Patent EA-003864-B1 (EA)
Title: COMPOSITION AND METHOD OF PREPARING OF PHARMACEUTICAL FORMULATION, LYOPHILIZED COMPOSITION AND USE OF IT, METHOD OF INHIBITING sPLA2-MEDIATED RELEASE OF FATTY ACID, METHOD OF TREATING A MAMMALS, METHOD OF TREATMENT OR PREVENTING SEPSIS, SEALED CONTAINER
Inventor: CONFER WILLIAM LESTER
IPC: A61K9/19
Filed: 1999-03-02
Abstract: 1. A composition which comprises sodium [[3-(2-amino-1, 2dioxoethyl)-2-ethyl-1 phenylmethyl)-1H-indol-4 yl]oxy]acetate as active ingredient; a solubilizers, selected from at least one compound selected from the group consisting of citric acid; edetic acid, polyphosphoric acid and their salts; and a stabilizer, selected from at least one compound selected from the group consisting of mannitol, xylitol, sorbitol, glucose, fructose, lactose and maltose. 2. The composition of claim 1 wherein the solubilizer is sodium citrate dihydrate or disodium EDTA; and the stabilizer is mannitol. 3. The composition of claim 1 wherein the composition is lyophilized. 4. The composition of claim 3 wherein the solubilizer is sodium citrate and the stabilizer is mannitol. 5. The composition of any one of claims 1, 2, 3, or 4 wherein per the amount of the equivalent acid of active ingredient, the stabilizer is present at 1 to 100 % (w/w) and the solubilizer is present at 50 to 200 % (w/w). 6. The composition of any one of claims 1- 4, which is salt-free, except for active ingredient, solubilizer and stabilizer. 7. A method of making the pharmaceutical formulation of the invention, composing dissolving is an aqueous solvent a composition comprising Sodium [[3-(2-amino-1, 2-dioxoethyl)-2-ethyl-1-phenylmethyl)-1H3-indol-4-yl]oxy]acetate as active ingredient, a solubilizer selected from at least one compound selected from the group consisting of citric acid, edetic acid, polyphosphoric acid and their salts, and a stabilizer selected from at least one compound selected from the group consisting of mannitol, xylitol, sorbitol, glucose, fructose, lactose and maltose; first cooling the processing solution to a temperature below about -33 degree C; first heating the product to a temperature above about -33 degree C; second cooling the product to a temperature below about -33 degree C; second heating the product to a temperature above -13 degree C, under subatmospheric pressure for a time sufficient to remove water from the aqueous solvent and yield a solid lyophilized product. 8. The process of claim 7 wherein in step of dissolving, the amount of solubilizer is 1 to 100 % (w/w) of the amount of the equivalent acid of active ingredient and the amount of stabilizer is 50 to 200 % (w/w) of the amount of the equivalent acid of active ingredient. 9. The process of claim 7 wherein each cooling and heating are conducted for a period of at least one - half hour and second heating is performed at a subatmospheric pressure less than 133 n/m. 10. The process of claim 7 wherein the Solubilizer is sodium citrate and the stabilizer is mannitol. 11. A lyophilized composition prepared by the process of claim 7 and for the treating of diseases, associated with inflammatory processes. 12. A method of inhibiting sPLA2 mediated release of fatty acid, which comprises contacting sPLA2 with a therapeutically effective amount of a solution prepared from the composition of claim 1 or 4. 13. A method of treating a mammal, including a human, to alleviate the pathological effects of inflammatory diseases; wherein the method comprises parenterally administering to said mammal a therapeutically effective amount of a solution prepared from the formulation of claim 1 or 4. 14. A method for the treatment or prevention of sepsis comprising administering a therapeutically effective amount of as aqueous solution comprising Sodium [[3-(2-amino-1,2-dioxoethyl)-2-ethyl-1-phenylmethyl)-1H-indol-4-yl]oxy]acetate, Trisodium Citrate Dihydrate, and Mannitol. 15. A lyophilized composition of claims 1 or 4 for the manufacture of a medicament for treating sepsis in a mammal, including a human, currently afflicted with susceptible to sepsis. 16. A dose-concentrate containing sealed container containing lyophilized composition of claim 1 or 4, said container having a space sufficient for introduction of a volume of aqueous solvent sufficient to form a concentrated solution of said formulation.