二维三七桂利嗪胶囊对大鼠局灶性脑缺血再灌注损伤的保护作用

目的:观察二维三七桂利嗪胶囊对大鼠局灶性脑缺血再灌注损伤的影响.方法:SD大鼠分别用292,146和73 mg·kg-1的二维三七桂利嗪胶囊灌胃10 d,线拴法制备大鼠大脑中动脉缺血模型(middle cerebral arteryocclusion,MCAO),缺血3 h后再灌注3 h,分别取脑组织测定脑梗死范围、脑指数、脑含水量并观察脑组织形态结构,取血测定血清乳酸脱氢酶(LDH)和超氧化物歧化酶(S0D)活性.结果:3个剂量的二维三七桂利嗪胶囊能够不同程度地缩小缺血再灌注损伤后脑梗死范围、降低脑指数、脑含水量和血清LDH活性,提高SOD活性并减轻光镜下脑组织缺血性损伤.结论:二维三七桂利嗪胶囊对大鼠局灶性脑缺血再灌注损伤具有保护作用.     

Cinnarizine in the prophylaxis of car sickness in children

Summary

An open study was carried out in 79 children known to be susceptible to car sickness to assess the efficacy and tolerance of cinnarizine used prophylactically. Each child received one 15?mg cinnarizine tablet 2 hours before a long car journey and a further half-tablet every 8 hours thereafter; if required. The results of the children's assessments indicated that 81% considered the preparation either ‘good' or ‘excellent ‘and 69% of the 68 who had previously received other medication for travel sickness rated it ‘better’ or ‘much better’. Only 4% of the children vomited and only 14% felt sleepy or drowsy. All but 3 of the 52 doctors who participated were prepared to give cinnarizine again to their charges based on the experience of this study.     

二维三七桂利嗪胶囊联合依达拉奉治疗脑梗死的临床研究

目的 探讨二维三七桂利嗪胶囊联合依达拉奉治疗脑梗死的临床效果.方法 选择2019年1月—2019年12月天津市宁河区医院收治的80例脑梗死患者,根据信封法分为对照组和治疗组,每组各40例.对照组静脉滴注依达拉奉注射液,30 mg依达拉奉注射液加入100 mL生理盐水,2次/d.治疗组在对照组的基础上口服二维三七桂利嗪胶囊,1粒/次,1次/d.两组连续治疗2周.观察两组患者临床疗效,比较治疗前后两组患者日常生活能力(ADL)、美国国立卫生研究所卒中量表(NIHSS)评分,脑动脉血流速度及血管内皮功能和炎症因子水平.结果 治疗后,治疗组总有效率明显高于对照组(P<0.05).治疗后,两组患者ADL评分升高,而NIHSS评分明显降低(P<0.05),且治疗组评分明显好于对照组(P<0.05).治疗后,两组患者大脑中动脉、大脑前动脉、大脑后动脉的血流速度明显加快,且治疗组明显快于对照组(P<0.05);治疗后,两组一氧化氮(NO)明显升高,而超敏C反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)、内皮素1(ET-1)明显降低(P<0.05),且治疗组血管内皮功能和炎症因子水平明显好于对照组(P<0.05).结论 二维三七桂利嗪胶囊联合依达拉奉治疗脑梗死具有较好的临床疗效,在改善神经功能、脑动脉血流速度、生活自理能力方面效果显著,其主要作用机制可能与调节炎症、血管内皮功能有关.     

脑益嗪抗运动病时大鼠脑中c-fos基因表达水平的变化(论著)

目的：探讨脑益嗪抗运动病作用的神经中枢机理与脑细胞ｃ－ｆｏｓ基因表达的关系。方法：采用正负交变加速度旋转刺激ＳＤ大鼠制备运动病模型，为运动病组；在脑益嗪组，ＳＤ大鼠预先注射脑益嗪，１小时后如运动病组进行旋转刺激；正常ＳＤ大鼠作为对照组。用ｃ－ｆｏｓ基因探针对３组大鼠的大脑皮质、小脑皮质及脑干前庭区进行原位杂交。用免疫组化方法检测３组大鼠脑组织中Ｆｏｓ蛋白的含量。观察运动病组大鼠和脑益嗪组大鼠大脑皮质、小脑皮质和脑干前庭区脑细胞ｃ－ｆｏｓ基因表达变化。结果：大鼠实施刺激后这三种脑组织中ｃ－ｆｏｓ转录水平增高及Ｆｏｓ蛋白含量均增高。在脑益嗪组ｃ－ｆｏｓ基因表达水平和Ｆｏｓ蛋白含量均低于运动病组。结论：脑益嗪抗运动病的中枢机理之一可能与ｃ－ｆｏｓ基因快速表达有关。     

Histamine H1-receptor antagonists against Leishmania (L.) infantum: an in vitro and in vivo evaluation using phosphatidylserine-liposomes

Considering the limited and toxic therapeutic arsenal available for visceral leishmaniasis (VL), the drug repositioning approach could represent a promising tool to the introduction of alternative therapies. Histamine H1-receptor antagonists are drugs belonging to different therapeutic classes, including antiallergics and anxyolitics. In this work, we described for the first time the activity of H1-antagonists against L. (L.) infantum and their potential effectiveness in an experimental hamster model. The evaluation against promastigotes demonstrated that chlorpheniramine, cinnarizine, hydroxyzine, ketotifen, loratadine, quetiapine and risperidone exerted a leishmanicidal effect against promastigotes, with IC₅₀ values in the range of 13–84 μM. The antihistaminic drug cinnarizine demonstrated effectiveness against the intracellular amastigotes, with an IC₅₀ value of 21 μM. The mammalian cytotoxicity was investigated in NCTC cells, resulting in IC₅₀ values in the range of 57–229 μM. Cinnarizine was in vivo studied as a free formulation and entrapped into phosphatidylserine-liposomes. The free drug was administered for eight consecutive days at 50 mg/kg by intraperitoneal route (i.p.) and at 100 mg/kg by oral route to L. infantum-infected hamsters, but showed lack of effectiveness in both regimens, as detected by real time PCR. The liposomal formulation was administered by i.p. route at 3 mg/kg for eight days and reduced the parasite burden to 54% in liver when compared to untreated group; no improvement was observed in the spleen of infected hamsters. Cinnarizine is the first antihistaminic drug with antileishmanial activity and could be used as scaffold for drug design studies for VL.     

高效液相色谱法测定桂利嗪胶囊的含量

目的建立HPLC测定桂利嗪胶囊含量的方法。方法采用Kromasil C18(4.6 mm×250 mm,5μl)色谱柱,流动相为甲醇-0.2%三乙醇胺-三乙胺(85∶15∶0.03),检测波长254 nm;柱温30℃;流速1 ml.min-1;样品处理方法:精密称取装量差异下的内容物(相当于桂利嗪25 mg),置25 ml量瓶中,加甲醇至刻度,滤过,再精密量取续滤液5 ml置50 ml量瓶中,摇匀,用0.45μm微孔滤膜滤过,取续滤液,即得。结果桂利嗪在19.79～197.94 mg.L-1的浓度范围内与峰面积呈良好的线性关系,r=0.999 9,平均回收率99.5%,RSD为0.6%(n=9)。结论该方法准确、重现性好,可作为该制剂的含量测定方法。     

Inhibition of voltage-gated calcium currents in type II vestibular hair cells by cinnarizine

Cinnarizine is pharmaceutically used in conditions with vestibular vertigo such as Menieres disease. It is thought to act on extra-vestibular targets. We hypothesized that cinnarizine, as a blocker of L-type Ca²⁺ channels, may directly target vestibular hair cells where Ca²⁺ currents are important for the mechano-electrical transduction and transmitter release. Our aim was to clarify whether cinnarizine affected voltage-dependent Ca²⁺ currents in vestibular type II hair cells. Such cells were isolated from inner ears of guinea pigs by enzymatic and mechanical dissection from the gelatinous otolithic membrane and studied with the patch-clamp technique in conventional whole-cell mode. Ca²⁺ currents were elicited by depolarizing pulses in a solution containing 1.8 mM Ca²⁺ and 40 mM Ba²⁺. These currents resembled L-type currents (I_Ca,L) with respect to their voltage-dependence and their inhibition by nifedipine and Cd²⁺ but did not show time-dependent inactivation. The currents were inhibited by cinnarizine in a concentration-dependent and reversible manner. The IC₅₀ was 1.5 M. A block exceeding 80% was achieved with 10 µM. The onset of current block was faster with higher concentrations but the reversibility after wash-out was less, suggesting accumulation in the membrane. We conclude that these direct actions of cinnarizine on hair cells should be considered as molecular mechanisms contributing to therapeutic effects of cinnarizine in vertigo.The first two authors contributed equally to the work     

Simple spectrophotometric determination of cinnarizine in its dosage forms

A direct, extraction-free spectrophotometric method has been developed for the determination of cinnarizine in pharmaceutical preparations. The method is based on ion-pair formation between the drug and three acidic (sulphonphthalein) dyes; namely bromocresol green (BCG), bromocresol purple (BCP) and bromophenol blue (BPB) which induces an instantaneous bathochromic shift of the maximum in the drug spectrum. Conformity to Beer's law enabled the assay of dosage forms of the drug. Compared with a reference method, the results obtained were of equal accuracy and precision. A more detailed investigation of the cinnarizine-BCG ion pair complex was made with respect to its composition, association constant and free energy change. In addition, this method was also found to be specific for the analysis of cinnarizine in the presence of some of the co-formulated drugs, such as pyridoxine hydrochloride and digoxin.     

黛力新联合西比灵治疗偏头痛疗效观察

目的评价黛力新联合西比灵治疗偏头痛的临床效果。方法将100例偏头痛患者随机分成两组,治疗组服黛力新每日2片,早晨、中午各1次;服西比灵5mg,每晚1次。对照组只服西比灵5mg,每晚1次。结果治疗组能显著减少头痛发作次数(P<0.05),显著减轻头痛程度(P<0.05),缩短头痛发作持续时间(P<0.05)。结论黛力新联合西比灵治疗偏头痛疗效优于单独应用西比灵,且无严重副反应。     

Method development and validation for the simultaneous determination of cinnarizine and co-formulated drugs in pharmaceutical preparations by capillary electrophoresis

Rapid and simple capillary electrophoresis (CE) methods were developed for the simultaneous determinations of cinnarizine and domperidone (CN/DOM) and cinnarizine and nicergoline (CN/NIC) in their co-formulated tablets. The optimized CE conditions were as follows: running buffer, methanol-acetate buffer (pH 3.0, 10 mM) (80:20 and 85:15 (v/v) for CN/DOM and CN/NIC, respectively); applied voltage, 20 kV; UV detection wavelengths, 215 and 227 nm for CN/DOM and CN/NIC, respectively; hydrodynamic injection was performed at a height of 25 mm for 30 s. Quinine hydrochloride and nicardipine hydrochloride were used as internal standards for the determination of CN/DOM and CN/NIC, respectively. Calibration curves were linear over the ranges 0.25-20/0.375-15 microg/ml (CN/DOM) and 0.25-25/0.4-10 microg/ml (CN/NIC) in each optimized condition. Detection limits were 0.074/0.119 microg/ml and 0.072/0.116 microg/ml for CN/DOM and CN/NIC, respectively. The proposed methods were successfully applied for the simultaneous determination of both CN/DOM and CN/NIC in their co-formulated tablets without interfering peaks due to the excipients present in the pharmaceutical tablets. The estimated amounts of CN/DOM and CN/NIC were almost identical with the certified values, and their percentage relative standard deviation values (%R.S.D.) were found to be < or =2.34% (n=3).