本文關(guān)鍵詞：鹽酸吡硫醇納米制劑的研究　出處：《吉林大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 鹽酸吡硫醇 PLGA 薄膜分散法 低刺激性

【摘要】：鹽酸吡硫醇是維生素B6的類似物，臨床上主要可以治療老年癡呆癥�，F(xiàn)上市的產(chǎn)品主要包括鹽酸吡硫醇片劑、鹽酸吡硫醇注射劑和鹽酸吡硫醇凍干粉針劑。而據(jù)臨床使用者反饋，該注射劑具有一定的血管刺激性。為了降低其血管刺激性，本研究將其制備成為納米制劑，主要制備為乳酸-羥基乙酸共聚物（PLGA）聚合物納米粒和脂質(zhì)體制劑，但所得PLGA納米粒制劑載藥量很低，還達(dá)不到脂質(zhì)體制劑的載藥量，，沒能達(dá)到預(yù)期效果。而制得的鹽酸吡硫醇脂質(zhì)體制劑，在前人的研究基礎(chǔ)上，本研究將其載藥量提高一倍，包封率略有增加，刺激性有所降低。 本研究對鹽酸吡硫醇進(jìn)行了處方前研究，確定了紫外吸收波長，建立了鹽酸吡硫醇HPLC體外分析方法和紫外分光光度法（UV），并進(jìn)行了方法學(xué)驗(yàn)證。還測定了鹽酸吡硫醇、鹽酸吡硫醇與膽固醇、鹽酸吡硫醇與膽固醇硫酸鈉、鹽酸吡硫醇與膽固醇琥珀酸單酯的油水分配系數(shù)，以此考察膽固醇、膽固醇硫酸鈉、膽固醇琥珀酸單酯對鹽酸吡硫醇油水分配系數(shù)的影響，為選定膜流動性調(diào)節(jié)劑提供了參考。 本研究對PLGA聚合物納米粒的制備工藝和處方篩選進(jìn)行了考察，但結(jié)果表明其載藥量低，沒有實(shí)用價值，因此放棄。在前人的研究基礎(chǔ)上，本研究運(yùn)用薄膜分散法制備了鹽酸吡硫醇脂質(zhì)體，并考察和優(yōu)化了其制備工藝。工藝方面主要對圓底燒瓶的傾斜角度、溶劑的選用、制備的溫度、成膜的速度以及超聲的方式進(jìn)行考察，得到最優(yōu)工藝，處方方面，將脂質(zhì)體的包封率作為主要評價指標(biāo)，篩選了膜穩(wěn)定劑的用量、所用磷脂的種類、水化介質(zhì)的離子強(qiáng)度及表面活性劑的種類，最終確定最優(yōu)處方。并對最優(yōu)處方制備的制劑進(jìn)行了表征。最后通過動物模型對脂質(zhì)體的刺激性進(jìn)行了初步評價，做了溶血實(shí)驗(yàn)驗(yàn)證制劑的安全性。表明刺激性有所降低且未發(fā)生很明顯的溶血現(xiàn)象。
[Abstract]:Pyritinol hydrochloride is a vitamin B6 analogue that can be used clinically to treat Alzheimer's disease. The main products on the market include pyritinol hydrochloride tablets. Pyritinol hydrochloride injection and pyritinol hydrochloride lyophilized powder injection. According to the feedback of clinical users, the injection has a certain vascular irritation. In order to reduce its vascular irritation, it was prepared into nanometer preparation in this study. The main preparation is lactic acid-glycolic acid copolymer polymer nanoparticles and liposome preparations, but the amount of drug loaded by PLGA nanoparticles is very low, which can not reach the drug load of liposome preparations. The preparation of pyritinol hydrochloride liposome was not able to achieve the desired effect. Based on previous studies, the drug loading was doubled, the entrapment efficiency was slightly increased, and the irritation was decreased. In this study, the pre-prescription study of pyritinol hydrochloride was carried out, the UV absorption wavelength was determined, and the in vitro analysis method and UV spectrophotometric method of pyritinol hydrochloride HPLC were established. The oil and water partition coefficients of pyritinol hydrochloride, pyritinol hydrochloride and cholesterol, pyritinol hydrochloride and sodium cholesterol sulfate, pyritinol hydrochloride and cholesterol succinate monoester were also determined. The effects of cholesterol, sodium cholesterol sulfate and mono-ester of cholesterol succinate on the partition coefficient of pyritinol hydrochloride oil and water were investigated, which provided a reference for the selection of membrane fluidity regulator. In this study, the preparation process and prescription screening of PLGA polymer nanoparticles were investigated, but the results showed that the drug loading was low and had no practical value, so it was abandoned. In this study, pyritinol hydrochloride liposomes were prepared by thin-film dispersion method, and the preparation process was investigated and optimized. The speed of membrane formation and ultrasonic method were investigated to obtain the optimal technology. The encapsulation efficiency of liposome was taken as the main evaluation index. The dosage of membrane stabilizer and the type of phospholipids were selected. The ionic strength of hydration medium and the kinds of surfactants were determined to determine the optimal prescription. The preparation of the optimal prescription was characterized. Finally, the irritability of liposomes was preliminarily evaluated by animal model. The safety of the preparation was verified by hemolysis test, which showed that the irritation was decreased and no obvious hemolysis occurred.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R94

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