本文選題：注射用替加環(huán)素 + 凍干工藝�。� 參考：《吉林大學(xué)》2017年碩士論文

【摘要】：本論文研制的注射用替加環(huán)素是基于規(guī)避市售品輔料乳糖的應(yīng)用缺點,以保證藥物安全性、穩(wěn)定性、可控性為目的而開發(fā)的一種不含賦形劑的凍干粉針劑。對注射用替加環(huán)素的生產(chǎn)處方工藝、質(zhì)量標(biāo)準(zhǔn)和穩(wěn)定性進(jìn)行了系統(tǒng)研究,并對其用藥安全進(jìn)行了初步評價。本論文研究肯定了不含乳糖賦形劑的注射用替加環(huán)素臨床用藥前景,為未來工業(yè)化市場化奠定了基礎(chǔ)。提供了一種工業(yè)化的注射用替加環(huán)素凍干粉針處方工藝。在樣品溶液中加入0.067%的抗氧化劑,采用依地酸二鈉保持樣品溶液p H值中性。38 h冷凍干燥階段無須氮氣保護。預(yù)凍階段快速降溫至-45℃,維持1 h;退火回溫至-20℃,保持2h后再緩慢降溫至-45℃,保溫2 h;升華干燥分3個階段逐步由-45℃升溫至0℃,用時21.5 h;繼續(xù)解析干燥至45℃,耗時7 h。對注射用替加環(huán)素的性狀、鑒別、檢查等進(jìn)行了詳細(xì)研究,建立了質(zhì)量標(biāo)準(zhǔn)草案。擬定單個最大雜質(zhì)不得過2.5%,總雜質(zhì)不得過3.0%。含量替加環(huán)素(C29H39N5O8)應(yīng)為標(biāo)示量的90.0%~110.0%。制定的質(zhì)量標(biāo)準(zhǔn)草案證明樣品質(zhì)量可控。本論文對注射用替加環(huán)素進(jìn)行了影響因素、加速和長期穩(wěn)定性試驗,各指標(biāo)差異在正常范圍內(nèi)。表明該處方、工藝、貯藏條件下的藥品性質(zhì)穩(wěn)定。對其家兔血管刺激試驗、體外溶血試驗、豚鼠主動全身過敏試驗及大鼠被動皮膚過敏試驗對注射用替加環(huán)素的臨床給藥安全性進(jìn)行了初步評價。結(jié)果顯示注射用替加環(huán)素對血管無明顯刺激性,對紅細(xì)胞無溶血及凝聚作用,未出現(xiàn)過敏反應(yīng)。初步判定注射用替加環(huán)素臨床用藥具備安全性。
[Abstract]:The tegacycline for injection is a freeze-dried powder injection without excipient developed in order to avoid the shortcomings of the market excipient lactose and to ensure the safety stability and controllability of the drug.The production process, quality standard and stability of tegacycline for injection were systematically studied, and the safety of tegacycline for injection was preliminarily evaluated.The clinical prospect of tegacyclin for injection without lactose excipient was confirmed in this paper, which laid a foundation for industrialization and marketization in the future.An industrial formulation process of tegacyclin lyophilized powder for injection was provided.0.067% antioxidant was added to the sample solution, and no nitrogen protection was needed during freeze-drying stage of the sample solution with neutral pH value (pH = 38 h) maintained by disodium eurate.In the pre-freezing stage, the temperature dropped rapidly to -45 鈩，

本文編號：1734135