CH618952A5 - Ceramic material - Google Patents

Abstract

The new sintered, polycrystalline, isotropic and translucent ceramic is made of substantially pure hydroxyapatite. The mean crystallite size of the hydroxyapatite is between 0.2 and 3 microns. The said ceramic has practically no pores and exhibits a cleavage along smooth curved planes. It can be employed in a tooth repair composition.

Description

The present invention relates to ceramics, 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 believed to be responsible for tooth decay and alveolodental periostitis.

The filling materials that are currently used in tooth repair compositions, such as quartz, aluminum, silicates, glass beads; etc.-hardly present any chemical or physical resemblance to tooth enamel. A particular defect 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 cavities. The dental profession has therefore long desired a dental filling composition whose physical properties closely resemble those of natural teeth.

In addition, 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, since the problem of non-rejection tissue and adhesion to tissue has not yet been fully 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. If they are perhaps sufficient for the study of the formation of the plaque as such, these materials hardly bear any resemblance to the surface of natural teeth, and they are therefore not perfectly suited for discovery effective anti-plate agents. 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, Cai0 (PO4) 6 (OH) 2, u also called basic calcium orthophosphate, which is the mineral phase of teeth and bones, is suitable for the various uses listed above and, in fact , EU-patent No. 2508816 discloses a process for obtaining the hydroxylapatite of tooth enamel, as well as its use in admixture with a synthetic resin 20 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." U, 695 (1973)] disclosed mixtures of hydroxylapatite and whitlockite produced by the. decomposition of powdered hydroxylapatite at various temperatures.

Bett et al., ["J. Bitter. 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 into the whitlockite phase.

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 4o form of hydroxylapatite. However, none of the already known forms of hydroxylapatite is completely satisfactory. Thus, Roy and Linnehan [“Nature”, 247, 220 (1974)] have described an elaborate hydrothermal exchange process making it possible to transform the calcium carbonate which forms the skeleton of the marine coral 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 disadvantage for a prosthetic material. , n / a 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 55 of formula Ca3 (PC> 4) 2, in the form of a mosaic network ordered of polyhedral crystallites, and seemed to have a porosity too great to be able to be used as dental material.

Rao and Bcehm [“Journal of Dental Research, 55” 1351 (1974)] m have revealed the obtaining of 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.

65 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 resistance

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mechanical strength of a non-degradable metallic or ceramic implant.

In accordance with patent application No. 618951, there is provided a process for preparing a sintered polycrystalline ceramic, 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 (which is in essence between the approximate molar ratio of calcium to phosphorus in l 'hydroxylapatite and in whitlockite), to separate the said precipitate from the solution, to heat the said precipitate to a temperature of at least 1000 ° C., but to a temperature below that at which an appreciable decomposition of the hydroxylapatite occurs , and to maintain said temperature for a time sufficient to cause sintering and a substantially maximum densification of the resulting product.

In general, it is desired to produce the ceramic in macroscopic form. This product is obtained by sintering an integral mass of this precipitate, if desired after shaping or molding.

The present invention relates to a sintered, polycrystalline, isotropic and translucent ceramic according to the definition of claim 1. From the chemical point of view, this shape generally looks a lot like 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 of hydroxylapatite in tooth repair compositions can provide a dense filling material, the coefficient of expansion of which is virtually identical to that of natural tooth enamel.

The dental and surgical implantation material which is thus provided is hard, resistant and perfectly biocompatible, and it can be manufactured in any desired form without using 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 manufactured object which is described and claimed here make it an ideal material for the manufacture of discs, plates or rods for the testing of dental anti-plaque agents.

The new physical form of hydroxylapatite, which differs from these biological and geological forms and from all the other known synthetic forms, as indicated below, and which is the object of this invention, consists of a sintered ceramic material. , polycrystalline, isotropic, which is resistant, hard, dense and translucent, and which comprises substantially pure hydroxylapatite whose average size of the crystallites ranges between 0.2 and 3 n, whose density ranges between 3 , 10 and 3.14 g / cm3, and which, moreover, has practically no pores and has a cleavage along smooth curved planes. In addition, as ordinarily produced, the material described above has a compressive strength which ranges from 2,500 to 8,800 kg / cm2, a tensile strength which ranges from 200 to 2,000 kg / cm2. cm2, a coefficient of linear thermal expansion which ranges 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 and dense ceramic, comprising substantially pure microcrystalline hydroxylapatite, forming a random isotropic network and having resistance to the compression which ranges between 2500 and 5300 kg / cm2, a tensile strength which ranges between 200 and 3500 kg / cm2, a coefficient of linear thermal expansion which ranges between 10 and 12 ppm per degree Celsius, a Knoop hardness which ranges between 470 and 500, and a modulus of elasticity approximately equal to 4 x 105 kg / cm2, and having a cleavage along smooth curved planes, and having no birefringence in polarized light .

The term dense, as used herein, denotes 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 synthetic hydroxylapatite, which are prepared by a hydrotheimic 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 20 of 100 kg / cm2.

In addition to the properties described above of the new ceramic form of hydroxylapatite which is the subject of this invention, this material is also perfectly biocompatible and, therefore, eminently suitable as a dental and surgical prosthesis material. Thus, the ceramic according to this invention can be molded or machined into dental crowns, artificial teeth, bone and joint prostheses, cannulas, devices for anchoring artificial limbs which can be fixed on the bones and protrude through the skin, and surfaces. test for the study of dental plaque, caries formation, arthritis, and other diseases which can affect teeth and bones. Properly ground, the novel ceramic of this invention can serve as synthetic cross-linked bone to repair bone defects, as an abrasive and, in combination with normal resins, as a tooth repair composition, as described below. .

For use as a test surface for the evaluation of agents which inhibit dental plaque, the ceramic of this invention can be manufactured in the form of bodies having any suitable size and shape, shape and form. dimension preferably being such that the body can easily be introduced into a normal test tube. This is conveniently achieved by cutting or machining large chunks, plate-shaped, dried filter cake, to 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 evaluate the plaque inhibitors according to the procedures described by Turesky et al., Supra. After use, the ceramic bodies are simply repolited to provide a new test surface.

As ordinarily produced, the ceramic of this invention is not only dense, but also practically non-porous, and if a non-porous material is essential for dental applications, a certain degree of porosity of the devices implantation can be beneficial by allowing the circulation of moods and internal tissue growth. A variable degree of porosity can be imparted to the ceramic of the invention, in a manner similar to that described by Monroe et al., Supra. “Thus, organic substances such as starch, powdered cellulose, cotton or collagen are mixed with the gelatinous precipitate of hydroxylapatite in quantities ranging from approximately 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 ceramic according to this aspect of the invention 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 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 EUA patent No. 3609867.

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 by 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 and calcium carbonate. The phosphate ion can be supplied by acidic diam-monium phosphate, ammonium phosphate and phosphoric acid.

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 is conveniently prepared in which the ratio of the reactants used in the reaction is chosen so that a precipitate is formed, essentially having the molar ratio of calcium to phosphorus. 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 hydroxylapatite suspension thus obtained is then allowed to 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 is conveniently achieved 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. It should be noted that there is usually a shrinkage of approximately 25% when the wet hydroxylapatite is dried, and that 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 heated slowly

4

up to the sintering temperature of 1000 to 1250 ° C, temperature at which all the remaining water will have been removed. Maintaining the temperature at 1000 to 1250 ° C, for 20 ma to 3 h, then causes sintering and a maximum densification of the product. Of-

5 nary, it is best to isolate the dry product before sintering. Thus, the wet product can be dried at around 90 to 900 ° C, for 3 to 24 hours, or until it contains only 0 to 2% water. It is generally preferable to use drying conditions of 90 to 95 ° C for about 15 hours, or alternatively 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 freshly precipitated hydroxylapatite 0.4 to 0.6% by weight of an organic binder such as collagen, powdered cellulose 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 amounts 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 precipitate to give it roughly the shape desired for the final product, taking into account the above-mentioned shrinkage which occurs during sintering.

The macroscopic bodies of the precipitate 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. The products are then sintered at 1000 at 1250 ° C, for 20 min to 3 h, the temperatures and times being in inverse ratio to each other. Sintering is preferably carried out at 1100 to 1200 ° C, for 0.5 to 1 hour. The dense and hard ceramic bodies thus obtained can then be polished or machined by conventional techniques.

It is crucial, in the preceding process, to prepare the hydroxylapatite in the form of a gelatinous precipitate from an aqueous solution, because it is only in this gelled state of cohesion that the hydroxylapatite can be shaped or 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, we put the hydroxylapatite powder in suspension in water and if we filter it, we obtain a particulate filter cake without cohesion which dries and crumbles simply and cannot be shaped, molded or transformed into a macroscopic form of ceramic. In addition, although the hydroxylapatite can be mechanically compressed into a powder to form a shaped body, for example a tablet, when it is sintered, the product obtained is very porous, and does not split along 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 initially combine to form a low-calcium hydroxylapatite, whose calcium / phosphorus ratio is equal to 1.5 approximately. 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 hydroxylapatite sen-

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so pure, it is imperative, in the process of this invention, to let the initial gelatinous precipitate of hydroxylapatite remain in contact with the original solution for a time sufficient to allow its calcium / phosphorus ratio to reach a value d '' about 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 following the precipitation, it is found that its calcium / phosphorus ratio is equal to approximately. 1.55 to 1.57, and that the ceramic which is finally obtained is opaque and appears to be, by X-ray diffraction, a mixture comprising hydroxylapatite and whitlockite. In fact,

as described in more detail below, a material whose calcium / phosphorus ratio is equal to about 1.44 to 1.60 is useful for the preparation of the biphasic ceramic described above. Thus, although the method 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 in order to s ensure that stoichiometry 20

desired calcium / phosphorus has been obtained and 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 temperature and duration of sintering are also crucial to the process. Thus, the unsintered hydroxylapatite, having the desired calcium / phosphorus ratio of 1.62 to 1.72, is transformed into the ceramic of this invention, by heating it to a temperature of at least 1000 ° C. At 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 sinter at a temperature of approximately 1100 ° C for about 1 hour. A temperature significantly lower than 1000 ° C will give only incomplete sintering, whatever the duration of the heating, while heating beyond 1250 ° C for more than 1 h will cause a partial decomposition of the hydroxylapatite into whitlockite. 40

A subject of the invention is also the use of the new ceramic in a composition for repairing teeth comprising a mixture of the ceramic hydroxylapatite according to the invention and of a polymerizable or polymerized binder which is compatible with the conditions which prevail in the oral cavity. The composition 4s for repairing the teeth, according to this invention, comprises from 10 to 90%, preferably 60 to 80%, by weight, of finely divided ceramic hydroxylapatite, the rest of said composition, ie 10 to 90% by weight, comprising a polymerizable or polymerized binder which is acceptable from a dental point of view. Normally, such a polymerizable composition contains suitable and known polymerization catalysts such as aliphatic ketone peroxides or benzoyl peroxide, reactive diluents such as di-, tri- and tetraethylene glycol dime thacrylate, hardeners such as aciylamides substituted on nitrogen by a 55 3-oxohydrocarbon group, such as those described in EUA patent No. 3277056, 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, which are present in amounts ranging from 0.01 to 45% of the weight of the total composition.

Although this 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, as the product of the reaction of the N-phenylglycine and glycidyl methacrylate 65 which is described in US Pat. No. 3,200,142, methacryloxy-propyltrimethoxysilane, 3,4-epoxycyclohexylethyltrimethoxy-silane or vinyltrichlorosilane, 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 5 to 100 n, using conventional grinding techniques, then it is mixed with an appropriate quantity of a normal resin known in the technique of repairing teeth, such as hydroxyethyl methacrylate, polymethyl methacrylate, polyacrylic acid, unsaturated polyesters of propylene glycol fumarate-phthalate such as those sold by the company Allied Chemical Co. under the reference 23 LS8275 and by the company Pittsburgh Plate Glass under the name Selectron 580001 (registered trademark), the unsaturated and styrene-modified polyesters such as Glidpol 1008, G-136 and 4CS50 (registered trademarks of the company Glidden, epoxy resins such as PAraldite 6020 (registered trademark) 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. 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. Resin, ceramic hydroxylapatite and optional ingredients such as silanes as binders, dyes, inorganic pigments or fluorescers should be mixed before adding the catalyst, hardener, crosslinking agent , the promoter and / or the accelerator. However, the order in which the ingredients are mixed is not crucial, and the ingredients can be mixed 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 caries resistance. Or, cavity resistance can be imparted to the finished ceramic by exposure 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 on 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. Consequently, the addition of a small quantity of barium or strontium ion to the calcium ion, before the latter reacts with the phosphate ion, will finally give a hydroxylapatite ceramic doped with barium or strontium which, when used in a tooth repair composition as described above, will ensure sufficient absorption of X-rays to allow detection of the closed tooth. However, it is known that magnesium, which also incorporates into the apatite crystal lattice, slows the crystallization

618,952

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sation of the hydroxylapatite, while promoting the crystallization of the whitlockite [Eanes et al., “Cale. Tiss. Res. " 2.32 (1968)].

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 mechanical properties.

The invention is illustrated by the following examples.

Example 1:

To a stirred mixture containing 130 ml of 1.63N calcium nitrate (0.212 mol) and 125 ml of concentrated ammonia, a mixture containing 16.75 g (0.127 mol) of dropper is added over about 20 minutes. diammonium acid phosphate, 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 Caio (PO 4) 6 (OH) 2:

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 stirring vigorously, we obtain u; homogeneous suspension, 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, intact and without cracks, is transferred to 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. Fragmen 20 of 1 to 4 cm2 and free from cracks and crazing are placed in an electric booster, and the temperature is brought to 1200 ° C. in 100 minutes, at the end of which the oven and its contents are allowed to return to the temp ambient rature. Pieces of hard, dense, non-porous, white and translucent ceramic material are obtained.

Analysis

Calculated

Dried hydroxylapatite

Ceramic

and not sintered

''

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

30

Analysis

Calculated

Dried, unsintered hydroxylapatite

Ceramic

It

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; 1.5

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 shape, orientation, limits, etc., of the de-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. 5668 (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 a vigorously 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

After having carried out the previous analyzes, it was found that the analysis technique used did not allow the complete dissolution of the samples and that the results were therefore impré eis and very variable. Notwithstanding the analytical results above, the substantial homogeneity of this sample has been confided. • driven 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 we also verified, 45 by ray diffraction X and electron microscopy, that it was indeed homogeneous hydroxylapatite.

Identical samples were prepared in two stages, by protecting a collodion reproduction of the sample surface with chromium, then coating this surface with carbon 50 The examination of identical samples by transmission electron microscopy revealed a particle size fairly uniform with no appearance of pores or precipitates of second phase either in the intervals between the grains or in the grains themselves, within the limit of about 0.5%, 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 µm diamond paste on a metallographic wheel covered with a fine canvas. Nylon. The sample was then stripped 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 15 kg / cm2, respectively.

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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 and 225 ° C, and had a value of llxlO-6 / ° 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:

A. Following a procedure similar to that described in Example 2, but using one sixth of the quantities 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 an amount 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 µi) 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 mixed for another 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 3A was then added and the mixing was continued for another 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 4:

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 3A.

The resulting mixture was filtered and the filter cake was dried and sintered according to Example 2. The ceramic product remained intact and was practically non-porous.

C. About 20% of the thick gelatinous collagen was mixed in a Waring mixer for 6 min with 150 ml of the homogeneous aqueous hydroxylapatite suspension which is described in Example 3A. 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 5:

Samples of the ceramic product prepared according to Example 2 were allowed to stand in 1% aqueous sodium fluoride for 12 h. These materials were then exposed to 10% lactic acid, as well as samples of untreated ceramic 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 did not had undergone only a slight decomposition while the untreated samples had strongly decomposed.

Example 6:

By following a procedure similar to that described in Example 2, but using only one sixth of the quantities used therein, an amount of hydroxylapatite estimated to be precipitated from the aqueous solution 50 g. 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 40 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 ml. Samples 6, 7 and 8 were treated respectively with 0.5, 1.0 and 4s 10.0 ml of aqueous ammonium fluoride containing 0.0085 g of fluoride ion per ml. To samples 9 and 10, 2.0 and 4.0 ml of ammonium fluoride containing 0.045 g of fluoride ion per ml were added respectively. The suspensions were then shaken on a rotary apparatus during A h and filtered. The 50 filter cakes were drained for 15 min 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. The resulting ceramics were ground into fine powders and screened with a No. 325 mesh screen (US ASTM Standard). 55 80 mg of each of the powder samples were mixed with 80 ml of sodium lactate buffer solution of pH 4.1 (0.4M) at 23 ° C, and 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, 60 of these fractions were immediately filtered to remove the undissolved sample, and determined by colorimetry the quantity of solubilized ceramic. 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, 65 washed thoroughly with water, dried, and then subjected to the dissolution test described above, designating it as sample 1 A. The results are included in Table A. will, of course, realize that the experimental conditions

618,952

8

described above do not reproduce well the conditions which prevail in vivo, but that they have been 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 the 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 buffer of lactate. -

Table A:

Relative speeds of dissolution of the hydroxylapatite ceramic fluorwrée

Sample No.

Fluoride content (ppm)

Added Found

2mn

% dissolved 9 min 25 min

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

a Apparently incorrect test

Example 7:

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.

The macroscopic ceramics obtained according to Examples 1, 2, 4B and 5 to 7 are resistant, hard, dense, white and translucent ceramic bodies, comprising isotropic and substantially pure polycrystalline hydroxylapatite, which is devoid of pores, and the compressive strength of which is approximately between 2500 and 8800 kg / cm2, the tensile strength of which is approximately between 200 and. 2000 kg / cm2, whose coefficient of linear thermal expansion is approximately between 10 and 12 ppm per degree Celsius, whose hardness Rnoop is approximately between 470 and 500 and whose elastic modulus is approximately equal to 4 x 105 kg / cm2, and which is characterized by a cleavage along smooth curved planes, and by the absence of birefringence in polarized light.

The macroscopic ceramics obtained according to Examples 3 and 4, although formed by the same material obtained according to Examples 1,2,4B and 5 to 7, 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. .

10 Example 8:

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

A. To a solution containing 20 mg of the condensation product of N-phenylglycine and glycidyl methacrylate (described 15 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

25 in EUA Patent No. 3066112 and designated in the art par. 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 30 1705 kg / cm2.

Example 9:

A mixture comprising 60 parts of powdered ceramic hydroxylapatite, 13 parts of hydroxyethyl methacrylate, 27 parts of the condensation product of bisphenol A and glycidyl methacrylate, 0.3 parts of N, N- was thoroughly mixed. bis- (2-hydroxyethyl) -p-toluidine, and 0.8 part of benzoyl peroxide, to obtain a fluid formula useful as dental alveolus and as agent for filling cracks. This mixture was poured into a cylindrical steel mold, into 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.

45 Example 10:

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 any water of hydration from the surface of the ceramic. 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, dimetha-55 crylate, are added to 120 mg of the powdered hydroxylapatite thus treated. triethylene glycol, 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 11:

65 To a solution containing 30 mg of the condensation product of N-phenylglycine and glycidyl methacrylate in 7 ml of ethanol, one gram of powdered ceramic hydroxylapatite is added by swirling. We evaporate the ethanol

9

618,952

under vacuum at room 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 condensation of bisphenol A and glycidyl methacrylate is added and 40 parts of triethylene glycol dimethacry-late 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 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 12:

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 respectively obtained in the form of: liquid and solid components of a commercial polycarboxylate cement sold by the company ESPE GmbH, RFA, under the registered trademark Durelon.

Example 13:

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 14

An example of a dental filling composition is given below:

Example 15

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

Ingredient

Percentage by weight

Ingredient

Percentage by weight

Epoxy resin (ERL 2774 from Union

Carbide) 67

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

Hydroxylapatite ceramic 10

30

35

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

Example 16:

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 methacrylate monomer liquid, 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 40 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.

45 ceramic hydroxylapatite pellets prepared by a process analogous to that described in Example 3 were surgically implanted in the femur of dogs. The implants were checked by vivo by periodic X-ray examination. and six months respectively, the animals were sacrificed and the femurs containing the implants were removed. So femurs were sectioned at the site of implantation and examined by light and electron microscopy. Both one-month and six-month implants were characterized by normal scarring, strong fixation of new bone on the surface of an implant with no intermediate fibrous tissue, no visible inflammation or visible reaction to foreign bodies and no absorption of the implanted material.

R

Claims (6)

618,952 1. Sintered, polycrystalline, isotropic and translucent ceramic, characterized in that it contains substantially pure hydroxylapatite, the average size of the crystallites of which is between 0.2 and 3 n, said ceramic having a density of between 3 , 10 and 3.14 g / cm3, having practically no pores and having a cleavage along smooth curved planes. 2. Ceramic according to claim 1, characterized in that it contains a quantity of fluoride ions capable of substantially reducing the speed of decomposition of said ceramic by lactic acid. 2 claims 3. Use of the ceramic according to claim 1 in a composition for repairing teeth, characterized in that this composition comprises 10 to 90% by weight of said ceramic in finely divided form, and a polymerizable or polymerized binder and acceptable on the plan dental. 4. Use according to claim 3, characterized in that the binder acceptable on the dental level is polyacrylic acid. 5. Use according to claim 3, characterized in that the binder acceptable on the dental level is the product of the condensation of bispbenol A and glycidyl methacrylate. 6. Use according to claim 3, of a ceramic containing an amount of fluoride ions capable of substantially reducing the speed of decomposition of said ceramic by lactic acid. -