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1. WO2020115508 - THERAPEUTIC HYDROGEL COMPOSITIONS

Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

[ EN ]

CLAIMS

1. A shear-thinning hydrogel composition comprising:

(i) 0.1 to 5wt.% (such as 0.1 to 2.5wt.%) of a microgel particle-forming polymer; and

(ii) 0.5 to 100mM of a monovalent and/or polyvalent metal ion salt as a cross-linking agent;

dispersed in an aqueous vehicle;

and wherein the hydrogel composition has a pH within the range of 3 to 8 and the viscosity of the gel composition reduces when the gel is exposed to shear.

2. A shear-thinning hydrogel composition according to claim 1 , wherein to composition does not comprise collagen and/or fibrin.

3. A shear-thinning hydrogel composition according to claim 1 or claim 2, wherein the composition comprises 0.5 to 2.5 wt.% of microgel particle-forming polymer.

4. A shear-thinning hydrogel composition according to any one of the preceding claims, wherein the composition comprises 0.8 to 1.8 wt.% of microgel particle-forming polymer. 5. A shear-thinning hydrogel composition according to any one of the preceding claims, wherein the composition comprises 0.8 to 1.0 wt.% (e.g. 0.9 wt.%) of a microgel particle-forming polymer.

6. A shear-thinning hydrogel composition according to any one of the preceding claim, wherein the microgel particles are formed from one or more polysaccharide microgel particle-forming polymers.

7. A shear-thinning hydrogel composition according to any one of the preceding claims, wherein the microgel particle-forming polymer is selected from one or more of the following groups: gellans, alginates, carrageenans, agarose, chitosan or gelatin.

8. A shear-thinning hydrogel composition according to any one of the preceding claims, wherein the microgel particles are transparent or translucent and are formed from a microgel particle-forming polymer selected from one or more of the following: gellans, alginates or carrageenans.

9. A shear-thinning hydrogel composition according to any one of the preceding claims, wherein the microgel particle-forming polymer is gellan.

10. A shear-thinning hydrogel composition according to any one of the preceding claims, wherein the microgel particles do not comprise decorin.

11. A shear-thinning hydrogel composition according to any one of the preceding claims, wherein the composition comprises 5 to 20 mM of a monovalent and/or polyvalent metal ion salt as a cross-linking agent.

12. A shear-thinning hydrogel composition according to any one of the preceding claims, wherein the composition comprises 5 to 15 mM of a monovalent and/or polyvalent metal ion salt as a cross-linking agent.

13. A shear-thinning hydrogel composition according to any one of the preceding claims, wherein the composition comprises 8 to 12 mM of a monovalent and/or polyvalent metal ion salt as a cross-linking agent.

14. A shear-thinning hydrogel composition according to any one of the preceding claims, wherein the composition comprises 10 mM of a monovalent and/or polyvalent metal ion salt as a cross-linking agent

15. A shear-thinning hydrogel composition according to any one of the preceding claims, wherein the microgel particle-forming polymer is gellan and the composition comprises 0.5 to 40 mM, 5 to 15 mM, 8 to 12 mM or 10 mM of a monovalent metal ion salt (e.g. NaCI) as a cross-linking agent

16. A shear-thinning hydrogel composition according to any one of claims 1 to 13, wherein the microgel particle-forming polymer is alginate and the composition comprises 0.5 to 40 mM, 5 to 15 mM, 8 to 12 mM or 10 mM of a polyvalent metal ion (e.g. Ca2*) salt as a cross-linking agent.

17. A shear-thinning hydrogel composition according to any one the preceding claims, wherein the hydrogel composition has a pH within the range of 6 to 8 or 6.5 to 8.

18. A shear-thinning hydrogel composition according to any one the preceding claims, wherein the hydrogel composition has a pH within the range of 7 to 7.5 (e.g. pH 7.4).

19. A shear-thinning hydrogel composition according to any one of the preceding claims, wherein the hydrogel composition has viscosity of:

(i) 1 Pa.s or greater (e.g. 1 Pa.s to 200 Pa.s) when exposed to zero shear and the viscosity reduces (e.g. to below 1 Pa.s) when the hydrogel composition is subjected to shear;

(ii) 2 Pa.s or greater (e.g. 2 Pa.s to 200 Pa.s) when exposed to zero shear and the viscosity reduces (e.g. to below 1 Pa.s) when the hydrogel composition is subjected to shear;

(iii) 5 Pa.s or greater (e.g. 5 Pa.s to 200 Pa.s) when exposed to zero shear and the viscosity reduces (e.g. to below 1 Pa.s) when the hydrogel composition is subjected to shear.

20. A shear-thinning hydrogel composition according to any one of the preceding claims, wherein the hydrogel composition has an elastic modulus of 5 Pa to 200 Pa at zero shear.

21. A shear-thinning hydrogel composition according to any one of the preceding claims, wherein the hydrogel composition further comprises one or more pharmacologically active agents.

22. A shear-thinning hydrogel composition according to claim21 , wherein the hydrogel composition comprises one or more pharmacologically active agents selected from the group consisting of: an anti-fibrotic agent (such as decorin); an anti-infective agent; a pain relief agent; an anti-inflammatory agent; an anti-proliferative agent; a keratolytic agent; an extracellular matrix modifying agent; a cell junction modifying agent; a basement membrane modifying agent; a biological lubricating agent; and a pigmentation modifying agent.

23. A shear-thinning hydrogel composition according to claim21 or claim22, wherein the hydrogel composition comprises decorin at a concentration of between about 0.1 pg/mL and 0.5pg/mL.

24. A topical gel composition suitable for topical administration, wherein the topical gel composition is a shear-thinning gel composition as defined in any one of claims 1 to 23. 25. An ocular gel composition suitable for administration to the eye, wherein the ocular gel composition is a shear-thinning gel composition as defined in any one of claims 1 to 23.

26. A method of making a shear-thinning gel composition according to claiml , the method comprising the steps of:

a) dissolving a microgel-forming polymer in an aqueous vehicle to form a polymer solution

b) mixing the microgel-fbrming polymer solution formed in step (a) with an aqueous solution of a monovalent or polyvalent metal ion salt at a temperature above the gelling temperature of the microgel particle-forming polymer; and

c) cooling the resultant mixture from step b) to a temperature below the gelling temperature of the microgel particle-forming polymer to form a composition according to any one of claims 1 to 24.

27. A method according to claim26, wherein step a) comprises heating and agitating the aqueous vehicle to facilitate the dissolution of the microgel forming polymer.

28. A method according to claim27, wherein the aqueous vehicle is heated to temperature above the gelling temperature of the microgel particle-forming polymer to 50 °C.

29. A method according to any one of claims 26 to 28, wherein, in step b), the mixing of the microgel particle-forming polymer solution formed in step (a) with an aqueous solution of a monovalent or polyvalent metal ion salt occurs at an elevated temperature and with shear mixing.

30. A method according to claim29, wherein, in step b), the mixing of the microgel-forming polymer solution formed in step (a) with an aqueous solution of a monovalent or polyvalent metal ion salt occurs at temperature of greater than 25 °C.

31. A method according to any one of claims 26 to 30, wherein, in step c), the mixture from step b) is cooled at a rate of 0.1 to 5 °C/min with continuous mixing.

32. A method according to any one of claims 26 to 3031 wherein, in step c), the mixture from step b) is cooled at a rate of 0.5 to 2 °C/min with continuous mixing.

33. A method according to any one of paragraphs 26 to 32, wherein, in step c), the mixture from step b) is cooled at a rate of 0.5 to 1.5 °C/min (e.g. 1 °C/min) with continuous mixing.

34. A method according to any one of claims 26 to 33, wherein, in step c), the mixture is cooled to a temperature within the range of 0 to 25 °C, 0 to 20°C, 0 to 10 °C, or 0 to 5 °C.

35. A shear-thinning gel composition obtainable by, obtained by or directly obtained by a method according to any one of claims 26 to 34.

36. A shear-thinning hydrogel composition according to any one of claims 1 to 25 or claim35 for use in therapy.

37. A shear-thinning hydrogel composition for use according to claim26, wherein the composition is for topical administration.

38. A shear-thinning hydrogel composition for use according to claim35 or claim37 in the inhibition of scarring.

39. A shear-thinning hydrogel composition for use according to claim38, comprising an anti-fibrotic agent.

40. A shear-thinning hydrogel composition for use according to claim39, wherein the anti-fibrotic agent is selected from the group consisting of: an anti-fibrotic extracellular matrix (ECM) component; an anti-fibrotic growth factor; and an inhibitor of a fibrotic agent.

41. A shear-thinning hydrogel composition for use according to any of claims 38 to 40, comprising the anti-fibrotic ECM component decorin.

42. A shear-thinning hydrogel composition for use according to claim 41 , wherein decorin is present at a concentration of between about 0.1 pg/mL and O.Spg/mL.

43. A shear-thinning hydrogel composition for use according to any of claims 36 to 42, wherein the composition is for administration to the surface of the eye.

44. A shear-thinning hydrogel composition for use according to claim 43, wherein the composition comprises a modified dextran sulphate.

45 A shear-thinning hydrogel composition for use according to claim 43, wherein the composition is for use in the treatment of microbial keratitis.

46. A shear-thinning hydrogel composition for use according to claim 45, wherein the composition Is for use in combination with one or more agents selected from the group consisting of: a steroid; and an antimicrobial agent.

47. A shear-thinning hydrogel composition for use according to claim 46, wherein the composition is for use in combination with one or more agents selected from the group consisting of: prednisolone; and gentamicin.

48. A shear-thinning hydrogel composition for use according to claim 47, comprising decorin, prednisolone, and gentamicin.

49. A shear-thinning hydrogel composition for use according to claim 43, for use in the prevention and/or treatment of glaucoma.

50. A shear-thinning hydrogel composition for use according to claim 49 in the prevention and/or treatment of glaucoma, wherein the composition does not comprise an active agent

51 A shear-thinning hydrogel composition for use according to claim 50, wherein the partide forming polymer comprises or consists of gellan.

52. A shear-thinning hydrogel composition for use according to any of claims 36 to 43 wherein the composition is for administration to a wound.

53. A shear-thinning hydrogel composition for use according to claim 52 wherein the composition is for administration to a dermal wound.

54. A shear-thinning hydrogel composition for use according to claim 52 or claim 50, wherein the wound is selected from the group consisting of: a bum; an incision; an excision; an abrasion; a chronic wound; and a wound arising from the body's reaction to a stimulus. 55. A shear-thinning hydrogel composition for use according to any one of claims 52 to

53, wherein the wound is a surgical incision or surgical excision.

56. A shear-thinning hydrogel composition for use according to claim 54, wherein the wound arising from the body's reaction to a stimulus Is selected from the group consisting

SUBSTITUTE SHEET (RULE 26)

of: a systemic chemical and/or allergic reaction; and a genetic-related disease such as epidermolysis bullosa or Kindler syndrome.