Heterofunctional copolymers of glycerol and polyethylene glycol, their conjugates and compositions

• US 20050048650A1
• Filed: 08/25/2004
• Published: 03/03/2005
• Est. Priority Date: 08/26/2003
• Status: Active Grant

• Current Assignee: GlaxoSmithKline LLC (GlaxoSmithKline PLC)
• Original Assignee: Smithkline Beecham Corporation (Smithkline Beecham PLC)
• Inventors: Ignatious, Francis
• Granted Patent: US 7,196,145 B2
• Time in Patent Office: Days
• US Class Current: 435/458
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: C07C 67/08 by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
• CPC Class Codes: C07C 69/52 Esters of acyclic unsaturated carboxylic acids having the esterified carboxyl group bound to an acyclic carbon atom
• CPC Class Codes: C08G 65/04 from cyclic ethers only
• CPC Class Codes: C08G 65/10 characterised by the catalysts used
• CPC Class Codes: C08G 65/26 from cyclic ethers and other compounds
• CPC Class Codes: C08G 65/34 from hydroxy compounds or their metallic derivatives C08G65/26 takes precedence
• CPC Class Codes: C08G 65/48 Polymers modified by chemical after-treatment
• CPC Class Codes: C12N 15/88 using microencapsulation, e.g. using amphiphile liposome vesicle

Abstract

The present invention relates to heterofunctional copolymers of glycerol and polyethylene glycol, conjugates of these heterofunctional copolymers with bioactive agents, nanoparticles, hydrophobic polymers and/or lipids; and to compositions containing these conjugates.

Claims

1. A compound represented by the structure:

7. A conjugate comprising the compound according to claim 1 with at least one agent selected from an active agent, a protein, a diagnostic agent, an imaging agent, and a polypeptide.

8. A conjugate comprising the compound according to claim 1 with at least one lipid.

9. A conjugate comprising the compound according to claim 1 with at least one hydrophobic polymer which results in an amphiphilic copolymer capable of forming a polymeric micelle.

10. A conjugate according to claim 1 with a hydrophobic polymer which results in an amphiphilic copolymer capable of forming a polymeric micelle.

11. A delivery vehicle comprising at least one conjugate according to claim 8, wherein the vehicle delivers a therapeutic active agent in an animal in need thereof.

12. A delivery vehicle comprising at least one conjugate according to claim 9, wherein the vehicle delivers a therapeutic active agent in an animal in need thereof.

13. A delivery vehicle comprising at least one conjugate according to claim 7, wherein the vehicle delievers at least one agent selected from the active agent, protein, diagnostic agent, imaging agent, and polypeptide to a human in need thereof.

14. A liposome comprising:

a) at least one composition according to claim 1;

b) at least one vesicle forming lipid;

c) optionally at least one targeting moiety;

d) and optionally at least one therapeutic active agent chosen from drugs, proteins, peptides, imaging agents, radioactive agents, and nucleic acids.

2. A compound represented by the structure:

3. A compound represented by the structure:

4. A compound represented by the structure:

5. A compound represented by the structure:

6. A compound represented by the structure:

15. A process of making a derivatized heterofunctional random architecture copolymer comprising adjusting the ratio of the monomers glycidol and ethylene oxide to each other;

and/or adjusting the order of addition in which monomers are added to a polymerization medium; and

/or adjusting the rate of addition of the monomers glycidol and ethylene oxide to the polymerization mixture, to yield the presence of two different functional groups at the termini of the resulting hyperbranched copolymer of polyethylene oxide and polyglycidol.

16. The process according to claim 15 wherein one of the functional termini groups is a carboxylic group which may be converted to any suitable or desired reactive species.

17. The process according to claim 15 wherein one of the functional termini groups is an amino group.

18. The process according to claim 15 wherein one of the functional termini groups is an aldehyde.

19. The process according to claim 15 wherein one of the functional termini groups is a hydroxyl group.