Search

EP-4734894-A2 - POLYMER COMPOSITIONS AND USES THEREOF

EP4734894A2EP 4734894 A2EP4734894 A2EP 4734894A2EP-4734894-A2

Abstract

The present invention relates to polymer compositions, in particular to biocompatible cross-linkable polymer compositions, methods of preparing the same and their use in the preparation of ocular implants.

Inventors

  • QIAO, GREG GUANGHUA
  • TITUS, Michael Sean
  • GURR, PAUL ANDREW
  • KARIMI, Fatemeh
  • SCHEERLINCK, Jean-Pierre Yves-Charles
  • DANIELL, Mark Davis
  • YANG, Gink Nathan
  • BROWN, Karl David
  • DUSTING, GREGORY JAMES
  • SAWANT, Onkar Balkrishna

Assignees

  • The University of Melbourne

Dates

Publication Date
20260506
Application Date
20240628

Claims (20)

  1. 1. A biocompatible cross-linkable polymer composition comprising: a cross-linkable branched polyether compound comprising a core moiety to which is covalently bonded to at least three polyether arms, wherein the at least three polyether arms each comprise a polymerisable ethylenically unsaturated group.
  2. 2. The biocompatible cross-linkable polymer composition according to claim 1, wherein the cross-linkable branched polyether compound has a structure A(BX) n wherein: A is an n-valent core moiety; BX is a polyether arm, wherein B is a polyether segment and X is a polymerisable ethylenically unsaturated group; and n is at least 3.
  3. 3. The biocompatible cross-linkable polymer composition according to claim 1 or claim 2, wherein the core moiety is a hydrocarbon, carbohydrate, heteroalkyl, heterocycloalkyl or heteroaryl moiety.
  4. 4. The biocompatible cross-linkable polymer composition according to claim 3, wherein the core moiety comprises from 1 to 12 carbon atoms, or from 3 to 8 carbon atoms, or from 3 to 5 carbon atoms.
  5. 5. The biocompatible cross-linkable polymer composition according to any one of claims 1 to 4, wherein the at least three polyether arms each comprise a poly(ethylene glycol) segment or a poly(propylene glycol) segment.
  6. 6. The biocompatible cross-linkable polymer composition according to any one of claims 1 to 5, wherein the polymerisable ethylenically unsaturated group forms part of a (meth)acryloyl, (meth)acryloyloxy, styrenyl, vinyl ether, vinyl ester or (meth)acrylamide group.
  7. 7. The biocompatible cross-linkable polymer composition according to any one of claims 1 to 6, wherein the cross-linkable branched polyether compound is: where each n is an integer independently ranging from about 4 to about 40.
  8. 8. The biocompatible cross-linkable polymer composition according to any one of claims 1 to 7, which is biodegradable.
  9. 9. An aqueous bioglue composition comprising the biocompatible cross-linkable polymer composition according to any one of claims 1 to 8, water and a biocompatible photoinitiator.
  10. 10. The aqueous bioglue composition according to claim 9, wherein the biocompatible photoinitiator is selected from: Eosin Y with triethanolamine and vinyl caprolactam; tris(2,2-bipyridyl)dichlororuthenium(II) hexahydrate (Rufbpyfa) with sodium persulfate, camphorquinone and A,A-dimethyl-p-toluidine, 2-ethyl- dimethylbenzoate, or A-phenylglycine; 2,2,2,6,6-tetramethylpiperidine; dl-2,3- diketo-l,7,7-trimethylnorcamphane (CQ); l-phenyl-l,2-propadione (PPD); 2,4,6- trimethylbenzoyl-diphenylphosphine oxide (TPO); bis(2,6-dichlorobenzoyl)-(4- propylphenyl)phosphine oxide (Ir819); 4,4'-bis(dimethylamino)benzophenone; 4,4'- bis(diethylamino)benzophenone; 2-chlorothioxanthen-9-one; 4- (dimethylamino)benzophenone; phenanthrenequinone, ferrocene; diphenyl(2,4,6- trimethylbenzoyl)phosphine oxide I 2-hydroxy-2- methylpropiophenone (50/50 blend); dibenzosuberenone; resazurin; resorufin; benzoyltrimethylgermane (Ivocerin®); derivatives thereof, and combinations thereof.
  11. 11. The aqueous bioglue composition according to claim 9 or claim 10 comprising the biocompatible cross-linkable polymer composition in an amount of from about 10 vol% to about 50 vol%.
  12. 12. A kit when used for adhering a biocompatible hydrogel to a biological substrate, the kit comprising: (a) a first part comprising the biocompatible cross-linkable polymer composition of any one of claims 1 to 8; and (b) a second part comprising water and a biocompatible photoinitiator.
  13. 13. A kit when used for preparing a biological substrate having adhered thereto a crosslinked network polymer scaffold, the kit comprising: (a) a first part comprising the biocompatible cross-linkable polymer composition of any one of claims 1 to 8; and (b) a second part comprising water and a biocompatible photoinitiator.
  14. 14. Use of the cross-linkable polymer composition according to any one of claims 1 to 8, the aqueous bioglue composition according to any one of claims 9 to 11, or the kit according to claim 12, for adhering a biocompatible hydrogel to a biological substrate.
  15. 15. Use of the cross-linkable polymer composition according to any one of claims 1 to 8, the aqueous bioglue composition according to any one of claims 9 to 11, or the kit according to claim 13, for preparing a biological substrate having adhered thereto a cross-linked network polymer scaffold.
  16. 16. A process for adhering a biocompatible hydrogel to a biological substrate comprising: (i) combining the biocompatible cross-linkable polymer composition according to any one of claims 1 to 8 with water and a biocompatible photoinitiator to form an aqueous bioglue composition according to any one of claims 9 to 11; (ii) providing the aqueous bioglue composition between a biocompatible hydrogel layer and a biological substrate layer to form a laminate structure; (iii) irradiating the laminate structure at a wavelength suitable to activate the biocompatible photoinitiator and initiate cross-linking of the cross-linkable branched polyether compound, the process of which promotes adhesion between the biocompatible hydrogel and the biological substrate.
  17. 17. The process according to claim 16, wherein the biocompatible hydrogel comprises a biodegradable and biocompatible polyether network polymer cross-linked via ester linkages.
  18. 18. The process according to claim 16 or claim 17, wherein the ratio of the aqueous bioglue composition to the biocompatible hydrogel layer is from about 3:1 to about 5:1 by volume.
  19. 19. A process for preparing a biological substrate having adhered thereto a cross-linked network polymer scaffold comprising: (i) combining the biocompatible cross-linkable polymer composition according to any one of claims 1 to 8 with water and a biocompatible photoinitiator to form an aqueous bioglue composition according to any one of claims 9 to 11 ; (ii) providing a layer of the aqueous bioglue composition on a biological substrate layer to form a laminate structure; (iii) irradiating the laminate structure at a wavelength suitable to activate the biocompatible photoinitiator and initiate cross-linking of the cross-linkable branched polyether compound, the process of which promotes formation of a cross-linked network polymer scaffold adhered to the biological substrate.
  20. 20. The process according to any one of claims 16 to 19, wherein step (i) is performed immediately prior to step (ii).

Description

POLYMER COMPOSITIONS AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority from Australian Provisional Patent Application No. 2023902079 filed 30 June 2023, the entire contents of which are incorporated herein by cross-reference. TECHNICAL FIELD [0002] The present invention relates in general to polymer compositions and uses thereof. In particular, the present invention relates to biocompatible cross-linkable polymer compositions, methods of preparing the same and their use in the preparation of laminate structures for use in tissue regeneration, such as ocular implants for the treatment of corneal endothelial dysfunction. BACKGROUND [0003] Globally over 8 million people suffer from corneal diseases with rising indications in ageing populations. Corneal endothelial dysfunction, which is characterised by damage to and loss of corneal endothelial cells, leads to a loss of transparency of the cornea and eventual blindness. Currently, the only treatment for corneal endothelial dysfunction is corneal transplantation. However, the technical difficulty of performing such surgeries limits adoption and patient outcomes. [0004] Surgical options for treating comeal endothelial dysfunction currently comprise two main techniques: Descemet’s stripping automated endothelial keratoplasty (DSAEK) and Descemet's membrane endothelial keratoplasty (DMEK). Both procedures involve removal of the damaged comeal endothelial cells and Descemet's membrane to which they are attached, and replacing them with a donor tissue graft. The grafts are typically inserted by a surgeon in the form of a scroll and, once positioned, are manually unscrolled. However, unlike the DSAEK graft, which contains stromal cells, the DMEK graft consists only of the thin Descemet's membrane and the attached endothelium layer (15 pm), making it difficult to unscroll and more susceptible tearing during surgery. [0005] Thus, although the DMEK graft leads to better patient outcomes, including greater improvements in vision and lower rejection rates, many surgeons still opt for the simpler DSAEK procedure, despite associated complications such as poorer optical clarity, aberrations (ripples) in the graft due to differences in curvature, and hyperopic shifts due to curvature differences when cutting (e.g., with a microkeratome). [0006] Accordingly, there is an ongoing need for improved or alternative methods for treating comeal endothelial dysfunction. SUMMARY [0007] The present invention provides a biocompatible cross-linkable polymer composition comprising: a cross-linkable branched polyether compound comprising a core moiety to which is covalently bonded at least three polyether arms, wherein the at least three polyether arms each comprise a polymerisable ethylenically unsaturated group. [0008] In another aspect, the present invention provides an aqueous bioglue composition comprising the biocompatible cross-linkable polymer composition of the invention, water and a biocompatible photoinitiator. [0009] In another aspect, the present invention provides a kit when used for adhering a biocompatible hydrogel to a biological substrate, the kit comprising: (a) a first part comprising the biocompatible cross-linkable polymer composition of the invention; and (b) a second part comprising water and a biocompatible photoinitiator. [0010] In another aspect, the present invention provides a kit when used for preparing a biological substrate having adhered thereto a cross-linked network polymer scaffold, the kit comprising: (a) a first part comprising the biocompatible cross-linkable polymer composition of the invention; and (b) a second part comprising water and a biocompatible photoinitiator. [0011] In another aspect, the present invention provides use of the cross-linkable polymer composition according to the invention for adhering a biocompatible hydrogel to a biological substrate. [0012] In another aspect, the present invention provides use of the cross-linkable polymer composition according to the invention for preparing a biological substrate having adhered thereto a cross-linked network polymer scaffold. [0013] In another aspect, the present invention provides a process for adhering a biocompatible hydrogel to a biological substrate comprising: (i) combining the biocompatible cross-linkable polymer composition according to the invention with water and a biocompatible photoinitiator to form an aqueous bioglue composition of the invention; (ii) providing the aqueous bioglue composition between a biocompatible hydrogel layer and a biological substrate layer to form a laminate structure; (iii) irradiating the laminate structure at a wavelength suitable to activate the biocompatible photoinitiator and initiate cross-linking of the cross-linkable branched polyether compound, the process of which promotes adhesion between the biocompatible hydrogel and the biological substrate. [0014] In another aspect, the present invention