LIPOSOMAL SYSTEMS COMPRISING SPHINGOMYELIN

• US 20110250266A1
• Filed: 10/11/2009
• Published: 10/13/2011
• Est. Priority Date: 10/07/2008
• Status: Abandoned Application

• Current Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. (Hebrew University of Jerusalem)
• Original Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. (Hebrew University of Jerusalem)
• Inventors: Barenholz, Yechezkel, Cohen, Rivka
• Application Number:
  US13/123,112
• Publication Number:
  US 20110250266A1
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61P 23/02 Local anaesthetics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

The present disclosure provides a liposomal system comprising an aqueous medium having dispersed therein liposomes encapsulating in their intraliposomal aqueous compartment at least one active agent, the aqueous medium being in iso-osmotic equilibrium with said intraliposomal aqueous compartment, the liposomes having a membrane comprising a liposome forming lipids, at least one of which being sphingomyelin (SPM), the liposomal system having increased stability as compared to the same liposomes free of SPM, and in one embodiment being stable during long-term storage, said stability being characterized in that no more than 30% of the at least one active agent is present in the aqueous medium after said storage. Further provided by the present disclosure are a method for storage of liposomes making use of the liposomal system; use of the liposomal system for the treatment of a medical condition or for the diagnostic of a medical condition; a pharmaceutical or diagnostic composition comprising the liposomal system, and a method of treating or diagnosing of a medical condition comprising administering to a subject an amount of the liposomal system.

Claims

1. A liposomal system comprising an aqueous medium having dispersed therein liposomes encapsulating in their intraliposomal aqueous compartment at least one active agent, the aqueous medium being in iso-osmotic equilibrium with said intraliposomal aqueous compartment, the liposomes having a membrane comprising liposome forming lipids, at least one of which being sphingomyelin (SPM), the liposomal system having increased stability as compared to the same liposomes free of SPM.

2. The liposomal system as claimed in claim 1, being stable during long-term storage, said stability being characterized in that no more than 30% of the at least one active agent is present in the aqueous medium after said storage.

3. The liposomal system as claimed in claim 2, wherein no more than 10% of the at least one active agent is present in the aqueous medium after said storage.

4. The liposomal system as claimed in claim 1, wherein said SPM is a C12-C24 SPM, and is selected from a synthetic or semi-synthetic SPM.

7. The liposomal system as claimed claim 1, wherein said membrane comprises SPM in an amount between 25 to 75 mole % of the total phospholipids in said membrane.

8. The liposomal system as claimed in claim 1, comprising a mole ratio between the liposome forming lipids other than SPM and said SPM in the range of 1:

1 to 2;

1.

9. The liposomal system as claimed in claim 1, wherein said liposome forming lipids have together a solid ordered to liquid disordered phase transition temperature (T_m) above 37°

C.

10. The liposomal system as claimed in claim 1, wherein said membrane comprises a sterol.

12. The liposomal system as claimed in claim 1, wherein said liposomes are multilamellar vesicles (MLVs) or multivesicular vesicles (MVVs).

14. The liposomal system as claimed in claim 1, wherein said aqueous medium and said intraliposomal aqueous compartment have an osmolarity between 50 to 600 mOsm/kg.

16. The liposomal system as claimed in claim 1, wherein said aqueous medium and said intraliposomal aqueous compartment have an osmolarity difference of no more than 50 mOsmole.

23. The liposomal system as claimed in claim 1, wherein the mole ratio between said active agent and said liposome forming lipids being above 0.5 mole/mole.

54. A method of treating or diagnosing of a medical condition comprising administering to a subject an amount of the liposomal system as claimed in claim 1.

5-6. -6. (canceled)

11. (canceled)

13. (canceled)

15. (canceled)

17-22. -22. (canceled)

24. (canceled)

25. A method for storage of liposomes encapsulating in their intraliposomal aqueous compartment at least one active agent, the liposomes having a membrane comprising liposome forming lipids, at least one liposome forming lipid being sphingomyelin (SPM), the method comprising forming a liposomal system where said liposomes are dispersed in an aqueous medium being in an iso-osmotic equilibrium with the intraliposomal aqueous compartment of said liposomes and storing said liposomal system, said liposomal system having increased stability as compared to the same liposomes free of SPM.

26. The method as claimed in claim 25, where no more than 30% of the at least one active agent is present in the aqueous medium after said storage.

34. The method as claimed in claim 25, wherein said membrane comprises SPM in an amount between 25 to 75 mole % of the total lipids in said membrane.

35. The method as claimed in claim 25, comprising a mole ratio between the liposome forming lipids other than SPM and said SPM in the range of 1:

1 to 2;

1.

36. The method as claimed in claim 25, wherein said liposome forming lipids have together a solid ordered to liquid disordered phase transition temperature (T_m) above 37°

C.

43. The method as claimed in claim 25, wherein said aqueous medium and said intraliposomal aqueous compartment have an osmolarity difference of no more than 50 mOsmole.

27-33. -33. (canceled)

37-42. -42. (canceled)

44-53. -53. (canceled)