Treatment of gout

Sodium 2-(5-bromo-4-(4-cyclopropyl-naphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetate is described. In addition, pharmaceutical compositions and uses such compositions for the treatment of a variety of diseases and conditions.

METHOD FOR TREATMENT OF CONSTIPATION-PREDOMINANT IRRITABLE BOWEL SYNDROME

The present invention provides methods for treating constipation-predominant irritable bowel syndrome comprising administering to a patient in need thereof, a polymeric proanthocyanidin composition from a species or species in an amount sufficient to treat constipation-predominant irritable bowel syndrome (c-IBS). Treatment of c-IBS includes the treatment of the constipation component of c-IBS as well as the pain and abdominal discomfort associated with c-IBS. In one embodiment, the polymeric proanthocyanidin compound is crofelemer. The present invention in an alternative embodiment also provides methods for treating alternating constipation-predominant/diarrhea-predominant irritable bowel syndrome. 111.-. (canceled)12CrotonCalophyllum. A method of treating alternating constipation-predominant/diarrhea-predominant irritable bowel syndrome (a-IBS) , comprising administering to a patient in need of such treatment , an amount of an extract or latex isolated from spp. or spp. effective to treat a-IBS.13CrotonCalophyllum. A method of treating alternating constipation-predominant/diarrhea-predominant irritable bowel syndrome (a-IBS) , comprising administering to a patient in need of such treatment , an amount of a polymeric proanthocyanidin composition isolated from spp. or spp. effective to treat a-IBS.14. The method of or , in which said amount is bioequivalent to an orally administered dose of about 50 mg per day to about 4000 mg per day of crofelemer.15. The method of claim 14 , in which said amount bioequivalent to an orally administered dose of about 500 mg per day to about 1500 mg per day of crofelemer.16. The method of claim 13 , in which the polymeric proanthocyanidin composition is crofelemer.17. The method of claim 13 , wherein the polymeric proanthocyanidin composition comprises at least one monomer selected from the group consisting of catechin claim 13 , epicatechin claim 13 , gallocatechin and epigallocatechin.18. The method of or claim 13 , wherein the ...

NOVEL COMPOUNDS AND COMPOSITIONS AND METHODS OF USE

Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid. 172-. (canceled)74. The method of claim 73 , wherein W is S.75. The method of claim 73 , wherein Rand R are H.76. The method of claim 74 , wherein Rand R are H.77. The method of claim 73 , wherein Ris Br.78. The method of claim 76 , wherein Ris Br.80. The method of claim 73 , wherein the pharmaceutically acceptable salt is administered to the human claim 73 , and wherein the pharmaceutically acceptable salt is an ammonium claim 73 , a primary amine claim 73 , a secondary amine claim 73 , a tertiary amine claim 73 , a lithium claim 73 , a sodium claim 73 , a potassium claim 73 , a calcium claim 73 , a magnesium claim 73 , or an aluminum salt.81. The method of claim 80 , wherein the pharmaceutically acceptable salt is a sodium salt.82. The method of claim 73 , wherein said administering is orally.83. The method of claim 73 , wherein said compound is administered in combination with a pharmaceutically acceptable carrier claim 73 , excipient claim 73 , or diluent claim 73 , in a pharmaceutical composition.84. The method of claim 83 , wherein the pharmaceutical composition is a tablet or capsule.85. The method of claim 83 , wherein the pharmaceutical composition is a tablet.86. The method of claim 85 , wherein the pharmaceutical composition is a coated tablet.87. The method of claim 85 , wherein the tablet comprises lactose.88. The method of claim 85 , wherein the tablet comprises microcrystalline cellulose.89. The method of claim 85 , wherein the tablet comprises sodium croscarmellose.90. The method of claim 84 , wherein the tablet or capsule comprises gelatin.91. The method of claim 85 , wherein the tablet comprises magnesium stearate.92. The method of claim 85 , wherein the tablet ...

TREATMENT OF GOUT

Sodium 2-(5-bromo-4-(4-cyclopropyl-naphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetate is described. In addition, pharmaceutical compositions and uses such compositions for the treatment of a variety of diseases and conditions. 1. A method of treating gout comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 ,2 ,4-triazol-3-ylthio)acetate , or a pharmaceutically acceptable salt thereof , and colchicine to a subject.2. The method of claim 1 , wherein said method provides greater mean gout flare reduction than co-administration of colchicine and a therapeutic agent that is not a dual inhibitor of URAT1 and an inflammasome.3. The method of claim 1 , wherein the total dosage of colchicine administered during co-administration with 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 1 ,2 claim 1 ,4-triazol-3-ylthio)acetate claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , is at least 50% less than the total dosage of colchicine that would be required for a similar effect when co-administered with a therapeutic agent that is not a dual inhibitor of URAT1 and an inflammasome.4. The method of claim 1 , wherein the amount of time that colchicine is co-administered with 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 1 ,2 claim 1 ,4-triazol-3-ylthio)acetate claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , is at least one week less than would be required for a similar effect when colchicine is co-administered with a therapeutic agent that is not a dual inhibitor of URAT1 and an inflammasome.5. A method of reducing monosodium urate induced inflammation in a subject in need thereof claim 1 , the method comprising administering a pharmaceutical composition comprising a pharmaceutical agent having both uricosuric and anti-inflammatory activity.6. The method of claim 5 , wherein the pharmaceutical agent is a URAT1 inhibitor with anti-inflammatory activity.7. The method of claim 5 , wherein the pharmaceutical ...

TREATMENT OF GOUT AND HYPERURICEMIA

Sodium 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetate is described. In addition, pharmaceutical compositions and uses of such compositions for the treatment of a variety of diseases and conditions are described. 1. A method of reducing serum uric acid levels , treating hyperuricemia , or treating gout in a human comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 ,2 ,4-triazol-3-ylthio)acetate , or a pharmaceutically acceptable salt thereof , and febuxostat to the human , wherein said method providesserum urate levels of less than 6 mg/dL.2. (canceled)3. (canceled)4. (canceled)5. (canceled)6. The method of claim 1 , wherein the gout in the human is characterized by the presence of large accumulated deposits of uric acid or tophi.7. (canceled)8. (canceled)9. (canceled)10. The method of claim 1 , wherein the daily dose of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 1 ,2 claim 1 ,4-triazol-3-ylthio)acetate claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , is about 400 mg.11. The method of claim 1 , wherein the daily dose of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 1 ,2 claim 1 ,4-triazol-3-ylthio)acetate claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , is about 200 mg.12. The method of claim 1 , wherein the daily dose is administered orally.13. The method of claim 1 , wherein the daily dose is administered in the morning.14. The method of claim 1 , wherein the daily dose is administered with food.15. A method of reducing serum uric acid levels claim 1 , treating hyperuricemia claim 1 , or treating gout in a human comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 1 ,2 claim 1 ,4-triazol-3-ylthio)acetate claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and allopurinol to the human claim 1 , wherein said method providesserum urate levels of less than 6 mg/dL.16. (canceled)17. (canceled)18. (canceled)19. ...

METHODS FOR TREATING HYPERURICEMIA AND RELATED DISEASES

Provided herein are methods of treating gout, treating hyperuricemia, lowering serum uric acid, or the like with compounds of formula (I) have the following structure Further, provided herein are compositions comprising a compound of formula (I). 120-. (canceled)28. The method of claim 27 , comprising administering from about 100 mg to about 1000 mg of the compound of formula (I).29. The method of claim 27 , comprising administering from about 100 mg to about 1000 mg of allopurinol.33. The method of claim 32 , wherein prior to administration the subject has a serum uric acid level greater than about 6.0 mg/dL.34. The method of claim 32 , wherein after administration the subject has a creatinine clearance rate of from about 30 mL/minute to about 60 mL/minute.35. The method of claim 32 , further comprising administering allopurinol. Gout is a condition that results from uric acid crystals depositing in tissues of the body. It is often related to an inherited abnormality in the body's ability to process uric acid, but may also be exacerbated by a diet high in purines. Defective uric acid processing may lead to elevated levels of uric acid in the blood causing recurring attacks of joint inflammation (arthritis), uric acid deposits in and around the joints, decreased kidney function, and kidney stones. Approximately 3-5 million people in the United States suffer from attacks of gout with attacks 6 to 9 times more common in men than in women (see Sanders and Wortmann, “Harrison's Principles of Internal Medicine”, 16th Edition; 2005; Food and Drug Administration (FDA) Advisory Committee Meeting, Terkeltaub presentation, June 2004; Terkeltaub, “Gout”, 349, 1647-55, 2003).Provided in certain embodiments herein is a method of treating gout or hyperuricemia in a subject, wherein the gout is refractory, non-responsive, and/or resistant to a monotherapy with an agent other than a compound of formula (I), the method comprising administering to the subject a therapeutically ...

NOVEL COMPOUNDS AND COMPOSITIONS AND METHODS OF USE

Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid. 2. The compound of claim 1 , wherein:X is N.3. The compound of claim 1 , wherein:W is S or O.5. The compound of claim 4 , wherein:{'img': {'@id': 'CUSTOM-CHARACTER-00008', '@he': '2.12mm', '@wi': '4.57mm', '@file': 'US20140005136A1-20140102-P00001.TIF', '@alt': 'custom-character', '@img-content': 'character', '@img-format': 'tif'}, 'represents a carbon-carbon double bond; and'}{'sup': 'P', 'Ris cyclopropyl.'}6. The compound of claim 1 , wherein:X is N;W is S; and{'sup': '1', 'sub': 3', '2', '2, 'Ris Cl, Br, I, optionally substituted methyl, CF, CHFor CHF.'}7. The compound of claim 1 , wherein:{'sup': 3', '3′, 'Rand R are not H.'}8. The compound of claim 1 , wherein:{'sup': 3', '3′, 'Rand R are H.'}9. The compound of claim 1 , wherein:{'sup': 3', '3′, 'Rand R together with the carbon to which they are attached form a 4-, 5-, or 6-membered ring, optionally containing 1 or 2 heteroatoms selected from N, S and O.'}10. The compound of claim 1 , wherein:{'sup': 3', '3′, 'Rand R together with the carbon to which they are attached form a 4-, 5-, or 6-membered ring.'}12. The compound of claim 11 , wherein:{'sup': '1a', 'Ris at least one amino acid.'}13. The compound of claim 11 , wherein:{'sup': '1a', 'Ris a peptide.'}14. The compound of claim 11 , wherein:{'sup': '1a', 'Ris a lipid.'}15. The compound of claim 11 , wherein:{'sup': '1a', 'Ris a phospholipid.'}16. The compound of claim 11 , wherein:{'sup': '1a', 'Ris a glycoside.'}17. The compound of claim 11 , wherein:{'sup': '1a', 'Ris a nucleoside.'}18. The compound of claim 11 , wherein:{'sup': '1a', 'Ris a nucleotide.'}19. The compound of claim 11 , wherein:{'sup': '1a', 'Ris an oligonucleotide.'}20. The compound of claim 11 , wherein:{'sup': ...

Treatment of Gout and Hyperuricemia

Sodium 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetate is described. In addition, pharmaceutical compositions and uses of such compositions for the treatment of a variety of diseases and conditions are described. 1. A method of treating gout comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 ,2 ,4-triazol-3-ylthio)acetate , or a pharmaceutically acceptable salt thereof , and febuxostat to a subject , wherein said method provides:a. serum urate levels of less than 6 mg/dL;b. serum urate levels of less than 5 mg/dL;c. serum urate levels of less than 4 mg/dL;d. serum urate levels of less than 3 mg/dL;e. serum urate levels intraday change of more than 50%;f. serum urate levels intraday change of more than 60%;g. or a combination thereof.2. A method of reducing serum uric acid levels in a human comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 ,2 ,4-triazol-3-ylthio)acetate , or a pharmaceutically acceptable salt thereof , and febuxostat to a subject , wherein said method provides:a. serum urate levels of less than 6 mg/dL;b. serum urate levels of less than 5 mg/dL;c. serum urate levels of less than 4 mg/dL;d. serum urate levels of less than 3 mg/dL;e. serum urate levels intraday change of more than 50%;f. serum urate levels intraday change of more than 60%;g. or a combination thereof.3. A method of treating hyperuricemia in a human comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 ,2 ,4-triazol-3-ylthio)acetate , or a pharmaceutically acceptable salt thereof , and febuxostat to a subject , wherein said method provides:a. serum urate levels of less than 6 mg/dL;b. serum urate levels of less than 5 mg/dL;c. serum urate levels of less than 4 mg/dL;d. serum urate levels of less than 3 mg/dL;e. serum urate levels intraday change of more than 50%;f. serum urate levels intraday change of more than 60%;g. or a combination thereof.4. A method of treating ...

METHOD FOR TREATMENT OF DIARRHEA-PREDOMINANT IRRITABLE BOWEL SYNDROME

The present invention provides methods for treating diarrhea-predominant irritable bowel syndrome comprising administering to a patient in need thereof, an inhibitor of chloride-ion transport in an amount sufficient to treat diarrhea-predominant irritable bowel syndrome (d-IBS). Treatment of d-IBS includes the treatment of the diarrhea component of d-IBS as well as the pain, abdominal discomfort and other symptoms associated with d-IBS. In one embodiment, the inhibitor of chloride-ion transport is crofelemer. 131-. (canceled)32. A method of treating a patient having pain associated with diarrhea-predominant irritable bowel syndrome (d-IBS) , comprising administering to the patient a composition comprising an inhibitor of cystic fibrosis transmembrane conductance regulator's (CFTR) chloride-ion channel function in an amount effective to treat pain associated with d-IBS.33. The method of claim 32 , wherein the inhibitor is a proanthocyanidin polymer.34CrotonCalophyllum. The method of claim 33 , wherein the proanthocyanidin polymer is derived from spp. or spp.35C. lechleri.. The method of claim 34 , wherein the proanthocyanidin polymer Is derived from36. The method of claim 32 , wherein the composition comprises at least one monomer selected from the group consisting of catechin claim 32 , epicatechin claim 32 , gallocatechin claim 32 , and epigallocatechin.37. The method of claim 32 , wherein the inhibitor is crofelemer.38. The method of claim 32 , wherein the composition is orally administered.39. The method of claim 38 , wherein the inhibitor is crofelemer.40. The method of claim 39 , wherein crofelemer is enteric coated.41. The method of claim 39 , wherein crofelemer is administered to the patient at about 50 mg per day to about 750 mg per day.42. The method of claim 39 , wherein crofelemer is administered to the patient at about 50 mg per day to about 500 mg per day.43. The method of claim 39 , wherein crofelemer is administered to the patient at about 500 mg ...

Compositions and methods for treating or preventing inflammatory bowel disease, familial adenomatous polyposis and colon cancer

The present invention provides methods for preventing colon cancer by administering, to a patient in need thereof, a polymeric proanthocyanidin composition from a Croton species or Calophyllum species in an amount sufficient to prevent colon cancer, which composition inhibits COX-2. The present invention also provides methods for treating inflammation locally in the intestines comprising administering to a patient in need thereof, a polymeric proanthocyanidin composition from a Croton species or Calophyllum species in an amount sufficient to treat inflammation. In one embodiment, the polymeric proanthocyanidin compound is crofelemer. The present invention in alternative embodiments provides methods for treating pain locally in the intestines and treating inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, as well as for treating familial adenomatous polyposis (FAP).

POST-SURGICAL PAIN TREATMENT

Disclosed herein are compositions and methods for treating post-surgical pain in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a NK-1 receptor antagonist and a pain medication. 1. A method for treating post-surgical pain in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a NK-1 receptor antagonist in combination with a pain medication.2. The method of claim 1 , wherein the post-surgical pain is not neuropathic.3. The method of claim 1 , wherein the NK-1 receptor antagonist is selected from aprepitant claim 1 , rolapitant claim 1 , netupitant claim 1 , lanepitant claim 1 , vestipitant claim 1 , orvepitant maleate claim 1 , casopitant claim 1 , ezlopitant claim 1 , serlopitant claim 1 , fosaprepitant claim 1 , befetupitant and maropitant claim 1 , and a pharmaceutically acceptable salt thereof.4. The method of claim 1 , wherein the pain medication is selected from local anesthetics claim 1 , opioids claim 1 , non-steroid anti-inflammatory drug (NSAID) claim 1 , anticonvulsants claim 1 , serotonin and norepinephrine reuptake inhibitors (SNRIs) claim 1 , acetaminophen claim 1 , and tricyclic antidepressants.5. The method of claim 1 , wherein the NK-1 receptor antagonist is aprepitant.6. The method of claim 1 , wherein the pain medication is a local anesthetic and a NSAID.7. The method of claim 4 , wherein the local anesthetic is selected from bupivacaine claim 4 , levobupivacaine claim 4 , ropivacaine claim 4 , etidocaine claim 4 , lidocaine claim 4 , mepivacaine claim 4 , prilocaine claim 4 , and tetracaine.8. The method of claim 7 , wherein the local anesthetic is bupivacaine or ropivacaine.9. The method of claim 4 , wherein the NSAID is selected from the group consisting of diflunisal claim 4 , indomethacin claim 4 , tolmetin claim 4 , sulindac claim 4 , etodolac claim 4 , ketorolac claim 4 , diclofenac claim 4 , nabumetone claim 4 , ibuprofen claim 4 , ...

TREATMENT OF GOUT AND HYPERURICEMIA

Sodium 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetate is described. In addition, pharmaceutical compositions and uses of such compositions for the treatment of a variety of diseases and conditions are described. 1. A method of reducing serum uric acid levels , treating hyperuricemia , or treating gout in a human comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 ,2 ,4-triazol-3-ylthio)acetate , or a pharmaceutically acceptable salt thereof , and febuxostat to the human , wherein said method providesserum urate levels of less than 6 mg/dL; andwherein said method provides a serum urate levels intraday change from baseline of more than 50%.2. A method of reducing serum uric acid levels , treating hyperuricemia , or treating gout in a human comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 ,2 ,4-triazol-3-ylthio)acetate , or a pharmaceutically acceptable salt thereof , and febuxostat to the human , wherein said method providesserum urate levels of less than 4 mg/dL.3. (canceled)4. (canceled)5. (canceled)6. A method of treating gout in a human comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 ,2 ,4-triazol-3-ylthio)acetate , or a pharmaceutically acceptable salt thereof , and febuxostat to the human , wherein said method provides serum urate levels of less than 6 mg/dL; and wherein the gout in the human is characterized by the presence of large accumulated deposits of uric acid or tophi.725.-. (canceled)26. A method of reducing serum uric acid levels , treating hyperuricemia , or treating gout in a human comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 ,2 ,4-triazol-3-ylthio)acetate , or a pharmaceutically acceptable salt thereof , and febuxostat to the human , wherein the method provides serum urate levels of less than 6 mg/dL , and wherein said method results in an adverse event in less than 15% of the subjects. This ...

3,4-DI-SUBSTITUTED PYRIDINE COMPOUND, METHODS OF USING AND COMPOSITIONS COMPRISING THE SAME

2-((3-(4-cyanonaphthalen-1-yl)pyridin-4-yl)thio)-2-methylpropanoic acid is useful in the modulation of blood or serum uric acid levels. In some embodiments, 2-((3-(4-cyanonaphthalen-1-yl)pyridin-4-yl)thio)-2-methylpropanoic acid is used in the treatment or prevention of disorders related to aberrant levels of uric acid. In some embodiments, 2-((3-(4-cyanonaphthalen-1-yl)pyridin-4-yl)thio)-2-methylpropanoic acid is used for reducing serum uric acid levels in a human. Also described herein are compositions comprising 2-((3-(4-cyanonaphthalen-1-yl)pyridin-4-yl)thio)-2-methylpropanoic acid, and their use in the modulation of blood or serum uric acid levels. 145-. (canceled)46. A pharmaceutical composition comprising between about 2 mg and less than 10 mg of 2-((3-(4-cyanonaphthalen-1-yl)pyridin-4-yl)thio)-2-methylpropanoic acid , or a pharmaceutically acceptable salt thereof , and a pharmaceutically acceptable excipient.47. The pharmaceutical composition of claim 46 , comprising about 4 mg of 2-((3-(4-cyanonaphthalen-1-yl)pyridin-4-yl)thio)-2-methylpropanoic acid claim 46 , or a pharmaceutically acceptable salt thereof.48. The pharmaceutical composition of claim 46 , comprising about 2 mg of 2-((3-(4-cyanonaphthalen-1-yl)pyridin-4-yl)thio)-2-methylpropanoic acid claim 46 , or a pharmaceutically acceptable salt thereof.49. The pharmaceutical composition of claim 46 , comprising about 5 mg of 2-((3-(4-cyanonaphthalen-1-yl)pyridin-4-yl)thio)-2-methylpropanoic acid claim 46 , or a pharmaceutically acceptable salt thereof.50. The pharmaceutical composition of claim 46 , comprising between about 2 mg and about 5 mg of 2-((3-(4-cyanonaphthalen-1-yl)pyridin-4-yl)thio)-2-methylpropanoic acid claim 46 , or a pharmaceutically acceptable salt thereof.51. The pharmaceutical composition of claim 46 , further comprising allopurinol.52. The pharmaceutical composition of claim 47 , further comprising allopurinol.53. The pharmaceutical composition of claim 48 , further comprising ...

Novel Compounds and Compositions and Methods of Use

Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid.

Methods for Treating Hyperuricemia and Related Diseases

Provided herein are methods of treating gout, treating hyperuricemia, lowering serum uric acid, or the like with compounds of formula (I) have the following structure Further, provided herein are compositions comprising a compound of formula (I).

3,4-DI-SUBSTITUTED PYRIDINE COMPOUND, METHODS OF USING AND COMPOSITIONS COMPRISING THE SAME

2-((3-(4-cyanonaphthalen-1-yl)pyridin-4-yl)thio)-2-methylpropanoic acid is useful in the modulation of blood or serum uric acid levels. In some embodiments, 2-((3-(4-cyanonaphthalen-1-yl)pyridin-4-yl)thio)-2-methylpropanoic acid is used in the treatment or prevention of disorders related to aberrant levels of uric acid. In some embodiments, 2-((3-(4-cyanonaph-thalen-1-yl)pyridin-4-yl)thio)-2-methylpropanoic acid is used for reducing serum uric acid levels in a human. Also described herein are compositions comprising 2-((3-(4-cyanonaphthalen-1-yl)pyridin-4-yl)thio)-2-methylpropanoic acid, and their use in the modulation of blood or serum uric acid levels.

Novel compounds and compositions and methods of use

Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid.

METHOD OF ADMINISTERING EMULSION FORMULATIONS OF AN NK-1 RECEPTOR ANTAGONIST

Disclosed herein are methods of administering pharmaceutical formulations of a neurokinin-1 (NK-1) receptor antagonist to a subject in need of treatment of emesis. 1. A method for treating a subject in need thereof , comprising intravenously administering to the subject a single dose of a stable emulsion at an average rate of about 6.5 to 70 mg/minute of an NK-1 receptor antagonist comprised in the stable emulsion , wherein the stable emulsion comprises:the NK-1 receptor antagonist;11 wt/wt % to 15 wt/wt % of an emulsifier;an oil;a co-surfactant which comprises an alcohol;a tonicity agent;a pH modifier; andwater;wherein the ratio of the emulsifier to the NK-1 receptor antagonist ranges from about 18:1 to 22:1 (wt/wt %),wherein the pH of the emulsion ranges from about 7.5 to 9.0.2. A method for treating a subject in need thereof , comprising intravenously administering to the subject a single dose of a stable emulsion over about 30 seconds to 15 minutes , wherein the stable emulsion comprises:an NK-1 receptor antagonist;11 wt/wt % to 15 wt/wt % of an emulsifier;an oil;a co-surfactant which comprises an alcohol;a tonicity agent;a pH modifier; andwater;wherein the ratio of the emulsifier to the NK-1 receptor antagonist ranges from about 18:1 to 22:1 (wt/wt %),wherein the pH of the emulsion ranges from about 7.5 to 9.0.3. The method according to claim 1 , wherein the average rate is about 8 to 65 mg/minute of the NK-1 receptor antagonist comprised in the stable emulsion.4. The method according to claim 1 , wherein the average rate is about 8 claim 1 , 20 claim 1 , 26 claim 1 , 50 claim 1 , or 65 mg/minute of the NK-1 receptor antagonist comprised in the stable emulsion.5. The method according to claim 2 , comprising intravenously administering the single dose of the stable emulsion to the subject over about 2 claim 2 , 5 claim 2 , or 15 minutes.6. The method according to claim 1 , wherein the ratio of the oil to the NK-1 receptor antagonist ranges from about 5:1 to 15:1 ...

NOVEL COMPOUNDS AND COMPOSITIONS AND METHODS OF USE

Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid. 172-. (canceled)74. The method of claim 73 , wherein the pharmaceutically acceptable salt is administered to the human claim 73 , and wherein the pharmaceutically acceptable salt is an ammonium claim 73 , a primary amine claim 73 , a secondary amine claim 73 , a tertiary amine claim 73 , a lithium claim 73 , a sodium claim 73 , a potassium claim 73 , a calcium claim 73 , a magnesium claim 73 , or an aluminum salt.75. The method of claim 74 , wherein the pharmaceutically acceptable salt is a sodium salt.76. The method of claim 73 , wherein said administering is orally.77. The method of claim 73 , wherein said compound is administered in combination with a pharmaceutically acceptable carrier claim 73 , excipient claim 73 , or diluent claim 73 , in a pharmaceutical composition.78. The method of claim 77 , wherein the pharmaceutical composition is a tablet or capsule.79. The method of claim 77 , wherein the pharmaceutical composition is a tablet.80. The method of claim 79 , wherein the pharmaceutical composition is a coated tablet.81. The method of claim 79 , wherein the tablet comprises lactose.82. The method of claim 79 , wherein the tablet comprises microcrystalline cellulose.83. The method of claim 79 , wherein the tablet comprises sodium croscarmellose.84. The method of claim 79 , wherein the tablet comprises gelatin.85. The method of claim 79 , wherein the tablet comprises magnesium stearate.86. The method of claim 79 , wherein the tablet comprises hydroxypropylcellulose or hydroxypropylmethyl-cellulose.87. The method of claim 79 , wherein the tablet comprises polyvinyl polypyrrolidone.88. The method of claim 73 , further comprising administering to the human a second agent effective ...

TREATMENT OF GOUT

Sodium 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio) acetate is described. In addition, pharmaceutical compositions and uses such compositions for the treatment of a variety of diseases and conditions. 1. A method of treating gout comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 ,2 ,4-triazol-3-ylthio)acetate , or a pharmaceutically acceptable salt thereof , and colchicine to a subject.2. The method of claim 1 , wherein said method provides greater mean gout flare reduction than co-administration of colchicine and a therapeutic agent that is not a dual inhibitor of URAT1 and an inflammasome.3. The method of claim 1 , wherein the total dosage of colchicine administered during co-administration with 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 1 ,2 claim 1 ,4-triazol-3-ylthio)acetate claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , is at least 50% less than the total dosage of colchicine that would be required for a similar effect when co-administered with a therapeutic agent that is not a dual inhibitor of URAT1 and an inflammasome.4. The method of claim 1 , wherein the amount of time that colchicine is co-administered with 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 1 ,2 claim 1 ,4-triazol-3-ylthio)acetate claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , is at least one week less than would be required for a similar effect when colchicine is co-administered with a therapeutic agent that is not a dual inhibitor of URAT1 and an inflammasome.5. A method of reducing monosodium urate induced inflammation in a subject in need thereof claim 1 , the method comprising administering a pharmaceutical composition comprising a pharmaceutical agent having both uricosuric and anti-inflammatory activity.6. The method of wherein the pharmaceutical agent is a URAT1 inhibitor with anti-inflammatory activity.7. The method of wherein the pharmaceutical agent is 2-(5-bromo-4-(4 ...

Compositions and methods for preparing and using same

This invention relates to compositions, methods for preparing the compositions and methods for treating or preventing diseases, comprising administering the compositions.

New compounds and compositions, and methods of use

Un compuesto para uso como un medicamento, el compuesto representado mediante la fórmula (III): en la que X es CH o N; W es O, S, S(O), S(O)2, NH, N(alquilo de C1-6 no sustituido), NC(O)(alquilo de C1-6 no sustituido) o CH2; R1 es H, Cl, Br, I, NH2, metilo, etilo, n-propilo, i-propilo, CF3, CHF2 o CH2F; R3 y R3' se seleccionan independientemente de H y alquilo de C1-6 no sustituido, o R3 y R3', junto con el carbono al que están unidos, forman un anillo de 4, 5, ó 6 miembros, que contiene opcionalmente 1 ó 2 heteroátomos seleccionados de N, S y O; R2 se selecciona del grupo que consiste en (a), (b), (c) y (d): en los que - - - - representa un enlace sencillo carbono-carbono o un doble enlace carbono-carbono; Q y Q' se seleccionan independientemente de N y CH; RP es metilo, etilo, propilo, i-propilo, ciclopropilo, ciclobutilo, ciclopentilo, ciclohexilo o ciclopropilmetilo; R8, R9 y R10 se seleccionan independientemente de H, F, Cl, Br, CH3, CF3, CFH2, CF2H, etilo, i-propilo, ciclopropilo, metoxi, OH, OCF3, NH2 y NHCH3; R11 es Cl, Br, I, CH3, CF3, metoxi, i-propilo, ciclopropilo, terc-butilo, ciclobutilo o metilo; y R12, R13, R14 y R15 son independientemente H o metilo; o una sal farmacéuticamente aceptable, solvato, o tautómero del mismo. A compound for use as a medicament, the compound represented by the formula (III): in which X is CH or N; W is O, S, S (O), S (O) 2, NH, N (unsubstituted C1-6 alkyl), NC (O) (unsubstituted C1-6 alkyl) or CH2; R1 is H, Cl, Br, I, NH2, methyl, ethyl, n-propyl, i-propyl, CF3, CHF2 or CH2F; R3 and R3 'are independently selected from H and unsubstituted C1-6 alkyl, or R3 and R3', together with the carbon to which they are attached, form a 4, 5, or 6-membered ring, optionally containing 1 or 2 heteroatoms selected from N, S and O; R2 is selected from the group consisting of (a), (b), (c) and (d): in which - - - - represents a carbon-carbon single bond or a carbon-carbon double bond; Q and Q 'are independently ...

3,4-di-substituted pyridine compound to reduce serum uric acid levels

[00256] 2-((3-(4-cyanonaphthalen-l-yl)pyridin-4-yl)thio)-2-methylpropanoic acid is useful in the modulation of blood or serum uric acid levels. In some embodiments, 2-((3-(4- cyanonaphthalen-l-yl)pyridin-4-yl)thio)-2-methylpropanoic acid is used in the treatment or prevention of disorders related to aberrant levels of uric acid. In some embodiments, 2-((3-(4- cyanonaphthalen-l-yl)pyridin-4-yl)thio)-2-methylpropanoic acid is used for reducing serum uric acid levels in a human. Also described herein are compositions comprising 2-((3-(4- cyanonaphthalen-l-yl)pyridin-4-yl)thio)-2-methylpropanoic acid, and their use in the modulation of blood or serum uric acid levels.

Compositions comprising 4-(2-(5-bromo-4-(1-cyclopropylnaphthalen-4-yl)-4h-1,2,4-triazol-3-ylthio) acetamido)-3-chlorobenzoic acid and pharmaceutically acceptable salts thereof

The present invention relates to compositions comprising 4-(2-(5-bromo-4-(1-cyclopropylnaphthalen-4-yl)-4H-1,2,4-triazol-3-ylthio)acetamido)-3-chlorobenzoic acid or pharmaceutically acceptable salts thereof, and to the preparation and use of such compositions, in particular for the treatment of diseases.

Treatment of gout

Sodium 2-(5-bromo-4-(4-cyclopropyl-naphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetate is described. In addition, pharmaceutical compositions and uses such compositions for the treatment of a variety of diseases and conditions.

HIS UNKNOWN RELATIONSHIPS AND PREPARATIONS AND PROCEDURES FOR USE THEREOF

Imidazole and triazole derivatives and methods of use

Described herein arc compounds useful in the modulation of blood uric, acid levels, formulations containing them and methods of using them. In some embodiments, the compounds described herein are used in the treatment or prevention of dis-orders relafed to aberrant levels of uric acid.

Treatment of gout and hyperuricemia

Compositions and methods for preparing and using same

This invention relates to compositions, methods for preparing the compositions and methods for treating or preventing diseases, comprising administering the compositions.

Treatment of gout

Sodium 2-(5-bromo-4-(4-cyclopropylnaphthalen- 1 -yl)-4H- 1,2,4-triazol-3-ylthio) acetate is described. In addition, pharmaceutical compositions and uses such compositions for the treatment of a variety of diseases and conditions.

Methods for treating hyperuricemia and related diseases

Methods for treating hyperuricemia and related diseases

Provided herein are methods of treating gout, treating hyperuricemia, lowering serum uric acid, or the like with compounds of formula (I) have the following structure Further, provided herein are compositions comprising a compound of formula (I).

Treatment of gout and hyperuricemia.

Sodyum 2-(5-bromo-4-(4-siklopropilnaftalen-1-il)-4H-1,2,4-triazol-3-iltiyo)asetat açıklanmıştır. Ek olarak, çeşitli hastalıklar ve durumların tedavisi için farmasötik bileşimler ve bu tür bileşimlerin kullanımları da açıklanmıştır. Sodium 2- (5-bromo-4- (4-cyclopropylnaphthalen-1-yl) -4H-1,2,4-triazol-3-ylthio) acetate is disclosed. In addition, pharmaceutical compositions for the treatment of various diseases and conditions and uses of such compositions are disclosed.

Treatment of gout and hyperuricemia

METHOD FOR THE TREATMENT OF THE IRRITABLE INTESTINE SYNDROME WITH DIARREA PRODOMINIUM

Métodos para tratar el síndrome del intestino irritable con predominio de diarrea que consiste en administrar a un paciente que lo necesita un inhibidor del transporte de iones de cloruro en una cantidad suficiente para tratar el síndrome del intestino irritable con predominio de diarrea (d-SII). El tratamiento del d-SII incluye el tratamiento del componente diarrea del d-SII, así como también el dolor, el malestar abdominal y otros síntomas asociados al d-SII. En una realizacion, el inhibidor del transporte de iones de cloruro es crofelemer. Reivindicacion 5: El método de acuerdo con cualquiera de las reivindicaciones 1 a 4, caracterizado porque el inhibidor es un extracto de Croton spp. o Calophyllum spp. Reivindicacion 8: El método de acuerdo con la reivindicacion 7, caracterizado porque el inhibidor de la funcion CFTR se selecciona entre el grupo que comprende compuesto de 2-tioxo-4-tiazolidinona y 3-[(3-trifluorometi)fenil]-5-[(3carboxifenil)metilen]-2-tioxo-4- tiazolidinona, tolbutamida, glibenclamida y fluoresceína o un derivado de ellas, diazoxido, lemakalim, sulfato de minoxidil y sus análogos; 8- bromo-cAMP, 8-(4-clorofeniltio) (CPT)-cAMP y 8-bromo-cGMP, CPT-cGMP; verapamil, nifeldipidina, diltiazem, compuestos de estilbeno disulfonicos, difenilamina-2-carboxilato (DPC) o 5-nitro-2(3-fenilpropilamino)benzoato (NPPB); ácido antraceno-9-carboxílico (9-AC); 3-[(3-trifluorometi)fenil]-5-[(3-carboxifenil)metilen]-2-tioxo-4-tiazolidinona; N-(2- naftalenil)-[3,5-dibromo-2,4-dihidroxifenil)metilen]glicina hidrazida (GlyH-101) o sus derivados; dihydrazidas del ácido malonico o sus derivados; loperamida; racecadotril; clorhidrato de lidamidina; lonidamina; vanadato; bumetamida; pp2a; PP1; PP2B, subsalicilato de bismuto; clorhidrato de difenoxilato; y esparteína. Reivindicacion 9: El método de acuerdo con cualquiera de las reivindicaciones 1 a 4, caracterizado porque el inhibidor es una composicion polimérica sintética o de origen natural. Reivindicacion 10: El mé ...

Compositions and methods for treating or preventing inflammatory bowel disease, familial adenomatous polyposis and colon cancer

The present invention provides methods for preventing colon cancer by administering, to a patient in need thereof, a polymeric proanthocyanidin composition from a Croton species or Calophyllum species in an amount sufficient to prevent colon cancer, which composition inhibits COX-2. The present invention also provides methods for treating inflammation locally in the intestines comprising administering to a patient in need thereof, a polymeric proanthocyanidin composition from a Croton species or Calophyllum species in an amount sufficient to treat inflammation. In one embodiment, the polymeric proanthocyanidin compound is crofelemer. The present invention in alternative embodiments provides methods for treating pain locally in the intestines and treating inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, as well as for treating familial adenomatous polyposis (FAP).

Post-surgical pain treatment

Disclosed herein are compositions and methods for treating post-surgical pain in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a NK-1 receptor antagonist and a pain medication.

Method for Treatment of Constipation-Predominant Irritable Bowel Syndrome

The present invention provides methods for treating constipation-predominant irritable bowel syndrome comprising administering to a patient in need thereof, a polymeric proanthocyanidin composition from a Croton species or Calophyllum species in an amount sufficient to treat constipation-predominant irritable bowel syndrome (c-IBS). Treatment of c-IBS includes the treatment of the constipation component of c-IBS as well as the pain and abdominal discomfort associated with c-IBS. In one embodiment, the polymeric proanthocyanidin compound is crofelemer. The present invention in an alternative embodiment also provides methods for treating alternating constipation-predominant/diarrhea-predominant irritable bowel syndrome.

Novel compounds and compositions and methods of use

Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid.

Imidazole and triazole derivatives and methods of use

Described herein are compounds useful in the modulation of blood uric acid levels, formulations containing them and methods of using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid.

COMPOSITIONS AND METHODS OF PREPARATION AND USE OF THE SAME

Composiciones, métodos para preparar las composiciones y métodos para tratar o prevenir enfermedades, que comprenden la administración de las composiciones.

TREATMENT OF URINARY ARTHRITIS AND HYPOTHESIS

Περιγράφεται το 2-(5-βρωμο-4-(4-κυκλοπροπυλοναφθαλιν-1-υλ)-4Η-1,2,4-τριαζολ-3-υλοθειο) οξικό άλας. Επιπλέον, περιγράφονται φαρμακευτικές συνθέσεις και οι χρήσεις τέτοιων συνθέσεων για τη θεραπεία μιας ποικιλίας ασθενειών και παθήσεων. The 2- (5-bromo-4- (4-cyclopropylonaphthalin-1-yl) -4H-1,2,4-triazol-3-ylthio) acetate is described. In addition, pharmaceutical compositions and uses of such compositions for the treatment of a variety of diseases and conditions are described.

Methods for treating hyperuricemia and related diseases

Provided herein are methods of treating gout, treating hyperuricemia, lowering serum uric acid, or the like with compounds of formula (I) have the following structure Further, provided herein are compositions comprising a compound of formula (I).

Method for treatment of diarrhea-predominant irritable bowel syndrome

The present invention provides methods for treating diarrhea-predominant irritable bowel syndrome comprising administering to a patient in need thereof, an inhibitor of chloride-ion transport in an amount sufficient to treat diarrhea-predominant irritable bowel syndrome (d-IBS). Treatment of d-IBS includes the treatment of the diarrhea component of d-IBS as well as the pain, abdominal discomfort and other symptoms associated with d-IBS. In one embodiment, the inhibitor of chloride-ion transport is crofelemer.