Pharmaceutical composition with excellent storage stability

Patent metadata

Field	Value
Publication number	US-12396987-B2
Application number	US-201916976270-A
Country	US
Kind code	B2
Filing date	Feb 27, 2019
Priority date	Mar 1, 2018
Publication date	Aug 26, 2025
Grant date	Aug 26, 2025

Abstract

The present invention provides a composition which effectively enhances the stability of N-(2-ethylsulfonylamino-5-trifluoromethyl-3-pyridyl)cyclohexanecarboxamide or a salt thereof in a liquid composition. More specifically, the present invention provides a liquid composition comprising N-(2-ethylsulfonylamino-5-trifluoromethyl-3-pyridyl)cyclohexanecarboxamide or a salt thereof, a water-soluble additive and water.

First claim

The invention claimed is:

1. A liquid composition comprising
a compound of formula (1) or a salt thereof:

a water-soluble additive, and
water,
wherein the water-soluble additive is at least one selected from the group consisting of polyoxyethylene hydroxy fatty acid ester, poloxamer, polyoxyethylene castor oil, polyoxyethylene hardened castor oil, hydroxypropyl-β-cyclodextrin, methyl-β-cyclodextrin, hydroxypropyl-α-cyclodextrin, sulfobutyl ether-β-cyclodextrin, cysteine, sodium sulfite and sodium azide,
wherein, after storage at 40° C. for 2 weeks, a residual rate of the compound of formula (1) or a salt thereof in the composition is 90% or more by mass,
wherein the content of the compound of formula (1) or a salt thereof in the composition is 0.01 to 1 w/v %, and
wherein a mass ratio of the compound of formula (1) or a salt thereof to the water-soluble additive [compound of formula (1) or salt thereof:water-soluble additive] is 1:0.02 to 1:1,300.

2. The composition according to claim 1 , wherein the pH is 4 to 10.

3. The composition according to claim 1 , wherein the composition is an aqueous solution, and the aqueous solution does not contain a precipitate after storage at 40° C. for 2 weeks.

4. A product comprising the composition according to claim 1 filled in a vial or a syringe.

5. The composition according to claim 1 , wherein a decomposition product from the compound of formula (1) or a salt thereof is at least one selected from compounds of formulas (2) to (4):

wherein R is an optionally substituted amino group or an optionally substituted alkoxy group.

6. A method for inhibiting decomposition of the compound of formula (1) or a salt thereof according to claim 1 , the method comprising making a water-soluble additive and the compound of formula (1) or a salt thereof coexist in a liquid composition containing water, wherein the water-soluble additive is at least one selected from the group consisting of polyoxyethylene hydroxy fatty acid ester, poloxamer, polyoxyethylene castor oil, polyoxyethylene hardened castor oil, hydroxypropyl-β-cyclodextrin, methyl-β-cyclodextrin, hydroxypropyl-α-cyclodextrin, sulfobutyl ether-β-cyclodextrin, cysteine, sodium sulfite and sodium azide, wherein the content of the compound of formula (1) or a salt thereof in the composition is 0.01 to 1 w/v %, and wherein a mass ratio of the compound of formula (1) or a salt thereof to the water-soluble additive [compound of formula (1) or salt thereof:water-soluble additive] is 1:0.02 to 1:1,300.

7. A method for stabilizing a liquid composition, the method comprising making coexist a water-soluble additive, the compound of formula (1) or a salt thereof according to claim 1 and water in the liquid composition, wherein the water-soluble additive is at least one selected from the group consisting of polyoxyethylene hydroxy fatty acid ester, poloxamer, polyoxyethylene castor oil, polyoxyethylene hardened castor oil, hydroxypropyl-β-cyclodextrin, methyl-β-cyclodextrin, hydroxypropyl-α-cyclodextrin, sulfobutyl ether-β-cyclodextrin, cysteine, sodium sulfite and sodium azide, wherein the content of the compound of formula (1) or a salt thereof in the composition is 0.01 to 1 w/v %, and wherein a mass ratio of the compound of formula (1) or a salt thereof to the water-soluble additive [compound of formula (1) or salt thereof:water-soluble additive] is 1:0.02 to 1:1,300.

Assignees

• Ishihara Sangyo Kaisha
• Shizuoka Prefectural Univ Corporation

Inventors

• Onoue Satomi
• Sato Hideyuki
• Shindo Takeshi

Classifications

• A61K47/40

  Cyclodextrins; Derivatives thereof · CPC title

• A61K47/22

  Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones · CPC title

• A61K47/183

  Amino acids, e.g. glycine, EDTA or aspartame · CPC title

• A61K47/02

  Inorganic compounds · CPC title

• A61P1/18

  for pancreatic disorders, e.g. pancreatic enzymes · CPC title