Hydrophilic, hydrophobic, and thermoreversible saccharide gels and forms, and methods for producing same

• US 6,018,033 A
• Filed: 05/13/1997
• Issued: 01/25/2000
• Est. Priority Date: 05/13/1997
• Status: Expired due to Fees

• Current Assignee: Purdue Research Foundation (Purdue University)
• Original Assignee: Purdue Research Foundation (Purdue University)
• Inventors: BongJo, Seong, Chen, Jun, Park, Kinam
• Primary Examiner(s): Wilson, James O.
• Application Number:
  US08/855,588
• Time in Patent Office: 987 Days
• Field of Search: 536/55.3, 536/123.1, 536/4.1, 536/17.2, 536/17.3, 536/17.9, 536/18.2, 536/18.5, 536/103, 536/123.13, 424/1.1, 424/456, 424/461, 424/466
• US Class Current: 536/4.1
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: C07H 17/04 Heterocyclic radicals containing only oxygen as ring hetero atoms
• CPC Class Codes: C08F 20/30 containing aromatic rings in the alcohol moiety
• CPC Class Codes: C08F 290/062 Polyethers
• CPC Class Codes: C08F 290/10 Polymers provided for in subclass C08B
• CPC Class Codes: C08J 2357/00 Characterised by the use of unspecified polymers obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: C08J 9/06 by a chemical blowing agent

Abstract

Polymerizable saccharide monomers are made by the reaction of a saccharose and a (meth)acrylate. Hydrophilic, hydrophobic and thermoreversible gels and foams are formed upon polymerization of the saccharide monomers. Hydrophilic sucrose monomers are synthesized by reaction of sucrose with an epoxy acrylate. Hydrophobic sucrose monomers are synthesized by reaction of sucrose with methacrylol chloride followed by acetyl chloride. Thermoreversible sucrose monomers are obtained by modifying sucrose with polymerizable substituents prepared from methacryloyl chloride and aminocarboxylic acids. The modified sucrose monomers are copolymerized with hydrophobic poly(alkyleneoxide) (meth)acrylates to produce hydrogels exhibiting inverse thermoreversible properties. The thermosensitive hydrogels are biodegradable and can be used in the area of controlled drug delivery.

Claims

1. A gel or foam formed by polymerizing a saccharide having a formula selected from formulas (I)-(VII) as follows:

##STR4## where S is a saccharide residue, R is hydrogen or a lower alkyl group, and n is an integer from 1 to 8;

R'"'"' is an alkyl, aryl or alkaryl group, and m is an integer from 0 to 7;

R" is an alkylene, arylene, or alkarylene diradical;

R₁ is a lower alkyl group;

R₂ is a lower alkyl group;

R₃ is hydrogen or methyl, and x is an integer from 1 to 10,000;

R₄ is an alkylene, arylene, or alkarylene diradical, and R₅ is hydrogen or lower alkyl.

2. A hydrophilic gel formed by polymerizing a saccharide monomer having formula (I) in claim 1.

3. A hydrophobic gel formed by polymerizing a saccharide monomer having formula (II) in claim 1.

4. A thermoreversible gel formed by polymerizing a saccharide monomer having formula (III) in claim 1.

5. A thermoreversible gel formed by polymerizing a saccharide monomer having formula (III) in claim 1 in the presence of a poly(alkyleneoxide) (meth)acrylate monomer.

6. A thermoreversible gel formed by polymerizing a saccharide monomer having formula (III) in claim 1 in the presence of a crosslinking agent.

7. A hydrophobic gel formed by polymerizing a saccharide monomer having formula (IV) in claim 1.

8. A hydrophobic gel formed by polymerizing a saccharide monomer having formula (V) in claim 1.

9. A hydrophilic gel formed by polymerizing a saccharide monomer having formula (VI) in claim 1.

10. A hydrophilic gel formed by polymerizing a saccharide monomer having formula (VII) in claim 1.

11. A foam prepared by polymerizing a saccharide monomer as in claim 1 in the presence of a blowing agent.

12. A foam prepared by dehydrating the foam of claim 11 with an organic solvent.

13. A foam prepared by dehydrating the foam of claim 11 by freeze-drying.

14. A method of forming a gel or foam comprising the steps of

(A) forming a saccharide monomer having a formula selected from formulas (I)-(VII) as follows:

##STR5## where S is a saccharide residue, R is hydrogen or a lower alkyl group, and n is an integer from 1 to 8;

R'"'"' is an alkyl, aryl or alkaryl group, and m is an integer from 0 to 7;

R" is an alkylene, arylene, or alkarylene diradical;

R₁ is a lower alkyl group;

R₂ is a lower alkyl group;

R₃ is hydrogen or methyl, and x is an integer from 1 to 10,000;

R₄ is an alkylene, arylene, or alkarylene diradical, and R₅ is hydrogen or lower alkyl; and

(B) polymerizing said saccharide to form said gel or foam.

15. The method of claim 14 wherein the polymerization step is accomplished by using mass polymerization, solution polymerization, suspension polymerization, emulsion polymerization, or radiation polymerization.

16. The method of claim 14 wherein said polymerizing step is accomplished by γ

-radiation.

17. The method of claim 14 wherein said polymerizing step is by solution polymerization.

18. The method of claim 17 wherein said polymerizing step is in the presence of a polymerization initiator.

19. The method of claim 14 wherein a hydrophilic gel is formed from said saccharaide monomer having formula (I).

20. The method as in claims 16 or 17 wherein said saccharide monomer is sucrose acrylate or sucrose methacrylate acetate.

21. The method of claim 14 wherein a hydrophobic gel is formed from said saccharide monomer having formula (II).

22. The method of claim 14 wherein a thermoreversible gel is formed by polymerizing said sucrose monomer having formula (III) in the presence of a poly(alkyleneoxide) (meth)acrylate monomer.

23. The method of claim 22 wherein the poly(alkyleneoxide) (meth)acrylate monomer is poly(propyleneglycol)methacrylate or poly(ethylene glycol)ethylether methacrylate.

24. The method of claim 14 wherein said polymerizing is conducted in the presence of a crosslinking agent.

25. The method of claim 14 wherein a hydrophobic gel is formed from said saccharide monomer having formula (IV).

26. The method of claim 14 wherein a hydrophobic gel is formed from said saccharide monomer having formula (V).

27. The method of claim 14 wherein a hydrophilic gel is formed from said saccharaide monomer having formula (VI).

28. The method of claim 14 wherein a hydrophilic gel is formed from said saccharaide monomer having formula (VII).

29. The method of claim 14 wherein said polymerizing step is conducted in the presence of a blowing agent to form a foam.

30. The method of claim 29 which includes an additional step following step (B) of dehydrating the foam with an organic solvent.

31. The method of claim 30 wherein said organic solvent is an alcohol.

32. A method of forming a hydrophilic gel comprising polymerizing a saccharide monomer having formula (I):

##STR6## where S is a saccharide residue, R is hydrogen or a lower alkyl group, and n is an integer from 1 to 8.

33. A method of forming a hydrophobic gel comprising polymerizing a saccharide monomer having formula (II):

##STR7## where S is a saccharide residue, R is hydrogen or a lower alkyl group, R'"'"' is an alkyl, aryl, or alkaryl group, n is an integer from 1 to 8, and m is an integer from 0 to 7.

34. A method of forming a thermoreversible gel comprising polymerizing a saccharide monomer having formula (III):

##STR8## where S is a saccharide residue, R is hydrogen or a lower alkyl group, R" is an alkylene, arylene, or alkarylene diradical, and n is an integer from 1 to 8.

35. The method of claim 34, wherein said polymerizing is conducted in the presence of a poly(alkyleneoxide) (meth)acrylate monomer.

36. The method of claim 34 in which the poly(alkyleneoxide) (meth)acrylate monomer is poly(propylene glycol)methacrylate or poly(ethylene glycol)ethylether methacrylate.

37. The method of claim 34, wherein said polymerizing is conducted in the presence of a crosslinking agent.

38. A method of forming a hydrophobic gel comprising polymerizing a saccharide monomer having formula (IV):

##STR9## where S is a saccharide residue, R₁ is hydrogen or a lower alkyl group, and n is an integer from 1 to 8.

39. A method of forming a hydrophobic gel comprising polymerizing a saccharide monomer having formula (V):

##STR10## where S is a saccharide residue, R₂ is hydrogen or a lower alkyl group, and n is an integer from 1 to 8.

40. A method of forming a hydrophilic gel comprising polymerizing a saccharide monomer having formula (VI):

##STR11## where S is a saccharide residue, R is hydrogen or lower alkyl, R₃ is hydrogen or lower alkyl, n is an integer from 1 to 8, and x is an integer from 1 to 10,000.

41. A method of forming a hydrophilic gel comprising polymerizing a saccharide monomer having formula (VII):

##STR12## where S is a saccharide residue, R is hydrogen or lower alkyl, R₄ is an alkylene, arylene, or alkarylene diradical, R₅ is hydrogen or lower alkyl, and n is an integer from 1 to 8.