Osteogenic device and a method for preparing the device

• US 20050142164A1
• Filed: 01/20/2004
• Published: 06/30/2005
• Est. Priority Date: 02/29/1996
• Status: Active Grant

• Current Assignee: Bioactive BONE Substitutes OY AB
• Original Assignee: Bioactive BONE Substitutes OY AB
• Inventors: Lindholm, Sam T., Marttinen, Aulis
• Granted Patent: US 7,186,811 B2
• Time in Patent Office: Days
• US Class Current: 424/426
• CPC Class Codes: A61F 2/00 Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents as cosmetic articles, see the relevant subclasses, e.g. wigs, hair pieces, A41G3/00, A41G5/00; artificial nails A45D31/00; dental prostheses A61C13/00; materials for prostheses A61L27/00; artificial hearts A61M60/00; artificial kidneys A61M1/14
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/3604 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• CPC Class Codes: A61L 27/365 Bones
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: C07K 14/51 Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: Y10S 530/84 Bones; tendons; teeth; cartilage

Abstract

The present invention is related to an osteogenic device and its preparation. Said device comprises a bone morphogenetic protein (BMP), preferably a modified BMP complex obtainable by a modification of the conventional guanidum hydrochloride extraction method and collagens, preferably collagen I or collagen IV, impregnated in and/or adsorbed on a bioceramic carrier, preferably a shapable body (block) originating from a coral skeleton. The method of isolating said modified BMP complex which lacks an immunogenic component and consists essentially of a 100-700 kD and a 15-25 kD protein with osteoinductive properties and preferably of the 15-25 kD protein which has improved storage properties as well as its use in the osteogenic device with improved osteoinductive properties is also disclosed.

Claims

1. An osteogenic device comprising the following components:

(a) a bone morphogenetic protein BMP selected from a group consisting of partially purified native BMP, recombinant BMP and modified BMP complex;

(b) a collagen component;

(c) a shapable porous carrier body;

(d) optional growth factors.

2. The device of claim 1, wherein the bone morphogenetic protein is a modified BMP complex from which Fraction II a medium MW protein with immunogenic properties is removed, said BMP complex consisting essentially of a mixture of Fraction I, a high MW (100-700 kD) protein with osteoinductive BMP activity, and a low MW (15-20 kD) protein with osteoinductive BMP activity.

3. The device of claim 1, wherein the bone morphogenetic protein is Fraction III a low MW (15-25 kD) protein with osteoinductive BMP activity with prolonged storage properties.

4. The device of claim 1, wherein the morphogenetic protein is obtainable by a method comprising the steps of

(a) pulverizing demineralized bone material;

(b) extracting the bone material in step (a) with guanidinium hydrochloride (GuHCl);

(c) performing at least one gel filtration with HPCL-reversed chromatography.

5. The device of claim 1, wherein the collagen is selected from a group consisting of collagen mixtures, atelopeptide collagens, Type IV collagen and Type I collagen I.

6. The device of claim 1, wherein the collagen component is Type IV collagen.

7. The device of claim 1, wherein the shapable, porous carrier body is selected from a group comprising hydroxyapatite, tricalcium phosphate, bioactive glass and biocoral originating from a coral skeleton.

8. The device of claim 1, wherein the shapable, porous carrier body is a biocoral selected from a coral skeleton.

15. The use of the component of the osteogenic device defined in claim 2 in the preparation of an osteogenic device with improved osteoinductive properties.

9. An osteogenic device comprising the following components:

(a) a modified BMP;

complex consisting essentially of a mixture of Fraction I, a high MW (100-700 kD) protein with osteoinductive BMP activity, and a low MW (15-25 kD) protein with osteoinductive BMP activity being essentially free from Fraction II, a medium MW (25-55 kD) immunogenically and inflammatory active protein;

(b) collagen IV; and

(c) a biocoral carrier.

10. A method for preparing an osteogenic device comprising the steps of:

(a) incubating collagen with dissolved a BMP complex;

(b) impregnating the bioceramic body by immersing it in the mixture from step (a);

(c) performing a dialysis of the BMP-collagen shapable porous body;

(d) separating the body and the solution used for dialysis;

(e) adsorbing BMP impregnated collagen containing precipitate from the solution of step (d) on the BMP-collagen shapable, porous body.

11. The method of claim 10, wherein the bone morphogenetic protein complex comprises a mixture of a high MW (100-700 kD) protein with osteoinductive BMP activity and a low MW (15-25 kD) protein with osteoinductive BMP activity.

12. The method of claim 10, wherein the modified BMP complex is obtainable by a method comprising the steps of claim 4.

13. The method of claim 10, wherein the collagen is selected from a group consisting of a collagen mixture, Type IV collagen and Type I collagen.

14. The method of claim 10, wherein the shapable, porous carrier body is selected from a group consisting of hydroxyapatite, tricalcium phosphate, bioactive glass and biocorals originating from coral skeleton.