JPH08165213A - Antimicrobial agent - Google Patents

Abstract

PURPOSE: To obtain an inorganic antimicrobial agent excellent in long acting property, chemical resistance and safety. CONSTITUTION: This antimicrobial agent contains one or two or more kinds of metal salts or one or more kinds of metal salts or complex metal salts of pyrophosphoric acid and/or metaphosphoric acid containing one or two or more kinds of metals having antimicrobial action or one or two or more kinds of metals not having antimicrobial action as component metals as active ingredients.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an inorganic antibacterial agent. More specifically, a pyrophosphate and / or metaphosphate, which is a metal in which some or all of the component metals have an antibacterial action, is used as an active ingredient, and the antibacterial activity is excellent in sustainability, chemical resistance, and safety. High antibacterial agents.

[0002]

BACKGROUND ART It has long been known that certain metals such as silver, copper, and zinc have an antibacterial action, but on the other hand, when metals are used as they are, they cause troubles due to the toxicity of metal ions and the surrounding substances. There is a problem in terms of safety, such as the danger that it will react with and change into a harmful substance. As a method for solving such a problem, a method of holding an antibacterial metal in an inorganic adsorption material such as activated carbon, alumina, or silica gel and using it has been proposed for a long time. However, there is a problem in that the amount of the antibacterial metal retained by the adsorbed substance is limited, and the retained metal gradually elutes and is lost during use in a liquid, resulting in lack of sustainability of the antibacterial activity.

Further, in recent years, a method of using a calcium phosphate compound such as hydroxyapatite or calcium carbonate as a carrier, and carrying a metal having an antibacterial action such as silver by an ion exchange action (JP-A-5-12).
No. 4919) and a method of supporting heavy metal ions on a phosphate or condensed phosphate that is insoluble or sparingly soluble in water (see Japanese Patent Application Laid-Open No. 2-96508). However, even in these methods, since the portion where the antibacterial metal is retained is a limited portion near the surface of the carrier, the amount of ion exchange is limited, and the antibacterial metal supported near the surface of the carrier is limited. If the supported metal disappears due to elution, the antibacterial action is lost even if the carrier remains.

Further, a method of intercalating a metal having an antibacterial action by using a layered phosphate such as zirconium phosphate or titanium phosphate as a carrier (Japanese Patent Laid-Open No. 3-190).
No. 806, refer to JP-A-5-32407),
Although a method of supporting an antibacterial metal using zeolite as a carrier has also been proposed, as in the case of the calcium phosphate-based carrier described above, a limited amount of the antibacterial metal carried near the surface of the carrier is eluted. Then, even if the carrier remains, the antibacterial action is lost, and the problem that the known antibacterial agent of this kind lacks in durability has not been solved at all. Further, since the zeolite-based antibacterial agent is basic and has sodium ions remaining, it has a problem that when it is added to a plastic or a film, it may cause discoloration or impair thermal safety.

[0005]

DISCLOSURE OF THE INVENTION As a result of intensive studies to solve the above problems, the present inventors have found that a metal phosphate having a part or all of its metal components has an antibacterial action. It has been found that the antibacterial agent has excellent antibacterial activity, and succeeded in developing a highly safe antibacterial agent. The present invention is based on such findings.

The present invention provides one or more metals having an antibacterial action, or one or more metals having an antibacterial action and one metal having no antibacterial action, or The present invention provides an antibacterial agent characterized by containing, as an active ingredient, one or more metal salts or complex metal salts of pyrophosphoric acid and / or metaphosphoric acid containing two or more metals as component metals. .

The present invention will be described in detail below. Most of pyrophosphate and metaphosphate, which are active ingredients of the antibacterial agent according to the present invention, are known substances and can be obtained by a commonly used production method. For example, in the case of a silver salt, it can be produced by various known techniques such as a production method by a reaction between a silver nitrate solution and a metaphosphoric acid solution, or a solid reaction between various metal oxides and ammonium dihydrogen phosphate. In particular, the synthesis by spray pyrolysis reaction,
This is a suitable synthetic method when producing a phosphoric acid complex metal salt, because a homogeneous composition in which a plurality of kinds of metals are uniformly distributed can be obtained. For example, when a composite metal salt of pyrophosphoric acid containing magnesium and calcium having no antibacterial action and silver having an antibacterial action as the component metals is synthesized by a spray pyrolysis reaction, the silver ion is pyrophosphorus as a component metal of pyrophosphate. It is incorporated into a magnesium acid lattice or a calcium pyrophosphate lattice in a uniform state, and both are obtained as white powder (see Examples 12 and 13).

In the antibacterial agent according to the present invention, since the metal having the antibacterial effect is uniformly distributed in the phosphate,
Even if a part of the phosphate is exhausted, the antibacterial action continues without loss as long as the phosphate remains. That is, the antibacterial agent according to the present invention is a conventional type of antibacterial agent in which a metal having antibacterial properties is supported only on the surface of a carrier such as alumina, silica gel, phosphate, zeolite, etc. Consumed by physical or chemical action,
Unlike that in which the antibacterial activity disappears, it is not necessary to support it on the carrier because the phosphate gradually elutes the metal having an antibacterial effect and exerts an antibacterial effect. Is completely undissolved, and the antibacterial action is maintained until it disappears.

The antibacterial metal used in the present invention includes silver, copper, zinc, nickel, cobalt, manganese,
In addition to lanthanum, it is possible to use gold, tin, lead, platinum, iron, aluminum, antimony, barium, cadmium, and other metals that have long been known to have an antibacterial action. These metals may be used not only as one kind but also as a composite metal salt by combining two or more kinds of metals. For example, a composite metal salt composed of a combination of metals having antibacterial action, such as copper and silver or zinc and silver,
It is possible to bring out preferable effects such as suppressing discoloration that occurs when silver is used alone, while making the most of the property of silver having a strong antibacterial activity.

The "composite metal salt" which is the active ingredient of the antibacterial agent according to the present invention is a combination of metals having an antibacterial effect or a combination of a metal having an antibacterial effect and a metal having no antibacterial effect. It means that two or more kinds of metals are contained as a component metal of the pyrophosphate or metaphosphate. As the existence state of these metals, it is not always necessary to form a uniform phase such as a solid solution or a compound. That is, in the present invention, "metal salt" means a phosphate composed of one kind of component metal,
“Composite metal salt” means a phosphate composed of plural kinds of component metals.

As the metal having no antibacterial action, metals such as calcium, magnesium, silicon, zirconium and titanium, which are highly safe and have excellent heat resistance and chemical resistance, can be preferably used. For example, a composite metal salt containing two kinds of metals, which are a combination of zirconium, which has excellent heat resistance and chemical resistance, and silver, which has an antibacterial action, as component metals, has excellent characteristics of both metals and is preferably used as an antibacterial agent. It is a mode. Although silicon is usually classified as a non-metal element, it forms silicon pyrophosphate as a metal component of pyrophosphate in the same manner as general metals, and also forms a complex salt of pyrophosphate with a metal having antibacterial action and silicon. In the present invention, silicon is "a metal having no antibacterial action" because it shows useful properties in terms of heat resistance and chemical resistance, like zirconium pyrophosphate and titanium pyrophosphate. Shall be included in.

The pyrophosphate or metaphosphate according to the present invention can be obtained in any state such as amorphous, crystalline or vitreous by selecting the production method and production conditions. The antibacterial agent of the present invention is not limited to a specific one, and any one can be used as the antibacterial agent of the present invention. Further, such a pyrophosphate or metaphosphate may be a single phase, or may be a substance in a state in which both coexist, and further, by-products and unreacted substances other than the phosphate are mixed. However, as long as they substantially exhibit an antibacterial action as pyrophosphate or metaphosphate, these are all included as the pyrophosphate and metaphosphate according to the present invention.

The dosage form (usage form) of the antibacterial agent according to the present invention may be any dosage form such as powder, granules, fibrous or irregular shape and is suitable for the purpose of use. The dosage form can be arbitrarily selected. Further, the antibacterial agent of the present invention can also be used by mixing it with plastic, cement or the like to form a composite. The antibacterial agent of the present invention is approximately 500 ° C. when silver is used as a component metal,
When other metals are used as component metals, they have heat resistance of approximately 800 to 1400 ° C, and they do not cause the inconvenience of hydroxyapatite such as decomposition due to elimination of hydroxyl groups at high temperature, and high temperature. Has high stability below. Such high heat resistance is a very preferable characteristic for sintering a molded article containing the antibacterial agent according to the present invention to prepare an antibacterial ceramic.

The pyrophosphate and metaphosphate according to the present invention exhibit various colors depending on the kind of the component metal. For example, cobalt pyrophosphate is blue purple, copper pyrophosphate is light blue, nickel metaphosphate is yellow, and silver pyrophosphate, zinc metaphosphate, and lanthanum metaphosphate are white. Therefore, the antibacterial agent according to the present invention can be extremely suitably used to add antibacterial action by being added to paints and pigments of various colors as well as white.

The present invention will be specifically described below with reference to examples of the present invention, but the present invention is not limited to these examples.

[0016]

【Example】

Example 1 A homogeneous mixture of silver oxide and ammonium dihydrogen phosphate (silver: phosphorus atomic ratio 2: 1) was heated and reacted at 500 ° C. for 4 hours. The resulting reaction product was silver pyrophosphate as a result of X-ray diffraction analysis. Examples 2 to 6 Under the reaction conditions shown in Table 1 below, according to the method described in Example 1, a pyrophosphate or metaphosphate containing each metal of copper, zinc, cobalt, nickel and lanthanum as a single metal component. The acid salt was synthesized. The product was confirmed by X-ray diffraction analysis.

Example 7 A mixture of silver oxide and ammonium dihydrogen phosphate (silver: phosphorus atomic ratio of 1: 1) was heated and melted in an air atmosphere at 600 ° C., rapidly cooled to room temperature, and then pulverized. Thus, a white vitreous powder having a metaphosphoric acid composition was obtained. The powder did not discolor even if left in a bright room for a long period of time. Example 8 A uniform mixture of silver oxide and ammonium dihydrogen phosphate (atom ratio of silver: phosphorus: 5: 3) was heated and reacted at 500 ° C. for 4 hours. As a result of X-ray diffraction analysis, this product was a powder consisting of two phases, silver pyrophosphate and silver metaphosphate.

Example 9 A solid solution obtained by heating and drying a solution of 17.0 g of silver nitrate and 44.6 g of zinc nitrate dissolved in distilled water with stirring and thermally decomposing at 450 ° C. and ammonium dihydrogen phosphate 23 .0
g was mixed and reacted by heating at 550 ° C. to obtain a pyrophosphate containing two metals, silver and zinc, as a metal component (atomic ratio of silver and zinc = 2: 3). Example 10 Zirconium oxynitrate 106.9 g, silver nitrate 17.0
g, 44.6 g of zinc nitrate dissolved in distilled water was dried up and pyrolyzed at 400 ° C. to obtain a solid product, and 115.0 g of ammonium dihydrogen phosphate was mixed, and the mixture was heated to 800 ° C.
By heating and reacting with, a pyrophosphate containing three metals of zirconium, silver and zinc as metal components was obtained.

Example 11 A solution of 6.79 g of silver nitrate dissolved in distilled water to 10 ml and 29.4 g of silicon dioxide were well kneaded, and further 132.1 g of diammonium hydrogen phosphate was added and thoroughly mixed. After heating at 600 ° C., pyrophosphate containing silicon and silver as metal components was obtained. Example 12 A slurry prepared by adding 28.6 g of magnesium hydroxide, 3.40 g of silver nitrate and 47.8 g of pyrophosphoric acid (93%) to a mixed solution of distilled water and methanol at a ratio of 1: 1 was 600 ±.
A spray pyrolysis reaction was carried out at 30 ° C. to obtain a white powder product. As a result of X-ray diffraction analysis, this product was a low crystalline powder of pyrophosphate having two metals, magnesium and silver, as metal components.

Example 13 A solution prepared by dissolving 115.7 g of calcium nitrate, 3.40 g of silver nitrate and 47.8 g of pyrophosphoric acid (93%) in a 1: 1 mixed solution of distilled water and methanol was prepared as 600 ± 3.
White powder obtained by spray pyrolysis reaction at 0 ° C.
It heat-processed at 00 degreeC, and the target product was obtained. As a result of chemical analysis, this product was found to have calcium, phosphorus, and silver, and was found to be a pyrophosphate containing two metals, calcium and silver, as metal components by X-ray diffraction analysis.

Comparative Example 1 10 g of hydroxyapatite (the molar ratio of Ca and P was 1.67, average particle size 15 μm) was suspended in 200 ml of distilled water, 0.16 g of silver nitrate was added, and the mixture was stirred for 24 hours. After performing an ion exchange treatment with water, it was washed with water and dried at 70 ° C. The product is calcium, phosphorus,
Silver was detected, and X-ray diffraction analysis only gave a diffraction pattern that matched that of hydroxyapatite.

Example 14 Antibacterial activity test Escherichia coli was added to a phosphate buffer containing 1% by weight of each of the products synthesized in Examples 1 to 13 and Comparative Example 1 in an amount of 5 × 10 5.
A bacterial solution containing ⁵ cells / ml was added, and the number of surviving cells after 24 hours of culture was measured. The results are shown in Table 2. As is clear from Table 2, the decrease in the number of bacteria was observed for all the compounds, and it was confirmed that they have antibacterial activity.

Example 15 Antibacterial Activity Sustainability Test Regarding the antibacterial activity sustainability of the antibacterial agent according to the present invention, the pyrophosphate powder containing the two metals of calcium and silver as the metal components synthesized in Example 13 is taken as an example. It was used for evaluation.
The powder synthesized in Example 13 was put into a nitric acid solution to dissolve about 90% by weight, and then the remaining powder was filtered, washed with water, and dried at 80 ° C. When the antibacterial activity test was conducted according to the method described in 14, the same antibacterial activity as the results obtained in Example 14 was recognized. On the other hand, a powder obtained by supporting silver on hydroxyapatite prepared in Comparative Example 1 and the powder were put into a nitric acid solution,
After dissolving about 20% by weight, the antibacterial activity of two samples of the powder obtained by filtering the remaining powder, washing with water and drying was evaluated, and the former was determined (the powder prepared in Comparative Example 1). Although an antibacterial action was observed in the latter, no antibacterial action was observed in the latter (residual powder obtained by dissolving the powder surface of Comparative Example 1). As a result of chemical analysis of the latter powder, the supported silver was not detected because it was eluted with the dissolution of the surface portion of the hydroxyapatite powder.

[0024]

[Table 1]

[0025]

[Table 2]

 ─────────────────────────────────────────────────── ─── Continued Front Page (72) Inventor Junji Takeishi 1-7-1 Inari, Soka City, Saitama Kanto Chemical Co., Ltd. Central Research Laboratory

Claims (2)

[Claims] 1. One or two metals having an antibacterial action.
Pyrophosphoric acid and / or metaphosphoric acid containing one or more kinds of metals, or one or more kinds of metals having antibacterial activity and one or more kinds of metals having no antibacterial effect as component metals An antibacterial agent containing one or more of the metal salts or complex metal salts of 1. as an active ingredient. 2. The antibacterial metal is silver,
The antibacterial agent according to claim 1, which is copper, zinc, nickel, cobalt, manganese, or lanthanum.