Method for drug loading hydroxyapatite coated implant surfaces

Patent metadata

Field	Value
Publication number	US-9662425-B2
Application number	US-201414786060-A
Country	US
Kind code	B2
Filing date	Apr 22, 2014
Priority date	Apr 22, 2013
Publication date	May 30, 2017
Grant date	May 30, 2017

Abstract

A method for loading a hydroxyapatite coated implant with a therapeutic agent including the steps of providing an implant and applying a hydroxyapatite coating on a surface of the implant. The hydroxyapatite coated implant is contacted with a solution including the therapeutic agent. The hydroxyapatite coated implant and solution is heated to temperature of about 60° C. to about 100° C. Pressure is applied to the hydroxyapatite coated implant and solution from about 2 bar to about 10 bar, to load the hydroxyapatite coated implant with the therapeutic agent. An implant made according to the method has sustained therapeutic agent delivery and includes a base and a biomimetic hydroxyapatite coating disposed on a surface thereof.

First claim

What is claimed is:

1. A method for loading a hydroxyapatite coated implant with a therapeutic agent, comprising the steps of:
providing an implant;
applying a hydroxyapatite coating on a surface of the implant;
contacting the hydroxyapatite coated implant with a solution including the therapeutic agent;
heating the hydroxyapatite coated implant and solution to a temperature of about 60° C. to about 100° C.; and
applying pressure to the hydroxyapatite coated implant and solution of about 2 bar to about 10 bar to load the hydroxyapatite coated implant with the therapeutic agent for improved therapeutic agent delivery at an implant site.

2. The method according to claim 1 , wherein the implant is a device selected from the group consisting of fixation pins, orthopedic devices, dental implants, stents, drug delivery devices, sheets, films, meshes, soft tissue implants, implantable electrodes, implantable sensors, drug delivery pumps, tissue barriers and shunts.

3. The method according to claim 1 , wherein the implant includes a surface metal coating selected from the group consisting of TiO2, TiO, TiCrO 2 , TiO 3 , Ti 3 O 5 , SiO 2 , MgO 2 , AlO 2 , and CrO 2 .

4. The method according to claim 1 , wherein the implant has a base metal of Titanium and Stainless Steel alloys and a surface coating selected from the group of TiO2, TiO, TiCrO 2 , Ti 2 O 3 , Ti 2 O 5 , SiO 2 , MgO 2 , AlO 2 , and CrO 2 .

5. The method according to claim 4 , further comprising the step of coating the implant with the surface coating prior to applying the hydroxyapatite coating.

6. The method according to claim 1 , wherein the therapeutic agent is selected from the group consisting of antibiotics, vitamins, chemotherapy drugs, bisphosphonates, strontium-ranelate, PTH, osteoporotic drugs, growth factors, and a combination thereof.

7. The method according to claim 1 , wherein the implant is a material selected from the group consisting of titanium, titanium alloy, nickel-titanium alloy, tantalum, platinum-iridium alloy, gold, magnesium, stainless steel, chromo-cobalt alloy, ceramics, biocompatible plastics or polymers and combinations thereof.

8. The method according to claim 1 , wherein the hydroxyapatite coating is grown biomimetically.

9. The method according to claim 8 , wherein the thickness of the biomimetic hydroxyapatite coating deposited is of about 1 μm to about 10 μm.

10. The method according to claim 1 , wherein the coating is an ion substituted hydroxyapatite.

11. The method according to claim 1 , wherein the thickness of the hydroxyapatite coating deposited is of about 1 μm to about 10 μm.

12. The method according to claim 1 , wherein the step of contacting the hydroxyapatite coated implant with the solution uses a solution of 20 mg or greater of therapeutic agent per ml of solution.

13. The method of according to claim 1 , wherein the therapeutic agent has a penetration depth of about 0.5 μm to about 8 μm.

14. A method for loading a hydroxyapatite coated implant with a therapeutic agent, comprising:
providing an implant;
coating the implant with a metal selected from the group consisting of TiO 2 , TiO, TiCrO 2 , Ti 2 O 3 , Ti 3 O 5 , SiO 2 , MgO 2 , AlO 2 , and CrO 2 ;
applying a hydroxyapatite coating on a surface of the implant;
thereafter placing the hydroxyapatite coated implant in a solution including the therapeutic agent;
heating the hydroxyapatite coated implant and the solution to a temperature of about 60° C. to about 100° C.; and
applying pressure to the hydroxyapatite coated implant and solution of about 2 bar to about 10 bar to load the hydroxyapatite coated implant with the therapeutic agent for improved therapeutic agent delivery at an implant site; and
thereafter removing the implant from the solution after about 5 minutes.

15. The method according to claim 14 , wherein the implant is a device selected from the group consisting of fixation pins, orthopedic devices, dental implants, stents, drug delivery devices, sheets, films, meshes, soft tissue implants, implantable electrodes, implantable sensors, drug delivery pumps, tissue barriers and shunts.

16. The method according to claim 14 , wherein the therapeutic agent is selected from the group consisting of antibiotics, vitamins, chemotherapy drugs, bisphosphonates, strontium-ranelate, PTH, osteoporotic drugs, growth factors, and a combination thereof.

17. The method according to claim 14 , wherein the implant is a material selected from the group consisting of titanium, titanium alloy, nickel-titanium alloy, tantalum, platinum-iridium alloy, gold, magnesium, stainless steel, chromo-cobalt alloy, ceramics, biocompatible plastics or polymers and combinations thereof.

18. The method according to claim 14 , wherein the hydroxyapatite coating is grown biomimetically.

19. The method according to claim 18 , wherein the thickness of the biomimetic hydroxyapatite coating deposited is of about 1 μm to about 10 μm.

20. The method according to claim 14 , wherein the hydroxyapatite coating contains ions selected from the group consisting of calcium, phosphates, fluorine, strontium, silicon, and magnesium.

21. A method for loading a hydroxyapatite coated implant with a therapeutic agent, comprising the steps of:
providing an implant;
applying a hydroxyapatite coating on a surface of the implant;
contacting the hydroxyapatite coated implant with a solution including the therapeutic agent;
heating the hydroxyapatite coated implant and solution to a temperature of about 60° C. to about 100° C.; and
applying pressure to the hydroxyapatite coated implant and solution of about 2 bar to about 10 bar to load the hydroxyapatite coated implant with the therapeutic agent for improved therapeutic agent delivery at an implant site; and
thereafter removing the implant from the solution after about 5 minutes.

Assignees

• Stryker European Holdings I Llc

Inventors

• Lilja Mirjam
• Sörensen Jan Henrik
• Procter Philip
• Steckel Hartwig
• Sörensen Torben Christian

Classifications

• A61L31/16 Primary

  Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)} · CPC title

• A61L27/32

  Phosphorus-containing materials, e.g. apatite · CPC title

• A61C19/063

  Medicament applicators for teeth or gums, e.g. treatment with fluorides · CPC title

• A61L31/086

  Phosphorus-containing materials, e.g. apatite · CPC title

• A61C8/0013

  with a surface layer, coating · CPC title