本文選題：蟾酥 + 溫敏凝膠　； 參考：《山東中醫(yī)藥大學(xué)》2015年碩士論文

【摘要】：目的:以中藥蟾酥為模型藥物,制備用于治療雛鴨肝炎的新型肌內(nèi)注射用溫敏型制劑,對其制備工藝、凝膠中藥效學(xué)成分的體外釋放規(guī)律、質(zhì)量標(biāo)準(zhǔn)進行考察研究,并對該凝膠制劑穩(wěn)定性及雛鴨病毒鴨肝炎在體藥效學(xué)進行初步研究。方法:以藥學(xué)指標(biāo)篩選模型藥物蟾酥的工藝制備路線;采用正交試驗法,多指標(biāo)優(yōu)選制備工藝路線參數(shù);以蟾酥為主藥,在參考文獻的基礎(chǔ)上,采用溫敏型輔料P407、P188,粘度調(diào)節(jié)劑MC、HPMC、SA、PEG4000等,以凝膠溫度和體外釋放速率為指標(biāo)對制劑的處方組成進行篩選。采用“冷溶法”制備空白及含藥凝膠,以“攪拌子法”測定不同處方溫敏凝膠的膠凝溫度。采用透析袋-漿法,測定并計算藥物的體外累計釋藥百分率,繪制累計釋藥百分率時間曲線。將數(shù)據(jù)用零級釋藥方程、一級釋藥方程、Higuchi方程進行擬合,對藥物的釋放機理進行研究。采用高效液相色譜法對新型制劑中的華蟾酥毒基和脂蟾毒配基進行了含量測定,并通過其于蟾酥注射液、西藥金剛烷胺粉劑比較在體肌注射療效,對該制劑藥效學(xué)進行初步研究。結(jié)果:模型藥物中藥蟾酥優(yōu)選的制備工藝路線為:蟾酥90%乙醇回流3次,每次加入量為8,6,6,每次1 h,過濾,合并濾液,濾液濃縮至0.5 g生藥/m L。溫敏制劑最佳處方為:蟾酥濃縮液-P407-P188-HPMC-PEG4000(0.08:20:2:0.5:0.5)。該處方下,制劑的膠凝溫度約為38.8℃。體外釋放結(jié)果表明,溫敏凝膠中有效成分釋放量逐漸增高,在12天時藥物累計釋放90%以上,說明所制備的溫敏凝膠對模型藥物蟾酥中有效成分具有明顯的緩釋作用。釋藥模型擬合符合Higuchi模型。通過定量分析,確定華蟾酥毒基和脂蟾毒配基含量總量不得低于15μg/ml。在體藥效學(xué)結(jié)果表明:蟾酥注射液存活率為74.3%,西藥金剛烷胺粉劑存活率為68.6%,蟾酥溫敏型注射液存活率為82.9%,三組進行卡方檢驗后,Pearsonx2=1.943,df=2,P=0.379(0.05),三種方法治療鴨病毒性肝炎效果沒有顯著性差異,但是在實際實驗進程中,由于蟾酥注射液及金剛烷胺粉劑注射次數(shù)較多,引起鴨的應(yīng)激反應(yīng),鴨體重的下降,而蟾酥溫敏型注射液組并沒有相關(guān)癥狀。結(jié)論:以上各項體內(nèi)外實驗證明,制備的蟾酥溫敏凝膠膠凝溫度適宜,制劑均勻穩(wěn)定,質(zhì)量控制方法準(zhǔn)確,重現(xiàn)性良好;溫敏凝膠經(jīng)肌內(nèi)注射給藥后,能明顯延緩中藥蟾酥中有效成分的釋放,不僅能夠提高藥物的生物利用度,而且降低其毒副作用,同時蟾酥溫敏凝膠展現(xiàn)出良好的肌內(nèi)注射應(yīng)用前景,制備工藝穩(wěn)定。
[Abstract]:Objective: to prepare a new type of thermo-sensitive preparation for intramuscular injection for the treatment of ducklings hepatitis with toad as model drug, and to investigate the preparation process, in vitro release rule of pharmacodynamic components in the gel and the quality standard. The stability of the gel and the pharmacodynamics of duck virus hepatitis in vivo were studied. Methods: the preparation route of the model drug was screened by pharmacological index, the parameters of the preparation process were optimized by orthogonal test, the main drug was toad cake, and based on the references, The temperature sensitive excipient P407 P188, the viscosity regulator MCHPMCSAPEG4000 and the gel temperature and release rate in vitro were used to screen the formulation of the preparation. The blank and drug-containing gels were prepared by "cold dissolution method", and the gelation temperature of thermo-sensitive gels with different prescriptions was determined by "agitation method". The cumulative drug release percentage in vitro was measured and calculated by dialysis bag-serous method, and the time curve of cumulative drug release percentage was plotted. The data were fitted with zero-order drug release equation and first-order drug release equation Higuchi equation to study the mechanism of drug release. The contents of bufo venom and bufagin ligand in the new preparation were determined by high performance liquid chromatography (HPLC), and the efficacy of intramuscular injection of amantadine powder was compared with that of bubufen injection. The pharmacodynamics of the preparation was preliminarily studied. Results: the optimal preparation route of the model drug Chinese medicine toad was as follows: the reflux of 90% ethanol was 3 times, the amount of each addition was 8 ~ 6 ~ 6, 1 hour each time, filtration, combined filtrate, filtrate was concentrated to 0.5 g crude drug / L ~ (-1) 路m ~ (-1) 路L ~ (-1) 路L ~ (-1) 路L ~ (-1). The best formulation of temperature sensitive preparation is toad crisp concentrate-P407-P188-HPMC-PEG4000 (0.08: 20: 2: 0.5: 0.5). The gelation temperature of the preparation is about 38.8 鈩，

本文編號：2075728