# US 12,214,039 B2 · Systems and methods for treatments of an eye with a photosensitizer

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- Number: US 12,214,039 B2
- Document ID: US12214039B2
- Status: Granted
- Kind: B2
- Application number: 17/509,238
- Filed: 2021-10-25
- Published: 2022-05-19
- Granted: 2025-02-04
- Earliest claimed: 2015-07-21
- Assignees: Advero, Inc.
- Applicants: Avedro, Inc.
- Inventors: Pavel Kamaev; Marc D. Friedman
- Web page: https://patentgrep.com/patent/US12214039B2

## CPC

- A61K 41/0057: {Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent}
- A61F 9/0017: {implantable in, or in contact with, the eye, e.g. ocular inserts}
- A61F 9/0079: {using non-laser electromagnetic radiation, e.g. non-coherent light or microwaves}
- A61K 9/0048: {Eye, e.g. artificial tears}
- A61K 31/525: Isoalloxazines, e.g. riboflavins, vitamin B2
- A61K 33/00: Medicinal preparations containing inorganic active ingredients
- A61K 33/26: Iron; Compounds thereof
- A61N 5/062: {Photodynamic therapy, i.e. excitation of an agent}
- A61P 27/02: Ophthalmic agents
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 33/02: Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61N 2005/0661: {ultraviolet}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C)
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A formulation for an eye treatment includes a photosensitizer and a permeability enhancing composition. The permeability enhancing composition includes one or more permeability enhancers. The permeability enhancing composition has a hydrophilic and lipophilic balance increases a permeability of an area of the eye for the photosensitizer. The hydrophilic and lipophilic balance can be characterized by a Hydrophile-Lipophile Balance (HLB) number. For example, the area of the eye may include a corneal epithelium, the photosensitizer may include riboflavin, and the permeability enhancing composition may have a corresponding HLB number between approximately 12.6 and approximately 14.6.

## Claims

### Claim 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/cm2 to about 45 mW/cm2 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.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

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

### Claim 4 (depends on 3)

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.

### Claim 5 (depends on 1)

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.

### Claim 6 (depends on 1)

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

### Claim 7 (depends on 1)

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

### Claim 8 (depends on 1)

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.

### Claim 9 (depends on 1)

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

### Claim 10 (depends on 1)

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

### Claim 11 (depends on 1)

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

### Claim 12 (depends on 1)

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.

### Claim 13 (depends on 4)

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.

### Claim 14 (depends on 1)

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.