本文選題：肺部緩釋 + 藥代動(dòng)力學(xué)��； 參考：《北京協(xié)和醫(yī)學(xué)院》2017年碩士論文

【摘要】：肺部給藥是治療呼吸道疾病的最佳給藥方式,然而臨床上使用的吸入制劑給藥頻次多,病人依從性差,因此需要開(kāi)發(fā)肺部緩釋制劑。然而,由于沒(méi)有合適的載體和評(píng)價(jià)技術(shù),目前并沒(méi)有成熟的制劑技術(shù)能夠?qū)崿F(xiàn)肺部緩釋。針對(duì)聚合物高分子材料肺部不相容,可使用輔料較少的現(xiàn)狀,我們選擇了布地奈德、環(huán)索奈德和丙酸氟替卡松作為模式藥物,選擇微米晶和納米晶的制劑形式,進(jìn)行體內(nèi)外一致性評(píng)價(jià)的探索。選擇不同粒徑的魚(yú)腥草揮發(fā)油固體脂質(zhì)納米粒和納米晶混懸液一起,進(jìn)行可吸入性的比較。本文首先建立了三種可吸入性糖皮質(zhì)激素的體內(nèi)外含量測(cè)定方法。以濕法球磨和高壓均質(zhì)的方法制備了環(huán)索奈德和丙酸氟替卡松納米晶和微米晶混懸液,并對(duì)丙酸氟替卡松納米晶進(jìn)行了磷脂修飾。以Spraytec和NGI評(píng)價(jià)了五種化合物的可吸入性,以改進(jìn)的Transwell溶出裝置測(cè)其體外溶出。微米晶和納米晶混懸液大鼠肺部給藥后,測(cè)其肺泡灌洗液、肺組織、腸組織和血中的藥物含量。其中肺泡灌洗液中含量代表藥物未溶出的藥物含量,腸組織中的藥物含量代表清除到腸道的藥物含量,血中代表吸收進(jìn)入系統(tǒng)循環(huán)的藥物含量。實(shí)驗(yàn)結(jié)果表明,以肺泡灌洗液中藥物含量代表藥物在肺內(nèi)的溶出和體外溶出具有一定的關(guān)聯(lián)性。環(huán)索奈德微米晶可以實(shí)現(xiàn)在肺部的長(zhǎng)時(shí)間駐留。納米晶制劑可以減少肺部纖毛清除,提高肺部生物利用度。磷脂修飾的納米晶可以減少肺部纖毛清除,提高藥物在肺部的有效生物利用度,其有效生物利用度是納米晶的1.7倍,是微米晶的4.2倍。
[Abstract]:Pulmonary administration is the best way to treat respiratory diseases. However, the inhaled drugs are used more frequently and the patients' compliance is poor, so it is necessary to develop the lung sustained-release preparation. However, due to the lack of suitable carrier and evaluation technology, there is no mature preparation technology to achieve sustained release of lung. In view of the pulmonary incompatibility of polymeric polymer materials and the low availability of excipients, we chose budesonide, cyclonide and fluticasone propionate as model drugs, and microcrystalline and nanocrystalline formulations. To explore the consistency evaluation in vivo and in vitro. The absorbability of Houttuynia cordata volatile oil solid lipid nanoparticles and nanocrystalline suspensions were compared. Three methods for the determination of inhalable glucocorticoids in vivo and in vitro were established. The suspension of fluticasone propionate and fluticasone propionate nanocrystals were prepared by wet ball milling and high pressure homogenization. The phospholipids of fluticasone propionate nanocrystals were modified by phospholipid. The absorbability of five compounds was evaluated by Spraytec and NGI, and the dissolution in vitro was measured by an improved Transwell dissolution device. The drug contents in alveolar lavage fluid, lung tissue, intestinal tissue and blood were measured after administration of microcrystalline and nanocrystalline suspension in lung of rats. The content in alveolar lavage fluid represents the drug content that the drug is not dissolved, the drug content in the intestinal tissue represents the drug content that clears the intestine, and the blood represents the drug content absorbed into the circulation of the system. The results showed that the drug content in alveolar lavage fluid was related to the dissolution of drugs in the lung and in vitro. Cysolide microcrystals can be used to stay in the lungs for a long time. Nanocrystalline preparation can reduce pulmonary cilia clearance and improve lung bioavailability. Phospholipid modified nanocrystalline can reduce the clearance of pulmonary cilia and improve the effective bioavailability of drugs in the lung. The effective bioavailability of phospholipid modified nanocrystals is 1.7 times as much as that of nanocrystals and 4.2 times of that of micron crystals.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R943
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本文編號(hào)：1853810