甲磺酸二氢麦角毒碱溶液鼻黏膜吸收的研究

目的:研究甲磺酸二氢麦角毒碱溶液鼻黏膜吸收规律。方法:考察甲磺酸二氢麦角毒碱在大鼠鼻腔洗出液中的稳定性,在此基础上,以大鼠在体鼻循环为实验模型,研究甲磺酸二氢麦角毒碱溶液的鼻黏膜吸收规律。结果:甲磺酸二氢麦角毒碱在鼻黏膜洗出液中稳定性良好,当循环液体积为5 mL,流速为2．5 mL·min-1时,甲磺酸二氢麦角毒碱溶液鼻黏膜吸收速率常数K不随药物浓度发生变化。结论:甲磺酸二氢麦角毒碱溶液鼻黏膜吸收机制为被动扩散,吸收符合一级动力学,其鼻黏膜平均吸收速率常数K为5．94×10-3min-1。     

甲磺酸二氢麦角碱缓释片的制备与体外释放特性研究

目的:制备甲磺酸二氢麦角碱缓释片,研究其体外释放特性。方法:以羟丙甲基纤维素(HPMC-K4M)为骨架材料,采用湿法制粒制备甲磺酸二氢麦角碱缓释片。以释放速率、累积释放度为指标,以载药材料(HPMC-K4M)、填充剂(乳糖、磷酸氢钙)和微环境p H调节剂(酒石酸)的用量为因素,采用单因素试验和正交试验对甲磺酸二氢麦角碱缓释片处方进行优化并验证;采用《中国药典》释放度测定方法比较进口和最优处方所制甲磺酸二氢麦角碱缓释片的体外释放特性。结果:最优处方为甲磺酸二氢麦角碱2.5 mg,HPMC-K4M 40 mg,乳糖70 mg,磷酸氢钙80 mg,酒石酸40 mg;所制甲磺酸二氢麦角碱缓释片可体外持续释药12h以上,12 h累积释放度为97.1%,与进口片剂比较累积释放度无明显变化,体外释药行为符合Higuchi方程。结论:成功制得具有缓释作用的甲磺酸二氢麦角碱缓释片。     

薄层色谱法检查甲磺酸双氢麦角毒碱片中的有关物质

目的 采用TLC法检查甲磺酸双氢麦角毒碱片中的有关物质.方法 使用硅胶G薄层板,以氨水饱和的氯仿-甲醇(9:1)为展开剂,1％对二甲氨基苯甲醛为显色剂.结果 该方法能有效分离并检测甲磺酸双氢麦角毒碱片中的有关物质.结论 所用方法专属性好、灵敏度高,可用于甲磺酸双氢麦角毒碱片中有关物质的检查.     

甲磺酸二氢麦角碱缓释片含量测定方法的优化

<正>甲磺酸二氢麦角碱由4种生物碱组成,分别为甲磺酸二氢麦角考宁、甲磺酸二氢麦角隐亭α、甲磺酸二氢麦角汀和甲磺酸二氢麦角隐亭β。该药品有兴奋多巴胺和5-羟色胺受体,阻断α-肾上腺素受体效应,临床上主要用于治疗血管性头痛及急慢性脑血管病后的功能,智力减退等症状[1]。现有质量标准和文献[2]的方法只能反映出3个色谱峰,将甲磺酸二氢麦角汀和甲磺酸二氢麦角隐亭β合并成一个峰测定。均匀度、释放度的测定采用中国药典     

注射用甲磺酸二氢麦角毒碱的稳定性研究

目的考察注射用甲磺酸二氢麦角毒碱的稳定性。方法采用高效液相色谱法测定其甲磺酸二氢麦角毒碱及有关物质的含量,以水-乙腈-三乙胺（62：40：2．1）为流动相,检测波长为280Nm。结果与放置0d时比较,放置6个月后3批样品的各项指标均无明显变化。结论注射用甲磺酸二氢麦角毒碱在避光、阴凉处保存时稳定性良好。     

HPLC法测定甲磺酸二氢麦角碱注射液的含量及有关物质

目的用HPLC法测定甲磺酸二氢麦角碱注射液的含量及有关物质。方法采用Dia-monsil C18（200mm×4．6mm，5μm）；水-乙腈-三乙胺（62：40：2）为流动相；流速1．5ml／min；检测波长280nm；柱温30℃；进样量20μl。结果在该色谱条件下，甲磺酸二氢麦角碱格峰与其相邻杂质峰能完全分离，在120～390μg／ml浓度范围内线性关系良好，r2=0．9996。结论该法简便、准确、专属性好，可以作为甲磺酸二氢麦角碱注射液中甲磺酸二氢麦角碱含量测定及有关物质检查。     

甲磺酸双氢麦角毒碱缓释微丸的研制

目的：制备甲磺酸双氢麦角毒碱缓释微丸,并研究其体外释药情况。方法：采用离心造粒法制备甲磺酸双氢麦角毒碱素丸,在流化床内采用丙烯酸树脂水分散体对其包衣,制备甲磺酸双氢麦角毒碱缓释微丸。用释放度测定法考察影响药物释放的各种因素,研究包衣微丸体外释药机制。结果：所制微丸体外释药过程基本符合Higuchi方程：Y=0．41＋29．22t1/2（r=0．9782）。结论：甲磺酸双氢麦角毒碱缓释微丸体外释药缓慢、平稳。     

可分剂量甲磺酸二氢麦角碱缓释微囊片的制备及体外释放机制的研究

目的对可分剂量甲磺酸二氢麦角碱缓释微囊片(EDDTEM)的处方进行研究,并研究其体外释放机制。方法以海藻酸钠-壳聚糖为囊材,采用复凝聚法制备甲磺酸二氢麦角碱缓释微囊(EEM)并压制成片,采用正交设计实验优化处方。结果EEM的最优处方为:海藻酸钠与药物比例为6∶1,海藻酸钠-壳聚糖比例为4∶1,海藻酸钠浓度为2.5%。所制缓释片释药行为符合Higuchi方程,释药机理为扩散和溶蚀并存。结论EDDTEM具有良好的体外缓释效果,可进一步进行体内释药行为考察。     

可分剂量甲磺酸二氢麦角碱缓释微囊片的制备及体外释放机制的研究

目的 对可分剂量甲磺酸二氢麦角碱缓释微囊片(EDDTEM)的处方进行研究,并研究其体外释放机制。方法 以海藻酸钠-壳聚糖为囊材,采用复凝聚法制备甲磺酸二氢麦角碱缓释微囊(EEM)并压制成片,采用正交设计实验优化处方。结果 EEM的最优处方为：海藻酸钠与药物比例为6∶1,海藻酸钠-壳聚糖比例为4∶1,海藻酸钠浓度为2.5%。所制缓释片释药行为符合Higuchi方程,释药机理为扩散和溶蚀并存。结论 EDDTEM具有良好的体外缓释效果,可进一步进行体内释药行为考察。     

二氢麦角碱在阿尔茨海默病治疗中的应用分析

目的:探讨二氢麦角碱治疗阿尔茨海默病的临床疗效及价值.方法:以我院于2014年1月~2016年1月收治的60例阿尔茨海默病患者为研究对象,按照时间顺序分为两组,采用脑复康治疗的对照组(30例)和采用二氢麦角碱治疗的观察组(30例),对比两种治疗方法的效果.结果:观察组治疗前后的MMSE、ADAS-Cog、ADL评分变化情况更加明显,两组差异有统计学意义(P<0.05).结论:对阿尔茨海默病实施二氢麦角碱治疗,效果显著,值得推广.     

双氢麦角碱对脑卒中恢复期患者的疗效观察

目的：评估双氢麦角碱(商品名：喜德镇)对脑卒中后功能恢复的疗效。方法：采用随机、对照研究。脑卒中后1周患者，随机服用双氢麦角碱3片/d，服用3个月，以神经功能缺损量表(NFDS)和简易智能量表(MMSE)作为疗效评估指标。结果：神经功能缺损量表分两组无显著性差异；简易智能量表分药物组优于对照组。结论：双氢麦角碱可以改善卒中后的认知功能障碍，在一定程度上促进脑卒中患者神经功能恢复。     

The rat mesenteric artery-intestinal loop preparation. Noradrenaline outflow and vascular responses to nerve stimulation and drugs

A new preparation, intestine-mesenteric blood vessels of the rat, was tested for simultaneous measure of noradrenaline (NA) overflow and vasoconstrictor response (delta p) induced by electric stimulations. Control experiments showed that this preparation could be used within a wide range of frequencies and repeatedly stimulated without any important decrease of response. The effects of phenoxybenzamine, dihydroergotoxine mesylate, imipramine and pargyline were investigated. All the drugs inhibited delta p and, except for dihydroergotoxine mesylate, increased NA outflow. The results were discussed in the light of the present knowledge. It is concluded that this preparation can be profitably used to study drug effects at pre- and post-synaptic level.     

Identification and human pharmacokinetics of dihydroergotoxine metabolites in man: preliminary results

Dihydroergotoxine is a mixture of semi-synthetic ergot alkaloids mainly used for age-related cognitive impairment. In this study, dihydroergotoxine (30 microM) was added to incubates of rat and bovine liver microsomes, and the resulting major metabolites were identified as hydroxy-dihydroergocornine, hydroxy-dihydroergocryptine and hydroxy-dihydroergocristine on the basis of molecular mass measurements, determined with a time-of-flight mass spectrometer. The relevance of these to humans was then investigated by simultaneously monitoring dihydroergotoxine and its hydroxy-metabolites in human plasma by LC-MS/MS after oral dosing of dihydroergotoxine mesylate (27 mg) to a healthy volunteer (male, age 45, height 1.93 m, weight 103 kg). In this preliminary approach, the peaks (C(max)) of dihydroergocornine, dihydroergocryptine and dihydroergocristine were about 0.04 microg/l. The peaks (C(max)) of their hydroxy-metabolites were 0.98, 0.53 and 0.30 microg/l, respectively. In conclusion, in this preliminary approach it was found that hydroxy-dihydroergocornine, hydroxy-dihydroergocryptine and hydroxy-dihydroergocristine were one order of magnitude higher in concentration than their parents in human plasma.     

Particle-size distribution of bitolterol mesylate solution delivered by four compressed-air nebulizer devices

The particle-size distribution of bitolterol mesylate solution delivered by four types of compressed-air nebulizers was determined. Before nebulization, bitolterol mesylate solution 0.2% w/v was diluted to 0.0833% w/v with 0.9% sodium chloride solution. The following commercially available nebulizers were tested: DeVilbiss Nebulizer Model 645, Hudson 1720 (Updraft) Hand Held Nebulizer, Bard Inspiron 002220 Mini-Neb Nebulizer, and Bunn Mini Mist Set model 0140-041. The particle-size distribution of nebulized solutions was determined with a cascade impactor contained in an in vitro apparatus designed to simulate use by a patient. Assays of bitolterol mesylate in the cascade impactor apparatus were done by high-performance liquid chromatography. Only slight differences were found in the particle-size distributions among the four types of nebulizers; the calculated average particle size ranged from 3.0 to 3.6 micron. All nebulizers tested showed satisfactory, comparable particle-size distributions and performance with bitolterol mesylate solution.     

Effects of the new eburnamenine derivative RU 24722 on EEG recovery and cerebral energy metabolism after complete ischemia

The influence of a new eburnamenine derivative RU 24722 [(3 beta, 14 alpha, 16 alpha)-(+/-)-14,15-dihydro-20,21-dinoreburnamenin -14-ol] on post-ischemic EEG recovery was studied in N2O anesthetized rats subjected to 1 min of global-compression cerebral ischemia. RU 24722 was compared with vincamine, dihydroergotoxine mesylate and nicergoline. Treatment with RU 24722 (2 mg/kg i.v.) significantly decreased the EEG recovery time and increased the electrocortical activity during the first phase of the post-ischemic recovery. Vincamine (2 mg/kg i.v.), dihydroergotoxine mesylate (0.5 mg/kg i.v.) and nicergoline (0.5 mg/kg i.v.) were devoid of activity. In an attempt to elucidate its mechanism of action, the influence of RU 24722 on changes in the cerebral metabolic energy reserves was studied in mouse brain after different periods of decapitation ischemia. The changes occurring during the first 10 s of ischemia were used to calculate the baseline cerebral metabolic rate (CMR). The activity of RU 24722 was compared with that of vincamine and pentobarbital. RU 24722 (10 mg/kg i.p.) significantly retarded glucose, phosphocreatine and adenosine triphosphate utilisation and lactate production. Vincamine (10 mg/kg i.p.) had no effect on cerebral energy substrates. Pentobarbital (100 mg/kg i.p.) markedly increased the tissue concentration of glucose and phosphocreatine and decreased lactate levels before and after ischemia. The improvement of EEG recovery suggests that RU 24722 may be therapeutically effective in cerebral insufficiency, and the decreased brain energy demand may be one of the mechanisms by which RU 24722 has a protective effect against cerebral ischemic damage.     

双氢麦角碱治疗椎-基底动脉供血不足

目的 :观察双氢麦角碱治疗椎 基底动脉供血不足的疗效。方法 ;双氢麦角碱组 30例 ,男性 19例 ,女性 11例 ,年龄 (60 .0±s 2 .7)a ,给双氢麦角碱0 .6mg加入氯化钠注射液 5 0 0mL静脉滴注 ,qd ,共7d。丹参组 2 5例 ,男性 17例 ,女性 8例 ,年龄 (61± 3)a ,给丹参 2 0mL加入低分子右旋糖酐 5 0 0mL静脉滴注 ,qd ,共 7d。观察临床疗效和椎 基底动脉血流变化。结果 :双氢麦角碱组有效率 83% ,丹参组有效率 36% ,2组疗效比较差异有非常显著意义(P <0 .0 1) ,双氢麦角碱组椎 基底动脉血流明显改善 ,与丹参组比较 ,差异有非常显著意义 (P <0 .0 1)。结论 :双氢麦角碱能迅速有效控制椎 基底动脉供血不足     

甲磺酸培氟沙星的示波极谱滴定法研究

对甲磺酸培氟沙星含量的示波极谱滴定法测定进行了研究。在 pH5 2的HCl NaAc缓冲溶液中 ,四苯硼钠 (Na TPB)与甲磺酸培氟沙星作用可生成 1∶1定量沉淀 ,过滤弃去初滤液 ,用硫酸亚铊标准溶液滴定续滤液中过量的Na TPB ,通过示波极谱图 (dE/dt=f(E)曲线 )上TPB的切口消失指示滴定终点。本法操作简单、快速 ,终点直观 ,应用于多批原料药样品的测定 ,获得了满意的结果 ,其回收率为 99 4 6 %～ 1 0 0 4 % ,相对误差 <± 0 .6 % ,与部颁标准非水滴定法测得的结果基本一致。     

盐酸曲马多注射液与甲磺酸罗哌卡因注射液配伍的稳定性考察

目的考察盐酸曲马多注射液与甲磺酸罗哌卡因注射液在0.9%氯化钠注射液中的配伍稳定性。方法采用高效液相色谱法（HPLC）测定配伍液中盐酸曲马多与甲磺酸罗哌卡因在72 h内的含量变化,并观察和检测配伍液的外观、不溶性微粒及pH值变化。结果盐酸曲马多注射液与甲磺酸罗哌卡因注射液在0.9%氯化钠注射液中配伍后,在室温条件下放置72 h内的配伍液含量、外观、不溶性微粒与pH值等几项指标均未见明显变化。结论在室温条件下,盐酸曲马多注射液与甲磺酸罗哌卡因注射液在0.9%氯化钠注射液中72 h内均保持稳定。     

Absorption kinetics of dihydroergotoxine following oral administration to man.

The absorption characteristics of dihydroergotoxine administered as an oral solution, tablet and retard capsule have been determined in a randomised cross-over investigation in 12 healthy males. The plasma concentrations of dihydroergotoxine produced by the three preparations, measured using a specific and sensitive radioimmuno-assay method over 24 h, exceeded 200 pg ml-1 for approximately 5 h and decayed in a biphasic manner with a slowest measured half-life of 12-14 h. The retard capsule differs from the other two preparations in having a low Cmax (50% of that recorded for the solution) and a clearly defined plateau. The bioavailability of the retard capsule was similar to that for the solution indicating that first-pass metabolism is not significantly increased following a three-fold prolongation in the absorption rate constant. The 20-40% greater bioavailability of dihydroergotoxine solution and retard capsule in comparison with the standard tablet may be due to a reduced contact time with gastric secretions achieved by means of rapid absorption from the stomach (solution) or delayed release at pH 1.5 (retard capsule).     

Effect of dihydroergotoxine on the susceptibility of rats to convulsions produced by different convulsant agents

The study was undertaken to test further whether diminished GABAergic transmission might be responsible for the increased susceptibility of rats to picrotoxin-induced convulsions. In rats kept individually in cages in a noise-free room, the time between the intraperitoneal injection of the convulsant agent and the onset of convulsions was measured. Acute and subacute treatment with low doses of dihydroergotoxine (0.01-1.0 mg/kg) increased the occurrence and decreased the latency of picrotoxin-induced convulsions. Acute administration of dihydroergotoxine, 1.0 mg/kg, caused convulsions in animals injected with the subconvulsive dose (3 mg/kg) of bicuculline and of 10.0 mg/kg dihydroergotoxine in animals injected with the subconvulsive dose (1.5 mg/kg) of strychnine. Some of the animals injected with the 100% convulsive dose of strychnine were protected by dihydroergotoxine pretreatment (1.0 mg/kg) as evidenced by the lower occurrence of convulsions and fewer animals dying, as well as by a delay in the appearance of convulsions at 10.0 mg/kg. These results together with the previous findings on the GABA system suggest that dihydroergotoxine potentiates the appearance of picrotoxin and bicuculline-induced convulsions by a diminution of GABAergic transmission.