CAJ | 학술논문

目的:考察降纤酶的质量现状及存在问题. 方法:对国家食品药品监督管理总局( CFDA)网站数据库上检索到的有降纤酶生产批文的生产企业进行问卷调查,对部分生产企业进行现场调研,针对上述两个环节中发现的问题,对降纤酶原液、中间体、半成品、成品开展了降纤酶原料(液)蛋白质序列分析等一系列实验室探索性研究,提升其安全性、有效性、稳定性和可控性. 结果:目前市场上流通的大部分样品的纯度均较低,其中尖吻蝮蛇降纤酶的主要成分为蕲蛇酶,白眉蝮蛇降纤酶的主要成分为NCBI蛋白数据库中编号为gi|143681919|(sp|P85109. 1|)的蛋白;降纤酶效价测定影响因素中Tris的浓度影响最大;加入大分子保护剂可以改善样品中的辅料右旋糖酐对效价测定结果的影响. 效价测定中两种仪器法(磁珠法和光学法)测定的结果差距较大,均比目测法低,目前尚不适用于降纤酶效价的测定. 热稳定性表明注射用降纤酶热稳定性较好,降纤酶注射液的热稳定性较差. 本研究采用浓缩一倍的Tris缓冲液稀释纤原,并加入适当的保护剂,建立了降纤酶半成品效价测定的方法. 结论:目前降纤酶的质量有待提高. 两种蛇毒来源的降纤酶结构、纯度等差别较大,现行的标准项目设置不全面;缺少专属性较强目前的鉴别;异常毒性、效价测定可操作性差等,不能有效地控制降纤酶的质量. 有必要将尖吻蝮蛇和白眉蝮蛇来源的降纤酶作为两个品种管理,同时加强降纤酶的标准化研究.
목적:고찰강섬매적질량현상급존재문제. 방법:대국가식품약품감독관리총국( CFDA)망참수거고상검색도적유강섬매생산비문적생산기업진행문권조사,대부분생산기업진행현장조연,침대상술량개배절중발현적문제,대강섬매원액、중간체、반성품、성품개전료강섬매원료(액)단백질서렬분석등일계렬실험실탐색성연구,제승기안전성、유효성、은정성화가공성. 결과:목전시장상류통적대부분양품적순도균교저,기중첨문복사강섬매적주요성분위기사매,백미복사강섬매적주요성분위NCBI단백수거고중편호위gi|143681919|(sp|P85109. 1|)적단백;강섬매효개측정영향인소중Tris적농도영향최대;가입대분자보호제가이개선양품중적보료우선당항대효개측정결과적영향. 효개측정중량충의기법(자주법화광학법)측정적결과차거교대,균비목측법저,목전상불괄용우강섬매효개적측정. 열은정성표명주사용강섬매열은정성교호,강섬매주사액적열은정성교차. 본연구채용농축일배적Tris완충액희석섬원,병가입괄당적보호제,건립료강섬매반성품효개측정적방법. 결론:목전강섬매적질량유대제고. 량충사독래원적강섬매결구、순도등차별교대,현행적표준항목설치불전면;결소전속성교강목전적감별;이상독성、효개측정가조작성차등,불능유효지공제강섬매적질량. 유필요장첨문복사화백미복사래원적강섬매작위량개품충관리,동시가강강섬매적표준화연구.
Objective: To research the quality level and problems of domestic defibrase. Methods: A questionnaire survey was performed in the factories with the production approval on the website database of CFDA, and a site survey was carried out in some of the factories. For the problems found out in the two surveys, a series of exploratory lab studies on the basis of ordinary analysis such as sequencing of proteins were performed on the materials, intermediates, semi-finished products and final products in order to improve their safety, validity, stability and controllability. Results:The purity of the most of the marketed products was low. Acutobin was the principal component in defibrase from Agkistrodon acutus, and the major ingredient in defibrase from Agkistrodon halys ussuriensis was an unknown protein, which was numbered by gi | 143681919 | (sp | P85109. 1 |) in NCBI protein database. Tris concentration was the main influencing factor in the test of biological potency. Macromolecular substances could decrease the effect of dextran. A new method for the test of biological potency of defibrase semi-products was developed by diluting the fiber with double enriched Tris buffer and adding the appropriate macromolecular substances. The results respectively measured by optical and magnetic method were notably different and both lower than that of the standard method, therefore, they were not suitable for the biological potency test of defibrase. Defibrase injection had poorer thermo-stability than defibrase for injection. Conclusion: The risk of defibrase is huge because of the poor quality. Defibrase from Agkistrodon acutus is notably different from that from Agkistrodon halys ussuriensis in protein structure and purity. The current standard method without the items including identification and specificity can not comprehensively evaluate the quality of defibrase. The operability is poor in the abnormal toxicity examination and biological potency test. It is necessary to intensify the supervision of defibrase from Agkistrodon acutus and Agkistrodon halys ussuriensis as two kinds of products. Meanwhile, the stand-ardization research on defibrase should be enhanced.