CH618951A5 - Process for the preparation of a sintered ceramic - Google Patents

Abstract

A new sintered ceramic, polycrystalline in microscopic form, comprising hydroxyapatite or a mixture of hydroxyapatite and whitlockkite is prepared. The preparative process consists in reacting the calcium ion with the phosphate ion in aqueous medium and at a pH of 10 to 12 to obtain a gelatinous precipitate of calcium phosphate, in separating the said precipitate from the solution and in heating the said precipitate to a temperature of at least 1000 DEG C, but lower than that at which an appreciable decomposition of the resulting ceramic takes place. This temperature is maintained for a sufficient time to cause the sintering and an essentially maximum densification of the resulting product. These new ceramics can be used for preparing tooth repair compositions and surgical prosthesis materials.

Description

The present invention relates to a process for the preparation of a polycrystalline sintered ceramic in macroscopic form, intended in particular for dentistry and orthopedics.

Much of current dental research is focused on the preparation of materials which can be used as tooth and bone substitutes, as tooth repair materials for fillings (fillings) and crowns and as prosthetic filling materials. for the bones. Dental research is also geared towards preventing the formation of dental plaque, which is thought to be responsible for tooth decay and alveolodental periostitis.

The filling materials currently used in tooth repair compositions, such as quartz, alumina, silicates, glass beads, etc., show little chemical or physical resemblance to enamel teeth. A particular shortcoming of these materials lies in the incompatibility of the coefficients of linear expansion of the filling material and the tooth, which can ultimately lead to marginal leaks and the formation of new caries. The dental profession has therefore long desired a dental filling composition whose physical properties closely approximate those of natural teeth.

On the other hand, in the field of surgical prosthesis materials, which is currently dominated by non-corrosive and very resistant alloys, there is a recognized need for a material which more closely resembles biological hard tissues, because the problem of non -rejection by tissue and adhesion to tissue has not yet been completely resolved [Hulbert et al., "Materials Science Research", 5, 417 (1971)].

In research directed towards the discovery of effective anti-plaque chemotherapeutic agents, there is a need for a standardized test material having a surface which resembles that of teeth, both in terms of plaque formation and the substantivity of the chemical agents. Although natural teeth are already used for this purpose, they have the disadvantages of being very variable, of not always being available in sufficient numbers, and of requiring a thorough cleaning before use. Therefore, other materials on which plaque builds up are used, for example powdered hydroxylapatite, acrylic teeth, glass and wire. While they may be sufficient for the study of plaque formation as such, these materials bear little resemblance to the surface of natural teeth, and therefore are not perfectly suited for the discovery of agents effective antiplates. For example, it is known that chemicals that inhibit plaque formation on teeth do not necessarily do so on glass and wire (Turesky et al., "J. Periodontology", 43, 263 (1972)] . There is a need for an inexpensive and readily available material which is chemically similar to tooth enamel, hard, dense and very polished.

It has been suggested that hydroxylapatite, Caio (PC> 4) 6 (OH) 2, also called basic calcium orthophosphate, which constitutes the mineral phase of teeth and bones, is suitable for the various uses indicated above and, in particular, fact, EUA patent No. 2508816 discloses a process for obtaining hydroxylapatite from tooth enamel as well as its use as a mixture with a synthetic resin as a composition of artificial teeth. This process is long and laborious and limited to the production of finely divided hydroxylapatite. In addition, the process depends, of course, on the number of natural teeth available.

Kutty [“Indian J. Chem.”, 11, 695 (1973)] disclosed mixtures of hydroxylapatite and whitlockite produced by the decomposition of powdered hydroxylapatite at various temperatures.

Bett et al., ["J. Amer. Chem. Soc. ”, 89, 5535 (1967)] described the preparation of particulate hydroxylapatite with a Ca / P stoichiometry ranging from 1.67 to 1.57. The materials thus produced contained large intercrystalline pores. It has also been reported that, by heating to 1000 ° C., the hydroxylapatites which are too poor in calcium undergo a partial transformation in phase, whitlockite.

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EUA Patent No. 3787900 discloses a prosthetic material for bones and teeth which comprises a refractory compound and a compound containing phosphate and calcium, for example whitlockite.

Several attempts have been made to obtain a hard and resistant macroscopic form of hydroxylapatite. However, none of the already known forms of hydroxylapatite has been found to be completely satisfactory. Thus, Roy and Linnehan [“Nature”, 247, 220 (1974)] described an elaborate hydrothermal exchange process allowing the calcium carbonate which forms the skeleton of the marine coral to be transformed into hydroxylapatite. The material thus produced necessarily retained the high porosity characteristic of the structure of the coral, and also had a relatively low tensile strength, of approximately 21 to 33 kg / cm 2, which constitutes a serious drawback for a prosthetic material.

Monroe et al. ["Journal of Dental Research", 50, 860 (1971)], reported the preparation of a ceramic material by sintering compressed tablets of hydroxylapatite. The material thus produced was in fact a mixture of hydroxylapatite and approximately 30% of α-whitlockite, which is the tricalcium phosphate of formula Ca3 (PC> 4) 2, in the form of an ordered mosaic network of crystallites polyhedral, and seemed to be too porous to be used as dental material.

Rao and Boehm [“Journal of Dental Research”, 53,1351 (1974)] revealed obtaining a polycrystalline form of hydroxylapatite by isostatic compression of powdered hydroxylapatite in a mold, and isothermal sintering of the molded form . The resulting ceramic was porous and had a maximum compressive strength of approximately 1200 kg / cm2.

Bhaskar et al. [“Oral Surgery”, 32, 336 (1971)] described the use of a ceramic material based on calcium phosphate and biodegradable to repair the defects of the bones. This material is very porous, is absorbed from the location and does not have the mechanical strength of a non-degradable metallic or ceramic implant.

In accordance with the present invention, there is provided a process for the preparation of a sintered polycrystalline ceramic, in macroscopic form which consists in reacting the calcium ion with the phosphate ion in an aqueous medium and at a pH of 10 to 12, so as to form a gelatinous precipitate of a calcium phosphate whose molar ratio of calcium to phosphorus is between 1.44 and 1.72 to separate said precipitate from the solution and to heat said precipitate to a temperature of 1000 ° C at least, but at a temperature below that at which appreciable decomposition of the resulting ceramic occurs.

A new, substantially pure ceramic form is obtained which is hard, dense and has a very good polish. Chemically, this shape is very similar to tooth enamel. In addition, this new material can be prepared in a relatively simple manner from inexpensive starting materials, and is obtained with uniform quality, which avoids the undesirable variability inherent in natural teeth.

The incorporation of the new ceramic form in the tooth repair compositions provides a dense filling material whose coefficient of expansion is virtually identical to that of natural tooth enamel.

The dental and surgical implantation material which is provided by the present invention is hard, resistant and perfectly biocompatible, and can be manufactured in any desired form without the use of high pressure techniques or other sophisticated techniques. In addition, as will be described in detail below, any desired degree of porosity can be imparted to this material, which allows the tissue to grow within it.

As will be seen, the characteristics of the new sintered ceramic which is described here can make it an ideal material for the manufacture of discs, plates, rods, etc., for the testing of dental anti-plaque agents.

An implementation of the method makes it possible to obtain a new biphasic ceramic material comprising hydroxylapatite and whitlockite. As will be described in more detail below, this biphasic ceramic is hard, dense, non-porous, biocompatible, easy to manufacture in any desired form, and by virtue of the known resorption properties of whitlockite, is useful as a material for resistant and partially absorbable surgical implant.

Although a certain degree of porosity of surgical implantation materials can be advantageous by allowing the circulation of moods and the growth of tissues inside them, this same porosity necessarily reduces the mechanical resistance of the implant. The new biphasic ceramic, although it is dense, mechanically resistant and practically non-porous, can nevertheless allow the circulation of moods and the internal growth of tissues, because the whitlockite phase it contains is slowly absorbed from the implant and is replaced by natural organic hard tissue.

The new physical form of hydroxylapatite, which is distinguished from these biological and geological forms and from all the other already known synthetic forms, as indicated below, consists of a sintered, polycrystalline, isotropic ceramic material which is resistant, hard, dense , white and translucent, and which comprises substantially pure hydroxylapatite, the average size of the crystallites of which ranges approximately from 0.2 to 3 | i, the density of which ranges from approximately 3.10 to 3.14 g / cm3, and which is further characterized by the absence of pores and by a cleavage along smooth curved planes. On the other hand, as ordinarily produced, the material described above has a compressive strength which ranges approximately between 2500 and 8800 kg / cm2, a tensile strength which ranges approximately between 200 and 2000 kg / cm2, a coefficient of linear thermal expansion which ranges approximately between 10 and 12 ppm per degree Celsius, a Knoop hardness which ranges approximately between 470 and 500, and a modulus of elasticity approximately equal to 4 x 105 kg / cm2, and it is not birefringent in polarized light. The initial evaluation of the new hydroxylapatite ceramic revealed that it was a translucent, resistant, hard, dense, white ceramic, comprising substantially pure microcrystalline hydroxylapatite, forming a random isotropic network and having a compressive strength which ranges from approximately 2,500 to 5,300 kg / cm2, tensile strength which ranges from approximately 200 to 3,500 kg / cm2, a coefficient of linear thermal expansion which ranges from approximately 10 to 12 ppm per degree Celsius, a Knoop hardness which ranges approximately between 470 and 500, and a modulus of elasticity approximately equal to 4 x 10s kg / cm2, and characterized by a cleavage along smooth curved planes, and by the absence of birefringence in polarized light.

The dense term, as used here, designates a very compact arrangement of particles leaving practically no empty spaces or unoccupied intervals between them.

Unlike the form of hydroxylapatite which is described above, the geological hydroxylapatite and the synthetic hydroxylapatite, which are prepared by a hydrothermal process, are macrocrystalline, split along flat planes and are birefringent. Biological hydroxylapatite is distinguished in that it generally contains significant amounts of carbonate ion in the apatite network and, in its purest state, that is to say in the tooth enamel, in that it is anisotropically arranged in spiral radiating rods, so that it splits along straight lines along the interface of these enamel rods and has a relatively low tensile strength, which is 100 kg / cm2.

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In addition to the properties described above of the new ceramic form of hydroxylapatite, this material is also perfectly biocompatible and therefore eminently suitable as a material for dental and surgical prostheses. Thus, ceramic can be molded or machined into dental crowns, artificial teeth, bone and joint prostheses, cannulas, artificial limb anchors that can be attached to bones and protrude through the skin, and test surfaces for the study of dental plaque, the formation of cavities, arthritis, and other diseases that can affect teeth and bones. Properly ground, the new ceramic of this invention can be used as cross-linked synthetic texture bone to repair bone defects, as an abrasive, and, in combination with normal resins, as a tooth repair composition, as described below. .

In order to use it as a test surface for the evaluation of agents which inhibit dental plaque, the new ceramic can be manufactured in the form of bodies having all appropriate dimensions and shapes, preferably shapes and dimensions such that the 'The body can easily be placed in a normal test tube. This is conveniently accomplished by cutting or machining large pieces, plate-shaped, dried filter cake, to the appropriate size, and then sintering. The sintered products are carefully polished using normal lap grinding techniques, and the resulting bodies are then used as substrates to assess the plaque inhibitors according to the procedures described by Turesky et al. (supra). After use, the ceramic bodies are simply repolited to have a new test surface.

As ordinarily produced, the ceramic prepared according to this invention is not only dense but also non-porous, and if a non-porous material is essential for dental applications, a certain degree of porosity of the implantation devices can be advantageous by allowing the circulation of moods and the internal growth of tissues. The ceramic obtained according to the invention can be given a variable degree of porosity, in a manner similar to that described by Monroe et al. (supra). Thus, organic substances such as starch, cellulose, cotton or collagen are mixed with the gelatinous hydroxylapatite precipitate in amounts ranging from 5 to 25% by weight. During the subsequent sintering process, these organic substances are burnt, which gives rise to holes and channels in the ceramic product which otherwise would not be porous. Alternatively, porosity can be obtained mechanically by drilling or machining holes and openings in the non-porous ceramic.

In this way, an artificial tooth composed of the ceramic which has just been described can be made porous at the implantation point, while the exposed surface of the tooth remains non-porous. Implantation can be done as reported by Hodosh et al., "Journal of the American Dental Association", 70, 362 (1965). Alternatively, the ceramic obtained according to the invention can be combined with a polymerizable or polymerized binder, as described below, and the resulting composition can be used as a coating for metallic implants as described in EU patent No. 3609867, issued on October 5 1971.

As mentioned above, it is possible to obtain a sintered, polycrystalline, isotropic ceramic product which is resistant, hard, dense and white, and which comprises as first phase from 14 to 98% by weight of hydroxylapatite, and as second phase from 2 to 86% by weight of whitlockite, and which is characterized by the absence of pores and by a cleavage along smooth curved planes.

Whitlockite, also called tricalcium phosphate, is a mineral with the chemical formula Ca3 <PO4) 2 and which can exist in the form of a crystal phase a or a crystal phase ß. The term whitlockite as used herein designates either the a phase, the ß phase, or a mixture of these two phases.

The new biphasic ceramic remains a porous polycrystalline material regardless of the relative concentrations of hydroxylapatite and whitlockite it contains. It will however be appreciated that the hydroxylapatite and the whitlockite have different physical properties, and therefore that the physical properties, for example the density and the optical properties of the biphasic ceramic, will depend on the relative proportions of hydroxylapatite and whitlockite that 'it contains. For example, the theoretical density of whitlockite is smaller than that of hydroxylapatite and therefore the observed density of a sample of biphasic ceramic containing about 40% hydroxylapatite and 60% whitlockite is 2 , 98 g / cm3, against a density of 3.10 g / cm3 for a sample of pure hydroxylapatite.

The biphasic ceramic described above is also biocompatible and therefore suitable as a surgical prosthesis material. Thus, this material can be molded or machined in the form of bone and joint prostheses, or else in any form suitable for filling a vacuum or a defect in a bone. The whitlockite that is contained in a prosthesis made from this biphasic ceramic will eventually absorb and be replaced by the internal growth of natural biological hard tissue. Of course, the amount of internal tissue growth will depend on the proportion of absorbable whitlockite contained in the ceramic.

As it is commonly produced, the new biphasic ceramic is not porous. However, a variable degree of porosity can optionally be imparted to the ceramic, as described above, for the new ceramic form of hydroxylapatite.

The biphasic ceramic can also be made acid-resistant by fluoriding it, as described below for ceramic hydroxylapatite.

The new ceramic form of hydroxylapatite which is described above can be prepared by precipitating, in an aqueous medium at a pH of 10 to 12, hydroxylapatite whose molar ratio of calcium to phosphorus is between 1.62 and 1.72, by separating the precipitated hydroxylapatite from the solution, and heating the hydroxylapatite thus obtained at a temperature and for a time sufficient to cause sintering and maximum densification of said hydroxylapatite practically without decomposing it.

Thus, the hydroxylapatite is precipitated in an aqueous medium by reacting the calcium ion with the phosphate ion at a pH of 10 to 12. All the compounds containing calcium or phosphate which give calcium ions and phosphate ions in an aqueous medium are suitable, provided that the ions which are respectively combined with the calcium ions and the phosphate ions in said compounds readily separate from the hydroxylapatite produced, do not incorporate themselves into the hydroxylapatite network, or do do not otherwise interfere with the precipitation or isolation of the substantially pure hydroxylapatite. The compounds which give the calcium ion are, for example, calcium nitrate, calcium hydroxide, calcium carbonate and the like. The phosphate ion can be provided by diammonium acid phosphate, ammonium phosphate, phosphoric acid and the like. In the present process, calcium nitrate and diammonium acid phosphate are the preferred sources of calcium ions and phosphate ions respectively.

The new form of hydroxylapatite can be conveniently prepared in the following manner. First, calcium nitrate and diammonium acid phosphate are interacted in a molar ratio of 1.67 to 1, in aqueous solution at a pH of 10 to 12, so as to form a gelatinous precipitate of hydroxylapatite. The procedure described by Hayek et al., "Inorganic Syntheses", 7, 63 (1963) is satisfactory for this. The gelatinous hydroxyl suspension is then left

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apatite thus obtained remain in contact with the original solution, for a time sufficient to allow the calcium / phosphorus ratio of the hydroxylapatite in suspension to reach a value of 1.62 to 1.72. This can be done conveniently, either by stirring the suspension at room temperature for at least 24 hours, or by boiling the suspension for 10 to 90 minutes, or by first boiling and then allowing it to stand at room temperature . Preferably, the suspension is boiled for 10 min, then it is left to stand at room temperature for 15 to 20 h. The hydroxylapatite is then separated from the solution by suitable means, for example by centrifugation and vacuum filtration. The gelatinous product thus collected contains a high proportion of trapped water, most of which can be removed by wringing. If desired, the resulting moist, clay-like material can be cut or shaped into a suitable form, or it can be poured into a suitable mold. Note that there is usually a shrinkage of approximately 25%

when the wet hydroxylapatite is dried, and a further shrinkage of about 25% occurs during the sintering described below. This must, of course, be taken into consideration when shaping or molding the material. The wet product can be slowly heated to the sintering temperature of 1000 to 1250 ° C, at which temperature all the remaining water will have been removed. Maintaining the temperature at 1000-1250 ° C for approximately 20 min to 3 h then causes sintering and maximum densification of the product. Usually it is best to isolate the dry product before sintering it. Thus, the wet product can be dried at 90 to 900 ° C for 3 to 24 hours, or until it contains only 0 to 2% of water. It is generally preferable to use drying conditions of 90 to 95 ° C for about 15 h, or until the water content has been reduced to 1 to 2%. The hydroxylapatite obtained in this way is brittle and porous, but it has considerable mechanical strength. Some drying or cracking of the clay-like material may occur on drying, especially if a thick filter cake is used. It is however easy to obtain pieces having a surface of 100 cm2 and a thickness of 3 mm. Fragmentation or cracking can be minimized or even prevented during drying by adding to the suspension of freshly precipitated hydroxylapatite 0.4 to 0.6% by weight of an organic binder such as collagen, cellulose powder or cotton, preferably about 0.5% collagen. The organic binder volatilizes during the subsequent sintering, and the physical characteristics of the ceramic product appear practically unchanged compared to those of the product obtained in the absence of such a binder. Of course, the use of much larger quantities of organic binder makes it possible to obtain a porous ceramic product as described above. It is also possible to use other conventional organic and mineral binders well known in the ceramic art.

It is usually convenient at this stage to cut or further shape the dry hydroxylapatite to give it roughly the shape desired for the final product, taking into account the above-mentioned shrinkage which occurs during sintering.

The hydroxylapatite bodies, before sintering, must be uniform and free from defects. The presence of cracks or cracks can cause the pieces to break during the sintering process. Normally, the products are then sintered at 1050-1250 ° C for 20 min to 3 h, the temperatures and times being in inverse ratio to each other. The sintering is preferably carried out at 1100-1200 ° C for 0.5 to 1 h. The dense and hard ceramic bodies thus obtained can then be polished or machined by conventional techniques.

It is crucial, in the above process, to prepare the hydroxylapatite in the form of a gelatinous precipitate from an aqueous solution, because it is only in this gelatinous state of cohesion that the hydroxylapatite can be shaped or

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molded then dried and sintered giving a macroscopic form of ceramic. Dry particulate or granular hydroxylapatite cannot be reconstituted in this gelatinous state of cohesion. If, for example, the hydroxylapatite powder is suspended in water and if it is filtered, a particulate and cohesive filter cake is obtained which simply dries and crumbles and cannot be shaped, molded or transformed into a macroscopic form of ceramic. On the other hand, although the hydroxylapatite can be mechanically compressed into a powder to form a shaped body, for example a tablet, when it is sintered according to the method of this invention, the product obtained is very porous, and does not split not in smooth planes, but just breaks up into coarse pieces.

Although the formation of hydroxylapatite in an aqueous medium is a complex and incompletely understood process, it is generally believed that calcium ions and phosphate ions combine initially to form a hydroxylapatite poor in calcium, whose ratio calcium / phosphorus is equal to 1 , About 5. In the presence of calcium ions, this species then undergoes a slow transformation into hydroxylapatite having a calcium / phosphorus ratio of 1.67. [Eanes et al., "Nature", 208, 365 (1965), and Bett et al., "J. Bitter. Chem. Soc. ”, 89, 5535 (1967)]. Thus, in order to obtain a ceramic comprising substantially pure hydroxylapatite, it is imperative, in the process of this invention, to allow the initial gelatinous precipitate of hydroxylapatite to remain in contact with the original solution for a sufficient time to allow its calcium / phosphorus ratio to reach a value of 1.62 to 1.72. If we deviate much from this interval, we obtain a less translucent ceramic product. For example, if the hydroxylapatite is precipitated at room temperature and if it is collected within 2 hours of the precipitation, it is found that its calcium / phosphorus ratio is equal to 1.55-1.57, and that the The ceramic that is finally obtained is opaque and appears, by X-ray diffraction, to be a mixture comprising hydroxylapatite and whitlockite. In fact, as described in more detail below, a material whose calcium / phosphorus ratio is equal to 1.44-1.60 is useful for the preparation of the biphasic ceramic described above. Thus, although the process of the invention provides a translucent ceramic comprising substantially pure hydroxylapatite, having regard to the mode of incompletely elucidated formation of hydroxylapatite in an aqueous medium, it may be advantageous to control the formation of hydroxylapatite to ensure that the desired calcium / phosphorus stoichiometry has been obtained and that the product, once sintered, will include substantially pure hydroxylapatite. This is conveniently achieved by removing a fraction of the hydroxylapatite suspension, separating the product, drying and sintering as described above and subjecting the ceramic thus produced to elemental analysis and X-ray analysis.

The sintering temperature is also crucial for the process of the invention. Thus, the unsintered hydroxylapatite having the desired calcium / phosphorus ratio of 1.32-1.72 can be transformed into the ceramic of this invention by heating it to a temperature of at least about 1000 ° C. temperature of 1000 ° C, complete sintering and maximum densification can take 2 to 3 hours, while at 1200 ° C, the process can be completed in 20 to 30 minutes. It is preferable to perform the sintering at a temperature of approximately 1100 ° C for approximately 1 hour. A temperature significantly lower than 1000 ° C will only give an incomplete sintering whatever the duration of the heating, while a heating beyond 1250 ° C for more than 1 h will cause a partial decomposition of the hydroxylapatite into whitlockite .

The biphasic ceramic described above, comprising a first phase of hydroxylapatite and a second phase of whitlockite, can be prepared by precipitating, in an aqueous solution at a pH of 10 to 12, a phosphate compound of cal-

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cium whose molar ratio of calcium to phosphorus is approximately between 1.44 and 1.60, preferably between 1.46 and 1.57, by separating the precipitate from the solution, and by heating the solid thus obtained to a temperature and for a time sufficient to cause its sintering and its maximum densification.

The calcium phosphate compound having the required stoichiometry, namely Ca / P = 1.44-1.60, is obtained by making the calcium ion and the phosphate ion interact in an aqueous medium at a pH of 10-12, using the same sources of calcium ions and phosphate ions as those described above for the preparation of single-phase hydroxylapatite. Calcium nitrate and diammonium acid phosphate are the preferred reagents.

Thus, the biphasic ceramic can be prepared by interacting calcium nitrate and diammonium acid phosphate in a molar ratio of 1.67 to 1, that is to say as described above for the preparation of hydroxylapatite single-phase ceramic, provided that the initial gelatinous precipitate is not heated and allowed to remain in contact with the original solution for no more than approximately 4 h, or else that the molar ratio of calcium is not allowed the phosphorus of the precipitate exceed a value of about 1.60.

As described above for the preparation of the single-phase ceramic hydroxylapatite, the calcium phosphate precipitate is separated from the solution, washed, optionally shaped or molded into a suitable form and, optionally, it is dried and isolated before sintering.

The suspension of freshly precipitated calcium phosphate can also be treated with organic binders or with fluoride ions as described above for the single-phase hydroxylapatite.

Sintering is carried out by heating at 1050-1350 ° C for 20 min to 3 h.

The proportion of whitlockite contained in the ceramic thus produced depends on the moment when the precipitate is separated from the original solution, and it can range between 2 and 83% approximately. Thus, when the product is isolated 5 minutes after precipitation, its calcium / phosphorus ratio is 1.55, and the ceramic that is finally obtained contains approximately 83% whitlockite. If the product is isolated 2 h after precipitation, its calcium / phosphorus ratio is 1.57 and the resulting ceramic contains approximately 61% whitlockite. The isolation of the product 4.5 h after precipitation finally provides a ceramic which is estimated to contain 2% whitlockite, that is to say a percentage which is hardly detectable by X-ray diffraction, this method with a minimum concentration sensitivity of 2 to 3%. Of course, if the product is allowed to remain in contact with the original solution for more than approximately 7 hours, the ceramic finally obtained is practically single-phase hydroxylapatite.

Alternatively, the new biphasic ceramic can be prepared by reacting the calcium ion with the phosphate ion in an approximate molar ratio of 1.50-1.60 to 1. In this way, the molar ratio of calcium to phosphorus in the calcium phosphate precipitate cannot exceed a value of approximately 1.60, whatever the time during which said precipitate remains in contact with the original solution.

Thus, the new biphasic ceramic can be prepared in the same way as that described above for the preparation of ceramic hydroxylapatite with a single phase, except that the reactants are made to interact, that is to say calcium nitrate and diammonium acid phosphate, in an approximate molar ratio of 1.50-1.60 to 1, to form ceramics comprising about 30 to 50% hydroxylapatite and about 50 to 70% whitlockite.

The ceramic in whitlockite phase can be further enriched by combining the characteristics of the two preceding processes, that is to say by making the calcium ion interact with the phosphate ion in an approximate molar ratio of 1.50-1.60 at 1, and isolating the precipitated calcium phosphate compound within a short time, preferably about 5 min to 4 h, after the precipitation. The ceramics thus produced comprise approximately 10 to 30% of hydroxylapatite and 70 to 90% of whitlockite.

It is known that the hydroxylapatite undergoes decomposition into whitlockite at approximately 1250 ° C., and it will therefore be appreciated that prolonged heating of the single-phase ceramic hydroxylapatite of this invention at temperatures of approximately 1250 ° C., or more, will cause a partial decomposition of said hydroxylapatite into whitlockite, thus providing yet another process for producing the biphasic ceramic according to the invention.

Another subject of the invention is the use of the new ceramic for preparing a composition for repairing teeth comprising a mixture of said finely divided ceramic and of a polymerizable or polymerized binder which is compatible with the conditions prevailing in the oral cavity. . The new composition for repairing teeth may comprise from 10 to 90%, preferably 60 to 80%, by weight, of finely divided ceramic, the rest of said composition, ie 10 to 90% by weight, comprising a polymerizable or polymerized binder. and acceptable from a dental standpoint, as well as suitable and known polymerization catalysts such as aliphatic ketone peroxides, benzoyl peroxide, etc., reactive diluents such as di-, tri-, and tetraethylene glycol dimethaciylate, hardeners such as acrylamides substituted on nitrogen by a 3-oxohydrocarbon group, such as those described in EUA patent No. 3277056, issued on October 4, 1966, promoters or accelerators such as metal acetylacetonates, tertiary amines, for example N, N-bis- (2-hydroxyethyl) -p-toluidine, etc., or crosslinking agents such as zinc oxide, etc., which are present in varying amounts of about 0.01 to 45% of the weight of the composition t otal. Although it is not essential, one can add to said composition, at a rate of 0.05 to 10% of its total weight, a surfactant comonomer or bonding agent, such as the reaction product of N- phenylgly-cine and glycidyl methacrylate which is described in EUA Patent No. 3200142, issued August 10, 1965, methacryloxypro-pyltrimethoxysilane, 3,4-epoxycyclohexylethyltrimethoxysilane, vinyltiichlorosilane, etc. This binder or bonding agent promotes the bonding of the ceramic material with the resin and of the dental filling composition with the natural tooth. Thus, the ceramic hydroxylapatite which is the subject of this invention is ground to a suitable particle size of about 5 to 100 µm, using conventional grinding techniques, and then mixed with an appropriate amount of a resin. normal known in the tooth repair technique, such as hydroxyethyl methacrylate, polymethyl methacrylate, polyacrylic acid, unsaturated polyesters of propylene glycol fumarate phthalate such as those sold by the Allied Chemical Co. under the reference 23 LS8275 and by the company Pittsburgh Plate Glass under the name Selectron 580001, the unsaturated and styrene-modified polyesters such as Glidpol 1008, G-136 and 4CS50 from the company Glidden, epoxy resins like Araldite 6020 from Ciba, ERL2774 from Union Carbide and the bisacrylate monomer prepared from glycidyl methacrylate and bisphenol A, which is described in EUA patent No. 3066112, issued on 27 November 1962. The resin may comprise a single monomer or a mixture of two or more comonomers. It is optionally possible to add to the preceding composition additives such as dyes, mineral pigments and fluorescent agents, according to the principles known in the art which relates to these products. The resin, ceramic hydroxylapatite and optional ingredients such as silanes serving as binders, dyes, mineral pigments or fluorescent agents should be mixed before the addition of the catalyst, hardener, crosslinking agent. , the promoter and / or the accelerator. However, the order in which we mix the

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ingredients is not crucial, and you can mix these ingredients at the same time. Using conventional techniques, the composition thus produced can be used as a dental filling material, as dental cement, as a coating for the dental socket, as a covering for dental pulp, or else the composition can be poured into a suitable mold. to produce an artificial tooth or an artificial denture.

It is of course very advantageous that the material used in the oral cavity is resistant to caries. This objective is easily achieved, in the practice of the present invention, by adding 0.01 to 1% of fluoride ion, for example in the form of ammonium fluoride or stannous fluoride, to the suspension of freshly precipitated hydroxylapatite. The ceramic produced by sintering the resulting product is very resistant to attack by lactic, acetic and citric acids, a standardized in vitro method for determining resistance to caries. Or we can give decay resistance to the finished ceramic by exposing it to an aqueous solution of 0.5 to 5% sodium fluoride, for 12 h to 5 d. Preferably, the ceramic body is allowed to stay in an aqueous solution of about 5% sodium fluoride for about 4 days.

Those skilled in the art will of course realize that, in addition to the organic and inorganic binders and the fluoride ion, the ceramic materials which are the subject of the present invention may also contain small amounts of other elements which, if they do not modify the essential nature of the ceramic products, can confer useful characteristics to them. For example, we know that barium and strontium are incorporated into the apatite crystal lattice and that these elements are considerably more opaque to X-rays than calcium. Therefore, adding a small amount of barium or strontium ion to the calcium ion before the calcium ion reacts with the phosphate ion will ultimately give a hydroxylapatite ceramic doped with barium or strontium which, when it will be used in a tooth repair composition as described above, will ensure sufficient absorption of X-rays to allow detection of the closed tooth. We know that magnesium, which is also incorporated into the apatite crystal lattice, slows the crystallization of hydroxylapatite while promoting the crystallization of whitlockite [Eanes et al., “Cale. Tiss. Res. ”, 2, 32 (1968)]. Thus, the addition of a small amount of magnesium ion to the calcium ion before the reaction of the latter with the phosphate ion will promote the formation of whitlockite by finally giving a biphasic ceramic enriched in whitlockite.

The ceramic materials obtained as described above have been characterized on the basis of one or more of the following methods: elementary analysis, density measurement, X-ray diffraction, transmission electron microscopy, polarized light microscopy and determination of the mechanical properties.

The invention is illustrated by the following examples, but without being limited by them.

Example 1:

A mixture containing 16.75 g (0.127 mol) of phosphate is added dropwise to a stirred mixture containing 130 ml of 1.63N calcium nitrate (0.212 mol) and 125 ml of concentrated ammonia. diammonium acid, 400 ml of distilled water and 150 ml of concentrated ammonia. The resulting suspension is boiled for 10 min, cooled in an ice bath and filtered. The filter cake is drained using a rubber pad, then dried overnight at 95 ° C. A sample of the resulting cake, which is hard, porous and brittle, is heated in an electric oven, for 115 min, to a final temperature of 1230 ° C, then it is cooled to room temperature to obtain a translucent ceramic product which is resistant, hard and white.

Normal elementary analyzes of the final ceramic product and also of the dried hydroxylapatite before sintering gave the following results reported to Cai0 (PO4) ö (OH) 2:

Calculated

Dried, unsintered hydroxylapatite

Ceramic

It

39.89%

37.4%

39.6%

P

18.5%

17.5%

18.9%

h2o

0%

1%

-

Ca / P

1.667

1.65

1.62

Examination of a thin section of the ceramic by polarized light microscopy with magnifications of 130 and 352 revealed that the material was practically free of whitlockite. The absence of birefringence and of discernible structural characters such as the shape, orientation, limits, etc., of the crystallites, revealed that it was a microcrystalline structure. A comparison with optical micrographs of a thin section of the compressed and sintered tablet, reported by Monroe et al. (supra), showed that the two materials were structurally dissimilar.

X-ray diffraction measurements were carried out in a conventional manner. The distances between the planes were calculated and found to be virtually identical to the values given for hydroxylapatite by Donnay et al., "Crystal Data", ACA Monogram No. 5,668 (1963). X-ray examination further revealed that the material contained no more than about 2-3% whitlockite, the minimum concentration sensitivity of the diffractometer.

Example 2:

A solution containing 79.2 g (0.60 mol) of diammonium acid phosphate in 1500 ml of distilled water is adjusted to pH 11-12, with approximately 750 ml of concentrated ammonia. Further distilled water is added to dissolve the precipitated ammonium phosphate, which gives a total volume of water of 3200 ml. If necessary, the pH is again adjusted to 11-12. This solution is added dropwise over 30 to 40 minutes to an energetically stirred solution containing 1 mol of calcium nitrate in 900 ml of distilled water previously adjusted to pH 12 with approximately 30 ml of concentrated ammonia, then diluted to a volume of 1800 ml with distilled water. Once the addition is complete, the resulting gelatinous suspension is stirred for a further 10 minutes, then boiled for 10 minutes, it is stopped heating, it is covered and it is left to stand for 15 to 20 hours at room temperature. The supernatant liquid is decanted and the remaining suspension is centrifuged at 2000 rpm for 10 min. The resulting deposit is resuspended in 800 ml of distilled water and centrifuged again at 2000 rpm for 10 min. Sufficient distilled water is added to the residual solids to have a total volume of 900 ml. By vigorous stirring, a homogeneous suspension is obtained, essentially devoid of large fragments or aggregates. The entire suspension is poured into a Büchner funnel all at once, and filtered by applying a slight vacuum. When the filter cake begins to crack, a rubber pad is applied and the vacuum is increased. After 1 h, the buffer is removed and the filter cake is intact and without cracks on a flat surface, and it is dried for 15 h at 90-95 ° C, to obtain 90 to 100 g of brittle, porous pieces and hydroxylapatite whites. Fragments of 1 to 4 cm2, free of cracks and crazing, are placed in an electric oven, and the temperature is brought to 1200 ° C. in 100 minutes, after which time the oven and its contents are allowed to return to room temperature. . Pieces of hard, dense, non-porous, white and translucent ceramic material are obtained.

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8

Analysis

Calculated

Dried, unsintered hydroxylapatite

Ceramic

VS

39.89%

36.5; 36.8%

31.7; 38.0%

P

18.5%

21.7%

22.8; 19.0; 18.8

Ca / P

1.667

1.30; 1.31

1.08; 1.55; 1.56

After carrying out the previous analyzes, it was found that the analysis technique used did not allow complete dissolution of the samples and that the results were therefore imprecise and very variable. Notwithstanding the above analytical results, the substantial homogeneity of this sample was confirmed by the following results of electron microscopy. Moreover, the product of Example 3, which was prepared by a process essentially identical to that of Example 2, did indeed have the expected analytical values, and it was further verified by X-ray diffraction and electron microscopy, that it was indeed homogeneous hydroxylapatite.

Identical samples were prepared in two stages, by protecting with chromium a collodion reproduction of the surface of the sample, then by coating this surface with carbon. Examination of identical samples by transmission electron microscopy revealed a fairly uniform particle size with no appearance of pores or second phase precipitate either in the intervals between the grains or in the grains themselves, within the limit of 0.5. approx.%, minimum concentration sensitivity of the electron microscope. We then polished to a grain of 600, with silicon carbide paper, a sample of the ceramic, then it was polished with 3 | im diamond paste on a metallographic wheel covered with a fine canvas. Nylon. The sample was then pickled with 4% hydrofluoric acid for 30 s. Reproductions of the polished and etched surface were then prepared and observed under the electron microscope. Again, no second phases were observed in the intervals between the grains, but there appeared to be some small second phase particles in the mass of the grains.

The compressive strength and modulus of elasticity were determined by conventional methods and found to be 3952 + 1171 kg / cm2 and 4.4 x 105 kg / cm2, respectively.

The tensile strength was determined by the standard three-point bending test and found to be 675 + 232 kg / cm2.

It was found that the coefficient of thermal expansion was linear between 25 ° C and 225 ° C, and had a value of

11 x 10- <5 / ° C ± 10%.

A hardness of 480 was found by the standard Knoop process. The same value was obtained for all directions of the applied force, which reveals that the material is isotropic.

The porosity was qualitatively determined by immersing the test material in a fuchsin dye for 15 min, washing it with water, drying it, and then examining whether the test material had traces of residual dye. This test was performed simultaneously on the non-porous form of the ceramic provided by this invention, a compressed and sintered tablet of hydroxylapatite, and on a natural tooth. The compressed and sintered tablet exhibited considerable dye retention, while the new ceramic of the present invention and the natural tooth exhibited no visible dye retention. In another method, the test material was immersed in 6 times normal ammonia for 15 min, then washed with water, dried and wrapped in wet litmus paper. Any ammonia remaining trapped in the surface pores causes the surrounding litmus paper to turn blue. When this test was performed simultaneously on the ceramic of this invention, a compressed and sintered tablet of hydroxylapatite, and on a natural tooth, the litmus paper in contact with the compressed and sintered tablet turned blue indicating the presence of ammonia trapped in the tablet. No change in color of the litmus paper was observed, either in contact with the new ceramic of the present invention, or with the natural tooth.

Example 3:

Following a procedure similar to that described in Example 2, but starting with 3 mol of calcium nitrate and 1.8 mol of diammonium acid phosphate, 304 g of brittle white hydroxylapatite was obtained. and porous.

Analysis

Calculated

Find

It

39.89

40.0

P

18.5

18.6

Ca / P

1.667

1.66

Sintering at 1100 ° C for 1 h gave a translucent, hard and white ceramic, whose density was 3.10 g / cm3. X-ray diffraction revealed that this material was homogeneous hydroxylapatite. Examination with an electron microscope revealed a particle size of the crystallites of 0.7 to 3 n and the absence of pores or precipitates of second phase.

Example 4:

A. By following a procedure similar to that described in Example 2, but using half of the amounts used therein, an amount of hydroxylapatite estimated at 50 g was precipitated from the aqueous solution. After centrifugation and decantation, the residual mineral deposit was resuspended in a quantity of water sufficient to obtain a total volume of 11, and it was homogenized in a Waring mixer for 2 min.

B. A mixture containing 0.5 g of powdered cellulose (<0.5 n) in 200 ml of water was mixed in a Waring mixer for 3 min. A 100 ml fraction of the homogeneous aqueous hydroxylapatite suspension was then added, and the resulting mixture was further mixed for 5 min. The suspension was then filtered, and the filter cake was dried and sintered according to Example 2. This filter cake had, after drying, very few cracks and the ceramic product obtained by sintering was slightly porous, according to the fuchsin dye test which is described above.

C. 0.5 g of shredded surgical cotton was mixed in 200 ml of water in a Waring mixer for 45 min or until an almost homogeneous suspension was obtained. A 100 ml fraction of the homogeneous aqueous hydroxylapatite suspension described in Example 4A was then added and the mixing was continued for a further 15 min. The resulting suspension was filtered, then the filter cake was dried and sintered according to Example 2. The ceramic product remained intact and was visibly porous.

Example 5:

A. 5 g of collagen (bovine Achilles tendon) were mixed in 300 ml of water in a Waring mixer for 5 min. Collagen has fixed large amounts of water, forming a thick gelatinous mass. A small amount of finely divided collagen (20-30 mg) remained in suspension.

B. The suspension of finely divided collagen (250 ml) was decanted and stirred in a Waring mixer for 5 min with a fraction of 100 ml of the homogeneous aqueous hydroxylapatite suspension which is described in the example 4A. The resulting mixture was filtered and the filter cake was dried and sintered according to Example 2. The ceramic product remained intact and was substantially non-porous.

C. About 20% of the thick gelatinous collagen was mixed in a Waring mixer for 6 min with 150 ml of the

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618,951

homogeneous aqueous hydroxylapatite suspension which is described in Example 4A. The resulting mixture was filtered and the filter cake was dried and sintered according to Example 2. This dried cake, before sintering, remained intact and had considerable mechanical strength. The ceramic obtained by sintering was hard, resistant and visibly porous.

Example 6:

Samples of the ceramic product prepared according to Example 2 were left to stand in 1% aqueous sodium fluoride for 12 hours. These materials were then exposed to 10% lactic acid, as well as ceramic samples. untreated and natural teeth. After 3 days, the fluoride-treated ceramic showed significantly less lactic acid attack than the untreated ceramic or the enamel of natural teeth. When allowed to stand in 1% aqueous sodium fluoride for 3 days, the ceramic was not visibly attacked by lactic acid after 3 days, and after a month it had not suffered only slight decomposition while the untreated samples had decomposed strongly.

Example 7:

By following a procedure similar to that described in Example 2, but using only half of the amounts used therein, an amount of hydroxylapatite estimated at 50 g was precipitated from the aqueous solution. After centrifugation, the mineral deposit was suspended in an amount of water sufficient to have a total volume of 500 ml. This suspension was divided into 10 equal parts, which were each diluted with 50 ml of water and treated with ammonium fluoride as follows. To samples 1, 2, 3, 4 and 5, 0.0.1,0.5.1.0 and 2.0 ml of aqueous ammonium fluoride containing 0.00085 g of fluoride ion per milliliter. Samples 6, 7 and 8 were treated respectively with 0.5, 1.0 and 10.0 ml of aqueous ammonium fluoride containing 0.0085 g of fluoride ion per milliliter. To samples 9 and 10, 2.0 and 4.0 ml of ammonium fluoride containing 0.045 g of fluoride ion per milliliter were added respectively. The suspensions were then shaken on a rotary apparatus for 1 hour and filtered. The filter cakes were drained for 15 minutes using a rubber pad, they were dried 2 days at 95 ° C., then they were heated in an electric oven at a temperature of 1200 ° C. crushed the resulting ceramics into fine powders and sieved with a No. 325 mesh sieve. 80 mg of each of the powder samples was mixed with 80 ml of sodium lactate buffer solution of pH 4.1 (0, 4M) at 23 ° C, and were shaken on a Burrell wrist device. After 2, 9, 25 and 40 min after mixing, a 3 ml fraction of each sample mixture was taken, these fractions were immediately filtered to remove the undissolved sample, and determined by colorimetry the quantity of ceramic dissolved. The results are given in Table A. For the purpose of comparison, a sintered part of sample No. 1 was left to stand for 4 days in 1 ml of 5% sodium fluoride. The solid was separated, washed thoroughly with water, dried, then subjected to the dissolution test described above, designating it as sample 1 A. The results are included in Table A. We will go of course take into account that the experimental conditions described above do not reproduce well the conditions which prevail in vivo, but that they were chosen so as to allow sufficient solubilization of the sample in a reasonable time giving precise indications on the relative effect of the concentration of fluoride ion. Thus, it is expected that the in vivo dissolution rates of the ceramic hydroxylapatite will be considerably less than the rates observed above in the powerful lactate buffer.

Table A:

Relative rates of dissolution of the fluorinated ceramic hydroxylapatite

Echan

Fluoride content

% dissolved

furrow

(ppm)

No.

Added

Found

2 mins

9 mins

25 mins

40 mins

1

0

9.2

18.5

32.0

39.7

2

17

19

9.2

18.8

29.3

39.0

3

85

190 "

8.9

17.6

30.0

38.3

4

170

190

10.3

18.3

30.5

37.5

5

340

216

9.9

18.1

29.7

35.2

6

850

226

8.8

17.1

27.7

33.0

7

1700

470

7.9

18.1

25.7

29.8

8

17000

1460

6.7

12.1

19.7

23.3

9

18000

1700

6.3

11.5

19.7

23.3

10

36000

2307

5.9

11.3

17.6

21.0

1A -

3.7

7.1

13.7

18.7

"Apparently incorrect test.

Example 8:

Large pieces of dried filter cake about 3-4 mm thick, prepared according to Example 2 and having a Ca / P ratio of 1.64 to 1.66, were creased and divided into rectangular plates. approximately 14 to 15 mm long and 7 to 8 mm wide, and • a small hole was drilled in one end of each plate.

A thousand of these plates were then sintered according to Example 2 and polished very carefully using normal lap grinding techniques. The resulting ceramic bodies, the density of which was 3.12 to 3.14 g / cm3, were in the form of rectangular plates approximately 10 to 11 mm long, approximately 4 to 5 mm wide, and thick d 'approximately 2 to 3 mm, and having at one of their ends a hole through which a certain length of wire has been passed. These plates were used, which could thus be hung to the desired depth in a test tube, as test surfaces for the evaluation of the inhibitors of dental plaque, as described above.

Example 9:

PH 11.4 was adjusted to 340 ml of concentrated ammonia, a solution containing 0.24 mol of diammonium acid phosphate in 600 ml of distilled water, and the final volume was brought to 1280 ml with distilled water. This solution was added dropwise over 30 min to a vigorously stirred solution containing 0.4 mol of calcium nitrate in 360 ml of distilled water, previously adjusted to pH 11 with concentrated ammonia, and diluted to a volume of 420 ml with distilled water. The resulting suspension was stirred without boiling, and 250 ml fractions were removed periodically and the products were isolated, washed and dried as described in Example 2. All samples 1 were then heated h at 1100 ° C, and the composition of the resulting ceramic products was determined by X-ray diffraction. The results are given in Table B.

(Table at the top of the next column)

Example 10:

A. By following a procedure similar to that described in Example 2, but using 0.3 mol of calcium nitrate and 0.2 mol of diammonium acid phosphate, we have

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618,951

Table B:

Echan

Duration

Duration

Analysis

Phases observed during the rest of the act

elementary by diffraction of

No.

before

X-rays

isolated

% Ca% P

Ca / P

(%)

is lying

Hydroxylapatite

Whitlockite

1

5 mins

36.6

18.2

1.55

17

83

2

45 mins

-

-

-

-

21

79

3

2h

-

36.6

18.0

1.57

39

61

4

4.5 hrs

-

-

-

-

98

2a

5

7 a.m.

-

37.0

17.0

1.68

98

2a

6

7 a.m.

5 p.m.

37.2

17.0

1.69

100

0

7

24h

-

37.4

17.1

1.69

100

0

8

48 h

-

37.4

16.8

1.72

100

0

"These values are at the limit of the minimum concentration sensitivity of the X-ray difractometer (2-3%), and their accuracy is therefore questionable.

obtained a porous, hard and brittle product, having the following elementary composition: Ca = 38.85%; P = 19.77%; Ca / P = 1.52. This material was heated for 1 hour at 1200 ° C. to obtain a resistant, hard, non-porous, white and fairly opaque ceramic material, comprising approximately 40% of hydroxylapatite and 60% of whitlockite, depending on the X-ray diffraction.

B. By carrying out the preceding reaction, but by adding the starting materials in reverse order, a product was obtained comprising approximately 40% of hydroxylapatite and 60% of whitlockite, and having a Ca / P ratio of 1, 52 and a density of 2.982 g / cm3.

Example 11:

A solution containing 0.0625 mol of diammonium acid phosphate in 150 ml of distilled water was treated with 95 ml of concentrated ammonia, and the final volume was brought to 320 ml with distilled water. This solution was added dropwise over 30 min to a vigorously stirred solution containing 0.1 mol of calcium nitrate and 2.5 ml of concentrated ammonia in 180 ml of distilled water. The resulting suspension was stirred for 5 min then cooled in ice for 45 min and the suspended solid was isolated, washed and dried as described in Example 2 to obtain a hard, brittle solid , porous and white, having the following elementary composition: Ca = 35.4%; P = 18.59%; Ca / P = 1.46. This material was heated for 1 hour at 1350 ° C to obtain a resistant, hard, non-porous and fairly opaque ceramic product, comprising approximately 14% hydroxylapatite and 86% whitlockite, depending on the X-ray diffraction.

The products of Examples 1 to 11 correspond to the manufactured articles of this invention and have their physical characteristics described above.

The manufactured articles obtained according to Examples 1, 2, 3, 5B and 6 to 8 are resistant, hard, dense, white and translucent ceramic bodies, comprising isotropic and substantially pure polycrystalline hydroxylapatite, which is devoid of pores, and whose compressive strength is approximately between 2,500 and 8,800 kg / cm2, whose tensile strength is approximately between 200 and 2,000 kg / cm2, whose coefficient of linear thermal expansion is approximately between 10 and 12 ppm per degree Celsius, whose Knoop hardness is approximately between 470 and 500 and whose elastic modulus is approximately equal to 4 x 105 kg / cm2, and which is characterized by cleavage along smooth curved planes, and by the absence of birefringence in polarized light.

The manufactured objects obtained according to Examples 4 and 5C, although formed by the same material obtained according to Examples 1,2, 3, 5B and 6 to 8, have empty spaces or pores whose number and size vary. It will, of course, be obvious that the introduction of pores into said objects causes a modification of their physical properties, for example a reduction in their compressive strength, their tensile strength, their elasticity and their hardness.

Example 12:

A suitable composition was prepared as dental cement and dental filling agent in the following manner:

A. A solution containing 20 mg of the condensation product of N-phenylglycine and glycidyl methacrylate (described in EUA patent No. 3200142 and designated here by the acronym NPG-GMA) in 7 ml of ethanol, added 2.0 g of powdered ceramic hydroxylapatite. After swirling the solution for 5 min, the ethanol was evaporated in vacuo at room temperature and the residual solid was dried for 2 h under

1 mm Hg.

B. An 80 mg sample of the above material was mixed with 0.4 mg benzoyl peroxide and 30 mg of a 1: 2 mixture of hydroxyethyl methacrylate and the reaction product of bisphenol A and glycidyl methacrylate described in EUA patent No. 3066112 and designated in the art by the abbreviation bis-GMA. The resulting mixture was placed in a cylindrical steel mold in which it hardened in 3 to 5 min. The compressive strength of four cylindrical plugs thus prepared was determined. The average value was

1705 kg / cm2.

Example 13:

A mixture comprising 60 parts of powdered ceramic hydroxylapatite, 13 parts of hydroxyethyl methacrylate, 27 parts of the product of the condensation of bisphenol A and glycidyl methacrylate, 0.3 parts of N, N-bis was carefully mixed. - (2-hydroxyethyl) -p-toluidine, and 0.8 part of benzoyl peroxide, to obtain a fluid formula useful as a dental alveolus and as an agent for filling cracks. This mixture was poured into a cylindrical steel mold, in which it hardened in about 3 minutes. The compressive strength of 7 cylindrical stoppers thus prepared was determined. The average value was 1430 kg / cm2.

Example 14:

An example of a formula which can be used as a dental filling material is given below.

To 5 ml of 2-propanol, 0.5 g of powdered ceramic hydroxylapatite is added. The 2-propanol is then evaporated under vacuum at room temperature, in order to remove from the surface of the ceramic any water of hydration. 0.3 mg of benzoyl peroxide and then 40 mg of a mixture comprising the product of the condensation of bisphenol A and glycidyl methacrylate, of triethylene glycol dimethacrylate, are added to 120 mg of the powdered hydroxylapatite powder thus treated. , and N, N-bis- (2-hydroxyethyl) -p-toluidine, mixture which is sold by the company Lee Pharmaceuti-cals under the registered trademark Epoxylite HL-72. With a spatula, put this mixture in the form of a smooth paste and place it in cylindrical steel molds in which it is left to stand for 4 h. The cylindrical plugs are removed from the molds and three samples are tested, and it is found that their average resistance to compression is 1560 kg / cm2.

Example 15:

To a solution containing 30 mg of the product of the condensation of N-phenylglycine and glycidyl methacrylate in 7 ml of ethanol, 1 g of powdered ceramic hydroxylapatite is added by swirling. The ethanol is evaporated in vacuo at

10

s

10

15

20

25

30

35

40

45

50

55

60

65

ambient temperature. To a mixture containing 180 mg of ceramic hydroxylapatite powder thus treated and 3.0 mg of benzoyl peroxide, 74 mg of a mixture containing 60 parts of the product of the condensation of bisphenol A and glycidyl methacrylate and 40 is added. parts of triethylene glycol dimethacrylate and, using a spatula, the resulting aggregate is put in the form of a smooth paste which is placed in cylindrical steel molds where it is left to stand for 3 h. The cylindrical plugs are removed from the molds and 4 samples are tested and it is found that their average resistance to compression is 1560 kg / cm2.

Example 16:

A suitable composition is prepared as dental and orthodontic cement or as a temporary dental filling agent, by mixing together 100 mg of ceramic hydroxylapatite powder, 300 mg of zinc oxide and 300 mg of aqueous polyacrylic acid at 40%. The resulting mixture is placed in cylindrical steel molds in which it hardens in approximately 3 to 5 minutes. The cylindrical plugs are removed from the molds and 4 samples are tested and it is found that their average resistance to compression is 868 kg / cm2. For 5 other samples, we find an average diametral tensile strength of 114 kg / cm2. The 40% aqueous polyacrylic acid and the zinc oxide were obtained respectively in the form of the liquid and solid components of a commercial polycarboxylate cement sold by the company ESPE GmbH, RFA, under the registered trademark Durelon.

Example 17:

A suitable composition is prepared as dental cement and as dental filling agent by mixing together 6 parts by weight of 40% aqueous polyacrylic acid with a mixture containing 6 parts by weight of ceramic hydroxylapatite powder and 4 parts by weight of 'zinc oxide. The resulting composition has a setting time of 5 to 10 minutes approximately. The 40% aqueous polyacrylic acid and the zinc oxide were obtained respectively in the form of the liquid and solid components of a commercial polycarboxylate cement sold by the company ESPE GmbH, RFA, under the registered trademark Durelon.

Example 18

An example of a dental filling composition is given below:

Ingredient Percentage by weight

Polyester resin modified with Styrene

(Glidpol G-136 from Glidden) 29.2

Benzoyl peroxide 0.7

Styrene 0.6

Methacryloxypropyltrimethoxysilane 1.5

Hydroxylapatite ceramic 68.0

618,951

Example 19

An example of a suitable composition is given below as dental cement, dental alveolus coating and dental pulp cover:

Ingredient Percentage by weight

Epoxy resin (ERL 2774 from Union

Carbide) 67

N-3-oxo-l, l-dimethylbutylacrylamide 23

Hydroxylapatite ceramic 10

Example 20:

An example of a composition suitable for the manufacture of an artificial tooth or an artificial denture is given below.

A mixture containing 60 parts by weight of ceramic hydroxylapatite having a grain of approximately 150 to 200 and 40 parts by weight of polymethyl methacrylate powder, is mixed with approximately 15 parts by weight of methyl monomer liquid monomer, and left rest the resulting mixture in a sealed container at room temperature until the material no longer adheres to the walls of the container and has a non-sticky plastic consistency. This material is then packed in a suitable mold and the mold and its contents are immersed in water which is brought to a boil in approximately 1 hour and which is maintained at this temperature for 30 minutes. The mold is then allowed to cool in air for about 15 minutes and finally cooled in cold tap water.

The biocompatibility of the new ceramic form of hydroxylapatite provided by the present invention has been confirmed by implantation studies in which it has been found that no inflammatory reaction was elicited when flakes of the ceramic prepared according to the process of l Example 1 were implanted intraperitoneally in rats or were inserted subcutaneously in the back of rabbits, and that no resorption of the ceramic was observable after 28 days.

Ceramic hydroxylapatite pellets prepared by a method analogous to that described in Example 3 were surgically implanted in the femur of dogs. The implants were checked in vivo by periodic X-ray examination. After 1 and 6 months respectively, the animals were sacrificed and the femurs containing the implants were removed. The femurs were sectioned at the site of implantation and examined by light microscopy and electron microscopy. Both 1-month and 6-month implants were characterized by normal scarring, strong fixation of new bone on the surface of an implant without intermediate fibrous tissue, no visible inflammation or visible reaction to foreign bodies and no absorption of the implanted material.

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Claims (16)

618,951 2 1. Process for the preparation of a polycrystal-line sintered ceramic in macroscopic form, characterized in that the calcium ion is reacted with the phosphate ion in an aqueous medium and at a pH of 10 to 12 so as to form a gelatinous precipitate of a calcium phosphate whose molar ratio of calcium to phosphorus is between 1.44 and 1.72, in that said precipitate is separated from the solution and in that said precipitate is heated to a temperature at least 1000 ° C, but lower than that at which appreciable decomposition of the resulting ceramic occurs. 2. Method according to claim 1, in which the precipitate is heated to a temperature of at least 1050 ° C. 3. The method of claim 1, wherein the molar ratio of calcium to phosphorus in the precipitate is between 1.62 and 1.72, the temperature being maintained at a value up to 1250 ° C, for 20 min at 3 h. 4. The method of claim 3, wherein the temperature is maintained at 1100 to 1200 ° C, for 0.5 to 1 h. 5. Method according to one of claims 1 or 2, in which a precipitate forms whose molar ratio of calcium to phosphorus is between 1.44 and 1.60, preferably between 1.46 and 1.57, said precipitate being heated to a temperature up to a value of 1350 ° C., for 20 min to 3 h. 6. Method according to one of the preceding claims, in which the calcium ion is supplied by calcium nitrate and the phosphate ion by diammonium acid phosphate. 7. Method according to one of the preceding claims, characterized in that an integral mass of the precipitate subjected to sintering is essentially uniform and free from defects. 8. Method according to one of the preceding claims, characterized in that a shaped product is obtained by cutting, shaping or molding while the precipitate is still in a gelatinous state of cohesion before sintering. 9. Method according to one of the preceding claims, characterized in that a shaped product is obtained by cutting or shaping the precipitate after a preliminary drying of the gelatinous precipitate. 10. Method according to one of the preceding claims, characterized in that the sintered ceramic obtained in aqueous sodium fluoride at 0.5 to 5% is left to remain for 12 h to 5 d. 11. Method according to one of claims 1 to 9, characterized in that 0.1 to 1% by weight of fluoride ion is added to the precipitate. 12. Method according to one of claims 1 to 4, characterized in that 0.4 to 0.6% by weight of an organic binder, for example collagen, is added to the precipitate, said organic binder volatilizing during said heater. 13. Method according to claim 1, making it possible to obtain a porous form of the ceramic, characterized in that 5 to 25% by weight of an organic binder, for example cellulose, cotton or cotton, is added to the precipitate. collagen, said organic binder volatilizing during said heating. 14. Use of the ceramic obtained by the method according to claim 1 in a composition for repairing teeth, characterized in that this composition comprises 10 to 90% by weight of said finely divided ceramic and a polymeric-sand or polymerized and acceptable binder on the dental side. 15. Use according to claim 14, characterized in that the binder acceptable on the dental level is polyacrylic acid. 16. Use according to claim 14, characterized in that the binder acceptable on the dental level is the product of the condensation of bisphenol A and glycidyl methacrylate.