【摘要】：利巴韋林是化學合成的核苷類藥物,具有廣譜抗病毒作用,對病毒的核糖核酸和脫氧核糖核酸有明顯抑制作用。作為老牌抗病毒藥,利巴韋林在國外的原發(fā)廠家為美國ICN Scientists,于1972年在美國首先上市。國內于1973年開始試制,1980年通過鑒定,1981年原料、針劑、滴鼻液等獲得生產批文,在國內已使用了三十多年,實踐表明,與同類藥物相比,利巴韋林具有強效、廣譜抗病毒作用,其抗病毒作用強于阿糖腺苷、阿糖胞苷、金剛烷胺、嗎啉胍、碘汞等,因此臨床適用范圍廣,是目前臨床上常用的抗病毒藥,用于治療多種病毒性疾病,特別對一些傳染性疾病的治療有較好的療效。 利巴韋林的制劑種類很多,但口服制劑存在藥物起效時間慢,吞咽困難患者不適用等缺點；外用劑型不可能取得全身效應,更不能用于急性病毒性感染的全身治療；注射劑作為臨床常用劑型,具有藥效迅速、胃腸道粘膜刺激性小,并可避免口服劑型的首過效應等特點。實際應用中,將利巴韋林制成葡萄糖注射液后,可以避免臨時將一些小針劑加到輸液中使用帶來的如熱原、微粒、pH變化等諸多醫(yī)療隱患,同時也使護士操作更輕松、更安全,并可有效地避免交叉污染,保證臨床用藥安全有效,且在顯效時間上優(yōu)于小針劑。 本研究以相關國家標準為依據(jù),通過處方篩選試驗確定了利巴韋林葡萄糖注射液的完整處方；通過滅菌工藝選擇和驗證研究,將滅菌參數(shù)提高到“121℃保溫8分鐘”,使本制劑的生產工藝符合國家化學藥品注射劑的技術要求；并且,針對在試驗中發(fā)現(xiàn)的活性炭對利巴韋林吸附較大的問題,在查找、研究文獻的基礎上,通過試驗對制備工藝進行了改進完善,確定了主藥后加的工藝流程。經過小試樣品的影響因素試驗驗證,最終確定了利巴韋林葡萄糖注射液的處方和制備工藝。 本研究通過對自制的利巴韋林葡萄注射液的質量標準開展系統(tǒng)的研究和方法學驗證,建立了本品科學完整的質量檢驗方法。對本品三種規(guī)格各三批樣品的質量檢查的結果均合格,表明采用本研究的處方和制備工藝生產的注射液質量符合國家藥典標準。通過影響因素試驗、加速試驗、長期試驗,確定了本品的貯藏條件和有效期,要求本品應當在遮光的陰涼處密閉保存。同時也證明了本品在合理儲存的情況下,一定時期內各項質量指標均無明顯變化。研究認為,利巴韋林葡萄糖注射液的工藝路線較短、操作簡便、成本較低、污染較小,生產工藝流程合理,可操作性強,可實現(xiàn)產業(yè)化大生產。摸索出的質量控制標準可行,為今后的產業(yè)化大生產提供了質量控制的參考依據(jù),也為利巴韋林葡萄糖注射液更安全有效地治療病毒性疾病提供質量保證。
[Abstract]:Ribavirin is a chemically synthesized nucleoside with broad-spectrum antiviral activity and obvious inhibition of ribonucleic acid and deoxyribonucleic acid. As an established antiviral agent, ribavirin was first listed in the United States in 1972 for the original manufacturer of ICN Scientists, in the United States. Domestic trial production began in 1973, passed identification in 1980, in 1981 raw materials, injections, nasal drops and so on obtained production approval, has been used in China for more than 30 years, practice shows that compared with similar drugs, ribavirin has a strong effect, Broad-spectrum antiviral effect, its antiviral effect is stronger than Ara adenosine, arabinoside, amantadine amine, morpholine guanidine, mercury iodide and so on, so it has a wide range of clinical application, it is a commonly used antiviral drug in clinic at present, it is used to treat many kinds of viral diseases. In particular, the treatment of some infectious diseases has a better curative effect. There are many kinds of ribavirin preparations, but oral preparations have many disadvantages, such as slow onset time of drugs, unsuitable for patients with dysphagia and so on, the external dosage form can not achieve systemic effect, and can not be used for the whole body treatment of acute viral infection. As a commonly used clinical dosage form, injection has the characteristics of rapid efficacy, small irritation of gastrointestinal mucosa and avoiding the first-pass effect of oral dosage form. In practical application, after ribavirin is made into glucose injection, it can avoid a lot of medical hidden dangers, such as pyrogen, microparticles, changes of pH, and so on, which are brought about by temporarily adding a few small needles to the infusion. At the same time, it also makes it easier and safer for nurses to operate. It can effectively avoid cross-contamination, ensure the safety and effectiveness of clinical use, and is superior to small injection in apparent effect time. According to the relevant national standards, the complete prescription of ribavirin glucose injection was determined by prescription screening test. Through the study of sterilization process selection and verification, the sterilization parameters were raised to "121 鈩，

本文編號：2453348