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72. 发明专利

NO329118B1 未知
公开(公告)号：NO329118B1
公开(公告)日：2010-08-30
申请号：NO993777
申请日：1999-08-04
申请人： INSPIRE PHARMACEUTICALS INC
发明人： PENDERGAST WILLIAM , RIDEOUT JANET L , JACOBUS KARLA M , YERXA BENJAMIN R
IPC分类号： A61K9/06 , A61K31/7068 , A61K9/00 , A61K9/08 , A61K9/10 , A61K9/12 , A61K9/127 , A61K9/14 , A61K31/7072 , A61K31/7076 , A61K31/7084 , A61K45/06 , A61K47/02 , A61K47/14 , A61K47/26 , A61K47/32 , A61K47/34 , A61K47/36 , A61P27/02 , A61P27/04 , C07H19/10 , C07H19/20 , C07H21/00
摘要： A method and preparation for the stimulation of tear secretion in a subject in need of such treatment is disclosed. The method comprises administering to the ocular surfaces of the subject a purinergic receptor agonist such as uridine 5′-triphosphate (UTP), dinucleotides, cytidine 5′-triphosphate (CTP), adenosine 5′-triphosphate (ATP), or their therapeutically useful analogs and derivatives, in an amount effective to stimulate tear fluid secretion and enhance drainage of the lacrimal system. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include: topical administration via a liquid, gel, cream, or as part of a contact lens or selective release membrane; or systemic administration via nasal drops or spray, inhalation by nebulizer or other device, oral form (liquid or pill), injectable, intra-operative instillation or suppository form.

73. 发明专利

NO328229B1 未知
公开(公告)号：NO328229B1
公开(公告)日：2010-01-11
申请号：NO996189
申请日：1999-12-14
申请人： INSPIRE PHARMACEUTICALS INC
发明人： PENDERGAST WILLIAM , YERXA BENJAMIN R
IPC分类号： C07H19/10 , C07H21/00 , A61K31/7084 , A61P11/00 , A61P11/10 , A61P15/02 , A61P27/02 , A61P27/16
摘要： The present invention provides a method of stimulating cervical and vaginal secretions in a mammal by treatment with P2Y 2 and/or P2Y 4 purinergic receptor agonists. Treatment of vaginal dryness associated with menopause, chemotherapy, and various disease states as well as the treatment of vulvar pain is discussed. Suitable agonists such as UTP, CTP, ATP, dinucleotides and analogs thereof are disclosed.

75. 发明专利

CA2279963C DINUCLEOTIDES AND THEIR USE 未知
公开(公告)号：CA2279963C
公开(公告)日：2008-04-22
申请号：CA2279963
申请日：1998-02-06
申请人： INSPIRE PHARMACEUTICALS INC
发明人： RIDEOUT JANET L , PENDERGAST WILLIAM , YERXA BENJAMIN R , SIDDIQI SUHAIB M
IPC分类号： C07H19/207 , C07H21/00 , A61K9/00 , A61K31/70 , A61K31/7084 , A61P9/10 , A61P11/00 , A61P11/10 , A61P27/00 , A61P27/02 , A61P27/16 , A61P43/00 , C07H19/10 , C07H19/20
摘要： The present invention relates to certain novel dinucleotides and formulation s thereof which are highly selective agonists of the P2Y2 and/or P2Y4 purinergic receptor. They are useful in the treatment of chronic obstructive pulmonary diseases such as chronic bronchitis, PCD, cystic fibrosis, as well as prevention of pneumonia due to immobility. Furthermore, because of their general ability to clear retained mucus secretions and stimulate ciliary beat frequency, the compounds of the present invention are also useful in the treatment of sinusitis, otitis media and nasolacrimal duct obstruction. They are also useful for treatment of dry eye disease and retinal detachment.

76. 发明专利

AU764452B2 Method of promoting cervical and vaginal secretions 未知
公开(公告)号：AU764452B2
公开(公告)日：2003-08-21
申请号：AU1741200
申请日：1999-11-19
申请人： INSPIRE PHARMACEUTICALS INC
发明人： PENDERGAST WILLIAM , SHAVER SAMMY R , DRUTZ DAVID J , RIDEOUT JANET L
IPC分类号： C07H19/10 , A61K31/00 , A61K31/7042 , A61K31/7052 , A61K31/7064 , A61K31/7068 , A61K31/7072 , A61K31/7076 , A61K31/708 , A61K31/7084 , A61P15/02 , C07H19/20 , C07H19/207 , C07H21/00
摘要： The present invention provides a method of stimulating cervical and vaginal secretions in a mammal by treatment with P2Y 2 and/or P2Y 4 purinergic receptor agonists. Treatment of vaginal dryness associated with menopause, chemotherapy, and various disease states as well as the treatment of vulvar pain is discussed. Suitable agonists such as UTP, CTP, ATP, dinucleotides and analogs thereof are disclosed.

77. 发明专利

BR0016021A 未知
公开(公告)号：BR0016021A
公开(公告)日：2003-07-15
申请号：BR0016021
申请日：2000-12-22
申请人： INSPIRE PHARMACEUTICALS INC
发明人： YERXA BENJAMIN R , PENDERGAST JANET L , PENDERGAST WILLIAM , SHAVER SAMMY R , ZHANG ZHEN , PETERSON WARD M , COWLEN MATHEW
IPC分类号： C07H19/048 , A61K9/02 , A61K31/00 , A61K31/706 , A61K31/7068 , A61K31/7072 , A61K31/7076 , A61K31/708 , A61K31/7084 , A61K45/00 , A61P1/00 , A61P1/02 , A61P1/04 , A61P1/10 , A61P1/12 , A61P31/10 , A61P43/00 , C07H19/10 , C07H19/20 , C07H19/207
摘要： The invention provides a method of regulating water and mucin secretions and fluid transport in the gastrointestinal tract. The invention also provides a method for treating a gastrointestinal disease in which the mucosal barrier of the gastrointestinal system is impaired. The invention additionally provides a method for correcting disorders of fluid secretion or absorption in the gastrointestinal system. The method comprises administering to a patient a pharmaceutical composition comprising a purinergic P2Y receptor agonist, in an amount effective to regulate water and mucin secretions or to correct abnormal fluid transport in the gastrointestinal tract. The pharmaceutical composition used in this invention comprises a P2Y purinergic receptor agonist such as uridine 5'-diphosphate (UDP), uridine 5'-triphosphate (UTP), cytidine 5'-diphosphate (CDP), cytidine 5'-triphosphate (CTP), adenosine 5'-diphosphate (ADP), adenosine 5'-triphosphate (ATP), and their analogs; and dinucleotide polyphosphate compounds of general Formula (IV). Said compound is prepared in an oral form, an injectable form, or a suppository form, and administered to a patient.

78. 发明专利

NZ337225A Dinucleotides useful for treating chronic pulmonary obstructive disorder 未知
公开(公告)号：NZ337225A
公开(公告)日：2002-03-28
申请号：NZ33722598
申请日：1998-02-06
申请人： INSPIRE PHARMACEUTICALS INC
发明人： PENDERGAST WILLIAM , YERXA BENJAMIN R , RIDEOUT JANET L , SIDDIQI SUHAIB M
IPC分类号： C07H19/207 , A61K9/00 , A61K31/7084 , A61P11/00 , A61P27/02 , A61P27/16 , A61P43/00 , C07H19/10 , C07H19/20 , C07H21/00 , A61K31/70 , C07H21/02
摘要： A di-nucleotide has the formula (I) wherein: X is oxygen, methylene, difluoromethylene or imido; n and m are independently 0, 1 or 2 so that n+m=0, 1, 2, 3 or 4; B and B' are each independently a purine residue or pyrimidine residue linked through the 9- or 1- position respectively; Z and Z' are independently OH or N3; Y and Y' are independently H or OH limited by the provisos listed in the specification. A pharmaceutical composition thereof is useful for treating dry eye, chronic obstructive pulmonary diseases, sinusitis, otitis media or nasolacrimal duct obstruction.

79. 发明专利

BR9814426A 未知
公开(公告)号：BR9814426A
公开(公告)日：2001-10-23
申请号：BR9814426
申请日：1998-12-23
申请人： INSPIRE PHARMACEUTICALS INC
发明人： LACROIX KAROL K , SHAFFER CHRISTY L , JACOBUS KARLA M , RIDEOUT JANET L , DRUTZ DAVID J , EVANS RICHARD M , PENDERGAST WILLIAM
IPC分类号： A61K9/00 , A61K9/08 , A61K9/72 , A61K31/70 , A61K31/7072 , A61K47/02 , A61P43/00
摘要： Novel pharmaceutical compositions of uridine 5'-triphosphate (UTP) for use in promoting increased mucociliary clearance of retained mucous secretions of the human airways, middle/inner ears or sinuses are disclosed. Novel Formulation I comprises UTP and aqueous solution having a therapeutic concentration between 5 and 45 mg/mL, a controlled tonicity within the range of 250 to 100 mOsM, a pH between 7.0 and 7.5, and is sterile. The pH-adjusted composition is capable of long-term storage in the refrigerated state with a shelf life of up to 30 months. Formulation I may be delivered therapeutically either in a nebulized form or in a liquid form. Novel Formulation II comprises UTP in an aqueous solution or suspension having a therapeutic concentration approaching the limit of UTP's solubility at ambient temperature. This high concentration allows delivery of a therapeutic amount of UTP in very small volumes (50 to 100 mu L) suitable for administration via portable hand-held devices such as metered dose inhalers. Formulation II has extended shelf life without the need for refrigeration after being dispensed to the patient.

80. 发明专利

NZ337405A Method of treating dry eye disease with UTP, ATP, and CTP sterile topical formulation 未知
公开(公告)号：NZ337405A
公开(公告)日：2001-07-27
申请号：NZ33740598
申请日：1998-02-06
申请人： INSPIRE PHARMACEUTICALS INC
发明人： YERXA BENJAMIN J , JACOBUS KARLA M , PENDERGAST WILLIAM , RIDEOUT JANET L
IPC分类号： A61K9/06 , A61K9/00 , A61K9/08 , A61K9/10 , A61K9/12 , A61K9/127 , A61K9/14 , A61K31/7068 , A61K31/7072 , A61K31/7076 , A61K31/7084 , A61K45/06 , A61K47/02 , A61K47/14 , A61K47/26 , A61K47/32 , A61K47/34 , A61K47/36 , A61P27/02 , A61P27/04 , C07H19/10 , C07H19/20 , C07H21/00 , C07H19/06
摘要： A method and ophthalmic preparation comprising compounds of Formula II, II(a) and II(b) for the stimulation of tear secretion. The method comprises administering to the ocular surfaces of the subject a purinergic receptor agonist such as uridine 5'-triphosphate [UTP], dinucleotides, cytidine 5'-triphosphate [CTP], adenosine 5'-triphosphate [ATP], or their therapeutically useful analogs and derivatives, in an amount effective to stimulate tear fluid secretion. Methods of administering would include: topical administration via a liquid, gel, cream, or as part of a contact lens or selective release membrane; or systemic administration via nasal drops or spray, inhalation by nebuliser or other device, oral form (liquid or pill), injectable, intra-operative instillation or suppository form. Wherein; X is oxygen, imido, methylene or difluoromethylene; n = 0 or 1; m = 0 or 1; n+m = 0, 1 or 2; and B and B' are each independently a purine residue, as in Formula II(a), or a pyrimidine residue, as in Formula II(b), linked through the 9- or 1-position, respectively; wherein R3 is hydrogen or NHR', R1 and R' of the 8-NHR' groups are chosen from the group consisting of hydrogen, C1-6aryalkyl groups with the aryl moiety optionally having functional groups alkyl, alky groups with functional groups w-A(aIkyl)CONH(alkyl)-, and w-A(alkyl)NHCO(alkyl)-, wherein A is amino, mercaptor, hydroxy, or carboxyl; R2 is O or is absent; or R1 and R2 taken together form a 5-membered fused imidazole ring optionally substituted on the 4' and 5' positions, wherein R4 is hydroxy, mercapto, amino, cyano, aralkoxy, C1-6alkoxy, C1-6alkylamino and dialkylamino, with the alkyl groups optionally linked to form a heterocycle; R5 is hydrogen, acyl, C1-6alkyl, aroyl, C1-5alkanoyl, benzoyl, or sulphonate; R6 is hydroxy, mercapto, alkoxy, aralkoxy, C1-6alkylthio, C1-5disubstitllted amino, triazolyl, alkylamino or dialkylamino, where the alkyl groups are optionally linked to form a heterocycle or linked to N3 to form an optionally substituted ring; R7 is hydrogen, hydroxy, cyano, nitro, alkenyl with the alkenyl moiety optionally linked through oxygen to form a ring optionally substituted on the carbon adjacent to the oxygen with alkyl or aryl groups, substituted alkynyl, halogen, alkyl, substituted alkyl, perhalomethyl, C2-6alkyl, C2-3alkenyl, or substituted ethenyl, C2-3alkynyl or substituted alkynyl; or together R6 -R7 form a 5 or 6-membered saturated or unsaturated ring bonded through N or O at R6, such a ring optionally contains substituents that themselves contain functionalities; provided that when R8 is amino or substituted amino, R7 is hydrogen; and R8 is hydrogen, alkoxy, arylalkoxy, alkylthio, arylalkylthio, carboxamidomethyl, carboxymethyl, methoxy, methylthio, phenoxy or phenylthio; R8 is hydrogen, alkoxy, arylalkoxy, alkylthio, arylalkylthio, carboxamidomethyl, carboxymethyl, methoxy, methylthio, phenoxy or phenylthio.

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