BIOCOMPATIBLE HYDROGEL TREATMENTS FOR RETINAL DETACHMENT

• US 20150273108A1
• Filed: 05/27/2015
• Published: 10/01/2015
• Est. Priority Date: 05/11/2012
• Status: Active Grant

• Current Assignee: Theragenics Corporation (Juniper Investment Co. LLC)
• Original Assignee: Medicus Biosciences, LLC
• Inventors: ASKARI, Syed H., CHOI, Yeon S.
• Granted Patent: US 9,623,144 B2
• Time in Patent Office: Days
• 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 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 acacia, agar, alginic acid, alginate, bentonite, carbomers, carboxymethylcellulose calcium, carboxymethylcellulose sodium, carrageenan, ceratonia, cetostearyl alcohol, chitosan, colloidal silicon dioxide, cyclomethicone, ethylcellulose, gelatin, glycerin, glyceryl behenate, guar gum, hectorite, hydrogenated vegetable oil type I, hydroxyethylmethyl cellulose, hydroxypropyl starch, hypromellose, magnesium aluminum silicate, maltodextrin, polycarbophil, polydextrose, polyethylene glycol, poly(methylvinyl ether/maleic anhydride), polyvinyl acetate phthalate, potassium chloride, propylene glycol alginate, saponite, sodium alginate, sodium chloride, stearyl alcohol, sucrose, sulfobutylether β

-cyclodextrin, tragacanth, xanthan gum, and derivatives and mixtures thereof;

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. The in vivo gelling pre-formulation of claim 1, wherein the viscosity enhancer is chitosan, alginate, or xanthum gum.

10. 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 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 acacia, agar, alginic acid, alginate, bentonite, carbomers, carboxymethylcellulose calcium, carboxymethylcellulose sodium, carrageenan, ceratonia, cetostearyl alcohol, chitosan, colloidal silicon dioxide, cyclomethicone, ethylcellulose, gelatin, glycerin, glyceryl behenate, guar gum, hectorite, hydrogenated vegetable oil type I, hydroxyethylmethyl cellulose, hydroxypropyl starch, hypromellose, magnesium aluminum silicate, maltodextrin, polycarbophil, polydextrose, polyethylene glycol, poly(methylvinyl ether/maleic anhydride), polyvinyl acetate phthalate, potassium chloride, propylene glycol alginate, saponite, sodium alginate, sodium chloride, stearyl alcohol, sucrose, sulfobutylether β

-cyclodextrin, tragacanth, xanthan gum, and derivatives and mixtures thereof;

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.

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

12. The method of claim 10, wherein the pre-formulation further comprises a therapeutic agent.

13. The method of claim 10, wherein the nucleophilic arms of the multi-ARM nucleophilic polyol monomers are selected from

14. The method of claim 10, wherein the multi-ARM nucleophilic polyol monomers are selected from

15. The method of claim 10, wherein the pre-formulation is prepared from the following multi-ARM polyol monomers:

16. The method of claim 10, wherein the viscosity enhancer is chitosan, alginate, or xanthum gum.