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.     

孟鲁司特联合丙酸氟替卡松鼻喷雾剂治疗儿童腺样体肥大疗效观察

目的:探讨孟鲁司特联合丙酸氟替卡松鼻喷雾剂治疗儿童腺样体肥大的临床效果。方法:选取2013 年3 月至2015年3月我院儿科收治的腺样体肥大患儿90例,依据随机数字表法分为观察组和对照组各45例。对照组给予丙酸氟替卡松气雾剂喷鼻腔治疗,观察组在对照组的治疗基础上给予孟鲁司特口服治疗,评估两组患儿临床症状积分改善情况、腺样体大小及治疗后的不良反应。结果:治疗前两组患儿症状积分、腺样体体积比较差异无统计学意义(P>0郾05);治疗后两组患儿症状积分、腺样体体积均有明显改善,差异有统计学意义(P<0.05);治疗后观察组患儿症状积分、腺样体体积改善明显优于对照组,差异有统计学意义(P<0.05);两组患儿不良反应发生率比较差异无统计学意义(P>0.05)。结论:应用孟鲁司特联合丙酸氟替卡松气雾剂治疗儿童腺样体肥大,能够显著改善患儿临床症状,减小腺样体体积,不良反应小,值得临床推广应用。     

吸入沙美特罗替卡松联合特异性脱敏防治支气管哮喘的研究

目的观察吸入沙美特罗替卡松联合特异性脱敏防治支气管哮喘的疗效。方法常见变应原皮内试验,根据试验结果,行特异性脱敏,阶梯式吸入沙美特罗替卡松干粉剂,峰速仪监测PEFam值,疗程1年。结果临床控制率80% ,显效率88% ,总有效率100%。结论特异性脱敏联合吸入沙美特罗替卡松可有效的防治支气管哮喘。     

清咳平喘颗粒联合沙美特罗替卡松治疗热伤肺络型咳嗽变异性哮喘的临床研究

目的 观察清咳平喘颗粒联合沙美特罗替卡松吸入粉雾剂治疗热伤肺络型咳嗽变异性哮喘的临床疗效。方法 选取2020年3月—2021年3月在哈尔滨市中医医院呼吸科门诊就诊的100例热伤肺络型咳嗽变异性哮喘患者,采用随机数字表法将所有患者分为对照组和治疗组,每组各50例。对照组患者给予沙美特罗替卡松吸入粉雾剂,1吸（泡）/次,2次/d。治疗组在对照组的基础上开水冲服清咳平喘颗粒,10 g/次,3次/d。两组患者均连续治疗4周。观察两组患者临床疗效,比较两组患者的中医证候积分、肺功能指标和血清免疫功能指标水平。结果 治疗后,治疗组患者的总有效率为90.00%,明显高于对照组的总有效率80.00%,差异有统计学意义（P<0.05）。治疗后,两组患者咳嗽、咳痰、喘息、哮鸣音评分均显著降低（P<0.05）,且治疗后治疗组患者咳嗽、咳痰、喘息、哮鸣音评分明显低于对照组,差异有统计学意义（P<0.05）。治疗后,两组患者第1秒用力呼气容积（FEVl）、最大呼气流速（PEF）、FEV1/FVC均显著升高（P<0.05）,且治疗组FEVl、PEF、FEV1/FVC显著高于对照组,差异有统...     

沙美特罗替卡松粉吸入剂治疗儿童哮喘疗效观察

目的探讨沙美特罗替卡松粉吸入剂(商品名舒利迭Seretide,葛兰素史克公司生产)治疗儿童哮喘的疗效及副作用.方法62例儿童哮喘按就诊顺序随机分成两组,治疗组患儿按病情严重程度分别予舒利迭50/100、100/200、150/300μg·d-1吸入,对照组按病情严重分别予丙酸氟替卡松吸入剂(商品名辅舒酮,葛兰素史克公司生产)125、250、375μg-1吸入,分别于治疗后4、8、12周评价其日、夜间哮喘症状计分及PEFR值变化.结果治疗后4、8、12周,治疗组与对照组相比,患儿日夜间哮喘症状计分明显减少(P＜0.01);治疗组PEFR值占预计值的百分比与对照组相比明显改善(P＜0.05),差异非常显著.且两组患儿在治疗期间均未发现明显副作用.结论联合应用糖皮质激素和长效β2-肾上腺素受体激动剂具有协同抗炎和平喘作用,且联合使用时可以减少糖皮质激素的用量,减少较大剂量的糖皮质激素的不良反应.舒利迭就是含有沙美特罗和丙酸氟替卡松的混合干粉吸入剂,用舒利迭治疗不同程度的儿童哮喘疗效明显优于辅舒酮.     

肺力咳合剂联合沙美特罗替卡松治疗儿童支气管哮喘的临床研究

目的探究肺力咳合剂联合沙美特罗替卡松粉吸入剂治疗儿童支气管哮喘的临床疗效。方法选取2016年12月—2018年12月天津市儿童医院收治的142例支气管哮喘患儿为研究对象,将所有患儿随机分为对照组和治疗组,每组各71例。对照组患儿吸入沙美特罗替卡松粉吸入剂,1吸/次,1次/d;治疗组在对照组治疗的基础上口服肺力咳合剂,10 mL/次,3次/d。两组患儿持续治疗3个月。观察两组的临床疗效,比较两组的临床症状缓解时间、肺功能指标、血气指标、血清炎性因子水平。结果治疗后,对照组和治疗组的总有效率分别为84.51%、95.77%,两组比较差异有统计学意义(P0.05)。治疗后,治疗组患儿喘憋、咳嗽、肺部啰音消失时间显著短于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患儿第一秒用力呼气容积(FEV1)、用力肺活量(FVC)和FEV1/FVC均显著升高,同组治疗前后比较差异有统计学意义(P0.05);且治疗组患儿肺功能指标明显高于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患儿全血氧分压(pO_2)水平明显升高,二氧化碳分压(pCO_2)水平明显下降,同组治疗前后比较差异有统计学意义(P0.05);且治疗组患儿血气指标水平显著优于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患儿肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平均显著降低,干扰素-γ(IFN-γ)水平显著升高,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组患儿血清炎性因子水平明显优于对照组,两组比较差异有统计学意义(P0.05)。结论肺力咳合剂联合沙美特罗替卡松粉吸入剂治疗儿童支气管哮喘具有较好的临床疗效,可缩短临床症状缓解时间,改善肺部功能,降低血清炎性因子水平,具有一定的临床推广应用价值。     

Evaluating fluticasone furoate + vilanterol for the treatment of chronic obstructive pulmonary disease (COPD)

Introduction: Inhaled corticosteroid/long-acting β-2 agonists (ICS/LABA) combination inhalers have been a lifeline for a generation of chronic obstructive pulmonary disease (COPD) and asthma patients. Fluticasone furoate and Vilanterol (FF/VI) as a once-daily ICS/LABA combination have an extensive clinical trial and real-world data to support its use in COPD patients.

Areas covered: The authors provide pharmacological profiles of fluticasone furoate, vilanterol and the FF/VI fixed dose combination. Salient clinical trials evaluating efficacy and safety of the FF/VI combination, and studies demonstrating the impact on COPD exacerbation risk and mortality are also discussed.

Expert opinion: ICS/LABA combinations provide bronchodilation and decrease the frequency of COPD exacerbations. Individualizing treatment of each COPD patient based on unique phenotypes will maximize chances of therapeutic responsiveness. Asthma-COPD overlap (ACO), patients with sputum and/or blood eosinophilia, patients with a brisk bronchodilator response, and patients with frequent exacerbations are more likely to show a therapeutic response to ICS than populations who have none of these features. FF/VI will likely remain a popular ICS/LBA combination to treat COPD, as a once-daily inhaled therapy delivered via the Ellipta device popular with COPD patients, with extensive clinical trial and real-world data to support its use.     

糠酸氟替卡松/维兰特罗复方剂治疗哮喘疗效与耐受性的Meta分析

目的 比较糠酸氟替卡松/维兰特罗复方剂（FF/VI）与吸入型糖皮质激素单药或联合长效β₂受体激动剂治疗哮喘患者的疗效与耐受性差异。方法 计算机检索CNKI、PubMed、Embase、Cochrane Library等数据库,纳入随机对照试验,采用Cochrane系统评价方法进行评价。结果 共纳入10个研究,共9 811例患者。在疗效上,FF/VI组与对照组相比,提高患者的1秒用力呼气量谷值[WMD=0.09,95% CI（0.05,0.13）,P=0.000]和哮喘控制测试评分[WMD=0.63,95% CI（0.24,1.03）,P=0.002]。在耐受性方面,FF/VI组与对照组相比不增加患者发生与治疗相关不良反应事件风险[RR=1.15,95% CI（0.98,1.36）,P=0.000]。结论 用FF/VI治疗哮喘在疗效方面具有优势,且具有良好的耐受性。其每日1次的用药频次可提高患者依从性,值得推荐使用。     

沙美特罗/丙酸氟替卡松对哮喘儿童肺功能的改善及临床意义

目的:观察沙美特罗/丙酸氟替卡松对哮喘儿童肺功能改善情况。方法:采用德国Jaeger公司的MasterscreenIOS测定仪,对61例支气管哮喘患儿在沙美特罗/丙酸氟替卡松治疗前后进行通气肺功能(F-V)和脉冲振荡(IOS)检测。观察用力肺活量(FVC)、第一秒用力呼气容积(FEV1)、最大呼气流速(PEF)、呼出25%肺活量时最大呼气流量(FEF25)、呼出50%肺活量时最大呼气流量(FEF50)、呼出75%肺活量时最大呼气流量(FEF75);呼吸阻抗(Zrs)、气道总阻力(R5)、中心气道阻力(R20)、响应频率(Fres)。结果:沙美特罗/丙酸氟替卡松治疗后FVC、FEV1、PEF均明显升高(P<0.001),而Zrs、R5、R20、Fres均明显降低(P<0.05),两者检查结果均有显著统计学意义。结论:吸入沙美特罗/丙酸氟替卡松能改善哮喘儿童的肺通气功能,降低气道阻力,是治疗儿童哮喘的理想药物之一。     

沙美特罗氟替卡松粉吸入剂治疗支气管哮喘的效果研究

目的：探讨沙美特罗氟替卡松粉吸入剂治疗支气管哮喘的临床疗效。方法：回顾性分析笔者所在医院收治的82例支气管哮喘患者的临床资料,根据治疗方法的不同分为治疗组和对照组各41例,其中对照组单用氟替卡松进行治疗,治疗组采用沙美特罗氟替卡松粉吸入剂治疗,比较治疗后两组患者的临床疗效以及肺功能指数用力肺活量（FVC）、呼气峰流速（PEF）、用力呼气容积（FEV1）、最大呼气中期流速（MMEF）。结果：疗程结束后,治疗组的总有效率高达92.68%,显著高于对照组的总有效率82.93%（P〈0.05）,治疗组的显效率为31.71%,显著高于对照组的24.39%（P〈0.05）;治疗组患者的FVC、PEF、FEV1、MMEF的改善率均显著高于对照组（P〈0.05）。结论：沙美特罗氟替卡松粉吸入剂治疗支气管哮喘,临床疗效显著,明显改善肺功能指数,患者依从性好。