Compositions for weight management

Abstract

Methods and compositions for preventing or reducing weight gain associated with drug treatment, which utilize an H 1 agonist such as betahistine, betahistine metabolite or a betahistine salt are disclosed.

1 . A method of reducing weight gain associated with a drug treatment in a human subject, the method comprising administering to a human subject treated with the drug a therapeutically effective amount of betahistine, a betahistine pharmaceutically acceptable salt or a betahistine metabolite being 2-(2-aminoethyl)-pyridine. 
   
   
       2 . The method of  claim 1 , wherein said drug is selected from the group consisting of an antipsychotic, an antidepressant, a mood-stabilizer, a calcium channel blocker, an anti-convulsant, a proton pump inhibitor, an antidiabetic agent, an antihypertensive, a hormone, an anti-smoking medication and any combination thereof. 
   
   
       3 . The method of  claim 2 , wherein said drug is selected from the group consisting of a selective serotonin-reuptake inhibitor, a monoamine oxidase inhibitor, a conventional antipsychotic, and an atypical antipsychotic. 
   
   
       4 . The method of  claim 3 , wherein said atypical antipsychotic is an antagonist of a receptor selected from the group consisting of a 5-HT 2A  receptor, a 5-HT 2C  receptor, a H 1 -histaminergic receptor, and a M 1 -muscarinic receptor. 
   
   
       5 . The method of  claim 2 , wherein said drug is selected from the group consisting of clozapine, olanzapine, risperidone, quetiapine, sertindole, aripiprazole, ziprasidone, bupropion hydrochloride, mirtazapine, nefazadone, trazadone, lithium, diltiazem, nicardipine, verapamil, nimopidipine, carbamazepine, divalproex, lamotrigine, sodium valproate, valproic acid, gabapentin, omeprazole, esomeprazole, lansoprazole, pantoprazole, a sulfonylurea, a meglitinide, a biguanide, a thiazolidinedione, an alpha-glucosidase inhibitor, insulin, chlorpropamide, glipizide, glyburide, glimepiride, chlorpropamide, glipizide, glyburide, glimepiride, an alpha-adrenergic blocker, a beta blocker and a steroid hormone. 
   
   
       6 . The method of  claim 1 , wherein said weight gain causes a metabolic disorder. 
   
   
       7 . The method of  claim 6 , wherein said metabolic disorder is selected from the group consisting of metabolic syndrome, diabetes and dyslipidemia. 
   
   
       8 . The method of  claim 1 , wherein said betahistine salt is selected from the group consisting of betahistine dihydrochloride, betahistine mesilate, and betahistine trimebutine maleate. 
   
   
       9 . The method of  claim 1 , wherein said administering is effected by a route selected from the group consisting of the oral, transdermal, intravenous, subcutaneous, intramuscular, intranasal, intraauricular, sublingual, rectal, transmucosal, intestinal, buccal, intramedullar, intrathecal, direct intraventricular, intraperitoneal, and intraocular routes. 
   
   
       10 . The method of  claim 1 , wherein said administering is effected orally. 
   
   
       11 . The method of  claim 1 , wherein said therapeutically effective amount ranges from about 2 mg per unit dosage to about 96 mg per unit dosage. 
   
   
       12 . The method of  claim 11 , wherein said therapeutically effective amount ranges from about 10 mg per day to about 50 mg per day. 
   
   
       13 . The method of  claim 1 , wherein said administering is effected from about 1 to about 4 times per day. 
   
   
       14 . The method of  claim 13 , wherein said administering is effected twice per day. 
   
   
       15 . The method of  claim 1 , wherein said betahistine, betahistine salt or betahistine metabolite forms a part of a pharmaceutical composition, said pharmaceutical composition further comprising a pharmaceutically acceptable carrier. 
   
   
       16 . The method of  claim 15 , wherein said pharmaceutical composition is a slow-release composition. 
   
   
       17 . The method of  claim 15 , wherein said pharmaceutical composition is in a form selected from the group consisting of a tablet, a pill, a dragee and a capsule. 
   
   
       18 . The method of  claim 1 , further comprising administering to the subject a therapeutically effective amount of an additional active agent. 
   
   
       19 . The method of  claim 18 , wherein said additional active agent is selected from the group consisting of a non-steroidal anti-inflammatory drug, a muscle relaxant, an antigout agent, an immunosuppressant, a drug affecting bone mineralization, an angiotensin-converting enzyme inhibitor, an antiarrhythmic drug, an anticoagulant, an antiplatelet, a thrombolytic, a centrally acting drug, a digitalis drug, a nitrate, a peripheral adrenergic antagonist, a vasodilator, an acne medication, an antipruretic agent, an anti-psoriasis agent, an anti-eczema agent, a hypnotic, an anti-histamine, a fibrate, an HMG-CoA reductase inhibitor, a nutritional supplement, a bile acid sequestrant, a cholesterol absorption inhibitor, nicotinic acid, a derivative, analog and metabolite thereof, and any mixture thereof. 
   
   
       20 . A pharmaceutical composition comprising a therapeutically effective amount of betahistine, a betahistine salt or a betahistine metabolite being 2-(2-aminoethyl)-pyridine, and a therapeutically effective amount of a drug, said drug being associated with weight gain. 
   
   
       21 . The pharmaceutical composition of  claim 20 , wherein said drug is selected from the group consisting of an antipsychotic, an antidepressant, a mood-stabilizer, a calcium channel blocker, an anti-convulsant, a proton pump inhibitor, an antidiabetic agent, an antihypertensive, a hormone, an anti-smoking medication and any combination thereof. 
   
   
       22 . The pharmaceutical composition of  claim 21 , wherein said drug is selected from the group consisting of a selective serotonin-reuptake inhibitor, a monoamine oxidase inhibitor, a conventional antipsychotic, and an atypical antipsychotic. 
   
   
       23 . The pharmaceutical composition of  claim 22 , wherein said atypical antipsychotic is an antagonist of a receptor selected from the group consisting of a 5-HT 2A  receptor, a 5-HT 2C  receptor, a H 1 -histaminergic receptor, and a M 1 -muscarinic receptor. 
   
   
       24 . The pharmaceutical composition of  claim 21 , wherein said drug is selected from the group consisting of clozapine, olanzapine, risperidone, quetiapine, sertindole, aripiprazole, ziprasidone, bupropion hydrochloride, mirtazapine, nefazadone, trazadone, lithium, diltiazem, nicardipine, verapamil, nimopidipine, carbamazepine, divalproex, lamotrigine, sodium valproate, valproic acid, gabapentin, omeprazole, esomeprazole, lansoprazole, pantoprazole, a sulfonylurea, a meglitinide, a biguanide, a thiazolidinedione, an alpha-glucosidase inhibitor, insulin, chlorpropamide, glipizide, glyburide, glimepiride, chlorpropamide, glipizide, glyburide, glimepiride, an alpha-adrenergic blocker, a beta blocker and a steroid hormone. 
   
   
       25 . The pharmaceutical composition of  claim 20 , being packaged in a packaging material and identified in print, in or on said packaging material, for use in the treatment of a medical condition in which treatment with said drug is beneficial while reducing or preventing weight gain associated with said drug treatment. 
   
   
       26 . The pharmaceutical composition of  claim 20 , wherein said therapeutically effective amount of said drug is associated with a weight gain, and said therapeutically effective amount of betahistine or betahistine salt is effective in reducing said weight gain. 
   
   
       27 . The pharmaceutical composition of  claim 20 , wherein said betahistine salt is selected from the group consisting of betahistine dihydrochloride, betahistine mesilate, and betahistine trimebutine maleate. 
   
   
       28 . The pharmaceutical composition of  claim 20 , wherein said therapeutically effective amount of said betahistine or said betahistine salt ranges from about 2 mg per unit dosage to about 96 mg per unit dosage. 
   
   
       29 . The pharmaceutical composition of  claim 20 , being formulated such that said betahistine or said betahistine salt is in a slow-release form. 
   
   
       30 . The pharmaceutical composition of  claim 20 , being formulated for oral administration. 
   
   
       31 . The pharmaceutical composition of  claim 30 , being in a form selected from the group consisting of a tablet, a pill, a dragee and a capsule. 
   
   
       32 . A method treating a medical condition in which treatment with a drug that causes weight gain is beneficial, while reducing weight gain associated with the drug treatment, the method comprising administering to a subject in need thereof a therapeutically effective amount of the drug and further administering to said subject a therapeutically effective amount of betahistine, a betahistine salt or a betahistine metabolite being 2-(2-aminoethyl)-pyridine. 
   
   
       33 . The method of  claim 1 , wherein said therapeutically effective amount of the drug is associated with weight gain, and said therapeutically effective amount of betahistine, betahistine salt or betahistine metabolite is effective in reducing said weight gain. 
   
   
       34 . The method of  claim 32 , wherein said drug is selected from the group consisting of an antipsychotic, an antidepressant, a mood-stabilizer, a calcium channel blocker, an anti-convulsant, a proton pump inhibitor, an antidiabetic agent, an antihypertensive, a hormone, an anti-smoking medication and any combination thereof. 
   
   
       35 . The method of  claim 34 , wherein said drug is selected from the group consisting of a selective serotonin-reuptake inhibitor, a monoamine oxidase inhibitor, a conventional antipsychotic, and an atypical antipsychotic. 
   
   
       36 . The method of  claim 35 , wherein said atypical antipsychotic is an antagonist of a receptor selected from the group consisting of a 5-HT 2A  receptor, a 5-HT 2C  receptor, a H 1 -histaminergic receptor, and a M 1 -muscarinic receptor. 
   
   
       37 . The method of  claim 34 , wherein said drug is selected from the group consisting of clozapine, olanzapine, risperidone, quetiapine, sertindole, aripiprazole, ziprasidone, bupropion hydrochloride, mirtazapine, nefazadone, trazadone, lithium, diltiazem, nicardipine, verapamil, nimopidipine, carbamazepine, divalproex, lamotrigine, sodium valproate, valproic acid, gabapentin, omeprazole, esomeprazole, lansoprazole, pantoprazole, a sulfonylurea, a meglitinide, a biguanide, a thiazolidinedione, an alpha-glucosidase inhibitor, insulin, chlorpropamide, glipizide, glyburide, glimepiride, chlorpropamide, glipizide, glyburide, glimepiride, an alpha-adrenergic blocker, a beta blocker and a steroid hormone. 
   
   
       38 . The method of  claim 32 , wherein said betahistine salt is selected from the group consisting of betahistine dihydrochloride, betahistine mesilate, and betahistine trimebutine maleate. 
   
   
       39 . The method of  claim 32 , wherein administering said betahistine, betahistine salt or betahistine metabolite is effected by a route selected from the group consisting of the oral, transdermal, intravenous, subcutaneous, intramuscular, intranasal, intraauricular, sublingual, rectal, transmucosal, intestinal, buccal, intramedullar, intrathecal, direct intraventricular, intraperitoneal, and intraocular routes. 
   
   
       40 . The method of  claim 32 , wherein administering said betahistine, betahistine salt or betahistine metabolite is effected orally. 
   
   
       41 . The method of  claim 32 , wherein said therapeutically effective amount of said betahistine, betahistine salt or betahistine metabolite ranges from about 2 mg per unit dosage to about 96 mg per unit dosage. 
   
   
       42 . The method of  claim 32 , wherein said betahistine, betahistine salt or betahistine metabolite forms a part of a pharmaceutical composition, said pharmaceutical composition further comprising a pharmaceutically acceptable carrier. 
   
   
       43 . The method of  claim 42 , wherein said pharmaceutical composition is a slow-release composition. 
   
   
       44 . The method of  claim 42 , wherein said pharmaceutical composition is in a form selected from the group consisting of a tablet, a pill, a dragee and a capsule.