Calcium granular phosphate cement and method for its production

A granular cement calcium phosphate to be loaded into the defective portions, hollow or bone or absorbed in the voids left after the extraction of a tooth, and a method for producing such a cement.

The hydroxyapatite having the size or minimum diameter of 0.1 to 3.0 mm and a factor Φ surface shape specific to 6.3 15, as backfill to be charged into a defective portions, hollow or absorbed bone or voids left after the extraction of a tooth, is known for example by the Japanese Patent Publication to public inspection n* 61-20558 (1986). The hydroxyapatite used for those portions or voids of the bone is known to have a higher biological affinity. Since filler for the defective portions or hollow shaped bone indefinite, granular hydroxyapatite having the minimum size above-mentioned factor and the specific surface shape mentioned above has been found most suitable.

However, granular hydroxyapatite cannot retain its form of a satisfactorily even after compaction so that, before a bone tissue is formed in the vicinity of the incision site after the elapse of 2 to 3 weeks after surgery, the charged material tends to escape the incision site for delaying the recovery of the loaded site. Therefore, it is crucial to maintaining the body of compacted hydroxyapatite granules loaded into its initial shape to promote therapy.

To eliminate this drawback, it has been proposed for example in the Japanese Patent publications made public inspection n* 3-45266 (1991) and 3-51051 (1991) a calcium phosphate cement in which a calcium phosphate cement hydraulic and granules of hydroxyapatite are combined to secure the hydroxyapatite granules with the hydraulic calcium phosphate cement. However, although the calcium phosphate cement is capable of setting the granules of hydroxyapatite, the fine powder of the calcium phosphate cement hydraulic enter and fit into the spaces defined between the granules of hydroxyapatite to stop the pores leading from the surface to the inside of the load, so that the living tissue or blood vessels cannot be introduced through the loaded site and to obstruct the transport of nutrients or growth of new bone.

An object of the present invention is to provide a granular cement calcium phosphate which can be loaded into the defective portions, hollow or absorbed of the bones of an arbitrary size one or in voids left after the extraction of a tooth without stimulating the living tissue, which can be converted in vivo to apatite readily and which has voids between the granules of cement in the load that are useful for transporting nutrients and for the formation of new bone, and a method of producing the granular calcium phosphate cement.

Another object of the present invention is to provide a granular cement calcium phosphate which can be cured immediately after loaded into the living body without risk of leakage and which has excellent shape retention at an initial stage after the end of surgery.

The previous objects and others of the present invention shall become apparent from the description that follows.

According to the present invention, there is provided a granular calcium phosphate cement comprising powders obtained by mixing the mixed calcium tertiary phosphate type with a calcium phosphate compound selected from calcium primary phosphate, calcium secondary phosphate and mixtures thereof in a Ca/P molar ratio of 1.35 to 1.49, the minimum diameter of each granule cement being 0.1 to 1.0 mm. The cement is hereinafter referred to as first granular calcium phosphate cement.

According to the present invention, there is also provided a method of producing a granular calcium phosphate cement comprising admixing a calcium tertiary phosphate type with a calcium phosphate compound selected from calcium primary phosphate, calcium secondary phosphate and mixtures thereof in a Ca/P molar ratio of 1.35 to 1.49, pressing the powder mixture resulting, and again dividing the pressed products granules each having a minimum diameter of 0.1 to 1.0 mm. The method is referred to herein as first method for producing the granular calcium phosphate cement.

According to the present invention, there is also provided a granular calcium phosphate cement comprising powders mixed obtained by mixing calcium phosphate quaternary with a calcium phosphate compound selected from calcium primary phosphate, calcium secondary phosphate and mixtures thereof, in a Ca/P molar ratio of 1.30 to 1.90, the minimum diameter of each granule cement being 0.1 to 1.0 mm. The granular cement is hereinafter referred to as second granular calcium phosphate cement.

Finally, is provides a method of producing a granular calcium phosphate cement comprising mixing the quaternary phosphate calcium calcium phosphate with a compound selected from calcium primary phosphate, calcium secondary phosphate and mixtures thereof in a Ca/P molar ratio of 1.30 to 1.90, pressing the powder mixture and the resulting product partitioning compressed to pellets each having a diameter minim u m of 0.1 to 1.0 mm. The method is referred to herein as second method for producing the granular calcium phosphate cement.

The present invention will be explained in detail below.

The powders used as main component of the first granular calcium phosphate cement according to the present invention are powders mixed composed of calcium tertiary phosphate type, of primary phosphate and calcium/or calcium secondary phosphate.

Referring specifically to the reaction of these components, the calcium tertiary phosphate type and calcium primary phosphate are components which react in the presence of water to give the calcium secondary phosphate and octacalcium phosphate to be hardened, while the calcium secondary phosphate and octacalcium phosphate are components readily convert in vivo to hydroxyapatite. Furthermore, the calcium tertiary phosphate type and the calcium secondary phosphate, when mixed together in the presence of water, react to give the octacalcium phosphate curing by entanglement of octacalcium phosphate crystals, while the octacalcium phosphate is a component tranforme granduellement apatite in vivo. Since calcium tertiary phosphate type, a calcium tertiary phosphate type produced by the wet synthesis using an aqueous solution of phosphoric acid and calcium hydroxide, or the calcium tertiary phosphate type produced by the dry synthesis of calcium phosphate powders and secondary calcium carbonate powders, may preferably be used. Since calcium primary phosphate, monohydrate calcium primary phosphate which is commercially available is preferred. Since calcium secondary phosphate, dihydrate or calcium secondary phosphate anhydride, which is similarly available commercially is preferred.

The calcium tertiary phosphate type, calcium primary phosphate and/or the calcium secondary phosphate are mixed in proportions such that the Ca/P molar ratio is in the range of 1.35 to 1.49. When the molar ratio is less than 1.35, the cured product has a resistance lowered, while, when the ratio exceeds 1.49, the granules of cement, while being cured, are not bonded together, so that the resulting product, when loaded into a living body, is unable to form a hardened mass shaped block. If a mixture of calcium primary phosphate and calcium secondary phosphate is employed, the ratio of mixing of the calcium secondary phosphate may preferably not more than 10% by weight and not more than 5% by weight, based on the total weight of the powders. When the mixing ratio exceeds 10% by weight, the strength of the hardened mass produced is undesirably decreased.

Furthermore, the powders used as main components of the second granular calcium phosphate cement of the present invention are mixtures of powders composed of quaternary calcium phosphate, calcium primary phosphate and/or calcium secondary phosphate.

Referring specifically to the reaction of these components, the quaternary calcium phosphate and calcium primary phosphate are components which, when mixed in the presence of water, react to give crystals of calcium secondary phosphate and octacalcium phosphate which are entangled together to be cured, while the quaternary phosphate and calcium the calcium secondary phosphate are components which, when mixed together in the presence of water, react to give crystals of octacalcium phosphate which are entangled together to be cured. Furthermore, the calcium secondary phosphate and octacalcium phosphate are components that are transformed in vivo to apatite granduellement.

Quaternary Since calcium phosphate, calcium phosphate quaternary obtained by synthesis dry, using the calcium secondary phosphate and calcium carbonate, calcium phosphate or the quaternary obtained by wet synthesis, using calcium hydroxide and phosphoric acid, can be used preferably, while calcium primary phosphate or calcium secondary phosphate can be exemplified by compounds similar to those listed in relation to the first granular calcium phosphate cement.

The compounding ratio of the quaternary phosphate and calcium of the calcium primary phosphate and/or calcium secondary phosphate is selected such that the Ca/P molar ratio is in the range of 1.30 to 1.90. The compounding ratio outside the previous interval is not desirable because it takes much time to harden and the hardened mass has only a low mechanical strength.

Although not of limiting to the compounding ratio of the primary phosphate and calcium of the calcium secondary phosphate, the curing time is shortened when calcium primary phosphate is used in excess, while the mechanical strength is increased when the calcium secondary phosphate is used in excess.

The first and second granular calcium phosphate cement of the present invention should have a size or diameter of granules cement 0.1 to 1.0 mm at least. When the minimum diameter is less than 0.1 mm, there is not enough space remaining between the granules, while, when it exceeds 1.0 mm, the granules of cement are in contact with each other with a surface which is exceedingly small, so that the granules are not bonded together and, therefore, the charged material as a whole is incapable of forming a hardened mass block-shaped. By controlling more finely the size of the granule, it becomes possible to control the size of the vacuum between the granules or resistance of the charged product in its entirety. For example, when the granular cement classified to a size of 0.1 to 0.3 mm granules is cured, the voids between the pellets are reduced in size with the charged material in its entirety having increased resistance. Furthermore, the granular cement classified to have a size granules of 0.7 to 1.0 mm has a size larger than the voids, although it does not have a mechanical strength as high, but a wider tissue, such as blood vessels may penetrate into the voids.

The first and second granular calcium phosphate cement of the present invention can be sufficiently cured by the components of water contained in the body fluid so as to provide satisfactory results with the powders claims only. However, these cements can also be mixed with water or with physiological saline sterilized, if desired. Furthermore, sodium succinate, sodium lactate, etc, may also be dissolved in the components of previous water to further reduce the curing time. The amount of the water component can desirably be 300 to 30 parts by weight per 100 parts by weight of the powders.

According to the first method for preparing the first granular calcium phosphate cement of the present invention, the powders of calcium tertiary phosphate type are mixed with the calcium primary phosphate powders and/or with powders calcium secondary phosphate in a Ca/P molar ratio of 1.35 to 1.49 to give a mixture of powders, which is pressed and re-divided to form the granules having a minimum diameter of 0.1 to 1.0 mm.

According to the second method for preparing the second granular calcium phosphate cement of the present invention, the quaternary calcium phosphate powders are mixed with the powders calcium primary phosphate and/or powders calcium secondary phosphate in a Ca/P molar ratio of 1.30 to 1.90 to give a mixture of powders, which is pressed and re-divided to form granules having a minimum diameter of 0.1 to 1.0 mm.

It is preferable that the powders used in the first and the second method of the present invention are separately divided by a automatic mortar, a ball mill or a jet mill, or by spray drying and sieved through a sieve having a mesh size of 88 μτη.

To obtain the mixing in the particular Ca/P molar ratio mentioned above, automatic mortar, a ball mill or a shaker mixer can be used.

In the first and in the second method of the present invention, the pressing operation can be carried out using a press or a hydrostatic press hydraulic manual. Pressure used for the pressing operation may preferably be not less than 200 kgf/cm² (19.6 MPa). Below 200 kgf/cm² (19.6 MPa) is not desirable because the individual pellet strength is lowered so that the granules tend to be easily destroyed during the step of handling before curing to produce the fine powders, which can be inserted and embedded in the interstices between the granules of cement. Although there is no limitation to the upper limit of the pressure, it is preferably not more than 2,000 kgf/cm² (196 MPa) taking into account the current hydrostatic press capacity and the possibility of spraying the compressed powders.

For the geographical pressed of the shaped body produced by pressing in the first and in the second method of the present invention, a mortar or a ball mill may be employed preferably. The powders produced can be sieved through a sieve to have a minimum size granules of 0.1 to 1.0 mm to produce the first or second granular calcium phosphate cement.

Furthermore, in accordance with the first and the second method of the present invention, the resulting powders are mixed together and pressed and the pressed mass is again divided to form granules to give a sufficient strength to the granules and also to produce a porous mass by curing and bonding of the granules to each other.

The first and second granular calcium phosphate cement of the present invention can be loaded easily hollow construction or absorbed bone or cavities left after the extraction of a tooth and can transform readily apatite after being cured. Furthermore, the load in its entirety can be cured into a block having voids or pores in a manner convenient for the transport of nutrients or for the formation of new bone. The cements of the present invention are superior as regards the characteristics of shape retention subsantiellement initial while being free of the risk of leakage of the charged site. The time required for the therapy may also be decreased. Furthermore, according to the first and second methods according to the present invention, the first and second granular calcium phosphate cements can be produced easily.

Is sprayed the calcium tertiary phosphate type using a automatic mortar, while is sprayed using a ball mill the dihydrate of calcium secondary phosphate produced by WAKO PURE CHEMICAL INDUSTRIES, LTD., extra quality. These resultant powders calcium tertiary phosphate type and calcium secondary phosphate are sifted through a sieve having a mesh width of 88 μτα and adjusted so that the Ca/P molar ratio is equal to 1.45. These resultant powders are mixed uniformly for 30 min using a shaker mixer, manufactured by SINMAL ENTERPRISES under the trade name " TYPE Tic ".

Is loaded 120 g the resulting mixture into a metal mold having a rectangular cross-section of 50 x 100 mm and is initially molded under a pressure of 200 kgf/cm² (19.6 MPa) by using a hydraulic press manufactured by RIKEN KK under the trade name "TYPE P-18". The resulting product is pressed by a hydraulic press manufactured by RIKEN KK in special control for producing a molded product pressed.

Pressed The molded product is divided by a mortar manufactured by automatic ISHIKAWA KOGYO KK under the trade name "TYPE 20" to give powders, which are sifted through sieves having mesh openings of 0,044, 0.1, 0.3, 0.5, 0.7, 1.0 and 3.0 mm to produce seven cement powders having different particle sizes in the ranges of 0.1 to 0.3 mm (example of preparing 1-1), of 0.3 to 0.5 mm (example of preparing 1-2), of 0.5 to 0.7 mm (example of preparing 1-3), of 0.7 to 1.0 mm (example of preparing 1-4), of 0.1 to 1.0 mm (example of preparing 1-5), of 0,044 to 1.0 mm (example of preparing 1-6) and 1.0 to 3.0 mm (example of preparing 1-7).

Example 1-1

5 g of each of the powders produced in the examples of cement preparation to 1-5 1-1 and 5 ml of physiological saline solution are mixed together to produce the first granular calcium phosphate cements of the present invention. Each of the calcium phosphate cements granular products is loaded into a cylindrical mold frame having a diameter of 20 mm and held in a dryer during h 37*C 3.

After drying, the cured products are removed from the mould frames. It has been found that cured products are in the form of porous blocks having voids between the granules.

The products block-shaped granules obtained by curing examples of preparation 1-1 1-2 and have compression strengths of 25.2 kgf/cm² (2.47 MPa) (example of preparing 1-1) and 20.2 kgf/cm² (1.98 MPa) (example of preparing 1-2). To measure the compressive strength, a universal Instron testing device available under the trade name "TYPE 1125" is employed at a cross head speed of 0.5 mm/min.

Is a process for curing the same way as to the example 1-1, except that the powders of cement produced in the examples of preparation and 1-7 1-6 are employed, to obtain the hardened cement products.

It has been found that the hardened mass produced using the powders obtained in the example of preparing 1-6 n 'no gap between the granules, while the product obtained by using the powders obtained in the example of preparing 1-7 n' is not been cured and cakes into pieces when removed from the cylindrical mold frame so that it cannot be loaded in place.

Example 1-2

Powders are produced in the same manner as examples of preparing 1-1 to 1-7, except that the compounding ratio of the calcium tertiary phosphate type and the calcium secondary phosphate is adjusted such that the Ca/P molar ratio is 1.35 and 1.49. The resulting powders are classified using screens of mesh openings of 0.3 mm and 0.7 mm for producing granulates cement having a size of 0.3 to 0.7 mm granules.

Cement The powders are prepared by granular calcium phosphate cements in the same manner as in the example 1-1 and cured. It has been found that the cured products are in the form of porous blocks.

Is sprayed the calcium tertiary phosphate type using a automatic mortar, while is sprayed using a ball mill monohydrate calcium primary phosphate produced by WAKO PURE CHEMICAL INDUSTRIES, LTD., for use as food additive. These resultant powders calcium tertiary phosphate type of primary phosphate and calcium are sifted through a sieve having a mesh width of 88 μτα and adjusted so that the Ca/P molar ratio is equal to 1.45. These resultant powders are uniformly mixed by a shaker mixer manufactured by SINMAL ENTERPRISES under the trade name "TYPE T2C" during 30 min.

120 g of the resultant mixture are loaded into a die having a rectangular cross-section of 50 x 100 mm and initially molded under a pressure of 200 kgf/cm² (19.6 MPa) using a hydraulic press manufactured by RIKEN KK under the trade name "TYPE P-18". The resulting product is pressed by a hydraulic press manufactured by RIKEN KK in special control for producing a molded product pressed.

Pressed The molded product is sprayed by a mortar manufactured by automatic ISHIKAWA KOGYO KK under the trade name "TYPE 20" to give powders that are then sieved through sieves having mesh openings of 0,044, 0.1, 0.3, 0.5, and 3.0 mm 0.7.1.0 to produce seven cement powders having different particle sizes in the ranges of 0.1 to 0.3 mm (example of preparing 2-1), of 0.3 to 0.5 mm (example of preparing 2-2), of 0.5 to 0.7 mm (example of preparing 2-3), of 0.7 to 1.0 mm (example of preparing 2-4), of 0.1 to 1.0 mm (example of preparing 2-5), of 0,044 to 1.0 mm (example of preparing 2-6) and 1.0 to 3.0 mm (example of preparing 2-7).

Example 2-1

5 g of each of the powders produced in the examples of cement preparation to 2-5 2-1 and 5 ml of physiological saline solution are mixed together to produce the first granular calcium phosphate cements of the present invention. Each of the calcium phosphate cements granular products is loaded into a cylindrical mold frame having a diameter of 20 mm and is held in a dryer during h 37*C 3.

After drying, the cured products are removed from the mould frames. It has been found that the cured products are in the form of blocks having voids between the granules.

Form products of blocks obtained by curing the granules examples of preparation and 2-1 2-2 have compression strengths of 20.7 kgf/cm² (2.03 MPa) (example of preparing 2-1) and 14.5 kgf/cm² (1.42 MPa) (example of preparing 2-2). To measure the compressive strength, a universal test device Instron commercially available under the trade name "TYPE 1125" is employed at a cross head speed of 0.5 mm/min.

Is a process for curing the same way as to the example 2-1, except that the powders of cement produced in the examples of preparation 2-6 2-7 and are employed to produce the hardened cement products.

It has been found that the hardened mass produced using the powders obtained in the example of preparing 2-6 n 'no gap between the granules, while the product obtained by using the powders obtained in the example of preparing 2-7 n' is not been cured and collects in pieces when the frame is removed from the cylindrical mold, so that it cannot be loaded in place.

Example 2-2

Powders are produced in the same manner as in the examples of preparation 2-1 to 2-7, except that the compounding ratio of the calcium tertiary phosphate type of the primary phosphate and calcium is adjusted such that the Ca/P molar ratio is 1.35 and 1.49. The resulting powders are classified using screens of mesh openings of 0.3 mm and 0.7 mm for producing granulates cement having a size of 0.3 to 0.7 mm granules.

Cement The powders are prepared by granular calcium phosphate cements in the same way as in the example and 2-1 cured.

It has been found that the cured products are in the form of porous blocks.

Example 2-3

Powders are produced in the same manner as examples of preparing 2-1 to 2-7, except that the dihydrate of calcium secondary phosphate manufactured by WAKO PURE CHEMICAL INDUSTRIES, extra LTD. quality, is added to a mixture of calcium tertiary phosphate type of primary phosphate and calcium prepared in the examples of preparation 2-1 to 2-7 in an amount of 3% by weight based on the total weight of the powders. The powders are sieved through sieves having mesh openings of 0.1, 0.3, 0.5, 0.7 and 1.0 mm to produce cement powders having particle sizes of 0.1 to 0.3 mm (powder 1), of 0.3 to 0.5 mm (powder 2), of 0.5 to 0.7 mm to 1.0 mm and 0.7.

2-1 In in example, these cement powders are prepared by granular calcium phosphate cements which are then cured. The resulting products are in the form of porous blocks having voids between the granules.

The resistances of the cured products obtained using the cement powders 1 and 2 are measured in the same manner as in the example and 2-1 are found equal to 23.4 kgf/cm² (2.29 MPa) for the powders 1 and 18.0 kgf/cm² (1.76 MPa) for the 2 powders.

Quaternary The calcium phosphate is sprayed using a automatic mortar, while the calcium primary phosphate monohydrate produced by WAKO PURE CHEMICAL INDUSTRIES, LTD. for use as food additives is sprayed using a ball mill. These resultant powders quaternary calcium phosphate and calcium primary phosphate are sifted through a sieve having a mesh width of 88/year and are adjusted so that the Ca/P molar ratio is equal to 1.80. These resultant powders are mixed uniformly for 30 min by a shaker mixer manufactured by SINMAL INTERPRISES under the trade name "TYPE T2C".

120 g of the resultant mixture are loaded into a die having a rectangular cross-section of 50 x 100 mm and initially molded under a pressure of 200 kgf/cm² (19.6 MPa) by using a hydraulic press manufactured by RIKEN KK under the trade name "TYPE P-18". The resulting product is pressed by a hydraulic press manufactured by RIKEN KK in special control under a pressure of 200 kgf/cm² (19.6 MPa) for producing a molded product pressed.

Pressed The molded product is sprayed by a mortar manufactured by automatic ISHIKAWA KOGYO KK under the trade name "TYPE 20" to give powders, which are then sieved through sieves having mesh openings of 0,044, 0.1, 0.3, 0.5, and 3.0 mm 0.7.1.0 to produce seven cement powders having different particle sizes in the ranges of 0.1 to 0.3 mm (example of preparing 3-1), of 0.3 to 0.5 mm (example of preparing 3-1), of 0.5 to 0.7 mm (example of preparing 3-3), of 0.7 to 1.0 mm (example of preparing 3-4), of 0.1 to 1.0 mm (example of preparing 3-5), of 0,044 to 1.0 mm (example of preparing 3-6) and 1.0 to 3.0 mm (example of preparing 3-7).

Example 3-1

5 g of each of the powders obtained in the examples of cement preparation to 3-5 3-1 and 5 ml of physiological saline solution are mixed together to produce the second granular calcium phosphate cement of the present invention. Each of the calcium phosphate cements granular products is loaded into a cylindrical mold frame having a diameter of 20 mm and held in a dryer during h 37*C 3.

After drying, the cured products are removed from the mould frames. It has been found that the cured products are in the form of porous blocks having voids between the granules.

Form products of blocks obtained by curing the examples of preparing granules 3-1 3-2 and have the compression forces 19.7 kgficm² (1.93 MPa) (example of preparing 3-1) and 13.8 kgf/cm² (1.35 MPa) (example of preparing 3-2). To measure the compressive force, a universal Instron testing device available under the trade name "TYPE 1125" is employed at a cross head speed of 0.5 mm/min.

Is a process for curing the same manner as in the example 3-1, except that the powders of cement produced in the examples of preparation 3-6 3-7 and are employed to produce the hardened cement products.

It has been found that the hardened mass produced using the powders obtained in the example of preparing 3-6 n 'no gap between the granules, while the product obtained by using the powders obtained in the example of preparing 3-7 n' is not been cured and gathers to pieces when it is removed from the cylindrical mold frame so that it cannot loaded in place.

Example 3-2

Powders are produced in the same manner as in the examples of preparation 3-1 to 3-7, except that the compounding ratio of the quaternary phosphate calcium primary phosphate and calcium is adjusted such that the Ca/P molar ratio of 1.30 is and 1.90. The resulting powders are classified using screens of mesh openings of 0.3 mm and 0.7 mm for producing granulates cement having a size of 0.3 to 0.7 mm granules.

Cement The powders are prepared by granular calcium phosphate cements in the same way as in the example 3-1 and cured. It has been found that the cured products are in the form of porous blocks.

Example 3-3

Powders are produced in the same manner as in the examples of preparation 3-1 to 3-7, except that the dihydrate of calcium secondary phosphate manufactured by WAKO PURE CHEMICAL INDUSTRIES, LTD., extra quality, is used instead of the calcium primary phosphate monohydrate and that the Ca/P molar ratio is attached to 1.67. The powders are sieved through sieves having mesh openings of 0.1, 0.3, 0.5, 0.7 and 1.0 mm to produce cement powders having particle sizes of 0.1 to 0.3 mm (powder 3), of 0.3 to 0.5 mm (powder 4), of 0.5 to 0.7 mm, of 0.7 to 1.0 mm and 0.1 to 1.0 mm.

Cement The powders are prepared in the same manner as in the example 3-1 in granular calcium phosphate cements which are then cured. The resulting products are in the form of porous blocks having voids between the granules.

The resistors cured products products utilizing the cement powders 3 and 4 are measured in the same manner as in the example 3-1 and are found equal to 21.0 kgf/cm² (2.05 MPa) for the 3 powders and 16.1 kgf/cm² (1.57 MPa) for the powders 4.

The curing time product prepared using the 3 powders is measured, and found equal to 10 min. Meanwhile, for measuring the curing time, 60 parts by weight of physiological saline solution are mixed and kneaded with 100 parts by weight of the 3 powders to produce a cement paste, which is then loaded into a mold frame having a diameter of 10 mm and a thickness of 3 mm. The cement paste with the frame outer mould is held in a container at a constant temperature and constant humidity at a temperature of 37*C and a humidity of 100%, a round bar supports a weight of 300 g is provided on the surface of the cement paste, and the curing time found is the cumulative time elapsing from the kneading until no mark of the bar is formed on the surface of the cement paste.

Example 3-4

Powders are produced in the same manner as in the examples of preparation 3-1 to 3-7, except that a mixture of primary phosphate monohydrate and calcium dihydrate of calcium secondary phosphate in a molar ratio of 1:10 is used instead of the calcium primary phosphate monohydrate and the Ca/P molar ratio is attached to 1,594. The powders are sieved through sieves having mesh openings of 0.1, 0.3, 0.5, 0.7 and 1.0 mm to produce cement powders having particle sizes of 0.1 to 0.3 mm (powder 5), of 0.3 to 0.5 mm, of 0.5 to 0.7 mm, of 0.7 to 1.0 mm and 0.1 to 1.0 mm.

Cement The powders are prepared in the same manner as in the example 3-1 in granular calcium phosphate cements which are then cured. The resulting products are in the form of porous blocks having voids between the granules.

The curing time cured body prepared using the powders 5 is measured in the same manner as in the example and 3-3 is found equal to 7 min.