Glycopeptide phosphonate derivatives
View Patent ↗Disclosed are glycopeptides that are substituted with one or more substituents each comprising one or more phosphono groups; and pharmaceutical compositions containing such glycopeptide derivatives. The disclosed glycopeptide derivatives are useful as antibacterial agents.
1. A lyophilized composition comprising:
(a) a compound of the formula:
or a pharmaceutically acceptable salt thereof; and
(b) a cyclodextrin.
2. The composition of claim 1 , wherein the cyclodextrin is hydroxypropyl-β-cyclodextrin.
3. The composition of claim 1 , wherein the cyclodextrin is sulfobutyl ether β-cyclodextrin.
4. The composition of claim 1 , wherein the weight ratio of the cyclodextrin to the compound is from about 1:1 to about 10:1.
5. The composition of claim 1 , wherein the pharmaceutically-acceptable salt is a hydrochloride salt.
6. The composition of claim 1 , wherein the composition further comprises an excipient selected from the group consisting of mannitol, sucrose, lactose and combinations thereof.
7. The composition of claim 6 , wherein the excipient is mannitol.
8. A lyophilized composition comprising:
(a) a compound of the formula:
or a hydrochloride salt thereof;
(b) hydroxypropl-β-cyclodextrin; and
(c) mannitol.
9. A process for preparing a lyophilized composition, wherein the lyophilized composition comprises:
(i) a compound of the formula:
or a pharmaceutically-acceptable salt thereof; and
(ii) a cyclodextrin;
wherein the process comprising the steps of:
(a) providing an aqueous solution comprising the compound or pharmaceutically-acceptable salt thereof and the cyclodextrin; and
(b) lyophilizing the aqueous solution to provide the lyophilized composition.
10. The process of claim 9 , wherein the cyclodextrin is hydroxypropyl-β-cyclodextrin.
11. The process of claim 9 , wherein the cyclodextrin is sulfobutyl ether β-cyclodextrin.
12. The process of claim 9 , wherein the weight ratio of the cyclodextrin to the compound is from about 1:1 to about 10:1.
13. The process of claim 9 , wherein the pharmaceutically-acceptable salt is a hydrochloride salt.
14. The process of claim 9 , wherein the composition further comprises an excipient selected from the group consisting of mannitol, sucrose, lactose and combinations thereof.
15. The process of claim 14 , wherein the excipient is mannitol.
16. The product prepared by the process of claim 9 .
17. A vial containing a lyophilized composition comprising:
(a) 250 mg to 1000 mg of a compound of the formula:
or a pharmaceutically-acceptable salt thereof; and
(b) 250 mg to 10 g of hydroxypropyl-β-cyclodextrin.
18. The vial of claim 17 , wherein the pharmaceutically-acceptable salt is a hydrochloride salt.
19. The vial of claim 17 , wherein the lyophilized composition further comprises from 0 to 50 g of an excipient selected from mannitol, sucrose, lactose and combinations thereof.
20. The vial of claim 19 , wherein the excipient is mannitol.