本文選題：微乳碘 + 偽三元相圖�。� 參考：《山西醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:本文以微乳作為藥物載體,制備微乳碘,優(yōu)化其制備工藝,并對(duì)微乳碘制劑進(jìn)行質(zhì)量評(píng)價(jià)、抗菌性評(píng)價(jià)和安全性評(píng)價(jià)。方法:(1)從主藥碘的化學(xué)性質(zhì)出發(fā),通過偽三元相圖篩選合適的油相(Oil)、表面活性劑(Surfactant,SF)、助表面活性劑(Cosurfactant,CoSF);確定微乳中油相、表面活性劑、助表面活性劑和水相的最適組成比例及制備工藝,將單質(zhì)碘制備成O/W型微乳碘。(2)根據(jù)2002版《消毒技術(shù)規(guī)范》項(xiàng)下有關(guān)規(guī)定對(duì)所得制劑進(jìn)行質(zhì)量評(píng)價(jià),通過外觀形態(tài)、pH、黏度、密度、粒徑等指標(biāo)進(jìn)行微乳碘的理化性質(zhì)評(píng)價(jià);利用高效液相色譜法(HPLC)建立微乳碘中碘的含量測(cè)定方法并對(duì)該方法進(jìn)行方法學(xué)考察;進(jìn)行藥物制劑穩(wěn)定性試驗(yàn),考察其儲(chǔ)存條件、時(shí)間等。(3)考察制備所得微乳碘對(duì)金黃色葡萄球菌、大腸桿菌、白色念珠球菌和銅綠假單胞菌的抗菌活性,為微乳碘中碘的有效濃度確定及其抗菌效果提供科學(xué)依據(jù);通過耐藥菌試驗(yàn),進(jìn)一步考察微乳碘對(duì)耐藥菌的殺滅效果;通過生物被膜試驗(yàn),初步探究微乳碘的抗菌機(jī)理。(4)以家兔皮膚為受試對(duì)象,進(jìn)行完整皮膚、破損皮膚試驗(yàn)及皮內(nèi)刺激性試驗(yàn),對(duì)微乳碘進(jìn)行安全性考察及評(píng)價(jià)。結(jié)果:(1)通過偽三元相圖,篩選得到微乳碘的油相(Oil)為乙酸丁酯、表面活性劑(SF)為吐溫-80、助表面活性劑(CoSF)為無水乙醇。處方組成為Km=1:1,SF/CoSF:Oil=8:2,SF/CoSF+Oil=55%,即乙酸丁酯為11%、吐溫-80為22%、無水乙醇為22%、蒸餾水為44.5%、碘為0.5%(g/100 mL)。制備工藝為:吐溫-80與無水乙醇混合均勻后,加入乙酸丁酯,再次加入主藥,最后加入水相。在25℃條件下,1300~2000 r/min磁力攪拌速度,攪拌30 min制備所得。(2)微乳碘的外觀為酒紅色澄清透明液體;粒徑分布均在10~100 nm之間;平均黏度值為35.8 mPa.s;平均密度值為1.0095 g/cm3;pH為3.30~4.00。采用HPLC測(cè)定微乳碘中有效碘的含量:I3-的線性范圍為0.08~0.50 mg/m L,日內(nèi)精密度的RSD值為0.5%~1.0%,日間精密度的RSD值為0.8%~1.3%,回收率結(jié)果在97.2%~105.6%之間,平均回收率為100.8%,RSD值為3.1%,自制微乳碘以碘二分子計(jì)有效碘的含量約為1.383~1.472 mg/mL,每批次之間含量測(cè)定結(jié)果的RSD值0.5%~1.0%。穩(wěn)定性試驗(yàn)結(jié)果表明,微乳碘除在高溫、強(qiáng)光條件下含量稍有下降外,在低溫條件及加速試驗(yàn)中穩(wěn)定性良好,各組分外觀均無明顯變化。(3)自制微乳碘對(duì)金黃色葡萄球菌、銅綠假單胞菌的最小抑菌濃度(MIC)為0.012mg/m L,對(duì)白色念珠菌和大腸桿菌的MIC為0.023 mg/m L;四種菌的最小殺菌濃度(MBC)不大于0.094 mg/mL;有效碘含量在0.012~0.090 mg/m L范圍,于2 min內(nèi)對(duì)四種菌的抑菌率、殺菌率均達(dá)100%。耐藥菌試驗(yàn)中微乳碘對(duì)耐咪唑類藥物的克柔念珠菌的MIC、MBC均為0.125 mg/m L。生物被膜試驗(yàn)結(jié)果初步顯示,微乳碘能有效抑制白色念珠菌菌體生物被膜的生長(zhǎng),從而達(dá)到殺菌或抑菌的作用。(4)有效碘含量為1.500 mg/m L時(shí)對(duì)家兔完整皮膚、破損皮膚及皮內(nèi)均無刺激性反應(yīng)。結(jié)論:本文從處方篩選、制備工藝考察、質(zhì)量評(píng)價(jià)、抗菌性評(píng)價(jià)和安全性評(píng)價(jià)等方面進(jìn)行探討,成功制備出微乳碘。該制劑將碘包裹具有增加水溶性、掩蓋碘刺激性氣味、減少碘揮發(fā)等特點(diǎn)。各項(xiàng)指標(biāo)完全符合2002版《消毒技術(shù)規(guī)范》“2.1.1”項(xiàng)下消毒劑殺微生物試驗(yàn),“2.3.3”項(xiàng)下皮膚刺激試驗(yàn)及2015版《中國(guó)藥典》第四部“原料藥與藥物制劑穩(wěn)定性試驗(yàn)指導(dǎo)原則”項(xiàng)下操作的有關(guān)規(guī)定。是一種有效碘的起效濃度低、殺菌抑菌時(shí)間短、皮膚無刺激、殺菌譜廣的安全高效的皮膚外用消毒制劑。擬為皮膚外用含碘消毒制劑提供一種新的劑型,具有一定的實(shí)際應(yīng)用價(jià)值。
[Abstract]:Objective: microemulsion was used as a drug carrier to prepare microemulsion iodine and optimize its preparation technology. The quality evaluation, antibacterial evaluation and safety evaluation of microemulsion iodine preparation were carried out. Methods: (1) screening suitable oil phase (Oil), surface active agent (Surfactant, SF), and surfactant (Cosu) from the chemical properties of the main drug iodine. Rfactant, CoSF); determine the optimum composition ratio and preparation process of oil phase, surfactant, surfactant and water phase in microemulsion, and prepare iodine to form O/W microemulsion iodine. (2) evaluate the quality of the obtained preparation according to the regulations of the 2002 edition < disinfection technical specification > by appearance morphology, pH, viscosity, density, particle size and so on. The physicochemical properties of microemulsion iodine were evaluated, the determination method of iodine content in microemulsion iodine was established by high performance liquid chromatography (HPLC) and the method was investigated. The stability test of drug preparation was carried out to investigate the storage conditions and time. (3) the microemulsion iodine was investigated for Staphylococcus aureus, Escherichia coli, Candida albicans and Candida albicans. The antibacterial activity of Pseudomonas aeruginosa provides a scientific basis for the determination of the effective concentration of iodine in microemulsion iodine and its antibacterial effect. Through the test of resistant bacteria, the killing effect of microemulsion iodine on the resistant bacteria is further investigated. Through the biofilm test, the antibacterial mechanism of microemulsion iodine is preliminarily explored. (4) the skin of rabbit is taken as the subject of the skin, and the whole skin is carried out. The safety of microemulsion iodine was investigated and evaluated in damaged skin test and intradermal stimulation test. Results: (1) through the pseudo three element phase diagram, the oil phase of microemulsion (Oil) was selected as butyl acetate, surface active agent (SF) was Twain -80, and surface active agent (CoSF) was anhydrous ethanol. The formulation was Km=1:1, SF/CoSF:Oil=8:2, SF/CoSF+Oil=55%, that is, Butyl acetate is 11%, Twain -80 is 22%, anhydrous ethanol is 22%, distilled water is 44.5%, iodine is 0.5% (g/100 mL). The preparation process is that Twain -80 and anhydrous ethanol are mixed evenly, adding butyl acetate, adding the main drug and adding the water phase. At 25 centigrade conditions, 1300~2000 r/min magnetic stirring speed and stirring 30 min are prepared. (2) microemulsion iodine The appearance is wine red clear clear liquid; the particle size distribution is between 10~100 nm, the average viscosity value is 35.8 mPa.s, the average density value is 1.0095 g/cm3; pH is 3.30~4.00. using HPLC to determine the content of effective iodine in microemulsion iodine: the linear range of I3- is 0.08~0.50 mg/m L, the RSD value of the intra day precision is 0.8%, and the value of the day precision is 0.8% ~1.3%, the recovery rate is between 97.2%~105.6%, the average recovery rate is 100.8%, the RSD value is 3.1%. The content of effective iodine for the self-made microemulsion iodine two molecular meter is about 1.383~1.472 mg/mL, and the RSD value 0.5%~1.0%. stability test results of the content determination results between each batch show that the content of microemulsion iodine is slightly lower than that under high temperature and strong light condition. The stability was good in low temperature and accelerated test. (3) the minimum inhibitory concentration (MIC) of self-made microemulsion for Staphylococcus aureus and Pseudomonas aeruginosa was 0.012mg/m L, MIC of Candida albicans and Escherichia coli was 0.023 mg/m L, and the minimum bactericidal concentration (MBC) of four bacteria was not more than 0.094 mg/mL; The iodine content was in the range of 0.012~0.090 mg/m L, the bacteriostasis rate of four bacteria in 2 min, the bactericidal rate reached MIC of microemulsion iodine to imidazole resistant Candida krilicus in the test of 100%. resistant bacteria, and MBC was 0.125 mg/m L. biological membrane test results preliminarily showed that microemulsion iodine could effectively inhibit the growth of the biofilm of Candida albicans. The effect of bactericidal or bacteriostasis was achieved. (4) when the effective iodine content was 1.500 mg/m L, there was no irritation response to the intact skin of the rabbit, the damaged skin and the skin. Conclusion: in this paper, the microemulsion iodine was successfully prepared from the prescription screening, preparation process, quality evaluation, antibacterial evaluation and safety evaluation. It has the characteristics of increasing water solubility, covering iodine irritating odor, reducing iodine volatilization and so on. Each index is fully in conformity with the 2002 edition of disinfectant microbicide test under "disinfection technical specification >" "2.1.1", skin irritation test under "2.3.3" and "guidelines for the stability test guiding principle of 2015 editions of Chinese Pharmacopoeia," "Chinese Pharmacopoeia" and "drug preparation". It is a kind of safe and efficient skin disinfectant preparation with low concentration of effective iodine, short time of bacteriostasis and bacteriostasis, no irritation of skin and wide sterilization spectrum. It will provide a new dosage form for iodine containing iodine disinfection preparation, which has certain practical application value.
【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

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 魏玉;蘇成福;;雙氯芬酸鈉微乳的家兔皮膚刺激性及體外透皮吸收性能評(píng)價(jià)[J];中國(guó)藥房;2017年04期

2 唐紅艷;陳曉蘭;吳玉梅;魏文珍;戴雅潔;;微乳在經(jīng)皮給藥系統(tǒng)中的應(yīng)用研究進(jìn)展[J];貴陽中醫(yī)學(xué)院學(xué)報(bào);2016年05期

3 陳浩;陳敏;劉蕊;;恩拉霉素自微乳制劑的研制及質(zhì)量評(píng)價(jià)[J];中國(guó)藥學(xué)雜志;2016年14期

4 趙惠茹;張鵬;劉少靜;靖會(huì);楊陽;邊軍昌;;偽三元相圖法研究蘆丁自微乳化釋藥系統(tǒng)的制備工藝[J];中國(guó)藥師;2016年07期

5 梅芬;曾維東;萬濤;黃杰偉;羅雙輝;吳傳斌;徐月紅;;醋酸地塞米松微乳的制備及對(duì)皮膚滲透性的影響[J];藥學(xué)學(xué)報(bào);2016年06期

6 郭為;菲索查克;黃燕;黃群;符靜泉;胡超;蔣偉哲;黃興振;;HPLC法測(cè)定漢防己甲素自微乳中漢防己甲素的含量[J];海峽藥學(xué);2016年04期

7 廖祥茹;方松;史瓊枝;陳鷹;;HPLC測(cè)定銀杏總黃酮自乳化微乳中銀杏總黃酮的含量[J];中國(guó)藥師;2016年04期

8 胡月明;謝茵;趙m:藝;郭銳;郭國(guó)亮;畢小平;;高效液相色譜法測(cè)定黑糯玉米軸黑色素凝膠中矢車菊素-3-葡萄糖苷的含量[J];中國(guó)藥物與臨床;2016年02期

9 景春娥;李萍;杜欣軍;伍小密;王碩;;黃芩苷對(duì)阪崎克羅諾桿菌生物膜的抑制作用[J];微生物學(xué)通報(bào);2016年08期

10 孫林芳;鄭廣娟;馮兵;朱瑩;賀嵩敏;劉映;牟潔;;白術(shù)揮發(fā)油微乳的制備[J];中成藥;2015年04期

相關(guān)會(huì)議論文 前1條

1 辛學(xué)俊;;聚維酮碘溶液“孕婦禁用”解讀[A];2008年中國(guó)藥學(xué)會(huì)學(xué)術(shù)年會(huì)暨第八屆中國(guó)藥師周論文集[C];2008年

相關(guān)碩士學(xué)位論文 前8條

1 郭亞萍;一種新型復(fù)合碘消毒液的研制及其相關(guān)性能實(shí)驗(yàn)研究[D];山東大學(xué);2016年

2 郭超;丁香提取物外用微乳劑研制及藥效評(píng)價(jià)[D];西北農(nóng)林科技大學(xué);2016年

3 牛亞楠;二氧化氯噴霧劑的制備與評(píng)價(jià)及其止血機(jī)理研究[D];山西醫(yī)科大學(xué);2014年

4 任秋月;布洛芬微乳經(jīng)皮給藥制劑的研究[D];復(fù)旦大學(xué);2014年

5 金偉;納米銀脂質(zhì)體凝膠的制備及質(zhì)量評(píng)價(jià)和藥效及安全性評(píng)價(jià)[D];山西醫(yī)科大學(xué);2013年

6 白波;甲基丁香酚微乳的研制及其殺螨活性研究[D];西北農(nóng)林科技大學(xué);2011年

7 閆薈羽;穿心蓮內(nèi)酯微乳經(jīng)皮給藥系統(tǒng)的研究[D];吉林大學(xué);2010年

8 王晶;氫溴酸東莨菪堿微乳透皮制劑的研究[D];第二軍醫(yī)大學(xué);2008年

，

本文編號(hào)：2100914