Sustained release drug carrier, and method of manufacturing sustained release drug carrier

• US 6,719,989 B1
• Filed: 09/08/2000
• Issued: 04/13/2004
• Est. Priority Date: 09/08/1999
• Status: Expired due to Fees

• Current Assignee: Pentax Corporation (Hoya Corporation)
• Original Assignee: Pentax Corporation (Hoya Corporation)
• Inventors: Otsuka, Makoto, Nakasu, Masanori, Matsushima, Asako
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Sheikh, Humera N.
• Application Number:
  US09/658,021
• Time in Patent Office: 1,313 Days
• Field of Search: 424/422, 424/423, 424/426, 424/484, 424/400, 623/16.11, 623/23.56, 623/23.57, 623/23.6, 623/23.61, 156/89.11
• US Class Current: 424/422
• 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 9/2009 Inorganic compounds
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 31/026 Ceramic or ceramic-like structures, e.g. glasses
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

A sustained release drug carrier comprises a ceramic composite which is formed by bonding a plurality of ceramic bodies together, and drugs impregnated into the ceramic composite. A method of manufacturing the sustained release drug carrier comprises the steps of: (i) preparing ceramic bodies to be bonded together, each of the ceramic bodies having a bonding surface; (ii) preparing a slurry in which primary particles of a bonding ceramics are dispersed; (iii) applying the slurry to the bonding surface of at least one of the ceramic bodies to be bonded; (iv) sintering the ceramic bodies between which the slurry has been interposed to bond them together, to obtain a ceramic composite; and (v) impregnating a drug into the obtained ceramic composite. According to the structure and method described above, it is possible to provide a sustained release drug carrier whose drug release properties can be controlled and which is capable of exhibiting better drug release action suitable for the application sites, type of drugs to be carried, and the like.

Claims

1. A sustained release carrier, comprising:

a ceramic composite which is formed by bonding at least a first porous ceramic body having its own overall porosity in the range of 15 to 60%, and a second porous ceramic body having its own overall porosity in the range of 15 to 60%;

the first and second porous ceramic bodies comprising a calcium phosphate-based ceramic compound;

the first and second porous ceramic bodies each having a bonding surface;

the first and second porous ceramic bodies being bonded together with a bonding ceramic applied as a slurry to the bonding surfaces of the first and second ceramic bodies;

wherein the slurry comprises primary particles of the same ceramic compound of which the first and second said bodies are comprised; and

active substance(s) impregnated into the first and second porous ceramic bodies;

wherein the overall porosity of the first porous ceramic body is different from the porosity of the second porous ceramic body thereby providing different release rates of the active substance(s).

2. The carrier of claim 1, wherein the first ceramic body has a lower porosity than the second ceramic body and the first ceramic body exhibits a release rate of the active substance(s) that is lower than the release rate of the second ceramic body as a result of the lower porosity of the first ceramic body.

3. The carrier of claim 1, wherein the first ceramic body has a higher strength than the strength of the second ceramic body.

4. The carrier of claim 1, wherein the average pore size of at least one of the ceramic bodies is 100 to 500 μ

m.

5. The carrier of claim 1, wherein the average pore size of at least one of the ceramic bodies is 200 to 400 μ

m.

6. The carrier of claim 1, wherein the pores of at least one of the ceramic bodies include three-dimensionally communicating pores comprising capillaries.

7. The carrier of claim 6, wherein the average pore size of the capillaries is 0.1 to 20 μ

m.

8. The carrier of claim 6, wherein the average pore size of the capillaries is 0.5 to 10 μ

m.

9. The carrier of claim 1, wherein at least one of the ceramic bodies comprises a Ca/P ratio of 1 to 2.

10. The carrier of claim 1, wherein the active substance(s) comprises a biologically active agent(s).

11. The carrier of claim 10, wherein the biologically active agent(s) comprises a drug(s).

12. The carrier of claim 9, wherein at least one of the ceramic bodies comprises hydroxyapatite.

13. A bone replacement material comprising the carrier of claim 1.

14. A vertebral spacer comprising the carrier of claim 1.

15. A bone implant comprising the carrier of claim 1.

16. A sustained release carrier for releasing an active substance(s) impregnated therein, comprising:

a ceramic composite into which the active substance(s) can be impregnated, the ceramic composite formed by bonding at least a first porous ceramic body having its own overall porosity in the range of 15 to 60%, and a second porous ceramic body having its own overall porosity in the range of 15 to 60%;

the first and second porous ceramic bodies comprising a calcium phosphate-based ceramic compound;

the first and second porous ceramic bodies each having a bonding surface;

the first and second porous ceramic bodies being bonded together with a bonding ceramic applied as a slurry to the bonding surfaces of the first and second ceramic bodies;

wherein the slurry comprises primary particles of the same ceramic compound of which the first and second said bodies are comprised;

wherein the overall porosity of the first porous ceramic body is different from the porosity of the second porous ceramic body thereby providing different release rates of the active substance(s).

17. A method of manufacturing a sustained release carrier comprising:

preparing first and second porous ceramic bodies from powder(s) comprising a calcium phosphate-based ceramic compound;

the first porous ceramic body having its own overall porosity in the range of 15 to 60%, and the second porous ceramic body having its own overall porosity in the range of 15 to 60%;

wherein the overall porosity of the first porous ceramic body is different from the overall porosity of the second porous ceramic body;

the first and second porous ceramic bodies each having a bonding surface;

preparing a slurry of bonding ceramics in which primary particles of the same ceramic compound of which the first and second said bodies are comprised are dispersed;

interposing the slurry between the first and second bodies;

sintering the first and second bodies to obtain a ceramic composite; and

impregnating an active substance(s) into the ceramic composite.

18. The method of claim 17, wherein the bonding ceramics comprise a calcium phosphate-based compound.