Hydrogel polymeric compositions and methods

• US 9,370,485 B2
• Filed: 08/27/2014
• Issued: 06/21/2016
• Est. Priority Date: 07/09/2007
• Status: Active Grant

• Current Assignee: Incept LLC
• Original Assignee: Incept LLC
• Inventors: Sawhney, Amarpreet S., Ransone, William H. II
• Primary Examiner(s): Shomer, Isaac
• Application Number:
  US14/470,081
• Publication Number:
  US 20140363498A1
• Time in Patent Office: 664 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/4422 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics

Abstract

Some aspects of this disclosure relate to a method of treating an ophthalmic disease affecting an eye of a patient comprising forming a covalently-crosslinked hydrogel in situ at a peri-ocular, intra-ocular, or intra-vitreal site for controlled release of a therapeutic agent.

Claims

1. A method of treating an ophthalmic disease affecting an eye of a patient comprising forming a covalently-crosslinked hydrogel in situ at a site in an eye, wherein the hydrogel, when formed, has a volume of less than 0.5 ml and comprises a hydrophobic particle entrapped as a suspension within the hydrogel, the particle comprising a therapeutic agent that is released into the eye to treat the ophthalmic disease, wherein a time at which a cumulative 80% w/w of the therapeutic agent has been released is between about 14 and 120 days.

2. The method of claim 1 wherein the disease is a back-of-the eye disease.

3. The method of claim 2 wherein the back-of-the-eye disease is a selected from the group consisting of wet macular degeneration, dry macular degeneration, diabetic macular edema, cystoid macular edema, and diabetic retinopathy.

4. The method of claim 2 wherein the back-of-the-eye disease is an ocular disease of a posterior segment of the eye that affects a retina, macula or choroid, with said disease leading to a visual acuity disturbance, loss of sight, or blindness.

5. The method of claim 1 wherein the site is in a sclera of the eye.

6. The method of claim 1 wherein the site is substantially disposed between a sclera and a conjunctiva.

7. The method of claim 1 wherein the site is a potential space of the eye.

8. The method of claim 7 further comprising puncturing a conjunctiva to access the potential space.

9. The method of claim 7 comprising mechanically creating the potential space.

10. The method of claim 7 wherein the potential space is natural.

11. The method of claim 1 wherein the site is a vitreous of the eye or a posterior chamber of the eye.

12. The method of claim 1 wherein the hydrogel is low-swelling, as measurable by the hydrogel having a weight increasing no more than about 50% upon exposure to a physiological solution for twenty-four hours relative to a weight of the hydrogel at the time of formation.

13. The method of claim 1 wherein the hydrogel is water-degradable, as measurable by the hydrogel being dissolvable in vitro in an excess of water by degradation of water-degradable groups.

14. The method of claim 1 wherein the water-degradable groups are esters.

15. The method of claim 1 wherein the hydrogel is formed by combining a first synthetic precursor comprising nucleophilic groups with a second synthetic precursor comprising electrophilic groups to form covalent crosslinks by reaction of the nucleophilic groups with the electrophilic groups to form the biocompatible hydrogel.

16. The method of claim 15 further comprising injecting an aqueous mixture of the precursors to the site.

17. The method of claim 16 wherein the polymeric hydrophilic portions comprise poly(ethylene) glycol repeats.

18. The method of claim 1 wherein the hydrogel is formed by combining a first synthetic precursor with a second synthetic precursor.

19. The method of claim 1 wherein the therapeutic agent is selected from the group consisting of an inhibitor of vascular endothelial growth factor, a small molecule drug, and a protein.

20. The method of claim 1, wherein the therapeutic agent is an antiangiogenic agent.

21. The method of claim 20, wherein the antiangiogentic agent is an inhibitor of vascular endothelial growth factor.