Aclidinium bromide and formoterol fumarate for the maintenance treatment of chronic obstructive pulmonary disease

ABSTRACT

Introduction: Treatment options for COPD have evolved rapidly in the last decade and inhaled bronchodilators have largely supplanted the use of oral bronchodilators because of their increased efficacy and excellent safety with topical delivery to the lung. Recently added to the therapeutic armamentarium are fixed-dose combinations (FDC) of two long acting bronchodilators. LAMAs (long acting muscarinic antagonists) and LABAs (long acting beta agonists) are the main classes available and use different pathways to effectively produce bronchial smooth muscle relaxation.

Areas covered: The most recent inhaled FDC LAMA/LABA to come to market is Aclidinium Bromide and Formoterol Fumarate. We searched databases of PubMed, Cochrane Library, and manufacturers’ websites and retrieved all the randomized-controlled trials (RCTs) conducted with these drugs up to September 2019.

Expert opinion: It is likely that FDCs will become the core of our COPD pharmacotherapy for all but the mildest COPD patients. These individual drugs have excellent efficacy and safety records for the maintenance treatment of COPD. Studies have demonstrated that twice daily treatment with aclidinium/formoterol resulted in significant improvement in lung function and an improved exercise tolerance when compared to placebo. Adverse effects are within the range of what is seen with other LAMA/LABA combinations.     

富马酸替诺福韦酯的合成工艺改进（英文）

目的合成抗病毒药物富马酸替诺福韦酯并进行工艺改进。方法以亚磷酸二乙酯和多聚甲醛为原料,经缩合、酯化反应制得对甲苯磺酰氧甲基膦酸二乙酯(4);再以(S)-缩水甘油为起始物,经氢化还原、缩合反应制得(R)-碳酸丙烯酯(7),7与腺嘌呤反应合成(R)-9-(2-羟丙基)腺嘌呤(8),8经醚化、水解反应得到替诺福韦(10),再经氯甲基碳酸异丙酯酯化、与富马酸成盐得到目标化合物。结果与结论目标化合物的结构经MS、1H-NMR谱予以确证,该合成路线的总收率提高到30.4%(文献报道的最高收率为21%)。     

In vitro deposition properties of nebulized formoterol fumarate: effect of nebulization time,airflow, volume of fill and nebulizer type

ABSTRACT

Objective: The aim of this study was to investigate in vitro the delivery of a new long-acting β₂-agonist (LABA) drug formoterol fumarate inhalation solution (20?µg/2?mL) nebulized with and without ipratropium bromide (0.5?mg/2.5?mL) at different administration times (2.5–22.5?min), airflows (5–28.3?L/min), nebulizer fill volumes (2–6?mL), and nebulizer brands (Pari LC+, Ventstream and DeVilbiss).

Method: Formoterol fumarate with and without ipratropium bromide was aerosolized at different administration times, airflows, nebulizer fill volumes, and nebulizer brands. The drug deposited on the throat, filter and stage plates was collected and analyzed by HPLC to determine the aerodynamic profiles of the nebulized drugs under each variable.

Results: In addition to altering the aerosol characteristics, increasing the nebulizer fill volume including the addition of ipratropium bromide produced a significant (p?<?0.05) increase in the drug output. As expected, sputtering time was significantly longer at low airflows, and vice versa at higher airflows but with a significant loss of drug delivered presumably due to greater solvent evaporation at higher airflows. Airflows between 10 and 28.3?L/min and a nebulization time of approximately 10?min appear sufficient for producing aerosols within the respirable range (1–5?µm MMAD) with the nebulizer/compressor combination used. While the drug output varied significantly (p?<?0.05) among the three brands of nebulizers tested, the LC+ nebulizer appears to produce aerosols (2.7?±?0.1?µm MMAD) capable of penetrating more deeply into the lung than the other nebulizers evaluated under the current test conditions. This study did not attempt to evaluate different nebulizer/compressor combinations. Also, the cascade impaction data may not necessarily reflect aerosol deposition in the airways in vivo, which may be different depending on the health status of the patient.

Conclusion: The results demonstrated that administration of nebulized formoterol fumarate require proper selection of a delivery system/method for safe and effective therapy of the medication with and without ipratropium bromide.     

顶空毛细管气相色谱法测定富马酸阿奇霉素中的残留溶剂

目的 建立毛细管气相色谱方法测定富马酸阿奇霉素中的残留溶剂.方法 采用气相色谱法测定,色谱柱为:DB-5(5％苯基-95％二甲基硅氧烷固定液)石英毛细管柱(Agilent 60m×0.320mm×1.00μm),载气为氮气;柱温为60℃;FID检测器温度为250℃;进样口温度为200℃;顶空瓶平衡温度55℃,平衡时间30min.结果 被测物均能得到良好的分离,峰面积与浓度呈良好的线性关系,精密度与回收率良好.结论 该法可用于富马酸阿奇霉素原料中残留溶剂的检查.     

聚丙烯网片在女性盆底重建手术中的应用

目的:初步探讨聚丙烯网片在女性盆底重建手术中的近期疗效和安全性。方法:从2008年8月～2010年7月上海市长宁区妇幼保健院采用聚丙烯网片完成盆底重建手术共119例。术前按盆腔器官脱垂定量(POP-Q)分期,其中Ⅲ度以上膀胱膨出、子宫脱垂及直肠膨出分别为84例(70.6%)、64例(53.8%)、19例(16.0%),阴道穹窿膨出4例(3.4%),同时存在2个以上部位缺陷91例(76.5%)。结果:前、后盆底重建及全盆底重建术各54例、13例及52例,其中保留子宫55例(46.2%),同时行经闭孔尿道中段悬吊术65例(54.6%)。术后平均随访时间17.8个月,网片外露6例(5.0%),新发膀胱过度活动症6例(5.0%),压力性尿失禁4例(3.4%),无症状膀胱Ⅱ度膨出3例(2.5%)。术后6月前盆底重建组Aa及C点值,后盆底重建组Ap及C点值,全盆底重建组Aa、Ap及C点值与术前比较差异均有统计学意义(P<0.05)。结论:应用聚丙烯网片的盆底重建手术是一种安全又经济的术式,可以同时治疗压力性尿失禁和保留脱垂的子宫,手术近期疗效满意,远期效果有待进一步随访观察。     

聚丙烯改性研究

采用马来酸酐、二甲基丙烯酸乙二醇酯、三羟甲基丙烷三基丙烯酸酯对聚丙烯进行改性。以自由基反应机理为基础，讨论了引发剂用量、反应时间、改性试剂的种类、用量等因素对改性ＰＰ凝胶含量及性能的影响，提出了力学性能的优选条件。得到了力学性能优良的改性ＰＰ，为其进一步功能化提供了理论参考。     

Spectrophotometric Estimation of Ketotifen Fumarate from Tablet Formulations

Two simple and sensitive visible spectrophotometric methods have been developed for the quantitative estimation of ketotifen fumarate from its tablet formulation. The developed methods are based on formation of chloroform extractable colored complex of with 2-nitroso- napthol-4- sulphonic acid and rhodizonic acid. The extracted complex of drug with 2-nitroso- napthol-4- sulphonic acid (method-I), showed absorbance maxima at 436.5 nm and with rhodizonic acid (method-II), showed absorbance maxima at 489.5 nm. The linearity range for both the developed methods was observed in the concentration range of 50-250 µg/ml of drug. Results of analysis for both the developed methods were validated statistically and by recovery studies.     

Local injection of thrombin‐related peptide (TP508) in PPF/PLGA microparticles–enhanced bone formation during distraction osteogenesis

We have previously demonstrated that injections of the thrombin‐related peptide, TP508, into the lengthening gap have significantly enhanced bone consolidation in a rabbit model of distraction osteogenesis. This study was to further test the effect of a single TP508 injection in slow release preparation on bone formation during distraction osteogenesis. Rabbits had left tibiae lengthened unilateral lengthener at rate of 1.4 mm/day for 6 days. TP508 was injected into as the following: Group 1, TP508 in saline; Group 2, in PPF/PLGA [poly(propylene fumarate)/poly(D,L ‐lactic‐co‐glycolic acid)] microparticles; and Group 3, dextran gel only. All the animals were killed 2 weeks after lengthening. On radiographies, more bone was formed in the two TP508‐treated groups at first and secnd week postlengthening than that of the control Group 3. Microcomputed tomography (microCT) at 2 weeks indicated that the most advanced bone formation and remodeling was seen in Group 2. The mean volumetric BMD of the regenerates was significantly higher in the TP508 treated groups compared to the control group (p < 0.05). Histological evaluations supported the radiographic and the microCT results. In conclusion, we have demonstrated that a single injection of small amount of TP508 (300 µg) at the end of lengthening phases has significantly enhanced bone consolidation process in a rabbit model of distraction osteogenesis. The delivery of TP508 in PPF/PLGA microparticles appears to lead to a better quality bone formation over the saline delivery, further examinations are needed to confirm if PPF/PLGA microparticles may be desirable drug delivery form in augmenting bone formation. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:539–546, 2008     

Medical textiles in orthopedics: An overview

The use of textile in the medical field is not new; this has given rise to a new branch known as medical textiles. These are being used to repair or replace various other musculoskeletal tissues. The most common uses of biomaterials are to create aseptic conditions for protection, general health care, and hygiene including bedding and clothing, surgical gowns, face masks, head and shoe covers, sterilization wraps, suture anchors, fiber cast and braces/orthotics. These are also used as materials for preparation of wipes, swabs, wound dressings, bandages, gauzes, plasters, pressure garments, orthopedic belts and for new applications, such as heart valves, vascular grafts, artificial veins, artificial ligaments, artificial joints, artificial skin, and artificial cartilage. The truth is that nowadays the use of biomedical textiles is more rampant than anyone realizes. Commonly used materials for preparation of biomedical textiles includes Cotton, Nylon, Silk, Ultra-high molecular weight polyethylene, Polyester, Polypropylene, Poly tetra-fluoro ethylene, Polyether ether ketone, and Polyether ketone. These are prepared from various monomers in varying proportions as per the requirement of the material to be used. Various methods are used in their preparation like Braiding, Knitting, and Weaving, which helps in the development of certain kinds of materials with different specificity and character. Other important measures in the preparation of the medical textile include Denier (the filament counts in multifilament fibers), Tenacity (the strength per denier) and Heat shrink (the amount of shrinkage at a particular time and temperature).