Method of treating inflammatory conditions with progesterone or progesterone analogs

a technology of progesterone and progesterone analogs, applied in the field of treating inflammatory conditions with progesterone or progesterone analogs, can solve the problems of macrophage accumulation, two billion dollars per year in the us, and the cost of disease, including productivity loss,

Inactive Publication Date: 2005-09-15
UNVERSITY OF PENNSYLVANIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The total cost of the disease, including lost productivity, in the US is two billion dollars per year.
Physicians and medical researchers have not been successful in identifying a cause for these diseases, although several theories have been postulated.
Stimulated neutrophils and macrophages accumulate and further damage the tissue by releasing reactive oxygen species and other biologically active products.
The uncertainty about the cause of IBD has lead to confusion about the appropriate treatment strategy.
Currently, no treatment exists that will cure or effectively manage both forms of inflammatory bowel dis...

Method used

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  • Method of treating inflammatory conditions with progesterone or progesterone analogs

Examples

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Effect test

example 1

Treatment of Mice with Medroxyprogesterone Acetate

[0053] The scid (severe combined immunodeficient) C.B.-17 line of mice provide an effective model of Inflammatory Bowel Disease. The disease state in these mice is triggered by the intraperitoneal injection of CD4+ T cells from a normal BALB / C mouse. The induced disease is characterized by intestinal inflammation in the large intestine, leukocytic infiltrates into the mucosa, submucosa, and mucularis, epithelial cell hyperplasia, loss of mucin-secreting cells, and ulcers with deep fissures, and diarrhea. In the mouse model, CD4+ T cells and macrophages infiltrate the bowel. The scid mouse is recognized by the art as a model for IBD. Powrie et al., Inhibition of Th1 Responses Prevents Inflammatory Bowel Disease in scid Mice Reconstituted with CD45RBhi CD4+ T Cells, Immunity 1:553-562 (1994).

[0054] 500,000 to 1×106 T cells derived from the lymph nodes of normal BALB / C mice were injected intraperitoneally into scid mice 6 weeks prior ...

example 2

Effect of Medroxyprogesterone Acetate on Macrophage TNF-α Release

[0057] The spleens of six of the mice from Example 1 were removed after the animals were sacrificed. Macrophages were isolated from the spleen of the medroxyprogesterone acetate or buffer control treated mice. TNF-α release from these macrophages was measured by ELISA following stimulation with either (1) rat anti-mouse macrophage Fc receptor antibody 2.4G2 and F(ab′)2 IgG goat anti-rat antibody, or (2) phorbol myristate acetate (“PMA”), a phorbol ester. The effect of medroxyprogesterone acetate on TNF-α release is illustrated in Table 2.

TABLE 2Effect of Medroxyprogesterone Acetate on TNF-α ReleaseTNF-αTNF-α RepeatMeasurementMeasurementMouseTreatmentStimulation(pg / ml)(pg / ml)1Buffer2.4G2 and F(ab′)2257520532IgG anti-rat187311123MPA184304231410265Buffer2.4G2 and F(ab′)2562209366MPAIgG anti-rat for 1st275630Measurement andPMA for RepeatMeasurement

[0058] Thus, these results suggest that medroxyprogesterone acetate may b...

example 3

Effect of Medroxyprogesterone Acetate on Macrophage IL-6 Release

[0059] The spleens of four of the mice from Example 1 were removed after the animals were sacrificed. Macrophages were isolated from the spleen of the medroxyprogesterone acetate or buffer control treated mice. IL-6 release from these macrophages was measured by ELISA following stimulation with rat anti-mouse macrophage Fc receptor antibody 2.4G2 and F(ab′)2 IgG goat anti-rat antibody. The effect of medroxyprogesterone acetate on IL-6 release is illustrated in Table 3.

TABLE 3Effect of Medroxyprogesterone Acetate on IL-6 ReleaseMouseTreatmentStimulationIL-6 Measurement1Buffer2.4G2 and F(ab′)2323,4062IgG anti-rat310,7503MPA298,9404266,557

[0060] Thus, these results suggest that medroxyprogesterone acetate may be inhibiting IL-6 release from macrophages, either by inhibiting its production, release, or down-regulating Fc receptors on the macrophages. Macrophages are involved in inflammatory processes, and infiltrate the ...

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Abstract

The present invention provides methods for treating inflammatory conditions, including but not limited to, inflammatory bowel disease (ulcerative colitis, Crohn's disease, and proctitis), other noninfectious, inflammatory conditions of the GI tract (microscopic colitis, allergic eosinophilic gastroenteritis, food allergies, pill induced esophagitis, celiac disease, recurrent polyps, and hemorrhoids), and psoriasis, using progesterone or progesterone analogs such as medroxyprogesterone acetate.

Description

PRIORITY INFORMATION [0001] This application claims priority to U.S. Provisional Patent Application No. 60 / 156,434, filed Sep. 28, 1999.TECHNICAL FIELD [0002] This invention provides methods for treating inflammatory conditions, including but not limited to, inflammatory bowel disease (ulcerative colitis, Crohn's disease, and proctitis), other noninfectious, inflammatory conditions of the GI tract (microscopic colitis, allergic eosinophilic gastroenteritis, food allergies, pill induced esophagitis, celiac disease, recurrent polyps, and hemorrhoids), and psoriasis using progesterone and progesterone analogs. BACKGROUND OF THE INVENTION [0003] Inflammatory Bowel Disease [0004]“Inflammatory bowel disease” (IBD) encompasses the idiopathic, chronic inflammatory bowel diseases ulcerative colitis (UC), Crohn's disease (CD), and proctitis. Researchers do not know the cause of these diseases, but believe that they involve genetic and immunologic influences on the gastrointestinal tract's abi...

Claims

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Application Information

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IPC IPC(8): A61K31/57A61P1/00A61P9/14A61P17/06A61P29/00A61P37/08C07J5/00
CPCA61K31/57A61P1/00A61P1/04A61P17/06A61P29/00A61P37/08A61P9/14
Inventor SCHREIBER, ALAN D.
Owner UNVERSITY OF PENNSYLVANIA
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