本文選題：利福噴丁　切入點(diǎn)：利奈唑胺　出處：《山西醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:本文以利福噴丁(Rifapentine,RIF)和利奈唑胺(Linezolid,LZD)為模型藥物,以聚乳酸-羥基乙酸[poly(lactic-co-glycolic acid),PLGA]為載體,制備了載利福噴丁與利奈唑胺聚乳酸-羥基乙酸緩釋微球(Rifapentine-linezolid-loaded poly(lactic acid-co-glycolic acid)microspheres,RLPMs),用于解決肺結(jié)核支氣管鏡介入治療時(shí)所選用的藥物緩釋效果差和有效藥物濃度維持時(shí)間短的問題。方法:首先,建立利福噴丁與利奈唑胺高效液相色譜檢測(cè)法(high-performance liquid chromatography,HPLC),繪制其標(biāo)準(zhǔn)曲線,用于檢測(cè)利福噴丁與利奈唑胺藥物濃度。然后,采用水包油(Oil-in-Water,O/W)的乳化溶劑揮發(fā)法制備載藥微球,并通過對(duì)不同制備工藝下所制備微球的形態(tài)、粒徑大小、載藥量和包封率等理化特性進(jìn)行考察,篩選出最佳制備工藝。最后,對(duì)緩釋微球的體外釋放特性、肺內(nèi)粘附性、留滯特性以及支氣管和肺組織病理觀察進(jìn)行了評(píng)價(jià)。結(jié)果:最佳制備工藝所制備的微球呈球形,表面有圓形凹陷,微球粒徑大小為27.38±1.28μm,利福噴丁與利奈唑胺的載藥量分別為18.51±0.26%和8.42±0.24%,包封率分別為55.53±0.78%和16.87±0.47%(n=3)。在體外釋放試驗(yàn)的突釋期內(nèi),利福噴丁3d內(nèi)釋放21.37±0.68%,利奈唑胺1d內(nèi)釋放43.56±2.54%,隨后二者進(jìn)入平穩(wěn)釋放期,最終利福噴丁與利奈唑胺14d累計(jì)釋放率分別為27.61±1.52%和51.01±3.31%(n=3)。通過肺內(nèi)粘附性試驗(yàn)、滯留性試驗(yàn)以及支氣管和肺組織病理觀察,緩釋微球能夠在犬支氣管黏膜表面緩慢釋放并滯留20d,并且不會(huì)對(duì)支氣管黏膜造成損害,安全可靠。結(jié)論:本研究所制備的微球具有明顯的緩釋效果以及能有效滯留于支氣管黏膜表面,安全可靠,達(dá)到了實(shí)驗(yàn)預(yù)期設(shè)計(jì)的目標(biāo)。
[Abstract]:Objective: in this paper, rifapentine rifapentine rifapentine (rifapentine) and linazolidine (LZD) were used as model drugs and poly(lactic-co-glycolic acidoglycolic acid (poly(lactic-co-glycolic) was used as the carrier. Rifapentine-linezolid-loaded poly(lactic acid-co-glycolic microspheres-RLPMs were prepared with rifapentine-linezolid-loaded poly(lactic acid-co-glycolic microspheres, which were used to solve the problem of low sustained release effect and short duration of effective drug concentration in bronchointerventional therapy for pulmonary tuberculosis. Methods: first of all, A high performance liquid chromatographic HPLC method was established for the determination of rifapentine and linazolamide. The standard curve was drawn for the determination of the concentration of rifapentine and linazolamide. Then, the emulsified solvent volatilization method was used to prepare the drug loaded microspheres. The physical and chemical properties such as morphology, particle size, drug loading and encapsulation efficiency of the microspheres prepared under different preparation processes were investigated, and the best preparation process was obtained. Finally, the in vitro release characteristics and intrapulmonary adhesion of sustained-release microspheres were studied. Results: the microspheres prepared by the best preparation technique were spherical and had a circular depression on the surface. The particle size of the microspheres was 27.38 鹵1.28 渭 m, the drug loading of rifapentine and linazolamide were 18.51 鹵0.26% and 8.42 鹵0.24.The entrapment rates were 55.53 鹵0.78% and 16.87 鹵0.47% respectively. The release rate of rifapentine was 21.37 鹵0.68 in 3 days, and that of linazolamine was 43.56 鹵2.54 in one day. The cumulative release rates of rifapentine and renazolamide in 14 days were 27.61 鹵1.52% and 51.01 鹵3.31% respectively. Retention test and pathological observation of bronchi and lung tissue showed that the sustained release microspheres could be released slowly and remained on the surface of canine bronchial mucosa for 20 days without causing damage to the bronchial mucosa. Conclusion: the microspheres prepared in this study have obvious slow-release effect and can effectively stay on the surface of bronchial mucosa.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R943

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