Preparations containing hepatocyte growth factor and hyaluronic acid and methods of making and using same

• US 9,511,119 B2
• Filed: 03/14/2014
• Issued: 12/06/2016
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: Prime Merger Sub LLC (Alight, Inc.)
• Original Assignee: NuTech Spine, Inc.
• Inventors: Walthall, Howard P. Jr.
• Primary Examiner(s): Allen, Marianne P
• Application Number:
  US14/211,929
• Publication Number:
  US 20140274899A1
• Time in Patent Office: 998 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2800/91 Injection
• CPC Class Codes: A61K 38/1833 Hepatocyte growth factor; Scatter factor; Tumor cytotoxic factor II
• CPC Class Codes: A61K 8/64 Proteins; Peptides; Derivatives or degradation products thereof
• CPC Class Codes: A61K 8/735 Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 2430/06 for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 2430/10 for reconstruction of tendons or ligaments
• CPC Class Codes: A61L 2430/24 for joint reconstruction
• CPC Class Codes: A61L 2430/32 for nerve reconstruction
• CPC Class Codes: A61L 2430/34 for soft tissue reconstruction
• CPC Class Codes: A61L 2430/38 for reconstruction of the spine, vertebrae or intervertebral discs
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61Q 19/08 Anti-ageing preparations
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

Preparations containing hepatocyte growth factor (HGF) and hyaluronic acid (HA) and methods of making and using same. The HGF and HA preparations can be prepared together in solution as an injectable fluid without gelatinization, or impregnated within a porous hydrophilic matrix material with, or without, cross-linking of the HA with the matrix material. The preparations can be used as a dermal filler or to generate and promote healing of cartilage, vertebral discs, connective tissues such as tendons and ligaments and bone in vivo.

Claims

1. A method of regenerating damaged or defective tissue comprising:

making a preparation by cross-linking hyaluronic acid (HA) in situ within a porous matrix, with limited or no chemical cross-linking of the hyaluronic acid with a material forming the porous matrix, by soaking the porous matrix with the hyaluronic acid, with the addition of cross-linking heavy chains of inter-alpha inhibitor and Tumor Necrosis Factor Stimulating Gene-6, wherein hepatocyte growth factor (HGF) is added to the preparation during the HA cross-linking stage or the HGF is added after the HA cross-linking stage by soaking the preparation in a solution containing HGF, and placing the preparation containing HGF into a synovial joint of the mammal.

2. The method according to claim 1 wherein the synovial joint includes a chondral defect.

3. The method according to claim 1 wherein the synovial joint includes a meniscal defect.

4. The method according to claim 1 wherein the synovial joint presents with osteoarthritis.

5. The method according to claim 1 wherein placing the preparation into the synovial joint promotes hyaline cartilage regeneration in the synovial joint.

6. The method according to claim 1 wherein the presence of HA in the preparation slows a rate of HGF degradation in the preparation.

7. The method according to claim 1 wherein the presence of HA in the preparation slows a rate of HGF degradation in vivo.

8. The method according to claim 1 where the HA is produced using a recombinant system involving genetic modification of bacteria.

9. The method according to claim 1 further comprising excluding gelatin from the preparation.

10. The method according to claim 1 further comprising excluding a synthetic polymer from the preparation.

11. A composition made by

a) making a preparation by cross-linking hyaluronic acid (HA) in situ within a porous matrix, with limited or no chemical cross-linking of the hyaluronic acid with a material forming the porous matrix, by soaking the porous matrix with the hyaluronic acid, with the addition of cross-linking heavy chains of inter-alpha inhibitor and Tumor Necrosis Factor Stimulating Gene-6, and

b) adding hepatocyte growth factor (HGF) to the preparation of a) during the HA cross-linking stage or adding HGF after the HA cross-linking stage by soaking the preparation in a solution containing HGF.

12. A method of promoting healing of a diseased or damaged tissue of a mammal comprising:

making a preparation by cross-linking hyaluronic acid (HA) in situ within a porous matrix, with limited or no chemical cross-linking of the hyaluronic acid with a material forming the porous matrix, by soaking the porous matrix with the hyaluronic acid, with the addition of cross-linking heavy chains of inter-alpha inhibitor and Tumor Necrosis Factor Stimulating Gene-6, wherein hepatocyte growth factor (HGF) is added to the preparation during the HA cross-linking stage or the HGF is added after the HA cross-linking stage by soaking the preparation in a solution containing HGF, and applying the preparation to a diseased or damaged tissue selected from the group consisting of cartilage tissue, nerve tissue, bone tissue, vertebral disc tissue, muscle tissue, and connective tissue, where the amount of HA is sufficient to decrease the rate of degradation of the HGF in the preparation and in vivo.

13. The method according to claim 12 further comprising selecting the porous matrix from the group consisting of collagen, hydroxyapatite, tri-calcium phosphate, cancellous bone, demineralized bone, processed human or animal soft tissues, processed human or animal nerves, and combinations thereof.