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EP-4739291-A2 - ADMINISTRATION OF KERATOLYTICS TO OCULAR AND PERIOCULAR SURFACES

EP4739291A2EP 4739291 A2EP4739291 A2EP 4739291A2EP-4739291-A2

Abstract

Provided herein are methods for treating conditions in or around the eye with a pharmaceutical composition comprising a keratolytic agent by spreading the pharmaceutical composition prior to administering the pharmaceutical composition to an ocular or periocular surface (e.g., eyelid) of an individual in need thereof.

Inventors

  • BOSWORTH, CHARLES
  • ALSTER, YAIR
  • RAFAELI, OMER
  • EPSTEIN-BARASH, HILA

Assignees

  • AZURA OPHTHALMICS LTD

Dates

Publication Date
20260513
Application Date
20240705

Claims (20)

  1. 1. A method for treating a disease or disorder in or around the eye in an individual in need thereof, the method comprising: providing a pharmaceutical composition comprising about 0.1 wt. % to about 10 wt. % (e.g., about 0.5 wt. % to about 5 wt. %) of selenium disulfide, administering about 2 pL or less (e.g., about 0.2 pL to about 2 pL) of the pharmaceutical composition to an eyelid of the individual.
  2. 2. A method for treating a disease or disorder in or around the eye in an individual in need thereof, the method comprising: providing a pharmaceutical composition comprising about 0.1 wt. % to about 10 wt. % (e.g., about 0.5 wt. % to about 5 wt. %) of selenium disulfide, administering about 1.6 mg or less (e.g., about 0.2 mg to about 1.6 mg) of the pharmaceutical composition to an eyelid of the individual.
  3. 3. The method of any one of the preceding claims, further comprising dispensing the pharmaceutical composition from a dispensing device.
  4. 4. The method of any one of the preceding claims, further comprising applying the pharmaceutical composition onto a finger of the individual.
  5. 5. The method of any one of the preceding claims, further comprising spreading the pharmaceutical composition over at least a portion of a surface of the finger (e.g., forming a thin film).
  6. 6. The method of any one of the preceding claims, wherein the pharmaceutical composition is administered to the eyelid using the finger.
  7. 7. A method for treating a disease or disorder in or around the eye in an individual in need thereof, the method comprising: dispensing a pharmaceutical composition from a dispensing device, the pharmaceutical composition comprising an effective amount of a keratolytic agent (e.g., selenium disulfide (SeS?)); applying the pharmaceutical composition onto a finger of the individual; spreading the pharmaceutical composition over at least a portion of a surface of the finger (e.g., forming a thin film); and using the finger, administering the pharmaceutical composition to an eyelid of the individual.
  8. 8. The method of any one of the preceding claims, wherein the pharmaceutical composition is a semi-solid, wherein the semi-solid is an ointment, a gel, a cream, or a paste.
  9. 9. The method of any one of the preceding claims, wherein the pharmaceutical composition is an ointment.
  10. 10. The method of any one of the preceding claims, wherein the pharmaceutical composition further comprises an oleaginous base.
  11. 11. The method of any one of the preceding claims, wherein the pharmaceutical composition further comprises an anhydrous base.
  12. 12. The method of any one of the preceding claims, wherein the pharmaceutical composition further comprises a petrolatum.
  13. 13. The method of any one of the preceding claims, wherein the pharmaceutical composition is dispensed in a predetermined amount from the dispensing device.
  14. 14. The method of any one of the preceding claims, wherein the pharmaceutical composition is dispensed and applied onto the finger (e.g., fingertip) as a strip.
  15. 15. The method of any one of the preceding claims, wherein the pharmaceutical composition is applied onto the finger (e.g., fingertip) as a globule or droplet.
  16. 16. The method of any one of the preceding claims, wherein the pharmaceutical composition is spread by increasing the surface area of the (e.g., globule or droplet) pharmaceutical composition on the finger (e.g., fingertip).
  17. 17. The method of any one of the preceding claims, wherein the pharmaceutical composition is spread by decreasing the thickness of the (e.g., globule or droplet) pharmaceutical composition on the finger (e.g., fingertip).
  18. 18. The method of any one of the preceding claims, wherein the pharmaceutical composition is spread over the finger (e.g., fingertip) using a device (e.g., lip balm, eye liner).
  19. 19. The method of any one of the preceding claims, wherein the pharmaceutical composition is spread between two fingers (e.g., fingertips), such as a forefinger and a thumb of the individual.
  20. 20. The method of any one of the preceding claims, wherein the pharmaceutical composition is administered to an eyelid of the individual.

Description

ADMINISTRATION OF KERATOLYTICS TO OCULAR AND PERIOCULAR SURFACES CROSS REFERENCE [0001] The present application claims the benefit of U. S. Provisional Application No. 63/525,551, filed July 7, 2023, which is entirely incorporated herein by reference. BACKGROUND OF THE INVENTION [0002] Selenium sulfide (SeS2) is indicated for the treatment of dermatological condition such as seborrheic dermatitis, tinea versicolor and dandruff. It is typically used as shampoo, foam or lotion at commercially available concentrations of 1% and 2.5% and is applied for several minutes, then rinsed off. The use of SeS2 can be associated with known side effects that are listed in the drug insert and which may include irritation, burning, and on rare occasion, loss and discoloration of hair. Contact of a significant amount of preparations containing high-concentration SeS2 with mucous membranes of the eye may cause irritation (e.g., stinging) and prolonged contact (e.g., overnight application) of preparations containing SeS2 with the skin may cause local irritation. [0003] Adverse events reported following topical ocular use of SeS2 containing products include: superficial punctate keratitis, punctate keratitis, eye irritation, eye pain, eye inflammation, and (increased) lacrimation. Adverse reactions reported for administration site conditions include: instillation/application site pain and application site irritation. The adverse events can resolve upon cessation of treatment. When SeS2 is applied topically for the treatment of tinea versicolor, skin irritation may occur in the genital areas and/or folds of the skin. SeS2 lotions can also cause rebound oiliness of the scalp. AHFS Drug Information 2010. [0004] In the 1950s and early 1960s, several investigators attempted to use ophthalmic preparation of SeS2 to treat seborrheic blepharitis, typically associated with scaling at the eyelid margin and which affects many of those patients suffering from seborrheic dermatitis. These clinicians treated hundreds of patients over a course of time ranging between 1 month and 1 year using different methods including in-office application, home application, daily application, or application on alternating days. Mixed results were observed in these various studies. [0005] Different means of application were described by the investigators including from careful application in the office with rinsing of excess material as well as at-home application with complete rinsing after a short period. It was clearly stated that careful application and rinsing were important to avoid harmful effects. It was further understood that patients who developed severe reactions were improperly applying the treatment to the eye or failed to observe thorough rinsing procedures. [0006] Lavyel 1960, described the use of Selsunef® ointment, a 0.5% SeS2 ointment produced by Abbott. Selsunef® was used in the clinic in 80 subjects, where gentle and controlled application was performed by a physician who also removed the ointment after 30 min by a swab of cotton wool. Great care was always taken not to introduce any of the ointment into the conjunctival sac. In one case, where the patient administered Selsunef® to himself, contrary to medical advice, a rather severe keratitis promptly developed. SUMMARY OF THE INVENTION [0007] In certain instances, administration of a SeS2 to an ocular or periocular surface can lead to undesirable results, including poor efficacy and/or poor tolerability, such as leading to discontinued use. In some instances, high concentrations and/or high volume of a selenium sulfide leads to poor tolerability in some individuals when administered to an ocular or periocular surface. Further, in certain instances, inadequate delivery and/or poor distribution of a SeS2 to a target location on an ocular and/or periocular surface leads to poor efficacy and/or poor tolerability. In specific instances, for example, uneven or misapplied administration of a SeS2 (or composition comprising a SeS2) leads to a large droplet or globule of a pharmaceutical composition comprising a SeS2 to a highly discrete area, such as within the target area, or even outside of the target area. For example, in some instances, application of a pharmaceutical composition (e.g., ointment comprising a SeS2) to a finger or other administration surface and subsequent administration to an ocular or periocular location leads to a globule of the ointment being applied to the eyelid, which may then sit in a single location, or may even migrate to an undesired location, such as the lower fornix of the eye associated with the ocular or periocular surface to which the pharmaceutical composition was administered. In other instances, the globule can be placed by error directly on the cornea or directly into the lower fornix, or directly onto the conjunctiva. [0008] Provided in certain embodiment herein is a method for treating a disease or disorder in or around the eye in an individual in ne