Compositions for treating joints comprising bone morphogenetic protein and hyaluronic acid

• US 9,561,260 B2
• Filed: 12/03/2014
• Issued: 02/07/2017
• Est. Priority Date: 12/28/2010
• Status: Active Grant

• Current Assignee: Depuy Mitek LLC (Johnson & Johnson)
• Original Assignee: Depuy Mitek LLC (Johnson & Johnson)
• Inventors: Byers, Benjamin A., Su, Dongling, Hwang, Julia
• Primary Examiner(s): KEMMERER, ELIZABETH
• Application Number:
  US14/559,319
• Publication Number:
  US 20150190469A1
• Time in Patent Office: 797 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: A61K 38/1875 Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61M 39/223 Multiway valves
• CPC Class Codes: A61M 5/19 having more than one chamber , e.g. including a manifold coupling two parallelly aligned syringes through separate channels to a common discharge assembly surgical glue applicators A61B17/00491
• CPC Class Codes: A61M 5/284 comprising means for injection of two or more media, e.g. by mixing
• CPC Class Codes: A61M 5/31 Details
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis

Abstract

Methods and compositions are disclosed for an intra-articular injection for the treatment of osteoarthritis. The methods and compositions comprising combinations of hyaluronic acid and a bone morphogenetic protein, like rhGDF-5, can be useful for any synovial joint, including the knee, shoulder, hip, ankle, hands, spinal facet, or temporomandibular joint, both for the relief of pain and for slowing disease progression.

Claims

1. A composition for treating a joint condition, comprising:

an injectable formulation comprising a precipitate of a bone morphogenetic protein (BMP) dispersed within a solution of hyaluronic acid (HA), the injectable formulation having a concentration of BMP in the range of about 5 μ

g/ml to about 90 μ

g/ml and a concentration of HA in the range of about 5 mg/ml to about 60 mg/ml, and the BMP being in its precipitated form and capable of becoming solubilized and biologically active after injection into an organism.

2. The composition of claim 1, wherein the BMP is a growth and differentiation factor (GDF) protein.

3. The composition of claim 2, wherein the GDF is growth and differentiation factor 5 (GDF-5), growth and differentiation factor 6 (GDF-6), growth and differentiation factor 7 (GDF-7), or a combination thereof.

4. The composition of claim 1, wherein the BMP is in a liquid state prior to combining with the solution of HA.

5. The composition of claim 1, wherein the BMP is in a lyophilized state prior to combining with the solution of HA.

6. The composition of claim 1, wherein the BMP is at least one of BMP2 and BMP7.

7. The composition of claim 1, wherein the mixture has a pH in the range of about 3 to 8.

8. The composition of claim 1, wherein the mixture has a pH in the range of about 5 to 7.5.

9. The composition of claim 1, wherein the HA has a molecular weight of at least about 500 kDa.

10. The composition of claim 1, wherein the solution of HA comprises HA and water.

11. The composition of claim 1, wherein the HA is at a concentration of at least 7 mg/ml in the mixture.

12. A kit, comprising:

a first component comprising a solution of hyaluronic acid (HA);

a second component comprising an amount of a bone morphogenetic protein (BMP), the BMP configured to form a precipitate when mixed with the HA and capable of becoming solubilized and biologically active after injection into an organism; and

a syringe for injecting a mixture of the first component and the second component, wherein the mixture has a concentration of BMP in the range of about 5 μ

g/ml to about 90 μ

g/ml and a concentration of HA in the range of about 5 mg/ml to about 60 mg/ml.

13. The kit of claim 12, wherein the syringe has a first chamber containing the first component, and a second container containing the second component, and wherein the syringe includes a plunger configured to inject the second component into the first chamber to mix the first component and the second component.

14. The kit of claim 12, wherein the BMP is at least one of BMP2 and BMP7.

15. The kit of claim 12, wherein the BMP is a growth and differentiation factor (GDF) protein.

16. The kit of claim 15, wherein the GDF is growth and differentiation factor 5 (GDF-5), growth and differentiation factor 6 (GDF-6), growth and differentiation factor 7 (GDF-7), or a combination thereof.

17. The kit of claim 12, wherein the mixture has a pH in the range of about 5 to 7.5.

18. The kit of claim 12, wherein the HA has a molecular weight of at least about 500 kDa.

19. The kit of claim 12, wherein the HA is at a concentration of at least 7 mg/ml in the mixture.