High-purity large-scale preparation of stannsoporfin

Patent metadata

Field	Value
Publication number	US-11078220-B2
Application number	US-202016864510-A
Country	US
Kind code	B2
Filing date	May 1, 2020
Priority date	Oct 4, 2006
Publication date	Aug 3, 2021
Grant date	Aug 3, 2021

Abstract

Large scale (bulk) compositions comprising high-purity stannsoporfin are disclosed, as well as methods of synthesizing such compositions.

First claim

What is claimed is:

1. A composition comprising stannsoporfin, wherein the stannsoporfin is at least about 97% pure, and wherein any individual impurity is present in an amount less than about 0.08%, the stannsoporfin formed by: a) contacting a solution or suspension of tin (II) oxide with a mesoporphyrin IX or salt thereof under conditions suitable to form a crude stannsoporfin; and b) purifying the crude stannsoporfin to form the stannsoporfin.

2. The composition of claim 1 , wherein the composition comprises palladium in an amount of less than about 20 ppm.

3. The composition of claim 1 , wherein the composition comprises palladium in an amount of less than about 10 ppm.

4. The composition of claim 1 , wherein the composition comprises at least about 10 grams of stannsoporfin.

5. The composition of claim 1 , wherein the composition comprises at least about 100 grams of stannsoporfin.

6. The composition of claim 1 , wherein the stannsoporfin is a single-batch preparation of stannsoporfin.

7. The composition of claim 1 , wherein the stannsoporfin is at least about 98.5% pure.

8. The composition of claim 1 , wherein any impurity present is present in an amount of about 0.07% or less.

9. The composition of claim 1 , wherein the purifying the crude stannsoporfin comprises a hot acid trituration, followed by treatment at high pH at or above pH 9 followed by re-acidification, and subsequent hot acid trituration.

10. The composition of claim 1 , wherein the mesoporphyrin IX of salt thereof is formed by contacting hemin with a pre-hydrogenated catalyst.

11. The composition of claim 10 , wherein the pre-hydrogenated catalyst is formed by exposing a metallic hydrogenation catalyst to a hydrogen atmosphere.

12. The composition of claim 1 , wherein the mesoporphyrin IX or salt thereof comprises mesoporphyrin IX dihydrochloride.

13. The composition of claim 1 , wherein the composition further comprises at least one impurity in an amount between about 0.05% and about 0.08%, the at least one impurity having a relative retention time of 0.72-0.73 in an HPLC analysis.

14. A composition comprising stannsoporfin, wherein the stannsoporfin is at least about 97% pure, and wherein any individual impurity is present in an amount less than about 0.08%, the stannsoporfin formed by: a) exposing a metallic hydrogenation catalyst to a hydrogen atmosphere to form a pre-hydrogenated catalyst; b) contacting hemin with the pre-hydrogenated catalyst to form a mesoporphyrin IX or salt thereof; c) contacting a solution or suspension of tin (II) oxide with the mesoporphyrin IX or salt thereof under conditions suitable to form a crude stannsoporfin; and d) purifying the crude stannsoporfin via hot acid trituration, followed by treatment at high pH at or above pH 9 followed by re-acidification, and subsequent hot acid trituration to form the stannsoporfin.

15. The composition of claim 14 , wherein the metallic hydrogenation catalyst comprises palladium on carbon.

16. The composition of claim 14 , wherein the mesoporphyrin IX or salt thereof comprises mesoporphyrin IX dihydrochloride.

17. The composition of claim 14 , wherein the composition comprises palladium in an amount of less than about 20 ppm.

18. The composition of claim 14 , wherein the composition comprises palladium in an amount of less than about 10 ppm.

19. The composition of claim 14 , wherein the composition comprises at least about 10 grams of stannsoporfin.

20. The composition of claim 14 , wherein the stannsoporfin is at least about 98.5% pure.

Assignees

• Mallinckrodt Hospital Products Ip Ltd

Inventors

• Drummond George S
• Caroselli Robert
• Cooke Keith A
• Levin Daniel
• Roe David G
• Boucher Christopher P

Classifications

• A61K31/555 Primary

  containing heavy metals, e.g. hemin, hematin, melarsoprol · CPC title

• C07D498/22

  in which the condensed system contains four or more hetero rings · CPC title

• C07F7/22 Primary

  Tin compounds · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title