Ceramic implants affording controlled release of active materials

• US 10,010,500 B2
• Filed: 08/21/2008
• Issued: 07/03/2018
• 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
• Primary Examiner(s): Crow, Robert T.
• Assistant Examiner(s): Nguyen, John P
• Application Number:
  US12/195,789
• Publication Number:
  US 20100047318A1
• Time in Patent Office: 3,603 Days
• Field of Search: None
• 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 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 the 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 the ceramic substrate.

Claims

1. An implantable drug delivery composition comprising:

a set of ceramic microsphere substrates including at least a first substrate and a second substrate, each substrate comprising;

(A) a loaded surface zone formed of a bioactive substance loaded on a surface of said ceramic substrate, the loaded surface zone operable to release said bioactive substance according to a release profile under physiological conditions; and

(B) a coating formed on an area of the loaded surface zone of said ceramic substrate, the coating being formed of a biodegradable polymer having an in vivo degradation period;

wherein the coatings of the first substrate and the second substrate differ in at least one of polymer type, molecular weight, thickness, and combinations thereof such that the coatings of the first substrate and the second substrate have different in vivo degradation periods such that cumulative release of the composition of said bioactive substance varies according to the release profile.

2. The composition according to claim 1, wherein the composition comprises substrates having coatings with at least three different in vivo degradation periods.

3. The composition according to claim 1, wherein the coating of the first substrate exhibits an in vivo degradation period of 1 to about 7 days and the coating of the second substrate exhibits an in vivo degradation period of about 1 to 4 weeks.

4. The composition according to claim 1, wherein the coating of at least one of the first substrate and the second substrate exhibits an in vivo degradation period of about 2 to 8 weeks.

5. The composition according to claim 1, wherein coating is discontinuous and the composition comprises a substrate wherein an area of the loaded surface zone is not coated with the biodegradable polymer.

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

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

8. The composition according to claim 7, wherein the biocompatible, biodegradable polymer comprises PLA, PGA, or PLGA , or any combination thereof.

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

m to about 500 μ

m thick.

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

11. 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 pg per mm² of the area of the loaded surface zone loaded therewith.

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

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