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US-20260124171-A1 - PHARMACEUTICAL DRUG CONTAINING HETEROCYCLIDENE ACETAMIDE DERIVATIVE

US20260124171A1US 20260124171 A1US20260124171 A1US 20260124171A1US-20260124171-A1

Abstract

The invention provides a means for treating a disease involving damage of corneal epithelial cells. In particular, the invention provides a composition for use in treating a disease involving damage of corneal epithelial cells, as well as a use thereof. The composition includes (E)-2-(7-trifluoromethyl-chroman-4-ylidene)-N-(7-hydroxy-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide, a pharmaceutically acceptable salt thereof, or a solvate thereof.

Inventors

  • Takeshi Tarui
  • Shinya Kobayashi

Assignees

  • SENJU PHARMACEUTICAL CO., LTD.
  • MOCHIDA PHARMACEUTICAL CO., LTD.

Dates

Publication Date
20260507
Application Date
20251230
Priority Date
20191004

Claims (6)

  1. 1 . A method for treating a disease involving damage of corneal epithelial cells in a patient in need thereof, comprising administering an effective amount of a composition comprising about 0.1 to about 1.0 w/v % (E)-2-(7-trifluoromethylchroman-4-ylidene)-N-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)acetamide or a pharmaceutically acceptable salt or solvate thereof to the patient.
  2. 2 . The method of claim 1 , wherein (E)-2-(7-trifluoromethylchroman-4-ylidene)-N-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)acetamide is (E)-2-(7-trifluoromethylchroman-4-ylidene)-N-((7R)-7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)acetamide.
  3. 3 . The method of claim 1 , wherein the damage of corneal epithelial cells is a wound or a defect.
  4. 4 . The method of claim 1 , wherein the disease is caused by a factor selected from the group consisting of post-operative damage, drug-induced injury, lesion-induced injury, and contact-lens-use-induced injury.
  5. 5 . The method of claim 1 , wherein the composition is an eye drop.
  6. 6 . The method of claim 1 , wherein the composition is a suspension.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This patent application is a continuation of copending U.S. patent application Ser. No. 17/766,090, filed Apr. 1, 2022, which is the U.S. national phase of International Patent Application No. PCT/JP2020/037548, filed Oct. 2, 2020, which claims the benefit of Japanese Patent Application No. 2019-184053, filed on Oct. 4, 2019, which are incorporated by reference in their entireties herein. TECHNICAL FIELD The present disclosure relates to the field of pharmaceuticals, healthcare, biology, biotechnology, etc. The present disclosure particularly relates to application of a Vi/Vc zone inhibitor and/or improvement in a dry eye symptom. BACKGROUND ART It is estimated that there are at least about 8 million dry eye patients in Japan, or about 22 million patients including potential patients who use commercially available eye drops without visiting a hospital, and 1 billion or more worldwide. It is well known that modern society provides more opportunities for gazing at screens from using televisions, computers, mobile terminals, etc., so that the number of blinking has decreased, and the air has dried with use of air conditioners, etc., resulting in increased evaporation of lachrymal fluid to induce dry eye. Refractive surgeries and use of contact lens use also result in dry eye. Examples of symptoms associated with dry eye include ocular discomfort, dryness, burning sensation, irritation, and the like on the ocular surface. More severe forms of dry eye include dry eye induced by destruction of a lachrymal gland due to a disease such as an autoimmune disease such as Sjogren's syndrome and Stevens-Johnson syndrome (Non Patent Literature 1). The effect of treatments for dry eye is evaluated from external observation or evaluation (objective finding) and a subjective viewpoint of a patient such as ocular discomfort or foreign body sensation (subjective symptom). Objective finding uses the amount of lachrymal fluid and observation of a site of disorder on the keratoconjunctive epithelium as endpoints. While each of sodium hyaluronate, diquafosol sodium, and Rebamipide sold in Japan, and ciclosporin sold in the US have been approved as a prescription eye drop for dry eye, few are approved as an eye drop satisfying improvement in subjective symptoms as a primary endpoint in addition to improvement in objective finding. CITATION LIST Non Patent Literature [NPL 1] Farumashia Vol. 50 No. 3 2014:201 to 206 SUMMARY OF INVENTION Solution to Problem The present disclosure relates to a novel dry eye therapeutic agent using a heterocyclidene acetamide derivative (E)-2-(7-trifluoromethylchroman-4-ylidene)-N-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)acetamide, use thereof, a method for treatment or prevention, and the like. The present disclosure also relates to a Vi/Vc zone inhibitor using said compound, use thereof, a method for treatment or prevention, and the like. Another aspect of the present disclosure relates to a composition for the treatment and/or prevention of dry eye using a Vi/Vc zone inhibitor, use thereof, a method for treatment or prevention, and the like. The treatment of dry eye can be improvement of a subjective symptom of dry eye. Dry eye treatment can also include improvement of an objective symptom of dry eye. In the present disclosure, dry eye treatment can include improvement of both a subjective symptom and an objective symptom of dry eye. Examples of the embodiments of the present disclosure include the following. (Item 1) A composition for use in treating dry eye, comprising (E)-2-(7-trifluoromethylchroman-4-ylidene)-N-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)acetamide or a pharmaceutically acceptable salt or solvate thereof. (Item 2) The composition of the preceding item for use in improving a subjective symptom of dry eye. (Item 2A) The composition of the preceding item, wherein the dry eye is accompanied by a subjective symptom. (Item 3) The composition of y of the preceding items for suppressing ocular discomfort associated with dryness. (Item 3A) The composition of any of the preceding items, wherein the dry eye is accompanied by ocular discomfort associated with dryness. (Item 4) The composition of any of the preceding items for use in improving an objective symptom of dry eye. (Item 4A) The composition of any of the preceding items, wherein the dry eye is accompanied by an objective symptom. (Item 5) The composition of any of the preceding items for use in improving a subjective symptom and an objective symptom of dry eye. (Item 5A) The composition of any of the preceding items, wherein the dry eye is accompanied by a subjective symptom and an objective symptom. (Item 6) The composition of any of the preceding items, wherein a concentration of the (E)-2-(7-trifluoromethylchroman-4-ylidene)-N-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)acetamide or a pharmaceutically acceptable salt or solvate thereof is about 0.1 to about 1.0 w/v %. (Item 7) The com