Method for coating a substrate with calcium phosphate

Technical area

p0001The invention relates to a method for coating a porous substrate with a calcium phosphate layer.

State of the art

p0002The plasma spray method is used for coating substrates, in particular with a bioactive calcium phosphate layer, for example hydroxyapatite. However, this method is not suitable when the substrate is made of small particles or is not heat-resistant. The electrochemical deposition of calcium phosphate is also not applicable to particles even if the particles are electrically conductive.

p0003In the <patcit id="pcit0001" dnum="US6153266A"><text>U.S. Patent No. 6,153,266</text></patcit> A process is described for producing a calcium phosphate layer, in which, in a first step, the substrate is immersed in a phosphate-containing bath which does not contain calcium. Subsequently, the substrate is removed from the solution, dried and immersed in a second solution having a pH of 8 and containing calcium. In this solution calcium phosphate is formed on the surface of the substrate. A disadvantage with this method is firstly that the coating is carried out with 2 process steps. A further disadvantage is that it is not possible with the two-step method to produce the layer thickness to the desired extent. For thick layers, the known method therefore provides a further process step,

p0004Alone <patcit id="pcit0002" dnum="EP0322250A1"><text>EP-A1-0 322 250</text></patcit> Are freed from the adhering water by air drying or sintering. In any case, work is carried out under normal pressure. In one case, the coating is applied by centrifugation.

p0005In <patcit id="pcit0003" dnum="US6232146B1"><text>US-B1-6 232 146</text></patcit> A calcium phosphate composite is prepared which may additionally contain silicon or titanium as an elemental component of the sol. These composites are separated from the preparation solution by centrifugation and then subjected to thermal treatment. Porosity is achieved, inter alia, by heating organic additives.

p0006In <patcit id="pcit0004" dnum="EP0347028A2"><text>EP-A2-0 347 028</text></patcit> The calcium phosphate compound is produced by kneading or mixing the phosphoric acid component with a calcium component with the addition of sodium hydroxide. In any case, work is carried out under normal pressure. The finished mixture can be administered subcutaneously or intramuscularly.

p0007The disadvantage of these solutions is that work is carried out under normal pressure, and gases present in the pores can thus remain or make adhesion of the coatings more difficult.

DESCRIPTION OF THE INVENTION

p0008The object of the invention is to eliminate the disadvantages of the known methods and to produce a calcium phosphate layer in a simple process which has a desired layer thickness.

p0009According to the invention, this object is achieved by the following steps: introduction of the substrate into a calcium phosphate gel, removal of the substrate located on the substrate by applying a negative pressure, aeration of the mixture of substrate and gel, drying of the substrate coated with the gel and separation Of calcium phosphate particles from the coated substrate or introducing the substrate into a calcium phosphate-containing SiO₂Gel or colloid, removing air and solvent by applying a vacuum and working up as described above.

p0010Advantageous embodiments of the invention are described in the subclaims.

p0011The advantage of the method according to the invention is that it is possible to provide a substrate with a calcium phosphate layer in one step. Since the layer thickness depends on the concentration of the calcium phosphate gel or the colloidal solution, a desired layer thickness can be produced by adjusting the concentration. The method is suitable for coating large area substrates and particles. It is independent of which material the substrate is made of. The adhesive strength of the layer on the substrate is increased by removing the gas (air) on the substrate by applying a vacuum. This method is particularly advantageous when the substrate has pores. It then removes the air from the pores and the calcium phosphate gel can penetrate into the pores.

p0012A further advantage is that it is possible to produce the layer of different calcium phosphate modifications by a suitable composition of the gel. This is particularly important for a bioactive layer. It is known that the degree of bioactivity of a layer increases with its instability in a physiological environment. Calcium phosphates, with a much higher solubility than bruschite and monetite, are particularly important for the healing phase in the bones. If the coated particles are to be used with the objective of improving the composite of the substrate with bone tissue, the gel consists of bruschite and / or monetite or a mixture of bruschite and / or monetite and hydroxylapatite. However, the gel may also consist of a mixture of silica gel and calcium phosphate. It may also contain fillers such as calcium sulfate or factors which have a bone-inducing effect. It is also possible to introduce into the layer medicaments such as antibiotics, the growth of the bone accelerating or inhibiting the breakdown of the bone inhibiting agent, for example by mixing into the gel.

p0013The substrates coated with the method according to the invention are particularly suitable as bone replacement material for filling bone defects or for filling a gap between an implant and a bone into which the implant has been inserted. For these purposes, preferably coated substrate particles are used, which are biocompatible. The particles can also serve to anchor the implant in the bone.

Route (s) for carrying out the invention

p0014The invention is explained in more detail below with the aid of examples, without being restricted to this.

p0015Example 1:

p0016A phosphate solution is added to a solution of calcium hydroxide with constant stirring. The fine precipitate formed is concentrated by centrifugation and separated from the clear solution which separates it from it. A titanium granulate, which was previously degreased and purified, is introduced into the calcium phosphate gel thus obtained and thoroughly mixed. This mixture is placed in a vacuum chamber. When a suitable negative pressure is applied, the air is removed from the pores of the titanium granulate. During the subsequent aeration, the calcium phosphate gel penetrates into the pores. The coated granules are dried, singulated and separated by screening of precipitated calcium phosphate particles. The layer thickness of the calcium phosphate is variable and can be adjusted via the concentration of the prepared gel.

p0017Example 2:

p0018Any calcium phosphate powder is mixed with a silica gel. A degreased and purified titanium granulate is introduced into this gel and thoroughly mixed. As in Example 1, the air is removed from the pores of the titanium granules in order to allow the calcium phosphate-silica gel to penetrate into the pores during venting. The coated granules are dried, singulated and separated by means of an air stream of precipitated calcium phosphate-silica particles. The layer thickness of the calcium phosphate silicate can be adjusted via the concentration of the gel.