Bone fracture repair by targeting of agents that promote bone healing

Patent metadata

Field	Value
Publication number	US-10744203-B2
Application number	US-201916264364-A
Country	US
Kind code	B2
Filing date	Jan 31, 2019
Priority date	May 29, 2015
Publication date	Aug 18, 2020
Grant date	Aug 18, 2020

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 a negatively charged oligopeptide;
Y is a linker; and
Z is an active compound selected from prostaglandin E1 or prostaglandin E2.

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 10 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 a linker comprising at least one molecule of 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-3,6-dioxaoctanoic acid.

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

9. The compound according to claim 1 , comprising the following formula:

wherein:
X 1 and X 2 are either branched or linear negatively charged oligopeptides which may or may not be identical to one another;
Y is a linker; and
W is at least one group comprising at least one amino acid.

10. The compound according to claim 9 , wherein W is at least one lysine.

Assignees

• Purdue Research Foundation
• Univ Utah Res Found
• Univ Utah

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

• A61K31/404

  Indoles, e.g. pindolol · CPC title

• A61P19/00

  Drugs for skeletal disorders · CPC title

• A61L27/54

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

• C07K7/08

  having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) · CPC title