發(fā)布時(shí)間：2018-03-01 19:45

  本文關(guān)鍵詞： 左氧氟沙星 緩釋顆粒 釋放度 穩(wěn)定性 質(zhì)量標(biāo)準(zhǔn)　出處：《武漢工程大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：細(xì)菌感染是一種嚴(yán)重危害家禽生長發(fā)育的疾病。據(jù)報(bào)道,全世界家禽細(xì)菌感染的發(fā)病率高達(dá)50%~70%,爆發(fā)細(xì)菌感染時(shí)家禽的死亡率達(dá)到20%~30%,我國養(yǎng)雞業(yè)每年由于細(xì)菌感染所導(dǎo)致的雞死亡數(shù)量約為3億只,造成的直接經(jīng)濟(jì)損失約30億元,造成的間接損失約100億元。細(xì)菌感染是集約化養(yǎng)雞業(yè)中最為重要的疾病之一,其防治方法主要有免疫控制法和藥物治療法,免疫控制法可起到預(yù)防作用,但是當(dāng)細(xì)菌感染爆發(fā)時(shí)則主要依賴藥物治療,據(jù)統(tǒng)計(jì),全球抗菌藥的年消費(fèi)額超過3億美元。所以,研究高效、低毒、廣譜的抗菌藥物的新劑型、新制劑成為抗細(xì)菌感染藥物開發(fā)和應(yīng)用的非常重要的途徑。在獸醫(yī)臨床上,已有恩諾沙星、二氟沙星、達(dá)氟沙星、氧氟沙星等多種類型抗細(xì)菌感染藥物使用。其中氟喹諾酮類藥物因具有低毒、抗菌譜廣和原料價(jià)格低等優(yōu)勢,在獸醫(yī)臨床上的應(yīng)用很廣泛,主要用于治療敏感菌所致的呼吸道、尿道感染,同時(shí)可以促進(jìn)動(dòng)物的日增重,并且提高飼料轉(zhuǎn)化率。左氧氟沙星是氧氟沙星的光學(xué)活性L-型異構(gòu)體,體外抗菌活性是消旋體的2倍,是右旋體的8~128倍,它是第一個(gè)成功上市的具有較好抗肺炎球菌活性的氟喹諾酮類藥物,分別于1993年和1997年在日本和美國上市,已經(jīng)用于3億多名患者的治療,出現(xiàn)耐藥性的情況極少,對多數(shù)腸桿菌科細(xì)菌有較強(qiáng)的抗菌活性,對化膿性鏈球菌、肺炎鏈球菌、金黃色葡萄球菌等革蘭氏陽性菌和肺炎支原體、衣原體也有一定的抗菌作用,在臨床上應(yīng)用廣泛。但是左氧氟沙星半衰期為6小時(shí),相對較短,在獸醫(yī)臨床使用中,給藥較頻繁,這將增加家禽的應(yīng)激反應(yīng),而且會(huì)因血藥濃度的波動(dòng)增大不良反應(yīng)的幾率,將其制成緩釋顆�；煊陲暳现薪o家禽使用正好可以解決這個(gè)問題。本文對高效廣譜抗菌藥左氧氟沙星的緩釋顆粒劑進(jìn)行了比較系統(tǒng)的研究,主要工作如下:(1)綜述了左氧氟沙星的結(jié)構(gòu)、理化性質(zhì)、作用機(jī)理,并介紹了新制劑技術(shù)緩釋制劑技術(shù),以期用緩釋制劑技術(shù)來減緩左氧氟沙星的釋放,減少服藥次數(shù),減少家禽的應(yīng)激反應(yīng)。在此基礎(chǔ)上,根據(jù)左氧氟沙星原料藥和輔料的理化性質(zhì)、質(zhì)量標(biāo)準(zhǔn),選擇不同用量的骨架材料、填充劑、粘合劑和潤滑劑制備左氧氟沙星緩釋顆粒劑,分別測定其在0.5、1、2、4、6、9、12h藥物的累積釋放度,以2、6、12h的累積釋放度為考察指標(biāo),初步確定處方由左氧氟沙星、蠟質(zhì)骨架材料硬脂酸、親水性骨架材料HPMC、填充劑淀粉、粘合劑PVP、潤滑劑滑石粉組成,制備方法為濕法制粒。(2)通過單因素考察和正交設(shè)計(jì)實(shí)驗(yàn),考查了左氧氟沙星緩釋顆粒的最佳處方。確定最優(yōu)處方為(以1000g計(jì)):左氧氟沙星:250g;硬脂酸:170g;HPMC:500g;淀粉:30g;PVP:50g,滑石粉:適量,用溶出度法對制備的緩釋顆粒釋放度進(jìn)行了考察,并研究了左氧氟沙星緩釋顆粒的釋藥機(jī)制,研究結(jié)果表明Higuchi方程是最優(yōu)的擬合模型。(3)為了能夠有效的控制產(chǎn)品的質(zhì)量,對左氧氟沙星緩釋顆粒的質(zhì)量標(biāo)準(zhǔn)進(jìn)行了比較系統(tǒng)的研究,包括性狀、鑒別、含量測定、釋放度測定等一系列研究,研究結(jié)果表明該制劑制備工藝和產(chǎn)品的質(zhì)量都比較穩(wěn)定。擬定的質(zhì)量標(biāo)準(zhǔn)(草案)可以有效地控制產(chǎn)品質(zhì)量。(4)對左氧氟沙星緩釋顆粒進(jìn)行了穩(wěn)定性考察。加速試驗(yàn)、長期試驗(yàn)結(jié)果表明:模擬市售包裝的左氧氟沙星緩釋顆粒在40±2℃,相對濕度75±5%的實(shí)驗(yàn)條件下放置6個(gè)月,溫度25±2℃,相對濕度60±5%的條件下放置12個(gè)月,樣品質(zhì)量穩(wěn)定。
[Abstract]:Bacterial infection is a serious harm to the growth and development of poultry disease. According to reports, the world poultry and the incidence of bacterial infection was as high as 50%~70%, the outbreak of bacterial infection in poultry mortality rate reached 20%~30%, the poultry industry in our country every year because the number of bacterial infections caused by chicken deaths of about 300 million, causing direct economic losses of about 3 billion yuan, indirect losses of about 10 billion yuan. Bacterial infection in intensive poultry industry is one of the most important disease prevention methods include immune control method and drug treatment method, immune control method can play a preventive role, but when the outbreak of bacterial infection is mainly dependent on the drugs, according to statistics, the year spending more than $300 million in global antibacterial drugs. Therefore, research on efficient, low toxicity, broad-spectrum antimicrobial new formulations, new preparation has become an important way to the development and application of anti bacteria drugs in animals. Clinical medicine, has two difloxacin, enrofloxacin, danofloxacin, ofloxacin and other types of anti infection drug use. The fluoroquinolones with low toxicity, wide antibacterial spectrum and raw materials, low price advantage, application in veterinary clinic is very extensive, mainly used for the treatment of sensitive bacteria caused by respiratory tract infection, at the same time. The increasing promotion of animal weight, and increase the feed conversion rate. Levofloxacin is optically active isomer of L- ofloxacin, in vitro antibacterial activity is 2 times that of racemic dextroisomer is 8~128 times, it is the first successful listing of fluoroquinolones has better anti pneumococcal activity, were listed in Japan and the United States in 1993 and 1997, has been used to treat more than 300 million patients, the emergence of drug resistance situation, has strong anti bacteria activity against Enterobacteriaceae, to fester Streptococcus, Streptococcus pneumoniae, Staphylococcus aureus and gram positive bacteria and Mycoplasma pneumoniae, Chlamydia has antibacterial effect, is widely used in clinic. However, levofloxacin has a half-life of 6 hours, relatively short, in veterinary clinical use, administered more frequently, which will increase the stress in poultry, and likely due to fluctuations in plasma concentrations increased adverse reactions, the sustained-release particles mixed in the feed for poultry use can solve this problem. Sustained-release granule antibiotic levofloxacin based on broad-spectrum were studied systemically. The main work is as follows: (1) reviews the structure of levofloxacin. Physical and chemical properties, action mechanism, and introduces the new preparation technology of sustained-release preparation technology, in order to use levofloxacin sustained-release preparation technology to slow down the release, reduce the frequency of administration, poultry should be reduced Shock response. On this basis, according to the physicochemical properties of levofloxacin, pharmaceutical raw materials and excipients quality standards, selection of skeleton material, different amount of fillers, binders and lubricants for preparation of levofloxacin sustained-release granules were measured in 0.5,1,2,4,6,9,12h drug cumulative release, the cumulative release ratio of 2,6,12h as index, preliminary to determine the prescription by levofloxacin, wax skeleton material, stearic acid, hydrophilic matrix material HPMC, starch filler, adhesive lubricant PVP, talc powder, preparation method for wet granulation. (2) by using single factor test and orthogonal experiment, to examine the best prescription of levofloxacin sustained-release granules. The optimal prescription for (to 1000g): levofloxacin: 250g; stearic acid: 170g; HPMC:500g; 30g; PVP:50g: starch, talcum powder amount, with the dissolution of sustained-release pellets prepared by release of the test The police, and study the drug release mechanism of levofloxacin sustained-release particles, the results show that the Higuchi equation was the best fitting model. (3) in order to effectively control the product quality to the quality standard of levofloxacin sustained-release granules were studied systematically, including character, identification, content determination, dissolution etc. a series of studies, the results show that the quality of the preparation process and products are relatively stable. The quality standard (Draft) can effectively control the quality of the products. (4) of levofloxacin sustained-release granules. Investigated the stability of accelerated test, long-term test results show that the levofloxacin particle simulation commercial packaging in the 40 plus or minus 2 DEG C for 6 months the experimental conditions of relative humidity of 75 + 5%, 25 + 2 degrees Celsius temperature, relative humidity for 12 months was 60 + 5%, the quality of the sample.

【學(xué)位授予單位】：武漢工程大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：S859.79

【相似文獻(xiàn)】

相關(guān)會(huì)議論文 前4條

1 徐志洲;周木陽;;國內(nèi)外單硝酸異山梨酯緩釋制劑釋放度比較[A];2003年藥物分析論壇藥物溶出度學(xué)術(shù)研討會(huì)論文集[C];2003年

2 鄭穩(wěn)生;李紹賢;文瑾;張會(huì)紅;王璐璐;;鹽酸二甲雙胍緩釋片釋放度的研究[A];第四屆中國新醫(yī)藥博士論壇論文集[C];1999年

3 常建元;;酮洛芬控釋膠囊釋放度檢查方法的改進(jìn)[A];2003年藥物分析論壇藥物溶出度學(xué)術(shù)研討會(huì)論文集[C];2003年

4 陳旭挺;傅紅興;周碧濤;潘榕;;反相高效液相色譜法測定硝苯地平控釋制劑的含量和釋放度[A];《醫(yī)藥導(dǎo)報(bào)》第八屆編委會(huì)成立大會(huì)暨2009年度全國醫(yī)藥學(xué)術(shù)交流會(huì)和臨床藥學(xué)與藥學(xué)服務(wù)研究進(jìn)展培訓(xùn)班論文集[C];2009年

相關(guān)重要報(bào)紙文章 前1條

1 國家食品藥品監(jiān)督管理局藥品審評(píng)中心藥學(xué)技術(shù)評(píng)價(jià)研究組;重視釋放度研究 切實(shí)控制緩、控釋制劑質(zhì)量[N];中國醫(yī)藥報(bào);2005年

相關(guān)碩士學(xué)位論文 前1條

1 余佩;獸用左氧氟沙星緩釋顆粒劑的研究[D];武漢工程大學(xué);2015年

，

本文編號(hào)：1553342