Pharmaceutical formulations of potassium ATP channel openers and uses thereof
AssigneeEssentialis, Inc.
InventorsNeil Cowen, Kenneth Kashkin
Life of this patent
Estimating the term…
Abstract
Provided are immediate or prolonged administration of certain potassium ATP (KATP) channel openers to a subject to achieve novel pharmacodynamic, pharmacokinetic, therapeutic, physiological, metabolic and compositional outcomes in the treatment of diseases or conditions involving KATP channels. Also provided are pharmaceutical formulations, methods of administration and dosing of KATP channel openers that achieve these outcomes and reduce the incidence of adverse effects in treated individuals. Further provided are method of co-administering KATP channel openers with other drugs to treat diseases of humans and animals.
Claims50
A controlled release pharmaceutical formulation of a KATP channel opener of formula II or formula III.
A salt of diazoxide other than a sodium salt.
A pharmaceutical formulation of a KATP channel opener according to formula II or formula III that upon administration to an obese, overweight or obesity prone individual results in at least one of the following:
- (a) inhibition of fasting insulin secretion (b) inhibition of glucose stimulated insulin secretion, (c) elevation of energy expenditure, (d) elevation of beta oxidation of fat, or (e) inhibition of hyperphagia for about 24 hours.
A pharmaceutical formulation of a KATP channel opener according to formula II or formula III that upon administration to an obese, overweight or obesity prone individual results in at least one of the following:
- (a) inhibition of fasting insulin secretion (b) inhibition of glucose stimulated insulin secretion, (c) elevation of energy expenditure, (d) elevation of beta oxidation of fat, or (e) inhibition of hyperphagia for about 18 hours.
A method of inducing weight loss in an obese or overweight subject, comprising administering daily dosages of the pharmaceutical formulation of a KATP channel opener of formula II or formula III, wherein the daily dosages of the KATP formulation are between 50 and 180 mg.
A method of treating obesity associated co-morbidities in an obese, overweight or obesity prone individual, said method comprising administering a therapeutically effective amount of a solid oral dosage form of a KATP channel opener of formula II or formula III no more than two times per 24 hours.
A method of achieving weight loss in an obese individual, said method comprising administering a therapeutically effective amount of a solid oral dosage form of a KATP channel opener of formula II or formula III no more than two times per 24 hours.
A method of elevating energy expenditure in an overweight, obese or obesity prone individual, said method comprising administering an effective amount of a solid oral dosage form of a KATP channel opener of formula II or formula III no more than two times per 24 hours.
A method of elevating beta oxidation of fat in an overweight, obese or obesity prone individual, said method comprising administering an effective amount of a solid oral dosage form of a KATP channel opener of formula II or formula III no more than two times per 24 hours.
A method of preventing the transition to diabetes of a prediabetic individual comprising administering an effective amount of KATP channel opener of formula II or formula III no more than two times per 24 hours.
A method of restoring normal glucose tolerance to a diabetic individual comprising administering an effective amount of KATP channel opener of formula II or formula III.
A method of restoring normal glucose tolerance to a prediabetic individual comprising administering an effective amount of KATP channel opener of formula II or formula III.
A method of delaying or preventing the progression of diabetes comprising administering an effective amount of KATP channel opener of formula II or formula III no more than two times per 24 hours.
A method of treating obesity or obesity associated co-morbidities or other diseases or conditions involving KATP channels by co-administration of an effective amount of a solid oral dosage form of a KATP channel opener of formula II or formula III and a drug that is selected from the group consisting of Sibutramine, Orlistat, Rimonabant, a non-thiazide diuretic, a drug that lowers cholesterol, a drug that raises HDL cholesterol, a drug that lowers LDL cholesterol, a drug that lowers blood pressure, a drug that is an anti-depressant, a drug that improves insulin sensitivity, a drug that improves glucose utilization or uptake, a drug that is an anti-epileptic, a drug that is an anti-inflammatory, a drug that is an appetite suppressant, a drug that lowers circulating triglycerides, and a drug that is used to induced weight loss in an overweight or obese individual.
A method of reducing the incidence of adverse effects from administration of a KATP channel opener in the treatment of diseases or conditions achieved by any of the following:
- (a) the use of a pharmaceutical formulation that delays release of the the method of preventing weight gain, dyslipidemia or impaired glucose tolerance in a subject treated with an anti-psychotic drug involving the administration of a pharmaceutical formulation of a KATP channel opener until gastric transit is complete, (b) the use of a pharmaceutical formulation that sustains release over more than 2 hours, (c) initiating dosing at subtherapeutic levels and in a stepwise manner increasing dose daily until the therapeutic dose is achieved wherein the number of steps is 2 to 10, (d) use of the lowest effective dose to achieve the desired therapeutic effect, and (e) optimizing the timing of administration of dose within the 24 hours and relative to meals.
A method of preventing weight gain, dyslipidemia or impaired glucose tolerance in a subject treated with an anti-psychotic drug, the method comprising administering a pharmaceutical formulation of a KATP channel opener.
A method of treating weight gain, dyslipidemia or impaired glucose tolerance in a subject treated with an anti-psychotic drug, the method comprising administering a pharmaceutical formulation of a KATP channel opener.
A method of treating diseases characterized by obesity, hyperphagia, dyslipidemia, or decreased energy expenditure including (a) Prader Willi Syndrome, (b) Froelich's syndrome, (c) Cohen syndrome, (d) Summit Syndrome, (e) Alstrom, Syndrome, (f) Borjesen Syndrome, (g) Bardet-Biedl Syndrome, or (h) hyperlipoproteinemia type I, II, III, and IV comprising administering a pharmaceutical formulation of a KATP channel opener.
A pharmaceutical formulation of a KATP channel opener of formula II or formula III further comprising a pharmaceutically active agent other than the KATP channel opener of formula II or formula III.
Dependencies are inferred from the claim text.