CN105061566A - 拟胰岛素多肽及其应用 - Google Patents
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
本发明涉及药物领域，具体涉及拟胰岛素多肽，能预防和治疗糖尿病的多肽。其序列为FVNQHLCGSHLVEALYLVCG是全新的序列，本发明的有益效益是可用于治疗糖尿病，具有潜在的新药开发价值。
Description
技术领域：
本发明涉及药物领域，具体涉及用于预防和治疗或预防糖尿病的拟胰岛素多肽。
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。注射胰岛素治疗始终是治疗糖尿病的“金指标”。但是胰岛素是具有65个氨基酸的大分子蛋白质。长期注射治疗，一方面会引起过敏反应；另一方面，患者体内会产生大量胰岛素抗体，会中和体内的胰岛素，导致胰岛素抵抗，是胰岛素治疗无效。
小分子蛋白质或多肽就不容易诱发免疫变态反应，以及胰岛素抵抗。因此，小分子拟胰岛素多肽就能解决这一问题。
发明内容：
本发明目的是针对现有胰岛素治疗糖尿病的特点，设计全新序列的拟胰岛素多肽，适用于临床治疗糖尿病的应用。
本发明技术方案是提供一种拟胰岛素多肽，其序列为FVNQHLCGSHLVEALYLVCG，及在治疗或预防糖尿病药物中的应用。
有益结果：
本发明中的拟胰岛素多肽序列FVNQHLCGSHLVEALYLVCG，具有拟胰岛素的作用，产生的胰岛素生理或病理的效应，达到预防或治疗糖尿病的效果。说明本发明设计的拟胰岛素多肽科学、合理、可行有效，能用于治疗或预防糖尿病。
具体实施方式
本发明多肽由上海吉尔合成
实施例1
拟胰岛素多肽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拟胰岛素多肽；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0.76nmol/L。
实施例2
拟胰岛素多肽的体内降糖实验
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(胰岛素)：20μg/kg皮下注射给药(溶于0.1mol/LPBS缓冲液)，一天两次，连续15d；样品组(拟胰岛素多肽)：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的作用与对照组胰岛素作用相当。
表1拟胰岛素多肽对小鼠降血糖作用
*p<0.05，**p<0.01与模型组相比
表2拟胰岛素多肽对小鼠糖耐量实验结果
*p<0.05，**p<0.01与模型组相比
结论：拟胰岛素多肽对糖尿病小鼠具有治疗作用。
SEQUENCELISTING
<110>苏州普罗达生物科技有限公司
<120>拟胰岛素多肽及其应用
<130>
<160>1
<170>PatentInversion3.5
<210>1
<211>20
<212>PRT
<213>人工序列
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PheValAsnGlnHisLeuCysGlySerHisLeuValGluAlaLeuTyr
151015
LeuValCysGly
20
Claims (2)
1.拟胰岛素多肽，其特征在于其序列为FVNQHLCGSHLVEALYLVCG。
2.拟胰岛素多肽，在治疗或预防糖尿病药物中的应用。
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130190476A1 (en) * | 2010-07-28 | 2013-07-25 | Thomas M. Lancaster | Recombinantly expressed insulin polypeptides and uses thereof |
| CN104080473A (zh) * | 2011-11-28 | 2014-10-01 | 费斯生物制药公司 | 包含胰岛素氨基酸序列的治疗剂 |
| CN104114183A (zh) * | 2011-12-20 | 2014-10-22 | 印第安纳大学研究及科技有限公司 | 用于治疗糖尿病的基于ctp的胰岛素类似物 |
| CN104231070A (zh) * | 2008-08-07 | 2014-12-24 | 益普生制药股份有限公司 | N-端修饰的葡萄糖依赖性促胰岛素多肽(gip)类似物 |
-
2015
- 2015-09-05 CN CN201510556865.0A patent/CN105061566A/zh active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104231070A (zh) * | 2008-08-07 | 2014-12-24 | 益普生制药股份有限公司 | N-端修饰的葡萄糖依赖性促胰岛素多肽(gip)类似物 |
| US20130190476A1 (en) * | 2010-07-28 | 2013-07-25 | Thomas M. Lancaster | Recombinantly expressed insulin polypeptides and uses thereof |
| CN104080473A (zh) * | 2011-11-28 | 2014-10-01 | 费斯生物制药公司 | 包含胰岛素氨基酸序列的治疗剂 |
| CN104114183A (zh) * | 2011-12-20 | 2014-10-22 | 印第安纳大学研究及科技有限公司 | 用于治疗糖尿病的基于ctp的胰岛素类似物 |
Non-Patent Citations (1)
| Title |
|---|
| CHANG WR等: "登录号：1DEI_B", 《GENBANK》 * |
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