JPH07101710A - Antibacterial grain - Google Patents

Abstract

PURPOSE:To impart a sterilizing effect to grains in an area not in contact with food and to improve mixing property with a molded product by mixing a slurry containing amorphous calcium phosphate particles with an org. antibacterial agent, and antifungal metal ions and granulating the mixture. CONSTITUTION:A water-soluble polymer dispersant is added by 0.1-10wt.% to a suspension of calcium hydroxide under stirring to prepare a mixture soln. An aq. soln. of phosphonic acid is dropped to this mixture soln. under stirring to control the soln. to pH10 to 5 to obtain a slurry containing amorphous calcium phosphate particles 1 having about <=0.1mum particle diameter. To this slurry, an org. antifungal agent 13 and antifungal metal ions 2 dissolved in ethanol or methanol are mixed to obtain <=50wt.% solid content. The obtd. mixture slurry 3 is supplied with a fixed delivery pump 4 to a spray dryer 5 having 1-3kg/h performance and sprayed into a hot air flow at 200-250 deg.C while an atomizer 6 is fast rotated. Thus, antifungal grains 7 which are spherical porous grains and have 8-100mum particle diameter and >=70m<2>/g specific surface area are obtd. in a cyclone 8 by spray-dry granulating method.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention relates to pharmaceuticals, quasi drugs,
The present invention relates to highly safe antibacterial particles used for imparting antibacterial properties to medical tools, cosmetics, foods, kitchen appliances, packaging materials, filters, clothing, sundries and the like.

[0002]

2. Description of the Related Art Conventionally, a strong antibacterial property and heat resistance of a metal such as silver having a bactericidal action and a metal salt thereof have been noted, and as described in JP-A-5-154, the above-mentioned metal and its An antibacterial composition in which an antibacterial silver compound is adsorbed and supported on a physiologically inert inorganic carrier in order to safely obtain a molded product having a long-term antibacterial property by mixing a metal salt with a synthetic resin or the like, or An antibacterial zeolite composition in which an antibacterial metal ion is supported on zeolite by ion exchange is known.

Further, as an antibacterial particle used for foods, etc., as disclosed in JP-A-3-47118, a hydroxyapatite antibacterial agent using a hydroxyapatite having high biocompatibility and high safety is disclosed. Agents are known. The hydroxyapatite antibacterial agent is one in which one or more kinds of antibacterial agents represented by hinokitiol, tannin, lysozyme, allylisothiocyanate, brotamine and sorbic acid are supported on hydroxyapatite.

Therefore, the above-mentioned hydroxyapatite antibacterial agent is one in which the antibacterial agent is strongly adsorbed specifically and does not elute / precipitate in a solution or the like. When used by being applied, the hydroxyapatite antibacterial agent that comes into contact with the food can sterilize or bacteriolyt bacteria that adhere to the food.

[0005]

However, although the food on the food tray has a bactericidal action and a bacteriostatic action on the part in contact with the food, hydroxyapatite strongly adsorbs the antibacterial agent. Therefore, there is a problem that no bactericidal action or bacteriostatic action is exerted on the non-contact portion with the food.

[0006]

In order to solve the above-mentioned problems, the antibacterial particle according to claim 1 comprises a slurry containing amorphous calcium phosphate particles, an organic antibacterial agent, and an antibacterial metal ion. It is characterized by being mixed and granulated.

The antibacterial particles according to claim 2 are obtained by mixing a slurry containing amorphous calcium phosphate particles and antibacterial metal ions, and adsorbing an organic antibacterial agent on the granulated particles. It is characterized by being.

The antibacterial particle according to claim 3 is the antibacterial particle according to claim 1 or 2, wherein the organic antibacterial agent is allyl isothiocyanate.

Antibacterial metals for supplying the antibacterial metal ions include gold, silver, zinc, copper, tin, lead, arsenic, platinum, iron,
At least one metal selected from antimony, nickel, aluminum, barium, cadmium, and manganese, a mixture thereof, a metal compound thereof, or an aqueous solution thereof can be used.

Examples of the above-mentioned organic antibacterial agents include allyl isothiocyanate (CH ₂ = CHCH ₂ NCS), hinokitiol and terpenes, which are volatile at room temperature and have a bactericidal / bacteriostatic action. The organic antibacterial agent is dissolved in an alcohol which is freely miscible with water and mixed with the slurry or adsorbed on the granulated particles.

The above amorphous calcium phosphate (Amorphous
Calcium Phosphate: hereinafter abbreviated as ACP) A slurry containing particles is prepared by adding 0.1 to 10% by weight of a water-soluble polymer dispersant, for example, ammonium triacrylate salt, to a calcium hydroxide suspension with stirring. After adding 0.1 to 3% by weight to obtain a mixed solution, the mixed solution under stirring is adjusted to pH 10 to 5 by dropwise addition of an aqueous phosphoric acid solution to contain ACP fine particles having a particle size of about 0.1 μm or less.

A mixture obtained by mixing an organic antibacterial agent and antibacterial metal ions dissolved in ethanol or methanol into the slurry so as to have a solid content of 50% by weight or less is granulated by a spray drying granulation method or the like. To obtain antibacterial particles.

The above-mentioned ACP fine particles were subjected to powder X-ray analysis, and their patterns revealed that calcium phosphate [Ca ₃ (PO ₄ ) ₂
nH ₂ O] and its pattern is broad, confirming that it is amorphous calcium phosphate. In addition, the ACP fine particles are considered to be an electrostatically active substance because they contain water of crystallization, and it is presumed that various microbes and viruses are easily adsorbed.

Further, in order that the obtained antibacterial particles have a large specific surface area, the particle size of the ACP fine particles in the slurry is preferably 0.1 μm or less. When the antibacterial metal ion is added to the slurry in the form of metal powder or metal compound powder, the particle size of the metal powder or metal compound powder is preferably 20 μm or less in order to improve the solubility. Moreover, when the organic antibacterial agent and the antibacterial metal ion are added to the slurry, it is desirable that the mixing be performed at room temperature.

On the other hand, 90 ACP particles in the slurry
If it is more than wt%, the viscosity of the slurry will increase, so
Not suitable for granulation. By changing the content of ACP fine particles in the slurry within the range of 1 to 90% by weight, antibacterial particles having a desired average particle diameter can be obtained.

As the granulation method, the obtained particles are
It is not particularly limited as long as it is porous and has a substantially spherical shape with a particle size of 200 μm or less and can have a specific surface area of 10 m ² / g or more. For example, a spray drying granulation method may be used. Alternatively, a granulation method obtained by freeze-drying and pulverization, or a high-speed stirring granulation method may be used.

[0017]

【Example】

[Embodiment 1] The following will describe one embodiment of the present invention as Embodiment 1 with reference to FIG. First, the method for producing the antibacterial particles will be described. In the method for producing, the amorphous calcium phosphate (amorphous calcium phosphate) is used.
osphate: hereinafter abbreviated as ACP) A slurry containing particles is produced as follows. First, 0.5% by weight of ammonium triacrylate as a water-soluble polymer dispersant was added to a calcium hydroxide suspension with stirring to obtain a mixed solution.

Thereafter, to the above mixed solution, a phosphoric acid aqueous solution diluted with water 2 to 4 times was added dropwise until the pH reached to around 11, and then a phosphoric acid aqueous solution diluted with water 5 to 8 times was added dropwise. Then, the pH of the mixed solution was adjusted to 10 to 9 to obtain a slurry containing ACP fine particles having a particle size of about 0.1 μm or less.

Next, in the method for producing antibacterial particles, the slurry is diluted with ion-exchanged water to obtain an ACP slurry having a concentration of 20% by weight, and the ACP content in the ACP slurry is adjusted. Against
Anhydrous silver nitrate solution dissolved in ion-exchanged water was added to the above ACP slurry so as to have a concentration of 0.5 mol%, and allyl isothiocyanate was added so as to have a concentration of 10 mol% with the above AC.
P slurry was added and mixed with a stirring motor for 1 hour to obtain a mixture slurry. The allyl isothiocyanate was dissolved in ethanol before use.

Then, as shown in FIG. 1, the above mixture slurry 3 containing ACP particles 1, silver ions 2 and allyl isothiocyanate 13 was spray-dried by a metering pump 4 (L-8 manufactured by Okawara Kako Kikai Co., Ltd.). Supply to 5. The atomizer 6 of the spray dryer 5 is rotated at a high speed, and the mixture slurry 3 is granulated and dried by a spray granulation method in which a hot air flow for drying in the spray dryer 5 is sprayed to give allyl isothiocyanate and silver ions. Thus, antibacterial particles 7 to which was added were obtained.

Each substantially spherical antibacterial particle 7, which is an ACP granule containing allyl isothiocyanate and silver ions, obtained by granulation and drying, is 8 to 100 μm by a cyclone 8.
Each particle size was collected. At this time, the ultrafine powder that could not be collected by the cyclone 8 was separately collected by a bag filter (not shown) and collected.

The antibacterial particles 7 are prepared by the spray granulation method.
ACP particles 1 that are spherical and have a particle size of about 0.1 μm or less
Since it is used, it becomes porous. Antibacterial particles 7
The specific surface area of 70m ² / g was measured by BET method.
That was all.

The operating conditions for the spray-drying granulation were as follows. The supply rate of the mixture slurry 3 as a raw material by the metering pump 4 is 1 to 3 kg / h, and the temperature of the hot air heated by the electric heater 10 through the air filter 9 is equal to the inlet temperature of the hot gas chamber 11. 200 to 2
The outlet temperature at the discharge hole 12 connected to the cyclone 8 was controlled to 50 ° C. so as to always exceed 100 ° C., and the rotation speed of the atomizer 6 was set within the range of 10,000 to 37,000 rpm.

Further, using two types of spray dryers (FOC-20, OD-25G, FOC-25, OC-25, manufactured by Okawara Kako Kikai Co., Ltd.) which are scale-ups of the above spray dryers 5,
When the slurry supply rate was 100 kg / hr and the antibacterial particles were prepared under the other conditions in the same manner as described above, the same antibacterial particles as the antibacterial particles 7 by the spray dryer 5 were obtained. The antibacterial particles 7 thus obtained were substantially spherical.

[Embodiment 2] Next, another embodiment of the present invention will be described as Embodiment 2 as follows. The slurry in Example 1 above was diluted with ion-exchanged water,
An ACP slurry prepared to have an ACP concentration of 20% by weight was obtained, and an anhydrous silver nitrate solution dissolved in ion-exchanged water was added to the ACP content in the ACP slurry to 0.5%.
It was added to the above ACP slurry so as to be a mol% and mixed for 1 hour with a stirring motor to obtain a mixture slurry. The mixture slurry is granulated and dried as in Example 1 above,
A silver ion-containing ACP granules (not shown) having a particle size of 8 to 100 μm were obtained.

10 g of the above silver ion-containing ACP granules were sampled, a solution of 0.1 g of allyl isothiocyanate dissolved in 50 ml of ethanol was added thereto, and the mixture was stirred, and the obtained product was washed with ion-exchanged water and freeze-dried. Machine dry,
Further, it was dried separately with a dryer at 60 ° C. to obtain the same antibacterial particles as in Example 1.

Next, with respect to the antibacterial particles obtained in Examples 1 and 2, the production phase of each antibacterial particle was examined by an X-ray diffraction method. Each antibacterial particle is composed of calcium phosphate [Ca ₃ (PO ₄ ) ₂
.NH ₂ O] and its pattern is broad, which indicates that it is amorphous calcium phosphate.

It was also identified that each of the above-mentioned antibacterial particles incorporates silver ions into calcium phosphate to form a solid solution state of both of them. That is, it is assumed that silver ions are incorporated in the above-mentioned calcium phosphate microcrystals, positions of calcium ions, and the like.

Further, the antibacterial activity of each antibacterial particle obtained in Examples 1 and 2 was measured. For comparison, commercially available antibacterial apatite particles were used.

Test method 1. Preparation of bacterial solution Test bacterial cells cultured at 37 ° C for 18 hours in an agar medium are suspended in a phosphate buffer (1 / 15M, pH 7.2) to prepare a stock solution of 10 ⁸ cells / ml, The stock solution was appropriately diluted and used for the test.

2. Antibacterial Test (Shake Flask Method) 0.1 g of each antibacterial particle 7 as a sample is weighed and put into a 200 ml Erlenmeyer flask containing 100 ml of the above phosphate buffer solution, and a suspension of the test bacteria of about 10 ⁵ cells is put into this. Then, the Erlenmeyer flask was shaken while being kept at 25 ° C ± 5 ° C, and the number of bacteria in the Erlenmeyer flask was measured with time. The strains used are as follows.

Strains used Escherichia coli IFO-1273
4 Staphylococcus aureus IFO-1273
2 Psedomonas aeruginosa IFO-1268
9 Candida albicans IFO-1060 Medium used Bacteria: Mueller Hinton 2 (BBL) Fungus: Potato dextrose agar medium (Eiken) The above measurement results are shown in Tables 1 to 4.

[0033]

[Table 1]

[0034]

[Table 2]

[0035]

[Table 3]

[0036]

[Table 4]

As described above, it was shown that the antibacterial particles of the above-mentioned examples have higher antibacterial action than the above-mentioned antibacterial apatite particles which are commercially available as conventional antibacterial particles. This is because the antibacterial particles of each of the above examples are porous,
The specific surface area, which is the area in contact with bacteria, is large, and in addition, the ACP used as a substrate has a high bacteria adsorption capacity (Asahi Shimbun, 1993).
It is presumed that the antibacterial properties of silver ion 2 and allyl isothiocyanate 13 can be efficiently exerted by having the evening edition of January 16, 2014).

Further, since such antibacterial particles have a spherical shape, they are easily dispersed evenly when blended with a resin molded product such as a foamed plastic tray on which fresh food is placed. It is possible to improve the miscibility with

Next, it is assumed that the above-mentioned antibacterial particles are blended with a plastic sheet and used for the white tray such as a foamed plastic tray on which fresh food is placed. From this fact, when the blended antibacterial particles are colored, the user may mistakenly recognize that the tray has dust or dirt. Then, when the color of each antibacterial particle was visually observed, all the antibacterial particles were colorless and white, and were not mistaken for dust or dirt.

As a result, the antibacterial particles can improve the mixing property with the resin molded product and are colorless.
It can be easily kneaded at the time of manufacturing a commercially available plastic container or the like, or even if it is easily mixed and molded into a sheet-shaped plastic, it can be prevented from being mistakenly recognized as dirt. Therefore, the deterioration of the appearance of the plastic container can be avoided.

The antibacterial particles can be mixed with a resin raw material to form a plastic container and exposed on the inner surface of the container, or can be coated on the surface of the plastic container such as a lamin pack. Therefore, silver ion and allyl isothiocyanate have a bactericidal and bacteriostatic action against bacteria of foods that come into contact with the antibacterial particles.

Furthermore, the above antibacterial particles were placed in the above plastic container after allyl isothiocyanate was gradually volatilized even in fresh food in a closed container such as a wrapped food tray. It is possible to suppress the growth of various bacteria on food.

From the above, the above-mentioned antibacterial particles can improve the shelf life of fresh foods, have the effect of preventing food poisoning due to foods in which various bacteria have proliferated, and further, fresh foods such as vegetables, fruits and fresh fish. It can also have a freshness-keeping effect on food products.

Further, since the antibacterial particles have ACP as a base material, there is a problem that the base material is decomposed by heating like an inclusion compound of allyl isothiocyanate using cyclodextrin as a base material. Instead, it is easy to mix and mold with a thermoplastic resin or the like that is heated and molded.

Allyl isothiocyanate as an organic antibacterial agent is an oily pungency component contained in mustard and horseradish, and is a compound safe to the human body at a normal intake, while silver ion 2 is It is strongly adsorbed on the ACP particles 1 and is prevented from being eluted to the outside, so that it is prevented from being taken into the human body.

As a result, the antibacterial particles 7 are safe,
Also, it has excellent antibacterial properties, can avoid deterioration of appearance, and is also excellent in moldability and mixability with resin molded products, so it can be suitably used as a tray for placing food such as fresh food. it can.

In the constitution of each of the above-mentioned examples, an example in which allyl isothiocyanate was used as the organic antibacterial agent was given, but the organic antibacterial agent is not particularly limited to the above, it has volatility at room temperature, and is sterilized. -It is also possible to use a substance having a bacteriostatic action, for example, hinokitiol or terpenes.

[0048]

The antibacterial particles according to claim 1 of the present invention are:
As described above, the slurry containing the amorphous calcium phosphate particles, the organic antibacterial agent, and the antibacterial metal ion are mixed and granulated.

Therefore, when the above structure is used on the inner surface of a food tray or the like on which fresh food or the like is placed, the antibacterial metal ions and the antibacterial agent of the organic antibacterial agent are absorbed by the adsorbing action of the bacteria contained in the amorphous calcium phosphate. The sex can be effectively exhibited.

In addition, the above structure can be made into a substantially spherical shape by granulation, the mixing property with the resin molded product can be improved, and in addition, a colorless white color can be obtained. From these facts, the above configuration can be prevented from being mistakenly recognized as dust or foreign matter when mixed into a resin molded product or the like, and can be suitably used for the inner surface of a tray for placing food such as fresh food. You can

In the above structure, the organic dispersant is gradually volatilized by installing it in a closed container such as a wrapped food tray, so that the non-contact portion of the food on the food tray can be removed. Since it can exhibit a high antibacterial property, it also has an effect of having an antibacterial property against a non-contact part of the food in the closed container.

As described above, the antibacterial particles according to claim 2 of the present invention are obtained by mixing the slurry containing the amorphous calcium phosphate particles with the antibacterial metal ions to form granulated particles, In this structure, the organic antibacterial agent is adsorbed.

Therefore, the above-mentioned constitution has the same effect as that of the constitution described in claim 1, because the organic antibacterial agent is adsorbed on the granulated particles.

As described above, the antibacterial particle according to claim 3 of the present invention is the antibacterial particle according to claim 1 or 2, wherein the organic antibacterial agent is allyl isothiocyanate.

Therefore, the above-mentioned constitution has an effect that the organic antibacterial agent is allyl isothiocyanate, which is mustard oil, so that it is highly safe and is safe even when it is attached to food or the like.

[Brief description of drawings]

FIG. 1 is a schematic configuration diagram of a spray granulator for obtaining antibacterial particles of the present invention.

[Explanation of symbols]

 1 ACP particles (amorphous calcium phosphate particles) 2 Silver ions (antibacterial metal ions) 13 Allyl isothiocyanate (organic antibacterial agents)

Claims (3)

[Claims] 1. An antibacterial particle characterized in that it is granulated by mixing a slurry containing amorphous calcium phosphate particles, an organic antibacterial agent, and an antibacterial metal ion. 2. An antibacterial property, characterized in that a slurry containing amorphous calcium phosphate particles and an antibacterial metal ion are mixed, and an organic antibacterial agent is adsorbed to the granulated granulated particles. particle. 3. The antibacterial particles according to claim 1 or 2, wherein the organic antibacterial agent is allyl isothiocyanate.