Preparation and uses of new prostaglandin derivatives which prot

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ester doai

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560116, 560121, C07C17700, A61K 31557

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active

048409685

ABSTRACT:
The invention provides novel compounds which can protect (i) organs, such as the brain, spinal cord, heart, lung, liver, kidney, stomach, duodenum and blood vessels, (ii) skin cells, and (iii) circulating cells such as red blood cells and white blood cells from ischemic, physical, chemical and biological injuries either by pre-administation or post-administration. The compounds can also protect red blood cells from malarial parasites. The compounds are synthesized from prostaglandin A.sub.1 or E.sub.1 first by alkaline treatment to form free-acid molecules, and then by converting them to hydrophobic ester-form compounds. Comparing with free-acid compounds, the ester-form compounds have the following advantageous features: (a) Unlike free-acids, they do not form insoluble micelles with calcium in the blood stream; (b) they are more soluble in lipids than free-acids, thus they are more easily incorporated into cells; (c) they are more stable than free-acids; (d) they are hydrolyzed by endogeneous esterases upon entering the cells, thereby forming the free-acid molecules within the cells. This causes continuous accumulation within the cells. This causes continuous accumulation of free-acid molecules within the cells, and makes their concentration higher than the external concentration of original ester-form compounds. Thus, they can manifest high efficacy; (e) the free-acid molecules thus accumulated within the cells protect the cell membranes by chelating calcium ions, by inhibiting membrane-degradating enzymes and by inhibiting undesirable enzymic reactions within the cell. These compounds can be administered orally, subcutaneously, intramuscularly, intravenously or topically. These compounds can also be used to protect organs during transplant surgery by administering to the donor before removal of the organ and by administering to the receipient after transplantation.

REFERENCES:
patent: 4153808 (1979-05-01), Polis
patent: 4245111 (1981-01-01), Polis
patent: 4338466 (1982-07-01), Nelson
patent: 4663486 (1987-05-01), Nelson
patent: 4668828 (1987-05-01), Nelson
Von Euler, Prostaglandins, pp. 20, 21, (1967).

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