Polymer-based serum albumin substitute

Patent metadata

Field	Value
Publication number	US-9789056-B2
Application number	US-201615131559-A
Country	US
Kind code	B2
Filing date	Apr 18, 2016
Priority date	Jun 6, 2005
Publication date	Oct 17, 2017
Grant date	Oct 17, 2017

Abstract

This invention provides the use of a polymer comprising a hyperbranched polyether polyol such as hyperbranched polyglycerol as a serum albumin substitute. Also provided are high molecular weight hyperbranched polyglycerol polymers suitable for a variety of medical and non-medical uses including methods for making such high molecular weight polymers.

First claim

We claim:

1. A hyperbranched polymer comprising a hyperbranched polyglycerol (HPG), wherein the HPG of the hyperbranched polymer has a number average molecular weight of 40,000 g/mol to 120,000 g/mol and a polydispersity of 1 to 3.5.

2. The hyperbranched polymer of claim 1 , wherein the HPG has a number average molecular weight of 50,000 g/mol to 100,000 g/mol.

3. The hyperbranched polymer of claim 1 , wherein the HPG has a number average molecular weight of 60,000 g/mol to 95,000 g/mol.

4. The hyperbranched polymer of claim 1 , wherein the HPG has a polydispersity of 1 to 2.5.

5. The hyperbranched polymer of claim 1 , further comprising one or more of polyalkyleneglycol-alkylether substituents, C 5 to C 30 alkyl substituents, polyalkylene glycol substituents and polyol substituents joined to alkoxide groups on the HPG.

6. The hyperbranched polymer of claim 1 , wherein the hyperbranched polymer further comprises amine groups.

7. The hyperbranched polymer of claim 1 , wherein the hyperbranched polymer further comprises one or more of sulfonic acid groups, phosphonic acid groups, and carboxylic acid groups.

8. The hyperbranched polymer of claim 1 , further comprising at least one biologically active moiety or drug linked to the HPG or associated therewith.

9. A sterile composition comprising the hyperbranched polymer of claim 1 and at least one physiologically acceptable salt, buffer, diluent or excipient.

10. The composition of claim 9 in aqueous solution.

11. The composition of claim 10 , having an intrinsic viscosity of less than 20 ml/g.

12. The hyperbranched polymer of claim 1 , wherein the HPG has a number average molecular weight of 70,000 g/mol to 80,000 g/mol.

13. The hyperbranched polymer of claim 1 , wherein the HPG has a polydispersity of 1 to 2.0.

14. The hyperbranched polymer of claim 1 , wherein the HPG has a polydispersity of 1 to 1.7.

15. The hyperbranched polymer of claim 1 , wherein the HPG has a polydispersity of 1 to 1.5.

16. The hyperbranched polymer of claim 3 , wherein the HPG has a polydispersity of 1 to 1.5.

17. The hyperbranched polymer of claim 1 , wherein the hyperbranched polymer comprises a branched polyether core.

18. The hyperbranched polymer of claim 17 , wherein the core has a focal point derived from a polyol initiator.

19. The hyperbranched polymer of claim 1 , wherein the HPG is derived from ring-opening polymerization of glycidol in the presence of an anionic initiator.

20. The hyperbranched polymer of claim 1 , wherein the hyperbranched polymer further comprises regions of hydrophobicity.

21. The hyperbranched polymer of claim 20 , wherein the regions of hydrophobicity are provided by the presence of aryl groups, alkyl groups, or both.

22. The hyperbranched polymer of claim 21 , wherein the hyperbranched polymer comprises C 5 to C 30 alkyl groups.

23. The hyperbranched polymer of claim 22 , wherein the alkyl groups are joined to up to 50% of alkoxide groups on the HPG.

24. The hyperbranched polymer of claim 22 , wherein the alkyl groups are joined to the HPG through ether linkages.

25. The hyperbranched polymer of claim 1 , wherein the hyperbranched polymer further comprises hydrophilic copolymer regions.

26. The hyperbranched polymer of claim 25 , wherein the copolymer is a polyol.

27. The hyperbranched polymer of claim 26 , wherein the polyol is polyglycerol.

28. The hyperbranched polymer of claim 25 , wherein the copolymer is a polyalkyleneglycol.

29. The hyperbranched polymer of claim 1 , wherein the polymer further comprises polyalkyleneglycol-alkylether moieties.

30. The hyperbranched polymer of claim 28 , wherein the polyalkyleneglycol is a PEG.

31. The hyperbranched polymer of claim 30 , wherein the PEG is an MPEG.

32. The hyperbranched polymer of claim 30 , wherein the PEG has a molecular weight of from 100 to 800 daltons.

33. The hyperbranched polymer of claim 31 , wherein the MPEG has a molecular weight of from 100 to 800 daltons.

34. The hyperbranched polymer of claim 32 , wherein the PEG has a molecular weight of 350 daltons.

35. The hyperbranched polymer of claim 33 , wherein the MPEG has a molecular weight of 350 daltons.

36. The hyperbranched polymer of claim 25 wherein the copolymers are joined to up to 80% of alkoxide groups on the HPG.

37. The hyperbranched polymer of claim 36 , wherein the copolymers are joined to from 5% to 50% of alkoxide groups on the HPG.

38. The composition of claim 9 , wherein the HPG of the hyperbranched polymer has a number average molecular weight of 60,000 g/mol to 95,000 g/mol and a polydispersity of 1 to 1.5.

39. The composition of claim 9 , wherein the hyperbranched polymer comprises a branched polyether core.

40. The composition of claim 39 , wherein the core has a focal point derived from a polyol initiator.

41. The composition of claim 9 , wherein the HPG is derived from ring-opening polymerization of glycidol in the presence of an anionic initiator.

42. The composition of claim 9 , wherein the hyperbranched polymer further comprises regions of hydrophobicity.

43. The composition of claim 42 , wherein the regions of hydrophobicity are provided by the presence of aryl groups, alkyl groups, or both.

44. The composition of claim 43 , wherein the hyperbranched polymer comprises C 5 to C 30 alkyl groups.

45. The composition of claim 44 , wherein the alkyl groups are joined to up to 50% of alkoxide groups on the HPG.

46. The composition of claim 44 , wherein the alkyl groups are joined to the HPG through ether linkages.

47. The composition of claim 9 , wherein the polymer further comprises hydrophilic copolymer regions.

48. The composition of claim 47 , wherein the copolymer is a polyol.

49. The composition of claim 48 , wherein the polyol is polyglycerol.

50. The composition of claim 47 , wherein the copolymer is a polyalkyleneglycol.

51. The composition of claim 9 , wherein the hyperbranched polymer further comprises polyalkyleneglycol-alkylether moieties.

52. The composition of claim 50 , wherein the polyalkyleneglycol is a PEG.

53. The composition of claim 52 , wherein the PEG is an MPEG.

54. The composition of claim 52 , wherein the PEG has a molecular weight of from 100 to 800 daltons.

55. The composition of claim 53 , wherein the MPEG has a molecular weight of from 100 to 800 daltons.

56. The composition of claim 54 , wherein the PEG has a molecular weight of 350 daltons.

57. The composition of claim 55 , wherein the MPEG has a molecular weight of 350 daltons.

58. The composition of claim 47 , wherein the copolymers are joined to up to 80% of alkoxide groups on the HPG.

59. The composition of claim 58 , wherein the copolymers are joined to from 5% to 50% of alkoxide groups on the HPG.

60. The composition of claim 9 , whe

Assignees

• Univ British Columbia

Inventors

• Brooks Donald E
• Kizhakkedathu Jayachandran N
• Kainthan Rajesh Kumar

Classifications

• C08L71/00

  Compositions of polyethers obtained by reactions forming an ether link in the main chain (of polyacetals C08L59/00; of epoxy resins C08L63/00; of polythioether-ethers C08L81/02; of polyether-sulfones C08L81/06); Compositions of derivatives of such polymers · CPC title

• A61K47/34

  Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) · CPC title

• A61K9/0026 Primary

  Blood substitute; Oxygen transporting formulations; Plasma extender · CPC title

• A61K47/60

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• C08G65/34

  from hydroxy compounds or their metallic derivatives {(C08G65/26 takes precedence)} · CPC title