穿琥宁及其复方注射液解热作用的比较研究

1、    穿琥宁及其复方注射液解热作用的比较研究        提要通过热反应法测量家兔给药前后直肠温度变化的数据，证明了以穿琥宁为主药，配伍适量异丙嗪，具有药物协同作用的复方穿琥宁制剂的解热作用优于单方制剂。关键词复方穿琥宁注射液协同作用解热作用 STUDY ON ANTIPYRETIC EFFECT OF CHUANHUNINGCOMPOUND INJECTION IN COMPARISON WITH OTHERRELATIVE PREPARATIONSWang Bingn

2、anHe YingjuWang XiangLong Bo(School Pharmacy, West China University of Medical SciencesChengdu 610041)Guo LingxiaoZhang YunweiDing ZhiyongChen Lin(Wuliangye Group-Yibin Pharmaceutical FactoryYibin 644002)ABSTRACTThe antipyretic effects of Chuanhuning compound injections with low and normal doses wer

3、e studied in this paper compared with Chuanhuning simplex injections with low and normal doses, promethazine simplex and normal saline injections. The results showed that the antipyretic effect of Chuanhuning compound injection with normal dose was stronger than that of any other relative preparatio

4、ns and the antipyretic effect of Chuanhuning compound injection with low dose was stronger than that of Chuanhuning simplex injection with low dose, promethazine simplex injection, normal saline injection and equivalent to that of Chuanhuning simplex injection with normal dose, both statistically an

5、d pharmacodynamically, respectively. The reasonable explanation should be atributed to the synergism of drugs.Key WordsChuanhuning compound injectionSynergismAntipyretic effect穿心莲Andrographis paniculata(Burm f.)Nees的有效成分穿心莲内酯与琥珀酸酐在氢氧化钾吡啶溶液中反应，生成脱水穿心莲内酯琥珀酸半酯单钾盐，商品名为穿琥宁(Chuanhuning)。穿琥宁对呼吸道感染及婴幼儿肺炎有较好

6、疗效。鉴于市售品仅有单方注射剂，制剂单调，疗效有待改善。为了增强单方制剂解热、镇痛和镇静效果，依据药物剂型设计原理，利用药物间协同作用1，2，作者研究、开发了复方穿琥宁注射剂。采用温差均数作为解热实验指标，生理盐水作为对照，评价正常剂量复方穿琥宁(穿琥宁100 mg/kg4、异丙嗪2.5 mg/kg2-3)、正常剂量单方穿琥宁(100 mg/kg)、低剂量复方穿琥宁(穿琥宁10 mg/kg、异丙嗪2.5 mg/kg)、低剂量单方穿琥宁(10 mg/kg)及单方异丙嗪(2.5 mg/kg)的解热作用。1药品、试剂、仪器单、复方穿琥宁注射液(五粮液集团-宜宾制药厂)；盐酸异丙嗪注射(上海天丰药厂)

7、；生理盐水(四川简阳制药厂)；伤寒、副伤寒甲、乙三联菌苗(卫生部成都生物制品研究所)。注射器、针头、体温表等。2实验方法与结果解热曲线的绘制实验动物大耳白兔，体重(1.62.0) kg，雌雄各半(华西医科大学实验动物中心)。选择体温波动不超过0.2者供用，随机分组，每组8只，共6组。测定家兔正常体温禁食6 h，每隔1 h测定一次肛温，连续三次，求其均值。实验过程中，保持室温相对稳定。2.1.3制作家兔病理模型按0.5 ml/kg的剂量给家兔耳沿静注伤寒、副伤寒甲、乙三联菌苗。所用菌苗应不低于100亿个/ml。菌苗注入1 h后，即见直肠温度上升(1.01.5) ，持续4 h以上。给药注射伤寒、副

8、伤寒甲、乙三联菌苗1 h后测定肛温，同时按制剂规格和家兔体重分别腹腔注射穿琥宁、异丙嗪及生理盐水注射液。2.1.5体温测定给药后，在1、2、3、4、6 h测定组内每只家兔肛温，计算各组不同时刻体温差均值，结果见表1。Table 1The averages of variance in body-temperature in each group of rabbits before/after intra-abdominal administration of various preparationsGroupDose(mg/kg)The averages of increase in body

9、-temperature at one hour after administration of tuphosumet paratyphoum A/B vacuumThe averages of decrease in body-temperature at different time after administration of various prepar-ations()()012346A (Chuanhuning simplex injection chuanhuning with low dose)10B (Promethazine simplex injection Prome

10、thazine with normal dose)C (Chuanhuning Chuanhuning compound injection with low dose Promethazine)D (Chuanhuning simplex injection Chuanhuning with normal dose)100E (Chuanhuning Chuanhuning compound injection with normal dose Promethzaine)F (Normal saline injection)2.2数据处理将每只家兔在不同时间测得的体温值，减去其正常体温均值，

11、差值即为体温差(T)。T有正负之分，正表示所测体温高于正常体温；负表示低于正常体温；零表示与正常体温相等。2.2.2绘制解热曲线以每组家兔体温差均值()为纵坐标，测定时间t(h)为横坐标，顺次连接各点得解热曲线(1)。 Fig 1The fever reduction curves of various preparationsA、B、C、D、E、F are the same as in table 1由可知，解热作用强弱顺序为E(正常剂量复方穿琥宁注射液)D(正常剂量单方穿琥宁注射液)C(低剂量复方穿琥宁注射液)B(单方异丙嗪注射液)A(低剂量单方穿琥宁注射液)F(生理盐水)。根据表1各组温

12、差变化均值，求出对应差，用统计学方法，两组配对作t检验，结果见表2。根据t检验结果，除C-D配对外，其余各对的解热作用均有显著差异，即C优于A，优于B；E优于其他所有制剂。C-D无显著差异说明低剂量穿琥宁配以适量异丙嗪，其解热效果与剂量高于它10倍的正常剂量单方穿琥宁相当，也显示出复方制剂的优越性。3讨论根据初步药理学研究，穿琥宁属于清热解毒类中草药4。解热镇痛类药物常与异丙嗪配伍以增强解热、镇静和镇痛效果，如热痛宁注射液、安热静注射液等5。穿琥宁配伍异丙嗪制成复方制剂，即为了达到增强解热、镇静和镇痛效果的目的。3.2解热曲线和两组配对t检验结果一致显示，各种制剂对家兔类毒素发热的解热作用由强至弱顺序为EDCBAF。综上所述，由于药物间协同作用，复方穿琥宁注射液增强了单方的解热作用，相应增加了镇静和镇痛效果，有利于急性感染所致的高热烦躁，特别对于小儿。因此开发复方穿琥宁注射液有重要意义。Table 2The Relative variances of A、B、C、D、E、F And the results of t testt(h)A-BA-CB-CB-EC-DC-ED-EF-AF-C012346t testThelevelof Singni-ficanc