Propofol formulations with non-reactive container closures

US 20050009731A1
Filed: 07/10/2003
Published: 01/13/2005
Est. Priority Date: 07/10/2003
Status: Active Grant

First Claim

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1. A sterile pharmaceutical composition for parenteral administration of propofol, said composition comprising propofol, and less than about 10% by weight solvent for propofol, wherein said composition is stored in a container having a closure wherein said closure is inert to propofol.

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Abstract

A sterile pharmaceutical composition for parenteral administration of propofol, said composition comprising propofol, optionally albumin, and less than about 10% by weight solvent for propofol, wherein said composition is stored in a container having a closure wherein said closure is inert to propofol.

Citations

64 Claims

1. A sterile pharmaceutical composition for parenteral administration of propofol, said composition comprising propofol, and less than about 10% by weight solvent for propofol, wherein said composition is stored in a container having a closure wherein said closure is inert to propofol.
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28)
- - 2. The composition of claim 1, wherein said composition further comprises an aqueous phase and protein.
  - 3. The sterile pharmaceutical composition of claim 2, wherein the protein is albumin.
  - 4. The sterile pharmaceutical composition of claim 3, wherein the albumin is present in an amount of from about 0.01% to about 5% by weight of the composition.
  - 5. The sterile pharmaceutical composition of claim 2, wherein the aqueous phase comprises water of injection and a pH modifier.
  - 6. The sterile pharmaceutical composition of claim 2, wherein the composition comprises a tonicity agent.
  - 7. The sterile pharmaceutical composition of claim 3, wherein the pH modifier is sodium hydroxide.
  - 8. The sterile pharmaceutical composition of claim 6, wherein the tonicity agent is glycerin.
  - 9. The sterile pharmaceutical composition of claim 2, wherein said composition further comprises surfactant.
  - 10. The sterile pharmaceutical composition of claim 1, wherein said composition further comprises a solvent for propofol.
  - 11. The sterile pharmaceutical composition of claim 10 wherein the solvent is a water-immiscible solvent.
  - 12. The sterile pharmaceutical composition of claim 11, wherein the water-immiscible solvent is selected from the group consisting of soybean, safflower, cottonseed, corn, coconut, sunflower, arachis, castor sesame, orange, limonene or olive oil, an ester of a medium or long-chain fatty acid, a chemically modified or manufactured palmitate, glyceral ester or polyoxyl, hydrogenated castor oil, a marine oil, fractionated oils, and mixtures thereof.
  - 13. The sterile pharmaceutical composition of claim 12, wherein the water-immiscible solvent is soybean oil.
  - 14. The sterile pharmaceutical composition of claim 10, wherein the solvent is selected from the group consisting of chloroform, methylene chloride, ethyl acetate, ethanol, tetrahydrofuran, dioxane, acetonitrile, acetone, dimethyl sulfoxide, dimethyl formamide, methylpyrrolidinone, C1-C20 alcohols, C2-C20 esters, C3-C20 ketones, polyethylene glycols, aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons and combinations thereof.
  - 15. The sterile pharmaceutical composition of claim 9, wherein the surfactant is selected from the group consisting of phosphatides, synthetic phospholipids, natural phospholipids, lecithins, ethoxylated ethers and esters, tocopherol polyethylene glycol stearate, polypropylene-polyethylene block co-polymers, polyvinyl pyrrolidone, and polyvinylalcohol and combinations thereof.
  - 16. The sterile pharmaceutical composition of claim 15, wherein the surfactant is selected from the group consisting of egg phosphatides, soya phosphatides, egg lecithins, soya lecithins, and compositions thereof.
  - 17. The sterile pharmaceutical composition of claim 16, wherein the surfactant is egg lecithin.
  - 18. The sterile pharmaceutical composition of claim 1, wherein said closure is coated with a material inert to propofol.
  - 19. The sterile pharmaceutical composition of claim 1, wherein said closure is comprised of a material that is itself inert to propofol.
  - 20. The sterile pharmaceutical composition of claim 19, wherein the material inert to propofol is selected from the group consisting of a fluoropolymer, silicone, and mixtures thereof.
  - 21. The sterile pharmaceutical composition of claim 19, wherein said material is selected from the group consisting of bromobutyl rubber, chlorobutyl rubber, a fluoropolymer, silicone, non-rubber, metal, and mixtures thereof.
  - 22. The sterile pharmaceutical composition of claim 19, wherein the material is selected from the group consisting of bromobutyl rubber, chlorobutyl rubber, a fluoropolymer, silicone, and mixtures thereof.
  - 23. The sterile pharmaceutical composition of claim 1, wherein said closure comprises bromobutyl rubber coated with a fluoropolymer.
  - 24. The sterile pharmaceutical composition of claim 1, wherein said closure comprises siliconized bromobutyl rubber.
  - 25. The sterile pharmaceutical composition of claim 1, wherein said closure comprises a non-rubber, or metal.
  - 26. The sterile pharmaceutical composition of claim 1, wherein said closure comprises chlorobutyl rubber coated with a fluoropolymer.
  - 27. The sterile pharmaceutical composition of claim 1, wherein said closure comprises siliconized chlorobutyl rubber.
  - 28. The sterile pharmaceutical composition of claim 1, wherein the composition comprises propofol in an amount of from about 0.1% to about 10% by weight of the composition, soybean oil in an amount of from about 0.5% to about 6% by weight of the composition, egg lecithin in an amount of from about 0.1% to about 5% by weight of the composition and human serum albumin in an amount of from about 0.1% to about 5% of the composition.

29. A sterile pharmaceutical composition in the form of an oil-in-water emulsion for parenteral administration of propofol, said composition comprising an oil phase comprising propofol, and less than about 10% by weight solvent for propofol and an aqueous phase comprising water for injection and wherein the composition includes a stabilizing layer for the oil phase, said stabilizing layer comprising a surfactant and a protein, wherein said composition is stored in a container having a closure wherein said closure is inert to propofol.
- View Dependent Claims (30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 47, 48, 49, 50, 51)
- - 30. The composition of claim 29, wherein said protein is selected from the group consisting of albumins, globulins, immunoglobulins, lipoproteins, caseins, insulins, hemoglobins, lysozymes, alpha-2-macroglobulin, fibronectins, vitronectins, fibrinogens, lipases, peptides, enzymes, antibodies and combinations thereof.
  - 31. The composition of claim 29, wherein the surfactant is selected from the group consisting of phosphatides, synthetic phospholipids natural phospholipids, lecithins, ethoxylated ethers and esters, tocopherol polyethylene glycol stearate, polypropylene-polyethylene block co-polymers, polyvinyl pyrrolidone, and polyvinylalcohol.
  - 32. The composition of claim 29, wherein said oil phase is propofol neat.
  - 33. The composition of claim 29, wherein said surfactant is lecithin and said protein is albumin.
  - 34. The composition of claim 29, wherein the oil phase includes a solvent, wherein said solvent is selected from the group consisting of soybean, safflower, cottonseed, corn, coconut, sunflower, arachis, castor sesame, orange, limonene or olive oil, an ester of a medium or long-chain fatty acid, a chemically modified or manufactured palmitate, glyceral ester or polyoxyl, hydrogenated castor oil, a marine oil, fractionated oils, and mixtures thereof, chloroform, methylene chloride, ethyl acetate, ethanol, tetrahydrofuran, dioxane, acetonitrile, acetone, dimethyl sulfoxide, dimethyl formamide, methylpyrrolidinone, C1-C20 alcohols, C2-C20 esters, C3-C20 ketones, polyethylene glycols, aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons and combinations thereof.
  - 35. The composition of claim 34, wherein the solvent is soybean oil.
  - 36. The composition of claim 35, wherein said soybean oil is present in an amount of from about 0.5% to about 6% by weight of the composition.
  - 37. The composition of claim 33, wherein said egg lecithin is present in the composition in an amount of from about 0.1% to about 5% by weight of the composition and said albumin is present in the composition in an amount of from about 0.01% to about 5% by weight of the composition.
  - 38. The composition of claim 37, wherein said oil phase includes soybean oil.
  - 39. The composition of claim 38, wherein said soybean oil is present in an amount of from about 0.5% to about 6% by weight of the composition.
  - 40. The composition of claim 38, wherein said soybean oil is present in said composition in an amount of from about 0.5% to about 3% by weight of the composition.
  - 41. The sterile pharmaceutical composition of claim 31 comprising:
    - a) about 1% to 2% by weight of propofol, b) 3-6% by weight of soybean oil, c) 0.2-1.0% by weight of egg lecithin, d) about 2.25% by weight of glycerin, e) sodium hydroxide, f) water to 100%, and g) pH between 5.0-8.5.
  - 42. The sterile pharmaceutical composition of claim 29, wherein said closure is treated with a material inert to propofol.
  - 43. The sterile pharmaceutical composition of claim 29, wherein said closure comprises a material that is itself inert to propofol.
  - 44. The sterile pharmaceutical composition of claim 42, wherein the material inert to propofol is selected from the group consisting of a fluoropolymer, silicone, and mixtures thereof.
  - 45. The sterile pharmaceutical composition of claim 43, wherein the material is selected from the group consisting of bromobutyl rubber, chlorobutyl rubber, a fluoropolymer, silicone, non-rubber, metal, and mixtures thereof.
  - 47. The sterile pharmaceutical composition of claim 29, wherein said closure comprises bromobutyl rubber coated with a fluoropolymer.
  - 48. The sterile pharmaceutical composition of claim 29, wherein said closure comprises siliconized bromobutyl rubber.
  - 49. The sterile pharmaceutical composition of claim 29, wherein said closure comprises non-rubber, or metal.
  - 50. The sterile pharmaceutical composition of claim 29, wherein said closure comprises chlorobutyl rubber coated with a fluoropolymer.
  - 51. The sterile pharmaceutical composition of claim 29, wherein said closure comprises siliconized chlorobutyl rubber.

46. The sterile pharmaceutical composition of claim 46, wherein the material is selected from the group consisting of bromobutyl rubber, chlorobutyl rubber, a fluoropolymer, silicone, and mixtures thereof.

52. A sterile, injectable pharmaceutical composition comprising:
- a) microdroplets having a mean size of from about 20 nanometers to about 1000 nanometers, said microdroplets comprising a sphere of propofol surrounded by a stabilizing layer comprising a phospholipid and devoid of oils capable of supporting bacterial growth; and
  
  b) a pharmaceutically acceptable injectable carrier, wherein said composition is stored in a container having a closure, wherein said closure is inert to propofol.
- View Dependent Claims (53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64)
- - 53. The composition of claim 52, wherein said composition further comprises albumin.
  - 54. The composition of claim 52, wherein said stabilizing layer includes albumin.
  - 55. The sterile pharmaceutical composition of claim 52, wherein said closure is coated with a material inert to propofol.
  - 56. The sterile pharmaceutical composition of claim 52, wherein said closure comprises a material that is itself inert to propofol.
  - 57. The sterile pharmaceutical composition of claim 55, wherein the material inert to propofol is selected from the group consisting of a fluoropolymer, silicone, and mixtures thereof.
  - 58. The sterile pharmaceutical composition of claim 56, wherein the material is selected from the group consisting of bromobutyl rubber, chlorobutyl rubber, a fluoropolymer, silicone, non-rubber, metal, and mixtures thereof.
  - 59. The sterile pharmaceutical composition of claim 55, wherein the material is selected from the group consisting of bromobutyl rubber, chlorobutyl rubber, a fluoropolymer, silicone, and mixtures thereof.
  - 60. The sterile pharmaceutical composition of claim 52, wherein said closure comprises bromobutyl rubber coated with a fluoropolymer.
  - 61. The sterile pharmaceutical composition of claim 52, wherein said closure comprises siliconized bromobutyl rubber.
  - 62. The sterile pharmaceutical composition of claim 52, wherein said closure comprises a non-rubber, or metal.
  - 63. The sterile pharmaceutical composition of claim 52, wherein said closure comprises chlorobutyl rubber coated with a fluoropolymer.
  - 64. The sterile pharmaceutical composition of claim 52, wherein said closure comprises siliconized chlorobutyl rubber.

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Current Assignee
Fresenius KABI USA LLC (Fresenius SE & Co. KGaA)
Original Assignee
American Bioscience, Inc. (Bristol-Myers Squibb Company)
Inventors
Desai, Neil P., Yang, Andrew, Ci, Sherry Xiaopei

Granted Patent

US 8,476,010 B2
Time in Patent Office

Days
Field of Search
US Class Current

435/6
CPC Class Codes

A61J 1/00   Containers specially adapte...

A61J 1/05   for collecting, storing or ...

A61J 1/06   Ampoules or carpules syring...

A61J 1/1412   Containers with closing mea...

A61J 1/1468   Containers characterised by...

A61K 31/05   Phenols cannabinoids A61K31...

A61K 47/10   Alcohols; Phenols; Salts th...

A61K 47/24   containing atoms other than...

A61K 47/44   Oils, fats or waxes accordi...

A61K 9/0019   Injectable compositions; In...

A61K 9/0075   for inhalation via a dry po...

A61K 9/107   Emulsions ; Emulsion precon...

A61K 9/1075   Microemulsions or submicron...

Propofol formulations with non-reactive container closures

First Claim

14 Assignments

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Abstract

Citations

64 Claims

Specification

Solutions

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Propofol formulations with non-reactive container closures

First Claim

14 Assignments

Subscription Required

Subscription Required

0 Petitions

Subscription Required

Accused Products

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Abstract

Citations

64 Claims

Specification

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Solutions

Use Cases

Quick Links