Biocompatible hydrogel treatments for retinal detachment

• US 10,507,262 B2
• Filed: 03/23/2017
• Issued: 12/17/2019
• Est. Priority Date: 05/11/2012
• Status: Active Grant

• Current Assignee: Theragenics Corporation (Juniper Investment Co. LLC)
• Original Assignee: C.P. Medical Corporation
• Inventors: Askari, Syed H., Choi, Yeon S.
• Primary Examiner(s): Rogers, James W
• Application Number:
  US15/467,019
• Publication Number:
  US 20180036452A1
• Time in Patent Office: 999 Days
• Field of Search: None
• CPC Class Codes: A61F 9/007 Methods or devices for eye surgery
• CPC Class Codes: A61F 9/00727 Apparatus for retinal reattachment
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 51/1213 Semi-solid forms, gels, hydrogels, ointments, fats and waxes that are solid at room temperature
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/7015 Drug-containing film-forming compositions, e.g. spray-on
• CPC Class Codes: A61L 2300/402 Anaestetics, analgesics, e.g. lidocaine
• CPC Class Codes: A61L 2300/406 Antibiotics
• CPC Class Codes: A61L 2300/41 Anti-inflammatory agents, e.g. NSAIDs
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/418 Agents promoting blood coagulation, blood-clotting agents, embolising agents
• CPC Class Codes: A61L 24/0031 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 24/0042 Materials resorbable by the body
• CPC Class Codes: A61L 24/046 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043 takes precedence
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 2430/16 for reconstruction of eye parts, e.g. intraocular lens, cornea
• CPC Class Codes: A61L 26/0019 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 26/0023 : Polysaccharides
• CPC Class Codes: A61L 26/0066 : Medicaments; Biocides
• CPC Class Codes: A61L 26/008 : Hydrogels or hydrocolloids
• CPC Class Codes: A61L 26/009 : Materials resorbable by the body
• CPC Class Codes: A61L 27/18 : obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/52 : Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/54 : Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/58 : Materials at least partially resorbable by the body
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: C08J 2300/206 : Star polymers
• CPC Class Codes: C08L 71/02 : Polyalkylene oxides

Abstract

Provided herein are in vivo gelling ophthalmic pre-formulations forming a biocompatible retinal patch comprising at least one nucleophilic compound or monomer unit, at least one electrophilic compound or monomer unit, and optionally a therapeutic agent and/or viscosity enhancer. In some embodiments, the retinal patch at least partially adheres to the site of a retinal tear. Also provided herein are methods of treating retinal detachment by delivering an in vivo gelling ophthalmic pre-formulation to the site of a retinal tear in human eye, wherein the in vivo gelling ophthalmic pre-formulation forms a retinal patch.

Claims

1. A method of delivering a therapeutic to an eye, the method comprising:

administering to the eye a therapeutic agent and a formulation comprising;

(a) multi-ARM nucleophilic polyol monomers having more than two nucleophilic arms, wherein each nucleophilic arm comprises a polyethyleneglycol chain and terminates in a nucleophilic amino group, wherein the nucleophilic arms of the multi-ARM nucleophilic polyol monomers are selected from

2. The method of claim 1, wherein the formulation polymerizes and/or gels at a target site of the eye.

3. The method of claim 1, wherein the therapeutic agent is an immunosuppressive agent.

4. The method of claim 3, wherein the immunosuppressive agent is a calcinuerin inhibitor, a mTor inhibitor, an anti-proliferative agent, a glucocorticosteroid, an antibody, or an agent acting on immunophilins.

5. The method of claim 3, wherein the immunosuppressive agent is ciclosporin, tacrolimus, sirolimus, everolimus, azathioprine, mycophenolic acid, prednisolone, hydrocortisone, basiliximab, daclizumab;

antithymocyte globulin (ATG), anti-lymphocyte globulin (ALG), rituximab, daclizumab, basiliximab, anakinra, rilonacept, ustekinumab, mepolizumab, tocilizumab, canakinumab, briakinumab, etanercept, infliximab, afelimomab, adalimumab, certolizumab pegol, golimumab, muromonab, mycophenolic acid, sirolimus, leflunomide, alefacept, everolimus, gusperimus, efalizumab, abetimus, natalizumab, abatacept, eculizumab, belimumab, fingolimod, belatacept, azathioprine, thalidomide, methotrexate, or lenalidomide.

6. The method of claim 1, wherein the viscosity of the formulation is between about 5 cP and 4000 cP.

7. The method of claim 1, wherein the multi-ARM nucleophilic polyol monomers are selected from

8. The method of claim 1, wherein the multi-ARM electrophilic polyol monomers are selected from

9. The method of claim 2, wherein the formulation is prepared from the following multi-ARM polyol monomers:

14. The method of claim 1, wherein the viscosity enhancer is hydroxypropylmethylcellulose or hydroxyethylcellulose.

15. The method of claim 1, wherein the viscosity enhancer is hydroxypropylmethylcellulose.

16. The method of claim 5, wherein the immunosuppressive agent is tacrolimus.

20. The method of claim 1, wherein the formulation further comprises a buffer providing a pH range of about 6.0 to about 8.5.

10. A pharmaceutical composition formulated for administration to an eye, the composition comprising a therapeutic and a formulation comprising:

(a) multi-ARM nucleophilic polyol monomers having more than two nucleophilic arms, wherein each nucleophilic arm comprises a polyethyleneglycol chain and terminates in a nucleophilic amino group, wherein the nucleophilic arms of the multi-ARM nucleophilic polyol monomers are selected from

11. The composition of claim 10, wherein the therapeutic agent is an immunosuppressive agent.

12. The composition of claim 11, wherein the immunosuppressive agent is a calcinuerin inhibitor, a mTor inhibitor, an anti-proliferative agent, a glucocorticosteroid, an antibody, or an agent acting on immunophilins.

13. The composition of claim 11, wherein the immunosuppressive agent is ciclosporin, tacrolimus, sirolimus, everolimus, azathioprine, mycophenolic acid, prednisolone, hydrocortisone, basiliximab, daclizumab, antithymocyte globulin (ATG), anti-lymphocyte globulin (ALG), rituximab, daclizumab, basiliximab, anakinra, rilonacept, ustekinumab, mepolizumab, tocilizumab, canakinumab, briakinumab, etanercept, infliximab, afelimomab, adalimumab, certolizumab pegol, golimumab, muromonab, mycophenolic acid, sirolimus, leflunomide, alefacept, everolimus, gusperimus, efalizumab, abetimus, natalizumab, abatacept, eculizumab, belimumab, fingolimod, belatacept, azathioprine, thalidomide, methotrexate, or lenalidomide.

17. The composition of claim 10, wherein the viscosity enhancer is hydroxypropylmethylcellulose or hydroxyethylcellulose.

18. The composition of claim 10, wherein the viscosity enhancer is hydroxypropylmethylcellulose.

19. The composition of claim 10, wherein the immunosuppressive agent is tacrolimus.

21. The composition of claim 10, wherein the formulation further comprises a buffer providing a pH range of about 6.0 to about 8.5.