Details for Patent: 9,072,656

Title:	Propofol formulations with non-reactive container closures
Abstract:	A container storing an anesthetic is disclosed. The container is sealed by a closure and stores a liquid anesthetic solution. The anesthetic is from 0.1% to 10% by weight of the liquid anesthetic solution. The container is made of a material that is inert to the anesthetic and the closure is made of siliconized rubber or a metal. A concentration of the anesthetic in a liquid anesthetic solution stored in the container following a predetermined time period is at least 93% of a concentration of the anesthetic in a liquid anesthetic solution before the liquid anesthetic solution is stored in the container.
Inventor(s):	Desai; Neil P. (Pacific Palisades, CA), Yang; Andrew (Rosemead, CA), Cl; Sherry Xiaopei (San Marino, CA)
Assignee:	FRESENIUS KABI USA, LLC (Lake Zurich, IL)
Filing Date:	Apr 23, 2014
Application Number:	14/259,381
Claims:	1. A pre-filled syringe storing an anesthetic, the pre-filled syringe comprising: a container configured to store an oil-in-water anesthetic emulsion or an anesthetic solution, the oil-in-water anesthetic emulsion or the anesthetic solution comprising an anesthetic and water, the anesthetic being from 0.1% to 10% by weight of the oil-in-water anesthetic emulsion or the anesthetic solution, and the container being made of a material that is inert to the anesthetic; a plunger having a portion made of siliconized bromobutyl rubber or siliconized chlorobutyl rubber that is inert to the anesthetic; and a stopper made of siliconized bromobutyl rubber or siliconized chlorobutyl rubber that is inert to the anesthetic, wherein: the portion of the plunger and the stopper seal the container configured to store the anesthetic emulsion, and the portion of the plunger and the stopper are in contact with at least some of the oil-in-water anesthetic emulsion or the anesthetic solution when the container is sealed by the portion of the plunger and the stopper. 2. The pre-filled syringe of claim 1, wherein the anesthetic is propofol. 3. The pre-filled syringe of claim 1, wherein the material that is inert to the anesthetic is glass. 4. The pre-filled syringe of claim 3, wherein the glass is siliconized glass. 5. The pre-filled syringe of claim 1, wherein the material that is inert to the anesthetic is plastic. 6. The pre-filled syringe of claim 1, wherein the portion of the plunger is made of siliconized bromobutyl rubber. 7. The pre-filled syringe of claim 1, wherein the portion of the plunger is made of siliconized chlorobutyl rubber. 8. The pre-filled syringe of claim 1, wherein: the container is configured to store the oil-in-water anesthetic emulsion; the oil-in-water anesthetic emulsion further comprises a solvent; and the solvent is less than 10% by weight of the oil-in-water anesthetic emulsion. 9. The pre-filled syringe of claim 8, wherein the solvent is a water-immiscible solvent. 10. The pre-filled syringe of claim 9, wherein the water-immiscible solvent is selected from the group consisting of soybean oil, safflower oil, cottonseed oil, corn oil, coconut oil, sunflower oil, arachis oil, castor sesame oil, orange oil, limonene oil, olive oil, hydrogenated castor oil, marine oil, fractionated oil, an ester of a medium-chain fatty acid, an ester of a long-chain fatty acid, a chemically modified palmitate, a glyceral ester, a polyoxyl, and mixtures thereof. 11. The pre-filled syringe of claim 1, wherein: the container is configured to store the oil-in-water anesthetic emulsion; and the oil-in-water anesthetic emulsion further comprises a surfactant. 12. The pre-filled syringe of claim 11, wherein the surfactant is selected from the group consisting of phosphatides, synthetic phospholipids, natural phospholipids, lecithins, ethoxylated ethers, ethoxylated esters, tocopherol polyethylene glycol stearate, polypropylene-polyethylene block co-polymers, polyvinyl pyrrolidone, polyvinylalcohol, and combinations thereof. 13. The pre-filled syringe of claim 12, wherein the surfactant is selected from the group consisting of egg phosphatides, soya phosphatides, egg lecithins, soya lecithins, and combinations thereof. 14. The pre-filled syringe of claim 1, wherein the container is configured to store the oil-in-water anesthetic emulsion or the anesthetic solution between the portion of the plunger and the stopper. 15. The pre-filled syringe of claim 1, wherein, following storage in the container for a predetermined time period, the percentage of anesthetic present in the oil-in-water anesthetic emulsion or the anesthetic solution is at least 93% of a starting amount of the anesthetic present in the oil-in-water anesthetic emulsion or the anesthetic solution. 16. The pre-filled syringe of claim 1, wherein the portion of the plunger and the stopper are located at opposite ends of the container. 17. The pre-filled syringe of claim 1, wherein: the container is configured to store the oil-in-water anesthetic emulsion; and the oil-in-water anesthetic emulsion further comprises a tonicity agent. 18. The pre-filled syringe of claim 1, wherein, following storage in the container for a predetermined time period, the percentage of anesthetic present in the oil-in-water anesthetic emulsion or the anesthetic solution is at least 93% of the anesthetic in the oil-in-water anesthetic emulsion or the anesthetic solution before the oil-in-water anesthetic emulsion or the anesthetic solution is stored in the container. 19. The pre-filled syringe of claim 1, wherein the stopper is made of siliconized bromobutyl rubber. 20. The pre-filled syringe of claim 1, wherein the stopper is made of siliconized chlorobutyl rubber. 21. The pre-filled syringe of claim 1, wherein both the portion of the plunger and the stopper are made of siliconized bromobutyl rubber. 22. The pre-filled syringe of claim 1, wherein both the portion of the plunger and the stopper are made of siliconized chlorobutyl rubber. 23. The pre-filled syringe of claim 1, wherein the container is configured to store the oil-in-water anesthetic emulsion. 24. The pre-filled syringe of claim 1, wherein the container is configured to store the anesthetic solution. 25. A pre-filled syringe storing propofol, the pre-filled syringe comprising: a container configured to store an oil-in-water propofol emulsion, the oil-in-water propofol emulsion comprising: propofol from 0.1% to 10% by weight of the oil-in-water propofol emulsion, water, a solvent, a surfactant, and a tonicity agent, wherein the container is made of a material that is inert to the propofol; a plunger having a portion made of siliconized bromobutyl rubber or siliconized chlorobutyl rubber that is inert to the propofol; and a stopper made of siliconized bromobutyl rubber or siliconized chlorobutyl rubber that is inert to the propofol, wherein: the portion of the plunger and the stopper seal the container configured to store the oil-in-water propofol emulsion, and the portion of the plunger and the stopper are in contact with at least some of the oil-in-water propofol emulsion when the container is sealed by the portion of the plunger and the stopper. 26. The pre-filled syringe of claim 25, wherein, following storage in the container for a predetermined time period, the percentage of propofol present in the oil-in-water propofol emulsion is at least 93% of the propofol in the oil-in-water propofol emulsion before the oil-in-water propofol emulsion is stored in the container. 27. The pre-filled syringe of claim 25, wherein, following storage in the container for a predetermined time period, the percentage of propofol present in the oil-in-water propofol emulsion is at least 93% of a starting amount of the propofol present in the oil-in-water propofol emulsion. 28. A pre-filled syringe storing propofol, the pre-filled syringe comprising: a container configured to store an oil-in-water propofol emulsion, the oil-in-water propofol emulsion comprising: propofol from 0.1% to 10% by weight of the oil-in-water propofol emulsion, water, soybean oil, egg phosphatide, and glycerin, wherein the container is made of a material that is inert to the propofol; a plunger having a portion made of siliconized bromobutyl rubber or siliconized chlorobutyl rubber that is inert to the propofol; and a stopper made of siliconized bromobutyl rubber or siliconized chlorobutyl rubber that is inert to the propofol, wherein: the portion of the plunger and the stopper seal the container configured to store the oil-in-water propofol emulsion, and the portion of the plunger and the stopper are in contact with at least some of the oil-in-water propofol emulsion when the container is sealed by the portion of the plunger and the stopper. 29. The pre-filled syringe of claim 28, wherein, following storage in the container for a predetermined time period, the percentage of propofol present in the oil-in-water propofol emulsion is at least 93% of the propofol in the oil-in-water propofol emulsion before the oil-in-water propofol emulsion is stored in the container. 30. The pre-filled syringe of claim 28, wherein, following storage in the container for a predetermined time period, the percentage of propofol present in the oil-in-water propofol emulsion is at least 93% of a starting amount of the propofol present in the oil-in-water propofol emulsion.