PVA hydrogels having improved creep resistance, lubricity, and toughness

Patent metadata

Field	Value
Publication number	US-10696802-B2
Application number	US-201815938036-A
Country	US
Kind code	B2
Filing date	Mar 28, 2018
Priority date	Apr 23, 2007
Publication date	Jun 30, 2020
Grant date	Jun 30, 2020

Abstract

The invention provides creep resistant, lubricious and tough PVA-PAAm-hydrogels, creep resistant, lubricious, tough PVA-PAAm-hydrogel-containing compositions, and methods of making the same. The invention also provides methods of implanting or administering the creep resistant, lubricious and tough PVA-PAAm-hydrogels, or the PVA-PAAm-hydrogel-containing compositions to treat a subject in need. Methods of cross-linking pre-solidified or pre-gelled hydrogel particles and making cross-linked PVA-PAAm-hydrogels, and cross-linked PVA-PAAm-hydrogel-containing compositions also are disclosed herein.

First claim

What is claimed is:

1. A method of making a creep resistant, lubricious and tough PVA-PAAm-hydrogel comprising:
(a) contacting an aqueous solution of poly(vinyl alcohol) (PVA) with an aqueous solution of acrylamide monomer (AAm) in presence of an initiator, thereby forming a PVA-AAm solution;
(b) heating or irradiating the PVA-AAm solution, thereby forming an interpenetrating network (IPN) structure of polymerized PAAm in the PVA solution; and
(c) subjecting the PVA-PAAm IPN to one or more freeze-thaw cycles, thereby forming a tough PVA-PAAm hydrogel,
wherein the PVA-PAAm-hydrogel has a PVA-PAAm weight ratio of 1:1 to 1:2, and the aqueous solution of acrylamide monomer comprises 5% to 30% of the acrylamide monomer wherein % acrylamide monomer equals a weight of acrylamide monomer/(the weight of acrylamide monomer+total water in PVA-AAm solution).

2. The method of claim 1 further comprising:
(d) dehydrating the tough PVA-PAAm hydrogel in a vacuum, thereby increasing the melting point of the PVA-PAAm hydrogel;
(e) annealing the dehydrated PVA-PAAm hydrogel at a temperature below the melting point of the dehydrated PVA-PAAm hydrogel; and
(f) re-hydrating the PVA-PAAm hydrogel, thereby forming a creep resistant, lubricious and tough PVA-PAAm-hydrogel.

3. The method of claim 1 , wherein the PVA-AAm solution is heated at a temperature below the boiling point of the PVA-AAm solution, thereby forming an inter-penetrating network (IPN) structure of polymerized PAAm in the PVA solution.

4. The method of claim 1 , wherein the PVA-AAm solution is heated at a temperature between about 40° C. and 45° C., thereby forming an interpenetrating network (IPN) structure of polymerized PAAm in the PVA solution.

5. The method of claim 1 , wherein the PVA-AAm solution is irradiated, thereby forming an inter-penetrating network (IPN) structure of polymerized PAAm in the PVA solution.

6. The method of claim 1 , further comprising dehydrating the PVA-PAAm hydrogel under an inert environment or in a dehydrating solvent.

7. The method of claim 1 , further comprising dehydrating the PVA-PAAm hydrogel by immersing in a PEG solution to allow diffusion of the PEG into the PVA-PAAm-hydrogel.

8. The method of claim 6 , further comprising annealing the dehydrated PVA-PAAm hydrogel at a temperature about 80° C. to about 200° C., for about an hour or less to a few weeks.

9. The method of claim 8 , further comprising rehydrating the PVA-PAAm hydrogel by soaking in a saline solution or in water.

10. The method of claim 1 , wherein the freeze-thaw step is repeated for at least 1 to 100 cycles.

11. The method of claim 1 , further comprising dehydrating the PVA-PAAm hydrogel to remove part or all of the water content.

12. The method of claim 1 , further comprising dehydrating the PVA-PAAm hydrogel by a method comprising the steps of:
(c) contacting the PVA-PAAm hydrogel with an organic solvent, wherein the PVA-PAAm hydrogel comprises a polymer which is not soluble in the solvent, and wherein the solvent is at least partially miscible in water;
(d) heating the PVA-PAAm hydrogel to a temperature below or above the melting point of the PVA-PAAm hydrogel; and
(e) cooling the heated PVA-PAAm hydrogel to room temperature.

13. The method of claim 1 , further comprising dehydrating the PVA-PAAm hydrogel by a method comprising the steps of:
(c) contacting the PVA-PAAm hydrogel with an organic solvent, wherein the hydrogel comprises a polymer which is not soluble in the solvent, and wherein the solvent is at least partially miscible in water; and
(d) air-drying the PVA-PAAm hydrogel at room temperature.

14. The method of claim 1 , further comprising dehydrating the PVA-PAAm hydrogel by a method comprising the steps of:
(c) contacting the PVA-PAAm hydrogel with an organic solvent, wherein the PVA-PAAm hydrogel comprises a polymer which is not soluble in the solvent, and wherein the solvent is at least partially miscible in water; and
(d) subjecting the PVA-PAAm hydrogel to at least one freeze-thaw cycle and allowing the PVA-PAAm hydrogel to warm-up room temperature.

15. The method of claim 1 , further comprising dehydrating the PVA-PAAm hydrogel by placing the PVA-PAAm hydrogel in:
(a) a non-solvent, wherein i) the non-solvent is PEG, alcohols, acetones, saturated salinated water, vitamin, or carboxylic acid, aqueous solution of a salt of an alkali metal, and ii) the non-solvent contains more than one ingredient including water, PEG, vitamin, polymer, ester, proteoglycan, and carboxylic acid, or
(b) in a supercritical fluid.

16. The method of claim 11 , further comprising rehydrating the dehydrated PVA-PAAm hydrogel by placing the dehydrated PVA-PAAm hydrogel: i) in water, saline solution, Ringer's solution, salinated water, or buffer solution, or ii) by placing the dehydrated PVA-PAAm hydrogel in a humid chamber, or iii) by placing the dehydrated PVA-PAAm hydrogel at room temperature or at an elevated temperature.

17. The method of claim 1 , wherein the method further comprises a step of heating the PVA-PAAm to a temperature about 40° C. to about 200° C. or more.

18. The method of claim 11 , further comprising rehydrating the dehydrated PVA-pAAm hydrogel to reach an equilibrium.

19. The method of claim 1 , wherein the tough PVA-PAAm hydrogel is a medical implant.

Assignees

• Massachusetts Gen Hospital

Inventors

• Muratoglu Orhun K
• Bodugoz-Senturk Hatice

Classifications

• C08J2205/022

  Hydrogel, i.e. a gel containing an aqueous composition · CPC title

• C08F261/04

  on to polymers of vinyl alcohol · CPC title

• C08F283/00

  Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G · CPC title

• C08J3/075 Primary

  Macromolecular gels · CPC title

• C08J2329/04

  Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids · CPC title