United States Patent: 6,004,583

Assignee:  Orex Pharmaceutical Development Corp. (St. Louis, MO)

Filed:  August 2, 1996

A therapeutic-containing composition adapted for the oral administration of a biologically active material which comprises a water insoluble but water swellable polymer chemically modified with an enzyme inhibitor containing a chemical functionality which has an interactive affinity for target receptors located on the transport barrier walls of the digestive tract of the intended recipient, and at least one therapeutic of low oral bioavailability.

SUMMARY OF THE INVENTION

It is a general object of the invention to provide a composition for oral administration of therapeutic and bioactive materials whose oral availability is sufficiently limited under normal circumstances that they cannot be effectively utilized with this route of administration. More specifically, this invention deals with a composition comprising a hydrophilic polymer chemically modified with an enzyme inhibitor and a therapeutical material, often a protein or peptide, said composition being adequate for oral administration.

A further object of the invention is to provide a therapeutic-containing composition for oral administration which contains a water swellable polymer modified with an enzyme inhibitor and a therapeutic material, protein or peptide, said composition being in a tablet or capsule form, typically such that it may safely pass through the gastric environment and release the therapeutic ingredient in the small intestines.

A still further object of the invention is to increase the resistance of protein or peptide therapeutics to the effects of various digestive enzymes so as to enable such therapeutics to be more effectively administered orally.

A further object of the invention is to increase the interaction of the therapeutic-containing polymer hydrogels with selected transport barriers, and interactive sites of the intestine and/or bowels to increase the efficacy of the therapeutic substances.

A further object of the invention is to physically incorporate and entrap within the chemically modified hydrogels a protein or a peptide or other hard to deliver therapeutics without reacting, binding or substantially modifying such therapeutics, to properly protect them from premature decomposition, degradation, modification or destruction prior to its delivery to the desired location in the body such as to the intestinal barrier.

A further object of the invention is to deliver a therapeutically useful amount of a therapeutic, bioactive, or biomimetic, protein or a peptide to the target location in humans or animals to achieve useful therapeutic effects at such dosing levels that may produce desirable results similar to those when such therapeutic materials are injected into the body and/or at levels significantly lower than would be required when the therapeutics are given orally in the absence of the invention.

A further specific object of the invention is to provide an insulin containing polymer composition which is chemically modified by an enzyme inhibitor, such composition being contained within in a protective coating or capsule such that the resulting tablet or capsule may be administered orally to produce therapeutically useful effects equivalent or similar to those produced when insulin is injected subcutaneously or intramuscularly, and/or at levels much lower than would be required if insulin were to be given orally in the absence of the invention.

Claim 1 of 69 Claims

1. A therapeutic-containing composition adapted for the oral administration of a biologically active material comprising

(a) a water insoluble, but water swellable, polymer which contains at least one enzyme inhibitor covalently bound to the polymer and a chemical functionality which has an interactive affinity for target receptors located on the transport barrier walls of the digestive tract of the intended human or animal specie, wherein said chemical functionality is either integral to the structure of said inhibitor or is covalently bound to the polymer and

(b) one or more of therapeutic or biologically active agents.

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