目的:建立健康人血浆淫羊藿苷的LC-MS/MS分析方法,探索淫羊藿提取物临床药动学特点.方法:色谱柱为Agilent ZORBAXSB-C18(2.1 mm×30mm,3.5 μm);流动相为乙腈:水(含0.1％甲酸)=22:78;流速0.3 mL/min;ESI离子源;定量离子对淫羊藿苷m/z:677.3→369.0,内标非那西丁m/z:180.1→110.0.健康受试者2例,单次口服含淫羊藿苷40.16 mg的淫羊藿提取物片剂制剂12片,分别于给药前和给药后0.5,1、1.5、2、2.5、3、3.5、4、5、6、7、8、10、12、24 h采血,检测血浆中淫羊藿苷.结果:血浆中内源性物质不干扰样品的测定,定量下限为0.05 μg/L,方法符合生物样品分析要求.在本试验血浆浓度线性范围0.05～21.48 μg/L内,人血浆中未测到淫羊藿苷原型.

Salvianolic acid B is one of the currently studied salvia miltiorrhiza phenolic acids.Its absorption is rapid,but the bioavailability is low.Its distribution depends on the physical and chemical properties,protein binding rate and characters of tissue and organs.Metabolism of salvianolic acid B shows a non-linear pharmacokinetic property,and P450 enzyme involves in the process.The major excretion organ for the component is via bile.In the article,we summarized the studies on the pharmacokinetics of salvianolic acid B,and focused on the following aspects: processing procedures of plasma sample,determination validation,absorption,distribution,metabolism,excretion and pharmacokinetic interaction with the other drugs.

Objective To observe and evaluate the tolerance and safety of Muxiangdongli capsule in Chinese volunteers.Methods Twenty four,twelve healthy subjects,seperated to 5 different dose(0.25,0.5 1.0,1.5,2.0 g) and 2 difference dose(1.5,2.0 g) respectively.Single-dose(n=24) and multipl dose(n=12) groups according to different gender randomly gender randomly.The clinical symptoms,signs of life,etc were observed.Results The result of routine blood tests,APTT and Cr beyond the normal range occurred in 6 persons in the single dose group.The result of routine blood tests,FIB and TT beyond the normal range were founded in 7 cases in the multiple dose groups.There was no clinical significance for the changes after combing with other indicators.Conclusion Healthy volunteers can tolerate single oral dose of 0.25-2.00 g·d-1 each day and multiple dose 1.5 or 2.0 g·d-1.

Objective To establish a liquid chromatography-mass spectrometry(LC-MS/MS) method for evaluating the bioequivalence of luofenpuxinnamin dispersible tabletsand compound zinc gluconate and ibuprofen granules in healthy volunteers .Methods According to a random opening, two-period crossover design(cleaning phase is two weeks). Twenty healthy volunteers take a single same oral dose of luofenpuxinnamin dispersible tablets (test)and compound zinc gluconate and ibuprofen granules(reference) (equal to 4 mg chlorpheniramine maleate). Using indapamide as internal standard, the content of chlorpheniramine maleate was determined by SRM model. The pharmacokinetic parameters was calculate by soft were. Results The main pharmacokinetic parameters of luofenpuxinnamin dispersible tablets(test) and ibuprofen granules (reference) of were as follows:Cmax were (12.27±3.04) and (13.47±3.52)ng·mL-1; tmax were (2.43±1.49) and (2.10±1.07) h; AUC0-t were (303.17±91.39) and (315.58±76.78) ng·h·mL-1; AUC0-∞ were (355.19±120.30) and (365.71±100.48) ng·h·mL-1; t1/2 were (24.86±5.83) and (24.71±5.96) h, resperitively. The relative bioavailability of test was (99.80± 41.20)%. Conclusion The chlorpheniramine maleate of test and reference was bioequivalence.

目的:运用实验研究方法,了解宫炎泡腾片的抑菌作用及对大鼠阴道黏膜实验性感染的治疗作用.方法:分别将金黄色葡萄球菌、白色念珠菌的混合液注入大鼠阴道内部,造成局部感染模型,然后将实验大鼠随机分组,分别经阴道不同间隔给药,每日1次,观察大鼠阴道局部炎症变化情况,并每日将大鼠阴道分泌物涂碟、培养,涂片检查菌落生长情况.结果:宫炎泡腾片对实验病菌有明显的抑制作用,使致病菌所引起的感染性大鼠阴道炎症有明显的改善.结论:宫炎泡腾片可以抑制金黄色葡萄球菌和白色念珠菌生长,并具有治疗由致病菌感染所致实验性阴道炎症的作用.

Objective:To assess the safety and tolerance of single-dose and continuous oral of Shusheweikexin Capsule in Chinese volunteers,thus to establish the effective clinical dosage.Methods:Tolerance test of single-dose intravenous drip:twenty-four healthy volunteers were allocation into 5 single-dose groups by different gender(0.3、0.6、1.2、2.4、and 3.9g respectively).Tolerance test of continuous intravenous drip:twelve healthy volunteers were allocation into 2 multiple-dose groups(2.4 or 3.9g respectively) by different gender,qd×7d.Subjective symptoms,objective signs,vital signs including blood pressure,heart rate,respiration were observed,and routine blood tests,routine urinetests,hepatic function,renal function,clotting function,electroca-rdiogram,abdominal CDFI were monitored after medication.Results:The single-dose groups have three cases of hemoglobin,three cases of hematocrit,four cases of PT,one case of APTT,one case of TT,one case of ECG abnormalities results after treatment,in conjunction with other indicators,judgement without clinical significance.The continuous oral groups have four cases of hematocrit,one case of PT,two cases of APTT,one case of TT abnormalities results after treatment,in conjunction with other indicators,judgement without clinical significance.Conclusions oral administration of a single-dose shusheweikexin capsules 0.3～3.9g/dose,and continuous oral of Shusheweikexin Capsule of 2.4 or 3.9/person in China healthy male or female volunteers is safe.In Phase II clinical trials,recommendate the clinical dosage of oral Shusheweikexin capsule for each person is 0.3 to 3.9g.

采用气管内注入博莱霉素(BLM5)复制小鼠肺纤维化模型,以肺指数、肺组织病理及肺组织羟脯氨酸(HYP)为观测指标,观察水蛭、疏血通、甘利欣对小鼠实验性肺纤维化的干预作用.结果显示,水蛭可以降低肺指数,改善肺泡炎及肺纤维化程度,降低肺组织HYP含量.提示水蛭粉剂能缓解BLM5所致的小鼠肺纤维化.

Objective To establish the clinical pharmacokinetics research method for Bawei Jiangu Tablet.Methods Drug blood concentration was estimated through analyzing the ingredients and preclinical pharmaceutical research results of Bawei Jiangu Tablet.Results Corresponding cardiac glycoside value in serum of animals treated with oral use of Bawei Jiangu Tablets and cortex periplocae extracts can be detected by drug monitor system of digoxin immunoreaction, which was similar to that in animals treated with digoxin.Corresponding cardiac glycoside value had also been detetected in serum of subjects in phaseⅠclinical tolerance trial,which was related to the time and dosage of administration.Clini- cal negative control trial showed that the reaction was specific.Conclusion Pharmacokinetics study on target of toxic components with cross-reaction of periplocoside is feasible through drug monitor system of digoxin immunoreaction.

目的:测定北细辛全草及根中马兜铃酸A的含量及其急性毒性。方法:马兜铃酸A的含量测定采用反相高效液相色谱法,色谱柱为phenom enex C18(4.6mm×250mm),流动相为甲醇-水-醋酸(63:36:1),检测波长为390nm,流速1.0mL/m in,柱温35℃;急性毒性试验采用小鼠灌胃给药最大给药量法。结果:HPLC法测定细辛中马兜铃酸A含量,线性范围为20.2~121.2ng,北细辛全草及细辛根的平均回收率分别为97.2%和98.1%;北细辛全草及根中马兜铃酸A的平均含量分别为61.40μg/g和45.80μg/g;北细辛全草及根1g/mL水提取物给小鼠灌胃给药,LD50不能测出,耐受量大于40g/kg。结论:马兜铃酸A的含量测定法准确、可靠,重现性好,精密度高;北细辛全草中马兜铃酸A的含量高于细辛根中马兜铃酸A的含量;小鼠对北细辛全草和细辛根的水提取物具有较高的耐受性,耐受倍数相当于药典规定的临床剂量的800倍,比较安全。

香加皮为临床常用中药材,历届中国药典均有收载.在国家药品监督管理部门正式公布的国家中成药标准品种中,处方组成含香加皮的不少于25种[1].2000年版药典记载香加皮"有毒[2].因为有毒,临床处方中出现的概率并不很高,相当数量的药房和医院饮片调剂斗架上甚至没有该品种,但由于品名(别名)、性状、功效、主治与五加皮相近,临床与五加皮混用情况相当严重[3～7],其不良反应的发生率也远高于实际报道.本研究就其原因及预防方法分析探讨,以期得到医药同道的重视,减少临床不良反应的发生率.

Objective To observe the effects of compound formula of Chinese herbal benefiting spleen and kidney and invigorating blood on kidney cortex transforming growth factor β1(TGF-β1)and type IV collagen mRNA expression,and probe its mechanism in rats with early diabetic nephropathy(DN).Methods DN is induced by streptozocin(STZ)in rats according to 53 mg/kg i.p,then random by assign to traditional Chinese medicine group(compound formula),western medicine group(Ruitai),model group and normal group.Eight weeks later,measure the expression of the rats kidney cortex TGFβ1 and collagen mRNA of type IV with RT-PCR.Results Compared with the model group,TGFβ1 and collagen mRNA of type IV(P 0.01)is obviously lower in the treating group.And the traditional Chinese medicine group is superior to the western medicine group(P 0.01).Conclusion Compound formula of Chinese herbal can protect kidney,delay pathology damage to kidney,and hold back from DN by lowering expression level of TGFβ1 and collagen mRNA of type IV.

Objective To observe the effects of complex Chinese herbal formula with the actions of tonifying spleen and kidney and invigorating blood on kidney structure and function in rats with early diabetic nephropathy(DN),and to probe its mechanism.Methods Rat models of DN was induced by one-dose streptozocin(STZ)53 mg / kg i.p.Then the rats were randomized into Chinese medicine(complex formula)group,western medicine(Ruitai)group,model group and normal group.Biochemical parameters such as blood sugar,ratio of body weight and kidney weight,serum creatinine(SCr),blood urea nitrogen(BUN)and urinary micro-albumin(UAlb)and the changes of kidney structure in rats with DN were observed.Results Compared with the model group,the damage of kidney structure and the damage of renal function such as blood sugar,UAlb,SCr and BUN were obviously reduced in the other treatment group(P 0.01),and the effect of Chinese medicine was superior to the western medicine(P 0.01).Conclusion Complex Chinese herbal formula has preventive and therapeutic effect on early DN by lowering the blood sugar,UAlb,SCr,BUN,etc.

目的:观察健康受试者单次服用八味健骨片临床治疗量(4片/人),安全大剂量(8片/人)后,Periplocin(杠柳毒苷)的药动行为.方法:筛选健康受试者18人,采用Access Immunoassay System Digoxin试剂盒(免疫测定系统测定人血清Digoxin,简称A.I.S.D.法)测定了不同时刻血浆中Periplocin的浓度,根据血药浓度-时间数据,求得两个剂量组Periplocin药代动力学参数.结论:口服八味健骨片临床治疗量是安全的.

阐述了香加皮临床应用情况、及其毒性杠柳毒苷来源情况,药理作用等.对香加皮、五加皮(南加皮、北五加皮)进行鉴别,并对香加皮市场药店流出误投现象进行调查.

目的:证明消积肥儿口服液的健脾消积作用.方法与结果:造成小鼠大黄性脾虚模型和游泳疲劳,观察结果表明,具有健脾补虚作用;对大鼠胃液分泌功能和小鼠小肠推进运动作用方面的实验研究,结果表明,具有促进消化、吸收功能等作用.结论:消积肥儿口服液具有健脾消积作用,其作用与原剂型消积肥儿丸相当.

酪蛋白是检测胰蛋白水解酶活力的常用底物之一,实验证明可以将其用于豆豉溶栓酶的酶活力测定.酪蛋白浓度大于0.6%,豆豉溶栓酶浓度在0.077～0.347mg/ml之间,要严格控制反应温度和反应时间.室温下放置基本不影响测定结果;缓冲系统对酶活性影响较大.

目的:观察鼻通水的抗炎作用.方法:观察鼻通水及对照药鼻通丸对小鼠耳肿胀及大鼠腹部毛细血管通透性的作用.并以二甲苯小鼠鼻腔滴注制作鼻炎模型,观察鼻通水及对照药的治疗作用.结果:鼻通水具有较好的抗炎作用,并呈一定的量效关系,并对二甲苯致小鼠鼻部炎症有良好的防治作用.结论:鼻通水是防治鼻炎的有效药物.