Claims for Patent: 7,375,216

Summary for Patent: 7,375,216

Title:	Preparation of metal mesoporphyrin compounds
Abstract:	A method of preparing metal mesoporphyrin compounds is described. A metal mesoporphyrin compound may be formed by forming a novel mesoporphyrin IX intermediate compound and then converting the mesoporphyrin IX intermediate to a metal mesoporphyrin compound 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 (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), Levin; Danny (Toronto, CA), Cooke; Keith A. (Milton, CA)
Assignee:	InfaCare Pharmaceutical Corporation (Trevose, PA)
Application Number:	10/812,156
Patent Claims:	1. A method of producing a metal mesoporphyrin compound comprising: isolating a mesoporphyrin formate; and converting the mesoporphyrin formate to a metal mesoporphyrin compound. 2. The method of claim 1, wherein the mesoporphyrin formate is converted directly to the metal mesoporphyrin compound. 3. The method of claim 1, wherein the mesoporphyrin formate is first converted to mesoporphyrin dihydrochloride and the mesoporphyrin dihydrochloride is converted to the metal mesoporphyrin compound. 4. The method of claim 3, wherein the mesoporphyrin dihydrochloride is reacted with an insert metal to form the metal mesoporphyrin compound. 5. The method of claim 3, further comprising purifying the mesoporphyrin formate in the presence of a metal scavenger. 6. The method of claim 5, wherein the metal scavenger includes Si-thiol. 7. The method of claim 4, further comprising catalytically hydrogenating hemin in the presence of an acid to form the mesoporphyrin formate. 8. The method of claim 7, wherein the catalytic hydrogenation of the hemin occurs in two steps. 9. The method of claim 8, 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. 10. The method of claim 9, wherein the first temperature is higher than the second temperature. 11. The method of claim 1, wherein the metal mesoporphyrin compound is a metal mesoporphyrin halide. 12. The method of claim 10, further comprising: a) subjecting a reaction mixture of hemin and a hydrogenation catalyst in an acid to hydrogen pressure of about 30-65 psi and then raising the temperature to about 85-95.degree. 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 30-65 psi at a temperature range of about 45-50.degree. C. for a period of about 24-48 hours; and c) recovering the mesoporphyrin formate from the reaction mixture by precipitation of the mixture with a solvent. 13. The method of claim 7, wherein the acid is formic acid. 14. The method of claim 12, wherein the solvent is an ether. 15. The method of claim 14, wherein the solvent is methyl tert-butyl ether. 16. The method of claim 15, wherein the hydrogenation catalyst is palladium on carbon. 17. The method of claim 1, wherein the quantity of metal mesoporphyrin compound formed by a single performance of the method exceeds 0.1 kg. 18. The method of claim 1, further comprising purifying the metal mesoporphyrin compound, including: a) dissolving the metal mesoporphyrin compound in an aqueous basic solution to obtain a dissolved metal mesoporphyrin compound; b) treating said dissolved metal mesoporphyrin compound with charcoal to obtain a treated metal mesoporphyrin compound; c) adding said treated metal mesoporphyrin compound to a first aqueous acid solution to obtain a precipitated metal mesoporphyrin compound; d) triturating said precipitated metal mesoporphyrin halide in a second aqueous acid solution at elevated temperature to obtain a substantially pure metal mesoporphyrin compound; and e) drying said substantially pure metal mesoporphyrin compound. 19. The method of claim 18, wherein the metal mesoporphyrin halide is tin (IV) mesoporphyrin IX dihydrochloride. 20. The method of claim 19, further comprising reacting the mesoporphyrin IX dihydrochioride with tin to form tin (IV) mesoporphyrin IX dichioride. 21. The method of claim 1, wherein the mesoporphyrin formate is isolated in substantially pure, solid form. 22. The method of claim 21, wherein the mesoporphyrin formate is converted to mesoporphyrin IX dihydrochloride. 23. The method of claim 22, further comprising reacting the mesoporphyrin IX dihydrochloride with tin to form tin (IV) mesoporphyrin IX dichioride. 24. The method of claim 23, wherein the quantity of tin (IV) mesoporphyrin IX dichioride formed by a single performance of the method exceeds 0.1 kilograms. 25. The method of claim 21, further comprising purifying the mesoporphyrin formate with a metal scavenger. 26. The method of claim 25, wherein the metal scavenger includes a silica bound metal scavenger. 27. The method of claim 23, further comprising purifying the tin (IV) mesoporphyrin IX dichioride includes trituration in hot acid at an elevated temperature. 28. The method of claim 27, wherein the acid is HCl. 29. The method of claim 11, wherein the metal mesoporphyrin halide is mesoporphyrin IX dihydrochloride. 30. The method of claim 18, wherein the metal mesoporphyrin compound is a metal mesoporphyrin halide. 31. The method of claim 4, wherein the mesoporphyrin dihydrochloride is reacted with the insert metal in the absence of any acetate ions. 32. The method of claim 23, wherein the mesoporphyrin dihydrochioride is reacted with the tin in the absence of any acetate ions. 33. The method of claim 17, wherein the quantity of metal mesoporphyrin compound formed by a single performance of the method exceeds 1 kg. 34. The method of claim 18, wherein the quantity of metal mesoporphyrin compound formed by a single performance of the methods exceeds 1 kg. 35. The method of claim 23, wherein the quantity of tin (IV) mesoporphyrin IX dichloride formed by a single performance of the methods exceeds 1 kg. 36. Tin (IV) mesoporphyrin IX dichioride produced by a single performance of the method of claim 23.

Details for Patent 7,375,216

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