Title:  Delayed release aspirin for vascular obstruction prophylaxis

United States Patent:  6,663,896

Issued:  December 16, 2003

Inventors:  Blum; Alvin S. (2350 Del Mar Pl., Fort Lauderdale, FL 33301)

Appl. No.:  920018

Filed:  August 1, 2001

Abstract

A method and controlled release oral unit dosage form of acetylsalicylic acid (aspirin) delays the release of the drug until a predetermined time interval after ingestion. This enables the drug to reach optimal therapeutic blood levels at a time in the early morning when the events leading up to a vascular obstruction culminating in a heart attack or stroke are most commonly occurring after the drug is taken in the evening. The convenience of taking the drug every evening should enhance compliance. By arranging for the optimal blood level to coincide with the peak incidence of strokes, a much smaller total dose of the drug may be used than is normally prescribed. This may reduce the incidence of side effects that are dose related. This will make the prophylactic use of aspirin available to more of the population.

SUMMARY OF THE INVENTION

It is accordingly an object of the invention to provide a method and medicament formulation that will prevent vascular obstructions that lead to heart attacks and strokes with minimal side effects. The medicament is aspirin (ASA) or its derivatives. It is prepared in oral dose form to be taken at a convenient time in the evening, such as with the evening meal, or at bedtime. It is to be taken daily rather than on alternate days to enhance compliance. The dose is so prepared that, after ingestion, there will be no release of the drug into the gut in absorbable form for a preset time interval. The purpose is to ensure that the drug will reach an optimal blood level in the early morning when it is most needed. It is well known that the incidence of heart attacks is greatest in the morning. If the attack occurs at this time, the precipitating events occur somewhat earlier. By arranging to reach an optimal blood level of ASA to approximately coincide with the time when the need for the drug is greatest, the amount of drug administered can be greatly reduced. If 80 mg. is effective on the second day after administration when the blood level is very low, then a very low dose, such as 8 mg. or 16 mg., may be effective with this new formulation. Such a low dose would be easily tolerated with very low incidence of side effects.

These and other objects, features, and advantages of the invention will become more apparent when the detailed description is studied.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The term aspirin as herein employed is meant to include acetylsalicylic acid (ASA) and derivatives thereof that have similar therapeutic effects.

The invention comprises the drug aspirin in oral dose form so formulated that it will release an insignificant amount of drug in absorbable form into the gastrointestinal tract for a preset time interval after ingestion of at least five to as much as eight hours. This is arranged so that the drug can be ingested the prior day, at dinner or bedtime. The drug is then absorbed from the gut over a time period arranged to most effectively elevate the blood level of the drug to a level that will coincide with the morning peak incidence of vascular obstruction commonly encountered.

Techniques are well known in the art for coating drugs with variously composed coating agents that dissolve very slowly in the intestine to delay release of the drug. Such coatings that delay release may be applied to pellets of ASA that are then enclosed in a capsule. All of the pellets may be coated to prevent release absorption before the preset time interval. Alternatively, the ASA maybe formed into a tablet that is then coated with a coating that dissolves slowly. Another well-known technique that may be used employs a coated tablet with a water-permeable but insoluble film. The film encloses an osmotic agent and the active ingredient. As water from the gut slowly diffuses through the film into the core, the core swells until the film bursts, releasing the drug. The film coating may be adjusted for selecting a suitable rate of water permeation, and thereby, ASA release time. In another embodiment, the tablet coating is impermeable, and water enters through a controlled aperture in the coating until the core bursts. When the tablet bursts, the contents may contain drug in freely absorbable form and some as sustained release pellets to release drug over a longer period of time, if desired.

These and other techniques may be employed to formulate tablets or capsules with the requisite time interval before aspirin release. The time interval may be between five and ten hours, for example. This time for optimal release may be earlier than the reported peak time of onset of heart attacks. Events occurring in the body that lead up to the actual heart attack such as activation of platelets, pooling and stagnation of blood in the extremities, dehydration, and the like may not lead to vascular occlusion in the presence of adequate blood levels of ASA. By administering the oral medication at a convenient time the previous night, the delay allows the drug to reach optimal levels when needed without disturbing a normal sleep pattern.

The method of the invention comprises administration of the low dose of the above composition in the evening with the time delay to release arranged to permit absorption into the blood in the early morning when it will be most effective in reducing the incidence of dangerous vascular obstructions.

While I have shown and described the preferred embodiments of my invention, it will be understood that the invention may be embodied otherwise than as herein specifically described, and that certain changes in form and arrangement and the specific manner of practicing the invention may be made within the underlying idea or principles of the invention.

Claim 1 of 14 Claims

What is claimed is:

1. A controlled release pharmaceutical composition in oral unit dosage form for releasing aspirin into the gastrointestinal tract in absorbable form at a predetermined time interval after ingestion and not before, the dosage form comprising:

a) a core comprising no more than 20 milligrams of aspirin;

b) a frangible coating of said core protecting said aspirin from dissolution by gastrointestinal fluids; and

c) means incorporated in said dosage form for releasing said core into said gastrointestinal fluids after a predetermined time interval of at least five hours after ingestion, the composition releasing no aspirin into the gastrointestinal tract in absorbable form until the expiration of the time interval.

____________________________________________
If you want to learn more about this patent, please go directly to the U.S. Patent and Trademark Office Web site to access the full patent.