IP Library › Granted Patent US 12,453,713
Granted Patent B2
US 12,453,713 · App. 17/618,888 · Granted Oct 28, 2025

Liquid formulation to treat a corneal tissue

Inventors: Giuseppe Lombardo (Rome, IT); Marco Lombardo (Rome, IT)
Assignee: VISION ENGINEERING ITALY SRL
A61K31/352A61K9/0048A61K31/525A61K41/0057A61P27/02
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Quick Facts
Patent No.
US 12,453,713
App. No.
17/618,888
Granted
Oct 28, 2025
Kind
B2
Abstract

A pharmaceutical composition for an ophthalmic use either in humans or mammalians for a treatment of eye disorders is provided. The pharmaceutical composition includes an effective amount of an oxidizing agent and an effective amount of a photo-sensitizing agent, in combination with pharmaceutically acceptable excipients; the photo-sensitizing agent is a molecule having an absorbance peak in a wavelength range between 340 nm and 440 nm and emits fluorescence in a wavelength range between 450 nm and 600 nm; the oxidizing agent is chosen among molecules, wherein the molecules partially or totally inhibit a mitochondrial electron transport chain activity, wherein the pharmaceutical composition is a liquid formulation further includes one or more substances chosen among: diluents, permeabilizers, disinfectants, buffer systems, salts, antiseptics, and the pharmaceutically acceptable excipients.

Claims (24)

1. A pharmaceutical composition for an ophthalmic use either in humans or mammalians, comprising

an effective amount of an oxidizing agent, wherein the oxidizing agent is a mitochondrial electron transport chain (mETC) inhibitor and partially or totally inhibits mitochondrial electron transport chain activity;

an effective amount of a photo-sensitizing agent, wherein the photo-sensitizing agent is a molecule having an absorbance peak in a wavelength range between 340 nm and 440 nm and emits fluorescence in a wavelength range between 450 nm and 600 nm; and

one or more pharmaceutically acceptable excipients; wherein

the pharmaceutical composition is a liquid formulation.

2. The pharmaceutical composition according to claim 1 , wherein a concentration of the oxidizing agent in the liquid formulation is between 0.1 μg/ml and 100 μg/ml.

3. The pharmaceutical composition according to claim 1 , wherein a concentration of the photo-sensitizing agent in the liquid formulation is between 0.01 mg/ml and 5.0 mg/ml.

4. The pharmaceutical composition according to claim 1 , wherein the photo-sensitizing agent is one or more selected from the group consisting of riboflavin, riboflavin-5-phosphate, fluorescein, coumarin, bengal rose, acridine yellow, and quinidine yellow.

5. The pharmaceutical composition according to claim 1 , wherein the oxidizing agent is non-toxic for the humans or the mammalians, and the oxidizing agent is one or more selected from the group consisting of adaphostin, alpha-tocopherol succinate, amobarbital, antimycin A, atpenin A5, benzyl isothiocyanate, carboxine, ciantraniliprole, deguelin, doxorubicin, fenretinide, HQNO, IACS-010759, lamellarin D, malonate, metformin, MPP+, MK-077, nitric oxide, nitropropionic acid, N-retinylidene-N-retinylethanolamine, oligomycin, phenformin hydrochloride, piceatannol, piericidin A, PM031379, porfimer sodium, resveratrol, rhein, rhodamine 123, rotenone, sodium azide, tamoxifen, TTFA, 3BP, 3-ter-butylated-4-hydroxyanisole, DIM, troglitazon, VLX600, xanthomumol, BRD56491, BRD5459, and BRD9092.

6. The pharmaceutical composition according to claim 1 , wherein the one or more pharmaceutically acceptable excipients comprise at least one of:

permeabilizers and/or stabilizers, wherein the permeabilizers and/or the stabilizers are selected from the group consisting of ethylenediaminetetraacetic acid (EDTA), tris(hydroxymethyl)aminomethane hydrochloride (trometamol), benzalkonium chloride (BAK), tocopheryl-polyethylene-glycol-succinate (TPGS), polyhexanide, ethanol, and dimethyl sulfoxide (DMSO);

disinfectants and/or antiseptics, wherein the disinfectants and/or antiseptics are antimicrobial chlorine compounds selected from the group consisting of benzyl alcohol, methyl paraben, povidone-iodine, chlorhexidine, ozone, ozonures, merbromine, silver nitrate, potassium permanganate, and hypochlorite; and/or

agents of tonicity and/or viscosity, wherein the agents of the tonicity and/or the viscosity are selected from the group consisting of glucose, dextran, mannitol, hydroxypropylmeticellulose, carboxymethylcellulose, and polyethylene glycol.

7. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is an aqueous solution or a suspension, and the pharmaceutical composition further comprises sterile diluting agents selected from the group consisting of a distilled water, a purified water, a saline solution, a physiological solution, a Ringer solution, an isotonic sodium chloride solution.

8. The pharmaceutical composition according to claim 1 , further comprising a buffer system, wherein the buffer system is selected from the group consisting of a neutral saline buffer, a phosphate buffer, an acetate, a citrate, and equivalent buffer systems.

9. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is hypotonic.

10. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is a formulation administered topically onto a cornea of an eye.

11. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is used in a treatment of ocular disorders, wherein the ocular disorders are degenerative diseases of ocular tissues, comprising a cornea and/or a sclera, wherein the degenerative diseases of the ocular tissues are keratoconus, corneal ectasias comprising iatrogenic corneal ectasia, eventually induced by an eye surgery;

a treatment of visual disorders caused by an altered corneal curvature or an abnormal axial length of an eye and/or a decreased focal power of the eye for distance and/or for near, wherein the visual disorders are myopia, hyperopia, astigmatism and presbyopia; and

for a prevention and a treatment of infectious diseases of an ocular surface caused by bacteria, viruses, fungi, chlamydiae, protozoa, parasites, wherein the infectious diseases are keratitis and septic corneal ulcers.

12. A packaging, comprising the pharmaceutical composition according to claim 1 contained in a container, wherein the container is one selected from the group consisting of: a bottle, a vial, a plastic syringe, a glass syringe, a disposable container, wherein the container is configured to be packaged in a sterile envelope or in a double sterile envelope.

13. A method for promoting a generation of Type II chemical bonds without inhibiting Type I bonds through a direct increase of a singlet oxygen by administering the pharmaceutical composition according to claim 1 onto a cornea of a human or mammalian.

14. The method according to claim 13 , wherein a concentration of the oxidizing agent that penetrates into a corneal stroma is between 2 μmol/l and 15 μmol/l.

15. The method according to claim 13 , wherein a concentration of the photo-sensitizing agent that penetrates into a corneal stroma is at least 20 μg/ml.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 14, 2021
From: LOMBARDO, GIUSEPPE; LOMBARDO, MARCO
To: VISION ENGINEERING ITALY SRL
Reel/Frame 058378/0098 →
Priority Claims (1)
IT 102019000011985 · Jul 17, 2019 · national
Continuity (1)
Related Publication 20230131004A1 · Apr 27, 2023
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