發(fā)布時(shí)間：2018-07-05 04:55

  本文選題：替米考星 + 長(zhǎng)效注射液��； 參考：《河南大學(xué)》2014年碩士論文

【摘要】：替米考星(Tilmicosin)為一種由泰樂(lè)菌素半合成的大環(huán)內(nèi)酯類禽畜用抗生素,具有很強(qiáng)的抗菌活性,抗菌譜廣,無(wú)交叉耐藥性。替米考星原料藥分為兩種：替米考星堿和替米考星磷酸鹽,受其理化性質(zhì)影響,臨床使用劑型多為其磷酸鹽制劑,如目前獸藥市場(chǎng)上較為常見(jiàn)的劑型主要為磷酸替米考星注射液(30%),飲水劑(25%),預(yù)混劑(20%)。本研究通過(guò)篩選合適的有機(jī)復(fù)合溶媒、緩釋劑、抗氧劑等,制備了替米考星長(zhǎng)效注射液,并對(duì)其穩(wěn)定性、安全性、有效性進(jìn)行了研究。具體研究?jī)?nèi)容包括： 1.文獻(xiàn)綜述 概述了國(guó)內(nèi)外替米考星的一些研究概況,包括替米考星的理化性質(zhì)、作用機(jī)制、抗菌活性、不良反應(yīng)、臨床應(yīng)用等,對(duì)替米考星及其制劑進(jìn)行了初步的概述。又介紹了獸用緩釋制劑的研究進(jìn)展,重點(diǎn)介紹了注射用長(zhǎng)效制劑的類型、優(yōu)點(diǎn)等,以及獸用長(zhǎng)效制劑的研究現(xiàn)狀、存在的問(wèn)題、發(fā)展前景等,對(duì)本研究的背景進(jìn)行了綜合性的闡述。 2.替米考星體外分析方法的建立 建立了替米考星的HPLC分析方法,替米考星進(jìn)樣量在0.16ug-0.8ug范圍內(nèi)線性關(guān)系良好；平均回收率為99.32%,重復(fù)性好,RSD為0.22%；日內(nèi)精密度和日間精密度RSD均小于2%；結(jié)果表明建立的替米考星長(zhǎng)效注射液的HPLC分析方法回收率、重復(fù)性和精密度均符合要求,可為長(zhǎng)效替米考星注射液的處方設(shè)計(jì)、穩(wěn)定性考察等提供一種靈敏,準(zhǔn)確,可靠的檢測(cè)方法。 3.替米考星長(zhǎng)效注射液的制備與處方優(yōu)化 通過(guò)處方前研究,考察了替米考星原料藥的理化性質(zhì),對(duì)其pH、溶解性、穩(wěn)定性等進(jìn)行了初步研究,為處方設(shè)計(jì)打下基礎(chǔ)。通過(guò)處方篩選初步確定了注射液規(guī)格、注射用非水溶媒、抗氧劑、金屬離子絡(luò)合劑、緩釋劑,利用正交試驗(yàn)優(yōu)化了替米考星長(zhǎng)效注射液的最佳處方,確定了最佳制備工藝。通過(guò)體外釋放試驗(yàn)驗(yàn)證了替米考星長(zhǎng)效注射液的緩釋效果,結(jié)果表明,制備的替米考星長(zhǎng)效注射液具有良好的緩釋效果。 4.替米考星長(zhǎng)效注射液的穩(wěn)定性評(píng)價(jià) 對(duì)替米考星長(zhǎng)效注射液進(jìn)行了影響因素試驗(yàn)(高溫試驗(yàn)、高濕試驗(yàn)、強(qiáng)光試驗(yàn)),加速試驗(yàn),長(zhǎng)期試驗(yàn),初步考察了替米考星長(zhǎng)效注射液的穩(wěn)定性。結(jié)果表明替米考星長(zhǎng)效注射液穩(wěn)定性較好,符合制劑要求。對(duì)光、熱敏感,保存時(shí)應(yīng)注意避免光照、高溫。 5.替米考星長(zhǎng)效注射液的安全性評(píng)價(jià) 研究制備的替米考星長(zhǎng)效注射液注射方法為皮下注射或肌注,禁止靜脈注射。根據(jù)相關(guān)規(guī)定,對(duì)替米考星長(zhǎng)效注射液進(jìn)行了皮膚刺激性實(shí)驗(yàn)、局部刺激性實(shí)驗(yàn)和急性毒性試驗(yàn)。結(jié)果顯示：替米考星長(zhǎng)效注射液對(duì)家兔皮膚刺激性很��；對(duì)家兔肌肉和兔耳無(wú)明顯刺激,判定該制劑能夠供肌注和皮下注射使用；對(duì)小鼠的急性毒性實(shí)驗(yàn)測(cè)得半數(shù)致死量LDso為595.36mg/kg,半數(shù)致死量LD5o的95%可信限為：528～689mg/kg,屬于低毒藥物。表明本研究制備的替米考星長(zhǎng)效注射液具有較低的毒性及刺激性,臨床使用比較安全,適用于皮下注射、肌肉注射。 6.替米考星長(zhǎng)效注射液的體外抑菌作用研究 采用2倍稀釋法考察替米考星長(zhǎng)效注射液、磷酸替米考星溶液、磷酸泰樂(lè)菌素溶液對(duì)致病性大腸桿菌、金黃色葡萄球菌、多殺巴氏桿菌和鏈球菌等常見(jiàn)致病菌的體外抑菌活性。結(jié)果表明替米考星長(zhǎng)效注射液對(duì)上述常見(jiàn)致病菌具有很好的抗菌活性,對(duì)常見(jiàn)致病菌的敏感性強(qiáng)于磷酸替米考星和磷酸泰樂(lè)菌素,最低抑菌濃度均小于磷酸替米考星溶液和磷酸泰樂(lè)菌素溶液,表明替米考星長(zhǎng)效注射液具有較好的抗菌作用。
[Abstract]:Tilmicosin ( Tilmicosin ) is a kind of macrolide semi - synthetic macrolide antibiotics . It has strong antibacterial activity , wide antibacterial spectrum and no cross - resistance . It is divided into two kinds : tilmicosin injection ( 30 % ) , drinking agent ( 25 % ) and premix ( 20 % ) .

1 . Literature review

This paper summarizes the research situation of tilmicosin at home and abroad , including the physical and chemical properties of tilmicosin , mechanism of action , antibacterial activity , adverse reaction , clinical application , etc . It also introduces the research progress of tilmicosin and its preparation .

2 . Establishment of external analytical method for tilmicosin

The HPLC analysis method of tilmicosin was established , and the linear relationship was good in the range of 0.16ug - 0.8ug for tilmicosin injection .
The average recovery was 99.32 % , the repeatability was good , RSD was 0.22 % .
The RSD of intra - day precision and inter - day precision was less than 2 % .
The results show that the HPLC analysis method of tilmicosin long - acting injection has satisfactory recovery , repeatability and precision , which can provide a sensitive , accurate and reliable detection method for the prescription design and stability study of tilmicosin injection .

Preparation and prescription optimization of tilmicosin long - acting injection

The physicochemical properties of tilmicosin drug substance were studied by pre - prescription study . The pH , solubility and stability of tilmicosin were studied . The optimal formulation of tilmicosin long - acting injection was determined by orthogonal test . The results showed that the sustained release effect of tilmicosin long - acting injection was verified by in vitro release test . The results showed that the prepared tilmicosin long - acting injection has good sustained - release effect .

4 . Evaluation of stability of tilmicosin long - acting injection

The stability of tilmicosin long - acting injection was investigated by high temperature test , high humidity test , strong light test , accelerated test and long - term test . The results showed that the tilmicosin long - acting injection has good stability and meets the requirements of the preparation .

Safety evaluation of tilmicosin long - acting injection

The injection method of tilmicosin long - acting injection prepared by the study was subcutaneous injection or intramuscular injection , and intravenous injection was inhibited . According to the relevant regulations , the skin irritation experiment , local irritation experiment and acute toxicity test were carried out on tilmicosin long - acting injection . The results showed that the tilmicosin long - acting injection had little irritation to skin of rabbits ;
There was no obvious irritation to rabbit muscle and rabbit ear , and it was determined that the preparation could be used for intramuscular injection and subcutaneous injection .
LD50 LDso was 595.36 mg / kg , and the 95 % confidence limit of LD50 LD5o was 528 锝，

本文編號(hào)：2099007