 1999, 20: 219~224
[154].王艳君,王玉霞,袁才登,等,可逆加成-断裂链转移聚合研究进展,高分子通报,2003,3:57 ~ 63
[155]. Chong Y.K., Julia K.K., Tam P.T., et al, Thiocarbonylthio compounds [S=C(Ph)S-R] in free-radical polymerization with reversible addition-fragmentation chain transfer (RAFT polymerization). role of the free-radical leaving group (R), Macromolecules, 2003, 36: 2256 ~ 2272
[156]. John C.R., Roshan T.A., Mayaduune T., et al, Thiocarbonylthio compounds (S=C(Z)S-R) in free radical polymerization with reversibleaddition-fragmentation chain transfer (RAFT polymerization). effect of the activating group (Z), Macromolecules, 2003, 36: 2273 ~ 2283
[157]. Christine M.S., Zhang M., Rizzardo E., et al, A new double-responsive block copolymer synthesized vis RAFT Polymerization, Macromolecules, 2004, 37:7861~ 7866
[158]. Chapman T.M., Shi L.J, Bechman E.J., Poly(ethylene glecol)-block-poly (N-vinylformamide) copolymers synthesized by the RAFT methodology, Macromolecules, 2003, 36(7): 2563~2567
[159]. Le T.P., Moad G., Rizzardo E., et al, Polymerization with living characteristics. PCT Int Appl. WO 9801478 Al. 9800115, 1998
[160]. Benicewicz B.C., Kanagasabapathy S., Sudalai A., Dithiocarboxylic ester synthetic process, USP 6458968, 2002
[161].戚桂村,基于咔唑新型RAFT试剂的合成与RAFT聚合研究:[硕士学位论文],天津:天津大学,2004
[162].荣国斌,苏克曼,大学有机化学基础,华东理工大学出版社,2000:228~236
[163]. Li J.S., Zhan W.Q., Rao W.Q., et al, Studies on the reaction of N,N-dialkyldithiocarbamate with cyanuric chloride, Chin. Org. Chem., 2001, 21(10):759~762
[164]. Moad G., Chong Y.K., Postma A., et al, Advances in RAFT polymerization: the synthesis of polymers with defined end-groups Polymer, 2005, 46: 8458~8468
[165]. Mitsukami Y., Donovan M.S., Lowe A.B., et al, Water-soluble polymers. 81. direct synthesis of hydrophilic styrenic-based homopolymers and block copolymers in aqueous solution via RAFT, Macromolecules, 2001, 34(7): 2248~2256
[166].张肖娟,高静,罗英武,单体组成对甲基丙烯酸甲酯/丙烯酸丁酯RAFT共聚合转移常数的影响,高分子学报,2008, (1): 82~87
[167]. Benaglia M, Rizzardo E, Alberti A, et al, Searching for more effective agents and conditions for the RAFT polymerization of mma: influence of dithioester substituents, solvent, and temperature, Macromolecules, 2005, 38(8):3129~3140
[168]. Barba A.A., Amore M., Chirico S., et al, A general code to predict the drug release kinetics from different shaped matrices, Eur. J. Pharm. Sci., 2009, 36: 359~366
[169]. Junginger H.E., Verhoef J.C., Macromolecules as safe penetration enhancers for hydrophilic drugs– a fiction? PSTT, 1998, 1(9): 370~374
[170]. Liu Y.Y., Fan X.D., Wei, B.R. et al, pH-responsive amphiphilic hydrogel networks with IPN structure: A strategy for controlled drug release, Int. J. Pharm., 2006, 308:205~216
[171].杨云松,彭红云,章国林,等,透皮控释给药研究,高分子通报, 2002, 1: 49~52
[172]. Ma X.H., Taw J., Chinan C.M., Control of drug crystallization in transdermal matrix system, Int. J. Pharm., 1996, 142:115~119
[173]. KotzéA.F., Lue?en H.L., de Boer A.G., et al, Chitosan for enhanced intestinal permeability:Prospects for derivatives soluble in neutral and basic environments, Eur. J. Pharm. Sci., 1999, 7(2):145~151
[174]. Miyajima M., Koshika A., Okada J., et al, Effect of polymer/basic drug interactions on the two-stage diffusion-controlled release from a poly(L-lactic acid) matrix, J. Control. Release, 1999, 61:295~302
[175].龚志超,董岸杰,邓联东,用于药物透皮吸收制剂的压敏胶的新进展,化学工业与工程, 2002, 19(6): 437~440
[176]. Georgiadis M. C., Kostoglou M., On the optimization of drug release from multi-laminated polymer matrix devices, J. Control. Release, 2001, 77: 273~278
[177]. Bairamov D.F., Markin V.S., Iordanskii A.L., et al, Drug diffusion in adhesive hydrogels, Proc. Int. Symp. Control Release Bioactive Mater., 1999, 26:389~390
[178]. Brandrup J., Immergut E.H., Polymer Handbook, 2 Volumes Set, Fourth Edition. Division: Polymer / John Wiley & Son, 2003
[179]. Fedors R.F., A method for estimating both the solubility parameters and molar volumes of liquids, Polym. Eng. Sci., 1974, 14:147~154
[180].李振吉,中医药现代化发展前景展望,中国科技产业,2003, 1:10~14
[181].张礼和,我对中药复方有效成分研究的一些看法,化学进展, 1998,11(2):186~189
[182].杨明,郑琴,万娜,从中药复方施药系统研究现状引发的思考,世界科学技术——中医药现代化,2007, 9(5):13~17
[183]. Thomas B. J., Finnin B. C., The transdermal revolution, DDT, 2004, 9(16):697~703
[184]. Zhai H., Maibach H.I., Occlusion vs. skin barrier function, Skin Res. Technol., 2002, 8 (1):1~6
[185]. Lee J.W., Park Robinson J.H., Bioadhesive-based dosage forms: the next generation, J. Pharm. Sci., 2000, 89:850~866
[186]. Schroeder Z., Franke P., Schaefer U.F., et al, Development and characterization of film forming polymeric solutions for skin drug delivery, Eur. J. Pharm. Biopharm., 2007, 65:111~121
[187]. Schroeder Z., Franke P., Schaefer U.F., et al, Delivery of ethinylestradiol from film forming polymeric solutions across human epidermis in vitro and in vivo in pigs, J. Control. Release, 2007, 118:196~203
[188]. Jones D.S., Woolfson A.D., Brown A.F., Textrual, viscoelastic and mucoadhesive properties of pharmaceutical gels composed of cellulose polymers, Int. J. Pharm., 1997, 151:223~233
[189]. Seal B.L., Otero T.C., Panitch A., Polymeric biomaterials for tissue and organ regeneration, Mater. Sci Eng., 2001, 34:147~230
[190]. Seabra B., de Oliveira M. G., Poly (vinyl alcohol) and poly (vinyl pyrrolidone) blended films for local nitric oxide release, Biomaterials., 2004, 25:3773~3782
[191]. Gholap S.G., Jog J.P., Badiger M.V., Synthesis and characterization of hydrophobically modified poly (vinyl alcohol) hydrogel membrane, Polymers, 2004, 45:5863~5873
[192]. Paul W., Sharma C.P., Acetylsalicylic acid loaded poly(vinyl alcohol) hemodialysis membranes: effect of drug release on blood compatibility and permeability, J. Biomed. Sci. Polym. Ed., 1997, 8 :755~764
[193]. Cascone M.G., Sim B., Downes S., Blends of synthetic and natural polymers as drug delivery systems for growth hormone, Biomaterials, 1995, 16: 569~574.
[194]. Gal A., Nussinovitch A., Plasticizers in the manufacture of novel skin-bioadhesive patches, Int. J. Pharm., 2009, 370:103~109
[195]. Kanis L.A., Generoso M., Meier M.M., et al, Poly(ethylene-co-methyl acrylate) membranes as rate-controlling barriers for drug delivery systems: characterization, mechanical properties and permeability, Eur. J. Pharm. Biopharm., 2005, 60:383~390
[196]. Uragami T., Okazaki K., Matsugi H., et al, Structure and permeationcharacteristics of an aqueous ethanol solution of organic-inorganic hybrid membranes composed of poly(vinyl alcohol) and tetraethoxysilane, Macromolecules., 2002, 35:9156~9163
[197]. Kulkarni S.S., Kittur A.A., Aralaguppi M.I., et al, Synthesis and characterization of hybrid membranes using poly (vinyl alcohol) and tetraethylorthosilicate for the tervaporation separation of water–isopropanol mixtures, J. Appl. Polymer Sci., 2004, 97:1304~1315
[198]. Peng F.B., Lu L.Y., Sun H.L., et al, Analysis of annealing effect on pervaporation properties of PVA-GPTMS hybrid membranes through PALS, J. Membr. Sci., 2006, 281:600~608
[199]. Tokumura F., Homma T., Tomiya T., et al, Properties of pressure-sensitive adhesive tapes with soft adhesives to human skin and their mechanism, Skin Res. Technol., 2007, 13: 211~216
[200]. Water-vapour Permeability, in: British Pharmacopoeia, 1993, Appendix XXJ.
[201]. Draize J.H., Woodard G., Calvery H.O., Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes, J. Pharmacol. Exp. Ther., 1944, 82:377~390
[202]. Robertson M.A., Rudkin R.A., Parsonage D., et al, Mechanical and thermal properties of organic/inorganic hybrid coatings, J. Sol-Gel. Sci. Tech., 2003, 26:291~297
[203]. Peng F.B., Lu L.Y., Sun H.L., et al, Correlations between free volume characteristics and pervaporation permeability of novel PVA–GPTMS hybrid membranes, J. Membr. Sci., 2006, 275: 97~104
[204]. Jang J., Lee D.K., Plasticizer effect on the melting and crystallization behavior of polyvinyl alcohol, Polymer, 2003, 44:8139~8146
[205]. Chukwumerije C., Nash R.A., Matias J.R., et al, Studies on the efficacy of methyl esters of n-Alkyl fatty acids as penetration enhancers, J. Invest. Dermatol., 1989, 93(3):349~352
[206]. Friend D.R., Catz P., Heller J., Simple alkyl esters as skin permeation enhancers, J. Control. Release, 1989, 9 (1):33~41
[207]. Catz P., Friend D.R., Alkyl esters as skin permeation enhancers for indomethacin, Int. J. Pharm., 1989, 55(1): 17~23
[208]. Sato K., Sugibayashi K., Morimoto Y., Effect and mode of action of aliphatic esters on the in vitro skin permeation of nicorandil, Int. J. Pharm., 1988,43(1-2):31~40
[209]. Datta R., Henry M., Lactic acid: recent advances in products, processes and technologies-a review, J. Chem. Technol. Biotechnol., 2006, 81:1119~1129
[210]. Clary J.J., Feron V.J., van Velthuijsen J.A., Safety assessment of lactate esters, Regul. Toxicol. Pharmacol., 1998, 27(2):88~97
[211]. Tung R.C., Bergfeld W.K., Vidimos A.T., et al, Alpha-hydroxy acid-based cosmetic procedures. Guidelines for patient management, Am. J. Clin. Dermatol, 2000, 1:81~88
[212].林敏,秦敬云,林静,乳酸酯的合成研究,厦门大学学报,1997,36(4):581~584
[213].李军,经皮给药压敏胶及聚合物纳米粒经皮药物传递的研究:[博士论文],天津:天津大学,2006
[214]. Kikwai L., Kanikkannan N., Babu R. J., et al, Effect of vehicles on the transdermal delivery of melatonin across porcine skin in vitro, J. Control. Release, 2002, 83:307~311
[215]. Trottet L., Merly C., Mirza M., et al, Effect of finite doses of propylene glycol on enhancement of in vitro percutaneous permeation of loperamide hydrochloride, Int. J. Pharm., 2004, 274:213~219
[216]. Kaiho F., Koike R., Nomura H., et al, Enhancing effect of cetyl lactate on the percutaneous absorption of indomethacin in rats, Chem. Pharm. Bull., 1989, 37: 1114~1116
[217]. Dohi M., Kaiho F., Suzuki A., et al, Enhancing effects of myristryl lactate and lauryl lactate on percutaneous absorption of indomethacin in rats, Chem. Pharm. Bull., 1990, 38:2877~2879
[218]. Lee E.S., Watanabe T., Gale R.M., et al, Monoglyceride/lactate ester permeation enhancer for oxybutynin, US Patent USA 5747065, 1998
[219]. Herkenne C., Naik A., Kalia Y.N., et al, Effect of propylene glycol on ibuprofen absorption into human skin in vivo, J. Pharm. Sci., 2008,97: 185~197
[220]. Al-Saidan S.M., Transdermal self-permeation enhancement of ibuprofen, J. Control. Release, 2004, 100:199~209
[221]. Sato K., Sugibayashi K., Morimoto Y., Effect and mode of action of aliphatic esters on the in vitro skin permeation of nicorandil, Int. J. Pharm., 1988, 43: 31~40
[222]. Dias M., Hadgraft J., Lane M.E., Influence of membrane-solvent-solute interactions on solute permeation in skin, Int. J. Pharm., 2007, 340:65~70
[223]. Yano T., Noda K., Skin permeability of various non-steroids anti-inflammatory drugs in man, Life Sci., 1986, 39:1043~1050
[224]. Han S.K., Park Y.H., Kim C.K., Preparation of N-adamantyl n-alkanamides and evaluation of their transdermal penetration in the rabbit, Int. J. Pharm., 1995, 126:35~40
[225]. Friend D.R., Catz P., Heller J., Simple alkyl esters as skin permeation enhancers, J. Control. Release, 1989, 9:33~41
[226]. Catz P., Friend D.R., Alkyl esters as skin permeation enhancers for indomethacin, Int. J. Pharm., 1989, 55:17~23
[227]. Megrab N.A., Williams A.C., Barry B.W., Oestradiol permeation through human skin and silastic membrane: Effects of propylene glycol and supersaturation, J. Control. Release, 1995, 36:277~294
[228]. Arellano A., Santoyo S., Martin C., et al, Influence of propylene glycol and isopropyl myristate on the in vitro percutaneous penetration of diclofenac sodium from carbopol gels, Eur. J. Pharm. Sci., 1999, 7:129~135
[229]. Sherertz E.F., Sloan K.B., Mctiernan. R.G., Use of theoretical partition coefficients determined from solubility parameters to predict permeability coefficients for 5-fluorouracil, J. Invest. Dermatol., 1987, 89:147~151
[230]. Sloan K.B., Koch S.A.M., Siver K.G., et al, Use of solubility parameters of drug and vehicle to predict flux through skin, J. Invest. Dermatol., 1986, 87: 244~252
[231]. Aungst B.J., Rogers N.J., Shefter E., Enhancement of naloxone penetration through human skin in vitro using fatty acids, fatty alcohols, surfactants, sulfoxides, and amides, Int. J. Pharm., 1986, 33: 225~234
[232]. Cooper E.R., Merritt E.W., Smith R.L., Effect of fatty acids and alcohols on the penetration of acyclovir across human skin in vitro, J. Pharm. Sci., 1985, 74:688~689
[233]. Quan D., Higuchi R.I., Takayama K., et al, Enhancement effect of piperidone derivatives on the percutaneous absorption of indomethacin, Drug Des. Deliv., 1990, 6:61~71
[234]. Li G.L., van der Geest R., Chanet L., et al, In vitro iontophoresis of R-apomorphine across human stratum corneum: Structure-transportrelationship of penetration enhancement, J. Control. Release, 2002, 84:49~57
[235]. Brain K.R., Walters K.A., Molecular modeling of skin permeation enhancement by chemical agents. In: Walters, K.A., Hadgraft, J. (Eds.), Pharmaceutical Skin Penetration Enhancement,Marcel Dekker, New York, 1993, pp:389~416
[236]. Mackay K.M.B., Williams A.C., Barry B.W., Effect of melting point of chiral terpenes on human stratum corneum uptake, Int. J. Pharm., 2001, 228:89~97
[237]. Okamoto H., Muta K., Hashida M., et al, Percutaneous penetration of acyclovir through excised hairless mouse and rat skin: Effect of vehicle and percutaneous penetration enhancer, Pharm. Res., 1990, 7:64~68
[238]. Barry B.W., In. Barry, B.W., Shroot, B., Schaefer, H. (Eds.), Skin Pharmacokinetics. Karger, Basel, Switzerland, 1987, pp:121~137
[239]. Liron Z., Cohen S., Percutaneous absorption of alkanoic acids II: Application of regular solution theory, J. Pharm. Sci., 1984, 73:538~542
[240]. Nanayakkara G.R., Bartlett A., Forbes B., et al, The effect of unsaturated fatty acids in benzyl alcohol on the percutaneous permeation of three model penetrants, Int. J. Pharm., 2005, 301:129~139
[241]. Guy R.H., Hadgraft J., Transdermal drug delivery: a simplified pharmacokinetic approach, Int. J. Pharm., 1985, 24:267~274
[242]. Barry B.W., Bennett S.L., Effect of penetration enhancers on the permeation of mannitol, hydrocortisone and progesterone through human-skin, J. Pharm. Pharmacol., 1987, 39:535~546
[243]. Taskovich L.T., Yum S.I., Crisologo N.M., Monoglyceride/lactate ester permeation enhancer for codelivery of steroids, US Patent USA 5686097, 1997
[2].郁正艳,金明飞,左翼,等,药物传输系统(DDS)的研究现状与发展前景,生命的化学,2004,24(5):428~431
[3]. Chen H., Langer R., Oral particulate delivery:status and future trends, Adv. Drug Delivery Rev.,1998,34(2-3):339~350
[4]. Kermode M., Unsafe injections in low-income country health settings: need for injection safety promotion to prevent the spread of blood-borne viruses, Health Promot. Int., 2004, 19:95~103
[5]. Nir Y., Paz A., Sabo E., et al, Fear of injections in young adults:prevalence and associations, Am. J. Trop. Med. Hyg., 2003, 68:341~344
[6]. Kane A., Lloyd J., Zaffran M., et al, Transmission of hepatitis B, hepatitis C and human immunodeficiency viruses through unsafe injections in the developing world: model-based regional estimates, Bull, World Health Organ., 1999, 77: 801~807
[7].梁秉文,中药经皮给药制剂技术,北京:化学工业出版社,2006:1~2
[8]. Prausnitz1 M R., Langer R., Transdermal drug delivery, Nat. Biotechnol., 2008, 26(11):1261~1268
[9]. Prausnitz M R., Mitragotri S., Langer R., Current status and future potential of transdermal drug delivery, Nat. Rev. Drug Discovery, 2004,3:115~124
[10].胡晋红,张立超,朱全刚,我国透皮给药的研究进展,解放军药学学报,2002,18(1):38~41
[11].杨华生,朱庆文,梁秉文,药用辅料在中药经皮给药制剂中的应用,中医外治杂志,2007,16(3):3~5
[12].梁秉文,中药经皮给药制剂技术,北京:化学工业出版社,2006:7~9
[13]. Barry B.W., Is transdermal drug delivery research still important today? Drug Discovery Today, 2001, 60:967~97l
[14].梁秉文,中药经皮给药制剂技术,北京:化学工业出版社,2006:4~5
[15].刘强,吕治平,中药经皮给药制剂的进展及发展趋势,中医外治杂志,2004,13(1):31~33
[16].马卓,沈雄,陈前锋,中药透皮吸收制剂的研究进展,中药材,2005, 28(12):1136~1138
[17]. Kretsos K., Transport phenomena in the human skin:[博士学位论文], New York: University of New York, 2003
[18].梁秉文,中药经皮给药制剂技术,北京:化学工业出版社,2006:10~16
[19].陈勇平,通过噬菌体文库鉴定透皮输运蛋白质肽:[博士学位论文],合肥:中国科学技术大学,2007
[20]. Moser K., Kriwet K., Naik A., et al, Passive skin penetration enhancement and its quantification in vitro, Eur. J. Pharm. Biopharm., 2001, 52:103~112
[21].梁文权,经皮给药新剂型,北京:人民卫生出版社,1998:253~256
[22].陆彬,药物剂型与新技术,北京:人民卫生出版社,1998:356~361
[23].梁秉文,中药经皮给药制剂技术,北京:化学工业出版社,2006: 19~33
[24]. Hadgraft J., Dermal and transdermal drug design, Int. J. Pharm. Med., 1999, 13: 155~158
[25]. Yano T., Noda K., Skin permeability of various non-steroids anti-inflammatory drugs in man, Life Sci., 1986, 39:1043~1050
[26]. Wuster R.C., Kramer S.F., Research of drug transdermal through skin, J. Pham. Sci., 1961, 50:288~291
[27]. Walke R.B., Smith E.W., The role of percutaneous penetration enhancers, Adv. Drug Delivery Rev., 1996, 18:295~301
[28]. Wester R.C., Maibach H.L., Effects of diffcrellt drug permeation, J. Invest. Dermatol., 1976, 67:518~521
[29]. Noonan P.K, Wester R.C., Enhanced transdermal delivery of drugs, J. Pharm. Sci., 1980, 69:365~372
[30].梁秉文,中药经皮给药制剂技术,北京:化学工业出版社,2006: 19~33
[31].梁秉文,中药经皮给药制剂技术,北京:化学工业出版社,2006: 34~35
[32]. Simon, G.A., Maibach, H.I., The pig as an experimental animal model of percutaneous permeation in man: qualitative and quantitative observations-an overview, Skin Pharmacol. Appl. Skin Physiol., 2000, 13: 229~234
[33]. Howes D, Guy R, Hadrgft J, et al, Methods for assessing percutaneous absorption. ECVAM workshop report 13. Altern. Lab. Anim., 1996, 24:81-106
[34]. Prausnitz M. R., Mitragotri S., Langer R., Current status and future potential of transdermal drug delivery, Nat. Rev. Drug Discov., 2004, 3:115~124
[35]. Bando H., Yamashita F., Takakura Y., et al, Theoretical design of skinpenetration enhancement via prodrug enhancer combination based on a diffusion model, Proceed. Intern. Symp. Control. Rel. Bioact. Mater., 1995, 22:668~671
[36]. Williams A.C., Barry B.W., Penetration enhancers, Adv. Drug Delivery Rev., 2004, 56:603~618
[37]. Kirjavainen M., Urtti A., Valjakka K.R., et al, Liposome-skin interactions and their effects on the skin permeation of drugs, Eur. J. Pharm. Sci., 1999, 7(4):279~286
[38]. Lawrence M.J., Rees G.D., Microemulsion-based media as novel drug delivery systems, Adv. Drug Delivery Rev., 2000, 45 (1):89~121
[39].朱振峰,杨菁,药物纳米控释系统的最新研究进展,国外医学生物医学工程分册,1998,21(6):327~333
[40]. Kreuter J., Alyautdin R.N., Kharkewich D.A., et al, Passage of peptides through the blood-brain barrier with colloidal polymer particles(nanoparticles), Brain Res., 1995, 674:171~174
[41]. Megrab N.A., Williams A.C., Barry B.W., Oestradiol permeation through human skin and silastic membrane: effects of propylene glycol and supersaturation, J. Control. Release, 1995, 36 :277~294
[42]. Barry B.W., Novel mechanisms and devices to enable successful transdermal drug delivery, Eur. J. Pharm. Sci., 2001, 14:101~114
[43].昝佳,蒋国强,陈军,等,经皮给药系统的研究进展和发展趋势,精细化工,2002,19(6):367~371
[44]. Kattan A.E., Asbill C.S., Haidar S., Transdermal testing aspects and methods, PSTT, 2000, (3):426~430
[45]. Higuehi W.I., Li S.K., Ghanem A.H., et a1, Mechanistic aspects of iontophoresis in human epidermal membrane, J. Control. Release, 1999, 62:13~23
[46]. Weaver J.C., Vaughan T.E., Chizmadzhev Y., Theory of electrical creation of aqueous pathways across skin transport barrier, Adv. Drug Delivery Rev., 1999, 35: 21~39
[47]. Mitracotri S., Ray D., Farrell J., et a1, Synergistic effect of ultrasound and sodium lauryl sulfate on transdermal drug delivery, J. Pharm. Sci., 2000, 89(7): 892~900
[48]. Mitracotri S., Ray D., Farrell J., et al, Enhancement of transdermal transportusing ultrasound and surfactants, Proceed. Intern. Symp. Control. Rel. Bioact. Mater., 1999, 6(2):176~177
[49]. Mark R.P., Microneedles for Transdermal drug delivery, Adv. Drug Delivery Rev., 2004, 56(5):581~587
[50].崔黎丽,江键,夏钟福,等,驻极体对皮肤角质层结构修饰作用的研究,功能材料,1998,29:892~895
[51].金一,内田昌希,超高速氮气系统经皮微球给药研究,药学学报,2001,36(2):140~144
[52]. Lee S., Meauliffe J., Flotte T.J., et a1, Photomeehaniea1 transderma1 delivery of maromolecules, J. Invest. Dermatol., 1998, 111:925~929
[53]. Doukas A.G., Transdermal drug delivery with a pressure wave, Adv. Drug Delivery Rev., 2004, 56, (5):559~579
[54]. Samir D., Elizabeth M., Permeability of ketorolac acid and its esteranglogs through human cadaver skin, J. Pharm. Sci., 1994, 83 (11):1548~1552
[55].朱全刚,胡晋红,范国荣,酮洛芬异丙脂在皮肤细胞中的代谢,中国医院药学杂志,2002, 22(4):195~198
[56].姜忠义,高蓉,许松伟,药物蛋白的聚乙二醇修饰,中国药学杂志,2002, 37(6 ): 409~412
[57]. Hudziak R.M., Barofsky D., Barofsky D.F., et al, Resistance of morpholino phosphorodiamidate oligomers to enzymatic degradation, Antisense Nucleic Acid Drug Dev., 1996, 6:267~271
[58]. Stein D., Foster E., Huang S.B., et al, A specificity comparison of four antisense types: Morpholino, 2'-O-methyl RNA, DNA and phosphorodiamidate DNA, Antisense Nucleic Acid Drug Dev., 1997, 7:15~21
[59]. Langer R., Transdermal drug delivery: past progress, current status, and future prospects, Adv. Drug Delivery Rev., 2004, 56:557~558
[60]. Finnin B.C., Morgan T.M., Transdermal Penetration Enhancers:Applications, Limitations,and Potential, J. Pharm. Sci., 1999, 88(10):955~958
[61]. Barry B.W., Lipid-protein-partitioning theory of skin penetration enhancement, J. Control. Release, 1991, 15:237~248
[62]. Pfister W., Dean S., Hsieh S., Permeation enhancers compatible with transdermal drug delivery systems. I. Selection and formulation considerations, Pharm. Tech., 1990, 8:132~140
[63]. Kanikkannan N., Kandimalla K., Lamba S., et al, Structure-activityrelationship of chemical penetration enhancers in transdermal drug delivery, Curr. Med. Chem., 2000, 7(6):593~608
[64]. Szente L., Szejtli J., Hightly soluble cyclodextrin derivatives: chemistry,properties, and trends in development, Adv. Drug Delivevry Rev., 1999, 36(1): 17~28
[65]. Lopez R.F., CollettOt J.H., Bentley M.V., Influenee of cyclodextrin complexation on the in vitro permeatian and skin metabolismof dexamethasone, Int. J. Pharm., 2000, 200(1): 127~132
[66]. Godwin D.A., Wiley C.J., Felton L.A., Using cyclodextrin complexation to enhance secondary photoprotection of topically applied ibuprofen, Eur. J. Pharm. Biopharm., 2006, 62:85~93
[67]. Vaddi H.K., Ho P.C., Chan Y.W., et a1, Terpenes in ethanol: haloperidol permeation and partition through human skin and stratum corneum changes, J. Control. Release, 2002, 81:121~133
[68]. Krishnaiah Y.S.R., Satyanarayana V., Bhaskar P., Influence of menthol and pressure-sensitive adhesives on the in vivo performance of membrane-moderated transdermal therapeutic system of nicardipine hydroehloride in human volunteers, Eur. J. Pharm. Biopharm., 2003, 55(3): 329~337
[69]. Higaki K., Amnuaikit C., Kimura T., Strategies for overcoming the stratum corneum; chemical and physical approaches, Am. J. Drug Deliv., 2003, 1(3): 187~214
[70]. Jain A.K., Narishetty S.T.K., Panchagnual R., Transdermal drug delivery of imipramine hydrochloride, I. Effect of terpenes, J. Control. Release, 2002, 79(1): 93~101
[71]. Amnuaikit C., Ikeuchi I., Ogawara K., et a1, Skin permeation of propranolol from polymeric film containing terpene enhancers for transdermal use, Int. J. Pharm., 2005, 289: 167~178
[72]. Williams A.C., Edwards H.G.M., Lawson E.E., Molecular interactions between the penetration enhancer 1,8-cineole and human skin, J. Raman Spectrosc., 2006, 37: 361~366
[73]. KlimentováJ., Hrabálek A., VávrováK., et al, Synthesis and transdermal penetration-enhancing activity of carbonic and carbamic acid esters-Comparison with transkarbam 12, Bioorg. Med. Chem. Lett., 2006, 16:1981~1984
[74]. Holas T., VávrováK., ?íma M., et al, Synthesis and transdermal permeation-enhancing activity of carbonate and carbamate analogs of Transkarbam 12, Bioorg. Med. Chem. Lett., 2006, 14: 2896~2903
[75]. Akimoto T., Nagase Y., Novel transdermal drug penetration enhancer: synthesis and enhancing effect of a1ky1disiloxane cornpounds containing g1ucopyranosy1 group, J. Control. Release, 2003, 88(2):243~252
[76]. Akimoto T., Kawahara K., Nagase Y., et al, Polymeric transdermal drug penetration enhancer the enhancing effect of oligodimethylsiloxane containing a g1ucopyranosy1 end group, J. Control. Release, 2001, 77: 49~57
[77]. Sim Y.C., Nam Y.S., Shin Y.H., et al, Proteolytic enzyme conjugated to SC-glucan as an enzymatic transdermal drug penetration enhancer. Pharmazie, 2003, 58(4):252~256
[78]. ChenY.P., Shen Y.Y., Guo X., et al, Transdermal protein delivery by a co-administered pcptide identified via phage display, Nat. Biatechnol., 2006, 24: 455~50
[79]. Bangham A.D., Liposomes: realizing their promise, Hospita1 Practice, 1992, 27:51~59
[80]. Mezei M., Gulasekharam V., Liposomes: a selective drug delivery system for the topical route of administration:Ι. Lotion dosage form, Life sci., 1980, 26:473~489
[81]. Chung S.J., Future drug delivery research in South Korea, J. Control. Release, 1999, 62:73~79
[82].赵会英,郑俊民,生物大分子药物的经皮给药,沈阳药科大学学报,2001, (2):68~72
[83]. Betz G., Imboden R., Imanidis G., Interaction of liposome formulations with human skin in vitro, Int. J. Pharm., 2001, 229:117~129
[84]. Cevc G., Gebauer D., Stieber J., et al, Ultraflexible vesicles, Transfersomes, have an extremely low pore penetration resistance and transport therapeutic amours of insulin across the intact nammalian skin, Biochim. Biophys. Acta., 1998, 1368: 2011~2023
[85]. Jain S., Jain P., Umamaheshwari R.B., et al, Transfersomes: a novel vesivular carrier for enhanced transdermal delivery: development, characterization, and performance evaluation, Drug Dev. Ind. Pharm., 2003,29(9):1013~1016
[86]. Hofer C., Lehemer A., Hartung R., A transdermal approach for IL-2 therapy by new untraderformable carriers-transfersomes, J. Urol., 2000, 163(4):114~119
[87]. Paul A., Cevc G., Noninvasive administration of protein antigens, transdermal immunization with the bovine serum albumin in transfersomes, Vaccine Res., 1995, 4:145~163
[88]. Touitou E., Dayan N., Bergelson L., et al, Ethosomes- novel vesicularcarriers for enhancer delivery:characterization and skin penetration properties, J. Control. Release, 2000, 65:401~403
[89]. Dayan N., Touitou E., Carriers for skin delivery of trihexyphenidyl HCl: ehosomes vs liposomes, Biomaterials, 2000, 21: 1879~1881
[90]. Schhreier H., Bouwstra J., Liposomes and niosomes as topical drug carriers: dermal and transdermal drug delivery, J. Control. Release, 1994, 30:1~5
[91]. Peltola S., Saarinen-Savolainen P., Kiesvaara J., et al, Microemulsion for topical delivery of estradio1, Int. J. Pharm., 2003, 254:99~107
[92]. Nistico S., Puglisi G., Fresta M., et al, Lecithin microemulsions for the topical administration of ketoprofen: percutaneous adsorption through human skin and in vivo human skin tolerability, Int. J. Pharm., 2002, 244:21~31
[93]. Kreilgaard M., Pedersen E.J, Jaroszewski J.W., NMR characterisation and transdermal drug delivery potential of microemulsion systems, J. Control. Release, 2000, 69:421~433
[94]. Chen H., Chang X., Weng T., et al, A study of microemulsion systems for transdermal delivery of triptolide, J. Control. Release, 2004, 98:427~436
[95]. Uhrich K.E., Cannizzaro S.M., Langer R.S., et al, Polymeric systems for controlled drug release, Chem. Rev., 1999, 99: 3181~3198
[96].黄际薇,张永明,黄凤爱,等,促进药物透皮吸收的方法,中国医院药学杂志,2000,20(11):680~682
[97]. Jenning V., Gysler A., Schafer-Korting M., et al, Vitamin A loaded solid lipid nanoparticles for topic use: occlusive properties and drug targeting to the upper skin, Eur. J. Pharm. Biopharm., 2000, 49(3): 211~218
[98].瞿文,陈庆华,朱宝泉,固体脂质纳米粒的研究进展,中国医药工业杂志,2001,32(9):424~429
[99]. Muller B., Kreuter J., Enhanced transport of nanoparticle associated drugsthrough natural and artificial membranes-a general phenomenon, Int. J. Pharm., 1999, 178:23~32
[100]. Moser K.K., Kriwet C., Froehlich Y.N., et al, Supersaturation: Enhancement of skin penetration and permeation of a lipophilic drug, Pharm. Res., 2001, 18(7): 1006-1011
[101]. Shibaji T., Yasuhara Y., Oda N., et a1, A mechanism of the high frequency AC iontophoresis, J. Control. Release, 2001, 73:37~ 47
[102]. Bao J.L., Ping Q.N., Enhanced transdermal delivery of tetracaine by electroporation, Int. J. Pharm., 2000, 202: 121~124
[103]. Hashmi S., Ling P., Hashmi G., et al, Genetic transformation of nematodes using arrays of micromechanical piercing structures, Biotechniques, 1995, 19: 766~770
[104]. Henry S., Mcallisiter D., Allen M.G., et al, Microfabricated microneedles: a novel method to increase transdermal drug delivery, J. Pharm. Sci., 1998, 87: 922~925
[105]. Matriano J.A., Cormier M., Johnson J., et al, Macroflux microprojection array patch technology: a new and efficient approach for intracutaneous immunization, Pharm. Res., 2002, 19:63~70
[106]. Lee S., Kollias N., Daniel J., et a1, Topical drug delivery in human with a single photomechanica1 wave, Pharm. Res., 1999, 16:1717~1721
[107].元英进,刘明言,董岸杰,中药现代化生产关键技术,北京:化学工业出版社,2002:231~232
[108]. Hurkmans M., Bodde H.E., Van Driel M.J., Skin irritation caused by transdermal drug delivery systems during long-term (5 days) application, Br. J. Dermatol., 1985, 112:461~476
[109]. Chien Y.W., Development of transdermal controlled release drug delivery system: An overview. In:Kydonieus AF and Berner B, eds, Transdermal Delivery of drugs, Raton B, CRC press , 1987: 81~100
[110]. Chien, Y.M., Microsealed drug delivery systems: Theoretical aspects and biomedical assessments, in Int. Symp. on recent advances in drug delivery systems, Anderson, J M and Kim S W, Eds., Plenum Press, New York, 1984:367
[111]. Tan H.S., Pfister W.R., Pressure-sensitive adhesives for transdermal drug delivery systems, PSTT, 1999, 2: 60~69
[112]. Higuchi T., Rates of release of medicaments from the ointment bases containing drugs in suspension, J. Pharm. Sci., 1961, 50:874~875
[113]. Baker R.W., Londsdale H.K., Controlled release: Mechanism and rates. In controlled release of biologically active agents, Tanquary, AC and Lacey Eds., Plenum press, New York, 1974:15~71
[114]. John H.R., Role of polymer permeability in the control of drug release, in polymer permeability, J. Comyn. Eds., Elsevier applied science publishers, 1986:242~244
[115]. Wolff M., Cordes G., Luckow V., In vitro and in vivo release of nitroglycerin from a new transdermal therapeutic system, Pharm, Res., 1985, 1:23~29
[116].梁秉文,中药经皮给药制剂技术,北京:化学工业出版社,2006: 49~53
[117]. Webster I., Recent developments in pressure-sensitive adhesives for medical applications, Int. J. Adhes. Adhes., 1997, 17:69~73
[118]. Venkatraman S., Gale R., Skin adhesives and skin adhesion: 1. Transdermal drug delivery systems, Biomaterials, 1998, 19 (13):1119~1136
[119]. Arrowsmith D.J., Adhesion of electroformed copper and nickel to plastic laminates, Trans. Inst. Met. Finsh., 1970, 48:88~97
[120]. Packham D.E., Adhesive aspects of polymeric coating, New York, Plenum Press, 1983
[121].陈子达,李玲,邹翰,医用胶粘剂的研究进展,化学与粘合,2001,1:21~28
[122].梁秉文,经皮给药制剂,北京:中国医药科技出版社,1992:223~226
[123]. Langer R.S., Medical applications of controlled release, CRC press, 1984, 1: 230~231
[124].阿方萨斯,V.波丘斯,粘接与胶黏剂技术导论,北京:化学工业出版社,2005,209~237
[125]. Temin S.C., In:Skeist I., Handbook of Adhesives, New York, NY NSA: Marcel Dekker, 1990:133~135
[126]. Royx S.D., Gutierrez M., Flynn G.L., Controlled transdermal delivery of fentanyl: characterizations of pressure-sensitive adhesives for matrix patch design, J. Pharm. Sci., 1996, 85:491~495
[127]. Satas D., Handbook of pressure sensitive adhesive technology, New York:Van Nostrand Reinhold,1989:71~74
[128]. Qinglin S., Qiang G., Shuqing Z., et al, Study on the composition design ofthe water emulsion acrylates pressure-sensitive adhesive, Chemical Engineering, 1996, 24(2):65~67
[129]. Christensen S.F., Mckinley G.H., Rheological modeling of the peeling of pressure-sensitive adhesives and other elastomers, Int. J. Adhes. Adhes., 1998, 18:333~343
[130]. Kinning D.J., Bulk, surface and interfacial characterization of silicone-polyurea segmented copolymers, J. Adhesion, 2001, 75(1): 1~26
[131]. Gordon G.V., Schmidt R.G., PSA release force profiles from silicone liners: probing viscoelastic contributions from release system components, J Adhes., 2000, 72(2): 133~156
[132]. Bunker S., Staller C., Miniemulsion polymerization of acrylated methyl oleate for pressure sensitive adhesives, Int. J. Adhes. Adhes., 2003, 23:29~38
[133]. Ozawa T., Ishiwata S., KanoY., Acrylate copolymer/ultraviolet curable oligomer blends as pressure-sensitive adhesives, J. Adhes., 2000, 72(1):1~16
[134]. Chiriac A.P., The improvement of adhesive character of an acrylovinylic macromolecular compound, Polym. Test., 2001, 20:873~877
[135]. Yamamoto M., Nakano F., Doi T., et al, Synthesis and PSA performance study for novel acrylic and butyl acrylate block copolymers, Int. J. Adhes. Adhes., 2002, 22:37~40
[136]. Francis E.G., Christian W.J., George E.S., Thermally reversible polyurethane hydrogels and cosmetic,biological and medical uses, US 5000955,1991-03-19
[137]. Minghetti Y., Cilurzo F., Tosi L., et al, Design of a new water-soluble pressure- sensitive adhesive for patch preparation, AAPS PharmSciTech., 2003, 4:8~14
[138]. Mukherjee B., Mahapatra S., Gupta R., et al, A comparison between povidone-ethylcellulose and povidone-eudragit transdermal dexamethasone matrix patches based on in vitro skin permeation, Eur. J. Pharm. Biopharm., 2005, 59:475~483
[139]. Zhang J.H., Liu Z.P., Deng L.D., et.al., A novel hydrophilic adhesive matrix with self-enhancement for transdermal drug delivery, Pharm. Res., 2009, 26(6):1398~1406
[140].翟茂林,哈鸿飞,水凝胶的合成、性质及应用,大学化学,2001,5:22~27
[141].吉井文男,有粘性的PVA水凝胶的制备方法,JP 9263671,1997-10-07
[142]. Razzak M.T., Irradiation of polyvinyl alcohol and polyvinyl pyrrolidoneblended hydrogel for wound dressing, Radiat. Phys. Chem., 2001, 62:107~113
[143].贾伟,高文远,王涛,中药巴布剂的研究现状,中国中药杂志,2003,28(1):7~11
[144].范碧亭,张兆旺,施顺清,中药药剂学[M],上海:上海科学技术出版社出版,1997:320~323
[145]. Lee J.W., Robinson J.H., Bioadhesive-based dosage forms: the next generation, J. Pharm. Sci., 2000, 89:850~ 866
[146].秦东梅,王恒,李海瑛,羟丙甲基纤维素在药剂学中的应用,安徽医药,2004, 8(3): 173~175
[147].庄越,曹宝成,萧瑞祥,实用药物制剂技术,北京:人民卫生出版社,1999:399~400
[148]. Gholap S.G., Jog J.P., Badiger M.V., Synthesis and characterization of hydrophobically modified poly (vinyl alcohol) hydrogel membrane, Polymer, 2004, 45:5863~5873
[149].虞绍铸,张曩玲,复方喜树碱涂膜剂的制备和疗效观察,中国药业,2001,10(6):19~23
[150].刘建平,虞宣,崔丽,酮基布洛芬涂膜剂的制备及控释机理研究,中国药科大学学报,1996,27 (11) :652~654
[151]. Schroeder I.Z., Franke P., Schaefer U.F., et al, Development and characterization of film forming polymeric solutions for skin drug delivery, Eur. J. Pharm. Biopharm.,2007,65: 111~121
[152]. Chiefari J., Chong Y.K., Rizzardo E., et al, Living free-radical polymerization by reversible addition-fragmentation chain transfer: the RAFT process, Macromolecules, 1998, 31:5559~5562
[153]. Jancova K., Kops J., Chem X., et al, The RAFT Polymerization, Macromole Rapid Commun, 1999, 20: 219~224
[154].王艳君,王玉霞,袁才登,等,可逆加成-断裂链转移聚合研究进展,高分子通报,2003,3:57 ~ 63
[155]. Chong Y.K., Julia K.K., Tam P.T., et al, Thiocarbonylthio compounds [S=C(Ph)S-R] in free-radical polymerization with reversible addition-fragmentation chain transfer (RAFT polymerization). role of the free-radical leaving group (R), Macromolecules, 2003, 36: 2256 ~ 2272
[156]. John C.R., Roshan T.A., Mayaduune T., et al, Thiocarbonylthio compounds (S=C(Z)S-R) in free radical polymerization with reversibleaddition-fragmentation chain transfer (RAFT polymerization). effect of the activating group (Z), Macromolecules, 2003, 36: 2273 ~ 2283
[157]. Christine M.S., Zhang M., Rizzardo E., et al, A new double-responsive block copolymer synthesized vis RAFT Polymerization, Macromolecules, 2004, 37:7861~ 7866
[158]. Chapman T.M., Shi L.J, Bechman E.J., Poly(ethylene glecol)-block-poly (N-vinylformamide) copolymers synthesized by the RAFT methodology, Macromolecules, 2003, 36(7): 2563~2567
[159]. Le T.P., Moad G., Rizzardo E., et al, Polymerization with living characteristics. PCT Int Appl. WO 9801478 Al. 9800115, 1998
[160]. Benicewicz B.C., Kanagasabapathy S., Sudalai A., Dithiocarboxylic ester synthetic process, USP 6458968, 2002
[161].戚桂村,基于咔唑新型RAFT试剂的合成与RAFT聚合研究:[硕士学位论文],天津:天津大学,2004
[162].荣国斌,苏克曼,大学有机化学基础,华东理工大学出版社,2000:228~236
[163]. Li J.S., Zhan W.Q., Rao W.Q., et al, Studies on the reaction of N,N-dialkyldithiocarbamate with cyanuric chloride, Chin. Org. Chem., 2001, 21(10):759~762
[164]. Moad G., Chong Y.K., Postma A., et al, Advances in RAFT polymerization: the synthesis of polymers with defined end-groups Polymer, 2005, 46: 8458~8468
[165]. Mitsukami Y., Donovan M.S., Lowe A.B., et al, Water-soluble polymers. 81. direct synthesis of hydrophilic styrenic-based homopolymers and block copolymers in aqueous solution via RAFT, Macromolecules, 2001, 34(7): 2248~2256
[166].张肖娟,高静,罗英武,单体组成对甲基丙烯酸甲酯/丙烯酸丁酯RAFT共聚合转移常数的影响,高分子学报,2008, (1): 82~87
[167]. Benaglia M, Rizzardo E, Alberti A, et al, Searching for more effective agents and conditions for the RAFT polymerization of mma: influence of dithioester substituents, solvent, and temperature, Macromolecules, 2005, 38(8):3129~3140
[168]. Barba A.A., Amore M., Chirico S., et al, A general code to predict the drug release kinetics from different shaped matrices, Eur. J. Pharm. Sci., 2009, 36: 359~366
[169]. Junginger H.E., Verhoef J.C., Macromolecules as safe penetration enhancers for hydrophilic drugs– a fiction? PSTT, 1998, 1(9): 370~374
[170]. Liu Y.Y., Fan X.D., Wei, B.R. et al, pH-responsive amphiphilic hydrogel networks with IPN structure: A strategy for controlled drug release, Int. J. Pharm., 2006, 308:205~216
[171].杨云松,彭红云,章国林,等,透皮控释给药研究,高分子通报, 2002, 1: 49~52
[172]. Ma X.H., Taw J., Chinan C.M., Control of drug crystallization in transdermal matrix system, Int. J. Pharm., 1996, 142:115~119
[173]. KotzéA.F., Lue?en H.L., de Boer A.G., et al, Chitosan for enhanced intestinal permeability:Prospects for derivatives soluble in neutral and basic environments, Eur. J. Pharm. Sci., 1999, 7(2):145~151
[174]. Miyajima M., Koshika A., Okada J., et al, Effect of polymer/basic drug interactions on the two-stage diffusion-controlled release from a poly(L-lactic acid) matrix, J. Control. Release, 1999, 61:295~302
[175].龚志超,董岸杰,邓联东,用于药物透皮吸收制剂的压敏胶的新进展,化学工业与工程, 2002, 19(6): 437~440
[176]. Georgiadis M. C., Kostoglou M., On the optimization of drug release from multi-laminated polymer matrix devices, J. Control. Release, 2001, 77: 273~278
[177]. Bairamov D.F., Markin V.S., Iordanskii A.L., et al, Drug diffusion in adhesive hydrogels, Proc. Int. Symp. Control Release Bioactive Mater., 1999, 26:389~390
[178]. Brandrup J., Immergut E.H., Polymer Handbook, 2 Volumes Set, Fourth Edition. Division: Polymer / John Wiley & Son, 2003
[179]. Fedors R.F., A method for estimating both the solubility parameters and molar volumes of liquids, Polym. Eng. Sci., 1974, 14:147~154
[180].李振吉,中医药现代化发展前景展望,中国科技产业,2003, 1:10~14
[181].张礼和,我对中药复方有效成分研究的一些看法,化学进展, 1998,11(2):186~189
[182].杨明,郑琴,万娜,从中药复方施药系统研究现状引发的思考,世界科学技术——中医药现代化,2007, 9(5):13~17
[183]. Thomas B. J., Finnin B. C., The transdermal revolution, DDT, 2004, 9(16):697~703
[184]. Zhai H., Maibach H.I., Occlusion vs. skin barrier function, Skin Res. Technol., 2002, 8 (1):1~6
[185]. Lee J.W., Park Robinson J.H., Bioadhesive-based dosage forms: the next generation, J. Pharm. Sci., 2000, 89:850~866
[186]. Schroeder Z., Franke P., Schaefer U.F., et al, Development and characterization of film forming polymeric solutions for skin drug delivery, Eur. J. Pharm. Biopharm., 2007, 65:111~121
[187]. Schroeder Z., Franke P., Schaefer U.F., et al, Delivery of ethinylestradiol from film forming polymeric solutions across human epidermis in vitro and in vivo in pigs, J. Control. Release, 2007, 118:196~203
[188]. Jones D.S., Woolfson A.D., Brown A.F., Textrual, viscoelastic and mucoadhesive properties of pharmaceutical gels composed of cellulose polymers, Int. J. Pharm., 1997, 151:223~233
[189]. Seal B.L., Otero T.C., Panitch A., Polymeric biomaterials for tissue and organ regeneration, Mater. Sci Eng., 2001, 34:147~230
[190]. Seabra B., de Oliveira M. G., Poly (vinyl alcohol) and poly (vinyl pyrrolidone) blended films for local nitric oxide release, Biomaterials., 2004, 25:3773~3782
[191]. Gholap S.G., Jog J.P., Badiger M.V., Synthesis and characterization of hydrophobically modified poly (vinyl alcohol) hydrogel membrane, Polymers, 2004, 45:5863~5873
[192]. Paul W., Sharma C.P., Acetylsalicylic acid loaded poly(vinyl alcohol) hemodialysis membranes: effect of drug release on blood compatibility and permeability, J. Biomed. Sci. Polym. Ed., 1997, 8 :755~764
[193]. Cascone M.G., Sim B., Downes S., Blends of synthetic and natural polymers as drug delivery systems for growth hormone, Biomaterials, 1995, 16: 569~574.
[194]. Gal A., Nussinovitch A., Plasticizers in the manufacture of novel skin-bioadhesive patches, Int. J. Pharm., 2009, 370:103~109
[195]. Kanis L.A., Generoso M., Meier M.M., et al, Poly(ethylene-co-methyl acrylate) membranes as rate-controlling barriers for drug delivery systems: characterization, mechanical properties and permeability, Eur. J. Pharm. Biopharm., 2005, 60:383~390
[196]. Uragami T., Okazaki K., Matsugi H., et al, Structure and permeationcharacteristics of an aqueous ethanol solution of organic-inorganic hybrid membranes composed of poly(vinyl alcohol) and tetraethoxysilane, Macromolecules., 2002, 35:9156~9163
[197]. Kulkarni S.S., Kittur A.A., Aralaguppi M.I., et al, Synthesis and characterization of hybrid membranes using poly (vinyl alcohol) and tetraethylorthosilicate for the tervaporation separation of water–isopropanol mixtures, J. Appl. Polymer Sci., 2004, 97:1304~1315
[198]. Peng F.B., Lu L.Y., Sun H.L., et al, Analysis of annealing effect on pervaporation properties of PVA-GPTMS hybrid membranes through PALS, J. Membr. Sci., 2006, 281:600~608
[199]. Tokumura F., Homma T., Tomiya T., et al, Properties of pressure-sensitive adhesive tapes with soft adhesives to human skin and their mechanism, Skin Res. Technol., 2007, 13: 211~216
[200]. Water-vapour Permeability, in: British Pharmacopoeia, 1993, Appendix XXJ.
[201]. Draize J.H., Woodard G., Calvery H.O., Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes, J. Pharmacol. Exp. Ther., 1944, 82:377~390
[202]. Robertson M.A., Rudkin R.A., Parsonage D., et al, Mechanical and thermal properties of organic/inorganic hybrid coatings, J. Sol-Gel. Sci. Tech., 2003, 26:291~297
[203]. Peng F.B., Lu L.Y., Sun H.L., et al, Correlations between free volume characteristics and pervaporation permeability of novel PVA–GPTMS hybrid membranes, J. Membr. Sci., 2006, 275: 97~104
[204]. Jang J., Lee D.K., Plasticizer effect on the melting and crystallization behavior of polyvinyl alcohol, Polymer, 2003, 44:8139~8146
[205]. Chukwumerije C., Nash R.A., Matias J.R., et al, Studies on the efficacy of methyl esters of n-Alkyl fatty acids as penetration enhancers, J. Invest. Dermatol., 1989, 93(3):349~352
[206]. Friend D.R., Catz P., Heller J., Simple alkyl esters as skin permeation enhancers, J. Control. Release, 1989, 9 (1):33~41
[207]. Catz P., Friend D.R., Alkyl esters as skin permeation enhancers for indomethacin, Int. J. Pharm., 1989, 55(1): 17~23
[208]. Sato K., Sugibayashi K., Morimoto Y., Effect and mode of action of aliphatic esters on the in vitro skin permeation of nicorandil, Int. J. Pharm., 1988,43(1-2):31~40
[209]. Datta R., Henry M., Lactic acid: recent advances in products, processes and technologies-a review, J. Chem. Technol. Biotechnol., 2006, 81:1119~1129
[210]. Clary J.J., Feron V.J., van Velthuijsen J.A., Safety assessment of lactate esters, Regul. Toxicol. Pharmacol., 1998, 27(2):88~97
[211]. Tung R.C., Bergfeld W.K., Vidimos A.T., et al, Alpha-hydroxy acid-based cosmetic procedures. Guidelines for patient management, Am. J. Clin. Dermatol, 2000, 1:81~88
[212].林敏,秦敬云,林静,乳酸酯的合成研究,厦门大学学报,1997,36(4):581~584
[213].李军,经皮给药压敏胶及聚合物纳米粒经皮药物传递的研究:[博士论文],天津:天津大学,2006
[214]. Kikwai L., Kanikkannan N., Babu R. J., et al, Effect of vehicles on the transdermal delivery of melatonin across porcine skin in vitro, J. Control. Release, 2002, 83:307~311
[215]. Trottet L., Merly C., Mirza M., et al, Effect of finite doses of propylene glycol on enhancement of in vitro percutaneous permeation of loperamide hydrochloride, Int. J. Pharm., 2004, 274:213~219
[216]. Kaiho F., Koike R., Nomura H., et al, Enhancing effect of cetyl lactate on the percutaneous absorption of indomethacin in rats, Chem. Pharm. Bull., 1989, 37: 1114~1116
[217]. Dohi M., Kaiho F., Suzuki A., et al, Enhancing effects of myristryl lactate and lauryl lactate on percutaneous absorption of indomethacin in rats, Chem. Pharm. Bull., 1990, 38:2877~2879
[218]. Lee E.S., Watanabe T., Gale R.M., et al, Monoglyceride/lactate ester permeation enhancer for oxybutynin, US Patent USA 5747065, 1998
[219]. Herkenne C., Naik A., Kalia Y.N., et al, Effect of propylene glycol on ibuprofen absorption into human skin in vivo, J. Pharm. Sci., 2008,97: 185~197
[220]. Al-Saidan S.M., Transdermal self-permeation enhancement of ibuprofen, J. Control. Release, 2004, 100:199~209
[221]. Sato K., Sugibayashi K., Morimoto Y., Effect and mode of action of aliphatic esters on the in vitro skin permeation of nicorandil, Int. J. Pharm., 1988, 43: 31~40
[222]. Dias M., Hadgraft J., Lane M.E., Influence of membrane-solvent-solute interactions on solute permeation in skin, Int. J. Pharm., 2007, 340:65~70
[223]. Yano T., Noda K., Skin permeability of various non-steroids anti-inflammatory drugs in man, Life Sci., 1986, 39:1043~1050
[224]. Han S.K., Park Y.H., Kim C.K., Preparation of N-adamantyl n-alkanamides and evaluation of their transdermal penetration in the rabbit, Int. J. Pharm., 1995, 126:35~40
[225]. Friend D.R., Catz P., Heller J., Simple alkyl esters as skin permeation enhancers, J. Control. Release, 1989, 9:33~41
[226]. Catz P., Friend D.R., Alkyl esters as skin permeation enhancers for indomethacin, Int. J. Pharm., 1989, 55:17~23
[227]. Megrab N.A., Williams A.C., Barry B.W., Oestradiol permeation through human skin and silastic membrane: Effects of propylene glycol and supersaturation, J. Control. Release, 1995, 36:277~294
[228]. Arellano A., Santoyo S., Martin C., et al, Influence of propylene glycol and isopropyl myristate on the in vitro percutaneous penetration of diclofenac sodium from carbopol gels, Eur. J. Pharm. Sci., 1999, 7:129~135
[229]. Sherertz E.F., Sloan K.B., Mctiernan. R.G., Use of theoretical partition coefficients determined from solubility parameters to predict permeability coefficients for 5-fluorouracil, J. Invest. Dermatol., 1987, 89:147~151
[230]. Sloan K.B., Koch S.A.M., Siver K.G., et al, Use of solubility parameters of drug and vehicle to predict flux through skin, J. Invest. Dermatol., 1986, 87: 244~252
[231]. Aungst B.J., Rogers N.J., Shefter E., Enhancement of naloxone penetration through human skin in vitro using fatty acids, fatty alcohols, surfactants, sulfoxides, and amides, Int. J. Pharm., 1986, 33: 225~234
[232]. Cooper E.R., Merritt E.W., Smith R.L., Effect of fatty acids and alcohols on the penetration of acyclovir across human skin in vitro, J. Pharm. Sci., 1985, 74:688~689
[233]. Quan D., Higuchi R.I., Takayama K., et al, Enhancement effect of piperidone derivatives on the percutaneous absorption of indomethacin, Drug Des. Deliv., 1990, 6:61~71
[234]. Li G.L., van der Geest R., Chanet L., et al, In vitro iontophoresis of R-apomorphine across human stratum corneum: Structure-transportrelationship of penetration enhancement, J. Control. Release, 2002, 84:49~57
[235]. Brain K.R., Walters K.A., Molecular modeling of skin permeation enhancement by chemical agents. In: Walters, K.A., Hadgraft, J. (Eds.), Pharmaceutical Skin Penetration Enhancement,Marcel Dekker, New York, 1993, pp:389~416
[236]. Mackay K.M.B., Williams A.C., Barry B.W., Effect of melting point of chiral terpenes on human stratum corneum uptake, Int. J. Pharm., 2001, 228:89~97
[237]. Okamoto H., Muta K., Hashida M., et al, Percutaneous penetration of acyclovir through excised hairless mouse and rat skin: Effect of vehicle and percutaneous penetration enhancer, Pharm. Res., 1990, 7:64~68
[238]. Barry B.W., In. Barry, B.W., Shroot, B., Schaefer, H. (Eds.), Skin Pharmacokinetics. Karger, Basel, Switzerland, 1987, pp:121~137
[239]. Liron Z., Cohen S., Percutaneous absorption of alkanoic acids II: Application of regular solution theory, J. Pharm. Sci., 1984, 73:538~542
[240]. Nanayakkara G.R., Bartlett A., Forbes B., et al, The effect of unsaturated fatty acids in benzyl alcohol on the percutaneous permeation of three model penetrants, Int. J. Pharm., 2005, 301:129~139
[241]. Guy R.H., Hadgraft J., Transdermal drug delivery: a simplified pharmacokinetic approach, Int. J. Pharm., 1985, 24:267~274
[242]. Barry B.W., Bennett S.L., Effect of penetration enhancers on the permeation of mannitol, hydrocortisone and progesterone through human-skin, J. Pharm. Pharmacol., 1987, 39:535~546
[243]. Taskovich L.T., Yum S.I., Crisologo N.M., Monoglyceride/lactate ester permeation enhancer for codelivery of steroids, US Patent USA 5686097, 1997