JPH0899801A - Antimicrobial inorganic porous fine particle - Google Patents

Abstract

PURPOSE: To obtain antimicrobial inorganic porous fine particles preventing thermal decomposition and heat denaturation of an antibiotic, not dropping antibacterial power and antifungal power even in addition to a synthetic resin, etc., to be processed under heating. CONSTITUTION: The antimicrobial inorganic porous fine particles are obtained by adding or impregnating an antibiotic, preferably a water-soluble base antibiotic or an azole-based antibiotic to inorganic porous fine particles. 0-[2,6- Diamino-2,6-dideoxy-α-D-gluconopyranosyl (1→4)1,3-diamino-4,5,6- trihydroxycyclohexane of formula I or 1-[2-(4-chlorobenzyloxy)-2-(2-chlorophenyl)- ethyl]imidazole nitrate may be cited as the antibiotic. The inorganic porous fine particles are obtained by making a water-inoil type emulsion from an organic solvent and a surfactant in an aqueous solution of an inorganic compound, blending the emulsion with another aqueous solution, causing precipitation reaction on the water drop interface, forming an inorganic shell and removing by-products and the surfactant.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an antibacterial inorganic porous fine particle capable of suppressing the growth or proliferation of bacteria and fungi including Gram positive bacteria and Gram negative bacteria.

[0002]

2. Description of the Related Art Conventionally, substances such as silver zeolite, chitin and chitosan, and quaternary ammonium salts have been mainly used as antibacterial substances mixed with synthetic resins. Further, when an antibacterial synthetic resin is produced using an antibiotic, the antibiotic is added in a large amount in the synthetic resin.

[0003]

Therefore, when a fiber is coated with a conventional synthetic resin mixed with silver zeolite, an allergic reaction occurs due to the metal, and there is a concern that it may affect the human body. In addition, antibacterial substances such as silver zeolite, chitin and chitosan, or quaternary ammonium salts cannot suppress growth selectively against various bacteria and fungi, and care must be taken in the range of use. did not become. Furthermore, by adding the above-mentioned antibiotics to heat-processed products such as synthetic resins, thermal decomposition and thermal denaturation occur due to direct contact with heat during heat processing, and the growth of bacteria and fungi is sufficiently suppressed. However, the minimum inhibitory concentration (hereinafter referred to as "MIC") and other values increase, leading to a decrease in antibacterial activity. In order to prevent this, a large amount must be added and there is a cost problem. It was

[0004]

[Means for solving the problem] Inorganic porous fine particles are encapsulated or impregnated with an antibiotic to prevent thermal decomposition or thermal denaturation,
It is intended to provide antibacterial inorganic porous fine particles whose antibacterial activity and antifungal activity are not deteriorated even when added to a synthetic resin or the like to be heat-processed.

The above-mentioned problems can be solved by the antibacterial inorganic porous fine particles in which the antibiotic is contained or impregnated in the inorganic porous fine particles. The antibiotics to be encapsulated or impregnated in such inorganic porous fine particles are generally organic compounds obtained from molds such as fungi, which suppress the growth of bacteria and fungi, and fermentation and synthetic methods. Those obtained according to the law can be used. Such antibiotics include water-soluble base antibiotics, azo (azo).
le) antibiotics, β-lactam antibiotics, peptide antibiotics, tetracycline
e) antibiotics, macrolide
Antibiotics, polyene antifungal antibiotics, nucleoside antibiotics, glutarimide
Antibiotic, anthracycline
line) antibiotics, ansamycin (ansamy)
cin antibiotic, bleomycin
Examples thereof include those belonging to (in) -ferreomycin-type antibiotics, polyether (polyether-type) antibiotics, and the like. Particularly preferably, one or more antibiotics selected from the group consisting of water-soluble base antibiotics and azole antibiotics may be used.

Here, there are aminoglycoside antibiotics belonging to water-soluble base antibiotics, and streptomycins,
It is roughly classified into neomachines, paromomycins, kanamycins, and gentamicins. And when it comes to a specific aminoglycoside antibiotic, o- [2,6-diamino-2,6-dideoxy-α-D-glucopyranosyl (1 → 4)] 1,3-diamino-4,5,6-tri Hydroxycyclohexane (trade name: ST-7, manufactured by Biomaterial Co., Ltd.) (hereinafter referred to as "ST-7"),
Streptomycin, dihydrostreptomycin, hydroxystreptomycin, mannoside streptomycin (mannosidostreptomycin)
n), glebomycin, zygomycin B, AC443
7, neomycin A, neomycin B neomycin C,
Paromomycin (paromomycin), lividomycin (lividomycin), kanamycin, tobramycin (tobramycin), NK100
1, NK1003, NK1012, NK1012, NK
1013, seldmycin, gentamicin, antibiotic JT-20 (antibiotic JT-2)
0), antibiotic G-418 (antibi
oticG-418), sagamicin (sagamic)
in), sisomicin, mutamicin, verdamycin (ve
rdmicin), antibiotic 66-40
(Antibiotic 66-40) etc. can be illustrated.
In addition to the above, specific examples of aminoglycoside antibiotics include trehalosamine,
Hygromycin (destromycin), A-396-I, actinospectacin (actinospectaci)
n), dihydrospectinomycin (dihydros)
pectinomycin, kasugamycin, validamycin, fortimicin (fortimici)
n), SF-1854, sporaricin (sporari)
cin), istamycin, sannamycin, dactinomycin, supramycin, saccharin.
ocin), LL-BM123α, nojirimycin (n
Ojirimycin), netilmycin, amikamycin, iseopamycin, astromycin and the like.

[0007] In addition, specific examples of the azole antibiotics include clotria.
zole), miconazole,
Bifonazole, ketoconazole, itraconazole, fluconazole (fl)
uconazole), 1- [2- (4-chlorobenzyloxy) -2- (2-chlorophenyl) -ethyl] imidazole (trade name: ST-5, manufactured by Biomaterial Co., Ltd.) (hereinafter referred to as ST-5). Etc. can be illustrated.

Antibiotics belonging to β-lactam antibiotics include penicillin antibiotics and cephalosporin antibiotics. First, specific examples of penicillin antibiotics are benzylpenicillin potassium and benzylpenicillin benzathine. , Flucloxacillin sodium, Methicillin sodium, Ampicillin, Ampicillin sodium, Amoxicillin, Bacampicillin hydrochloride, Tarampicillin hydrochloride, Renampicillin hydrochloride, Cyclacillin, Pibmecillinam hydrochloride, Potassium clavulanate, Sultamicillin tosylate, Carbenicillin sodium,
Sulbenicillin sodium, ticarcillin sodium,
Examples include piperacillin sodium and aspoxycillin. Next, specific examples of cephalosporin antibiotics include cephalexin, cefloxazin, cefatrizine propylene glycol, cefaclor, cefradine, cefadroxil, cefuroxime acetyl, cefixime, cefteram pivoxil, cefpodoxime proxetil, cephaloridine, cefaroxine. Sodium tin, cefazolin sodium, cefuroxime sodium, cefamandole sodium, cefotiam hydrochloride, cefotaxime sodium, ceftizoxime sodium, cefmenoxime hydrochloride, ceftriaxone sodium, cefoperazone sodium, cefzonam sodium, cefpyramide sodium, ceftazidime , Sulbactam sodium, cefsulodin sodium, cefoxitin sodium, cefotetan sodium Cefbuperazone sodium, Joseph Mino box sodium, rata liver Joseph sodium, flomoxef sodium, cephalosporins and the like.

Peptide antibiotics include depepsid antibiotics, lactone-containing peptide antibiotics, cyclic peptide antibiotics, chain cyclic peptide antibiotics, chain peptide antibiotics and the like. Specific examples thereof include amidomycin (a
midomicin), valinomycin, actinomycin, cyclosporine, polymyxin, gramicidin A, gramicidin B and the like, respectively.

Specific examples of the tetracycline antibiotics include tetracycline, oxytetracycline, monocycline, doxycycline and the like.

Specific examples of the macrolide antibiotics include erythromycin, erythromycin ethyl succinate, erythromycin stearic acid, erythromycin lactobionate, josamycin, josamycin propionate, midecamycin, rokitamycin, lincomycin, clindamycin, and cucumber. Examples thereof include lindamycin.

Specific examples of polyene antifungal antibiotics include fandicidin.

Further, specific examples of the nucleoside antibiotics include nucleocidin,
Gogreotin, toyocamycin, oxamycetin (o
xamicetin), bamisetin
n) etc. can be illustrated.

Glutariimide
Specific examples of the e) antibiotics include cycloheximide and naramycin B.

Specific examples of the anthracycline antibiotics include α-rhodomycinin.
one), α ₁ -rhodomicinone (rhodomatic)
inone), α ₂ -rhodomycinone (rhodoma)
icineone), β-rhodomycinone (rhodom)
aicinone), γ-rhodomycinone (rhodo)
maicinone) etc. can be illustrated.

Specific examples of ansamycin antibiotics include rifamycin (rifa).
mycin), streptovaricin (sterepto)
varicin), protostreptovaricin (pro
tostereptovaricin, damavaricin, trypomycin (tol)
ypomycin), halomicin (halomici)
n), naphthomycin and the like.

Bleomycin-
Specific examples of the phleomycin-type antibiotics include ferreomycin (phleomycin).
cin), bleomycin and the like.

Specific examples of the polyether antibiotics include nigericin.
in), grisorixin, lasalocid and the like.

Specific examples of other antibiotics include sulfamethizole, sulfamethoxazole, nalidixic acid, cinoxacin, pipemidic acid trihydrate, norfloxacin, ofloxacin, enoxin, ciprofloxacin, tosfloxacin. Examples include tosyl, lomefloxacin, and chloramphenicol. Furthermore, o- [2
6-Diamino-2,6-dideoxy-α-D-glucopyranosyl (1 → 4)] 1,3-diamino-4,5,6-
Specific examples of the Schiff base-forming product of trihydroxycyclohexane and a compound having an aldehyde group include o
-[2,6-Diamino-2,6-dideoxy-α-D-
Glucopyranosyl (1 → 4)] 1,3-diamino-4,
Schiff base-forming products represented by a polymer of 5,6-trihydroxycyclohexane and terephthalaldehyde (trade name: ST-8, manufactured by Biomaterial Co., Ltd.), o-
[2,6-Diamino-2,6-dideoxy-α-D-glucopyranosyl (1 → 4)] 1,3-diamino-4,
Schiff base-forming product of 5,6-trihydroxycyclohexane and p-methoxybenzaldehyde (trade name: ST
-9, manufactured by Biomaterial Co., Ltd.) and the like.
Moreover, glyoxal can be illustrated as a compound which has the said aldehyde group.

Further, as the above-mentioned antibiotics, derivatives such as sodium salts, potassium salts, sulfates, nitrates, hydrochlorides and phosphates can be appropriately used. Inorganic porous fine particles can be encapsulated or impregnated with one or more antibiotics selected from the above-listed antibiotics according to bacteria and fungi. is there.
By using such an antibiotic, antibacterial activity and antifungal activity are exhibited against bacteria and fungi such as Gram-positive bacteria and Gram-negative bacteria, and their growth and proliferation can be suppressed.

The inorganic porous fine particles used in the present invention and the method for producing the antibacterial inorganic porous fine particles of the present invention will be described in detail below. The inorganic porous fine particles are produced by the interfacial reaction method already proposed by the present applicant. This interfacial reaction method creates a water-in-oil emulsion (emulsion) with an organic solvent and a surfactant in an aqueous solution of an inorganic compound, and mixes this with another aqueous solution to cause a precipitation reaction at the water-drop interface. After forming the inorganic shell, by-products and surfactants are removed to obtain hollow or solid inorganic porous fine particles.

The inorganic porous fine particles can be encapsulated or impregnated with an antibiotic. In particular, as the inorganic porous fine particles, those described in JP-B-57-55454 can be preferably used. Examples of the inorganic compound forming such inorganic porous fine particles include carbonates, silicates, phosphates, sulfates and metal oxides of alkaline earth metals, metal hydroxides, other metal silicates, and other Metal carbonate or the like can be used.

Specifically, the carbonates of alkaline earth metals include calcium carbonate and barium carbonate, and the silicates of alkaline earth metals include calcium silicate, barium silicate and magnesium silicate, and the alkaline earth metals. Examples of the phosphate include calcium phosphate, barium phosphate, magnesium phosphate and the like, and examples of the alkaline earth metal sulfate include calcium sulfate, barium sulfate, magnesium sulfate and the like.

Further, as the metal oxide, silica, titanium oxide, iron oxide, cobalt oxide, zinc oxide, nickel oxide, manganese oxide, aluminum oxide and the like are used, and as the metal hydroxide, iron hydroxide, nickel hydroxide, and hydroxide are used. Examples thereof include aluminum, calcium hydroxide, chromium hydroxide and the like.

Examples of other metal silicates include zinc silicate, aluminum silicate and magnesium silicate, and examples of other metal carbonates include zinc carbonate, aluminum carbonate, copper carbonate and magnesium carbonate.

Further, the antibacterial inorganic porous fine particles can be obtained by encapsulating or impregnating the inorganic porous fine particles thus produced with the antibiotic. Then, by kneading the antibacterial inorganic porous fine particles into a synthetic resin or the like, an antibacterial synthetic resin capable of suppressing the growth of bacteria and fungi can be produced. The amount of the inorganic porous fine particles mixed with the synthetic resin is 0.01% to
The amount of 50% is possible, and if it is less than 0.01%, the amount of antibiotics is small and the antibacterial activity is reduced, and if it is mixed more than 50%, the shape retention is poor and fragile when molding a synthetic resin. Become. Further, when the antibacterial inorganic porous fine particles are contained in a synthetic resin, the content of the antibiotic in the synthetic resin depends on the content of the antibiotic contained in the antibacterial inorganic porous fine particles. Is preferably 50 to 5000 ppm, and particularly preferably 100 to 2000 pp.
It is better to set m. When it is less than 50 ppm, the antibacterial activity and antifungal activity are weakened, and when it is more than 5000 pmm, the product cost of the synthetic resin increases, so it is desirable to set the content within the above range. In the examples described below, the content of the antibacterial inorganic porous fine particles with respect to the synthetic resin is shown in%, and the content of the antibiotic is shown in ppm. Further, the value of% in the present invention indicates% by weight or%.

As the synthetic resin, a thermoplastic synthetic resin is used as appropriate, and specifically, polyvinyl alcohol, polystyrene, polyethylene, polyurethane, polyvinyl chloride, polyvinylidene chloride, polyethylene terephthalate, polyamide, polypropylene. Examples include polyethylene vinyl acetate, polyvinyl acetate, polyacetal resin, nylon, and the like, and copolymers and the like can also be used. Further, as the synthetic resin, a thermosetting synthetic resin or an electromagnetic wave curable synthetic resin can be used.

Synthetic resins containing such antibacterial inorganic porous fine particles are applied to coatings on wrapping paper, wood preservatives, flooring materials, antifungal sprays, slime control agents for papermaking, non-woven fabrics, filters and fibers. It can be applied to coating agents, antibacterial treatment of tatami mats, bathtubs, kitchen utensils, agricultural chemicals such as bactericides.

[0029]

[Function] By including or impregnating the inorganic porous fine particles with the antibiotics, the thermal conductivity of the inorganic porous fine particles is low, so that the heat transfer rate to the antibiotics is slowed, and as a result, thermal decomposition and thermal denaturation are prevented. be able to. The encapsulated solid antibiotic elutes in the liquid or solid from the pores of the inorganic porous fine particles, sublimates in the gas, and the encapsulated antibiotic in the liquid state exudes or evaporates. It inhibits the synthesis of cell walls and cell membranes against bacteria and fungi and suppresses growth and proliferation. In particular, when a water-soluble base antibiotic or an azole antibiotic is used, it acts on the cell membranes of bacteria and fungi to cause inhibition of cell membrane synthesis during cell division, so that proliferation can be prevented more efficiently.
In addition, 1- [2- (4-chlorobenzyloxy) -2-
(2-chlorophenyl) -ethyl] imidazole, o-
[2,6-Diamino-2,6-dideoxy-α-D-glucopyranosyl (1 → 4)] 1,3-diamino-4,
5,6-trihydroxycyclohexane, o- [2,6
-Diamino-2,6-dideoxy-α-D-glucopyranosyl (1 → 4)] 1,3-diamino-4,5,6-trihydroxycyclohexane from among Schiff base-forming products of a compound having an aldehyde group When one or more selected ones are used, they show better efficacy against bacteria and fungi, so that growth and proliferation can be suppressed.

[0030]

EXAMPLES Details of the present invention will be described based on examples. (Production of Inorganic Porous Fine Particles) That is, when silica is used as the inorganic compound, as an example, first, a water glass solution is emulsified with a liquid paraffin solution of a mixture of sorbitan monostearate and polyoxyethylene sorbitan monooleate, and then in oil. A water-drop type emulsion is prepared, further added to an ammonium sulfate solution, reacted, and allowed to stand. Then, filtration, washing and drying are performed to obtain non-hollow inorganic porous fine particles whose wall substance is silicic acid anhydride.

(Method for Producing Antibacterial Inorganic Porous Fine Particles) Next, the void portion 2 of the inorganic porous fine particles 1 shown in FIG. 2 obtained by the above steps under the equipment structure shown in FIG.
Into, antibiotic 3 was introduced. This device comprises a vacuum chamber 6 provided with an exhaust valve 4 and a leak valve 5, and an antibiotic substance 3.
The tank 7 containing the solution of 1 is connected via the introduction valve 8, and by depressurizing the inorganic porous fine particles 1 in the vacuum chamber 6, the antibiotic 3 under normal pressure is removed. The solution was introduced into the void 2 by utilizing the pressure difference. An example of the schematic process is shown below.

First, the inorganic porous fine particles 1 are set in the vacuum chamber 6, the exhaust valve 4 is opened while the leak valve 5 and the introduction valve 8 are closed, and the vacuum chamber 6 is depressurized to 10 to 10 ^-3 torr. To do. Next, the exhaust valve 4 is closed to end the exhaust of the vacuum chamber 6, and the introduction valve 8 is opened. At this time, since the inside of the tank 7 containing the solution of the antibiotic 3 is at atmospheric pressure, the antibiotic 3 is introduced into the vacuum chamber 6 due to the pressure difference. Since the voids 2 of the inorganic porous fine particles 1 are also depressurized by the exhaust in the vacuum chamber 6, the antibiotic 3 introduced into the vacuum chamber 6 penetrates into the voids 2 inside the inorganic porous fine particles 1. Subsequently, the leak valve 5 is opened and the vacuum chamber 6 is returned to the atmospheric pressure, and then the excess solution of the antibiotic 3 is separated by filtration or the like to obtain the antibacterial inorganic porous fine particles containing the antibiotic 3. . The inorganic porous fine particles 1 used here have, for example, a particle diameter of 0.1 to 300 μm, a wall thickness of 0.05 to 150 μm, and a pore diameter of 2 nm to 2 μm.
The bulk density is about 0.1 to 5 cc / g,
The content of the antibiotic 3 after encapsulation is preferably about 1 to 80%, and particularly preferably 20 to 50%. A schematic cross-sectional structure of the inorganic porous fine particles 1 containing the antibiotic 3 thus produced is shown in FIG. In the example shown in the figure, the antibiotic substance 3 is contained in the non-hollow inorganic porous fine particles 1 whose wall substance is anhydrous silicic acid. It gradually evaporates, and the antibacterial and antifungal effects of antibiotics can be maintained for a long time. It is also possible to impregnate the hollow portion 9 of the hollow inorganic porous fine particles 1 with the antibiotic 3 as shown in FIG.

Example 1 By using silica as a metal oxide and the method for producing inorganic porous fine particles, the inorganic porous fine particles shown in FIG. 2 (trade name: Godball E-2C,
Suzuki Yushi Kogyo Co., Ltd.) was obtained. Further, according to the method for producing antibacterial inorganic porous fine particles, 50 g of ST-5 nitrate represented by Chemical Formula 1 (hereinafter referred to as “ST-5 nitrate”) was used as an antibiotic and dissolved in 50 g of special grade methyl alcohol. did. Then, in the method for producing the antibacterial inorganic porous fine particles, as shown in FIG. 1, a container containing 100 g of inorganic porous fine particles (trade name: Godball E-2C) made of hydrosilica as a raw material is provided in the vacuum chamber 6. After installation, the pressure was reduced to 10 ^-1 toor. Further, a methyl alcohol solution of ST-5 nitrate was placed in one tank 7 and the introduction valve 8 was opened to obtain 200 g of antibacterial inorganic porous fine particles. Next, this was heated to 80 ° C. to vaporize and evaporate methyl alcohol to obtain 150 g of antibacterial inorganic porous fine particles. Further, the inorganic porous fine particles are dipped in a solution of sodium hydroxide adjusted to pH 10 and subjected to an insolubilization treatment to prevent elution from the inorganic porous fine particles of ST-5 in water, thereby increasing the amount of ST-5 contained. As a result, 155 g of water-insoluble and organic solvent-insoluble antibacterial inorganic porous fine particles as 40% was obtained.

Example 2 In Example 2, the chemical formula 1 is used.
The same procedure as in Example 1 was carried out except that the amount of ST-5 nitrate contained in the above-mentioned was set to 20% to obtain antibacterial inorganic porous fine particles.

[0035]

[Chemical 1]

Example 3 In Example 3, the chemical formula 2
Example 1 except that the inclusion amount of ST-7 shown in FIG.
The same operation as above was performed to obtain antibacterial inorganic porous fine particles.

[0037]

[Chemical 2]

Comparative Example 1 In Comparative Example 1, a water-soluble ST-5 nitrate was used as the antibiotic.

(Comparative Example 2) In Comparative Example 2, ST-7 was used as the antibiotic.

(Measurement of Minimum Inhibitory Concentration (MIC) Before Heat Treatment in Examples 1 and 2 and Comparative Example 1) Next, the heat resistance of these Examples was evaluated. It was performed by MIC measurement. First, the MIC before heat treatment in Examples 1, 2 and Comparative Example 1 was measured. The MICs of the water-insoluble and organic solvent-insoluble Examples 1 and 2 and the water-soluble Comparative Example 1 were measured using the bacteria and fungi shown in Table 1. The results are shown in Table 1. The MIC was measured by the surface coating method. The method is such that when water-insoluble and organic solvent-insoluble ones are used as in Examples 1 and 2, 2 ml of a suspension containing an appropriate amount of Examples 1 and 2 is used.
Muller with agar and agar (Muller-
Hinton) (hereinafter referred to as "Muller-Hinton") medium (18 ml) was mixed in a test tube, and the mixture was transferred to a circular glass dish having a diameter of 9 cm to prepare a Muller-Hinton solid medium. Then, on the surface of this solid medium, streak smearing was performed with a platinum loop having a bacterial count of 1.0 × 10 ⁵ cells / ml attached, and the lid of the petri dish was closed and the temperature was adjusted to about 37 ° C. in a constant temperature bath. Move inside, about 20
Culturing was carried out for a period of time. Then, after about 20 hours, the formation of colonies on the surface of the solid medium was observed, and when the number of colonies was 5 or less per petri dish, it was considered that the growth of the strain was inhibited.
When a water-soluble antibiotic was used as in Comparative Example 1, the MIC was measured by the same procedure as in Example 1 except that an aqueous solution was used instead of the suspension. The results are shown in Table 1.

[0041]

[Table 1]

From Table 1, it was revealed that the antibacterial activity and the antifungal activity did not change even if they were encapsulated in the inorganic porous fine particles, and the staphylo which is a mesitillin-resistant bacterium has a resistance ability to all antibiotics. Coccus Aureus TY-
5548 strain (Staphylococcus aureus TY-5548, hereinafter "TY
-5548 strain ". ), The antibacterial activity was maintained.

(MI after heat treatment of Example 1 and Comparative Example 1
C measurement) After performing a heat resistance test on Example 1 and Comparative Example 1 by dry heat treatment and wet heat treatment, TY-5548
The MIC for the strain was measured. As a method for performing the dry heat treatment, a diameter of 10 including about 1 g of Example 1 and Comparative Example 1 was used.
A stainless petri dish having a size of cm was heated in a dryer in which the temperature inside the chamber was adjusted to 200 ° C. for three types of heating time of about 10 minutes, about 30 minutes, and about 60 minutes. The wet heat treatment was performed by using a stainless petri dish (diameter 20 cm, depth 2 cm) containing about 1 g of Example 1 and Comparative Example 1 at 121 ° C. for about 10 minutes, about 30 minutes, and about 60 minutes using an autoclave. Processed. The results are shown in Table 2.

[0044]

[Table 2]

As can be seen from Table 2, in Example 1, even when exposed to a high temperature environment such as wet heat treatment and dry heat treatment,
It was revealed that the antibacterial activity was sufficiently maintained and that neither thermal decomposition nor thermal denaturation occurred even at high temperatures. On the other hand, in Comparative Example 1, since it was not included in the inorganic porous fine particles, the measurement result of MIC was higher than that of Example 1, and it was revealed that thermal decomposition or thermal denaturation occurred.

(MIC measurement after dry heat treatment of Example 2) Since the MICs of the respective bacteria and fungi before heat treatment of Examples 1 and 2 showed almost the same value, Example 2
The heat resistance test of dry heat treatment at a temperature higher than 200 ° C. was conducted. Then, the method was performed by performing the same operation as in the dry heat treatment of Example 1 and Comparative Example 1 described above, while changing the temperature inside the chamber and the treatment time. And MIC measurement is TY
-5548 strain and Aspergillus niger JCM 5548 strain (Aspergillus niger JCM 5548) (hereinafter referred to as "black koji mold"). The results are shown in Table 3.

[0047]

[Table 3]

As is clear from Table 3, the antibacterial inorganic porous fine particles of the present invention show heat resistance even at 300 ° C., and are stable to heat. It was suggested that it could be mixed with.

(MI before heat treatment of Example 3 and Comparative Example 2
C measurement) Regarding Example 3 and Comparative Example 2, as in Example 1, first, the MIC before the heat treatment was measured. The results are shown in Table 4.

[0050]

[Table 4]

As shown in Table 4, the MIC of Example 3 showed the same antibacterial activity and antifungal activity as those of Comparative Example 2, and similarly to Example 1, the MIC of the inorganic porous fine particles contained therein had no antibacterial activity. It did not fade.

(Preparation of Antibacterial Polyethylene Film and Antibacterial Cloth) Furthermore, in Application Examples 1 to 4, an antibacterial polyethylene film prepared by kneading Example 1 into polyethylene is used, and in Application Example 5, urethane resin is used as a binder. A cotton cloth to which Example 1 was attached was prepared.

(Application Example 1) In Application Example 1, the length is 5
In order to adjust the concentration as ST-5 to 1000 ppm with respect to polyethylene (product name: F522, manufactured by Ube Industries, Ltd.) with a kneader using two rolls of 0 cm and a diameter of 20 cm, the antibacterial of Example 1 was adjusted. Porous inorganic fine particles were mixed at a ratio of 0.25% and kneaded at 120 to 130 ° C. for about 5 minutes. Furthermore, 300 mm heated to 190 ° C
× 300mm press machine (30t pressurizing capacity)
After preheating for 2 minutes, press at 3.5t for 1 minute, and then press at another room temperature at 18t pressure for 2 minutes by another 300mm x 300mm press machine. Was produced. Then, the polyethylene film was immersed in an ammonium solution adjusted to pH 9.0 for 30 minutes and washed with running water to prepare an antibacterial polyethylene film.

(Application Example 2) As an application example 2, ST-5
Except that the polyethylene film was mixed with Example 1 at a ratio of 0.125% in order to adjust the concentration to be 500 ppm, the same operation as in Application example 1 was performed and the same thickness as in Application example 1 was obtained. A 0.5μ antibacterial polyethylene film was prepared.

(Application Example 3) As an application example 3, ST-5
Example 1 was repeated except that the polyethylene film was mixed with Example 1 at a ratio of 0.05% in order to adjust the concentration to be 200 ppm.
An antibacterial polyethylene film having a thickness of 0.5 μm was prepared in the same manner as in.

(Application Example 4) As an application example 4, ST-5
Except that the polyethylene film was mixed with Example 1 at a ratio of 0.025% in order to adjust the concentration to 100 ppm, the same operation as in Application example 1 was performed and the same thickness as in Application example 1 was obtained. A 0.5μ antibacterial polyethylene film was prepared.

(Application Example 5) As Application Example 5, the antibacterial inorganic porous fine particles of Example 1 were prepared by padding.
Using a 1% aqueous polyurethane resin (trade name: Hydran HW-930, Dainippon Ink and Chemicals, Inc.) aqueous solution dispersed at a rate of 05% by weight, cotton cloth (30 cm × 40 c)
m) is padded so that the pickup becomes 70%, and dried in hot air for 3 minutes in a dryer with an internal temperature of 110 ° C.
Further, curing was performed at 170 ° C. for 1 minute to prepare an antibacterial cotton cloth.

Reference Example 1 As Reference Example 1, Application Example 1
The same polyethylene film with a thickness of 0.5 μm was used.

Reference Example 2 As Reference Example 2, Application Example 5
The cotton cloth used for was used in the untreated state without antibacterial treatment.

(Evaluation Test of Antibacterial Activity by Halo Test Method in Application Examples 1 to 4 and Reference Example 1) Then, when the antibacterial activity was evaluated by the bacterial count method using a sample of polyethylene film, the water repellency of the polyethylene film was evaluated. Due to the action, the inoculum solution forms droplets on the film surface, and it is difficult for the surface of the microorganisms to come into contact with the film surface, and a stable evaluation of antibacterial activity cannot be obtained.
Using the application examples 1 to 4 and the reference example 1, the TY-5548 strain before washing and after 10 times of durability test, which is a durability test,
Black koji mold, Penicillium funiculosum IFO 6345 strain (hereinafter “blue mold”)
Called. ) Was evaluated for antibacterial activity against 3 strains. The method of washing 10 times was performed according to JIS L-0217-103 method (convenient method of washing with hot water 10 times). The antibacterial activity was evaluated by the hello test method. First, TY-
Regarding the 5548 strain, a plate broth medium (trade name: standard agar medium, manufactured by Nissui Pharmaceutical Co., Ltd.) was used in a petri dish having a diameter of 9 cm, and the number of bacteria was 5 to 30 × 10 ⁵ cells / surface.
Using the preculture liquid of TY-5548 strain prepared in ml,
Application Examples 1 to 4 and Reference Example 1 prepared by uniformly spreading, air-drying, and preparing a size of 15 cm × 15 cm were brought into close contact with the surface of the solid medium, and the dish was closed, and the temperature was adjusted to about 5 ° C. After allowing to stand for about 24 hours in the above constant temperature bath, the culture was carried out for about 24 hours in the constant temperature bath whose internal temperature was adjusted to about 37 ° C. Then, it was confirmed whether or not a zone of inhibition was formed after the culture. Regarding the halo test method for two types of mold, black mold and green mold, the plate potato dextrose medium was used instead of the plate broth medium, the culture temperature was 25 ° C, and the strain was collected from the slant medium precultured with platinum loops. TY-5548 except that the filtrate obtained by filtering the product with sterile gauze was used.
Exactly the same operation as for the strain was performed. The results are shown in Table 5.

[0061]

[Table 5]

As is clear from Table 5, the growth of the 3 strains was not observed in any of the application examples, and the effect of inhibiting the growth was recognized.

(Evaluation Test of Antibacterial Activity of Application Example 5 and Reference Example 2) With regard to Application Example 5 and Reference Example 2, TY-5548 strain and Staphylococcus aureus TY-5552 strain (Staphylococcus aureus) which are mesicillin-resistant Staphylococcus aureus
TY-5552) (hereinafter referred to as "TY-5552 strain") 2
The antibacterial activity for each type was measured by the following method. The measurement method is as follows. First, 0.2 g of Application Example 5 and Reference Example 2
Were placed in separate 30 ml capacity vial bottles with screw caps and sterilized in an autoclave at about 121 ° C. for about 15 minutes. Then, the number of each of the TY-5548 strain and the TY-5552 strain was adjusted to ⁵ to 30 × 10 ⁵ cells / ml.
Using a micropipette, 0 μl of the preculture liquid was uniformly inoculated into the vial bottle with a screw cap having a capacity of 30 ml containing Application Example 5 and Reference Example 2, respectively, and the temperature inside the chamber was about 37.
Culturing was carried out for about 18 hours in a constant temperature bath adjusted to ° C. And
After culturing, 20 ml of sterilized physiological saline was added, stirred, and then appropriately diluted with physiological saline, surface-sprayed on the surface of the solid broth medium, and the inside temperature was about 37 ° C. After culturing for about 18 hours in a constant temperature bath adjusted to 2, the number of growing colonies was measured. The results are shown in Table 6.

[0064]

[Table 6]

As is clear from Table 6, in Application Example 5 which was subjected to the antibacterial treatment, the viable cell count was below the detection limit (2.0 × 10 ² cells / ml) in this test method, and colonies were detected. It turned out to be antibacterial.

[0066]

According to the antibacterial inorganic porous fine particles of the present invention according to claim 1, since the antibiotics are included in the inorganic porous fine particles having a low heat conductivity, the heat transfer rate to the antibiotics becomes slow and the heat is reduced. It can be used for products that undergo heat processing without decomposition or thermal transformation. In addition, since the antibiotic that has not undergone thermal decomposition or thermal denaturation is gradually released from the pores of the inorganic porous fine particles, it becomes possible to always maintain the antibacterial activity and antifungal activity. Furthermore, when applied to heat-processed synthetic resins, it is possible to suppress the growth of bacteria and fungi with a much smaller addition amount compared to those not treated with antibiotics, so it is also cost effective. An inexpensive antibacterial synthetic resin can be produced.

In addition, the antibacterial inorganic porous fine particles using one or more selected from the water-soluble base antibiotics and the azole antibiotics according to claim 2 are more excellent. It also exhibits antibacterial activity and antifungal activity, and can suppress the growth of bacteria and fungi selectively and efficiently, resulting in further cost reduction.

Furthermore, when the antibacterial inorganic porous fine particles according to claim 3 are used in a product which is heat-processed, the growth of mesitillin-resistant staphylococcus which is a problem of nosocomial infection is prevented,
The hospital can be kept hygienic and patients can be treated with peace of mind. Also, those exhibiting antifungal activity can prevent the generation of mold and the like, and can be made into an antibacterial synthetic resin that does not grow mold even when added to synthetic resins, and can be applied to building materials such as walls. You can always make things clean.

[Brief description of drawings]

FIG. 1 is an explanatory view showing an example of a method for injecting an antibiotic into inorganic porous fine particles of the present invention.

FIG. 2 is a sectional explanatory view showing an example of inorganic porous fine particles containing an antibiotic of the present invention.

FIG. 3 is a sectional explanatory view showing an example of inorganic porous fine particles impregnated with an antibiotic of the present invention.

[Explanation of symbols]

 1. Inorganic porous fine particles 2. Void 3. Antibiotics 4. Exhaust valve 5. Leak valve 6. Vacuum chamber 7. Tank 8. Introduction valve 9. Hollow part

Continuation of front page (51) Int.Cl. ⁶ Identification number Office reference number FI Technical indication location A01N 63/02 B B01J 13/02 C04B 38/00 // C08K 9/04 KCP (72) Inventor Kohei Wakabayashi Fukui 1-11-1 Tahara, Fukui City, Fukui Prefecture (72) Inventor, Hikaru Inaba 2-14-10, Joto, Fukui City, Fukui Prefecture (72) Inventor, Naoyuki Fujii 3-3-10, Fukui City School, Fukui Prefecture (72) Inventor, Yoshihide Tajima 3-1-19 Hanazono Higashimachi, Higashiosaka City, Osaka Prefecture

Claims (3)

[Claims] 1. An antibacterial inorganic porous fine particle comprising an inorganic porous fine particle encapsulated or impregnated with an antibiotic. 2. The antibiotic is selected from water-soluble base antibiotics and antibiotics belonging to azole antibiotics.
The antibacterial inorganic porous fine particles according to claim 1, which are one kind or two or more kinds. 3. 1- [2- (4-chlorobenzyloxy)
-2- (2-chlorophenyl) -ethyl] imidazole, o- [2,6-diamino-2,6-dideoxy-α-D
-Glucopyranosyl (1 → 4)] 1,3-diamino-
4,5,6-trihydroxycyclohexane, o- [2,6-diamino-2,6-dideoxy-α-D
-Glucopyranosyl (1 → 4)] 1,3-diamino-
Inorganic porous fine particles are encapsulated or impregnated with one or more selected from Schiff base-forming products of 4,5,6-trihydroxycyclohexane and a compound having an aldehyde group. Antibacterial inorganic porous particles.