JP2007191453A - Noncrystalline calcium citrate-calcium carbonate composite and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a noncrystalline calcium citrate-calcium carbonate composite enabling itself to be made into a compressed form by a simple operation, controllable in the rate of disintegration in a solvent, thus usable as a functional calcium material or the like, and to provide a method for easily producing the composite. <P>SOLUTION: The noncrystalline calcium citrate-calcium carbonate composite is composed by compounding a noncrystalline calcium citrate and a noncrystalline or crystalline calcium carbonate together. This composite is obtained, for example, by adding 300 g of quicklime powder to a 0.3M aqueous citric acid solution to effect a reaction followed by blowing carbon dioxide into the resultant suspension. In this process, by blowing the carbon dioxide for 4-5 h, the objective composite with no crystal peak as shown in Figure 1 is obtained; whereas, by blowing the carbon dioxide for 6 h, the objective composite with vaterite-type crystal peak and calcite-type crystal peak as shown in Figure 1 is obtained. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to an amorphous calcium citrate / calcium carbonate composite used for transportation of an environmental pollution cleaner and the like, which can control the disintegration rate of the solidified body in water, for example, and a method for producing the same. It is about.

  In recent years, reports on environmental pollution have increased, and countermeasures using physicochemical techniques and biological techniques have been attempted according to various pollutants and pollution situations, while countermeasures are urgently needed. ing. Among purification methods, there are in-situ treatment methods that introduce various active ingredients into the contaminated environment, such as adding substances that promote the degradation of pollutants and introducing chemicals that activate microorganisms in the soil. is there. Examples of the method for introducing the active ingredient include a method in which the ingredient is directly kneaded into the soil or put into a well that circulates the ground part and groundwater, but the purification ability is lost before reaching the contaminated spot. There were problems such as being unable to exert the effect continuously. Active ingredients include, for example, redox agents, microorganisms and enzymes, or their activators. These active ingredients are solidified so that they can easily reach contaminated sites, and the amount of elution or elution rate is controlled for a long time. Materials that can sustain their effects over a wide range are required not only in the environmental field but also in the medical field.

Calcium material is a useful substance in the field of environmental purification and environmental protection, quick lime (CaO, calcium oxide) is used as a soil and water pollution purification material, calcium acetate (CH ₃ COOCa) is used as an environmentally friendly antifreeze agent Has been. In addition, calcium carbonate (CaCO ₃ ) is abundant in raw materials and can be supplied stably in a sufficient amount, is inexpensive, non-toxic, odorless, does not cause inflammation, is highly stable to the living body, and can be adjusted to a wide range of particle sizes, etc. Because of its many advantages, it is widely used as a filler for rubber and plastic. Furthermore, calcium citrate [C ₃ H ₄ (OH) (COOCa) ₃ ] is useful as a calcium supplement in the food field, and is used as a food additive together with calcium carbonate. Thus, the calcium material is considered to be a material that is easy to apply to the environment and the medical field because of its excellent handleability and versatility.

  By the way, industrial production of calcium carbonate is generally performed by the carbon dioxide gas method. In this carbon dioxide method, calcium carbonate is precipitated by blowing carbon dioxide into lime milk (calcium hydroxide suspension) prepared by adding quick lime to water to react with calcium hydroxide. In the carbon dioxide gas method, the crystal system, shape, particle size, or dispersibility of calcium carbonate is improved by adding additives to the reaction field of the carbonation reaction or applying surface treatment to the precipitated calcium carbonate. The desired physical properties such as can be imparted. Calcium carbonate is a versatile calcium material that easily imparts functionality.

  As a method for imparting functionality to calcium carbonate, a technique of adding a complex-forming substance to perform a carbonation reaction has been shown (for example, see Patent Document 1). According to Patent Document 1 concerned, after preparing a calcium hydroxide aqueous suspension, a complex-forming substance such as sodium citrate or sodium oxalate is added to produce precipitated calcium carbonate with fine particles. Can do.

  In addition, an organic acid such as citric acid and calcium carbonate are reacted at a temperature of 30 ° C. or less, and after aging, spray-dried to form an amorphous citric acid / organic acid / calcium composition (substantially soluble in water). A method of obtaining the above calcium citrate composition) has been proposed (see, for example, Patent Document 2).

By the way, as described above, in order to knead various active ingredients in soil or groundwater, it is preferable to use a solidified material (solidified body) held on a carrier such as calcium carbonate. It is difficult to make it. For this reason, calcium carbonate can be considered to produce a solidified body by a sintering method, but it requires a large heat energy cost and has the disadvantages that the function of the active ingredient to be mixed is impaired by heat. Therefore, a method of adding a solidification aid such as chitosan and heating and pressurizing (for example, refer to Patent Document 3), a method of making a complex with polylactic acid (for example, refer to Patent Document 4), And a method of obtaining a solidified body by a method of forming a composition comprising calcium carbonate, carboxylic acid, chitosan and an appropriate amount of water (see, for example, Patent Document 5).
JP-A-10-72215 (Pages 2 and 4) JP-A-8-157380 (pages 2 and 3) JP-A-8-290949 (pages 2 and 3) JP 2001-294673 A (pages 2 and 3) JP 2000-226402 A (pages 2 and 3)

  However, these methods require an additive corresponding to a binder such as chitosan and polylactic acid, and there are problems that the operation becomes complicated and the production cost increases. In addition, there has been a problem that the function of active ingredients such as drugs, microorganisms and enzymes to be mixed is lost during heating to dissolve the binder or exposure to a solvent. Furthermore, in the material obtained by the method described in Patent Documents 1 to 5, since the solidified body is formed with an additive corresponding to the binder, the solidified body is easily disintegrated in water, for example, It was difficult to arbitrarily control the disintegration rate (and thus the elution amount and elution rate of the active ingredient held in the solidified body).

  The present invention has been made by paying attention to such problems existing in the prior art, and the object of the present invention is that it can be solidified by a simple operation alone and has a disintegration rate in a solvent. An object of the present invention is to provide an amorphous calcium citrate / calcium carbonate complex that can be controlled and used as a functional calcium material, and an easy production method thereof.

  As a result of diligent research to achieve the above object, the present inventors prepared lime milk in which quick lime was added to a high concentration citric acid aqueous solution, and conducted carbon dioxide gas through the lime milk, thereby allowing conventional calcium to flow. It was found that an amorphous calcium citrate / calcium carbonate composite having properties not found in the material was deposited. The present inventors have found that this amorphous calcium citrate / calcium carbonate complex can be solidified by a simple operation. It was also clarified that in the solidified product of a mixture of this composite and normal crystalline calcium carbonate, the disintegration rate of the solidified product can be adjusted by changing the blending amount of the amorphous calcium citrate / calcium carbonate composite. As a result, the inventors have found that the elution rate or elution amount of active ingredients (for example, physiologically active substances such as pharmaceuticals, microorganisms, enzymes, etc.) mixed at the same time can be controlled, and the present invention has been completed.

  That is, the amorphous calcium citrate / calcium carbonate complex of the invention according to claim 1 is constituted by combining amorphous calcium citrate and amorphous calcium carbonate or crystalline calcium carbonate. It is characterized by.

  The amorphous calcium citrate / calcium carbonate complex of the invention according to claim 2 is configured by combining amorphous calcium citrate and amorphous calcium carbonate in the invention according to claim 1. It is characterized by this.

  The method for producing an amorphous calcium citrate / calcium carbonate composite according to claim 3 is to prepare a suspension obtained by adding quick lime to an aqueous citric acid solution, introduce carbon dioxide into the suspension, Crystalline calcium citrate and amorphous calcium carbonate or crystalline calcium carbonate are compounded and precipitated.

  A method for producing an amorphous calcium citrate / calcium carbonate complex according to a fourth aspect of the present invention is the method according to the third aspect, wherein 7 to 9 moles of quicklime is added to 1 mole of citric acid in the aqueous citric acid solution. Used to produce an amorphous calcium citrate / amorphous calcium carbonate complex.

According to the present invention, the following effects can be exhibited.
The amorphous calcium citrate / calcium carbonate complex according to the first aspect of the present invention is configured by combining amorphous calcium citrate and amorphous calcium carbonate or crystalline calcium carbonate. For this reason, it is speculated that amorphous calcium citrate expresses an alternative action of the binder or that both components are combined to strengthen the interaction and suppress disintegration in the solvent. . Accordingly, the amorphous calcium citrate / calcium carbonate composite can be suitably used as a functional calcium material that can be solidified by a simple operation alone and can control the disintegration rate in a solvent. In addition, the property that this disintegration rate can be controlled is to control the elution amount of the active ingredient from the solidified body in a solvent by mixing this complex with various active ingredients to form a solidified body. Connected.

  Furthermore, the amorphous calcium citrate / calcium carbonate composite can be used as a modifier or filler of a polymer material for which conventional calcium carbonate has been used. For example, if a composite material with polylactic acid is used, it can be used as a bone repair material because apatite formation is observed in a simulated body fluid.

  The amorphous calcium citrate / calcium carbonate complex according to the second aspect of the present invention is configured by combining amorphous calcium citrate and amorphous calcium carbonate. For this reason, in addition to the effect of the invention according to claim 1, it is presumed that the solidified product made of a complex of amorphous calcium citrate and crystalline calcium carbonate exhibits different disintegration properties. Therefore, the elution rate or elution amount of the active ingredient can be controlled with high accuracy.

  In the method for producing an amorphous calcium citrate / calcium carbonate composite according to claim 3, a suspension is prepared by adding quick lime to an aqueous citric acid solution, carbon dioxide gas is introduced into the suspension, Crystalline calcium citrate and amorphous calcium carbonate or crystalline calcium carbonate are compounded and precipitated. For this reason, the amorphous calcium citrate / calcium carbonate complex of the invention according to claim 1 or claim 2 can be easily produced by a simple process.

  In the method for producing an amorphous calcium citrate / calcium carbonate complex of the invention according to claim 4, 7-9 mol of quicklime is used for 1 mol of citric acid in the aqueous citric acid solution, An amorphous calcium carbonate complex is produced. Therefore, in addition to the effect of the invention according to claim 3, it is possible to easily produce an amorphous calcium citrate / amorphous calcium carbonate composite.

In the following, embodiments that are considered to be the best of the present invention will be described in detail.
The amorphous calcium citrate / calcium carbonate complex (hereinafter also simply referred to as complex) of the present embodiment is a composition in which amorphous calcium citrate and amorphous or crystalline calcium carbonate are simply mixed. It is considered that the amorphous calcium citrate and the amorphous or crystalline calcium carbonate are complexed by some interaction and formed integrally. .

  Here, in this embodiment, in the X-ray diffraction, not only the calcium citrate and calcium carbonate peaks are not recognized in the diffraction pattern (chart), but also some peaks are observed for calcium carbonate. Those that are not clearly determined to have grown crystals are amorphous calcium citrate / amorphous calcium carbonate composites. On the other hand, when the peak of calcium carbonate crystal such as vaterite type crystal (hexagonal crystal), calcite type crystal (rhombohedral crystal) is clearly recognized in the diffraction pattern in X-ray diffraction An amorphous calcium citrate / crystalline calcium carbonate complex is used. Here, the term “amorphous” is a term for a crystalline substance and means a state in which a peak indicating the presence of a crystalline substance is not substantially observed in X-ray diffraction.

  Amorphous calcium citrate / calcium carbonate complex is presumed that amorphous calcium citrate exerts an alternative function of the binder. A solidified body can be obtained alone without adding a binder as in the art. Moreover, by mixing this complex with known calcium carbonate or the like in various proportions, it can be controlled to promote or suppress the collapse of the solidified body. Therefore, if various functional components such as drugs, microorganisms or enzymes are mixed in the solidified body, the amount and the rate of the active ingredient eluted or released by the collapse of the solidified body can be arbitrarily controlled.

Next, a method for producing the amorphous calcium citrate / calcium carbonate composite will be described.
That is, the production method is to add quick lime (calcium oxide) to a citric acid aqueous solution and react to form a suspension of calcium citrate and slaked lime (calcium hydroxide), introduce carbon dioxide into the suspension, Amorphous calcium citrate and calcium carbonate are combined. Amorphous calcium citrate / calcium carbonate complex is formed by the formation of calcium citrate or calcium carbonate, which is different from the conventional method using water and quicklime as raw materials or provided by the prior art. It is thought that it is important. The reaction leading to the formation of the complex in this reaction field is assumed as follows.

First, quick lime (CaO) is added to a citric acid [C ₃ H ₄ (OH) (COOH) ₃ ] aqueous solution to form a suspension of slaked lime [Ca (OH) ₂ ]. It is considered that the complex is precipitated by the reaction with the acid or carbon dioxide gas. In this case, slaked lime is first produced by the digestion reaction shown in the following reaction formula (1).

CaO + H ₂ O → Ca (OH) ₂ (1)
A part of the produced slaked lime reacts with citric acid based on the following reaction formula (2) to produce calcium citrate [C ₃ H ₄ (OH) (COOCa) ₃ ].

2C ₃ H ₄ (OH) (COOH) ₃ + 3Ca (OH) ₂
→ 2C ₃ H ₄ (OH) (COOCa) ₃ + 6H ₂ O (2)
In this way, the slaked lime suspension becomes a suspension containing calcium citrate or unreacted citric acid together with slaked lime.

Subsequently, carbon dioxide gas (CO ₂ ) is blown into the suspension, and a carbonation reaction based on the following reaction formula (3) is performed.
C ₃ H ₄ (OH) (COOCa) ₃ + Ca (OH) ₂ + CO ₂
→ C ₃ H ₄ (OH) (COOCa) ₃ + CaCO ₃ + H ₂ O (3)
In this way, it is presumed that an amorphous calcium citrate / calcium carbonate complex is produced.

  In this case, by controlling the time of the carbonation reaction, the calcium citrate remains amorphous and the calcium carbonate can be produced in any complex from amorphous to vaterite or calcite crystalline. Can do. Further, after the carbonation reaction is completed, no special method is required, and the intended amorphous calcium citrate / calcium carbonate complex can be obtained by drying according to a conventional method.

  The amorphous calcium citrate / calcium carbonate complex varies depending on the concentration of citric acid and the amount of quick lime used in the production, but includes 50 to 60% by mass of calcium carbonate and varies as long as the purpose can be achieved. There may be. The citric acid concentration in the citric acid aqueous solution is preferably 0.2 to 0.35 M (molar concentration). When the citric acid concentration is less than 0.2M or exceeds 0.35M, the balance of reaction efficiency is deteriorated and the desired amorphous calcium citrate may not be obtained.

  In addition, when obtaining an amorphous calcium citrate / amorphous calcium carbonate complex, it is preferable to add 7 to 9 mol of quicklime with respect to 1 mol of citric acid. When the molar ratio of quicklime and citric acid is out of the above range, it becomes difficult to form an amorphous state of calcium carbonate, and it is difficult to obtain an amorphous calcium citrate / amorphous calcium carbonate complex.

  In order to obtain an amorphous calcium citrate / amorphous calcium carbonate composite, the blowing rate of carbon dioxide gas is preferably 0.5 to 2.0 L / min. The carbon dioxide blowing time is preferably 4 to 5 hours. The carbonation reaction by introduction of carbon dioxide gas is preferably set to a temperature of 30 ° C. or lower, more preferably set to 15 to 20 ° C. In order to obtain an amorphous calcium citrate / crystalline calcium carbonate complex, among the above conditions, it is desirable to set the blowing time of carbon dioxide gas to 5 hours or more.

  For example, carbon dioxide is blown into a suspension prepared by adding 300 g of quicklime to 2 L of a citric acid aqueous solution having a concentration of 0.3 to 0.4 M at a flow rate of 2.0 L / min at 20 ° C. for 4 to 5 hours. A crystalline calcium citrate / amorphous calcium carbonate complex is obtained. By blowing carbon dioxide for a longer time, that is, for more than 5 hours and for 6 hours, an amorphous calcium citrate / crystalline calcium carbonate composite containing vaterite-type and calcite-type crystalline calcium carbonate can be obtained.

Next, it is preferable to use the amorphous calcium citrate / calcium carbonate composite as a solidified material with good handleability, but without using a binder such as polylactic acid or chitosan, and by a pressure molding method according to a conventional method. A solidified body can be produced. The conditions of the pressure molding method vary depending on the equipment used and the amount of the composite used and the material to be mixed, so it is not possible to set conditions unconditionally. For example, 1 to 2 g of the composite is It can be performed by applying a pressure of ² t / cm ² .

  In addition, the amorphous calcium citrate / calcium carbonate composite itself has functionality and is also a component (filler, modifier) of the composite material with other materials (resins). For example, an amorphous calcium citrate / calcium carbonate complex is added to and mixed with a polylactic acid solution in which polylactic acid is dissolved in dichloromethane (methylene chloride). Obtainable.

  Now, the operation of the present embodiment will be described. In the complex in the present embodiment, it is considered that amorphous calcium citrate and calcium carbonate are present in a complex state rather than a mixture. Here, when a mixture of crystalline calcium citrate and crystalline calcium carbonate is pressure-molded in the same manner as in the composite, the obtained solidified body quickly disintegrates in water. From this, it is surmised that in the composite, amorphous calcium citrate expresses an alternative action of the binder, so that it can be solidified alone and a solidified body such as a tablet that does not easily disintegrate in water can be obtained. The Therefore, the solidified body of the amorphous calcium citrate / calcium carbonate complex can adjust the disintegration rate in water by adjusting the compounding amount of the complex.

The effects exhibited by the embodiment described in detail above are collectively described below.
The amorphous calcium citrate / calcium carbonate complex in the present embodiment is configured by combining amorphous calcium citrate and amorphous calcium carbonate or crystalline calcium carbonate. Therefore, the amorphous calcium citrate / calcium carbonate complex can be solidified by a simple operation alone and can control the disintegration rate in a solvent, and can be suitably used as a functional calcium material. . Specifically, environmental purification materials that are carriers of drugs that decompose environmental pollutants, cosmetic ingredients that are ingredients of cosmetics or pharmaceutical carriers, pharmaceutical ingredients that are ingredients of pharmaceuticals, foods that are calcium supplements It can be used as industrial materials that serve as fillers or modifiers for industrial materials, rubber, plastics, etc., and agricultural chemical materials that serve as agricultural chemical carriers.

  -Among the composites, the amorphous calcium citrate / amorphous calcium carbonate composite is formed by combining amorphous calcium citrate and amorphous calcium carbonate. The solidified body using this complex of amorphous calcium citrate / amorphous calcium carbonate is considered to show different disintegration from the solidified body using amorphous calcium citrate / crystalline calcium carbonate. The speed can be finely controlled.

  In the method of manufacturing the composite, quick lime is added to a citric acid aqueous solution to form a suspension, carbon dioxide gas is introduced into the suspension, and amorphous calcium citrate / calcium carbonate composite is precipitated. is there. For this reason, the amorphous calcium citrate / calcium carbonate complex can be easily manufactured by a simple process, and the manufacturing cost can be reduced.

  -In the production of the complex, it is possible to easily produce an amorphous calcium citrate / amorphous calcium carbonate complex by using 7 to 9 mol of quick lime with respect to 1 mol of citric acid in the citric acid aqueous solution. it can.

  -The composite can produce a solidified body (tablet) according to a conventional method, and can improve handling properties. In addition, the amorphous calcium citrate / calcium carbonate complex can be a composite material with polylactic acid or the like. When this composite material was immersed in a simulated body fluid and apatite formation was confirmed by electron microscope observation and X-ray diffraction, the formation of hydroxyapatite and carbonate apatite was observed. It may be applicable as a material.

Hereinafter, although the embodiment will be described more specifically with reference to examples and comparative examples, the present invention is not limited to these examples.
Example 1
After adding 300 g of quicklime powder to 2 L of an aqueous citric acid solution having a concentration of 0.3 M and reacting for 140 minutes, carbon dioxide gas was blown into the suspension at 20 ° C. at a flow rate of 2 L / min. Citric acid: quicklime = 1 mol: 9 mol. Then, after 2 hours, 3 hours, 4 hours, 5 hours and 6 hours, the products were collected by filtration and dried at about 105 ° C. to obtain Sample 1. FIG. 1 shows an X-ray diffraction pattern of each sample. In FIG. 1, P represents slaked lime (calcium hydroxide), L represents quick lime (calcium oxide), V represents calcium carbonate of a vaterite type crystal, and C represents a calcium carbonate peak of a calcite type crystal.

As shown in the X-ray diffraction diagram of FIG. 1, by blowing carbon dioxide gas for 4 to 5 hours, an amorphous calcium citrate / amorphous calcium carbonate complex as shown in FIG. 2 can be obtained. It was. When carbon dioxide gas was blown for 6 hours, an amorphous calcium citrate / crystalline calcium carbonate composite containing calcium carbonate of vaterite type crystals and calcite type crystals was obtained.
(Example 2)
300 g of quicklime powder is added to 2 liters of three kinds of citric acid aqueous solutions having concentrations of 0.2M, 0.3M and 0.35M, respectively, so that citric acid: quicklime = 1 mol: 7.7, 8.9 and 13.4 mol. The molar ratio was added. The blowing time of carbon dioxide gas is 4.5 hours when the molar ratio is 7.7, 5.0 hours when the molar ratio is 8.9, and 5.5 hours when the molar ratio is 13.4. Reaction and treatment were carried out in the same manner as in 1. In this case, when the citric acid concentration is 0.2M, the molar ratio is 13.4, when the citric acid concentration is 0.3M, the molar ratio is 8.9, and when the citric acid concentration is 0.35M. Has a molar ratio of 7.7.

An X-ray diffraction diagram of the obtained powder is shown in FIG. In FIG. 3, CaO / CA represents the molar ratio of quicklime / citric acid. From the results shown in FIG. 3, amorphous calcium citrate / amorphous calcium carbonate composites could be obtained when the molar ratio was 7.7 and 8.9. When the molar ratio was 13.4, calcium carbonate peaks of the vaterite type crystal and the calcite type crystal were observed, and it was an amorphous calcium citrate / crystalline calcium carbonate complex.
(Example 3)
Sample prepared in the same manner as in Example 1, a mixture of commercially available calcium citrate (manufactured by Nacalai Tesque) and commercially available calcium carbonate (manufactured by Wako Pure Chemical Industries, Ltd.) or calcium carbonate (commercially available product or vaterite type) Crystals), 1 g each, were pressure-molded (pressure 1 t / cm ² ) to produce tablets. As a result, tablets were not obtained using only commercially available calcium carbonate, but tablets could be prepared for the sample, the mixture or the vaterite-type calcium carbonate prepared by the same method as in Example 1.

As shown in FIGS. 4A to 4C, the obtained tablets 10 were immersed in 3 ml of water 12 in the petri dish 11 and allowed to stand for 5 hours. 4A shows the tablet 10a of the sample 1, FIG. 4B shows the tablet 10b of the mixture, and FIG. 4C shows the tablet 10c of the vaterite type calcium carbonate. From the results shown in FIG. 4A, the tablet 10a of the sample 1 produced by the same method as in Example 1 did not disintegrate, whereas the tablet 10b of the mixture shown in FIG. 4B and FIG. The vaterite-type calcium carbonate tablet 10c shown in c) disintegrated without maintaining its shape.
Example 4
Samples obtained in the same manner as in Example 1, commercially available calcium carbonate and food pigments were mixed at various ratios, and 1.05 g of each was pressure-molded (pressure 1 t / cm ² ) to give tablets (Sample 4-1 ~ 4-4) were produced. Table 1 shows the blending amount (mass%) of the amorphous calcium citrate / calcium carbonate complex (sample 1) and commercially available calcium carbonate. Food coloring is used as an example of an active ingredient, and 0.05 g was added to all samples.

得られた各錠剤をそれぞれ３ｍｌの水に浸して、１５分後と２４時間後に水の一部を回収し、波長４０５ｎｍの光の吸光度を測定した。そして、各試料において、食品色素溶出量（％）を１５分後と２４時間後について図５に示した。図５に示した結果より、食品色素は時間の経過とともに溶出量が増加し、その溶出速度は試料１の割合が低いほど速いことが判明した。言い換えれば、試料１の非晶質クエン酸カルシウム・炭酸カルシウムで作製した固化体は溶媒中で崩壊しにくく、その配合量を変化させることにより、溶媒中での有効成分（食品色素、微生物又は酵素）の溶出速度（放出速度）又は溶出量（放出量）を制御できることが分かった。
（実施例５）
ポリ乳酸２ｇを２０ｍｌのジクロロメタンで溶解した液と、実施例１と同様な方法で得た試料２ｇを１０ｍｌのジクロロメタンで懸濁した液とを混合した。この混合液を脱気した後、シャーレ上にキャストし、乾燥させて、試料１とポリ乳酸の複合材料（図６参照）を作製した（キャスト法）。この複合材料を擬似体液中に３７℃で２１日間浸漬した後、表層を走査型電子顕微鏡で観察した（図７参照）。さらに、Ｘ線回折による解析を行い、その結果を図８に示した。図８（ｂ）は複合材料のＸ線回折図を示し、図８（ａ）は擬似体液に浸漬後の状態を示す。

Each of the obtained tablets was immersed in 3 ml of water, and a part of the water was collected after 15 minutes and 24 hours, and the absorbance of light having a wavelength of 405 nm was measured. And in each sample, food coloring matter elution amount (%) was shown in FIG. 5 after 15 minutes and after 24 hours. From the results shown in FIG. 5, it was found that the amount of elution of food dye increased with time, and the elution rate was faster as the ratio of sample 1 was lower. In other words, the solidified material prepared from the amorphous calcium citrate / calcium carbonate of Sample 1 is not easily disintegrated in the solvent, and the active ingredient (food pigment, microorganism or enzyme in the solvent is changed by changing the amount of the solidified product. It was found that the elution rate (release rate) or the elution amount (release amount) can be controlled.
(Example 5)
A solution in which 2 g of polylactic acid was dissolved in 20 ml of dichloromethane was mixed with a solution in which 2 g of a sample obtained in the same manner as in Example 1 was suspended in 10 ml of dichloromethane. After degassing this mixed solution, it was cast on a petri dish and dried to produce a composite material of sample 1 and polylactic acid (see FIG. 6) (casting method). The composite material was immersed in a simulated body fluid at 37 ° C. for 21 days, and then the surface layer was observed with a scanning electron microscope (see FIG. 7). Further, analysis by X-ray diffraction was performed, and the results are shown in FIG. FIG. 8 (b) shows an X-ray diffraction pattern of the composite material, and FIG. 8 (a) shows a state after immersion in the simulated body fluid.

From the results shown in FIG. 8 (a), precipitation of hydroxyapatite [Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ] and carbonate apatite [Ca ₁₀ (PO ₄ ) ₆ CO ₃ ] was confirmed (FIG. 8 ( a)). Therefore, a calcium material composed of an amorphous calcium citrate / calcium carbonate complex can be used as an active ingredient, and has been found to be usable as a biomaterial used for bone repair.

It should be noted that the embodiment described above can be modified and embodied as follows.
The calcium carbonate in the amorphous calcium citrate / calcium carbonate complex may contain Aragonite type crystals (orthorhombic crystals) and the like.

-Chitosan or the like can also be used as a material for forming the composite material.
Next, the technical idea that can be grasped from the embodiment will be described below.
・ Add quick lime to citric acid aqueous solution and react to form a suspension of calcium citrate and slaked lime, introduce carbon dioxide into the suspension, and combine amorphous calcium citrate and calcium carbonate The method for producing an amorphous calcium citrate / calcium carbonate complex according to claim 1 or 2. According to this production method, the amorphous calcium citrate / calcium carbonate complex can be easily produced in a simple process.

  Solidification of the amorphous calcium citrate / calcium carbonate composite obtained by pressurizing and molding the amorphous calcium citrate / calcium carbonate composite according to claim 1 body. This solidified body is easy to handle and can control the disintegration rate in the solvent.

The X-ray diffraction diagram which shows the result of having analyzed the powder produced in Example 1 by X-ray diffraction. The electron micrograph of the powder obtained when it was made to react for 5 hours among Example 1. FIG. The X-ray diffraction diagram which shows the result of having analyzed the powder produced in Example 2 by X-ray diffraction. (A) is explanatory drawing which shows the state which immersed the powder tablet produced in Example 1 in water, (b) is explanatory drawing which shows the state which immersed the tablet of the mixture of calcium citrate and calcium carbonate in water, c) Explanatory drawing which shows the state which immersed the tablet of the vaterite type | mold calcium carbonate powder in water. The graph which shows the food pigment elution amount in 15 minutes and 24 hours after about Sample 4-1 to Sample 4-4. An electron micrograph of a composite material of amorphous calcium citrate / amorphous calcium carbonate and polylactic acid. The electron micrograph after the material of FIG. 6 was immersed in the simulated body fluid for 21 days. (A) is an X-ray diffraction pattern for the composite material shown in FIG. 7, and (b) is an X-ray diffraction pattern for the composite material shown in FIG.

Claims (4)

An amorphous calcium citrate / calcium carbonate composite comprising a composite of amorphous calcium citrate and amorphous calcium carbonate or crystalline calcium carbonate. 2. The amorphous calcium citrate / calcium carbonate composite according to claim 1, wherein the amorphous calcium citrate / amorphous calcium carbonate is composed of a composite. Prepare a suspension of quick lime added to citric acid aqueous solution, introduce carbon dioxide into the suspension, and combine amorphous calcium citrate and amorphous calcium carbonate or crystalline calcium carbonate to precipitate The method for producing an amorphous calcium citrate / calcium carbonate complex according to claim 1 or 2, wherein: The amorphous calcium citrate / amorphous calcium carbonate complex is formed using 7 to 9 moles of quicklime with respect to 1 mole of citric acid in the citric acid aqueous solution. A method for producing a crystalline calcium citrate / calcium carbonate complex.

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