公开(公告)号：US07827989B2

公开(公告)日：2010-11-09

申请号：US12050495

申请日：2008-03-18

申请人： Noel Butterworth ,  Stephen John Minshull ,  Simon Paul Wells ,  Duncan Grant Young

发明人： Noel Butterworth ,  Stephen John Minshull ,  Simon Paul Wells ,  Duncan Grant Young

IPC分类号： A61M11/00

CPC分类号： A61M15/0065 ,  A61M15/0073 ,  A61M2202/064 ,  G06M1/163 ,  G06M1/241

摘要： A rotatably actuated counter is disclosed. The counter includes a ratchet driven unit wheel nested within a tens wheel. Each wheel has a radial face displaying counting indicia. The tens wheel is transparent, allowing the indicia on the unit wheel to be viewed adjacent to the indicia on the tens wheel to provide a total count. A slave wheel is positioned between the unit and tens wheels. A gear on one face of the slave wheel engages gear teeth on the tens wheel. A Geneva mechanism on the other face is engaged by a foot on the unit wheel once per rotation. The wheels are rotatably mounted within a housing having a sidewall with a window through which the count indicia may be viewed. The unit wheel rotates in ten increments and then rotates the tens wheel through one increment by engaging and rotating the slave wheel.

摘要翻译： 公开了一种可旋转驱动的计数器。 该计数器包括嵌在十轮内的棘轮驱动单元轮。 每个轮具有显示计数标记的径向面。 十号轮是透明的，允许在十轮上的标记附近看到单位轮上的标记以提供总计数。 从轮定位在单元和十轮之间。 从轮的一个面上的齿轮啮合十轮上的齿轮齿。 另一面的日内瓦机构每转一次由单脚轮一脚接合。 车轮可旋转地安装在具有侧壁的外壳内，该侧壁具有窗口，通过该窗可以看到计数标记。 单位轮以十个增量旋转，然后通过啮合和旋转从轮来使十轮旋转一个增量。

公开(公告)号：US20080210226A1

公开(公告)日：2008-09-04

申请号：US12050495

申请日：2008-03-18

申请人： Noel BUTTERWORTH ,  Stephen John MINSHULL ,  Simon Paul WELLS ,  Duncan Grant YOUNG

发明人： Noel BUTTERWORTH ,  Stephen John MINSHULL ,  Simon Paul WELLS ,  Duncan Grant YOUNG

IPC分类号： A61M15/00

CPC分类号： A61M15/0065 ,  A61M15/0073 ,  A61M2202/064 ,  G06M1/163 ,  G06M1/241

摘要： A rotatably actuated counter is disclosed. The counter includes a ratchet driven unit wheel nested within a tens wheel. Each wheel has a radial face displaying counting indicia. The tens wheel is transparent, allowing the indicia on the unit wheel to be viewed adjacent to the indicia on the tens wheel to provide a total count. A slave wheel is positioned between the unit and tens wheels. A gear on one face of the slave wheel engages gear teeth on the tens wheel. A Geneva mechanism on the other face is engaged by a foot on the unit wheel once per rotation. The wheels are rotatably mounted within a housing having a sidewall with a window through which the count indicia may be viewed. The unit wheel rotates in ten increments and then rotates the tens wheel through one increment by engaging and rotating the slave wheel.

摘要翻译： 公开了一种可旋转驱动的计数器。 该计数器包括嵌在十轮内的棘轮驱动单元轮。 每个轮具有显示计数标记的径向面。 十号轮是透明的，允许在十轮上的标记附近看到单位轮上的标记以提供总计数。 从轮定位在单元和十轮之间。 从轮的一个面上的齿轮啮合十轮上的齿轮齿。 另一面的日内瓦机构每转一次由单脚轮一脚接合。 车轮可旋转地安装在具有侧壁的外壳内，该侧壁具有窗口，通过该窗可以看到计数标记。 单位轮以十个增量旋转，然后通过啮合和旋转从轮来使十轮旋转一个增量。

公开(公告)号：US07211586B2

公开(公告)日：2007-05-01

申请号：US10715662

申请日：2003-11-18

申请人： Garry Fenton ,  Neil Victor Harris

发明人： Garry Fenton ,  Neil Victor Harris

IPC分类号： A61K31/4709 ,  A61K31/47 ,  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): wherein: R1 represents optionally substituted aryl, optionally substituted heteroaryl, R3NH—Ar1—L2— or R3—NH—C(═O)—NH—Ar2—L2—; R3 represents aryl or heteroaryl; Ar1 represents a saturated, partially saturated or fully unsaturated 8- to 10-membered bicyclic ring system containing at least one heteroatom selected from O, S or N; Ar2 represents aryldiyl 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 (α4β1).

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 - 或 - R 3 -NH-C（ - ） - -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的杂原子的饱和的，部分饱和的或完全不饱和的8至10元双环体系; Ar 2代表芳基二基或杂芳基二基; L 1表示连接，例如亚烷基键; L 2代表亚烷基链键; 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。

公开(公告)号：US07166616B2

公开(公告)日：2007-01-23

申请号：US10427598

申请日：2003-05-01

申请人： Neil Victor Harris ,  Garry Fenton

发明人： Neil Victor Harris ,  Garry Fenton

IPC分类号： C07D263/58 ,  C07D261/02 ,  A61K31/423 ,  A61K31/445

CPC分类号： C07D263/58 ,  A61K31/423 ,  C07C275/42 ,  C07C2601/08 ,  C07C2602/08 ,  C07D413/12

摘要： The invention is directed to physiologically active compounds of general formula (I): wherein: represents (i) a saturated 3 to 6 membered carbocycle, optionally substituted by one or more alkyl groups, (ii) indanyl or (iii) a saturated 4 to 6 membered heterocyclic ring; R1 represents R3Z1-Het- or R4N(R5)—C(═O)—NH—Ar1—; L1 represents an —R6—R7— linkage; R2 represents hydrogen, halogen, lower alkyl or lower alkoxy; L2 represents an alkylene linkage; Y is carboxy or an acid bioisostere; and their corresponding N-oxides or prodrugs, and pharmaceutically acceptable salts and solvates of such compounds and their corresponding N-oxides or prodrugs. Such compounds have valuable pharmaceutical properties, in particular the ability to regulate the interaction of VCAM-1 and fibronectin with the integrin VLA-4 (α4β1).

摘要翻译： 本发明涉及通式（I）的生理活性化合物：其中：（i）饱和的3至6元碳环，任选被一个或多个烷基取代，（ii）茚满基或（iii）饱和的4至 6元杂环; R 1表示R 3 Z 1或H 4 - 或R 4 N（R 5） （O）-NH-Ar 1 - ; L 1表示-R 6-6R 7 - 键; R 2表示氢，卤素，低级烷基或低级烷氧基; L 2表示亚烷基键; Y是羧基或酸生物电子等排体; 及其相应的N-氧化物或前体药物，以及这些化合物的药学上可接受的盐和溶剂合物及其相应的N-氧化物或前体药物。 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。

公开(公告)号：US20060104917A1

公开(公告)日：2006-05-18

申请号：US11325875

申请日：2006-01-05

申请人： Ruth Wayland

发明人： Ruth Wayland

IPC分类号： A61K9/14 ,  A61L9/04

CPC分类号： A61K9/0075 ,  A61K31/167 ,  A61K31/573 ,  A61K2300/00

摘要： Provided herein is a stable pharmaceutical product comprising a dry powder inhalation device, and a pharmaceutical composition that comprises R,R-Formoterol L-tartrate salt, in particular crystalline R,R-formoterol L-tartrate; and ciclesonide.

摘要翻译： 本文提供了一种稳定的药物产品，其包含干粉吸入装置和包含R，R-福莫特罗L-酒石酸盐，特别是结晶R，R-福莫特醇L-酒石酸盐的药物组合物; 和环索奈德。

公开(公告)号：US07041318B2

公开(公告)日：2006-05-09

申请号：US09871876

申请日：2001-06-01

申请人： Jean-Rene Authelin ,  Patrick Hosek

发明人： Jean-Rene Authelin ,  Patrick Hosek

IPC分类号： A61K9/00 ,  A61K9/14 ,  A61K31/357

CPC分类号： A61K9/14 ,  B02C19/06 ,  B02C19/186

摘要： The present invention is a method of milling materials to form a fine powder with a median particle size below 10 micrometer which is suitable for inhalation and which has substantially no amorphous content generated during milling. The method is particularly suitable for milling materials which are soft. The method comprises milling the material in a fluid energy mill at reduced temperature using helium, or helium mixed with another gas, as milling fluid. Temperatures of −30° C. or less are used.

公开(公告)号：US20060002864A1

公开(公告)日：2006-01-05

申请号：US11221186

申请日：2005-09-07

申请人： Jean-Rene Authelin ,  Patrik Hosek

发明人： Jean-Rene Authelin ,  Patrik Hosek

IPC分类号： A61K31/58 ,  A61L9/04 ,  A61K9/14

CPC分类号： A61K9/14 ,  B02C19/06 ,  B02C19/186

摘要： The present invention is a method of milling materials to form a fine powder with a median particle size below 10 micrometer which is suitable for inhalation and which has substantially no amorphous content generated during milling. The method is particularly suitable for milling materials which are soft. The method comprises milling the material in a fluid energy mill at reduced temperature using helium, or helium mixed with another gas, as milling fluid. Temperatures of −30° C. or less are used.

公开(公告)号：USD509296S1

公开(公告)日：2005-09-06

申请号：US29177849

申请日：2003-03-17

申请人： Stephen J. Minshull ,  Martin Miller ,  Duncan G. Young

设计人： Stephen J. Minshull ,  Martin Miller ,  Duncan G. Young

公开(公告)号：US08129537B2

公开(公告)日：2012-03-06

申请号：US12693791

申请日：2010-01-26

申请人： Garry Fenton ,  Tahir Nadeem Majid ,  Malcolm Norman Palfreyman

发明人： Garry Fenton ,  Tahir Nadeem Majid ,  Malcolm Norman Palfreyman

IPC分类号： C07D211/72 ,  A61K31/44

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.

摘要翻译： 本发明涉及[二（醚或硫醚）杂芳基或氟取代的芳基]化合物或其N-氧化物或其药学上可接受的盐，其可用于抑制TNF在治疗中的产生或生理作用 患有与生理上有害的肿瘤坏死因子（TNF）过量相关的疾病状态的患者。 本发明范围内的化合物还抑制环AMP磷酸二酯酶，并且可用于治疗与通过抑制环AMP磷酸二酯酶调节的病理状况相关的疾病状态，所述疾病状态包括炎性和自身免疫性疾病，特别是IV型环AMP 磷酸二酯酶。 因此，本发明涉及其用于抑制TNF和/或环AMP磷酸二酯酶的药理学用途，包含该化合物的药物组合物及其制备方法。

公开(公告)号：US20080132706A1

公开(公告)日：2008-06-05

申请号：US11764317

申请日：2007-06-18

申请人： Garry FENTON ,  Tahir Nadeem MAJID ,  Malcolm Norman PALFREYMAN

发明人： Garry FENTON ,  Tahir Nadeem MAJID ,  Malcolm Norman PALFREYMAN

IPC分类号： C07D213/02 ,  C07C233/00

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.

摘要翻译： 本发明涉及[二（醚或硫醚）杂芳基或氟取代的芳基]化合物或其N-氧化物或其药学上可接受的盐，其可用于抑制TNF在治疗中的产生或生理作用 患有与生理上有害的肿瘤坏死因子（TNF）过量相关的疾病状态的患者。 本发明范围内的化合物还抑制环AMP磷酸二酯酶，并且可用于治疗与通过抑制环AMP磷酸二酯酶调节的病理状况相关的疾病状态，所述疾病状态包括炎性和自身免疫性疾病，特别是IV型环AMP 磷酸二酯酶。 因此，本发明涉及其用于抑制TNF和/或环AMP磷酸二酯酶的药理学用途，包含该化合物的药物组合物及其制备方法。