JP7083975B2 - Antibacterial composition, bone regeneration material containing antibacterial composition, and method for producing the same. - Google Patents

Description

The present invention relates to an antibacterial composition composed of calcium carbonate particles carrying silver, a bone regeneration material containing the antibacterial composition, and a method for producing the same.

Bacterial postoperative infections may occur when performing surgical procedures to implant implant material into the affected area. As a countermeasure for this, in addition to administering an antibiotic to the affected area, attempts have been made to make the implant material itself have antibacterial properties.

Recently, biodegradable fibers contain particles of calcium phosphate compounds such as β-tricalcium phosphate (β-TCP) and hydroxyapatite (HAp), and after being implanted in vivo, the biodegradable fibers are decomposed and absorbed. A type of bone regeneration material that elutes calcium phosphate and promotes bone formation has been proposed (Patent No. 6039076, etc.). As a method of giving antibacterial properties to this type of bone regeneration implant material, silver is carried on calcium phosphate particles contained in biodegradable fibers, and the biodegradable fibers are decomposed in the body to dissolve the calcium phosphate particles. A design has been proposed in which the silver carried along with it is eluted to exert antibacterial properties (Flexible, silver containing nanocomposites for the repair of bone defects: antimicrobial effect against E. coli infection and comparison to tetracycline, Journal of Materials). Chemistry 2008 Oliver D. Schneider et al. Etc.)

Silver is an excellent antibacterial metal with a broad antibacterial spectrum and is widely used for antibacterial treatment of various types of materials. The exact mechanism of silver's antibacterial properties has not yet been elucidated, but Ag ⁺ ions are known to have a strong bactericidal effect. Recently, it has been reported that silver nanoparticles having a particle size of 100 nm or less have antibacterial properties. The reason why silver nanoparticles exert antibacterial properties has not been clarified yet, and the possibility that silver nanoparticles attack bacteria in a metallic state and that silver nanoparticles partially ionize in solution to attack bacteria. (Analysis of silver chemical state in antibacterial fibers carrying silver nanoparticles March 9, 2016 (Wednesday) Nagoya City, Aichi Prefecture "Aichi Synctro Hikari Center Achievement Presentation" Kiyono et al.). Comparing the degree of influence of silver ions and silver nanoparticles on the living body, experimental results have been reported that silver ions cause cell death at a lower concentration than silver nanoparticles (Forum 2008: Sanitary Pharmacy / Environmental Toxicology). 2008.10.17 (Kumamoto) Nobuhiko Miura et al.).

After implanting a type of bone regeneration implant material in which particles of a calcium compound carrying silver are contained in biodegradable fibers in a living body, the biodegradable resin is hydrolyzed by body fluid or calcium is formed by osteoclasts. When the compound is dissolved and decomposed, the silver carried on the calcium compound is eluted. The eluted silver metal or its Ag ⁺ ions have antibacterial properties that kill bacteria, but at the same time may be cytotoxic to osteoblasts and surrounding cells that need to proliferate. Therefore, in order to suppress the development of cytotoxicity, the amount of silver eluted from the calcium compound must be controlled below a certain level. Since there is a trade-off between antibacterial properties and cytotoxicity, it is important to select the optimum carrying amount of silver.

Furthermore, in the above-mentioned type of bone regeneration implant material, silver is eluted in the process of dissolving the calcium compound in the body. Therefore, in order to develop postoperative antibacterial properties, the calcium compound must be implanted in the body and then the calcium compound. Needs to be dissolved. Although β-TCP has excellent bone-forming ability, it dissolves slowly in contact with body fluids, so that the expression of antibacterial activity is delayed when the partner calcium compound carrying silver is β-TCP.

Japanese Patent No. 5179124

Flexible, silver containing nanocomposites for the repair of bone defects: antimicrobial effect against E. coli infection and comparison to tetracycline, Journal of Materials Chemistry 2008 Oliver D. Schneider et al. "Analysis of silver chemical state in silver nanoparticle-supported antibacterial fiber" March 9, 2016 (Wednesday) Nagoya City, Aichi Prefecture "Aichi Synctro Hikari Center Achievement Presentation" Kiyono et al. "Biological Impact Assessment of Silver Nanoparticles" Forum 2008: Hygiene Pharmacy / Environmental Toxicology 2008.10.17 (Kumamoto) Nobuhiko Miura et al.

Under the above circumstances, it is contained in the bone regeneration material, and after the bone regeneration material is implanted in the body, it exhibits antibacterial properties at an early stage along with the decomposition and absorption of calcium compounds, and also exhibits cytotoxicity. There has been a demand for a highly safe silver-based antibacterial composition with less fear.

The inventors of the present invention have conceived to use calcium carbonate as a partner for supporting silver in order to solve the above-mentioned problems. Calcium carbonate is an inexpensive material with high biocompatibility. In addition, since the rate of decomposition and absorption in the living body is high, it can be expected that the carried silver will be eluted at an early stage. Based on this idea, the inventors of the present invention added nitric acid to prevent the formation of a white precipitate in a calcium acetate solution, and then added a silver nitrate solution to prepare a sample solution, which was subjected to an ultrasonic spray thermal decomposition method. As a result, it was found that most of the silver ions in the silver nitrate solution were not combined with the carbonate ions and were precipitated as silver nanoparticles on the surface of the synthesized hollow-shaped calcite phase calcium carbonate particles.

Based on the above findings, the inventors of the present invention, as a result of further studies, use silver nanoparticles-supported calcium carbonate particles synthesized by the ultrasonic spray thermal decomposition method as an antibacterial inorganic filler (antibacterial composition). I came up with the idea of using it. Since the antibacterial composition of the present invention has a high rate of dissolution and decomposition when calcium carbonate comes into contact with a biological liquid, the carried silver nanoparticles are eluted at an early stage. Although it depends on the elution concentration of silver ions from silver nanoparticles, the concentration at which silver nanoparticles kill cells is considerably lower than the concentration at which silver ions kill cells (see Non-Patent Document 3), so that after implanting It is considered unlikely that the eluted silver nanoparticles will cause cytotoxicity. Based on this idea, the inventors of the present invention can decompose biodegradable fibers and calcium carbonate by incorporating calcium carbonate particles (calcite phase) carrying silver nanoparticles into the biodegradable fibers. By going through the steps of dissolution / decomposition and elution of silver nanoparticles, antibacterial properties can be exhibited at an early stage, and in that case, cytotoxicity is exhibited as long as the elution amount of silver nanoparticles is below a certain level. We have found that there is little risk of calcium carbonate, and have arrived at the present invention.

The antibacterial composition of the present invention can be used as an auxiliary addition as an antibacterial inorganic filler to a bone regeneration material made of biodegradable fibers containing calcium phosphate such as β-TCP.

The antibacterial composition of the present invention is also used as an antibacterial inorganic filler to be supplementarily added to a bone regeneration material composed of biodegradable fibers together with silver-supported β-TCP powder in which β-TCP is supported by silver. be able to. That is, when the biodegradable fiber contains a powder prepared by adding a small amount of the silver nanoparticles-supported calcium carbonate particles of the present invention to the silver-supported β-TCP particles, the dissolution after implantation is faster than that of β-TCP. Silver is eluted early from calcium carbonate and develops antibacterial properties earlier than silver-bearing β-TCP. Then, by dissolving β-TCP later than calcium carbonate, the silver ion carried on β-TCP is eluted and the late antibacterial property is exhibited. The system has the potential to respond to both early and late infections by synthesizing and mixing two differently soluble powders (both carrying Ag).

According to the present invention, since it is synthesized by using an ultrasonic spray thermal decomposition method, silver nanoparticles-supported calcium carbonate having a desired particle size (median diameter) can be obtained by adjusting the frequency of ultrasonic waves and the interfacial tension of the sample solution. Particles can be obtained. The preferable particle size of the calcium carbonate particles carrying silver nanoparticles is determined by the relationship with the outer diameter (median diameter) of the biodegradable fiber containing the silver nanoparticles. When spinning biodegradable fibers by the electrospinning method, if the particle size of the silver nanoparticles-supported calcium carbonate particles is as large as the outer diameter of the biodegradable fibers, biodegradation containing silver nanoparticles-supported calcium carbonate particles is performed. Spinning of sex fibers becomes difficult. When the outer diameter of the biodegradable fiber is about 30 to 50 μm, the particle size of the silver nanoparticles-supported calcium carbonate particles is preferably about 0.1 to 10 μm, more preferably about 1 to 5 μm. ..

Since the calcium carbonate particles supported by silver nanoparticles of the present invention are hollow and substantially spherical, they are lightweight and advantageous for kneading into a polymer in terms of shape.

Since the silver nanoparticles-supported calcium carbonate particles of the present invention are synthesized directly from the solution, the distribution of silver in the particles is uniform, and since the supported silver is nanoparticles, it is highly soluble and antibacterial. It is advantageous for the expression of. When silver is homogeneously dispersed on the surface of calcium carbonate particles, properties on the material side such as solubility are also uniformly expressed, and as a result, high reproducibility of product performance can be obtained.

The particle size of the silver nanoparticles precipitated on the surface of the silver nanoparticles-supported calcium carbonate particles of the present invention is as small as 10 nm to 500 nm. When the particle size of the silver nanoparticles is small, the specific surface area is large, so that the apparent solubility of the silver nanoparticles is high.

As the biodegradable resin containing the silver nanoparticles-supported calcium carbonate particles of the present invention, poly L-lactic acid (PLLA) and poly (lactide-co-glycolide) copolymer (PLGA) can be preferably used. Since PLGA has a higher rate of hydrolysis than PLLA, it is a more suitable resin for early elution of the contained silver nanoparticles-supported calcium carbonate particles.

A sample solution for synthesizing silver-supported calcium carbonate and a method for preparing silver-supported calcium carbonate powder by the ultrasonic spray pyrolysis method of the present invention are shown. The ultrasonic spray thermal decomposition apparatus used in the ultrasonic spray thermal decomposition method of this invention is shown. The results of measuring the crystal phase of silver-containing calcium carbonate (hereinafter sometimes abbreviated as Ag-CaCO3) synthesized by the ultrasonic spray pyrolysis method of the present invention by powder X-ray diffraction method (XRD) are shown. The results of elemental analysis (high frequency inductively coupled plasma emission spectroscopy; ICP-AES) of Ag-CaCO3 synthesized by the ultrasonic spray thermal decomposition method of the present invention are shown. A scanning electron microscope (SEM) photograph of Ag-CaCO3 particles synthesized by the ultrasonic spray pyrolysis method of the present invention is shown. The particle size distribution of Ag-CaCO3 particles synthesized by the ultrasonic spray pyrolysis method of the present invention is shown. The specific surface area of Ag-CaCO3 particles synthesized by the ultrasonic spray pyrolysis method of the present invention is shown. The outline of the ion elution test performed by immersing the Ag-CaCO3 particles synthesized by the ultrasonic spray pyrolysis method of the present invention in HEPES Buffer is shown. The results of immersing Ag-CaCO3 particles synthesized by the ultrasonic spray pyrolysis method of the present invention in HEPES Buffer and examining the elution of Ca ²⁺ ions are shown. The results of immersing Ag-CaCO3 particles synthesized by the ultrasonic spray pyrolysis method of the present invention in HEPES Buffer and examining the elution of Ag ⁺ ions are shown. The results of the ion elution test conducted by immersing the Ag-CaCO3 particles synthesized by the ultrasonic spray pyrolysis method of the present invention in HEPES Buffer are shown in comparison with the minimum inhibitory concentration (MIC). The antibacterial property was evaluated by inoculating the Ag-CaCO ₃ particles synthesized by the ultrasonic spray pyrolysis method of the present invention in an LB medium, inoculating the bacteria in the immersion liquid obtained, and measuring the number of bacteria after culturing. An overview is given. (1) Staphylococcus aureus (S. aureus) and (2) Escherichia coli (E) were inoculated into the dipping solution obtained by immersing Ag-CaCO ₃ particles synthesized by the ultrasonic spray thermal decomposition method of the present invention in an LB medium. The results of evaluating the antibacterial property by measuring the number of bacteria after culturing E. coli) are shown. The appearance (pattern A) of the kneaded product prepared by the above method is shown. The appearance (pattern A) of the cotton-like material produced by the above method is shown. The fiber surface microstructure (low enlargement, pattern A) of the produced cotton-like material is shown. The fiber surface microstructure (high enlargement, pattern A) of the produced cotton-like material is shown.

Hereinafter, embodiments for carrying out the present invention will be described with reference to the drawings.

(A) Synthesis of Ag-CaCO ₃
(1) Preparation of sample solution Add nitric acid to prevent white precipitation to each predetermined amount of calcium acetate monohydrate (CH ₃ COO) ₂ Ca · H ₂ O) solution shown in Fig. 1, and silver nitrate (AgNO ₃ ). ) Solutions were mixed to obtain sample solutions (Ag-CaCO ₃ (0), Ag-CaCO3 (1), Ag-CaCO3 (5), Ag-CaCO3 (10)). In FIG. 1, the prepared sample is represented by the abbreviation Ag-CaCO3 (x). x indicates the amount of Ag added. The amount of Ag added [mol /%] was calculated by the formula of Ag [mol] / CaCO3 [mol] x 100.

(2) Ultrasonic spray pyrolysis Silver-supported calcium carbonate was synthesized from the above sample solution using the ultrasonic spray pyrolysis apparatus shown in FIG. The solution is sprayed by ultrasonic waves, and heat of 600 ° C. is applied in an electric furnace to precipitate a salt (precursor of calcium carbonate). As a result of the thermal decomposition of acetate ions from the salt, hollow substantially spherical calcium carbonate particles containing silver were synthesized. Then, the obtained powder was subjected to a washing treatment (ultrapure water 3 times, acetone 3 times) and freeze-dried over 1 day.

(3) XRD, ICP measurement of silver nanoparticles-supported calcium carbonate particles Silver synthesized from the above sample solutions AgCaCO3 (0), Ag-CaCO3 (1), Ag-CaCO3 (5), Ag-CaCO3 (10) The results of XRD and ICP measurement of the carried calcium carbonate particles are shown in FIGS. 3 (1) and 3 (2). From the results of XRD and ICP-AES measurements, the synthesized silver-bearing calcium carbonate was a mixed phase of calcite-type calcium carbonate and silver. The silver content of the adjusted powder was almost equal to the silver loading expected from the charged solution.

(4) SEM measurement of silver nanoparticle-bearing calcium carbonate particles Synthesized from the above sample solutions Ag-CaCO ₃ (0), Ag-CaCO ₃ (1), Ag-CaCO ₃ (5), Ag-CaCO ₃ (10) FIG. 4 shows the results of taking SEM photographs of each of the silver-supported calcium carbonate particles. In Ag-CaCO ₃ (5) and Ag-CaCO ₃ (10), it was observed that silver was distributed almost uniformly on the surface of CaCO ₃ particles as nanoparticles.

(5) Measurement of particle size distribution and specific surface area of silver-supported calcium carbonate particles From the sample solutions AgCaCO3 (0), Ag-CaCO3 (1), Ag-CaCO3 (5), Ag-CaCO3 (10) in Fig. 5 (1). The particle size distribution of each synthesized silver-supported calcium carbonate particle is shown, and FIG. 5 (2) shows the specific surface area of each particle. Most of the prepared powders were micro-sized, and the median diameter of each was in the range of 1.8 to 3.5 μm, which is a size suitable for use as an inorganic filler.

(6) Ion elution test Fig. 6 shows each silver carrier synthesized from the sample solutions Ag-CaCO ₃ (0), Ag-CaCO ₃ (1), Ag-CaCO ₃ (5), Ag-CaCO ₃ (10). The ion elution test performed on the calcium carbonate particles is shown.
Weigh 0.1 g of sample Ag-CaCO ₃ (0), Ag-CaCO ₃ (1), Ag-CaCO ₃ (5), Ag-CaCO ₃ (10) in 10 mL of 20 mM HEPES Buffer (pH = 7.30). After soaking in 1 day, 3 days, 5 days, 7 days, 10 days, 14 days, 21 days and 28 days, the concentration of Ca and Ag contained in the supernatant was measured by ICP-AES. The results of the ion elution test are shown in FIGS. 7 (1) and 7 (2). From the results of the test, it was confirmed that calcium continued to dissolve during the test period with almost the same behavior regardless of the silver content. In addition, it was confirmed that silver was eluted during the test period in all of the samples (1), (5), and (10). From this result, it is considered that silver-supported calcium carbonate particles may promote bone formation over a long period of time and develop antibacterial properties.

(7) Antibacterial evaluation FIG. 8 shows Ag-CaCO3 (1), Ag-CaCO3 (5), Ag-CaCO3 in comparison with the minimum inhibitory concentration (the lowest concentration at which the antibacterial agent suppresses bacterial growth). The result of observing the ion elution concentration from (10) is shown. Since the minimum inhibitory concentration of Staphylococcus aureus is 2.0 ppm, the results above that are shown in bold. It is considered that antibacterial activity is exhibited against Staphylococcus aureus at the silver concentration and the number of days in bold.

FIG. 9 shows the method of antibacterial evaluation test performed on the samples AgCaCO ₃ (0), Ag-CaCO ₃ (1), Ag-CaCO ₃ (5), and Ag-CaCO ₃ (10). FIGS. 10 (1) and 10 (2) show antibacterial evaluation tests performed on the samples AgCaCO ₃ (0), Ag-CaCO ₃ (1), Ag-CaCO ₃ (5), and Ag-CaCO ₃ (10). .. Ag-CaCO ₃ (1), Ag-CaCO ₃ (5), and Ag-CaCO ₃ (10) greatly suppressed the growth of bacteria. This result is considered to indicate that the antibacterial property was exhibited by the Ag ⁺ ion eluted from the powder.

(B) Production of biodegradable fiber containing Ag-CaCO3
Ag-CaCO ₃ (5) (concentration is calculated as "[Ag mol / CaCO ₃ mol] x 100") powder and biodegradable resin (PLLA) and β, which are materials for cotton-shaped artificial bone. -Using TCP and silicon-containing batelite (SiV), knead while heating with a heat kneader (kneader) to prepare a complex (kneaded product). In the preparation of the kneaded product, the composition is "30% PLLA: 40% β-TCP: 24.76% SiV: 5.24% Ag-CaCO ₃ " (Pattern A) and "30% PLLA: 40% β-TCP: 26.86%". SiV: 3.14% Ag-CaCO ₃ ”(Pattern B) was prepared with two composition patterns. In the manufacturing procedure, the temperature of the kneader kneading tank was set to 190 degrees, and after 90 minutes of preheating, PLLA was first added. After 3 minutes and 30 seconds, a premixed powder of β-TCP, SiV, and Ag-CaCO ₃ was added. Nine minutes and twelve minutes after the start of kneading, the kneader's mixing blade was rotated in the reverse direction for about 20 seconds to improve kneading. After 14 minutes and 30 seconds from the start of kneading, the kneaded material was collected. FIG. 11 shows the appearance (pattern A) of the kneaded product produced by the above method.

Ag-CaCO ₃ is formed by dissolving the kneaded material in an organic solvent to prepare an electrospinning (ES) spinning solution, forming it into biodegradable fibers by discharging it under a voltage, and depositing it in a cotton-like form in a collector. A cotton-like artificial bone made of contained biodegradable fibers is obtained. The organic solvent for dissolving the kneaded product was chloroform, and the solution was prepared so that the concentration of PLLA in the ES spinning solution was 8% by weight. The mixture was rotated overnight (about 15 hours) with a stirrer, and the kneaded product dissolved in chloroform was used as an ES spinning solution and installed in an ES device. A collector filled with ethanol was installed in the ES device, and the fibers spun with the ethanol liquid level as the ground were adjusted so that they jumped into the liquid, and electrospinning was performed. The equipment setting items were an applied voltage of 20 kV, a solution extrusion speed of 15 mL / hr, and a Taylor cone cleaning interval of 2 minutes. The inside of the ES device during spinning was controlled so that the temperature was 30 degrees or less and the humidity was less than 50% in order to adjust the volatilization timing of the organic solvent from the fibers in flight. FIG. 12 shows the appearance (pattern A) of the cotton-like material produced by the above method.

When performing ES, by selecting an appropriate organic solvent and adjusting the extrusion amount of the spinning solution, the applied voltage, and the concentration of the resin (PLLA, etc.) in the spinning solution, ES, which is originally a nano-unit fiber molding method, is used. While using the device, it is possible to increase the diameter of the fiber to produce a fiber of 30 to 100 μm. Micro-unit fibers tend to serve as scaffolds for cell colonization, and the complex shape of cotton shape has the aim of increasing the surface area three-dimensionally and enhancing cell colonization and proliferation. As a result of observation with a scanning electron microscope (SEM), it was confirmed that the produced cotton-like material is an aggregate of flat fibers of 30-100 μm, which is a feature of the cotton-shaped artificial bone filler. It was confirmed that the supported inorganic fillers (β-TCP, SiV, Ag-CaCO ₃ ) were evenly supported on the fiber surface. FIG. 13 shows the fiber surface microstructure (low enlargement, pattern A) of the produced cotton-like material. It can be seen that it is a flat fiber and the fiber diameter is about 50 μm. FIG. 14 shows the fiber surface microstructure (high enlargement, pattern A) of the produced cotton-like material. It can be seen that the inorganic fillers (β-TCP, SiV, Ag-CaCO ₃ ), which are the materials, are evenly supported on the fiber surface.

(C) Evaluation of antibacterial and cytotoxicity of biodegradable fibers containing Ag-CaCO3
For Ag-CaCO3, three patterns of control "0", silver-containing "1", "5", and "10" are prepared for each concentration. The concentration is calculated by "[Ag mol / CaCO ₃ mol] x 100". Analysis of the synthesized Ag-CaCO ₃ by X-ray diffraction (XRD) revealed that it was a mixed phase of calcite-type calcium carbonate and silver. When used as a medical material, it was washed with ultrapure water and acetone as a step to remove "nitric acid" which is considered to be harmful to the living body. Since the peak of ion (NO _3- ⁾ did not appear, it is considered that the removal of nitric acid was successful. In addition, as a result of elemental quantitative analysis of Ag-CaCO3 powder by ICP-AES, the expected amount of silver was carried at all silver concentrations. In the observation of the surface morphology of the powder by SEM, when the silver concentration was high, many particles with a distorted shape and particles with small protrusions were observed.

XRD analysis showed no silver carbonate formation in the synthesized Ag-CaCO3. Since silver carbonate has low solubility, if it is produced as a by-product in the process of synthesis, the synthesis of silver nanoparticles-supported calcium carbonate particles is suppressed by that amount. As a result, silver is taken in a relatively large amount in the synthesis of silver carbonate, so that the antibacterial property is lowered. Therefore, it is considered that the fact that silver carbonate is not produced as a by-product using the ultrasonic spray pyrolysis method has a positive effect on the antibacterial properties of the material.

In the antibacterial test of Ag-CaCO3 as a material, the antibacterial property was confirmed in all the samples of "1" or more in the shake method.
Regarding cytotoxicity, it has been confirmed that Ag of Ag-CaCO3 exists as silver nanoparticles, and since the cytotoxicity of silver nanoparticles is lower than that of silver ions of the same concentration, cells of the material of Ag-CaCO3 The toxicity is expected to be low.

Although the embodiments for carrying out the present invention have been described above, the present invention is not limited to these, and various modifications can be made within the scope of the technical idea of the present invention.
The material for bone regeneration containing silver nanoparticles-supported calcium carbonate particles is not limited to the material made of biodegradable fibers, and may be other molded products or granules.

Claims (11)

An antibacterial composition contained in biodegradable fibers.
The antibacterial composition is hollow substantially spherical calcium carbonate particles in which silver nanoparticles are distributed substantially uniformly on the surface and precipitated.
An antibacterial composition having a median diameter of 0.1 to 10 μm.
The antibacterial composition according to claim 1, wherein the calcium carbonate contained in the calcium carbonate particles is a calcite phase.
The silver-based antibacterial composition according to claim 1 or 2, wherein the silver nanoparticles have a median diameter of 10 to 500 nm.
A method for producing an antibacterial composition contained in biodegradable fibers.

After adding nitric acid to the calcium acetate solution, the sample solution prepared by mixing the silver nitrate solution is subjected to ultrasonic spray pyrolysis.

By synthesizing hollow, substantially spherical calcium carbonate particles in which silver nanoparticles are distributed substantially uniformly on the surface and precipitated.
A method for producing an antibacterial composition, wherein the ultrasonic spray pyrolysis is adjusted so that the median diameter of the antibacterial composition is 0.1 to 10 μm.
The method for producing an antibacterial composition according to claim 4, wherein the calcium carbonate is a calcite phase.
The method for producing an antibacterial composition according to any one of claims 4 to 5, wherein the silver nanoparticles have a median diameter of 10 to 500 nm.
A material for bone regeneration comprising biodegradable fibers containing the antibacterial composition according to any one of claims 1 to 3.

The biodegradable fiber contains at least one of poly Llactic acid or a poly (lactide-co-glycolide) copolymer and calcium phosphate.

The antibacterial composition and the calcium phosphate are contained in the biodegradable fibers in a substantially uniformly dispersed manner.
Silver nanoparticles-supported calcium carbonate particles Bone regeneration material.
The outer diameter of the biodegradable fiber is 10 to 50 μm.
The material for bone regeneration according to any one of claims 7.
A method for producing a bone regeneration material comprising biodegradable fibers containing the antibacterial composition according to any one of claims 1 to 3.

After adding nitric acid to the calcium acetate solution, the sample solution prepared by mixing the silver nitrate solution is subjected to ultrasonic spray pyrolysis.

By synthesizing hollow, substantially spherical calcium carbonate particles in which silver nanoparticles are distributed substantially uniformly on the surface and precipitated.
The ultrasonic spray pyrolysis was adjusted so that the median diameter of the antibacterial composition was 0.1 to 10 μm.

A biodegradable fiber is produced using a spinning solution prepared by containing the antibacterial composition in a biodegradable resin.

A method for manufacturing a material for bone regeneration.
The method for producing a bone regeneration material according to claim 9, wherein the biodegradable fiber contains at least one of poly L-lactic acid or a poly (lactide-co-glycolide) copolymer and calcium phosphate.
The outer diameter of the biodegradable fiber is 10 to 50 μm.
The method for producing a bone regeneration material according to claim 9 or 10.

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