Ursodeoxycholic acid-containing agent for treating or preventing presbyopia

Patent metadata

Field	Value
Publication number	US-11419880-B2
Application number	US-202117546895-A
Country	US
Kind code	B2
Filing date	Dec 9, 2021
Priority date	Dec 18, 2018
Publication date	Aug 23, 2022
Grant date	Aug 23, 2022

Abstract

The present disclosure provides an agent for treating or preventing eye diseases such as presbyopia, comprising, as an active ingredient, ursodeoxycholic acid or an amide conjugate of ursodeoxycholic acid, or an ester thereof, or a pharmaceutically acceptable salt thereof.

First claim

The invention claimed is:

1. A method for treating presbyopia, comprising administering to a subject in need thereof an effective amount of ursodeoxycholic acid, an amide conjugate of ursodeoxycholic acid, or an ester of ursodeoxycholic acid, or a pharmaceutically acceptable salt thereof, wherein the amide conjugate of ursodeoxycholic acid is an amide conjugate formed by dehydration condensation of the carboxyl group of ursodeoxycholic acid with an amino group of an amino compound selected from alanine, leucine, arginine, lysine, asparagine, methionine, aspartic acid, cysteine, glutamine, serine, glutamic acid, threonine, glycine, isoleucine, valine, 2-aminoadipic acid, 3-aminoadipic acid, 2-aminobutanoic acid, 4-aminobutanoic acid, 2,4-diaminobutanoic acid, 2-aminohexanoic acid, 6-aminohexanoic acid, β-alanine, 2-aminopentanoic acid, 2,3-diaminopropanoic acid, 2-aminopimelic acid, 2,6-diaminopimelic acid, cysteic acid, 2,4-diaminobutanoic acid, 2,6-diaminopimelic acid, 2,3-diaminopropanoic acid, 4-carboxyglutamic acid, homocysteine, homoserine, 5-hydroxylysine, allohydroxylysine, alloisoleucine, norleucine, norvaline, ornithine, allothreonine, and taurine; and
the ester of ursodeoxycholic acid is an ester formed by dehydration condensation of the carboxyl group of ursodeoxycholic acid with a monohydric alcohol having 1 to 6 carbon atoms.

2. The method according to claim 1 , wherein the ursodeoxycholic acid, an amide conjugate of ursodeoxycholic acid, or an ester of ursodeoxycholic acid, or a pharmaceutically acceptable salt thereof is administered ophthalmically.

3. The method according to claim 1 , wherein the ursodeoxycholic acid, an amide conjugate of ursodeoxycholic acid, or an ester of ursodeoxycholic acid, or a pharmaceutically acceptable salt thereof is administered as an eye drop or an eye ointment.

4. The method according to claim 3 , wherein the amount of ursodeoxycholic acid, an amide conjugate of ursodeoxycholic acid, or an ester of ursodeoxycholic acid, or a pharmaceutically acceptable salt thereof comprised in the eye drop or the eye ointment is 0.00001 to 10% (w/v).

5. The method according to claim 1 , wherein the amide conjugate of ursodeoxycholic acid is an amide conjugate formed by dehydration condensation of the carboxyl group of ursodeoxycholic acid with an amino group of an amino compound selected from alanine, leucine, asparagine, methionine, aspartic acid, cysteine, serine, threonine, glycine, isoleucine, valine, 2-aminobutanoic acid, β-alanine, 2-aminopentanoic acid, 2,3-diaminopropanoic acid, cysteic acid, homocysteine, homoserine, alloisoleucine, norvaline, allothreonine, and taurine.

6. The method according to claim 1 , wherein the ursodeoxycholic acid, an amide conjugate of ursodeoxycholic acid, or an ester of ursodeoxycholic acid, or a pharmaceutically acceptable salt thereof is selected from ursodeoxycholic acid, tauroursodeoxycholic acid, glycoursodeoxycholic acid, ursodeoxycholic acid methyl ester, ursodeoxycholic acid ethyl ester, ursodeoxycholic acid n-propyl ester, ursodeoxycholic acid isopropyl ester, ursodeoxycholic acid n-butyl ester, ursodeoxycholic acid isobutyl ester, ursodeoxycholic acid sec-butyl ester, ursodeoxycholic acid tert-butyl ester, ursodeoxycholic acid n-pentyl ester, ursodeoxycholic acid n-hexyl ester, and a pharmaceutically acceptable salt thereof.

7. The method according to claim 1 , wherein the ursodeoxycholic acid, an amide conjugate of ursodeoxycholic acid, or an ester of ursodeoxycholic acid, or a pharmaceutically acceptable salt thereof is selected from ursodeoxycholic acid, tauroursodeoxycholic acid, glycoursodeoxycholic acid, ursodeoxycholic acid methyl ester, ursodeoxycholic acid ethyl ester, ursodeoxycholic acid n-propyl ester, ursodeoxycholic acid isopropyl ester, and a pharmaceutically acceptable salt thereof.

8. The method according to claim 1 , wherein the ursodeoxycholic acid, an amide conjugate of ursodeoxycholic acid, or an ester of ursodeoxycholic acid, or a pharmaceutically acceptable salt thereof is ursodeoxycholic acid or a sodium salt thereof.

9. The method according to claim 3 , wherein the eye drop or the eye ointment comprises water, and an additive selected from ethyl pyruvate, sodium dihydrogenphosphate monohydrate, disodium hydrogenphosphate, hydroxypropyl methylcellulose, NaCl, and a mixture thereof.

Assignees

• Santen Pharmaceutical Co Ltd

Inventors

• Kato Masatomo
• Oda Tomoko
• Kido Kazutaka

Classifications

• A61K31/575 Primary

  substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61K9/0048

  Eye, e.g. artificial tears · CPC title

• A61P27/10

  for accommodation disorders, e.g. myopia · CPC title

• A61K47/38

  Cellulose; Derivatives thereof · CPC title