CN114712427B - 一种桃树根药物的应用 - Google Patents
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Abstract
本发明涉及中医药技术领域，为了发现及验证桃树根及其提取物在疾病治疗方面的药用价值，本发明提供了一种桃树根药物的应用，桃树根处理物在制备改善或/和治疗器官纤维化或/和硬化疾病的药物中的应用；尤其是在治疗肾纤维化疾病上的应用；结果表明桃树根具有良好的抗肾纤维化病变的作用效果，可以降低UUO肾脏促纤维化肌成纤维细胞细胞的数量，显著抑制了纤维化基因的RNA和蛋白水平。
Description
技术领域
本发明涉及中医药技术领域，具体而言，涉及一种桃树根药物的应用。
背景技术
纤维化本质上是一种过度的伤口愈合反应，可使几乎所有组织和器官发生渐进性结构重建，导致器官衰竭和患者死亡。在工业化世界中，高达 45％的死亡是由器官纤维化造成的。临床上尚缺乏针对器官纤维化病变的针对性治疗药物。
桃树根，蔷薇科李属植物桃Prunus Persica(L.)Batsch或山桃Prunus davidiana(Carr.)Franch的根或根皮。性苦，平，无毒。功效：清热利湿，活血止痛，截疟，杀虫。现代研究表明，桃树根具有良好的抗炎、抗肿瘤、抑菌、提高免疫力、止血等作用，其主要成分含酮类、蒽醌、酚与鞣质、糖类、三萜类、植物甾醇等物质；也有研究表明桃根乙醇提取物通过诱导细胞周期阻滞和迁移抑制体内肿瘤生长以及抑制肝癌HepG2细胞的体外生长。
但目前尚未发现桃树根及其提取物在纤维化疾病中药用价值方面的相关报道，本文件以最为常见的肾和肝纤维化疾病为例，论证了桃树根及其提取物在多种器官纤维化病变中的药用价值。
发明内容
本发明的目的在于提供一种含有桃树根的药物在制备改善或/和治疗器官纤维化或/和硬化疾病的药物中的应用，尤其是在治疗肾纤维化疾病上的应用；结果表明桃树根具有良好的抗肾纤维化病变的作用效果，可以降低 UUO肾脏促纤维化肌成纤维细胞细胞的数量，显著抑制了纤维化基因的 RNA和蛋白水平。
本发明的实施例通过以下技术方案实现：
一种桃树根药物的应用，桃树根处理物在制备改善或/和治疗器官纤维化或/和硬化疾病的药物中的应用。
进一步地，所述桃树根选用山桃树根和/或其桃树根提取物。
进一步地，所述器官纤维化疾病包括：肾纤维化病、脾纤维化病、胰腺纤维化病、肺纤维化病、肝纤维化病。
进一步地，所述器官硬化疾病包括：肾硬化病、脾硬化病、胰腺硬化病、肺硬化病、肝硬化病。
进一步地，所述桃树根处理物包括桃树根和/或桃树根提取物以及药学上可接受的辅料。
进一步地，所述桃树根的重量与所述药物的总重量之比为60-80:100。
进一步地，所述桃树根的重量与所述药物的总重量之比为70:100。
进一步地，所述药物的剂型包括片剂、胶囊剂、丸剂、散剂、颗粒剂或糖浆剂。
进一步地，所述含有桃树根的药物的制备方法，包括如下步骤：将山桃树根洗净、切段，50-80℃下烘干，粉碎、研磨；然后按比例加入药学上可接受的辅料，加水混合，塑形烘干；然后制成所需剂型。
本发明实施例的技术方案至少具有如下优点和有益效果：
1.本发明对桃树根、桃树根提取物及其组合发掘了新的药用价值，将其用于制备改善或/和治疗器官纤维化或/和硬化的药物，从而为桃树根、桃树根提取物的应用开拓了一个新的领域。
2.本发明桃树根药物对肾纤维化和肝纤维化病变均具有显著的治疗效果，并且安全无毒，因此可望用于制备治疗多器官纤维化，尤其是治肾纤维化和肝纤维化病变的药物，更优地是，可望用于制备治疗由输尿管梗阻所致引起的肾小管扩张，间质增生和胶原沉积引起的肾纤维化的药物，以及经过慢性CCl4诱导的肝纤维化和肝硬化病变的药物，具有明显的应用前景和临床应用价值。
附图说明
为了更清楚地说明本发明实施例的技术方案，下面将对实施例中所需要使用的附图作简单地介绍。
图1为本发明提供的正常肾脏、模型肾脏和给药肾脏的病理染色结果；
图2为本发明提供的正常肾脏、模型肾脏和给药肾脏的羟脯氨酸定量结果；
图3为本发明提供的正常肝脏、模型肝脏和给药肝脏的病理染色结果；
图4为本发明提供的正常肝脏、模型肝脏和给药肝脏的羟脯氨酸定量结果；
具体实施方式
为使本发明实施例的目的、技术方案和优点更加清楚，下面将对本发明实施例中的技术方案进行清楚、完整地描述。实施例中未注明具体条件者，按照常规条件或制造商建议的条件进行。所用试剂或仪器未注明生产厂商者，均为可以通过市售购买获得的常规产品。
实施例1-桃树根片剂
将山桃树根，洗净、切段，65℃下烘干，粉碎、研磨，然后以30g山桃树根粉末与70g淀粉，加水混合，塑形烘干，制成颗粒，加入滑石粉和硬脂酸镁混合均匀后压制成约100个片剂。
实施例2-桃树根胶囊剂
将山桃树根，洗净、切段，65℃下烘干，粉碎、研磨，然后以30g山桃树根粉末与70g淀粉，混合均匀后装胶囊，制成约100个胶囊剂。
实施例3-桃树根颗粒剂
将山桃树根，洗净、切段，65℃下烘干，粉碎、研磨，然后以30g山桃树根粉末与70g淀粉及维生素C，混合均匀后装袋，制成约100个袋。
实施例4-桃树根片剂
将山桃树根，洗净、切段，50℃下烘干，粉碎、研磨，然后以40g山桃树根粉末与60g淀粉，加水混合，塑形烘干，制成颗粒，加入滑石粉和硬脂酸镁混合均匀后压制成约100个片剂。
实施例5-桃树根胶囊剂
将山桃树根，洗净、切段，50℃下烘干，粉碎、研磨，然后以40g山桃树根粉末与60g淀粉，混合均匀后装胶囊，制成约100个胶囊剂。
实施例6-桃树根颗粒剂
将山桃树根，洗净、切段，50℃下烘干，粉碎、研磨，然后以40g山桃树根粉末与60g淀粉及维生素C，混合均匀后装袋，制成约100个袋。
实施例7-桃树根片剂
将山桃树根，洗净、切段，80℃下烘干，粉碎、研磨，然后以20g山桃树根粉末与80g淀粉，加水混合，塑形烘干，制成颗粒，加入滑石粉和硬脂酸镁混合均匀后压制成约100个片剂。
实施例8-桃树根胶囊剂
将山桃树根，洗净、切段，80℃下烘干，粉碎、研磨，然后以20g山桃树根粉末与80g淀粉，混合均匀后装胶囊，制成约100个胶囊剂。
实施例9-桃树根颗粒剂
将山桃树根，洗净、切段，80℃下烘干，粉碎、研磨，然后以20g山桃树根粉末与80g淀粉及维生素C，混合均匀后装袋，制成约100个袋。
实施例10-桃树根糖浆剂
将山桃树根30g用乙醇溶解后加入葡萄糖糖浆，最终加去离子水至 100ml，即得。
实施例11-桃树根糖浆剂
将山桃树根40g用乙醇溶解后加入葡萄糖糖浆，最终加去离子水至 100ml，即得。
实验例1、桃树根药物对肾纤维化病变的影响
单侧输尿管梗阻(UUO)模型
1.1实验对象：随机选取20只、8周龄雄性C57BL/6J小鼠，采用1％戊巴比妥麻醉后，行左侧输尿管结扎术，然后随机分为模型组、给药组，每组10只。
1.2用药和观察方法：
模型组：用药为SPF级大小鼠维持饲料。
给药组：用药为含药饲料；即本发明实施例1的片剂+SPF级大小鼠维持饲料。
术后：模型组给予SPF级大小鼠维持饲料；给药组给予含药饲料，即本发明实施例1的片剂+SPF级大小鼠维持饲料；分别喂养7天。第8天取材，以模型组的右肾(非结扎肾)作为正常对照，模型组的左肾(UUO肾) 作为纤维化病变肾模型，以给药组的左肾(UUO肾+药)作为药物干预后的给药纤维化肾脏；
1.3实验结果：
分别对正常肾脏、模型肾脏和给药肾脏进行检测分析，结果见图1-2。
由图1-2的结果可知：通过对比正常肾脏、模型肾脏和给药肾脏的病理染色(HE和Masson)结果显示，给药肾脏的病理结果明显优于其他两组，说明，本发明桃树根可以显著抑制单侧输尿管结扎(UUO)所致引起的肾小管扩张，间质增生和胶原沉积；羟脯氨酸定量发现桃树根处理可以显著降低UUO肾脏胶原来源羟脯氨酸含量。免疫组化染色a-SMA显示桃树根可以降低UUO肾脏促纤维化肌成纤维细胞细胞的数量。同时，RT-PCR和 western blot结果显示桃树根显著抑制了纤维化基因Fibronectin(Fn， Col1a1，a-SMA的RNA和蛋白水平。由此可知，桃树根药物可显著减轻小鼠肾纤维化病变。
实验例2、桃树根药物对肝纤维化病变的影响
四氯化碳(CCl4)诱导的肝纤维化模型
2.1实验对象：随机选取30只6-8周龄雄性ICR小鼠，随机分为三组：正常组，模型组，给药组；每组10只。
2.2用药和观察方法：
正常组：小鼠给予每周两次腹腔注射橄榄油(2ul/g体重)+饲料；
模型组：小鼠给予每周两次腹腔注射20％CCl4(溶于橄榄油，2ul/g体重)+饲料；
给药组：小鼠给予腹腔注射20％CCl4(溶于橄榄油，2ul/g体重)+含药饲料；含药饲料即：本发明实施例3的颗粒剂+SPF级大小鼠维持饲料。
持续8周，取肝脏进行纤维化指标分析，包括采用定量PCR分析纤维化相关基因的表达；肝组织石蜡切片经苏木素伊红(HE)和天狼星红染色；肝组织经羟脯氨酸含量测定测试盒分析组织中纤维胶原来源羟脯氨酸含量；采用血清测定肝功(ALT)。
2.3实验结果：
分别对正常组肝脏、模型组肝脏和给药组肝脏进行检测分析，结果见图3-4。
由图3-4的结果可知：模型组小鼠经过慢性CCl4注射诱导显著的肝纤维化/肝硬化病变。相对于正常组小鼠肝脏，CCl4处理小鼠肝脏出现萎缩，肝脏表面丧失光滑触感，呈粗糙颗粒状；给药组小鼠由于给予桃树根含药饲料可以显著改善CCl4引起的萎缩，恢复肝脏色泽。通过病理染色(HE和天狼猩红)的结果可以发现桃树根可以改善CCl4引起的肝结节硬化和纤维化，羟脯氨酸定量揭示桃树根显著降低了CCl4处理小鼠肝脏的胶原羟脯氨酸含量，与此对应，定量RT-PCR提示桃树根药物处理小鼠肝脏纤维化基因a-SMA和Fn表达水平显著低于模型组。值得注意的是桃树根可以降低CCl4处理小鼠血清AST(谷草转氨酶)水平，改善受损的肝功能。由此可知，桃树根药物具有改善CCl4肝纤维化的作用。
综上所述，本发明桃树根药物对肾纤维化和肝纤维化病变均具有显著的治疗效果，尤其是对由单侧输尿管结扎(UUO)所致引起的肾小管扩张，间质增生和胶原沉积引起的肾纤维化的药物，以及经过慢性CCl4诱导的肝纤维化病变具有显著治疗效果；因此，本发明桃树根及来源于桃树根的药物活性成分可望用于改善多器官纤维化，如：肺纤维化病、心肌纤维化病、胰腺纤维化病。
Claims (5)
1.一种桃树根药物的应用，其特征在于，桃树根或/和桃树根提取物作为唯一活性成分在制备改善或/和治疗器官纤维化或/和硬化疾病的药物中的应用，所述器官纤维化或/和硬化疾病为：肾纤维化病、肝纤维化病或肝硬化病；
所述桃树根药物的制备方法，包括如下步骤：将桃树根洗净、切段，50-80℃下烘干，粉碎、研磨；然后按比例加入药学上可接受的辅料，加水混合，塑形烘干；然后制成所需剂型。
2.根据权利要求1所述的桃树根药物的应用，其特征在于，所述桃树根选用山桃树根和/或桃树根提取物。
3.根据权利要求1所述的桃树根药物的应用，其特征在于，所述桃树根的重量与所述药物的总重量之比为20-40:100。
4.根据权利要求3所述的桃树根药物的应用，其特征在于，所述桃树根的重量与所述药物的总重量之比为30:100。
5.根据权利要求1所述的桃树根药物的应用，其特征在于，所述药物的剂型为片剂、胶囊剂、丸剂、散剂、颗粒剂或糖浆剂。
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| 管鹏声.肾病综合征治疗经验.云南中医学院学报.1996,(04),第34-37页. * |
| 郎晓猛等.刘建平治疗脾胃病用药心得.河北科学技术出版社,2019,(第1版),第207页. * |
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