CN112641780A - 小檗红碱用于制备抗失眠药物的用途 - Google Patents
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Abstract
本发明属于医药技术领域,具体涉及小檗红碱用于制备抗失眠药物的用途。临床前动物研究显示小檗红碱或其溶剂化物或其药用盐或水合物或前药具有提高海马和下丘脑中5‑HT含量,提高血清激素中MT含量,提高海马中GABA含量,降低血清激素中ACTH和CRH含量,降低海马中GLU含量的作用,有明确的抗失眠作用,有助于小檗红碱的进一步开发利用。
Description
技术领域
本发明属于医药技术领域,具体涉及小檗红碱用于制备抗失眠药物的用途。
背景技术
小檗红碱(Berberrubine)又称9-脱甲基小檗碱,9-脱甲基黄连素等,因其红色而得名, 是高共轭电中性醌式结构,暗红色针状晶体,熔点280℃-282℃,碘化铋钾反应和亚甲二氧基 反应阳性。已有研究和临床应用结果表明,小檗红碱具有抗炎、抑菌、抗肿瘤和降血糖等药 理活性,但是未见其具有抗失眠作用的报道。
发明内容
本发明公开了小檗红碱用于制备抗失眠药物的用途。
小檗红碱的结构式如下:
本发明所述的小檗红碱采用现有技术制备或者购买获得。
本发明的目的之一是提供小檗红碱或其溶剂化物或其药用盐或水合物或前药在制备抗失 眠药物中的应用。
所述的小檗红碱或其溶剂化物或其药用盐或水合物或前药作用于下丘脑-垂体-肾上腺轴。
所述的小檗红碱或其溶剂化物或其药用盐或水合物或前药用于提高海马和下丘脑中 5-HT含量。
所述的小檗红碱或其溶剂化物或其药用盐或水合物或前药用于降低血清激素中ACTH和 CRH含量,提高血清激素中MT含量。
所述的小檗红碱或其溶剂化物或其药用盐或水合物或前药用于提高海马中GABA含量, 降低海马中GLU含量。
本发明的第二个目的是提供一种抗失眠的药物组合物,所述药物组合物包括小檗红碱或 其溶剂化物或其药用盐或水合物或前药及可药用载体。
本发明所述小檗红碱的治疗有效量为60mg/kg。
本发明所述的可药用载体可以采用本领域常规的可药用载体。
本发明开辟了一种全新的小檗红碱或其溶剂化物或其药用盐或水合物或前药的新用途, 将其应用于制备抗失眠药物,并且对其作用机制进行了进一步的研究,有助于小檗红碱的进 一步开发利用。
附图说明
图1为正常组、模型组、阳性对照组、小檗红碱组中测得的血清激素中ACHT含量;
图2为正常组、模型组、阳性对照组、小檗红碱组中测得的血清激素中MT含量;
图3为正常组、模型组、阳性对照组、小檗红碱组中测得的血清激素中CRH含量;
图4为正常组、模型组、阳性对照组、小檗红碱组中测得的下丘脑和海马中5-HT含量;
图5为正常组、模型组、阳性对照组、小檗红碱组中测得的下丘脑和海马中GLU含量;
图6为正常组、模型组、阳性对照组、小檗红碱组中测得的下丘脑和海马中GABA含量。
具体实施方式
抗失眠药效学试验及结果。
实验材料:Wistar雄性大鼠,动物随机分组,入组时体重180-200g,室温22℃±1℃, 光照时间:8:00-22:00,食水不限。适应性饲养5天。
药物:小檗红碱用蒸馏水完全溶解后配置到所需浓度。
试验方法:
1.分组造失眠模型。将40只大鼠随机分为4组,正常组、模型组、阳性对照组(阳性对照药是地西泮)、小檗红碱组,每组10只,除正常组外,其余三组均于上午8:00-9:00间 腹腔注射5-HT抑制剂PCPA造模(400mg/kg,每只2.5mL),注射三天后造模结束。
2.模型评价:(1)行为学评价:与正常组比较,模型组大鼠出现昼夜节律消失,日间活 动频繁,对声音、光线等外界刺激比较敏感;精神状态焦躁、亢奋,对人的攻击性增强;毛发粗糙、无光泽;饮食量明显减少,饮水量增多,排尿增多。以上症状表明大鼠处于失眠状态,提示造模成功。本发明所述的PCPA大鼠失眠模型的证候属性与中医心肾不交型。
3.(1)ELISA法测定大鼠脑组织海马和下丘脑中5-HT含量:与正常组相比,模型组5-HT含量明显降低(P<0.05),具有统计学意义;与模型组比较,小檗红碱组5-HT含量显 著升高(P<0.05)。说明小檗红碱对治疗失眠起了药效,同时也说明了造模成功。
(2)ELISA法测定大鼠血清中ACHT、CRH、MT含量:与正常组相比,模型组ACTH 和CRH含量显著升高(P<0.05),MT含量显著降低,具有统计学意义;与模型组比较,小 檗红碱组ACTH和CRH含量显著降低(P<0.05),MT含量显著升高。
(3)ELISA法测定海马和下丘脑GLU、GABA含量:与正常组相比,模型组GABA含 量显著降低(P<0.05),GLU含量显著升高,具有统计学意义;与模型组比较,小檗红碱组GABA含量显著升高(P<0.05),GLU含量显著降低。 血清激素:
下丘脑:
海马:
Claims (7)
1.小檗红碱或其溶剂化物或其药用盐或水合物或前药在制备抗失眠药物中的应用。
2.根据权利要求1所述的小檗红碱或其溶剂化物或其药用盐或水合物或前药在制备抗失眠药物中的应用,其特征在于,所述的小檗红碱或其溶剂化物或其药用盐或水合物或前药作用于下丘脑-垂体-肾上腺轴。
3.根据权利要求1所述的小檗红碱或其溶剂化物或其药用盐或水合物或前药在制备抗失眠药物中的应用,其特征在于,所述的小檗红碱或其溶剂化物或其药用盐或水合物或前药用于提高海马和下丘脑中5-HT含量。
4.根据权利要求1所述的小檗红碱或其溶剂化物或其药用盐或水合物或前药在制备抗失眠药物中的应用,其特征在于,所述的小檗红碱或其溶剂化物或其药用盐或水合物或前药用于降低血清激素中ACTH和CRH含量,提高血清激素中MT含量。
5.根据权利要求1所述的小檗红碱或其溶剂化物或其药用盐或水合物或前药在制备抗失眠药物中的应用,其特征在于,所述的小檗红碱或其溶剂化物或其药用盐或水合物或前药用于提高海马中GABA含量,降低海马中GLU含量。
6.一种抗失眠的药物组合物,其特征在于,所述药物组合物包括小檗红碱或其溶剂化物或其药用盐或水合物或前药及可药用载体。
7.根据权利要求6所述的一种抗失眠的药物组合物,其特征在于,所述小檗红碱的治疗有效量为60mg/kg。
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