乳猪肝胶原蛋白水解物注射液研制及对荷瘤小鼠肿瘤生长影响.doc

乳猪肝胶原蛋白水解物注射液研制及对荷瘤小鼠肿瘤生长影响 　 ; 作者：邹晓军 廖汉雄 王耐勤 杨联萍，刘彤，邹清雁 【摘要】; 目的与方法 摸索乳猪肝胶原蛋白水解物注射液（HCH）的制备方法,同时对其进行质量检验和初步稳定性试验；并观察其对荷瘤昆明小鼠HepA肝瘤和S180纤维肉瘤及小鼠体内肝癌H22移植瘤的影响。结果 HCH生产工艺路线合理，质量达到拟定标准要求。HCH能明显抑制HepA肝瘤生长，25、50、100、200 mg·kg-1·d-1的抑制率分别为43.26％、55.06％、74.71％、40.47％；对荷瘤小鼠S180纤维肉瘤25、50、100 mg·kg-1·d-1的抑制率分别为53.87％、76.53％、58.20％，而阿霉素（2 mg·kg-1·d-1 ）阳性对照组的抑制率为62.41％；对小鼠体内肝癌H22移植瘤生长的抑制呈剂量相关性，50、100、200 mg·kg-1·d-1的抑制率分别为48.1％、60.0％、74.8％，而卡铂（20 mg·kg-1·d-1 ）阳性对照组的抑制率为63.7％。结论 此法可制备合格的HCH，且适合于大规模生产；HCH能明显地抑制荷瘤小鼠肿瘤的生长。 【关键词】; 胶原；肿瘤；生长抑制；小鼠 　　Abstract:Objective To investigate the methods to prepare the hepatic collagenous hydrolysates(HCH) for injection, the rudiment stability test, and the quality control study of the HCH, and to observe its effect on the tumor growth in the tumor bearing mice. Methods The dissolvability collagen were extracted from the suckling pig liver with the biochemical approach, the tumor inhibiting polypeptides for injection were prepared with the pepsin hydrolysis. The quality criteria of the product were studied. The effects of TIP on the Hep A hepatoma, H22 hepatoma and S180 fibrosarcoma were investigated.Results The products quality reached the quality criteria showed that the production procedure of TIP was suitable. The results showed that TIP could apparently inhibit the growth of Hep A hepatoma in the tumor-bearing mice with the inhibitory rates of 43.26％, 55.06％, 74.71％, 40.47％ at the doses of 25, 50, 100, 200 mg·kg-1·d-1 TIP; and inhibit the growth of S180 fibrosarcoma with the inhibitory rates of 53.87％, 76.53％, 58.20％ at the respective doses of 50, 100, and 200 mg·kg-1·d-1 TIP, the relative inhibitory rate of the positive adriamycin（2 mg·kg-1·d-1）control was 62.41%; TIP could apparently inhibit the growth of H22 hepatoma transplanted in the mice at a dose-dependant way with the inhibitory rates of 48.1％, 60.0％, 74.8％ at the respective doses of 50, 100, and 200 mg·kg-1·d-1 HCH, and the relative inhibitory rate of the positive adriamycin（