利巴韦林葡萄糖注射液制剂工艺及质量标准研究
发布时间：2019-04-03 16:03
【摘要】：利巴韦林是化学合成的核苷类药物,具有广谱抗病毒作用,对病毒的核糖核酸和脱氧核糖核酸有明显抑制作用。作为老牌抗病毒药,利巴韦林在国外的原发厂家为美国ICN Scientists,于1972年在美国首先上市。国内于1973年开始试制,1980年通过鉴定,1981年原料、针剂、滴鼻液等获得生产批文,在国内已使用了三十多年,实践表明,与同类药物相比,利巴韦林具有强效、广谱抗病毒作用,其抗病毒作用强于阿糖腺苷、阿糖胞苷、金刚烷胺、吗啉胍、碘汞等,因此临床适用范围广,是目前临床上常用的抗病毒药,用于治疗多种病毒性疾病,特别对一些传染性疾病的治疗有较好的疗效。 利巴韦林的制剂种类很多,但口服制剂存在药物起效时间慢,吞咽困难患者不适用等缺点；外用剂型不可能取得全身效应,更不能用于急性病毒性感染的全身治疗；注射剂作为临床常用剂型,具有药效迅速、胃肠道粘膜刺激性小,并可避免口服剂型的首过效应等特点。实际应用中,将利巴韦林制成葡萄糖注射液后,可以避免临时将一些小针剂加到输液中使用带来的如热原、微粒、pH变化等诸多医疗隐患,同时也使护士操作更轻松、更安全,并可有效地避免交叉污染,保证临床用药安全有效,且在显效时间上优于小针剂。 本研究以相关国家标准为依据,通过处方筛选试验确定了利巴韦林葡萄糖注射液的完整处方；通过灭菌工艺选择和验证研究,将灭菌参数提高到“121℃保温8分钟”,使本制剂的生产工艺符合国家化学药品注射剂的技术要求；并且,针对在试验中发现的活性炭对利巴韦林吸附较大的问题,在查找、研究文献的基础上,通过试验对制备工艺进行了改进完善,确定了主药后加的工艺流程。经过小试样品的影响因素试验验证,最终确定了利巴韦林葡萄糖注射液的处方和制备工艺。 本研究通过对自制的利巴韦林葡萄注射液的质量标准开展系统的研究和方法学验证,建立了本品科学完整的质量检验方法。对本品三种规格各三批样品的质量检查的结果均合格,表明采用本研究的处方和制备工艺生产的注射液质量符合国家药典标准。通过影响因素试验、加速试验、长期试验,确定了本品的贮藏条件和有效期,要求本品应当在遮光的阴凉处密闭保存。同时也证明了本品在合理储存的情况下,一定时期内各项质量指标均无明显变化。研究认为,利巴韦林葡萄糖注射液的工艺路线较短、操作简便、成本较低、污染较小,生产工艺流程合理,可操作性强,可实现产业化大生产。摸索出的质量控制标准可行,为今后的产业化大生产提供了质量控制的参考依据,也为利巴韦林葡萄糖注射液更安全有效地治疗病毒性疾病提供质量保证。
[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，
本文编号：2453348
[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，
本文编号：2453348
本文链接：https://www.wllwen.com/yixuelunwen/yiyaoxuelunwen/2453348.html
最近更新
教材专著
