| 引用本文: | 李静,王梦静,陈杰鹏,段丽丽,骆翔,邓意辉,宋艳志.新型纳豆激酶-γ-聚谷氨酸复合物注射液的制备和毒性评价[J].中国现代应用药学,2020,37(2):180-186. |
| LI Jing,WANG Mengjing,CHEN Jiepeng,DUAN Lili,LUO Xiang,DENG Yihui,SONG Yanzhi.Preparation and Toxicity Evaluation of a Novel Nattokinase-γ-polyglutamic Acid Complex Injection[J].Chin J Mod Appl Pharm(中国现代应用药学),2020,37(2):180-186. |
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| 新型纳豆激酶-γ-聚谷氨酸复合物注射液的制备和毒性评价 |
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李静1, 王梦静2, 陈杰鹏3, 段丽丽3, 骆翔2, 邓意辉2, 宋艳志2
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1.锦州医科大学附属第三医院, 辽宁 锦州 121000;2.沈阳药科大学药学院, 沈阳 110016;3.广东双骏生物科技有限公司, 广东 汕头 515000)
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| 摘要: |
| 目的 制备一种低毒性的纳豆激酶（nattokinase，NK）注射液。方法 在NK注射液中加入γ-聚谷氨酸（γ-polyglutamicacid，γ-PGA），制备NK-γ-PGA复合物注射液。采用急性毒性试验，以小鼠给药后的生存时间、生存状态和注射后48 h存活小鼠尾部的状态作为毒性评价的指标，分别考察pH和γ-PGA浓度对NK与γ-PGA复合情况的影响。利用体外溶栓试验对NK-γ-PGA注射液毒性降低的原因进行分析。结果 当以120 kU·kg-1的剂量单次尾静脉注射NK-γ-PGA复合物注射液（NK 10 kU·mL-1，γ-PGA 0.924 mg·mL-1，pH 6.0）时，48 h后小鼠的死亡率为0，且尾部无红肿及坏死，说明在pH 6.0和γ-PGA的浓度为0.924 mg·mL-1时，NK与γ-PGA复合得最好。体外溶栓试验结果表明，γ-PGA的加入未降低NK活性，毒性的降低主要是因为NK与γ-PGA形成了复合物，起到了缓释作用。结论 本研究中制备的NK-γ-PGA复合物注射液（NK 10 kU·mL-1，γ-PGA 0.924 mg·mL-1，pH 6.0）在不改变NK活性的前提下，降低了NK注射液毒性。 |
| 关键词: 纳豆激酶 注射液 聚谷氨酸 复合物 急性毒性试验 体外溶栓试验 |
| DOI：10.13748/j.cnki.issn1007-7693.2020.02.011 |
| 分类号:R944.1 |
| 基金项目: |
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| Preparation and Toxicity Evaluation of a Novel Nattokinase-γ-polyglutamic Acid Complex Injection |
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LI Jing1, WANG Mengjing2, CHEN Jiepeng3, DUAN Lili3, LUO Xiang2, DENG Yihui2, SONG Yanzhi2
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1.The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China;2.School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China;3.Sungen Biotech Co., Ltd., Shantou 515000, China
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| Abstract: |
| OBJECTIVE To prepare a low toxicity nattokinase(NK) injection. METHODS By adding the γ-polyglutamic acid(γ-PGA) to the NK solution, the NK-γ-PGA complex injection was prepared. Taking survival time, survival state and the tail state of the surviving mouse at 48 h after a single tail intravenous injection as toxicity evaluation indexes, the acute toxicity test was used to study the effects of pH and γ-PGA concentration on the complexation of NK and γ-PGA separately. The in vitro thrombolytic test was used to analyze the reason of the toxicity reduction of NK-γ-PGA complex injection. RESULTS When the NK-γ-PGA complex injection(NK 10 kU·mL-1, γ-PGA 0.924 mg·mL-1, pH 6.0) was administrated by a single tail intravenous injection at a dose of 120 kU·kg-1, the death rate of mice was 0, and the mouse tail had no swelling and necrosis, which indicated that when the pH was 6.0 and the concentration of γ-PGA was 0.924 mg·mL-1, the complexation of NK and γ-PGA was the best. The results of in vitro thrombolytic test showed that the addition of γ-PGA did not reduce the activity of the NK, but had a sustained-release effect to reduce drug toxicity. CONCLUSION The NK-γ-PGA complex injection(NK 10 kU·mL-1, γ-PGA 0.924 mg·mL-1, pH 6.0) prepared in this study achieved the goal of reducing NK injection toxicity without changing NK activity. |
| Key words: nattokinase injection γ-polyglutamic acid complex acute toxicity test in vitro thrombolytic test |
