Compositions containing policosanol and biotin and their pharmaceutical uses

• US 20060020007A1
• Filed: 07/26/2004
• Published: 01/26/2006
• Est. Priority Date: 07/26/2004
• Status: Abandoned Application

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: Wyeth (Pfizer Inc.)
• Inventors: Berlin, Roger
• Application Number:
  US10/898,889
• Publication Number:
  US 20060020007A1
• Time in Patent Office: Days
• US Class Current: 514/393
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/045 Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
• CPC Class Codes: A61K 31/4188 condensed with other heterocyclic ring systems, e.g. biotin, sorbinil

Abstract

A composition is provided which contains policosanol and biotin and which may be used for treating, preventing and or reducing metabolic syndrome, hypercholesterolemia and hypoglycemia related diseases, total cholesterol, LDL-cholesterol, LDL/HDL ratio, triglycerides, coronary heart disease (heart attacks and strokes), inflammation, deep-vein thrombosis, immunoregulatory diseases, cardiovascular diseases, obesity, insulin resistance, dyslipidemia, raised blood pressure, fatigue, premenstrual syndrome, anxiety, depression and/or neurodegenerative disorders, and/or raising HDL cholesterol in humans and animals. The method comprises administering policosanol and biotin which together effectively lower blood glucose levels and lower the LDL/HDL cholesterol ratio. Typically, the administered composition includes about 0.1-10:1 parts by weight of policosanol to biotin.

Claims

1. A composition comprising policosanol and biotin.

2. The composition of claim 1, wherein said policosanol comprises a mixture of straight chain primary aliphatic alcohols from 20 to 36 carbons in length.

3. The composition of claim 2, wherein said mixture of straight chain primary aliphatic alcohols includes:

1-eicosanol (C-20) 0-5%

1-docosanol (C-22) 0-5%

1-tetracosanol (C-24) 0-30%

1-hexacosanol (C-26) 5-30%

1-heptacosanol (C-27) 0-5%

1-octacosanol (C-28) 5-80%

1-nonacosanol (C-29) 0-5%

1-triacontanol (C-30) 5-40%

1-dotriacontanol (C-32) 1-25%

1-tetratriacontanol (C-34) 0-7%

1-hexatriacontanol (C-36) 0-5%.

4. The composition of claim 2, wherein said mixture of straight chain primary aliphatic alcohols includes:

1-eicosanol (C-20) 0-5%

1-docosanol (C-22) 0-5%

1-tetracosanol (C-24) 12-27%

1-hexacosanol (C-26) 13-28%

1-heptacosanol (C-27) 0-5%

1-octacosanol (C-28) 15-25%

1-triacontanol (C-30) 25-40%

1-dotriacontanol (C-32) 5-15%

1-tetratriacontanol (C-34) 0-5%.

5. The composition of claim 1, further comprising a pharmaceutically acceptable carrier, excipient or dilutant.

6. The composition of claim 5, in the form of a capsule, tablet, liquid or powder.

11. The composition of claim 1 wherein said policosanol comprises at least one higher primary aliphatic alcohol selected from stright chain primary aliphatic alcohols having 20 to 36 carbon atoms, and biotin, wherein said composition is further characterized by a combination of policosanol and biotin in a quantitative ratio from 100:

1 to 0.01;

1 by weight.

12. The composition of claim 11 wherein said policosanol comprises 1-tetracosanol, 1-hexacosanol, 1-octacosanol, 1-triacontanol, 1-dotriacontanol and 1-tetratriacontanol, said composition is further characterized by a combination of policosanol and biotin in a quantitative ratio from 10:

1 to 0.10;

1 by weight.

13. The composition of claim 12, wherein said policosanol has the following quantitative composition:

1-docosanol (C-22) 0-5 wt %

1-tetracosanol (C-24) 0-30 wt %

1-hexacosanol (C-26) 5-30 wt %

1-heptacosanol (C-27) 5-10 wt %

1-octacosanol (C-28) 10-20 wt %

1-nonacosanol (C-29) 0-5 wt %

1-triacontanol (C-30) 5-40 wt %

1-dotriacontanol (C-32) 1-25 wt %

1-tetratriacontanol (C-34) 0 7 wt %;

and said composition is further characterized by a combination of policosanol and biotin in a quantitative ratio from 3;

1 to 0.33;

1 by weight.

33. The composition of claim 1, wherein said biotin is administered in a daily dose within a range from 0.05 mcg/day to 20,000 mcg/day.

34. The composition of claim 1, wherein said biotin is administered in a daily dose in the range of 1-2,000 mcg/day.

35. The composition of claim 1, wherein said biotin is administered in a daily dose in the range of 5-1,000 mcg/day.

47. The composition of claim 1, further comprising aspirin.

48. The composition of claim 1, further comprising aspirin administered in a dose in the range of 162-325 mg.

7. A method for treating or preventing metabolic syndrome, hypercholesterolemia related diseases, and/or hypoglycemia related diseases, which comprises administering a pharmaceutically effective amount of a composition comprising policosanol and biotin to a human or mammal.

8. A method for reducing total cholesterol, LDL-cholesterol and blood glucose and increasing HDL-cholesterol levels, which comprises administering a pharmaceutically effective amount of a composition comprising policosanol and biotin to a human or mammal.

9. A method for lowering LDL-cholesterol, total cholesterol, blood glucose levels, increasing HDL-cholesterol, and improving LDL-cholesterol/HDL-cholesterol ratio which comprises administering a composition comprising policosanol and biotin in a pharmaceutically acceptable amount to an individual in need thereof.

10. A method for lowering blood glucose levels which comprises administering a composition comprising policosanol and biotin in a pharmaceutically acceptable amount to an individual in need thereof.

45. The methods of claims 7, 8, 9, and 10, further comprising administering asprin.

46. The method of claim 45, wherein said aspirin is administered in a dose in the range of 162-325 mg.

14. A method of treating metabolic syndrome, hypercholesterolemia and hypoglycemia related diseases, total cholesterol, LDL-cholesterol, LDL/HDL ratio, triglycerides, coronary heart disease (heart attacks and strokes), inflammation, deep-vein thrombosis, immunoregulatory diseases, cardiovascular diseases, obesity, insulin resistance, dyslipidemia, raised blood pressure, fatigue, premenstrual syndrome, anxiety, depression and/or neurodegenerative disorders, and/or raise HDL cholesterol in a patient, comprising delivering to said patient a composition comprising policosanol and biotin in an amount effective to reduce and/or prevent metabolic syndrome, hypercholesterolemia and hypoglycemia related diseases, total cholesterol, LDL-cholesterol, LDL/HDL ratio, triglycerides, coronary heart disease (heart attacks and strokes), inflammation, deep-vein thrombosis, immunoregulatory diseases, cardiovascular diseases, obesity, insulin resistance, dyslipidemia, raised blood pressure, fatigue, premenstrual syndrome, anxiety, depression and/or neurodegenerative disorders, and/or raise HDL cholesterol in an individual in need thereof, wherein said composition is delivered to said patient as a controlled/sustained/extended/prolonged release composition.

15. The method of claim 14, wherein said controlled/sustained/extended/prolonged release composition comprises a flowable thermoplastic polymer composition comprising a biocompatible polymer, a biocompatible solvent, policosanol and biotin and said controlled/sustained/extended/prolonged release composition is delivered to a bodily tissue or fluid in said patient, wherein the amounts of the polymer and the solvent are effective to form a biodegradable polymer matrix containing policosanol and biotin in situ when said composition contacts said bodily fluid tissue or fluid.

16. The method of claim 15, wherein said polymer is a poly(alkylene glycol) or a polysaccharide.

17. The method of claim 14, wherein the composition further comprises a controlled/sustained/extended/prolonged release additive.

18. The method of claim 15, wherein said biocompatible polymer is selected from the group consisting of polylactides, polyglycolides, polyanhydrides, polyorthoesters, polycaprolactones, polyamides, polyurethanes, polyesteramides, polydioxanones, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyalkylene oxalates, polyacrylates, polyalkylene succinates, poly(malic acid), poly(amino acids) and copolymers, terpolymers, cellulose diacetate, ethylene vinyl alcohol, and copolymers and combinations thereof.

19. The method of claim 15, wherein said biodegradable polymer matrix releases policosanol and biotin by diffusion, erosion, or a combination of diffusion or erosion as the polymer matrix biodegrades in said patient.

20. The method of claim 15, wherein said policosanol and biotin are added to said polymer composition prior to administration such that said solid polymer matrix further contains said policosanol and biotin.

21. The method of claim 14, wherein said controlled/sustained/extended/prolonged release composition is in film form.

22. The method of claim 21, wherein said film comprises polylactic acid, polyglycolic acid and mixtures and copolymers thereof.

23. The method of claim 14, wherein said controlled/sustained/extended/prolonged release is in tablet form.

40. The method of claim 14, wherein said controlled/sustained/extended/prolonged release composition comprises applying a transdermal delivery system containing a mixture of policosanol and biotin to the skin of a patient and maintaining the transdermal delivery system in contact with the skin for a time sufficient to provide a pharmaceutically effective steady state plasma concentration in the patient.

44. The method of claim 14, wherein said controlled/sustained/extended/prolonged release composition comprises administering subcutaneously to the patient a mixture of policosanol and biotin.

24. A kit comprising a first container comprising a controlled/sustained/extended/prolonged release formulation of policosanol and biotin, said formulation comprising an amount of policosanol and biotin effective to treat or reduce and/or prevent metabolic syndrome, hypercholesterolemia and hypoglycemia related diseases, total cholesterol, LDL-cholesterol, LDL/HDL ratio, triglycerides, coronary heart disease (heart attacks and strokes), inflammation, deep-vein thrombosis, immunoregulatory diseases, cardiovascular diseases, obesity, insulin resistance, dyslipidemia, raised blood pressure, fatigue, premenstrual syndrome, anxiety, depression and/or neurodegenerative disorders, and/or raise HDL cholesterol.

25. The kit of claim 24, further comprising a puncture needle or catheter.

26. An article of manufacture comprising:

(a) a stent body comprising a surface; and

(b) a coating comprising at least one layer disposed over at least a portion of the stent body, wherein the said layer comprises polymer film having at least one biologically active agent dispersed therein.

27. The article of manufacture of claim 26, wherein said biologically active agent is policosanol and biotin.

28. A method of reducing LDL-cholesterol, triglyceride and/or blood glucose levels comprising:

administering to a mammal a pharmaceutical composition in an amount that inhibits VLDL triglyceride output and inhibits the conversion of acetate to acetyl CoA while not raising uric acid levels, glucose levels and/or homocysteine levels.

29. The method of claim 28, wherein the administration of said composition further comprises raising HDL-cholesterol levels.

30. The method of claim 28, wherein the triglyceride output is inhibited by biotin.

31. The method of claim 28, wherein the blood glucose levels are reduced by biotin.

32. The method of claim 28, wherein the conversion of acetate to acetyl CoA is inhibited by policosanol.

36. A controlled/sustained/extended/prolonged release preparation comprising a pharmaceutically active mixture of policosanol and biotin.

37. A transdermal preparation designed to administer a pharmaceutically effective amount of policosanol and biotin into the blood stream.

38. The transdermal preparation of claim 37, wherein the policosanol and biotin are present in a concentration sufficient that when applied to the skin a pharmaceutically effective steady state plasma concentration in the patient of said biotin is produced.

39. A transdermal delivery system for application to the skin of a patient, comprising:

(a) a drug impermeable backing layer;

(b) an adhesive layer;

(c) a drug permeable membrane, wherein the membrane is positioned relative to the backing layer so as to form at least one drug reservoir compartment between the membrane and the backing layer; and

(d) a composition comprising policosanol and biotin contained within the drug reservoir compartment in a concentration sufficient such that the transdermal delivery system has an input rate when applied to the skin sufficient to produce a pharmaceutically effective steady state plasma concentration in the patient.

41. A subcutaneous implant comprising policosanol and biotin.

42. The subcutaneous implant of claim 41 wherein said implant is effective to release levels of policosanol and biotin over an extended period of time when subcutaneously implant in a human or animal in need thereof.

43. A method for administering policosanol and biotin to a human or animal which comprises subcutaneously implanting either a biodegradeable or nonbiodegradable polymer comprising a mixture of policosanol and biotin.

49. A method for improving insulin activities and fat, protein and carbohydrate metabolism, which comprises administering a composition comprising policosanol and biotin in a pharmaceutically acceptable amount to an individual in need thereof.

50. The composition of claim 49 wherein said policosanol comprises at least one higher primary aliphatic alcohol selected from stright chain primary aliphatic alcohols having 20 to 36 carbon atoms, and biotin.

51. The composition of claim 50 wherein said policosanol comprises 1-tetracosanol, 1-hexacosanol, 1-octacosanol, 1-triacontanol, 1-dotriacontanol and 1-tetratriacontanol, said composition is further characterized by a combination of policosanol and biotin in a quantitative ratio from 10:

1 to 0.10;

1 by weight.

52. The composition of claim 51, wherein said policosanol has the following quantitative composition:

1-docosanol (C-22) 0-5 wt %

1-tetracosanol (C-24) 0-30 wt %

1-hexacosanol (C-26) 5-30 wt %

1-heptacosanol (C-27) 5-10 wt %

1-octacosanol (C-28) 10-20 wt %

1-nonacosanol (C-29) 0-5 wt %

1-triacontanol (C-30) 5-40 wt %

1-dotriacontanol (C-32) 1-25 wt %

1-tetratriacontanol (C-34) 0 7 wt %.