NOVEL COMPOSITIONS AND METHODS OF TREATMENT OF TYPE II DIABETES AND HYPERTENSION

Abstract

The subject invention relates to a composition and method for treating a patient employing co-formulation or co-administration of a thiazolidinedione (TZD) and a diuretic.

Description

DETAILED DESCRIPTION OF THE INVENTION

Thiazide-type diuretics include HCTZ, chlorothiazide, chlorthalidone, and many others as are found in standard textbooks such as Goodman and Gilman's The Pharmacological Basis of Therapeutics (2006) 11^th Ed. Included for discussion and inventive purposes herein are other diuretics such as indapamide that are often not considered to be TTDs.

Loop diuretics useful in the compositions and method of the subject invention include without limitation furosemide, torsemide, bumetamide, ethacrynic acid, and the like.

TZDs include with limitation piogliatazone, rosiglitazone, troglitazone, and the like.

Doses used comprise those known in the art to be safe and effective for their approved purpose. In addition, it would be recognized that the active ingredient used in the compositions and methods of the subject invention can include the use of a pharmaceutical salt, active metabolite, prodrug, derivative, polymorph or hydrate of the active ingredient, or a combination or mixture thereof.

Another benefit of the invention involves preventing the onset of diabetes in a patient, such as one with pre-diabetes, which is variously defined quantitatively as blood sugar in the 100-200 range or in dictionaries as, for example, an asymptomatic abnormal state that precedes the development of clinically evident diabetes (Merriam-Webster's Medical Dictionary, 2002).

Formulations of the invention include the use of known pharmaceutically acceptable excipients as would be readily understood in the art in view of the subject disclosure. Such excipients and carriers are described, for example, in “Remington's Pharmaceutical Sciences” Mack Pub. Co., New Jersey (1991), which is incorporated herein by reference.

It is recognized that related inventions may be within the spirit of the disclosures herein. Also no omission in the current application is intended to limit the inventors to the current claims or disclosures. While certain preferred and alternative embodiments of the invention have been set forth for purposes of disclosing the invention, modifications to the disclosed embodiments may occur to those who are skilled in the art.

Claims

1. A pharmaceutical composition or co-packaging comprising a TZD plus a diuretic selected from the group consisting of a thiazide-type diuretic (“TTD”), a loop diuretic, and a potassium-retaining diuretic.

2. A method of treatment comprising administering within the same day a TZD plus a diuretic.

3. The method of treatment to claim 2, wherein said TZD and diuretic are administered within about 12 hours of each other.

4. The method of claim 2 wherein said TZD and diuretic are administered within about 4 hours of each other.

5. The method of claim 2 wherein said TZD and diuretic are administered within about 1 hour of each other.

6. The method of claim 2 wherein said TZD and diuretic are administered concomitantly.

7. The method of claim 6 wherein said TZD and diuretic are concomitantly administered within a single dosage form.

8. The composition as in claim 1, in which the TZD and the diuretic are additive with respect to blood pressure lowering in a hypertensive patient.

9. The composition of claim 1 wherein said TZD and diuretic are synergistic with regard to blood pressure lowering in a patient suffering from hypertension.

10. The composition of claim 1 wherein neither of said TZD and diuretic has a statistically significant (demonstrable) BP benefit vs. placebo but the combination effects a statistically significant BP benefit.

11. The composition of claim 1, wherein the TZD lacks a statistically significant or otherwise demonstrable benefit vs. placebo and the diuretic is statistically significantly better than placebo, and the combination demonstrates a benefit of the combination vs. the diuretic, the parameter referred to in this claim being blood pressure lowering in a patient suffering from hypertension.

12. The composition of claim 1, wherein the diuretic lacks a statistically significant or otherwise demonstrable benefit vs. placebo and the TZD is statistically significantly better than placebo, and the combination demonstrates a benefit of the combination vs. the TZD, the parameter being referred to in this claim being blood pressure lowering in a patient suffering from hypertension.

13. A pharmaceutical composition comprising at least two active drug components in which the at least two components each offset or mitigate a side effect of the other component, involving other than the situation in which each drug has opposing actions on the same parameter.

14. A method of treating a patient with a diuretic to prevent either the onset of edema, the worsening of edema, the onset of congestive heart failure, or the worsening of congestive heart failure, by treating with said diuretic a patient receiving or scheduled to being to receive TZD.

15. A method of treating edema caused or worsened by a TZD by concomitant administration of a TTD with said TZD, either in separate dosage forms or in a co-formulation.

16. A method of preventing the onset of diabetes mellitus (“diabetes”) in patients with pre-diabetes, said method comprising administering a TZD in said patient.

17. The method of claim 16 wherein said patient is further administered a diuretic.

18. The method of claim 16 wherein said patient is receiving or scheduled (about) to receive a diuretic.

19. A method of preventing the worsening of glycemic status in a patient scheduled (about) to receive a diuretic by co-administering a TZD, said method comprising administering a diuretic.

20. A method of preventing or ameliorating a rise in serum cholesterol due to a diuretic by co-administration of a TZD.

21. The composition of claim 1 wherein said TZD is pioglitazone.

22. The composition of claim 1 wherein said diuretic is HCTZ or chlorthalidone.