WO2015170056A1

WO2015170056A1 - Coating material for implantable medical device, implantable medical device coated with such a material and corresponding manufacturing method

Info

Publication number: WO2015170056A1
Application number: PCT/FR2015/051206
Authority: WO
Inventors: Richard Vandevelde
Original assignee: Rv Finances
Priority date: 2014-05-06
Filing date: 2015-05-06
Publication date: 2015-11-12
Also published as: FR3020759A1; EP3139970A1; FR3020759B1

Abstract

The invention relates to a coating material (1) for an implantable medical device, said material (1) consisting mostly of calcium phosphate and including a first additive containing copper, characterised in that said material includes a second additive containing strontium and consists of at least one upper layer (2) and one lower layer (3) which are vertically adjacent, said upper (2) and lower (3) layers each mostly consisting of calcium phosphate, said first additive being localised mostly in the upper layer (2) while the second additive is localised mostly in the lower layer (3). The invention also relates to coating materials for an implantable medical device.

Description

COATING MATERIAL FOR IMPLANTABLE MEDICAL DEVICE, IMPLANTABLE MEDICAL DEVICE COATED WITH SUCH MATERIAL AND

CORRESPONDING MANUFACTURING PROCESS

TECHNICAL FIELD The present invention relates to the general technical field of artificial devices intended to be implanted within the body of a patient, for example surgically, for a therapeutic and / or aesthetic purpose.

The present invention relates more particularly to a coating material for impiantable medical device, said material being mainly formed of calcium phosphate.

The present invention also relates to an impiantable medical device covered at least in part by a coating.

The invention finally relates to a method for manufacturing a coating for impiantable medical device, said method comprising a step of synthesizing a material formed mainly of calcium phosphate.

PRIOR ART

It is known to coat implantable medical devices with functional layers intended to improve the integration of the implant into the body of the patient concerned. In particular, hydroxyapatite coatings are known for improving the osseointegration of the coated surgical prosthesis, in order to ensure the success of the surgical procedure. Hydroxyapatite indeed promotes bone rehabilitation around the implant, which improves the secondary fixation of the latter in the body.

Nevertheless, the bone density of the bony parts that grow back around the known implants coated with hydroxyapatite is not always optimal. does not promote bone reformation and implant integration. This problem also increases with the age of the patient concerned.

In addition, it is known that implantation of devices coated with hydroxyapatite gives rise to a risk of nosocomial infection which represents a significant threat for the patient concerned, particularly when the implantation area is close to a vital organ. . This threat generally concerns the first three to five months (approximately 90 to 150 days) following implantation, during which the risk of infection is maximal, with potentially serious consequences (in the "best" case: explantation of the device to implant a temporary device during disinfection, then new operation with a new infectious risk, in the worst case: death of the patient).

In this regard, it is known to use copper as antibacterial agent of an implantable device coating, without however the implementation of copper in the known coatings does not allow to obtain an optimal effect. SUMMARY OF THE INVENTION

The objects assigned to the invention therefore aim to remedy the various disadvantages listed above and to propose a new coating material for an implantable medical device which, while being of particularly simple composition, cheap and safe, is easy to apply by conventional means and has improved properties in terms of bone regrowth and reducing the risk of infection.

Another object of the invention is to provide a new coating material which is particularly well tolerated by the body while being very safe in terms of health. Another object of the invention is to propose a novel coating material which is easily identifiable by practitioners (surgeons and nurses in particular), and which makes it possible to limit errors. Another object of the invention is to propose a new coating material that can be deposited by any conventional method and apparatus in the field, without any significant modification or prior adaptation being necessary.

Another object of the invention is to propose a new coating material which, while having significantly improved antibacterial and bone regrowth properties, as well as a distinctive specific appearance, has an optimum degree of crystallinity.

Another object of the invention is to provide a novel coating material which exhibits not only an improved in vivo lifetime but also significant associated antibacterial properties and a bioactive character.

Another object of the invention is to provide a new coating material which can directly substitute for known calcium phosphate coating materials.

Another object of the invention is to propose a new process for manufacturing a coating for an implantable medical device which makes it possible to obtain, in a particularly simple, easily reproducible and inexpensive manner, a coating which reduces the risk of infection while promoting the bone regrowth.

Another object of the invention is to propose a new method of manufacturing a coating for an implantable medical device that relies on the implementation of simple operations that do not require specific equipment.

The objects assigned to the invention are achieved by means of a coating material for an implantable medical device, said material being mainly formed of calcium phosphate and incorporating a first additive including copper, said material being characterized in that it incorporates a second additive including strontium and in that it is formed of at least one upper layer and one lower layer superimposed, said upper and lower layers being each predominantly formed of calcium phosphate, said first additive being mainly located in the upper layer while the second additive is mainly located in the lower layer.

The objects assigned to the invention are also achieved by means of an implantable medical device covered at least in part by a coating formed from a material mainly consisting of calcium phosphate and incorporating a first additive including copper, said material being characterized in that it incorporates a second additive including strontium and in that it is formed of at least one upper layer and one lower layer superimposed, said upper and lower layers being each predominantly formed of calcium phosphate , said first additive being mainly located in the upper layer while the second additive is mainly located in the lower layer

The objects assigned to the invention are also achieved by means of a method for manufacturing a coating for an implantable medical device, said method comprising a step of synthesizing a material formed mainly of calcium phosphate and incorporating a first additive including copper, said method being characterized in that it comprises a step of incorporating in said material a second additive including strontium, said synthesis step comprising the formation of at least one upper layer and one lower layer superimposed to confer on said material a multilayer character, said upper and lower layers being each predominantly formed of calcium phosphate, said step of incorporation being carried out so that said first additive is mainly located in the upper layer and for said second additive to be predominantly located in the lower layer.

SUMMARY OF THE DRAWINGS Other objects and advantages of the invention will appear better on reading the description which follows, as well as with reference to the appended FIG. 1, which illustrates an implantable device coated with a titanium layer. and a coating based on a bilayer material according to a preferred embodiment of the invention. BEST MODE OF REALIZING THE INVENTION

According to a first aspect, the invention relates to a coating material 1 for an implantable medical device 5.

By "implantable medical device" is meant any element, of the prosthesis or implant type, which is intended to be incorporated, preferably integrally, within the body of a patient, who is preferably a human patient, particularly with therapeutic and / or aesthetic purposes. The implantation of the medical device in question can be carried out by natural means or surgically. The coating material 1 according to the invention can take all kinds of implantable medical devices, regardless of the mode of implantation of the latter. Preferably, however, the coating material 1 according to the invention is intended primarily to cover all or part of a surgically implantable medical device, and preferably intended to replace or repair a missing or damaged bone element because of a accident or illness for example. In this preferred embodiment, the coating material 1 according to the invention is designed to coat a bone and / or joint implant. The coating material 1 according to the invention is intended to superficially cover the implantable medical device, so as to form, at least locally, the external surface of the latter, intended to come into contact with the tissues of the organism in which the medical device 5 covered with said coating material 1 is intended to be implanted.

The coating material 1 according to the invention is mainly formed of calcium phosphate, whatever the nature of the latter. Preferably, said calcium phosphate is a synthetic calcium phosphate. I! However, it is perfectly possible, without departing from the scope of the invention, to use a natural calcium phosphate instead.

Preferably, the calcium phosphate which forms the majority of said material 1 is constituted at least in part, and preferably mostly or even entirely, by hydroxyapatite. Alternatively, the calcium phosphate in question may consist at least in part, if not predominantly or entirely, of brushite. According to another embodiment perfectly conceivable, the material of coating 1 according to the invention may be mainly formed of a mixture of hydroxyapatite and brushite, or any other type of calcium phosphate or mixture of calcium phosphates.

According to the invention, the coating material 1 incorporates first and second additives respectively including copper and strontium.

The concomitant presence of copper and strontium within the material 1, mainly consisting of calcium phosphate, makes it possible to produce a bioactive functional layer which, while allowing the osteoblasts to be stimulated and favored, and to penalize or inhibit the activity of the osteoblasts. osteoclasts, has a pronounced antibacterial effect, which comes in particular from a synergistic joint action of copper and strontium. The coating material 1, because of the presence in it of copper and strontium, thus proves to play both a preventive role (reducing the risk of infection and reducing the risk of poor osseointegration) and curative (in situ treatment of a possible infection and promotion of bone regrowth, especially in the case of resumption of prosthesis).

Preferably, the first additive is substantially entirely made of copper (it being understood that "copper" here means both copper itself and all its derivatives and compounds, ions, salts or other). In the same way, the second additive is substantially entirely composed of strontium (it being understood that here again "strontium" refers to not only strontium itself but also all its derivatives and compounds, ions, salts or others). Advantageously, said first and second additives are respectively formed of copper ions and strontium ions. Preferably, the incorporation of the first and second additives referred to above is carried out so that copper and strontium atoms are substituted for calcium atoms in calcium phosphate forming mainly the material 1.

Preferably, the second additive is incorporated in the material 1 so that the strontium atoms replace at most 10% of the calcium atoms of said calcium phosphate. It appears indeed that a substitution rate which exceeds substantially 10% could lead to an alteration of the dimensions of the crystal, to a decreased growth of the latter and the increase of its rate of dissolution in vitro, especially when the calcium phosphate consists of synthetic hydroxyapatite.

Preferably, the degree of substitution of the calcium atoms (calcium phosphate constituting the majority of the material) by strontium atoms is between substantially 5 and 10%, and still more preferably between substantially 7 and 10%, which In particular, it makes it possible to significantly increase the activity of alkaline phosphatase, osteocalcin and the formation of type I collagen, without unjustifiably affecting the degree of crystallinity of the coating obtained. Ultimately, a substitution rate of the calcium atoms of the calcium phosphate by strontium atoms which is less than or equal to 10% makes it possible to significantly increase the contact area with the bone, to increase the percentage of osteo - integration, increase the volume and mechanical properties of bone regrowth on the surface of the implanted implantable medical device and increase the bone density around it. Preferably, a degree of substitution of the calcium atoms by strontium atoms of between substantially 7 and 10% leads to an excellent compromise between coating bioactivity on the one hand and coating crystallinity (and thus in vivo lifetime). 'somewhere else.

In view of the foregoing, the weight ratio strontium / calcium phosphate within the coating material 1 according to the invention is preferably advantageously between substantially 0.2 and 10%. Even more preferably, the weight ratio strontium / calcium phosphate is between substantially 5 and 10%, and even more preferably between 7 and 10%.

Advantageously, the copper content of the coating material 1 according to the invention is, for its part, high enough to provide a tangible antibacterial effect. Preferably, the copper content is also sufficiently high to color the coating, i.e. to give it a color different from the white color. For example, the mass ratio copper / calcium phosphate is also between substantially 0.2 and 10%. Even more preferably, the mass ratio copper / calcium phosphate is between substantially 5 and 10%, and even more preferably between 7 and 10%. Preferably, the copper atoms of the first additive are substituted for some of the calcium atoms of the calcium phosphate which mainly comprises the coating material 1 according to the invention. Preferably, the degree of substitution of the calcium atoms (calcium phosphate constituting the majority of the material) by copper atoms is between substantially 2 and 10%, and still more preferably between substantially 5 and 10%, which allows in particular to confer an anti-bacterial activity to the coating obtained.

Thus, the joint addition, as additives, of copper and strontium makes it possible to benefit from a material 1 whose degree of crystallinity is preserved (including when the calcium phosphate is of a synthetic nature) and which presents excellent preventive and curative properties, particularly in terms of bone regrowth and antibacterial control.

Advantageously, the coating material according to the invention is in a form enabling it to be deposited on the implantable medical device 5 by electrodeposition. In this specific embodiment, the material 1 is preferably predominantly formed of brushite and may for example be in the form of a liquid ionic solution. More specifically, in this particular embodiment, the material (and thus the copper and strontium ions advantageously forming the additives) is dissolved in a solvent to form an electrolytic bath intended to allow the electroplating of the coating (incorporating calcium phosphate, copper and strontium) by electrodeposition.

Alternatively, the coating material 1 may be in a form allowing it to be deposited on the implantable medical device by thermal spraying, and preferably by plasma spraying. In this case, the coating material 1 is advantageously in the form of a powder, and preferably in the form of an atomized powder incorporating calcium phosphate, copper and strontium.

Advantageously, the coating material 1 according to the invention also incorporates a third additive including manganese, preferably with a mass ratio manganese / calcium phosphate of between substantially 0.2 and 10%. Even more preferably, the mass ratio manganese / calcium phosphate is between substantially 5 and 0%, and even more preferably between 7 and 10%. The presence of manganese, the atoms of which are preferably substituted for the calcium atoms of the calcium phosphate (with a substitution ratio of preferably between 0.2 and 10%) is particularly beneficial because of a synergistic effect. particular obtained with strontium. Indeed, manganese (especially in the form of Mn ²⁺ ions) not only makes it possible to obtain a coloration of the resulting coating material 1 (so that a whole range of color can be obtained, for example by adjusting the concentration in copper and manganese) but also and above all to increase the crystallinity of the coating, by counterbalancing, and even surmounting, the effect of reducing the crystallinity induced by the presence of strontium. For example, the coating material 1 according to the invention may advantageously be predominantly formed of calcium phosphate, with a degree of substitution of the calcium atoms with manganese atoms of less than or equal to 5%, and preferably of the order by 5%, and a degree of substitution of the calcium atoms with strontium atoms of less than or equal to 10%, preferably of between 7 and 10%.

The joint presence of copper, strontium and manganese thus makes it possible to obtain a colored, antibacterial, osteoconductive coating whose crystallinity is preserved (thanks to the manganese as explained above). The coating thus obtained therefore also has in this case an optimal life in vivo, because of its high degree of crystallinity which prevents it from resorbing too quickly.

A coating material 1 mainly consisting of calcium phosphate and incorporating, as an additive, strontium and manganese (but not necessarily copper) is also an independent invention as such. According to the invention, the coating material 1 is formed of at least one upper layer 2 and one lower layer 3 superimposed. The coating material 1 is therefore a multilayer material, with at least one inner layer (corresponding to the lower layer 3) which is covered, preferably substantially uniformly, continuously, by a superficial layer corresponding to the upper layer 2. In the example of FIG. 1, the material 1 is formed solely of two layers, namely the upper layer 2 and the lower layer 3. It is however entirely possible, without departing from the scope of the invention, the material 1 is formed of more than two layers. Said upper 2 and lower 3 layers are preferably each predominantly formed of calcium phosphate.

Preferably, the first additive (which includes copper) is predominantly, and preferably totally, located in said upper layer 2, and preferably in a continuous, homogeneous distribution, while said second additive (which includes strontium) is predominantly , and preferably completely located in the lower layer 3, and preferably in a continuous, homogeneous distribution. Thus, in this preferred embodiment, the copper is contained in the upper layer 2, which advantageously does not contain strontium while the strontium is contained in the lower layer 3, which advantageously does not contain copper. With this feature, copper and strontium can act sequentially. Indeed, copper may be particularly active in the first weeks and months after surgery, thanks to its superficial positioning (in the upper layer 2). Thus, the coating formed by the material 1 will provide an effective anti-infectious function during the critical period (generally between 90 and 150 days after the intervention) in terms of infectious risks. Then, the progressive disappearance of the upper layer 2 will clear the lower layer 3, thus allowing an optimal action of strontium which will promote osteoblasts in the competition osteoblasts / osteoclasts. The coating formed by the material 1 allows in this case a particularly safe implantation, which significantly reduces the risks to which the patient is exposed, and in particular the risk of having to undergo a re-operation, in the short or long term, in because of infection and / or insufficient bone integration. In order to control this sequential operation, said upper and lower layers 3 respectively have a first and a second resorption time, said first resorption time being less than said second resorption time, so that the surface layer of the coating, whose function anti-infectious (thanks to the presence of copper) is of interest mainly for a limited time after implantation, disappeared by bioresorption to allow strontium to play its full role. For this purpose, the first resorption time is for example substantially between 3 and 12 months, preferably between 90 and 150 days, while the second resorption time is between 5 and 15 years, and is preferably greater than 10 years. This differential of bioresorption thus allows the copper, then the strontium, to ensure their respective functions in an optimal way. In order to obtain the above-mentioned bioresorption times, the upper layer 2 is for example predominantly formed of brushite, while the lower layer 3 is mainly formed of hydroxyapathite, whose rate of bioresorption is slower than that of the brushite. Thus, the invention relates, in the particularly advantageous embodiment mentioned above, to a multilayer coating material 1 with a lower strontium-loaded layer 3 covered by a top layer 2 loaded with copper.

Preferably, each of said upper 2 and lower 3 layers is substantially homogeneously charged respectively with copper and strontium. To this end, the copper (and thus in this case the first additive) is uniformly dispersed in the upper layer 2, just as the strontium (and thus in this case the second additive) is dispersed uniformly in the lower layer 3.

Advantageously, the third additive referred to above, which includes manganese, is predominantly localized (in the form of, for example, a uniform dispersion) in the lower layer 3, with the second additive. This co-localization of strontium and manganese in the same layer (in this case the lower layer 3) makes it possible to obtain the synergic effect mentioned above.

Advantageously, the coating material 1 further incorporates a fourth additive including magnesium, said fourth additive being preferably exclusively composed of magnesium. Preferably, the mass ratio magnesium / calcium phosphate is between substantially 0.2 and 10%. The addition of magnesium makes it possible to increase the solubility of the material 1, at the expense however of the activity of the osteoblasts, which tends to be inhibited by the presence of magnesium. The fourth additive may be located in the lower layer 3 and / or the upper layer 2. The invention relates of course, in a second aspect, a functional coating for implantable device formed of the material 1 described above.

The invention also relates, according to a third aspect, to an implantable medical device 5 covered at least in part by a coating formed from a material 1 according to the foregoing description.

In a particular embodiment, the implantable medical device 5 in question is coated at least partially with a layer 4 of titanium, itself covered at least partially by said coating according to the invention, which thus forms a second layer ( itself formed in this case two superposed layers 2, 3) superimposed on the layer 4 of titanium.

Finally, the invention also relates to a method for manufacturing a coating for an implantable medical device, said coating being in accordance with the foregoing description.

The method according to the invention comprises a step of producing a substance formed mainly of calcium phosphate.

The method according to the invention further comprises a step of incorporating into said substance first and second additives respectively including copper and strontium, to thereby obtain a coating material 1 mainly consisting of calcium phosphate and incorporating copper and strontium, as described above, which remains applicable, mutatis mutandis, to the process according to the invention.

As stated above, the calcium phosphate is preferably at least partly composed of hydroxyapatite and / or brushite. The aforementioned development step may therefore for example correspond to a calcium phosphate synthesis step, preferably in the form of hydroxyapatite and / or brushite.

In a particular embodiment, where it is desired to obtain a coating material 1 in the form of a powder, the step of incorporating the first and second additives are carried out during the manufacture of the powder. For example, said step of incorporating comprises adding said first and second additives (that is to say copper and strontium) to said substance formed mainly of calcium phosphate, during the step of producing said substance . Advantageously, the method comprises, after the step of producing said substance, an atomization step to give said substance a form of atomized powder. In this case, it is conceivable that the incorporation step comprises incorporating said first and second additives (copper and strontium) to said substance during the atomization step. Advantageously, when the strontium is added to the substance mainly formed of calcium phosphate during the synthesis step of the latter, the strontium is added in the form of Sr (NO 3) 2, or of Sr (CO 3) 2, or of Sr (OH) 2.

When the strontium is added to said substance during the atomization step, the strontium is advantageously in the form of strontium sulfate SrS0 ₄ . In the embodiments described above, the manufacturing method according to the invention thus makes it possible to obtain a pulverulent material loaded with copper and strontium which lends itself to a plasma spraying operation.

Alternatively, the method may comprise, prior to the step of incorporating said first and second additives (copper and strontium), a step of producing an electrolytic bath in which is dissolved said substance formed mainly of calcium phosphate, said step of incorporating incorporating said first and second additives (copper and strontium) in said electrolytic bath, thereafter for depositing the coating on the surface of the implantable medical device by electroplating. As explained above, the first and second additives are advantageously formed, respectively, of copper ions and strontium ions.

Preferably, the incorporation step is designed so that the mass ratio copper / calcium phosphate is between substantially 0.2 and 10% within said material 1. Similarly, the incorporation step is advantageously designed for that the strontium / calcium phosphate mass ratio is between substantially 0.2 and 10% within said material 1. Preferably, as explained in the foregoing in relation to the description of the coating material 1, the incorporation step is implemented so that strontium atoms are substituted for less than 10% of the calcium atoms of the calcium phosphate.

Advantageously, the process according to the invention comprises a step of incorporating into said substance a third additive including manganese, in order to obtain the effects and properties described above, and in particular to optimize the degree of crystallinity of the material. obtained in order to improve its lifetime in vivo and counterbalance the negative effects of the incorporation of strontium in this regard. A method of manufacturing a coating for an implantable medical device comprising a step of synthesizing a substance formed mainly of calcium phosphate and a step of incorporating into said substance, as additives, strontium and manganese, constitutes besides, an independent invention as such.

Advantageously, the method according to the invention also comprises a step of incorporating into said substance formed mainly of calcium phosphate a fourth additive including magnesium, in order to obtain the effects and properties described above. The invention thus makes it possible to obtain, in an extremely simple manner, a colored coating in the mass (of a color other than white), and therefore easily and easily identifiable, and which improves the patient's safety by virtue of its antibacterial properties. and rehabilitation and bone conduction. Said forming step comprises the formation of at least one upper layer 2 and one lower layer 3 superimposed to give said material 1 a multilayer character, said upper layers 2 and lower 3 being each predominantly formed of calcium phosphate.

Said step of incorporation is in this case carried out so that said first additive is mainly located in the upper layer 2 and for said second additive is mainly located in the lower layer 3, as exposed previously. Advantageously, as explained by the description of the material 1 above, said upper 2 and lower 3 layers respectively have a first and a second resorption time, said first resorption time being less than said second resorption time, to promote an action. sequential copper and strontium (the latter possibly being associated with manganese) and thus reduce the risk of postoperative complications while increasing the chances of long-term success of the intervention.

Preferably, the preparation step consists in forming on the one hand a first composition based on calcium phosphate (for example based on brushite) and on the other hand a second composition based on calcium phosphate (for example based on hydroxyapatite), said first and second compositions collectively forming said substance mentioned above. The incorporation step consisting for its part on the one hand to incorporate in the first composition ie the first additive (containing or formed by copper), preferably homogeneously and secondly to disperse in the second composition the second additive (containing, or formed by, strontium), preferably homogeneously.

The step of forming the upper 2 and lower 3 layers is carried out by depositing, on a temporary or definitive substrate (device 5 to be coated) a first layer of said second composition loaded as a second additive, and then depositing on said first layer a second layer of said first composition loaded first additive, optionally after a drying time and / or hardening of the first layer, to obtain a material 1 bilayer as shown in Figure 1. For example, the first layer is deposited on the device is implantable by plasma spraying, while the second layer is deposited on said first layer by electrodeposition.

The method according to the invention thus makes it possible to obtain in a simple, fast and inexpensive way a particularly effective implantable functional coating. POSSIBILITY OF INDUSTRIAL APPLICATION

The invention finds its industrial application in the design, manufacture and use of coating materials for implantable medical devices.

Claims

1 - coating material (1) for an implantable medical device, said material (1) being mainly formed of calcium phosphate and incorporating a first additive including copper, said material being characterized in that it incorporates a second additive including strontium and in that it is formed of at least one upper layer (2) and one lower layer (3) superimposed, said upper (2) and lower (3) layers being each predominantly formed of calcium phosphate, said first additive being mainly located in the upper layer (2) while the second additive is mainly located in the lower layer (3).

2 - coating material (1) according to claim 1 characterized in that said calcium phosphate is constituted at least in part by hydroxyapatite.

3 - coating material (1) according to claim 1 or 2 characterized in that said calcium phosphate is formed at least in part by brushite. 4 - coating material (1) according to one of the preceding claims characterized in that its copper content is sufficiently high to color the coating.

5 - coating material (1) according to one of the preceding claims characterized in that it is in a form allowing it to be deposited on said implantable medical device by electrodeposition. 6 - coating material (1) according to claim 5 characterized in that it is in the form of an ionic solution.

7 - coating material (1) according to one of the preceding claims characterized in that it is in a form allowing it to be deposited on said implantable medical device by plasma projection. - coating material (1) according to claim 7 characterized in that it is in the form of a powder. - coating material (1) according to one of the preceding claims characterized in that said first and second additives are respectively formed of copper ions and strontium ions, - coating material (1) according to one of the preceding claims characterized in that the mass ratio copper / calcium phosphate is between substantially 0.2 and 10%. - Coating material (1) according to one of the preceding claims characterized in that the mass ratio strontium / calcium phosphate is between substantially 0.2 and 10%. - Coating material (1) according to one of the preceding claims characterized in that it further incorporates a third additive including manganese. - Coating material (1) according to claim 12characterized in that said third additive is mainly located in the lower layer (3), with the second additive. - coating material (1) according to one of claims 1 to 13 characterized in that said upper layer (2) and lower (3) respectively have a first and second resorption time, said first resorption time being less than said second resorption time. - coating material (1) according to claim 14 characterized in that the first resorption time is substantially between 3 and 12 months, while the second resorption time is between 5 and 15 years. - coating material (1) according to one of claims 1 to 15 characterized in that said upper layer (2) is predominantly formed of brushite, while said lower layer (3) is predominantly formed of hydroxyapatite. 17 - coating material (1) according to one of the preceding claims characterized in that it further incorporates a fourth additive including magnesium.

18 - Implantable medical device (5) covered at least in part by a coating formed from a material (1) according to any one of the preceding claims.

19 - implantable medical device (5) according to claim 18 characterized in that it is coated at least partially with a layer (4) of titanium, itself covered at least partially by said coating.

20 - A method for manufacturing a coating for an implantable medical device, said method comprising a step of producing a substance formed mainly of calcium phosphate and incorporating a first additive including copper, said method being characterized in that comprises a step of incorporating into said substance a second additive including strontium, to thereby obtain a coating material (1) predominantly formed of calcium phosphate and incorporating copper and strontium, said forming step comprising forming at least one upper layer (2) and one lower layer (3) superimposed to impart to said material (1) a multilayer character, said upper (2) and lower (3) layers being each predominantly formed of calcium phosphate, said step of incorporation being carried out so that said first additive is mainly located in the upper layer (2) and for said second additive to be mainly located in the lower layer (3).

22-2 - Process according to claim 20 characterized in that said calcium phosphate is constituted at least in part by hydroxyapatite and / or brushite.

22. The method of claim 20 or 21, characterized in that said step of incorporating comprises adding said first and second additives to said substance during the step of developing the latter. - Process according to claim 20 or 21, characterized in that it comprises, after the step of producing said substance, an atomization step for conferring on said substance a form of atomized powder, said step of incorporation consisting in incorporating said first and second additives to said substance before or during the atomization step. - Process according to claim 20 or 21 characterized in that it comprises, prior to said step of incorporating said first and second additives, a step of elaboration of an electrolytic bath in which said substance is dissolved, said step d incorporating incorporating said first and second additives into said electrolytic bath. - Method according to one of claims 20 to 24 characterized in that said first and second additives are respectively formed of copper ions and strontium ions. - Process according to one of claims 20 to 25 characterized in that the incorporation step is designed so that the mass ratio copper / calcium phosphate is between substantially 0.2 and 10% within said material (1) . - Method according to one of claims 20 to 26 characterized in that the step of incorporation is designed so that the weight ratio strontium / calcium phosphate is between substantially 0.2 and 10% within said material (1) . - Method according to one of claims 20 to 27 characterized in that said upper layers (2) and lower (3) respectively have a first and a second resorption time, said first resorption time being less than said second resorption time .