Crosslinked hydrogels and related method of preparation

Patent metadata

Field	Value
Publication number	US-9987225-B2
Application number	US-201013499088-A
Country	US
Kind code	B2
Filing date	Sep 29, 2010
Priority date	Sep 30, 2009
Publication date	Jun 5, 2018
Grant date	Jun 5, 2018

Abstract

The present invention provides a method of manufacturing a hydrogel comprising the step of crosslinking a biopolymer using a carbodiimide crosslinker of Formula I wherein at least one of R 1 and R 2 is a functional group that is a bulky organic functional group. R 1 and R 2 can each independently be an optionally substituted saturated or unsaturated functional group selected from the group consisting of an alkyl, a cycloalkyl, a heterocyclic, and an aryl. The bulky organic functional group will slow down the crosslinking reaction of carbodiimide due to the steric effects and/or electronic effects, in comparison to a crosslinking reaction using EDC. Also provided are the hydrogels and ophthalmic devices prepared using the method of the invention and uses thereof.

First claim

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A method of manufacturing a hydrogel having a white light transmission of at least 70%, the method comprising:
a) mixing at room temperature a collagen and a carbodiimide crosslinker, wherein the carbodiimide crosslinker is (N-Cyclohexyl-N′-(2-morpholinoethyl)carbodiimide) (CMC) or a metho-p-toluenesulfonate salt thereof,
and the molar equivalent ratio of carbodiimide crosslinker to collagen amine groups is from about 0.3 to about 0.7; and
b) casting the mixture into a mold prior to gelation, wherein the time to gelation at room temperature is increased relative to use of the crosslinker 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide (EDC).

2. The method of claim 1 , wherein the carbodiimide crosslinker is water soluble.

3. The method of claim 1 , wherein the collagen is recombinant human type III collagen.

4. The method of claim 1 , wherein the hydrogel is a composite additionally comprising a water-soluble acrylic, methacrylic, or acrylamide.

5. The method of claim 4 , wherein the water-soluble acrylic, methacrylic, or acrylamide is one or more of MPC (2-methacryloyloxyethyl phophorylcholine) and PEG-DA (polyethylene glycol-diacrylate).

6. The method of claim 1 , wherein prior to mixing, the collagen is treated to photo polymerization.

7. The method of claim 1 , wherein the molar equivalent ratio of carbodiimide crosslinker to collagen amine groups is about 0.5.

8. The method of claim 1 , wherein gelation time is 2.5- to 4-fold longer compared to crosslinking using EDC.

Assignees

• Griffith May
• Li Fengfu
• Ahn Jae Il
• Ottawa Hospital Res Inst

Inventors

• Griffith May
• Li Fengfu
• Ahn Jae-Il

Classifications

• A61P31/22

  for herpes viruses · CPC title

• C08H1/06

  derived from horn, hoofs, hair, skin or leather · CPC title

• A61L2430/16

  for reconstruction of eye parts, e.g. intraocular lens, cornea · CPC title

• A61K38/39

  Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG] · CPC title

• C08J2300/16

  Biodegradable polymers · CPC title