本文選題：氯硝柳胺　切入點：納米懸浮液　出處：《華中科技大學(xué)》2007年碩士論文　論文類型：學(xué)位論文

【摘要】： 氯硝柳胺是一種水楊酰替苯胺類化合物,因殺螺效果好,對人畜毒性低,為WHO唯一推薦使用的殺螺藥。但由于氯硝柳胺溶解度小,水中分散度差,因而懸浮率低,限制了其滅螺效果的充分發(fā)揮。因此如何增加溶解度和懸浮率,是提高氯硝柳胺滅螺效果的關(guān)鍵問題。藥物納米懸浮液是近幾年發(fā)展起來的一種納米載藥系統(tǒng),它能夠增加難溶性藥物的溶解度和藥物溶出速率,提高難溶性藥物的藥用效果,另外,具有制備工藝簡單、載藥量高等特點。本文將納米懸浮液引入氯硝柳胺的制劑研究,對難溶性藥物的制劑研究具有一定的參考意義。同時,開展了氯硝柳胺涂膜劑的制劑工藝與質(zhì)量研究,為氯硝柳胺外用制劑的研究發(fā)展開創(chuàng)了新的思路。主要完成的研究工作有: (1)采用高壓勻質(zhì)法,制備了氯硝柳胺納米懸浮液�？疾炝藵櫇駝┑姆N類和用量、助懸劑的種類和用量、載體的種類對懸浮性能的影響,以及勻質(zhì)壓力、循環(huán)次數(shù)對粒徑的影響和該方法的重現(xiàn)性。結(jié)果表明,影響藥物納米粒粒徑的主要因素是勻質(zhì)壓力和循環(huán)次數(shù):隨著勻質(zhì)壓力和循環(huán)次數(shù)的增加,藥物納米懸浮液的粒徑呈減小趨勢,并呈現(xiàn)良好的分散性。通過對勻質(zhì)壓力及循環(huán)次數(shù)的控制,可以制得符合粒徑要求的氯硝柳胺納米懸浮液。并且高壓勻質(zhì)法具有高度重現(xiàn)性。另外,表面活性劑的存在,可以在一定程度上抑制納米顆粒的團(tuán)聚,維持體系的穩(wěn)定性。 (2)對用高壓勻質(zhì)法制備的氯硝柳胺納米懸浮液,進(jìn)行了表征及理化性質(zhì)研究。透射電鏡顯示為球形或近球形顆粒。納米懸浮液的懸浮率遠(yuǎn)高于可濕性粉劑。而且,懸浮穩(wěn)定性提高,懸浮時間明顯延長。 (3)為提高氯硝柳胺納米懸浮液的穩(wěn)定性,采用噴霧干燥技術(shù)制備了氯硝柳胺納米懸浮液的噴干粉�？疾炝烁邏簞蛸|(zhì)法制備的氯硝柳胺納米懸浮液噴霧干燥后的性質(zhì),圖像分析顯示為交聯(lián)狀結(jié)構(gòu)。噴干粉中氯硝柳胺的溶解百分率遠(yuǎn)高于氯硝柳胺原藥,懸浮率也高于氯硝柳胺可濕性粉劑,潤濕性有了明顯改善。而且,懸浮穩(wěn)定性提高,懸浮時間延長。 (4)進(jìn)行了氯硝柳胺納米懸浮液的藥效學(xué)研究。試驗結(jié)果表明:在相同條件下,氯硝柳胺納米懸浮液的滅螺效果是市售可濕性粉劑的2倍;為達(dá)到相同的滅螺效果,納米懸浮液的用藥量是市售可濕性粉劑的一半,大大減少了用藥量。而且,隨著用藥量的減少,藥物產(chǎn)生的毒副作用相應(yīng)降低,同時也減少了對環(huán)境的污染,這具有較強(qiáng)的實際應(yīng)用價值。 (5)進(jìn)行了氯硝柳胺涂膜劑的處方及工藝研究。制成的不含藥物的制劑為無色透明、澄清狀液體,含有藥物的涂膜劑為亮黃色、透明澄清狀液體。藥物和成膜材料之間無沉淀、變色等配伍禁忌現(xiàn)象發(fā)生,易涂展,涂布后具有快干性能,能夠形成干燥的薄膜。薄膜具有良好的附著性、均勻性和一定的抗撕裂性,不易破碎脫落,涂于皮膚表面后手感滑爽、無異物感;與皮膚具有良好的藕合性,使用后易去除,不污染衣物。 (6)進(jìn)行了氯硝柳胺涂膜劑的質(zhì)量研究。制劑具有較好的流動性和成膜性,可均勻涂布于皮膚上,所成藥膜具有較好的可塑性,易于揭布。含量測定準(zhǔn)確可行,方法簡便。制劑質(zhì)量穩(wěn)定,無明顯的皮膚刺激性。配成液體制劑后,基質(zhì)質(zhì)量穩(wěn)定,不含可見固體成分。常溫下密閉儲藏,粘稠度很少變化,不發(fā)生敗壞等變質(zhì)現(xiàn)象。用乙基纖維素作為成膜材料制成的涂膜劑,符合涂膜劑所規(guī)定的質(zhì)量要求和標(biāo)準(zhǔn),可以作為一種成膜材料在某些難溶性藥物的涂膜劑配制中使用。
[Abstract]:Niclosamide is a salicyloyl aniline compound, with excellent molluscicidal effect, low toxicity to human and animals, WHO is the only recommended molluscacide. But because of niclosamide low solubility and poor dispersion in water, so the suspension rate is low, limiting its full play of molluscicidal effect because of this. How to increase the solubility and suspension rate, is a key problem to improve the molluscicidal effect. Nano drug suspension is a kind of nanoparticle drug delivery system developed in recent years, it can increase the solubility of drugs and drug dissolution rate, improve the insoluble medicinal effects of drugs in addition, it has simple preparation process, high drug loading characteristics. This paper will study on Preparation of nano suspension into niclosamide, has certain reference value for the preparation of poorly soluble drugs. At the same time, to carry out the research process and quality of preparation of niclosamide film coating agent, chlorine The research and development of the external use of nitrine has created new ideas. The main research work is as follows:
(1) by high-pressure homogenization method, niclosamide nano suspension was prepared. The influences of the type and amount of wetting agent, suspending agent type and dosage, the effect of carrier type on suspension performance, and homogenization pressure, reproducibility of the effects of the number of cycles to the particle size and the method. The results show that the main factors affecting drug particle size is the homogenization pressure and cycle number: with the increase of homogenization pressure and cycle number, nano drug suspension particle size decreased, and showed good dispersion. Based on the homogenization pressure and cycle number control, can be prepared in accordance with the size requirement of niclosamide nano suspension and high pressure homogenization method has high reproducibility. In addition, the existence of surfactant, nano particles may be inhibited to a certain extent, reunion, maintaining the stability of the system.
(2) the prepared by high-pressure homogenization of niclosamide nano suspension, studied the characterization and physicochemical properties. TEM showed the spherical or nearly spherical particles. The nano suspension suspension rate is much higher than that of WP. Moreover, suspension stability, suspension time was prolonged.
(3) in order to improve the stability of niclosamide nano suspension, spray powder of niclosamide nano suspension was prepared by spray drying process was studied. The properties of niclosamide nano suspension spray prepared by high-pressure homogenization after drying, the image analysis showed that the crosslinking structure dissolved percentage. Niclosamide spray powder of niclosamide is much higher than that of TC, suspension rate is also higher than niclosamide wettable powders, the wettability is improved significantly. Moreover, the suspension stability, suspension time prolonged.
(4) the efficacy of niclosamide nano suspension was studied. Experimental results show that under the same conditions, the molluscicidal effect of niclosamide nano suspension is commercially available WP 2 times; in order to achieve the molluscicidal effect of the same dosage of nanoparticles suspension is the sale of half wet powder, greatly reducing the dosage. Moreover, with reducing the dosage of the drug, the toxic and side effects caused by decreased, but also reduce the pollution of the environment, which has a strong practical value.
(5) studied the prescription and process of niclosamide film. Preparations made without drugs are colorless and transparent, clear liquid, containing the drug coating agent for the bright yellow, transparent liquid. No precipitation between drug and membrane materials, occurrence of discoloration incompatibility phenomenon, easy to spread show, after coating with quick drying performance, can form a dry film. The film has good adhesion, uniformity and tear resistant, not easy to be broken off, coating on the skin surface smooth, no foreign body sensation; has good coupling with the skin, easy removal after use, no pollution to clothes.
(6) studied the quality of niclosamide film. The preparation has good fluidity and film-forming properties can be uniformly coated on the skin, the medicine film has good plasticity, easy to peel cloth. Content determination method is simple, accurate and feasible. The quality is stable, no obvious skin irritation. With liquid preparation, matrix quality and stability, do not contain visible solid components. Under normal temperature and airtight storage, the viscosity of little change, no corrupt phenomenon. Using ethyl cellulose as metamorphosed into membrane material coating agent, coating agent to meet the quality requirements stipulated and standard, can be used as a membrane material in some insoluble drug coating agent prepared in use.

【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2007
【分類號】：R184

【引證文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前1條

1 范彥令;CA口服納米制劑的研究[D];河北醫(yī)科大學(xué);2011年

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本文編號：1645942