Method for enhancing the lowering of plasma-cholesterol levels

• US 5,376,383 A
• Filed: 02/01/1993
• Issued: 12/27/1994
• Est. Priority Date: 11/21/1988
• Status: Expired due to Term

• Current Assignee: Merck & Co., Inc.
• Original Assignee: Merck & Co., Inc.
• Inventors: Alberts, Alfred W., Scolnick, Edward M., Repta, Arnold J.
• Primary Examiner(s): BROUILLETTE, D GABRIELLE
• Application Number:
  US08/013,111
• Time in Patent Office: 694 Days
• Field of Search: 424/473, 514/460
• US Class Current: 424/473
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/215 of carboxylic acids
• CPC Class Codes: A61K 31/22 of acyclic acids, e.g. pravastatin
• CPC Class Codes: A61K 31/365 Lactones
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Abstract

The instant invention is directed to a method for enhancing the lowering of plasma cholesterol level in a subject in need thereof which comprises the time-controlled administration of a nontoxic therapeutically effective amount of an HMG-CoA reductase inhibitor to said subject which surprisingly affords an equivalent or improved reduction of plasma cholesterol levels while significantly reducing the amount of HMG-CoA reductase inhibitor circulating in the bloodstream of the subject as compared to the same parameters when the oral administration of a conventional rapid release dosage form is utilized.

Claims

1. A method for enhancing the lowering of plasma cholesterol levels in a subject in need thereof which comprises the controlled release of a nontoxic therapeutically effective amount of an HMG-CoA reductase inhibitor to the subject which affords an equivalent lowering or greater lowering of plasma cholesterol levels while reducing the amount of HMG-CoA reductase inhibitor circulating in the bloodstream of the subject when compared to the oral administration of a rapid release dosage form, wherein the controlled release comprising the continuous introduction of the HMG-CoA reductase inhibitor into the environment of use over a period of six (6) to twenty-four (24) hours, utilizing a drug delivery device wherein the drug delivery device comprises:

(A) a core composition comprising

(a) a diffusible water soluble HMG-CoA reductase inhibitor, and

(b) an osmotically effective agent; and

(B) a water insoluble wall surrounding said core composition and prepared from

(i) a polymer material that is permeable to water but substantially impermeable to solute and

(ii) 0.1 to 75% by weight, based on the total weight of (i) and (ii), of at least one water leachable pore forming additive dispersed throughout said wall;

or

(C) a substantially imperforate water insoluble wall surrounding said core composition and prepared from a semipermeable material substantially impermeable to core composition and permeable to the passage of an external fluid in the environment of use, with said wall having a means for release of the therapeutic agent through the water insoluble wall.

2. The method of claim 1 wherein the core composition of the drug delivery device comprises

(a) a water insoluble, nondiffusible charged resin entity, and

(b) a diffusible water soluble ionizable HMG-CoA reductase inhibitor carrying the same charge as said resin entity.

3. The method of claim 1 wherein the core composition of the drug delivery device comprises

(a) a solubility modulating agent which is either (i) surrounded by a water insoluble coat containing at least one pore forming additive dispersed throughout said coat, or (ii dispersed in a matrix substrate, and

(b) a diffusible water soluble HMG-CoA reductase inhibitor.