妥洛特罗经皮给药系统的研究进展

妥洛特罗为临床上广泛使用的选择性β2-受体激动剂,用于缓解支气管哮喘、急慢性支气管炎、肺气肿、矽肺、尘肺等疾病的呼吸道阻塞性症状.该文介绍了国内外关于妥洛特罗作为活性药物的经皮给药系统的研制现状,为药学工作者进一步研究开发、规模化生产以及临床应用推广提供参考.     

妥洛特罗贴剂经皮给药治疗小儿支气管哮喘的疗效

目的监测小儿支气管哮喘患者在综合治疗过程中经皮给予妥洛特罗贴剂后病情的缓解及症状的改善。方法将104例轻中度小儿支气管哮喘患者分为2组:对照组50例,给予综合治疗,抗感染、抗病毒、止咳、化痰等常规治疗;治疗组54例,除综合治疗外,根据年龄的不同,给予妥洛特罗贴剂0.5mg或1mg,观察两组咳嗽时限及痰液排出时间。结果治疗组咳嗽及排痰时限均短于对照组,差异有统计学意义(P<0.05)。结论妥洛特罗经皮给药治疗小儿支气管哮喘,能缩短咳嗽、排痰时限,达到缩短病程的效果。     

妥洛特罗贴剂经皮给药治疗婴幼儿哮喘急性发作的临床观察

目的探讨婴幼儿哮喘急性发作时采用妥洛特罗贴剂经皮给药治疗临床效果。方法婴幼儿哮喘患儿80例,随机分为对照组和观察组,每组40例,对照组采用平喘、抗炎、化痰、止咳等常规治疗,观察组采用加用妥洛特罗贴剂经皮给药治疗,对两组效果进行比较。结果观察组患儿总有效率为95%,对照组为80%,组间比较差异有统计学意义(P<0.05)。结论婴幼儿哮喘急性发作时采用妥洛特罗贴剂经皮给药治疗,改善患儿预后,保障患儿正常生长发育有非常重要的作用,值得临床普遍推广。     

妥洛特罗经皮给药佐治婴幼儿毛细支气管炎临床观察

目的观察妥洛特罗贴剂佐治婴幼儿毛细支气管炎的临床疗效和安全性。方法 158例毛细支气管炎患儿,随机分为两组,在采用综合治疗的基础上,治疗组加用妥洛特罗贴剂(0.5mg/贴,睡前贴于前胸),与采用口服丙卡特罗溶液(0.2mL.kg-1,12h1次)的对照组进行比较,评价两组临床疗效及不良反应发生率。结果治疗组患儿的主要症状、体征消失时间等临床特征均短于对照组,差异有统计学意义(P<0.05);不良反应发生率治疗组(2.53%)显著低于对照组(11.39%),差异有统计学意义(P<0.05);治疗有效率治疗组高于对照组,但差异无统计学意义(P>0.05)。结论妥洛特罗贴剂在婴幼儿毛细支气管炎治疗中疗效确切,依从性佳,使用的方便性和安全性明显优于丙卡特罗口服溶液。     

妥洛特罗经皮给药佐治呼吸道合胞病毒肺炎疗效观察

目的：观察妥洛特罗经皮给药佐治呼吸道合胞病毒肺炎的临床疗效。方法：将100例确诊为呼吸道合胞病毒肺炎患儿随机分为治疗组和对照组各50例。对照组给予常规治疗,治疗组在常规治疗的基础上每晚睡前应用妥洛特罗贴剂（每贴0．5mg）贴于前胸,比较两组患儿呼吸道症状的变化情况。结果：治疗组咳嗽消失时间（6．90±1．04）d、气喘消失时间（3．55±1．03）d,哆音消失时间（5．87±1．87）d,总疗程（8．35±1．81）d,均短于对照组的（7．35±1．84）d、（4．56±1．52）d和（10．76±0．78）d、（10．76±0．78）d,差异有统计学意义（P〈0．05）,两组均未发现明显不良反应。结论：妥洛特罗对呼吸道合胞病毒肺炎疗效肯定,未发现明显的不良反应,值得临床推广应用。     

妥洛特罗透皮贴剂对58例支气管哮喘持续期患儿的辅助治疗作用

目的：探讨妥洛特罗透皮贴剂对支气管哮喘持续期患儿的辅助治疗作用。方法：选取我院儿科支气管哮喘持续期患儿115例,其中对照组57例,采用常规治疗,观察组58例,在对照组基础上采用妥洛特罗透皮贴剂经皮治疗,比较两组患儿临床疗效的差异。结果：观察组治愈率明显高于对照组,观察组咳痰、咳嗽、哮鸣音和喘憋消失时间均明显短于对照组（P<0.05）。治疗前,两组肺功能指标（FVC、FEV1、PEF、MMEF、V50）与免疫指标（EOS、TIgE）水平比较差异无统计学意义（P>0.05）,治疗后,全部患儿肺功能指标水平均明显高于治疗前,免疫指标水平均明显低于治疗前（P<0.05）。观察组肺功能指标水平明显高于对照组,免疫指标水平明显低于对照组（P<0.05）。两组患儿药物总不良反应率比较差异无统计学意义（P>0.05）。结论：妥洛特罗透皮贴剂对支气管哮喘持续期患儿具有重要的辅助治疗作用,有助于显著改善临床症状、肺功能与免疫功能,且药物安全性较高,值得临床推广应用。     

妥洛特罗两种透皮贴剂临床药动学特性及其对临床疗效的可能影响

目的 评价妥洛特罗两种透皮贴剂和口服片剂的临床药动学特性及其对临床疗效的影响.方法 健康受试者分别单次接受2 mg妥洛特罗透皮贴剂A、贴剂B或口服1 mg盐酸妥洛特罗片剂,采血测试受试者不同时间点的血药浓度,并计算药动学参数.结果 贴剂A、贴剂B和片剂达峰时间(T<,max>)分别为(9.5±2.1)、(24.7±5.4)和(1.5±0.6)h;峰浓度(C<,max>)分别为(1.13±0.4)、(0.271±0.262)和(1.70±0.56) ng/mL.结论 两种贴剂药动学参数存在差异,有可能对临床疗效产生影响.预期贴剂A具有良好的临床疗效.     

妥洛特罗贴剂对喘息性肺炎的疗效观察

目的探讨妥洛特罗贴剂对喘息性肺炎的治疗效果。方法选取我院从2012年1月至2013年1月所收治的120例喘息性肺炎患者作为临床研究对象,将所有患者随机分为观察组和对照组两组,两组患者均进行常规治疗,包括吸痰以保持呼吸道畅通,糖皮质激素雾化吸入并予以抗生素抗感染。观察组在此基础上加用妥洛特罗贴剂进行治疗。观察两组疗效,同时记录两组患者呼吸困难的消失时间和血氧饱和度回复至正常的时间,以综合考察疗效。结果观察组的显效率为56．7％,对照组的显效率为38.3％,两组比较,显效率差异有统计学意义（P〈O．05）。观察组患者在呼吸困难消失时间和血氧饱和度回复至正常时间均短于对照组患者,差异有统计学意义（P〈0．05）。结论妥洛特罗贴剂对喘息性肺炎的效果显著且安全可靠,尤其对口服与雾化吸入有困难的患者。是一种安全有效的治疗喘息性肺炎的新药,值得在临床当中推广应用。     

妥洛特罗贴剂治疗轻中度儿童哮喘急性发作56例

目的观察妥洛特罗贴剂治疗轻中度儿童哮喘急性发作的疗效。方法将符合诊断的102例入选患者随机分为治疗组56例和对照组46例。治疗组给予妥洛特罗贴剂,3-9岁为1mg,9岁以上为2mg,每晚20：00至21：00贴1贴于上臂、前胸或后背处;对照组口服沙丁胺醇0．1-0．15mg／kg,每日3次。其他治疗无差异。结果治疗组总有效率为96．43％,对照组总有效率为67．39％,两组比较差异有统计学意义（P〈0．05）。结论妥洛特罗贴剂治疗轻中度儿童哮喘急性发作临床疗效较好,不良反应少。     

Protective effect of tulobuterol on methacholine-induced bronchospasm in asthmatic children

Summary In a single-blind, placebo-controlled trial 19 asthmatic children aged 10–14 years were studied during a stable phase of the disease. All patients were tested with a methacholine inhalation test on two consecutive days, on the first day after oral administration of a placebo, and on the second day following an oral dose of tulobuterol HCl.The cumulative methacholine dose required to produce at least a 20% decrease in FEV₁ was significantly higher after tulobuterol than after the placebo.It is concluded that tulobuterol HCl reduces methacholine-induced bronchospasm in children.     

妥洛特罗治疗肺心病

妥洛特罗用于４４例慢性肺心病患者，男性３０例，女性１４例，年龄６２±ｓ９ａ。有明显气短或喘息症状，基础肺功能为中度或重度阻塞性通气功能障碍。服妥洛特罗１ｍｇ，ｂｉｄ，连服１０ｄ，服药后肺功能显著好转，ＦＶＣ，ＦＥＶ１，ＰＥＦＲ，Ｖ７５，Ｖ５０差别均有非常显著意义Ｐ＜０．０１；ＭＭＦ相差显著Ｐ＜０．０５；Ｖ２５虽有改善，但Ｐ＞０．０５。妥洛特罗可选用于上述患者。     

Characterization of monolithic matrix patch system containing tulobuterol

The aim of this study was to investigate the effect of the functional groups in acrylic adhesive on tulobuterol uptake, release rate and permeation rate across rat dorsal skin. In addition, the relationship between these parameters was identified in order to formulate the monolithic matrix patch system. Seven acrylate pressure sensitive adhesives were used in this study with three different functional groups as follows: (1) no functionality (DT-4098), (2) hydroxyl group (DT-2287, DT-2510, DT-2525, DT-2516), and (3) carboxyl group (DT-2353, DT-2852). Tulobuterol-uptake in PSA was determined by the drug-uptake method. The amount of tulobuterol-uptake in acrylic polymers with a carboxyl group was higher than those in acrylate pressure sensitive adhesives with either a hydroxyl group or a nonfunctional group. The release rate of tulobuterol from the monolithic patches was evaluated and DT-2353 and DT-2852, which contained a carboxyl group, showed lower release rates of tulobuterol than the other acrylate pressure sensitive adhesives. The skin permeation of tulobuterol was investigated using excised rat dorsal skin and the permeation rate of tulobuterol from DT-2353 and DT-2852 was also lower than the other acrylate pressure sensitive adhesives. Taking into consideration the relationship between all the parameters, pressure sensitive adhesives can be categorized into two groups: those containing a carboxylic acid functional group and those containing a non-carboxylic group. These results indicate that there was an interaction between the secondary amino group of tulobuterol and the carboxyl group of the acrylate polymer. Therefore, we suggest that a drug's chemical structure and functional groups in pressure sensitive adhesives must be considered in order to formulate a transdermal patch system.     

药物敏感场效应晶体管测定丁氯喘片剂含量

将离子敏感场效应晶体管与药物敏感膜相结合，制成药物敏感效应晶体管传感器，测定丁氯喘片剂含量。以磷钨酸为电活性物质，制成PVC膜，对丁氯喘的线性响应范围为100～0．03mmol／L，斜率为59mV，适宜pH范围为3．0～8．0，检测下限为0．01mmol／L。     

Comparison of the effects of tulobuterol patch and salmeterol in moderate to severe asthma

1. Although the clinical effects of the tulobuterol patch have been reported to include an increase in morning peak expiratory flow (PEF) values and a decrease of symptoms and the frequency of the rescue use of inhaled short-acting beta2-adrenoceptor agonists, no trials comparing the efficacy of the tulobuterol patch to other standard inhaled long-acting beta2-adrenoceptor agonists have yet been conducted. The aim of the present study was to compare the clinical effects of the patch formulation of tulobuterol with those of inhaled salmeterol in moderate to severe asthma. 2. Fifty-four patients with moderate to severe asthma, whose conditions were suboptimally controlled despite receiving inhaled corticosteroids, were recruited. The study was a prospective, randomized trial of cross-over design comparing the effects of 4 weeks treatment with tulobuterol patch, 2 mg once daily, and salmeterol, 50 mg twice daily. The mean prebronchodilator morning PEF during the last 14 days of each treatment period and health-related quality of life (HRQoL) were the primary outcome variables. The HRQoL was assessed using the St George's Respiratory Questionnaire. 3. Forty-four patients (81.5%) completed the trial and were included in the analysis. The mean morning PEF and HRQoL score were significantly improved in both the salmeterol (P < 0.0001 and P < 0.05, respectively) and the tulobuterol patch (P < 0.01 and P < 0.05, respectively) treatment periods compared with the run-in period. Although the mean morning PEF was significantly higher in the salmeterol-treated group than in the tulobuterol-treated group (P < 0.001), the HRQoL scores were comparable. 4. The tulobuterol patch may be useful as a controller medication in addition to inhaled corticosteroids in moderate to severe asthma.     

盐酸尼卡地平贴剂的大鼠离体皮肤渗透研究

目的 :研制盐酸尼卡地平贴剂 ,考察其释药影响因素。方法 :采用正交试验法 ,对盐酸尼卡地平贴剂进行大鼠离体皮肤体外渗透实验 ,考察其最优处方。结果 :盐酸尼卡地平贴剂中药物的渗透可用Higuchi方程来表达。最佳处方中盐酸尼卡地的浓度为 15mg·g-1,氮酮的浓度 4 0mg·g-1,丁酮的浓度为 75mg·g-1。结论 :氮酮和丁酮可以提高盐酸尼卡地平的皮肤渗透性。     

妥洛特罗贴剂治疗儿童喘息性疾病的临床评价

目的:评价妥洛特罗贴剂治疗儿童喘息性疾病的有效性、依从性和安全性。方法:试验组(n=13)给予妥洛特罗贴剂治疗,对照组(n=13)给予盐酸丙卡特罗口服溶液治疗,均进行7 d的治疗随访观察,比较2组治疗总有效率、临床评分、患儿用药依从性及用药不良事件。结果:(1)试验组与对照组总有效率分别为92.31%和84.62%,差异无显著性(P<0.05);(2)3次随访,2组临床评分均显著降低(P<0.05);(3)试验组用药依从性优于对照组(P<0.05);(4)2组患儿均未出现严重不良。结论:妥洛特罗贴剂治疗儿童喘息性疾病安全、有效、依从性好,值得临床应用推广。