Salmeterol/fluticasone through breath-actuated inhaler versus pMDI: a randomized,double-blind, 12 weeks study

Objective: Salmeterol/fluticasone combination (SFC) formulated in a breath-actuated inhaler (BAI) overcomes the co-ordination problem associated with the pressurized-metered dose inhaler (pMDIs). Our aim was to compare the efficacy and the safety of SFC given through the BAI versus the conventional pMDI in moderate-to-severe asthmatics. Methods: In this randomized, double-blind, double-dummy, prospective, active-controlled, parallel group, multicenter, 12 weeks study, 150 asthmatics were randomized to receive SFC (25/125?mcg) through either BAI or pMDI. The primary efficacy endpoint was mean change in pre-dose morning PEFR value at 12 weeks and the secondary efficacy endpoints included, mean change in FEV_1, pre-bronchodilator FVC, pre-dose morning and evening PEFR, symptom scores at 2, 4, 8, and 12 weeks. Patient preferences for device and safety were also assessed. Results: At 12 weeks, the mean change in pre-dose morning PEFR in BAI and pMDI groups was 50.72?L/min and 48.82?L/min, respectively (p?<?0.0001; both groups) and the difference between the two groups was not significant. Both the treatment groups showed a statistically significant improvement in secondary endpoints at all-time points compared with baseline. The usability questionnaire assessment results showed that the BAI device was preferred by 75% of patients as compared with 25% preferring pMDI. SFC in both BAI and pMDI devices was found to be safe and well tolerated. Conclusion: This is the first study to demonstrate that SFC given through the BAI produces comparable efficacy and safety endpoints as pMDI. Additionally, BAI was the preferred inhaler by patients compared to conventional pMDI.     

Treatment with mPEG-SPA improves the survival of corneal grafts in rats by immune camouflage

We investigated the immune camouflage effects of methoxy polyethylene glycol succinimidyl propionate (mPEG-SPA) on corneal antigens and explored a novel approach for reducing corneal antigenicity, thereby decreasing corneal graft rejection. Importantly, this approach did not alter normal local immunity. Corneal grafts were treated with mPEG-SPA 5KD or 20KD (3% W/V), which could shield major histocompatibility antigen class I molecules (RT1-A) of corneal grafts. Skin grafts of Wistar rats were transplanted to SD rats. Then the splenic lymphocytes were isolated from SD rats. Subsequently, the lymphocytes were co-cultured with autologous corneal grafts or untreated corneal grafts and PEGylated grafts treated with mPEG-SPA 5KD or 20KD obtained from the counterpart skin donors, which were used as autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group, respectively. Lymphocyte proliferation was lower in mPEG-SPA 5KD group and mPEG-SPA 20KD group than in the allogeneic control. SD rats with corneal neovascularisation were used as recipients for high-risk corneal transplantation and were randomly divided into four groups: autologous control, allogeneic control, mPEG-SPA 5KD group and mPEG-SPA 20KD group. The recipients received corneal grafts from Wistar rats. Corneal graft survival was prolonged and graft rejection was reduced in the mPEG-SPA 5KD group and the mPEG-SPA 20KD group compared to the allogeneic control. Thus, we think that mPEG-SPA could immunologically camouflage corneal antigens to prolong corneal grafts survival in high-risk transplantation.     

经鼻吸入丙酸氟替卡松同步治疗儿童变应性鼻炎合并哮喘的临床观察

[目的]探讨采用面罩储雾罐方式给药,经鼻吸入丙酸氟替卡松气雾剂,同步治疗儿童变应性鼻炎合并哮喘的临床疗效及安全性。[方法]将80例中、重度变应性鼻炎合并轻、中度持续性哮喘的患儿随机分为实验组和对照组。实验组以面罩储雾罐经鼻吸入丙酸氟替卡松气雾剂(200μg/d);对照组经口吸入丙酸氟替卡松气雾剂(200μg/d)联合使用丙酸氟替卡松鼻喷雾剂(200μg/d)。之后进行鼻炎症状、儿童哮喘控制测试(C-ACT)评分,比较晨起呼气峰流速值(PEF,L/min)。[结果]经16周临床观察,实验组和对照组的鼻炎症状评分、哮喘症状评分均明显下降(F=71.22～277.41,P均<0.00),实验组和对照组的PEF均逐渐升高,治疗前后实验组差别有统计学意义(F=4.79,P<0.009),而对照组差别无统计学意义(F=1.49,P=0.19);不良反应比较,实验组鼻腔出血的发生数低于对照组(χ2=4.80,P<0.05),但激素使用量实验组仅为对照组的1/2。[结论]面罩式储雾罐经鼻吸入丙酸氟替卡松气雾剂可同时有效控制儿童变应性鼻炎和哮喘,并有依从性高、不良反应少的特点,激素使用剂量明显少于对照组,应用于轻、中度持续性哮喘合并变应性鼻炎患儿效果良好。     

联合吸入噻托溴铵及沙美特罗替卡松对稳定期COPD患者血清炎症细胞因子及肺功能的影响

目的探讨联合吸入噻托溴铵及沙美特罗替卡松对稳定期重度、极重度COPD患者血浆炎症细胞因子及肺功能的影响。方法选取我院呼吸科门诊就诊的稳定期重度、极重度COPD患者80例,应用完全随机方法将患者分成两组,一组联合应用噻托溴铵及沙美特罗替卡松干粉剂(联合组),一组单用沙美特罗替卡松干粉剂(单药组),共治疗12个月。并分别于治疗前及治疗3个月、6个月、12个月测定患者血清炎症细胞因子(IL-8、TNF-α)及肺功能(FEV1、FVC、IC)。结果两组患者于治疗后各时期血清IL-8、TNF-α较治疗前均有明显下降,肺功能指标均较治疗前明显改善,差异有统计学意义(P<0.05)。结论噻托溴铵与沙美特罗替卡松联合能明显降低稳定期COPD患者IL-8、TNF-α水平,减轻气道炎症,并改善患者的肺功能。     

Stepping-across controlled asthmatic patients to extrafine beclometasone/formoterol combination

BackgroundAsthma management focuses on achieving and maintaining asthma control. Few studies have assessed whether complete and sustained asthma control is maintained in clinical practice after stepping-across ICS/LABA fixed combinations. Aim of this double-blind, double-dummy, randomized, parallel group, controlled study was to demonstrate clinical equivalence between equipotent doses of extrafine beclometasone/formoterol (BDP/F) pMDI and fluticasone/salmeterol (FP/S) Diskus^® in maintaining lung function and asthma control.MethodsA total of 416 asthmatic patients already controlled with FP/S 500/100 μg/day (Diskus^®, pMDI or separate inhalers) were randomized to a 12-week treatment with extrafine BDP/F 400/24 μg/day pMDI or FP/S 500/100 μg/day Diskus^®. Pre-dose 1-s forced expiratory volume (FEV₁) was the primary efficacy variable; secondary variables included asthma control questionnaire (ACQ-7) and FEV₁0-1 h area under the curve (FEV₁AUC_0–1h). Safety was assessed through adverse events monitoring and vital signs.ResultsAfter 12 weeks of treatment, pre-dose FEV₁ did not differ between treatments (difference between means 0.01 L; 95% CI –0.03–0.06 L) with no significant changes from baseline in both groups (p = 0.726 and p = 0.783 in BDF/F arm and FP/S, respectively). ACQ-7 score showed that control was maintained after stepping-across to extrafine BDP/F. FEV₁AUC_0–1h was significantly higher in BDP/F arm at the beginning (p = 0.004) and at the end of the 12-week treatment period (p = 0.019). No safety issues were reported in both groups.ConclusionsPatients previously controlled with FP/S in any device formulation can effectively step-across to extrafine BDP/F pMDI, maintaining lung function and asthma control with a 5-min onset of action.     

止痛消结膏对乳腺增生动物模型的作用

选用健康雌性日本大耳白兔60只,随机分为6组,用雌二醇复制乳腺增生病模型。在制模过程中和制模成功后分别使用止痛消结膏和丙酸睾丸酮软膏外贴乳房部位,对照观察了乳房的大体形态、组织学形态、乳腺上皮细胞的雌激素受体活性和血浆中雌二醇含量。结果提示止痛消结膏能一定程度地抑制和治疗乳腺增生病模型, 能对血将中雌二醇含量和乳腺上皮细胞雌激素受体活性产生一定的影响。     

睾酮和LRH-A对家犬睾丸及垂体的形态学影响

本文研究了丙酸睾酮以及丙酸睾酮合用LRH-A对家犬睾丸及垂体的形态学影响。结果发现:短期大剂量外源性丙睾使睾丸及垂体均出现抑制性形态学改变,LRH-A合用丙睾使这种改变更加明显。表明该两种药物对睾丸及垂体均有抑制作用     

Effect of Drug Loading and Molecular Weight of Cellulose Acetate Propionate on the Release Characteristics of Theophylline Microspheres

Microspheres with 40, 50, and 60% drug loading of anhydrous theophylline core material were prepared by the emulsion-solvent evaporation method. Three different molecular weights of cellulose acetate propionate were used as encapsulating polymers. The geometric mean diameter of the microspheres increased with drug loading for all polymers. Dissolution rate for a given particle size fraction also increased with drug loading for all polymers. Higuchi/Baker-Lonsdale spherical matrix dissolution kinetics were followed by narrow particle size fractions of the microspheres. A linear relationship between the T-50% (time required for 50% of the drug to be released) and the square of microsphere diameter was observed with all three molecular weights of the encapsulants. The slowest drug release was obtained with the high molecular weight polymer, which also produced the smoothest microspheres.