Colonic delivery of nicotine to treat inflammatory bowel disease

• US 5,889,028 A
• Filed: 08/07/1997
• Issued: 03/30/1999
• Est. Priority Date: 02/09/1996
• Status: Expired due to Fees

• Current Assignee: Mayo Foundation For Medical Education And Research (Mayo Clinic)
• Original Assignee: Mayo Foundation For Medical Education And Research (Mayo Clinic)
• Inventors: Rhodes, Peter, Evans, Brian Kenneth, Rhodes, John, Sandborn, William
• Primary Examiner(s): Rose, Shep K.
• Application Number:
  US08/908,433
• Time in Patent Office: 600 Days
• Field of Search: 514/343, 424/469, 424/474, 424/482, 424/486
• US Class Current: 514/343
• CPC Class Codes: A61K 31/465 Nicotine; Derivatives thereof
• CPC Class Codes: A61K 9/0031 Rectum, anus

Abstract

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.

Claims

1. A therapeutic method of treating inflammatory bowel disease comprising locally administering to the rectum, colon and/or terminal ileum of a patient in need of such treatment, an amount of a complex of nicotine and a carbomer, effective to reduce the symptoms of said inflammatory bowel disease.

2. The method of claim 1 wherein the inflammatory bowel disease is ulcerative colitis.

3. The method of claim 1 wherein the inflammatory bowel disease is Crohn'"'"'s disease.

4. The method of claim 1 wherein the inflammatory bowel disease is pouchitis.

5. The method of claim 1 wherein the complex is administered to the lower colon of said patient by rectal liquid enema.

6. The method of claim 5 wherein said enema comprises the complex in combination with a hydrophobic vehicle.

7. The method of claim 1 wherein the complex is administered to the lower colon of said patient by rectal foam enema.

8. The method of claim 1 wherein the complex is administered by means of an orally ingested post-gastric release enterically coated unit dosage form comprising an effective amount of the complex which is released from the dosage form in the ileum and/or in the colon of said patient.

9. The method of claim 1 wherein said carbomer is a Carbopol.

10. The method of claim 8 wherein the enteric coating disintegrates at about pH 7.

11. The method of claims 5 or 7 wherein a dosage of about 0.001 to about 1.5 mg of nicotine per kg body weight is administered.

12. The method of claim 11 wherein said dosage is about 0.04 to about 0.10 mg of nicotine per kg body weight.

13. The method of claim 12 wherein the total daily dosage is about 0.04 to about 0.20 mg of nicotine per kg body weight.

14. The method of claim 8 wherein a dosage of about 0.001 to about 1.5 mg of nicotine per kg body weight is administered.

15. The method of claim 14 wherein said dosage is about 0.04 to about 0.10 mg per kg body weight.

16. The method of claim 15 wherein the total daily dosage is about 0.04 to about 0.40 mg of nicotine per kg body weight.

17. A complex of nicotine and a carbomer.

18. A rectally administrable pharmaceutical enema composition comprising an amount of a complex of nicotine and a carbomer together with a pharmaceutically acceptable carrier.

19. The enema composition of claim 18 which further comprises a buffer of triethanolamine.

20. The enema composition of claim 18 wherein the amount of nicotine present is about 0.5 mg to about 10 mg.

21. A post-gastric delayed release oral enterically coated capsule comprising a complex of nicotine and a carbomer.

22. A method of preparing a carbomer-nicotine complex comprising mixing carbomer with a pharmaceutically acceptable aqueous solvent;

and adding nicotine to the carbomer-solvent mixture.

23. The method of claim 22 wherein said nicotine has been dissolved in a pharmaceutically acceptable organic solvent.

24. The method of claim 23 wherein said organic solvent is an alcohol.

25. The method of claim 22 wherein said carbomer-solvent mixture is prepared by adding carbomer to the solvent;

and allowing the mixture to form a colloidal suspension.

26. The method of claim 22 wherein said complex comprises the equivalent of 1 gram of nicotine per 1 to 50 grams of carbomer.

27. A therapeutic method of treating inflammatory bowel disease comprising administering to the rectum, colon and/or terminal ileum of a patient in need of such treatment an amount of a complex of nicotine and a carbomer and an amount of a compound selected from the group consisting of 5-amino salicylic acid, sulphasalazine, asalazine, prednisolone, and budesonide, said active agents being delivered in a therapeutic amount to reduce the symptoms of said inflammatory disease.