【作者】 魏亚东；

【导师】 阮时宝； 吴符火；

【作者基本信息】 福建中医学院 ， 方剂学， 2003， 硕士

【摘要】 目的：通过对缩泉固尿合剂的急性毒性试验与对家兔离体膀胱平滑肌和尿道括约肌收缩活动影响的观察及临床预试，初步评价该药的安全性及有效性，为开发治疗压力性尿失禁的中药新药打下坚实的基础。 方法：急性毒性试验：预试验用300％的缩泉固尿合剂（3g/ml）一次给小鼠灌胃，若小鼠死亡数＞70％，则测定半数致死量(LD₅₀)；若毒性很小，测不出LD₅₀，则改用一日内以小鼠能耐受的最大浓度300％和最大容积0.3ml／10g，灌胃3次，测定最大给药量。离体实验：取家兔膀胱体背侧纵行肌条及尿道括约肌肌条，将其分别分次置于平滑肌槽中，经肌肉张力换能器将信号输入二道生理记录仪，记录肌条的等长收缩活动。临床预试：对54例脾肾两虚型压力性尿失禁患者进行临床治疗观察。 结果：急性毒性试验中预试验发现300％的缩泉固尿合剂一次给小鼠灌胃，未引起小鼠死亡，测不出LD₅₀，改测最大给药量，其值为180g/kg，相当临床日用量的108倍。 离体实验发现，缩泉固尿合剂在25mg／ml（高剂量）时能显著增强家兔尿道括约肌收缩力，并能抑制膀胱平滑肌的自动节律性收缩，同时可使平滑肌松弛，基础张力降低；对KCL引起的离体膀胱平滑肌的收缩具有一定的抑制作用。 临床预试表明，缩泉固尿合剂可明显改善脾肾两虚型尿失禁患者的小便失禁症状，其他伴随症状亦有显著改善；尿动力学检查最大尿流率、平均尿流率、排尿时间有显著改善；逼尿肌压力变化无显著性差异；功能性尿道长度有一定延长；最大尿道关闭压显著回升；且患者血中雌二醇含量有一定的升高。总体疗效明显优于对照组。未见毒、副作用与不良反应。 结论：缩泉固尿合剂毒、副作用小，测得最大给药量的结果为药物的安全性提供了实验依据。该合剂能显著增强家兔离体尿道括约肌收缩力，对膀胱平滑肌收缩力有一定 福建中医学院硕士学位论文巴巴里巴生里里里巴巴巴里巴里巴巴三绝里里抑制作用。该方可明显改善脾肾两虚型压力性尿失禁患者的小便失禁及其他伴随症状;对尿动力学指标也有显著改善，且患者血中雌二醇含量有一定升高，其疗效明显优于对照组。本合剂治疗压力性尿失禁的机理初步认为可能与提高体内雌激素水平有关。更多还原

【Abstract】 Objective:To assess the security and effectiveness of the mixture of Suo Quan Gu Niao(SQGN) through trial of acute toxicity,effects of contractile activity of bladder smooth muscle and sphincter urethrae in vitro and clinical research. In order to develop the new traditional Chinese medicine to treat Stress Urinary Incontinence on the base of this study .Methods:Trial of acute toxicity.The mice were given once the mixture of SQGN 300% by oral irrigation in the pre-trival.If the number of dead mice exceeds 70%, 50% lethal dose(LD50) was measured ;when LD50 could not be measured because of lower toxicity,the maximum tolerance dose(MTD) was measured with the highest concentration 300% and the largest volume 0.3ml/10g by irrigating gastric(ig) for 3 times in one day. Trial in vitro:The bladder muscle strip prepare along the dorsal iongitudinal axis in rabbit bladder body and sphincter urethrae were suspended in a tissue chamber, their isometric contractile activity signals were measured by the multichannel recorder through musde-tension transducer; 54 pre-clinical cases were proceed in order to observe the clinical effects of the mixture of suo quan gu niao.Results: The pre-trials showed that the LD50 could not be measured in the trials of acute toxicity , and the MTD was 180g/Kg after the revision of its measurment which was corresponding to 108 times of daily clinical dosage. Trial in vitro made clear that it could remarkably increase the contractile of sphincter urethrae , inhibite the urinary bladder smooth muscle contraction and lower the baseline; when the mixture of Suo Quan Gu Niao was 25mg /ml(high dosage), it could inhibit the urinary bladder strip contraction induced by KCL,too.Pre-clinical made clear that it could remarkably improve the smptoms of patients who were diagnosed as weakness of spleen and kidney.The examination of urine dynamics showed that the MFR,AMFR and S were remarkably improved, FUL was prolonged, MCUP was incrcascd;but their was not remarkable difference between the bladder dctrusor, and the negative stress wave did not appear;and the serum estradiol(E2) lever was increased.The overall effect was better than the control group and did not has obvious poisonous effect and side-effect.Conclusion:The Mixture of SQGN has little poisonous effect and side-effect. The MTD measured has important significance to research the dosage of long toxicity trial, and we could research the safe and effective dosage in clinic,avoid acute side-effect according to it.It could remarkably increase the contractilation of Sphincter Urethrae of rabbits in vitro and inhibite contractile of urinary blader strip.It has effect of invigorating the kidney and spleen, supplementing the vital energy and pycnosising. It could improve paraments of urine dynamics, and increase the serum E2 level. Its overall effect is better than the contorl group. The treatment mechanism probably is relative to increase the serum E2 lever, and excite the a epinephrine receptor.更多还原