Mpc-based copolymers and hydrogels, and uses thereof in regenerative medicine
Polymers and hydrogels with MPC and CLPs are used to seal and protect wounds and tissue injuries, addressing the need for effective sealing materials in existing treatments, enhancing healing and protection.
Patent Information
- Authority / Receiving Office
- HK · HK
- Patent Type
- Applications
- Current Assignee / Owner
- RSEM SOCIÉTÉ & COMMANDITE
- Filing Date
- 2026-05-27
- Publication Date
- 2026-07-10
AI Technical Summary
Existing treatments for wounds and tissue injuries, such as corneal injuries, lack effective materials for sealing and protecting the affected areas, particularly in the context of corneal perforations.
Polymers and hydrogels containing 2-methacryloyloxyethyl phosphocholine (MPC) and collagen or collagen-like peptides (CLPs) are used as fillers and occluders to seal and protect wounds and tissue injuries, including corneal perforations, with apparatus and systems for their application.
The polymers and hydrogels effectively seal and protect wounds and tissue injuries, providing a barrier that promotes healing and prevents further damage.
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Abstract
Description
Abstract This application relates to polymers, conjugates, hydrogels, and kits comprising 2-methacryloyloxyethyl phosphocholine (MPC) and / or copolymers containing MPC, as well as collagen or collagen-like peptides (CLPs). The polymers, conjugates, hydrogels, and kits can be used as fillers and occluders for various applications, such as for treating wounds or tissue injuries, such as corneal injuries or perforations. This application also discloses apparatus and systems for applying the polymers, conjugates, and hydrogels.
Claims
WHAT IS CLAIMED IS:1 . A conjugate comprising:(a) 2-methacryloyloxyethyl phosphorylcholine (MPC) and collagen or a collagen-like peptide (CLP) crosslinked to the MPC;(b) (i) a copolymer comprising monomers of 2-methacryloyloxyethyl phosphorylcholine (MPC) and polymerizable monomers comprising one or more functional groups; and (ii) collagen or a CLP crosslinked to the copolymer; or(c)(i) a copolymer comprising a core comprising a multi-arm polymer; monomers of 2-methacryloyloxyethyl phosphorylcholine (MPC) attached to one or more arms of the multi-arm polymer; optionally polymerizable monomers or polymers comprising one or more functional groups and(ii) collagen or a CLP attached to one or more arms of the multi-arm polymer and / or to the MPC.
2. The conjugate of claim 1 , wherein the one or more functional groups comprise carboxylic acid groups, hydroxyl groups, thiol groups, and / or amine groups.
3. The conjugate of claim 1 or 2, wherein the polymerizable monomers comprising one or more functional groups are acrylic acid (AA) or 2-hydroxyethyl acrylate (HEA).
4. The conjugate of any one of claims 1 to 3, wherein the copolymer of (b) has one of the following structures:PMPC-PAA PMPC-PHEA wherein PC is phosphorylcholine, x represents the Mw of polymeric MPC (PMPC), and y represents the Mw of polyacrylic acid (PAA) or poly 2-hydroxyethyl acrylate (PHEA), preferably wherein the Mw of PMPC-PAA is about 387,000 kDa, and the Mw of PMPC-PHEA is about 532,000 kDa.
5. The conjugate of claim 4, wherein the Mw of PMPC-PAA is about 350,000 to about 400,000 kDa.
6. The conjugate of claim 5, wherein the Mw of PMPC-PAA is about 387,000 kDa.
7. The conjugate of claim 4, wherein the Mw of PMPC-PHEA is about 500,000 to about 550,000 kDa.
8. The conjugate of claim 4, wherein the Mw of PMPC-PHEA is about 532,000 kDa.
9. The conjugate of any one of claims 1 to 8, wherein the conjugate comprises (i) a first copolymer comprising monomers of MPC and polymerizable monomers comprising hydroxyl groups; (ii) a second copolymer comprising monomers of MPC and polymerizable monomers comprising carboxylic acid groups.
10. The conjugate of any one of claims 1 to 9, wherein the multi-arm polymer comprises 2 to 8 arms.
11. The conjugate of any one of claims 1 to 10, wherein the multi-arm polymer comprises a multi-arm polyethyleneglycol (PEG).
12. The conjugate of claim 11 , wherein the PEG has a molecular weight of 2000 to 5000 kDa.
13. The conjugate of any one of claims 1 to 12, wherein the copolymer of (c) has the following structure:wherein PC is phosphorylcholine, n represents the Mw of the polymer (300,000 to 500,000 kDa) and m is an integer of 2 to 8.
14. The conjugate of any one claims 1 to 13, wherein the MPC is directly linked to the collagen or CLP.
15. The conjugate of any one claims 1 to 13, further comprising a linker between the MPC and the collagen or CLP.
16. The conjugate of claim 15, where the linker is / V, / V'-methylenebisacrylamide (BIS).
17. The conjugate of any one of claims 1 to 16, wherein the conjugate comprises a CLP.
18. The conjugate of claim 17, wherein the CLP has a length of 27 to 36 amino acids.
19. The conjugate of claim 17 or 18, wherein the CLP comprises or consist of the following sequence:(PKG)3 or4(POG)3 or4(DOG)2 or3(DOX), wherein X is G or C.
20. The conjugate of claim 19, wherein the CLP comprises or consist of the following sequence: (PKG)3(POG)3(DOG)2(DOX) (SEQ ID NO: 13), wherein X is G or C.21 . The conjugate of claim 17, wherein the CLP comprises or consist of the following sequence: X1X2X3(PKG)3or4(POG)3or4(DOG)2or3(DOC), wherein X1 , X2 and X3 are independently any amino acid, and wherein at least one of X1 , X2 and X3 is C.
22. The conjugate of claim 21 , wherein X1X2X3is GCG, CGG, SCG, or SCS23. A hydrogel comprising the conjugate of any one of claims 1 to 22.
24. The hydrogel of claim 23, further comprising additional proteins, peptides, cells, and / or drugs.
25. A collagen-like peptide (CLP) having a length of 27 amino acids.
26. The CLP of claim 25, wherein the CLP has the following structure: (PKG)3(POG)3(DOG)2(DOX) (SEQ ID NO: 13), wherein X is G or C.
27. The CLP of claim 26, wherein X is G.
28. The CLP of claim 26, wherein X is C.
29. A collagen-like peptide (CLP) of one of the following structures: X1X2X3(PKG)3(POG)3(DOG)2X4X5X6; or X1X2X3(PKG)3(POG)5X4X5X6wherein X1, X2, X3, X4, X5and X6are independently any amino acid, and wherein at least one of X1, X2, and X3is C, and at least one of X4, X5, and X6is C.
30. The CLP of claim 29, wherein X4X5X6is DOC, SCS, GCG, SCG, or CGG.31 . The CLP of claim 29 or 30, wherein X1X2X3is SCS, GCG, SCG, or CGG.
32. An injection device comprising the conjugate of any one of claims 1 to 22 or the hydrogel of claim 23 or 24.
33. The injection device of claim 32, wherein the device comprises a plurality of barrels or compartments and a mixer connected to the plurality of barrels or compartments34. An injection device comprising a plurality of barrels or compartments and a mixer connected to the plurality of barrels or compartments.
35. The device of claim 33 or 34, comprising two barrels or compartments.
36. The device of any one of claims 33 to 35, wherein the mixer is a static mixer.
37. The device of any one of claims 33 to 36, wherein a first barrel or compartment comprises 2-methacryloyloxyethyl phosphorylcholine (MPC), copolymers comprising MPC, and / or collagen or a collagen-like peptide, and a second barrel or compartment comprises a cross-linking agent.
38. The device of claim 37, wherein the second barrel or compartment further comprises polymerizable monomers or a polymer comprising one or more functional groups.
39. The device of any one of claims 33 to 38, wherein the barrels or compartments have a maximum capacity of 500 pL each.
40. The device of any one of claims 33 to 39, wherein the mixer has a dead volume of less than 40 pL.41 . The device of any one of claims 33 to 40, which comprises a third barrel or compartment.
42. A system comprising the injection device of any one of claims 33 to 41 , and a heater adapted to heat one or more of the barrels or compartments of the device.
43. A kit comprising:(I)(a) 2-methacryloyloxyethyl phosphorylcholine (MPC), and collagen or a collagen-like peptide (CLP);(b) (i) monomers of 2-methacryloyloxyethyl phosphorylcholine (MPC) and polymerizable monomers comprising one or more functional groups; and (ii) collagen or a CLP; or(C)(i) a copolymer comprising a core comprising a multi-arm polymer; monomers of 2-methacryloyloxyethyl phosphorylcholine (MPC) attached to one or more arms of the multi-arm polymer; optionally polymerizable monomers or polymers comprising one or more functional groups and(ii) collagen or a CLP attached to one or more arms of the multi-arm polymer and / or to the MPC; and(II) optionally a cross-linking agent.
44. The kit of claim 43, wherein the cross-linking agent is 4-(4,6-dimethoxy-1 ,3,5-triazin-2-yl)- 4-methylmorpholinium chloride (DMTMM).
45. The kit of claim 43 or 44, further comprising additional proteins, peptides, cells, nanoparticles and / or drugs.
46. The kit of claim 45, further comprising an inhibitor of angiogenesis.
47. The kit of any one of claims 43 to 46, wherein the kit further comprises the device of any one of claims 32 to 41 or the system of claim 42.
48. Use of the conjugate of any one of claims 1 to 22 or the hydrogel of claim 23 or 24 for treating a wound or tissue injury.
49. The use of claim 25, wherein the wound or tissue injury is corneal wound or injury.
50. The use of claim 25 or 26, wherein the wound or injury is burn or perforation.51 . The use of any one of claim 25 to 27, wherein the conjugate or hydrogel is for administration by injection into or in the vicinity of said wound or injury.
52. The use of any one of claim 25 to 27, wherein the conjugate or hydrogel is for administration using the device of of any one of claims 32 to 41 .
53. A method for treating a wound or tissue injury in a subject comprising contacting the wound or tissue with the conjugate of any one of claims 1 to 22 or the hydrogel of claim 23 or 24.
54. The method of claim 53, wherein the wound or tissue injury is corneal wound or injury.
55. The method of claim 53 or 54, wherein the wound or injury is burn or perforation.
56. The method of any one of claims 53 to 55, wherein the conjugate or hydrogel is injected into or in the vicinity of said wound or injury.
57. The method of any one of claims 53 to 56, wherein the conjugate or hydrogel is injected using the device of of any one of claims 32 to 41 .