IP Library Granted Patent US 10,660,989
Granted Patent B2
US 10,660,989 · App. 13/579,809 · Granted May 26, 2020

Microgel compositions

Inventors: Brian Saunders (Manchester, GB); Amir Hossein Milani (Manchester, GB); Ruixue Liu (Manchester, GB); Anthony Freemont (Manchester, GB)
Assignee: Gelmetix Limited
A61L27/52A61L27/00C08F299/024C08L33/064C08L51/003A61L2300/62A61L2430/38C08L2205/04
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Quick Facts
Patent No.
US 10,660,989
App. No.
13/579,809
Granted
May 26, 2020
Kind
B2
Abstract

This invention relates to microgel compositions, and in particular, to gel compositions formed by binding a plurality of individual microgel particles together. The present invention also relates to processes for the preparation of these compositions and their use for particular applications, especially medical applications such as the repair of damaged, degenerated or inappropriately formed load-bearing tissue (such as, for example, intervertebral discs).

Claims (31)

1. A composition, comprising a plurality of microgel particles wherein adjacent microgel particles are covalently bound together as a result of a free-radical coupling reaction of vinyl-containing moieties of formula -L-B grafted onto the surfaces of unreacted microgel particles, and wherein the free-radical coupling occurs while the microgel particles are in a swollen state and in the absence of bridging aggregation, wherein:

B is a group comprising a vinyl functional group; and

L is a linking group between B and the unreacted microgel particles to which L-B is grafted;

wherein the microgel particles comprises a co-polymerized polymer particle defined by formula I:

Poly(Y-co-P-co-X)  (I)

wherein:

P is a pH-responsive co-monomer;

X is a functional cross-linking co-monomer;

Y is a hydrophobic co-monomer; and

wherein X constitutes 0.1 to 2 wt % of all of co-monomers P, X, and Y, and wherein the microgel particles are pH responsive in that prior to the free-radical coupling reaction, the microgel particles underwent a pH dependent transition from a collapsed state to a swollen state, and wherein the microgel particles in the composition are in the form of a hydrated gel, and further wherein the average diameter of the microgel particles in the swollen state is at least 100% greater than the average diameter of microgel particles in the collapsed state;

wherein: the microgel particles comprise carboxylic acid groups and each vinyl-containing moiety of formula L-B is formed by reaction of one of said carboxylic acid groups with an epoxide group of glycidyl methacrylate to form an ester of the carboxylic acid group; and

wherein:

the vinyl-containing moieties of formula -L-B are present at a concentration of between 1.8 and 60 mol. % with respect to all of the co-monomers of the microgel particles; and wherein the composition is buffered at pH 6.5-8.

2. The composition according to claim 1 , wherein the microgel particles comprise a polymer combination selected from the group consisting of: poly(ethylacrylate/methacrylic acid/ethyleneglycol dimethacrylate), poly(methylmethacrylate/methacrylic acid/ethyleneglycol dimethacrylate), poly(ethylacrylate/methacrylic acid/1,4-butanediol diacrylate) and poly(methylmethacrylate/methacrylic acid/1,4-butanediol diacrylate).

3. The composition according to claim 1 , wherein the elastic modulus (G′) of the composition of claim 1 is higher than a composition of the corresponding non-covalently bound microgel particles.

4. The composition according to claim 1 , wherein the elastic modulus (G′), as measured by dynamic rheology, is greater than 10 Pa.

5. The composition according to claim 4 , wherein the composition has a critical strain value (γ*) of 2 to 500%, wherein the critical strain value (γ*) is the value for the strain, measured by a rheometer, at which the elastic modulus (G′) first reaches a value of 95% of that measured when γ=1.0%.

6. The composition according to claim 1 , wherein the composition is non-porous.

7. The composition according to claim 1 , wherein the adjacent microgel particles of the compositions are in contact with each other.

8. The composition according to claim 1 , wherein the pH-responsive co-monomer (P) of the microgel particles comprises a substituted acrylic acid.

9. The composition according to claim 1 , wherein the functional cross-linking co-monomer contains two or more double bonds that are susceptible to chain addition through free-radical polymerization.

10. The composition according to claim 1 , wherein the composition further comprises sodium hydroxide or potassium hydroxide.

11. The composition according to claim 10 , wherein the composition further comprises ammonium persulfate.

12. The composition according to claim 1 , wherein the composition further comprises ammonium persulfate.

13. The composition according to claim 12 , further comprising ascorbic acid.

14. The composition according to claim 1 , wherein the vinyl-containing moieties of formula -L-B are present at a concentration of between 3.0 and 30 mol. % with respect to all of the co-monomers of the microgel particles.

15. The composition according to claim 1 , wherein the vinyl-containing moieties of formula -L-B are present at a concentration of between 5.8 and 30 mol. % with respect to all of the co-monomers of the microgel particles.

16. The composition according to claim 1 , wherein the composition is buffered at pH 6.6-7.5.

17. The composition according to claim 1 , wherein the microgel particles comprise poly(methylmethacrylate/methacrylic acid/ethyleneglycol dimethacrylate).

18. The composition according to claim 1 , wherein the composition further comprises sodium hydroxide and ammonium persulfate.

19. The composition according to claim 1 , wherein the composition further comprises potassium hydroxide and ammonium persulfate.

Assignments (5)
CORRECTIVE ASSIGNMENT TO CORRECT THE RECEIVING PARTY ADDRESS PREVIOUSLY RECORDED AT REEL: 49645 FRAME: 991. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Apr 23, 2020
From: GELEXIR HEALTHCARE LIMITED
To: GELMETIX LIMITED
Reel/Frame 052481/0190 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 20, 2020
From: SAUNDERS, BRIAN; MILANI, AMIRHOSSEIN; LIU, RUIXUE; FREEMONT, ANTHONY
To: THE UNVERSITY OF MANCHESTER
Reel/Frame 052201/0909 →
CHANGE OF NAME Recorded Jul 1, 2019
From: GELEXIR HEALTHCARE LIMITED
To: GELMETIX LIMITED
Reel/Frame 049645/0991 →
CHANGE OF ADDRESS OF ASSIGNEE Recorded Jun 30, 2016
From: GELEXIR HEALTHCARE LIMITED
To: GELEXIR HEALTHCARE LIMITED
Reel/Frame 039220/0888 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 22, 2014
From: THE UNIVERSITY OF MANCHESTER
To: GELEXIR HEALTHCARE LIMITED
Reel/Frame 033360/0004 →
Priority Claims (1)
GB 1002862.9 · Feb 19, 2010 · national
Continuity (1)
Related Publication 20120308508A1 · Dec 6, 2012
Cited By (1)
US 12,357,727