昔萘酸沙美特罗气雾剂的HPLC测定

目的：采用高效液相色谱法测定昔萘酸沙美特罗气雾剂中昔萘酸沙美特罗的含量。方法：采用Ophenomenex色谱柱，甲醇－水（85：15用磷酸调PH为3．0）为流动相，紫外检测波长为280nm测定。结果：回归方程Y＝65185X－0．3363，r=0.9998,加样回收率平均值为99．8％，RSD＝1．02％。结论：本方法简便，快速，重现性及精密度好。     

小鼠血浆及肺组织中昔萘酸沙美特罗HPLC分析方法的建立

昔萘酸沙美特罗(salmeterol xinafoate,SalX)是一种长效、选择性β2肾上腺素受体激动剂,也是一个具有抗炎活性的支气管扩张药物。作为平喘、抗炎的首选药物,它是近20多年来在哮喘治疗方面的首次重大突破,主要用于治疗长期哮喘(包括夜间哮喘和运动性哮喘)、慢性支气管炎和慢性阻塞性肺病(chronic obstructive pulmonary disease,COPD)。     

吸入沙美特罗丙酸氟替卡松治疗学龄儿童哮喘失败因素分析

儿童哮喘发病率逐年上升,家属对疾病的认识有所提高,但诸多因素影响治疗中断,导致吸入沙美特罗丙酸氟替卡松(商品名舒利迭)失败。本科从2003年2月至2006年2月通过对吸入沙美特罗丙酸氟替卡松失败因素分析,并针对失败因素逐一采取对策,取得一定效果,现报告如下。1临床资料本组36     

长效抗哮喘药沙美特罗和福莫特罗的研究进展

近年发现的长产支气管扩张剂沙美特罗和福莫特罗是β２受体激动剂，其药效强，持续时间要长达１２－２４ｈ，副作用少，适用于治疗中，重度或伴有夜间发作的哮喘。它们的长艇机理与其分子结构有关。沙美特罗的长脂肪族侧链使其脂溶性增强，因而与细胞膜脂质怪不易分离，长侧链又可与受体的附加结合位点牢固结合，从而延长药效。福莫特罗的甲酰氨基则使其内在活性及其与受体的亲和力增高，从而增强其药效；福莫特罗的中等强度脂溶性也     

疏水性药物昔奈酸沙美特罗纳米粒-微粒系统的研制

目的:制备疏水性药物昔奈酸沙美特罗的纳米粒-微粒给药系统。方法:以壳聚糖为载体材料,采用离子交联法联合喷雾干燥工艺制备昔奈酸沙美特罗纳米粒-微粒给药系统,并考察其体外释药及沉降特性。结果:制得的纳米粒-微粒粉末外观较为圆整、规则,粒径分布主要集中在2～8μm范围内,堆密度和休止角分别为(217.28±1.47)mg/ml和(30.24±0.77)°,粉末流动性较好,包封率和载药量分别为(71.40±2.88)%和(7.67±0.31)%。昔奈酸沙美特罗纳米粒-微粒和昔奈酸沙美特罗原药在体外释放初期均表现出一定的突释效应(2h累积释药百分数达到50%以上),24h达到95%以上,其中昔奈酸沙美特罗纳米粒-微粒的体外释药速度与其原药相比较慢。微粒粉末的有效部位沉积百分比为22.07%。结论:本研究可以成功制得昔奈酸沙美特罗纳米粒-微粒给药系统,其载药量和包封率较高,体外释药可控,可吸入性良好,为进一步的载体修饰奠定了基础。     

HPLC法测定羟萘甲酸沙美特罗气雾剂含量

目的建立羟萘甲酸沙美特罗气雾剂药物含量测定的方法。方法采用HPLC法。色谱柱为Hypersil C18柱(250 mm×4.6 mm,5μm),流动相为甲醇乙腈水冰醋酸三乙胺(体积比为50∶20∶30∶0.07∶0.05),流速1.0 mL.min-1,紫外检测波长225 nm,室温测定。结果在选择的色谱条件下,理论塔板数以沙美特罗峰计为3 520,沙美特罗保留时间为7.5 min,辅料不干扰药物的测定。沙美特罗质量浓度在20~120 mg.L-1内,线性关系良好(r=0.999 8),平均回收率在99%以上,日内日间RSD均小于2%,重复性小于0.5%。稳定性试验表明,样品溶液稳定性良好。结论本方法可用于羟萘甲酸沙美特罗气雾剂的质量控制。     

沙美特罗替卡松吸入粉雾剂递送剂量均一性的测定

目的：使用递送剂量均一性测定装置(DUSA管)方法对沙美特罗替卡松吸入粉雾剂的递送剂量均一性进行研究。分析和比较递送剂量均一性与排空率和含量均匀度数据的区别与关系。方法: 沙美特罗替卡松吸入粉雾剂连接DUSA管,调节真空泵控制空气流速为90L/min,采用高效液相色谱法测定9批样品的递送剂量均一性。结果:采用DUSA管方法测定了沙美特罗替卡松吸入粉雾剂中沙美特罗及氟替卡松的递送剂量均一性,并与排空率及含量均匀度测定结果比较。结论:与排空率及含量均匀度相比,DUSA管法测定递送剂量均一性,更符合患者用药的实际剂量。     

羟萘甲酸沙美特罗气雾剂的HPLC测定

建立了羟萘甲酸沙美特罗气雾剂含量的HPLC测定法.采用Shim-packODS色谱柱,以甲醇-2.5×10-3mol/L十二烷磺酸钠溶液-冰醋酸(750∶250∶1)为流动相,检测波长276nm.方法平均回收率为99.75%,RSD为0.48%.方法简便快速,结果准确.     

高效液相色谱法测定沙美特罗的含量

沙美特罗为新型长效 β2 -肾上腺素受体兴奋剂。能抑制气道高过敏性反应 ,且长期使用不会引起气道反应性增高。该药抗炎作用较强 ,对延迟哮喘反应有较明显的预防作用。如何有效地测定其含量 ,对控制药品质量十分重要。本文介绍一种采用高效液相色谱法测定沙美特罗含量的较为有效的方法。1　仪器与试药高效液相色谱仪 (WATERS- 5 10泵 ,WATERS-490检测器 ,岛津 G- R3A记录仪 ) ,沙美特罗气雾剂与原料药 (厂家提供 )。甲醇、三乙胺、冰醋酸均为分析纯试剂 ,十二烷基磺酸钠为化学纯。2　实验方法2 .1　对照品溶液的制备　取沙美特罗原料 …     

吸入给药治疗哮喘中的不合理用药

吸入给药是哮喘治疗的一种基本的给药方式。吸入给药可直接作用于靶器官,起效快、给药剂量小、毒副作用少。目前常用的吸入装置主要有四种：定量压力气雾剂、定量压力气雾剂＋储雾罐、干粉吸入器和射流雾化器（Nebulizer）。应根据病情和病人的特点选择适当的药物和吸入装置。在临床实践中发现存在一些不合理应用的现象,需要引起临床医师和临床药师的注意。     

沙美特罗／丙酸氟替卡松治疗儿童咳嗽变异性哮喘临床观察

目的观察沙美特罗与丙酸氟替卡松治疗儿童咳嗽变异性哮喘的疗效和安全性。方法将65例咳嗽变异性哮喘患儿随机分为治疗组32例和对照组33例。对照组予氨茶碱口服,治疗组予沙美特罗／丙酸氟替卡松粉吸入剂治疗。结果显效率治疗组为56％,对照组为27％,两组差异有显著性（P〈0．05）。治疗组和对照组的总有效率分别为97％和77％,两组差异也有统计学意义（P〈0．05）。未见明显不良反应。结论沙美特罗／丙酸氟替卡松粉吸入剂治疗儿童咳嗽变异性哮喘疗效好,使用方便。     

Formulation of a novel fixed dose combination of salmeterol xinafoate and mometasone furoate for inhaled drug delivery

Co-administration of an inhaled corticosteroid and long acting beta agonist for chronic obstructive pulmonary disease has reduced mortality compared to either drug alone. This combination reduces exacerbations, hospitalization, emergency department visits and health care costs. A novel fixed-dose combination of the long acting beta-2 agonist salmeterol xinafoate (SX) and the corticosteroid mometasone furoate (MF) were prepared in a composite particle formulation as brittle matrix powder (BMP) and investigated for suitability as an inhaled combination product. In this study, BMP fixed dose combinations of SX and MF with or without stabilizing excipients (lactose, mannitol, glycine and trehalose) were prepared and characterized with respect to their thermal properties, morphology, aerodynamic performance and physical stability. BMP combination formulations of SX and MF exhibited improved aerodynamic properties when delivered by dry powder inhalation as compared to the micronized blends of the same substances. Aerodynamic evaluation was carried out by next generation pharmaceutical impactor (NGI) with a marketed DPI device. Results demonstrated that co-deposition occurred when SX and MF were formulated together as composite particles in a BMP, while physical blends resulted in inconsistent deposition and dose uniformity. As a result of the bottom-up particle engineering approach, combination BMP formulations allow for dual API composite formulations to be dispersed as aerosolized particles. Aerosolized BMP combination formulations resulted in delivered dose uniformity and co-deposition of each API. Further, an excipient-free formulation, BMP SXMF, delivered approximately 50% of the loaded dose in the respirable range and demonstrated stability at ambient conditions for 6 months. Single dose 24-h pharmacokinetic studies in rats demonstrated that lung tissue deposition and blood circulation (AUC_0–24h) of two APIs were higher for the BMP combination group exhibiting a significantly higher lung concentration of drugs than for the crystalline physical blend. While high system drug levels are generally undesirable in lung targeted therapies, high blood levels in this rodent study could be indicative of increased pulmonary tissue exposure using BMP formulations.     

沙美特罗替卡松粉吸入剂治疗哮喘的临床疗效分析

目的：观察吸入沙美特罗替卡松粉治疗成人哮喘的临床疗效。方法：将80例哮喘患者分为治疗组与对照组,治疗组给予沙美特罗替卡松粉吸入治疗,对照组给予布地奈德粉吸入剂治疗。观察患者治疗前后临床症状及肺功能[用力呼气肺活量（FVC）,第1秒用力呼气容积率（FEV1%）和用力呼气峰流速（PEFR）]的变化。结果：与治疗前比较,两组患者治疗后临床症状、肺功能各项指标、血清IL-4和IgE水平均得到明显改善;治疗后治疗组临床疗效、肺功能FVC、FEV1%和PEFR均明显优于对照组,但两者血清IL-4和IgE水平差异无统计学意义。结论：沙美特罗替卡松粉吸入剂治疗成人哮喘疗效显著,适于临床应用。     

Influence of polymorphism on the surface energetics of salmeterol xinafoate crystallized from supercritical fluids

Purpose. To characterize the surface thermodynamic properties of two polymorphic forms (I and II) of salmeterol xinafoate (SX) prepared from supercritical fluids and a commercial micronized SX (form I) sample (MSX). Methods. Inverse gas chromatographic analysis was conducted on the SX samples at 30, 40, 50, and 60°C using the following probes at infinite dilution: nonpolar probes (NPs; alkane C5-C9 series); and polar probes (PPs; i.e., dichloromethane, chloroform, acetone, ethyl acetate, diethyl ether, and tetrahydrofuran). Surface thermodynamic parameters of adsorption and Hansen solubility parameters were calculated from the retention times of the probes. Results. The free energies of adsorption (-G_A) of the three samples obtained at various temperatures follow this order: SX-II > MSX SX-I for the NPs; and SX-II > MSX > SX-I for the PPs. For both NPs and PPs, SX-II exhibits a less negative enthalpy of adsorption (H_A) and a much less negative entropy of adsorption (S_A) than MSX and SX-I, suggesting that the high -G_A of SX-II is contributed by a considerably reduced entropy loss. The dispersive component of surface free energy (_s ^D) is the highest for MSX but the lowest for SX-II at all temperatures studied, whereas the specific component of surface free energy of adsorption (-G_A ^SP) is higher for SX-II than for SX-I. That SX-II displays the highest -G_A for the NP but the lowest _s ^D of all the SX samples may be explained by the additional -G_A change associated with an increased mobility of the probe molecules on the less stable and more disordered SX-II surface. The acid and base parameters, K_A and K_D, that were derived from H_A ^SP reveal significant differences in the relative acid and base properties among the samples. The calculated Hansen solubility parameters (_D, _P, and _H) indicate that the surface of SX-II is the most polar and most energetic of all the three samples in terms of specific interactions (mostly hydrogen bonding). Conclusions. The metastable SX-II polymorph possesses a higher surface free energy, higher surface entropy, and a more polar surface than the stable SX-I polymorph.     

Formulation of novel dry powder inhalation for fluticasone propionate and salmeterol xinafoate with capsule-based device

The aim of this study was to develop a novel fluticasone propionate (FP) and salmeterol xinafoate (SX)-loaded dry powder inhaler (DPI) system, which was composed of powder formulation and performance. The air flow resistances were determined with various types of DPI device, showing that the modified RS01 device gave the specific resistance similar to the commercial DPI device. The particle properties of FP, SX, and inhalation grade lactose particles, such as particle size, size distribution, and fine content, were assessed. Subsequently, the aerodynamic behaviors of the DPI powder formulations were evaluated by the in vitro deposition of drugs in the DPI products using Andersen cascade impactor. Amongst the DPI powder formulations tested, the formulation composed of FP, SX, Respitose^® SV003, Respitose^® SV010, and Respitose^® ML006 at the weight ratio of 0.5/0.145/19/19/2 gave depositions, emitted dose, fine particle dose, fine particle fraction, and mass median aerodynamic diameter of drugs similar to the commercial product, suggesting that they had similar aerodynamic behaviors. Furthermore, it gave excellent content uniformity. Thus, this DPI using the modified RS01 device would be recommended as a candidate for FP and SX-loaded pharmaceutical DPI products.     

Pharmacokinetic analysis of inhaled salmeterol in asthma patients: Evidence from two dry powder inhalers

Salmeterol (SAL) is a long‐acting β2‐adrenergic agonist, which is widely used in the therapy of asthma. The aim of this study was to investigate the pharmacokinetics (PK) of inhaled salmeterol in asthma patients using two different dry powder inhalers. This analysis was based on data from 45 subjects who participated in a two‐sequence, four‐period crossover bioequivalence (BE) study after single administration of the test (T) and reference (R) products. In order to mimic more closely the real treatment conditions, activated charcoal was not co‐administered. Plasma concentration–time (C–t) data were initially analysed using classic non‐compartmental PK approaches, while the main objective of the study was to apply population PK modeling. The relative fraction of the dose absorbed via the lungs (R_L) was set as a parameter in the structural model. The plasma C–t profiles of salmeterol showed a biphasic time course indicating a parallel pulmonary and gastrointestinal (GI) absorption. A two‐compartment disposition model with first order absorption from the GI and very rapid absorption from lungs (like an i.v. bolus) was found to describe successfully the C–t profiles of salmeterol. The estimated R_L value was 13% suggesting a high gut deposition of inhaled salmeterol. Women were found to exert less capability to eliminate salmeterol than men, while body weight (in allometric form) was found to be an important covariate on the peripheral volume of distribution.     

靶向递释系统的研究进展

靶向递释系统(targeting drug delivery system,TDDS)能够选择性作用于病变部位,控制药物的分布与释放,提高药效和降低毒副作用,已成为癌症等疾病治疗领域的研究热点之一。本文综述了各类TDDS的机制、载体类型、制备技术和体内外靶向性,对近年来靶向递释系统的研究现状、未来产品研发与临床应用的可行性进行了探讨。     

噻托溴铵粉雾剂联合沙美特罗替卡松粉吸入剂治疗慢性阻塞性肺疾病急性加重期伴呼吸衰竭的临床研究

目的观察噻托溴铵粉雾剂联合沙美特罗替卡松粉吸入剂治疗慢性阻塞性肺疾病(COPD)急性加重期伴呼吸衰竭的临床疗效及安全性。方法将76例COPD急性加重期伴呼吸衰竭患者随机分为对照组38例和试验组38例。对照组予以常规治疗配合呼吸机辅助通气治疗;试验组在对照组治疗的基础上,予以沙美特罗替卡松粉吸入剂每次1吸,bid,吸入治疗+噻托溴铵粉雾剂每次18μg,qd,吸入治疗。2组患者均治疗2周。比较2组患者的临床疗效、动脉血气指标、降钙素原和免疫功能,以及药物不良反应的发生情况。结果治疗后,试验组和对照组的总有效率分别为92.11%(35例/38例)和73.68%(28例/38例),差异有统计学意义(P<0.05)。治疗后,试验组和对照组的动脉血氧分压分别为(86.35±7.04)和(77.49±6.85)mm Hg,氧合指数分别为(310.89±29.87)和(281.34±27.53)mm Hg,降钙素原分别为(1.42±0.54)和(1.93±0.61)ng·m L^-1,肿瘤坏死因子-α分别为(275.49±48.62)和(310.05±54.73)ng·L^-1,白细胞介素-8分别为(312.62±75.64)和(389.75±78.76)pg·m L^-1,超敏C-反应蛋白分别为(4.73±2.45)和(8.34±2.53)mg·L^-1,差异均有统计学意义(均P<0.05)。2组患者治疗期间均未发生药物不良反应。结论噻托溴铵粉雾剂联合沙美特罗替卡松粉吸入剂治疗COPD急性加重期伴呼吸衰竭的临床疗效确切,其能显著降低患者的降钙素原水平,改善患者的血气指标和免疫功能,且安全性较好。     

Evaluation of salmeterol xinafoate plus fluticasone propionate for the treatment of chronic obstructive pulmonary disease

Introduction: Current clinical guidelines recommend long-acting bronchodilators as the mainstay of the pharmacotherapy of patients with chronic obstructive pulmonary disease (COPD). Inhaled corticosteroids (ICS), in conjunction with long-acting beta-agonists (LABA), are routinely considered at severe and very severe stages of COPD when patients lack adequate response to single-therapy with LABAs. Although the study methodologies evaluating the clinical effectiveness of the combination therapy using salmeterol and fluticasone (SAL/FLU) for patients with COPD have been questioned, a number of studies have suggested that using ICS, in combination with a LABA agent, may improve survival of patients with COPD.

Areas covered: This article attempts to review the most current evidence for using SAL/FLU in the management of COPD and summarizes the results of outcome measures reported in randomized controlled trials.

Expert opinion: Until new forms of drug combinations are made available, the use of dual-therapy containing a LABA and ICS remain as the most logical and appropriate approach for the treatment of patients suffering from severe and very severe COPD with repeated exacerbations.     

沙美特罗替卡松粉吸入剂治疗慢性阻塞性肺疾病的疗效观察

目的观察沙美特罗替卡松粉吸入剂治疗慢性阻塞性肺疾病(COPD)的临床疗效。方法 108例COPD患者,随机分为实验组和对照组,各54例。对照组予口服盐酸氨溴索片、茶碱缓释片等进行常规治疗,实验组在常规治疗的基础上同时给予沙美特罗替卡松粉吸入治疗。比较两组患者治疗前后的肺功能指标[第1秒用力呼气容积(FEV1)、第1秒用力呼气容积占用力肺活量的比值(FEV1/FVC)]、动脉血气分析指标[动脉血氧分压(PaO2)、动脉血二氧化碳分压(PaCO2)]、COPD评估测试(CAT)评分及不良反应发生情况。结果治疗后,对照组患者的FEV1为(1.68±0.13)L、FEV1/FVC为(52.44±6.81)%、PaO2为(64.40±7.89)mm Hg(1 mm Hg=0.133 kPa)、PaCO2为(51.60±6.50)mm Hg及CAT评分为(32.6±6.5)分,与本组治疗前的(1.61±0.13)L、(51.10±6.08)%、(62.00±7.15)mm Hg、(52.20±6.42)mm Hg及(33.1±6.7)分比较,差异均无统计学意义(P>0.05)。实验组患者的FEV1(1.94±0.11)L、FEV1/FVC (63.48±6.52)%、PaO2 (74.80±8.21)mm Hg均高于本组治疗前的(1.58±0.16)L、(50.90±5.96)%、(61.60±7.08)mm Hg, PaCO2 (40.80±6.35)mm Hg、CAT评分(21.8±5.8)分低于本组治疗前的(52.50±6.36)mm Hg、(32.4±6.5)分,差异均具有统计学意义(P<0.05)。实验组患者治疗后的FEV1、FEV1/FVC、PaO2水平均高于对照组, PaCO2、CAT评分低于对照组,差异均具有统计学意义(P<0.05)。两组患者均未出现明显的不良反应。结论采用沙美特罗替卡松粉吸入剂治疗COPD,能够显著改善患者的临床症状和肺功能。