Topical formulation for delivery of interleukin-11

a technology of interleukin-11 and topical formulation, which is applied in the direction of pharmaceutical delivery mechanism, peptide/protein ingredients, pharmaceutical active ingredients, etc., can solve the problems of relatively unsuitable concomitant parenteral administration of il-11 and relatively unsuitable adverse event profile of parenteral il-11

Inactive Publication Date: 2005-06-16
WARNE NICK W +4
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In certain classes of patients, the toxicity profile of chemotherapeutic agents may be such that concurrent parenteral administration of IL-11 is relatively unsuited.
Other patients may have medical conditions for which the adverse event profile of parenteral IL-11 is relatively unsuited.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Treatment of Inflammatory Bowel Disease

[0054] In two well-established models it has been shown that subcutaneous rhIL-11 is able to significantly reduce the clinical signs and histologic lesions of gastrointestinal inflammation: acetic acid-induced colitis, a model of acute injury; and the HLA-B27 transgenic rat, a model of chronic inflammation. While conducting further studies of the mechanism of rhIL-11 action, oral topical activity was seen in hamsters with 5-FU induced oral mucositis and mucosal activity was documented in in vitro / ex vivo studies of intestinal transport. Subsequently, these models have been used to confirm the effectiveness of topically and orally administered rhIL-11.

[0055] Applicants first examined local topical delivery of rhIL-11 to the colon by enema. To determine the stability of rhIL-11 in the lumen of the gut, rhIL-11 and intestinal chyme from HLA-B27 rats were combined and incubated at 37° C. for up to several hours in the presence or absence of a pro...

example 2

Treatment of Oral Mucositis

[0058] 95 male Golden Syrian hamsters were equally divided into five groups. Group 1 [control] received phosphate buffered saline and 0.5% hamster serum (vehicle) topically on days 3-14. Groups 2 and 4 received 50 μg IL-11 subcutaneously, twice daily, on days 0-14 and 3-14, respectively. Groups 3 and 5 received 100 μg IL-11 topically, four times daily, on days 3-14 and 0-14, respectively. Ulcerative mucositis was induced by administration of 60 mg / kg body weight of 5-fluorouracil on days 0 and 2. The left buccal pouch was superficially irritated on day 4. Ulcerative mucositis was evaluated blindly starting on day 6 by scoring standardized photographs. The scoring was done on a scale of 0-10, with 10 being the most severe. Animals were weighed daily. Blood was taken from 3 animals per group on days 6, 10 and 14.

[0059] For the entire experiment, average mean ulcerative mucositis scores for all groups were significantly [p<0.05] lower than control. [G1=5.0;...

example 3

Treatment of Colitis (Colonic Ulcers)

[0073] The effects of three different dosages of recombinant human interleukin-11 (rhIL-11), given subcutaneously (SC) either prior to or subsequent to intracolonic administration of trinitrobenzene sulfonic acid (TNB), were studied in Sprague-Dawley rats. The TNB or control were given in a 40% ethanol solution to 312 anesthetized adult male rats allotted to one of 26 groups (n=12). Control groups were: subcutaneous (SC); saline alone; intrarectal (IR); 40% ethanol alone; TNB alone; 40% ethanol alone, and SC, rhIL-11 at the highest dosage alone and groups combining TNB with rhIL-11 therapy, testing three dosages (100, 300, and 1,000 μg / kg), given either before or after induction of colitis with TNB. Body weight changes were monitored. Rats were euthanized at 3 days, 7 days, or 14 days after TNB administration. At necropsy, samples were collected to evaluate fecal occult blood, mucosal myeloperoxidase activity and mucosal gross indexes of ulcerat...

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Abstract

Provided by the present invention are topical formulations of Interleukin-11 and methods for treating a variety of disorders, including inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis, indeterminate colitis, and infectious colitis), mucositis (e.g., oral mucositis, gastrointestinal mucositis, nasal mucositis, and proctitis), necrotizing enterocolitis, inflammatory skin disorders (e.g., psoriasis, atopic dermatitis, and contact hypersensitivity), aphthous ulcers, pharyngitis, esophagitis, peptic ulcers, gingivitis, periodontitis, and ocular diseases (e.g., conjunctivitis, retinitis, and uveitis).

Description

RELATED APPLICATION(S) [0001] This is a Continuation of U.S. application Ser. No. 09 / 179,026, filed Oct. 26, 1998, which is a continuation-in-part of U.S. application Ser. No. 08 / 892,407, filed Jul. 15, 1997, which is a divisional of U.S. application Ser. No. 08 / 495,724, filed Jun. 27, 1995, now Pat. No. 5,679,339, issued Oct. 21, 1997, the entire teachings of which are incorporated herein by reference.FIELD OF INVENTION [0002] The present invention relates generally to novel compositions and methods for topical delivery of interleukin-11 (IL-11). In preferred embodiments, patients are treated employing topical delivery of recombinant human IL-11 for inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis, indeterminate colitis, and infectious colitis), mucositis (e.g., oral mucositis, gastrointestinal mucositis, nasal mucositis, and proctitis), necrotizing enterocolitis, inflammatory skin disorders (e.g., psoriasis, atopic dermatitis, and contact hypersensitivity), a...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/00A61K38/19A61K38/20
CPCA61K9/0031A61K38/2073A61K9/006A61K9/0056
Inventor WARNE, NICK W.BEDROSIAN, CAMILLE L.KEITH, JAMES C. JR.SCHWERTSCHLAG, ULLRICH S.SCHENDEL, PAUL F.
Owner WARNE NICK W
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