Protection and delivery of multiple therapeutic proteins

Patent metadata

Field	Value
Publication number	US-11298423-B2
Application number	US-201716080812-A
Country	US
Kind code	B2
Filing date	Mar 3, 2017
Priority date	Mar 4, 2016
Publication date	Apr 12, 2022
Grant date	Apr 12, 2022

Abstract

Compositions are provided herein comprising a coacervate of a polycationic polymer, a polyanionic polymer, and platelet-rich plasma and/or serum, or a fraction or concentrate thereof. The composition is useful in wound healing. Compositions also are provided that comprise a hydrogel comprising TIMP-3; and a complex of a polycationic polymer, a polyanionic polymer, FGF-2 and SDF-1α embedded in the hydrogel, which is useful in treating a myocardial infarction.

First claim

We claim:

1. A composition comprising a coacervate of:
a polycationic polymer,
a polyanionic polymer, and
a fraction or concentrate of platelet-rich plasma wherein platelets of platelet-rich plasma are activated to produce a fibrin clot, and wherein:
the fraction or concentrate of platelet-rich plasma comprises pure platelet-rich fibrin;
the fraction or concentrate of platelet-rich plasma comprises leukocyte-rich platelet-rich fibrin; or
the fibrin clot is removed and the protein content of the platelet-rich plasma is concentrated.

2. The composition of claim 1 , wherein the fibrin clot is removed and the protein content of the platelet-rich plasma is concentrated.

3. The composition of claim 1 , further comprising a mixture of proteins or growth factors prepared from a bodily fluid of an organism, a cell or tissue lysate, or conditioned media in which cells or a tissue is grown.

4. The composition of claim 1 , further comprising a mixture of proteins or growth factors prepared from a bodily fluid of an organism, a cell or tissue lysate, or conditioned media in which cells or a tissue is grown, wherein the cells,
tissues, or organism is genetically-modified.

5. The composition of claim 1 , wherein the polyanionic polymer is a sulfated or sulfamated polysaccharide.

6. The composition of claim 1 , wherein the ratio of the polycationic polymer to the polyanionic polymer in the composition results in a neutral charge in the coacervate.

7. A method of treating a wound in a patient, comprising administering a composition according to claim 1 at or adjacent to a wound in the patient, in an amount effective to treat a wound in a patient.

8. A method of preparing a therapeutic composition for use in treating a wound in a patient, comprising:
a. mixing a polyanionic polymer with a fraction or concentrate of platelet-rich plasma, wherein platelets of platelet-rich plasma are activated to produce a fibrin clot, and wherein:
the fraction or concentrate of platelet-rich plasma comprises pure platelet-rich fibrin;
the fraction or concentrate of platelet-rich plasma comprises leukocyte-rich platelet-rich fibrin; or
the fibrin clot is removed and the protein content of the platelet-rich plasma is concentrated; and
b. mixing a polycationic polymer with the mixture of the polyanionic polymer and the fraction or concentrate of platelet-rich plasma.

9. The method of claim 8 , wherein the polyanionic polymer is a sulfated or sulfamated polysaccharide.

10. The method of claim 8 , wherein the ratio of the polycationic polymer to the polyanionic polymer in the composition results in a neutral charge in the coacervate.

11. A medical device or wound dressing comprising a composition according to claim 1 .

12. The composition of claim 1 , wherein the polycationic polymer is a copolymer comprising a polyester backbone comprising a copolymer of ethylene glycol diglyceride and either aspartic acid or glutamic acid, and pendant arginine groups.

13. The method of claim 8 , wherein the polycationic polymer is a copolymer comprising a polyester backbone comprising a copolymer of ethylene glycol diglyceride and either aspartic acid or glutamic acid, and pendant arginine groups.

14. The composition of claim 1 , wherein the polycationic polymer is a copolymer comprising a polyester backbone comprising a copolymer of ethylene glycol diglyceride and either aspartic acid or glutamic acid, and pendant lysine groups.

15. The composition of claim 1 , wherein the polycationic polymer is poly(ethylene arginylaspartate diglyceride).

16. The composition of claim 1 , wherein the polycationic polymer is poly(ethylene lysinlyaspartate diglyceride).

17. The medical device or wound dressing of claim 11 , wherein the medical device or wound dressing is a bandage, suture, surgical mesh, limb or joint prosthesis, or a non-woven material.

18. The composition of claim 1 , wherein the fraction or concentrate of platelet-rich plasma is pure platelet-rich fibrin.

19. The composition of claim 1 , wherein the fraction or concentrate of platelet-rich plasma is leukocyte-rich platelet-rich fibrin.

20. The composition of claim 1 , wherein the polyanionic polymer is heparin or heparin sulfate.

Assignees

• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Jeffries Eric M
• Johnson Noah R
• Long Daniel
• Wang Yadong

Classifications

• A61L2430/20

  for reconstruction of the heart, e.g. heart valves · CPC title

• A61L2300/25

  Peptides having up to 20 amino acids in a defined sequence · CPC title

• A61K38/18

  Growth factors; Growth regulators · CPC title

• A61L2300/414

  Growth factors · CPC title

• A61L2300/252

  Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines · CPC title