Compositions and methods for treating or preventing diseases associated with oxidative stress

• US 10,729,716 B2
• Filed: 09/20/2018
• Issued: 08/04/2020
• Est. Priority Date: 03/29/2012
• Status: Active Grant

• Current Assignee: CXL Ophthalmics, LLC
• Original Assignee: CXL Ophthalmics, LLC
• Inventors: Rubinfeld, Roy S., Hartman, Raymond A., Feldman, Sandy T.
• Primary Examiner(s): Stevens, Mark V
• Application Number:
  US16/137,114
• Publication Number:
  US 20190022134A1
• Time in Patent Office: 684 Days
• CPC Class Codes: A61K 31/525 Isoalloxazines, e.g. riboflavins, vitamin B2
• CPC Class Codes: A61K 33/18 Iodine; Compounds thereof
• CPC Class Codes: A61K 38/44 Oxidoreductases (1)
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61L 2300/106 Halogens or compounds thereof, e.g. iodine, chlorite
• CPC Class Codes: A61L 2300/254 Enzymes, proenzymes
• CPC Class Codes: A61L 26/0066 Medicaments; Biocides
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: C12Y 111/01006 Catalase (1.11.1.6)

Abstract

Methods and compositions for treating various indications by lessening oxidative stress in a patient are provided. A pharmaceutical composition comprises between about 0.001% to about 10.0%, or more specifically between about 0.015% to about 5%, sodium iodide or catalase by weight. The iodine ion or the catalase dissociates hydrogen peroxide into water and molecular oxygen to interrupt biological events that result in negative side effects. The pharmaceutical composition further comprises in some cases a reducing agent or various carrier materials. The pharmaceutical composition is in some cases formulated for a variety of delivery methods.

Claims

1. A stable pharmaceutical composition for use in corneal collagen cross-linking, comprising (a) about 0.001% to about 10.0% by weight of iodide, (b) riboflavin, and (c) a pharmaceutically-acceptable excipient appropriate for ocular administration, wherein the pharmaceutical composition maintains a basic pH that permits iodide ion to catalytically break hydrogen peroxide into water and oxygen.

2. The pharmaceutical composition of claim 1, wherein the basic pH is between 7 and 8.4.

3. The pharmaceutical composition of claim 2, further comprising a reducing agent.

4. The pharmaceutical composition of claim 3, wherein the reducing agent is thiosulfate, vitamin C, or sodium bisulfate.

5. The pharmaceutical composition of claim 1, wherein the pharmaceutically-acceptable excipient is an artificial tear solution.

6. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is a solution adapted for introduction into the eye and diffusion into the cornea for promoting photochemical corneal cross-linking and reducing oxidative stress.

7. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises about 0.015% to about 5% iodide by weight.

8. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises about 0.015% iodide by weight and about 0.5% riboflavin by weight.

9. A method of treating a disease, disorder or condition characterized by unwanted or excessive oxidative stress in an individual in need thereof, comprising administering to the individual the pharmaceutical composition of claim 1.

10. The method of claim 9, wherein the disease, disorder or condition is Glaucoma;

Dry Eyes;

Degenerative Retinal Damage (ARMD);

Cataractogenesis;

Retinopathy of Prematurity (ROP);

Ocular Uveitis;

Presbyopia;

or Cataracts.

11. A method for photochemical crosslinking comprising administering the pharmaceutical composition of claim 1 to a tissue in need thereof.

12. The method of claim 11, wherein the pharmaceutical composition comprises between about 0.015% to about 5% iodide by weight.

13. The method of claim 11, wherein the pharmaceutical composition comprises about 0.015% iodide by weight and about 0.5% riboflavin by weight.

14. The method of claim 11, wherein the basic pH is between 7 and 8.4.

15. The method of claim 11, wherein the pharmaceutical composition further comprises a reducing agent.

16. The method of claim 15, wherein the reducing agent comprises thiosulfate, vitamin C, or sodium bisulfate.

17. The method of claim 11, wherein the pharmaceutical composition is used to treat wounds associated with refractive corneal surgery, thermokeratoplasty treatment, lens-based refractive surgery, retinal surgery, scleral surgery, retinal or glaucoma laser surgery, cataract and eye lid surgery, PRK, LASIK, Intacs, lamellar corneal procedures, CK, or any combinations thereof.

18. A method of reducing oxidative stress in a tissue undergoing photochemical crosslinking, comprising contacting the tissue with the pharmaceutical composition of claim 1.

19. The method of claim 18, wherein the composition has a basic pH between 7 and 8.4.