CN1243436A - 注入堆积密度为0.28～0.38g/ml的吸入用新配方、该配方的制备方法及其用途 - Google Patents

注入堆积密度为0.28～0.38g/ml的吸入用新配方、该配方的制备方法及其用途 Download PDF

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CN1243436A
CN1243436A CN98801900A CN98801900A CN1243436A CN 1243436 A CN1243436 A CN 1243436A CN 98801900 A CN98801900 A CN 98801900A CN 98801900 A CN98801900 A CN 98801900A CN 1243436 A CN1243436 A CN 1243436A
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Abstract

一种干粉剂组合物,其中包含一种或多种强效药物活性物质和载体物质,这些物质全部都呈微细形式,其中该配方的注入堆积密度为0.28—0.38g/ml。这种干粉剂组合物在治疗呼吸系统疾病方面是有用的。

Description

注入堆积密度为0.28～0.38g/mL的 吸入用新配方、该配方的制备方法及其用途
发明领域
本发明提供一种新药物配方、其制备及其用途。
发明背景
吸入法给药用的强效药因其制备精确剂量的问题，一般是与乳糖等载体相缔合来配制的。当这样的药物稀释时，配方重量的差异导致与它们未被稀释时比较更小的药物剂量差异。这些配方一般由载体的粗大颗粒和药物的微细颗粒组成，这种组合一般称为订做的混合物。
本发明提供一种改进的配方，在为模仿吸入而设计的系统中，已发现该配方能改善药物的分散。
本发明说明
按照本发明，提供的是一种干粉剂组合物，其中包含一种或多种强效药物活性物质和一种载体物质，这些物质全部都呈微细形式，其中该配方的注入堆积密度为0.28～0.38g/mL，较好为0.30～0.36g/mL。
按照本发明的注入堆积密度是用已知技术测定的，例如“粉末测试指南：散装粉末物理性能测定方法”L.Svarovsky，ElsevierApplied Science 1987，pp 84-86中描述的那些。
适用于本发明的一种强效药物活性物质是诸如一种抗心律失常药、安定药、强心甙、激素、高血压药、抗糖尿病或抗癌药、镇静或止痛药、抗生素、抗风湿药、免疫治疗、抗真菌或抗低血压药、菌苗、抗病毒药、蛋白质(例如胰岛素)、肽、维生素、或一种细胞表面受体阻滞剂。较好的是一种糖皮质类甾醇、尤其一种能迅速代谢者，例如双丙酸倍氯美松(BDP)、单丙酸倍氯美松(BMP)、氟尼缩松、丙酮缩去炎舒松、氟替卡松丙酸盐、ciclesonide、布地奈德、rofleponide或其衍生物、momethasone、替泼尼旦、RPR106541和/或一种β2-兴奋剂，例如特布他林、舒喘灵、福莫特罗(formoterol)、沙美特罗、TA2005、pircumarol或其药物上可接受的盐；和/或一种预防性药剂，例如sodium chromoglycate或奈多罗米钠盐。
适用的生理上可接受的盐包括从无机酸和有机酸衍生的酸加成盐，例如氯化物、溴化物、硫酸盐、磷酸盐、马来酸盐、富马酸盐、酒石酸盐、柠檬酸盐、苯甲酸盐、4-甲氧基苯甲酸盐、2-或4-羟基苯甲酸盐、4-氯苯甲酸盐、对甲苯磺酸盐、甲磺酸盐、抗坏血酸盐、乙酸盐、琥珀酸盐、乳酸盐、戊二酸盐、葡糖酸盐、丙三羧酸盐、羟基萘羧酸盐或油酸盐或其溶剂化物。
载体物质较好的是一种单糖、二糖或多糖，一种糖醇或一种多醇。适用的载体是诸如乳糖、葡萄糖、棉子糖、松三糖、乳糖醇、麦牙糖醇、茧蜜糖、蔗糖、甘露糖；和淀粉。乳糖是特别好，特别是其一水合物形式。
按照本发明的配方的各组分必须均呈微细形式，即它们的质量中值直径一般应当小于10μm，较好的是1～7μm，是用激光衍射仪或coulter计数器测定的。这些组分可以用有本门技术技能的人员已知的方法例如研磨、微粉化或直接沉淀，以所希望的粒度产生。
布地奈德和福莫特罗的组合是特别好的。福莫特罗较好以其富马酸盐、特别是二水合物的形式使用。
当本发明中使用的一种或多种强效药物活性物质是福莫特罗和布地奈德时，本发明组合物中福莫特罗与布地奈德的摩尔比较好的是1∶2500～12∶1，更好的是1∶555～2∶1，最好的是1∶133～1∶6。按照本发明的组合物，较好的是配制得能提供2～120nmol(更好的是7～70nmol)福莫特罗的日剂量。当福莫特罗是以福莫特罗富马酸盐二水合物的形式使用时，该组合物较好配制得能提供1～50μg，更好的是3～30μg福莫特罗富马酸盐二水合物的日剂量。按照本发明的组合物较好配制得能提供45～2200μg、更好的是65～1700μg布地奈德的日剂量。
更好的是，本发明的组合物以单元剂量形式含有6μg福莫特罗富马酸盐二水合物和100μg布地奈德，或4.5μg福莫特罗富马酸盐二水合物和80μg布地奈德，其中任意一种均可一天给药多达4次。此外，本发明组合物也可以单元剂量形式含有12μg福莫特罗富马酸盐二水合物和200μg布地奈德，或9μg福莫特罗富马酸盐二水合物和160μg布地奈德，其中任意一种均可一天给药一次或两次。
最好的是，本发明中使用的组合物，作为单元剂量，含有6μg福莫特罗富马酸盐二水合物和200μg布地奈德，或4.5μg福莫特罗富马酸盐二水合物和160μg布地奈德，其中任意一种均可一天给药多达4次。此外，本发明组合物，作为单元剂量，含有12μg福莫特罗富马酸盐二水合物和400μg布地奈德，或9μg福莫特罗富马酸盐二水合物和320μg布地奈德，其中任意一种均可一天给药一次或两次。
按照本发明，进一步提供的是按照本发明的一种组合物的制备方法，包括
(a)  使一种或多种强效药物活性物质和载体物质微粉化；
(b)  任选地调理该产品；和
(c)  球形化直至得到所希望的堆积密度。
本工艺在步骤(b)之后较好进一步包含一个低能量再微粉化步骤。
按照本发明的配方可以用本身已知的常用技术制作。这样的生产工艺一般包括使这些组分微粉化成所需要的粒度，用诸如WO92/18110或WO 95/05805中所述的方法除去所得到颗粒上的任何无定形区域，然后将所得到的粉末造粒、球形化和过筛。所得到团粒的粒度较好在100～2000μm的范围内，更好的是在100～800μm。所生产配方的堆积密度可以根据经验通过改变成分和工艺来调节，例如，可以通过延长颗粒在球形化装置中翻滚的时间来提高堆积密度。
在固-固混合中，最重要的特色之一是确保含量均匀。微细粉末的粉末混合中遇到的主要问题是混合机不能使粉末团粒破碎。已经发现，微细粉末调理步骤之后用低能量输入的再微粉化步骤是有利的。它一般应当用足以使粉末团粒破碎的能量进行，但不要用如此多的能量，以致影响颗粒本身的粒度。这样一个步骤给出一种组合物，其中，活性物质和载体物质大体上均匀分布，例如相对标准偏差小于3％(较好小于1％)，且不影响微细颗粒的结晶性。
按照本发明的配方可用任何已知干粉吸入器给药，例如该吸入器可以是单剂量或多剂量吸入器，还可以是一种呼吸驱动干粉吸入器，例如Turbuhaler(商品名)。本发明进一步提供按照本发明的组合物在制造用于治疗的药物方面的用途。按照本发明的组合物在治疗呼吸系统疾病，特别是气喘病方面是有用的。本发明也提供治疗受呼吸系统疾病困扰的病人的方法，该方法包括对患者施用治疗有效量的按照本发明的组合物。
下列实例说明，但不限制本发明。
实例1
0.0315份福莫特罗富马酸盐二水合物和2.969份乳糖一水合物在转鼓混合机(Turbula)中混合成均匀分布的混合物，然后以某一压力和适合于获得小于3μm粒度(用coulter计数计测得的质量平均直径)的进料速率将混合物送入螺旋喷射磨中进行微粉化。然后用WO95/05805中所公开的方法对微粉化后的颗粒进行处理，以除去其晶体结构中的非晶区域。然后将该粉末喂入双螺杆进料机(K-Tron)中使粉末聚集，在振动筛(0.5mm目径)中过筛，在圆周速度0.5m/s的旋转盘中进行球形化4分钟，然后再用同样的筛子过筛，随后再球形化6分钟，最后再过筛(目径1.0mm)，得到堆积密度为0.32g/ml的粉末。
实例2
重复实例1，但粉末在微粉化之后在螺旋喷射磨中在低压(约1巴)下再次进行微粉化，并作如下调整，即无需按WO 95/05805中所述方法处理颗粒这一步骤，得到堆积密度为0.32g/ml的粉末。
实例3
9份布地奈德和91份乳糖一水合物在约6～7巴压力下分别在螺旋喷射磨中单独进行微粉化，得到小于3μm的颗粒尺寸，然后在Turbula混炼机中充分混合。混合之前，乳糖一水合物粉末按WO 95/05805所述方法进行处理。混合物在仅约1巴的压力下在螺旋喷射磨中再次进行微粉化，以便得到均匀的混合物。然后按实例1所述方法使粉末聚集和球形化，得到0.35g/ml的堆积密度。
实例4
60份特布他林硫酸盐在Alpin磨100 AFG中进行微粉化直至质量平均直径小于2μm，然后按US 5562923所述方法处理。40份乳糖一水合物微粉化至质量平均直径小于3μm，然后按WO 95/05805所述方法进行处理。经微粉化和处理后的特布他林硫酸盐和乳糖一水合物在Turbula混炼机中充分混合。混合物在螺旋喷射磨中在仅约1巴的压力下再次微粉化，得到均匀分布的混合物。然后按实例1所述方法使粉末聚集和球形化，得到0.28g/ml的堆积密度。
实例5
用30份特布他林硫酸盐和70份乳糖一水合物重复实例4，得到堆积密度为0.31g/ml的粉末。
实例6
5.2份福莫特罗富马酸盐二水合物和896.8份乳糖一水合物在转鼓混合机(Trubula)中混合成均匀分布的混合物，然后以某一压力和适合于获得小于3μm粒度(用coulter计数计测得的质量平均直径)的进料速率将混合物送入螺旋喷射磨中进行微粉化。然后用WO 95/05805中所述方法对微粉化后的颗粒进行处理，以除去其晶体结构中的非晶区域。加入98份微粉化布地奈德，混合物在低压下在螺旋喷射磨中再次微粉化，成为均匀混合物。然后将该粉末喂入螺杆进料机(K-Tron)中使粉末聚集，在振动筛(0.5mm目径)中过筛，在转速为23rpm的旋转盘中进行球形化10分钟，然后再过筛(0.5m目径)，再球形一次，最后再过筛(目径0.8mm)，得到堆积密度为0.34g/ml的粉末。
实例7
以同样的条件，但用5.2份微粉化的福莫特罗富马酸盐二水合物、798.8份微粉化的乳糖一水合物和196份微粉化的布地奈德重复实例6。所得到的堆积密度为0.34g/ml。

Claims (9)

1.一种干粉剂组合物，其中包含一种或多种强效药物活性物质和载体物质，这些物质全部都呈微细形式，其中该配方的注入堆积密度为0.28～0.38g/ml。
2.按照权利要求1的组合物，其中所述一种或多种强效药物活性物质是布地奈德和福莫特罗。
3.按照权利要求1或2的组合物，其中所述堆积密度是0.30～0.36g/ml。
4.按照权利要求1、2或3的组合物，其中所述活性物质和载体物质实际上是均匀分布的。
5.用于治疗呼吸系统疾病的按照权利要求1-4中任何一项的组合物。
6.制备按照权利要求1的组合物的方法，该方法包括：
(a)  使一种或多种强效药物活性物质和载体物质微粉化；
(b)  任选地调理该产品；和
(c)  球形化直至得到所希望的堆积密度。
7.按照权利要求6的方法，该方法还包括在步骤(b)之后的低能量再微粉化步骤。
8.按照权利要求1-4中任何一项的组合物在制造用于治疗的药物方面的用途。
9.一种治疗受呼吸系统疾病困扰的病人的方法，该方法包括对患者施用治疗有效量的按照权利要求1-4中任何一项的组合物。
CNB988019000A 1997-01-20 1998-01-13 注入堆积密度为0.28～0.38g/ml的吸入用新配方、该配方的制备方法及其用途 Expired - Lifetime CN1271993C (zh)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100370986C (zh) * 2003-02-27 2008-02-27 奇斯药制品公司 包含高效长效β2－激动剂和其它活性成分的药物组合物

Families Citing this family (93)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE9700135D0 (sv) * 1997-01-20 1997-01-20 Astra Ab New formulation
US6495167B2 (en) 1997-03-20 2002-12-17 Schering Corporation Preparation of powder agglomerates
US6503537B2 (en) 1997-03-20 2003-01-07 Schering Corporation Preparation of powder agglomerates
SE9703407D0 (sv) * 1997-09-19 1997-09-19 Astra Ab New use
SE9802073D0 (sv) 1998-06-11 1998-06-11 Astra Ab New use
GB9826284D0 (en) * 1998-12-01 1999-01-20 Rhone Poulence Rorer Limited Process
GB9826286D0 (en) * 1998-12-01 1999-01-20 Rhone Poulence Rorer Limited Process
ATE251447T1 (de) * 1998-12-11 2003-10-15 Pharmachemie Bv Pharmazeutische zubereitungen zur inhalation eines opioids
US8722668B2 (en) * 1998-12-23 2014-05-13 Daryl W. Hochman Methods and compositions for the treatment of neuropathic pain and neuropsychiatric disorders
AR022695A1 (es) * 1999-01-28 2002-09-04 Schering Corp PORTADOR SoLIDO PARTICULADO Y MÉTODO PARA PROVEER CONTROL DE LA PARTICULADA PARA LA DISTRIBUCIoN DE TAMANO DE PARTíCULAS Y DE CONTENIDO AMORFO CONVERTIBLE DURANTE SU PREPARACION
US6623760B1 (en) * 1999-01-28 2003-09-23 Schering Corporation Method of preparing particles for agglomeration
GB9903759D0 (en) * 1999-02-18 1999-04-14 Novartis Ag Organic compounds
GB9904919D0 (en) * 1999-03-03 1999-04-28 Novartis Ag Organic compounds
JP2002541213A (ja) * 1999-04-13 2002-12-03 インヘール セラピューティック システムズ， インコーポレイテッド 不妊症の処置のための乾燥粉末処方物の肺投与
CA2273585A1 (en) 1999-05-28 2000-11-28 Canpolar East Inc. Sensors for detecting changes in temperature, ph, chemical conditions, biological conditions, radiation, electrical field and pressure
DE19962926A1 (de) * 1999-12-24 2001-06-28 Bayer Ag Verfahren zur Co-Mahlung von Stoffen und Lactose mittels Strahlmühlen
US6369115B1 (en) * 2000-03-20 2002-04-09 Dura Pharmaceuticals, Inc. Stabilized powder formulations
JP2003531123A (ja) * 2000-04-13 2003-10-21 イノバータ・バイオミッド・リミテッド 医薬品
GB0012261D0 (en) * 2000-05-19 2000-07-12 Astrazeneca Ab Novel process
GB0012260D0 (en) * 2000-05-19 2000-07-12 Astrazeneca Ab Novel composition
CA2417973A1 (en) * 2000-08-04 2002-02-14 Longwood Pharmaceutical Research, Inc. Formulations of mometasone and a bronchodilator for pulmonary administration
FI20002177A0 (fi) * 2000-10-02 2000-10-02 Orion Yhtymae Oyj Uusi yhdistelmä astman hoitoon
FI20002216A0 (fi) * 2000-10-06 2000-10-06 Orion Yhtymae Oyj Yhdistelmäpartikkelit astman hoitoon
FI20002215A0 (fi) * 2000-10-06 2000-10-06 Orion Yhtymae Oyj Yhdistelmäpartikkelit
WO2002062317A2 (en) * 2001-02-06 2002-08-15 Innovata Biomed Limited Bimodal dry powder formulation for inhalation
US20030055026A1 (en) 2001-04-17 2003-03-20 Dey L.P. Formoterol/steroid bronchodilating compositions and methods of use thereof
US6667344B2 (en) 2001-04-17 2003-12-23 Dey, L.P. Bronchodilating compositions and methods
TWI324934B (en) * 2001-08-28 2010-05-21 Schering Corp Pharmaceutical compositions for the treatment of asthma
US7931022B2 (en) * 2001-10-19 2011-04-26 Respirks, Inc. Method and apparatus for dispensing inhalator medicament
US20030140920A1 (en) * 2001-10-26 2003-07-31 Dey L.P. Albuterol inhalation soultion, system, kit and method for relieving symptoms of pediatric asthma
US20030191151A1 (en) * 2001-10-26 2003-10-09 Imtiaz Chaudry Albuterol and ipratropium inhalation solution, system, kit and method for relieving symptoms of chronic obstructive pulmonary disease
US20030203930A1 (en) * 2001-10-26 2003-10-30 Imtiaz Chaudry Albuterol and ipratropium inhalation solution, system, kit and method for relieving symptoms of chronic obstructive pulmonary disease
JP2003221335A (ja) 2001-10-26 2003-08-05 Dey Lp 慢性閉塞性肺疾患の症状を緩和するためのアルブテロールおよびイプラトロピウム吸入溶液、システム、キットおよび方法
US6702997B2 (en) 2001-10-26 2004-03-09 Dey, L.P. Albuterol inhalation solution, system, kit and method for relieving symptoms of pediatric asthma
GB0208609D0 (en) * 2002-04-13 2002-05-22 Glaxo Group Ltd Compositions
EA200401454A1 (ru) * 2002-05-07 2005-06-30 Алтана Фарма Аг Новая комбинация из обратимо действующих ингибиторов протонного насоса и используемых в терапии дыхательных путей лекарственных веществ, предназначенных для лечения респираторных заболеваний
US20040023935A1 (en) * 2002-08-02 2004-02-05 Dey, L.P. Inhalation compositions, methods of use thereof, and process for preparation of same
EP1599209B1 (en) * 2002-08-21 2011-08-17 Norton Healthcare Limited Inhalation composition
GB0219512D0 (en) * 2002-08-21 2002-10-02 Norton Healthcare Ltd Inhalation compositions with high drug ratios
GB0219511D0 (en) * 2002-08-21 2002-10-02 Norton Healthcare Ltd Method of preparing dry powder inhalation compositions
US20050158248A1 (en) * 2002-08-21 2005-07-21 Xian-Ming Zeng Method of preparing dry powder inhalation compositions
US20040105821A1 (en) * 2002-09-30 2004-06-03 Howard Bernstein Sustained release pharmaceutical formulation for inhalation
US20040109826A1 (en) * 2002-12-06 2004-06-10 Dey, L.P. Stabilized albuterol compositions and method of preparation thereof
US7879833B2 (en) * 2002-12-12 2011-02-01 Nycomed Gmbh Combination medicament
US6962006B2 (en) * 2002-12-19 2005-11-08 Acusphere, Inc. Methods and apparatus for making particles using spray dryer and in-line jet mill
US20040121003A1 (en) * 2002-12-19 2004-06-24 Acusphere, Inc. Methods for making pharmaceutical formulations comprising deagglomerated microparticles
US20040191176A1 (en) * 2003-03-28 2004-09-30 Kaplan Leonard W Formulations for treatment of pulmonary disorders
JP2006528228A (ja) * 2003-05-22 2006-12-14 アルタナ　ファルマ　アクチエンゲゼルシャフト サルメテロール及びシクレソニドの組合せ物
SE526850C2 (sv) * 2003-06-19 2005-11-08 Microdrug Ag Farmaceutisk kombinerad torr pulverdos separerade på gemensam dosbädd
SE526509C2 (sv) * 2003-06-19 2005-09-27 Microdrug Ag Kombinerade doser av formoterol och budesonid separerade på en gemensam dosbädd
SE527200C2 (sv) * 2003-06-19 2006-01-17 Microdrug Ag Inhalatoranordning samt kombinerade doser av formaterol och fluticason
SE527189C2 (sv) * 2003-06-19 2006-01-17 Microdrug Ag Inhalatoranordning samt kombinerade doser för formaterol och ett antikolinergiskt medel
SE527190C2 (sv) * 2003-06-19 2006-01-17 Microdrug Ag Inhalatoranordning samt kombinerade doser av en beta2-agonist, ett antikolinergiskt medel och ett antiinflammatorisk steroid
TWI359675B (en) 2003-07-10 2012-03-11 Dey L P Bronchodilating β-agonist compositions
GB0316335D0 (en) * 2003-07-11 2003-08-13 Glaxo Group Ltd Pharmaceutical formulations
US9345664B2 (en) 2003-09-02 2016-05-24 Norton Healthcare Ltd Process for preparing a medicament
EP1670482B2 (en) * 2003-09-16 2022-06-29 Covis Pharma B.V. Use of ciclesonide for the treatment of respiratory diseases
US20070020299A1 (en) 2003-12-31 2007-01-25 Pipkin James D Inhalant formulation containing sulfoalkyl ether cyclodextrin and corticosteroid
US20070020298A1 (en) * 2003-12-31 2007-01-25 Pipkin James D Inhalant formulation containing sulfoalkyl ether gamma-cyclodextrin and corticosteroid
EA011167B1 (ru) * 2004-01-22 2009-02-27 Пфайзер Инк. Производные сульфонамида для лечения заболеваний
JO3102B1 (ar) * 2004-03-17 2017-09-20 Chiesi Framaceutici S P A صيغ صيدلانية لوسائل استنشاق بها مسحوق جاف تشتمل على مكون فعال بقوة منخفضة الجرعة
AR048339A1 (es) * 2004-03-24 2006-04-19 Chiesi Farma Spa Monoclorhidrato de 8- hidroxi-5-((1r)) -1- hidroxi-2- (((1r)-2 ( 4-metoxifenil) -1- metiletil) amino ) eti l) -2 (1h) - quinolinona en form acristalina y el proceso para su preparacion
AU2005235384B2 (en) * 2004-04-20 2010-09-09 Covis Pharma B.V. Use of ciclesonide for the treatment of respiratory diseases in a smoking patient
BRPI0509348A (pt) 2004-04-21 2007-09-11 Innovata Biomed Ltd inalador
GB0409197D0 (en) 2004-04-24 2004-05-26 Innovata Biomed Ltd Device
MX2007007378A (es) * 2004-12-17 2007-08-14 Cipla Ltd Compuestos y composiciones farmaceuticas.
RU2007133547A (ru) * 2005-02-10 2009-03-20 Глаксо Груп Лимитед (GB) Способы получения лактозы с использованием методов предварительной сортировки и приготовляемые из нее фармацевтические композиции
ATE552032T1 (de) 2005-07-14 2012-04-15 Lithera Inc Verbesserte lipolytikum-formulierung mit hinhaltender wirkstofffreigabe für die arealbehandlung von fettgewebe
WO2007009164A1 (en) * 2005-07-15 2007-01-25 Eiffel Technologies Limited Method of particle formation
WO2007011989A2 (en) * 2005-07-15 2007-01-25 Map Pharmaceuticals, Inc. Multiple active pharmaceutical ingredients combined in discrete inhalation particles and formulations thereof
EP1978933A2 (en) * 2005-12-15 2008-10-15 Acusphere, Inc. Processes for making particle-based pharmaceutical formulations for oral administration
EP1973523A2 (en) * 2005-12-15 2008-10-01 Acusphere, Inc. Processes for making particle-based pharmaceutical formulations for pulmonary or nasal administration
US7913223B2 (en) * 2005-12-16 2011-03-22 Dialogic Corporation Method and system for development and use of a user-interface for operations, administration, maintenance and provisioning of a telecommunications system
AU2007313077B2 (en) * 2006-10-17 2011-06-02 Neothetics, Inc. Methods, compositions, and formulations for the treatment of thyroid eye disease
US8604080B2 (en) 2007-02-14 2013-12-10 W. Louis Cleveland High dose glycine as a treatment for obsessive-compulsive disorder and obsessive compulsive spectrum disorders
ES2493641T3 (es) * 2007-06-28 2014-09-12 Cydex Pharmaceuticals, Inc. Administración nasal de soluciones acuosas de corticosteroides
GB0714134D0 (en) * 2007-07-19 2007-08-29 Norton Healthcare Ltd Dry-powder medicament
DE102007049931A1 (de) 2007-10-18 2009-04-23 Pharmatech Gmbh Vorrichtung und Verfahren zur kontinuierlichen Herstellung von sphärischen Pulveragglomeraten
US20100120737A1 (en) * 2008-11-10 2010-05-13 Martin Feth Amorphous ciclesonide
US20100291221A1 (en) * 2009-05-15 2010-11-18 Robert Owen Cook Method of administering dose-sparing amounts of formoterol fumarate-budesonide combination particles by inhalation
US9132084B2 (en) 2009-05-27 2015-09-15 Neothetics, Inc. Methods for administration and formulations for the treatment of regional adipose tissue
RU2580315C3 (ru) 2009-05-29 2021-06-18 Перл Терапьютикс, Инк. Композиции для респираторной доставки активных веществ и связанные с ними способы и системы
US8815258B2 (en) 2009-05-29 2014-08-26 Pearl Therapeutics, Inc. Compositions, methods and systems for respiratory delivery of two or more active agents
SG182485A1 (en) * 2010-01-15 2012-08-30 Lithera Inc Lyophilized cake formulations
WO2011110852A1 (en) 2010-03-10 2011-09-15 Astrazeneca Ab Polymorphic forms of 6- [2- (4 -cyanophenyl) - 2h - pyrazol - 3 - yl] - 5 -methyl - 3 - oxo - 4 - (trifluoromethyl - phenyl) 3,4-dihydropyrazine-2-carboxylic acid ethylamide
CN107998109A (zh) 2010-10-12 2018-05-08 西普拉有限公司 药物组合物
GB2485885B (en) 2010-11-24 2015-06-17 Neothetics Inc Selective, lipophilic, and long-acting beta agonist monotherapeutic formulations and methods for the cosmetic treatment of adiposity and contour bulging
CA2869355A1 (en) 2012-04-11 2013-10-17 Cipla Limited Pharmaceutical composition
RU2510267C2 (ru) * 2012-06-15 2014-03-27 Шолекс Девелопмент Гмбх Ингаляционный препарат для лечения бронхиальной астмы и хронической обструктивной болезни легких и способ его получения
SG11201507286QA (en) 2013-03-15 2015-10-29 Pearl Therapeutics Inc Methods and systems for conditioning of particulate crystalline materials
EP2821061B1 (en) 2013-07-01 2017-12-20 Arven Ilac Sanayi Ve Ticaret A.S. Novel inhalation formulations
AU2018318123B2 (en) 2017-08-15 2024-07-25 Nephron Pharmaceuticals Corporation Aqueous nebulization composition
MX2021014343A (es) * 2019-05-24 2022-01-06 Glenmark Pharmaceutical Ltd Una composicion de polvo inhalable de dosis fijas que comprende glicopirronio, formoterol y propionato de fluticasona.

Family Cites Families (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1429184A (en) * 1972-04-20 1976-03-24 Allen & Hanburys Ltd Physically anti-inflammatory steroids for use in aerosols
US4161516A (en) † 1975-07-25 1979-07-17 Fisons Limited Composition for treating airway disease
GB1571629A (en) * 1977-11-30 1980-07-16 Fisons Ltd Pharmaceutical compositions containing beclomethasone dipropionate
EP0069715B1 (en) * 1981-07-08 1986-11-05 Aktiebolaget Draco Powder inhalator
SE438261B (sv) * 1981-07-08 1985-04-15 Draco Ab Anvendning i dosinhalator av ett perforerat membran
EP0072046B1 (en) * 1981-07-24 1986-01-15 FISONS plc Inhalation drugs, methods for their production and pharmaceutical formulations containing them
GB8825541D0 (en) † 1988-11-01 1988-12-07 Fisons Plc Formulation
ATE224748T1 (de) * 1989-04-28 2002-10-15 Riker Laboratories Inc Inhalationsvorrichtung für trockenpulver
US5176132A (en) * 1989-05-31 1993-01-05 Fisons Plc Medicament inhalation device and formulation
EP0441740B1 (de) † 1990-01-29 1993-09-22 Ciba-Geigy Ag Verfahren und Vorrichtung zur Dosierung eines feinkörnigen Pulvers
US5192548A (en) * 1990-04-30 1993-03-09 Riker Laboratoires, Inc. Device
SE9100341D0 (sv) * 1991-02-04 1991-02-04 Astra Ab Novel steroids
SE9100342D0 (sv) * 1991-02-04 1991-02-04 Astra Ab Novel steroid esters
SE9101090D0 (sv) * 1991-04-11 1991-04-11 Astra Ab Process for conditioning of water-soluble substances
SE9302777D0 (sv) * 1993-08-27 1993-08-27 Astra Ab Process for conditioning substances
ATE246497T1 (de) * 1991-06-10 2003-08-15 Schering Corp Fluorchlorkohlenwasserstoffreie aerosolformulierungen
US5736124A (en) * 1991-12-12 1998-04-07 Glaxo Group Limited Aerosol formulations containing P134a and particulate medicament
CZ288032B6 (cs) * 1991-12-18 2001-04-11 Aktiebolaget Astra Farmaceutický prostředek pro podání inhalací
US5355872B1 (en) * 1992-03-04 1998-10-20 John H Riggs Low flow rate nebulizer apparatus and method of nebulization
ES2177544T3 (es) † 1992-06-12 2002-12-16 Teijin Ltd Polvo ultrafinno para inhalar y metodo para su preparacion.
EP0665010B1 (en) * 1992-10-16 2002-09-11 Nippon Shinyaku Company, Limited Method of manufacturing wax matrices
AU7653294A (en) * 1993-08-18 1995-03-14 Unilever Plc Shaving composition
IS1736B (is) * 1993-10-01 1999-12-30 Astra Ab Aðferð og tæki sem stuðla að aukinni samloðun agna
IL111080A (en) † 1993-10-01 1999-08-17 Astra Ab Method for treating a finely divided powder medicament
GB9404945D0 (en) † 1994-03-15 1994-04-27 Glaxo Group Ltd Pharmaceutical composition
US5503869A (en) * 1994-10-21 1996-04-02 Glaxo Wellcome Inc. Process for forming medicament carrier for dry powder inhalator
US5647347A (en) * 1994-10-21 1997-07-15 Glaxo Wellcome Inc. Medicament carrier for dry powder inhalator
US5654007A (en) * 1995-06-07 1997-08-05 Inhale Therapeutic Systems Methods and system for processing dispersible fine powders
SE9603669D0 (sv) * 1996-10-08 1996-10-08 Astra Ab New combination
SE9700135D0 (sv) * 1997-01-20 1997-01-20 Astra Ab New formulation

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100370986C (zh) * 2003-02-27 2008-02-27 奇斯药制品公司 包含高效长效β2－激动剂和其它活性成分的药物组合物

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