鹽酸沃尼妙林制劑的制備及抗菌效果研究
發(fā)布時(shí)間：2019-03-26 15:32
【摘要】：鹽酸沃尼妙林(VAlnemulin,縮寫(xiě)為：VA)為新一代半合成類(lèi)動(dòng)物專用抗生素,屬于二萜烯類(lèi)。在獸醫(yī)臨床上國(guó)外主要用于預(yù)防和治療由革蘭氏陽(yáng)性菌及支原體引起的各種動(dòng)物疾病。具有抗菌譜廣、抗菌活性相對(duì)較強(qiáng),半衰期短、首過(guò)效應(yīng)顯著、血漿濃度受給藥方法影響等特點(diǎn)。本文制備了VA透皮軟膏劑、甘油明膠栓及顆粒劑,并且對(duì)其抗菌效果進(jìn)行了研究。 1.甘油明膠栓的制備及其對(duì)陰道炎效果的研究 1.1甘油明膠栓的制備 水溶性基質(zhì)PEG類(lèi)、甘油明膠類(lèi)；油脂性基質(zhì)主要是半合成脂肪酸甘油酯為基質(zhì),采用熱熔法,以栓劑的溶出度、融變時(shí)限為考察指標(biāo)篩選基質(zhì)的種類(lèi)與用量。結(jié)果顯示：用熱熔法制備的甘油明膠栓性質(zhì)穩(wěn)定。 1.2甘油明膠栓的質(zhì)量評(píng)價(jià) 參照《中國(guó)獸藥典》(2010版)對(duì)制備的栓劑進(jìn)行外觀、重量差異、融變時(shí)限及溶出度檢查,結(jié)果可知,各項(xiàng)均符合《中國(guó)獸藥典》(2010版)要求,且質(zhì)量穩(wěn)定。 1.3甘油明膠栓對(duì)細(xì)菌性陰道炎治療效果研究 對(duì)大鼠分別采用單次及多次陰道給藥,進(jìn)行刺激性試驗(yàn),并用金黃色葡萄球菌感染大鼠的陰道,再用VA栓治療,并評(píng)價(jià)其藥效。結(jié)果表明,該制劑對(duì)大鼠的陰道無(wú)刺激性；VA栓低、中、高(50、100、150mg·Kg-1)劑量陰道給藥對(duì)金黃色葡萄球菌的總的轉(zhuǎn)陰率分別為60%、100%、100%,VA栓中、高劑量與奧硝唑栓(100mg·Kg-1)療效相當(dāng),無(wú)顯著性差異(P0.05)。 2.軟膏劑的制備及抗菌效果研究 采用乳化法分別制備W/O型和O/W型VA軟膏劑,并用高效液相色譜法測(cè)定軟膏劑中VA的體外透皮釋藥率。結(jié)果表明,W/O型、O/W型軟膏劑10h的體外透皮釋藥率分別為30%±0.42%、18.45%±0.69%。體外抑菌實(shí)驗(yàn)表明,W/O型對(duì)金黃色葡萄球菌的抑制作用更顯著,制備的兩種軟膏劑穩(wěn)定性均良好。 3.顆粒劑的制備及其對(duì)大腸桿菌性腹瀉治療效果研究 3.1顆粒劑的制備工藝優(yōu)化 采用濕法制粒制備VA顆粒劑,以顆粒劑的成型性、吸濕率和溶化性為考察指標(biāo),篩選輔料的種類(lèi)及用量。結(jié)果表明,制備的顆粒劑質(zhì)量符合《中國(guó)獸藥典》(2010版)要求,篩選出的最優(yōu)處方工藝合理可行。 3.2顆粒劑的質(zhì)量評(píng)價(jià) 采用濕法制粒制備VA顆粒劑,利用紫外分光光度法測(cè)定顆粒劑中VA的含量,結(jié)果顯示,用UV測(cè)定顆粒劑中VA的含量,方法較簡(jiǎn)便可靠,重現(xiàn)性好。外觀性狀、粒度、干燥失重、溶化性等均符合《中國(guó)獸藥典》(2010版)要求。 3.3顆粒劑對(duì)大腸桿菌性腹瀉治療效果試驗(yàn) 以小鼠為實(shí)驗(yàn)動(dòng)物,用致病性大腸桿菌經(jīng)腹腔注射感染小鼠建立腹瀉模型,4h后給予不同劑量的VA顆粒劑灌胃治療。治療3d后,結(jié)果顯示,VA顆粒劑對(duì)大腸桿菌性腹瀉的治療效果顯著。
[Abstract]:VAlnemulin, (: VA) for short) is a new generation of semi-synthetic antibiotics for animals, belonging to diterpene. In veterinary clinic, it is mainly used to prevent and treat all kinds of animal diseases caused by gram-positive bacteria and mycoplasma. It has broad antibacterial spectrum, relatively strong antibacterial activity, short half-life, remarkable first-pass effect, and the plasma concentration is affected by the method of administration. In this paper, VA transdermal ointment, glycerol gelatin suppository and granules were prepared, and their antibacterial effects were studied. 1. Study on the preparation of Glycerin Gelatin suppository and its effect on vaginitis 1.1 preparation of Glycerin-Gelatin suppository Water soluble Matrix PEG and Glycerol Gelatin; The fatty matrix is mainly semisynthetic fatty acid glyceryl ester as the matrix. The type and dosage of the matrix are screened by hot melt method, the dissolution degree of suppository and the melting time. The results showed that the properties of glycerol gelatin suppository prepared by hot melt method were stable. The quality evaluation of glycerol gelatin suppositories was carried out according to the Chinese Veterinary Pharmacopoeia (2010 Edition), including the appearance, weight difference, melting time and dissolution of the suppositories. All the items meet the requirements of China Veterinary Pharmacopoeia (version 2010), and the quality is stable. 1.3 effect of Glycerol Gelatin suppository on bacterial vaginitis: single and multiple vaginal administration of glycerol gelatin suppositories were performed in rats, and staphylococcus aureus was used to infect the vaginas of rats, and then VA suppository was used to treat the vaginitis of rats. And evaluate its efficacy. The results showed that the preparation had no vaginal irritation in rats. The total negative conversion rates of VA suppositories to staphylococcus aureus were 60%, 100%, 100% in low, middle and high dose (50100150mg Kg-1) vaginal administration, respectively. In VA suppository, the efficacy of high dose was similar to that of ornidazole suppository (100mg Kg-1). There was no significant difference (P0.05). 2. Study on preparation and antibacterial effect of ointment the W / O and O / W VA ointment were prepared by emulsion method, and the in vitro transdermal release rate of VA in the ointment was determined by high performance liquid chromatography (HPLC). The results showed that the in vitro transdermal release rates of W / O and O / W ointment for 10 h were 30% 鹵0.42% and 18.45% 鹵0.69%, respectively. The bacteriostatic test in vitro showed that W / O type had more obvious inhibitory effect on Staphylococcus aureus, and the stability of two kinds of ointment prepared was good. 3. Study on the preparation of granules and their Therapeutic effects on Escherichia coli diarrhea; 3.1.The preparation process of VA granules was optimized by wet granulation. The formability, moisture absorption and solubility of the granules were used as the indexes, and the results were as follows: (1) the size of the granules was higher than that of the control group. Screening the type and dosage of auxiliary materials. The results showed that the quality of the prepared granules met the requirements of China Veterinary Pharmacopoeia (2010 Edition), and the optimal prescription process was reasonable and feasible. The quality of VA granules was evaluated by wet granulation. The content of VA in granules was determined by ultraviolet spectrophotometry. The results showed that the method was simple and reliable for the determination of VA in granules by UV. Good reproducibility. Appearance properties, grain size, drying weight loss, solubility and so on meet the requirements of China Veterinary Pharmacopoeia (2010 Edition). Experimental study on the therapeutic effect of granule on coliform diarrhea in mice. Diarrhea model was established by intraperitoneal injection of pathogenic Escherichia coli in mice. Four hours later, different doses of VA granules were given intragastrically to treat diarrhea in mice. After 3 days treatment, the results showed that VA granules were effective in the treatment of coliform diarrhea.
【學(xué)位授予單位】：西南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R943;R965
本文編號(hào)：2447686
[Abstract]:VAlnemulin, (: VA) for short) is a new generation of semi-synthetic antibiotics for animals, belonging to diterpene. In veterinary clinic, it is mainly used to prevent and treat all kinds of animal diseases caused by gram-positive bacteria and mycoplasma. It has broad antibacterial spectrum, relatively strong antibacterial activity, short half-life, remarkable first-pass effect, and the plasma concentration is affected by the method of administration. In this paper, VA transdermal ointment, glycerol gelatin suppository and granules were prepared, and their antibacterial effects were studied. 1. Study on the preparation of Glycerin Gelatin suppository and its effect on vaginitis 1.1 preparation of Glycerin-Gelatin suppository Water soluble Matrix PEG and Glycerol Gelatin; The fatty matrix is mainly semisynthetic fatty acid glyceryl ester as the matrix. The type and dosage of the matrix are screened by hot melt method, the dissolution degree of suppository and the melting time. The results showed that the properties of glycerol gelatin suppository prepared by hot melt method were stable. The quality evaluation of glycerol gelatin suppositories was carried out according to the Chinese Veterinary Pharmacopoeia (2010 Edition), including the appearance, weight difference, melting time and dissolution of the suppositories. All the items meet the requirements of China Veterinary Pharmacopoeia (version 2010), and the quality is stable. 1.3 effect of Glycerol Gelatin suppository on bacterial vaginitis: single and multiple vaginal administration of glycerol gelatin suppositories were performed in rats, and staphylococcus aureus was used to infect the vaginas of rats, and then VA suppository was used to treat the vaginitis of rats. And evaluate its efficacy. The results showed that the preparation had no vaginal irritation in rats. The total negative conversion rates of VA suppositories to staphylococcus aureus were 60%, 100%, 100% in low, middle and high dose (50100150mg Kg-1) vaginal administration, respectively. In VA suppository, the efficacy of high dose was similar to that of ornidazole suppository (100mg Kg-1). There was no significant difference (P0.05). 2. Study on preparation and antibacterial effect of ointment the W / O and O / W VA ointment were prepared by emulsion method, and the in vitro transdermal release rate of VA in the ointment was determined by high performance liquid chromatography (HPLC). The results showed that the in vitro transdermal release rates of W / O and O / W ointment for 10 h were 30% 鹵0.42% and 18.45% 鹵0.69%, respectively. The bacteriostatic test in vitro showed that W / O type had more obvious inhibitory effect on Staphylococcus aureus, and the stability of two kinds of ointment prepared was good. 3. Study on the preparation of granules and their Therapeutic effects on Escherichia coli diarrhea; 3.1.The preparation process of VA granules was optimized by wet granulation. The formability, moisture absorption and solubility of the granules were used as the indexes, and the results were as follows: (1) the size of the granules was higher than that of the control group. Screening the type and dosage of auxiliary materials. The results showed that the quality of the prepared granules met the requirements of China Veterinary Pharmacopoeia (2010 Edition), and the optimal prescription process was reasonable and feasible. The quality of VA granules was evaluated by wet granulation. The content of VA in granules was determined by ultraviolet spectrophotometry. The results showed that the method was simple and reliable for the determination of VA in granules by UV. Good reproducibility. Appearance properties, grain size, drying weight loss, solubility and so on meet the requirements of China Veterinary Pharmacopoeia (2010 Edition). Experimental study on the therapeutic effect of granule on coliform diarrhea in mice. Diarrhea model was established by intraperitoneal injection of pathogenic Escherichia coli in mice. Four hours later, different doses of VA granules were given intragastrically to treat diarrhea in mice. After 3 days treatment, the results showed that VA granules were effective in the treatment of coliform diarrhea.
【學(xué)位授予單位】：西南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R943;R965
【參考文獻(xiàn)】
相關(guān)期刊論文 前10條
1 謝冬梅,劉叢彬;桂枝茯苓混懸型無(wú)糖顆粒劑的制備工藝研究[J];安徽醫(yī)藥;2005年05期
2 劉艷艷;盛尊來(lái);李繼昌;;獸用藥劑學(xué)的教學(xué)改革與探討[J];東北農(nóng)業(yè)大學(xué)學(xué)報(bào)(社會(huì)科學(xué)版);2007年05期
3 吳廣輝;方炳虎;劉小艷;陳良柱;;新獸藥鹽酸沃尼妙林研究進(jìn)展及使用[J];獸醫(yī)導(dǎo)刊;2007年11期
4 張少華;任麗琴;包永占;秦建華;史萬(wàn)玉;鐘秀會(huì);;復(fù)方中藥軟膏劑的透皮效果研究[J];動(dòng)物醫(yī)學(xué)進(jìn)展;2010年01期
5 顏丹丹;劉小艷;方炳虎;時(shí)書(shū)寧;陳良柱;;鹽酸沃尼妙林預(yù)混劑的研制及其對(duì)豬增生性腸的炎療效觀察[J];動(dòng)物醫(yī)學(xué)進(jìn)展;2012年03期
6 吳潔;段慧琴;楊彩霞;張倩;穆祥;;白頭翁湯對(duì)大腸桿菌造模腹瀉小鼠血清和小腸組織中MPO含量的影響[J];北京農(nóng)學(xué)院學(xué)報(bào);2012年04期
7 章靜;;復(fù)方奧硝唑栓劑的制備及質(zhì)量控制[J];海峽藥學(xué);2007年04期
8 陳興榮;劉曉莎;方炳虎;時(shí)書(shū)寧;劉小艷;;高效液相色譜法測(cè)定沃尼妙林含量的研究[J];黑龍江畜牧獸醫(yī);2011年03期
9 李維;于慧斌;董俊仕;張昭君;王佩琪;;環(huán)丙沙星中空栓的制備及其質(zhì)量控制[J];遼寧醫(yī)學(xué)院學(xué)報(bào);2010年02期
10 梁莉婕;焦立波;高明;;建立動(dòng)物腹瀉模型的常用藥物及方法的研究進(jìn)展[J];遼寧中醫(yī)雜志;2011年08期
，本文編號(hào)：2447686
本文鏈接：http://sikaile.net/yixuelunwen/yiyaoxuelunwen/2447686.html
最近更新
教材專著
