淀粉支载氧氟沙星前药的合成及其体外释放研究
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摘要
以淀粉和氧氟沙星为原料,合成了淀粉支载的氧氟沙星高分子前药,用核磁共振氢谱对其结构进行了结构表征、紫外分光光度计测定了氧氟沙星的接入率,并在人工胃液和人工肠液中进行了体外释放研究。结果清楚显示氧氟沙星成功接入到淀粉分子上,该高分子前药在不同介质的体外释放中均呈现零级缓慢释药,与氧氟沙星相比较,其作用时间明显增长,可以有效减缓药物成分的释放,控制血药浓度,有望大大减轻药物对胃粘膜和肠的刺激作用,并解决氧氟沙星的味苦及难溶等问题。
In order to obtain a sustained-release nicotinic acid,starch-nicotinic acid conjugation was synthesized by coupling between starch and nicotinyl chloride. Its structure was characterized with FTIR and 1HNMR. The drug-loading ratio of the product was measured by ultraviolet spectrophotometer. And in vitro drug release investigation was carried out in artificial gastric juice and artificial intestinal juice. The results clearly showed that nicotinic acid was coupled with the starch molecule successfully and the drug release rate of the conjugatation was nearly zero order without abrupt release. Compared with nicotinic acid,the effective therapeutic time of the polymer prodrug was prolonged. So it may lead to less side-effect and relieving stimulation on gastrointestinal tract.
In order to obtain a sustained-release nicotinic acid,starch-nicotinic acid conjugation was synthesized by coupling between starch and nicotinyl chloride. Its structure was characterized with FTIR and 1HNMR. The drug-loading ratio of the product was measured by ultraviolet spectrophotometer. And in vitro drug release investigation was carried out in artificial gastric juice and artificial intestinal juice. The results clearly showed that nicotinic acid was coupled with the starch molecule successfully and the drug release rate of the conjugatation was nearly zero order without abrupt release. Compared with nicotinic acid,the effective therapeutic time of the polymer prodrug was prolonged. So it may lead to less side-effect and relieving stimulation on gastrointestinal tract.
引文
[1]杜璇,屠锡德.氧氟沙星的临床用药进展[J].江苏药学与临床研究,2005,13(5):16-19.
[2]Oliphant C M,Green G M.Quinolones:a comprehensive review[J].American Family Physician,2002,65(3):455-465.
[3]Hayakawa I,Atarashi S,Yokohama S,et al.Synthesis and antibacterial activities of optically active ofloxacin[J].Antimicrob Agents Chemother,1986,29(1):163-164.
[4]单爱莲,吕媛,李家泰.左旋氧氟沙星和氧氟沙星的临床应用进展与评价[J].中国临床药理学杂志,1997,13(2):115-119.
[5]龙琪,陈昌云,马美华.β-环糊精与左氧氟沙星超分子配合物的合成、表征及其与DNA的结合性质[J].光谱实验室,2007,24(1):24-27.
[6]唐建华,姜波,刘昌林,等.氧氟沙星药物的研究进展[J].中国兽药杂志,2007,41(9):29-33.
[7]Sahoo S,Sahoo D,Sasmal A,et al.Synthesis of chitosan-polycaprolactone blend for control delivery of ofloxacin drug[J].Carbohydrate Polymers,2010,79(1):106-113.
[8]Guan J,Cheng P,Huang S J,et al.Mathematic simulating of levofloxacin release from chitosan nano/microparticles[J].Przegld Elektrotechniczny,2012,88(7):345-349.
[9]Jay S,Dutta P K.Preparation,antibacterial and physiochemical behavior of chitosan/ofloxacin complexes[J].International Journal of Polymeric Materials,2010,59(10):793-807.
[10]Santosh K,Joonseok K,Dilip K T,et al.Optical study of chitosan-ofloxacin complex for biomedical applications[J].Journal of Macromolecular Sciences-Pure&Applied Chemistry,2011,48:789-795.
[11]Sobczak M,Na?cz-Jawecki G,Ko?odziejski W L,et al.Synthesis and study of controlled release of ofloxacin from polyester conjugates[J].International Journal of Pharmaceutics,2010,402(1/2):37-43
[12]王建国.葡萄糖-阿司匹林共价复合物的合成及体外释放研究[D].赣州:赣南师范学院,2009.
[2]Oliphant C M,Green G M.Quinolones:a comprehensive review[J].American Family Physician,2002,65(3):455-465.
[3]Hayakawa I,Atarashi S,Yokohama S,et al.Synthesis and antibacterial activities of optically active ofloxacin[J].Antimicrob Agents Chemother,1986,29(1):163-164.
[4]单爱莲,吕媛,李家泰.左旋氧氟沙星和氧氟沙星的临床应用进展与评价[J].中国临床药理学杂志,1997,13(2):115-119.
[5]龙琪,陈昌云,马美华.β-环糊精与左氧氟沙星超分子配合物的合成、表征及其与DNA的结合性质[J].光谱实验室,2007,24(1):24-27.
[6]唐建华,姜波,刘昌林,等.氧氟沙星药物的研究进展[J].中国兽药杂志,2007,41(9):29-33.
[7]Sahoo S,Sahoo D,Sasmal A,et al.Synthesis of chitosan-polycaprolactone blend for control delivery of ofloxacin drug[J].Carbohydrate Polymers,2010,79(1):106-113.
[8]Guan J,Cheng P,Huang S J,et al.Mathematic simulating of levofloxacin release from chitosan nano/microparticles[J].Przegld Elektrotechniczny,2012,88(7):345-349.
[9]Jay S,Dutta P K.Preparation,antibacterial and physiochemical behavior of chitosan/ofloxacin complexes[J].International Journal of Polymeric Materials,2010,59(10):793-807.
[10]Santosh K,Joonseok K,Dilip K T,et al.Optical study of chitosan-ofloxacin complex for biomedical applications[J].Journal of Macromolecular Sciences-Pure&Applied Chemistry,2011,48:789-795.
[11]Sobczak M,Na?cz-Jawecki G,Ko?odziejski W L,et al.Synthesis and study of controlled release of ofloxacin from polyester conjugates[J].International Journal of Pharmaceutics,2010,402(1/2):37-43
[12]王建国.葡萄糖-阿司匹林共价复合物的合成及体外释放研究[D].赣州:赣南师范学院,2009.