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
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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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