KR820001147B1 - Process for preparing polycrystalline foamed ceramic body comprising whitlockite - Google Patents

Abstract

β-Whitlockite for dental and surgical prosthetic mat'ls was prepd. by adjusting a (NH4)2PO4 soln. to pH 11, adding Ca (NO3)2, suspending the ppt. in (NH4)2SO4, mixing the sediment with egg albumin and azodicarboxamide, leaving at 80≰C overnight, and sintering 1h at 1050≰to give a porous ceramic with av. pore size 100μm. The ceramic, when implanted in dogs, was resorbed in 2 mo and replaced by dense bone tissue.

Description

Method for preparing polycrystalline porous ceramics made of wittrokite

The present invention relates to a method for preparing crystalline urinary companies that are specifically used in the orthopedic field. In recent years, much research has been conducted in the field of biomaterials, which mainly focuses on manufacturing biomaterials suitable for living organisms that can be used as bone substitutes.

Calcium phosphates, such as wit trokite [Ca ₃ phosphate: Ca ₃ (PO ₄ ) ₂ ], are of particular interest because their chemical compositions are biologically similar to hard tissues, and have been adopted as numerous research topics. have. Although many attempts have been made in the past to produce large whitlockite, it is generally subjected to processes such as powder manufacturing, filling processing, and pressure sintering. What is produced in this way is that it is generally porous and lacks strength, a characteristic required for implant use in orthopedic surgery.

A high-density, dense, pore-free polycrystalline sintered manufacturer made of a mixture of wit trokite and hydroxylatite is used as a dental and surgical implant material, which precipitates and separates calcium phosphate from the liquid phase at 1000 ℃ -1350. It is manufactured by sintering at ℃.

In addition, the preparation method is prepared by sedimentation and separation of wittrokite produced by rapid mixing in a stoichiometric amount of calcium and phosphate ions.

According to the present invention, a polycrystalline porous insulator of wittrokite can be prepared, and the crystal lattice of wittrokite contains about 0.1-2.2% of sulfate ions in weight percent and has an average single crystal size of about 0.3- 3μ, total porosity is about 20-80%, open pores of about 50-300μ of pore diameter are fairly uniformly dispersed. This agent is used as a resorbable prosthetic material for dental and surgical applications.

As a polycrystalline porous insulator of wittrokite according to the present invention, it contains 0.1-2.2% of sulfate ion by weight percent in the crystal lattice of wittrokite, the average single crystal size is about 0.3-3μ and the total porosity is about 20 As a manufacturing method for urine companies in which the pores having a pore diameter of about 50-300μ are uniformly dispersed at -80%, calcium ions and phosphate ions are reacted in a liquid medium having a pH of 10-12 with a molar ratio of about 1.2-1.5: 1. Calcium phosphate precipitates of about 1.50-1.53: 1 calcium phosphate precipitates were formed in the gelatin state, separated from the solution and washed until the soluble salts disappeared. The suspension is uniformly dispersed in -3% ammonium sulfate solution. The precipitate is separated from the ammonium sulfate solution, and the precipitate is mixed with 0.5-10% (% by weight) of blowing agent and 0.5-10% (% by weight) of foam stabilizer and heated at 70 ° C-90 ° C to decompose the blowing agent. And the foamed mixture is completely dried.

When the dried foam is fired at 1000 ° C.-1350 ° C., the bubble stabilizer is volatilized and completely sintered to become a product.

In filling the pores present in the bone, it can be a polycrystalline urinary carrier having a porous biocompatibility according to the present invention. Likewise, in the form of a porous crystalline polycrystalline uric acid having a porous bioconjugation according to the present invention, it is possible to reconstruct the defective bone by using artificial bone prosthetic technology.

Wittrokite exists in two crystalline forms, one of which is alpha (α), which is metastable at high temperatures, and the other is beta (β), which is thermodynamically stable. Unless otherwise indicated, the term "witrokite" as used herein may be interpreted as an alpha or beta form, or a mixture thereof.

The ceramic quattrokite according to the present invention can be produced in a required shape by using a conventional method such as molding, casting, machining, milling, and the like. In this way, the urine manufacturer can be formed into thin plates with various required thicknesses or in the form of cones, cylinders, spheres, particles, powders, and the like.

In addition to the properties described above, wittrokite according to the present invention has sufficient biocompatibility and resorption and therefore is extremely suitable for surgical implants, especially bone formation and reconstitution. Therefore, if the bone is defective or voids can be made to have a certain shape using the present agent or to form a granular shape. The urinary tract is slowly reabsorbed and can be used as a new biological hard tissue.

The extremely high strength is due to the small size of the single crystals, for example the special microstructure, which has the importance as a prosthetic material that can be implanted in special parts of the bone that are heavily loaded.

Also, in some cases, it can be properly promoted by using this porous graft for conditions such as fluid circulation, tissue growth and new bone formation when intended to be used. This phenomenon is very important.

In this case, as will be described in detail below, the pores having pores of the pores of the present invention prepared in the present invention have a porosity of 20-80% to uniformly disperse pores having an average diameter of about 50-300 µ. Exert value.

This material is particularly used for the treatment of root lesions or reconstruction of facial bones, and is prepared to have a separate composition in the present invention for use for this purpose.

Of course, what can be seen here is that the formation of pores in the ceramic toptrokite lowers the compressive and tensile strengths. However, due to the small size of the single crystal and the absence of fine matrix pores, the porous ceramics have considerable mechanical strength.

As described above, in order to prepare a novel wittrokite subcontractor according to the present invention, calcium phosphate should be initially precipitated from the liquid medium. The reaction process between phosphate ion and calcium ion in the liquid medium is complicated and the reaction mechanism is incompletely identified. Generally, the equilibrium reaction varies according to various reaction rates and thus different products are produced. As you might guess, the result of this interaction is greatly influenced by stoichiometry, for example, the molar ratio of calcium to phosphorus (Ca / P), reaction time, temperature and pH. In general, the calcium ion phosphate ions initially bind to produce apatite lacking insoluble calcium content, and the ratio of apatite calcium to phosphorus is about 1.5, indicating that the stoichiometry for wittrokite is accurately established.

However, the apatite crystal lattice has the most stable form in the calcium phosphate system. When excess calcium ions are present, the initial precipitate is gradually converted into a hydroxylatatite having a calcium and phosphorus ratio of 1.67.

If the ratio of calcium and phosphorus is intermediate, e.g. 1.5-1.67, then when the precipitate is heated, it is a mixture of wittrakite and hydroxylapatite, so what is evident here is that the ratio of calcium and phosphorus You should keep it at 1.5. Simply reacting with a molar ratio of calcium and phosphate ions of 1.5 produces wittrokite containing impurities and is not an effective method because it produces a mixture of wittrakite and hydroxylatite. In fact, reducing the molar ratio of calcium and phosphate to 1.2: 1 produces a mixture of wit trokite and hydroxy lapatite. If the initial product (precipitate) is separated immediately after reacting calcium and phosphate ions with the stoichiometry of wittrokite, ie Ca / P = 1.5, no further equilibrium will occur. Some have been successfully manufactured.

However, this method has been found to be non-reproducible and is not suitable for large scale production.

What is known by the present invention is that when sulphate ions are added to a small amount of calcium phosphate precipitate and collected and heated, the calcium phosphate is completely converted to wittrakite free of hydroxylatite. Moreover, the sintering of the produced wittrokite thus becomes a high quality urine with excellent physical and mechanical properties, which can be most appropriately used as a biological graft material.

Therefore, calcium ions and phosphate ions are reacted at pH 10-12 to precipitate witkite in the liquid medium.

Compounds containing calcium ions and phosphates that provide calcium ions and diacid ions in the liquid medium are used, in which the corresponding counterions can be easily separated from the wittrokite product, or they can themselves It does not bind and should not interfere with the sedimentation or segregation of wittrokite.

For example, compounds that provide calcium ions include calcium nitrate, calcium hydroxide, calcium acetate and the like, and compounds that provide phosphate ions include diammonium hydrogen phosphate, ammonium phosphate, and phosphoric acid. In the process of the present invention, calcium nitrate and ammonium hydrogen phosphate are used as sources of calcium ions and phosphate ions, respectively.

First, the molar ratio of calcium nitrate to diammonium hydrogen phosphate is set at about 1.2-1.5: 1 to react at pH 10-12 in a liquid phase to produce a gelatinous precipitate of calcium phosphate. At this time, the reaction temperature is not very important and precipitation can proceed at about 0 ℃ -100 ℃, but it is usually done at room temperature. The gelatinous precipitate is separated from the solution using a suitable method such as centrifugation and supernatant decantation, and the remaining mineral sludge is suspended by distilled water and washed until there is no remaining soluble salt. Separation and decantation.

Although not essential to this process, the last separation process can be used to minimize cracks in the sintering process. The washed product is dispersed suspended in a small amount of distilled water and left for use in the next process.

The primary cracked dispersion of mineral sludge in 1-3% ammonium sulfate solution is converted to crystalline wittrokite. As a rule, use 10-20 ml of 1-3% ammonium sulphate solution per gram of wittrokite subcontractor estimate.

Solids are separated from the solution by centrifugation and vacuum filtration. The collected gelatinous product contains a large amount of occlusion water, and most of the moisture is pressurized to remove the product, and then the product, such as clay, is cut into a suitable shape or dried by drying, resulting in about 25% of dry shrinkage. Sintering it again shrinks about 25% more.

Importantly in the chemical process described above, the ratio of calcium and phosphorus in the sediment isolated is approaching the theoretical value for wittrokite, ie Ca / P = 1.50, which results in the hydrociramite content in the sediment. In addition to minimizing the amount of ammonium sulfate required to produce the pure witkite according to the present invention can be reduced to a minimum. Therefore, when the ratio of calcium and phosphorus in the precipitate exceeds about 1.53, it is not appropriate to produce pure thyroxite by contacting 1-3% ammonium sulfate, but rather, a mixture of wit and hydroxy lapatite is produced. will be.

A calcium anthrate precipitate with a calcium and phosphorus ratio of 1.53 or higher can be completely converted to wittrokite using a large amount of ammonium sulfate. Indeed, pure hydroxylapatite precipitates (Ca / P = 1.67) can be converted to wittrokite using sufficient amounts of ammonium sulfate. However, the wittrokite prepared in this way is contaminated by the incorporation of calcium sulfate in a large amount, and it is not seen that such excellent physical and mechanical properties are exhibited by the witrokite urea produced by the present invention. Therefore, if the ratio of calcium to phosphorus does not exceed about 1.53, the molar ratio of calcium and phosphate is mixed to 1.5 or 1 or less, and generally 1.2 -1.4: 1 is preferable. The calcium phosphate precipitate thus prepared has a ratio of calcium and phosphorus of about 1.50-1.53, and is treated with 1-3% aqueous ammonium sulfate (10-20 ml per g of gyrotrokite estimate) to obtain pure wittrokite according to the present invention. do.

As described above, the production of wittrokite in the liquid phase as a gelatinous precipitate is that the gelatinous material is cohesive and can be molded or cast, which can then be dried and sintered if necessary to form a urine. It is important in that respect. Dry powdery or granular wittrokite cannot be reconstituted into this cohesive gelatin state. For example, if disperse and filter wittrokite powder in water, a cohesive granular filtercake is produced, which simply collapses when dried, and therefore cannot be molded or converted into a major supplier. Moreover, even if the witkite powder can be press-molded by a mechanical method to form a tablet, the sintered product becomes an opaque product with many pores, and does not exhibit the high strength properties of the urethane manufacturer manufactured in the present invention. .

As described above, the method according to the present invention in preparing a porous urinary ware is made by reacting the molar ratio of calcium ion and phosphate ion to 1.2-1.5: 1 to pH 10-12 in a liquid medium, so that the molar ratio of calcium and phosphorus is about 1.50. -1.53: Generate calcium phosphate precipitate on monogelatin, which is separated from solution and washed with water until the soluble salt is removed, in about 10-20 ml 1-3% aqueous solution of 1-3% by weight ammonium sulfate After dispersion suspension, the precipitate is again separated from the ammonium sulfate solution. The separated precipitate was mixed with 0.5-10% (wt%) of foaming agent and 0.5-10% (wt%) foam stabilizer and heated at 70 ° C-90 ° C to decompose the blowing agent, and then dried sufficiently to become porous. Sintering is performed at 1350 ° C., whereby the bubble stabilizer is volatilized, resulting in a sintered product. Calcium phosphate precipitates are mixed with known foam stabilizers such as albumin, polyvinyl alcohol or polyethylene glycol and known blowing agents such as azodicarbonamide, hydrogen peroxide or ammonium carbonate. When the mixture is heated, the blowing agent decomposes and releases the sesame, which is captured by the bubble stabilizer, thereby forming a stable bubble. When dried and sintered, it becomes a porous urinary agent.

Another method is to omit the blowing agent and to incorporate air into the mixture by mechanical means to form bubbles. In some cases, a bubble stabilizer may be omitted and a fibrous organic compound such as starch, collagen and cellulose or a volatile organic compound such as naphthalene may be used.

Therefore, the urine company according to the present invention can be conveniently given porosity using the following method.

That is, as described above, calcium phosphate is precipitated and washed until there is no soluble salt, followed by washing with ammonium sulfate solution. 10-100 mg (typically about 15-20 mg is good) of sprayed egg whites at least equal to, eg, 10-200 mg (approximately 15) -30mg is good) azodicarbon amide is added and mixed, water is added as needed to adjust the viscosity of the mixture. By doing so, it is not only well stirred, but also contains a lot of air to form large bubbles. Will not. Spray-dried egg whites are a bit difficult to homogeneously mix with the toptrokite sludge because they do not wet well. Therefore, it may not be necessary, but it is better to add water before adding dried egg white to the toptrokite sludge. The mixture is dried at 70 ° C.-90 ° C. for about 8-20 hours and, if necessary, may be poured into a suitable mold prior to drying the mixture.

In general, the mixture should be covered in a dry way before the zodicarbonamide is completely decomposed. As another method, drying may be performed in a high humidity chamber. The dried product is sintered at 1000 ° C-1350 ° C for about 0.5-2 hours (preferably 1 hour at 1050 ° C-1150 ° C), at which temperature the remaining blowing agent or bubble stabilizer is volatilized, thus the witkite is completely sintered. do. The porous ceramics thus produced are then cut or processed in the form of a disturbance by mechanical means.

As described above, it is possible to make the porous material in the form of pure β-witrokite or a mixture of β-witrokite and α-witrokite.

As mentioned above, the urinary agent imparted porosity by the present invention is used as a resorbable biological implant. The resorption rate depends in part on the crystal phase of the upper trokite, and the α type resorbs faster than the β type. Therefore, the rate of resorption of the graft material of thyroxtrokite can be controlled by varying the ratio of α-: β-thyrokite.

The present invention will be described according to the embodiment (but not limited to the embodiment).

Example 1

264.1 g (2 mol) of diammonium hydrogen phosphate was added to a sufficient amount of distilled water, and a solution having a total volume of 5.4 L was added with 3.0 L of concentrated ammonia water to adjust the pH to 11. The precipitate produced in the above solution was dissolved and diluted by adding distilled water to make the total solution 10 l. To the solution diluted by adding 5.4 L of distilled water to 1499 ml of 1.735 M calcium nitrate, the mixture was stirred and mixed, and the pH was adjusted to 11 using 90 ml of concentrated ammonia water as described above. The reaction mixture is further stirred for 5 hours and then left at room temperature overnight. The supernatant was decanted, the residual suspension was centrifuged, and the supernatant was decanted again, and the remaining sludge was subjected to powder suspension in distilled water and washed twice. Centrifuge again and disperse the washing sludge from which the supernatant was decanted in 1500 ml of distilled water, and then rapidly stirred to a homogeneous state. 175 ml are taken, centrifuged, the supernatant decanted and the remaining material dispersed suspended in 100 ml of 1% (% by weight) ammonium sulfate solution. The suspension was centrifuged and the supernatant was decanted, and the remaining slurry was mixed with 180 ml of spray-dried egg whites (this was sufficiently adjusted by adding 10 ml of distilled water as described above, and the ingredients were adjusted), followed by 180 mg of azodicarbonamide. After the mixture was stirred vigorously for 0.25 hours, the cube was poured into a mold, and the lid was loosely covered to dry at 80 ° C. Sintering of the dried foam material at 1050 ° C. for 1 hour yields a porous whittrokite insulator with an average pore size of about 100 μ.

Example 2

After treatment in a manner similar to that of Example 1, the dried wicklockite foam was sintered at 1050 ° C., 1100 ° C. and 1125 ° C. for 1 hour, and the specific gravity was 1.41, 16 and 1.72 g / cm ³ , respectively. Three different porous wittrokite subcontractors are obtained, 54.7, 52.0 and 35.1%.

The biosynthesis of thyroidkite urea in accordance with the present invention was confirmed by transplanting thyrotropite urea prepared according to the method as described above in the form of fillers and granules into pores in the femur of the dog.

In other words, the graft area was normally healed, there was no inflammation or foreign object rejection, and the resorption of the graft material was almost complete in two months, and the new bone was developed by replacing the graft material.

By the seventh month, the new bone had been regenerated in spaces previously filled with wittrokite ureters, and the bone surrounding the original graft was also being remodeled.

As used herein, the term "crystalline" refers to a substance or object having properties that appear in crystals in which the atoms are arranged regularly in the crystal lattice. Thus, "polycrystalline" also refers to a substance or object composed of a plurality of crystals. On the other hand, "single crystal" means a single particle present in one entity, a polycrystalline object. Single crystals can also be defined as microscopic incompletely formed crystals or microscopic objects formed at the initial stage of crystallization.

Claims (1)

The molar ratio of calcium ions to phosphate ions is about 1.2-1.5: 1 and reacted in a liquid medium with a pH of about 10-12 to form a gelatinous calcium phosphate precipitate having a molar ratio of calcium and phosphorus of about 1.50-1.53: 1 Is separated from the solution and washed until there is no soluble salt, homogeneously dispersing the washed precipitate in about 10-20 ml 1-3 wt% ammonium sulfate solution per gram of wittrokite and then precipitated from the ammonium sulfate solution. After separating about 0.5-10% by weight of the blowing agent and the bubble stabilizer, or mixing about 0.5-10% by weight of the foam stabilizer and blowing the air, or after mixing with the pore-forming agent, the resulting mixture is decomposed Heat at about 70-90 ° C. until completion and the resulting foam is dried, then heat at about 1000-1350 ° C. until volatilization of the bubble stabilizer and pore former and sintering of the resulting product are substantially complete. It consists of wittrokite, containing about 0.1-2.2% by weight of sulfate ion, average single crystal size of about 0.3-3 microns, polycrystalline total porosity of about 0.20-80%, pore diameter of about 50-300 microns A method of providing a porous ceramics in which pores are substantially uniformly dispersed.