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CN1097455C - 用于制造无推进剂气溶胶的新颖含水药物制剂 - Google Patents

用于制造无推进剂气溶胶的新颖含水药物制剂 Download PDF

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CN1097455C
CN1097455C CN97180735A CN97180735A CN1097455C CN 1097455 C CN1097455 C CN 1097455C CN 97180735 A CN97180735 A CN 97180735A CN 97180735 A CN97180735 A CN 97180735A CN 1097455 C CN1097455 C CN 1097455C
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伯恩哈德·弗罗因德
伯恩德·齐伦伯格
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Abstract

本发明是关于用于制造无推进剂气溶胶的水溶液形式的药物制剂。

Description

用于制造无推进剂气溶胶的新颖含水药物制剂
本发明是关于用于制造吸入用无推进剂气溶胶的水溶液形式的药物制剂。
过去二十年来，使用适量气溶胶以治疗妨碍性肺部疾病已成为疗程中的重要部分，特别是治疗气喘这种肺部疾病。通常，推进剂气体以氟氯碳氢化合物为主。但由于认识到这种推进剂气体具有对臭氧层的破坏可能性，开发替代品的需求日渐提高。其中开发出的一种方法是使用喷雾器，可将药物活性物质的水溶液在高压下喷出而产生雾状可吸入的粒子，这些喷雾器的优点是他们可完全不需要推进剂气体。
这类喷雾器在如PCT专利申请WO 91/14468中有描述，在此列入作为参考文献。使用这里所叙述的喷雾器，可将特定体积的活性成分溶液在高压下经由小的喷嘴进行喷洒，以使可吸入的气溶胶的平均颗粒大小在3至10微米之间。所述喷雾器的另一种发展的具体实例描述在PCT/EP 96/04351中。在图6中所描述的喷雾器其商标为雷斯皮美特(Respimat)。
通常，将要吸入的某种药物溶解在水或酒精溶液中，且根据活性物质的溶液特性，也适合在水及乙醇的溶剂混合物中。
除了水和/或乙醇外，溶剂的其他成分必要时可为其他的共溶剂，同时药物制剂也可含有调味剂和其他药理学上的助剂。其共溶剂的实例为那些含有羟基或其他极性基团的物质，例如醇类-特别是异丙醇，乙二醇-特别是丙二醇，聚乙二醇，聚丙二醇，乙二醇醚，甘油，聚氧乙烯醇和聚氧乙烯脂肪酸酯。它用于增加助剂和必要时的活性成分的溶解度。
溶解的药物在已制成的药物制剂中的比例为在0.001至30％之间，优选0.001至3％或0.05至3％之间，特别优选0.001至2％或0.01至2％(全部为重量/体积比)。一般地，药物制剂中包含浓度为0.001至2克/100毫升溶液的活性成分。药物的最大浓度依溶剂的溶解度和所需达到预期治疗效果的剂量而定。
适于吸入施用并溶解于给定溶剂的所有物质都可在新的制剂中作为药物。治疗呼吸道疾病的药物尤为有用。因此，特别值得注意的是贝他类似物(betamimetics)，抗胆碱药，抗过敏药，抗组胺药，及类固醇，以及这些活性成分的组合物。
在一系列的研究中发现，开始所述的喷雾器在使用药物水溶液时(一般，使用双蒸馏或去离子(离子交换的)水作为溶剂)表明喷雾的异常。这些喷雾的异常说明气溶胶喷雾形式的改变，结果在极端的例子中由于平均液滴大小分布的改变(气溶胶进入肺的部分的改变)，而使得无法再确保病人的精确的使用剂量。这些喷雾异常特别是在间歇使用喷雾器时发生，例如在使用之间有将近3或3天以上的中断。在这种极端例子中会导致喷雾器故障的喷雾异常可能是由于在喷嘴开口区域有细微沉积物的结果。
令人惊讶的是，发现当喷雾的含水药物制剂中含有一定的有效量的配合剂，特别是EDTA(乙二胺四醋酸)或其盐类，这种喷雾异常就不再发生。根据本发明的含水药物制剂含有水作为溶剂，必要时，可加入乙醇以增加溶解度至70％(体积比)，优选地在30％至60％之间(V/V)。
也可加入其他的药物助剂如防腐剂，尤其是氯苄烷铵。防腐剂的优选加入量，尤其是氯苄烷铵是在8到12毫克/100毫升溶液。
适当的配合剂是那些药学上可接受的，尤其是那些药物上已合法的。EDTA，氮川三醋酸，柠檬酸和抗坏血酸及其盐类特别适合。乙二胺四醋酸的二钠盐特别优选。
选择配合剂的量要以所加入的有效量的配合剂以防止喷雾异常的发生。
配合剂Na-EDTA的有效量为介于10及1000毫克/100毫升溶液之间，特别是介于10至100毫克/100毫升溶液之间。配合剂量的优选范围为25至75毫克/100毫升溶液之间，特别是25至50毫克/100毫升溶液之间。
以下所提出的化合物可在本发明的含水药物制剂中基本上用作活性成分或活性组合物。在个别情况下，可加入较高量的乙醇或溶液调节剂以增加溶解度。
溴化硫托品(Tiotropiumbrimid)，3-[(羟基二-2-噻吩基乙酰基)氧]-8，8-二甲基-8-氮鎓二环[3，2，1]辛-6-烯-溴化物。作为贝他类似物：
间羟舒喘灵酯(bambuterol)双甲苯喘定(Bitolterol)卡布特罗(Carbuterol)福莫特罗(Formoterol)克喘素(Clenbuterol)酚丙喘宁(Fenoterol)异丙喘宁(Hexoprenaline)美喘清(Procaterol)伊比特罗(Ibuterol)吡布特罗(Pirbuterol)塞尔米特罗(Salmeterol)氯丁喘安(Tulobuterol)利浦特罗(Reproterol)沙丁胺醇(Salbutamol)磺丁喘宁(Sulfonterol)特比他林(Terbutaline)
1-(2-氟-4-羟基苯基)-2-[4-(1-苯并咪唑基)-2-甲基-2-丁基氨基]乙醇，
赤-5′-羟基-8′-(1-羟基-2-异丙基氨基丁基)-2H-1，4-苯并噁嗪-3-(4H)-酮，
1-(4-氨基-3-氯-5-三氟甲基苯基)-2-叔丁基-氨基)乙醇，
1-(4-乙氧基羰基氨基)-3-氰基-5-氟苯基)-2-(叔丁氨基)乙醇。作为抗胆碱药：
溴化异丙托品(Ipratropium bromide)
溴乙东莨菪碱(Oxitropium bromide)
氯化托螺吡咯(Trospium chloride)
二苯基羟乙酸-N-β-氟乙烯降托品酯甲溴化物作为类固醇：
布地缩松(Budesonide)
丙酸贝氯米松(Beclometasone)或其17，21-二丙酸盐
地塞米松(Dexamethasone)-21-异烟酸酯
9-去氟肤轻松(Flunisolide)作为抗过敏药：
色甘酸二钠
萘多罗米(Nedocromil)
依匹那丁(Epinastine)可用作本发明的药物制剂中作为活性成分的类固醇实例为：沙拉楚达斯特(Seratrodast)                        霉酚酸莫非替克(Mycophenolate mofetil)普朗鲁克斯特(Pranlukast)                         弃白通(Zileutone)布提索可特(Butixocort)                           布地缩松(Budesonide)去氟可特(Deflazacort)氟地松(Fluticasone)                              普罗米卓(Promedrol)糠酸毛他松(Mometasone furoate)                   提普雷敦(Tipredane)丙酸倍氯米松，道格拉斯(Beclomethasone，Douglas)  伊可美松英比特盐(Icomethasone enbutate)环米他松(Ciclometaseone)                         氯泼尼醇(Cloprednol)丁基氟考酸(Fluocortin butyl)                     氯二氟美松(Halometasone)去氟可特(Deflazacort)                            别氯地米松(Alclometasone)环米他松(Ciclometasone)                             艾利沙克泰德(Alisactide)泼尼卡酯(Prednicarbate)                             氢化可的松丁酸丙酸酯(Hydrocortisone-butyrate)巯氢可的松-戊酸酯(Tixocortol-Pivalate)              二丙酸别氯地米松(Alclometasone-dipropionate)罗翠松(Lotrisone)                                   克霉唑-HC(Canesten-HC)地泼罗酮(Deprodone)                                 丙酸氟地松(Fluticasone-propionate)甲基强的松龙亚西波酯(Methylprednisolone-Aceponate)  哈罗普雷敦-乙酸盐(Halopredone-acetate)毛他松(Mometasone)                                  糠酸毛他松(Mometasone-furoate)氢化可的松亚西波酯(Hydrocortisone-aceponate)        毛他松(Mometasone)屋罗贝塔索-丙酸酯(Ulobetasol-propionate)            氨基导眠能(Aminoglutethimide)三安西诺龙(Triamcinolone)                           氢化可的松(Hydrocortisone)美普尼松(Meprednisone)                              丙酮缩氟氢羟龙(Fluorometholone)地塞米松(Dexamethasone)                             倍他米松(Betamethasone)6α-甲-11β-羟孕酮(Medrysone)                       氟二氯松(Fluclorolone acetonide)肤轻松(Fluocinolone acetonide)                      醋酸对氟米松(Paramethasone-acetate)丙酸21-去羟强的松龙(Deprodone Propionate)           二醋酸去炎松(Aristocort-diacetate)氟轻松(Fluocinonide)                                甲哌地强松(Mazipredone)醋丁二氟龙(Difluprednate)                           戊酸倍他米松(Betamethasone valerate)异烟酸地塞米松(Dexamethasone isonicotinate)         二丙酸倍氯米松(Beclomethasone-Dipropionate)已酸氟考龙(Fluocortolone capronate)                 氟甲酰龙(Formocortal)己酸丙炎松(Triamcinolone-Hexacetonide)              氯泼尼醇(Cloprednol)甲酰烯龙(Formebolone)                               氯氟美松酮(Clobetasone)甲地松(Endrisone)                                   9-去氟肤轻松(Flunisolide)氯氟舒松(Halcinonide)                               氟噁米松(Fluazacort)氯氟美松(Clobetsasol)                               氢化可的松17-丁酸酯(Hydroccrtisone-17-Butyrate)二氟松(Diflorasone)                                 氟考酸(Fluocortin)安西诺耐德(Amcinonide)                              二丙酸倍他米松(Betamethasone Dipropionate)可的伐唑(Corivazol)                                 金刚酸倍他米松(Betamethasone adamantoate)弗罗迪森(Fluodexane)                                腈环氧雄烷(Trilostane)布迪松耐德(Budesonide)                              氯氟美松酮(Clbetasone)迪美德克斯(Demetex)                                 三美西诺龙班纳托耐德(Trimacinolon Benetonide)9-α-氯-6-α-氟-11-β-17-α-二羟基-16-α-甲基-3-氧-1，4-雄二烯-17-β-羧酸-甲基酯-17-丙酸盐。
其他特别适合用于生产吸入施用的含水药物制剂的活性成分为：
β-辛帕提柯类似物(β-Sympatico-mimetics)
例如酚丙喘宁(Fenoterol)，沙丁胺醇(Salbutamol)，福莫特罗(Formoterol)，特布塔林(Terbutalin)；
抗胆碱药；
例如异丙托品(Ipatropium)，乙东莨菪碱(Oxitropium)，硫托品(Thiortopium)；
类固醇；
例如，贝氯米松二丙酸盐(Beclomethasone dipropionate)，布地缩松(Budesonide)，9-去氟肤轻松(Flunisolide)；
肽；
例如，胰岛素；
止痛剂；
例如，芬太尼(Fentanyl)。
明显地，如果需要的话，使用那些溶在本发明溶剂的药物可接受的盐类。
在以下的文章中，将以实例更清楚地解释本发明的药物制剂的优点。
作为药物溶液，使用溴化异丙托品(Ipatropium bromid)溶液(c＝333毫克/100毫升)，pH值为3.4，及防腐剂氯苄烷铵(c＝10毫克/100毫升)。测试溶液-不含EDTA或浓度为c＝0.1毫克，1毫克，50毫克及75毫克/100毫升的EDTA二钠盐。
使用未用过的雷斯皮美特(Respimat)喷雾器来做测试(技术数据：施用的药物制剂的体积约15微升，压力约300巴，从两个大小为5×8微米的喷嘴开口喷出两条水流)。设定测试的操作方式是使设备使用5次，并使其静置3天，然后再使用5次，重复这种形式。在每一个连续的测量中检视15个设备，喷雾异常的结果示于表1。
表1
测试号     EDTA的浓度(毫克/100毫升)   有喷雾异常的喷雾器的数目     测试的时间(以天计)
    1     0毫克/100毫升     2     20
    2     0毫克/100毫升     5     9
    3     0.1毫克/100毫升     5     6
    4     1毫克/100毫升     6     6
    5     50毫克/100毫升     0     200
    6     50毫克/100毫升     0     200
    7     75毫克/100毫升     0     200
    8     75毫克/100毫升     0     200
配方实例(酚丙喘宁及溴化异丙托品)
    成分     组合物(以毫克/100毫升)
    酚丙喘宁     833.3毫克
    氯苄烷铵     10.0毫克
    EDTA*     50.0毫克
    HCl(1N)     至pH3.2
    成分     组合物(毫克/100毫升)
    溴化异丙托品     333.3毫克
    氯苄烷铵     10.0毫克
    EDTA*     50.0毫克
    HCl(1N)     至pH3.4
类似于以上的实施例，制备以下的溶液。
    活性成分 浓度(毫克/100毫升) 氯苄烷铵 EDTA* 溶剂
    非诺特罗(Berotec)     104-1667  10毫克 50毫克   水
    爱喘乐(Atrovent)     83-1333  10毫克 50毫克   水
异丙托溴铵-氢溴酸非诺特罗(Berodual)
  (爱喘乐)(非诺特罗)     41-667104-1667 10毫克 50毫克 水
  沙丁胺醇(Salbutamol)     104-1667  10毫克 50毫克   水
  康比凡特(Combivent)(爱喘乐)(沙丁胺醇) 167-667833-1667 10毫克 50毫克 水
  Ba679Br(溴化硫托品)     4-667  10毫克 50毫克   水
  BEA 2108 Br     17-833  10毫克 50毫克   水
  氧凡特(Oxivent)     416-1667  10毫克 50毫克   水
*以二钠盐的形式
活性成分的浓度范围为10毫克至20,000毫克/100毫升为可接受的，它是按每一次操作的剂量及其溶解度而定。所给定的剂量是基于每一次操作约12微升的治疗上有效的单一剂量来计算。当个别剂量的体积改变时可改变药物制剂的活性成分浓度。
配合剂(例如二钠-EDTA)的浓度范围为10到1000毫克/100毫升之间(依溶液的pH值而定)。优选的范围为25毫克至100毫克/100毫升之间。
氯苄烷铵的量应在8到12毫克/100毫升的范围之间。
溶液以0.1或1N的HCl设定溶液的pH值在3.2至3.4之间。所有的浓度都涉及100毫升制成的活性成分溶液。

Claims (9)

1.含水药物制剂在制备包含药物活性成分或活性成分组合的用于吸入的无推进剂气溶胶中的用途，其特征在于，该药物制剂含有选自EDTA、氮川三乙酸、柠檬酸、抗坏血酸或其盐的配合剂及任选的用量达70％体积的乙醇。
2.权利要求1的用途，其特征在于，所述活性成份或活性成分组合用于治疗肺部疾病的吸入应用。
3.权利要求1或2的用途，其特征在于，所述活性成份选自贝他类似物、抗胆碱药、抗过敏药和/或抗组胺药。
4.权利要求1或2的用途，其特征在于，该活性成分酚丙喘宁、溴化异丙托品、沙丁胺醇、溴化硫托品、3-[(羟基二-2-噻吩基乙酰基)氧]-8，8-二甲基-8-氮鎓二环[3，2，1]辛-6-烯-溴化物、溴乙东莨菪碱、溴化异丙托品-酚丙喘宁、溴化异丙托品-沙丁胺醇。
5.权利要求1或2的用途，其特征在于，该配合剂为EDTA或其盐。
6.权利要求1或2的用途，其特征在于，该配合剂的浓度为25至100毫克/100毫升溶液。
7.权利要求1或2的用途，其特征在于，该药物制剂包含60％体积的乙醇。
8.权利要求1或2的用途，其特征在于，该药物制剂包含30％至60％体积的乙醇。
9.权利要求1或2的用途，其特征在于，该药物制剂中包含浓度为0.001至2克/100毫升溶液的活性成分。
CN97180735A 1996-12-20 1997-12-16 用于制造无推进剂气溶胶的新颖含水药物制剂 Expired - Lifetime CN1097455C (zh)

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Families Citing this family (92)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19615422A1 (de) 1996-04-19 1997-11-20 Boehringer Ingelheim Kg Zweikammer-Kartusche für treibgasfreie Dosieraerosole
DE19733651A1 (de) * 1997-08-04 1999-02-18 Boehringer Ingelheim Pharma Wässrige Aerosolzubereitungen enthaltend biologisch aktive Markomoleküle und Verfahren zur Erzeugung entsprechender Aerosole
DE19808295A1 (de) 1998-02-27 1999-11-11 Boehringer Ingelheim Int Behälter für eine medizinische Flüssigkeit
DE19847968A1 (de) * 1998-10-17 2000-04-20 Boehringer Ingelheim Pharma Verschlußkappe und Behälter als Zweikammer-Kartusche für Vernebler zur Erzeugung von Aerosolen
SE9803770D0 (sv) * 1998-11-05 1998-11-05 Astra Ab Dry powder pharmaceutical formulation
DE19940713A1 (de) 1999-02-23 2001-03-01 Boehringer Ingelheim Int Kartusche für eine Flüssigkeit
DE19921693A1 (de) * 1999-05-12 2000-11-16 Boehringer Ingelheim Pharma Neuartige Arzneimittelkompositionen auf der Basis von anticholinergisch wirksamen Verbindungen und ß-Mimetika
US20100197719A1 (en) * 1999-05-12 2010-08-05 Boehringer Ingelheim Pharma Kg Medicament compositions containing anticholinergically-effective compounds and betamimetics
US20040002548A1 (en) * 1999-05-12 2004-01-01 Boehringer Ingelheim Pharma Kg Medicament compositions containing anticholinergically-effective compounds and betamimetics
DE19954516A1 (de) * 1999-11-12 2001-05-17 Boehringer Ingelheim Int Epinastin-haltige Lösungen
EP1326642A2 (en) * 2000-09-29 2003-07-16 Board of Trustees operating Michigan State University Catecholamine pharmaceutical compositions and methods
US20020137764A1 (en) 2000-10-31 2002-09-26 Karin Drechsel Inhalable formulation of a solution containing a tiotropium salt
UA76435C2 (en) * 2000-10-31 2006-08-15 Boehringer Ingelheim Pharma Inhalation formulation of tiotropium salt
WO2002036104A2 (de) * 2000-10-31 2002-05-10 Boehringer Ingelheim Pharma Gmbh & Co. Kg Inhalative lösungsformulierung mit einem tiotropiumsalz
DE10062712A1 (de) * 2000-12-15 2002-06-20 Boehringer Ingelheim Pharma Neue Arzneimittelkompositionen auf der Basis von Anticholinergika und Corticosteroiden
US20020193392A1 (en) * 2000-11-13 2002-12-19 Christel Schmelzer Pharmaceutical compositions based on tiotropium salts of salts of salmeterol
DE10111843A1 (de) * 2001-03-13 2002-09-19 Boehringer Ingelheim Pharma Verbindungen zur Behandlung von inflammatorischen Erkrankungen
GB2375958B (en) * 2001-04-09 2005-03-02 George Margetts The use of steroids to lower the levels of cortisol
DE10136555A1 (de) 2001-07-27 2003-02-13 Boehringer Ingelheim Int Optimierte Verfahren zur Bestimmung der Aerosol-Partikelgrößenverteilung und Vorrichtung zur Durchführung derartiger Verfahren
DK1446119T3 (da) * 2001-09-18 2006-07-10 Nycomed Danmark Aps Præparater omfattende Ipratropium og xylometazolin til behandling af almindelig forkölelse
AU3297402A (en) * 2001-10-26 2003-10-30 Dey, L.P. An albuterol and ipratropium inhalation solution, system, kit and method for relieving symptoms of chronic obstructive pulmonary disease
MXPA04003928A (es) * 2001-10-26 2005-03-31 Dey L P Solucion para inhalacion de albuterol, sistema, equipo y metodo para aliviar sintomas de asma pediatrica.
JP2010184937A (ja) * 2001-10-26 2010-08-26 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、キット、吸入溶液を中に有する１容器を作成する方法、および、吸入溶液を作成する方法
US7754242B2 (en) * 2002-03-20 2010-07-13 Alkermes, Inc. Inhalable sustained therapeutic formulations
US20040019073A1 (en) * 2002-04-11 2004-01-29 Boehringer Ingelheim Pharma Gmbh Co. Kg Aerosol formulation for inhalation containing a tiotropium salt
DE10216036A1 (de) * 2002-04-11 2003-10-23 Boehringer Ingelheim Pharma Aerosolformulierung für die Inhalation enthaltend ein Tiotropiumsalz
US20050220720A1 (en) * 2002-05-02 2005-10-06 David Edwards Formulations limiting spread of pulmonary infections
JP2005535581A (ja) 2002-05-02 2005-11-24 プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ 肺感染の拡大を制限する処方物
US20040048886A1 (en) * 2002-07-09 2004-03-11 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pharmaceutical compositions based on new anticholinergics and NK1 receptor antagonists
US20040058950A1 (en) * 2002-07-09 2004-03-25 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pharmaceutical compositions based on anticholinergics and PDE-IV inhibitors
AU2003298473B9 (en) * 2002-08-14 2011-06-09 Boehringer Ingelheim Pharma Gmbh & Co. Kg Aerosol formulation for inhalation containing an anticholinergic agent
EP2319584A1 (en) * 2002-08-29 2011-05-11 Cipla Ltd. Pharmaceutical products and compositions comprising salmeterol, ciclesonide and tiotropium
US7056916B2 (en) 2002-11-15 2006-06-06 Boehringer Ingelheim Pharma Gmbh & Co. Kg Medicaments for the treatment of chronic obstructive pulmonary disease
US9808471B2 (en) * 2003-04-16 2017-11-07 Mylan Specialty Lp Nasal pharmaceutical formulations and methods of using the same
GB2400554B (en) * 2003-04-16 2007-04-18 George Margetts Treatment of angiotensin II-induced cardiovascular disease
US8912174B2 (en) * 2003-04-16 2014-12-16 Mylan Pharmaceuticals Inc. Formulations and methods for treating rhinosinusitis
US20040265238A1 (en) * 2003-06-27 2004-12-30 Imtiaz Chaudry Inhalable formulations for treating pulmonary hypertension and methods of using same
US20050107417A1 (en) * 2003-07-28 2005-05-19 Boehringer Ingelheim International Gmbh Medicaments for inhalation comprising a novel anticholinergic and a betamimetic
US20050042176A1 (en) * 2003-07-28 2005-02-24 Boehringer Ingelheim International Gmbh Medicaments for inhalation comprising a novel anticholinergic and a steroid
US20050025718A1 (en) * 2003-07-31 2005-02-03 Boehringer Ingelheim International Gmbh Medicaments for inhalation comprising an anticholinergic and a betamimetic
US20050059643A1 (en) * 2003-08-05 2005-03-17 Boehringer Ingelheim International Gmbh Medicaments for inhalation comprising a steroid and a betamimetic
DE102004001451A1 (de) 2004-01-08 2005-08-11 Boehringer Ingelheim International Gmbh Vorrichtung zum Haltern eines fluidischen Bauteiles
US20050203088A1 (en) * 2004-01-09 2005-09-15 Boehringer Ingelheim International Gmbh Medicament combinations based on scopine- or tropene acid esters with EGFR-kinase inhibitors
US20050207983A1 (en) * 2004-03-05 2005-09-22 Pulmatrix, Inc. Formulations decreasing particle exhalation
US20050272726A1 (en) * 2004-04-22 2005-12-08 Boehringer Ingelheim International Gmbh Novel medicaments for the treatment of respiratory diseases
US20050256115A1 (en) * 2004-05-14 2005-11-17 Boehringer Ingelheim International Gmbh Aerosol formulation for the inhalation of beta-agonists
US20050255050A1 (en) * 2004-05-14 2005-11-17 Boehringer Ingelheim International Gmbh Powder formulations for inhalation, comprising enantiomerically pure beta agonists
US7220742B2 (en) 2004-05-14 2007-05-22 Boehringer Ingelheim International Gmbh Enantiomerically pure beta agonists, process for the manufacture thereof and use thereof as medicaments
PL1756594T3 (pl) 2004-05-25 2010-10-29 Enel Distribuzione Spa Sposób oraz urządzenie do wykrywania fazy przewodu dowolnego nieznanego napięcia fazowego względem napięcia fazowego odniesienia
WO2005123064A1 (en) * 2004-06-10 2005-12-29 Board Of Trustees Of Michigan State University Adrenergic complement inhaler comprising compounds such as ascorbates tocopherols or polycaboxylic acid chelators
US8627821B2 (en) * 2005-01-10 2014-01-14 Pulmatrix, Inc. Method and device for decreasing contamination
NZ564110A (en) * 2005-05-18 2010-06-25 Pulmatrix Inc Formulations for alteration of biophysical properties of mucosal lining
DK1917253T3 (da) * 2005-08-15 2015-03-30 Boehringer Ingelheim Int Fremgangsmåde til fremstilling af betamimetika
EP1948186A1 (en) * 2005-11-09 2008-07-30 Boehringer Ingelheim International Gmbh Aerosolformulation for inhalation
WO2007134965A1 (de) * 2006-05-19 2007-11-29 Boehringer Ingelheim International Gmbh Aerosolformulierung enthaltend ipratropiumbromid und salbutamolsulfat
US20100056559A1 (en) 2006-05-19 2010-03-04 Boehringer Ingelheim International Gmbh Propellant-free aerosol formulation for inhalation
DE102006023756A1 (de) * 2006-05-20 2007-11-29 Boehringer Ingelheim Pharma Gmbh & Co. Kg Ethanolhaltige Aerosolformulierung für die Inhalation
UY30542A1 (es) * 2006-08-18 2008-03-31 Boehringer Ingelheim Int Formulacion de aerosol para la inhalacion de agonistas beta
UY30543A1 (es) * 2006-08-18 2008-03-31 Boehringer Ingelheim Int Formulacion de aerosol para la inhalacion de beta- agonistas
PE20080425A1 (es) * 2006-08-22 2008-06-16 Boehringer Ingelheim Int Formulacion aerosol para la inhalacion de beta-agonistas
EP2205311B1 (en) * 2007-09-13 2016-01-06 Medtronic, Inc. Method of fabricating a medical electrical lead with jacketed conductive elements
FR2924344B1 (fr) * 2007-12-04 2010-04-16 Pf Medicament Utilisation de la mequitazine sous la forme de racemate ou d'enantiomeres pour la preparation d'un medicament destine au traitement ou a la prevention de pathologies impliquant les recepteurs histaminiques h4.
EP2077132A1 (en) 2008-01-02 2009-07-08 Boehringer Ingelheim Pharma GmbH & Co. KG Dispensing device, storage device and method for dispensing a formulation
EP2093219A1 (de) 2008-02-22 2009-08-26 Boehringer Ingelheim International Gmbh Kristalline, enantiomerenreine Salzform eines Betamimetikums und dessen Verwendung als Arzneimittel
JP5670421B2 (ja) 2009-03-31 2015-02-18 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング コンポーネント表面のコーティング方法
EP2432531B1 (de) 2009-05-18 2019-03-06 Boehringer Ingelheim International GmbH Adapter, inhalationseinrichtung und zerstäuber
WO2011064164A1 (en) 2009-11-25 2011-06-03 Boehringer Ingelheim International Gmbh Nebulizer
JP5658268B2 (ja) 2009-11-25 2015-01-21 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング ネブライザ
US10016568B2 (en) 2009-11-25 2018-07-10 Boehringer Ingelheim International Gmbh Nebulizer
WO2011160932A1 (en) 2010-06-24 2011-12-29 Boehringer Ingelheim International Gmbh Nebulizer
AU2011296343B2 (en) 2010-08-30 2015-12-10 Pulmatrix Operating Company, Inc. Dry powder formulations and methods for treating pulmonary diseases
US20130164338A1 (en) 2010-08-30 2013-06-27 Pulmatrix, Inc. Treatment of cystic fibrosis using calcium lactate, leucine and sodium chloride in a respiraple dry powder
ES2710537T3 (es) 2010-09-29 2019-04-25 Pulmatrix Operating Co Inc Polvos secos catiónicos
CN107096014B (zh) 2010-09-29 2022-07-15 普马特里克斯营业公司 吸入用单价金属阳离子干粉剂
EP2694220B1 (de) 2011-04-01 2020-05-06 Boehringer Ingelheim International GmbH Medizinisches gerät mit behälter
DK2704724T3 (en) * 2011-05-03 2017-01-09 Chiesi Farm Spa Improved suspension formulation of beclomethasone dipropionate for administration by inhalation
US9827384B2 (en) 2011-05-23 2017-11-28 Boehringer Ingelheim International Gmbh Nebulizer
CN107596518B (zh) 2012-02-29 2021-04-23 普马特里克斯营业公司 可吸入干粉剂
WO2013152894A1 (de) 2012-04-13 2013-10-17 Boehringer Ingelheim International Gmbh Zerstäuber mit kodiermitteln
RU2479304C1 (ru) * 2012-05-29 2013-04-20 Шолекс Девелопмент Гмбх, Стабильный раствор фенотерола гидробромида
RU2493827C1 (ru) * 2012-10-03 2013-09-27 Шолекс Девелопмент Гмбх Стабильный комбинированный раствор фенотерола гидробромида и ипратропия бромида
AU2014248455B2 (en) 2013-04-01 2018-12-06 Pulmatrix Operating Company, Inc. Tiotropium dry powders
EP3030298B1 (en) 2013-08-09 2017-10-11 Boehringer Ingelheim International GmbH Nebulizer
PL2835146T3 (pl) 2013-08-09 2021-04-06 Boehringer Ingelheim International Gmbh Nebulizator
WO2015065223A1 (ru) * 2013-10-28 2015-05-07 Шолекс Девелопмент Гмбх Стабильный раствор фенотерола гидробромида
WO2015065219A1 (ru) * 2013-10-28 2015-05-07 Шолекс Девелопмент Гмбх Раствор ипратропия бромида
ES2874029T3 (es) 2014-05-07 2021-11-04 Boehringer Ingelheim Int Nebulizador
EA032850B1 (ru) 2014-05-07 2019-07-31 Бёрингер Ингельхайм Интернациональ Гмбх Контейнер, небулайзер и способ изготовления контейнера
LT4242916T (lt) 2014-05-07 2025-12-29 Boehringer Ingelheim International Gmbh Purkštuvas
SG10201912198WA (en) * 2015-05-18 2020-02-27 Glenmark Specialty Sa Tiotropium inhalation solution for nebulization
CN109925300A (zh) * 2017-12-19 2019-06-25 北京盈科瑞创新药物研究有限公司 一种福多司坦雾化吸入用溶液制剂及其制备方法
MX2023001201A (es) 2020-07-31 2023-05-03 Chemo Res S L Terapia combinada para la administracion por inhalacion.

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4919919A (en) * 1987-09-30 1990-04-24 Nippon Kayaku Kabushiki Kaisha Nitroglycerin spray
WO1994013262A1 (en) * 1992-12-09 1994-06-23 Boehringer Ingelheim Pharmaceuticals, Inc. Stabilized medicinal aerosol solution formulations

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX3864E (es) * 1975-05-27 1981-08-26 Syntex Corp Un proceso para prepara el compuesto cristalino 6-fluiro-11b 21-dihiroxi-16 17-isopropilidendioxipregna-1 4-dien-3 20-diona
DE3431727A1 (de) * 1984-08-29 1986-03-13 Robugen GmbH Pharmazeutische Fabrik, 7300 Esslingen Nasenspray gegen schnupfen und grippe mit einem gehalt an zinkglukonat
GB8825892D0 (en) * 1988-11-04 1988-12-07 Fisons Plc Pharmaceutical composition
SG45171A1 (en) * 1990-03-21 1998-01-16 Boehringer Ingelheim Int Atomising devices and methods
EP0754450A1 (en) * 1990-10-16 1997-01-22 Mayor Pharmaceuticals Laboratories,Inc. Vitamin-mineral treatment methods and compositions
TW431888B (en) * 1994-02-03 2001-05-01 Schering Plough Healthcare Nasal spray compositions
EP0726075A1 (en) * 1995-02-08 1996-08-14 Therapicon Srl Pharmaceutical non-inorganic saline solutions for endonasal administration
MX9800125A (es) * 1995-06-27 1998-03-31 Boehringer Ingelheim Kg Nuevas composiciones medicinales estables para generar aerosoles libres de gas propulsor.
DE19536902A1 (de) * 1995-10-04 1997-04-10 Boehringer Ingelheim Int Vorrichtung zur Hochdruckerzeugung in einem Fluid in Miniaturausführung
DE19536916A1 (de) * 1995-10-04 1997-04-10 Boehringer Ingelheim Kg Inhalative Applikation von 2-Amino-6n-propyl-amino-4,5,6,7-tetrahydrobenzothiazol, insbesondere seines (-)-Enantiomeren, sowie deren pharmakologisch verträgliche Säureadditionssalze
DE19620509A1 (de) * 1996-05-22 1997-11-27 Hoechst Ag Verwendung nicht-peptidischer Bradykinin-Antagonisten zur Behandlung und Prävention von chronisch-fibrogenetischen Lebererkrankungen, akuten Lebererkrankungen und den damit verbundenen Komplikationen
EP0808627A2 (de) * 1996-05-22 1997-11-26 Hoechst Aktiengesellschaft Verwendung nicht-peptidischer Bradykinin-Antagonisten zur Behandlung und Prävention von chronisch-fibrogenetischen Lebererkrankungen, akuten Lebererkrankungen und den damit verbundenen Komplikationen
US5976573A (en) * 1996-07-03 1999-11-02 Rorer Pharmaceutical Products Inc. Aqueous-based pharmaceutical composition
DE19644646A1 (de) * 1996-10-26 1998-04-30 Mann & Hummel Filter Filter, insbesondere zur Filtrierung des Schmieröls einer Brennkraftmaschine
US20030215396A1 (en) * 1999-09-15 2003-11-20 Boehringer Ingelheim Pharma Kg Method for the production of propellant gas-free aerosols from aqueous medicament preparations
US20060239930A1 (en) * 1997-08-04 2006-10-26 Herbert Lamche Process for nebulizing aqueous compositions containing highly concentrated insulin
DE19847969A1 (de) * 1998-10-17 2000-04-20 Boehringer Ingelheim Pharma Lagerfähig flüssige Formulierung mit Formoterol
DE19921693A1 (de) * 1999-05-12 2000-11-16 Boehringer Ingelheim Pharma Neuartige Arzneimittelkompositionen auf der Basis von anticholinergisch wirksamen Verbindungen und ß-Mimetika
US20020111363A1 (en) * 2000-10-31 2002-08-15 Karin Drechsel Inhalable formulation of a solution containing a tiotropium salt
US20020137764A1 (en) * 2000-10-31 2002-09-26 Karin Drechsel Inhalable formulation of a solution containing a tiotropium salt
US20020193392A1 (en) * 2000-11-13 2002-12-19 Christel Schmelzer Pharmaceutical compositions based on tiotropium salts of salts of salmeterol
US20040019073A1 (en) * 2002-04-11 2004-01-29 Boehringer Ingelheim Pharma Gmbh Co. Kg Aerosol formulation for inhalation containing a tiotropium salt

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4919919A (en) * 1987-09-30 1990-04-24 Nippon Kayaku Kabushiki Kaisha Nitroglycerin spray
WO1994013262A1 (en) * 1992-12-09 1994-06-23 Boehringer Ingelheim Pharmaceuticals, Inc. Stabilized medicinal aerosol solution formulations

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