Bone fracture repair by targeting of agents that promote bone healing

Patent metadata

Field	Value
Publication number	US-10279044-B2
Application number	US-201615578226-A
Country	US
Kind code	B2
Filing date	May 29, 2016
Priority date	May 29, 2015
Publication date	May 7, 2019
Grant date	May 7, 2019

Abstract

Aspects of the present disclosure generally relate to compounds for targeting and healing bone fractures. Some of these compounds include a negatively charged oligopeptide comprising an acidic oligopeptide, a linker, which may be hydrolyzable or may be a substrate for the protease cathepsin K, and at least one molecule that promotes bone healing. In some compounds the molecule that promotes bone healing is an anabolic compound that inhibits GSK3β, in some compounds the molecule that promotes the healing of bone fracture is a pro-inflammatory agent such as PGE1. Other embodiments include methods of treating a bone fracture comprising administering a therapeutic amount of any one of the compounds disclosed herein.

First claim

We claim:

1. A compound for treating bone fractures, comprising:
a compound of the formula X—Y—Z,

wherein:
X is at least one negatively charged oligopeptide;
Y is at least one linker; and
Z is at least one active compound comprising at least one anabolic compound, wherein the anabolic compound is 6′-bromoindirubin-3′-oxime.

2. The compound according to claim 1 , wherein X is an acidic oligopeptide.

3. The compound according to claim 2 , wherein the acidic oligopeptide comprises not less than 4 and not more than 20 amino acids.

4. The compound according to claim 3 , wherein the acidic oligopeptide comprises one or more amino acids selected from the group consisting of D-aspartic acid, L-aspartic acid, D-glutamic acid, and L-glutamic acid.

5. The compound according to claim 1 , wherein Y is a hydrolysable linker.

6. The compound according to claim 1 , wherein Y is at least one agent selected from the group consisting of an oxime-ester linkage and the molecule 11-aminoundecanoic acid.

7. The compound according to claim 1 , further comprising at least one spacer, wherein the spacer comprises at least one molecule of 8-amino-2,6-dioxaoctanoic acid.

8. The compound according to claim 1 , wherein the negatively charged oligopeptides comprises D-aspartic acid.

9. The compound according to any one of claims 1 - 8 , wherein the compound is:

10. The compound according to claim 1 , wherein the compound is:

11. A method of treating a bone fracture, comprising the steps of:
administering a therapeutic amount of the compound of claim 1 to a patient suffering from the bone fracture.

12. A kit for treating a bone fracture comprising:
at least one therapeutically effective dose of any of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

Assignees

• Purdue Research Foundation Office Of Tech Commercialization
• Univ Utah Res Found
• Kopecek Jindrich
• Yang Jiyan
• Purdue Research Foundation

Inventors

• Low Stewart Andrew
• Low Philip S
• Galliford Christopher
• Kopecek Jindrich
• Yang Jiyan

Classifications

• A61L27/22 Primary

  Polypeptides or derivatives thereof {, e.g. degradation products} · CPC title

• A61M5/002

  Packages specially adapted therefor, e.g. for syringes or needles, kits for diabetics (needle protection, e.g. caps, A61M5/3202; for sharps A61B50/3001) · CPC title

• A61P19/00

  Drugs for skeletal disorders · CPC title

• A61L2400/06

  Flowable or injectable implant compositions · CPC title

• A61L2430/02

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