JP2991902B2 - Antibacterial particles - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

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, food, kitchenware, 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 JP-A-3-47118. Hydroxyapatite antibacterial agents are known. The hydroxyapatite antibacterial agent,
One or more of antibacterial agents represented by hinokitiol, tannin, lysozyme, allylisothiocyanate, brotamine and sorbic acid are carried on hydroxyapatite.

[0003] Therefore, the above-mentioned hydroxyapatite antibacterial agent is one in which the antibacterial agent is specifically strongly adsorbed and does not elute or precipitate in a solution or the like. When applied and used, the bacteria attached to the food can be sterilized or bacteriostatic by the hydroxyapatite antibacterial agent that has come into contact with the food.

[0004]

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

[0005]

Means for Solving the Problems The present inventors have conducted various studies on a carrier that adsorbs a volatile organic antibacterial agent. The present inventors have found that the organic antibacterial agent is volatilized gradually after the adsorption, and the present invention has been completed.

That is, in order to solve the above-mentioned problems, the antibacterial particles according to the first aspect of the present invention are obtained by mixing a slurry containing amorphous calcium phosphate particles with an organic antibacterial agent and granulating the mixture. It is characterized in that it is.

In order to solve the above-mentioned problems, the antibacterial particles according to the second aspect of the present invention are characterized by adding an organic antibacterial agent to granulated particles obtained by granulating a slurry containing amorphous calcium phosphate particles. Is adsorbed.

According to a third aspect of the present invention, there is provided an antibacterial particle according to the first or second aspect, wherein the organic antibacterial agent is allyl isothiocyanate.

Examples of the above-mentioned organic antibacterial agents include allyl isothiocyanate (CH ₂ = CHCH ₂ NCS), hinokitiol and terpenes, which have volatility 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 with the slurry.
Alternatively, it is adsorbed on the granulated particles.

The above amorphous calcium phosphate (Amorphous
Calcium Phosphate (hereinafter abbreviated as ACP) The slurry containing particles is prepared by adding a water-soluble polymer dispersant, for example, ammonium triacrylate to a suspension of calcium hydroxide under stirring at 0.1 to 10% by weight, preferably 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.

In this slurry, a mixture obtained by mixing an organic antibacterial agent dissolved in ethanol or methanol 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 form antibacterial particles. Obtained.

The ACP microparticles were obtained by analyzing the pattern of calcium phosphate [Ca ₃ (PO ₄ ) _2.
nH ₂ O] and its pattern is broad, confirming that it is amorphous calcium phosphate. In addition, since the ACP fine particles contain water of crystallization, they are considered to be electrostatically active substances, and are presumed to be easy to adsorb various bacteria and viruses.

In order for the obtained antibacterial particles to have a large specific surface area, the ACP fine particles in the slurry preferably have a particle size of 0.1 μm or less. In addition, when an organic antibacterial agent is added to the slurry, it is desirable that the mixing be performed at room temperature.

On the other hand, the ACP fine particles in the slurry
If the content is more than 10% by weight, the viscosity of the slurry increases.
It is not suitable for granulation. By changing the content of the ACP fine particles in the slurry within the range of 1 to 90% by weight, antibacterial particles having a desired average particle size can be obtained.

In the granulation method, the particles obtained are as follows:
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 a specific surface area of 10 m ² / g or more.For example, it is possible to use a spray drying granulation method. Alternatively, a granulation method of crushing after freeze-drying, or a high-speed stirring type 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. First, the method for producing the antibacterial particles will be described. In the method, amorphous calcium phosphate (amorphous calcium phosphate) is used.
calcium phosphate (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 under stirring to obtain a mixed solution.

Thereafter, an aqueous solution of phosphoric acid diluted 2 to 4 times with water is added dropwise to the above mixed solution until the pH reaches around 11, and subsequently, an aqueous solution of phosphoric acid diluted 5 to 8 times with water is added dropwise. 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 prepared so that the concentration of ACP becomes 20% by weight. The addition amount of allyl isothiocyanate as an antibacterial agent is 8 to
The mixture was mixed so as to have a concentration of 10 mol%, and the mixture was stirred for 1 hour with a stirring motor to obtain a mixture slurry. The allyl isothiocyanate was dissolved in ethanol and mixed with the slurry.

Next, as shown in FIG. 1, the mixture slurry 3 containing the ACP particles 1 and the allyl isothiocyanate 2 is supplied to a spray drier (L-8, manufactured by Okawara Kakohki Co., Ltd.) 5 by a metering pump 4. . The atomizer 6 of the spray drier 5 is rotated at a high speed, and the mixture slurry 3 is granulated and dried by a spray granulation method in which the mixture slurry 3 is sprayed into a hot air flow for drying in the spray drier 5. Of the antibacterial particles 7 were obtained.

Each of the substantially spherical antibacterial particles 7 which are ACP granules containing allyl isothiocyanate obtained by granulation drying
The particles having a particle size of 8 to 100 μm were collected by cyclone 8. At this time, the ultrafine powder that could not be completely collected by the cyclone 8 was separately collected and collected by a bag filter (not shown). The specific surface area of each of the antibacterial particles 7 was measured to be 70 m ² / g or more by the BET method.

The operating conditions in the above spray-drying granulation were as follows. The feed rate of the mixture slurry 3 as a raw material by the metering pump 4 is 1 to 3 kg / h. 200-2
At 50 ° C., the outlet temperature at the discharge hole 12 connected to the cyclone 8 was controlled so as to always exceed 100 ° C., and the rotation speed of the atomizer 6 was set in 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 Kakohki Co., Ltd.) obtained by scaling up the spray dryer 5,
Antibacterial particles were prepared in the same manner as described above except that the slurry supply rate was 100 kg / hr. As a result, antibacterial particles similar to the antibacterial particles 7 obtained by the spray dryer 5 were obtained. The antibacterial particles 7 thus obtained were substantially spherical.

Second Embodiment Next, another embodiment of the present invention will be described as a second embodiment. The slurry in Example 1 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 to obtain an ACP granule having a particle size of 8 to 100 μm (shown in FIG. Zu).

10 g of the above-mentioned ACP granules were collected, and a solution prepared by dissolving 0.5 g of allyl isothiocyanate in 50 ml of ethanol was added thereto, followed by stirring to prepare a mixed solution. The mixed solution was filtered, and the product obtained was washed with ion-exchanged water, dried with a freeze dryer, and further dried with a dryer at 60 ° C. Sex particles 7
I got

The filtrate obtained by filtering the above product and the washing solution obtained by washing were examined for the presence or absence of allyl isothiocyanate. As a result, since the allyl isothiocyanate was not detected, it was considered that almost 100% of the added allyl isothiocyanate was adsorbed to the product.

Next, the antibacterial particles 7 having allyl isothiocyanate obtained above and the simple substance of ACP particles were analyzed by X-ray diffraction, respectively.
As shown in the figure, the peak A at a position assumed to be a calcium phosphate adsorption site is large, and it can be seen that allyl isothiocyanate is adsorbed.

The antibacterial particles 7 having allyl isothiocyanate obtained above and the ACP particles alone were measured by thermogravimetric analysis (TG) / differential thermal analysis (DTA). 3 is shown. From this result, A
It was considered that the crystallization water was volatilized in the CP particles alone, and the crystallization water and allyl isothiocyanate were volatilized in the antibacterial particles 7.

Further, the antibacterial activity of each of the antibacterial particles 7 obtained in Examples 1 and 2 was measured. As a comparison, commercially available antibacterial apatite particles were used.

Test method Preparation of bacterial solution The test cells cultured on an agar medium at 37 ° C. for 18 hours are suspended in a phosphate buffer solution (1/15 M, pH 7.2), and a stock solution as a suspension of 10 ⁸ cells / ml is prepared. 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 was weighed as a sample, put into a 200 ml Erlenmeyer flask containing 100 ml of the above-mentioned phosphate buffer, and about 10 ⁵ cells were added to the suspension of the test bacteria. After the addition, the Erlenmeyer flask was shaken while keeping it at 25 ° C. ± 5 ° C., and the number of bacteria in the Erlenmeyer flask was measured over time. The strains used are as follows.

Escherichia coli (Escherichia coli) IFO-12734 Staphylococcus aureus (Staphylococcus aureus) IFO-12732 Psedomonas aeruginosa (Pseudomonas aeruginosa) IFO-12689 Candida albicans (Candida) IFO-1060 Media used Bacteria: Mueller Hinton 2 (BBL) ) Fungus: Potato dextrose agar medium (Eiken) The results of the above measurements are shown in Tables 1-4.

[0032]

[Table 1]

[0033]

[Table 2]

[0034]

[Table 3]

[0035]

[Table 4]

As described above, the antibacterial particles 7 of the above embodiment are
It was shown that the antibacterial effect was higher than that of the antibacterial apatite particles commercially available as conventional antibacterial particles. This is because the antibacterial particles 7 of each of the above examples are porous, so that the specific surface area, which is the area in contact with the bacteria, is large, and the ACP used as the base material has a high bacterial adsorption capacity (Asahi Shimbun, (See evening paper, January 16, 1993).

Since such antibacterial particles 7 are spherical in shape, they are easily dispersed even when blended into a resin molded product such as a foamed plastic tray on which fresh food is placed. The mixing property with respect to the product can be improved as compared with the related art.

Next, it is assumed that the antibacterial particles 7 are blended into a plastic sheet and used in the white tray such as a foamed plastic tray on which fresh food is placed. From this, the compounded antibacterial particles 7
Is colored, there is a possibility that the user may mistakenly recognize that the dust is attached to the tray. Therefore, 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 article and are colorless, so that they can be easily kneaded during the production of a commercially available plastic container or the like, or can be formed into a sheet-like plastic. Even if it is easily mixed and molded, the possibility of being mistakenly recognized as dirt can be prevented.

Accordingly, the 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. Because you can
It is possible to suppress the growth of various germs on the food placed in the plastic container and also to prevent the appearance of the plastic container from deteriorating.

From the above, the antibacterial particles 7 can improve the shelf life of fresh foods, have the effect of preventing food poisoning due to the multiplied food of bacteria, and have the freshness of agricultural products such as mushrooms and fruits. It can also have a holding effect.

Further, since the antibacterial particles 7 are made of ACP as a base material, the antibacterial particles 7 may be formed of an inclusion compound of allyl isothiocyanate using cyclodextrin as a base material.
There is no problem such as decomposition of the base material due to heating, and it is easy to mix with a thermoplastic resin or the like that is molded by heating.

Further, allyl isothiocyanate as an organic antibacterial agent is an oily pungent component contained in mustard and wasabi, and is a compound which is safe for 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 mixing property with resin molded articles, so that fresh foods and the like can be used. It can be suitably used for a food tray or the like.

In each of the above embodiments, examples using allyl isothiocyanate as the organic antibacterial agent have been described.
It is not particularly limited to the above, and it is also possible to use hinokitiol and terpenes which 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 on the inner surface of a food tray or the like on which fresh foods or the like are placed, the antibacterial properties of the organic antibacterial agent can be effectively exhibited by the action of absorbing the bacteria possessed by amorphous calcium phosphate. can do.

In addition, the above-mentioned structure can be formed into a substantially spherical shape by granulation, so that the mixing property with the resin molded article can be improved, and furthermore, the colorless white can be obtained. For these reasons, the above configuration can be suitably used for the inner surface of a tray for placing food such as fresh food.

In the above-mentioned structure, since the organic dispersant gradually volatilizes, it can exhibit a high antibacterial property even to a non-contact portion of the food on the food tray. By disposing the molded article in a closed container such as a wrapped food tray, there is an effect of having an antibacterial property even on a non-contact portion of food in the closed container.

The antibacterial particles according to the second aspect of the present invention have a structure in which an organic antibacterial agent is adsorbed on granulated particles obtained by granulating a slurry containing amorphous calcium phosphate particles as described above. It is.

Therefore, in the above configuration, since the organic antibacterial agent is adsorbed on the granulated particles, the same effect as the configuration of the first aspect is obtained.

As described above, the antibacterial particles according to claim 3 of the present invention have a constitution in which the organic antibacterial agent is allyl isothiocyanate in the antibacterial particles according to claim 1 or 2.

Therefore, in the above structure, the organic antibacterial agent is
Since it is allyl isothiocyanate, which is mustard oil, it is highly safe and has an effect of being safe even if it adheres to foods.

[Brief description of the drawings]

FIG. 1 is a schematic configuration diagram of a spray granulator for 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 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)

────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-3-47118 (JP, A) JP-A-5-49394 (JP, A) JP-A-1-235567 (JP, A) JP-A-2- 257866 (JP, A) JP-A-2-113876 (JP, A) JP-A-4-357953 (JP, A) JP-A-5-193676 (JP, A) JP-A-2-273165 (JP, A) JP-A-6-319500 (JP, A) JP-A-7-51039 (JP, A) (58) Fields investigated (Int. Cl. ⁶ , DB name) A23L 3/3454 B01J 20/04 C01B 25/32

Claims (3)

(57) [Claims] 1. Antibacterial particles characterized by being mixed with a slurry containing amorphous calcium phosphate particles and an organic antibacterial agent and granulated. 2. Antibacterial particles 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, wherein the organic antibacterial agent is allyl isothiocyanate.