Megalin antagonist

Patent metadata

Field	Value
Publication number	US-10420741-B2
Application number	US-201615216225-A
Country	US
Kind code	B2
Filing date	Jul 21, 2016
Priority date	Jan 24, 2014
Publication date	Sep 24, 2019
Grant date	Sep 24, 2019

Abstract

The present invention includes cilastatin or a pharmaceutically acceptable salt thereof as an active component and a suppressant for renal impairment or inner ear disorders, induced via megalin by at least one megalin ligand which is selected from the group consisting of polymyxins, aminoglycoside antibiotics, glycopeptide antibiotics, cisplatin, and pharmaceutically acceptable salts thereof.

First claim

The invention claimed is:

1. A formulation which combines cilastatin or a pharmaceutically acceptable salt thereof with at least one active component which is selected from the group consisting of colistin, colistin methanesulfonate, and pharmaceutically acceptable salts thereof,
wherein an amount of the cilastatin or the pharmaceutically acceptable salt thereof is 0.5 parts by mass to 100 parts by mass with respect to 1 part by mass of the active component, and
the combined formulation is for use simultaneously, separately, or at time intervals.

2. A pharmaceutical composition, comprising:
cilastatin or a pharmaceutically acceptable salt thereof;
at least one active component which is selected from the group consisting of colistin, colistin methanesulfonate, and pharmaceutically acceptable salts thereof; and
a pharmaceutically acceptable carrier,
wherein the cilastatin or the pharmaceutically acceptable salt thereof is included in an amount of 0.5 parts by mass to 100 parts by mass with respect to 1 part by mass of the active component.

3. An anti-microbial agent, comprising:
cilastatin or a pharmaceutically acceptable salt thereof;
at least one active component which is selected from the group consisting of colistin, colistin methanesulfonate, and pharmaceutically acceptable salts thereof; and
a pharmaceutically acceptable carrier,
wherein the cilastatin or the pharmaceutically acceptable salt thereof is included in an amount of 0.5 parts by mass to 100 parts by mass with respect to 1 part by mass of the active component.

4. The anti-microbial agent according to claim 3 ,
wherein the cilastatin or the pharmaceutically acceptable salt thereof is included in an amount of 1.5 parts by mass to 3 parts by mass with respect to 1 part by mass of the active component.

5. A pharmaceutical kit, comprising:
cilastatin or a pharmaceutically acceptable salt thereof in a first compartment; and
at least one megalin ligand which is selected from the group consisting of colistin, colistin methanesulfonate, and pharmaceutically acceptable salts thereof in a second compartment,
wherein the first compartment contains 0.5 parts by mass to 100 parts by mass of the cilastatin or the pharmaceutically acceptable salt thereof with respect to 1 parts by mass of the megalin ligand in the second compartment.

6. A method for treating or preventing infections caused by at least one multidrug-resistant Gram-negative bacteria selected from the group consisting of Pseudomonas aeruginosa, Acinetobacter spp., Escherichia coli, Citrobacter spp., Enterobacter spp., and Klebsiela spp., the method comprising:
administering to a subject in need thereof a therapeutically effective amount of cilastatin or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of colistin, colistin methanesulfonate, or pharmaceutically acceptable salts thereof,
wherein 0.5 parts by mass to 100 parts by mass of the cilastatin or the pharmaceutically acceptable salt thereof is administered with respect to 1 part by mass of the colistin, the colistin methanesulfonate, or the pharmaceutically acceptable salts thereof.

7. The pharmaceutical composition according to claim 2 , wherein the cilastatin or the pharmaceutically acceptable salt thereof is included in an amount of from 0.1 mass % to 1 mass %.

8. The pharmaceutical composition according to claim 2 , wherein the pharmaceutically acceptable carrier comprises at least one selected from the group consisting of distilled water, a lidocaine hydrochloride solution, saline, a glucose aqueous solution, ethanol, polyethylene glycol, propylene glycol, an aqueous solution of citric acid, an aqueous solution of sodium citrate, and an electrolyte solution.

9. The method according to claim 6 , wherein the at least one multidrug-resistant Gram-negative bacteria includes multidrug-resistant Pseudomonas aeruginosa.

10. The method according to claim 6 , wherein the at least one multidrug-resistant Gram-negative bacteria includes multidrug-resistant Acinetobacter spp.

11. The method according to claim 6 , wherein the at least one multidrug-resistant Gram-negative bacteria includes multidrug-resistant Klebsiella spp.

Assignees

• Ea Pharma Co Ltd
• Univ Niigata

Inventors

• Saito Akihiko
• Aoki Nobumasa
• Hori Yoshihisa
• Kuwahara Shoji
• Hosojima Michihiro
• Iwata Hiroshi
• Matsuda Saori

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P27/16

  Otologicals · CPC title

• A61P13/12

  of the kidneys · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title