Claims for Patent: 5,834,448

Summary for Patent: 5,834,448

Title:	Dosage form of hydroxocobalamin and its use in cyanide poisoning
Abstract:	The invention relates to a new dosage form of hydroxocobalamin which serves in the treatment of cyanide poisoning and contains hydroxocobalamin in freeze-dried form. The hydroxocobalamin is freeze-dried in an acidic medium so as to be practically instantly redissolved in a neutral saline solution. The present invention also relates to a process for producing hydroxocobalamin-based pharmaceutical compositions as well as to first aid kits containing these compositions and methods of using such kits for the treatment of cyanide poisoning.
Inventor(s):	Pouchol; Gerard (Paris, FR), Bonhomme; Yves (Charbonnieres, FR), Poulain; Marie-Laure (St-Cyr-En-Val, FR), Duran; Michel (St-Cyr-Au-Mont-d'or, FR)
Assignee:	Merck Patent Gesellschaft mit beschrankter Haftung (DE)
Application Number:	08/748,790
Patent Claims:	1. A pharmaceutical composition comprising hydroxocobalamin in freeze-dried form, wherein the hydroxocobalamin is freeze-dried in an acidic medium so as to be rapidly redissolved in a neutral saline solution. 2. A pharmaceutical composition according to claim 1, wherein the freeze-dried hydroxocobalamin is redissolved in a saline solution. 3. A pharmaceutical composition comprising hydroxocobalamin in freeze-dried form according to claim 1, characterized in that the acidic medium within which the hydroxocobalamin is freeze-dried is selected so as to make it possible to obtain a stable solution. 4. A process for producing a freeze-dried hydroxocobalamin product according to claim 1, which comprises preparing the hydroxocobalamin solution in an acidic medium, optionally supplemented with a filler, and freeze-drying the hydroxocobalamin in the container intended to be used. 5. A process for producing a hydroxocobalamin product according to claim 1 which comprises preparing a hydroxocobalamin solution in an acidic medium, optionally supplemented with a filler, and freeze-drying the hydroxocobalamin, wherein said hydroxocobalamin solution has a pH ranging from 3.5 to 5.5. 6. A process for producing a freeze-dried hydroxocobalamin product according to claim 1 which comprises preparing a hydroxocobalamin solution in an acidic medium, optionally supplemented with a filler, and freeze-drying the hydroxocobalamin, wherein said hydroxocobalamin solution has a pH ranging from 4.0 to 5.0. 7. A process for producing a freeze-dried hydroxocobalamin product according to claim 1 which comprises preparing a hydroxocobalamin solution in an acidic medium, optionally supplemented with a filler, and freeze-drying the hydroxocobalamin, wherein the acidic pH is obtained by adding to a solution of hydroxocobalamin a strong inorganic acid or an organic acid in a calculated amount. 8. A process according to claim 5, wherein a filler chosen from arginine hydrochloride, lactose, glycine or sodium acetate is added to the hydroxocobalamin solution. 9. A process according to claim 5, wherein a buffering agent consisting of a sodium salt of an organic acid is added to the hydroxocobalamin solution. 10. A process according to claim 5, wherein the concentration of hydroxocobalamin in the solution to be freeze-dried ranges from 1 to 5 g per 100 ml. 11. A process according to claim 10, wherein the concentration of hydroxocobalamin in the solution to be freeze-dried is between 2 and 3 g per 100 ml. 12. A process for producing hydroxocobalamin-based pharmaceutical compositions which comprises preparing a solution of hydroxocobalamin in water, adjusting the pH to a value ranging from 3 to 5 by the controlled addition of an inorganic or organic acid and, where appropriate, a filler and/or a buffering agent, freeze-drying the hydroxocobalamin and preparing ampoules of saline solution having a volume of between 20 and 150 ml. 13. A process for producing hydroxocobalamin-based pharmaceutical compositions according to claim 12, in which the saline solution is a solution of sodium chloride. 14. A first aid kit for the treatment of cyanide poisoning consisting of a vial of freeze-dried hydroxocobalamin product, obtained according to the process of claim 5 containing between 1 and 5 g of hydroxocobalamin and an ampoule containing from 20 to 150 ml of a saline solution allowing redissolution of said freeze-dried hydroxocobalamin. 15. A method of using the hydroxocobalamin-based first aid kits according to claim 14, for the treatment of acute or chronic cyanide poisoning, which comprises intravenously administering the aqueous solution of redissolved hydroxocobalamin. 16. A pharmaceutical composition comprising hydroxocobalamin in freeze-dried form according to claim 1, characterized in that the acidic medium within which the hydroxocobalamin is freeze-dried is selected so as to make it possible to obtain a stable solution, with a hydroxocobalamin concentration in the range of 1 to 5 g per 100 ml. 17. A pharmaceutical composition consisting essentially of freeze-dried hydroxocobalamin redissolved in a saline solution.