Naturally extracted and synthetic hypoglycemic or hypolipidemic compositions

• US 20010022979A1
• Filed: 04/26/2001
• Published: 09/20/2001
• Est. Priority Date: 09/14/1999
• Status: Active Grant

• Current Assignee: Alon Margalit, Anat Aharoni, Nitsa Mirsky, Sherbel Sussan
• Original Assignee: Alon Margalit, Anat Aharoni, Nitsa Mirsky, Sherbel Sussan
• Inventors: Margalit, Alon, Mirsky, Nitsa, Sussan, Sherbel, Aharoni, Anat
• Granted Patent: US 6,458,351 B2
• Time in Patent Office: Days
• US Class Current: 424/725
• CPC Class Codes: A61K 36/21 Amaranthaceae (Amaranth family), e.g. pigweed, rockwort or globe amaranth
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/12 Keratolytics, e.g. wart or anti-corn preparations
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

Compositions having hypoglycemic and/or hypolipidemic activity are isolated from natural sources including yeast and Saltbush (Atriplex halimus). In addition, synthetic chromium complexes were prepared. Compositions possessing hypoglycemic and/or hypolipidemic activity with or without chromium containing natural and synthetic compounds are formulated for use in animals and humans. Methods for use of the compositions alone, or in combination with antioxidant agents, for regulating glucose and lipid levels in diabetes, cardiovascular diseases, inflammatory and cell proliferative diseases and in skin conditions, are presented.

Claims

1. A process for isolating a composition possessing hypoglycemic or hypolipidemic activity from a natural source, said process comprising the steps of:

(a) mixing water extracts obtained from natural sources with a polar organic solvent selected from the group consisting of ethanol, methanol and acetonitrile with a non polar organic solvent selected from the group consisting of butanol, chloroform and hexane, to produce a suspension;

(b) allowing the suspension to first separate into a non-polar phase and a polar phase, and then collecting the polar phase;

(c) purifying the polar phase using a polar organic solvent to produce said composition possessing hypoglycemic or hypolipidemic activity; and

(d) separating the composition possessing hypoglycemic or hypolipidemic activity.

2. The process according to

claim 1

, wherein the source material is a strain of yeast.

3. The process according to

claim 2

, wherein the strain of yeast comprises S. carlsbergensis, S. cerevisiae, elipsoideus, or any commercial yeast extract.

4. The process according to

claim 1

, wherein the source material is Saltbush.

5. The process according to

claim 2

, comprising eluting all material having a molecular weight below 3000 dalton.

6. The process according to

claim 4

, comprising eluting all material having a molecular weight below 3000 dalton.

29. The method according to

claim 2

wherein the composition possessing hypoglycemic or hypolipidemic activity is isolated from natural sources including yeast or Saltbush.

7. A purified composition possessing hypoglycemic or hypolipidemic activity said, composition being, isolated from a yeast strain selected from the group consisting of S. carlsbergensis, S. cerevisiae, elipsoideus, or any commercial yeast extract.

8. A purified composition possessing hypoglycemic or hypolipidemic activity, said composition being isolated from Saltbush.

20. The composition according to

claim 8

, wherein said composition having the hypoglycemic or hypolipidemic activity has a mass spectrum comprising peaks at 104, 118, 140, 156, 186, 235, 257, 273, 315, 374, or 432 m/z.

21. The composition according to

claim 8

, wherein said composition having the hypoglycemic or hypolipidemic activity has a mass spectrum comprising peaks at 86, 120, 136, 241, 288, 399,453, or 485 m/z.

9. A process for synthesizing organo-metal complex, said process comprising reacting an organic ligand with a transition metal.

10. The process according to

claim 9

, wherein the organic ligand is selected from the group consisting of ascorbic acid, N-acetyl cysteine, cysteine and glutathione, and the transition metal is selected from the group consisting of chromium, cobalt, magnesium, manganese, selenium and zinc.

11. A process for synthesizing an organo-metal complex possessing a hypoglycemic or anti-diabetic activity, said process comprising the steps of:

(a) preparing a reaction mixture by adding water to a metal salt,

(b) dissolving an organic ligand in the reaction mixture and adjusting the pH of the reaction mixture to the pK₁ of said organic ligand.

(c) heating the reaction mixture to 40°

C. to 70°

C. while stirring for at least 2 to 4 hours, and

(d) concentrating the reaction mixture in vacuum, precipitating the organo-metal complex by adding a large volume of a polar organic solvent, followed by filtering, washing and drying.

12. A composition suitable for administering to a human subject, said composition further comprising a chromium containing natural compound in the range of 0.05 to 5000 milligrams per day per subject.

13. The composition according to

claim 12

, said composition comprising a combination of compositions containing natural compounds isolated from natural sources including yeast or Saltbush.

14. The composition of

claim 13

further comprising an antioxidant selected from the group consisting of vitamin C, vitamin E, reduced glutathione, manganese, beta-carotene, ergothioneine, zinc, selenium cysteine, N-acetyl cysteine, methionine or 2-mercaptoethanol.

15. The composition of

claim 14

further comprising at least two antioxidants selected from the group consisting of vitamin C, vitamin E, reduced glutathione, manganese, beta-carotene, ergothioneine, zinc, selenium, cysteine, N-acetyl cysteine, methionine or 2-mercaptoethanol.

16. The composition according to

claim 13

, said composition being administered in an effective amount to a human subject suffering from a condition including hyperglycemia, hypertriglyceridemia, hypercholesterolemia, peripheral vascular disease, neuropathy, inflammatory diseases, warts, cell proliferative diseases, eczema, anthropathy, psoriasis or glucose intolerance, diabetes type I, diabetes type II, steroid diabetes.

17. The composition according to

claim 14

, said composition being administered in an effective amount to a human subject suffering from a condition including hyperglycemia, hypertriglyceridemia, hypercholesterolemia, peripheral vascular disease, neuropathy, inflammatory diseases, warts, cell proliferative diseases, eczema, anthropathy, psoriasis or glucose intolerance.

18. The composition according to

claim 15

, said composition being administered in an effective amount to a human subject suffering from a condition including hyperglycemia, hypertriglyceridemia, hypercholesterolemia, peripheral vascular disease, neuropathy, inflammatory diseases, warts, cell proliferative diseases, eczema, anthropathy, psoriasis or glucose intolerance.

19. The composition according to

claim 13

, said composition being administered in an effective amount to potentiate insulin action.

22. A method for regulating serum glucose levels in an animal, said method comprising administering an effective amount of a composition having a hypoglycemic or hypolipidemic activity extracted from a natural source.

23. The method according to

claim 22

wherein the natural sources include yeast or Saltbush.

24. The method according to

claim 23

further comprising administering an antioxidant selected from the group consisting of vitamin C, vitamin E, reduced glutathione, manganese, beta-carotene, ergothioneine, zinc, selenium, cysteine, N-acetyl cysteine, methionine or 2-mercaptoethanol.

25. A method for regulating triglyceride levels in an animal, said method comprising administering an effective amount of a chromium containing natural complex.

26. The method according to

claim 25

wherein the composition is isolated from natural sources including yeast or Saltbush.

27. The method according to

claim 25

further comprising administering an antioxidant selected from the group consisting of vitamin C, vitamin E, reduced glutathione, manganese, beta-carotene, ergothioneine, zinc, selenium, cysteine, N-acetyl cysteine, methionine or 2-mercaptoethanol.

28. A method for inhibiting production of lipid peroxides in an animal, said method comprising administering an effective amount of a composition possessing hypoglycemic or hypolipidemic activity.

30. The method according to

claim 28

further comprising administering an antioxidant selected from the group consisting of vitamin C, vitamin E, reduced glutathione, manganese, beta-carotene, ergothioneine, zinc, selenium, cysteine, N-acetyl cysteine, methionine or 2-mercaptoethanol.

31. A method of treating at least one of cardiovascular disease, hypercholesterolemia, inflammatory disease, warts, eczema, psoriasis, arthropathy or cell proliferative disease, said method comprising administering an effective amount of a composition possessing hypoglycemic or hypolipidemic activity.

32. The method according to

claim 31

wherein the composition possessing hypoglycemic or hypolipidemic activity is isolated from natural sources including yeast or Saltbush.

33. The method according to

claim 31

further comprising administering an antioxidant selected from the group consisting of vitamin C, vitamin E, reduced glutathione, manganese, beta-carotene, ergothioneine, zinc, selenium cysteine, N-acetyl cysteine, methionine or 2-mercaptoethanol.

34. A method of treating at least one of the conditions:

diabetes type I, diabetes type II, cardiovascular diseases, hypercholesterolemia, inflammatory disease, warts, eczema, psoriasis, arthropathy or cell proliferative disease, said method comprising administering an effective amount of a chromium containing synthetic complex selected from the group consisting of chromium gluconate, chromium sulfate, chromium-cysteine, chromium-N-acetyl cysteine, chromium-glutathione, chromium acetate, chromium citrate, chromium ascorbate or chromium tartarate.

35. The method according to

claim 34

further comprising administering an antioxidant selected from the group consisting of vitamin C, vitamin E, reduced glutathione, manganese, beta carotene, ergothioneine, zinc, selenium, cysteine, N-acetyl cysteine, methionine or 2-mercaptoethanol.

36. A method for potentiating insulin action, said method comprising administering an effective amount of a composition possessing hypolycemic or hypolidemic activity, isolated from natural sources including yeast or salt bush.

37. The method according to

claim 36

further administering an antioxidant selected from the group consisting of vitamin C, vitamin E, reduced glutathione, manganese, beta-carotene, ergothioneine, zinc, selenium, cysteine, N-acetyl cysteine, methionine or 2-mercaptoethanol.