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公开(公告)号：US09295793B2
公开(公告)日：2016-03-29
申请号：US11910678
申请日：2006-04-07
CPC分类号： A61M15/0065 , A61M15/0081 , A61M15/0095 , A61M2016/0021 , A61M2202/066
摘要： An inhaler device (1) contains, or is capable of accepting, a plurality of doses of a medicament to be dispensed from the inhaler (1). To ameliorate the problem of double dosing from the inhaler (1), the device further comprises prevention means (26, 28, 40) for preventing, at least temporarily, the dispensing of a dose of medicament, and detection means (32) for detecting the inhalation of a previously dispensed dose of medicament. When the detection means (32) detects the inhalation of the previously dispensed dose of medicament, it releases the prevention means (26, 28, 40), allowing the device to dispense a further dose of medicament. The detection means (32) may be a pressure sensor, and the prevention means (26, 28, 40) may operate by causing a disengagement of an actuation mechanism.
摘要翻译： 吸入器装置（1）包含或能够接受多个剂量的从吸入器（1）分配的药物。 为了改善来自吸入器（1）的双重剂量的问题，该装置还包括防止装置（26,28,40），用于至少暂时地防止一剂药物的分配，以及用于检测的检测装置（32） 吸入先前分配剂量的药物。 当检测装置（32）检测到先前分配剂量的药物的吸入时，其释放预防装置（26,28,40），允许装置分配另外剂量的药物。 检测装置（32）可以是压力传感器，并且防止装置（26,28,40）可以通过致动机构的分离来操作。
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公开(公告)号：US08083127B2
公开(公告)日：2011-12-27
申请号：US12790530
申请日：2010-05-28
申请人： Stephen J. Minshull , Duncan G. Young , Andrew J. Ledgeway , Simon P. Wells , Graham K. Lacy , Julian F. R. Swan
发明人： Stephen J. Minshull , Duncan G. Young , Andrew J. Ledgeway , Simon P. Wells , Graham K. Lacy , Julian F. R. Swan
IPC分类号： G06C27/00
CPC分类号： G06M1/163 , A61M15/0065 , A61M15/0068 , A61M15/0073 , A61M2202/064 , G06M1/041 , G06M1/241
摘要： A counter mechanism useable with a dry powder inhaler is disclosed. The mechanism features first and second indicator members rotatable about a central axis. The indicator members have counting indicia visible to indicate inhaler doses remaining or dispensed. A coupling transmits rotary motion from the inhaler to the second indicator member when the inhaler is charged with a dose. A slave wheel, rotatable about an axis offset from the central axis, has a drive transfer wheel on one face and a gear on an opposite face. The gear engages the second indicator member, the drive transfer wheel intermittently engages and rotates the first indicator member in response to rotary motion of the second indicator member.
摘要翻译： 公开了一种可用于干粉吸入器的对抗机构。 该机构具有围绕中心轴可旋转的第一和第二指示器构件。 指示器成员具有可见的计数标记，以指示剩余或分配的吸入剂剂量。 当吸入器以剂量充电时，联接器将旋转运动从吸入器传递到第二指示器构件。 一个可绕中心轴线偏移的轴可转动的从轮在一个面上具有一个驱动传递轮，在一个相对的面上有一个齿轮。 齿轮接合第二指示器构件，驱动传递轮响应于第二指示器构件的旋转运动而间歇地接合并旋转第一指示器构件。
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公开(公告)号：US20110067695A1
公开(公告)日：2011-03-24
申请号：US12790530
申请日：2010-05-28
申请人： Stephen John Minshull , Duncan Grant Young , Andrew J. Ledgeway , Simon Paul Wells , Graham Keith Lacy , Julian Francis R. Swan
发明人： Stephen John Minshull , Duncan Grant Young , Andrew J. Ledgeway , Simon Paul Wells , Graham Keith Lacy , Julian Francis R. Swan
IPC分类号： A61M15/00
CPC分类号： G06M1/163 , A61M15/0065 , A61M15/0068 , A61M15/0073 , A61M2202/064 , G06M1/041 , G06M1/241
摘要： A counter mechanism useable with a dry powder inhaler is disclosed. The mechanism features first and second indicator members rotatable about a central axis. The indicator members have counting indicia visible to indicate inhaler doses remaining or dispensed. A coupling transmits rotary motion from the inhaler to the second indicator member when the inhaler is charged with a dose. A slave wheel, rotatable about an axis offset from the central axis, has a drive transfer wheel on one face and a gear on an opposite face. The gear engages the second indicator member, the drive transfer wheel intermittently engages and rotates the first indicator member in response to rotary motion of the second indicator member.
摘要翻译： 公开了一种可用于干粉吸入器的对抗机构。 该机构具有围绕中心轴可旋转的第一和第二指示器构件。 指示器成员具有可见的计数标记，以指示剩余或分配的吸入剂剂量。 当吸入器以剂量充电时，联接器将旋转运动从吸入器传递到第二指示器构件。 一个可绕中心轴线偏移的轴可转动的从轮在一个面上具有一个驱动传递轮，在一个相对的面上有一个齿轮。 齿轮接合第二指示器构件，驱动传递轮响应于第二指示器构件的旋转运动而间歇地接合并旋转第一指示器构件。
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公开(公告)号：US07726555B2
公开(公告)日：2010-06-01
申请号：US11946389
申请日：2007-11-28
申请人： Stephen J. Minshull , Duncan G. Young , Andrew J. Ledgeway , Simon P. Wells , Graham K. Lacy , Julian F. R. Swan
发明人： Stephen J. Minshull , Duncan G. Young , Andrew J. Ledgeway , Simon P. Wells , Graham K. Lacy , Julian F. R. Swan
IPC分类号： G06C27/00
CPC分类号： G06M1/163 , A61M15/0065 , A61M15/0068 , A61M15/0073 , A61M2202/064 , G06M1/041 , G06M1/241
摘要： A counter mechanism useable with a dry powder inhaler is disclosed. The mechanism features first and second indicator members rotatable about a central axis. The indicator members have counting indicia visible to indicate inhaler doses remaining or dispensed. A coupling transmits rotary motion from the inhaler to the second indicator member when the inhaler is charged with a dose. A slave wheel, rotatable about an axis offset from the central axis, has a drive transfer wheel on one face and a gear on an opposite face. The gear engages the second indicator member, the drive transfer wheel intermittently engages and rotates the first indicator member in response to rotary motion of the second indicator member.
摘要翻译： 公开了一种可用于干粉吸入器的对抗机构。 该机构具有围绕中心轴可旋转的第一和第二指示器构件。 指示器成员具有可见的计数标记，以指示剩余或分配的吸入剂剂量。 当吸入器以剂量充电时，联接器将旋转运动从吸入器传递到第二指示器构件。 一个可绕中心轴线偏移的轴可转动的从轮在一个面上具有一个驱动传递轮，在一个相对的面上有一个齿轮。 齿轮接合第二指示器构件，驱动传递轮响应于第二指示器构件的旋转运动而间歇地接合并旋转第一指示器构件。
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公开(公告)号：US07479501B2
公开(公告)日：2009-01-20
申请号：US09871564
申请日：2001-05-31
申请人： Alan Collis , Frank Halley , Iain McLay
发明人： Alan Collis , Frank Halley , Iain McLay
IPC分类号： A61K31/4439 , C07D405/14
CPC分类号： C07D409/14 , C07D405/14 , C07D413/14
摘要： Compounds of formula (I) are described in which Het is a five or six membered heteroaromatic ring of the formula in which one of R1 and R2 is optionally substituted heteroaryl and the other is optionally substituted heteroaryl or optionally substituted aryl; X1 is a bond, X3 and X4 are each independently N or C and X2 and X5 are independently CH, N, NH, O or S; or X3 and X4 are C, one of X1, X2 and X5 is N and the others are N or CH; but excluding compounds in which X1 is a bond, one of X2 and X5 is N and the other is NH and X3 and X4 are both C; R3 represents a group -L1-R6; R4 represents hydrogen, alkyl or hydroxyalkyl; or R3 and R4, when attached to the same carbon atom, may form with the said carbon atom a cycloalkyl, cycloalkenyl or heterocycloalkyl ring or a group C═CH2; R5 represents hydrogen or alkyl; and m is zero or an integer 1 or 2; and N-oxides thereof, and their prodrugs; and pharmaceutically acceptable salts and solvates of compounds of formula (I) and N-oxides thereof, and their prodrugs. The compounds are TNF inhibitors and are useful as pharmaceuticals.
摘要翻译： 描述式（I）的化合物，其中Het是下式的五或六元杂芳族环，其中R 1和R 2中的一个是任选取代的杂芳基，另一个是任选取代的杂芳基或任选取代的芳基; X1是键，X3和X4各自独立地是N或C，X2和X5独立地是CH，N，NH，O或S; 或X3和X4为C，X1，X2和X5之一为N，其余为N或CH; 但不包括X1为键的化合物，X2和X5之一为N，另一个为NH，X3和X4均为C; R3表示基团-L1-R6; R4表示氢，烷基或羟烷基; 或者R 3和R 4在连接到相同的碳原子时可与所述碳原子一起形成环烷基，环烯基或杂环烷基环或基团C-CH 2; R5代表氢或烷基; m为零或整数1或2; 和N-氧化物及其前药; 和式（I）化合物及其N-氧化物的药学上可接受的盐和溶剂合物及其前药。 这些化合物是TNF抑制剂，可用作药物。
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公开(公告)号：US20080066750A1
公开(公告)日：2008-03-20
申请号：US11946389
申请日：2007-11-28
申请人： Stephen Minshull , Duncan Young , Andrew Ledgeway , Simon Wells , Graham Lacy , Julian Swan
发明人： Stephen Minshull , Duncan Young , Andrew Ledgeway , Simon Wells , Graham Lacy , Julian Swan
IPC分类号： A61M15/00
CPC分类号： G06M1/163 , A61M15/0065 , A61M15/0068 , A61M15/0073 , A61M2202/064 , G06M1/041 , G06M1/241
摘要： A counter mechanism useable with a dry powder inhaler is disclosed. The mechanism features first and second indicator members rotatable about a central axis. The indicator members have counting indicia visible to indicate inhaler doses remaining or dispensed. A coupling transmits rotary motion from the inhaler to the second indicator member when the inhaler is charged with a dose. A slave wheel, rotatable about an axis offset from the central axis, has a drive transfer wheel on one face and a gear on an opposite face. The gear engages the second indicator member, the drive transfer wheel intermittently engages and rotates the first indicator member in response to rotary motion of the second indicator member.
摘要翻译： 公开了一种可用于干粉吸入器的对抗机构。 该机构具有围绕中心轴可旋转的第一和第二指示器构件。 指示器成员具有可见的计数标记，以指示剩余或分配的吸入剂剂量。 当吸入器以剂量充电时，联接器将旋转运动从吸入器传递到第二指示器构件。 一个可绕中心轴线偏移的轴可转动的从轮在一个面上具有一个驱动传递轮，在一个相对的面上有一个齿轮。 齿轮接合第二指示器构件，驱动传递轮响应于第二指示器构件的旋转运动而间歇地接合并旋转第一指示器构件。
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公开(公告)号：US07329675B2
公开(公告)日：2008-02-12
申请号：US10933077
申请日：2004-09-01
申请人： Paul Joseph Cox , Shelley Bower , David John Aldous , Peter Charles Astles , Daniel Gerard McGarry , Christopher Hulme , John Robinson Regan , Fu-Chih Huang , Stevan Wakefield Djuric , Kevin Joseph Moriarty , Rose Mappilakunnel Mathew , Gregory Bernard Poli
发明人： Paul Joseph Cox , Shelley Bower , David John Aldous , Peter Charles Astles , Daniel Gerard McGarry , Christopher Hulme , John Robinson Regan , Fu-Chih Huang , Stevan Wakefield Djuric , Kevin Joseph Moriarty , Rose Mappilakunnel Mathew , Gregory Bernard Poli
IPC分类号： A61K31/44 , A61K43/40 , C07D405/00
CPC分类号： C07D235/24 , C07D209/12 , C07D209/42 , C07D401/06 , C07D401/12 , C07D401/14 , C07D403/04 , C07D403/12 , C07D405/14 , C07D409/14 , C07D413/12 , C07D413/14 , C07D417/14
摘要： This invention is directed to physiologically active compounds of formula (I) wherein represents a bicyclic ring system, of about 10 to about 13 ring members, in which the ring is an azaheterocycle, and the ring represents an azaheteroaryl ring, or an optionally halo substituted benzene ring; and N-oxides thereof, and pharmaceutically acceptable salts of the compounds of formula (I) and N-oxides thereof, Such compounds inhibit the production or physiological effects of TNF and inhibit cyclic AMP phosphodiesterase. The invention is also directed to pharmnaceutical compositions comprising compoundS of formula (I), their phatmaceUtical use and methods for their preparation.
摘要翻译： 本发明涉及式（I）的生理活性化合物，其中代表双环体系，约10至约13个环成员，其中该环是氮杂环，并且该环代表氮杂杂芳基环，或任选地被卤素取代 苯环; 和其N-氧化物，以及式（I）化合物及其N-氧化物的药学上可接受的盐。这些化合物抑制TNF的产生或生理作用并抑制环AMP磷酸二酯酶。 本发明还涉及包含式（I）化合物S的药物组合物，其药理学用途及其制备方法。
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公开(公告)号：US07045660B2
公开(公告)日：2006-05-16
申请号：US10792579
申请日：2004-03-03
IPC分类号： C07C233/64 , A61K31/165
CPC分类号： C07D213/70 , C07C43/247 , C07C217/58 , C07C235/56 , C07C237/30 , C07C255/60 , C07C327/48 , C07C2601/08 , C07C2603/64 , C07C2603/66 , C07D213/65 , C07D213/69 , C07D213/75 , C07D213/79 , C07D213/81 , C07D213/82 , C07D213/89 , C07D401/12 , C07D409/12 , C07D413/12 , C07D417/12
摘要： This invention is directed to a [di(ether or thioether)heteroaryl or fluoro substituted aryl] compound or an N-oxide thereof or a pharmaceutically acceptable salt thereof, which is useful for inhibiting the production or physiological effects of TNF in the treatment of a patient suffering from a disease state associated with a physiologically detrimental excess of tumor necrosis factor (TNF).Compounds within the scope of the present invention also inhibit cyclic AMP phosphodiesterase, and are useful in treating a disease state associated with pathological conditions that are modulated by inhibiting cyclic AMP phosphodiesterase, such disease states including inflammatory and autoimmune diseases, in particular type IV cyclic AMP phosphodiesterase. The present invention is therefore directed to their pharmacological use for inhibiting TNF and/or cyclic AMP phosphodiesterase, pharmacological compositions comprising the compounds and methods for their preparation.
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公开(公告)号：US20050214228A1
公开(公告)日：2005-09-29
申请号：US11135543
申请日：2005-05-23
申请人： Dominique Begon , Guillaume Pfefer , Michael Kohl
发明人： Dominique Begon , Guillaume Pfefer , Michael Kohl
IPC分类号： A61K9/14 , A61K9/00 , A61K9/12 , A61K9/16 , A61K31/57 , A61L9/04 , A61P11/06 , B01D9/00 , B01D9/02 , B01F3/08 , B01F5/00 , B01F5/02 , B01F13/00 , B29B9/00
CPC分类号： A61K9/0075 , A61K9/1688 , B01D9/0027 , B01D9/005 , B01F3/08 , B01F5/0256 , B01F13/0059 , B01F2005/0025 , B01F2215/0032
摘要： A method of producing fine medicament particles suitable for inhalation, particles produced by the method and apparatus suitable for carrying out the method. The method comprises contacting a stream or streams of a solution of medicament with a stream or streams of a liquid in which the medicament is insoluble in a confined chamber such that a region of intense turbulence and mixing is formed. The medicament crystallises as fine particles with minimal inclusion of solvent or anti-solvent impurities. The crystallised medicament is separated from suspension by standard techniques. Careful control of relative stream velocity, solution concentration and proportion of solution and anti-solvent in the streams ensures a uniform product.
摘要翻译： 一种生产适于吸入的精细药物颗粒的方法，通过适用于实施该方法的方法和装置产生的颗粒。 该方法包括使药物溶液的流或物流与液体的流或液体接触，其中药物不溶于限制室，使得形成强烈湍流和混合的区域。 药物作为细颗粒结晶，溶剂或抗溶剂杂质含量最小。 通过标准技术将结晶的药物与悬浮液分离。 仔细控制流中的相对流速，溶液浓度和溶液和反溶剂的比例确保了均匀的产物。
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公开(公告)号：US20040122047A1
公开(公告)日：2004-06-24
申请号：US10715662
申请日：2003-11-18
发明人： Garry Fenton , Neil Victor Harris
IPC分类号： A61K031/4709 , A61K031/47 , C07D217/12
CPC分类号： C07D413/06 , C07D217/06 , C07D217/16 , C07D413/14
摘要： The invention is directed to physiologically active compounds of formula (I): 1 wherein: R1 represents optionally substituted aryl, optionally substituted heteroaryl, R3NHnullAr1nullL2null or R3nullNHnullC(nullO)nullNHnullAr2nullL2null; R3 represents aryl or heteroaryl; Ar1 represents a saturated, partially saturated or fully unsaturated 8- to 10-membered bicyclic ring systerm containing at least one heteroatom selected from O, S or N; Ar2 represents aryldiye or heteroaryldiyl; L1 represents a linkage, such as an alkylene linkage; L2 represents an alkylene chain linkage; R2 represents hydrogen, halogen, C1-4alkyl or C1-4alkoxy; and Y is carboxy or an acid bioisostere; but excluding compounds where an oxygen, nitrogen or sulfur atom is attached directly to a carbon carbon multiple bond of an alkenylene or alkynylene residue; and the corresponding N-oxides and ester prodrugs thereof, and the pharmaceutically acceptable salts and solvates of such compounds, and the N-oxides and ester prodrugs thereof. Such compounds have valuable pharmaceutical properties, in particular the ability to regulate the interaction of VCAM-1 and fibronectin with the integrin VLA-4 (null4null1).
摘要翻译： 本发明涉及式（I）的生理活性化合物：其中：R 1表示任选取代的芳基，任选取代的杂芳基，R 3 NH -Ar 1 -L 2 - 或R 3 -NH-C（= O）-NH-Ar 2 -L 2 - ; R 3表示芳基或杂芳基; Ar 1表示含有至少一个选自O，S或N的杂原子的饱和，部分饱和或完全不饱和的8至10元双环系统; Ar 2表示芳基二或杂芳基二; L 1表示连接，例如亚烷基键; L 2表示亚烷基链键; R 2表示氢，卤素，C 1-4烷基或C 1-4烷氧基; Y为羧基或酸式生物电子等排体; 但不包括其中氧，氮或硫原子直接连接到亚烯基或亚炔基残基的碳碳多重键上的化合物; 和其相应的N-氧化物和酯前体药物，以及这些化合物的药学上可接受的盐和溶剂化物，及其N-氧化物和酯前体药物。 这些化合物具有有价值的药物性质，特别是调节VCAM-1和纤连蛋白与整联蛋白VLA-4（α4β1）的相互作用的能力。
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