CN102861063B - Houttuynoid C在制备治疗或预防肾纤维化的药物中的应用 - Google Patents
Houttuynoid C在制备治疗或预防肾纤维化的药物中的应用 Download PDFInfo
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Abstract
本发明提供了Houttuynoid C在制备治疗或预防肾纤维化的药物中的应用，属于药物新用途技术领域。本发明涉及的Houttuynoid C在制备治疗或预防肾纤维化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，而且其对于肾纤维化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，同时用于肾纤维化的防治显然具有显著的进步。
Description
技术领域
本发明涉及一种药物新用途，具体地涉及Houttuynoid C在制备治疗或预防肾纤维化的药物中的应用。
背景技术
肾纤维化（包括肾间质纤维化和肾小球硬化）是各种原因引起的肾脏损害最后阶段的主要病理基础，肾纤维化发生机制较为复杂，与多种因素有关，其中主要与细胞外基质细胞产生细胞的增殖和活化，血管活性物质、细胞因子以及细胞外基质转换失衡有关，肾间质纤维化几乎是所以原发或继发肾脏疾病进展到终末期肾衰竭的共同途径。
本发明涉及的化合物Houttuynoid C是一个2012年发表（Chen, S. D. et al., 2012. Houttuynoid C_E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772–1775.）的新骨架化合物，该化合物拥有全新的骨架类型，目前的用途仅仅涉及抗单纯疱疹病毒活性（Chen, S. D. et al., 2012. Houttuynoid C_E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772–1775.），对于本发明涉及的Houttuynoid C在制备治疗或预防肾纤维化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，而且其对于肾纤维化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，同时用于肾纤维化的防治显然具有显著的进步。
发明内容
本发明提供Houttuynoid C在制备预防或治疗肾纤维化的药物中的应用。
所述化合物Houttuynoid C结构如式（Ⅰ）所示：
本发明涉及的Houttuynoid C在制备治疗或预防肾纤维化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，而且其对于肾纤维化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，同时用于肾纤维化的防治显然具有显著的进步。
具体实施方式
本发明所涉及化合物Houttuynoid C的制备方法参见文献（Chen, S. D. et al., 2012. Houttuynoid C_E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772–1775.）。
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Houttuynoid C片剂的制备：
取20克化合物Houttuynoid C，加入制备片剂的常规辅料180克，混匀，常规压片机制成1000片。
实施例2：本发明所涉及化合物Houttuynoid C胶囊剂的制备：
取20克化合物Houttuynoid C，加入制备胶囊剂的常规辅料如淀粉180克，混匀，装胶囊制成1000片。
下面通过药效学实验来进一步说明其药物活性。
试验 Houttuynoid C对单侧输尿管结扎大鼠肾间质纤维化的影响
1.1 材料
贝那普利，北京诺华制药有限公司生产；羟脯氨酸（HYP）试剂盒，南京建成生物公司；纤维连结蛋白（FN）试剂盒购自上海生物制品所。
实验动物：普通级Wistar大鼠，雄性，体重150-200g，SD大鼠。
1.2 试验方法与结果
大鼠90只，随机分9组，即假手术组、模型组、苯那普利灌胃10mg/kg组、Houttuynoid C静脉注射2.5 mg/kg组、Houttuynoid C静脉注射5 mg/kg组、Houttuynoid C静脉注射25 mg/kg组、Houttuynoid C灌胃5mg/kg组、Houttuynoid C灌胃10mg/kg组、Houttuynoid C灌胃50mg/kg组，动物喂养1周，各大鼠以10%水合氯醛3.0mL/kg腹腔注射麻醉后，将大鼠右侧卧位固定与手术台上，剪毛后用碘酒、75%酒精消毒手术区，行左侧腹切口，逐层切开皮肤、肌肉及腹壁各层，暴露并分离左侧输尿管，假手术组仅切开腹腔并游离左侧输尿管，但不结扎和剪断，其他各组大鼠用4-0丝线结扎两道，上一道结扎点位于左肾下极水平，然后在两道结扎点剪断输尿管，逐层缝合，术后10天10%水合氯醛麻醉后处死各组动物，取血，按纤维连结蛋白测定说明测定说明纤维联接蛋白（FN）。生理盐水反复灌洗后留取左侧肾脏，肾组织经4%的多聚甲醛缓冲液固定。切取适量肾组织，按羟脯氨酸试剂盒测定说明测定羟脯氨酸。
常规病理学检①肉眼观察：假手术组肾脏颜色鲜红，表明光滑，包膜光泽，无粘连。其他各组肾脏体积增大，颜色苍白，表明呈颗粒状，类似人体大白肾，少数区域肾包膜粘连。②光镜检查：假手术组肾单位结果清晰，肾小球囊无扩张或炎细胞浸润。模型对照组大片肾小管坏死，肾间质纤维细胞增生，肾小管扩张，内有大量棕黄色遮光物质或坏死脱落的上皮细胞，肾小球数目减少，部分肾小球纤维化并与包曼氏囊壁粘连，囊腔消失。给药各组病变与模型对照组类似，但均有不同程度的形态学改善，尤以Houttuynoid C灌胃大剂量各组显著，与模型对照组比较有明显差异。
表1 Houttuynoid C对单侧输尿管结扎大鼠肾间质纤维化的影响
*p<0.05，**p<0.01，与模型组相比较
对各组FN、HYP进行T检验。结果见表1， Houttuynoid C静脉注射5 mg/kg组、Houttuynoid C静脉注射25 mg/kg组、Houttuynoid C灌胃10mg/kg组、Houttuynoid C灌胃50mg/kg组降低FN、HYPP水平（与模型对照组比较，P<0.05或0.01）。
结论：Houttuynoid C能够显著降低肾间质纤维化FN、HYPP水平的升高，抑制肾间质纤维化，可以用来制备抗肾纤维化药物。
Claims (1)
1.Houttuynoid C在制备治疗或预防肾纤维化的药物中的应用，所述化合物Houttuynoid C结构如式（Ⅰ）所示：
式（Ⅰ）。
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Non-Patent Citations (6)
| Title |
|---|
| Houttuynoids A-E, anti-herpes simplex virus active flavonoids with novel skeletons from houttuynia cordata;Shao-Dan Chen et al;《Organic Letters》;20120313;第14卷(第7期);第1773页 * |
| Shao-DanChenetal.HouttuynoidsA-E anti-herpes simplex virus active flavonoids with novel skeletons from houttuynia cordata.《Organic Letters》.2012 |
| 排毒合剂对慢性肾衰竭纤维指标和肾功能影响的临床研究;高智 等;《新中医》;20071031;第39卷(第10期);第91页 * |
| 李爽 等.鱼腥草的有效成分、药理作用及临床应用的研究进展.《沈阳药科大学学报》.1997,第14卷(第2期),第144-146页. |
| 高智 等.排毒合剂对慢性肾衰竭纤维指标和肾功能影响的临床研究.《新中医》.2007,第39卷(第10期),第91页. |
| 鱼腥草的有效成分、药理作用及临床应用的研究进展;李爽 等;《沈阳药科大学学报》;19970430;第14卷(第2期);第144-146页 * |
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