JPH0799948A - Antibacterial particles - Google Patents

Abstract

(57) [Summary] [Structure] A slurry containing amorphous calcium phosphate particles 1 and an organic antibacterial agent 2 are mixed to form granulated antibacterial particles 7. [Effect] When the above-mentioned antibacterial particles 7 are used in a sealed container such as a wrapped food tray, the organic dispersant 2 is gradually volatilized so that the non-contact portion of the food in the sealed container is also removed. Since it can exhibit high antibacterial properties, it also has antibacterial properties against non-contact parts of food in the closed container.

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, as antibacterial particles used in foods and the like, hydroxyapatite having high biocompatibility and high safety has been used as disclosed in Japanese Patent Laid-Open No. 3-47118. Hydroxyapatite antibacterial agents are known. The above hydroxyapatite antibacterial agent,
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.

[0004]

However, the above-mentioned conventional structure has a bactericidal action and a bacteriostatic action for a portion of the food on the food tray in contact with the food,
Since hydroxyapatite strongly adsorbs the antibacterial agent, there is a problem that no bactericidal action or bacteriostatic action is exerted on the non-contact portion with the food.

[0005]

[Means for Solving the Problems] The inventors of the present invention have conducted various studies on a carrier that adsorbs a volatile organic antibacterial agent. As a result, amorphous calcium phosphate particles are often used as the carrier. The present invention has been completed by discovering that the organic antibacterial agent is adsorbed and the organic antibacterial agent is gradually vaporized.

That is, in order to solve the above-mentioned problems, the antibacterial particles according to claim 1 of the present invention are granulated by mixing a slurry containing amorphous calcium phosphate particles with an organic antibacterial agent. It is characterized by being

In order to solve the above-mentioned problems, the antibacterial particles according to claim 2 of the present invention include an organic antibacterial agent added to granulated particles obtained by granulating a slurry containing amorphous calcium phosphate particles. Is adsorbed.

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.

Examples of the above 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 that is freely miscible with water and mixed into a slurry,
Alternatively, it is adsorbed on the granulated particles.

The 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.

Into this slurry, a mixture of an organic antibacterial agent dissolved in ethanol or methanol so that the solid content is 50% by weight or less is granulated by a spray drying granulation method or the like to obtain antibacterial particles. Obtained.

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, it is preferable that the ACP fine particles in the slurry have a particle size of 0.1 μm or less. In addition, when the organic antibacterial agent is added to the slurry, it is desirable that the above 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.

[0016]

【Example】

[Embodiment 1] The following will describe one embodiment of the present invention as Embodiment 1 with reference to FIGS. 1 to 3. First, the manufacturing method of the antibacterial particles will be described. In the manufacturing method, amorphous calcium phosphate (amorphous
Calcium phosphate: hereinafter abbreviated as ACP) A slurry containing particles is manufactured 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 until pH of about 11 is dropped, and then a phosphoric acid aqueous solution diluted with water 5 to 8 times is dropped. 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 ACP of 20% by weight. The addition amount of allyl isothiocyanate as a system antibacterial agent is 8 to the above ACP.
Mixing was carried out so that it might be 10 mol%, and it stirred by the stirring motor for 1 hour, and each mixture slurry was obtained. The allyl isothiocyanate was dissolved in ethanol and mixed with the slurry.

Then, as shown in FIG. 1, the mixture slurry 3 containing ACP particles 1 and allyl isothiocyanate 2 is supplied to a spray dryer (L-8, manufactured by Okawara Kako Kikai Co., Ltd.) 5 by a metering pump 4. . 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 stream for drying in the spray dryer 5 is sprayed. Antibacterial particles 7 were obtained.

Each spherical antibacterial particle 7 which is an ACP granule containing allyl isothiocyanate obtained by granulation drying
Cyclone 8 has a particle size of 8 to 100 μm. 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 specific surface area of each of the antibacterial particles 7 was 70 m ² / g or more as a result of measurement by the BET method.

The operating conditions in the above 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, two kinds of spray dryers (FOC-20, OD-25G, FOC-25, OC-25 manufactured by Okawara Kako Kikai Co., Ltd.) which are scaled up versions of the above spray dryer 5 are used.
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 the ACP slurry was granulated and dried in the same manner as in Example 1 above to obtain an ACP granule having a particle size of 8 to 100 μm (not shown). I got).

10 g of the above ACP granules were sampled, a solution of 0.5 g of allyl isothiocyanate dissolved in 50 ml of ethanol was added thereto, and the mixture was stirred to prepare a mixed solution. The product obtained by filtering the above mixed solution was washed with ion-exchanged water, dried with a freeze dryer and further dried with a dryer at 60 ° C. to obtain the same antibacterial properties as in Example 1. Particles 7
Got

The presence or absence of allyl isothiocyanate was detected in the filtrate obtained by filtering the above product and the washing liquid after washing. As a result, since allyl isothiocyanate was not detected, it was considered that almost 100% of the added allyl isothiocyanate was adsorbed on the product.

Next, the antibacterial particles 7 containing allyl isothiocyanate obtained above and the ACP particles alone were analyzed by an X-ray diffraction method.
As shown in, the peak A at the position assumed to be the calcium phosphate adsorption site is large, and it is understood that allyl isothiocyanate is adsorbed.

Further, the thermogravimetric analysis (TG) / differential thermal analysis (DTA) of the antibacterial particles 7 containing allyl isothiocyanate obtained above and the ACP particles alone were measured, and the results are shown in FIG. Shown in 3. From this result, A
It was considered that the crystal water was volatilized in the CP particles alone, and the crystal water and allyl isothiocyanate were volatilized in the antibacterial particles 7.

Further, the antibacterial activity of each antibacterial particle 7 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-12734 Staphylococcus aureus IFO-12732 Psedomonas aeruginosa IFO-12689 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.

[0032]

[Table 1]

[0033]

[Table 2]

[0034]

[Table 3]

[0035]

[Table 4]

As described above, the antibacterial particles 7 of the above-mentioned embodiment are
It was shown that the antibacterial action is higher than that of the above-mentioned antibacterial apatite particles which are commercially available as conventional antibacterial particles. This is because the antibacterial particles 7 of each of the above-mentioned examples are porous and thus have a large specific surface area which is an area in contact with bacteria, and further, the ACP used as the base material has a high bacteria adsorption capacity (Asahi Shimbun, It is assumed to have the evening edition of January 16, 1993).

Further, since such antibacterial particles 7 are spherical, they are easily dispersed evenly when blended with a resin molded product such as a foamed plastic tray on which fresh food is placed, and thus resin molding is possible. The mixability with respect to the product can be improved as compared with the conventional one.

Next, it is assumed that each of the antibacterial particles 7 is mixed with a plastic sheet and used for the white tray such as a foamed plastic tray on which fresh food is placed. From this, the compounded antibacterial particles 7
When the tray is colored, the user may mistakenly recognize that dust or dirt is attached to the tray. Then, when the color of each antibacterial particle 7 was visually observed, all the antibacterial particles 7 were white, and were not mistaken for dust or dirt.

As a result, the antibacterial particles 7 can improve the mixing property with the resin molded product and are colorless, so that they can be easily kneaded during the production of a commercially available plastic container or the like, or a sheet-shaped plastic. Even if the mixture is easily mixed and molded, it is possible to prevent the risk of being mistakenly recognized as dirt or the like.

Therefore, the above-mentioned antibacterial particles 7 can be mixed with a resin raw material to form a plastic container and exposed on the inner surface of the container. Moreover, the surface of the plastic container such as a lamin pack is coated. Because you can
It is possible to suppress the growth of germs on the food placed in the plastic container, and avoid the deterioration of the appearance of the plastic container.

From the above, the above-mentioned antibacterial particles 7 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 the freshness of agricultural products such as mushrooms and fruits. It can also have a holding effect.

Since the antibacterial particles 7 have ACP as the base material, like the inclusion compound of allyl isothiocyanate using cyclodextrin as the base material,
There is no problem of decomposition of the above-mentioned base material by heating, and it is easy to mix and mold with a thermoplastic resin or the like to be 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. As a result, the antibacterial particles 7 are excellent in safety and antibacterial properties, can avoid deterioration of appearance, and are also excellent in moldability and mixability with a resin molded product, and thus can be used in fresh foods and the like. It can be suitably used for a food tray or the like.

In each of the above examples, an example using allyl isothiocyanate as the organic antibacterial agent is given.
There is no particular limitation to the above, and it is also possible to use hinokitiol or terpenes that have volatility at room temperature and have a bactericidal / bacteriostatic action.

[0045]

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

Therefore, when the above structure is used for the inner surface of a food tray or the like on which fresh foods are placed, the antibacterial property of the organic antibacterial agent is effectively exhibited by the adsorption action of the bacteria contained in the amorphous calcium phosphate. can do.

In addition, the above-mentioned constitution 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 can be obtained. From these things, the above-mentioned composition can be conveniently used for inner surfaces, such as a loading tray of foods, such as fresh foods.

Further, in the above constitution, since the organic dispersant is gradually volatilized, high antibacterial property can be exerted even on the non-contact part of the food on the food tray. By placing the molded product in a closed container such as a wrapped food tray, it is possible to obtain an effect of having an antibacterial property even for a non-contact portion of the food in the closed container.

As described above, the antibacterial particles according to claim 2 of the present invention have a structure in which the organic antibacterial agent is adsorbed on the granulated particles obtained by granulating the slurry containing the amorphous calcium phosphate particles. Is.

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

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, in the above constitution, the organic antibacterial agent is
Since it is allyl isothiocyanate, which is mustard oil, it is highly safe and has the effect of being safe even when attached to foods and the like.

[Brief description of drawings]

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

FIG. 2 is an X-ray diffraction diagram showing the composition of ACP particles having allyl isothiocyanate as the antibacterial particles and the composition of the ACP particles alone.

FIG. 3 is a graph of a TG / DTA curve showing a thermogravimetric change of ACP particles having allyl isothiocyanate as the antibacterial particles and ACP particles alone.

[Explanation of symbols]

 1 ACP particles (amorphous calcium phosphate particles) 2 Allyl isothiocyanate (organic antibacterial agent)

Claims (3)

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