SE425563B - TRANSPARENT, ISOTROPIC, POLYCRYSTALLIN, SINTERED CERAMIC PRODUCT AND USE OF THE CERAMIC PRODUCT - Google Patents

Abstract

1522182 Calcium phosphate ceramics STERLING DRUG Inc 22 July 1975 [2 Aug 1974 7 July 1975] 30706/75 Heading C1A A polycrystalline, sintered ceramic for use as a bone or tooth substitute is made by reacting calcium ion with phosphate ions in aqueous medium at pH of 10-12 to produce a gelatinous calcium phosphate precipitate having a Ca:P molar ratio of 1À44-1À72, separating the precipitate from the solution and heating the precipitate to above 1000‹C but below the temperature at which appreciable decomposition of hydroxylapatite occurs and maintaining said temperature for a sufficient time to effect sintering and maximum densification. When the Ca:P molar ratio is in the range 1À62-1À72 a translucent, isotropic, polycrystalline hydroxylapatite having an average crystalite size of 0À2-3 microns, a density of 3À1-3À14 g/cm3, substantially no pores and having cleavage along smooth curved planes is obtained. When the Ca:P ratio is in the range 1À44-1À60, preferably 1À46-1À57 a dense isotropic two-phase ceramic is obtained comprising 14-98% hydroxylapatite and 2-86% whitlockite, said ceramic having substantially no pores and having cleavage along smooth curved planes. The reactants are preferably Ca(NO 3 ) 2 and (NH 4 ) 2 HPO 4 . 0À4-0À6% of an organic binder, e.g. collagen, may be added to the precipitate to prevent cracking during drying. Porous forms of the ceramic may be made by including 5-25% by weight of organic binders such as powdered cellulose, starch, cotton or collagen to the precipitate. Fluoride ions may be introduced into the ceramic, e.g. by standing in 0À5-5% aqueous NaF for 12 hours-5 days.

Description

7804812-1 2 an affordable, easily accessible material that is chemically similar to tooth enamel and hard, dense and highly polished. Hydroxylapatite, Cal0 (PO4) 6 (OH) 2, which is also called alkaline calcium orthophosphate, constitutes the mineral phase in teeth and bones and has been suggested to be suitable for the various purposes stated above, and thus stated in the U.S. Pat. No. 2,508,316 discloses a process for producing hydroxylapatite in tooth enamel and "using it in admixture with a synthetic resin such as a prosthetic tooth composition. This method is time consuming and cumbersome and limited to the production of finely divided hydroxylapatite.

Furthermore, the procedure is of course dependent on the availability of a supply of natural teeth.

Kutty [Indian J. Chem. 11,695 (l973f] describes mixtures of hydroxylapatite and whitlockite prepared by decomposition of powdered hydroxylapatite at different temperatures.

Betaet el., Ü. Mner. cnem. see. gg, 5535 (isev fl describes the preparation of particulate hydroxylapatite with stoichiometrically deviating composition ranging from Ca / P = 1.67 to 1.57. The materials thus prepared contained large intercrystalline pores. It was also stated that upon heating to 10 ° C hydroxylapatite with calcium deficiency partial conversion to whitlockite phase _ U.S. Pat. No. 3,787,900 discloses a prosthetic material for bone and tooth containing a refractory material and a calcium phosphate compound, for example whitlockit.

Many attempts have been made to produce a hard, strong macroform of hydroxylapatite. To date, however, no known form of hydroxylapatite has been found to be completely satisfactory. Thus, Roy and Linnehan f, ature, g§1,220 (l974í] describe a complicated hydrothermal exchange process in which calcium carbonate in the marine coral skeleton is converted to hydroxylapatite. The material thus prepared necessarily retained the high porosity, which also has a low coral structure. of about 19 - 33 kp / cmz, which is a serious inconvenience for prosthetic materials.

Monroe, et al. The Journal of Dental Research, §Q, 860 (l97lí] described the preparation of a ceramic material by sintering of pressed tablets of hydroxylapatite, the material thus prepared was in fact a mixture of hydroxylapatite and about 30% 8.- whitlockit, which consists of Ca3 (PO¿) 2 or 78048124 3 tricalcium phosphate, such as an ordered mosaic row of polyhedral crystal liters, and the material appears to have had too high a porosity to be suitable for use in a dental material.7 Rao and Boehm Išournal of Dental Research, â € œ 1351 (1974) described a polycrystalline form of hydroxylapatite prepared by isostatic pressing of powdered hydroxylapatite in a mold and isothermal sintering of the molded material. kp / cmz.

Bhasker et al. [§Ral Surgery, åg, 336 (l97lí] described the use of a biodegradable calcium phosphate ceramic material to fill defects in bone. Was removed from the implant site and lacked the strength of a The material was highly porous and travel metal or non-degradable ceramic implant material.

Swedish patent 7508751-0 relates to a process for the preparation of a crystalline, sintered ceramic material which comprises reacting calcium ion with phosphate ion in aqueous medium at a pH of about 10-12 to form a gelatinous precipitate of calcium phosphate with a molar ratio of calcium to phosphorus in the range 1.44 to 1.72 (which is mainly between the approximate molar ratio of calcium to phosphorus in hydroxylapatite and this molar ratio in whitlockit), after which the precipitate is separated from the solution, the precipitate is heated to a temperature of at least 100 ° C but below the temperature at which considerable decomposition of the hydroxylapatite takes place, and maintains this temperature for a period of time sufficient to effect sintering and essentially maximum densification of the product obtained. It is generally desirable to produce the ceramic material in macro form, which is a product obtained by sintering a coherent mass of the precipitate, if desired after molding or casting.

According to one aspect of the invention, there is provided a novel ceramic form of hydroxylapatite comprising substantially pure hydroxylapatite which is hard, dense and highly polished. Chemically, the material is very similar to tooth enamel. Furthermore, this new material can be produced in a relatively simple manner based on inexpensive starting materials and can be obtained with uniform quality, thereby avoiding undesired variations which are characteristic of natural dental materials.

The incorporation of the new ceramic form of hydroxyl anatite into dentifrice compositions provides a dense filler material which has a coefficient of thermal expansion which is substantially identical to the coefficient of thermal expansion of natural tooth enamel. Dental and surgical implant materials prepared according to the invention are hard, strong and completely biologically compatible and acceptable and can be produced in any desired shape without the need for high pressure or other complicated methods. Furthermore, as described in more detail below, any desired degree of porosity can be achieved in such materials which enables tissue ingrowth. It is obvious that the properties of the new material according to the invention make this ideally suitable for the production of discs, plates or rods for use in testing dental anti-plaque agents and in particular for dental repairs. The new physical form of hydroxylapatite, which differs from the biological and geological forms as well as from all prior art synthetic forms, as set forth below, and is the subject of the present invention, is a strong, hard, dense, white, transparent , isotropic, polycrystalline, sintered ceramic material containing mainly pure hydroxylapatite with an average crystallite size of about 0.2 - 3 μm, a density of about 3.10 - 3.14 g / cm3, and has essentially no pores and has cleavage along even curved surfaces. Furthermore, in the manner usually prepared, this material has a compression strength of about 2450 - 8800 kp / cmz, a breaking point of about 210 - 2100 kp / cmz and a coefficient of thermal expansion of about 10 - 12 ppm (parts per million) per OC. a Knoop hardness of about 470 - 500 and a modulus of elasticity of about 4.2 x 104 kp / cmz, and is non-birefringent under polarized light.

A first evaluation of the new hydroxyl-apatite ceramic material showed that it consisted of a strong, hard, dense, white, translucent ceramic material containing substantially pure microcrystalline hydroxylapatite in a random, isotropic device with a compression strength of approx. 2450 - 5300 kp / cmz, a tensile strength of about 210 - 3500 kp / cm2, a linear coefficient of thermal expansion of about 10 ~ 12 ppm / OC, a Knoop hardness of about 470 - 500 and a modulus of elasticity of about 4.2 x 104 kp / cmz and shows cleavage along evenly curved planes, as well as the absence of birefringence under polarized light.

The term dense in this context refers to a highly compact arrangement of particles which essentially have no gaps or no intervals between them. Unlike the form of hydroxylapatite described above, geological hydroxylapatite and synthetic hydroxylapatite are produced by a hydrothermal process macrocrystalline, exhibit cracking or fission along flat planes, and are birefringent. Biological hydroxylapatitis differs in that it generally contains significant amounts of carbonate ion in the apatite lattice and in the purest state, ie, in tooth enamel, in that it is anisotropically arranged in wound, radially directed rods so that the material exhibits cracking in straight lines along the interface between these enamel rods and has a relatively low tensile strength of 105 kp / cm 2.

In addition to the foregoing properties of the new ceramic form of hydroxylapatite according to the invention, this material is also characterized by complete biological compatibility (compatible) and is therefore highly suitable as a dental and surgical prosthetic material. The ceramic material according to the invention can thus be cast or machined into dental crowns, artificial teeth, bones and joint prostheses, cannulae, anchoring means for artificial limbs, which can be attached to bones and stretched through the skin, and samples for examination of dental plaque, caries image arthritis, and other diseases that can affect the teeth and bones.

Suitably ground, the novel ceramic material of the invention can be used as a synthetic canncellus bone for the repair of bone defects, such as abrasives, and in admixture with standard resins such as a denture composition, as described below.

As a test surface for evaluating agents for inhibiting dental plaque, the ceramic material of the invention can be prepared and processed into bodies of any size and shape, preferably of a size and shape that allows the bodies to be easily inserted into a standard test tube. This is accomplished in a simple manner by cutting or machining large sheet-like pieces of dried filter cake to the appropriate size and then sintering them.

The sintered products are subjected to high polishing using standard gemstone technology, and the resulting bodies are then used as a substrate in the evaluation of dental plaque inhibitors according to the procedure described by Turesky, et al. and referred to in the foregoing. After use, the ceramic bodies can be easily repolarized so that they can be used again as a test surface.

When producing in a conventional manner the ceramic material according to the invention, it is not only dense but also non-porous, and while a non-porous material is substantially suitable for dental use, a certain degree of porosity may be advantageous in channels in the otherwise non-porous ceramic product. 7804812-1 '6 implant products to allow circulation of body fluids and tissue ingrowth. Varying degrees of porosity can be achieved in ceramic materials according to the invention in a manner similar to that described by Monroe, et al. in the aforementioned publication. Thus, organic materials, e.g. starch, cellulose powder, cotton or collagen in amounts ranging from about 5 to 25% by weight are mixed with the gelatinous precipitate of hydroxylapatite. During the subsequent sintering process, the organic material is combusted, thereby giving rise to voids and Alternatively, porosity can be achieved mechanically by drilling or machining holes and openings in the non-porous ceramic material. In this way, an artificial tooth composed of the ceramic material according to the invention can be made porous at the implantation site, while the exposed tooth surface remains non-porous.

Implantation can be accomplished as indicated by Hodosh, et al., Journal of the American Dental Association, 22, 362 (1965). Alternatively, the ceramic material of the invention may be combined with polymeric or polymerized binders, as described below, and the resulting composition used as a coating for metal implants, as described in U.S. Pat. No. 3,609,867.

The novel ceramic form of hydroxylpatite described above can be prepared by precipitation from aqueous medium at a pH of 10-12 of hydroxylapatite with a molar ratio of calcium phosphorus in the range 1.62 - 1.72, separating the precipitated hydroxylapatite from the solution and heating of the hydroxylapatite thus obtained to a temperature and for a period of time sufficient to effect sintering and maximum densification of the hydroxylapatite substantially without decomposition thereof.

Hydroxylapatite is thus precipitated from aqueous medium by reacting calcium ion with phosphate ion at a pH of 10-12. Calcium and phosphate ions in aqueous medium can be used for suitable calcium or phosphate-containing compounds which give the respective counterions in the compounds can be easily separated from the hydroxylapatite product, not per se incorporated into the hydroxylapatite lattice or otherwise interfere with the precipitation or isolation of substantially pure hydroxylapatite. Compounds that supply calcium ion are, for example, calcium nitrate, calcium hydroxide and calcium carbonate.

Phosphate ion can be added with diammonium hydrogen phosphate, ammonium phosphate and phosphoric acid. In the process of the invention, calcium nitrate and diammonium hydrogen phosphate are preferred as sources of calcium and phosphate ion.

The preparation of the new form of hydroxylapatite is conveniently carried out with such a choice of the proportions of the reactants in the reaction that a precipitate with a substantially molar ratio of calcium to phosphorus in the hydroxylapatite is obtained.

First, calcium nitrate and diammonium hydrogen phosphate are reacted in a molar ratio of 1.67: 1 in aqueous solution at a pH of 10-12 to form a gelatinous precipitate of hydroxylapatite. The approach described by Hayek, et al., Inorganic Syntheses, 1, 63 (1963), is satisfactory for this purpose. The gelatinous suspension of hydroxylapatite thus obtained may then remain in contact with the original solution for a period of time sufficient for the calcium: phosphorus content in the suspended hydroxylapatite to reach a value of 1.62 - 1.72. This can be conveniently accomplished either by stirring the suspension at room temperature for a period of not less than 24 hours or by boiling the suspension for a period of 10 to 90 minutes, or by combining boiling followed by allowing the suspension to stand at room temperature. It is advisable to boil the suspension for 10 minutes and then allow it to stand at room temperature for 15-20 hours. The hydroxylapatite is then separated from the solution in a suitable manner, for example by centrifugation and vacuum filtration. The gelatinous product collected in this way contains a large amount of occluded water, a large part of which can be removed by pressing. If desired, the resulting wet clay-like material can be cut or shaped into a suitable shape, or alternatively molded into a suitable shape. It can be observed that normally a shrinkage of about 25% is obtained when the wet hydroxylapatite is dried and a further shrinkage of about 25% during the sintering, as described below. This should of course be taken into account when shaping the material. The wet product can be heated slowly to the sintering temperature of about 1000 - 1050 to 1250 ° C, whereby all remaining water is evaporated. If the temperature is maintained at 1000 - 250 ° C for about 20 minutes to 3 hours, sintering and maximum densification of the product is obtained. It is usually convenient to recover or isolate the dried product before sintering. The wet product can thus be dried at 90 - 900 ° C for 3 - 24 hours until the water content is reduced to 0 - 2 1. It is generally suitable to use: 7804812-1 8 drying conditions of 90 ° C to 95 ° C for approx. 15 hours or until the water content has been reduced to about 1-2%. The hydroxylapatite thus obtained is brittle and porous but has considerable mechanical strength. Some separation or cracking in the clay-like material may occur during drying, especially if a thick filter cake is used. However, pieces as large as 100 cm 2 and 3 mm thick can be obtained without difficulty.

Separation or cracking during drying can be minimized or prevented by the addition of freshly precipitated hydroxylapatite, usually the freshly precipitated suspension of about 0.4 - 0.6% by weight of an organic binder, for example collagen, powdered cellulose or cotton, with about 0.5% collagen is preferred. The organic binder is volatilized during the subsequent sintering, and the physical properties of the ceramic product appear to remain essentially unchanged compared to the properties of the product prepared in the absence of such binder. The use of significantly larger amounts of organic binder will of course result in a porous ceramic product, as described above. Other conventional organic and inorganic binders hidden in the ceramic technique can also be used.

It is usually convenient at this stage to cut or shape the dried precipitate into substantially the desired shape of the final product, taking into account the aforementioned shrinkage which occurs during sintering.

Prior to sintering, the macroform bodies of the precipitate should be uniform and free from defects. The presence of cracks or fractures can cause the pieces to crack during the sintering process.

The products are then sintered at 1000-150 ° C for 20 minutes to 3 hours, with the temperatures and the time being inversely related. The sintering is suitably carried out at 1100 - 120,000 for 0.5 - 1 hour. The hard, dense ceramic objects produced in this way can be polished or machined by conventional methods.

In the foregoing process, it is critical to prepare the hydroxylapatite as a gelatinous precipitate from an aqueous solution because it is only in this cohesive gelatinous state that the hydroxylapatite can be formed and then dried and sintered to obtain the ceramic material in macro form.

Dry particulate or granular hydroxylapatite cannot be reconstituted to this cohesive gelatinous state. For example, if powdery hydroxylapatite is suspended in water and filtered, a non-cohesive, particulate filter cake is obtained which only dries and crumbles and cannot be formed, cast or converted into a macroform of the ceramic material. Although powdery hydroxylapatite can be mechanically compressed into a shaped body, for example a tablet, upon sintering the product obtained will become highly porous and will not crack along even planes but will only rupture into uneven pieces. Although the formation of hydroxylapatite in aqueous medium is a complicated and incompletely elucidated process, it is generally believed that calcium and phosphate ions are first combined to form hydroxylapatite with calcium deficiency and with a calcium: phosphorus ratio of about 1.5. In the presence of calcium ion, this material then undergoes slow conversion to hydroxylapatite with a calcium: phosphorus ratio of 1.67 Isanes et al., Nature, ggg, 365 (1965) and Bett et al., J. Amer. Chem. Soc., §2, 5535 (l967i]. Shall obtain a ceramic containing substantially pure hydroxyl- In order to obtain apatite, it is therefore necessary in the process according to the invention to allow the original gelatinous precipitate of hydroxylapatite to remain in contact with the original solution. for a period of time sufficient to allow the calcium: phosphorus ratio to reach a value of about 1.62 - 1.72. Significant deviation from this range If, for example, hydroxylapatite precipitates at room temperature and collects, a less translucent ceramic product is obtained. within a period of two hours after the precipitation it has been found that the calcium: phosphorus ratio of the material is about 1.55 - 1.57 and that the ceramic material finally obtained therefrom is opaque and by X-ray diffraction examination has been found to be a mixture containing hydroxylapatite and whitlockite As described in more detail below, materials with a calcium: phosphorus ratio of about 1 , 44 - 1,60 useful in the preparation of it While the process gives a translucent ceramic material containing in the aforementioned biphasic ceramic material. In the case of substantially pure hydroxylapatite, in view of the incompletely defined mode of formation of hydroxylapatite in aqueous medium, it may be appropriate to control the hydroxylapatite formation to ensure that the desired stoichiometric ratio of calcium: phosphorus is achieved and that the product during sintering will be essentially pure. This can be conveniently accomplished by removing a certain portion of the hydroxylapatite suspension, separating the product, drying and sintering in the manner set forth above, and subjecting the ceramic material thus prepared to elemental analysis and X-ray analysis.

The temperature and duration of sintering are also critical to the process. Thus, unsintered hydroxyl apatite with the desired calcium: phosphorus ratio of 1.62 - 1.72 is converted to the ceramic material of the invention by heating to a temperature of at least about 1000 ° C. At 1000 ° C, complete sintering and maximum densification may require 2-3 hours, while at 1200 ° C the process can be completed within a period of 20-30 minutes. It is convenient to carry out the sintering at a temperature of about 100 DEG C. for about one hour. Temperatures well below 1000 ° C cause incomplete sintering regardless of the duration of the heating while heating to temperatures above 220 ° C for more than one hour causes partial decomposition of the hydroxylapatite to whitlockit.

The invention also relates to a denture composition comprising a mixture of the ceramic hydroxylapatite according to the invention and a polymerizable or polymerized binder which is compatible with and useful under the conditions of the oral cavity.

The denture composition according to the invention contains from 10 to 90% and preferably 60 - 80%, by weight, of finely divided ceramic hydroxylapatite, the remainder of the composition, from 10 to 90% by weight, being a dentally acceptable polymerizable or polymerized binder together with known suitable polymerization catalysts, for example aliphatic ketone peroxides, or benzoyl peroxide, which can be used together with reactive diluents, for example di-, tri- and tetraethylene glycol dimethacrylate, hardeners, for example N-3-oxohydrocarbon-substituted acrylamides, as described in U.S. Pat. . 056, promoter materials or accelerators, for example metal acetyl acetonates, tertiary amines, for example N, N-bis (2-hydroxyethyl) -p-toluidine, etc., or crosslinking agents (crosslinking agents), for example zinc oxide, which are present in a variety of from 0.01 to 45% by weight * of the total composition. Although not necessary, a surfactant comonomer or "keying agent", for example the reaction product of N-phenylglycine and glycidyl methacrylate, as described in U.S. Pat. No. 3,200,142, methacryloxypropyltrimethoxysilane, 3,4-epoxycyclohexylethyltrimethoxysilosilane, vinylsilane, vinyl to the composition in amounts ranging from 0.05 to 10% by weight of the total composition. The binder or "keying agent" promotes bonding of the ceramic material to the resin and of the dentifrice composition to the natural tooth. Thus, ceramic hydroxylapatite prepared according to the invention is comminuted to a suitable particle size of from 5 to 100 microns by conventional milling methods and then mixed with a suitable amount of a standard resin known in the dental repair art, for example hydroxyethyl methacrylate, polymethyl methacrylate, polyacrylate, polyacrylate, polyesters, such as those pursued by Allied Chemical Co. LS8275 and Pittsburgh Plate Glass, such as Selectron 580001, styrene-modified unsaturated polyesters, for example Glidden Glidpol 1008 G-136 and 4CS50, epoxy-Ci), Union Carbide ERL2774 and bisacrylate monomer made from glycidyl methacrylate and bisphenol resins, for example Ciba A as shown in U.S. Pat. No. 3,066,112. The resin may comprise a single monomer or a mixture of two or more comonomers. Additives, such as dyes, inorganic pigments and fluorescent agents, may, if desired, be added to the foregoing composition according to known principles in the art for these materials. It is convenient to mix resin, ceramic hydroxylapatite and optional ingredients, for example silane binders, dyes, inorganic pigments or fluorescent agents before the addition of catalyst, hardener, crosslinking agent, promoter material or accelerator material. However, the order in which the ingredients are mixed together is not critical and the ingredients can be mixed simultaneously. Using conventional methods, the composition prepared in this way can be used such as dental filling material, dental cement, cavity liner, pulp capping agent or the composition can be cast in a suitable form to form an artificial tooth or a dental set.

It is of course very advantageous that materials used in the oral cavity are caries-resistant. This is easily achieved according to the invention by adding 0.01 to 1% fluoride ion, for example ammonium or stannous fluoride to the suspension of freshly precipitated hydroxylapatite. The ceramic material produced by sintering the resulting product is highly resistant to attack by lactic acid, acetic acid or citric acid, which is a standard in vitro method for determining caries resistance. Alternatively, resistance to caries can be achieved in the finished ceramic material by subjecting it to the action of a 0.5 - 5% aqueous solution of sodium fluoride for 12 hours to 5 days.

Preferably, the ceramic body is allowed to stand in about 5% aqueous sodium fluoride solution for about 4 days.

As will be apparent to those skilled in the art of ceramics, in addition to organic and inorganic binders and fluoride ions, ceramic materials may also contain small amounts of other elements which, although not altering the essential nature of barium and strontium, are known to can be incorporated into the apatite ceramic product, it imparts valuable properties. the crystal lattice and that these elements are significantly more opaque to X-rays than calcium. Thus, the addition of a small amount of barium or strontium ion to the calcium ions prior to their reaction with phosphate ion will ultimately yield a barium or stronlium doped hydroxylapatite ceramic material which can be used in a dentifrice composition as described above and thereby provides adequate X-ray absorption. to enable observation in the filled tooth. the lattice, however, is known to be able to retard the crystallization Magnesium, which can also be incorporated into the apatite crystal of hydroxylapatite and favors the crystallization of whitlockit Isanes et al., calc. triss. Res., G, 32 (lsss fl.

The ceramic materials obtained in the manner described above were characterized on the basis of one or more of the following properties: elemental analysis, density, X-ray diffraction, transmission electron microscopy, polarized light microscopy and mechanical properties.

The invention is further illustrated by the following embodiments. Example 1. To a stirred mixture containing 130 ml of 1.63N calcium nitrate (0.2l2 mol) and 125 ml of concentrated ammonia was added dropwise over a period of about 20 minutes a mixture containing 16.75 g (0.127 g). mol) ml of concentrated ammonia. diammonium hydrogen phosphate, 400 ml of distilled water and 150 The resulting suspension was boiled for 10 minutes, cooled in an ice bath and filtered. The filter cake was pressed with a rubber press (rubber dam) and then dried overnight at 95 ° C. A sample of the resulting hard, porous, crispy cake was heated in an electric oven for a period of 115 minutes up to a final temperature of 132 ° C and then cooled to room temperature to give a strong, hard, 7804812-1 13 white translucent ceramic product.

Standard elemental analysis of the final ceramic material as well as of the dried hydroxylapatite before sintering gave the following results based on CalO (PO4) 6 (OH) 2: Dried, unsintered 'Ceramic Analysis Calculated,% hydroxylagatite,% Q Product,% Ca 39.89 37, 4 39.6 P 18.5 17.5 18.9 H 2 O 0 l - Ca / P 1.667 - 1.65 1.62 Examination of a thin section of the ceramic material with a microscope and polarized light at the magnification degrees l30X and 352X showed that the material was essentially free of whitlockit.

The absence of birefringence and observable structural properties, such as crystallite shape, orientation, boundaries, etc., indicated a microcrystalline structure. A comparison with optical photomicrographs of a thin section of the sintered, compressed tablet, reported by Monroe et al. (in previously cited publication), showed that the two materials had different structures.

X-ray diffraction measurements were performed in a conventional manner. The distances between the planes were calculated and found to be apparently identical to the values given for hydroxylapatite by Donnay et al., Crystal Data, ACA Monogram No. 5, 668 (1963). The X-ray values further showed the absence of whitlockit in amounts exceeding about 2 ~ 3%, which constitutes the mini-concentration sensitivity of the diffractometer.

Example 2.

A solution containing 79.2 g (0.60 mol) of diammonium hydrogen phosphate in 1500 ml of distilled water was adjusted to pH 11-1 with about 750 ml of concentrated ammonia. An additional amount of distilled water was added to dissolve precipitated ammonium phosphate to a total volume of 3200 ml. If necessary, the pH was readjusted to 11-12. This solution was added dropwise over a period of 30-40 minutes to a vigorously stirred solution containing 1 mole of calcium nitrate in 900 ml of distilled water, which was previously adjusted to pH = 12 with approx. 30 ml of concentrated aqueous ammonia solution and then diluted to a volume of 1800 ml with distilled water. After the addition was complete, the resulting gelatinous suspension was stirred for an additional 10 minutes for 14 minutes and then boiled for 10 minutes, removed from the heat, covered, and allowed to stand for 15-20 hours at room temperature.

The saturated solution was decanted and the remaining suspension was centrifuged at 2000 rpm for 10 minutes. The resulting slurry was resuspended in 800 ml of distilled water and centrifuged again at 2000 rpm for 10 minutes.

Sufficient distilled water was added to the remaining solid to give a total volume of 900 ml. Strong shaking gave a homogeneous suspension, which was substantially free of large fragments or aggregates. The whole suspension was poured into a Buechner funnel at once and filtered using a slight vacuum. When the filter cake began to crack, a rubber cloth was applied and the vacuum was increased. After one hour, the rubber cloth was removed and the crack-free, intact filter cake was transferred to a flat surface and dried for 15 hours at 90 DEG-95 DEG C. to obtain 90-100 g of white, porous, brittle pieces of hydroxylapatite. Pieces with a size of from 1 to 4 cm 2, which were free from cracks, were introduced into an electric oven and the temperature was raised to 1200 ° C for a period of 100 minutes, after which the oven and its contents were allowed to cool to room temperature. Pieces of a hard, dense, non-porous, white translucent ceramic material were obtained.

Dried, unsintered Ceramic Analysis Calculated,% hydroxylapatite,% material,% Ca 39.89 7 36.5, 36.8 31.7, 38.0 1 = 18.5 Ü 21.7 22.8, 19.0, 18.8 1.08, 1.55, 1.56 Ca / P 1.667 1.30, 1.31 After carrying out this analysis, it was discovered that the analysis method used did not allow complete dissolution of the samples and the results are therefore inaccurate and highly variable. . Nevertheless, despite the analysis values given above, it was found that the good homogeneity of the sample could be confirmed by the following electron microscope data. Furthermore, it was found that the product of Example 3, prepared by a method substantially identical to the method of the experiment of Example 2, had the expected assay values and was further characterized as homogeneous hydroxylapatite by X-ray diffraction examination and electron microscopy.

Two-step replica samples were prepared by shading a collodion casting of the sample surface with chromium and then coated with carbon. Transmission electron microscopic examination of the sample casts showed a substantially uniform grain size with no signs of pores or precipitation of any other phase neither in the grain boundaries nor in the grains themselves in any amount exceeding about 0.5% which is the minimum concentration sensitivity of the electron microscope examination.

A sample of the ceramic material was then polished on SiC paper to 600 grit, then polished to 3 μm diamond paste on a metallograph sample preparation disk covered with fine nylon cloth. The sample was then etched with 4% hydrofluoric acid for 30 seconds. Castings were then made of the polished and etched surface and then examined by electron microscopy. In this case, too, no other phases could be observed in the grain boundaries, but some signs of small particles of a second phase in the main part of the grains were observed.

The compressive strength and modulus of elasticity were determined by conventional methods and were found to be 3962 É 122 kp / cm 2, respectively. 4.4 x 104 kp / cm 2.

The tensile strength was determined by standard three-point bending test and found to be 680 É 233 kp / cmz.

The coefficient of thermal expansion was found to be linear between zs ° c and 225 ° c with a value of 11 x 10 6 / ° c ï 10%.

A hardness value of 480 was obtained using the standard Knoop method. The same value was obtained regardless of the direction of the applied force, indicating that the material was isotropic.

The porosity was determined qualitatively by immersing the sample material in fuchsin paint for 15 minutes, washing with water, drying and then examining the sample material for traces of residual paint. This test was performed simultaneously on the non-porous form of the ceramic material obtained according to the invention, on a sintered pressed tablet of hydroxylapatite and on a natural tooth. The sintered compressed tablet showed considerable retention of color while the new ceramic material according to the invention and the natural tooth did not show any visible retention of color. In another method, the sample material was immersed in 6N aqueous ammonia solution for 15 minutes, then washed with water, dried and wrapped in a damp litmus paper. Any ammonia that remains trapped in surface pores causes the surrounding litmus paper to turn blue. When using this test simultaneously on the ceramic material according to the invention, a sintered pressed tablet of hydroxylapatite and a natural tooth, the litmus paper became in contact with the sintered tablet, which indicates the presence of entrapped ammonia in the tablet. No color change was observed in the litmus paper which was in contact with the new ceramic material according to the invention resp. with the natural tooth. Example 3.

A. Using a method similar to that described in Example 2 but with one-sixth of the amounts set forth in Example 2, about 50 g of hydroxylapatite precipitated from aqueous solution. After centrifugation and decantation, the remaining mineral slurry was reslurried in sufficient water to give a total volume of 1 liter and homogenized in a Waring mixer for 2 minutes.

B.f A mixture containing 0.5 g of powdered cellulose (¿0.5 μm) in 200 ml of water was mixed in a Waring mixer for 3 minutes. A quantity of 100 ml of the homogeneous aqueous suspension of hydroxylapatite was then added and the resulting mixture was mixed for a further 5 minutes. The suspension was then filtered and the filter cake was dried and sintered as in Example 2. After drying, the filter cake showed very little cracking and the ceramic product obtained during sintering was slightly porous, which was demonstrated by the fuchsin color test described above.

C. A mixture containing 0.5 g of grated surgical cotton in 2CO ml of water was mixed in a Waring mixer for 45 minutes or until a nearly homogeneous suspension was obtained. A quantity of 100 ml of the homogeneous aqueous suspension of hydroxylapatite described in Example 3A was then added and mixing was continued for a further 15 minutes. The resulting suspension was filtered and the filter cake was dried and sintered as in Example 2. The ceramic product remained intact and was visibly porous.

Example 4.

A. V A mixture containing 5 g of collagen (Achilles tendon of ox) in 300 ml of water was mixed in a Waring mixer for 5 minutes.

The collagen absorbed large amounts of water and formed a thick gelatinous mass. A small amount of finely divided collagen (20 - 30 mg) remained in suspension.

B. The suspension of the atomized collagen (250 ml) was decanted and mixed in a Waring mixer for 5 minutes in a 100 ml quantity of the homogeneous aqueous suspension of hydroxylapatite, as described in Example 3A. The resulting mixture was filtered. 17 and the filter cake was dried and sintered as in 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 minutes with 150 ml of the homogeneous aqueous suspension of hydroxylapatite, as described in Example 3A. The resulting mixture was filtered and the filter cake was dried and sintered as in Example 2. Prior to sintering, the dried cake remained intact and had considerable mechanical strength. The ceramic material produced by the sintering was hard, strong and visibly porous.

Example 5.

Samples of the ceramic product prepared according to Example 2 were allowed to stand in a 1% aqueous solution of sodium fluoride for 12 hours. These materials and samples of untreated ceramic material as well as natural tooth were then subjected to the action of 10% lactic acid. After 3 days, the fluoride-treated ceramic material showed significantly less attack of lactic acid than both the untreated ceramic material and the natural tooth enamel. When the material was allowed to stand in 1% aqueous sodium fluoride solution for 3 days, the ceramic material was not visibly infested with lactic acid after 3 days, and after 1 month the material had undergone only slight decomposition while the untreated samples were heavily decomposed. .

Example 6.

Using an approach similar to that described in Example 2 but with one-sixth of the amounts of the materials listed in Example 2, an estimated 50 g of hydroxylapatite precipitated from aqueous solution. After centrifugation, the mineral slurry was suspended in sufficient water to give a total volume of 500 ml. The suspension was divided into ten equal portions, each of which was diluted with 50 ml of water and treated with ammonium fluoride as follows: To samples 1, 2, 3, 4 and 5 were added 0, 0.1, 0.5. 1.0 resp. 2.0 ml aqueous solution of ammonium fluoride containing 0.00085 g Fe / ml. Samples 6, 7 and 8 were treated with 0.5, 1.0 and 10.0 ml aqueous ammonium fluoride solution containing 0.0085 g Fe / ml. To samples 9 and 10, 2.0 and 4.0 m 'aqueous solution of ammonium fluoride containing 0.045 g Fe / ml. The suspensions were then shaken on a rotary shaker for 1.5 hours and filtered. The filter cakes were pressed for 15 minutes with a rubber cloth, dried for 2 days at 95 ° C and heated in an electric oven to a temperature of 1200 ° C. The obtained ceramic materials were ground to fine powder and sieved through a 325 mesh screen (US ASTM Standard). 80 mg of each powdered sample was mixed with 80 ml of sodium lactate buffer solution with a pH value of 4.1 (0.4M) at 23 ° C and shaken on a Burrel wrist-action shaker. At times 2, 9, 25 and 40 minutes after mixing, 3 ml volumes were taken from each sample landing, filtered immediately to remove undissolved sample and subjected to determination of the amount of dissolved ceramic material by a colorimetric measurement method. The results are given in Table A. For comparison, a sintered portion of Sample 1 was allowed to stand for 4 days in 1 * ml of 5% sodium fluoride. The solid was separated, washed thoroughly with water, dried and then subjected to the dissolution treatment described above with sampling as sample 1A. The results are given in Table A. It is given that the experimental conditions given above do not mimic in vivo conditions but have been chosen to allow sufficient dissolution of the sample within an acceptable period of time to enable an accurate evaluation of the relative efficacy. of the fluoride ion content. Thus, the in vivo dissolution rates of ceramic hydroxylapatite materials are assumed to be significantly lower than the above rates in the strong lactate buffer. In Table A; Relative dissolution rate of fluoride-treated ceramic hydroxylapatite materials.

Sample Fluoride content (PPm)% undissolved no. Added Found 2 min. ' 9 min. 25 min. 40 min¿ 11 o - 9,2 18,5 i '32,0 39,7 2 17 19a 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 1,700 470 7.9 18.1 25.7 29.8 8 17,000 1,460 6.7 12.1 19.7 23.3 9 18,000 1,700 6.3 11.5 19.7 23.3 10 f36,000 2,307 5.9 11.3 17.6 21.0 1A - - 3.7 7.1 -13.7 18.7 ra. Obviously incorrect measured value.

Example 7.

Large pieces of dried filter cake with a thickness of about 3 - 78048124 19 4 mm were prepared in the manner given in Example 2 with a ratio Ca / P = 1.64 - 1.66 and were drawn and broken into rectangular plates with a length of approx. 14 - 15 mm and a width of about 7 - 8 mm and with a small hole drilled through one end. 1000 such plates were then sintered according to Example 2 and polished to high gloss using standard gemstone polishing methods. The obtained ceramic bodies with a density of 3.12 - 3.14 g / cm3 were obtained in the form of rectangular plates with a length of about 10 - 11 mm and a width of 4 - 5 mm and a thickness of 2 - 3 mm with a hole at one end through which a piece of wire is attached. The plates, which could thereby be hung to the desired depth in a test tube, were used as a test surface in the evaluation of agents for inhibiting dental plaque, as described above.

The ceramic products prepared according to Examples 1, 2, 4B and 5-7 are macro-strong, hard, dense, white, translucent ceramic bodies containing mainly pure, isotropic polycrystalline hydroxylapatite, which is free of pores and has a pressure-resistant firmness mainly in the range 3950 - 8800 kp / cmz, a breaking limit mainly in the range 210 - 2100 kp / cmz, a linear coefficient of thermal expansion of about 10 - 12 ppm per OC, a Knoop hardness of about 470 - 4 kp / cmz, and is characterized by 500 and a modulus of elasticity of about 4.2 x 10 by splitting along even curved planes and by the absence of birefringence under the influence of polarized light.

The ceramic products in macro form, which were prepared in the experiments according to examples 3 and 4, contain, despite the fact that they consist of the same material as prepared according to examples 1, 2, 4B and 5 - 7 cavities or pores of varying number and size. It is obvious that the introduction of pores in these objects entails a change in the physical properties, for example a reduction in the compressive strength, the breaking point, the elasticity and the hardness.

Example 8. In a composition suitable as a dental cement and land filler was prepared as follows: A. To a solution containing 20 mg of the condensation product of N-phenylglycine and glycidyl methacrylate (as described in U.S. Pat. No. 3,200,142). and in this is designated NPG-GMA) in 7 ml of ethanol was added 2.0 g of powdered ceramic hydroxylapatite. After stirring for 5 minutes (swirling), the ethanol was evaporated in vacuo at room temperature and the solid residue was dried for 2 hours at 1 mm Hg. 7804812-1 20 B. Z A sample weighing 80 mg of the above material was mixed with 0.4 mg of benzyl peroxide and 30 mg of a 1: 2 mixture of hydroxyethyl methacrylate and the reaction product of bisphenol A and glycidyl methacrylate, as described in U.S. Pat. No. 3,066,112 and herein is referred to as "Bis-GMA". The resulting mixture was introduced into a cylindrical steel mold in which the mixture was cured within a period of 3-5 minutes. The compressive strength was determined on four cylindrical plugs manufactured in this way. The average value was 1600 kp / cmz.

Example 9. A mixture containing 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-bis (2-hydroxyethyl) -p-toluidine and 0.8 parts of benzoyl peroxide were carefully mixed into a thin, free-flowing composition which was useful as a filler for pits and cracks in teeth. The mixture was cast in a cylindrical steel mold in which it was cured for about 3 minutes. posed in this way.

Example 10.

The following example indicates a composition which is suitable as the compressive strength was determined on seven cylindrical plugs. The mean value was 1430 kp / cm 2. dental fillers.

To 5 ml of 2-propanol was added 0.5 g of powdered ceramic hydroxylapatite. The 2-propanol was then evaporated under vacuum at room temperature to remove any hydrated water from the surface of To 120 mg of the powdered hydroxylapatite thus treated was added 0.3 mg of benzoyl peroxide and the ceramic, then 40 mg of a mixture consisting of of the condensation product of bisphenol A and glycidyl methacrylate, triethylene glycol dimethacrylate and »LN-bis (z-hydroxyethyl fi / l) -p-tceliain under the trademark Epoxylite This mixture is marketed B; the breath was processed with a spatula into a smooth paste and introduced into HL-72 by Lee Pharmaceuticals. cylindrical standing arms were allowed to stand for 4 hours ten. The cylindrical plugs were removed from the molds and 3 test pieces were tested and found to have an average compression strength of 1535 kp / cm 2. åšçmpel ll.

To a solution containing 30 mg of the condensation product of N-phenylglycine and glycidyl methacrylate in 7 ml of ethanol was added with rotary stirring (swirling) 1 g of powdered ceramic hydroxyl apatite. The ethanol was evaporated in vacuo at room temperature. To a mixture containing 180 mg of powdered ceramic hydroxylapatite treated in this way and 3.0 mg of benzoyl peroxide was added 74 mg of a mixture containing 60 parts of the condensation product of bisphenol A and glycidyl methacrylate and 40 parts of triethylene glycol dimethacrylate, and the obtained the mixture was processed with a spatula to a smooth paste, which was introduced into cylindrical steel molds and allowed to stand for 3 hours. The cylindrical plugs were removed from the molds and 4 test pieces were tested and found to have an average compressive strength of 1535 kp / cm 2.

Example 12.

A composition suitable as a dental and orthodontic cement or as a temporary dental filler was prepared by mixing 100 mg of powdered ceramic hydroxylapatite, 300 mg of zinc oxide and 300 mg of 40% aqueous solution of polyacrylic acid. The resulting mixture was introduced into cylindrical steel molds in which the mixture hardened within a period of about 3-5 minutes. The cylindrical plugs were removed from the molds and 4 test pieces were tested and found to have an average compressive strength of 870 kp / cm 2.

An additional 5 test pieces were found to have an average diametrical tensile strength of 115 kp / cm 2. The 40% aqueous solution of polyacrylic acid resp. the zinc oxide was obtained as liquid resp. solid components of a commercially available polycarboxylate cement, marketed by ESPE G.m.b.H., Federal Republic of Germany, under the trademark Durelon. In Example 13.

A composition suitable as a dental cement and dental filler was prepared by mixing 6 parts by weight of 40% aqueous solution of polyacrylic acid with a mixture containing 6 parts by weight of powdered ceramic hydroxylapatite and 4 parts by weight of zinc oxide.

The resulting composition had a curing time of about 5-10 minutes.

The material containing 40% aqueous solution of polyacrylic acid and zinc oxide was obtained in the form of the liquid resp. solid components of a commercially available polycarboxylate cement, marketed by ESPE G.m.b.H., Federal Republic of Germany, under the trademark Durelon. 'fš> - ¥: 3 _ !!? Bs “_1.v __, l__fl _-_ The following is an example of a dental filling composition = 7804812-1 22 Ingredient 6% by weight Styrene-modified polyester resin 29.2 (Glidden Glidpol G-l36) Benzoyl peroxide _ '07 Styrene '0.6 Methacryloxypropyltrimethoxysilane _ 1.5 Ceramic hydroxylapatite 68.0 Example 15.

The following is an example of a composition suitable as a dental cement, cavity cladding agent and pulp capping agent: Component 1 Victorocent Epoxy Resin (Union Carbide ERL2774) 67 N43-oxo-1,1-dimethylbutylacrylamide 23 Ceramic hydroxylapatite. Example 16.

The following is an example of a composition suitable for the manufacture of artificial teeth or toothpicks.

A mixture containing 60 parts by weight of ceramic hydroxylapatite having a pereikeieerlek or about iso-zoomen ounces.) And 40 parts by weight of powdered polymethyl methacrylate was mixed with about 15 parts by weight of liquid methyl methacrylate polymer and the resulting mixture was left in a closed vessel at room temperature no longer adhered to the walls of the vessel and had a non-stick plastic consistency. The material was then packed in a suitable mold and the mold containing it was immersed in water, which was heated to boiling point for a period of about one hour and kept at this temperature for 30 minutes. The mold was then allowed to cool in air for about 15 minutes and finally cooled in cold tap water.

The biocompatibility of the new hydroxylapatite ceramic mold of the invention was confirmed by implantation studies showing that no inflammatory response was obtained when chips of the ceramic material prepared according to Example 1 were implanted intraperitoneally in rats or by insertion subcutaneously on the spine. rabbits, and no absorption of the cul- malic material could be observed after 28 days.

Pellets of ceramic hydroxylapatite prepared by a procedure similar to that described in connection with Example J were surgically implanted in the femur of dogs. The implants were examined

Claims (3)

7804812-1 23 in vivo with periodic X-ray examination. After a period of 1 month resp. At 6 months, the animals were sacrificed and the femur containing the implants was removed. The femur was sectioned at the implant site and examined both optically and by electron microscope scanning. Both after 1 month and 6 months, the implants were characterized by normal healing, strong binding of new bone to the implant surface without any intermediate fibrous tissue, no signs of inflammation or foreign body response and no resorption of the implant material. PATENT REQUIREMENTS Transparent, isotropic, polycrystalline, sintered ceramic product, characterized in that it consists essentially of pure hydroxylapatite with an average crystallite size of 0,2-3 μm, a density in the range 3,10-3,14 g / cm3 and is essentially free of pores and shows cleavage along evenly curved surfaces. 2. A ceramic product according to claim 1, characterized in that the product contains an amount of fluoride ion incorporated which is sufficient to substantially reduce the rate of decomposition of the ceramic product by the action of lactic acid. Use of the transparent, isotropic, polycrystalline, sintered ceramic product according to claim 1 or 2, which consists of substantially pure hydroxylapatite with an average crystallite size of 0.2-3 μm, a density in the range 3,10 3.14 g / cm3 and is substantially free of pores and exhibits cleavage along evenly curved surfaces, in a dentifrice composition which contains 10-90% by weight of the comminuted ceramic product and a dentally acceptable polymerizable oil polymeric binder, preferably bonded to polyacrylic acid or the condensation product of bisphenol A and glycidyl methacrylate. BEFORE PUBLICATIONS: