CN103356689B - Polyflavanostilbene A在制备治疗肾功能不全药物中的应用 - Google Patents

Polyflavanostilbene A在制备治疗肾功能不全药物中的应用 Download PDF

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CN103356689B
CN103356689B CN201310331714.6A CN201310331714A CN103356689B CN 103356689 B CN103356689 B CN 103356689B CN 201310331714 A CN201310331714 A CN 201310331714A CN 103356689 B CN103356689 B CN 103356689B
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renal insufficiency
polyflavanostilbene
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polyflavanostilbenea
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CN103356689A (zh
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汪贤荣
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Wang Yayan
Yang Jianbo
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Abstract

本发明公开了Polyflavanostilbene？A在预防和/或治疗肾功能不全药物中的应用，属于药物新用途技术领域。本发明涉及的Polyflavanostilbene？A在制备预防、治疗肾功能不全药物中的用途属于首次公开，由于骨架类型属于全新的骨架类型，而且其对于肾功能不全抑制活性强得意想不到，不存在由其他化合物给出任何启示的可能，具备突出的实质性特点，同时用于肾功能不全的防治显然具有显著的进步。

Description

Polyflavanostilbene A在制备治疗肾功能不全药物中的应用
技术领域
本发明涉及化合物PolyflavanostilbeneA的新用途，尤其涉及PolyflavanostilbeneA在制备治疗肾功能不全药物中的应用。
背景技术
慢性肾脏疾病（包括各慢性肾炎、糖尿病肾病及高血压性肾损害等）是一种最为常见的慢性的难治性疾病。不论何种病因，肾组织病变均会从早期病变逐渐进展为肾小球硬化和/或肾间纤维化的晚期病变。如果得不到有效治疗，终将导致慢性肾功能不全和不可逆的终末期肾衰竭（即尿毒症）。目前临床上用于治疗肾功能不全的药物主要是Benazepril和Losartan，但主要依赖进口，这类药物价格昂贵，毒副作用较大。如造成部分病人高血钾、不可克服的咳嗽、降血压作用不够强等。
本发明涉及的化合物PolyflavanostilbeneA是一个2013年发表（FushuangLi,etal.,PolyflavanostilbeneA,aNewFlavanol-FusedStilbeneGlycosidefromPolygonumcuspidatum.OrganicLetters,2013,3(15),674–677.）的新化合物，该化合物拥有全新的骨架类型，目前的用途仅仅抑制α-糖苷酶活性（FushuangLi,etal.,PolyflavanostilbeneA,aNewFlavanol-FusedStilbeneGlycosidefromPolygonumcuspidatum.OrganicLetters,2013,3(15),674–677.），本发明涉及的PolyflavanostilbeneA在制备治疗肾功能不全药物中的用途属于首次公开。
发明内容
本发明通过药理实验表明，用顺铂致小鼠急性肾损伤后3天，模型组血清肌酐、尿素氮显著升高。PolyflavanostilbeneA1.25mg/kg剂量组能降低血肌酐、尿素水平，其作用强度与阳性药Benazepril10mg/kg剂量组相当。
造模组后5天，模型组血清肌酐、尿素氮仍保持较高水平。PolyflavanostilbeneA1.25mg/kg剂量组可降低血肌酐，明显强于阳性药Benazepril10mg/kg剂量组。PolyflavanostilbeneA0.625mg/kg剂量组降低血尿素氮水平，与阳性药物Benazepril5mg/kg剂量组的作用相当。
造模型后7天，模型组及给药组血肌酐水平恢复正常（Benazepril10mg/kg剂量组血肌酐水平低于正常水平）。但模型组血尿素氮水平仍显著高于阴性对照组，PolyflavanostilbeneA0.625mg/kg、1.25m/kg剂量组可降低血尿素氮水平，强于阳性药。
实验结果表明，PolyflavanostilbeneA对顺铂造成的小鼠肾损伤有一定的保护作用，作用与阳性对照药Benazepril相当。
所述化合物PolyflavanostilbeneA结构如式（Ⅰ）所示：
本发明涉及的PolyflavanostilbeneA在制备预防、治疗肾功能不全药物中的用途属于首次公开，由于骨架类型属于全新的骨架类型，而且其对于肾功能不全治疗活性强得意想不到，不存在由其他化合物给出任何启示的可能，具备突出的实质性特点，同时用于肾功能不全的防治显然具有显著的进步。
术语：BUN：尿素难
Cre：肌酐
具体实施方式
本发明所涉及化合物PolyflavanostilbeneA的制备方法参见文献（FushuangLi,etal.,PolyflavanostilbeneA,aNewFlavanol-FusedStilbeneGlycosidefromPolygonumcuspidatum.OrganicLetters,2013,3(15),674–677.）
以下通过实施例对本发明作进一步详细的说明，但本发明的保护范围不受具体实施例的任何限制，而是由权利要求加以限定。
实施例1：本发明所涉及化合物PolyflavanostilbeneA片剂的制备：
取5克化合物PolyflavanostilbeneA加入糊精195克，混匀，常规压片制成1000片。
实施例2：本发明所涉及化合物PolyflavanostilbeneA胶囊剂的制备：
取5克化合物PolyflavanostilbeneA加入淀粉195克，混匀，装胶囊制成1000粒。
下面通过药效学实验来进一步说明其药物活性。
1、顺铂所致小鼠急性肾损伤模型的建立
取雄性昆明KM小鼠，16～18g，按体重随机分为溶剂对照组和顺铂模型组、给药组，共6组，每组8只。对照组腹腔注射生理盐水，顺铂以生理盐水溶解，腹腔注射，按7mg/kg注射给药。本发明化合物于注射顺铂前2天开始口服给药，每天一次，共给药五次；阳性对照药Benazepril（K），在注射顺铂时同时口服给药，每天一次，共给药三次（在注射顺铂前2天开始给药的效果不及同时给药，给药五次的效果不及三次），以上各给药体积均为0.4ml/20g。注射顺铂后第3天、5天、7天分别眼球取血，用试剂盒检测血清BUN、Cre，并称体重。
2、研究结果
表1PolyflavanostilbeneA对顺铂造成的小鼠肾损伤的保护作用（造模后3天）
*P<0.05，与模型组比较
表2PolyflavanostilbeneA对顺铂造成的小鼠肾损伤的保护作用（造模后5天）
*P<0.05，与模型组比较
表3PolyflavanostilbeneA对顺铂造成的小鼠肾损伤的保护作用（造模后7天）
*P<0.05，与模型组比较
上述实验结果表明，在造模后3天，模型组血清结果、尿素氮显著升高，PolyflavanostilbeneA1.25mg/kg剂量组能降低血肌酐、尿素氮水平，作用与阳性药Benazepril10mg/kg剂量组的作用相当。
造模型后5天，模型组血清结果、尿素氮仍保持较高水平，PolyflavanostilbeneA1.25mg/kg剂量组能降低血肌酐，明显强于阳性药Benazepril10mg/kg剂量组。PolyflavanostilbeneA0.625mg/kg剂量组能降低尿素氮水平，与阳性药Benazepril5mg/kg剂量组的作用相当。造模后7天，模型组及各给药组血肌酐水平恢复正常（Benazepril10mg/kg剂量组血肌酐水平低于正常水平），模型组血尿素氮水平仍显著高于阴性对照组，PolyflavanostilbeneA0.625mg/kg、1.25mg/kg剂量组可降低血尿素氮水平，强于阳性药Benazepril。
结论：PolyflavanostilbeneA对顺铂造成的小鼠肾损伤有一定的保护作用，作用与阳性对照药Benazepril相当，可以用来制备预防、治疗肾功能不全药物。

Claims (1)

1.PolyflavanostilbeneA在制备治疗肾功能不全药物中的应用，所述化合物PolyflavanostilbeneA结构如式（Ⅰ）所示：
CN201310331714.6A 2013-08-01 2013-08-01 Polyflavanostilbene A在制备治疗肾功能不全药物中的应用 Expired - Fee Related CN103356689B (zh)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1316244A (zh) * 2000-04-03 2001-10-10 陈建操 茶多酚用于治疗肾脏疾病的新用途

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1316244A (zh) * 2000-04-03 2001-10-10 陈建操 茶多酚用于治疗肾脏疾病的新用途

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
polyflavanostilbene A,a New Flavanol-Fused Stilbene Glycoside from Polygonum cuspidatum;Fushuang Li,et al;《Organic Letter》;20130115;第3卷(第15期);674-677 *

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