Use of mtor inhibitors for prevention of intestinal polyp growth and cancer

a technology of mtor inhibitors and polyps, which is applied in the direction of heterocyclic compound active ingredients, biocide, drug compositions, etc., can solve the problems of limiting the use of cox-2 inhibitors and no effective therapies for preventing intestinal cancer, and achieves the prevention of intestinal polyps or intestinal cancer, preventing the development of new adenomas or polyps, and reducing the number or severity of adenomatous polyps

Inactive Publication Date: 2016-02-04
BOARD OF RGT THE UNIV OF TEXAS SYST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0017]In some embodiments, the composition comprising rapamycin or an analog of rapamycin prevents intestinal polyps or intestinal cancer. In some embodiments, the composition comprising rapamycin or an analog of rapamycin prevents the development of new adenomas or polyps, decreases the number or severity of the adenomatous polyps, induces a reduction in size or number of existing adenomas or polyps, prevents the conversion of adenomas or polyps into adenocarcinomas and cancer tissue, or prevents the adenomas or polyps from converting into malignant cancer that spread into other bodily tissues, organs and blood systems in a patient that has been diagnosed as having intestinal adenomas, intestinal polyps or Familial Adenomatous Polyposis (FAP).
[0023]In some embodiments, the composition comprising eRapa, nanoRapa, or e-nanoRapa prevents intestinal polyps or intestinal cancer. In some embodiments, the composition comprising eRapa, nanoRapa, or e-nanoRapa prevents the development of new adenomas or polyps, decreases the number or severity of the adenomatous polyps, induces a reduction in size or number of existing adenomas or polyps, prevents the conversion of adenomas or polyps into adenocarcinomas and cancer tissue, or prevents the adenomas or polyps from converting into malignant cancer that spread into other bodily tissues, organs and blood systems in a patient that has been diagnosed as having intestinal adenomas, intestinal polyps or Familial Adenomatous Polyposis (FAP).

Problems solved by technology

To date, there are no effective therapies for prevention of intestinal cancers.
Despite apparent effectiveness, reports of potential cardiovascular toxicity with COX-2 inhibitors limit their use in FAP (Solomon 2005).

Method used

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  • Use of mtor inhibitors for prevention of intestinal polyp growth and cancer
  • Use of mtor inhibitors for prevention of intestinal polyp growth and cancer
  • Use of mtor inhibitors for prevention of intestinal polyp growth and cancer

Examples

Experimental program
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Effect test

example 1

[0123]Encapsulated rapamycin, sometimes referred to as eRapa, increases life span in a mouse model of colon cancer, referred to as ApcMin / +. This mouse model carries a germ line mutation in one copy of the mouse tumor suppressor gene encoding adenomatous polyposis coli (Apc). Min in ApcMin / + refers to a condition called multiple intestinal neoplasms, which in this mouse model develop very early in life, resulting in a short life span of about 180 days. The cause of death of ApcMin / − mice is usually severe anemia due to bleeding from the multiple neoplastic polyps in the intestine. ApcMin / + mice model in part an inherited condition in humans called familial adenomatous polyposis (FAP).

[0124]Familial adenomatous polyposis (FAP) is an autosomal dominant disease caused by mutation of the Adenomatous Polyposis Coli (APC) gene, located on chromosome 5 (Kinzler, 1991). This germline defect accelerates the initiation of adenoma-carcinoma, resulting in the development of numerous adenomatous...

example 2

[0135]Development of methods to produce rapamycin nanoparticles. Rapid solvent exchange was used to examine the formation of rapamycin nanoparticles. Three water-miscible solvents and three water-soluble surfactants were selected to study their respective effects on the formation and morphology of rapamycin nanoparticles. The water-miscible solvents were isopropyl alcohol (Solvent 1), acetone (Solvent 2), and methanol (Solvent 3). The water-soluble surfactants were Pluronic F-68 (Dispersant 1, a non-ionic PEO-PPO-PEO block copolymer), Pluronic F-127 (Dispersant 2, a non-ionic PEO-PPO-PEO block copolymer), and sodium cholate (Dispersant 3, an anionic surfactant). Rapamycin was dissolved in each of the water-miscible solvents at a concentration of 0.25% w / v. The water-soluble surfactants were dissolved in deionized water at concentrations of 0.5% w / v, 0.5% w / v, and 1.0% w / v, respectively, for each of the dispersants. Each experimental combination (e.g. NP-1 to NP-9 in following table)...

example 3

[0136]Preparation of a high concentration rapamycin nanoparticle dispersion. The water-miscible solvent and water-soluble dispersant of NP-9 from Example 1 was used to prepare rapamycin nanoparticles. 656 mg of rapamycin were dissolved in 6.56 mL of Solvent 3 to yield a 1.0% w / v solution. This volume of rapamycin solution was injected into 26.25 mL of 1.0% w / v Dispersant 1 in deionized water. The resulting rapamycin nanoparticle dispersion had a final rapamycin content of 2.4% w / w. The particle size of the dispersion was determined by dynamic light scattering to be 230 nm±30 nm with a single peak.

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Abstract

Disclosed are methods and compositions for the treatment or prevention of intestinal polyps or prevention of cancer in a patient who has been identified as being at risk for developing intestinal polyps or intestinal cancer. The disclosed methods and compositions include rapamycin, a rapamycin analog, or another such inhibitor of the target of rapamycin (TOR).

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of priority of U.S. Provisional Application No. 61 / 778,670, filed on Mar. 13, 2013, which is hereby incorporated by reference in its entirety.GOVERNMENTAL RIGHTS[0002]This invention was made with government support under agreement number AG036613 awarded by the National Institutes of Health (NIH). The government has certain rights in the invention.BACKGROUND OF THE INVENTION[0003]A. Field of the Invention[0004]The invention relates to methods and compositions for treating or preventing intestinal adenomas or polyps or preventing cancer in a patient who has been identified as being at risk for developing intestinal polyps or intestinal cancer. The methods and compositions include rapamycin, rapamycin analogs, or other inhibitors of the mammalian target of rapamycin (“mTOR” or “mTORC1”).[0005]B. Description of Related Art[0006]Intestinal cancer encompasses a variety of cancers, including cancer of the sma...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/436A61K9/51A61K45/06
CPCA61K31/436A61K45/06A61K9/5138A61K31/192A61K31/415A61P35/00A61P35/04A61K2300/00
Inventor SHARP, ZELTON DAVESTRONG, RANDYHASTY, PAULLIVI, CAROLINARICHARDSON, ARLAN
Owner BOARD OF RGT THE UNIV OF TEXAS SYST
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