US2013122053A1PendingUtilityA1

Synthetic triterpenoids and tricyclic-bis-enones for use in stimulating bone and cartilage growth

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Assignee: DARTMOUTH COLLEGEPriority: Nov 17, 2006Filed: Sep 24, 2012Published: May 16, 2013
Est. expiryNov 17, 2026(~0.3 yrs left)· nominal 20-yr term from priority
Inventors:Michael B. SpornKaren T. LibyTadashi HondaGregory R. MundyRoss GarrettHari ReddiGordon W. GribbleTakahiro NiikuraNanjoo Suh
A61K 38/1841A61P 19/00A61K 35/32A61K 31/277A61K 9/00A61P 19/10A61P 19/08C12N 5/0655A61K 31/26A61K 31/4164C12N 2501/999Y02A50/30
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Claims

Abstract

The present invention concerns methods for stimulating the growth and repair of bone and cartilage using synthetic triterpenoids and tricyclic-bis-enones. Examples of suitable triterpenoids include CDDO, CDDO-Me, CDDO-Im, and CDDO-Ethylamide. Examples of tricyclic-bis-enones include TBE-31 and TBE-34.

Claims

exact text as granted — not AI-modified
1 - 64 . (canceled) 
     
     
         65 . A three-dimensional matrix comprising a matrix material and a compound having the structure: 
       
         
           
           
               
               
           
         
       
       wherein,
 R 2  is —H, hydroxy, amino, cyano, halo, or substituted or unsubstituted versions of C 1 -C 15 -alkyl, C 2 -C 15 -alkenyl, C 2 -C 15 -alkynyl, C 6 -C 15 -aryl, C 7 -C 15 -aralkyl, C 1 -C 15 -heteroaryl, C 2 -C 15 -heteroaralkyl, C 1 -C 15 -acyl, C 1 -C 15 -alkoxy, C 2 -C 15 -alkenyloxy, C 2 -C 15 -alkynyloxy, C 6 -C 15 -aryloxy, C 7 -C 15 -aralkoxy, C 1 -C 15 -heteroaryloxy, C 2 -C 15 -heteroaralkoxy, C 1 -C 15 -acyloxy, C 1 -C 15 -alkylamino, C 2 -C 15 -alkenylamino, C 2 -C 15 -alkynylamino, C 6 -C 15 -aryl amino, C 7 -C 15 -aralkylamino, C 1 -C 15 -heteroaryl amino, C 2 -C 15 -heteroaralkylamino, or C 2 -C 15 -amido; 
 R 7  is —H, hydroxy, amino, cyano, halo, or substituted or unsubstituted versions of C 1 -C 15 -alkyl, C 2 -C 15 -alkenyl, C 2 -C 15 -alkynyl, C 7 -C 15 -aralkyl, C 2 -C 15 -heteroaralkyl, C 1 -C 15 -acyl, C 1 -C 15 -alkoxy, C 2 -C 15 -alkenyloxy, C 2 -C 15 -alkynyloxy, C 6 -C 15 -aryloxy, C 7 -C 15 -aralkoxy, C 1 -C 15 -heteroaryloxy, C 2 -C 15 -heteroaralkoxy, C 1 -C 15 -acyloxy, C 1 -C 15 -alkylamino, C 2 -C 15 -alkenylamino, C 2 -C 15 -alkynylamino, C 6 -C 15 -aryl amino, C 7 -C 15 -aralkylamino, C 1 -C 15 -heteroaryl amino, C 2 -C 15 -heteroaralkylamino, or C 2 -C 15 -amido, or 
 a pharmaceutically acceptable salt or tautomer thereof. 
 
     
     
         66 . The three-dimensional matrix of  claim 65 , wherein the three-dimensional matrix comprises an orthopedic implant, interface, artificial joint, or dental implant. 
     
     
         67 . The three-dimensional matrix of  claim 66 , wherein the compound is coated on the surface of the orthopedic implant, interface or artificial joint. 
     
     
         68 . The three-dimensional matrix of  claim 65 , further comprising a bone-producing, cartilage-producing or osteochondrogenic cell. 
     
     
         69 . The three-dimensional matrix of  claim 65 , wherein the matrix material comprises an alginate gel, collagen gel, fibrin gel, polylactic acid, polyglycolic acid, poly(lactide-co-glycolide), hydroxyapatite, devitalized animal bone, devitalized human bone, or a porous ceramic structure. 
     
     
         70 . The three-dimensional matrix of  claim 65 , further comprising a bone or cartilage growth factor. 
     
     
         71 . A hydrogel comprising an organic polymer and a compound having the structure: 
       
         
           
           
               
               
           
         
       
       wherein,
 R 2  is —H, hydroxy, amino, cyano, halo, or substituted or unsubstituted versions of C 1 -C 15 -alkyl, C 2 -C 15 -alkenyl, C 2 -C 15 -alkynyl, C 6 -C 15 -aryl, C 7 -C 15 -aralkyl, C 1 -C 15 -heteroaryl, C 2 -C 15 -heteroaralkyl, C 1 -C 15 -acyl, C 1 -C 15 -alkoxy, C 2 -C 15 -alkenyloxy, C 2 -C 15 -alkynyloxy, C 6 -C 15 -aryloxy, C 7 -C 15 -aralkoxy, C 1 -C 15 -heteroaryloxy, C 2 -C 15 -heteroaralkoxy, C 1 -C 15 -acyloxy, C 1 -C 15 -alkylamino, C 2 -C 15 -alkenylamino, C 2 -C 15 -alkynylamino, C 6 -C 15 -aryl amino, C 7 -C 15 -aralkylamino, C 1 -C 15 -heteroaryl amino, C 2 -C 15 -heteroaralkylamino, or C 2 -C 15 -amido; 
 R 7  is —H, hydroxy, amino, cyano, halo, or substituted or unsubstituted versions of C 1 -C 15 -alkyl, C 2 -C 15 -alkenyl, C 2 -C 15 -alkynyl, C 7 -C 15 -aralkyl, C 2 -C 15 -heteroaralkyl, C 1 -C 15 -acyl, C 1 -C 15 -alkoxy C 2 -C 15 -alkenyloxy, C 2 -C 15 -alkynyloxy, C 6 -C 15 -aryloxy, C 7 -C 15 -aralkoxy, C 1 -C 15 -heteroaryloxy, C 2 -C 15 -heteroaralkoxy, C 1 -C 15 -acyloxy, C 1 -C 15 -alkylamino, C 2 -C 15 -alkenylamino, C 2 -C 15 -alkynylamino, C 6 -C 15 -aryl amino, C 7 -C 15 -aralkylamino, C 1 -C 15 -heteroaryl amino, C 2 -C 15 -heteroaralkylamino, or C 2 -C 15 -amido, or 
 a pharmaceutically acceptable salt or tautomer thereof. 
 
     
     
         72 . The hydrogel of  claim 71 , further comprising a bone-producing, cartilage-producing or osteochondrogenic cell. 
     
     
         73 . The hydrogel of  claim 71 , wherein the polymer comprises a polysaccharide, polyphosphazene, polyacrylate, block copolymer, or protein. 
     
     
         74 . The hydrogel of  claim 71 , further comprising a bone or cartilage growth factor. 
     
     
         75 . A medium for ex vivo culturing of bone and cartilage cells comprising a serum free culture medium that supports growth and differentiation of a bone-producing, cartilage-producing or osteochondrogenic cell and a compound having the structure: 
       
         
           
           
               
               
           
         
       
       wherein,
 R 2  is —H, hydroxy, amino, cyano, halo, or substituted or unsubstituted versions of C 1 -C 15 -alkyl, C 2 -C 15 -alkenyl, C 2 -C 15 -alkynyl, C 6 -C 15 -aryl, C 7 -C 15 -aralkyl, C 1 -C 15 -heteroaryl, C 2 -C 15 -heteroaralkyl, C 1 -C 15 -acyl, C 1 -C 15 -alkoxy, C 2 -C 15 -alkenyloxy, C 2 -C 15 -alkynyloxy, C 6 -C 15 -aryloxy, C 7 -C 15 -aralkoxy, C 1 -C 15 -heteroaryloxy, C 2 -C 15 -heteroaralkoxy, C 1 -C 15 -acyloxy, C 1 -C 15 -alkylamino, C 2 -C 15 -alkenylamino, C 2 -C 15 -alkynylamino, C 6 -C 15 -aryl amino, C 7 -C 15 -aralkylamino, C 1 -C 15 -heteroaryl amino, C 2 -C 15 -heteroaralkylamino, or C 2 -C 15 -amido; 
 R 7  is —H, hydroxy, amino, cyano, halo, or substituted or unsubstituted versions of C 1 -C 15 -alkyl, C 2 -C 15 -alkenyl, C 2 -C 15 -alkynyl, C 7 -C 15 -aralkyl, C 2 -C 15 -heteroaralkyl, C 1 -C 15 -acyl, C 1 -C 15 -alkoxy, C 2 -C 15 -alkenyloxy, C 2 -C 15 -alkynyloxy, C 6 -C 15 -aryloxy, C 7 -C 15 -aralkoxy, C 1 -C 15 -heteroaryloxy, C 2 -C 15 -heteroaralkoxy, C 1 -C 15 -acyloxy, C 1 -C 15 -alkylamino, C 2 -C 15 -alkenylamino, C 2 -C 15 -alkynylamino, C 6 -C 15 -aryl amino, C 7 -C 15 -aralkylamino, C 1 -C 15 -heteroaryl amino, C 2 -C 15 -heteroaralkylamino, or C 2 -C 15 -amido, or 
 a pharmaceutically acceptable salt or tautomer thereof. 
 
     
     
         76 . The medium of  claim 75 , further comprising one or more of albumin, a soluble carrier-fatty acid complex, an iron source, or insulin growth factor. 
     
     
         77 . The medium of  claim 75 , further comprising a bone or cartilage growth factor.

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