Self forming, thermodynamically stable liposomes and their applications

• US 6,958,160 B1
• Filed: 09/30/2002
• Issued: 10/25/2005
• Est. Priority Date: 12/20/2000
• Status: Expired due to Term

• Current Assignee: BioZone Laboratories, Incorporated (Ceba-Tech Specialty Solutions, Inc.)
• Original Assignee: Biozone Technologies Incorporated
• Inventors: Keller, Brian Charles
• Primary Examiner(s): Kishore, Gollamudi S.
• Application Number:
  US10/262,284
• Time in Patent Office: 1,121 Days
• Field of Search: 424/450, 424/1.21, 424/9.321, 424/9.51, 424/417, 428/402.2, 264/4.1, 264/4.3, 264/4.6
• US Class Current: 424/450
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543
• CPC Class Codes: A61K 9/1277 Processes for preparing; Proliposomes
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: Y10T 428/2984 Microcapsule with fluid core [includes liposome]

Abstract

A liposome suspension forms spontaneously upon adding a lipid composition to an aqueous solution. The liposomes include diacylglycerol-PEG compounds. The melting point of the diacylglycerol-PEG is below about 40 degrees C., and the acyl chains of the diacylglycerol-PEG are greater than or equal to 14 carbons in length. Such liposome suspensions are useful for a variety of purposes, including the delivery of therapeutic agents.

Claims

1. A liposome comprising:

one or more lipids where the total lipids have a P_a between about 0.84 and 0.88 and a P_v between about 0.88 and 0.93,

where P_a is the packing parameter with respect to surface and P_v is the packing parameter with respect to volume,

where one or more of the lipids is a diacylglycerol-PEG,

where the melting point of the diacylglycerol-PEG is below about 40 degrees C., and

where the acyl chains of the diacylglycerol-PEG are greater than or equal to 14 carbons in length.

2. The liposome of claim 1, where the PEG chain of the diacylglycerol-PEG has a molecular weight between about 300 Daltons and 5000 Daltons.

3. The liposome of claim 1, where the diacylglycerol-PEG comprises dioleolylglycerol-PEG-12.

4. The liposome of claim 1, further comprising an active compound.

5. The liposome of claim 4, where the active compound is selected from the group consisting of proteins, peptides, nucleic acids, agents for treating neoplasms, agents for treating inflammation, agents for treating infections, agents for treating gasterointestinal diseases, agents for treating immunological diseases, agents for treating skin diseases eye diseases, agents uses in diagnosing disease, nutrients, agents for treating blood diseases, agents for treating metabolic diseases, agents for treating cardiovascular diseases, agents for treating renal diseases, agents for treating genitourinary diseases, agents for treating respiratory diseases, and agents for treating central nervous system diseases.

6. The product of a process consisting essentially of:

providing one or more lipids where the total lipids have a P_a between about 0.84 and 0.88 and a P_v between about 0.88 and 0.93, where P_a is the packing parameter with respect to surface and P_v is the packing parameter with respect to volume and where one or more of the lipids is a diacylglycerol-PEG having a melting point below about 40 degrees C. and also having acyl chains greater than or equal to 14 carbons in length, and

combining the lipid or lipids with an aqueous solution at a temperature above the melting point of the lipid or lipids.

7. The product of claim 6, where the PEG chain of the diacylglycerol-PEG has a molecular weight between about 300 Daltons and 5000 Daltons.

8. The product of claim 6, where the diacylglycerol-PEG comprises dioleolylglycerol-PEG-12.

9. The product of claim 6, further comprising an active compound.

10. The product of claim 9, where the active compound is selected from the group consisting of proteins, peptides, nucleic acids, agents for treating neoplasms, agents for treating inflammation, agents for treating infections, agents for treating gasterointestinal diseases, agents for treating immunological diseases, agents for treating skin diseases eye diseases, agents uses in diagnosing disease, nutrients, agents for treating blood diseases, agents for treating metabolic diseases, agents for treating cardiovascular diseases, agents for treating renal diseases, agents for treating genitourinary diseases, agents for treating respiratory diseases, and agents for treating central nervous system diseases.