PEG-POE, PEG-POE-PEG, and POE-PEG-POE block copolymers

• US 5,939,453 A
• Filed: 06/04/1998
• Issued: 08/17/1999
• Est. Priority Date: 06/04/1998
• Status: Expired due to Term

• Current Assignee: Heron Therapeutics Inc.
• Original Assignee: Advanced Polymer Systems Incorporated
• Inventors: Heller, Jorge, Ng, Steven Y.
• Primary Examiner(s): Richter, Johann
• Assistant Examiner(s): Solola, Taofiq A.
• Application Number:
  US09/090,648
• Time in Patent Office: 439 Days
• Field of Search: 514/452, 514/456, 514/772.1, 549/335
• US Class Current: 514/452
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61K 9/204 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: C08G 63/664 derived from hydroxy carboxylic acids
• CPC Class Codes: C08G 65/002 from unsaturated compounds unsaturated oxiranes C08G65/14
• CPC Class Codes: C08G 65/34 from hydroxy compounds or their metallic derivatives C08G65/26 takes precedence
• CPC Class Codes: C08L 2666/14 Macromolecular compounds according to C08L59/00 - C08L87/00; Derivatives thereof
• CPC Class Codes: C08L 71/02 Polyalkylene oxides

Abstract

PEG-POE, PEG-POE-PEG, and POE-PEG-POE block copolymers have both hydrophilic and hydrophobic blocks. They form micelles in aqueous solution, making them suitable for encapsulation or solubilization of hydrophobic or water-insoluble materials; and they also form bioerodible matrices for the sustained release of active agents, especially when the POE block(s) contain at least one unit containing an α-hydroxy acid.

Claims

1. A block copolymer of formula I:

##STR15## in which;

m and n are independently an integer from 5 to 500;

p and q are independently an integer from 5 to 100;

R¹ and R² are independently C₁ -C₄ alkyl;

R³ is H or C₁ -C₄ alkyl; and

A is --O--R⁴ --, --O--R¹ --, or a mixture thereof, where;

R⁴ is selected from ##STR16## where t is an integer from 1 to 12, R⁶ is C₁ -C₄ alkyl, and

R⁷ is H or C₁ -C₄ alkyl; and

R⁵ is ##STR17## in which;

x is an integer from 1 to 10, and

R⁸ is H or C₁ -C₆ alkyl.

2. The copolymer of claim 1 which is a compound of formula I.

3. The copolymer of claim 2 where m is an integer from 50 to 250, and p is an integer from 10 to 50.

4. The copolymer of claim 2 where R¹ is ethyl and R² is methyl.

5. The copolymer of claim 2 where A is --O--R⁴ -- and HO--R⁴ --OH is cyclohexanedimethanol.

6. The copolymer of claim 1 which is a compound of formula II.

7. The copolymer of claim 6 where m and n are independently an integer from 50 to 250, and p is an integer from 10 to 50.

8. The copolymer of claim 6 where R¹ is ethyl and R³ is hydrogen or methyl.

9. The copolymer of claim 6 where A is --O--R⁴ -- and HO--R⁴ --OH is cyclohexanedimethanol.

10. The copolymer of claim 1 which is a compound of formula III.

11. The copolymer of claim 10 where n is an integer from 50 to 250, and p and q are independently an integer from 10 to 50.

12. The copolymer of claim 10 where R¹ is ethyl.

13. The copolymer of claim 10 where A is --O--R⁴ -- and HO--R⁴ --OH is cyclohexanedimethanol.

14. A micellar pharmaceutical composition for the delivery of a hydrophobic or water-insoluble active agent, comprising the active agent physically entrapped within but not covalently bonded to a drug carrier comprising a block copolymer of claim 1.

15. A micellar pharmaceutical composition for the delivery of a hydrophobic or water-insoluble active agent, comprising the active agent physically entrapped within but not covalently bonded to a drug carrier comprising a block copolymer of claim 2.

16. The composition of claim 15 where the active agent is an anticancer agent.

17. A composition for the sustained release of an active agent, comprising the active agent dispersed in a matrix comprising the block copolymer of claim 1.

18. The composition of claim 17 where the active agent is an anticancer agent.

19. A composition for the sustained release of an active agent, comprising the active agent dispersed in a matrix comprising the block copolymer of claim 2.

20. The composition of claim 19 where the active agent is an anticancer agent.