Implant with an bioactive coating and method for providing the same

Abstract

The present invention relates to an implant having a surface comprising a coating on at least a portion of the surface of the implant, wherein the coating comprises at least two coating layers of bioactive compounds adjacent to each other, obtainable in a process comprising the following steps: providing an implant with a surface, providing a first suspension comprising at least one first bioactive compound in a first solvent, wherein the first bioactive compound is non-soluble or partially soluble in the first solvent, applying said first suspension comprising the at least one first bioactive compound onto at least a part of the implant surface forming a first coating layer; drying the first coating layer, providing a second solution comprising at least one second bioactive compound in a second solvent, wherein the second bioactive compound is soluble or readily soluble in the second solvent; applying said second solution comprising the at least one second bioactive compound onto the first coating layer forming a second coating layer, and drying the second coating layer.

Claims

1. An implant having a surface comprising a coating on at least a portion of the surface of the implant, wherein the coating comprises at least two coating layers of bioactive compounds adjacent to each other, wherein the first coating layer is a patch-like, non-continuous powder coating layer, and the second coating layer is a continuous coating layer concealing or agglutinating the first coating layer, the implant obtainable in a process comprising the steps of: providing an implant with a surface; providing a first suspension comprising at least one first bioactive compound in a first solvent, wherein the first bioactive compound is non-soluble or partially soluble in the first solvent; applying said first suspension comprising the at least one first bioactive compound onto at least a part of the implant surface forming a first coating layer; drying the first coating layer; providing a second solution comprising at least one second bioactive compound in a second solvent, wherein the second bioactive compound is soluble or readily soluble in the second solvent; applying said second solution comprising the at least one second bioactive compound onto the first coating layer forming a second coating layer; and drying the second coating layer.

2. The implant according to claim 1, wherein the first and second bioactive compounds are selected from the group consisting of antibiotics, pain reliever, anti-coagulation substances, heparins, hormones, cytostatic substances, growth factors and inflammation inhibitors.

3. The implant according to claim 1, wherein the first coating layer comprises more than one bioactive compound.

4. The implant according to claim 1, wherein the at least one first coating layer which is adjacent to the surface of the implant comprises at least one antibiotic that affects the bacterial cell wall or its synthesis.

5. The implant according to claim 4, wherein the at least one antibiotic is selected from the group consisting of glycopeptides, fosfomycin and polypeptides.

6. The implant according to claim 1, wherein the second coating layer arranged on the first coating layer comprises at least one antibiotic, wherein the at least one antibiotic comprises a bacterial RNA polymerase inhibitor.

7. The implant according to claim 6, wherein the antibiotic comprises a rifamycin.

8. The implant according to claim 1, wherein the first coating layer adjacent to the implant surface comprises fosfomycin and the second coating layer arranged on the first layer comprises a rifamycin.

9. The implant according to claim 1, wherein the concentration of the bioactive compound in the first coating layer adjacent to the implant surface is between 50 and 500 g/cm.sup.2.

10. The implant according to claim 9, wherein the concentration of the bioactive compound in the second coating layer arranged on the first coating layer is between 30 and 350 g/cm.sup.2.

11. The implant according to claim 1, wherein at least one of the coating layers comprises at least one antioxidative agent.

12. The implant according to claim 1, wherein the implant is a hip prosthesis, a shoulder prosthesis, an elbow prosthesis, a knee prosthesis or a vertebral implant or an implant for trauma surgery.

13. The implant according to claim 1, wherein the implant surface is pre-treated before applying the coating by sand blasting or glass bead blasting.

14. A method for obtaining an implant comprising: providing an implant with a surface; providing a first suspension comprising at least one first bioactive compound in a first solvent, wherein the first bioactive compound is non-soluble in the first solvent; applying said first suspension comprising the at least one first bioactive compound onto at least a part of the implant surface forming a first coating layer; drying the first coating layer, resulting in a first patch-like, non-continuous coating layer; providing a second solution comprising at least one second bioactive compound in a second solvent, wherein the second bioactive compound is soluble in the second solvent; applying said second solution comprising the at least one second bioactive compound onto the first coating layer forming a second coating layer; and drying the second coating layer, resulting in a continuous coating layer concealing or agglutinating the first coating layer.

15. The implant according to claim 5, wherein the at least one antibiotic is vancomycin or teicoplanin.

16. The implant according to claim 5, wherein the at least one antibiotic is bacitracin or daptomycin.

17. The method according to claim 14, wherein said first suspension is applied using at least one first ink jet.

18. The method according to claim 14, wherein said second solution is applied using at least one second ink jet.

Description

EXAMPLE 1

(1) A suspension of fosfomycin-calcium-monohydrate in 2-propanol/water=2:1 Vol/Vol is provided and is homogenized in an appropriate high pressure homogenizer. The concentration of the fosfoymicin salt in the suspension is such that after application onto the implant surface a fosfomycin concentration in the coating layer is 300 g/cm.sup.2 per implant surface area is defined.

(2) The fosfomycin suspension contains 80% of particles, which have a diameter less than 10 m. Such a fosfomycin suspension is stable for about 35 days. The fosfomycin suspension is subsequently applied to the implant surface using a first ink jet.

(3) In parallel, a second solution comprising the second antibiotic for the second coating layer is provided by dissolving rifampicin and vitamin C in methanol. The rifampicin concentration in the solution is chosen such that the final rifampicin concentration on the implant is 60 g/cm.sup.2.

(4) Said second solution comprising rifampicin and vitamin C is subsequently coated onto the first fosfomycin coating layer using a second separated ink jet.

EXAMPLE 2

(5) The adherence of the fosfomycin-rifampicin double coating layer was determined applying a wiping test. A substrate, here a glass substrate, was coated at first with a fosfomycin-Ca monohydrate suspension. Subsequently, a part of the glass substrate coated with fosfomycin-Ca was partially coated with rifampicin.

(6) The fosfomycin-Ca particles are distributed over the surface with a density of about 430 g/cm.sup.2 (corresponding to about 300 g/cm.sup.2 active fosfomycin). The density of rifampicin applied to the fosfomycin-Ca layer is about 60 g/cm.sup.2.

(7) The completely coated substrate was then wiped using a polyester cloth. By doing so in areas where only fosfomycin-Ca was applied (i.e. without a second layer of rifampicin) the fosfomycin-Ca was largely removed. In contrast, those areas, where the fosfomycin was coated with rifampicin, stayed intact. Thus, the application of a second layer of rifampicin prevented a removal of the first fosfomycin layer.

EXAMPLE 3

(8) A suspension of Dexamethason in water/ethanol was prepared in a high pressure homogenizer. The suspension was applied to an implant surface using a first ink jet. The first coating layer is dried.

(9) In parallel a methanol solution of Lidocain(hydrochlorid) was provided and applied to the first layer using a second ink jet.