TW201608065A - Magnesium and strontium-containing calcium phosphate compound and preparation method thereof - Google Patents

Abstract

The present invention provides a magnesium and strontium-containing calcium phosphate compound and a preparation method thereof, comprising the steps of: adding an acidic solution and phosphoric acid into an egg shell powder-containing water solution by using a magnetic stirrer, and stirring for an appropriate time interval and at an appropriate speed to produce a calcium phosphate solution; then adding the calcium phosphate solution into an alkaline solution to produce a reactant solution; putting the reactant solution, after being mixed, inside a microwave generator for a crystal-growth reaction, thereby precipitating nano-crystals. The manufacturing method provided by the present invention is to reduce impurities by using microwave radiant energy, its cost is lower than other synthetic methods, the nano-crystal formation is controllable, and it only requires even heating to enhance the reaction rate for producing hydroxyapatite-containing nano-crystals.

Description

Calcium and phosphorus compound containing magnesium and strontium and method thereof

The invention relates to a calcium and phosphorus compound containing magnesium and strontium and a method thereof, in particular to a hydrogen oxyapatite which has a high heating rate and uniform heating of a solution and can synthesize high purity in a short time.

Bioceramics are biomedical ceramic particles such as hydroxyapatite, calcium-deficient hydroxyapatite (CDHA), and nano-calcium hydroxyapatite (nCDHA). The composition contains elements such as calcium (Ca) and phosphorus (P) which can be converted and converted by the human body, or contains a group such as a hydroxyl group (-OH) which can bond with human tissues. It is biocompatible and can be degraded in vivo and can be used to adsorb proteins.

There are many methods for synthesizing apatite, which are mainly divided into a dry synthesis method and a wet synthesis method, a dry synthesis method includes a solid phase sintering method, and a wet synthesis method includes a microwave synthesis method, a hydrothermal method, and a hydrothermal method. A co-precipitation method and a sol-gel method. The raw materials prepared are mainly chemical raw materials, animal bones and corals. Hydroxyapatite prepared from chemical raw materials due to the use of high purity reagents It is more expensive; it is derived from natural animal bones such as bovine bone and fish bone. Although it has the porous structure of raw materials and bicarbonate-containing apatite, it is constantly changing due to the physical and chemical properties of raw materials. If there is a problem, some pathogens carried by the raw materials may cause harm to the human body. The pathogen can only solve the problem of spreading diseases after being calcined at a high temperature of 850 °C or higher.

About the hydrothermal synthesis of hydroxyapatite by the eggshell disclosed in the Journal of Hebei Normal University in January 2013, the method of manufacturing is as follows: firstly collect the egg shell of the commercially available egg, clean the soil and adhere the impurities after washing with tap water, and boil the hot water. After a while, the inner membrane is removed after drying. The dried eggshell is broken into small pieces, placed in a crucible, and calcined in a box type electric resistance furnace. In order to completely remove the organic matter in the eggshell, the calcination experiment was carried out in two steps. The temperature was raised to 450 ° C for 2 hours; then the temperature was raised to 900 ° C, held for 4 hours, and cooled to room temperature with the furnace. The eggshell calcined into white was ground into a powder in a mortar, passed through a 125 μm sieve, and bagged for use.

The hydrothermal synthesis experiment was carried out in a water bath reactor, and the reaction solvent was analytically pure diammonium hydrogen phosphate ((NH ₄ ) ₂ HPO ₄ , Shantou Xiqiao Chemical Co., Ltd.). Hydroxyapatite is synthesized according to the following reaction formula: 5CaO+3(NH ₄ ) ₂ HPO ₄ +2H ₂ O→Ca ₅ (PO ₄ ) ₃ OH+6NH ₄ OH......(1)

Deionized water is prepared into a 0.5 mol/L (NH ₄ ) ₂ HPO ₄ solution, and a certain amount of calcined eggshell powder (component is CaO) is weighed according to the reaction molar ratio of (1), in order to ensure complete reaction, the experiment Time control (NH ₄ ) ₂ HPO4 excess 5%. The thermostatic water bath was heated to 90 ° C and kept warm, and the eggshell powder was gradually added to the (NH ₄ ) ₂ HPO ₄ solution under vigorous stirring. After stirring at 90 ° C for 3 hours, a suspension was obtained, and the suspension was repeatedly washed with deionized water several times. After static precipitation, the supernatant was filtered off and placed in a resistance sintering furnace for 3 hours, and the calcination temperature was 200800 ° C. The heating rate is 8 ° C / min. The disadvantage is that the eggshell must be calcined at 900 ° C for 4 hours to obtain a relatively pure CaO powder.

In view of the above-mentioned shortcomings derived from the above-mentioned conventional calcium and phosphorus-containing calcium-phosphorus compounds and their methods, the inventors of the present invention succeeded in researching and developing the calcium-phosphorus compound containing magnesium and barium and the method thereof.

The object of the present invention is to provide a calcium and phosphorus compound containing magnesium and barium, and a method thereof, which mainly uses an eggshell of an egg as a starting material, and removes an organic component in an egg by an ultrasonic cleaning method to obtain an inorganic component. Hydroxyl apatite powder.

A second object of the present invention is to provide a calcium-phosphorus compound containing magnesium and barium and a method thereof, which are a preparation method for preparing a biomedical material by taking natural biological waste, which is obtained from a natural organism. The hydroxyapatite powder has safety characteristics and is environmentally friendly in terms of waste.

The magnesium-containing and barium-containing calcium phosphorus compound and the method thereof can be achieved, comprising: taking 2 g of micronized eggshell powder and 15 ml of deionized water, sequentially adding to a container for dissolution, and then adding an acidic solution (hydrochloric acid) 5 ml) to dissolve The organic matter in the eggshell powder is dissolved, and after the eggshell powder is uniformly dissolved for 30 minutes, 0.85 ml of phosphoric acid is added to fix the calcium-phosphorus ratio (Ca/P) to 1.67, and after mixing, a calcium phosphate solution is formed (or the calcium phosphate solution may be further Adding mulberry leaf extract 1% for uniform mixing; the above process is uniformly stirred by magnetic stirrer; adding calcium phosphate solution to alkaline solution to form a reactant solution, wherein calcium phosphate solution provides calcium ion and phosphate Ions; the above processes are uniformly stirred by a magnetic stirrer; then the mixed reactant solution is placed in a microwave generator, and microwaves are respectively performed at different powers and times generated by the microwave generator to facilitate subsequent growth of the crystal growth.

The reaction solution is placed in a microwave generator for a growth reaction to precipitate nanocrystals, and the crystal growth reaction is carried out under microwave heating, and the reaction time is about 5 to 60 minutes, preferably About 1 minute, more preferably about 5 to 10 minutes. The nanocrystals produced above have a width of about 15 to 35 nm and a length of about 55 to 130 nm.

The above solution was rinsed with deionized water, ultrasonic cleaning for 30 minutes (the ultrasonic oscillator was shaken for 30 minutes), and the liquid and nano crystals were quickly separated by suction filtration and filtered several times. (Repeat the washing step three times), and finally send it to the oven for baking at a temperature of about 30~60 °C, and the drying time is two days, then the apatite powder of the nano crystal can be obtained.

Figure 1 is a flow chart for the preparation of a calcium-phosphorus compound containing magnesium and strontium according to the present invention; and the synthesis of hydroxyapatite at different times by microwave heating treatment in Annexes I to IV, the microwave powers are (a) 100 watts, respectively. b) Diffraction pattern of 300 watts, (c) 500 watts and (d) 1000 watts of X-ray diffractometer; Annex 5 uses microwave power of 300 watts, microwave radiation time of 5 minutes, and pH values of 4 and 7 respectively. , 10 and 14 synthetic apatite X-ray diffraction diagram; Annex VI with microwave power of 300 watts, microwave irradiation time of 5 minutes, pH of 7, 10 and 14 synthetic apatite crystals Annex 7: Microwave heating treatment of various parameters to synthesize the crystallinity of hydroxyapatite; Annex VIII: Microwave heating treatment of various parameters to synthesize the crystallite size of hydroxyapatite; Annex IX is synthesized by microwave heating treatment of various parameters Micrograph of a field emission scanning electron microscope of hydroxyapatite; Annex 10 has a microwave power of 300 watts, a microwave irradiation time of 5 minutes, and a pH value of (a) 4, (b) 7, (c) 10 and (d) 14 microscopic photographs of field emission scanning electron microscopy of synthetic apatite; A microwave power of 300 watts, irradiation time of 5 minutes for the spectrum analysis synthesis of hydroxyapatite EDS elemental composition; annex XII various parameters in the microwave heating synthetic hydroxyl apatite The calcium to phosphorus ratio of the stone; Annexes XIII to XVI are synthesized by microwave heating at different times, and the microwave power is (a) 100 watts, (b) 300 watts, (c) 500 watts and ( d) FTIR functional group analysis of 1000 watts; X-ray diffractometer diffraction of hydroxyapatite synthesized by adding mulberry leaves with microwave power of 300 watts and microwave irradiation time of 1, 5 and 10 minutes respectively Figure 18; Annex 18: Microwave power is 300 watts, microwave irradiation time is 1, 5 and 10 minutes, respectively, adding mulberry leaves and no added mulberry leaves to synthesize the grain size of hydroxyapatite; For 300 watts, the microwave irradiation time was 1, 5, and 10 minutes, respectively, and the crystallinity of the hydroxyapatite was synthesized by adding mulberry leaves and no mulberry leaves; (a) to (c) of Annex 20 are microwave power respectively. For 300 watts, the microwave irradiation time is 1, 5 and 10 minutes respectively, and the size change of single-phase hydroxyapatite is synthesized by adding mulberry leaves; the microwave power is 300 watts in Annex 21, and the microwave irradiation time is 1 respectively. , 5 and 10 minutes of addition of mulberry leaves and no added mulberry leaves to synthesize the particle size of hydroxyapatite; Annex 22 Microwave power of 300 watts, irradiation time were added over 10 minutes and 1,5 mulberry synthesized FTIR analysis of the functional group of the hydroxyapatite; Annex Twenty-three X-ray diffraction diagram of hydroxyapatite synthesized by adding mulberry leaves with microwave power for 5 minutes and microwave power of 100, 300, 500 and 1000 watts respectively; Radiation time 5 minutes, microwave power is 100, 300, 500 and 1000 watts respectively added mulberry leaves and no added mulberry leaves to synthesize the crystal size of hydroxyapatite; Annex 25 is microwave irradiation time 5 minutes, microwave The crystallinity of the hydroxyapatite synthesized by the addition of mulberry leaves and mulberry leaves without power is 100, 300, 500 and 1000 watts respectively; the microwave radiation time is 5 minutes in Annex 26, and the microwave power is (a) 100 respectively. Micrographs of field emission scanning electron microscopy of watts, (b) 300 watts, (c) 500 watts and (d) 1000 watts of mulberry leaves synthesized with hydroxyapatite; Annex 27 by microwave irradiation time 5 Minutes, the microwave power is 100, 300, 500, and 1000 watts respectively. The particle size of the hydroxyapatite synthesized by the mulberry leaves without adding mulberry leaves is added. The microwave radiation time is 5 minutes and the microwave power is 100. 300, 500 and 1000 watts of mulberry leaves to synthesize FTIR of hydroxyapatite Analysis can yl; Annex twenty-nine microwave power of 300 watts of microwave radiation the heat time of 5 minutes the difference between the synthetic hydroxyapatite / thermogravimetric analysis; annex XXX microwave power of 300 W microwave irradiation for 5 minutes Clock, heat difference/thermogravimetric analysis of mulberry-synthesized hydroxyapatite; Annex XI 1 with reagent-grade calcium-deficient hydroxyapatite and microwave power of 300 watts, microwave irradiation time of 5 minutes Hydroxyapatite was taken out and analyzed for WST-1 reagent for 1 and 4 days.

Referring to FIG. 1 , a calcium-phosphorus compound containing magnesium and strontium according to the present invention and a method thereof, wherein the hydroxyapatite is mainly composed of calcium and phosphorus, and the present invention utilizes micronized eggshell powder and phosphoric acid, respectively. Used as a source of calcium and phosphorus ions. The micronized eggshell powder was analyzed by X-ray Diffractometer (XRD). The eggshell powder content was mostly calcium carbonate, which was obtained by comparing the standard chart of JCPD card: 72-1214. The eggshell powder is known as single phase calcium carbonate.

The preparation method of the micronized eggshell powder of the present invention comprises the steps S1 to S5, the steps of which are as follows: S1: first clean the egg shell and remove the shell membrane to obtain cleaning After the eggshell; S2: a cleaned eggshell and deionized water are placed in a container; S3: the container is ultrasonically cleaned for 30 minutes, this step is repeated twice, thereby removing the egg The residual eggshell membrane and the surface of the shell are dirty; S4: taking out the cleaned eggshell and heating it to a certain temperature to dry to a constant weight. In this embodiment, the oven heating temperature is set at 30-50. °C is dried for 48 hours; and S5: the eggshell is micronized and ground into powder by physical pulverization, and the powder is filtered and screened by a 325 mesh screen. To obtain a water-soluble eggshell powder having a particle diameter of less than 45 μm. Among them, the eggshell is originally a water-insoluble protein and mineral, which is physically pulverized and micronized, and is easily water-soluble. The physical pulverization is performed by a grinder, and the grinder may be a wet grinder, a dry grinder, and a dry low-temperature nano-grinding machine.

The invention relates to a method for preparing nano crystals with hydroxyapatite, which is applied to a biomedical material, and the preparation method comprises the steps S1 to S9, the steps of which are as follows: S1: taking the micronized egg The shell powder and the deionized water are sequentially dissolved in a container, and the weight ratio of the eggshell powder to the deionized water is about 10% (W/V), such as 1 gram of eggshell powder + 10 ml of deionized water; the eggshell The weight ratio of powder to deionized water is preferably 13% (W/V), such as 2 grams of eggshell powder + 15 milliliters of deionized water; S2: stirring the eggshell powder and deionized water in the container, wherein The eggshell powder aqueous solution is stirred at a stirring rate of 80 to 300 rpm by using a magnetic stirrer and a stirrer connected to the magnetic stirrer; S3: an aqueous solution of the eggshell powder is added to an acidic solution, and stirring is continued. In order to dissolve the organic matter in the eggshell powder, the weight ratio of the eggshell powder to the acidic solution is about 40% (W/V), such as 2 grams of eggshell powder + 5 ml of an acidic solution; the above acidic solution may include nitric acid ( HNO _3), hydrochloric acid (HCl), phosphoric acid (H ₃ PO _4), carbonic acid (H ₂ CO _3), sodium dihydrogen phosphate (NaH ₂ PO ₄ ), potassium dihydrogen phosphate (KH ₂ PO ₄ ), ammonium dihydrogen phosphate (NH ₄ H ₂ PO ₄ ), acetic acid (CH ₃ COOH), malic acid (C ₄ H ₆ O ₅ ), citric acid ( C ₆ H ₈ O ₇ ), lactic acid ( C ₃ H ₆ O ₃ ), oxalic acid (H ₂ C ₂ O ₄ ), malonic acid ( CH ₂ ( COOH ) ₂ ). However, the acidic solution is not limited thereto, and an aqueous solution having a pH of less than 7 may be used as the acidic solution of the present invention, and preferably has a pH of less than 5.

S4: Waiting for the eggshell powder to be uniformly dissolved in the eggshell powder aqueous solution for 30 to 60 minutes; S5: adding monophosphoric acid and mixing and stirring, wherein the weight ratio of the eggshell powder to the phosphoric acid is about 235% (W/V), such as 2 g of eggshell powder + 0.85 ml of phosphoric acid, and the ratio of calcium in the aqueous solution of the eggshell powder to phosphorus in the phosphoric acid was 1.67:1, and after mixing, a calcium monophosphate solution was formed. Further, the calcium phosphate solution can be mixed with the mulberry leaf powder extract by 1 to 3%, and then subjected to a growth reaction in a microwave generator. And the phosphoric acid is added to the container after the aqueous solution of the eggshell powder is added to the container, and then stirred; S6: adding the calcium phosphate solution to the alkaline solution, and continuously stirring to form a reactant solution, and the nanocrystal is generated. Precipitation, it should be particularly noted that the calcium phosphate solution is a mixture of the eggshell powder, the deionized water, the acidic solution and the phosphoric acid, and is started by stirring the calcium phosphate solution until the container is moved to the microwave generator The total internal stirring time is 30 to 60 minutes; the alkaline solution is ammonia water to adjust the pH value to 10; or the alkaline solution is ammonia water and potassium hydroxide, and the ammonia water adjusts the pH value to 4, 7 or 10, the potassium hydroxide adjusts the pH to 14 again.

S7: moving the container to a microwave generator for a long crystal reaction to precipitate nanocrystalline, the crystal growth reaction is carried out under microwave heating, and the microwave heating time is about 1 to 10 minutes. It is preferably about 1 minute, more preferably about 5 to 10 minutes. The nanocrystals produced above have a width of about 15 to 35 nm and a length of about 55 to 130 nm.

S8: collecting the nano crystal precipitated on the bottom of the container and performing washing and suction filtration treatment; and S9: collecting the nano crystal by filtration and sending it to an oven, and drying at a temperature of about 30 to 60 ° C Bake, dry for two days, you can get the nanocrystalline apatite powder. Wherein the molar percentage of the calcium element is in the range of 20% molar to 45% molar and the molar percentage of the phosphorus element is in the range of 9% molar to 20% molar.

Please refer to Table 1 for the particle size of the apatite powder synthesized by treating the calcium phosphate solution and the alkaline solution with a microwave generator.

In the first embodiment, the calcium phosphate solution has no additive, the alkaline solution is ammonia water, and the pH value is adjusted to 10 by ammonia water; the microwave power of the microwave generator is 100, 300, 500 and 1000 watts (W) The microwave irradiation time was 1, 5 and 10 minutes, respectively.

In the second embodiment, if the calcium phosphate solution has no additive, the alkaline solution is ammonia water and potassium hydroxide, and the pH value is adjusted to 4, 7 or 10 by ammonia water, and the pH value is adjusted by potassium hydroxide. To 14; the microwave generator has a microwave power of 300 watts and a microwave irradiation time of 5 minutes.

In the third embodiment, the calcium phosphate solution is added with a mulberry leaf powder extract, the alkaline solution is ammonia water, and the pH value is adjusted to 10 by ammonia water, and the microwave power of the microwave generator is 100, 300, 500 and 1000 watts. The microwave irradiation time is 5 minutes.

In the fourth embodiment, the calcium phosphate solution is added with a mulberry leaf powder extract, the alkaline solution is ammonia water, and the pH value is adjusted to 10 by ammonia water. The microwave power of the microwave generator is 300 watts, and the microwave irradiation time is respectively 1, 5 and 10 minutes.

The invention utilizes an X-ray diffraction instrument to observe the crystal structure, calculate the grain size and crystallinity. The sputtering target used by the X-ray diffractometer is a copper target with a wavelength λ of 0.15406 nm, an operating voltage of 30 kV, an operating current of 30 mA, a scanning speed of 2°/min, and a scanning range of 20 to 60. °, and the reference figure was taken as a crystal phase by the reference JCPD card: 09-0432 (Joint Committee on Powder Diffraction. Standards).

By comparing the standard chart of JCPD card: 09-0432, it can be confirmed that the present invention can synthesize single-phase hydroxyapatite by microwave method, and the main diffraction peak positions 2θ are at 25.88°, 31.76° and 32.89°. From Annex 1 to Annex 4, the microwave power is 100, 300, 500 and 1000 watts respectively. The microwave radiation time is 1, 5 and 10 minutes respectively. From the figure, it can be found that when the same microwave power, the different time increases from 1 minute to 1 minute. At 10 minutes, the crystallinity will get better and better. After observing the same time, the different microwave power is increased from 100 watts to 1000 watts. It can be found that the crystallinity is better as the microwave power increases. It is pointed out from the literature that when the reaction time and energy are sufficient, the crystallinity can be increased to make the diffraction peak of the hydroxyapatite more obvious.

Crystallinity hydroxyapatite of the present invention is calculated for the use of the following _{formula: Xc = 1- (V 112/300 /} I 300) (1)

Xc: crystallinity (%); V _112/300 : diffraction peak intensity of the depression in the middle of the ( ₁₀₄ ) and (300) plane diffraction peaks; I ₃₀₀ : diffraction peak intensity of the (300) plane.

The grain size of the hydroxyapatite is calculated by calculating the full width at half maximum of the diffraction peak in the (002) plane growing along the C-axis, and calculating the grain size of the powder by using the Scherrer formula: D=K λ/FWHM×cosθ (2)

D: grain size (nano); K: shape factor (K=0.9); λ: wavelength of copper target (0.15406 nm); FWHM: full width at half maximum (radian) of the diffraction peak; θ: Bragg angle (°).

It is known from Annex VII that by calculating the formula of crystallinity as shown in formula (1), the microwave power is calculated to be 100 watts, and the crystallinities of microwave irradiation time of 1, 5 and 10 minutes are respectively 35.5%, 45.6% and 48.3. %, when the microwave irradiation time is 5 minutes, the crystal powers of microwave power of 100, 300, 500 and 1000 watts are 45.6%, 50.7%, 50.8% and 51.1%, respectively, so it can be proved that the microwave irradiation time and the microwave power are higher. When the crystallinity increases, the result can be attached The X-ray diffraction diffractograms of Parts 1 to 4 correspond.

It is known from Annex VIII that the grain size is calculated by the Scherrer formula as Equation (2) using the diffraction peak of the (002) plane, and the microwave power is calculated to be 100 watts, and the microwave irradiation time is 1, 5, and 10 minutes, respectively. The grain sizes are 21.23 nm, 25.29 nm and 27.17 nm. When the microwave irradiation time is 5 minutes, the grain sizes of microwave power of 100, 300, 500 and 1000 watts are 25.29 nm and 25.47 nm, respectively. 29.36 nm and 30.28 nm, so it can be proved that the higher the microwave irradiation time and the microwave power, the larger the grain size, and the diffraction pattern of the X-ray diffractometer from Annex I to Annex IV can be found when the diffraction peak The narrower the grain size, the larger the result, which corresponds to the Scherrer formula.

The crystal phase was analyzed by an X-ray diffraction instrument affected by the pH value, and observed from Annex V, and synthesized by the standard chart of JCPD card: 75-1520 and JCPD card: 09-0432, when the pH value was 4 Single-phase hydroxyapatite synthesized by dicalcium phosphate anhydrous (DCPA) with pH values of 7, 10 and 14 due to the stability of hydroxyapatite in alkaline solution Therefore, the hydroxyapatite cannot be synthesized at a pH of 4, wherein it is known from Annex VI that the pH is 7, 10 and 14 respectively, and the hydroxyapatite is in the form of acid. The base number is the highest at 10.

In addition, the present invention utilizes a field emission scanning electron microscope (FE-SEM) to observe the morphology of the apatite powder and calculate the average particle size. The apatite powder is adhered to the stage by using carbon glue, since the apatite powder is a non-conductive ceramic powder, Therefore, the conductive film was coated by a vacuum sputtering gold film apparatus, and the gold plating time was 50 seconds, and the gold plating current was 10 mA for analysis.

Annex IX is a photomicrograph of a field emission scanning electron microscope that synthesizes hydroxyapatite with various parameters for microwave heating. Observed from Annex IX, the morphology of the synthetic hydroxyapatite was rod-shaped, the microwave power was 100 watts, and the microwave irradiation time was 1,5 and 10 minutes, respectively. The particle lengths were 59.4±12.2 nm and 110.9±11.3, respectively. Nano and 121.1±15.2 nm, when the microwave irradiation time is 5 minutes, the microwave power is 100, 300, 500 and 1000 watts, and the particle lengths are 110.9±11.3 nm, 113.6±17.6 nm, and 116.5±14.7 nm. The meter and 116.2 ± 20.4 nm, it can be proved that the higher the microwave irradiation time and the microwave power, the larger the particle size, and the result echoes with Table 1.

Annex 10 is 300 watts by microwave heating, microwave irradiation time is 5 minutes, and the acid and alkali values are (a) 4, (b) 7, (c) 10 and (d) 14 synthetic apatite. Field emission scanning electron microscopy photomicrograph. From (a) to (d) of Annex X are pH values 4, 7, 10 and 14, respectively, adjusting the pH value of 4 apatite powder morphology whiskers, pH 7 and 10 apatite The powder has a rod shape and a pH value of 14 apatite powder is a spheroidal shape, and the particle size can be known from Table 2.

Further, the present invention performs elemental component analysis using an Energy Dispersive Spectrometer (EDS) with a function of a field emission scanning electron microscope, and the analysis is semi-quantitative analysis. The atomic percentage of calcium and phosphorus will be obtained to calculate the calcium/phosphorus (Ca/P) molar ratio, and to explore the difference in the synthesized calcium/phosphorus (Ca/P) molar ratio; the hydroxyapatite is mainly calcium, The composition of phosphorus and oxygen, from the energy spectrum of the EDS elemental analysis in Annex XI, it can be proved that the hydroxyapatite component synthesized by the present invention contains calcium, phosphorus and oxygen elements, and the carbon element is contained in the present invention. The carbon glue adheres the powder to the stage, and carbon is also analyzed when the composition is analyzed. The calcium to phosphorus ratio is calculated by the percentage of calcium and phosphorus after component analysis, and the ideal calcium to phosphorus ratio of the hydroxide apatite is 1.67. Annex 12 is the ratio of calcium to phosphorus for various parameters of microwave heating. It can be seen from the figure that the higher the microwave irradiation time and the microwave power, the closer the ratio of calcium to phosphorus will be 1.67.

Further, the present invention analyzes the functional group position using a Fourier transform infrared spectrometer (FTIR). The apatite powder was placed on a stage for analysis, and the instrument parameter scanning resolution was set to 8 cm ^-1 , and the scanning range was 600 cm ^-1 to 4000 cm ^-1 . Annexes XIII to XVI are synthesized by microwave heating at different times. The microwave powers are (a) 100 watts, (b) 300 watts, (c) 500 watts and (d) 1000 watts of FTIR. Functional group analysis. The invention can determine the position of the functional group by using a Fourier transform infrared spectrometer. It can be known from the chemical formula Ca ₁₀ (PO ₄ ) ₆ (OH) _{2 of the} hydroxyapatite that the hydroxyapatite is composed of CO ₃ ^2- , PO ₄ ^3- and OH ^- , from (a) to (d) of Annex XIII to Annex 16, microwave powers of 100, 300, 500 and 1000 watts, respectively, microwave radiation time of 1, 5 and 10 minutes, respectively. observation wavelength of approximately 623,730 in position ^-1 and 1023cm PO ₄ ^3- of position; 1328,1430 and 1522cm ^-1 when the CO ₃ ^2- position; when 3697,3737 and 3858cm ^-1 of OH ^- of Position; 1689, 1784, and 3619 cm ^-1 is the position of H ₂ O; 2816, 3057 cm ^-1 are CH ₂ and CH _{3 respectively} , CH ₂ and CH ₃ are proteins derived from eggshell; in the position of CO ₃ ^2- 1328 and 1430 cm ^-1 belong to type B hydroxyapatite, which is CO ₃ ^2- substituted PO ₄ ^3- , CO ₃ ^2- position is 1430 and 1522 cm ^-1 belongs to type A hydroxyapatite, which is CO ^_32- substituted OH ^-, so that AB type mixing hydroxyapatite of the present invention is synthesized.

The following is the calcium phosphate solution, such as the addition of mulberry leaf powder extract, the alkaline solution of which is ammonia water, and the crystallinity and grain size of the hydroxyapatite adjusted to pH 10 by ammonia water; The microwave power is 300 watts, the microwave irradiation time is 1, 5 and 10 minutes, respectively, and the product of the mulberry leaf reaction is added by X-ray. According to the observation of the diffractometer, the synthesized products are all single-phase hydroxyl apatite, and as the microwave irradiation time increases, the crystallinity and grain size increase, there will be added mulberry leaves and no added mulberry leaves. For comparison, there is no difference in the crystal phase of the X-ray diffractometer, but the degree of crystallinity and grain size of the mulberry leaves will be small. It can be seen from Appendix 18 and Annex 19 using equation (1) and The crystallinity and grain size calculated by the formula (2) are small with the addition of mulberry leaves. The present invention is defined as a control group of hydroxyapatite without added mulberry leaves.

In (a) to (c) of Annex 20, the microwave power is 300 watts, the microwave irradiation time is 1, 5 and 10 minutes respectively, and the mulberry leaves are added to synthesize single-phase hydroxyapatite. It is rod-shaped, and as the time of microwave irradiation increases, the particle size changes significantly. It can be seen from Annex 21 that the particle size of the added mulberry leaves is smaller than the particle size of the unadded particles.

The position of the functional groups was analyzed by Fourier transform infrared spectroscopy (FTIR) with pH values of 4, 7, 10, and 14, respectively, and positions of PO ₄ ^{3- at} the observation wavelength positions of about 712, 1039, and 1211 cm ^-1 , 1371 . 1459 and 1517cm ^-1 as the position of CO ₃ ^2-, 3676,3743 and 3856cm ^-1 when is OH ^- the position, 1693,1747 and 3630cm ^-1 when H ₂ O is the position, 2817,2900cm ^-1 respectively CH ₂ and CH ₃ , CH ₂ and CH ₃ are proteins derived from eggshells. In the CO ₃ ^2- position, 1371 and 1459 cm ^-1 belong to type B hydroxyapatite, which is CO ₃ ^2- substituted PO ₄ ^3- , CO ₃ ^2- position is 1459 and 1517 cm ^-1 belongs to type A hydroxyl group. The apatite is a CO ₃ ^2- substituted OH ^- , and thus the AB-type mixed hydroxyapatite synthesized by the present invention is known. Annex XX FTIR functional analysis of hydroxyapatite synthesized by adding mulberry leaves with microwave power of 300 watts and microwave irradiation time of 1, 5 and 10 minutes respectively.

From Annex Twenty-three, we can synthesize single-phase hydroxyapatite with mulberry leaves with microwave irradiation time of 5 minutes and microwave power of 100, 300, 500 and 1000 watts respectively, and crystallinity increases with microwave power. The better. From Annex 24 and Annex 25, the crystallinity and grain size are calculated by using formula (1) and formula (2). It can be found that the crystallinity and grain size of the added mulberry leaves are small.

From (a) to (d) of Annex 26, the microwave power is 100, 300, 500 and 1000 watts respectively, and the microwave irradiation time is 5 minutes. The hydroxyapatite synthesized by mulberry leaves is added. It can be seen from the picture. The shape is rod-shaped, and compared with the twenty-seventh attachment, it can be found that as the microwave power increases, the particle size will increase. Annex 27: Hydroxyl apatite is synthesized by adding mulberry leaves without adding mulberry leaves with microwave irradiation time of 5 minutes and microwave power of 100, 300, 500 and 1000 watts respectively.

The position of the functional group can be determined by Fourier transform infrared spectrometer, the pH values are 4, 7, 10 and 14, respectively. When the observation wavelength is about 700, 1048 and 1219 cm ^-1 , it is the position of PO ₄ ^3- , 1380, 1459 and 1524 cm ^-1 when the CO ₃ ^2- position, when 3672,3748 and 3869cm ^-1 of OH ^- of positions, 1689,1740 3621cm ^-1 is the position of H ₂ O and, 2817,2888cm ^-1 respectively CH ₂ And CH ₃ , CH ₂ and CH ₃ are proteins derived from eggshells. In the CO ₃ ^2- position, 1380 and 1459 cm ^-1 belong to type B hydroxyapatite, which is CO ₃ ^2- substituted PO ₄ ^3- , CO ₃ ^2- position is 1459 and 1524 cm ^-1 belongs to type A hydroxyl group. The apatite is a CO ₃ ^2- substituted OH ^- , and thus the AB-type mixed hydroxyapatite synthesized by the present invention is known. Annex XX. The FTIR functional group analysis of hydroxyapatite synthesized by adding mulberry leaves with microwave power for 5 minutes and microwave power of 100, 300, 500 and 1000 watts respectively.

Finally, the present invention utilizes thermal differential/thermogravimetric analysis (DTA/TGA) to determine the endothermic and exothermic reactions and weight losses of the apatite powder at different temperatures. Approximately 7 to 8 mg of the apatite powder was placed in the crucible, and the alumina powder was used as a control group at an elevated temperature of 10 ° C per minute, and the temperature ranged from 40 ° C to 1400 ° C.

The weight loss in Annex 29 and Annex 30 is the evaporation of surface-adsorbed water or lattice water at 447 and 454 °C, respectively. The weight loss at 814 and 818 °C is the dehydrogenation of hydroxyapatite. Finally, the weight loss at 1400 ° C is the dehydroxylation of the hydroxyapatite, and the total weight loss is not added mulberry leaves and the added mulberry leaves are 12% and 18% respectively (after the end of the thermogravimetric analysis, the total weight is respectively Reduce the weight by 12% and 18%, only 88% and 82% of the weight respectively, which means that in the thermogravimetric analysis, as the temperature rises, there is gas loss and the weight is reduced.) The addition of mulberry leaves is more because of the loss. The mulberry leaves contain many organic matter, and the organic matter disappears with increasing temperature. At 814 and 818 ° C, the thermal difference (DTA) has a distinct exothermic peak, which belongs to the decarboxylation of hydroxyapatite.

The present invention utilizes the cell activity evaluation (WST-1) to measure the trial drug-grade calcium-deficient hydroxyapatite (Shijiku Co., Ltd., Japan) and the microwave power of 300 watts, and the microwave irradiation time is 5 minutes to synthesize the phosphorus oxyphosphate. Analysis of WST-1 reagents for 1 and 4 days of graystone. The first step is to add the test piece for 1 and 4 days of incubation to the WST-1 reagent under closed light, and then place it in a 37 ° C incubator for 4 hours. The 100-μm test tube is placed in a 96-well test dish, and the absorbance at a wavelength of 450 nm is read by an enzyme immunoassay analyzer. The color of the WST-1 reagent can be judged from the color of the WST-1 reagent. The faster the cell proliferation, on the other hand, the lighter the color, the greater the cytotoxicity. The number of cells in the 1 and 4 days of the calcium-deficient hydroxyapatite from the test sample of Annex 31 is about 0.679 times, and the microwave power is 300. The number of cells in the 1 and 4 days after the synthesis of the hydroxyapatite was about 1.152 times, and the number of cells in the cell culture and microwave heat treatment was about 8.72 times. From the growth of this, it can be seen that the activity of synthesizing hydroxyapatite by microwave heat treatment is larger than that of the reagent-grade calcium-deficient hydroxyapatite.

The trace element analysis was determined by inductively coupled plasma luminescence spectrometry (ICP-AES). It can be seen from Table 3 that the hydroxyapatite of the present invention has a small amount in addition to calcium (Ca) and phosphorus (P). The trace elements magnesium (Mg) and strontium (Sr), according to the literature, indicate that magnesium can help bone cells to adhere and stimulate the formation of new bone. In addition to promoting osteoblast differentiation and inhibiting the absorption of osteoclasts, strontium can also It can reduce the rate of bone loss, so it can be used clinically to treat osteoporosis. These trace elements of magnesium and barium are of great help to the human body. Wherein the molar percentage of the magnesium element is in the range of 0.1% molar to 0.7% molar. Wherein the molar percentage of the lanthanum element is in the range of 0.01% molar to 0.4% molar.

Table 3 added 1% mulberry leaf extract and adjusted the acid-base value of 10, and the control group adjusted the pH value of 10 and 14 respectively, with microwave power of 300.

In summary, this case is not only innovative in terms of space type, but also can enhance the above-mentioned multiple functions compared with the customary items. It should fully meet the statutory invention patent requirements of novelty and progressiveness, and apply for it according to law. This invention patent application, in order to invent invention, to the sense of virtue.

Claims (6)

A method for containing a calcium and phosphorus compound of magnesium and strontium, comprising the steps of: dissolving micronized eggshell powder and deionized water sequentially into a container, and then adding an acidic solution to dissolve the organic matter in the eggshell powder And waiting for the eggshell powder to be uniformly dissolved, adding phosphoric acid to fix the calcium to phosphorus ratio to 1.67, mixing to form a calcium phosphate solution; adding the calcium phosphate solution to the alkaline solution to form a reactant solution, and then placing the mixed reactant solution To the microwave generator; the reactant solution is placed in a microwave generator for a long crystal reaction to precipitate the nano crystal, and the crystal growth reaction is carried out under microwave heating; the solution is rinsed with deionized water and ultrasonically cleaned. Then, the liquid and the nano crystals are quickly separated by suction filtration, filtered several times, and finally sent to an oven for baking to obtain a nanocrystalline apatite powder. The method of claim 1, wherein the nanocrystal has a width of about 15 to 35 nm and a length of about 55 to 130 nm. A calcium-phosphorus compound containing magnesium and strontium, comprising: an eggshell powder, a deionized water, an acidic solution and a phosphoric acid mixed calcium phosphate solution for long crystal reaction in a microwave generator, and the microwave heating time is about 1~10 Minutes, and the nanocrystals are formed, and after drying, the apatite powder containing magnesium and strontium elements is obtained; Wherein the molar percentage of the calcium element is in the range of 20% molar to 45% molar and the molar percentage of the phosphorus element is in the range of 9% molar to 20% molar. The calcium-phosphorus compound containing magnesium and barium as described in claim 3, wherein the molar percentage of the magnesium element is in the range of 0.1% molar to 0.7% molar. The calcium-phosphorus compound containing magnesium and barium as described in claim 3, wherein the molar percentage of the barium element is in the range of 0.01% by mole to 0.4% by mole. The calcium-phosphorus compound containing magnesium and barium as described in claim 3, wherein the calcium phosphate solution can be mixed with the mulberry leaf powder extract by 1 to 3%, and then subjected to a growth reaction in a microwave generator.