Sphingosomes for enhanced drug delivery

Patent 5741516 Issued on April 21, 1998. Estimated Expiration Date:

December 14, 2015. Estimated Expiration Date is calculated based on simple USPTO term provisions. It does not account for terminal disclaimers, term adjustments, failure to pay maintenance fees, or other factors which might affect the term of a patent.

Abstract Claims Description Full Text

Patent References

Liposomes with enhanced circulation time
Patent #: 4837028
Issued on: 06/06/1989
Inventor: Allen

Liposomes with enhanced circulation time
Patent #: 4920016
Issued on: 04/24/1990
Inventor: Allen, et al.

Liposome-encapsulated vinca alkaloids and their use in combatting tumors
Patent #: 4952408
Issued on: 08/28/1990
Inventor: Rahman

Method of amphiphatic drug loading in liposomes by pH gradient
Patent #: 5192549
Issued on: 03/09/1993
Inventor: Barenolz, et al.

Sphingosomes for enhanced drug delivery Patent #: 5543152
Issued on: 08/06/1996
Inventor: Webb, et al.

Inventors

Assignee

Inex Pharmaceuticals Corporation

Application

No. 572555 filed on 12/14/1995

US Classes:

424/450, Liposomes514/27, Oxygen of the saccharide radical bonded directly to a nonsaccharide hetero ring or a polycyclo ring system which contains a nonsaccharide hetero ring514/283Ring nitrogen in the pentacyclo ring system is shared by five-membered cyclo and six-membered cyclo (e.g., vincamine, etc.)

Examiners

Primary: Nutter, Nathan M.

Attorney, Agent or Firm

Townsend and Townsend and Crew

Foreign Patent References

88/04924 WO. 07/13/1988
88/06442 WO. 09/13/1988
90/14105 WO. 11/13/1990

International Classes

A61K 009/127
A01N 043/04

Abstract

Liposomal formulations having extended circulation time in vivo and increased drug retention are comprised of sphingomyelin and cholesterol and have an acidic intraliposomal pH. The formulations have enhanced stability and thus are used in methods which provide improved drug delivery and more effective treatment. The delivery of ciprofloxacin, and alkaloid drugs, particularly swainsonine, vincristine and vinblastine, is significantly improved.

Other References

Weereratne et al., "Toxicity of Sphingomyelin-containing Liposomes after Chronic Injection into Mice," Brit. J. Exp. Pathol. 64:670-676 (1983)
Allen et al., "Chronic Liposome Administration in Mice: Effects on Reticuloendothelial Function and Tissue Distribution," J. Pharmacol. Exp. Therap. 229:267-275 (1984)
Allen et al., "Liver Pathology Accompanying Chronic Liposome Administration in Mouse," Res. Commun. Chem. Pathol. Pharmacol. 50:281-290 (Nov., 1985)
Mayer et al., "Solute Distributions and Trapping Efficiencies Obsered in Freeze-Thawed Multilamellar Vesicles," Biochim. Biophys. Acta 817:193-196 (1985)
Allen et al., "Large Unilamellar Liposomes with Low Uptake into the Reticuloendothelial System," FEBS Lett. 223:42-46 (Oct., 1987)
Allen et al., "Liposomes with Prolonged Circulation times; Factors Affecting Uptake by Reticuloendothelial and Other Tissues," Biochim. Biophys. Acta 981:27-35 (1989)
Mayer et al., "Liposomal Vincristine Preparations Which Exhibit Decreased Drug Toxicity and Increased Activity against Murine L1210 and P388 Tumors," Cancer Res. 50:575-579 (Feb. 1, 1990)
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Mayer et al., Characterization of Liposomal Systems Containing Doxorubicin Entrapped in Response to pH Gradients, Biochim. Biophys. Acta 1025:143-151 (1990)
Allen et al., "Lipsomes Containing Synthetic Lipid Derivatives of Poly(ethyleneglycol) Show Prolonged Circulation Half-Lives in Vivo," Biochim. Biophys. Acta. 1066:29-36 (1991)
Allen et al., "Pharmacokinetics of Stealth versus Conventional Liposomes: Effect of Dose," Biochim. Biophys. Acta. 1068:133-141 (1991)
Mayer et al., "Identification of Vesicle Properties that Enhance the Antitumour Activity of Liposomal Vincristine Against Murine L1210 Leukemia," Cancer Chemother. Pharmacol. 33:17-24 (1993)
Grit et al., "Chemical Stability of Liposomes: Implicatioons for their Physical Stability," Chem. Phys. Lipids 64:3-18 (1993)
Boman et al., "Liposomal Vincristine Which Exhibits Increased Drug Retention and Increased Circulation Longevity Cures Mice Bearing P388 Tumors," Cancer Res. 54: 2830-2833 (Jun. 1, 1994)
Hope et al., "Generation of Multilamellar and Unilamellar Phospholipid Vesicles", Chemistry and Physics of Lipids, 40:89-107 (1986