CN103463005A - Racemosins A在制备治疗和预防肾纤维化药物中的应用 - Google Patents
Racemosins A在制备治疗和预防肾纤维化药物中的应用 Download PDFInfo
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Abstract
本发明提供了Racemosins A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，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，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
本发明涉及化合物Racemosins A的新用途，尤其涉及Racemosins A在制备治疗和预防肾纤维化药物中的应用。
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Racemosins A是一个2013年发表（Ding-Quan Liu，et al.,Racemosins A and B,two novel bisindole alkaloids from the green alga Caulerpa racemosa.Fitoterapia,91(2013):15–20.）的新化合物，该化合物拥有全新的骨架类型，目前的用途发现其能减弱β淀粉样肽25-35(Aβ25–35)导致的人神经母细胞瘤细胞SH-SY5Y细胞损伤（Ding-Quan Liu，et al.,Racemosins A and B,two novel bisindole alkaloids from the green alga Caulerpa racemosa.Fitoterapia,91(2013):15–20.），本发明涉及的Racemosins A在制备治疗和预防肾纤维化药物中的用途属于首次公开。
发明内容
本发明的目的在于根据现有Racemosins A研究中未发现其具有治疗和预防肾纤维化活性的报道的现状，提供了Racemosins A在制备治疗和预防肾纤维化药物中的应用。
所述化合物Racemosins A结构如式（Ⅰ）所示：
本发明涉及的Racemosins A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，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Racemosins A的制备方法参见文献（Ding-Quan Liu，et al.,Racemosins A and B,two novel bisindole alkaloids from the green alga Caulerpa racemosa.Fitoterapia,91(2013):15–20.）
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Racemosins A片剂的制备：
取5克化合物Racemosins A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Racemosins A胶囊剂的制备：
取5克化合物Racemosins A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。
试验例1：Racemosins A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，南京医科大学实验动物中心。
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、贝那普利灌胃10mg/kg组、Racemosins A静脉注射2.5mg/kg组、Racemosins A静脉注射5mg/kg组、Racemosins A静脉注射25mg/kg组、Racemosins A灌胃5mg/kg组、Racemosins A灌胃10mg/kg组、Racemosins A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。
常规病理学检查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Racemosins A灌胃大剂量各组显著，与模型对照组比较有明显差异。
表1Racemosins A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，Racemosins A静脉注射5mg/kg组、Racemosins A静脉注射25mg/kg组、Racemosins A灌胃10mg/kg组、Racemosins A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：Racemosins A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.Racemosins A在制备治疗和预防肾纤维化药物中的应用，所述化合物RacemosinsA结构如式（Ⅰ）所示：
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102429901A (zh) * | 2011-11-03 | 2012-05-02 | 合肥博太医药生物技术发展有限公司 | 吲哚-3-甲醇、二吲哚甲烷及其衍生物在制备防治肾纤维化药物中的应用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102429901A (zh) * | 2011-11-03 | 2012-05-02 | 合肥博太医药生物技术发展有限公司 | 吲哚-3-甲醇、二吲哚甲烷及其衍生物在制备防治肾纤维化药物中的应用 |
Non-Patent Citations (1)
| Title |
|---|
| DING-QUAN LIU,ET AL.: "Racemosins A and B, two novel bisindole alkaloids from the green alga Caulerpa racemosa", 《FITOTERAPIA》, vol. 91, 24 August 2013 (2013-08-24), pages 15 - 20 * |
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