CN1186430A - 舒喘宁的计定剂量吸入器 - Google Patents

舒喘宁的计定剂量吸入器 Download PDF

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CN1186430A
CN1186430A CN96194411A CN96194411A CN1186430A CN 1186430 A CN1186430 A CN 1186430A CN 96194411 A CN96194411 A CN 96194411A CN 96194411 A CN96194411 A CN 96194411A CN 1186430 A CN1186430 A CN 1186430A
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salbutamol
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I·C·阿舒尔斯特
C·S·赫尔曼
L·利－博韦
M·T·里伯
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SmithKline Beecham Corp
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Abstract

计定剂量吸入器,该吸入器的内表面由一种或多种氟烃高聚物涂衬,该氟烃高聚物随意与一种或多种非氟烃高聚体组合,用于分散吸入药物制剂,该药物制剂包含舒喘宁或它的生理上可以接受的盐和氟烃抛射剂基质,随意与一种或多种其它药理活性剂和一种或多种赋型剂组合。

Description

舒喘宁的计定剂量吸入器
发明背景
治疗呼吸道和鼻腔疾患的药物常常以气溶胶制剂由口腔或鼻腔给药。配制这类气溶胶药物制剂的一种广泛应用的方法包括制作药物的悬浮制剂，将药物以分散很好的粉末悬浮在称为抛射剂基质的液化气体中。该悬浮剂储存在封口容器里，该封口容器可以耐受保持抛射剂为液态所需的压力。当安装在容器上的剂量计量阀被触发时，悬浮剂即喷出。
设计剂量阀时是使阀每次触发时一致地释放出固定的、预先确定量的药物制剂。由于悬浮剂经过剂量计量阀通过抛射剂的蒸气高压由容器受力，抛射剂迅速蒸发而留下药物制剂的极细小颗粒的快速运动的云状物。通过渠道形成装置，例如通过园筒或开口的锥形该颗粒云状物射向病人的鼻或口。与气溶胶剂量计量阀触发的同时，病人将药物颗粒吸入肺或鼻腔。按这种方式喷雾药物的系统称为“计定剂量吸入器”(MDI′s)。Peter Byron、Respiratory Drug Delivery，CRCPress，Boca Raton，FL(1990)描述了这种形式治疗的一般背景。
病人常常依赖于MDI′s释放的药物迅速治疗可使人体虚弱，在有些情况下甚至可以危及生命的呼吸道疾病。所以释放给病人的气溶胶药物制剂剂量必须始终满足制药公司声明的规格要求以及必须遵守FDA和别的管理机构的规定。也就是说，罐中的每次剂量在接近的公差范围内必须相同。
一些气溶胶药物趋向于粘附在内表面上，即粘附在MDI的罐、阀和帽壁上。这可导致每次触发MDI时病人获得的药量明显少于处方规定的药量。这个问题对于氢氟烷(亦简称“氟烃”)抛射剂基质系统，例如P134a和P227尤其尖锐，该系统是近年开发用于取代氯氟烃例如P11、P114和P12的。
我们发现用氟烃高聚物涂衬MDI′s罐的内部表面，显著减少或基本消除舒喘宁(albuterol)的粘附或沉淀在容器壁上的问题从而保证气溶胶中的药物从MDI始终如一地释放。
本发明的概述
内表面部分或全部用一种或多种氟烃高聚物作衬的计定剂量吸入器，该高聚物随意与一种或多种非氟烃高聚物组合，该计量剂量吸入器用于喷雾吸入药物制剂，该制剂含舒喘宁或它的生理上可以接受的盐及氟烃抛射剂基质，并随意地与一种或多种其它药理活性物质或一种或多种赋型剂联用。
本发明的详述
术语“计量剂量吸入器”或“MDI”是指一种由一个罐、盖隹罐口的缩边帽和安装在帽上的药物计量阀组成的装置，而术语“MDI系统”还包括适当渠道形成装置。术语“MDI罐”指无帽和无阀的罐。术语“药物计量阀“或”MDI阀”指MDI阀每次触发时从中释放预先决定量药物制剂的阀及它的有关机械。渠道形成装置可以包括例如阀驱动器和园筒或锥样通道，药物可经过该装置从填充的MDI罐经MDI阀释放到病人的鼻或口中，例如唇状驱动器。美国专利5,261,538中描述了典型的MDI部件的关联，该专利这里列为参考文献。
术语“氟烃高聚物”指烃链中一个或多个氢原子被氟原子取代的高聚物。这样，“氟烃高聚物”包括全氟烃-、氢氟烃-、氯氟烃-、氢氯氟烃高聚物或它们的其它卤素取代的衍生物。这类“氟烃高聚物”可以是支链的、均聚物或共聚物。
美国专利No.3,644,363发明了一组支气管扩张化合物，这些化合物可用于治疗气喘和其它呼吸道疾病，该专利这里作为参考文献。该专利中优选的化合物为α1-叔丁氨甲基-4-羟基-间-二甲苯基-α1、α3-二醇，在美国的普通名为albuterol“舒喘宁”，在其它大多数国家叫salbutamol“羟甲叔丁肾上腺素”。舒喘宁以游离碱和酸的加合盐(特别是作为硫酸盐)特别是以气溶胶的形式，已经被医药社会广泛接受用于治疗气喘并以”Ventolin”和“Proventil”的商标上市。
术语“药物制剂”指舒喘宁或它的生理上可以接受的盐(特别是硫酸盐)随意与一种或多种其它药理活性剂例如抗炎剂，镇痛剂或其它呼吸道药物联合，并随意含一种或多种赋形剂。这里使用的术语“赋型剂”指有小的药理活性或根本没有药理活性(对用量而言)但可加强药物制剂或完善MDI系统的效能。例如，赋型剂包括表面活性剂，防腐剂、芳香剂、抗氧化剂、抗凝聚剂和助溶剂，例如乙醇和乙醚，但不限于这些。舒喘宁或它的盐可以使用R异构体。
适宜的表面活性剂为文献已知，例如欧洲专利申请No，0327777中发明的那些表面活性剂。表面活性剂的理想用量范围为相对于药物重量的0.0001％至50％，特别为0.05％至5％。特别有用的表面活性剂为1，2-二〔7-(F-己基)己酰基〕-甘油基-3-磷-N，N，N-三甲基乙醇胺，亦称为3，5，9-三氧杂-4-磷杂二十二碳-1-铵，17，17，18，18，19，19，20，20，21，21，22，22，22-十三氟-7-〔(8，8，9，9，10，10，11，11，12，12，13，13，13-十三氟-1-氧代十三烷基)氧基〕-4-羟基-N，N，N-三甲基-10-氧代-，内盐，4-氧化物。
该药物制剂中能够包括的极性助溶剂有C2-6的脂肪醇和多元醇，例如乙醇、异丙醇和丙二醇，乙醇为优选，这类助溶剂按期待的量使用，或作为唯一的赋型剂使用，或再加上其它赋型剂，例如加上表面活性剂。适当地，该药物制剂可以含极性助溶剂例如含乙醇的量可占抛射剂基质重量的0.01％至5％，优选含0.1％至5％，例如含大约0.1％至1％。
技术人员应当认识到，希望的话本发明中使用的药物制剂可以含舒喘宁或它的盐(例如硫酸盐)与一种或多种其它药理活性剂的组合。这类药物可以选自吸入治疗中适宜的任何药物。例如合适的药物可选自镇痛药，例如可待因，二氢吗啡，麦角胺、芬太尼或吗啡；咽类制品，例如diltiazem；抗过敏药，例如色甘酸酯、Ketotifen或nedocromil；抗感染药，例如头孢菌素、青霉素、链霉素、磺胺、四环素和戊烷脒；抗组胺药，例如麦沙非林；抗炎药，例如氯地米松(例如它的二丙酸盐、flunisolide、budesonide、tipredane或去炎松；镇咳药，例如诺斯卡品；支气管扩张剂，例如舒喘灵、Salmeterol、麻黄素、肾上腺素、芬成醇、formoterol、异丙肾上腺素、二羟苯基异丙氨基乙醇、脱羟肾上腺素、去甲麻黄碱、pirbuterol、reproterol、羟哌甲苯二酚、间羟叔丁肾上腺素、新异丙肾上腺素、tulobuterol、间羟异丙肾上腺素、或(-)-4-氨基-3，5-二氯-α-〔〔〔6-〔2-(2-吡啶基)乙氧基〕己基〕氨基〕甲基〕苯甲醇；利尿药，例如氨氯吡啶脒；抗胆碱能药，例如ipratropiun、阿托品或oxitropium；激素，例如可的松、氢化可的松或盘的松龙；黄嘌呤，例如氨荼碱、胆碱荼碱、赖氨酸荼碱、或荼碱；以及治疗用的蛋白和多肽，例如胰岛素或胰高血糖素。技术人员应当明确，适当时这些药物可以以盐的形式使用(例如以碱金属盐、铵盐或酸加合盐的形式使用)，或以酯的形式使用(例如以低级烷基酯的形式使用)，或以溶剂化物的形式使用(例如以水合物的形式使用)，以便优化药物的活性和/或稳定性和/或降低药物在抛射剂基质中的溶解度。
特别优选的药物制剂含舒喘宁或它的生理上可以接受的盐与一种抗炎甾体，例如与丙酸fluticasone或二丙酸氯地米松或它们的生理上可以接受的溶剂化物组合。
特别优选的药物组合是硫酸舒喘宁和二丙酸氯地米松。
这里使用的“抛射剂基质”是指沸点为大约室温(25℃)至大约25℃的生理惰性液体，室温下该惰性液体单独或以组合的方式产生高蒸气压。MDI系统触发时，MDI中的抛射剂基质的高蒸气压先通过计量阀往外推动计量的药物制剂，然后抛射剂基质迅速蒸发分散药物颗粒。本发明中使用的抛射剂基质为低沸点氟烃；特别是1，1，1，2-四氟乙烷，亦称为“抛射剂基质134a”或“P134a”和1，1，1，2，3，3，3-七氟丙烷，亦称为“抛射剂基质227”或“P227”。不过，本发明中优选使用的MDI罐由铝或它的合金制作。
本发明中使用的药物制剂可以不含或基本不含制剂赋型剂，例如不含表面活性剂和助溶剂等。这类药物制剂由于本质上是无味和无臭的，比起含赋型剂的制剂来刺激性和毒性都小，所以是有利的制剂。这样，-种优选的药物制剂主要由舒喘宁或它的生理上可以接受的盐组成，随意与一种或多种其它药理活性剂特别是与Salmeterol(例如以xinafoate盐的形式)以及氟烃抛射剂基质组合。优选的抛射剂基质为1，1，1，2-四氟乙烷、1，1，1，2，3，3，3-七氟正丙烷或它们的混合物，1，1，1，2-四氟乙烷特别优选。
本发明中使用的进一步的药物制剂可以不含或基本不含表面活性剂。这样，进一步优选的药物制剂，包括或主要由舒喘宁(或它的生理上可以接受的盐)组成，随意与一种或多种其它药理活性剂、一种氟烃抛射剂基质，以及占抛射剂基质重量0.01％至5％的极性助溶剂组合，该制剂本质上不含表面活性剂。优选的抛射剂基质为1，1，1，2-四氟乙烷、1，1，1，2，3，3，3-七氟正丙烷或它们的混合物，特别优选为1，1，1，2-四氟乙烷、或1，1，1，2，3，3，3-七氟正丙烷。
虽然其它不受药物制剂影响的金属，例如不锈钢、铜的合金或锡板都可以使用，但MDI罐和盖最常用铝或铝合金制作。MDI罐亦可用玻璃或塑料制作。本发明中MDI罐优选用铝或它的合金制造。有利地可以使用强化铝或铝合金MDI罐。这类强化的MDI罐能够耐受特别高压的加衬和加工处理条件，例如耐受特别的高温，这类条件对一些氟烃高聚物可能是必须的。高温下具有降低变形趋势的加强的MDI罐包括由侧壁和增厚底组成的MDI罐和由本质椭园形底(该形状底增大了侧壁和罐底的角度)构成的MDI罐，而不是标准MDI罐的半球底，具有椭园底的MDI罐为进行加衬工艺提供了进一步的好处。
本发明中使用的氟烃高聚物体包括由一个或多个下述单体单元的多重复合构成的氟烃：四氟乙烯(PTFE)、氟化的乙烯丙烯(FEP)。全氟烷氧基烷(PFA)、乙烯四氟乙烯(ETFE)、乙烯二烯氟化物(PVDF)，和氯化的乙烯四氟乙烯。具有相对高氟/碳比的氟化高聚物例如全氟烷高聚物PTFE、PFA和FEP为优选。
氟化高聚物可以与非氟高聚物掺合，例如与聚酰胺、聚酰亚胺、聚醚砜、对聚苯硫和胺醛热固树脂掺合。加这些高聚物可改善高聚物衬与罐壁的粘着性能。优选的高聚掺合物为PTFE/FEP/聚酰胺酰亚胺、PTFE/聚醚砜(PES)和FEP-苯并胍胺。优选地，本发明使用的氟烷高聚物涂衬到金属制作的MDI罐上。特别是涂衬到由铝或铝合金制作的MDI罐上。
特别优选的衬(涂层)为纯PFA和PTFE和聚醚砜(PES)的掺合物。
市场销售的氟烷高聚物的商标为聚四氟乙烯、Tefzel、Halar和Hostaflon、Polyflon和Neoflon。高聚物的级别包括FEP杜邦856-200、PFA杜邦857-200、PTFE-PES杜邦3200-100、PTFE-FEP-聚酰胺酰亚胺杜邦856P23485、FEP粉杜邦532和PFA Hoechst6900n。衬厚度的范围为大约1μm至大约1mm。适宜的衬厚度范围为大约1μm至大约100μm，例如1μm至25μm。可以使用一层或多层衬。
特殊的(例如粉碎的)药物的粒度应为在施用气溶胶制剂时允许将基本上所有的药物吸入肺部，因此应小于100微米，理想情况下小于20微米，特别是在1至10微米范围内，例如在1至5微米范围内。
理想情况下气溶胶制剂的药物与制剂总重量的相对比例为0.005％至10％，尤其为0.005％至5％，特别为0.01％至1.0％。
本发明的进一步的方面是计定剂量的吸入器，该吸入器金属内表面部分或全部用一种或多种氟烷高聚体涂衬，随意与一种或多种非氟烷高聚体合用，用于分散由舒喘宁或它的盐类和氟烷抛射剂基质，并随意与一种或多种其它药理活性剂以及一种或多种赋形剂组合的药物制剂。
本发明的特别方面是全部内部金属表面基本都由PFA或FEP，或掺合的氟高聚体树脂系统例如PTFE-PES加衬的MDI，该MDI可有或可无聚酰胺酰亚胺或聚醚砜底衬，用于分散上面定义的药物制剂。
本MDI中使用的优选药物制剂主要由舒喘宁(或它的生理上可以接受的盐，例如硫酸盐)组成，随意与一种或多种其他药理活性剂、特别是与二丙酸氯地米松(或它的溶剂化物)，和氟烷抛射剂基质，尤其是1，1，1，2-四氟乙烷、1，1，1，2，3，3，3-七氟丙烷或它们的混合物，和特别是1，1，1，2-四氟乙烷组合。优选的MDI罐由铝或其合成制成。
本MDI可采用文献已知的金属涂衬方法加衬。例如铝或不锈钢一类的金属在冲压和成形为罐状之前可作为卷盘预涂衬并处理。由于两个原因，该方法很适合高容量生产。首先，卷盘涂衬技术很发达，几家制造商可以常规地涂金属卷盘达到高标准的均匀性和广泛的厚度。第二，预涂的卷盘可以高速和高精度冲压和拉伸，使用的方法与未加衬的卷盘基本相同。
得到涂衬罐的其他技术是静电干粉涂衬或先往制好的MDI罐里侧喷氟化高聚物/高聚物掺合物涂层的制剂，然后再处理。制好的MDI罐亦可浸到氟烷高聚物/高聚物掺合物涂层制剂中并处理，这样在内侧和外侧均形成涂层。该氟烷高聚物/高聚物掺合物制剂亦可倾到MDI罐内，然后排出来，使内侧留下高聚物衬。为容易制作，适宜地将制好的MDI罐用氟烷高聚物/高聚物掺合物喷涂加衬。
氟烷高聚物/高聚物掺合物亦可采用氟烷单体等离子聚合在罐壁就地生成。氟烷高聚膜可吹入MDI罐内侧以便形成袋。各种氟烷高聚物例如ETFE、FEP和PTFE都可用作膜料。
适宜的处理温度取决于选择作衬的氟烷高聚物/高聚物掺合物和使用的涂衬方法。不过，对于卷盘和喷涂加衬来说，典型地需要温度高于高聚物熔点，例如比熔点高大约50℃至多20分钟，例如大约5至10分钟，例如8分钟或所需要的时间。对于上面提到的优选或特别优选的氟烷高聚物/高聚物掺合物，处理温度的范围为大约300℃至大约400℃，例如大约350℃至大约380℃为宜。对于等离子聚合可以使用的典型的温度范围为大约20℃至大约100℃。
这里发明的MDI可按文献方法制造(例如见于上面的Byron和美国专利5,345,980)，其中用常规罐代替用氟化高聚物/高聚物掺合物作衬的罐。也就是说舒喘宁或它的盐和制剂的其它组分充入用氟化高聚物/高聚物掺合物涂衬的气溶胶罐中。该罐连有在适当的地方打褶的帽装置。药物在液压氟烷抛射剂基质中的悬浮液可以按美国专利5,345,980(本文引作参考文献)中所示通过计量阀引起罐内。
这里发明的内部用氟烷高聚物/高聚物掺合物涂衬的MDI可采用与目前临床用的无衬MDI类似的方式用于医疗。不过本发明的MDI对于含有和喷施含有氢氟烷氟烷抛射剂基质例如134a和少含或基本不含赋形剂、以及倾向于沉淀或粘着到MDI系统的内壁和部件的药物制剂特别有用。有些情况下调配基本不含赋形剂的吸入药物是有利的，例如当病人对赋型剂过敏或药物与赋形剂反应时就是如此。
含上面描述的制剂的MDI、MDI系统和用这类MDI系统治疗呼吸道疾病，例如治疗哮喘包括本发明的进一步的方面。
对于本领域技术人员来说，修饰这里描述的发明可以在不偏离本发明的精神下容易做到是明确的。寻求的对这里描述的一切题材保护中也包括任何这类修饰。
下面的非限制性实施例解释本发明。
实施例
实施例1
标准的12.5ml MDI罐(Presspart Inc，Cary，NC)先喷涂衬以(Livingstone Coatings，Charlotte，NC)底漆(杜邦851-204)和按照卖主的标准方法处理，然后再喷涂衬以FEP或PFA(分别为杜邦856-200和857-200)，并按照卖主的标准方法处理。涂层的厚度为大约10μm至50μm。这些罐然后清除空气(见于PCT申请号WO94/22722PCT/EP94/00921)，阀门弯边定位，通过阀门往里充大约29mg硫酸舒喘宁和大约18.2g P134a的悬浮液。
实施例2
标准的0.46mm厚的铝片(United Aluminum)喷涂衬以(杜邦，Wilmington，DE)FEP(杜邦856-200)并处理。涂层的厚度为大约10μm至50μm。该片然后深拉成罐(Presspart Inc，Cary，NC)。这些罐然后清除空气，阀门弯边定位，通过阀门往里充大约12mg硫酸舒喘宁与大约7.5g P134A的悬浮液。
实施例3
标准的12.5ml MDI罐(Presspart Inc，Cary，NC)啧涂衬以PTFE-PES掺合物(杜邦)为单一衬，并按卖主的标准方法处理。涂层的厚度为大约1μm至大约20μm之间。这些罐然后清除空气，阀门弯边定位，通过阀门往里充大约31.8mg或大约15.4mg微粉化的硫酸舒喘宁分别与大约19.8g或大约9.6gP134a的悬浮液。
实施例4
标准的12.5ml MDI罐(Presspart Inc，Cary，NC)啧涂衬以PTFE-FEP-聚酰胺酰亚胺掺合物(杜邦)并按卖主的标准方法处理。涂层的厚度在大约1μm至大约20μm之间。这些罐然后清除空气，阀门弯边定位，通过阀门往里充大约31.8mg或大约15.4mg微粉化的硫酸舒喘宁分别与大约19.8g或大约9.6gP134a的悬浮液。
实施例5
标准的12.5ml MDI罐(Presspart Inc，Cary，NC)用静电枪喷涂衬以FEP粉(杜邦FEP532)。涂层的厚度在大约1μm至大约20μm之间。这些罐然后清除空气，阀门弯边定位，通过阀门往里充大约31.8mg或15.4mg微粉化的硫酸舒喘宁分别与大约19.8g或大约9.6gP134a的悬浮液。
实施例6
标准的0.46mm厚的铝片(United Aluminum)喷涂衬以FEP-苯并胍胺并处理。该铝片然后深拉成罐。这些罐然后清除空气，阀门弯边定位，通过阀门往里充大约31.8mg或大约15.4mg微粉化的硫酸舒喘宁分别与大约19.8g或大约9.6gP134a的悬浮液。
实施例7
标准的12.5ml MDI罐(Presspart Inc，Cary，NC)喷涂衬以PFA的水性分散液(Hoechst PFA-6900n)并处理。涂层的厚度为大约1μm至大约20μm之间。这些罐然后清除空气，阀门弯边定位，通过阀门往里充大约31.8mg或大约15.4mg粉碎的硫酸舒喘宁分别与大约19.8g或大约9.6gP134a的悬浮液。
实施例8
标准的12.5ml MDI罐(Presspart Inc，Cary，NC)喷涂衬以PTFE-PES掺合物(杜邦)为单一衬，并按卖主的标准方法处理。涂层的厚度在大约1μm至大约20μm之间。这些罐然后清除空气，阀门弯边定位，通过阀门往里充28.9mg微粉化的硫酸舒喘宁与大约18gP134a的悬浮液。
实施例9
标准的12.5ml MDI罐(Presspart Inc，Cary，NC)喷涂衬以PTFE-FEP-聚酰胺酰亚胺掺合物(杜邦)并按卖主的标准方法处理。涂层的厚度为大约1μm至大约20μm之间。这些罐然后清除空气，阀门弯边定位，通过阀门往里充28.9mg微粉化的硫酸舒喘宁与大约18gP134a的悬浮液。
实施例10
标准的12.5ml MDI罐(Presspart Inc，Cary，NC)用静电枪喷涂衬以FEP粉(杜邦FEP532)。涂层的厚度为大约1μm至大约20μm之间。这些罐然后清除空气，阀门弯边定位，通过阀门往里充28.9mg微粉化的硫酸舒喘宁与大约18gP134a的悬浮液。
实施例11
标准的0.46mm厚的铝片(United Aluminum)喷涂衬以FEP-苯并胍胺并处理。该铝片然后深拉成罐。这些罐然后清除空气，阀门弯边定位，通过阀门往里充大约28.9mg微粉化的硫酸舒喘宁与大约18gP134a的悬浮液。
实施例12
标准的12.5ml MDI罐(Presspart Inc，Cary，NC)喷涂衬以PFA的水性分散液(Hoechst PFA-6900n)并处理。涂层的厚度为大约1μm至大约20μm之间。这些罐然后清除空气，阀门弯边定位，通过阀门往里充28.9mg微粉化的硫酸舒喘宁与大约18g P134a的悬浮液。
实施例13至17
重复实施例3至7，不同的是通过阀门往里通大约29mg硫酸舒喘宁与大约21.4gP227的悬浮液。
实施例18至22
重复实施例3至7，不同的是通过阀门往里通大约24mg或15mg微粉化的硫酸舒喘宁分别与大约364mg或182mg乙醇及18.2gP134a的悬浮液。
实施例23至42
重复实施例3至22，不同的是使用修饰的基本为椭园形底的12.5mlMDI罐(Presspart Inc，Cary，NC)。
在模拟使用的条件下测定发现从MDIS释放的药物剂量是恒定的，而对照的充入未涂衬的罐中的MDIs在应用中显示明显的剂量释放降低。

Claims (22)

1.一种计定剂量的吸入器，该吸入器的部分或全部内表面涂有一种或多种氟烃高聚体，该氟烃高聚体随意与一种或多种非氟烃高聚体组合，用于喷施含舒喘宁(albuterol)或它的生理上可以接受的盐及一种氟烃抛射剂基质、并随意与一种或多种其它药理活性剂或一种或多种赋型剂组合的吸入药物制剂。
2.含所述药物制剂的权利要求1的吸入器。
3.权利要求2的吸入器，其中所说的药物制剂进一步包括一种表面活性剂。
4.权利要求2或3的吸入器，其中所说的药物制剂进一步包括一种极性助溶剂。
5.权利要求2的吸入器，其中所说的药物制剂包括占抛射剂基质重量的0.01％至5％的极性助溶剂，该制剂本质上不含表面活性剂。
6.权利要求2至5中任一的吸入器，其中所述的药物制剂含的舒喘宁或它的生理上可以接受的盐与一种甾体抗炎药或抗过敏药组合。
7.权利要求6的吸入器，其中所述的药物制剂含的舒喘宁或它的生理上可以接受的盐与二丙酸氯地米松或它的生理上可以接受的溶剂化物组合。
8.权利要求2的吸入器，其中所述的药物制剂主要包含舒喘宁或它的生理上可以接受的盐，随意与一种或多种其它药理活性剂及氟烷抛射剂基质组合。
9.权利要求8的吸入器，其中所说的药物制剂主要由舒喘宁或它的生理上可以接受的盐与一种甾体抗炎药或一种抗过敏药组合成。
10.权利要求9的吸入器，其中所说的药物制剂主要由舒喘宁或它的生理上可以接受的盐与二丙酸氯地米松或它的生理上可以接受的溶剂化物组合成。
11.权利要求2的吸入器，其中所说的药物制剂由舒喘宁或它的生理上可以接受的盐和氟烷抛射剂基质组成。
12.权利要求2至11中之任一的吸入器，其中所说的舒喘宁为它的硫酸盐形式。
13.权利要求2至12中之任一的吸入器，其中氟烃抛射剂基质为1，1，1，2-四氟乙烷或1，1，1，2，3，3，3-七氟正丙烷或它们的混合物。
14.权利要求13的吸入器，其中氟烃抛射剂基质为1，1，1，2-四氟乙烷。
15.权利要求1至14中之任一的吸入器，该吸入器包含一个由金属制作的罐，该罐的内部金属表面一部分或全部涂衬。
16.权利要求15的吸入器，其中的金属为铝或它的合金。
17.权利要求1至16中之任一的吸入器，其中所说的氟烃高聚体为全氟烃高聚体。
18.权利要求17的吸入器，其中所说的氟烃高聚体选自PTFE、PFA、FEP和它们的混合物。
19.权利要求1至18中之任一的吸入器，其中所说的氟烃高聚体与选自聚酰胺酰亚胺和聚醚砜的非氟烃高聚体组合。
20.权利要求1至19中之任一的吸入器，该吸入器含基本为椭园的底。
21.包含权利要求1至20中之任一的计定剂量吸入器的计定剂量吸入器系统，该系统装有用于经口或鼻吸入药物制剂的适合的管道装置。
22.权利要求21的计定剂量吸入系统在治疗呼吸道疾病中的应用。
CN961944110A 1995-04-14 1996-04-10 舒喘宁的计定剂量吸入器 Expired - Lifetime CN1217654C (zh)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110840864A (zh) * 2019-12-20 2020-02-28 广州健康元呼吸药物工程技术有限公司 一种β2受体激动剂吸入气雾剂及包含该吸入气雾剂的产品

Families Citing this family (174)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EE04004B1 (et) * 1995-04-14 2003-04-15 Glaxo Wellcome Inc. Flutikasoonpropionaati doseeriv inhalaator
BR9604977A (pt) * 1995-04-14 1998-06-09 Glaxo Wellcome Inc Inalador de dose medida sistema inalador de dose medida e uso do mesmo
CA2361954C (en) * 1995-04-14 2003-07-08 Smithkline Beecham Corporation Metered dose inhaler for albuterol
KR19980703850A (ko) * 1995-04-14 1998-12-05 그레이엄브레레톤 베클로메타손 디프로피오네이트용 계량 흡입기
GB9526392D0 (en) 1995-12-22 1996-02-21 Glaxo Group Ltd Medicaments
US6120752A (en) * 1997-05-21 2000-09-19 3M Innovative Properties Company Medicinal aerosol products containing formulations of ciclesonide and related steroids
TW533865U (en) * 1997-06-10 2003-05-21 Glaxo Group Ltd Dispenser for dispensing medicament and actuation indicating device
US20010031244A1 (en) * 1997-06-13 2001-10-18 Chiesi Farmaceutici S.P.A. Pharmaceutical aerosol composition
GB2338951B (en) * 1997-09-03 2000-06-21 Bespak Plc Improvements in or relating to metering valves for pressuriseddispensing containers
US20030103906A1 (en) * 1997-10-14 2003-06-05 Smithkline Beecham Corporation Metered dose inhaler having internal surfaces coated with fluorocarbon polymer
US6086376A (en) * 1998-01-30 2000-07-11 Rtp Pharma Inc. Dry aerosol suspension of phospholipid-stabilized drug microparticles in a hydrofluoroalkane propellant
GB9814717D0 (en) * 1998-02-23 1998-09-02 Bespak Plc Improvements in drug delivery devices
EA002639B1 (ru) † 1998-02-23 2002-08-29 Глаксо Груп Лимитед Усовершенствования в устройствах для дозирования лекарств
GB9805938D0 (en) * 1998-03-19 1998-05-13 Glaxo Group Ltd Valve for aerosol container
EP1102579B1 (de) * 1998-08-04 2003-03-19 Jago Research Ag Medizinische aerosolformulierungen
GB2340759B (en) * 1998-08-26 2003-05-07 Bespak Plc Improvements in drug delivery devices
GB9820937D0 (en) * 1998-09-26 1998-11-18 Glaxo Group Ltd Inhalation device
IT1303788B1 (it) * 1998-11-25 2001-02-23 Chiesi Farma Spa Formulazioni di aerosol medicinali.
DZ2947A1 (fr) * 1998-11-25 2004-03-15 Chiesi Farma Spa Inhalateur à compteur de dose sous pression.
US6352152B1 (en) 1998-12-18 2002-03-05 Smithkline Beecham Corporation Method and package for storing a pressurized container containing a drug
US6390291B1 (en) 1998-12-18 2002-05-21 Smithkline Beecham Corporation Method and package for storing a pressurized container containing a drug
US6315112B1 (en) 1998-12-18 2001-11-13 Smithkline Beecham Corporation Method and package for storing a pressurized container containing a drug
US6315985B1 (en) * 1999-06-18 2001-11-13 3M Innovative Properties Company C-17/21 OH 20-ketosteroid solution aerosol products with enhanced chemical stability
IT1313553B1 (it) 1999-07-23 2002-09-09 Chiesi Farma Spa Formulazioni ottimizzate costituite da soluzioni di steroidi dasomministrare per inalazione.
GB9918573D0 (en) * 1999-08-07 1999-10-06 Glaxo Group Ltd Valve
CO5270018A1 (es) * 1999-12-11 2003-04-30 Glaxo Group Ltd Distribuidor de medicamento
EP1235606A1 (en) * 1999-12-11 2002-09-04 Glaxo Group Limited Medicament dispenser
IT1317720B1 (it) * 2000-01-07 2003-07-15 Chiesi Farma Spa Dispositivo per la somministrazione di aerosol dosati pressurizzati inpropellenti idrofluoroalcani.
IT1317846B1 (it) 2000-02-22 2003-07-15 Chiesi Farma Spa Formulazioni contenenti un farmaco anticolinergico per il trattamentodella broncopneumopatia cronica ostruttiva.
DE60133723T2 (de) 2000-02-28 2009-07-02 PharmaKodex Ltd., Chippenham Verabreichungssystemen für oral anzuwendende arzneimittel
EP1263491A2 (en) * 2000-03-01 2002-12-11 Glaxo Group Limited Metered dose inhaler
IT1318514B1 (it) * 2000-05-12 2003-08-27 Chiesi Farma Spa Formulazioni contenenti un farmaco glucocorticosteroide per iltrattamento di patologie broncopolmonari.
HU230804B1 (hu) 2000-05-22 2018-06-28 Chiesi Farmaceutici S.P.A Gyógyászati célú stabil aeroszol összetétel, inhalátor az aeroszol pontos adagolásához és eljárás ennek feltöltésére
GB0015043D0 (en) 2000-06-21 2000-08-09 Glaxo Group Ltd Medicament dispenser
AU2001270074A1 (en) 2000-06-22 2002-01-02 Glaxo Group Limited Method and package for storing a pressurized container containing a drug
GB0021024D0 (en) * 2000-08-29 2000-10-11 Glaxo Group Ltd Inhalation device
EP1318952A2 (en) 2000-09-18 2003-06-18 Glaxo Group Limited Coated can for a metered dose inhaler
GB2367756B (en) 2000-10-12 2003-01-08 Bespak Plc Dispensing apparatus
US7247704B2 (en) * 2000-12-18 2007-07-24 Arriva Pharmaceuticals, Inc. Multifunctional protease inhibitors and their use in treatment of disease
MXPA03005697A (es) * 2000-12-22 2003-10-06 Glaxo Group Ltd Inhalador de dosis medida para xinafoato de salmeterol.
GB0106046D0 (en) * 2001-03-12 2001-05-02 Glaxo Group Ltd Canister
EP1241113A1 (en) 2001-03-12 2002-09-18 CHIESI FARMACEUTICI S.p.A. Inhaler with means for improving chemical stability of medicinal aerosol solution contained therein
US6455028B1 (en) 2001-04-23 2002-09-24 Pharmascience Ipratropium formulation for pulmonary inhalation
GB2375098B (en) 2001-04-30 2003-08-27 Bespak Plc Improvements in valves for pressurised dispensing containers
US7645442B2 (en) 2001-05-24 2010-01-12 Alexza Pharmaceuticals, Inc. Rapid-heating drug delivery article and method of use
US7458374B2 (en) 2002-05-13 2008-12-02 Alexza Pharmaceuticals, Inc. Method and apparatus for vaporizing a compound
US20030051728A1 (en) 2001-06-05 2003-03-20 Lloyd Peter M. Method and device for delivering a physiologically active compound
US20070122353A1 (en) 2001-05-24 2007-05-31 Hale Ron L Drug condensation aerosols and kits
ATE267591T1 (de) 2001-07-02 2004-06-15 Chiesi Farma Spa Optimierte tobramycin-formulierung zur aerosolbildung
GB2377694A (en) * 2001-07-17 2003-01-22 Bespak Plc Dispensing apparatus
US7767872B2 (en) * 2001-09-06 2010-08-03 Mpg Biotechnologies, Llc Thimerosal removal device
US8440791B2 (en) * 2001-09-06 2013-05-14 Mgp Biotechnologies, Llc Thimerosal removal device
GB0122725D0 (en) * 2001-09-21 2001-11-14 Glaxo Group Ltd Drug dispensing components
GB0130703D0 (en) * 2001-12-21 2002-02-06 Glaxo Group Ltd Particles
GB2384190A (en) * 2002-01-22 2003-07-23 Bespak Plc Dispensing device for a powdered product
PL372106A1 (en) 2002-02-13 2005-07-11 Glaxo Group Limited Carboxylic acid compounds for use as surfactants
JP2005523905A (ja) * 2002-03-01 2005-08-11 キエシ・フアルマチエウテイチ・ソチエタ・ペル・アチオニ ホルモテロール（ｆｏｒｍｏｔｅｒｏｌ）超微細調合物
GB0205327D0 (en) 2002-03-06 2002-04-17 Glaxo Group Ltd compounds
GB0207906D0 (en) * 2002-04-05 2002-05-15 3M Innovative Properties Co Formoterol and mometasone aerosol formulations
GB0207899D0 (en) * 2002-04-05 2002-05-15 3M Innovative Properties Co Formoterol and cielesonide aerosol formulations
US6830046B2 (en) 2002-04-29 2004-12-14 Hewlett-Packard Development Company, L.P. Metered dose inhaler
WO2004024308A1 (en) * 2002-09-13 2004-03-25 Glaxo Group Limited Coated blending system
US20030051727A1 (en) * 2002-11-04 2003-03-20 Haan Richard J Aerosol mdi overcap containing desiccant
US20040105818A1 (en) 2002-11-26 2004-06-03 Alexza Molecular Delivery Corporation Diuretic aerosols and methods of making and using them
US7913688B2 (en) 2002-11-27 2011-03-29 Alexza Pharmaceuticals, Inc. Inhalation device for producing a drug aerosol
WO2004052835A1 (en) * 2002-12-10 2004-06-24 Sepracor Inc. Levalbuterol salt
AU2003293361A1 (en) * 2002-12-18 2004-07-29 Glaxo Group Limited Drug delivery system with vented mouthpiece
US20040234916A1 (en) 2003-05-21 2004-11-25 Alexza Molecular Delivery Corporation Optically ignited or electrically ignited self-contained heating unit and drug-supply unit employing same
JP4607112B2 (ja) 2003-08-11 2011-01-05 グラクソ グループ リミテッド 医薬定量噴霧式吸入器及び前記吸引器に関連する方法
US20050172958A1 (en) * 2003-08-20 2005-08-11 The Brigham And Women's Hospital, Inc. Inhalation device and system for the remote monitoring of drug administration
CA2536876A1 (en) 2003-08-29 2005-03-17 Glaxo Group Limited Pharmaceutical metered dose inhaler and methods relating thereto
JP2007509941A (ja) * 2003-10-28 2007-04-19 グラクソ　グループ　リミテッド ラクトース無水物を用いる吸入医薬製剤およびその投与方法
US7481213B2 (en) * 2004-02-11 2009-01-27 Hewlett-Packard Development Company, L.P. Medicament dispenser
US7467630B2 (en) * 2004-02-11 2008-12-23 Hewlett-Packard Development Company, L.P. Medicament dispenser
EP1595531A1 (en) 2004-05-13 2005-11-16 CHIESI FARMACEUTICI S.p.A. Stable pharmaceutical solution formulations for pressurized metered dose inhalers
IL177103A0 (en) * 2004-02-27 2006-12-10 Chiesi Farma Spa Stable pharmaceutical solution formulations for pressurized metered dose inhalers
US7540286B2 (en) 2004-06-03 2009-06-02 Alexza Pharmaceuticals, Inc. Multiple dose condensation aerosol devices and methods of forming condensation aerosols
GB0418045D0 (en) 2004-08-12 2004-09-15 Glaxo Group Ltd Compounds
SI1831227T1 (sl) * 2004-12-17 2013-09-30 Glenmark Pharmaceuticals S.A. Nove heterociklične spojine uporabne za zdravljenje vnetnih in alergijskih motenj
MX2007007345A (es) * 2004-12-17 2007-09-07 Glenmark Pharmaceuticals Sa Compuestos heterociclicos novedosos utiles para el tratamiento de trastornos inflamatorios y alergicos.
ES2613391T3 (es) 2005-02-10 2017-05-24 Glaxo Group Limited Procedimientos de fabricación de lactosa que utilizan técnicas de preclasificación y formulaciones farmacéuticas formadas a partir de la misma
EP1858528A2 (en) * 2005-02-10 2007-11-28 Glaxo Group Limited Process for crystallizing lactose particles for use in pharmaceutical formulations
BRPI0614548A2 (pt) * 2005-08-08 2011-03-29 Novartis Ag embalagem isolada para inaladores de dose medida
US8367734B1 (en) 2005-08-11 2013-02-05 Amphastar Pharmaceuticals Inc. Stable epinephrine suspension formulation with high inhalation delivery efficiency
EA200801997A1 (ru) 2006-04-20 2009-04-28 Глаксо Груп Лимитед Новые соединения
US20070272768A1 (en) * 2006-05-26 2007-11-29 Williams Donald R Water-Based Airless Adhesive Application Container
US20070286814A1 (en) * 2006-06-12 2007-12-13 Medispray Laboratories Pvt. Ltd. Stable aerosol pharmaceutical formulations
GB0611587D0 (en) 2006-06-12 2006-07-19 Glaxo Group Ltd Novel compounds
US8342172B2 (en) * 2007-02-05 2013-01-01 The Brigham And Women's Hospital, Inc. Instrumented metered-dose inhaler and methods for predicting disease exacerbations
MX2009008582A (es) 2007-02-11 2009-10-30 Map Pharmaceuticals Inc Metodo para la administracion terapeutica de dihidroergotamina para permitir un rapido alivio de la migraña mientras se minimiza el perfil de efectos secundarios.
US20080216828A1 (en) 2007-03-09 2008-09-11 Alexza Pharmaceuticals, Inc. Heating unit for use in a drug delivery device
WO2009006137A1 (en) * 2007-07-03 2009-01-08 Glaxo Group Limited Aerosol canister employing a polymeric film having improved moisture barrier properties
JP5571560B2 (ja) 2007-11-06 2014-08-13 スリーエム イノベイティブ プロパティズ カンパニー 医薬品吸入装置及びそれらの構成要素
GB0721737D0 (en) 2007-11-06 2007-12-19 3M Innovative Properties Co Medicinal inhalation devices and components thereof
GB0721739D0 (en) 2007-11-06 2007-12-19 3M Innovative Properties Co medicinal inhalation devices and components thereof
US8227027B2 (en) 2007-12-07 2012-07-24 Presspart Gmbh & Co. Kg Method for applying a polymer coating to an internal surface of a container
EP2077132A1 (en) 2008-01-02 2009-07-08 Boehringer Ingelheim Pharma GmbH & Co. KG Dispensing device, storage device and method for dispensing a formulation
JP5502077B2 (ja) 2008-06-05 2014-05-28 グラクソ グループ リミテッド 新規な化合物
ES2566339T3 (es) 2008-06-05 2016-04-12 Glaxo Group Limited Derivados de 4-carboxamida indazol útiles como inhibidores de PI3-quinasas
GB2467758A (en) * 2009-02-12 2010-08-18 Consort Medical Plc Metered dose inhaler with internal coating of siloxane and/or silazane
JP5656880B2 (ja) 2009-03-09 2015-01-21 グラクソ グループ リミテッドＧｌａｘｏ Ｇｒｏｕｐ Ｌｉｍｉｔｅｄ Ｐｉ３キナーゼの阻害剤としての４−オキサジアゾール−２−イル−インダゾール
WO2010102968A1 (en) 2009-03-10 2010-09-16 Glaxo Group Limited Indole derivatives as ikk2 inhibitors
EP2408769A1 (en) 2009-03-17 2012-01-25 Glaxo Group Limited Pyrimidine derivatives used as itk inhibitors
EP2408915A2 (en) 2009-03-19 2012-01-25 Merck Sharp&Dohme Corp. RNA INTERFERENCE MEDIATED INHIBITION OF GATA BINDING PROTEIN 3 (GATA3) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US20120035247A1 (en) 2009-03-19 2012-02-09 Merck Sharp & Dohme Corp. RNA Interference Mediated Inhibition of Signal Transducer and Activator of Transcription 6 (STAT6) Gene Expression Using Short Interfering Nucleic Acid (siNA)
CN102439151A (zh) 2009-03-19 2012-05-02 默沙东公司 使用短干扰核酸（siNA）的RNA干扰介导的BTB和CNC同系物1，碱性亮氨酸拉链转录因子1（Bach1）基因表达的抑制
US20120016011A1 (en) 2009-03-19 2012-01-19 Merck Sharp & Dohme Corp. RNA Interference Mediated Inhibition of Connective Tissue Growth Factor (CTGF) Gene Expression Using Short Interfering Nucleic Acid (siNA)
WO2010111464A1 (en) 2009-03-27 2010-09-30 Merck Sharp & Dohme Corp. RNA INTERFERENCE MEDIATED INHIBITION OF APOPTOSIS SIGNAL-REGULATING KINASE 1 (ASK1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
JP2012521764A (ja) 2009-03-27 2012-09-20 メルク・シャープ・エンド・ドーム・コーポレイション 低分子干渉核酸（ｓｉＮＡ）を用いた胸腺間質性リンパ球新生因子（ＴＳＬＰ）遺伝子発現のＲＮＡ干渉媒介性阻害
WO2010111468A2 (en) 2009-03-27 2010-09-30 Merck Sharp & Dohme Corp. RNA INTERFERENCE MEDIATED INHIBITION OF THE NERVE GROWTH FACTOR BETA CHAIN (NGFß) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (SINA)
SG174581A1 (en) 2009-03-27 2011-10-28 Merck Sharp & Dohme RNA INTERFERENCE MEDIATED INHIBITION OF THE INTERCELLULAR ADHESION MOLECULE 1 (ICAM-1)GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
EP2411019A2 (en) 2009-03-27 2012-02-01 Merck Sharp&Dohme Corp. RNA INTERFERENCE MEDIATED INHIBITION OF SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 1 (STAT1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US10011906B2 (en) 2009-03-31 2018-07-03 Beohringer Ingelheim International Gmbh Method for coating a surface of a component
DK2899191T3 (da) 2009-04-30 2017-11-13 Glaxo Group Ltd Oxazol-substituerede indazoler som pi3-kinaseinhibitorer
BRPI1007653A2 (pt) 2009-05-06 2019-09-24 3M Innovative Properties Co "dispositivos para inalação de insumos medicinais e componentes dos mesmos"
CN102460635B (zh) 2009-05-06 2014-12-24 3M创新有限公司 对容器进行等离子体处理的装置和方法
WO2010129753A1 (en) 2009-05-06 2010-11-11 3M Innovative Properties Company Medicinal inhalation device
EP3508239B1 (de) 2009-05-18 2020-12-23 Boehringer Ingelheim International GmbH Adapter, inhalationseinrichtung und zerstäuber
US20110070555A1 (en) * 2009-09-21 2011-03-24 Garrison Dental Solutions Matrix band for dental applications
US20120180785A1 (en) 2009-09-29 2012-07-19 Helen Mary Trill Pressurized Metered Dose Inhalers
GB0918150D0 (en) 2009-10-16 2009-12-02 Jagotec Ag Improved formulations
MX2012005711A (es) 2009-11-17 2012-10-05 Cipla Ltd Soluciones de inhalacion.
EP2504051B1 (en) 2009-11-25 2019-09-04 Boehringer Ingelheim International GmbH Nebulizer
US10016568B2 (en) * 2009-11-25 2018-07-10 Boehringer Ingelheim International Gmbh Nebulizer
JP5715640B2 (ja) 2009-11-25 2015-05-13 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
JP2013512880A (ja) 2009-12-03 2013-04-18 グラクソ グループ リミテッド Ｐｉ３−キナーゼ阻害剤としてのインダゾール誘導体
EP2507226A1 (en) 2009-12-03 2012-10-10 Glaxo Group Limited Novel compounds
JP2013512879A (ja) 2009-12-03 2013-04-18 グラクソ グループ リミテッド Ｐｉ３キナーゼの阻害剤としてのベンズピラゾール誘導体
WO2011110575A1 (en) 2010-03-11 2011-09-15 Glaxo Group Limited Derivatives of 2-[2-(benzo- or pyrido-) thiazolylamino]-6-aminopyridine, useful in the treatment of respiratoric, allergic or inflammatory diseases
EP2585151B1 (en) 2010-06-24 2018-04-04 Boehringer Ingelheim International GmbH Nebulizer
CN103068980B (zh) 2010-08-02 2017-04-05 瑟纳治疗公司 使用短干扰核酸（siNA）的RNA干扰介导的联蛋白（钙粘蛋白关联蛋白质），β1（CTNNB1）基因表达的抑制
KR102072631B1 (ko) 2010-08-17 2020-02-03 시르나 쎄러퓨틱스 인코퍼레이티드 짧은 간섭 핵산 （ｓｉＮＡ）을 사용한 Ｂ형 간염 바이러스 （ＨＢＶ） 유전자 발현의 ＲＮＡ 간섭 매개 억제
EP2609106A4 (en) 2010-08-26 2014-03-19 Merck Sharp & Dohme RNA INTERFERENCE-MEDIATED INHIBITION OF EXPRESSION OF PHD2 GENE (PROLYL HYDROXYLASE DOMAIN 2) USING SMALL INTERFERING NUCLEIC ACID (PANI)
RS54286B1 (en) 2010-09-08 2016-02-29 Glaxosmithkline Intellectual Property Development Limited POLYMORPHS AND SALTS N- [5- [4- (5 - {[(2R, 6S) -2,6-DIMETHYL-4-MORPHOLINYL] METHYL} -1,3-OXAZOL-2-yl) -1H-INDAZZOL- 6-IL] -2 (methyloxy) -3-pyridinyl] -methanesulfonamide
JP5876051B2 (ja) 2010-09-08 2016-03-02 グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ インフルエンザウィルス感染の治療に使用するためのインダゾール誘導体
WO2012035055A1 (en) 2010-09-17 2012-03-22 Glaxo Group Limited Novel compounds
GB201018124D0 (en) 2010-10-27 2010-12-08 Glaxo Group Ltd Polymorphs and salts
EP3766975A1 (en) 2010-10-29 2021-01-20 Sirna Therapeutics, Inc. Rna interference mediated inhibition of gene expression using short interfering nucleic acid (sina)
USD666097S1 (en) 2010-11-01 2012-08-28 Colgate-Palmolive Company Cap for a container
USD666096S1 (en) 2010-11-01 2012-08-28 Colgate-Palmolive Company Cap for a container
USD666099S1 (en) 2010-11-01 2012-08-28 Colgate-Palmolive Company Cap for a container
USD666098S1 (en) 2010-11-01 2012-08-28 Colgate-Palmolive Company Cap for a container
USD666493S1 (en) 2010-11-01 2012-09-04 Colgate-Palmolive Company Cap for a container
USD666492S1 (en) 2010-11-01 2012-09-04 Colgate-Palmolive Company Cap for a container
EP2694220B1 (de) 2011-04-01 2020-05-06 Boehringer Ingelheim International GmbH Medizinisches gerät mit behälter
US9827384B2 (en) 2011-05-23 2017-11-28 Boehringer Ingelheim International Gmbh Nebulizer
CA2861496A1 (en) 2012-02-06 2013-08-15 Glaxosmithkline Intellectual Property (No.2) Limited Pi3k inhibitors for treating cough
WO2013152894A1 (de) 2012-04-13 2013-10-17 Boehringer Ingelheim International Gmbh Zerstäuber mit kodiermitteln
US20150299696A1 (en) 2012-05-02 2015-10-22 Sirna Therapeutics, Inc. SHORT INTERFERING NUCLEIC ACID (siNA) COMPOSITIONS
PL2877467T3 (pl) 2012-07-26 2017-08-31 Glaxo Group Limited 2-(azaindolo-2-ylo)benzoimidazole jako inhibitory pad4
MX2015006457A (es) 2012-11-30 2015-08-14 Hoffmann La Roche Inhibidores de la tirosina cinasa de bruton.
AU2013356383B2 (en) 2012-12-06 2017-08-31 Merck Sharp & Dohme Corp. Disulfide masked prodrug compositions and methods
WO2015018904A1 (en) 2013-08-09 2015-02-12 Boehringer Ingelheim International Gmbh Nebulizer
EP2835146B1 (en) 2013-08-09 2020-09-30 Boehringer Ingelheim International GmbH Nebulizer
MY184292A (en) 2013-09-22 2021-03-30 Sunshine Lake Pharma Co Ltd Substituted aminopyrimidine compounds and methods of use
CA2923995A1 (en) 2013-10-17 2015-04-23 Glaxosmithkline Intellectual Property Development Limited Pi3k inhibitor for treatment of respiratory disease
JP6475707B2 (ja) 2013-10-17 2019-02-27 グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ 呼吸器疾患の治療のためのｐｉ３ｋ阻害剤
HUE055604T2 (hu) 2014-05-07 2021-12-28 Boehringer Ingelheim Int Porlasztó
JP6580070B2 (ja) 2014-05-07 2019-09-25 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 容器、ネブライザ、及び使用
BR112016023932B1 (pt) 2014-05-07 2022-11-29 Boehringer Ingelheim International Gmbh Nebulizador
AU2015338717B2 (en) 2014-10-31 2018-12-20 Glaxosmithkline Intellectual Property Development Limited Powder formulation
US11324746B2 (en) 2014-12-22 2022-05-10 Arovella Therapeutics Limited Use of anagrelide for treating cancer
CN107849015B (zh) 2015-05-21 2021-03-19 葛兰素知识产权发展有限公司 作为pad4抑制剂的苯并咪唑衍生物
CA3004492A1 (en) 2015-11-18 2017-05-26 Glaxosmithkline Intellectual Property (No.2) Limited Pharmaceutical compositions of ribavirin
GB201602527D0 (en) 2016-02-12 2016-03-30 Glaxosmithkline Ip Dev Ltd Chemical compounds
EP3497100A1 (en) 2016-08-08 2019-06-19 GlaxoSmithKline Intellectual Property Development Limited Chemical compounds
DE112017007053T5 (de) 2017-02-14 2019-10-31 Presspart Gmbh & Co. Kg Verfahren zum dichtenden Verbinden eines Kanisters und einer oberen Abdeckung
GB201706102D0 (en) 2017-04-18 2017-05-31 Glaxosmithkline Ip Dev Ltd Chemical compounds
GB201712081D0 (en) 2017-07-27 2017-09-13 Glaxosmithkline Ip Dev Ltd Chemical compounds
GB201717996D0 (en) * 2017-10-31 2017-12-13 Portal Medical Ltd Medicament dispenser device
UY38051A (es) 2018-01-17 2019-08-30 Glaxosmithkline Ip Dev Ltd INHIBIDORES DE LA PI4KIIIß
US10751339B2 (en) 2018-01-20 2020-08-25 Sunshine Lake Pharma Co., Ltd. Substituted aminopyrimidine compounds and methods of use
EP3806939B1 (en) * 2018-06-13 2024-04-10 Puff-Ah Pty Ltd Apparatus for use in delivering respiratory drugs
WO2022179967A1 (en) 2021-02-23 2022-09-01 Glaxosmithkline Intellectual Property (No.2) Limited Vadadustat for treating covid-19 in a hospitalized subject

Family Cites Families (118)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2562118A (en) * 1950-02-09 1951-07-24 Du Pont Polytetrafluoroethylene coating compositions
US2968427A (en) * 1955-06-28 1961-01-17 Meshberg Philip Valve for aerosol container
NL95166C (zh) * 1954-09-20
GB878409A (en) * 1957-03-26 1961-09-27 United Drug And Chemical Compa Improvements in or relating to dispensing devices
US2886217A (en) * 1957-05-20 1959-05-12 Riker Laboratories Inc Dispensing device
US2892576A (en) * 1957-11-14 1959-06-30 Lawrence T Ward Metering button valve assembly
US2980301A (en) * 1958-09-02 1961-04-18 Riker Laboratories Inc Metering valve for aerosol container
GB864392A (en) * 1958-11-10 1961-04-06 Rexall Drug Company Ltd Improvements in or relating to dispensing devices for aerosols
US3506737A (en) * 1965-10-23 1970-04-14 Owens Illinois Inc Glass aerosol bottles and method for making same
GB1200886A (en) * 1966-09-23 1970-08-05 Allen & Hanburys Ltd Phenylaminoethanol derivatives
GB1191700A (en) * 1967-02-27 1970-05-13 Ekco Prod Inc Coated Metalware
FR1584784A (zh) * 1968-08-13 1970-01-02
BE755555A (fr) 1969-09-02 1971-03-01 Richardson Merrell Inc Derives de quinoxaline
FR2082593A5 (en) * 1970-03-20 1971-12-10 Oreal Aerosol can prodn
US3739950A (en) * 1971-04-05 1973-06-19 J Gorman Aerosol inhalation apparatus
NO134730L (zh) 1971-07-19 1900-01-01
LU63737A1 (zh) * 1971-08-17 1972-01-04
US4087026A (en) * 1971-09-15 1978-05-02 Petterson Tor H Barrier package
US3896602A (en) * 1971-09-15 1975-07-29 Tor H Petterson Method of manufacturing of a barrier package
FR2159593A5 (fr) * 1971-11-04 1973-06-22 Skm Sa Installation de peinture par pulverisation
US4143204A (en) * 1971-12-27 1979-03-06 E. I. Du Pont De Nemours And Company Articles coated with fluorocarbon resins
DE2227142A1 (de) * 1972-06-03 1973-12-13 Pampus Kg Rohre und behaelter aus glasfaserverstaerktem kunststoff und einer auskleidung, zum beispiel aus ptfe
US3962171A (en) * 1973-03-02 1976-06-08 Mcgarry & Waters Composition for protecting surfaces
US3929537A (en) * 1973-07-19 1975-12-30 Austral Erwin Engineering Co Preparation of plastic-metal laminates
GB1426342A (en) * 1973-11-19 1976-02-25 Ici Ltd Coating compositions
FR2267496A1 (en) 1974-04-11 1975-11-07 Sidel Sa Method of sealing valve on aerosol container - uses internally ribbed sleeve over ribbed valve and sleeve
US4180609A (en) * 1975-07-11 1979-12-25 E. I. Du Pont De Nemours And Company Article coated with fluoropolymer finish with improved scratch resistance
US4167605A (en) * 1975-07-29 1979-09-11 Imperial Chemical Industries Limited Article with antistick coating and composition
BE858111A (fr) * 1976-08-26 1978-02-27 Union Carbide Corp Enveloppe de recipient distributeur d'aerosol et son procede de realisation
GB2003415A (en) * 1977-09-02 1979-03-14 American Can Co Improvements relating to the manufacture of containers
US4125152A (en) * 1977-09-19 1978-11-14 Borg-Warner Corporation Scale resistant heat transfer surfaces and a method for their preparation
JPS5920547B2 (ja) * 1979-07-04 1984-05-14 東洋製罐株式会社 溶接缶
DE2947025A1 (de) * 1979-11-22 1981-06-04 Glyco-Metall-Werke Daelen & Loos Gmbh, 6200 Wiesbaden Zwei- oder mehrschicht-verbundwerkstoff
ZA807387B (en) * 1979-12-08 1981-11-25 Metal Box Co Ltd Containers
PH24267A (en) * 1980-02-15 1990-05-29 Glaxo Group Ltd Androstane carbothioates and pharmaceutical compositions containing the same
GB2077229B (en) * 1980-05-16 1983-08-03 Neotechnic Eng Ltd Valve assembly for a pressurized aerosoldispensing container
GB2105189B (en) 1981-07-24 1985-03-20 Fisons Plc Inhalation drugs
ZW6584A1 (en) * 1983-04-18 1985-04-17 Glaxo Group Ltd Phenethanolamine derivatives
NZ212911A (en) * 1984-07-31 1988-06-30 Glaxo Group Ltd Aerosol dispensing device; actuator lever acts when cover in open position
DE3677811D1 (de) * 1985-04-19 1991-04-11 Nippon Steel Corp Buechse und verfahren zur herstellung von buechsen.
NL8501767A (nl) * 1985-06-19 1987-01-16 Euro Technical Oilservices Bv Inrichting voor het behandelen van een verontreinigingen bevattende vloeistof.
DE3778727D1 (de) * 1986-02-27 1992-06-11 Nippon Kokan Kk Grundbeschichtete metallplatte.
JPS6312445A (ja) * 1986-06-24 1988-01-19 東洋製罐株式会社 イ−ジイオ−プン蓋付缶体及びその製法
US5536583A (en) * 1986-07-01 1996-07-16 Edlon Products, Inc. Polymer metal bonded composite and method of producing same
US4897439A (en) * 1986-07-01 1990-01-30 Edlon Products, Inc. Polymer-metal bonded composite and method of producing same
EP0260084B1 (en) * 1986-09-08 1992-12-30 Asia Can Company Limited Metal container and method of manufacturing the same
US4819834A (en) * 1986-09-09 1989-04-11 Minnesota Mining And Manufacturing Company Apparatus and methods for delivering a predetermined amount of a pressurized fluid
EP0327777A1 (fr) 1988-02-12 1989-08-16 S.A. DES ETABLISSEMENTS STAUBLI (France) Capteur de déplacement pour machines automatiques
GB2205297B (en) * 1987-06-05 1991-06-19 Lin Pac Mouldings A container assembly
BR8807106A (pt) * 1987-06-26 1989-10-31 Werding Winfried J Dispositivo para armazenagens e fornecimento controlado de produtos que se encontram sob pressao
DE8709978U1 (zh) * 1987-07-21 1987-10-08 A. U. K. Mueller Gmbh & Co Kg, 4000 Duesseldorf, De
GB8724242D0 (en) * 1987-10-15 1987-11-18 Metal Box Plc Laminated metal sheet
GB8724243D0 (en) * 1987-10-15 1987-11-18 Metal Box Plc Laminates of polyolefin-based film
IT1223451B (it) * 1987-11-24 1990-09-19 Coster Tecnologie Speciali Spa Procedimento per ottenere fondelli metallici protetti per valvole per aerosol e simili
GB2214891A (en) * 1988-02-05 1989-09-13 Fibrenyle Ltd Containers for pressurized material
JP2562343B2 (ja) * 1988-02-23 1996-12-11 北海製罐株式会社 エアゾール容器及びエアゾール製品
EP0338670B1 (en) 1988-03-22 1994-05-11 FISONS plc Pharmaceutical Compositions
FI94342C (fi) 1988-03-29 1995-08-25 Ciba Geigy Ag Menetelmä uusien alkanofenonien valmistamiseksi
JPH0289633A (ja) * 1988-05-20 1990-03-29 Sumitomo Electric Ind Ltd フッ素樹脂被覆物
US4902318A (en) * 1988-05-25 1990-02-20 The United States Of America As Represented By The Administrator Of The Environmental Protection Agency Inlet apparatus for gas-aerosol sampling
US4961966A (en) * 1988-05-25 1990-10-09 The United States Of America As Represented By The Administrator Of The Environmental Protection Agency Fluorocarbon coating method
JPH0267374A (ja) * 1988-08-31 1990-03-07 Takeuchi Press Ind Co Ltd エアゾール缶容器
GB8828477D0 (en) * 1988-12-06 1989-01-05 Riker Laboratories Inc Medical aerosol formulations
US5225183A (en) * 1988-12-06 1993-07-06 Riker Laboratories, Inc. Medicinal aerosol formulations
GB8903629D0 (en) * 1989-02-17 1989-04-05 Metal Box Plc Metal/polymer laminates
US5176132A (en) * 1989-05-31 1993-01-05 Fisons Plc Medicament inhalation device and formulation
US5006383A (en) * 1989-06-28 1991-04-09 The Dow Chemical Company Polymeric blend and laminated structures prepared therefrom
FR2650219B1 (fr) * 1989-07-06 1991-10-04 Pechiney Rhenalu Procede d'obtention de materiaux multicouches aptes a etre transformes par emboutissage ou emboutissage-etirage en corps creux
FR2649359B1 (fr) * 1989-07-06 1993-02-12 Cebal Bande ou portion de bande pour emboutissage ou emboutissage-etirage, et son utilisation
JP2600387B2 (ja) * 1989-09-06 1997-04-16 東洋紡績株式会社 金属貼合せ用ポリエステルフィルム
US5208226A (en) * 1989-09-08 1993-05-04 Glaxo Group Limited Medicaments
US5270305A (en) * 1989-09-08 1993-12-14 Glaxo Group Limited Medicaments
GB8921222D0 (en) * 1989-09-20 1989-11-08 Riker Laboratories Inc Medicinal aerosol formulations
US5345980A (en) 1989-09-21 1994-09-13 Glaxo Group Limited Method and apparatus an aerosol container
JPH03199699A (ja) * 1989-12-27 1991-08-30 Ntn Corp ターボ分子ポンプ
GB9000984D0 (en) * 1990-01-16 1990-03-14 Hoechst U K Limited Polymers D Aerosol container
US5043191A (en) * 1990-02-27 1991-08-27 Miles Inc. Method of protecting hard surfaces
DE4009397A1 (de) * 1990-03-23 1991-09-26 Weidenhammer Packungen Dosenartige verpackung fuer fliessfaehige produkte
US5083685A (en) * 1990-06-28 1992-01-28 Mitsui Toatsu Chemicals, Inc. Vessel for aerosol
GB9015522D0 (en) * 1990-07-13 1990-08-29 Braithwaite Philip W Inhaler
DE4023909A1 (de) * 1990-07-27 1992-01-30 Wild Rudolf Gmbh & Co Wiederverwendbarer behaelter aus kunststoff sowie seine herstellung und verwendung
GB9024365D0 (en) * 1990-11-09 1991-01-02 Glaxo Group Ltd Medicaments
EP0487200B1 (en) * 1990-11-14 2000-06-21 Titeflex Corporation Fluoropolymer aluminium laminate
WO1992010309A1 (en) * 1990-12-12 1992-06-25 E.I. Du Pont De Nemours And Company Non-stick coating system with ptfe and pfa or fep for concentration gradient
US5168107A (en) * 1990-12-12 1992-12-01 E. I. Du Pont De Nemours And Company Non-stick coating system with PTFE of two low melt viscosities for concentration gradient
JPH06501974A (ja) * 1990-12-12 1994-03-03 イー・アイ・デユポン・ドウ・ヌムール・アンド・カンパニー 濃度勾配のために熔融粘度の異なるｐｔｆｅを用いた非−粘着塗料系
GB9027234D0 (en) * 1990-12-15 1991-02-06 Harris Pharma Ltd An inhalation device
US5290539A (en) * 1990-12-21 1994-03-01 Minnesota Mining And Manufacturing Company Device for delivering an aerosol
EP0499142A3 (en) 1991-02-09 1993-05-05 Hoechst Aktiengesellschaft Potentiation of the antireactive-antiasthmatic effect of inhaled loop diuretics by inhaled non steroidal anti-flammatory drugs
EP0504112A3 (en) * 1991-03-14 1993-04-21 Ciba-Geigy Ag Pharmaceutical aerosol formulations
RU2027448C1 (ru) 1991-04-25 1995-01-27 Государственное предприятие "ВЭЛТ" Ингалятор
JPH089215B2 (ja) * 1991-05-30 1996-01-31 新日本製鐵株式会社 容器用樹脂複合鋼板の製造方法
RU2008939C1 (ru) 1991-06-10 1994-03-15 Вячеслав Николаевич Поздняков Физиотерапевтический ингалятор
RU2012362C1 (ru) 1991-06-24 1994-05-15 Юрий Алексеевич Волгин Ингалятор
DE4124730C3 (de) * 1991-07-25 2001-09-06 Ahc Oberflaechentechnik Gmbh Anodisierte Gegenstände aus Aluminium oder Magnesium mit in die Oxidschicht eingelagerten Fluorpolymeren und Verfahren zu deren Herstellung
AU663906B2 (en) * 1991-12-12 1995-10-26 Glaxo Group Limited Medicaments
US5683676A (en) * 1991-12-12 1997-11-04 Glaxo Group Limited Canister containing aerosol formulations containing P134a and particulate medicaments
IL104068A (en) * 1991-12-12 1998-10-30 Glaxo Group Ltd Pharmaceutical preparations in a spray without surfactant containing 1, 1, 1, 2 tetrafluoroethane or 1,1,2,3,3 petafluor N propane as propellant
US5363842A (en) * 1991-12-20 1994-11-15 Circadian, Inc. Intelligent inhaler providing feedback to both patient and medical professional
US5202110A (en) * 1992-01-22 1993-04-13 Virginia Commonwealth University Formulations for delivery of beclomethasone diproprionate by metered dose inhalers containing no chlorofluorocarbon propellants
US5261538A (en) * 1992-04-21 1993-11-16 Glaxo Inc. Aerosol testing method
WO1994000921A1 (en) * 1992-06-25 1994-01-06 Nippondenso Co., Ltd. Mobile object identification device
US5376359A (en) * 1992-07-07 1994-12-27 Glaxo, Inc. Method of stabilizing aerosol formulations
MX9304585A (es) * 1992-07-31 1994-03-31 Glaxo Group Ltd Formulacion farmaceutica en aerosol, lata adecuada para liberar la formulacion e inhalador de dosis dosificada que comprende la lata.
JP2863389B2 (ja) * 1992-11-13 1999-03-03 三菱樹脂株式会社 エアゾール缶用容器及びエアゾール缶
WO1994013263A1 (en) * 1992-12-09 1994-06-23 Jager Paul D Stabilized medicinal aerosol solution formulations
GB9306292D0 (en) 1993-03-26 1993-05-19 Glaxo Group Ltd Method
US5437267A (en) * 1993-08-03 1995-08-01 Weinstein; Allan Device for delivering aerosol to the nasal membranes and method of use
US6596260B1 (en) * 1993-08-27 2003-07-22 Novartis Corporation Aerosol container and a method for storage and administration of a predetermined amount of a pharmaceutically active aerosol
US5421492A (en) * 1993-11-02 1995-06-06 Glaxo Inc. Metered aerosol dispensing apparatus and method of use thereof
US5468798A (en) * 1994-02-18 1995-11-21 Whitford Corporation Basecoat for a coating system
US5508023A (en) * 1994-04-11 1996-04-16 The Center For Innovative Technology Pharmaceutically acceptable agents for solubilizing, wetting, emulsifying, or lubricating in metered dose inhaler formulations which use HFC-227 propellant
US5597433A (en) * 1994-05-27 1997-01-28 Panoramic, Inc. Method and apparatus for manufacturing plastic canisters
BR9604977A (pt) * 1995-04-14 1998-06-09 Glaxo Wellcome Inc Inalador de dose medida sistema inalador de dose medida e uso do mesmo
EE04004B1 (et) * 1995-04-14 2003-04-15 Glaxo Wellcome Inc. Flutikasoonpropionaati doseeriv inhalaator
CA2361954C (en) * 1995-04-14 2003-07-08 Smithkline Beecham Corporation Metered dose inhaler for albuterol
US5674592A (en) * 1995-05-04 1997-10-07 Minnesota Mining And Manufacturing Company Functionalized nanostructured films
JP3199699B2 (ja) 1999-04-14 2001-08-20 核燃料サイクル開発機構 弁座面の平坦度測定装置

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110840864A (zh) * 2019-12-20 2020-02-28 广州健康元呼吸药物工程技术有限公司 一种β2受体激动剂吸入气雾剂及包含该吸入气雾剂的产品
CN110840864B (zh) * 2019-12-20 2022-02-22 广州健康元呼吸药物工程技术有限公司 一种β2受体激动剂吸入气雾剂及包含该吸入气雾剂的产品

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