# US 10,478,427 B2 · Therapeutic agent for fibrosis and inhibitor of nuclear translocation of phosphorylated smad

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- Number: US 10,478,427 B2
- Document ID: US10478427B2
- Status: Granted
- Kind: B2
- Application number: 15/641,805
- Filed: 2017-07-05
- Published: 2018-01-11
- Granted: 2019-11-19
- Earliest claimed: 2016-07-07
- Assignees: National University Corporation Chiba University
- Applicants: National University Corporation Chiba University
- Inventors: Hiroyuki Nakamura; Toshihiko Murayama
- Web page: https://patentgrep.com/patent/US10478427B2

## CPC

- A61K 31/445: Non condensed piperidines, e.g. piperocaine
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

A therapeutic agent for fibrosis, whose active ingredient is constituted by a glucosylceramide synthase inhibitor or lactosylceramide synthase inhibitor, or both, inhibits the nuclear translocation of phosphorylated Smad, thereby treating and preventing fibrosis.

## Claims

### Claim 1

A method for treating fibrosis caused by nuclear translocation of phosphorylated Smad, wherein the fibrosis is idiopathic pulmonary fibrosis, comprising administrating a therapeutic agent for the fibrosis whose active ingredient is constituted by a glucosylceramide synthase inhibitor or lactosylceramide synthase inhibitor, or both, which inhibitor has the activity of inhibiting nuclear translocation of phosphorylated Smad and is contained in a therapeutically effective amount, said inhibitor(s) being a sole inhibitor or sole inhibitors administrated during and for treatment of the fibrosis.

### Claim 2 (depends on 1)

A method according to claim 1, wherein the glucosylceramide synthase inhibitor is one or more substance(s) selected from the group consisting of 1-phenyl-2-hexadecanoyl amino-3-morpholino-1-propanol (PPM)), 1-phenyl-2-decanoyl amino-3-morpholino-1-propanol (PDMP), N-butyl deoxynojirimycin (miglustat, NB-DNJ), N-butyl deoxygalactonojirimycin (NB-DGJ), deoxynojirimycin (DNJ), and N-[(1R,2R)-1-(2,3-dihydrobenzo[b][1,4] dioxine-6-yl)-1-hydroxy-3-(pyrrolidine-1-yl) propane-2-yl] octane amide hemi-(2R,3R)-tartrate (Eliglustat tartrate).

### Claim 3 (depends on 1)

A method according to claim 1, wherein the lactosylceramide synthase inhibitor is one or more substances selected from the group consisting of N-dodecyl deoxynojirimycin, nojirimycin sulfite adduct, nojirimycin sulfite adduct hydrophobic derivative, and salts thereof.