Substantiallymonodispersed mixtures of polymers having polyethylene glycol moieties

• US 6,815,530 B2
• Filed: 02/14/2003
• Issued: 11/09/2004
• Est. Priority Date: 06/04/2001
• Status: Expired due to Term

• Current Assignee: Biocon Limited (Biocon Incorporated)
• Original Assignee: Nobex Corporation (Biocon Incorporated)
• Inventors: Ekwuribe, Nnochiri N., Odenbaugh, Amy L., Price, Christopher H., Ansari, Aslam M.
• Primary Examiner(s): Truong, Duc
• Application Number:
  US10/367,047
• Publication Number:
  US 20030144468A1
• Time in Patent Office: 634 Days
• Field of Search: 528/425, 528/373, 528/391, 528/396, 568/613, 568/622, 524/155, 524/167
• US Class Current: 528/425
• CPC Class Codes: C08G 65/334 containing sulfur
• CPC Class Codes: C08L 71/00 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 Class Codes: C08L 71/02 Polyalkylene oxides

Abstract

Methods of synthesizing a substantially monodispersed mixture of polymers comprising polyethylene glycol moieties include:

reacting a substantially monodispersed mixture of compounds having the structure of Formula I:

R¹(OC₂H₄)_n—O⁻X⁺  (I)

wherein R¹ is H or a lipophilic moiety; n is from 1 to 25; and X⁺ is a positive ion, with a substantially monodispersed mixture of compounds having the structure of Formula II:

R²(OC₂H₄)_m—OMS  (II)

wherein R² is H or a lipophilic moiety; and m is from 1 to 25, under conditions sufficient to provide a substantially monodispersed mixture of polymers comprising polyethylene glycol moieties and having the structure of Formula III:

R²(OC₂H₄)_m+n—OR¹  (III).

Substantially monodispersed mixtures of polymers comprising polyethylene glycol moieties are also disclosed.

Claims

1. A substantially monodispersed mixture of polymers, wherein at least 95 percent of the polymers in the mixture each comprise a polyethylene glycol moiety having from 7 to 50 polyethylene glycol subunits, and wherein the at least 95 percent of the polymers in the mixture each have the same number of polyethylene glycol subunits.

2. The mixture of polymers of claim 1, wherein at least 96 percent of the polymers in the mixture have the same molecular weight, wherein the at least 96 percent of the polymers in the mixture each comprise a polyethylene glycol moiety having from 7 to 50 polyethylene glycol subunits, and wherein the at least 96 percent of the polymers in the mixture each have the same number of polyethylene glycol subunits.

3. The mixture of polymers of claim 1, wherein at least 97 percent of the polymers in the mixture have the same molecular weight, wherein the at least 97 percent of the polymers in the mixture each comprise a polyethylene glycol moiety having from 7 to 50 polyethylene glycol subunits, and wherein the at least 97 percent of the polymers in the mixture each have the same number of polyethylene glycol subunits.

4. The mixture of polymers of claim 1, wherein at least 98 percent of the polymers in the mixture have the same molecular weight, wherein the at least 98 percent of the polymers in the mixture each comprise a polyethylene glycol moiety having from 7 to 50 polyethylene glycol subunits, and wherein the at least 98 percent of the polymers in the mixture each have the same number of polyethylene glycol subunits.

5. The mixture of polymers of claim 1, wherein at least 99 percent of the polymers in the mixture have the same molecular weight, wherein the at least 99 percent of the polymers in the mixture each comprise a polyethylene glycol moiety having from 7 to 50 polyethylene glycol subunits, and wherein the at least 99 percent of the polymers in the mixture each have the same number of polyethylene glycol subunits.

6. The mixture of polymers of claim 1, wherein the at least 95 percent of the polymers in the mixture each further comprise an ester of a fatty acid moiety covalently coupled to the polyethylene glycol moiety.

7. The mixture of polymers of claim 6, wherein the fatty acid moiety has from 1 to 24 carbon atoms.

8. The mixture of polymers of claim 6, wherein the fatty acid moiety has from 1 to 18 carbon atoms.

9. The mixture of polymers of claim 6, wherein the fatty acid moiety has from 3 to 20 carbon atoms.

10. The mixture of polymers of claim 6, wherein the fatty acid moiety has from 6 to 18 carbon atoms.

11. The mixture of polymers of claim 6, wherein the ester is a lower alkyl ester.

12. The mixture of polymers of claim 6, wherein the ester is an ethyl ester.

13. The mixture of polymers of claim 6, wherein the at least 95 percent of the polymers in the mixture each further comprise a benzyl moiety covalently coupled to the polyethylene glycol moiety.

14. The mixture of polymers of claim 1, wherein the at least 95 percent of the polymers in the mixture each further comprise a fatty acid moiety coupled to the polyethylene glycol moiety.

15. The mixture of polymers of claim 14, wherein the fatty acid moiety has from 1 to 24 carbon atoms.

16. The mixture of polymers of claim 14, wherein the fatty acid moiety has from 1 to 18 carbon atoms.

17. The mixture of polymers of claim 14, wherein the fatty acid moiety has from 3 to 20 carbon atoms.

18. The mixture of polymers of claim 14, wherein the fatty acid moiety has from 6 to 18 carbon atoms.

19. The mixture of polymers of claim 14, wherein the at least 95 percent of the polymers in the mixture are activated polymers.

20. The mixture of polymers of claim 19, wherein the activated polymers each comprise an activating moiety selected from the group consisting of an N-hydroxysuccinimide moiety, an active phenyl chloroformate moiety, a tresylate moiety, and an acetal moiety.

21. The mixture of polymers of claim 1, wherein the at least 95 percent of the polymers in the mixture each further comprise an alkyl moiety coupled to the polyethylene glycol moiety.

22. The mixture of polymers of claim 21, wherein the alkyl moiety is a lower alkyl moiety.

23. The mixture of polymers of claim 21, wherein the at least 95 percent of the polymers in the mixture each further comprise a lipophilic moiety.

24. A substantially monodispersed mixture of polymers, wherein at least 95 percent of the polymers in the mixture each comprise a fatty acid moiety covalently coupled to a polyethylene glycol moiety having from 7 to 50 polyethylene glycol subunits, and wherein the at least 95 percent of the polymers in the mixture each have the same number of polyethylene glycol subunits.

25. The mixture of polymers of claim 24, wherein at least 96 percent of the polymers in the mixture have the same molecular weight, wherein the at least 96 percent of the polymers in the mixture each comprise a fatty acid moiety covalently coupled to a polyethylene glycol moiety having from 7 to 50 polyethylene glycol subunits, and wherein the at least 96 percent of the polymers in the mixture each have the same number of polyethylene glycol subunits.

26. The mixture of polymers of claim 24, wherein at least 97 percent of the polymers in the mixture have the same molecular weight, wherein the at least 97 percent of the polymers in the mixture each comprise a fatty acid moiety covalently coupled to a polyethylene glycol moiety having from 7 to 50 polyethylene glycol subunits, and wherein the at least 97 percent of the polymers in the mixture each have the same number of polyethylene glycol subunits.

27. The mixture of polymers of claim 24, wherein at least 98 percent of the polymers in the mixture have the same molecular weight, wherein the at least 98 percent of the polymers in the mixture each comprise a fatty acid moiety covalently coupled to a polyethylene glycol moiety having from 7 to 50 polyethylene glycol subunits, and wherein the at least 98 percent of the polymers in the mixture each have the same number of polyethylene glycol subunits.

28. The mixture of polymers of claim 24, wherein at least 99 percent of the polymers in the mixture have the same molecular weight, wherein the at least 99 percent of the polymers in the mixture each comprise a fatty acid moiety covalently coupled to a polyethylene glycol moiety having from 7 to 50 polyethylene glycol subunits, and wherein the at least 99 percent of the polymers in the mixture each have the same number of polyethylene glycol subunits.

29. The mixture of polymers of claim 24, wherein the fatty acid moiety has from 1 to 24 carbon atoms.

30. The mixture of polymers of claim 24, wherein the fatty acid moiety has from 1 to 18 carbon atoms.

31. The mixture of polymers of claim 24, wherein the fatty acid moiety has from 3 to 20 carbon atoms.

32. The mixture of polymers of claim 24, wherein the fatty acid moiety has from 6 to 18 carbon atoms.

33. A substantially monodispersed mixture of polymers, wherein at least 95 percent of the polymers in the mixture each consist of a polyethylene glycol moiety having from 7 to 50 polyethylene glycol subunits and a terminal methyl group at one end of the polyethylene glycol moiety, and wherein the at least 95 percent of the polymers in the mixture each have the same number of polyethylene glycol subunits.

34. The mixture of polymers of claim 33, wherein at least 96 percent of the polymers in the mixture have the same molecular weight, wherein the at least 96 percent of the polymers in the mixture each consist of a polyethylene glycol moiety having from 7 to 50 polyethylene glycol subunits and a terminal methyl group at one end of the polyethylene glycol moiety, and wherein the at least 96 percent of the polymers in the mixture each have the same number of polyethylene glycol subunits.

35. The mixture of polymers of claim 33, wherein at least 97 percent of the polymers in the mixture have the same molecular weight, wherein the at least 97 percent of the polymers in the mixture each consist of a polyethylene glycol moiety having from 7 to 50 polyethylene glycol subunits and a terminal methyl group at one end of the polyethylene glycol moiety, and wherein the at least 97 percent of the polymers in the mixture each have the same number of polyethylene glycol subunits.

36. The mixture of polymers of claim 33, wherein at least 98 percent of the polymers in the mixture have the same molecular weight, wherein the at least 98 percent of the polymers in the mixture each consist of a polyethylene glycol moiety having from 7 to 50 polyethylene glycol subunits and a terminal methyl group at one end of the polyethylene glycol moiety, and wherein the at least 98 percent of the polymers in the mixture each have the same number of polyethylene glycol subunits.

37. The mixture of polymers of claim 33, wherein at least 99 percent of the polymers in the mixture have the same molecular weight, wherein at least 99 percent of the polymers in the mixture each consist of a polyethylene glycol moiety having from 7 to 50 polyethylene glycol subunits and a terminal methyl group at one end of the polyethylene glycol moiety, and wherein the at least 99 percent of the polymers in the mixture each have the same number of polyethylene glycol subunits.