NO138802B - PROCEDURE FOR PREPARING A POLYCRYSTALLINIC, SINTERED CERAMIC MATERIAL - Google Patents

Description

The present invention relates to ceramic material, in particular material to be used for odontological and orthopedic purposes.

Much of the research that takes place in dentistry concerns the production of materials that can be used as substitutes for teeth and bones, e.g. as repair material for fillings, bridges and crowns, as well as prosthetic material for bones. Odontological research also works to prevent the formation of tartar, which is assumed to be the cause of both tooth decay and periodontitis or root inflammation.

Commonly used filling materials for dental purposes are e.g. quartz, aluminum oxide, silicates, glass beads etc., and these substances have little chemical or physical resemblance to tooth enamel. A particular disadvantage of these materials is that they have a different linear expansion coefficient than the tooth enamel itself, and this can possibly lead to crack formation and new tooth decay. It has therefore long been desirable within dentistry to have a dental filling material that has physical properties that are very close to those found in natural tooth enamel.

Furthermore, it can be stated that when it comes to surgical prosthetic materials, which are usually dominated by non-corroding and very strong alloys, there is a need for a material that has a strong resemblance to biological hard tissue, as problems in connection with tissue acceptance and attachment has not been completely resolved (Hulbert et al., Materials Science Research 5, 'il? (1971).

When it comes to research that concerns finding effective chemotherapeutic agents against calculus, there is also a need for a standard sample material that has a tooth-like surface both with regard to calculus formation and resistance to chemical agents. Although natural teeth have been used for this purpose, the disadvantage is that they are highly variable, it is often difficult to obtain them in large quantities, and they require very immediate cleaning before use. Consequently, other materials have been used which yield significant amounts of calculus, such as powdered hydroxyapatite, acrylic dental material, glass and wires. Although these materials are to a certain extent satisfactory for studies on the formation of tartar, they bear little resemblance to the natural tooth surface and are therefore not suitable for studies to find remedies against said tartar. It is e.g. It is known that chemicals which inhibit calculus formation on teeth do not necessarily do this on glass and other types of materials (Turesky et al., J. Perio-dontology ^3, 263 (1972). There is thus a need for a cheap and easy available material that is chemically similar to tooth enamel, and which is hard, dense and can be highly polished.

Hydrosylapatite, Ca^^(PO^)^(OH)2, is also known as basic calcium orthophosphate, i.e. the mineral phase in teeth and bones, has been proposed as a material for the various purposes mentioned above, and US patent no. 2 508 816 thus describes a method for obtaining said hydroxylapatite from tooth enamel and using this material in mixture with a synthetic resin as a prosthetic material. This method is very labor-intensive and expensive, and is limited by the production of finely divided hydroxylapatite. Furthermore, the method obviously depends on having a large amount of natural teeth available.

Kutty ("Indian J. Chem." 11, 695 (1973) describes mixtures of hydroxylapatite and whitlockite prepared by decomposing powdered hydroxylapatite at various temperatures.

Bett, et al., ("J. Amer. Chem. Spe." 89, 5535 (196?) describe the preparation of particulate hydroxylapatite with a stoichiometric ratio ranging from Ca/P = 1.6/ to 1.57. It material produced in this way contains large inter-crystalline pores. It was thus indicated that by heating up to 1000° C, a partial transformation of said hydroxylapatite, which has a deficit of calcium, into the so-called whitlockite phase was obtained.

U.S. Patent No. 3,787,900 describes a prosthetic material for teeth and bones, which consists of a refractory compound and a calcium phosphate compound, ie, whitlockite.

Several attempts have been made to provide a new and hard and strong macroform of hydroxylapatite. However, it has been found that none of the previously known forms of hydroxylapatite have proved fully satisfactory. Thus, Roy and Linnehan (Nature, 2^7, 220 (197^) have described a labor-intensive hydrothermal extraction process, where a grid of calcium carbonate from marine corals was converted into hydroxylapatite. The material that was produced, however, had the same highly porous properties as found in the coral itself, and also had a relatively low tensile strength of from 19»5 - ^0 kg, per cm , a very serious disadvantage for the prosthetic material.

Monroe et al. ("Journal of Dental Research" 50,

860 (1971) stated the preparation of a ceramic material by sintering compressed tablets of hydroxylapatite. The material that was produced was in reality a mixture of hydroxylapatite and approx. 30$ a-whitlockite, which is Ca^

(PO^^ or tricalcium phosphate, as an ordered mosaic pattern of polyhedral crystalline bodies, and it was clear that this material had too high a porosity to be used for dental purposes.

Rao and Boehm ("Journal of Dental Research" 53, 1351 (197^) describe a polycrystalline form of hydroxylapatite prepared by isostatically compacting powdered hydroxylapatite in a mold and isothermally sintering the material in the mold. The resulting ceramic material was porous,

and had a maximum compression strength of approx. 1220 kg/cm .

Bhaskar et al. ("Oral Surgery" 32, 336 (1971) describes the use of a biodegradable calcium phosphate ceramic material for bone filling. This material is highly porous, and is absorbed from the place where the material is placed, and the material also lacks the strength found 1 ot metal oller in a non-degradable ceramic material.

The present invention thus relates to a method for the production of a polycrystalline, sintered ceramic material in macroform where calcium ions are reacted with phosphate ions in an aqueous medium and at a pH of 10 - 12, whereby a gelatinous precipitate of a calcium phosphate with a molar ratio is produced between calcium and phosphorus between the approximate molar ratio between calcium and phosphorus found in hydroxylapatite and the corresponding ratio in whitelockite, after which said precipitate is separated from the solution, and this method is characterized by heating an integral mass of the separated precipitate, if desired after forming <p>g cutting, to a temperature of at least 1000°C, but below the temperature at which a significant decomposition of hydroxylapatite occurs, and maintaining said temperature for a sufficiently long time to obtain sintering and a substantially maximum densification of the resulting product.

According to the present invention, a new ceramic form of hydroxylapatite is thus provided which essentially consists of pure hydroxylapatite which is hard, dense and which can be highly polished. Chemically, this material is very similar to tooth enamel. Furthermore, the new material can be produced in a relatively simple way from cheap starting materials and can be obtained in uniform quality, thereby avoiding the undesirable variations found in natural teeth.

By using the new ceramic form of hydroxylapatite in compositions for dental purposes, a dense filling material is obtained that has a linear expansion coefficient that is very nearly identical to that found in natural tooth enamel.

The replacement material for surgical and dental purposes that is available by means of the present invention is hard, strong and completely biocompatible material, and it can be manufactured or produced in any desired shape, without the need for high pressure or other labor-intensive techniques. Furthermore, as described below, it is very easy to give the material any desired degree of porosity, so that it can be used in different types of tissue.

The properties found in the new material make it very suitable for the production of disks, plates, rods etc., which can be used for testing anti-tartar agents.

With the method according to the invention, a two-phase ceramic material consisting of hydroxylapatite and whitlockite can also be produced. As will be described in more detail below, this new ceramic material is hard, dense, non-porous, bio-compatible and easily manufactured in any desired shape, and due to the known resorption properties found in whitlockite, the material can is used as a strong, partially resorbable surgical implant material.

A certain degree of porosity is often beneficial for surgical purposes, because this allows circulation of body fluids and intergrowth with natural tissue, so this porosity obviously reduces the mechanical strength of the piece. The biphasic ceramic material which is provided by means of the present invention, although it is dense mechanically strong and essentially non-porous, still allows for a circulation of body fluids and an intergrowth with natural wood, because the whitlockite phase present is slowly resorbed from the surrounding tissue and replaced with natural biological hardwood.

The new physical form of hydroxylapatite, which differs from all known biological and geological forms as well as from all previously known synthetic forms, consists of a strong, hard, dense, white, translucent isotropic, polycrystalline sintered ceramic material consisting of essentially pure hydroxylapatite with an average crystalline size of from 0.2 to 3 microns, a density varying from 3.10 to 3.14 g/cm 2 , and is further characterized by an absence of pores and by cleavage along smooth curved planes. As the material is usually manufactured, it has a compressive strength of 2500 to 9000 kg/cm, a tensile strength varying from 215 to 2150 kg// cm 2, on linear thermal expansion coefficient varying from 10 to 12 ppm per degrees Celsius, a Knoop hardness varying from ^70 to 500 and a modulus of elasticity of approx. 0.'(2 x 10 6 kg/cm~2<,> and is a non-birefringent material under polarized light. The first evaluation of the new hydroxylapatite ceramic material indicated that it was a strong, hard, dense, white, translucent ceramic material, consisting essentially of pure microcrystalline hydroxylapatite in an arbitrary, isotropic pattern and with a compressive strength varying from 2500 to 5300 kg/cm 2 , a tensile strength varying from 215 to 360O kg/cm 2 , a linear thermal expansion coefficient varying from 10 to 12 ppm per degree Celsius, a Knoop hardness varying from 470 to 500 and a modulus of elasticity of about 0.42

x 10 6 kg/cm 2 , and the material is characterized by cleavage along smooth curved planes, and by the absence of birefringence under polarized light.

The term dense, as used here, denotes a highly compact arrangement of the particles where there is essentially no space between the individual particles.

In contrast to the above-described form of hydroxylapatite, geological hydroxylapatite and synthetic hydroxylapatite produced by a hydrothermal process are macrocrystalline, and split along flat planes, and are birefringent. Biological hydroxylapatite is distinguished by containing significant amounts of carbonate ions in the apatite pattern, and is in its purest state, i.e. in tooth enamel, being anisotropically arranged in twisted radial rods, so that it breaks in straight lines along the interface between these enamel rods, and has a relatively low tensile strength of approx. 132 kg/cm2.

In addition to the above-described properties in the new ceramic form of hydroxylapatite provided by means of the present invention, the material is also completely biocompatible and is therefore very well suited as a prosthetic material, both for surgical and dental purposes. Thus, the ceramic material can be cast or processed into dental crowns, artificial teeth, bone and joint prostheses, tubes and fastening devices for artificial limbs, which can be attached to the bone and pass through the skin, as well as test surfaces for studies of calculus, caries formation, arthritis and other diseases. which can affect teeth and bones. If it is properly ground, the new ceramic material can be used as a synthetic material for the repair of bone defects, as an abrasive material and can be combined with standard resins into an odontological repair material, as will be described in the following .

As a test surface for evaluating tartar inhibiting agents, the ceramic material can be worked up into bodies of any suitable shape and size, preferably of a shape and size that can easily be inserted into a standard test tube. This can conveniently be achieved by cutting or machining large plate-like pieces of a dried filter cake to a suitable size, after which they are sintered. The sintered products are then highly polished using conventional techniques, after which the resulting pieces are used as a basis for the evaluation of dental caries inhibitors, as described by Turesky et al, reference as above. After use, the ceramic bodies can only be polished again and can thus be used again.

As it is usually produced, the ceramic material will not only be dense, but also non-porous, and although non-porous materials are important for dental purposes, it may be desirable to have a certain degree of porosity in artificial pieces that can allow circulation of body fluid and tissue growth. Varying degrees of porosity can be provided in the present ceramic material in a similar manner, as described by Monroe, et al, in the aforementioned reference. Thus, organic compounds such as starch, cellulose, cotton or collagen in amounts varying from 5 to 25 percent by weight can be mixed with the gelatinous precipitate of hydroxylapatite. During the subsequent sintering process, the organic material will be burned out and will thereby create holes or channels in an otherwise non-porous ceramic product. - Alternatively, the porosity can be produced mechanically by drilling or milling holes and openings in the material.

In this way, an artificial tooth made from the present ceramic material can be made porous at the point of implantation, while the exposed tooth surface can remain non-porous. Implantation can be performed as indicated by Hodosh et al, Journal of the American Dental Association,

70, 362, (1965). Alternatively, the ceramic product can be compounded with a polymerizable or polymerized binder as described hereinafter, and the resulting composition can be used as a coating for metal implant pieces, as described in US Patent 3,609,867 issued October 5 197L

As mentioned, according to the present invention, a strong, hard, dense, white, isotropic, polycrystalline sintered ceramic product can be produced which contains as one phase from 1 to 98 percent by weight hydroxylapatite and as another phase from 2 to 86 percent by weight whitlockite, and which is characterized by the absence of pores and by a cleavage along the smooth, curved plane.

Whitlockite, which is also known as tricalcium phosphate, is a mineral with the chemical formula Ca.^(PO^)^ and the mineral can exist either in a- or ^-crystalline phase. The term whitlockite as used here is understood either with the a or (3) phase or a mixture of the two phases.

The biphasic ceramic material remains a non-porous polycrystalline material regardless of the relative concentrations of hydroxylapatite and whitlockite.

However, it is understood that hydroxylapatite and whitlockite have different physical properties, and that the physical properties such as density and optical properties of the biphasic ceramic material will depend on the relative amounts of hydroxylapatite and whitlockite. Thus, the theoretical density of whitlockite is less than that found in hydroxylapatite, and consequently the observed density for a sample of a biphasic ceramic material will contain approx. coffee hydroxylapatite and 60$ whitlockite be 2.98 g/cm compared to a density of 3.10 g/cm for a sample of a pure hydroxylapatite ceramic material.

The biphasic ceramic material described above is also biocompatible and therefore very well suited as a prosthetic material for surgical purposes. The material can thus be molded or processed into bones or joint prostheses and can be worked up into any shape that is suitable for filling a cavity or a defect in a bone or leg piece. The whitlockite that may be present in a prosthetic article made from the present biphasic ceramic material will eventually be resorbed and replaced by a natural biological hard tissue. Of course, the degree of tissue ingrowth will depend on the amount of resorbable whitlockite in the material.

As it is usually produced, the two-phase ceramic material will be non-porous. However, if desired, varying degrees of porosity can be provided in the ceramic material as described above for the ceramic form of hydroxylapatite.

The ceramic material can also be made acid-resistant by adding fluorides as described below for ceramic hydroxylapatite.

The form of hydroxylapatite described above can be produced by precipitation from an aqueous medium at a pH of from 10 - 12 of hydroxylapatite where you have a molar ratio between calcium and phosphorus varying from 1.62 - 1.72, after which the precipitated hydroxylapatite is separated from the solution, the precipitated hydroxylapatite is heated to a temperature for a sufficiently long period of time to achieve sintering and a maximum densification of said hydroxylapatite without decomposition of the material occurring.

Thus, hydroxylapatite is precipitated from an aqueous medium by a reaction between calcium ions and phosphate ions at a pH of 10 - 12. Any calcium- or phosphate-containing compound that can provide calcium and phosphate ions in aqueous media is suitable provided that the respective counterions in said compounds easily can be separated from a hydroxylapatite product, and does not itself become incorporated into the hydroxylapatite lattice, or otherwise affect the precipitation or isolation of the essentially pure hydroxylapatite. Compounds that can provide calcium ions are e.g. calcium nitrate, calcium hydroxide, calcium carbonate and the like. Phosphate ions can be provided by diammonium hydrogen phosphate, ammonium phosphate, phosphoric acid and the like. In the present method, calcium nitrate and diammonium hydrogen phosphate are the preferred sources of calcium and phosphate ions, respectively.

The production of the new present form of hydroxylapatite can conveniently be carried out in the following way: First, calcium nitrate and diammonium hydrogen phosphate in a molar ratio of 1.67 to 1 are reacted in an aqueous solution at a pH of 10 - 12, whereby a gelatinous precipitate is obtained of hydroxylapatite. The method described by Hayek, et al., "Inorganic Syntheses" 7, 63 (l<c>>63) is satisfactory for this purpose. The gelatinous suspension of hydroxylapatite then remains in contact with the original solution for a sufficient period of time to allow the calcium to phosphorus ratio of the suspended hydroxylapatite to reach a value of 1.62 - 1.72. This can conveniently be achieved either by stirring the suspension at room temperature for a period of not less than 2k hours, or by boiling the suspension for a period from 10 - 90 minutes, or by a combination of boiling followed by a rest at room temperature. Preferably, the suspension is boiled for 10 min., and then left at room temperature for from 15 to 20 hours. The hydroxylapatite is then separated from the solution in a suitable manner, e.g. by centrifugation and vacuum filtration. The gelatinous product contains large amounts of trapped water, and this can be removed by pressing. If desired, the resulting clay-like material can be sheared or cut into appropriate shapes, or it can be cast into a suitable mold. It should be noted that you usually get one shrinkage of approx. 25$ when the wet. hydroxylapatite is dried, and you get a further shrinkage of approx. 25$ when sintering occurs as described below. This must of course be taken into account when shaping or casting the material. The wet product can be slowly heated to a sintering temperature of from 1000°C to 1250°C, and at these temperatures all water present will be driven off. A temperature is maintained in the said area for approx. 20 min., to 3 hours and will then achieve sintering and maximum densification of the product. Generally, it is preferred to isolate the dried product before sintering. Thus, the wet product can be dried at temperatures from 90°C to 95°C for approx. 15 hours or until the water content has been reduced to 1 to 2$. Hydroxylapatite obtained in this way is brittle and porous, but has considerable mechanical strength. Some separation or cracking of the clay-like material may occur during drying, especially if a thick filter cake is used. However, pieces with a surface area of 100 cm 2 and a thickness of 3 mm can easily be obtained. The separation or cracking during drying can be minimized or prevented by adding to the suspension of newly precipitated hydroxylapatite from 0.4 to 0.6 weight percent of an organic binder such as collagen, powdered cellulose or cotton, about. 0.5$ collagen is preferred. The organic binder will evaporate during the subsequent sintering, and the physical properties of the ceramic product appear to be essentially unchanged compared to those obtained when the product is produced in the absence of such a binder. Generally, the use of significantly larger amounts of organic binder will result in a porous ceramic product, as described above. You can of course also use other commonly known organic or inorganic binders.

It is usually appropriate at this stage to further cut or shape the dried hydroxylapatite into the desired shape of the final product, taking into account the shrinkage mentioned above that occurs during sintering.

Bodies of hydroxylapatite should be smooth and free of defects before sintering. The presence of cracks of any type can cause the pieces to completely crack during sintering. The products are then sintered at 1000°C to 1250°C for a period of 20 minutes to 3 hours, temperature and time being inversely proportional. Sintering is preferably carried out at 1100°C to 1200°C from 1/2 to 1 hour. The hard and dense ceramic material that is produced can then be polished or processed in a commonly known manner.

It is critical in the above-mentioned method to produce the hydroxylapatite as a gelatinous precipitate from an aqueous solution, because it is only in this context-the gelatinous state that the hydroxylapatite can be shaped or cast and then dried and then sintered to produce the ceramic material in macro form . Dry particulate or granular hydroxylapatite cannot be reproduced in this gelatinous state. If, for example, powdered hydroxylapatite is suspended in water and filtered, then you get a disjointed, particle-shaped filter cake which, when dried, will crack into crumbs and small pieces and which cannot be shaped, cast or converted into a macro form of the ceramic material. Although powdered hydroxylapatite can be mechanically compressed into a shaped body, e.g. a tablet, such a product upon sintering according to the present invention will only give a highly porous product which will not crack open along smooth planes, but will only fall from

each other in large pieces by' loads.

Although the formation of hydroxylapatite in an aqueous medium is a complex process and not fully understood, it is generally assumed that calcium and phosphate ions initially combine to form a hydroxylapatite with a deficit of calcium and with a ratio between calcium and phosphorus of about. 1.5. In the presence of calcium ions, this compound will then slowly be converted to a hydroxylapatite with a calcium to phosphorus ratio of 1.67.

(Eanes et al. "Nature" 208, 365 (1965) and Bett et al.,

"J. Amer. Chem. Soc." 89, 5535 (1967). In order to thus obtain a ceramic product which consists essentially of pure hydroxylapatite, it is thus important in the present invention that the first gelatinous precipitate of hydroxylapatite must be in contact with the original solution for a sufficiently long period of time to allow the ratio between calcium and phosphorus in said product reach a value of from 1.62 to 1.72. A significant deviation from this range results in a less translucent ceramic product. If e.g. hydroxylapatite is precipitated at room temperature and filtered off within 2 hours after precipitation, it will be found that the ratio between calcium and phosphorus is from 1.55 to 1.57 and

a ceramic product made from said compound will be opaque and by X-ray diffraction it can be found to be a mixture of hydroxylapatite and whitlockite. As indicated below, it has been found that materials with a ratio between calcium and phosphorus of from l, hh - 1.60 can be used in the production of the two-phase ceramic material described above. The method described here produces a translucent ceramic material which consists of essentially pure hydroxylapatite, so on the basis of the not fully understood mechanism with regard to the formation of hydroxylapatite in an aqueous medium, it may be advantageous to control the formation of hydroxylapatite so that it is ensured that the desired ratio between calcium and phosphorus is achieved, so that when the product is sintered, it will consist of essentially pure hydroxylapatite. This can conveniently be achieved by removing a sample of the hydroxyapatite suspension, separating the product, drying and sintering it as described above, after which the ceramic pro-

the duct is examined by elemental analysis and by X-ray analysis.

Temperature and duration of sintering are also critical in the present method. Thus, unsintered hydroxylapatite with the desired ratio between calcium and phosphorus of 1.62 - 1.72 can be converted into a ceramic product by heating it to a temperature of at least approx. 1000°C to 1200 C. At 1000 C, complete sintering and maximum densification can be achieved in a period of 2-3 hours, while at 1200°C this can be achieved within 20-30 minutes. It is preferred to carry out a sintering at temperatures of approx. 1100°C

for about. one hour. A temperature substantially below 1000°C will result in incomplete sintering regardless of the length of the heating time, while heating above 1250°C for more than an hour will result in a partial decomposition of hydroxylapatite into whit tlocki tea.

The two-phase ceramic material described above consists of a phase of hydroxylapatite and another phase of whitlockite, and the product can be produced by precipitating a calcium phosphate compound with a molar ratio between calcium and phosphorus varying from 1 from an aqueous solution at a pH of 10 - 12 .44 - 1.60, preferably 1.46 - 1.57, after which the precipitate is separated from the solution and the thus obtained solid is heated to a temperature and for a sufficiently long period of time to obtain sintering and maximum densification.

The calcium-phosphate compound having the desired stoichiometric ratio, i.e. a Ca/P ratio of from 1.44 - 1.60 can be prepared by allowing calcium siumiojier <p>g phosphate ions to react in an aqueous medium at a pH of 10 - 12, using the same sources for calcium and phosphate ions as described above for the production of single-phase hydroxylapatite. Calcium nitrate and diammonium hydrogen phosphate are the preferred reagents in this respect.

The two-phase ceramic material can thus be produced by reacting calcium nitrate and diammonium hydrogen phosphate in a molar ratio of 1.67 to 1, i.e. as described above for the production of single-phase ceramic hydroxylapatite, provided that the first gelatinous precipitate is not heated but placed in contact with the original resolution in a period of time that does not exceed approx. 4 hours, or by not allowing the molar ratio between calcium and phosphorus in the precipitate to exceed a value of approx. 1.6 o.

As described above, the calcium phosphate precipitate can be separated from the solution, washed, optionally shaped or cast in an appropriate form, and optionally dried and isolated before sintering.

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

Sintering is carried out at temperatures from 1000°C to 1350°C for a period of 20 min. to 3 hours.

The amount of whitlockite in the ceramic material will depend on the time when the precipitate is separated from the original solution, and can vary from 2 to 83$. When e.g. the product is isolated 5 minutes after precipitation, a ratio between calcium and phosphorus of approx. 1.55 and the ceramic material will in this case contain approx. 83$ whitlockite. If the product is isolated 2 hours after precipitation, the calcium/phosphorus ratio will be 1.57 and the resulting ceramic material will contain approx. 6l$ whitlockite. An isolation of the product 4.5 hours after precipitation gave ceramic material with approx. 2$ whitlockite, an amount almost undetectable by X-ray diffraction which has a concentration sensitivity of from 2-3$. If, however, the product was left in contact with the original solution for more than 7 hours, a ceramic substance was obtained which essentially consisted of pure hydroxylapatite.

Alternatively, the two-phase ceramic material can be produced by reacting calcium ions with phosphate ions in an approximate molar ratio of 1.50 - 1.60 to 1. In this way, the molar ratio between calcium and phosphorus in the precipitated product will not exceed a value of 1.60 regardless of how long the precipitate is in contact with the original solution.

Thus, the preparation of the present two-phase ceramic material can be carried out as described above, for the preparation of the pure hydroxylapatite, except that the reactants, i.e. calcium nitrate and diammonium hydrogen phosphate, are reacted in an approximate molar ratio of from 1.50 - 1.60 to 1, whereby one obtains ceramic materials containing from 30-50 # hydroxylapatite and from 50-70 $ whitlockite.

The ceramic material can be further enriched with respect to the whitlockite phase by combining features from the two previous variants, i.e. reacting calcium ions with phosphate ions in an approximate molar ratio of 1.50 -

1.6o to 1 and isolates the precipitated calcium phosphate compound within a short time, preferably from 5 min. to k hours, after the precipitation. Ceramic materials produced in this way contain approx. $10-30 hydroxylapatite and $70-90 whit-locki te.

It is known that hydroxylapatite decomposes to whitlockite at approx. 1250°C, and it is therefore understood that a prolonged heating of the single-phase ceramic product consisting of hydroxylapatite to temperatures of

1250 C ell is higher, will result in a partial decomposition of said hydroxylapatite to whitlockite, whereby the said two-phase ceramic material is obtained.

The products produced according to the present invention can be used in logical repair compositions consisting of a mixture of the ceramic hydroxylapatite and a polymerizable or polymerized bonding material which is compatible with the conditions found in the oral cavity. Said dental compositions consist of from 10-90%, preferably 60-80% by weight of finely divided ceramic hydroxylapatite, while the rest of the composition, i.e. 10-90% by weight, consists of odontologically acceptable polymerizable or polymerized binder materials together with known suitable polymerization catalysts, such as aliphatic ketone peroxy der, benzoyl peroxide etc., as well as reactive thinning agents such as di-, tri- and tetraethylene glycol dimethacrylate, hardeners such as N-3-oxohydrocarbon-substituted acrylamides as described in US patent 3,277,056 issued in October 1966, as well as accelerating compounds such as metal acetylacetonates, tertiary amines ie N,N-bis-(2-hydroxyethyl)-p-toludine etc., cross-linking agents such as zinc oxide etc., all of which may be present in amounts varying from 0.01 to 45 weight percent of the total composition. Although not critical, it is usual to add a surface-active co-monomer, such as the reaction product of N-phenylglycine and glycidyl methacrylate as described in US patent 3,200 lh2, issued August 10, 1965" methacryloxypropyltrimethoxysilane, 3 in 4 -epoxycyclohexylethyltrimethoxysilane, vinyltrichlorosilane, etc., in said composition in amounts from 0.05 to 10% by weight of the total composition. The binder promotes the bonding of the ceramic material to the resin and of the dental filling material to the natural tooth. Thus, ceramic hydroxylapatite will often be worked up to suitable particle sizes of from 5 to 100 µm using common measuring techniques, and can then be mixed with a suitable amount of a standard resin such as these are known for dental purposes, e.g. hydroxyethyl methacrylate, polymethyl methacrylate, polyacrylic acid, propylene glycol fumarate phthalate unsaturated polyesters as obtainable such as "23 LS8275" and "Selectron 580001", styrene-modified unsaturated polyesters such as "Glidpol 1008", "G-136" and "4CS50", epoch- sewing resins such as "Araldite 6020", "ERL277V and the bisacrylate monomer prepared from glycidyl methacrylate and Bisphenol S, as stated in US patent 3066112. The resin can consist of a single monomer or a mixture of two or more comonomers. Furthermore additives such as dyes, inorganic pigments or fluorescent agents can be used as known from such compounds. It is convenient to mix the resin, the ceramic hydroxylapatite and possibly other ingredients such as silane binder, dyes, inorganic pigments or fluorescent agents before mixing the ingredients is however, not critical, and they can also be mixed at the same time.Using conventional techniques, the composition can be used as a ta filling material or the composition can be cast in a suitable form, so that an artificial tooth or a set of teeth is produced.

li

It is very advantageous if the material to be used in the oral cavity is resistant to caries. Such a property can be easily achieved according to the present invention by adding from 0.01 to 1% of fluoride ions such as ammonium or stannous fluoride to the suspension of newly precipitated hydroxylapatite. The ceramic product produced by sintering is highly resistant to lactic acid, acetic acid or citric acid, in a standard in vitro method used to determine resistance to tooth decay or caries. Alternatively, the resistance to tooth decay can be improved by exposing the finished ceramic material to an aqueous solution of sodium fluoride with a strength of from 0.5 to 5 $ for a period of 12 hours to five days. Preferably, the ceramic body should be placed in a 5% aqueous sodium fluoride solution for approx. k days.

It is of course understood that in addition to organic or inorganic binders and fluoride ions, the ceramic material may also contain smaller amounts of other elements, which do not, however, change the essential properties of the ceramic products. It is e.g. known that barium and strontium can form part of the apatite crystal lattice and that these elements make the material more opaque to X-rays than calcium. Adding smaller amounts of barium or strontium ions to the calcium ions before reacting the latter with the phosphate ions will thus result in a barium or strontium-added hydroxylapatite ceramic material that can be used in a dental repair material as described above, and will provide sufficient X-ray absorption to easily can demonstrate filled teeth. Magnesium can also form part of the apatite crystal lattice and will prevent the crystallization of hydroxylapatite, but will promote the crystallization of whitlockite (Eanes et al., "Calc. Tiss. Res." 2, 32 (1968). An addition of a small amount of magnesium ions to the calcium ions before these react with the phosphate ions will thus promote the formation of whitlockite so that a whitlockite-enriched two-phase ceramic material is obtained.

Ceramic materials produced as described above were characterized on the basis of one or more of the following analysis techniques: Elemental analysis, density, X-ray diffraction, transmission electron microscopy, light microscopy using polarized light and mechanical properties.

The following examples illustrate the invention.

EXAMPLE 1.

A stirred mixture containing 130 ml of 1.63N calcium nitrate (0.212 mol) and 125 ml of concentrated ammonia was added dropwise over approx. 20 minutes added a mixture containing 16.75 g (0.127 mol) of diammonium hydrogen phosphate, 100 ml of distilled water and 150 ml of concentrated ammonia. The resulting suspension was boiled for 10 minutes, cooled in an ice bath and then filtered. The filter cake was pressed using a rubber piece and then dried overnight at 95°C. A sample of the resulting hard, porous, brittle cake was heated in an electric oven for 115 min. to a final temperature of 1230°C. The product was then cooled to room temperature to give a brittle, hard, white, translucent ceramic product.

A standard elemental analysis of the finished product as well as of the dried hydroxylapatite before sintering gave the following results based on Ca1Q(P0^)^(OH)2:

An examination of a thin layer of the ceramic product by means of polarized light microscopy at 130X and 352X magnification clearly indicated that the material in all significant and clearly discernible structural features, such as crystal form, orientation, boundary lines, etc., clearly indicated a microcrystalline structure. A comparison between optical images of a thin film of a sintered compressed tablet as reported by Monroe et al. (for reference see above), showed that the two materials were completely of different structure.

X-ray diffraction measurements were carried out in the usual way. The distance between the inner planes was calculated and found that these were essentially identical to the values given for hydroxylapatite by Donnay et al., "Crystal Data", ACA Monogram No. 5668 (1963). X-ray data further indicated an absence of whitlockite in an amount of more than 2 to 3, i.e. the minimal concentration one has on 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 11-12 with approx. 750 ml of concentrated ammonia. Additional distilled water was added so that the precipitated ammonium phosphate was dissolved, and a total volume of 3200 ml was obtained. If necessary, the pH was again adjusted to 11-12. This solution was added dropwise over the course of 30--'*0 minutes to a vigorously stirred solution containing 1 mol of calcium nitrate in 900 ml of distilled water previously adjusted to pH 12 with approx. 30 ml of concentrated ammonia and sieve diluted to a volume of 1800 ml with distilled water. When the addition was complete, the resulting gelatinous suspension was stirred for an additional 10 minutes and then boiled for 10 minutes, removed from the heat source, covered and left for from 15-20 hours at room temperature. The supernatant was skimmed off and the remaining suspension centrifuged at 2000 rpm. for 10 minutes. The resulting precipitate was resuspended in 800 ml of distilled water and again centrifuged at 2000 rpm. for 10 minutes. Sufficient distilled water was added to the remaining solids to give a total volume of 900 ml. Vigorous shaking produced a homogeneous suspension, which was essentially free of large fragments or aggregates. The entire suspension was immediately transferred to a Buchner bath and filtered using a weak vacuum. When the filter cake started to crack, a piece of rubber was put on and the vacuum bJo ekot.

After one hour, the piece was removed and the crack-free and intact filter cake was transferred to a flat surface, dried for 15 hours at <l>)0-95°C and yielded from ')()-100 g of white, porous , brittle chunks of hydroxylapatite. Pieces with a surface area of from 1 to U cm^ and free of cracks were placed

in an electric furnace and the temperature was raised to 1200°C i

during 100 min., after which the oven and its contents were cooled to room temperature. The resulting pieces were hard, tufted, non-porous, white, translucent straight ceramic pieces.

After carrying out the above analysis, it was discovered that the analysis technique used was not complete with regard to the resolution of the samples, and that the results are therefore inaccurate and somewhat variable. Without regard to the aforementioned data, it can be determined that the sample was essentially homogeneous, which was confirmed with the help of electron microscopic data. The product from example 3, which was produced by a method which is essentially identical to the method in example 2, further had the expected analytical values and could further be characterized as a homogeneous hydroxylapatite by means of X-ray diffraction and electron microscopy.

Two-stage casting samples were made by shadowing a collodion impression of the sample surface using chromium which was then coated with carbon. The transmission electron microscope of these samples showed a uniform grain size without signs of pores or a precipitation of other phases, either along the grain boundaries or inside the grains themselves in amounts of more than approx. 0.5$", which is the minimum concentration for the electromicroscope. A sample of the ceramic piece was then polished using SiC paper to 600 grit, and then polished to 3 pm using a diamond paste on a metallographic wheel covered with fine nylon cloth. The sample was then etched with 4% hydrofluoric acid for 30 seconds. Impressions were made on both the polished and etched surfaces and then assessed using electromicroscopy. Even now, no other phases could be observed in the boundaries between the grains, but there was, however, a certain sign of small sweeps of other phases inside the grains themselves.

The compressive strength and modulus of elasticity were determined in the usual way and were found to be 4050l 1195 kg/cm^ and 0.'*5 x 10^ kg/cm^, respectively.

The tensile strength was determined by the standard three-point bending test and it was 690^ 235 kg/cm^.

The coefficient of thermal expansion was found to be linear between 25°C and 225°C, with a value of 11 x 10~ 6/ °C± 10 $.

A hardness value of 480 was found using the commonly known Knoop method. The same value was obtained regardless of the direction of the applied force, which clearly indicates that the material was isotropic.

Porosity was determined qualitatively by immersing the sample in a fuchsin dye solution for 15 minutes, washing the sample with water, drying it, and then examining the sample for traces of dye. This test was carried out simultaneously on the non-porous form of the ceramic material produced according to the present invention, a sintered compressed tablet of hydroxylapatite, and a natural tooth. The sintered compressed tablet showed significant dye retention, while the new ceramic material and the natural tooth showed no signs of dye absorption. In another method, the sample material was immersed in 6N aqueous ammonia for 15 minutes, then washed with water, dried and then folded into moist litmus paper. Any ammonia that may be present on the surfaces will cause the surrounding litmus paper to turn blue. When this test is performed simultaneously on the ceramic material produced according to the invention, a sintered compressed tablet of hydroxylapatite and a natural tooth, the litmus paper in contact with the sintered compressed tablet turned blue, indicating that ammonia was present in the tablet . No color change could be observed on the litmus paper that was in contact with either the ceramic material or the natural tooth.

EXAMPLE 3.

By using the same method as described in example 2, but by using 3 mol of calcium nitrate and 1.8 mol of diammonium hydrogen phosphate, 304 g of a white, brittle and porous hydroxylapatite was obtained.

A sintering was carried out at 1100°C for one hour and

this gave a hard, white, translucent ceramic product with a density of 3.10 g/cm . The X-ray diffraction indicated that the material was homogeneous hydroxylapatite. Electron microscope examination showed a crystalline size distribution i

the range from 0.7 to 3 microns and an absence of pores and precipitation of other phases.

EXAMPLE k.

A. The same procedure as in example 2 was used, but half of the amounts indicated there were used, and approx. 50 g of hydroxylapatite from an aqueous solution. After centrifugation and decanting, the resulting mineral sludge was resuspended in - sufficient water to a volume of 1 liter and then the whole was homogenized in a Varing mixer for 2 minutes.

B. A mixture containing 0.5 g of powdered cellulose (< 0.5 u) in 200 ml of water was mixed in a Waring mixer for 3 minutes. A 100 ml sample of the homogeneous aqueous suspension of hydroxylapatite was then added and the resulting mixture mixed for a further 5 minutes. The suspension was then filtered, and the filter cake dried and sintered as indicated in example 2. After drying, the filter cake showed very little tendency to crack and the ceramic product produced by sintering was slightly porous, which could be indicated by the fuchsin test described above. C. A mixture containing 0.5 g of shredded surgical cotton in 200 ml of water was mixed in a Waring blender for 45 minutes or until an almost homogeneous suspension was obtained. A 100 ml sample of an aqueous homogeneous suspension of hydroxylapatite as described in Example 4a was then added and mixing continued for a further 15 minutes. The resulting suspension was filtered and the filter cake dried and sintered as described in Example 2. The ceramic product remained intact and was visibly porous.

EXAMPLE 5.

A. A mixture containing 5 S collagen (Achilles, tendons from cattle) 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 smaller amount of finely divided collagen (20-30 mg) remained in the suspension.

B. The suspension of finely divided collagen (250 ml) was decanted and mixed in a Waring blender for 5 minutes with a 100 ml sample of the homogeneous aqueous suspension of hydroxylapatite described in Example hA. The resulting mixture was filtered and the filter cake dried and sintered as described in Example 2. The ceramic product remained intact and was substantially non-porous. C. Approx. 20% of the thick gelatinous collagen was mixed in a Waring blender for 6 minutes with 150 ml of the homogeneous aqueous suspension of hydroxylapatite described in Example 4A. The resulting mixture was filtered and the filter cake dried and sintered as described in example 2. The dried filter cake was intact before sintering and had considerable mechanical strength. The ceramic product produced was hard, strong and visibly porous.

EXAMPLE 6.

Samples of the ceramic product prepared as described in Example 2 were placed in a 1% aqueous sodium fluoride solution for 12 hours. These samples together with samples of untreated ceramic material and natural teeth were then expanded against 10% lactic acid. After 3 days, the fluoride-treated ceramic product showed significantly less attack by the lactic acid than was the case with the untreated product and the natural tooth enamel. When left in 1$ aqueous sodium fluoride for 3 days, there was no visible attack on the ceramic product after 3 days, and after 1 month there was only slight decomposition, while the untreated samples were strongly decomposed.

EXAMPLE 7.

The same procedure as described in example 2 was used, but half of the amounts used there were used, and approx. 50 g of hydroxylapatite from an aqueous solution. After centrifugation, the mineral precipitate was suspended in sufficient water to obtain 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: Samples 1 to 5 were respectively added with 0, 0.1, 0.5, 1.0 and 2.0 ml of a aqueous ammonium fluoride solution containing 0.00085 g F~ /ml. Samples 6, 7 and 8 were treated with 0.5, 1.0 and 10.0 ml, respectively, of an aqueous ammonium fluoride solution containing 0.0085 g F™ / ml. Samples 9 and 10 were added 2.0 and 4.0 ml respectively of an aqueous ammonium fluoride solution containing 0.045 g F/ml. The suspensions were then shaken in a rotary shaker for 1.5 hours and then filtered. The filter cakes were pressed for 15 minutes using a piece of rubber, dried for 2 days at 95°C and then heated in an electric oven to a temperature of 1200°C. The resulting ceramic products were ground to a fine powder and sieved through a 325 mesh sieve. Eighty mg samples of each of the aforementioned powders were mixed with 80 ml of a pH of 4.1 sodium lactate buffer solution (0.4 mol) at 23°C and shaken in a Burrell shaker. 2, 9, 25 and 40 minutes after shaking, a 3 ml sample was taken from each mixture, this was immediately filtered to remove undissolved samples, and the amount of dissolved ceramic product was undissolved samples, and the amount of dissolved ceramic product was determined colometric. The results are given in table A. For comparison purposes, a sintered part of sample 1 was taken and left to stand for 4 days in 1 ml solution of 5% sodium fluoride. The solid was separated, washed with water, dried and then examined in the same manner as sample IA. The results are shown in table A. It appears from the experimental conditions described above that these do not resemble in vivo conditions, but were chosen so that sufficient solubilization of a sample was obtained within a reasonable period of time, whereby an accurate assessment of the relative effect was obtained of the fluoride ion concentration. Thus, the in vivo dissolution rates for the ceramic hydroxylapatite will be considerably less than the above-mentioned rates which were thus found in a strong lactate buffer.

EXAMPLE 8.

Large fragments of dried filter cake approx. 3-4 mm wide prepared as described in example 2 and with a Ca/P = 1.64 - 1.66 were broken loose into rectangular plates approx. 14 - 15 mm long and 7-8 mm wide, and a small hole was drilled through each end. One thousand of these plates were then sintered as described in example 2, and then polished to a high-gloss surface using commonly known techniques. The resulting ceramic bodies had a density of 3.12 - 3.14 g/cm and were in the form of rectangular plates approx. 10 - 11 mm long, 4 - 5 mm wide and 2-3 mm thick, and had a hole in each eye through which a thread was threaded. The plates, which could be lowered to any desired depth in a test tube with the help of these threads, were used as test surfaces for the assessment of tartar-inhibiting agents, as described previously.

EXAMPLE 9.

A solution containing 0.24 mol of diammonium hydrogen phosphate in 600 ml of distilled water was adjusted to pH 11.4 with 340 ml of concentrated ammonia, and the final volume was adjusted to 1280 ml with distilled water. This solution was added dropwise over 30 minutes to a vigorously stirred solution containing 0.4 mol of calcium nitrate in 360 ml of distilled water previously adjusted to pH 11 with concentrated ammonia and diluted to a volume of 720 ml with distilled water. The resulting suspension was stirred without boiling and periodically 250 ml samples were taken which were washed and dried as described in example 2. All samples were then heated for one hour at 1100°C, and the composition of the resulting ceramic product was determined by x-ray -re diffraction. The results obtained are shown in table B.

a. These values are at the limit of the minimum concentration that can be detected using the X-ray diffractometer (2-3$) and the accuracy indicated thereby is somewhat questionable.

EXAMPLE 10.

A. The same procedure as described in example 2 was used, but 0.3 mol of calcium nitrate and 0.2 mol of diammonium hydrogen phosphate were used, and a hard, brittle, porous product with the following chemical composition was obtained: Ca =

$38.85; P = $19.77; Ca/P = 1.52. This material was held for 1 hour at 1200°C and produced a strong, hard, non-porous,

white, somewhat opaque ceramic, material which consisted of approx. 4o$ hydroxylapatite and 60$ whitlockite as this could be detected by X-ray diffraction.

B. When the above reaction was carried out with the opposite addition of the starting materials, a product was obtained which consisted of approx. 40$ hydroxylapatite and 60$ whitlockite, and with a Ca/P = 1.52 and a density of 2.982 g/cm<3>.

EXAMPLE 11.

A solution containing 0.0625 mol of diammonium hydrogen phosphate in 150 ml of distilled water was treated with 95 ml of concentrated ammonia, and the final volume was adjusted to 320 ml of distilled water. This solution was added dropwise over the course of 30 minutes to a vigorously stirred solution containing 0.1 mol of calcium nitrate and 2.5 ml of concentrated ammonia in 180 ml of distilled water. The resulting suspension was stirred for 5 minutes, then cooled in ice for 45 minutes, after which the suspended solids were isolated, washed and dried as described in Example 2 to give a hard, brittle and porous white solid with following chemical composition: Ca = 35.4 $; P = $18.59> Ca/P = 1.46. This material was held for 1 hour at 1350°C and produced a strong, hard, non-porous somewhat opaque ceramic product consisting of approx. l4 $ hydroxylapatite and 86% whitlockite, as this could be demonstrated by X-ray diffraction.

The products from examples 1-11 correspond to products manufactured according to the present invention, and have physical properties as described above.

Articles prepared as described in Examples 1, 2, 3, 5B and 6-8 are strong, hard, dense, white, translucent ceramic bodies consisting substantially of pure isotropic polycrystalline hydroxylapatite, free from pores, and having a compressive strength in the range from 2500 to 9000 kg/cm 2 , a tensile strength in the range from 215 to 2150 kg/cm 2 , a linear thermal expansion coefficient varying from 10 to 12 ppm per degree Celsius, a Knoop hardness in the range from 470 to 500 and a modulus of elasticity of approx. 0.43 x 10 6 kg/cm 2 , and the material is characterized by cleavage, along smooth, curved planes, and by an absence of birefringence under polarized light.

Articles prepared as described in Examples k and 5C are the same material as prepared as described in Examples 1, 2, 3, 5B and 6-8, but have different types of pores with varying numbers and sizes. It is of course obvious that the appearance of pores in said articles significantly affects these articles' physical properties, e.g. a reduction in compressive strength, tensile strength, elasticity and hardness.

Examples of areas of application for products manufactured according to the invention will be given below.

I. A composition suitable as dental cement and

Dental filler was prepared as follows:

A. A solution containing 20 mg of the condensation product of N-phenylglycine and glycidyl methacrylate (described in US patent 3,200 l42 and described there as NPG-GMA) in 7 ml of ethanol, was added 2.0 g of powdered ceramic hydroxylapatite. After stirring for 5 minutes, the ethanol was evaporated under vacuum at room temperature and the resulting solid was dried for 2 hours at 1 mm Hg. B. An 80 mg sample of the above material was mixed with 0.4 mg of benzyl peroxide and 30 mg of a 1:2 mixture of hydroxylethyl methacrylate and the reaction product of bisphenol A and glycidyl methacrylate as described in US Patent 3,066,112 and therein described as bis-GMA. The resulting mixture was placed in a cylindrical steel mold and was cured there from 3-5 minutes. The compressive strength was determined on four cylindrical plugs, prepared as described above. The mean value was 17^0 kg/cm 2. II. A mixture consisting of 60 parts of powdered ceramic hydroxylapatite, 13 parts of hydroxylethyl 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 was mixed and produced a thin, free-flowing mixture that can be used as a dental filling material and as a sealing material for fissures. The mixture was poured into a cylindrical steel mold and hardened there for approx. 3 minutes. The compression strength of seven cylindrical bodies was determined, and the average value was 1460 kg/cm. III. The following is an example of a composition that can be used as a dental filling material. 5 ml of 2-propanol was added to 0.5 g of powdered ceramic hydroxylapatite. The 2-propanol was then evaporated under vacuum at room temperature to remove any water of hydrate ions from the surface of the ceramic material.

120 mg of powdered hydroxylapatite is treated as described

known above, 0.3 mg of benzoyl peroxide and 40 mg of a mixture consisting of the condensation product of bisphenol A and glycidyl methacrylate, triethylene glycol dimethacrylate and N,N-bis-('2-hydroxyethyl)-p-toluidine were added and this mixture is sold under trademark "Epoxylite HL-72". The mixture was smoothed to a smooth paste and placed in cylindrical steel molds and left for 4 hours. The cylindrical plugs were removed from the molds and 3 pieces were examined and these had an average compression strength of 1580. IV. A solution of 30 mg of the condensation product of N-phenylglycine and glycidyl methacrylate in 7 ml of ethanol was added with stirring to 1 g of powdered ceramic hydroxylapatite. The ethanol was evaporated under vacuum at room temperature. A mixture consisting of 180 mg of powdered ceramic hydroxylapatite treated as described above, and 3.0 mg of benzoyl peroxide was added to 7^ mg of a mixture containing 60 parts of the condensation product of bisphenol A and glycidyl methacrylate and 4-0 parts of triethylene glycol dimethacrylate, and the resulting material was leveled into a smooth paste which was placed in cylindrical steel molds and left for 3 hours. The cylindrical pieces were removed from the molds and k pieces were tested and these had an average compression strength of 1580 kg/cm. V. A composition suitable as a dental cement or dental cement or as a short-term dental filling agent was prepared by mixing 100 mg of powdered ceramic hydroxylapatite, 300 mg of zinc oxide and 300 mg of 40% aqueous polyacrylic acid. The resulting mixture was placed in cylindrical steel molds and cured from 3-5 minutes. The cylindrical pieces were removed from the molds and k pieces were tested and had an average compressive strength of 870 kg/cm'<o>""<.>

5 other pieces were examined for mean diametric tensile strength and this was 116 kg/cm 2 . The aqueous polyacrylic acid and the zinc oxide were obtained as the liquid and solid components, respectively, a commercial polycarboxylate cement available under the trademark "Durelon".

WE. A composition suitable as dental cement and tooth filling agent was prepared by mixing 6 parts of a kO$ aqueous polyacrylic acid with a mixture containing 6 parts by weight of zinc oxide. The resulting composition had

a curing time of from 5 to 10 minutes. Said high % aqueous polyacrylic acid and the zinc oxide were obtained as the liquid and solid component respectively in a commercial polycarboxylate cement available under the trademark "Durelon".

VII. The following is an example of a dental filling ma-o

material:

VIII. The following is an example of a composition that is suitable as dental cement, cavity liner and as crown material:

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

A mixture containing 60 parts by weight ceramic hydroxylapatite approx. 150 to 200 mesh and k0 parts by weight of powdered polymethyl methacrylate were mixed with approx. 15 parts by weight of gliding monomeric methyl methacrylate, and the resulting mixture was allowed to stand in a closed vessel at room temperature until the material no longer adhered to the walls of the vessel and had a non-sticky plastic consistency. The material was then packed into a suitable mold and the mold and its contents immersed in water which was heated to boiling point within an hour and held at this temperature for approx. 30 minutes. The mold was set aside for air cooling for approx. 15 minutes and then cooled in cold, running water.

The biocompatibility of the ceramic form of hydroxylapatite provided by the present invention was confirmed by implantation studies, where it was found that no inflammatory reaction occurred when pieces of the ceramic material prepared as described in Example 1 were implanted intraperitoneally in rats or inserted sub-cutaneously on the back of rabbits, and no resorption of the ceramic material could be detected after 28 days.

Pellets of the ceramic hydroxylapatite prepared as described in Example 3 were surgically implanted into the thigh muscles of dogs. The implanted piece was examined in vivo by periodic X-ray examination. After periods of one month and six months respectively, the animals were necropsied and the thigh muscles containing the implanted piece were removed. The muscles were cut at the place where the implantation had taken place and examined both optically and with the help of scanning electron microscopy. Both the pieces that were implanted for 1 month and for six months were characterized by normal growth, strong attachment to the new bone to the implanted surface without fibrous tissue, there were no signs of inflammation or reaction to foreign pieces, and no resorption of the implanted material.

Claims (13)

1. Process for the production of a polycrystalline, sintered ceramic material in macro form where calcium ions are reacted with phosphate ions in an aqueous medium and at a pH of 10-12, whereby a gelatinous precipitate of a calcium phosphate with a molar ratio between calcium and phosphorus between the approximate molar ratio between calcium and phosphorus found in hydroxylapatite and the corresponding ratio in whitelockite, after which one secretes said precipitate from the dissolution, character! served by heating an integral mass of the separated precipitate, if desired after shaping and cutting, to a temperature of at least 1000°C, but below the temperature at which a significant decomposition of hydroxylapatite occurs, and maintaining said temperature for a sufficiently long time time to achieve sintering and substantially maximum densification of the resulting product. 2. Method according to claim 1, characterized in that the precipitate is heated to a temperature of at least 1050°C. 3. Method according to claim 1 or 2, characterized in that the ratio between the reactants used in the reaction is chosen so that a precipitate is formed with a molar ratio between calcium and phosphorus essentially as in hydroxylapatite. k. Method according to claim 3, characterized in that the precipitate has a molar ratio between calcium and phosphorus in the range from 1.62 - 1.72, and in that the material is kept at a temperature of 1250°C for a period of time from 20 minutes to 3 hours. , 5. Method according to claim 2, characterized in that the temperature is kept at between 1100°C and 1200°C for a period of 0.5 to 1 hour. 6. Method according to claim 1 or 2, characterized in that the precipitate has one molar ratio between calcium and phosphorus in the range from 1.44 - 1.60, preferably from 1.46 - 1.57", after which said precipitate is heated to a temperature at around 1350°C for a period of 20 minutes to 3 hours. 7. Method according to any of the preceding claims, characterized in that the calcium ions present are provided by means of calcium nitrate while the phosphate ions are provided by means of diammonium hydrogen phosphate. 8. Method according to any one of the preceding claims, characterized in that the produced ceramic in macro form is placed in a 0.5 to 5% aqueous sodium fluoride solution for a period of time from 12 hours to five days. 9. Method according to any one of claims 1-7, characterized in that a source of fluoride ions is added to the precipitate before it is separated from the solution. 10. Method according to any of the preceding claims, characterized in that from 0.4 to 0.6 weight-$ of an organic binder is added to said precipitate, and in that said organic binder evaporates during said heating. 11. Method according to claim '9, characterized in that the organic binder is collagen. 12. Method according to any one of claims 1 to 8, for producing a porous form of the ceramic material, characterized in that from 5 to 25 wt% of an organic binder is added to the precipitate, and in that said organic binder evaporates or disappears -ner during said heating process. 13. Method according to claim 12, characterized in that the organic binder is powdered cellulose, cotton or collagen.