Biocompatible hydrogel treatments for retinal detachment

• US 9,072,809 B2
• Filed: 05/08/2014
• Issued: 07/07/2015
• Est. Priority Date: 05/11/2012
• Status: Active Grant

• Current Assignee: Theragenics Corporation (Juniper Investment Co. LLC)
• Original Assignee: Medical Biosciences LLC
• Inventors: Askari, Syed H., Choi, Yeon S.
• Primary Examiner(s): ROGERS, JAMES WILLIAM
• Application Number:
  US14/273,408
• Publication Number:
  US 20140248231A1
• Time in Patent Office: 425 Days
• Field of Search: None
• US Class Current: 1/1
• 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. An in vivo gelling pre-formulation for the treatment of retinal detachment, 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 group selected from a hydroxyl, thiol, and amino;

(b) multi-ARM electrophilic polyol monomers having more than two electrophilic arms, wherein each electrophilic arm comprises a polyethyleneglycol chain and terminates in an electrophilic group selected from an epoxide, maleimide, succinimidyl, and an alpha-beta unsaturated ester; and

(c) a viscosity enhancer selected from hydroxyethylcellulose, hydroxypropylmethylcellulose, methylcellulose, hydroxypropyl cellulose, carboxymethyl cellulose, sodium hyaluronate, polyvinyl alcohol, and polyvinylpyrrolidone;

wherein the viscosity of the in vivo gelling pre-formulation is between about 5 cP and 4000 cP; and

wherein the in vivo gelling pre-formulation polymerizes and/or gels at a target site of an eye to form a biocompatible retinal patch.

2. The in vivo gelling pre-formulation of claim 1, wherein the pre-formulation further comprises a buffer providing a pH range of about 6.0 to about 8.5.

3. The in vivo gelling pre-formulation of claim 1, wherein the pre-formulation further comprises a therapeutic agent.

4. The in vivo gelling pre-formulation of claim 1, wherein the nucleophilic arms of the multi-ARM nucleophilic polyol monomers are selected from

5. The in vivo gelling pre-formulation of claim 1, wherein the multi-ARM nucleophilic polyol monomers are selected from

6. The in vivo gelling pre-formulation of claim 1, wherein the electrophilic arms of the multi-ARM electrophilic polyol monomers are selected from

7. The in vivo gelling pre-formulation of claim 1, wherein the multi-ARM electrophilic polyol monomers are selected from

8. The in vivo gelling pre-formulation of claim 1, wherein the pre-formulation is prepared from the following multi-ARM polyol monomers:

9. A method of treating retinal detachment, comprising delivering an in vivo gelling pre-formulation to a site of a retinal tear in a human eye, the in vivo gelling pre-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 group selected from a hydroxyl, thiol, and amino;

(b) multi-ARM electrophilic polyol monomers having more than two electrophilic arms, wherein each electrophilic arm comprises a polyethyleneglycol chain and terminates in an electrophilic group selected from epoxide, maleimide, succinimidyl, and an alpha-beta unsaturated ester; and

(c) a viscosity enhancer selected from hydroxyethylcellulose, hydroxypropylmethylcellulose, methylcellulose, hydroxypropyl cellulose, carboxymethyl cellulose, sodium hyaluronate, polyvinyl alcohol, and polyvinylpyrrolidone;

wherein the viscosity of the in vivo gelling pre-formulation is between about 5 cP and 4000 cP; and

wherein the in vivo gelling pre-formulation polymerizes and/or gels at a target site of an eye to form a biocompatible retinal patch.

10. The method of claim 9, wherein the pre-formulation further comprises a buffer providing a pH range of about 6.0 to about 8.5.

11. The method of claim 9, wherein the pre-formulation further comprises a therapeutic agent.

12. The method of claim 9, wherein the nucleophilic arms of the multi-ARM nucleophilic polyol monomers are selected from

13. The method of claim 9, wherein the multi-ARM nucleophilic polyol monomers are selected from

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