Claims for Patent: 10,472,365

Summary for Patent: 10,472,365

Title:	Short-acting benzodiazepine salts and their polymorphic forms
Abstract:	The invention relates to besylate salts of the compound of formula (I): ##STR00001## Methods of preparing the salts, and their use as medicaments, in particular for sedative or hypnotic, anxiolytic, muscle relaxant, or anticonvulsant purposes is also described.
Inventor(s):	Tilbrook; Gary Stuart (Huntingdon, GB), Quegan; Louisa Jane (Cambridge, GB)
Assignee:	PAION UK LIMITED (Cambridge, Cambridgeshire, GB)
Application Number:	15/908,081
Patent Claims:	1. A method of producing sedation in a subject, comprising: (a) reconstituting a lyophilized composition with an aqueous solution to afford an aqueous pharmaceutical composition; and (b) administering to the subject an effective amount of the aqueous pharmaceutical composition; wherein the lyophilized composition comprises a besylate salt of the compound of formula (I) ##STR00005## and at least one pharmaceutically acceptable carrier, excipient or diluent, and wherein the lyophilized composition maintains at least 96.7% of the original amount of the compound of formula (I) comprising the lyophilized composition following storage of the lyophilized composition at 40.degree. C. and 75% relative humidity for a time period of from 1 week to 4 weeks, and wherein the amount of the compound of formula (I) in the lyophilized composition is measured by high-performance liquid chromatography. 2. The method according to claim 1, wherein the aqueous solution comprises dextrose or saline. 3. The method according to claim 2, wherein the aqueous solution comprises saline. 4. The method according to claim 2, wherein the aqueous solution comprises dextrose. 5. The method according to claim 1, wherein the aqueous pharmaceutical composition is administered to the subject by subcutaneous, intramuscular, intradermal or intravenous administration. 6. The method according to claim 5, wherein the aqueous pharmaceutical composition is administered to the subject by intravenous administration. 7. The method according to claim 6, wherein the intravenous administration comprises a bolus injection or a continuous infusion. 8. The method according to claim 7, wherein the intravenous administration comprises a bolus injection. 9. The method according to claim 7, wherein the intravenous administration comprises a continuous infusion. 10. The method according to claim 1, wherein the aqueous pharmaceutical composition is administered to the subject during the time the subject is undergoing a diagnostic, operative or endoscopic procedure. 11. The method according to claim 10, wherein the aqueous pharmaceutical composition is administered to the subject during the time the subject is undergoing a diagnostic procedure. 12. The method according to claim 10, wherein the aqueous pharmaceutical composition is administered to the subject during the time the subject is undergoing an operative procedure. 13. The method according to claim 10, wherein the aqueous pharmaceutical composition is administered to the subject during the time the subject is undergoing an endoscopic procedure. 14. The method according to claim 1, wherein the aqueous pharmaceutical composition is administered to the subject by intravenous administration during the time the subject is undergoing a diagnostic, operative or endoscopic procedure. 15. The method according to claim 1, wherein: (a) the aqueous solution comprises dextrose or saline; (b) the aqueous pharmaceutical composition is administered to the subject by subcutaneous, intramuscular, intradermal or intravenous administration; and (c) the aqueous pharmaceutical composition is administered to the subject during the time the subject is undergoing a diagnostic, operative or endoscopic procedure. 16. The method according to claim 15, wherein, the aqueous pharmaceutical composition is administered to the subject by intravenous administration. 17. The method according to claim 16, wherein the intravenous administration comprises a bolus injection or a continuous infusion. 18. The method according to claim 15, wherein: (a) the aqueous solution comprises saline; (b) the aqueous pharmaceutical composition is administered to the subject by intravenous administration; and (c) the intravenous administration is a bolus injection or a continuous infusion. 19. The method according to claim 18, wherein the intravenous administration is a bolus injection. 20. The method according to claim 18, wherein the intravenous administration is a continuous infusion. 21. The method according to claim 1, wherein the lyophilized composition maintains at least 96.7% of the original amount of the compound of formula (I) comprising the lyophilized composition following storage of the lyophilized composition at 40.degree. C. and 75% relative humidity for 1 week, and wherein the amount of the compound of formula (I) in the lyophilized composition is measured by high-performance liquid chromatography. 22. The method according to claim 1, wherein the lyophilized composition maintains at least 96.7% of the original amount of the compound of formula (I) comprising the lyophilized composition following storage of the lyophilized composition at 40.degree. C. and 75% relative humidity for 2 weeks, and wherein the amount of the compound of formula (I) in the lyophilized composition is measured by high-performance liquid chromatography. 23. The method according to claim 1, wherein the lyophilized composition maintains at least 96.7% of the original amount of the compound of formula (I) comprising the lyophilized composition following storage of the lyophilized composition at 40.degree. C. and 75% relative humidity for 3 weeks, and wherein the amount of the compound of formula (I) in the lyophilized composition is measured by high-performance liquid chromatography. 24. The method according to claim 1, wherein the lyophilized composition maintains at least 96.7% of the original amount of the compound of formula (I) comprising the lyophilized composition following storage of the lyophilized composition at 40.degree. C. and 75% relative humidity for 4 weeks, and wherein the amount of the compound of formula (I) in the lyophilized composition is measured by high-performance liquid chromatography.