Patent EA-000534-B1 (EA)
Title: Carbapenem antibiotic, composition and method of preparation
Inventor: ZIMMERMAN JEFFREY A
IPC: C07D477/20
Filed: 1997-05-23
Abstract: 1. A pharmaceutical composition which is comprised of a compound represented by formula I:   or a pharmaceutically acceptable salt, stabilized form, prodrug or hydrate thereof, in combination with a carbon dioxide source. 2. A pharmaceutical composition in accordance with Claim 1, comprising sodium carbonate and sodium bicarbonate as a carbon dioxide source. 3. A pharmaceutical composition in accordance with Claim 2 comprising about 3-6 parts by weight of compound I, or a pharmaceutically acceptable salt, stabilized form, prodrug or hydrate thereof, and about 1 part by weight sodium bicarbonate. 4. A pharmaceutical composition in accordance with Claim 3 comprising about 4.5 parts of a compound of formula I, or a pharmaceutically acceptable salt, stabilized form, prodrug or hydrate thereof. 5. A pharmaceutical composition in accordance with Claim 2 comprising about 3-6 parts by weight of compound I, or a pharmaceutically acceptable salt, stabilized form, prodrug or hydrate thereof, and about 1 part by weight sodium carbonate. 6. A pharmaceutical composition in accordance with Claim 5 comprising about 4.5 parts of a compound of formula I, or a pharmaceutically acceptable salt, stabilized form, prodrug or hydrate thereof. 7. A pharmaceutical composition in accordance with Claim 2 comprising about 4-10 parts by weight of the compound of formula I, or a pharmaceutically acceptable salt, stabilized form, prodrug or hydrate thereof and 1 part by weight sodium carbonate. 8. A pharmaceutical composition in accordance with Claim 7 wherein about 6.7 parts by weight of the compound of formula I, or a pharmaceutically acceptable salt, stabilized form, prodrug or hydrate thereof, are combined with 1 part by weight of sodium carbonate. 9. A pharmaceutical composition in accordance with Claim 1 comprising about 4-10 parts by weight of the compound of formula I, or a pharmaceutically acceptable salt, stabilized form, prodrug or hydrate thereof and 1 part by weight sodium bicarbonate. 10. A pharmaceutical composition in accordance with Claim 8 wherein about 6.7 parts by weight of the compound of formula I, or a pharmaceutically acceptable salt, stabilized form, prodrug or hydrate thereof, arc combined with 1 part by weight of sodium bicarbonate. 11. A pharmaceutical composition in accordance with Claim 2 further comprising a dehydropeptidase inhibitor. 12. A pharmaceutical composition in accordance with Claim 11 wherein the dehydropeptidase inhibitor is cilastatin. 13. A compound represented by the formula II:   or a pharmaceutically acceptable salt, prodrug or hydrate thereof. 14. A pharmaceutical composition which is comprised of a compound represented by formula II:   or a pharmaceutically acceptable salt, prodrug or hydrate thereof, in combination with a pharmaceutically acceptable carrier. 15. A compound in accordance with Claim 13 wherein the pharmaceutically acceptable salt is selected from the group consisting of:     wherein X<+> represents a pharmaceutically acceptable cationic group. 16. A pharmaceutical composition which is produced by combining a compound of formula I:   or a pharmaceutically acceptable salt, prodrug or hydrate thereof with a carbon dioxide source. 17. A pharmaceutical composition in accordance with Claim 16 wherein the carbon dioxide source is selected from carbon dioxide, sodium carbonate and sodium bicarbonate. 18. A pharmaceutical composition in accordance with Claim 17 wherein the carbon dioxide source is sodium carbonate or sodium bicarbonate. 19. A method of stabilizing a carbapenem of the formula I:   or a pharmaceutically acceptable salt, prodrug or hydrate thereof, comprising adding to the compound a sufficient amount of a carbon dioxide source to form a compound of formula II:   or a pharmaceutically acceptable salt, prodrug or hydrate thereof. 20. A method in accordance with Claim 19 wherein the carbon dioxide source is selected from carbon dioxide, sodium carbonate and sodium bicarbonate. 21. A method in accordance with Claim 20 wherein the carbon dioxide source is selected from sodium carbonate and sodium bicarbonate.