US2021077505A1PendingUtilityA1

Method to enhance tissue regeneration

63
Assignee: CHILDRENS MEDICAL CENTERPriority: Oct 20, 2006Filed: Jun 30, 2020Published: Mar 18, 2021
Est. expiryOct 20, 2026(~0.2 yrs left)· nominal 20-yr term from priority
Inventors:Leonard I. ZonTrista E. NorthWolfram Goessling
A61P 7/00A61K 45/06A61K 31/404A61K 31/41A61K 31/201A61K 31/5575A61K 31/557A61P 17/00A61P 19/00A61K 31/655A61P 9/00A61P 35/00A61P 1/16A61P 43/00A61K 33/14A61K 31/558A61P 1/00A61K 31/5585
63
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Claims

Abstract

The present invention provides for compositions and methods for modulating tissue growth using tissue growth modulators, which are agents that either enhance or inhibit tissue growth as desired by a particular indication by modulating the PG or Wnt signaling pathways, or employing modulators of both PG and Wnt signaling pathways for a synergistic effect or highly selective effect.

Claims

exact text as granted — not AI-modified
1 - 3 . (canceled) 
     
     
         4 . A pharmaceutical composition comprising at least one prostaglandin signaling pathway activator and a wnt pathway activator, wherein the at least one prostaglandin signaling pathway activator is a PGE 2  receptor agonist. 
     
     
         5 . The composition of  claim 4 , wherein the at least one PGE 2  receptor agonist comprises at least one prostaglandin signaling pathway activator selected from the group consisting of: PGE2, PGI 2 , 16-phenyl tetranor PGE 2 , 16,16-dimethyl PGE 2 , 19(R)-hydroxy PGE 2 , 16,16-dimethyl PGE 2  p-(p-acetamidobenzamido) phenyl ester, 9-deoxy-9-methylene-16,16-dimethyl PGE 2 , PGE 2  methyl ester, Butaprost, 15(S)-15-methyl PGE 2 , 15(R)-15-methyl PGE 2 , 20-hydroxy PGE 2 , 11-deoxy-16,16-dimethyl PGE 2 , 9-deoxy-9-methylene PGE 2 , PGE serinol amide, and Sulprostone. 
     
     
         6 . The composition of  claim 4 , wherein the wnt pathway activator is selected from the group consisting of a GSK-3 inhibitor and a soluble Wnt ligand. 
     
     
         7 . The composition of  claim 5 , wherein the wnt pathway activator is selected from the group consisting of a GSK-3 inhibitor and a soluble Wnt ligand. 
     
     
         8 . The composition of  claim 6 , wherein the GSK-3 inhibitor is LiCl or 6-bromoindirubin-3′-oxime (BIO). 
     
     
         9 . The composition of  claim 7 , wherein the GSK-3 inhibitor is LiCl or 6-bromoindirubin-3′-oxime (BIO). 
     
     
         10 . The composition of  claim 6 , wherein the soluble Wnt ligand is Wnt2b, Wnt3, or Wnt8. 
     
     
         11 . The composition of  claim 7 , wherein the soluble Wnt ligand is Wnt2b, Wnt3, or Wnt8. 
     
     
         12 . A pharmaceutical composition comprising at least one prostaglandin signaling pathway activator or a downstream mediator of the prostaglandin signaling pathway, and a wnt pathway activator;
 wherein the at least one prostaglandin signaling pathway activator is a PGE 2  receptor agonist;   wherein the downstream mediator of the prostaglandin signaling pathway is selected from the group consisting of: Forskolin, 8-bromo-cAMP, Sp-5,6,-DCI-cBiMPS, Bapta-AM, Fendiline, Nicardipine, Nifedipine, Pimozide, Strophanthidin, and Lanatoside; and   wherein the wnt pathway activator is selected from the group consisting of a GSK-3 inhibitor and a soluble Wnt ligand.   
     
     
         13 . The pharmaceutical composition of  claim 12 , wherein the PGE 2  receptor agonist comprises at least one prostaglandin signaling pathway activator selected from the group consisting of: PGE 2 , PGI 2 , 16-phenyl tetranor PGE 2 , 16,16-dimethyl PGE 2 , 19(R)-hydroxy PGE 2 , 16,16-dimethyl PGE 2  p-(p-acetamidobenzamido) phenyl ester, 9-deoxy-9-methylene-16,16-dimethyl PGE 2 , PGE 2  methyl ester, Butaprost, 15(S)-15-methyl PGE 2 , 15(R)-15-methyl PGE 2 , 20-hydroxy PGE 2 , 11-deoxy-16,16-dimethyl PGE 2 , 9-deoxy-9-methylene PGE 2 , PGE serinol amide, and Sulprostone. 
     
     
         14 . A method for promoting tissue growth or regeneration, comprising:
 contacting a tissue with at least one prostaglandin signaling pathway activator or a downstream mediator of the prostaglandin signaling pathway, and a wnt pathway activator;   wherein the at least one prostaglandin signaling pathway activator is a PGE 2  receptor agonist;   wherein the downstream mediator of the prostaglandin signaling pathway is selected from the group consisting of: Forskolin, 8-bromo-cAMP, Sp-5,6,-DCI-cBiMPS, Bapta-AM, Fendiline, Nicardipine, Nifedipine, Pimozide, Strophanthidin, and Lanatoside; and   wherein the wnt pathway activator is selected from the group consisting of a GSK-3 inhibitor and a soluble Wnt ligand.   
     
     
         15 . A method for promoting tissue growth or regeneration, comprising:
 contacting a tissue the tissue with a prostaglandin signaling pathway activator, and a wnt pathway activator;   wherein the prostaglandin signaling pathway activator is a PGE 2  receptor agonist; and   wherein the wnt pathway activator is selected from the group consisting of a GSK-3 inhibitor and a soluble Wnt ligand.   
     
     
         16 . The method of  claim 15 , wherein the PGE 2  receptor agonist is selected from the group consisting of: PGE 2 , PGI 2 , 16-phenyl tetranor PGE 2 , 16,16-dimethyl PGE 2 , 19(R)-hydroxy PGE 2 , 16,16-dimethyl PGE 2  p-(p-acetamidobenzamido) phenyl ester, 0-deoxy-9-methylene-16,16-dimethyl PGE 2 , PGE 2  methyl ester, Butraprost, 15(S)-15-methyl PGE 2 , 15(R)-15-methyl PGE 2 , 20-hydroxy PGE 2 , 11-deoxy-16,16-dimethyl PGE 2 , 9-deoxy-9-methylene PGE 2 , PGE 2  serinol amide, and Sulprostone. 
     
     
         17 . The method of  claim 14 , wherein the prostaglandin signaling pathway activator is selected from the group consisting of: PGE 2  and 16,16-dimethyl PGE 2 . 
     
     
         18 . The method of  claim 14 , wherein the GSK-3 inhibitor is LiCl or 6-bromoindirubin-3′-oxime (BIO). 
     
     
         19 . The method of  claim 15 , wherein the GSK-3 inhibitor is LiCl or 6-bromoindirubin-3′-oxime (BIO). 
     
     
         20 . The method of  claim 14 , wherein the soluble Wnt ligand is Wnt2b, Wnt3, or Wnt8. 
     
     
         21 . The method of  claim 15 , wherein the soluble Wnt ligand is Wnt2b, Wnt3, or Wnt8. 
     
     
         22 . The method of  claim 14 , wherein the tissue is selected from the group consisting of liver tissue, myocardial tissue, bone tissue, and skin tissue. 
     
     
         23 . The method of  claim 14 , wherein the tissue is a non-cancerous tissue. 
     
     
         24 . The method of  claim 14 , wherein the contact is ex vivo or in vivo.

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