【作者】 张艳霞；

【导师】 杨桂明；

【作者基本信息】 黑龙江中医药大学 ， 药剂学， 2010， 硕士

【摘要】 目的：蝙蝠葛酚性碱(phenolic alkaloids of menispermumdauricum，PAMD)是从常用中药防己科植物蝙蝠葛(menispermumdauricum DC.)根茎中提取的多种化学结构相似的脂溶性生物碱的混合物，主要成分为蝙蝠葛碱(dauricine) [ 1 ]。蝙蝠葛酚性碱具有活血化瘀，行气止痛，扩张冠脉血管，改善心肌缺血作用，用于预防和治疗冠心病、心律失常，心绞痛以及瘀血内阻之胸痹、眩晕、气短、心悸，胸闷）等病症[ 2 ]。目前市场上只有普通口服片剂，胶囊剂，粉针剂等剂型的研究使用[ 2～4 ]。根据蝙蝠葛碱理化性质，及心血管疾病需长期用药的特点，本文将其研制成巴布膏剂，使其能够避免肝脏的首过效应和胃肠道降解；一次给药就可长时间使药物以恒定速率进入体内，减少给药次数，并延长给药间隔；保持平稳的血药浓度，降低其毒副反应；使用方便，可以克服病人睡眠期间心脏病发作不能及时给药的弊端，特别适合不宜口服的病人。方法：本研究以改良Franz扩散池为主要实验装置，家兔皮为透皮扩散皮肤，采用HPLC法测定取样点浓度，计算累积渗透量Q值，以Q-t方程和透皮速率常数J为考察指标，筛选蝙蝠葛碱透皮扩散的最佳接收液，最佳促渗剂，通过正交试验设计，选择适宜的基质和最佳的制备工艺，制备最佳的蝙蝠葛酚性碱巴布膏剂。并对蝙蝠葛酚性碱巴布膏剂成品进行质量及体外安全性评价。结果：综合比较Q-t方程和透皮速率常数J，选择pH 5.8磷酸盐生理盐水溶液为最佳接收液；3%氮酮为较好透皮渗透促进剂；巴布膏剂基质最佳配比为：明胶:D-山梨醇:Ca(OH)2:PANa:PVP-K30:CMC-Na:高岭土:丙二酮:甘油:PEG 400=4:20:0.15:1: 7: 4: 4: 3.5: 4: 10。最佳制备工艺是称取处方量明胶加适量水浸泡溶胀后，加入D-山梨醇、Ca(OH)2、PAMD原料药，水浴加热溶胀得I相溶液；另取PANa、PVP-K30、CMC-Na、高岭土、丙二酮、甘油、PEG 400混合均匀，溶涨过夜，得Ⅱ相溶液；将I、Ⅱ相溶液混合；最后加入Azone充分搅拌数分钟，至膏体均匀、光滑，得含药巴布膏剂基质；将基质均匀涂布于无纺布上，50℃烘90min，覆盖上防粘层，密封包装。结论：本方法简单﹑稳定易行，可控性强，重复性好。更多还原

【Abstract】 Objective: PAMD is commonly used in Chinese medicine Menispermaceae from plant roots to extract the menispermum dauricum DC various chemical structure similar to a mixture of fat-soluble alkaloids, mainly composed of dauricine. With blood circulation, promoting qi movement and relieving pain, expansion of coronary vessels, improve myocardial ischemia, for the prevention and treatment of coronary heart disease, arrhythmia, angina, and bleeding resistance of the Chest, dizziness, shortness of breath, palpitations, chest tightness or pain disorders . Nowadays, only regular oral tablets, capsules, injection and other formulations of use. According to physical and chemical properties dauricine, and cardiovascular disease requires long-term drug use characteristics, this article will be developed into cataplasms to enable it to avoid the liver first pass effect and gastrointestinal drug degradation; a long time of drug administration can enter the body at a constant rate, reducing delivery times, and extend the dosing interval; to maintain a stable blood concentration, reduce its toxicity side effects; easy to use, can be interrupted at any time delivery, especially for patients should not be taken orally.Method: The modified Franz diffusion cell study, the main experimental device, the skin of rabbit for the transdermal diffusion, determined by HPLC sampling points were calculated cumulative permeation amount Q value to Q-t equation and the penetration rate constant J for evaluation, transdermal diffusion filter dauricine the best receiver solution, the best penetration enhancers, Orthogonal experimental design, appropriate choice of matrix and the best preparation, preparation of the best dauricine cataplasms. Conducted on dauricine cataplasms product quality and safety evaluation in vitro.Result: The comparison of Q-t equation and transdermal speed constant showed that pH5.8 phosphate buffer solution- saline was the best for the study;3% Azone as skin permeation enhancers better;the best ratio of matrix is Gelatin: D-sorbitol: Ca(OH)2 : PANa : PVP-K30 : CMC-Na : Kaolin : propanedione : glycerol : PEG 400 =4:20:0.15:1: 7: 4: 4: 3.5: 4: 10. The best preparation is to obtain prescriptions, said additional amount of water soaked gelatin swelled by adding D-sorbitol, Ca (OH) 2, dauricine raw material medicine, the swelling water bath was I phase solution; for an alternative PANa, PVP-K30, CMC-Na, kaolin, propanedione, glycerol, PEG 400 were mixed overnight swelling may beⅡphase solution; I phase andⅡphase solution was mixed; the last to join Azone to mix a few minutes to paste uniform, smooth, may contain drug cataplasms; will evenly coated on the non-woven on the matrix, 50℃bake 90min, covered with anti-sticking layer, sealed packaging.Conclusion: This method is simple and easy, stability, controllability, good repetition.更多还原