Claims for Patent: 6,818,763

Summary for Patent: 6,818,763

Title:	Preparation of metal mesoporphyrin halide compounds
Abstract:	A method of preparing metal mesoporphyrin halide compounds is described. The metal mesoporphyrin halide compound may be formed by forming a novel mesoporphyrin IX intermediate compound and then converting the mesoporphyrin IX intermediate to the metal mesoporphyrin halide through metal insertion. The novel intermediate compound may be formed by a catalytic hydrogenation of hemin in acid and subsequent recovery.
Inventor(s):	Vukovich; Robert A. (Holmdel, NJ), Levinson; Benjamin (Montgomery, NJ), Drummond; George S. (New York, NY), Caroselli; Robert (East Brunswick, NJ), Antczak; Kazimierz G. (Culver, IN), Boucher; Christopher (Newmarket, CA), Mortimer; Richard (Toronto, CA)
Assignee:	Wellspring Pharmaceutical Corporation (Neptune, NJ)
Application Number:	10/453,815
Patent Claims:	1. A method of producing a metal mesoporphyrin halide comprising: isolating a mesoporphyrin formate in substantially pure solid form; and reacting the mesoporphyrin formate with insert metals to form the metal mesoporphyrin halide. 2. The method of claim 1, further comprising forming a mesoporphyrin formate. 3. The method of claim 2, further comprising catalytically hydrogenating hemin in the presence of an acid to form the mesoporphyrin formate. 4. The method of claim 3, wherein the step of catalytically hydrogenating the hemin occurs in two steps. 5. The method of claim 4, further comprising heating a mixture of hemin and a hydrogenation catalyst under pressure at a first temperature for a first period of time and subjecting the mixture to a second temperature under pressure for a second period of time. 6. The method of claim 5, wherein the first temperature is higher than the second temperature. 7. The method of claim 1, wherein metal mesoporphyrin halide is a tin mesoporphyrin halide. 8. The process of claim 6, further comprising: a) subjecting a reaction mixture of hemin and a hydrogenation catalyst in an acid to hydrogen pressure of about 30-60 psi and then raising the temperature to about 85-95 C. and maintaining the temperature within that range for a period of about 1-3 hours; b) subjecting the reaction mixture to a further hydrogen pressure of about 30-60 psi at a temperature range of about 45-50 C. for a period of about 3-6 hours; and c) recovering the formate salt of mesoporphyrin IX from the reaction mixture by precipitation of the mixture with a solvent. 9. The process of claim 3, wherein the acid is formic acid. 10. The process of claim 7, wherein the solvent is an ether. 11. The process of claim 10, wherein the solvent is methyl tert-butyl ether. 12. The process of claim 11, wherein the hydrogenation catalyst is palladium on carbon. 13. The method of claim 1, wherein the quantity of metal mesoporphyrin halide formed by the process exceeds 1 kg. 14. A formate salt of mesoporphyrin IX. 15. The formate salt of claim 14, wherein the purity is greater than or equal to about 97%. 16. A formate salt of mesoporphyrin IX produced according to the process of claim 1. 17. The formate salt of claim 16, wherein the purity is greater than or equal to about 97%. 18. A process of converting a formate salt of mesoporphyrin IX to a metal mesoporphyrin halide, which comprises: a) drying the formate salt of mesoporphyrin IX to obtain a mesoporphyrin IX formate; b) subjecting the mesoporphyrin IX formate to a chemical metal insertion process reaction with a metal halide compound in the presence of an oxidant under buffered, acidic reaction conditions; and c) recovering the metal mesoporphyrin halide from the reaction mixture. 19. The process of claim 18 further comprising purification of the recovered metal mesoporphyrin halide. 20. A process of purifying a metal mesoporphyrin halide, which comprises: a) dissolving the metal mesoporphyrin halide in an aqueous basic solution to obtain a dissolved metal mesoporphyrin halide; b) treating said dissolved metal mesoporphyrin halide with charcoal to obtain a treated metal mesoporphyrin halide; c) adding said treated metal mesoporphyrin halide to a first aqueous acid solution to obtain a precipitated metal mesoporphyrin halide; d) triturating said precipitated metal mesoporphyrin halide in a second aqueous acid solution at elevated temperature to obtain a substantially pure metal mesoporphyrin halide; and e) drying said substantially pure metal mesoporphyrin halide. 21. The process of claim 20, wherein the metal mesoporphyrin halide is tin (IV) mesoporphyrin IX chloride. 22. A method of producing stannsoporfin comprising: isolating mesoporphyrin formate in substantially pure, solid form; and reacting the mesoporphyrin formate with a tin insert metal to form stannsoporfin. 23. The method of claim 22, wherein the isolating includes subjecting hemin to catalytic hydrogenation in formic acid. 24. The method of claim 23, wherein the catalytic hydrogenation is performed in reactor pressurized with hydrogen. 25. The method of claim 24, wherein the catalytic hydrogenation is performed in two steps. 26. The method of claim 25, wherein the first step in the catalytic hydrogen involves heating a reaction mixture of hemin and a hydrogenation catalyst to a first temperature for a first period of time and lowering the reaction mixture to a second temperature for a second period of time. 27. The method of claim 26, wherein the pressure in the reaction vessel is between about 30 psi and 60 psi. 28. The method of claim 27, wherein the first temperature exceeds about 850.degree. C. 29. The method of claim wherein 28, wherein the second temperature is below about 50 .degree. C. 30. The method of claim 29, further comprising recovering the reaction mixture in an organic solvent. 31. The method of claim 30, further comprising reacting the recovered reaction mixture with a metal halide. 32. The method of claim 31, wherein the reaction is performed under buffered, acid reaction conditions in the presence of an oxidant to form tin mesoporphyrin halide. 33. The method of claim 32, further comprising purifying the tin mesoporphyrin halide.

Details for Patent 6,818,763

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	PANHEMATIN	hemin for injection	For Injection	101246	07/20/1983		2022-06-04