Title:  Colonic delivery of nicotine to treat inflammatory bowel disease

United States Patent:  6,166,044

Assignee:  Mayo Foundation for Medical Education and Research (Rochester, MN)

Filed:  March 23, 1999

A method is provided to treat inflammatory bowel disease by locally administering to the colon an effective amount of nicotine or a pharmaceutically acceptable salt thereof, preferably via formulations adapted for delayed oral release or rectal administration. Further provided is a novel formulation for the oral administration of nicotine comprising a polyacrylic polymer complexed with nicotine.

SUMMARY OF THE INVENTION

The inventors have now surprisingly discovered that nicotine delivered to the terminal ileum, rectum, and/or colon of a patient suffering from IBD is at least as efficacious as high dosage transdermal patch and substantially reduces the aforementioned side-effects which plagued the patch treatment. This is even more surprising because existing treatments such as cyclosporin which are very efficacious when given systemically fail completely when delivered colonically. Furthermore it would not be expected that an addictive and toxic agent such as nicotine whose side effects caused many patients to discontinue treatment could subsequently be reformulated to provide a safe and long term treatment substantially free of the previous side-effects.

The present invention provides a therapeutic method of treating inflammatory bowel disease (IBD) comprising locally administering to the rectum, colon and/or terminal ileum of a patient in need of such treatment, an amount of nicotine effective to reduce the symptoms of IBD. In one embodiment of the present method, the nicotine is administered orally, by means of a unit dosage form that selectively releases nicotine in the terminal ileum and/or colon of the patient. In another embodiment of the method, the nicotine can be effectively administered to the colon by rectal administration of an enema formulation or rectal foam comprising nicotine. Nicotine can also be delivered to the ileum or colon of an IBD patient by administration of an enterically coated unit dosage form. The present invention also provides a novel composition particularly suitable for the colonic administration of nicotine comprising crosslinked polyacrylic acid polymers complexed with nicotine.

Accordingly in a first aspect of the invention there is provided a nicotine or a pharmaceutically acceptable salt or derivative thereof in the preparation of a medicament for administering to the rectum, colon and/or terminal ileum of a patient for the treatment, prophylaxis, or maintenance of remission of inflammatory bowel disease.

By colon we mean to include the cecum, ascending colon, hepatic flexure, splenic flexure, descending colon, and sigmoid.

During studies with liquid enemas of nicotine bitartrate salt, the inventors found that the side effects were very limited if the patient lay on his side in the left lateral position, but increased if the patient adopted the sitting position. A preferred embodiment of the invention delivers nicotine as a complex of nicotine and polyacrylate which is much less dependent on the adopted position of the patient, and so increases the comfort of the patient during treatment. The nicotine-polyacrylate complex can be delivered rectally as an enema or foam, or orally as a post-gastrically delayed release product. Other nicotine containing post-gastrically delayed release tablets such as described herein are thought to also confer similar benefits.

In a particularly preferred embodiment of an enema comprising the nicotine-polyacrylate complex and triethanolamine (TRIS) as a buffer, the side-effects are further limited to a minimum.

By enema we mean to include liquid enemas which can be thickened by gums and the like, and foam enemas which expand in the colon after expulsion from a pressurised container.

Claim 1 of 7 Claims

What is claimed is:

1. A rectally administrable pharmaceutical enema composition comprising an amount of an active substance selected from the group consisting of nicotine and pharmaceutically acceptable salts thereof, together with a pharmaceutically acceptable carrier.

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