COMPOSITIONS AND METHODS FOR LOWERING SERUM CHOLESTEROL

• US 20090163452A1
• Filed: 11/19/2008
• Published: 06/25/2009
• Est. Priority Date: 12/20/2007
• Status: Abandoned Application

• Current Assignee: Griffin & Schwartz, Inc.
• Original Assignee: Griffin & Schwartz, Inc.
• Inventors: SCHWARTZ, Janice B.
• Application Number:
  US12/274,189
• Publication Number:
  US 20090163452A1
• Time in Patent Office: Days
• US Class Current: 514/167
• 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 31/59 Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

The invention provides a method for lowering circulating LDL-cholesterol or total cholesterol in a human in need thereof, comprising: orally administering to the human a therapeutically effective amount of a statin and vitamin D daily for at least about 6 weeks, wherein the vitamin D is administered by one or more pharmaceutical compositions.

Claims

1. A method for lowering circulating LDL-cholesterol or total cholesterol in a human in need thereof, comprising:

orally administering to the human a therapeutically effective amount of a statin and vitamin D daily for at least about 6 weeks,

wherein the human is selected from the group consisting of;

a human unable to tolerate the statin when administered in a therapeutically effective dose and in the absence of vitamin D;

a pre-menopausal female;

a male without congestive heart failure; and

a male with congestive heart failure; and

wherein the vitamin D is administered by one or more pharmaceutical compositions;

with the proviso that when the human is a male with congestive heart failure, the total daily amount of vitamin D administered by the one or more pharmaceutical compositions is equipotent to about 600 to about 1800 International Units (IU) of ergocalciferol or cholechalciferol.

2. The method of claim 1, wherein the human is unable to tolerate the statin when administered in a therapeutically effective dose and in the absence of vitamin D.

3. The method of claim 1, wherein the human is a pre-menopausal female.

4. The method of claim 3, wherein the human has congestive heart failure.

5. The method of claim 3, wherein the human does not have congestive heart failure.

6. The method of claim 1, wherein the human is a male without congestive heart failure.

7. The method of claim 1, wherein the human is a male with congestive heart failure.

8. The method of claim 1, wherein the human is selected from the group consisting of:

a human unable to tolerate the statin when administered in a therapeutically effective dose and in the absence of vitamin D;

a pre-menopausal female; and

a male without congestive heart failure; and

the total daily amount of vitamin D administered by the one or more pharmaceutical compositions is equipotent to about 600 to about 2500 IU of ergocalciferol or cholechalciferol.

9. The method of claim 1, wherein the human is selected from the group consisting of:

a human unable to tolerate the statin when administered in a therapeutically effective dose and in the absence of vitamin D;

a pre-menopausal female; and

a male without congestive heart failure; and

the total daily amount of vitamin D administered by the one or more pharmaceutical compositions is equipotent to about 1200 to about 2500 IU of ergocalciferol or cholechalciferol.

10. The method of claim 1, wherein the human is selected from the group consisting of:

a human unable to tolerate the statin when administered in a therapeutically effective dose and in the absence of vitamin D;

a pre-menopausal female; and

a male without congestive heart failure; and

the total daily amount of vitamin D administered by the one or more pharmaceutical compositions is equipotent to about 600 to about 2000 IU of ergocalciferol or cholechalciferol.

11. The method of claim 1, wherein the total daily amount of vitamin D administered by the one or more pharmaceutical compositions is equipotent to about 600 to about 1800 IU of ergocalciferol or cholechalciferol.

12. The method of claim 1, wherein the total daily amount of vitamin D administered by the one or more pharmaceutical compositions is equipotent to about 600 to about 1200 IU of ergocalciferol or cholechalciferol.

13. The method of claim 1, wherein the total daily amount of vitamin D administered by the one or more pharmaceutical compositions is equipotent to about 800 to about 1000 IU of ergocalciferol or cholechalciferol.

14. The method of claim 1, wherein the vitamin D comprises one or more of:

cholecalciferol, ergocalciferol, alfacalcidol, calcitriol, 22-oxacalcitriol, paricalcitol, doxercalciferol, and dihydrotachysterol₂.

15. The method of claim 1, wherein the vitamin D comprises ergocalciferol.

16. The method of claim 1, wherein the vitamin D comprises cholecalciferol.

17. The method of claim 1, wherein the statin is metabolized by cytochrome p450(CYP) enzyme (CYP3A).

18. The method of claim 1, wherein the statin is selected from the group consisting of:

lovastatin, simvastatin, and atorvastatin.

19. The method of claim 1, wherein the statin is atorvastatin.

20. The method of claim 1, wherein the amount of statin required to achieve a particular decrease in LDL-cholesterol or total cholesterol is less than that required when the statin is administered in the absence of the one or more pharmaceutical compositions comprising vitamin D.

21. The method of claim 1, further comprising orally administering to the human calcium daily for at least about 6 weeks.

22. The method of claim 1, further comprising administering one or more additional therapeutic agents selected from the group consisting of:

a non-statin lipid lowering agent, a HDL-raising agent, insulin, and a non-insulin diabetic agent.

23. The method of claim 22, wherein the one or more additional therapeutic agents are selected from the group consisting of:

a bile acid sequestrant, a fibric acid derivative, an omega-3 fatty acid, niacin, a cholesterol absorption inhibitor, a cholesteryl ester transfer protein (CETP) inhibitor, insulin, a sulfonylurea, a biguanide, a meglitinide, a thiazolidinedione, a 6-alpha-glucosidase inhibitor, a glucagon-like peptide (GLP) analog, and a gastric inhibitory peptide (GIP) analog.

24. The method of claim 22, wherein the one or more additional therapeutic agents comprise ezetimide.

25. The method of claim 1, wherein the one or more pharmaceutical compositions comprises a pharmaceutical composition comprising vitamin D and calcium.

26. The method of claim 1, wherein the one or more pharmaceutical compositions comprises a pharmaceutical composition comprising a multivitamin composition comprising vitamin D.

27. The method of claim 1, wherein the human is at least about 12 years of age.

28. The method of claim 1, wherein the human does not have psoriasis.

29. The method of claim 1, wherein the human does not have osteoporosis.

30. The method of claim 1, wherein the human does not have multiple sclerosis.

31. The method of claim 1, wherein the human is diabetic.

32. The method of claim 1, wherein the human has not previously been treated with at least about 600 IU of ergocalciferol or cholecalciferol or equipotent amount thereof per day for at least about 6 weeks.

33. The method of claim 1, wherein prior to administration of the statin and vitamin D, the human has a combined 25-OH vitamin D₂ and 25-OH vitamin D₃ serum level of less than about 20 ng/ml, wherein the combined 25-OH vitamin D₂ and 25-OH vitamin D₃ serum level is measured by mass spectroscopy.

34. The method of claim 33, wherein after at least about 6 weeks of the administration of the statin and vitamin D, the human has a combined 25-OH vitamin D₂ and 25-OH vitamin D₃ serum level of greater than about 30 ng/ml, wherein the combined 25-OH vitamin D₂ and 25-OH vitamin D₃ serum level is measured by mass spectroscopy.

35. The method of claim 1, wherein prior to administration of the statin and vitamin D, the human has a combined 25-OH vitamin D₂ and 25-OH vitamin D₃ serum level of about 20 to about 30 ng/ml, wherein the combined 25-OH vitamin D₂ and 25-OH vitamin D₃ serum level is measured by mass spectroscopy.

36. The method of claim 35, wherein after at least about 6 weeks of the administration of the statin and vitamin D, the human has a combined 25-OH vitamin D₂ and 25-OH vitamin D₃ serum level of greater than about 30 ng/ml, wherein the combined 25-OH vitamin D₂ and 25-OH vitamin D₃ serum level is measured by mass spectroscopy.