SALTS OF POTASSIUM ATP CHANNEL OPENERS AND USES THEREOF
Provided are immediate or prolonged administration of certain salts of K ATP channel openers such as diazoxide to a subject to achieve novel pharmacodynamic, pharmacokinetic, therapeutic, physiological, metabolic and compositional outcomes in the treatment of diseases or conditions involving K ATP channels. Also provided are pharmaceutical formulations, methods of administration and dosing of the salts that achieve these outcomes and reduce the incidence of adverse effects in treated individuals. Further provided are method of co-administering the salts with other drugs to treat diseases of humans and animals.
1 - 129 . (canceled)
130 . A method for activating K ATP channels in an obese, overweight, or obesity prone subject, comprising administering to the subject a therapeutically effective amount of polymorph B of diazoxide choline in combination with a melanocortin-4-receptor agonist.
131 . The method of claim 130 wherein the polymorph B of diazoxide choline has characteristic peaks in the XRPD pattern at values of two-theta (Cu Kα, 40 kV, 40 mA) at approximately 8.9, 10.3, 12.0, 18.3, 20.6, 24.1, 24.5, 26.3, 27.1, and 28.9 degrees.
132 . The method of claim 130 wherein the polymorph B of diazoxide choline has characteristic infrared absorbances at 3256, 2174, 2890, 1605, 1463, and 1235 cm −1 .
133 . The method of claim 130 wherein the polymorph B of diazoxide choline has characteristic peaks in the XRPD pattern substantially as shown in FIG. 13( b ) and an NMR spectrum substantially as shown in FIG. 17( b ) .
134 . The method of claim 130 wherein between 10 and 100 mg of the polymorph B of diazoxide choline is administered per dose.
135 . The method of claim 130 wherein between 100 and 200 mg of the polymorph B of diazoxide choline is administered per dose.
136 . The method of claim 130 wherein between 200 and 300 mg of the polymorph B of diazoxide choline is administered per dose.
137 . The method of claim 130 wherein between 300 and 500 mg of the polymorph B of diazoxide choline is administered per dose.
138 . The method of claim 130 wherein between 500 and 2000 mg of the polymorph B of diazoxide choline is administered per dose.
139 . The method of claim 130 , wherein the therapeutically effective amount of polymorph B of diazoxide choline is separate from the melanocortin-4-receptor agonist.
140 . The method of claim 130 , wherein the subject is administered a mixture of the therapeutically effective amount of polymorph B of diazoxide choline and the melanocortin-4-receptor agonist.