本文選題：鹽酸阿莫羅芬 + 真菌��； 參考：《湖北中醫(yī)藥大學(xué)》2014年碩士論文

【摘要】：在日常生活中，皮膚真菌病很常見，它容易感染、傳染性也比較大、并且經(jīng)常復(fù)發(fā)，嚴(yán)重影響著病人的生活質(zhì)量，目前臨床上主要使用局部外用抗真菌藥來治療皮膚真菌病。阿莫羅芬作為抗真菌藥物中的新類型，其抗菌作用比較強，很多常見致病菌都對它比較敏感，如皮膚癬菌、酵母菌、暗色孢科真菌、雙相型真菌和一些條件致病真菌等。鹽酸阿莫羅芬局部外用時可被甲蛋白吸收,對14位還原酶和7~8位異構(gòu)酶具有雙重抑制作用,并且能夠有效殺滅和抑制灰指甲的常見致病菌(皮膚癬菌、酵母菌和霉菌)，具有極高的體外藥理活性。 本課題以鹽酸阿莫羅芬為模型藥物，劑型為乳膏劑，其規(guī)格為0.25%，并對其進(jìn)行了以下四方面的研究： 在處方工藝研究部分，根據(jù)防治疾病的需要，皮膚病一般選擇軟膏劑為最佳劑型，而乳劑型基質(zhì)的軟膏更易涂布，吸收也較好，對皮膚也有保護(hù)作用。我們在處方中加入了防腐劑、pH調(diào)節(jié)劑等功能性輔料，對乳化劑和油相的用量進(jìn)行了處方篩選來確定最優(yōu)處方。在初步確定處方之后，，以性狀、pH值、分層現(xiàn)象等作為初步評價指標(biāo)，并對制備的乳膏樣品進(jìn)行留樣，根據(jù)留樣結(jié)果再來設(shè)計處方，最后挑選出的處方既滿足性狀、pH值（6.0～7.5）、分層現(xiàn)象等評價指標(biāo)，又能通過穩(wěn)定性試驗，作為最優(yōu)處方。 在質(zhì)量標(biāo)準(zhǔn)研究部分，據(jù)藥物劑型的特點和制劑的標(biāo)準(zhǔn)，對各項指標(biāo)進(jìn)行質(zhì)量監(jiān)控。為保證藥物臨床應(yīng)用的安全性，我們對雜質(zhì)進(jìn)行了限量考察，對防腐劑苯氧乙醇進(jìn)行了定量考察。用高效液相色譜法進(jìn)行有關(guān)物質(zhì)檢測和主藥含量測定，防腐劑的測定采用的是氣相色譜法。對小試三批的樣品進(jìn)行測定，防腐劑的平均含量為0.498，主藥平均含量為99.67%，有關(guān)物質(zhì)均未檢出。 為保證制劑的有效性及臨床應(yīng)用安全性，我們對鹽酸阿莫羅芬乳膏進(jìn)行穩(wěn)定性試驗，其考察項目主要有影響因素試驗、加速試驗和長期穩(wěn)定性試驗和開包裝穩(wěn)定性試驗。在影響因素試驗中，高溫情況下降解出了雜質(zhì)Ro16-8652，5天為0.159%、10天為0.183%。穩(wěn)定性試驗結(jié)果給藥物制劑的儲藏條件提供了理論依據(jù)，該制劑應(yīng)該密封置于涼暗處。 最后，我們對所研制的鹽酸阿莫羅芬乳膏的體外透皮吸收試驗進(jìn)行了方法學(xué)驗證，測定其體外透皮量，并與市售乳膏進(jìn)行了比對，透皮速率分別為2.2401g·(cm2)-1·h-1和2.3359　g·(cm2)-1·h-1，實驗結(jié)果表明自制乳膏與市售乳膏的單位面積累積透皮量相近，它們的療效相當(dāng)，自制乳膏能夠達(dá)到臨床可替代性。
[Abstract]:In daily life, dermatomycosis is very common, it is easy to be infected, infectious and recurrent frequently, which seriously affects the quality of life of patients. At present, topical antifungal drugs are mainly used in the treatment of dermatomycosis.As a new type of antifungal drugs, amoxifene has strong antimicrobial activity, and many common pathogenic bacteria are sensitive to it, such as dermatophytes, yeasts, cytosporaceae, biphasic fungi and some conditional pathogenic fungi.Amoxifene hydrochloride can be absorbed by nail protein when it is used locally, it has double inhibitory effect on 14 reductase and 78 isomerase, and can effectively kill and suppress common pathogenic bacteria (dermatophytes, dermatophytes).Yeasts and molds have very high pharmacological activity in vitro.In this paper, amoxifen hydrochloride was used as the model drug, and the dosage form was used as cream, its specification was 0.25, and the following four aspects were studied.In the research part of prescription technology, according to the need of preventing and treating diseases, the cream of skin disease is generally chosen as the best dosage form, while the cream of emulsion type matrix is easier to coat, absorb better, and also has protective effect on skin.Functional excipients such as preservative and pH regulator were added to the prescription and the dosage of emulsifier and oil phase was selected to determine the optimal formulation.After the prescription was preliminarily determined, the pH value and stratification were taken as the initial evaluation indexes, and the samples of the prepared cream were retained, and the prescription was designed according to the retention results.The selected prescription can not only meet the evaluation indexes of pH value 6.0 and 7.5, stratification, but also can be used as the best prescription through the stability test.In the part of quality standard research, according to the characteristics of drug dosage form and the standard of preparation, the quality control of each index is carried out.In order to ensure the safety of drug clinical application, the impurity was limited and the preservative phenoxyethanol was quantitatively investigated.High performance liquid chromatography (HPLC) was used for the determination of related substances and main drug content, and gas chromatography was used for the determination of preservatives.The results showed that the average content of preservative was 0.498, the average content of main drug was 99.677.All the related substances were not detected.In order to ensure the efficacy of the preparation and the safety of clinical application, the stability test of amoxifene hydrochloride cream was carried out. The main items of the study were factor test, accelerated test, long-term stability test and open package stability test.In the experiment of influencing factors, the impurity Ro16-8652O5 days was 0.159% and 0.183% in 10 days.The stability test results provide a theoretical basis for the storage conditions of the drug preparation, which should be sealed in a cool dark place.Finally, the method of in vitro transdermal absorption test of amoxifene hydrochloride cream was verified, and the amount of in vitro transdermal absorption was determined and compared with that of commercial cream.The transdermal rate was 2.2401g / cm ~ (2) ~ (-1) h ~ (-1) and 2.3359 g / cm ~ (-2) 路h ~ (-1), respectively. The experimental results showed that the cumulative transdermal amount per unit area of self-made cream was similar to that of marketable cream, and the efficacy of self-made cream was similar, and the self-made cream could be substituted clinically.
【學(xué)位授予單位】：湖北中醫(yī)藥大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R944

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