Granted Patent B2

US 12,214,039 · App. 17/509,238 · Granted Feb 4, 2025

Inventors: Pavel Kamaev (Lexington, MA); Marc D. Friedman (Needham, MA)

Assignee: Advero, Inc.

A61K41/0057A61F9/0017A61F9/0079A61K9/0048A61K31/525A61K33/00A61K33/26A61N5/062A61P27/02A61P43/00A61N2005/0661

Abstract

Claims (31)

1. A method for treating corneal damage associated with a pathogen infection in an eye, comprising:

identifying an eye infected by a pathogen;

applying an eye drop formulation to an area of the eye infected by the pathogen, the formulation including:

a photosensitizer;

one or more non-ionic permeability enhancers; and

at least one additive selected from the group consisting of iron, copper, manganese, chromium, vanadium, aluminum, cobalt, mercury, cadmium, nickel, arsenic, 2,3-butanedione, and folic acid; and

delivering a dose of illumination having a fluence rate ranging from about 15 mW/cm 2 to about 45 mW/cm 2 in combination with pulsed oxygen to the area of the eye thereby photoactivating the photosensitizer and cross-linking corneal tissue at a depth that does not damage endothelium.

2. The method of claim 1 , wherein the at least one additive includes iron (II).

3. The method of claim 1 , wherein applying the formulation includes applying the formulation to a corneal epithelium.

4. The method of claim 3 , wherein the photosensitizer includes riboflavin or riboflavin-5′-monophosphate, and the permeability enhancing composition has a Hydrophile-Lipophile Balance (HLB) number between approximately 12.6 and approximately 14.6.

5. The method of claim 1 , wherein the one or more permeability enhancers include at least one of IGEPAL CO-630, Triton X-100, Polidocanol, or IGEPAL CO-720.

6. The method of claim 1 , wherein the formulation includes a concentration of at least 0.1% riboflavin or riboflavin-5′-monophosphate.

7. The method of claim 1 , wherein the illumination includes ultraviolet light.

8. The method of claim 1 , wherein identifying the eye infected by the pathogen includes identifying a cyst or an ulcer caused by the pathogen, applying the formulation to the area of the eye includes applying the formulation to the cyst or the ulcer, and the permeability enhancing composition increases penetration of the photosensitizer into the cyst or the ulcer.

9. The method of claim 1 , wherein the formulation includes a concentration of 0.1%, 0.22%, 0.25%, or 0.5% photosensitizer.

10. The method of claim 1 , wherein the formulation includes a concentration of 1%, 3%, 5%, or 10% of the one or more permeability enhancers.

11. The method of claim 1 , wherein the formulation comprises 2.5 mM Fe(II).

12. The method of claim 1 , wherein the formulation comprises:

(1) 0.25% riboflavin, and 1% polidocanol;

(2) 0.25% riboflavin, and 5% polidocanol;

(3) 0.25% riboflavin, and 10% polidocanol;

(4) 0.22% riboflavin, and 1% polidocanol;

(5) 0.22% riboflavin, and 3% polidocanol;

(6) 0.22% riboflavin, and 5% polidocanol;

(7) 0.22% riboflavin, 1% polidocanol, and 2.5 mM Fe(II);

(8) 0.22% riboflavin, 3% polidocanol, and 2.5 mM Fe(II);

(9) 0.22% riboflavin, and 1% IGEPAL CO-630;

(10) 0.22% riboflavin, and 1% IGEPAL CO-720; or

(11) 0.22% riboflavin, and 1% 1:1 IGEPAL CO-630: IGEPAL CO-720.

13. The method of claim 4 , wherein the one or more permeability enhancers include at least one of IGEPAL CO-630, Triton X-100, Polidocanol, or IGEPAL CO-720.

14. The method of claim 1 , wherein the one or more permeability enhancers include at least one of IGEPAL CO-630, Triton X-100, Polidocanol, or IGEPAL CO-720, and the formulation includes a concentration of 1%, 3%, 5%, or 10% of the one or more permeability enhancers.

Continuity (6)

References Cited (400)