Method of creating hydrogels through oxime bond formation

Patent metadata

Field	Value
Publication number	US-10201613-B2
Application number	US-201314426259-A
Country	US
Kind code	B2
Filing date	Aug 20, 2013
Priority date	Sep 7, 2012
Publication date	Feb 12, 2019
Grant date	Feb 12, 2019

Abstract

A method of creating a hydrogel, comprising the step of condensing first and second functional groups, wherein the first group comprises a molecule or macromolecule of interest containing two or more hydroxylamine or aminooxy groups and the second group comprises a molecule or macromolecule of interest containing two or more aldehyde/ketone/other reactive oxo groups, under conditions such that a hydrogel forms.

First claim

We claim:

1. A method of creating a hydrogel, comprising the step of condensing first and second functional groups, wherein the first group comprises a molecule or macromolecule of interest containing two or more hydroxylamine or aminooxy groups and the second group comprises a molecule or macromolecule of interest containing two or more aldehyde, ketone, or other reactive oxo groups, under conditions such that a hydrogel forms, wherein at least one of the molecules or macromolecules of interest is a polyethylene glycol-based molecule or macromolecule and the molecules or macromolecules of interest are alkyl-or alkoxy-based molecules with two or more hydroxylamine or aminooxy groups or with two or more aldehyde, ketone, or other reactive oxo groups, wherein oxime bonds of the hydrogel are non-degradable for up to seven days under physiological conditions.

2. The method according to claim 1 , wherein the molecules or macromolecules of interest are selected from the group consisting of polyethylene glycol, polyethylene glycol (PEG) derivative, polystyrene sulfonate, poly(styrene sulfonate-co-polyethylene glycol methacrylate), polypropylene oxide, polyethylene oxide, and poly(styrene sulfonate-co-polyethylene glycol acrylate).

3. The method according to claim 1 , wherein the conditions for the hydrogel formation comprises at room temperature, in aqueous solutions and under pH=6-7.4.

4. The method according to claim 1 , wherein the molecule or macromolecule of interest further comprises bio-degradable bonds.

5. The method according to claim 1 , wherein the molecule or macromolecule of interest in the first group is a polyethylene glycol (PEG) derivative.

6. The method according to claim 5 , wherein the PEG derivative comprises two or more groups of NH 2 —O—CH 2 CH 2 O) n —, wherein n =1- 1000.

7. The method according to claim 1 , wherein the molecule or macromolecule of interest in the second group comprises two or more groups of R 1 CO-L-COR 2 , wherein R 1 and R 2 are independently selected from the group consisting of H, Cl, Br, I, -Alkyl, -Alkenyl, -Alkynyl, -Aryl, -Heteroaryl, -Heterocyclyl, OR3, SR4, NR5, and biomolecules and L is a linker molecule, and wherein R 3 , R 4 and R 5 are independently selected from the group consisting of H, Cl, Br, I, -Alkyl, -Alkenyl, -Alkynyl, -Aryl, -Heteroaryl and -Heterocyclyl.

8. The method according to claim 7 , wherein L is selected from the group consisting of -Alkyl-, -Alkenyl-, Alkynyl-, -Aryl-, -Heteroaryl-, -Heterocyclyl-, and -(CH 2 CH 2 O)n—, wherein n =0-1000.

9. The method according to claim 8 , wherein the biomolecules are selected from the group consisting of proteins, enzymes, antibodies, peptides, and nucleic acids.

10. The method of claim 9 wherein the nucleic acid is selected from the group consisting of DNA, RNA, siRNA, antisense RNA, RNAi, snRNA, miRNA, and cDNA.

11. The method according to claim 1 , wherein the molecule or macromolecule of interest in the first and second group is a polyethylene glycol (PEG) derivative.

12. The method according to claim 11 , wherein the polyethylene glycol (PEG) derivative comprises two or more groups of R 6 CO—(CH 2 ) m —COO—(CH 2 CH 2 O) n —, where R 6 is selected from the group consisting of H, Cl, Br, I, -Alkyl, -Alkenyl, -Alkynyl, -Aryl, -Heteroaryl, - Heterocyclyl, -OR3, -SR4, -NR5, and biomolecules and wherein m=1-1000 and n =0-1000, wherein R 3 , R 4 and R 5 are independently selected from the group consisting of H, Cl, Br, I, -Alkyl, -Alkenyl, -Alkynyl, -Aryl, -Heteroaryl and -Heterocyclyl.

13. The method according to claim 12 , wherein m=1-20.

14. The method according to claim 12 , wherein the biomolecule is selected from the group consisting of proteins, enzymes, antibodies, peptides, and nucleic acids.

15. The method of claim 14 wherein the nucleic acid is selected from the group consisting of DNA, RNA, RNAi, antisense RNA, snRNA, miRNA, siRNA, and cDNA.

16. The method according to claim 11 , wherein the polyethylene glycol (PEG) derivative comprises two or more groups of HCO—(CH 2 ) m —O—(CH 2 CH 2 O)n—, wherein m =1-1000and wherein n =0-1000.

17. The method according to claim 16 , wherein m =1-20.

18. A method of creating a hydrogel, comprising the step of condensing functional groups, wherein the functional groups comprise a molecule or macromolecule of interest containing two or more hydroxylamine or aminooxy groups and two or more aldehyde, ketone, or other reactive oxo groups, under conditions such that a hydrogel forms, wherein at least one of the molecules or macromolecules of interest is a polyethylene glycol-based molecule or macromolecule and the molecules or macromolecules of interest are alkyl- or alkoxy-based molecules with two or more hydroxylamine or aminooxy groups or with two or more aldehyde, ketone, or other reactive oxo groups, wherein oxime bonds of the hydrogel are non-degradable for up to seven days under physiological conditions.

19. A hydrogel formed by the method of claim 1 .

20. The hydrogel according to claim 19 , wherein the hydrogel is bio-degradable.

21. The hydrogel according to claim 19 , wherein the hydrogel is bio-compatible.

22. A hydrogel comprising a condensation product wherein the condensation product forms from condensing first and second functional groups, and wherein the first group comprises a molecule or macromolecule of interest containing two or more hydroxylamine or aminooxy groups and the second group comprises a molecule or macromolecule of interest containing two or more aldehyde, ketone, or other reactive oxo groups, wherein at least one of the molecules or macromolecules of interest is a polyethylene glycol-based molecule or macromolecule and the molecules or macromolecules of interest are alkyl- or alkoxy-based molecules with two or more hydroxylamine or aminooxy groups or with two or more aldehyde, ketone, or other reactive oxo groups, wherein oxime bonds of the hydrogel are non-degradable for up to seven days under physiological conditions.

Assignees

• Univ California

Inventors

• Maynard Heather D
• Segura Tatiana
• Grover Gregory
• Lam Jonathan

Classifications

• C08J3/246

  Intercrosslinking of at least two polymers · CPC title

• C08J2300/104

  containing oxygen atoms · CPC title

• C08L2203/02

  for biomedical use · CPC title

• A61K9/0024 Primary

  Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L) · CPC title

• C08G65/33337

  cyclic · CPC title