Method of using dihydro-resveratrol or its stilbenoid derivatives and/or chemical variants in treatments of fibrotic and diabetic conditions

Patent metadata

Field	Value
Publication number	US-9738581-B2
Application number	US-201615351636-A
Country	US
Kind code	B2
Filing date	Nov 15, 2016
Priority date	Jun 16, 2015
Publication date	Aug 22, 2017
Grant date	Aug 22, 2017

Abstract

A polyphenol derivative of the stilbenoid family, namely trans-3,5,4′-trihydroxybibenzyl, also known as dihydro-resveratrol, is disclosed as a remedial agent. In particular, the usage of dihydro-resveratrol as an anti-fibrotic agent in suppressing the activation of pancreatic stellate cells (PSCs) is presented. One embodiment also relates to the management of pancreatic fibrosis, which is often accompanied with chronic pancreatitis and desmoplastic reaction of pancreatic cancer. Another embodiment has applications in preventing or alleviating or treating pancreatic cancer or pancreatogenic diabetes.

First claim

The invention claimed is:

1. A method for suppressing fibrotic mediator(s) in stellate cells present in an internal organ of a subject in the need by using a composition comprising a compound with a formula of

wherein
R 2 and R 4 are each independently selected from —OR 11 and —OC(O)R 11 ;
R 1 , R 3 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 are each independently selected from hydrogen, halogen, trifluoromethyl, —OR 11 and —OC(O)R 11 ; or R 2 and R 3 , or R 7 and R 8 may be taken together with the carbon atoms to which they are attached to form a cyclic group;
R 11 is independently hydrogen or selected from hydrocarbyl and heterocyclyl, either of which is optionally substituted with 1, 2, 3, 4 or 5 R 12 ;
R 12 is independently selected from halogen, trifluoromethyl, cyano, nitro, oxo, —OR 13 , —C(O)R 14 , —C(O)N(R 13 )R 14 , —C(O)OR 13 , —OC(O)R 14 , —S(O) 2 R 13 , —S(O) 2 N(R 13 )R 14 , —N(R 13 )R 14 ;
R 13 and R 14 are each independently hydrogen or selected from hydrocarbyl and heterocyclyl, either of which is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from halogen, cyano, amino, hydroxy, C 1-6 alkyl and C 1-6 alkoxy;
or an enantiomer thereof;
or a pharmaceutically acceptable salt or prodrug thereof;
or a mixture of said compound, the derivative and/or chemical variants thereof.

2. The method according to claim 1 wherein the composition is administered to a subject in need thereof with a dosage of at least 1.622 mg/kg/day wherein said composition consists of a compound

3. The method according to claim 2 wherein the said subject is human.

4. The method according to claim 2 wherein the composition is administered orally to said subject in need thereof.

5. The method according to claim 2 wherein the internal organ comprises pancreas, liver, kidney and lung.

Assignees

• Univ Hong Kong Baptist Univ

Inventors

• Zhang Hongjie
• Tsang Siu Wai
• Chen Yegao

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07C39/16

  Bis-(hydroxyphenyl) alkanes; Tris-(hydroxyphenyl)alkanes · CPC title

• A61K31/09

  having two or more such linkages · CPC title

• C07C39/21

  with at least one hydroxy group on a non-condensed ring · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title