丙二醇与月桂氮(艹卓)酮对咖啡因透皮吸收的影响

透皮吸收是通过皮肤给药以达到局部或全身治疗作用的一种给药途径。丙二醇(propylene glycol,PG)与月桂氮(艹卓)酮(azone,AZ)都能影响药物的透皮吸收。我们以咖啡因(caffeine,CA)为模型药物，研究了PG、AZ单用及合用对其透皮吸收的影响。 1 材料与仪器 丙二醇，北京化学试剂公司；月桂氮(艹卓)酮，广州……     

丙二醇与月桂氮酮对咖啡因透皮吸收的影响

透皮吸收是通过皮肤给药以达到局部或全身治疗作用的一种给药途径。丙二醇 (propyleneglycol,PG)与月桂氮卓艹 酮 (azone,AZ)都能影响药物的透皮吸收。我们以咖啡因 (caffeine ,CA)为模型药物 ,研究了PG、AZ单用及合用对其透皮吸收的影响。1　材料与仪器丙二醇 ,北京化学试剂公司 ;月桂氮 卓艹 酮 ,广州精细化学工业公司 ;咖啡因标准品 ,中国药品生物制品检定所 ;咖啡因原料药 ,杭州民生制药厂。75 2紫外分光光度计 ,上海第三仪器厂。2　方法与结果2 .1　测定波长的选择　取咖啡因适量用蒸馏水配成 6μg/mL的溶液 ,在紫外分光光度计上…     

月桂氮Zuo酮和月桂酸对利多卡因经皮渗透的促进作用

以离体大鼠皮肤为渗透屏障，研究了月桂氮Ｚｕｏ酮，月桂酸对利多卡因经皮渗透的促进作用，利多卡因皮渗透符合零级动力学过程，月桂氮Ｚｕｏ酮，月桂酸均可显著促进利多卡因渗透，以月桂酸的促透效果为佳，２％月桂氮Ｚｕｏ酮，１：１月桂酸为它们各自的较佳作用浓度，月桂氮Ｚｕｏ酮，月桂酸主要通过增加利多卡因在皮肤中的分配促进药物渗透，它们增加分配的作用与它们对药物溶解度的影响无关。     

不同促渗剂对秦皮甲素乳膏透皮吸收的影响

目的：制备秦皮甲素乳膏,并通过动物离体透皮吸收实验,选择秦皮甲素乳膏中最佳透皮吸收促渗剂。方法：采用透皮扩散装置,以生理盐水为接收介质,以小鼠离体腹部皮肤为透皮屏障,优选出最佳的透皮吸收促渗剂。结果：最优的透皮吸收促渗剂为5％冰片,最佳处方的动力学方程为：y=0．668x＋1．8256,r=0.9991。结论：5％的冰片作为秦皮甲素乳膏的透皮吸收促渗剂具有良好的效果。     

不同浓度氮酮对黄芩苷体外透皮吸收的影响

目的研究氮酮对黄芩苷体外透皮吸收的影响。方法以裸鼠皮肤为实验屏障,观察氮酮浓度(体积比)分别为0、2%、4%、6%、8%、10%时黄芩苷透皮吸收速率常数。结果氮酮浓度为0、2%、4%、6%、8%、10%时黄芩苷的透皮吸收速率常数分别为76.07、89.23、167.36、238.61、200.45、171.49μg·cm-2·h-1。结论氮酮可以促进黄芩苷的透皮吸收,在实验浓度范围内,氮酮浓度为6%时有最大的透皮速率常数。     

不同透皮促进剂对复方黄芩巴布剂中黄芩苷透皮吸收的影响

目的 研究氮酮、丙二醇、油酸及两者配伍对复方黄芩巴布剂中黄芩苷透皮吸收的影响.方法 制备含不同吸收促进剂的复方黄芩巴布剂,以Franz扩散池为透皮吸收装置,采用HPLC法对黄芩苷进行测定,考察不同透皮促进剂的促渗效果.结果 与不含吸收促进剂的巴布剂比较,吸收促进剂对黄芩苷透皮吸收的影响为丙二醇(PG) 氮酮(azone)＞丙二醇 油酸(OA)＞油酸 氮酮＞不含促进剂.其中丙二醇与氮酮浓度各为1.5%时,黄芩苷有最大渗透速率154.36μg/(cm2·h).结论 复合促进剂对黄芩苷的透皮吸收均有促进作用,1.5%丙二醇 1.5%氮酮作为本复方的透皮促进剂效果较好.     

阿司匹林对卡托普利引起的咳嗽的逆转作用

目的观察卡托普利相关的咳嗽特点及应用卡托普利、氯沙坦血栓素B2（TxB2）和昏酮前列环素F1α（6-Keto-PGF1α）的变化,并对卡托普利咳嗽者换用氯沙坦或加用阿斯匹林后咳嗽特点进行分析。方法心血管病患者598例,分为卡托普利组300例和氯沙坦组298例,观察两组咳嗽发生率及咳嗽特点,对56例卡托普利咳嗽者28例改服氯沙坦,另28例加用阿斯匹林。应用放射免疫分析法检测用药前后血、尿TXB2和16-Keto-PGF1α含量。结果（1）咳嗽发生率在卡托普利组为18．67％,氯沙坦组为1．68％。卡托普利组咳嗽者28例换用氯沙坦后,27例咳嗽停止;另28例加用阿斯匹林300mg／d后,21．43％咳嗽消失,25％咳嗽减轻;（2）卡托普利咳嗽者血TXB2升高,血、尿中P6-Keto-PGF1α下降,TXB2／6-Keto-PGF1α比值增加（均P〈0．05）;（3）卡托普利咳嗽者,TXB2／6-Keto-PGF1α比值在改服氯沙坦或加阿斯匹林后下降fP〈0．05或P〈0．01）。结论血栓素和前列环素变化失衡是卡托普利咳嗽的原因之一。卡托普利咳嗽患者可换用氯沙坦,加服阿斯匹林可增加卡托普利在心血管病患者中应用的比例．降低治疗费用。     

基于紫外吸收及导数光谱监测乙酸钠催化合成阿司匹林的反应研究

目的 采用乙酸钠为催化剂,对合成阿司匹林的反应体系进行监测研究。方法 分别建立阿司匹林和水杨酸在289 nm和308 nm处的紫外二阶导数值与浓度的标准工作曲线,实时监测不同温度条件下反应体系中阿司匹林和水杨酸的含量变化情况。结果 当控制合成阿司匹林的反应温度分别为45、55、65和75℃时,反应完成的时间约为20、10、4和3 min。结论 随着反应温度提高,乙酸钠催化合成阿司匹林反应的时间显著变短。采用紫外吸收及导数光谱法,可以实现对阿司匹林合成过程的监测和判断反应终点。     

角质层与真皮层对氟尿嘧啶贴剂经皮吸收的影响

目的 比较皮肤角质层和真皮层及促透剂对药物经皮吸收的影响。方法　制备氟尿嘧啶（5-FU）贴剂为模型药剂,以肉豆蔻酸异丙酯（TPM）为促透剂,采用Franz扩散池法,用高效液相色谱法和气相色谱法分别检测5-FU和IPM浓度,计算5-FU在各种皮肤状态下的透皮能力（Kp）。结果剥离角质层后,5-FU的Kp是经完整皮肤的2.3倍;在IPM作用下5-FU的Kp为原来的1.8倍（经完整皮肤）和2.4倍（经剥离角质层皮肤）。结论剥离角质层能增加5-FU的吸收;IPM主要降低角质层对5-FU的屏障作用,在剥离角质层后其对5-FU的吸收也没有增加作用。     

巴比妥经不同皮肤层吸收差异的评价

目的评价皮肤角质层和活性皮肤层对药物经皮吸收的差异.方法选择巴比妥(BB)为模型药物,采用Franz吸收池法,考察药物经完整皮肤和剥离角质层皮肤的体外透皮能力Kp,并比较吸收促进剂肉豆蔻酸异丙酯(IPM)共存时的促透能力大小.结果BB经剥离角质层皮肤的Kp是经完整皮肤的2.37倍,加入IPM后BB的Kp分别提高到原来的2.59倍(经完整皮肤)和6.92倍(经剥离角质层皮肤).结论本实验为皮肤病态条件,如皮肤受伤或溃疡等时的药物经皮吸收提供实验依据.     

Influence of different layers of skin on the percutaneous absorption of drugs with different lipophilicity

Objectives: To evaluate the barrier function of different skin layers in the process of percutaneous drug absorption. Methods: In vitro permeability via intact or stripped skin of 6 drugs (5-fluorouracil, theo-phylline, hydroquinone, barbital, isosorbide dinitrate and ketoprofen) with a wide span of lipophilicity were investigated in the patch dosage forms. Results: Characteristic parabolic relations was observed between the permeability (Kp, cm/h) of the drugs with different lipophilicity and their LogPc via either intact or stripped skin. However, due to the absence of the stratum corneum, increased Kp ratio for the tested drugs was proportional to their solubility in water other than their LogKp. When isopropyl myristate was used as absorption promoter of the drugs, the parabolic relationship no longer existed. For the intact skin, increase of Kp ratio of the drugs was enhanced resulting from IPM as drug's LogPc decreased. On the other hand, in the case of stripped skin, this enhancement was positivel     

Earlier application of loading doses of aspirin and clopidogrel decreases rate of recurrent cardiovascular ischemic events for patients undergoing percutaneous coronary intervention

Background  Aspirin and clopidogrel resistance plays a significant role in the development of cardiovascular ischemic events for ninety patients undergoing percutaneous coronary intervention. Recent studies have indicated that increasing the dose of antiplatelet drugs maybe a potent method to improve the inhibition of platelet aggregation.

Methods  Thrombelastograph (TEG) determinations were used to evaluate the effect of antiplatelet therapy. According to the results, 90 patients were divided into three groups and given different doses of aspirin and clopidogrel. Thirty patients with both an inhibition rate of aspirin >50% and an inhibition rate of clopidogrel >50% were defined as the control group. Sixty patients with an inhibition rate for aspirin <50% and an inhibition rate for clopidogrel <50% were defined as the resistance group. Patients in resistance group were randomly assigned to be given a routine dose (100 mg aspirin plus 75 mg clopidogrel per day, which we called a resistance plus routine dose group, R+R) and a loading dose (200 mg aspirin and 150 mg clopidogrel per day, which we called resistance plus loading dose group, R+L) of antiplatelet therapy. A 12-month follow-up was observed to examine the change of inhibition rate of antiplatelet therapy and to estimate the relationship between inhibition rate and the occurrence of cardiovascular ischemic events.

Results  After 6 months of antiplatelet therapy, the inhibition rate of aspirin in the R+L group increased from (31.4±3.7)% to (68.6±7.1)%, which was significantly higher than that in R+R group, (51.9±8.2)% (P <0.01). The inhibition rate of clopidogrel in the R+L group increased from (22.1±3.8)% to (60.2±7.4)%, which was significantly higher than in the R+R group, (45.9±4.3)% (P <0.01). The occurrence rates of cardiovascular ischemic events, stent thrombosis, recurrent unstable angina and myocardial infarction in the R+R group were 20%, 36% and 17%, respectively. Occurrence was significantly increased compared with that in the control group, 3%, 10% and 1%, respectively (P <0.01). In contrast, the occurrence rates in the R+L group (10%, 23% and 6%, respectively) were attenuated compared with those in the R+R group (P <0.01), although still higher than in the control group (P <0.01).

Conclusions  Almost all of the cardiovascular ischemic events occurred in the first six months after percutaneous coronary intervention. According to the result of TEG determinations, earlier application of a loading dose of aspirin and clopidogrel can decrease the rate of recurrent cardiovascular ischemic events.

     

阿司匹林分别与替格瑞洛或氯吡格雷联合对PCI术后抗凝疗效的观察

观察阿司匹林分别与替格瑞洛或氯吡格雷联合对经皮冠状动脉介入术(PCI) 后抗凝疗效和防治心血管意外效果,初步探讨这两种药物联合在PCI术后的治疗价值。结果显示,两组联合用药后患者左室射血分数(LVEF)、每搏心输出量(SV)、中心静脉压(CVP)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、血小板(PLT)、血小板抑制率明显高于治疗前。阿司匹林联合替格瑞洛对 LVEF、SV、CVP、PT、APTT、PLT、血小板抑制率明显高于联合氯吡格雷,在预防左室舒张末内径(LVEDD)、出血率、心脏不良事件发生率与阿司匹林联合氯吡格雷差异不显著。结果提示,阿司匹林与替格瑞洛联合治疗不仅能够有效改善患者的凝血功能和血小板抑制能力,而且临床不良事件少、出血风险小,是PCI术后安全、有效的抗凝治疗方案之一。