CN104262463A - 蚕蛹多肽及其制备方法、应用 - Google Patents
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Abstract
本发明涉及药物领域，具体涉及蚕蛹多肽2，能预防或治疗糖尿病。所述的多肽2序列为PYERQADEPETKVTKKI。所述多肽2的制备方法，步骤包括（1）煎煮，（2）酶解，（3）蛋白质分离，（4）半制备RP-HPLC分离纯化，（5）冻干。所述的酶解采用中性蛋白酶、复合蛋白酶酶解。所述的蛋白质分离采用大孔树脂、葡聚糖凝胶。所述多肽2在治疗糖尿病及糖尿病并发症中的应用。所述的糖尿病并发症是糖尿病肾病、糖尿病高血压、糖尿病眼疾、糖尿病神经性病变。本发明中的蚕蛹多肽2，是从蚕蛹中提取多肽，安全性好，而且能有效的预防或治疗糖尿病。
Description
技术领域：
本发明涉及药物领域，具体涉及用于治疗糖尿病的多肽提取物。
背景技术
糖尿病是一组以高血糖为特征的代谢性疾病，是由于胰岛素不足或胰岛素的细胞代谢作用缺陷所引起的葡萄糖、蛋白质及脂质代谢紊乱的一种综合症。近年来，糖尿病患者的人数逐渐增多，分为I型糖尿病和II型糖尿病。其中II型糖尿病患者的人数占糖尿病总人数的85-90％，严重威胁着病人的健康和生命。如果糖尿病得不到良好的控制，可能引起很多并发症，例如：糖尿病肾病、视网膜病变、高血压等。
目前，大多数患者通过注射胰岛素或者口服降糖药物来帮助控制体内血糖，或调节胰岛素分泌等方法治疗糖尿病。但是这些药物副作用较大，临床上不能长期使用，不能满足糖尿病患者的临床需要。如果能够从自然产物中提取的安全、有效的治疗糖尿病的药物，将为广大糖尿病患者带来福音。
蚕蛹作为“普通食品管理的食品新资源名单”中唯一的昆虫类食品，具有很高的药用价值，药理作用也很广泛，除了可以促进生长、提高免疫力，还具有降血糖的作用。然而，蚕蛹是蚕丝的主要副产品，我国每年可产鲜蚕蛹五十万吨以上。但是因为技术欠缺，相当一段时期内蚕蛹基本上都被用作词料，导致了一定的资源浪费。因此，如果能从蚕蛹中提取出治疗糖尿病的化合物成为药物开发的热点。尽管如此，并没有成熟开发的从蚕蛹中提取化合物问世，用于预防或治疗糖尿病。
发明内容：
本发明目的是针对现有降血糖的药物的特点，设计一种蚕蛹多肽2，能安全、有效治疗糖尿病。
技术方案
一种蚕蛹多肽2，其序列为PYERQADEPETKVTKKI。所述多肽2的制备方法，其特征在于：步骤包括(1)煎煮，(2)酶解，(3)蛋白质分离，(4)半制备RP-HPLC分离纯化，(5)冻干。所述的酶解采用中性蛋白酶、复合蛋白酶酶解。所述的蛋白质分离采用大孔树脂、葡聚糖凝胶。所述多肽2在治疗糖尿病及糖尿病并发症中的应用。所述的糖尿病并发症是糖尿病肾病、糖尿病高血压、糖尿病眼疾、糖尿病神经性病变。
有益结果：
本发明中的蚕蛹多肽2，是从蚕蛹中提取多肽，安全性好，而且能有效的预防或治疗糖尿病。更优选是治疗糖尿病和/或糖尿病并发症药物中的用途。所述的糖尿病包括I型糖尿病和II型糖尿病；所述的糖尿病并发症包括但不限于：糖尿病肾病、糖尿病高血压、糖尿病眼疾、糖尿病神经性病变等。
具体实施方式
实施例1
多肽的制备方法
将蚕蛹加水煎煮1.5h后，冷却至室温；加入0.5％中性蛋白酶和1％复合蛋白酶酶解2h；采用大孔树脂按照分子量分离蛋白质，再用半制备RP-HPLC分离纯化，得到的产物冻干后，即为蚕蛹多肽2。应用上述方法提取的蚕蛹多肽2，经过质谱鉴定，序列为PYERQADEPETKVTKKI，该序列为全新序列。也可以由上海生工委托合成。
实施例2
蚕蛹多肽2的体外细胞活性测定
采用MTT比色法。将对数生长的胰岛瘤细胞(INS-1细胞)，以1.0×105加入96孔培养板中，培养24h，实验孔、阳性药物对照孔分别加入不同浓度的实验药物蚕蛹多肽2；空白组加入相同体积的溶剂。每孔设五个复孔，培养48h，每孔加入MTT，作用4h后，加入DMSO，孵育30min，在酶标仪570nm处测定吸光度A值，按公式细胞生长增殖率＝(实验组吸光值/对照组吸光值-1)×100％。计算出实验药物的EC50为25.76nmol/L。
实施例3
蚕蛹多肽2的体内降糖实验
昆明小鼠，高脂高糖喂养至体重18～22g，雌雄各半，实验前禁食不禁水24h，腹腔一次性注射链脲佐菌素(STZ)50mg/kg(1％的柠檬酸盐缓冲液溶解配制)。1周后小鼠尾静脉采血测血糖(BS)，BS高于16mmol/L为造模成功。造模后将小鼠分为3组，每组10只，糖尿病模型组(DM组)：给予等量的PBS缓冲液皮下注射；对照组(拜糖平)：20μg/kg皮下注射给药(溶于0.1mol/L PBS缓冲液)，一天两次，连续15d；样品组(蚕蛹多肽2)：同对照组；另取10只正常小鼠做为空白组。用药后第15d于尾静脉取血快速测量血糖。15d之后，在停药1周后，禁食不禁水16小时进行葡萄糖耐量试验。用25％葡萄糖溶液(2g/kg)灌胃，灌胃后0、120分钟尾静脉取血检测血糖。
结果：葡萄糖转运体蛋白多肽2具有降低糖尿病模型小鼠血糖的作用(P<0.05，表1)；同时，可以缓解糖尿病模型小鼠的糖耐量(表2)。其多肽2的作用与对照组拜糖平作用相当。
表1 蚕蛹多肽2对小鼠降血糖作用
*p<0.05，**p<0.01与模型组相比
表2 蚕蛹多肽2对小鼠糖耐量实验结果
*p<0.05，**p<0.01与模型组相比
结论：蚕蛹多肽2对糖尿病小鼠具有治疗作用。
SEQUENCE LISTING
<110> 苏州普罗达生物科技有限公司
<120> 蚕蛹多肽及其制备方法、应用
<130>
<160> 1
<170> PatentIn version 3.3
<210> 1
<211> 17
<212> PRT
<213> 人工序列
<400> 1
Pro Tyr Glu Arg Gln Ala Asp Glu Pro Glu Thr Lys Val Thr Lys Lys
1 5 10 15
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Claims (6)
1.一种蚕蛹多肽，其特征在于：其序列为PYERQADEPETKVTKKI。
2.一种权利要求1 所述多肽的制备方法，其特征在于：步骤包括（1）煎煮，（2）酶解，（3）蛋白质分离，（4）半制备RP-HPLC分离纯化，（5）冻干。
3.根据权利要求2所述的多肽的制备方法，其特征在于：步骤（2）所述的酶解采用中性蛋白酶、复合蛋白酶酶解。
4.根据权利要求所述的多肽2的制备方法，其特征在于：步骤（3）所述的蛋白质分离采用大孔树脂、葡聚糖凝胶。
5.权利要求1所述的多肽2在制备治疗糖尿病及糖尿病并发症药物中的应用。
6.根据权利要求4的用途，其特征在于所述的糖尿病并发症是糖尿病肾病、糖尿病高血压、糖尿病眼疾、糖尿病神经性病变。
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| CN108395467A (zh) * | 2018-03-08 | 2018-08-14 | 浙江汇能生物股份有限公司 | 蚕蛹蛋白多肽的分离纯化方法 |
| CN109200062A (zh) * | 2017-07-07 | 2019-01-15 | 张桂珍 | 蚕蛾头部多肽混合物在制备治疗糖尿病口服药物中的应用 |
| CN109480054A (zh) * | 2018-11-01 | 2019-03-19 | 苏州卫生职业技术学院 | 一种降糖多肽组合物及其制备方法 |
| CN114404568A (zh) * | 2022-01-16 | 2022-04-29 | 重庆理工大学 | 一种丝胶蛋白多肽注射制剂及其应用 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5710157B2 (ja) * | 2010-06-03 | 2015-04-30 | 株式会社ゲノム創薬研究所 | 血糖降下物質 |
| CN104031963B (zh) * | 2014-04-02 | 2016-08-24 | 浙江省农业科学院 | 利用蚕蛹制备降血糖肽的方法 |
-
2014
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Non-Patent Citations (2)
| Title |
|---|
| ZUOWEI SONG，ET AL.: "Reducing blood glucose levels in TIDM mice with an orally administered extract of sericin from hIGF-I-transgenic silkworm cocoons", 《FOOD AND CHEMICAL TOXICOLOGY》 * |
| 张海娜: "蚕蛹活性多肽的制备及降血压、降血糖活性研究", 《万方学术期刊数据库》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109200062A (zh) * | 2017-07-07 | 2019-01-15 | 张桂珍 | 蚕蛾头部多肽混合物在制备治疗糖尿病口服药物中的应用 |
| CN108395467A (zh) * | 2018-03-08 | 2018-08-14 | 浙江汇能生物股份有限公司 | 蚕蛹蛋白多肽的分离纯化方法 |
| CN108395467B (zh) * | 2018-03-08 | 2021-06-15 | 浙江汇能生物股份有限公司 | 蚕蛹蛋白多肽的分离纯化方法 |
| CN109480054A (zh) * | 2018-11-01 | 2019-03-19 | 苏州卫生职业技术学院 | 一种降糖多肽组合物及其制备方法 |
| CN114404568A (zh) * | 2022-01-16 | 2022-04-29 | 重庆理工大学 | 一种丝胶蛋白多肽注射制剂及其应用 |
| CN114404568B (zh) * | 2022-01-16 | 2023-12-26 | 重庆理工大学 | 一种丝胶蛋白多肽注射制剂及其应用 |
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| CN104262463B (zh) | 2016-11-30 |
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