Claims for Patent: 7,960,371

Summary for Patent: 7,960,371

Title:	High-purity large-scale preparation of stannsoporfin
Abstract:	Large scale (bulk) compositions comprising high-purity stannsoporfin are disclosed, as well as methods of synthesizing such compositions.
Inventor(s):	Drummond; George S. (New York, NY), Caroselli; Robert (East Brunswick, NJ), Cooke; Keith A. (Milton, CA), Levin; Daniel (Toronto, CA), Roe; David G. (Rockwood, CA), Boucher; Christopher P. (Newmarket, CA)
Assignee:	Infacare Pharmaceutical Corporation (Trevose, CA)
Application Number:	11/867,559
Patent Claims:	1. A pharmaceutical composition comprising stannsoporfin and a pharmaceutically acceptable carrier, wherein said stannsoporfin is at least about 98.5% pure and wherein any individual impurity is present in an amount of less than about 0.1%. 2. The pharmaceutical composition of claim 1, wherein said stassoporfin is at least about 99% pure. 3. The pharmaceutical composition of claim 2, wherein any individual impurity present is present in an amount of less than about 0.09%. 4. The pharmaceutical composition of claim 1, wherein said stannsoporfin is present in an amount suitable for delivering up to a 4.5 mg/kg dose by birth weight. 5. The pharmaceutical composition of claim 1, wherein said stannsoporfin is present in an amount suitable for delivering from about 1.5 mg/kg to about 3.0 mg/kg by birth weight. 6. A method of making stannsoporfin, comprising: a) exposing a metallic hydrogenation catalyst to a hydrogen atmosphere to form pre-hydrogenated catalyst; and b) contacting hemin with the pre-hydrogenated catalyst and maintaining the hemin and catalyst under one or more combinations of temperature, hydrogen pressure, and time sufficient to remove iron from the hemin and reduce the vinyl groups of the hemin to ethyl groups, thus forming mesoporphyrin IX. 7. The method of claim 6, further comprising: c) reacting mesoporphyrin IX with a tin (II) salt to form stannsoporfin using a controlled rate of oxidation. 8. The method of claim 6, wherein the metallic hydrogenation catalyst is palladium on carbon. 9. The method of claim 8, wherein in step a), the palladium on carbon is exposed to a hydrogen atmosphere of about 30 to 50 psi at a temperature of about 45-50 degree. C. for about 8 to 16 hours. 10. The method of claim 7, wherein the reacting of mesoporphyrin IX with a tin (II) salt is performed in the absence of proton scavengers. 11. The method of claim 7, wherein step c) takes place in a reaction vessel having a headspace, and the rate of oxidation is controlled by introducing an oxygen-containing gas into the headspace of the reaction vessel. 12. The method of claim 11, wherein the oxygen-containing gas is about 6% oxygen in nitrogen. 13. The method of claim 6, further comprising, after step b), a step b1) of isolating the mesoporphyrin IX as mesoporphyrin IX formate. 14. The method of claim 13, further comprising, after step b1), an additional step b2) of purifying the mesoporphyrin IX formate. 15. The method of claim 14, wherein the additional step b2) of purifying the mesoporphyrin IX formate involves treating the mesoporphyrin IX formate with diatomaceous earth and activated carbon. 16. The method of claim 13, further comprising, after step b1), a step of converting the mesoporphyrin IX formate into mesoporphyrin IX dihydrochloride. 17. The method of claim 16, wherein the mesoporphyrin IX dihydrochloride is readily filterable. 18. The method of claim 7, further comprising, after step c), a step d) of dissolving the stannsoporfin into a basic solution, treating with activated carbon, and re-precipitating the stannsoporfin. 19. The method of claim 18, further comprising, after step d), a step e) of triturating the stannsoporfin with hot aqueous acid. 20. A method for producing a tin (IV) porphyrin compound or salt thereof comprising: a) preparing a solution or suspension of an unmetallated porphyrin compound or a salt thereof; b) preparing a solution or suspension of tin (II) oxide, wherein steps (a) and (b) can occur in any order or simultaneously; and (c) contacting the solution or suspension of tin (II) oxide with the solution or suspension of unmetallated porphyrin compound or salt thereof under conditions suitable to form the tin (IV) porphyrin compound or salt thereof. 21. The method of claim 20, wherein the solution or suspension of tin (II) oxide and the solution or suspension of unmetallated porphyrin compound or salt thereof are independently prepared with formic acid or acetic acid. 22. The method of claim 20, wherein the solution or suspension of tin (II) oxide is prepared with acetic acid. 23. The method of claim 20, wherein the solution or suspension of unmetallated porphyrin compound or salt thereof is prepared with formic acid. 24. The method of claim 20, wherein the unmetallated porphyrin compound is selected from mesoporphyrins, protoporphyrins, hematoporphyrins, and salts thereof. 25. The method of claim 20, wherein the unmetallated porphyrin compound is mesoporphyrin IX or a salt thereof. 26. The method of claim 20, wherein the unmetallated porphyrin compound is mesoporphyrin IX dihydrochloride. 27. The method of claim 20, wherein step c) comprises adding the solution or suspension of unmetallated porphyrin compound or salt thereof in a dropwise manner to the solution or suspension of tin (II) oxide under conditions suitable to form the tin (IV) porphyrin compound or salt thereof. 28. The method of claim 27, wherein the adding in a dropwise manner is completed within about 3 to 9 hours. 29. The method of claim 27, wherein the solution or suspension of tin (II) oxide is maintained at a temperature of about 60 to 65.degree. C. during the adding in a dropwise manner. 30. The method of claim 29, wherein after completion of the adding of the solution or suspension of unmetallated porphyrin compound or salt thereof in a dropwise manner to the solution or suspension of tin (II) oxide, the reaction mixture is maintained at a temperature of about 60 to 65.degree. C. for about 18 to 24 additional hours. 31. The method of claim 20, wherein the step of contacting the solution or suspension of tin (II) oxide with the solution or suspension of unmetallated porphyrin compound or salt thereof under conditions suitable to form the tin (IV) porphyrin compound or salt thereof is performed in the absence of a proton scavenger or proton sponge.

Details for Patent 7,960,371

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		2026-10-04