Enhanced osteogenic activity of daidzein analogs on human mesenchymal stem cells

Patent metadata

Field	Value
Publication number	US-11098053-B2
Application number	US-201414781494-A
Country	US
Kind code	B2
Filing date	Apr 4, 2014
Priority date	Apr 4, 2013
Publication date	Aug 24, 2021
Grant date	Aug 24, 2021

Abstract

Disclosed are daidzein analogs having the formula (I). Also disclosed are compositions, include a disclosed daidzein analogs, methods of preventing or treating bone disease or bone injury and/or stimulating bone growth, in a subject that include administering to the subject an effective amount of disclosed daidzein analog. Disclosed are isolated mesenchymal stem cell that has been altered by treatment a disclosed daidzein analog, daidzein, glycinol, glyceollin I, or glyceollin II, to increase the osteogenic potential of the mesenchymal stem cells.

First claim

We claim:

1. A compound, having the formula:

wherein
R 1 is OR 9 , and wherein the R 9 is hydrogen;
R 2 is hydrogen;
R 3 is n-propyl, isobutyl, cyclopentyl, n-hexyl, propyne, or 2-(Piperdin-1-yl)ethyl;
R 4 is hydrogen;
R 5 is one or more of hydrogen, oxygen, or OR 10 , wherein R 10 is hydrogen or alkyl having one to four carbons, and when R 5 is oxygen, R 3 is 2-(Piperdin-1-yl)ethyl.

2. The compound of claim 1 , wherein R 5 is oxygen or two hydrogens.

3. The compound of claim 1 , wherein the compound is 3-(4-Hydroxyphenyl)-7-(2-(piperidin-1-yl)ethoxy)-4H-chromen-4-one.

4. A composition, comprising the compound of claim 1 , and a pharmaceutically acceptable carrier.

5. The composition of claim 4 , wherein the composition is formulated for oral, intravenous, intradermal, intramuscular, and subcutaneous administration.

6. The composition of claim 5 , wherein the composition comprises a product for oral delivery comprising a concentrate, a dried powder, a liquid, a capsule, a pellet, and a pill.

7. The composition of claim 4 , further comprising mesenchymal stem cells, wherein in the mesenchymal stem cells have optionally been pretreated with the compound of claim 1 , daidzein, glycinol, glyceollin I, glyceollin II, or any combination thereof.

8. A method of preventing or treating a bone defect in a subject, comprising:
administering to the subject an effective amount of the compound of claim 1 to a subject, thereby preventing or treating bone disease or bone injury.

9. The method of claim 8 , wherein the subject has or is believed to have osteoporosis, has been diagnosed as having osteoporosis, and/or has a bone fracture.

10. A method of stimulating bone growth in a subject, comprising:
administering to the subject an effective amount of the compound of claim 1 to a subject, thereby stimulating bone growth.

Assignees

• The Administrators Of The Tulane Educational Fund
• Xavier Univ Of Louisiana
• Us Agriculture

Inventors

• Strong Amy
• Boue Stephen
• Burow Matthew
• Bunnell Bruce
• Jiang Quan
• Zheng Shilong
• Wang Guangdi

Classifications

• A61K31/352

  condensed with carbocyclic rings, e.g. methantheline  {(cannabinoids A61K31/658)} · CPC title

• C07D311/36

  not hydrogenated in the hetero ring, e.g. isoflavones · CPC title

• A61L2300/412

  Tissue-regenerating or healing or proliferative agents · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title

• A61L2430/02

  for reconstruction of bones; weight-bearing implants · CPC title