Title:  Local delivery of non steroidal anti inflammatory drugs (NSAIDS) to the colon as a treatment for colonic polyps

United States Patent:  6,231,888

Assignee:  Perio Products Ltd. (Jerusalem, IL)

Filed:  November 12, 1998

A composition and method for the treatment of polyp and colon cancer is described, such composition and method providing for the colonic delivery and/or preferential metabolism of a drug or desired agent, especially an NSAID, in the colon of the patient in need such treatment.

SUMMARY OF THE INVENTION

Recognizing the need for treating colonic polyps in a manner that results in a minimal number of systemic side effects, and cognizant of the problem of delivering efficacious levels of drugs to the colonic environment, the inventors investigated methods by which therapeutic levels of drugs might be presented to the colonic environment.

These studies cumulated in the discovery of a method of administering sulindac to a patient in need of same, which method enhances the amount of sulindac which is converted into the more active metabolite, sulindac sulfide, in such patient, when compared to the amount that is converted into sulindac's less active metabolite, sulindac sulfone, in the same patient, by minimizing the amount of sulindac that is absorbed into the bloodstream and by maximizing the amount of sulindac that is delivered to the colon--at which location the sulindac is preferentially metabolized into sulindac sulfide by the colonic environment and absorbed therefrom.

These studies also cumulated in the discovery of a novel composition or formulation for the oral administration of a colonic delivery system (CDS), and method for use of the same, for providing a desired agent to the colon of human and animal patients in need of the same.

Thus, in a first embodiment, a method is provided for the administration of sulindac to a patient in need of the same wherein the most if not all of the dose of sulindac that is administered to such patient is delivered to the colon of the patient.

In a further embodiment, a composition or formulation designed for oral administration of a colonic delivery system (CDS) is provided, such formulation containing the structure of a coated core in which the core contains a desired agent. The coat of the coated core is based on a formulation that comprises water insoluble hydrophilic particulate matter embedded in a water-insoluble carrier; the formulation is such that when exposed to an aqueous environment, the particulate matter in the coat absorbs water, thus forming channels that interconnect the inner core with the outer surface of the coating. These channels allow aqueous solutions to enter the core and drug to diffuse out.

In a further embodiment, the invention is directed to a method of administering the compositions as above, wherein the most or all of the dose of a desired agent is delivered to the colon. In a preferred embodiment, the colonic contents or cell walls metabolize the drug to a more desired form, for example, a more active metabolite, such more desired form thus being synthesized in a preferential manner and locally higher concentration by such delivery directly to the colon than when the drug is administered systemically or orally in a conventional manner.

In a further embodiment, the invention is directed to compositions and the administration of the same as above, wherein the drug is an NSAID.

In a further embodiment, the invention is directed to compositions and the administration of the same as above, wherein the more active metabolite is a COX-2 inhibitor.

In a further embodiment, the invention is directed to compositions and administration of the same as above, wherein the drug and metabolite are sulindac and sulindac sulfide, respectively.

In a further embodiment, the invention is directed to compositions and administration of the same as above, especially NSAID and most especially sulindac, for the treatment and prevention of polyps or cancer, especially colonic cancer.

Claim 1 of 61 Claims

What is claimed is:

1. A composition or drug delivery device for localized drug release in the colon, said composition or device comprising one or more drugs in a core, and a coating surrounding said core, said coating having an outer surface, wherein said coating comprises water insoluble hydrophilic particulate matter embedded in a water-insoluble carrier, such that when said composition or device enters the gastrointestinal tract, said particulate matter absorbs liquid, thus forming channels that interconnect said core with said outer surface of said coating, and through which channels, said one or more drugs are released into the colon, such that at least one of said drugs is preferentially metabolized to a more active metabolite in the colon.

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