CN112137996A - 一种预防钩吻中毒的药物 - Google Patents
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Abstract
本发明公开了一种预防钩吻中毒的药物，该药物的活性成分为N‑甲基‑D‑天冬氨酸，该药物可以有效预防动物或人钩吻中毒，特别是预防动物或人由于钩吻中的钩吻生物碱钩吻素己引起的中毒反应，通过急性毒性动物实验表明：N‑甲基‑D‑天冬氨酸(NMDA)的提前给药，可以显著升高动物吸收钩吻素己后的存活率，动物对钩吻素己的毒性症状明显减轻。
Description
技术领域
本发明涉及一种药物，具体涉及一种预防钩吻中毒的药物，特别涉及一种预防钩吻中生物碱钩吻素己中毒的药物，属于生物医药技术领域。
背景技术
钩吻是世界著名的毒性植物，钩吻主要分为三种，一是亚洲钩吻，又称为断肠草，主要产于中国福建、广西、浙江等地，和两个北美物种，Gelsemium sempervirens和Gelsemium rankinii Small，主要产于北美。在中国，钩吻常被用于皮肤病、神经痛、癌症、坐骨神经痛等。由于钩吻的给药剂量与毒性剂量十分接近，限制了钩吻的临床使用。钩吻素己是钩吻中毒性最强的生物碱，其腹腔注射的LD50为0.185mg/kg，根据急性毒性分级标准属于极毒物质。因此钩吻素己的毒性研究对于钩吻毒性的研究具有极大的意义。
临床上钩吻中毒的原因主要分为三种，一是误服，如将钩吻认错为其他的中草药如金银花、大血藤等，这也是钩吻的中毒案例中占比最高的；二是当作中药材使用，将其当作治癌药使用或农村地区非法行医等。三是自杀或者凶杀。大多数死亡的病例都是由于钩吻在人体内的吸收速率很快，中毒程度太深，呼吸骤停为其主要死因。但目前对于钩吻中毒并没有特效的解毒药物，多数以对症治疗为主。因此，寻找能够预防或者解救钩吻中毒的药物迫在眉睫。
发明内容
针对现有技术中对钩吻中毒还未见较好的预防药物，本发明的目的是在于提供一种可以有效预防动物或人钩吻中毒，特别是由于钩吻中钩吻生物碱钩吻素己引起中毒反应的预防药物，通过急性毒性动物实验表明：N-甲基-D-天冬氨酸(NMDA)的提前给药可以显著升高动物吸收钩吻素己后的存活率，动物对钩吻素己的毒性症状明显减轻。
为了实现上述技术目的，本发明提供了一种预防钩吻中毒的药物，其活性成分为N-甲基-D-天冬氨酸。
作为一个优选方案，所述N-甲基-D-天冬氨酸的纯度高于98％。N-甲基-D-天冬氨酸(NMDA)可以直接购买于，AbMole，美国，纯度＞98％；CAS号：6384-92-5。
作为一个优选方案，所述药物为注射方式给药的药物。
作为一个优选方案，所述药物为纯度高于98％的N-甲基-D-天冬氨酸注射试剂，或者为包含辅剂的注射试剂。作为一个优选方案，所述包含辅剂的注射试剂包含水、15～20mg/LN-甲基-D-天冬氨酸和0.4～0.6g/L亚硫酸氢钠，还包括冰醋酸，冰醋酸控制注射试剂pH在5.5～6.5范围内。N-甲基-D-天冬氨酸可以直接以购买的标准品给药，或者配入现有技术中常见辅剂配制成注射药剂进行给药。
作为一个优选方案，所述药物的给药剂量为10～15mg/kg(人或动物质量)，以活性成分质量计量。
相对现有技术，本发明技术方案带来的有益技术效果：
本发明提供的预防钩吻中毒的药物以N-甲基-D-天冬氨酸为活性成分，经过大量动物实验证明，其对钩吻素己(引起钩吻中毒的主要钩吻生物碱)中毒具有良好的预防作用，提前通过注射方式给药可以显著提高动物吸收钩吻素己后的存活率，动物的毒性症状明显减轻，该药物对钩吻中毒具有预防作用。
本发明提供的预防钩吻中毒的药物相对现有技术中常见的氟马西尼、维生素B6注射液、MK-801、士的宁、地西泮等注射药物，在预防钩吻中毒方面具有显著性，有潜力作为预防钩吻中毒的临床用药。
附图说明
【图1】NMDA预防小鼠钩吻素己中毒生存曲线图。
具体实施方式
以下实施例是对本发明的进一步说明，而不会限制本发明权利要求的保护范围。
实施例1
预防小鼠钩吻素己中毒药物筛选
1、药品与试剂
氟马西尼(纯度99％；批号：M5653-01；AbMole；美国)、维生素B6注射液(批号：1903320；国药集团荣生制药有限公司、中国)、MK-801(纯度：＞98％；批号：M7581-01；AbMole；美国)、士的宁(纯度＞98％；批号：DST191026-026；成都曼斯特生物科技有限公司；中国)、地西泮
2、动物
雄性ICR小鼠，18-22g，由湖南斯莱克景达实验动物有限公司提供。于25℃室温光暗周期12h/12h下饲养，自由饮食，适应实验室7天后用于正式实验。
3、方法
取25只小鼠随机分为5组：钩吻素己组、氟马西尼+钩吻素己组、维生素B6+钩吻素己组、士的宁+钩吻素己组、MK-801+钩吻素己组、地西泮+钩吻素己；每组5只，苦味酸标记。钩吻素己组腹腔注射0.2mg/kg的钩吻素己溶液；氟马西尼+钩吻素己组先腹腔注射2.5mg/kg的氟马西尼溶液，15分钟后腹腔注射0.2mg/kg的钩吻素己溶液；维生素B6+钩吻素己组先腹腔注射30mg/kg的维生素B6溶液，15分钟后腹腔注射0.2mg/kg的钩吻素己溶液；士的宁+钩吻素己组先腹腔注射0.8mg/kg的士的宁溶液，15分钟后腹腔注射0.2mg/kg的钩吻素己溶液；MK-801+钩吻素己组先腹腔注射0.4mg/kg的MK-801溶液，30分钟后腹腔注射0.2mg/kg的钩吻素己溶液。地西泮+钩吻素己组先腹腔注射20mg/kg的地西泮溶液，30分钟后腹腔注射0.2mg/kg的钩吻素己溶液。给药后观察小鼠中毒症状和死亡情况。
4、结果
第一组小鼠在钩吻素己给药4-5分钟后产生毒性反应。表现为静卧、活动减少等，继而出现呼吸加深，头部震颤，中毒后期出现惊厥，弹跳、呼吸抑制直至死亡。其余5组对小鼠中毒症状稍微有所减轻，但是从小鼠存活率来看结果并不具有显著性。后续实验将钩吻素己的给药剂量调整为0.18mg/kg，再次筛选其它药物。具体结果见表1
表1不同药物预防小鼠钩吻素己中毒实验结果
NMDA预防小鼠钩吻素己中毒的作用
1、药品与试剂
试剂：NMDA(纯度：＞98％；批号：M2884-01；CAS号：6384-92-5；AbMole；美国)、钩吻素己(纯度99.53％；批号：MUST-18070701；成都曼斯特生物科技有限公司；中国)
2、动物
雄性ICR小鼠，18～22g，由湖南斯莱克景达实验动物有限公司提供。于25℃室温光暗周期12h/12h下饲养，自由饮食，适应实验室7天后用于正式实验。
3、方法
将20只小鼠ICR小鼠随机分为两组：钩吻素己组和NMDA+钩吻素己组。钩吻素己组腹腔注射0.18mg/kg的钩吻素己溶液；NMDA+钩吻素己组先腹腔注射12.5mg/kg的NMDA溶液，5分钟后腹腔注射0.18mg/kg的钩吻素己溶液；给药后观察小鼠中毒症状和死亡情况。
4、结果
钩吻素己组小鼠给药后相继出现行动减少、俯卧等毒性症状，随着中毒程度的加深出现头部震颤、腹式呼吸，抽搐、弹跳最后出现强直性惊厥死亡。NMDA提前给药组，NMDA显著延长小鼠的存活时间，解救成功的小鼠几乎全程俯卧直到恢复行动，不出现抽搐弹跳等症状，中毒症状减轻，并且动物的存活率显著升高。
表2钩吻素己预防小鼠钩吻素己中毒实验结果
Claims (6)
1.一种预防钩吻中毒的药物，其特征在于：活性成分为N-甲基-D-天冬氨酸。
2.根据权利要求1所述的一种预防钩吻中毒的药物，其特征在于：所述N-甲基-D-天冬氨酸的纯度高于98％。
3.根据权利要求1所述的一种预防钩吻中毒的药物，其特征在于：所述药物为注射方式给药的药物。
4.根据权利要求1所述的一种预防钩吻中毒的药物，其特征在于：所述药物为纯度高于98％的N-甲基-D-天冬氨酸注射试剂，或者为包含辅剂的注射试剂。
5.根据权利要求1所述的一种预防钩吻中毒的药物，其特征在于：所述包含辅剂的注射试剂包含水、15～20mg/LN-甲基-D-天冬氨酸和0.4～0.6g/L亚硫酸氢钠，还包括冰醋酸，冰醋酸控制注射试剂pH在5.5～6.5范围内。
6.根据权利要求1～4任一项所述的一种预防钩吻中毒的药物，其特征在于：所述药物的给药剂量为10～15mg/kg，以活性成分质量计量。
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