發(fā)布時(shí)間：2019-04-11 11:20

【摘要】：近年來由于脂質(zhì)體制劑等新劑型的不斷研發(fā)上市,該類制劑特殊的工藝、構(gòu)造和性質(zhì)使其與傳統(tǒng)制劑的質(zhì)控方法有所不同。由于目前無論在脂質(zhì)體藥物的研究、開發(fā)方面還是上市藥物的質(zhì)控標(biāo)準(zhǔn)中,釋放度測(cè)定方法各異、缺乏方法間驗(yàn)證、規(guī)范性較差,甚至有的品種的標(biāo)準(zhǔn)未設(shè)置釋放度測(cè)定方法,因此亟需建立并優(yōu)化該類制劑的質(zhì)量控制標(biāo)準(zhǔn),尤其是釋放度檢查項(xiàng)目,以確保其安全、有效、質(zhì)量可控。本文首先選擇大量專家學(xué)者研究的透析法進(jìn)行研究,通過探究透析法測(cè)定的儀器裝置,改善檢測(cè)方法中影響檢測(cè)結(jié)果的不可控因素,使測(cè)定裝置標(biāo)準(zhǔn)化;同時(shí)通過對(duì)性質(zhì)各異的模型藥物鹽酸多柔比星、硫酸長(zhǎng)春新堿、紫杉醇的研究,考察透析法測(cè)定脂質(zhì)體制劑釋放度的適用范圍和影響透析法釋放度測(cè)定結(jié)果的關(guān)鍵因素,提煉釋放度透析測(cè)定法建立和驗(yàn)證的基本原則,規(guī)范方法建立、驗(yàn)證和使用的基本要求。本文設(shè)計(jì)和改進(jìn)了透析膜裝置,使其在穩(wěn)定性、重現(xiàn)性、操作可行性、規(guī)范性等方面達(dá)到了預(yù)期效果,目前在進(jìn)一步的深入優(yōu)化中。使用自行設(shè)計(jì)的透析膜裝置考察了透析法測(cè)定3種脂質(zhì)體藥物的相關(guān)影響因素,獲取了驗(yàn)證數(shù)據(jù)。在此基礎(chǔ)上建立了鹽酸多柔比星脂質(zhì)體注射液的釋放度透析檢測(cè)方法,同時(shí)總結(jié)了透析法的適用性及可行性,為其他脂質(zhì)體制劑及更多微粒給藥系統(tǒng)制劑釋放度檢測(cè)方法的建立提供了基礎(chǔ)研究及參考。
[Abstract]:In recent years, due to the continuous research and development of new formulations such as liposomes, the special technology, structure and properties of these preparations make them different from the traditional methods of quality control. At present, both in the research and development of liposomes and in the quality control standards of listed drugs, there are different methods for the determination of release degree, lack of inter-method verification, poor standardization, and even the standard of some varieties does not set up a method for the determination of release degree. Therefore, it is urgent to establish and optimize the quality control standard of this kind of preparation, especially the release inspection item, so as to ensure its safety, effectiveness and quality control. In this paper, we first choose a large number of experts and scholars to study the dialysis method. By exploring the instrument and equipment of the dialysis method, we can improve the uncontrollable factors in the testing method and standardize the measuring device. At the same time, through the study of doxorubicin hydrochloride, vincristine sulfate and paclitaxel, which have different properties, the scope of application of dialysis to determine the release of liposomes and the key factors affecting the results of dialysis were investigated. Basic principles for the establishment and validation of dialysis determination of refining release, and basic requirements for the establishment, verification and use of standardized methods. In this paper, the dialysis membrane device has been designed and improved to achieve the expected effect in the aspects of stability, reproducibility, operation feasibility, standardization and so on. At present, it is in the process of further in-depth optimization. The factors related to the determination of three kinds of liposomes by dialysis were investigated by a self-designed dialysis membrane device, and the verification data were obtained. On this basis, a dialysis method for the determination of the release of doxorubicin hydrochloride liposome injection was established, and the applicability and feasibility of the dialysis method were summarized. It provides a basic research and reference for the determination of the release degree of other liposomes and more microparticle delivery system.
【學(xué)位授予單位】：中國(guó)食品藥品檢定研究院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R927

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