LIPID-LOWERING ANTIDIABETIC AGENT
A composition which includes a salt of metformin and the use of the composition for treatment of or use in prediabetes, diabetes, lowering triglycerides and/or other conditions in mammals.
1 . A composition of structure I, which is a salt of metformin
with at least one polyunsaturated fatty acid represented by RH or a mixture of metformin and at least one acid RH or a pharmaceutically acceptable solvate or hydrate thereof.
2 . The composition of claim 1 in which the polyunsaturated fatty acid RH is an omega-3 fatty acid.
3 . A composition of claim 1 wherein RH is an omega-3 polyunsaturated C 16-24 fatty acid optionally substituted with from 1-3 hydroxy groups
4 . A composition as claimed in claim 2 wherein RH is a fatty acid of 20 or 22 carbon atoms with a total of 4- or 5 unsaturated linkages in the fatty acid chain in addition to the omega-3 unsaturated bond.
5 . A composition of claim 1 , wherein RH is selected from the group consisting of resolvins D1, D2, D3, D4, E1, and E2.
6 . The composition of claim 1 in which the polyunsaturated fatty acid RH is eicosapentaenoic acid.
7 . The composition of claim 1 in which the polyunsaturated fatty acid RH is docosahexaenoic acid.
8 . A composition according to claim 1 , wherein R is a mixture of polyunsaturated fatty acids.
9 . The mixture of claim 8 in which the polyunsaturated fatty acid comprises a mixture of eicosapentaenoic acid and docosahexaenoic acid.
10 . A pharmaceutical composition comprising a compound according to claim 6 and a pharmaceutically acceptable carrier, vehicle or diluent.
11 . A pharmaceutical composition comprising a compound according to claim 7 and a pharmaceutically acceptable carrier, vehicle or diluent.
12 . A pharmaceutical composition comprising a mixture according to claim 8 and a pharmaceutically acceptable carrier, vehicle or diluent.
13 . A kit comprising a) a unit dosage form comprising the compound of claim 6 ; b) instructions on how to use the kit; and c) at least one container for holding the unit dosage forms.
14 . A kit comprising a) a unit dosage form comprising the compound of claim 7 ; b) instructions on how to use the kit; and c) at least one container for holding the unit dosage forms.
15 . A kit comprising a) a unit dosage form comprising the salts of claim 8 b) instructions on how to use the kit; and c) at least one container for holding the unit dosage forms.
16 . A method for treating diabetes in a mammal, comprising administering a therapeutically effective amount of a compound according to claim 6 .
17 . A method for treating diabetes in a mammal, comprising administering to said mammal a therapeutically effective amount of a composition according to claim 7 .
18 . A method for treating diabetes in a mammal, comprising administering to said mammal a therapeutically effective amount of a composition according to claim 8 .
19 . A method for treating diabetes in a mammal, comprising administering to said mammal a therapeutically effective amount of a composition according to claim 9 .
20 . A method of lowering triglycerides in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 6 .
21 . A method of lowering triglycerides in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 7 .
22 . A method of lowering triglycerides in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 8 .
23 . A method of lowering triglycerides in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 9 .
24 . A method of treating prediabetes in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 6 .
25 . A method of treating prediabetes in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 7 .
26 . A method of treating prediabetes in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 8 .
27 . A method of treating prediabetes in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 9 .
28 . A method of treating obesity in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 6 .
29 . A method of treating obesity in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 7 .
30 . A method of treating obesity in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 8 .
31 . A method of treating obesity in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 9 .
32 . A method of treating cardiac arrhythmia in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 6 .
33 . A method of treating cardiac arrhythmia in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 7 .
34 . A method of treating cardiac arrhythmia in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 8 .
35 . A method of treating cardiac arrhythmia in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 9 .
36 . A method of treating cardiomyopathy in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 6 .
37 . A method of treating cardiomyopathy in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 7 .
38 . A method of treating cardiomyopathy in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 8 .
39 . A method of treating cardiomyopathy in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 9 .
40 . A method of treating myocardial infarction in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 6 .
41 . A method of treating myocardial infarction in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 7 .
42 . A method of treating myocardial infarction in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 8 .
43 . A method of treating myocardial infarction in a mammal, comprising administering to said mammal a therapeutically effective amount of the composition according to claim 9 .
44 . A method for the manufacture of the composition of claim 1 comprising: a) freshly preparing the free base of metformin from a suitable metformin salt; and b) reacting the freshly prepared free base of metformin with eicosapentaenoic acid, docosahexaenoic acid or a mixture thereof at a temperature between about 1 degree C. and about 60 degree C.