CN101002760A - 绿原酸在制备抗糖尿病并发症的药中的应用 - Google Patents
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Abstract
本发明涉及绿原酸在制备抗糖尿病并发症的药中的应用。本发明可将绿原酸与药用载体和/或赋形剂制得药用组合物。所制得的药用组合物用于抑制醛糖还原酶活性，预防、治疗糖尿病并发症，具有疗效好，副作用少等优点。
Description
技术领域
本发明涉及绿原酸的用途，尤其涉及在制药领域中的用途。
背景技术
糖尿病长期高血糖状态会对体内许多组织和器官产生危害，可引起糖尿病性肾脏、视网膜、神经等病变，其发病机制与多元醇途径中必需的限速酶——醛糖还原酶活性的升高关系密切，应用醛糖还原酶抑制剂可预防和治疗这些并发症。临床上已有较多醛糖还原酶抑制剂被应用，如索比尼尔、依泊斯它、多克斯等，但是因为毒副作用较大，限制了使用。因此，从我国传统中药中筛选毒副作用小、醛糖还原酶抑制作用强的药物是当务之急。
绿原酸chlorogenicacid，CGA，又名咖啡鞣酸，以金银花、杜仲中的含量较高，具有广泛的药理作用，如：心血管保护作用；抗诱变及抗癌作用；抗菌及抗病毒作用；降脂作用；抗白血病作用；免疫调节作用及降糖作用，国内外文献均未见有关绿原酸抑制醛糖还原酶活性的报道，本发明提供绿原酸作为一种新的醛糖还原酶抑制剂，用于治疗糖尿病并发症。
发明内容
本发明就是针对上述问题提供绿原酸在制备糖尿病并发症的药中的用途，用绿原酸制备醛糖还原酶抑制剂的药物对糖尿病并发症具有较好的疗效，且副作用少。
本发明提供的技术方案是：绿原酸在制备糖尿病并发症的药中的应用。
上述绿原酸可作为醛糖还原酶抑制剂在制备抗糖尿病并发症的药中的应用。
上述抗糖尿病并发症的药为有效剂量的绿原酸与药用载体和/或赋形剂的组合物。
上述抗糖尿病并发症的药可为口服制剂、注射剂或滴眼剂。
本发明可将绿原酸与药用载体和/或赋形剂制得药用组合物。所制得的药用组合物用于抑制醛糖还原酶活性，预防、治疗糖尿病并发症，具有疗效好，副作用少等优点。
附图说明
图1为绿原酸对醛糖还原酶抑制作用图；
图2为绿原酸对糖尿病鼠肾损伤的影响图。
具体实施方式
本发明通过以下实施例作进一步说明
实施例1：绿原酸组合物由绿原酸1～50克、纤维素450～499克制成1000粒。其制备方法为：将绿原酸与纤维素制粒，然后压片或灌装胶囊，每粒(片)含绿原酸1-50mg。
实施例2：绿原酸组合物由1～50克绿原酸加注射用水至1升，分装成1000支制得。其制法为：将绿原酸溶于注射用水中，加至1升，灭菌，分装。每支含1-50mg绿原酸。
实施例3：绿原酸组合物由1～50克绿原酸加注射用水至1升，分装成1000支制得。其制法为：将绿原酸溶于注射用水中，调节pH4.5-7.0，加水至1升，灭菌，分装，制成滴眼液。每支含1-50mg绿原酸。
绿原酸对醛糖还原酶抑制作用的研究
实验方法
醛糖还原酶(AR)活性测定：在NADPH的存在下，AR催化DL-甘油醛还原为甘油，同时NADPH转化为NADP，而还原态NADPH在340nm处有特征吸收，可以测定340nm处光密度的下降速率，间接测定AR的活性.在实验条件下，每min()减少0.001单位的吸光度定义为一个酶活力U。从鼠肾中提取醛糖还原酶用于筛选。NaPi缓冲液pH6.2、适量的酶液和样品的DMSO溶液，37℃保温15min，加入DL-甘油醛和NADPH，测定340nm处每minOD值的减少量A.
I＝[A对照-A样品/A对照-A空白]×100％.
实验结果
绿原酸对醛糖还原酶的抑制活性的测定结果见图1，从图1可以看出，绿原酸对醛糖还原酶呈现出剂量依赖的抑制作用，其IC50为4.54μg/mL；当10.00μg/mL其抑制率为95％。
绿原酸对糖尿病鼠肾损伤的保护作用
实验方法：
试剂和仪器：NADPH Roche公司，NADP华美公司，DL2甘油醛Sigma公司，四氧嘧啶，Sigma公司，其余均为国产分析纯试。
动物处理：适应性喂养3d禁食12h，按200mg/kg体重单次腹腔注射四氧嘧啶溶液，72h后测定血糖，选取血糖在16-25mmol/L的小鼠作为实验鼠。实验分为5组：糖尿病模型组(M)；模型+绿原酸低剂量组(M+CGA1，ig绿原酸10mg/kg，一天一次)；模型+绿原酸中剂量组(M+CGA2，ig绿原酸20mg/kg，一天一次)；模型+绿原酸高剂量组(M+CGA3，ig绿原酸40mg/kg，一天一次)；模型+二甲双胍组(M+SG，ig二甲双胍25mg/kg，一天一次)；连续给药30d，剪尾采血，血糖测定仪测定血糖值，取肾，称重，计算脏器指数，其中一个肾用甲醛固定，石蜡包埋，进行病理学检查，另一个肾匀浆，观察绿原酸对糖尿病鼠肾抗氧化功能的影响。
实验结果
1.绿原酸对糖尿病鼠死亡率、肾指数及血糖的影响
结果可见，绿原酸可降低糖尿病鼠死亡率、肾指数及空腹血糖，提示绿原酸对糖尿病的有益作用，结果见表1。
表1.绿原酸对糖尿病鼠死亡率、肾指数及血糖的影响
| 组别 | 例数 | 死亡率(％) | 肾指数g/kg体重 | 空腹血糖mmol/L |
| MM+CGA1M+CGA2M+CGA3M+SG | 1010101010 | 5040202040 | 0.16±0.050.14±0.030.12±0.05**0.12±0.02**0.14±0.02* | 18.2±2.315.1±1.6**13.4±3.1**11.5±2.7**13.4±3.3** |
与模型组相比*P＜0.05；**P＜0.01
2.绿原酸对糖尿病鼠肾抗氧化功能的影响
结果可见，绿原酸可明显降低糖尿病鼠肾MDA含量，提高SOD及GSHpx酶活性，并呈剂量依赖关系，见表2。
表2.绿原酸对糖尿病鼠肾抗氧化功能的影响
| 组别 | 例数 | MDAnmol/mg.protein | SODU/mg.protein | GSHpxU/mg.protein |
| MM+CGA1M+CGA2M+CGA3M+SG | 56886 | 0.45±0.080.40±0.120.32±0.07**0.26±0.13**0.36±0.11* | 25.32±2.3526.12±1.3341.22±6.87**45.69±7.41**25.88±4.34 | 50.33±10.1063.41±5.41**79.15±10.45**89.64±13.56**60.35±4.23** |
与模型组相比*P＜0.05； **P＜0.01
3.绿原酸对糖尿病鼠肾病理学变化的影响
结果如图2所示，糖尿病鼠肾脏细胞明显水肿(模型组)，绿原酸组可改善这一病理变化，其中中剂量组和高剂量组效果尤其显著，未见脏细胞明显水肿；低剂量组效果与M+SG组类似，但仍可见少量脏细胞水肿；提示绿原酸对糖尿病肾病的保护作用。
Claims (6)
1.绿原酸在制备抗糖尿病并发症的药中的应用。
2.根据权利要求1所述的应用，其特征是：绿原酸作为醛糖还原酶抑制剂在制备抗糖尿病并发症的药中的应用。
3.根据权利要求1或2所述的应用，其特征是：所述抗糖尿病并发症的药为有效剂量的绿原酸与药用载体和/或赋形剂的组合物。
4.根据权利要求3所述的应用，其特征是：所述抗糖尿病并发症的药为口服制剂。
5.根据权利要求3所述的应用，其特征是：所述抗糖尿病并发症的药为注射剂。
6.根据权利要求3所述的应用，其特征是：所述抗糖尿病并发症的药为滴眼剂。
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| CNB2007100513411A CN100502854C (zh) | 2007-01-23 | 2007-01-23 | 绿原酸在制备抗糖尿病并发症的药中的应用 |
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| CN101002760A true CN101002760A (zh) | 2007-07-25 |
| CN100502854C CN100502854C (zh) | 2009-06-24 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009096773A (ja) * | 2007-10-18 | 2009-05-07 | Ucc Ueshima Coffee Co Ltd | ＡＧＥｓ生成阻害剤 |
| WO2011129399A1 (ja) * | 2010-04-15 | 2011-10-20 | 花王株式会社 | Ｓｒｅｂｐ抑制剤 |
| CN104906167A (zh) * | 2015-07-06 | 2015-09-16 | 四川农业大学 | 灰毡毛忍冬咖啡酰奎宁酸类提取物的制备方法及用途 |
| WO2023016389A1 (zh) * | 2021-08-10 | 2023-02-16 | 成都川宇健维生物科技有限公司 | 包含β-烟酰胺单核苷酸和绿原酸的组合物及其应用 |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR3062795B1 (fr) * | 2017-02-16 | 2019-06-07 | Valbiotis | Principe actif pharmaceutique et utilisation en particulier dans la prevention et le traitement des dereglements metaboliques chez l'homme et l'animal. |
-
2007
- 2007-01-23 CN CNB2007100513411A patent/CN100502854C/zh not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009096773A (ja) * | 2007-10-18 | 2009-05-07 | Ucc Ueshima Coffee Co Ltd | ＡＧＥｓ生成阻害剤 |
| WO2011129399A1 (ja) * | 2010-04-15 | 2011-10-20 | 花王株式会社 | Ｓｒｅｂｐ抑制剤 |
| JP2011225455A (ja) * | 2010-04-15 | 2011-11-10 | Kao Corp | Ｓｒｅｂｐ抑制剤 |
| CN104906167A (zh) * | 2015-07-06 | 2015-09-16 | 四川农业大学 | 灰毡毛忍冬咖啡酰奎宁酸类提取物的制备方法及用途 |
| WO2023016389A1 (zh) * | 2021-08-10 | 2023-02-16 | 成都川宇健维生物科技有限公司 | 包含β-烟酰胺单核苷酸和绿原酸的组合物及其应用 |
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| Publication number | Publication date |
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| CN100502854C (zh) | 2009-06-24 |
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