Combination of dehydroepiandrosterone or dehydroepiandrosterone-sulfate with a glucocorticosteroid for treatment of asthma, chronic obstructive pulmonary disease or allergic rhinitis 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
WO2005099720 A2 2005-10-27 [WO200599720]WO2005099720 A3 2009-04-23 [WO200599720] / 2005-10-272009-04-23
申请号/申请日
2005WO-US08636 / 2005-03-15
发明人
ROBINSON CYNTHIA B;BALL HOWARD A;
申请人
EPIGENESIS PHARMACEUTICALS;
主分类号
IPC分类号
A01N-045/00A61K-031/56A61K-031/573A61K-031/58A61K-031/704
摘要
(WO200599720) A pharmaceutical or veterinary composition, comprises a fist active agent selected from a dehydroepiandrostexone and/or dehydroepiandrosterone-sulfate, or a salt thereof, and a second active agent comprising a glucocorticosteroid for the treatment of asthma, chronic obstructive pulmonary disease, allergic rhinitis, or any other respiratory disease.  The composition is provided in various formulations and in the form of a kit.  The products of this patent are applied to the prophylaxis and treatment of asthma, chronic obstructive pulmonary disease, or any other respiratory disease.
机翻摘要
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地址
代理人
代理机构
;
优先权号
2004US-10815576 2004-03-31 2004US-11020652 2004-12-22
主权利要求
(WO200599720) WHAT IS CLAIMED IS: 1. A pharmaceutical composition, comprising a pharmaceutically or veterinarily acceptable carrier, a first active agent and a second active agent effective to treat asthma, chronic obstructive pulmonary disease, or a respiratory or lung disease, the first active agent is at least one of a non-glucocorticoid steroid selected from a non- glucocorticoid steroid having the chemical formula and a non-glucocorticoid steroid of the chemical formula wherein RI, R2, R3, R4, R5, R7, R8, R9, R10, R12, R13, R14 and R19 are independently H, OR, halogen, (Cl-Cl 0) alkyl or (C1-C10) alkoxy, R5 and RI 1 are independently OH, SH, H, halogen, pharmaceutically acceptable ester, pharmaceutically acceptable thioester, pharmaceutically acceptable ether, pharmaceutically acceptable thioether, pharmaceutically acceptable inorganic esters, pharmaceutically acceptable monosaccharide, disaccharide or oligosaccharide, spirooxirane, spirothirane, -OSO2R20, -OPOR20R21 or (C1-C10) alky, R5 and R6 taken together are =O, R10 and RI 1 taken together are =0; R15 is (1) H, halogen, (C1-C10) alkyl, or (C1-C10) alkoxy when R16 is -C(O)OR22, (2) H, halogen, OH or (C1-C10) alkyl when R16 is halogen, OH or (C1-C10) alkyl, (3) H, halogen, (Cl-ClO) alkyl, (C1-C10) alkenyl, (C1-C10) alkynyl, formyl, (C1-C10) alkanoyl or epoxy when R16 is OH, (4) OR, SH, H, halogen, pharmaceutically acceptable ester, pharmaceutically acceptable thioester, pharmaceutically acceptable ether, pharmaceutically acceptable thioether, pharmaceutically acceptable inorganic esters, pharmaceutically acceptable monosaccharide, disaccharide or oligosaccharide, spirooxirane, spirothirane, -OSO2R20 or - OPOR20R21 when R16 is H, or R15 and R16 taken together are =O; R17 and R18 are independently (1) H, -OH, halogen, (Cl-ClO) alkyl or -( C1-C10) alkoxy when R6 is H OR, halogen. (Cl-ClO) alkyl or -C(O)OR22, (2) H, (Cl-ClO alkyl).amino, ((Cl-ClO) alkyl)n amino-( Cl-ClO) alkyl, (Cl-ClO) alkoxy, hydroxy - (Cl-ClO) alkyl, (Cl-ClO) alkoxy - (Cl-ClO) alkyl, (halogen)m (Cl-ClO) alkyl, (Cl-ClO) alkanoyl, formyl, (Cl-ClO) carbalkoxy or (Cl-ClO) alkanoyloxy when R15 and R16 taken together are =O, (3) R17 and R18 taken together are =O; (4) RI 7 or RI 8 taken together with the carbon to which they are attached form a 3-6 member ring containing 0 or 1 oxygen atom; or (5) R15 and R17 taken together with the carbons to which they are attached form an epoxide ring; R20 and R21 are independently OH, pharmaceutically acceptable ester or pharmaceutically acceptable ether; R22 is H, (halogen)m (Cl-ClO) alkyl or (Cl-ClO) alkyl; n is 0, 1 or 2; and m is 1, 2 or 3; or pharmaceutically or veterinarily acceptable salts thereof; and (b) the second active agent is a glucocorticosteroid. 2. , The pharmaceutical composition of claim 1 , wherein the first active agent is a non- glucocorticoid steroid having the chemical formula (I), wherein said multivalent organic dicarboxylic acid is SO2OM, phosphate or carbonate, wherein M comprises a counterion, wherein said counterion is H, sodium, potassium, magnesium, aluminum, zinc, calcium, lithium, ammonium, amine, arginine, lysine, histidine, triethylamine, ethanolamine, choline, triethanolamine, procaine, benzathine, tromethanine, pyrrolidine, piperazine, diethylamine, sulfatide -SO2O-CH2CHCH2OCOR3; OCOR2or phosphatide O -P-OCH2CHCH2OCOR3 O OCOR2 wherein R2and R3, which are the same or different, and are straight or branched (Cι-Cι4) alkyl or glucuronide  3. The pharmaceutical composition ofclaim 2, wherein said first active agent is dehydroepiandrosterone. 4. The pharmaceutical composition of claim 2, wherein said first active agent is dehydroepiandrosterone-sulfate. 5. The pharmaceutical composition ofclaim 1, wherein said glucocorticosteroid is a compound having the formula: where X is halogen, R is a C2-C6alkanoyl group and RI is a grouping selected from the group consisting of hydrogen and Cι-C alkanoyl groups, wherein the total number of carbon atoms in the groups R and RI being from 3 to 9. 6. The pharmaceutical composition of claim 5, wherein said glucocorticosteroid is beclomethasone dipropionate. 7. The pharmaceutical composition of claim 1 , wherein said glucocorticosteroid is a compound having the formula: wherein X and Y are independently selected from hydrogen and fluorine, wherein X is selected from hydrogen and X being fluorine when Y is fluorine, Z is selected from hydroxyl and esterified hydroxyl and containing 12 or fewer carbon atoms in the esterifying group, R is selected from straight and branched hydrocarbon chains having 2-10 carbon atoms. 8. The pharmaceutical composition of claim 1, wherein said glucocorticosteroid is budesonide. 9. The pharmaceutical composition ofclaim 1, wherein said glucocorticosteroid is a compound having the formula: wherein R and RI is hydrogen or the residue of a hydrocarbon of up to 8 carbon atoms of straight, branched, cyclic or mixed aliphatic-cyclic chain, saturated or unsaturated, wherein X represents fluorine or chlorine, wherein XI represents hydrogen, fluorine or chlorine, wherein Y represents =O or β-OH, wherein Z represents a double bond between C-1 and C-2, wherein R2 represents hydrogen or a hydrocarbon carboxylic acyl group of up to 12 carbon atoms. 10. The pharmaceutical composition of claim 9, wherein said glucocorticosteroid is flunisolide. 11. The pharmaceutical composition of claim 1 , wherein said glucocorticosteroid is a compound having the formula: (Villa) wherein RI represents a fluoro-, chloro- or bromo-methyl group or a 2'-fluoroethyl group, R2 represents a group COR6 where R6 is a Cι-C3alkyl group or OR2 and R3 together form a 16α, 17α-isopropylidenedioxy group; R3 represents a hydrogen atom, a methyl group (which may be in either the α- or β- configuration) or a methylene group; R4 represents a hydrogen, chlorine or fluorine atom; R5 represents a hydrogen or fluorine atom and the symbol — — - — represents a single or double bond. 12. The pharmaceutical composition of claim 11 , wherein said glucocorticosteroid is a fluticasone propionate. 13. The pharmaceutical composition of claim 1 , wherein said glucocorticosteroid is a compound having the formula: wherein >CC-Cd-Ce- is a trivalent substituted three carbon chain of the group consisting of 7 A and B are hydrogen or lower alkyl radicals; Ca-Cbis a divalent radical of the group consisting of-CH2CH2-; -CH=CH-; — CBjt— CHCHs} M3BβO--<JH and Y is a monovalent radical of the group consisting of-CH3; -CH2OH;  14. The pharmaceutical composition of claim 13, wherein said glucocorticosteroid is triamcinolone acetonide. 15. The pharmaceutical composition of claim 1 , further comprising a ubiquinone or pharmaceutically or veterinarily acceptable salt thereof, wherein the ubiquinone has the chemical formula wherein n is 1 to 12. 16. The pharmaceutical composition ofclaim 1, wherein the pharmaceutical composition comprises particles of inhalable or respirable size. 17. The pharmaceutical composition ofclaim 16, wherein the particles are about 0.01 μm to about 10 μm in size. 18. The pharmaceutical composition ofclaim 16, wherein the particles are about 10 μm to about 100 μm in size. 19. A kit comprising a delivery device and the pharmaceutical composition of claim 1. 20. The kit of claim 19, wherein the delivery device is an aerosol generator or spray generator. 21. The kit of claim 20, wherein the aerosol generator comprises an inhaler. 22. The kit of claim 21 , wherein the inhaler delivers individual pre-metered doses of the formulation 23. The kit of claim 22, wherein the inhaler comprises a nebulizer or insufflator. .24. A method for reducing the probability of or treating asthma in a subject, comprising administering to a subject in need of such treatment a prophylactically or therapeutically effective amount of the pharmaceutical composition ofclaim 1. 25. A method for reducing the probability of or treating of chronic obstructive pulmonary disease in a subject, comprising administering to a subject in need of such treatment a prophylactically or therapeutically effective amount of the pharmaceutical composition ofclaim 1. 26. A method for treatment of respiratory, lung or malignant disorder or condition, or for reducing levels of, or sensitivity to, adenosine or adenosine receptors in a subject, comprising administering to a subject in need of such treatment a prophylactically or therapeutically effective amount of the pharmaceutical composition of claim 1. 27. The method ofclaim 26, wherein the disorder or condition comprises asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis, cystic fibrosis (CF), dyspnea, emphysema, wheezing, pulmonary hypertension, pulmonary fibrosis, hyper-responsive airways, increased adenosine or adenosine receptor levels, adenosine hyper-sensitivity, infectious diseases, pulmonary bronchoconstriction, respiratory tract inflammation or allergies, lung surfactant or ubiquinone depletion, chronic bronchitis, bronchoconstriction, difficult breathing, impeded or obstructed lung airways, adenosine test for cardiac function, pulmonary vasoconstriction, impeded respiration, Acute Respiratory Distress Syndrome (ARDS), administration of adenosine or > adenosine level increasing drugs, infantile Respiratory Distress Syndrome (infantile RDS), pain, allergic rhinitis, cancer, or chronic bronchitis.
法律状态
(WO200599720) LEGAL DETAILS FOR WO2005099720  Actual or expected expiration date=2007-09-30    Legal state=DEAD    Status=LAPSED     Event publication date=2005-03-15  Event code=WO/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=WO WOUS2005008636  Application date=2005-03-15  Standardized application number=2005WO-US08636     Event publication date=2005-10-27  Event code=WO/A2  Event type=Examination events  International application published without international search report  Publication country=WO  Publication number=WO2005099720  Publication stage Code=A2  Publication date=2005-10-27  Standardized publication number=WO200599720     Event publication date=2005-10-27  Event code=WO/AL  Event indicator=Pos  Event type=Designated states  Designated countries for regional patents BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG    Event publication date=2005-10-27  Event code=WO/AK  Event indicator=Pos  Event type=Designated states  Designated states AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SM SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW    Event publication date=2007-09-30  Event code=WO/EETL  Event type=Event indicating Not In Force  PCT Application validity period expired.    Event publication date=2009-04-23  Event code=WO/A3  Event indicator=Pos  Event type=Examination events  Later publication of ISR with revised front page  Publication country=WO  Publication number=WO2005099720  Publication stage Code=A3  Publication date=2009-04-23  Standardized publication number=WO200599720  LEGAL DETAILS FOR DESIGNATED STATE AU2005232532  Actual or expected expiration date=2012-10-11    Legal state=DEAD    Status=EXPIRED   Corresponding cc:  Designated or member state=AU Corresponding appl: AU2005232532  Application date in the designated or member state=2005-03-15   Application number in the designated or member state=2005AU-0232532 Corresponding cc:  Designated or member state=AU Corresponding pat: AU2005232532  Publication stage code in the designated or member state=A1  Publication date in the designated or member state=2005-10-27   Publication number in the designated or member state=AU2005232532    Event publication date=2007-01-19  Event code=WO/WWE  Event indicator=Pos  Event type=Entry into national phase  Wipo information: entry into national phase Corresponding cc:  Designated or member state=AU     Event publication date=2007-03-22  Event code=WO/WWP  Event indicator=Pos  Event type=Examination events  Wipo information: published in national office Corresponding cc:  Designated or member state=AU     Event publication date=2007-03-22  Event code=WO/ENP  Event type=Entry into national phase  Entry into the national phase in: Corresponding cc:  Designated or member state=AU     Event publication date=2012-10-11  Event code=AU/STCHG  Patent Status changed by the national office Corresponding cc:  Designated or member state=AU  LEGAL DETAILS FOR DESIGNATED STATE CA2575602  Actual or expected expiration date=2013-02-11    Legal state=DEAD    Status=LAPSED   Corresponding cc:  Designated or member state=CA Corresponding appl: CA2575602  Application date in the designated or member state=2005-03-15   Application number in the designated or member state=2005CA-2575602 Corresponding cc:  Designated or member state=CA Corresponding pat: CA2575602  Publication stage code in the designated or member state=A1  Publication date in the designated or member state=2005-10-27   Publication number in the designated or member state=CA2575602    Event publication date=2007-01-29  Event code=WO/WWE  Event indicator=Pos  Event type=Entry into national phase  Wipo information: entry into national phase Corresponding cc:  Designated or member state=CA     Event publication date=2013-04-08  Event code=CA/STCHG  Patent Status changed by the national office Corresponding cc:  Designated or member state=CA  LEGAL DETAILS FOR DESIGNATED STATE DE  Actual or expected expiration date=2006-10-03    Legal state=DEAD    Status=LAPSED   Corresponding cc:  Designated or member state=DE     Event publication date=2006-10-03  Event code=WO/WWW  Event indicator=Neg  Event type=Event indicating Not In Force  Wipo information: withdrawn in national office Corresponding cc:  Designated or member state=DE     Event publication date=2006-10-03  Event code=WO/NENP  Event type=Event indicating Not In Force  Non-entry into the national phase in: Corresponding cc:  Designated or member state=DE  LEGAL DETAILS FOR DESIGNATED STATE EP1784197  Actual or expected expiration date=2011-11-03    Legal state=DEAD    Status=LAPSED   Corresponding cc:  Designated or member state=EP Corresponding appl: EP05725668  Application date in the designated or member state=2005-03-15   Application number in the designated or member state=2005EP-0725668 Corresponding cc:  Designated or member state=EP Corresponding pat: EP1784197  Publication stage code in the designated or member state=A2  Publication date in the designated or member state=2007-05-16   Publication number in the designated or member state=EP1784197    Event publication date=2005-12-21  Event code=WO/121  Event type=Designated states  EP: The EPO has been informed by wipo that ep was designated in this application Corresponding cc:  Designated or member state=EP     Event publication date=2007-01-19  Event code=WO/WWE  Event indicator=Pos  Event type=Entry into national phase  Wipo information: entry into national phase Corresponding cc:  Designated or member state=EP     Event publication date=2007-05-16  Event code=WO/WWP  Event indicator=Pos  Event type=Examination events  Wipo information: published in national office Corresponding cc:  Designated or member state=EP     Event publication date=2012-06-06  Event code=EP/STCHG  Patent Status changed by the national office Corresponding cc:  Designated or member state=EP
专利类型码
A2A3
国别省市代码
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