【摘要】：利巴韋林是化學(xué)合成的核苷類藥物,具有廣譜抗病毒作用,對(duì)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(guó)外的原發(fā)廠家為美國(guó)ICN Scientists,于1972年在美國(guó)首先上市。國(guó)內(nèi)于1973年開(kāi)始試制,1980年通過(guò)鑒定,1981年原料、針劑、滴鼻液等獲得生產(chǎn)批文,在國(guó)內(nèi)已使用了三十多年,實(shí)踐表明,與同類藥物相比,利巴韋林具有強(qiáng)效、廣譜抗病毒作用,其抗病毒作用強(qiáng)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(duì)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(shí)間慢,吞咽困難患者不適用等缺點(diǎn)；外用劑型不可能取得全身效應(yīng),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(guò)效應(yīng)等特點(diǎn)。實(shí)際應(yīng)用中,將利巴韋林制成葡萄糖注射液后,可以避免臨時(shí)將一些小針劑加到輸液中使用帶來(lái)的如熱原、微粒、pH變化等諸多醫(yī)療隱患,同時(shí)也使護(hù)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(shí)間上優(yōu)于小針劑。 本研究以相關(guān)國(guó)家標(biāo)準(zhǔn)為依據(jù),通過(guò)處方篩選試驗(yàn)確定了利巴韋林葡萄糖注射液的完整處方；通過(guò)滅菌工藝選擇和驗(yàn)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(chǎn)工藝符合國(guó)家化學(xué)藥品注射劑的技術(shù)要求；并且,針對(duì)在試驗(yàn)中發(fā)現(xiàn)的活性炭對(duì)利巴韋林吸附較大的問(wèn)題,在查找、研究文獻(xiàn)的基礎(chǔ)上,通過(guò)試驗(yàn)對(duì)制備工藝進(jìn)行了改進(jìn)完善,確定了主藥后加的工藝流程。經(jīng)過(guò)小試樣品的影響因素試驗(yàn)驗(yàn)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(guò)對(duì)自制的利巴韋林葡萄注射液的質(zhì)量標(biāo)準(zhǔn)開(kāi)展系統(tǒng)的研究和方法學(xué)驗(yàn)證,建立了本品科學(xué)完整的質(zhì)量檢驗(yàn)方法。對(duì)本品三種規(guī)格各三批樣品的質(zhì)量檢查的結(jié)果均合格,表明采用本研究的處方和制備工藝生產(chǎn)的注射液質(zhì)量符合國(guó)家藥典標(biāo)準(zhǔn)。通過(guò)影響因素試驗(yàn)、加速試驗(yàn)、長(zhǎng)期試驗(yàn),確定了本品的貯藏條件和有效期,要求本品應(yīng)當(dāng)在遮光的陰涼處密閉保存。同時(shí)也證明了本品在合理儲(chǔ)存的情況下,一定時(shí)期內(nèi)各項(xiàng)質(zhì)量指標(biāo)均無(wú)明顯變化。研究認(rèn)為,利巴韋林葡萄糖注射液的工藝路線較短、操作簡(jiǎn)便、成本較低、污染較小,生產(chǎn)工藝流程合理,可操作性強(qiáng),可實(shí)現(xiàn)產(chǎn)業(yè)化大生產(chǎn)。摸索出的質(zhì)量控制標(biāo)準(zhǔn)可行,為今后的產(chǎn)業(yè)化大生產(chǎn)提供了質(zhì)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(zhì)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(hào)：2453348