静脉注射地尔硫卓治疗心脏术后高血压危象

目的观察静脉注射地尔硫卓治疗心脏术后高血压危象的疗效与安全性。方法应用地尔硫卓治疗心脏术后发生高血压危象的患者26例,非体外冠状动脉旁路移植术13例,胸主动脉手术6例,主动脉瓣置换术6例,部分肺静脉异位连接矫治1例。给药方法为起始剂量地尔硫卓10μg·kg-1·min-1静脉滴注,然后根据患者血压情况进行调整,观察用药前后血压(BP)、心率(HR)以及心率与收缩压乘积(RPP)等指标的变化。结果应用地尔硫卓10min后全部患者的BP、HR及RPP即明显下降(P<0.01),并于用药后2h达到相对稳定的状态,随心率、血压的下降,地尔硫卓用量也明显减少。治疗期间仅1例患者用药2h后因出现窦性心动过缓(55次/min)而停用地尔硫卓,其他患者无低血压、心动过缓等不良反应发生。结论静脉注射地尔硫卓治疗心脏术后高血压危象起效迅速、降压效果显著且平稳,治疗剂量未见明显不良反应。     

地尔硫对老年患者下肢手术围拔管期血流动力学的影响

目的观察地尔硫对老年患者下肢手术麻醉苏醒期间血流动力学变化的影响。方法将40例老年下肢手术患者随机分成0.9%氯化钠注射液组(N组)和地尔硫组(D组)。观察并记录两组患者苏醒期间收缩压(SBP)、舒张压(DBP)、心率(HR)、脑电双频指数(BIS)、收缩压乘积(RPP)变化;记录血管活性药物使用情况。结果吸痰拔管时、拔管后5 min,N组的HR,SBP,DBP和RPP明显升高(P<0.05),D组较平稳,两组间比较差异有统计学意义(P<0.05);D组乌拉地尔及艾司洛尔的使用次数低于N组(P<0.05)。结论应用地尔硫能有效维持老年患者下肢手术麻醉苏醒期间血流动力学平稳。     

美托洛尔和地尔硫卓治疗高血压的疗效评价

目的临床探讨采用美托洛尔和地尔硫卓缓释胶囊治疗高血压合并无症状性心肌缺血(SMI)的疗效。方法本文将选取2010年5月至2011年12月在我院心内科住院102例轻、中度高血压合并SMI患者临床资料进行回顾分析。结果两组患者通过服药治疗之后患者的SBP和DBP指标均有所下降;24hAECG检测显示两组患者在服药后其心率均呈现显著下降趋势,其中美托洛尔组与地尔硫卓组相比其下降更为显著;心肌缺血的时间与次数方面,美托洛尔组较治疗前减低了45.8%和59.2%,而地尔硫卓组较治疗前减低了85.7%和85.6%;两组患者的生化指标均未出现异常变化现象;不良反应方面:美托洛尔组有4例(7.8%),而地尔硫卓组有3例(5.9%)。结论通过临床实践,我们发现临床采用美托洛尔和地尔硫卓对治疗SMI均具有良好疗效,其中在减少心肌缺血作用方面地尔硫卓明显优于美托洛尔,而减慢心率作用方面美托洛尔明显优于地尔硫卓,因而笔者建议临床治疗高血压合并SMI首选地尔硫卓胶囊为宜。     

美托洛尔与地尔硫卓治疗不稳定性心绞痛的疗效分析

目的：比较美托洛尔与地尔硫卓治疗不稳定性心绞痛病人的疗效。方法：44例不稳定性心绞痛患者随机分成两组,一组给予美托洛尔6．25mg．口服,2次／天,另一组给地尔硫卓30mg,口服,3次／天．疗程均为1个月。结果：美托洛尔组的疼痛症状缓解,疼痛再发和心肌梗死的发生率减少均显著优于地尔硫卓组（P〈0．05）。结论：小刺量美托洛尔选择性阻断岛受体,降低心肌的耗氧量。有对抗儿茶酚胺的心脏毒性作用,在预防心肌梗死及改善心绞痛症状上优于地尔硫卓,其长期效果仍需继续观察。     

美托洛尔与地尔硫卓治疗心肌反复梗死患者的疗效比较

目的比较美托洛尔与地尔硫卓治疗心肌反复梗死患者的疗效。方法40例急性心肌反复梗死患者随机分成两组，一组给予美托洛尔6．25mg，口服，1次／d，另一组给地尔硫卓30mg，口服，1次／d。疗程均为1个月。结果两组患者短期死亡率没有明显差别（P〉0．05），美托洛尔组的疼痛症状缓解，疼痛再发和心衰的减少均显著优于地尔硫卓组（P〈0．05）。结论小剂量美托洛尔选择性阻断β1受体，降低心肌的耗氧量，有对抗儿茶酚胺的心脏毒性作用，在防止心肌梗死的面积扩大和改善症状方面优于地硫尔卓，其长期效果仍需继续观察。     

地尔硫的临床应用现状

地尔硫(廾卓)为临床上常用治疗冠心病心绞痛和轻中度高血压的药物,具有疗效确切、副作用少等特点.本文简介了地尔硫(廾卓)的药动学、药理作用及临床新应用.     

地尔硫卓在非体外循环下冠状动脉旁路移植术中的应用

目的 评价地尔硫卓在非体外循环冠状动脉旁路移植术(OPCABG)中的临床效果.方法 接受OPCABG的40例冠心病患者,随机均分为两组,麻醉诱导后分别泵注地尔硫卓1～3μg·kg-1·min-1(A组)或硝酸甘油0.5～2.0μg·kg-1·min-1(B组).记录诱导前、用药30 min、移植血管远端吻合中、出手术室前4个时点的血流动力学指标;术后24、48h采血测量血清肌酸激酶同工酶(CK-MB)和肌钙蛋白T(cTnT).结果 与B组比较,A组术中血流动力学较为稳定(P<,0.05);A组术后24 h和48 h血清CK-MB[(24.32±42.75)U/L vs.(39.37±35.50)U/L和(21.50±14.12)U/L vs.(35.40±46.59)U/L]和cTnT[(0.17±0.23)ng/ml vs.(0.32±0.28)ng/ml和(0.20±0.25)ng/ml vs.(0.37±0.48)ng/ml]水平均明显低于B组(P<0.05).结论 在OPCABG手术期间使用地尔硫卓能显著降低心肌氧耗,提供较好的心肌保护,无明显不良反应.     

调变山楂叶有效组分比例对犬血流动力学的影响

目的:探讨改变山楂叶心血管活性有效部位中2类主要有效组分原花青素和总黄酮的比例对实验犬心脏血流动力学的影响.方法:72只健康成年犬随机分为空白对照组(给予0.9%氯化钠注射液1mL·kg-1)、美托洛尔注射液阳性对照组(0.25mL·kg-1)、丹参注射液阳性对照组(0.6mL·kg-1)、1号样品组(10mL·kg-1)、2号样品组(10mL·kg-1)、3号样品组(10mL·kg-1)等6组,分别观测冠脉血流量及心排血量和每搏输出量、总外周阻力等血流动力学指标.结果:牡荆素鼠李糖苷与牡荆素葡萄糖苷为2:1、总黄酮与原花青素含量为3:1时显著增加心排血量和每搏输出量并且显著降低总外周阻力.结论:改变山楂叶中原花青素和总黄酮的比例对实验犬血流动力学有显著影响.     

地尔硫(卓)复合小量异丙酚对脑肿瘤全麻拨管血流动力学的影响

目的:观察盐酸地尔硫革(合贝爽)复合小剂量异丙酚对脑外科患者全麻拔管期血流动力学的影响。方法:选择ASAⅠ-Ⅱ级脑肿瘤择期手术的患者30例,随机分为C组(对照组)和D组(地尔硫组),各15例。术毕符合拔管条件时,C组开始拔管,D组拔管前予地尔硫革0．15mg·kg-1和并丙酚0．5mg·kg-1缓慢静注。观察两组麻醉前、拔管前5min,吸痰时、拔管即刻、拔管后2min及5min的6个时点的血流动力学变化,同时进行评估镇静程度水平及术后24h颅内引流量。结果:在吸痰和拔管即刻、拔管后:血流动力学与术前基础值比较,D组差异不显著(P＞0．05);而C组各指标明显升高(P＜0．01),组间比较D组明显低于C组(P＜0．05)。D组患者吸痰、拔管时、拔管后2min、拔管后5min,镇静程度良好,明显优于C组(P＜0．01),术后24h颅内引流量两组相比差异显著(P＜0．01)。结论:地尔硫复合小剂量异丙酚能有效地抑制脑外科气管拔管引起的血流动力学反应,减少术后出血量,有利于患者的恢复。     

地尔硫(艹卓)对大鼠心肌梗死后金属蛋白酶表达的影响

地尔硫(艹卓)是一种近年来开始应用的苯并硫氮(艹卓)类的短效钙通道阻滞剂(CCAs),可通过阻断细胞壁中L型钙通道而具有增加冠状动脉血流和降压等作用.本研究欲通过建立大鼠的心肌梗死模型,观察地尔硫(艹卓)对金属蛋白酶-2(MMP-2)、金属蛋白酶-9(MMP-9)及胶原的影响,探讨地尔硫(艹卓)的心脏保护作用.     

Safety assessment of poloxamers 101, 105, 108, 122, 123, 124, 181, 182, 183, 184, 185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 284, 288, 331, 333, 334, 335, 338, 401, 402, 403, and 407, poloxamer 105 benzoate, and poloxamer 182 dibenzoate as used in cosmetics

Poloxamers are polyoxyethlyene, polyoxypropylene block polymers. The impurities of commercial grade Poloxamer 188, as an example, include low-molecular-weight substances (aldehydes and both formic and acetic acids), as well as 1,4-dioxane and residual ethylene oxide and propylene oxide. Most Poloxamers function in cosmetics as surfactants, emulsifying agents, cleansing agents, and/or solubilizing agents, and are used in 141 cosmetic products at concentrations from 0.005% to 20%. Poloxamers injected intravenously in animals are rapidly excreted in the urine, with some accumulation in lung, liver, brain, and kidney tissue. In humans, the plasma concentration of Poloxamer 188 (given intravenously) reached a maximum at 1 h, then reached a steady state. Poloxamers generally were ineffective in wound healing, but were effective in reducing postsurgical adhesions in several test systems. Poloxamers can cause hypercholesterolemia and hypertriglyceridemia in animals, but overall, they are relatively nontoxic to animals, with LD(50) values reported from 5 to 34.6 g/kg. Short-term intravenous doses up to 4 g/kg of Poloxamer 108 produced no change in body weights, but did result in diffuse hepatocellular vacuolization, renal tubular dilation in kidneys, and dose-dependent vacuolization of epithelial cells in the proximal convoluted tubules. A short-term inhalation toxicity study of Poloxamer 101 at 97 mg/m(3) identified slight alveolitis after 2 weeks of exposure, which subsided in the 2-week postexposure observation period. A short-term dermal toxicity study of Poloxamer 184 in rabbits at doses up to 1000 mg/kg produced slight erythema and slight intradermal inflammatory response on histological examination, but no dose-dependent body weight, hematology, blood chemistry, or organ weight changes. A 6-month feeding study in rats and dogs of Poloxamer 188 at exposures up to 5% in the diet produced no adverse effects. Likewise, Poloxamer 331 (tested up to 0.5 g/kg day(-1)), Poloxamer 235 (tested up to 1.0 g/kg day(-1)), and Poloxamer 338 (at 0.2 or 1.0 g/kg day(-1)) produced no adverse effects in dogs. Poloxamer 338 (at 5.0 g/kg day(-1)) produced slight transient diarrhea in dogs. Poloxamer 188 at levels up to 7.5% in diet given to rats in a 2-year feeding study produced diarrhea at 5% and 7.5% levels, a small decrease in growth at the 7.5% level, but no change in survival. Doses up to 0.5 mg/kg day(-1) for 2 years using rats produced yellow discoloration of the serum, high serum alkaline phosphatase activity, and elevated serum glutamicpyruvic transaminase and glutamic-oxalacetic transaminase activities. Poloxamers are minimal ocular irritants, but are not dermal irritants or sensitizers in animals. Data on reproductive and developmental toxicity of Poloxamers were not found. An Ames test did not identify any mutagenic activity of Poloxamer 407, with or without metabolic activation. Several studies have suggested anticarcinogenic effects of Poloxamers. Poloxamers appear to increase the sensitivity to anticancer drugs of multidrug-resistant cancer cells. In clinical testing, Poloxamer 188 increased the hydration of feces when used in combination with a bulk laxative treatment. Compared to controls, one study of angioplasty patients receiving Poloxamer 188 found a reduced myocardial infarct size and a reduced incidence of reinfarction, with no evidence of toxicity, but two other studies found no effect. Poloxamer 188 given to patients suffering from sickle cell disease had decreased pain and decreased hospitilization, compared to controls. Clinical tests of dermal irritation and sensitization were uniformly negative. The Cosmetic Ingredient Review (CIR) Expert Panel stressed that the cosmetic industry should continue to use the necessary purification procedures to keep the levels below established limits for ethylene oxide, propylene oxide, and 1,4-dioxane. The Panel did note the absence of reproductive and developmental toxicity data, but, based on molecular weight and solubility, there should be little skin penetration and any penetration of the skin should be slow. Also, the available data demonstrate that Poloxamers that are introduced into the body via routes other than dermal exposure have a rapid clearance from the body, suggesting that there would be no risk of reproductive and/or developmental toxicity. Overall, the available data do not suggest any concern about carcinogenesis. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used, and at what concentration, indicates a pattern of use. Based on these safety test data and the information that the manufacturing process can be controlled to limit unwanted impurities, the Panel concluded that these Poloxamers are safe as used.     

HPLC法测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱

目的 采用高效液相色谱（HPLC）法同时测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱10种活性成分。方法 采用InerSustain AQ-C₁₈色谱柱（250 mm×4.6 mm,5 μm）,流动相A：乙腈–无水乙醇（80∶20）,流动相B：0.1%磷酸溶液,梯度洗脱,检测波长220 nm,体积流量1.0 mL/min,柱温30℃,进样量10 μL。结果 木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱分别在2.69～134.50、1.95～97.50、0.63～31.50、0.86～43.00、11.95～597.50、0.59～29.50、6.08～304.00、4.85～242.50、1.66～83.00、19.79～989.50 μg/mL线性关系良好（r≥0.999 3）;平均回收率分别为99.11%、98.23%、96.95%、97.78%、100.02%、97.21%、99.66%、99.52%、98.81%、100.08%,RSD值分别为1.04%、1.23%、1.37%、1.65%、0.70%、1.28%、0.65%、0.81%、1.11%、0.63%。结论 建立的HPLC法可用于抗妇炎胶囊中10种活性成分的测定,作为抗妇炎胶囊质量控制方法。     

Arformoterol: (R,R)-eformoterol, (R,R)-formoterol, arformoterol tartrate, eformoterol-sepracor, formoterol-sepracor, R,R-eformoterol, R,R-formoterol

Sepracor in the US is developing arformoterol [R,R-formoterol], a single isomer form of the beta(2)-adrenoceptor agonist formoterol [eformoterol]. This isomer contains two chiral centres and is being developed as an inhaled preparation for the treatment of respiratory disorders. Sepracor believes that arformoterol has the potential to be a once-daily therapy with a rapid onset of action and a duration of effect exceeding 12 hours. In 1995, Sepracor acquired New England Pharmaceuticals, a manufacturer of metered-dose and dry powder inhalers, for the purpose of preparing formulations of levosalbutamol and arformoterol. Phase II dose-ranging clinical studies of arformoterol as a longer-acting, complementary bronchodilator were completed successfully in the fourth quarter of 2000. Phase III trials of arformoterol began in September 2001. The indications for the drug appeared to be asthma and chronic obstructive pulmonary disease (COPD). However, an update of the pharmaceutical product information on the Sepracor website in September 2003 listed COPD maintenance therapy as the only indication for arformoterol. In October 2002, Sepracor stated that two pivotal phase III studies were ongoing in 1600 patients. Sepracor estimates that its NDA submission for arformoterol, which is projected for the first half of 2004, will include approximately 3000 adult subjects. Sepracor stated in July 2003 that it had completed more than 100 preclinical studies and initiated or completed 15 clinical studies for arformoterol inhalation solution for the treatment of bronchospasm in patients with COPD. In addition, Sepracor stated that the two pivotal phase III studies in 1600 patients were still progressing. In 1995, European patents were granted to Sepracor for the use of arformoterol in the treatment of asthma, and the US patent application was pending.     

欧洲刺柏（Juniper）

活性成分与药理作用欧洲刺柏药用部位是其浆果，具有促水排泄、防腐、抗胃肠胀气和抗风湿作用，还可改善胃功能。用作促水排泄药可增加尿量（水丢失），但不增加钠排泄。成分萜品烯-4-醇可增加肾小球滤过率，但刺激肾。欧洲刺柏浆果对单纯疱疹病毒体外显示抗病毒活性，并具抗真菌活性。动物实验显示，欧洲刺柏浆果提取物具有堕胎、抗生育、抗炎、抗胚胎植入、降血压、升血压和降血糖作用。欧洲刺柏浆果油具有兴奋子宫的活性，以及利尿、胃肠道抗菌和刺激作用，该油对平滑肌有阻止解痉作用。     

Oral Presentations (LDD, LPES, LNM, LPAT, LNT, LPPT, LPM)

Probiotic microorganisms have been shown to provide specific health benefits when consumed as food supplements or as food components. The main problem of such products is the poor survival of the probiotic bacteria in the low pH of gastric fluid. However the use of synthetic excipients for enteric coating to prevent the exposure of microorganisms to gastric fluid is limited in food supplementary industry. Therefore the aim of this study was to develop an enteric coating formulation containing shellac as a natural polymer. Shellac possesses good resistance to gastric juice; the major disadvantage of this polymer is its low solubility in the intestinal fluid [1, 2]. Thus films containing different ratios of shellac and water-soluble polymers (sodium alginate, hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidon (PVP)) or plasticizers (glycerol and glyceryl triacetate (GTA)) were prepared in order to analyse the films’ melting temperatures (T_m), the changes in enthalpy (ΔH), their capability of taking up water, and their solubility in different media. The release characteristics of the films were studied by loading pellets with Enterococcus faecium M74 and coating them with formulations containing different amounts of shellac and polymer or plasticized shellac. Using dissolution tests, performed according to USP XXXI paddle method, the resistance of the coatings to simulated gastric fluid (SGF, pH 1.2) and the release of cells in simulated intestinal fluid (SIF, pH 6.8) was investigated.The trials showed that an increasing amount of plasticizer results in a decrease of T_m and ΔH of the films whereat glycerol had a superior plasticization effect to GTA. The compatibility of films made of water-soluble polymers and shellac was also concentration dependent. HPMC and PVP showed superior compatibility with shellac compared to sodium alginate, since films containing shellac and more than 10% [w/w] sodium alginate tended to separate into two phases. In the end five formulations containing shellac and either 5% [w/w] glycerol, 10% [w/w] PVP, 20% [w/w] PVP, 10% [w/w] HPMC, or 5% [w/w] sodium alginate emerged as feasible for enteric coating purposes.