聚β-环糊精缓释微球的制备、结构表征及其释药性能的研究
|
摘要
本文以四种不同性质的药物:双氯芬酸钠(Diclofenac Sodium, DFS)、磺胺甲恶唑(Sulfamethoxazole, SMZ)、扑热息痛(Paracetamol)和盐酸环丙沙星(Ciprofloxacin Hydrochloride, CPFX HCl)为模型药物,以β-CD为原料,使用两种方法研究制备四种药物的载药微球,并对它们的体外释药行为进行了深入的探讨。
在微球制备方法的研究中,本文首先采用反相乳液聚合技术制备聚β-环糊精微球(β-CDP微球),对β-CDP微球的合成工艺进行了单因素考察和正交实验设计,以微球形态、粒径、产率等作为评价指标,判断各种因素对实验结果的影响,最终优选处方并制备出性质优良的空白微球。实验结果表明,影响粒径的最大因素是搅拌速度,影响产率的最大因素是乳化剂。制备β-CDP微球的最佳工艺条件为:交联剂(EPI)的用量是n(EPI):n(β-CD)=15:1、交联温度为30℃、交联聚合时间为1.5h、乳化剂用量比为Span80:Tween20=3:1、以煤油为油相、乳化温度为50℃、乳化时间为6小时、搅拌速度为800r/min。优化后的处方工艺重现性良好,制得的微球大小均一,表面光滑圆整,平均粒径为102.14±4.6μm,跨距为1±0.14(n=5)。制成的微球保留了环糊精本身的结构特点且β-CD的含量较高,内部结构疏松成蜂窝状,具有交联三维网状结构,并具有良好的流动性和较高的吸水性。热分析研究表明,β-CDP微球具有较好的热稳定性。对于三种方法求得的β-CDP微球热分解反应动力学参数(表观失重活化能、反应级数、半衰期等),结果基本一致:Ea=120～170 kJ·mol-1,n=1,A=7.4×1012,k298=1.305×10-16s-1,k273=3.037×10-19s-1, t 12/928=1.68亿年、t 12/723=723.67亿年。在298K和273K条件下,β-CDP-MS的使用寿命相当长。β-CDP微球的热分解反应机理属于随机成核。
在确定了空白微球的最佳制备工艺后,本文采用了两种方法制备载药微球。一种是浸泡载药法,即将制备好的空白微球浸泡到药物溶液中载药。另一种是直接载药法,即在制备微球的过程中将药物直接加入到水相中参与微球的生成而最终载药。实验结果表明,(1)浸泡法载药的载药率明显高于直接载药法;(2)药物分子与β-CD/β-CDP微球之间的作用力对载药率有一定的影响;(3)直接载药法制备的载药微球表面有药物结晶,而浸泡载药法制备的微球表面没有药物结晶。
在微球的体外释药研究中,本文采用的是透析释药法。在本实验中,首先考察了浸泡法制备的四种载药微球的释药行为,然后以双氯芬酸钠-β-CDP微球为重点,考察了不同制备方法、释放介质pH值、透析袋内溶液体积、透析袋外溶液体积、载药率及粒径等因素对微球释药的影响。实验结果表明:(1)β-CDP微球对四种药物有不同程度的缓释作用,其中对双氯芬酸钠和磺胺甲恶唑的缓释作用效果明显,可分别达到24h和20h。说明β-CDP微球网状结构的空腔能够选择性地包结与之相配的药物分子,从而使药物达到缓释的效果。(2)对于双氯芬酸钠-β-CDP微球,不同的体外释放条件对药物释放也有着明显的影响,其中微球微球材料本身的性质——粒径,对释药速率的影响最大。
对于微球的体外释药结果,本文首先使用经验和半经验数学模型进行拟合,结果证明,对于双氯芬酸钠-β-CDP微球和磺胺甲恶唑-β-CDP微球,一级释放方程和Korsmeyer-Peppas模型方程拟合较好,由n值推断,这两种药物从β-CDP微球网状结构中的释放以单纯扩散为主。然后根据Crank提出的球形释放机理模型,计算出不同载药微球的有效扩散系数D值。最后根据本文的实际情况(透析释药法),测定出游离药物双氯芬酸钠在透析膜中的渗透常数K值,并用透析释药模型求出各种载药微球的药物释放动力学参数——释药速率常数km(或km,)。
In this paper, Diclofenac Sodium, Sulfamethoxazole, Paracetamol and Ciprofloxacin Hydrochloride were chosen as model drug andβ-CD was used as material to prepare drug-β-CDP microspheres(MS). Furthermore, drug release behavior in vitro and their release mechanism were deeply studied.
In the study of preparation method,β-CDP MS was first prepared by the technique of inverse emulsion polymerization. And the synthesis ofβ-CDP MS was optimized by using the single factor investigation and the orthogonal test to test the effect of various factors on results. The criteria to evaluate the MS included the appearance, particle’s size and yield. Optimal formulation was chosen and MS were formed with good quality. The results showed that the stirring rate and emulsifier mainly affect the particle’s size and yield separately. The test technological conditions were: n(EPI):n(β-CD)=15:1; crosslinking temperature=30℃; crosslinking time=1.5h; Span80:Tween20=3:1; kerosene as the oil phase; emulsion temperature=50℃;emulsion time is 6h; the stirring rate is 800r/min. The repeatability of the technology was precise.β-CDP MS were shape spherical, size equality, regular in morphology, surface smooth, with the mean diameter of 102.14±4.6μm and the span of 1±0.14(n=5). Prepared microsphere reserved the cavity structure ofβ-CD and with a high content of it. Theβ-CDP MS had a unconsolidated, honeycomb, cross-linking three dimensions, reticular internal structure. They also had a good liquidity and high water-absorbent. In the study of thermal stability, three method were used to calculate E a, n , t1 /2 and k. The results indicated thatβ-CDP MS had a good thermal stability. Results of three methods were basically consistent: Ea=120～170 kJ·mol-1, n=1, A=7.4×1012, k298=1.305×10-16s-1, k273=3.037×10-19s-1, t 12/928=1.68 hundred million years and t 12/723=723.67 hundred million years. The storage period ofβ-CDP MS was very long in 298K and 273K. Thermal decomposition reaction mechanism ofβ-CDP MS belonged to random successive nucleation.
After establishment of optimal formulation of synthesizingβ-CDP MS, we prepared drug-β-CDP MS with two methods. One was infusion method, and the other one was direct method. The experimental results indicate that: first, drug content percent of the infusion method was higher than the direct method; second, drug content percent was affected by acting force between drug andβ-CD/β-CDP MS; third, drug crystals were seen on the surface of drug-β-CDP MS by the direct method.
In the study of drug release from MS in vitro, commonly used dialysis method was studied comprehensively. In this experiment, drug release behavior in vitro of four drug-β-CDP MS by the infusion method was studied. Then DFS-β-CDP MS was the key point, and studied the effect of various factors (preparation method, pH of media, solution volume inside the dialytic-bags, solution volume outside the dialytic-bags, drug content percent and particle’s size) on drug release behavior. The experimental results indicate that: first,β-CDP MS had a sustained release effect on four drugs, especially for DFS and Sulfamethoxazole, achieving 24h and 20h respectively. This indicated that cavity structure ofβ-CDP MS intercalated with drug selectively to make it release slowly; second, for DFS-β-CDP MS, all the factors, especially the particle’s size, had an effect on drug release behavior.
The article also valuated the results of drug release from MS in vitro with two mathematical models. Firstly, empirical and half-empirical mathematical model were used to prove that release of DFS-β-CDP MS and SMZ-β-CDP MS according with first - order release and Korsmeyer-Peppas model. The mechanism of drug release was diffusion mainly. Secondly, diffusivity (D) was calculated by model of“radial diffusion in a sphere”(Crank). Thirdly, dialysis release drug models were used. Mathematic formula were deduced and the permeation constant (K) of free drug through dialysis membrane was determined. Then the drug release kinetics and drug release rate constants (km or km,) were achieved.
在微球制备方法的研究中,本文首先采用反相乳液聚合技术制备聚β-环糊精微球(β-CDP微球),对β-CDP微球的合成工艺进行了单因素考察和正交实验设计,以微球形态、粒径、产率等作为评价指标,判断各种因素对实验结果的影响,最终优选处方并制备出性质优良的空白微球。实验结果表明,影响粒径的最大因素是搅拌速度,影响产率的最大因素是乳化剂。制备β-CDP微球的最佳工艺条件为:交联剂(EPI)的用量是n(EPI):n(β-CD)=15:1、交联温度为30℃、交联聚合时间为1.5h、乳化剂用量比为Span80:Tween20=3:1、以煤油为油相、乳化温度为50℃、乳化时间为6小时、搅拌速度为800r/min。优化后的处方工艺重现性良好,制得的微球大小均一,表面光滑圆整,平均粒径为102.14±4.6μm,跨距为1±0.14(n=5)。制成的微球保留了环糊精本身的结构特点且β-CD的含量较高,内部结构疏松成蜂窝状,具有交联三维网状结构,并具有良好的流动性和较高的吸水性。热分析研究表明,β-CDP微球具有较好的热稳定性。对于三种方法求得的β-CDP微球热分解反应动力学参数(表观失重活化能、反应级数、半衰期等),结果基本一致:Ea=120～170 kJ·mol-1,n=1,A=7.4×1012,k298=1.305×10-16s-1,k273=3.037×10-19s-1, t 12/928=1.68亿年、t 12/723=723.67亿年。在298K和273K条件下,β-CDP-MS的使用寿命相当长。β-CDP微球的热分解反应机理属于随机成核。
在确定了空白微球的最佳制备工艺后,本文采用了两种方法制备载药微球。一种是浸泡载药法,即将制备好的空白微球浸泡到药物溶液中载药。另一种是直接载药法,即在制备微球的过程中将药物直接加入到水相中参与微球的生成而最终载药。实验结果表明,(1)浸泡法载药的载药率明显高于直接载药法;(2)药物分子与β-CD/β-CDP微球之间的作用力对载药率有一定的影响;(3)直接载药法制备的载药微球表面有药物结晶,而浸泡载药法制备的微球表面没有药物结晶。
在微球的体外释药研究中,本文采用的是透析释药法。在本实验中,首先考察了浸泡法制备的四种载药微球的释药行为,然后以双氯芬酸钠-β-CDP微球为重点,考察了不同制备方法、释放介质pH值、透析袋内溶液体积、透析袋外溶液体积、载药率及粒径等因素对微球释药的影响。实验结果表明:(1)β-CDP微球对四种药物有不同程度的缓释作用,其中对双氯芬酸钠和磺胺甲恶唑的缓释作用效果明显,可分别达到24h和20h。说明β-CDP微球网状结构的空腔能够选择性地包结与之相配的药物分子,从而使药物达到缓释的效果。(2)对于双氯芬酸钠-β-CDP微球,不同的体外释放条件对药物释放也有着明显的影响,其中微球微球材料本身的性质——粒径,对释药速率的影响最大。
对于微球的体外释药结果,本文首先使用经验和半经验数学模型进行拟合,结果证明,对于双氯芬酸钠-β-CDP微球和磺胺甲恶唑-β-CDP微球,一级释放方程和Korsmeyer-Peppas模型方程拟合较好,由n值推断,这两种药物从β-CDP微球网状结构中的释放以单纯扩散为主。然后根据Crank提出的球形释放机理模型,计算出不同载药微球的有效扩散系数D值。最后根据本文的实际情况(透析释药法),测定出游离药物双氯芬酸钠在透析膜中的渗透常数K值,并用透析释药模型求出各种载药微球的药物释放动力学参数——释药速率常数km(或km,)。
In this paper, Diclofenac Sodium, Sulfamethoxazole, Paracetamol and Ciprofloxacin Hydrochloride were chosen as model drug andβ-CD was used as material to prepare drug-β-CDP microspheres(MS). Furthermore, drug release behavior in vitro and their release mechanism were deeply studied.
In the study of preparation method,β-CDP MS was first prepared by the technique of inverse emulsion polymerization. And the synthesis ofβ-CDP MS was optimized by using the single factor investigation and the orthogonal test to test the effect of various factors on results. The criteria to evaluate the MS included the appearance, particle’s size and yield. Optimal formulation was chosen and MS were formed with good quality. The results showed that the stirring rate and emulsifier mainly affect the particle’s size and yield separately. The test technological conditions were: n(EPI):n(β-CD)=15:1; crosslinking temperature=30℃; crosslinking time=1.5h; Span80:Tween20=3:1; kerosene as the oil phase; emulsion temperature=50℃;emulsion time is 6h; the stirring rate is 800r/min. The repeatability of the technology was precise.β-CDP MS were shape spherical, size equality, regular in morphology, surface smooth, with the mean diameter of 102.14±4.6μm and the span of 1±0.14(n=5). Prepared microsphere reserved the cavity structure ofβ-CD and with a high content of it. Theβ-CDP MS had a unconsolidated, honeycomb, cross-linking three dimensions, reticular internal structure. They also had a good liquidity and high water-absorbent. In the study of thermal stability, three method were used to calculate E a, n , t1 /2 and k. The results indicated thatβ-CDP MS had a good thermal stability. Results of three methods were basically consistent: Ea=120～170 kJ·mol-1, n=1, A=7.4×1012, k298=1.305×10-16s-1, k273=3.037×10-19s-1, t 12/928=1.68 hundred million years and t 12/723=723.67 hundred million years. The storage period ofβ-CDP MS was very long in 298K and 273K. Thermal decomposition reaction mechanism ofβ-CDP MS belonged to random successive nucleation.
After establishment of optimal formulation of synthesizingβ-CDP MS, we prepared drug-β-CDP MS with two methods. One was infusion method, and the other one was direct method. The experimental results indicate that: first, drug content percent of the infusion method was higher than the direct method; second, drug content percent was affected by acting force between drug andβ-CD/β-CDP MS; third, drug crystals were seen on the surface of drug-β-CDP MS by the direct method.
In the study of drug release from MS in vitro, commonly used dialysis method was studied comprehensively. In this experiment, drug release behavior in vitro of four drug-β-CDP MS by the infusion method was studied. Then DFS-β-CDP MS was the key point, and studied the effect of various factors (preparation method, pH of media, solution volume inside the dialytic-bags, solution volume outside the dialytic-bags, drug content percent and particle’s size) on drug release behavior. The experimental results indicate that: first,β-CDP MS had a sustained release effect on four drugs, especially for DFS and Sulfamethoxazole, achieving 24h and 20h respectively. This indicated that cavity structure ofβ-CDP MS intercalated with drug selectively to make it release slowly; second, for DFS-β-CDP MS, all the factors, especially the particle’s size, had an effect on drug release behavior.
The article also valuated the results of drug release from MS in vitro with two mathematical models. Firstly, empirical and half-empirical mathematical model were used to prove that release of DFS-β-CDP MS and SMZ-β-CDP MS according with first - order release and Korsmeyer-Peppas model. The mechanism of drug release was diffusion mainly. Secondly, diffusivity (D) was calculated by model of“radial diffusion in a sphere”(Crank). Thirdly, dialysis release drug models were used. Mathematic formula were deduced and the permeation constant (K) of free drug through dialysis membrane was determined. Then the drug release kinetics and drug release rate constants (km or km,) were achieved.
引文
[1] Freudenberg K.et al., Ann. Chem, 1935, 5182:10.
[2] Szejtli, Comprehensive Supramolecular Chemistry, 1996, 3:1.
[3] French D., Levine M.L., Pazur J.H. and Norberg E, J. Am Chem. Soc,1949, 71:353.
[4] Cramer F.and Dietsche W., Chem.Ber, 1959, 92:378.
[5] Freudenberg K., Cramer, F. & Plieninger, H. Verfahren zur Herstellung von Einschlussverbindungen physiologisch wirksamer organischer Verbindungen. German Pat.895, 769 (1953).
[6] French D., Adv. Carbohydr.Chem., 1957, 12:189.
[7] Griffiths D.W.and Bender A.L., Adv. Catal., 1973, 23:209.
[8] Bender M.L.and Komiyama M., Cyclodextrin hemistry, Springer, Berlin 1978.
[9] V. T. D′Souza, K. B. Lipkowitz, chem. Rev., 1998, 98:1974.
[10] K. Horikoshi, N. Nakamura, N. Matsuzawa,M. Yamamoto, Proceedings of the 1st International Symposium on Cyclodextrins,Budapest,1981,Ed.J. Szejtli, Reidel, Dordrecht, 1981:25.
[11] S. Kobayashi, K. Kainuma, J. Jpn. Soc. Starch Sci.,1981,28(2),132.
[12] S. Kobayashi, Denpun Kagaku, 1993, 40(2):103.
[13] 童林荟.环糊精化学——基础与应用.科学出版社,2001 年 3 月,第一版,20.
[14] Kaneto Uekama, Fumitoshi Hirayama, Tetsumi Irie. Cyclodextrin Drug Carier Systems. Chwm. Rev., 1998,98(5):2045-2076.
[15] 陈敏, 蔡同一, 阎红.β-CD 的化学改性及其在食品工业中应用的前景[J].食品与发酵工业, 1998,24 (5) : 68 – 71.
[16] Brewster M. E., et al. The Potenitial use of branched β-Cyclodextrins and their inclusion characteristics [J]. J Parenteral Sci Tec, 1989, 43 (5): 231.
[17] 程池.歧化环糊精的研究进展[J].食品与发酵工业, 1992, 18 (3) : 77–80.
[18] 吴剑峰.环糊精及其衍生物在药学领域的应用[J].时珍国医国药,2004,15(3):181– 182.
[19] 冯波,高红旺,许英爱等.地尔硫卓-乙基化 β-环糊精包合物的释放度测定.第四军医大学吉林军医学院学报,2003,25(2):76–78.
[20] 关家彦.岩白菜素包结物的研制[J].中成药,1991,13(1):4.
[21] 宋庆君,王建华.香附胶囊制备工艺研究[J].中成药,1995,17(12):6–8.
[22] 姚广滨.硝酸甘油 β-环糊精包合物的研究[J].中国医药工业杂,1993,24(10):445.
[23] 奚念术,顾学裘.药剂学,人民卫生出版社, 1990 年第 2 版,156.
[24] 方晓玲.β-环糊精包合技术在大蒜精油新剂型研究中的应用[J].上海医科大学学报,1993,20(4):285.
[25] 张秀荣,林天幕,牛松青.中国药学杂志,2000,25(10): 649–652.
[26] 聂 淑 芳 , 潘 卫 三 , 郭 宏 . 环 糊 精 在 靶 向 给 药 系 统 中 的 应 用 . 药 品 评价,2005,2(1):69–72.
[27] Mark E. Davis, Marcus E. Brewster.Cyclodextrin-baesd pharmaceutics:past, present, future. Nature, Drug discovery, 2004.12,(3):1023–1035.
[28] 刘琼,范晓东.环糊精高分子.高分子通报,2000(5):41–48.
[29] 童林荟.环糊精化学.北京科学出版社,2001 年 3 月,第一版,81.
[30] 周玉燕, 潘丽娟,郑瑛等.β-环糊精与聚丙烯酰胺的接枝化合物及其对水中污染物的絮凝作用.化工环保,2003,23(6):362–366.
[31] 王南平,余晓冬,陈洪渊.环糊精超分子化学研究的新进展.
[32] Sugiura lzuru, Komiyama Makoto, Toshima Naoki, Hirai Hidefumi.Bull Chem Soc Jpn, 1989, 62 (5):1643.
[33] Kosak KM. US, 6048736,1998 - 12 - 30.Rohrvach R P. US, 4917956, 1988 - 7 - 11.
[34] García-González N, Kellaway I W, Blanco-Fuente H, et al. Int J Pharm,1993,100:25.
[35] Bibby D C, Davies N M, Tucker I G. J Microencapsulation, 1998, 15:629.
[36] Crini G, Cosentino C, Bertini S, et al. Carbohydr Res, 1998, 308:37.
[37] Crini G, Morcellet M. J Appl Polym Sci, 1998, 68:1973.
[38] 苏小笛,刘六战,沈含熙.分析科学学报,1997,13(2):102.
[39] 罗春花,许鸿生,田文荣.分析测试学报,1999,18(1):61.
[40] 唐课文,许鸿生.湘潭大学自然科学学报,1998, (12):63.
[41] 黎瑞敏,孟德彬,夏丽娟.齐齐哈尔大学学报,1999,15(3):76.
[42] 李英杰,齐齐哈尔大学学报,1999,15(4):15.
[43] 韩家军,原向红,张晓惠.齐齐哈尔大学学报,1998,14(3):36.
[44] 韩树波,朱敏,袁倬斌.高等学校化学学报,1999,20(7):1036.
[45] 袁倬斌,朱敏,韩树波.中国科学院研究生院学报,1998,15(2):134.
[46] 毛陆原,朱敏,黄雪梅,沈含熙.高等学校化学学报,1997,18(10):1611.
[47] 李荣,毛陆原,朱敏,黄雪梅,沈含熙.分析科学学报,1998,14(2):94.
[48] Komiyama M, Hirai H.PolymJ, 1987, 19(6):773.
[49] Szejtli J, Fenyvesi E, Zoltan S, Zsadon B, Tūdos F. US ,4274985 ,1981,6(23).
[50] Fenyvesi E, Szejtli J, Zsadon B, Antal B, Wagner nee K I. US,4547572,1984,2(6).
[51] García-González N, Kellaway I W, Blanco-Fuente H, et al. Int J Pharm,1993,100:25.
[52] Bibby D C, Davies N M, Tucker I G. J Microencapsulation,1998,15:629.
[53] 刘琼,范晓东.功能高分子学报,2001,14,279.
[54] 李英杰,韩家军.以 β-环糊精树脂为载体提纯肌醇的研究.吉林大学自然科学学报,2001(2):99–102.
[55] 程坷伟,李新华.环糊精的改性及其应用.沈阳农业大学学报,2001,32(4):313–316.
[56] 南京药学院药剂学教研组编著.药剂学.人民卫生出版社,1985,969.
[57] Prentis.R. A, Lis.Y. & Walker,S. R. Pharmaceuticalinnovation by seven UK-owned pharmaceutical companies(1964–1985). Br. J. Clin. Pharmacol. 25,387–396 (1988).
[58] 魏树礼,高智慧.控释缓释微球制剂的研究进展.中国医药工业杂志,1990,21:29.
[59] 崔福德.药剂学.人民卫生出版,第五版,制剂新技术.
[60] 陆彬,张景勍,杨红.肺靶向卡铂明胶微球的研究. 药学学报,1999,34(10):786–789.
[61] 张景,陆彬.肺靶向卡铂明胶微球的药物动力学和体内分布研究.中国医药工业杂志, 2001,32 (6):251–253.
[62] 张军,翟光喜,刘世宽.卡铂肺靶向明胶微球的实验研究.中国现代应用药学杂志,2002 .4, 19 (2):123–125.
[63] 王剑红,陆彬,胥佩菱,包定元,张自然.肺靶向米托蒽醌明胶微球的研究.药学学报,1995,30(7):549–555.
[64] 詹国平,黄可龙,谢恩伟.肺靶向硫酸链霉素明胶微球的制备. 中国医院药学杂志2005,25(7):625–628.
[65] 杨云霞,包定元,曾昭贤,何晓,陆彬. 肺靶向制剂——硫酸链霉素明胶微球的药理学研究.中国抗生素杂志,1998.6,23(3):205–208.
[66] 张自然,陆彬,舒广晔,谢华,易秋艳,贺英菊,王剑红.硫酸链霉素肺靶向明胶微球的研究.华西医大学报,1995,26(2):167–171.
[67] 邓时贵,孟凡,莫莉莉,常钢,区勇全,杨志刚,斯方元.莪术油明胶微球肝动脉给药的一般药理研究.中国现代应用药学杂志,2003.2,20(1):1–3.
[68] 邓嵘,陈济民,高声传,丁懿.莪术油明胶微球剂的含量测定.中国医院药学杂志. 2001, 21 (2):79–81.
[69] 杨志刚,孟凡喆,常钢,徐勤.莪术油明胶微球栓塞犬肝动脉的病理改变.现代临床医学生物工程学杂志,2004,10 (2):88–90.
[70] 邓嵘,陈济民,姚崇舜,吴万垠.莪术油明胶微球用于肝动脉栓塞.药学学报,2000,35(7) :539 – 543.
[71] 邓时贵,莫莉莉,区勇全,欧润妹.莪术油明胶微球制剂急性毒性实验.医药导报2002 .4, 21 (4):200–202.
[72] 钟延强,蒋雪涛,孙其荣.白蛋白微球制剂. 药学实践,1995,13(4):208–211.
[73] 胡新、候新朴.新型药物载体——淀粉微球.中国药学,1995.2,30(2):69–71.
[74] 苏秀霞,李仲谨,马素德,白国强.载药淀粉微球合成条件的研究.应用化学,2003.8,32(4)33–35.
[75] 郑 文 杰 , 何 燕 岭 , 黄 宁 兴 . 靶 向 给 药 系 统 材 料 与 制 剂 . 中 国 药 学 杂志,1996.11,31(11):664–667.
[76] 郑彩虹,梁文权,虞和永,章亦立.亲水/亲酯性附加剂对乳酸–羟乙醇酸共聚物微球中蛋白释放的影响.中国药学 2005.7,40(13):999–1001.
[77] 王峰,涂家生,张钧寿,卢晶.PLGA 微球控释系统的突释及其控制.药学进展,2003 ,27( 3):142–146.
[78] 鞠 秀 兰 .PLGA 控 释 微 球 注 射 剂 的 研 究 进 展 . 卫 生 职 业 教 育 ( 教 学 参考),2005,23(10):123–124.
[79] 郑彩虹,梁文权,虞和永.乳酸羟乙醇酸共聚物微球中蛋白包封率的测定.中国医院药学,2005,25 (1):34–37.
[80] 康继超,魏树礼.单分散、大粒径聚苯乙烯微球的研制.北京医科大学学报,1997,29(3):238–240.
[81] 张岩,陈岚,李保国,华泽钊,伍贻文,刘哲鹏,陆伟跃.超临界 CO2抗溶剂法制备乙纤维素微球试验.化学工程,2005.6,33(3):63–67.
[82] 魏树礼,高智慧. 控释缓释微球制剂的研究进展.中国医药工业杂志,1990,21:29.
[83] 张志荣,王丹,廖方义,廖工铁.肝动脉栓塞米托蒽醌乙基纤维素微球的研究. 药学学报 1996 ,31(8) :626–631.
[84] 彭方兴,严律南,林琦远,白绍櫆,张旋波.阿霉素乙基纤维素微球肝动脉栓塞化疗的实验研究.中国普外基础与临床杂志,2001.5,8(3):138–140.
[85] 张强,武鳯兰主编.药剂学.北京大学医学出版社,最新版,385.
[86] 徐希明,余江南,张均寿.氟尿嘧啶白蛋白微球剂的制备工艺研究[J].中国现代应用药学,2000,17(6):546.
[87] 范田园,周喜林,魏树礼.利福平乙基纤维素微球的制备及质量评价[J].北京医科大学学报,1999,31(2) (增刊):28.
[88] TAN Zai-You, LIAO Qing-Jiang, Robin Y Xiao, Deniel Q. G. So. Characteristics of Epristeride Microspheres with TwoEmulsifying Preparation Methods.Journal of China Pharmaceutical University,2003,34 (4):309～312.
[89] 罗兰,潘金火.微粒作为靶向制剂载体的研究进展,中国医药工业杂志,1998,29 (9):424–428.
[90] 杨帆,林茵,谭载友,赵耀明,麦杭珍.肺靶向红霉素聚乳酸微球的研究.中国药科大学学报,2002,33 (3):211～215.
[91] Shaker D, William B, Kyung C et al. Cancer, 1982, 50:631.
[92] Yashioka T, Hasida M, Muranishi S, et al. Int J Pharmaceutics,1981; 81:131.
[93] Roath S, Smith AR,Watson JHP. J MagnMater, 1990,85:285.
[94] 宋群亮,张平.中药微球制剂研究进展.安徽医药,2004.2,9(2):87–88.
[95] 黎维勇,杜端明,冯敢生等.白及微球的研制及其肝动脉栓塞实验研究[J] . 同济医科大学学报,1999, 28(1):62.
[96] 黄园,侯世祥,林江宇.草乌肝靶向白蛋白微球的制剂学研究[J].中国中药杂志,1999,24(12):731.
[97] 严英,钟秀驰,周伟生等.中药制剂介入治疗恶性肿瘤的要利于临床研究概述[J] .中药新药与临床药理,2000,11(5):187.
[98] 瞿文,陈庆华等.多肽、蛋白质药物的微球给药系统研究进展[J].综述国外医学药学分册,1997.6, 24(3):921.
[99] Tabata Y, Langer R. Polyanhydride microshperes that display near-constant release of water-soluble model drug compounds.Pharm Res, 1993, 10(3):391.
[100] 鞠 秀 兰 .PLGA 控 释 微 球 注 射 剂 的 研 究 进 展 . 卫 生 职 业 教 育 ( 教 学 参考),2005,23(10):123–124.
[101] 孟丽.聚合物微球控释抗原投递系统研究的发展概况.微生物学免疫学进展,1995,23(3):192～194.
[102] Nakaoka R, Yasuhiko TB, Yoshito IK.Potentiality of gelatin microsphere as immunological adjuvant.Vaccine, 1995, 13(7):653–661.
[103] 赵晶,王立新.明胶微球乙肝疫苗动物免疫效果研究.中华微生物学和免疫学杂志,2000,20 (3):236–239.
[104] 王亚敏,石庭.微球制剂药物控释研究进展.中国药学,1996.3,31(3):131–134.
[105] 任晓慧,郑伟,刘松财,张永亮.多肽、蛋白质药物的微球缓释/控释系统.吉林畜牧兽医,2004,1,22–25.
[106] Narayani R, Rao KP.Preparation, characterization and in vitro Stability of hydrophilic gelatin microspheres using a gelatin-methotrexate conjugate. Int J Pharm,1993,95:85.
[107] 王亚敏,石庭森.微球制剂药物控释研究进展.中国药学,1996.3,31(3):131–134.
[108] Pekarek KJ, et al. J Nature,1994:367.258～260.王小敏翻译收载于:Pekarek K J, et al.用于药物控释的双层聚合物微球.国外医学药学分册,1994,21(5):300～302.
[109] Nykamp G, Carstensen U, Muller B W, et al. Jet m illing——a new technique for microparticle preparation [J]1 Int J Pharm,2002,242(122):792–861.
[110] 张洪涛,黄锦霞.乳液聚合新技术及应用.化学工业出版社,2007 年 1 月,第一版,102.
[111] 林浩,高建村,地木拉提.丙烯酰胺系反相乳液聚合研究进展.新疆石油学院学报, 2001 .3, 13(1):58–60.
[112] 杜定准,汪月生,徐文英.1H NMR 研究 β-环糊精与环氧氯丙烷共聚物的反应机理和分子链结构.波谱学杂质,1992,9(2):121–129.
[113] 严春美,刘郁杨,范晓东.β-环糊精球的制备及其药物控释行为研究.化工新型材料,2004,32(6):39–42.
[114] Baille W E, Huang W Q, Nichifor M, Zhu X X. [J ]. J. Macromol. Sci. Pure Appl. Chem, 2000, A37 (7):677～690.
[115] Mark E. Davis, Marcus E. Brewster.Cyclodextrin-baesd pharmaceutics:past, present, future.Nature,Drug discovery, 2004.12,(3):1023–1035.
[116] 刘郁杨.用于新型抗癌药物定向控制释放的高分子载体的合成与表征.西北工业大学博士学位论文,2003 年.
[117] 陈镜泓,李传儒.热分析及其应用.科学出版社.1985 年,第一版.
[118] Ozawa T. Bull Chem Soc Japan, 1965, 38:1881.
[119] Kissinger H E. Anal Chem, 1957, 29:1702.
[120] Freeman E S, Carrol B. J Phys Chem, 1958, 62:394.
[121] 谭载友,钟智敏,黄国超.ATP 热稳定性的 DSC 动力学研究.广东医药学院学报,1993,9(3):1–3.
[122] 蒋学华,廖工铁.靶向微球给药系统质量评价.华西药学杂志,1993,8(2):99–104.
[123] tella V J, et al. J Pharm Res, 1997, 14:556. ibby D C, et al. Int J Pharm,2000,197:1.
[124] ee Y B, et al. Pharm Res, 1991,8:531.
[125] 徐文,王中彦,何中贵,崔升淼.高效液相色谱法测定复方磺胺甲恶唑片的溶出度.药物分析杂志,2003(23):11–15.
[126] 周学琴,张丽,王迎春.盐酸环丙沙星片剂体外溶出度的比较.数理医药学杂志,2003,16(5):439–440.
[127] 刘莉 , 葛卫红 . 扑热息痛片的体外溶出度考察比较 . 江苏药学与临床研究,1996,4(3):12–15.
[128] 潘吉铮.聚乳酸微球载体的结构与控释性能关系及模型.华南理工大学博士论文,2004 年.
[129] 中国药典,2005 版,附录 XI X D 缓释、控释制剂指导原则
[130] Mulye, N. V., Turco, S. J., A simple model based on first order kinetics to explain release of highly water soluble drugs from porous dicalcium phosphate dehydrate matrices, Drug Dev. Ind. Pharm., 21, 943–953.
[131] Higuchi, T., Rate of release of medicaments from ointment bases containing drugs in suspensions, J. Pharm. Sci., 1961,50,874–875.
[132] John W. Skoug, Martin V. Mikelsons, Cynthia N.,et al. Qualitative evaluation of the mechanism of release of matrix sustained release dosage forms by measurement of polymer release. Journal of Controlled Release, 1993(27):227–245.
[133] JEAN-MAURICE VERGNAUD. CONTROLLED DRUG RELEASE OF ORAL DOSAGE FORMS. Ellis Horwood Limited, 1993:59–69.
[134] Washington C. Evaluation of non-sink dialysis methods for the mearurement of drug release from colloids: effects of drug partition. Int J Pharm, 1989, 56: 71–74.
[135] Friedman D, Benita S. A mathematical model for drug release from O/W emulsions: application to control release morphine emulsions. Drug Dev Ind Pharm, 1987, 13(9-11): 2067–2085.
[136] Soppimath K S, Aminabhavi T M, Kulkarni A R, et al. Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release, 2001, 70: 1–20.
[2] Szejtli, Comprehensive Supramolecular Chemistry, 1996, 3:1.
[3] French D., Levine M.L., Pazur J.H. and Norberg E, J. Am Chem. Soc,1949, 71:353.
[4] Cramer F.and Dietsche W., Chem.Ber, 1959, 92:378.
[5] Freudenberg K., Cramer, F. & Plieninger, H. Verfahren zur Herstellung von Einschlussverbindungen physiologisch wirksamer organischer Verbindungen. German Pat.895, 769 (1953).
[6] French D., Adv. Carbohydr.Chem., 1957, 12:189.
[7] Griffiths D.W.and Bender A.L., Adv. Catal., 1973, 23:209.
[8] Bender M.L.and Komiyama M., Cyclodextrin hemistry, Springer, Berlin 1978.
[9] V. T. D′Souza, K. B. Lipkowitz, chem. Rev., 1998, 98:1974.
[10] K. Horikoshi, N. Nakamura, N. Matsuzawa,M. Yamamoto, Proceedings of the 1st International Symposium on Cyclodextrins,Budapest,1981,Ed.J. Szejtli, Reidel, Dordrecht, 1981:25.
[11] S. Kobayashi, K. Kainuma, J. Jpn. Soc. Starch Sci.,1981,28(2),132.
[12] S. Kobayashi, Denpun Kagaku, 1993, 40(2):103.
[13] 童林荟.环糊精化学——基础与应用.科学出版社,2001 年 3 月,第一版,20.
[14] Kaneto Uekama, Fumitoshi Hirayama, Tetsumi Irie. Cyclodextrin Drug Carier Systems. Chwm. Rev., 1998,98(5):2045-2076.
[15] 陈敏, 蔡同一, 阎红.β-CD 的化学改性及其在食品工业中应用的前景[J].食品与发酵工业, 1998,24 (5) : 68 – 71.
[16] Brewster M. E., et al. The Potenitial use of branched β-Cyclodextrins and their inclusion characteristics [J]. J Parenteral Sci Tec, 1989, 43 (5): 231.
[17] 程池.歧化环糊精的研究进展[J].食品与发酵工业, 1992, 18 (3) : 77–80.
[18] 吴剑峰.环糊精及其衍生物在药学领域的应用[J].时珍国医国药,2004,15(3):181– 182.
[19] 冯波,高红旺,许英爱等.地尔硫卓-乙基化 β-环糊精包合物的释放度测定.第四军医大学吉林军医学院学报,2003,25(2):76–78.
[20] 关家彦.岩白菜素包结物的研制[J].中成药,1991,13(1):4.
[21] 宋庆君,王建华.香附胶囊制备工艺研究[J].中成药,1995,17(12):6–8.
[22] 姚广滨.硝酸甘油 β-环糊精包合物的研究[J].中国医药工业杂,1993,24(10):445.
[23] 奚念术,顾学裘.药剂学,人民卫生出版社, 1990 年第 2 版,156.
[24] 方晓玲.β-环糊精包合技术在大蒜精油新剂型研究中的应用[J].上海医科大学学报,1993,20(4):285.
[25] 张秀荣,林天幕,牛松青.中国药学杂志,2000,25(10): 649–652.
[26] 聂 淑 芳 , 潘 卫 三 , 郭 宏 . 环 糊 精 在 靶 向 给 药 系 统 中 的 应 用 . 药 品 评价,2005,2(1):69–72.
[27] Mark E. Davis, Marcus E. Brewster.Cyclodextrin-baesd pharmaceutics:past, present, future. Nature, Drug discovery, 2004.12,(3):1023–1035.
[28] 刘琼,范晓东.环糊精高分子.高分子通报,2000(5):41–48.
[29] 童林荟.环糊精化学.北京科学出版社,2001 年 3 月,第一版,81.
[30] 周玉燕, 潘丽娟,郑瑛等.β-环糊精与聚丙烯酰胺的接枝化合物及其对水中污染物的絮凝作用.化工环保,2003,23(6):362–366.
[31] 王南平,余晓冬,陈洪渊.环糊精超分子化学研究的新进展.
[32] Sugiura lzuru, Komiyama Makoto, Toshima Naoki, Hirai Hidefumi.Bull Chem Soc Jpn, 1989, 62 (5):1643.
[33] Kosak KM. US, 6048736,1998 - 12 - 30.Rohrvach R P. US, 4917956, 1988 - 7 - 11.
[34] García-González N, Kellaway I W, Blanco-Fuente H, et al. Int J Pharm,1993,100:25.
[35] Bibby D C, Davies N M, Tucker I G. J Microencapsulation, 1998, 15:629.
[36] Crini G, Cosentino C, Bertini S, et al. Carbohydr Res, 1998, 308:37.
[37] Crini G, Morcellet M. J Appl Polym Sci, 1998, 68:1973.
[38] 苏小笛,刘六战,沈含熙.分析科学学报,1997,13(2):102.
[39] 罗春花,许鸿生,田文荣.分析测试学报,1999,18(1):61.
[40] 唐课文,许鸿生.湘潭大学自然科学学报,1998, (12):63.
[41] 黎瑞敏,孟德彬,夏丽娟.齐齐哈尔大学学报,1999,15(3):76.
[42] 李英杰,齐齐哈尔大学学报,1999,15(4):15.
[43] 韩家军,原向红,张晓惠.齐齐哈尔大学学报,1998,14(3):36.
[44] 韩树波,朱敏,袁倬斌.高等学校化学学报,1999,20(7):1036.
[45] 袁倬斌,朱敏,韩树波.中国科学院研究生院学报,1998,15(2):134.
[46] 毛陆原,朱敏,黄雪梅,沈含熙.高等学校化学学报,1997,18(10):1611.
[47] 李荣,毛陆原,朱敏,黄雪梅,沈含熙.分析科学学报,1998,14(2):94.
[48] Komiyama M, Hirai H.PolymJ, 1987, 19(6):773.
[49] Szejtli J, Fenyvesi E, Zoltan S, Zsadon B, Tūdos F. US ,4274985 ,1981,6(23).
[50] Fenyvesi E, Szejtli J, Zsadon B, Antal B, Wagner nee K I. US,4547572,1984,2(6).
[51] García-González N, Kellaway I W, Blanco-Fuente H, et al. Int J Pharm,1993,100:25.
[52] Bibby D C, Davies N M, Tucker I G. J Microencapsulation,1998,15:629.
[53] 刘琼,范晓东.功能高分子学报,2001,14,279.
[54] 李英杰,韩家军.以 β-环糊精树脂为载体提纯肌醇的研究.吉林大学自然科学学报,2001(2):99–102.
[55] 程坷伟,李新华.环糊精的改性及其应用.沈阳农业大学学报,2001,32(4):313–316.
[56] 南京药学院药剂学教研组编著.药剂学.人民卫生出版社,1985,969.
[57] Prentis.R. A, Lis.Y. & Walker,S. R. Pharmaceuticalinnovation by seven UK-owned pharmaceutical companies(1964–1985). Br. J. Clin. Pharmacol. 25,387–396 (1988).
[58] 魏树礼,高智慧.控释缓释微球制剂的研究进展.中国医药工业杂志,1990,21:29.
[59] 崔福德.药剂学.人民卫生出版,第五版,制剂新技术.
[60] 陆彬,张景勍,杨红.肺靶向卡铂明胶微球的研究. 药学学报,1999,34(10):786–789.
[61] 张景,陆彬.肺靶向卡铂明胶微球的药物动力学和体内分布研究.中国医药工业杂志, 2001,32 (6):251–253.
[62] 张军,翟光喜,刘世宽.卡铂肺靶向明胶微球的实验研究.中国现代应用药学杂志,2002 .4, 19 (2):123–125.
[63] 王剑红,陆彬,胥佩菱,包定元,张自然.肺靶向米托蒽醌明胶微球的研究.药学学报,1995,30(7):549–555.
[64] 詹国平,黄可龙,谢恩伟.肺靶向硫酸链霉素明胶微球的制备. 中国医院药学杂志2005,25(7):625–628.
[65] 杨云霞,包定元,曾昭贤,何晓,陆彬. 肺靶向制剂——硫酸链霉素明胶微球的药理学研究.中国抗生素杂志,1998.6,23(3):205–208.
[66] 张自然,陆彬,舒广晔,谢华,易秋艳,贺英菊,王剑红.硫酸链霉素肺靶向明胶微球的研究.华西医大学报,1995,26(2):167–171.
[67] 邓时贵,孟凡,莫莉莉,常钢,区勇全,杨志刚,斯方元.莪术油明胶微球肝动脉给药的一般药理研究.中国现代应用药学杂志,2003.2,20(1):1–3.
[68] 邓嵘,陈济民,高声传,丁懿.莪术油明胶微球剂的含量测定.中国医院药学杂志. 2001, 21 (2):79–81.
[69] 杨志刚,孟凡喆,常钢,徐勤.莪术油明胶微球栓塞犬肝动脉的病理改变.现代临床医学生物工程学杂志,2004,10 (2):88–90.
[70] 邓嵘,陈济民,姚崇舜,吴万垠.莪术油明胶微球用于肝动脉栓塞.药学学报,2000,35(7) :539 – 543.
[71] 邓时贵,莫莉莉,区勇全,欧润妹.莪术油明胶微球制剂急性毒性实验.医药导报2002 .4, 21 (4):200–202.
[72] 钟延强,蒋雪涛,孙其荣.白蛋白微球制剂. 药学实践,1995,13(4):208–211.
[73] 胡新、候新朴.新型药物载体——淀粉微球.中国药学,1995.2,30(2):69–71.
[74] 苏秀霞,李仲谨,马素德,白国强.载药淀粉微球合成条件的研究.应用化学,2003.8,32(4)33–35.
[75] 郑 文 杰 , 何 燕 岭 , 黄 宁 兴 . 靶 向 给 药 系 统 材 料 与 制 剂 . 中 国 药 学 杂志,1996.11,31(11):664–667.
[76] 郑彩虹,梁文权,虞和永,章亦立.亲水/亲酯性附加剂对乳酸–羟乙醇酸共聚物微球中蛋白释放的影响.中国药学 2005.7,40(13):999–1001.
[77] 王峰,涂家生,张钧寿,卢晶.PLGA 微球控释系统的突释及其控制.药学进展,2003 ,27( 3):142–146.
[78] 鞠 秀 兰 .PLGA 控 释 微 球 注 射 剂 的 研 究 进 展 . 卫 生 职 业 教 育 ( 教 学 参考),2005,23(10):123–124.
[79] 郑彩虹,梁文权,虞和永.乳酸羟乙醇酸共聚物微球中蛋白包封率的测定.中国医院药学,2005,25 (1):34–37.
[80] 康继超,魏树礼.单分散、大粒径聚苯乙烯微球的研制.北京医科大学学报,1997,29(3):238–240.
[81] 张岩,陈岚,李保国,华泽钊,伍贻文,刘哲鹏,陆伟跃.超临界 CO2抗溶剂法制备乙纤维素微球试验.化学工程,2005.6,33(3):63–67.
[82] 魏树礼,高智慧. 控释缓释微球制剂的研究进展.中国医药工业杂志,1990,21:29.
[83] 张志荣,王丹,廖方义,廖工铁.肝动脉栓塞米托蒽醌乙基纤维素微球的研究. 药学学报 1996 ,31(8) :626–631.
[84] 彭方兴,严律南,林琦远,白绍櫆,张旋波.阿霉素乙基纤维素微球肝动脉栓塞化疗的实验研究.中国普外基础与临床杂志,2001.5,8(3):138–140.
[85] 张强,武鳯兰主编.药剂学.北京大学医学出版社,最新版,385.
[86] 徐希明,余江南,张均寿.氟尿嘧啶白蛋白微球剂的制备工艺研究[J].中国现代应用药学,2000,17(6):546.
[87] 范田园,周喜林,魏树礼.利福平乙基纤维素微球的制备及质量评价[J].北京医科大学学报,1999,31(2) (增刊):28.
[88] TAN Zai-You, LIAO Qing-Jiang, Robin Y Xiao, Deniel Q. G. So. Characteristics of Epristeride Microspheres with TwoEmulsifying Preparation Methods.Journal of China Pharmaceutical University,2003,34 (4):309～312.
[89] 罗兰,潘金火.微粒作为靶向制剂载体的研究进展,中国医药工业杂志,1998,29 (9):424–428.
[90] 杨帆,林茵,谭载友,赵耀明,麦杭珍.肺靶向红霉素聚乳酸微球的研究.中国药科大学学报,2002,33 (3):211～215.
[91] Shaker D, William B, Kyung C et al. Cancer, 1982, 50:631.
[92] Yashioka T, Hasida M, Muranishi S, et al. Int J Pharmaceutics,1981; 81:131.
[93] Roath S, Smith AR,Watson JHP. J MagnMater, 1990,85:285.
[94] 宋群亮,张平.中药微球制剂研究进展.安徽医药,2004.2,9(2):87–88.
[95] 黎维勇,杜端明,冯敢生等.白及微球的研制及其肝动脉栓塞实验研究[J] . 同济医科大学学报,1999, 28(1):62.
[96] 黄园,侯世祥,林江宇.草乌肝靶向白蛋白微球的制剂学研究[J].中国中药杂志,1999,24(12):731.
[97] 严英,钟秀驰,周伟生等.中药制剂介入治疗恶性肿瘤的要利于临床研究概述[J] .中药新药与临床药理,2000,11(5):187.
[98] 瞿文,陈庆华等.多肽、蛋白质药物的微球给药系统研究进展[J].综述国外医学药学分册,1997.6, 24(3):921.
[99] Tabata Y, Langer R. Polyanhydride microshperes that display near-constant release of water-soluble model drug compounds.Pharm Res, 1993, 10(3):391.
[100] 鞠 秀 兰 .PLGA 控 释 微 球 注 射 剂 的 研 究 进 展 . 卫 生 职 业 教 育 ( 教 学 参考),2005,23(10):123–124.
[101] 孟丽.聚合物微球控释抗原投递系统研究的发展概况.微生物学免疫学进展,1995,23(3):192～194.
[102] Nakaoka R, Yasuhiko TB, Yoshito IK.Potentiality of gelatin microsphere as immunological adjuvant.Vaccine, 1995, 13(7):653–661.
[103] 赵晶,王立新.明胶微球乙肝疫苗动物免疫效果研究.中华微生物学和免疫学杂志,2000,20 (3):236–239.
[104] 王亚敏,石庭.微球制剂药物控释研究进展.中国药学,1996.3,31(3):131–134.
[105] 任晓慧,郑伟,刘松财,张永亮.多肽、蛋白质药物的微球缓释/控释系统.吉林畜牧兽医,2004,1,22–25.
[106] Narayani R, Rao KP.Preparation, characterization and in vitro Stability of hydrophilic gelatin microspheres using a gelatin-methotrexate conjugate. Int J Pharm,1993,95:85.
[107] 王亚敏,石庭森.微球制剂药物控释研究进展.中国药学,1996.3,31(3):131–134.
[108] Pekarek KJ, et al. J Nature,1994:367.258～260.王小敏翻译收载于:Pekarek K J, et al.用于药物控释的双层聚合物微球.国外医学药学分册,1994,21(5):300～302.
[109] Nykamp G, Carstensen U, Muller B W, et al. Jet m illing——a new technique for microparticle preparation [J]1 Int J Pharm,2002,242(122):792–861.
[110] 张洪涛,黄锦霞.乳液聚合新技术及应用.化学工业出版社,2007 年 1 月,第一版,102.
[111] 林浩,高建村,地木拉提.丙烯酰胺系反相乳液聚合研究进展.新疆石油学院学报, 2001 .3, 13(1):58–60.
[112] 杜定准,汪月生,徐文英.1H NMR 研究 β-环糊精与环氧氯丙烷共聚物的反应机理和分子链结构.波谱学杂质,1992,9(2):121–129.
[113] 严春美,刘郁杨,范晓东.β-环糊精球的制备及其药物控释行为研究.化工新型材料,2004,32(6):39–42.
[114] Baille W E, Huang W Q, Nichifor M, Zhu X X. [J ]. J. Macromol. Sci. Pure Appl. Chem, 2000, A37 (7):677～690.
[115] Mark E. Davis, Marcus E. Brewster.Cyclodextrin-baesd pharmaceutics:past, present, future.Nature,Drug discovery, 2004.12,(3):1023–1035.
[116] 刘郁杨.用于新型抗癌药物定向控制释放的高分子载体的合成与表征.西北工业大学博士学位论文,2003 年.
[117] 陈镜泓,李传儒.热分析及其应用.科学出版社.1985 年,第一版.
[118] Ozawa T. Bull Chem Soc Japan, 1965, 38:1881.
[119] Kissinger H E. Anal Chem, 1957, 29:1702.
[120] Freeman E S, Carrol B. J Phys Chem, 1958, 62:394.
[121] 谭载友,钟智敏,黄国超.ATP 热稳定性的 DSC 动力学研究.广东医药学院学报,1993,9(3):1–3.
[122] 蒋学华,廖工铁.靶向微球给药系统质量评价.华西药学杂志,1993,8(2):99–104.
[123] tella V J, et al. J Pharm Res, 1997, 14:556. ibby D C, et al. Int J Pharm,2000,197:1.
[124] ee Y B, et al. Pharm Res, 1991,8:531.
[125] 徐文,王中彦,何中贵,崔升淼.高效液相色谱法测定复方磺胺甲恶唑片的溶出度.药物分析杂志,2003(23):11–15.
[126] 周学琴,张丽,王迎春.盐酸环丙沙星片剂体外溶出度的比较.数理医药学杂志,2003,16(5):439–440.
[127] 刘莉 , 葛卫红 . 扑热息痛片的体外溶出度考察比较 . 江苏药学与临床研究,1996,4(3):12–15.
[128] 潘吉铮.聚乳酸微球载体的结构与控释性能关系及模型.华南理工大学博士论文,2004 年.
[129] 中国药典,2005 版,附录 XI X D 缓释、控释制剂指导原则
[130] Mulye, N. V., Turco, S. J., A simple model based on first order kinetics to explain release of highly water soluble drugs from porous dicalcium phosphate dehydrate matrices, Drug Dev. Ind. Pharm., 21, 943–953.
[131] Higuchi, T., Rate of release of medicaments from ointment bases containing drugs in suspensions, J. Pharm. Sci., 1961,50,874–875.
[132] John W. Skoug, Martin V. Mikelsons, Cynthia N.,et al. Qualitative evaluation of the mechanism of release of matrix sustained release dosage forms by measurement of polymer release. Journal of Controlled Release, 1993(27):227–245.
[133] JEAN-MAURICE VERGNAUD. CONTROLLED DRUG RELEASE OF ORAL DOSAGE FORMS. Ellis Horwood Limited, 1993:59–69.
[134] Washington C. Evaluation of non-sink dialysis methods for the mearurement of drug release from colloids: effects of drug partition. Int J Pharm, 1989, 56: 71–74.
[135] Friedman D, Benita S. A mathematical model for drug release from O/W emulsions: application to control release morphine emulsions. Drug Dev Ind Pharm, 1987, 13(9-11): 2067–2085.
[136] Soppimath K S, Aminabhavi T M, Kulkarni A R, et al. Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release, 2001, 70: 1–20.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |