CERAMIC IMPLANTS AFFORDING CONTROLLED RELEASE OF ACTIVE MATERIALS

• US 20100047318A1
• Filed: 08/21/2008
• Published: 02/25/2010
• Est. Priority Date: 08/21/2008
• Status: Active Grant

• Current Assignee: Biomet Manufacturing, LLC (Zimmer Biomet Holdings, Inc.)
• Original Assignee: Biomet Manufacturing, LLC (Zimmer Biomet Holdings, Inc.)
• Inventors: Kumar, Mukesh
• Granted Patent: US 10,010,500 B2
• Time in Patent Office: Days
• US Class Current: 424/426
• 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: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Implantable compositions capable of providing release of bioactive agents according to a predetermined release profile and methods for their use. Such compositions include at least one ceramic substrate; a bioactive substance loaded on a surface of a said ceramic substrate forming a loaded surface zone operable to release said bioactive substance according to a release profile under physiological conditions; and a biodegradable polymer having an in vivo degradation period, forming a continuous or discontinuous coating on an area of a said ceramic substrate. The composition comprises at least two said loaded surface zones having different release profiles, or at least two said coatings having different in vivo degradation periods.

Claims

1. An implantable drug delivery composition comprising:

(A) at least one ceramic substrate;

(B) a bioactive substance loaded on a surface of a said ceramic substrate forming a loaded surface zone operable to release said bioactive substance according to a release profile under physiological conditions; and

(C) a biodegradable polymer having an in vivo degradation period, forming a continuous or discontinuous coating on an area of a said ceramic substrate;

wherein the composition comprises at least two said loaded surface zones having different release profiles, or at least two said coatings having different in vivo degradation periods.

2. The composition according to claim 1, wherein the ceramic composition comprises a plurality of ceramic substrates that are particles that have an average diameter of about 1 to about 500 μ

m.

3. The composition according to claim 2, wherein the particles comprise ceramic microspheres.

4. The composition according to claim 1, wherein the composition comprises at least three said loaded surface zones having different release profiles, or at least three said coatings having different in vivo degradation periods.

5. The composition according to claim 1, wherein one of the coatings exhibits an in vivo degradation period of 1 to about 7 days and another of the coatings exhibits an in vivo degradation period of about 1 to 4 weeks.

6. The composition according to claim 1, wherein one of the coatings exhibits an in vivo degradation period of about 2 to 8 weeks.

7. The composition according to claim 1, wherein the composition comprises at least one loaded surface zone that is not in a said area of said coating.

8. The composition according to claim 1, wherein the ceramic substrate comprises any of the physiologically acceptable hydroxyapatites, calcium phosphates, calcium sulfates, or combinations thereof.

9. The composition according to claim 1, wherein the biocompatible, biodegradable polymer comprises any of the physiologically acceptable polylactides, polyhydroxyalkanoates, copolymers thereof, or combinations thereof.

10. The composition according to claim 9, wherein the biocompatible, biodegradable polymer comprises PLA, PGA, or PLGA, or any combination thereof.

11. The composition according to claim 1, wherein the biocompatible, biodegradable polymer coating is from about 1 μ

m to about 500 μ

m thick.

12. The composition according to claim 1, comprising at least one said coating that is a vapor-deposited layer of said polymer.

13. The composition according to claim 12, wherein said vapor-deposited layer is formed by chemical vapor deposition.

14. The composition according to claim 12, wherein a vapor-deposited layer contacts at least 95% of the surface area of the ceramic pore walls and struts of said area that it coats.

15. The composition according to claim 14, wherein the layer contacts at least 98% of the surface area of said area.

16. The composition according to claim 1, wherein a ceramic-polymer nanocomposite material occupies an interface between the ceramic substrate and at least one of the polymer layers.

17. The composition according to claim 1, wherein the bioactive substance comprises a pharmaceutically acceptable polypeptide.

18. The composition according to claim 1, wherein the bioactive substance is present in or on the surface of the ceramic substrate in an amount that is from about 0.01 to about 100 μ

g per mm² of the zone loaded therewith.

19. The composition according to claim 1, wherein the composition comprises a set of said ceramic substrates, which set exhibits a smoothly decreasing in vivo drug release profile.

20. The composition according to claim 1, wherein the composition comprises a set of said ceramic substrates, which set exhibits an increase-decrease profile of in vivo drug release.

21. The composition according to claim 20, wherein the increase-decrease profile is periodic, with the period occurring at least twice.

22. The composition according to claim 21, wherein the periodic increase-decrease profile exhibits about 12-, 24-, 48-, or 72-hour periodicity.