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KR-102961961-B1 - Method and composition for the treatment of presbyopia, pupil dilation, and other eye disorders

KR102961961B1KR 102961961 B1KR102961961 B1KR 102961961B1KR-102961961-B1

Abstract

The present invention provides a method, a composition, and a kit containing an alpha-adrenergic antagonist, such as phentolamine, for use in monotherapy or as part of combination therapy to treat patients suffering from presbyopia, mydriasis, and/or other ocular disorders.

Inventors

  • 피틀릭, 윌리엄 에이치.
  • 메이어, 알랜 알.
  • 수치, 미나
  • 카리자니스, 콘스탄티노스
  • 호프만, 버나드

Assignees

  • 오큐파이어 파마, 인크.

Dates

Publication Date
20260511
Application Date
20191025
Priority Date
20181026

Claims (20)

  1. A pharmaceutical composition for treating presbyopia comprising phentolamine mesylate, wherein the pharmaceutical composition is intended to administer a dose of phentolamine mesylate in an amount of 0.2 mg to 0.7 mg to the eye of a patient requiring treatment for presbyopia, the dose is in the form of eye drops, and the dose is administered to the eye only once a day, and the pharmaceutical composition is used in combination with an additional agent selected from pilocarpine and pharmaceutically acceptable salts thereof, and the additional agent is administered to the eye of the patient in an amount ranging from 0.1 mg to 1.0 mg.
  2. A pharmaceutical composition according to claim 1, administered at or near the patient's bedtime.
  3. A pharmaceutical composition according to claim 1, containing phentolamine mesylate in a dosage of 0.25 mg.
  4. A pharmaceutical composition according to claim 1, containing phentolamine mesylate in a dosage of 0.4 mg to 0.6 mg.
  5. A pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is a 1% (w/w) phentolamine mesylate solution and is administered as one eye drop containing the pharmaceutical composition in an amount of 0.03 mL to 0.05 mL.
  6. A pharmaceutical composition comprising phentolamine mesylate for treating presbyopia while minimizing eye redness during the patient's waking hours, wherein the pharmaceutical composition is intended to administer a dose of phentolamine mesylate in an amount of 0.2 mg to 0.7 mg to the eye of a patient requiring treatment of presbyopia while minimizing eye redness during the patient's waking hours, wherein the dose is administered to the patient's eye only at or near the patient's bedtime, and the dose is in the form of eye drops, wherein the pharmaceutical composition is used in combination with an additional agent selected from pilocarpine and its pharmaceutically acceptable salts, and the additional agent is administered to the patient's eye in an amount ranging from 0.1 mg to 1.0 mg.
  7. A pharmaceutical composition according to claim 6, containing phentolamine mesylate at a dosage of 0.25 mg.
  8. A pharmaceutical composition according to claim 6, containing phentolamine mesylate in a dosage of 0.4 mg to 0.6 mg.
  9. A pharmaceutical composition according to claim 6, wherein the pharmaceutical composition is a 1% (w/w) phentolamine mesylate solution and is administered as one eye drop containing the pharmaceutical composition in an amount of 0.03 mL to 0.05 mL.
  10. A pharmaceutical composition according to claim 1, wherein the additional agent is pilocarpine hydrochloride.
  11. A pharmaceutical composition according to claim 5, wherein the additional agent is pilocarpine hydrochloride.
  12. A pharmaceutical composition according to claim 6, wherein the additional agent is pilocarpine hydrochloride.
  13. A pharmaceutical composition according to claim 9, wherein the additional agent is pilocarpine hydrochloride.
  14. A pharmaceutical composition according to claim 1, wherein an additional preparation is administered to the patient's eye in an amount ranging from 0.1 mg to 0.5 mg.
  15. A pharmaceutical composition according to claim 5, wherein an additional preparation is administered to the patient's eye in an amount ranging from 0.1 mg to 0.5 mg.
  16. A pharmaceutical composition according to claim 6, wherein an additional preparation is administered to the patient's eye in an amount ranging from 0.1 mg to 0.5 mg.
  17. A pharmaceutical composition according to claim 9, wherein an additional preparation is administered to the patient's eye in an amount ranging from 0.1 mg to 0.5 mg.
  18. A pharmaceutical composition according to claim 10, wherein an additional preparation is administered to the patient's eye in an amount ranging from 0.1 mg to 0.5 mg.
  19. A pharmaceutical composition according to claim 11, wherein an additional preparation is administered to the patient's eye in an amount ranging from 0.1 mg to 0.5 mg.
  20. A pharmaceutical composition according to claim 1, wherein an additional preparation is administered to the patient's eye in an amount ranging from 0.125 mg to 0.25 mg.

Description

Method and composition for the treatment of presbyopia, pupil dilation, and other eye disorders Cross-reference of related applications This application claims the benefit and priority of U.S. provisional patent application serial number 62/751,391 filed on October 26, 2018; the contents thereof are incorporated by reference in their entirety. Field of invention The present invention provides a method, composition, and kit containing an alpha-adrenergic antagonist, e.g., phentolamine, for use as a monotherapy or as part of a combination therapy to treat patients suffering from presbyopia, mydriasis, and/or other ocular disorders. Presbyopia is an age-related eye disorder characterized by an inability to focus on surrounding objects. It is generally caused by the hardening of the eye's lens, which reduces its ability to bend. People often first notice the effects of presbyopia around the age of 40, and these effects become increasingly pronounced over the following 20 years. The impact of presbyopia can have a significant negative effect on quality of life, for example, by interfering with activities related to reading. Conventional treatments for presbyopia are ineffective and/or undesirable for all patients. Common treatments for presbyopia involve the use of corrective lenses (e.g., reading glasses or bifocals), which patients must carry. Additionally, bifocal or multifocal lenses, including contact lenses, can be difficult to use, particularly when performing tasks that require frequent switching between viewing near and far objects. Monovision treatment approaches, where one eye is optimized for distance vision and lenses or surgical methods compensate for presbyopia in the other eye, can impair depth perception and cause disorientation. Surgical approaches, such as LASIK and corneal inlays, also carry all the risks inherent in surgical procedures. Despite ongoing research, there are currently no non-invasive pharmacological treatments for presbyopia approved by the U.S. Food and Drug Administration (FDA) as safe and effective. Mydriasis is an eye disorder characterized by an abnormally dilated pupil, often caused by one or more of disease, trauma, or pharmacological agents. Pharmacological agents may be preparations administered to the eye to induce pupil dilation, for example, as part of an eye examination. Alternatively, pharmacological agents may be preparations administered to the patient for other reasons, and may be administered as a single dose or multiple doses. Negative effects of mydriasis may include sensitivity to light and an inability to focus, particularly in bright environments. Existing treatments for mydriasis vary based on the cause of the condition but are ineffective and/or undesirable for all patients. One treatment for mydriasis described in the literature is REV-EYES™ (dapiprazole hydrochloride ophthalmic solution). A typical administration protocol for REV-EYES™ involves administering two drops of the ophthalmic solution to the patient's eye, followed by an additional two drops of the solution five minutes later. Some drawbacks of REV-EYES™ have been reported to cause a significant burning sensation upon administration, as well as severe eye redness, which is unpleasant for patients. A better treatment for pupil dilation is needed. The present invention addresses the aforementioned need for a method and composition for treating patients suffering from presbyopia, pupil dilation, and other ocular disorders while minimizing undesirable side effects, and the present invention provides other related advantages. Figure 1 illustrates exemplary eye redness measured according to (1) the CCLRU Redness Grading Scale and (2) the NYX-OOl Redness Grading Scale. Figure 2 is a graph showing the change in pupil diameter observed in the clinical study described in Example 5. Figure 3 is a graph showing the observed eye redness in the clinical study described in Example 5. The present invention provides a method, composition, and kit containing an alpha-adrenergic antagonist, e.g., phentolamine, for use as a monotherapy or as part of a combination therapy to treat patients suffering from presbyopia, mydriasis, and/or other ocular disorders. The alpha-adrenergic antagonist, e.g., phentolamine, is administered topically to the patient's eye, preferably in the form of a liquid aqueous ophthalmic formulation. Preferably, the alpha-adrenergic antagonist is administered to the patient once daily, either alone or in combination with additional agents, to reduce the patient's pupil diameter, e.g., to a pupil diameter of less than 2 mm, 1.8 mm, or 1.6 mm, or to a pupil diameter reduction of at least 1 mm, 2 mm, 3 mm, or more. In a specific embodiment, an alpha-adrenergic antagonist is administered to a patient once daily, either alone or in combination with an additional agent, to reduce the patient's pupil diameter, e.g., to a pupil diameter of less than 3.0, 2.8, 2.6, 2.4, or 2.2 mm. The reduction in p