JP2963133B2 - Antibacterial apatite - Google Patents

Description

Description: FIELD OF THE INVENTION The present invention relates to an antibacterial apatite, and more specifically, an antibacterial apatite which is safe for humans and animals by carrying an antibacterial metal ion on so-called apatite such as tribasic calcium phosphate. About.

[Prior Art] In an environment surrounding us, for example, many kinds of fungicides and antibacterial agents are used in the fields of industry, agriculture and food supplementation.

Most of the antibacterial agents are organic antibacterial agents, but recently, antibacterial agents of aluminosilicate compounds represented by zeolite A have attracted attention as inorganic antibacterial agents, and many proposals have been made.

It converts Na ⁺ in sodium aluminosilicate to Ag ⁺ ,
It is carried by substituting with a metal ion having a bactericidal action such as Cu ⁺⁺ or Zn ⁺⁺ (JP-A-60-181002, JP-A-60-181002).
62-70220, JP-A-62-70221, JP-A-63-702
265809, etc.).

On the other hand, apatite has Ca ⁺⁺ in the structure with other cations,
OH ^- is F ^- and Cl ^- that are known to be anion and the ion exchange or the like.

For this reason, there is a proposal as an adsorbent because the substituted product obtained by exchanging Ca ⁺⁺ of phosphate rock with another metal ion has a gas adsorbing ability such as H ₂ S and NH ₃ (Japanese Patent Application Laid-Open No. 64-7014
No. 0).

[Problems to be Solved by the Invention] However, zeolite-based antibacterial agents are basic and have an effect of residual Na ⁺ , and when added to a synthetic resin molded product or film, discoloration and thermal stability of the resin are reduced. There is a problem of inhibition, and its use and method of use are extremely difficult.

On the other hand, apatite has been attracting attention as a bioactive material because it has a good affinity for living bone tissue and exhibits a function of inducing new bone and having excellent bonding properties with bone tissue.

In addition, hydroxy-based particles of apatite have been increasingly applied in the field of separation of trace components in order to efficiently adsorb useful organic substances such as nucleic acids and proteins.

Thus, apatite has attracted attention as a bioceramic, but its metal substitute has not been developed for any use other than the above-mentioned publication, and antibacterial apatite has been used as a dental material. However, it has not been disclosed in detail (Japanese Patent Laid-Open No. 1-238508).

In view of the above facts, the present inventors have conducted intensive research on the development of an inorganic antibacterial agent that is completely different from zeolite antibacterial agents and safe for humans and animals.First, the apatite was replaced with an antibacterial metal ion by ion exchange. An antimicrobial agent carried by the above method was proposed (Japanese Patent Application No. 1-2224577). However, it was found that the apatite loaded with silver ions was discolored to a dark color over time, not only when exposed to light, but also when left naturally, and exhibited unfavorable properties in appearance.

It is an object of the present invention to provide an apatite-based inorganic antibacterial agent which is excellent in discoloration resistance, ie, an antibacterial apatite, which improves this disadvantage.

[Means for Solving the Problems] That is, the antibacterial apatite to be provided by the present invention is obtained by supporting silver and zinc and / or copper antibacterial metal ions on apatite, and the amount of these supported is It is characterized in that (Zn + Cu) / Ag is 0.5 or more in a molar ratio, and silver ions are at least 0.2% by weight of the total weight as Ag.

 Hereinafter, the present invention will be described in detail.

As described above, the antibacterial apatite according to the present invention is one in which at least one of zinc ions and copper ions is supported on apatite particles in addition to silver ions as metal ions having antibacterial properties.

The supported amount is such that the molar ratio (Zn + Cu) / Ag is 0.5 or more, preferably in the range of 1 to 20, and the silver ion is at least 0.2% by weight, preferably 0.25 to 5% by weight of Ag as a total weight.
In the range.

The reason for this is that if the molar ratio is less than 0.5, the discoloration resistance is insufficient and either in sunlight or artificial light,
This is because the antibacterial apatite turns black, and when the amount of Ag carried is less than 0.2% by weight, the antibacterial effect is weak even if Zn or Cu is carried. The upper limit is naturally limited due to the economical reason that the key is high. However, in general, when the amount is large, the discoloration tendency becomes strong.

In the present invention, the fact that the antibacterial metal ion is carried on the apatite means that the antibacterial metal ion such as silver, zinc or copper (which may be a complex ion) is used for Ca ⁺⁺ or Mg ^{++ in the} apatite. And ion exchange or reaction (hereinafter,
It refers to a state of being replaced by "ion exchange or the like" and taken into apatite.

If the apatite in the present invention has a composition in which the molar ratio of Mg / P (Me represents Ca or Mg) is 1.4 to 1.8,
Natural or artificially synthesized ones may be used, but halogen elements increase the photosensitivity of silver, so it is better not to contain them as much as possible, and include halogens such as fluorapatite and chloroapatite. Apatite is not suitable. Good synthetic hydroxyapatite,
In many cases, calcium apatite and hydroxyapatite are used, but magnesium hydroxyapatite or carbonated apatite thereof may be used.

The reason why the molar ratio of apatite is in the above range is that when the molar ratio is outside the range, calcium or magnesium phosphate having an apatite structure is not used. In the case of a synthetic product, the production history does not need to be particularly limited. Hereinafter, the present invention will be described using calcium apatite.

Apatite may be in the form of powder or granules, granules or a molded product having a specific shape, and its appearance is designed depending on the application.

However, in many cases, they are in the form of powder, and the degree of fineness also depends on the application. For example, additives such as films, synthetic resins or rubbers, and additives are preferably fine powders as much as possible. In this case, the average particle diameter is preferably in the range of 5 μm at most. Various shapes are known for the primary particles of apatite, but any of them can be applied without limitation.

The antibacterial apatite according to the present invention is a metal-substituted apatite obtained by ion-exchanging metal ions having a bactericidal action as described above with Ca ^{++ in} apatite, but Cu ⁺⁺ , Zn ^{++ and the} like are subjected to cation exchange operation. Depending on how the apatite structure is destroyed and replaced until a crystal of Zn ₃ (PO ₄ ) ₂ .nH ₂ O or Cu ₃ (PO ₄ ) ₂ .nH ₂ O is formed, the antibacterial property is reduced. Such substitutes should be avoided, and the substitution amount is limited to an amount that does not destroy the apatite crystal structure. Although this amount varies depending on the application, the physical properties of apatite, the type of metal ions, etc., it is often necessary that the substitution rate of other metal ions of Ca ^{++ be} in the range of 0.5 to 60% of the initial CaO amount. In particular, as described above, it is necessary that silver ions have a substitution amount of 0.2% by weight based on the total weight of Ag. Although a metal ion having a bactericidal action develops an antibacterial activity in accordance with the amount of substitution, the antibacterial activity is substantially insufficient if the substitution rate is less than 0.5%. On the other hand, if it exceeds 60%, the crystal structure of apatite tends to be damaged depending on the production method or the type of metal ion. However, this is not the case as long as the apatite structure can be maintained.

As described above, the antibacterial apatite according to the present invention mainly has the crystal structure of apatite, and depending on the amount of the metal ion carried, crystals of metal phosphate are also recognized.

Such a metal-substituted apatite can be easily obtained as follows.

That is, it can be easily obtained by holding the apatite and the antibacterial metal salt aqueous solution for a time necessary for performing ion exchange or the like and performing the contact treatment.

In many cases, this treatment is carried out by mixing and stirring the apatite slurry and the aqueous solution of the metal salt at room temperature or under heating.

Although the concentration of the apatite slurry is not particularly limited, the range of 5 to 20% by weight is practical in many cases,
The same applies to the concentration of the aqueous metal salt solution, but in most cases, the range of 0.1 to 50 g / is practical.

There are several modes for mixing the apatite slurry and the aqueous metal salt solution.

For example, representative methods include a method of mixing an apatite slurry with an aqueous solution of a silver salt such as silver nitrate and then mixing with an aqueous solution of zinc and / or copper salt, and a method of mixing and processing an apatite slurry with a mixed aqueous solution of each of the metal salts. However, the apatite molded product may be further subjected to a substitution treatment by bringing an aqueous metal salt solution into contact therewith.

The processing time for mixing and replacing the apatite slurry or apatite molded product with the aqueous metal salt solution is the time required for ion exchange and the like, and may be generally 0.5 to 25 hours, and is preferably in the range of 1 to 5 hours. .

The aqueous solution of the metal salt may be a soluble chloride, sulfate or nitrate, but may be a metal salt solution which generates a metal complex ion such as a copper-aluminum complex.

In addition, during treatment such as ion exchange, apatite is more stable in liquid properties than in the case of zeolite, so that it can be widely applied to acidic or alkaline regions.

However, since a metal hydroxide is easily formed on the alkali side, a chelating agent and a desired metal salt should be appropriately selected.

After the treatment such as ion exchange, it is washed with water in a usual manner, and then dried. If a powder is to be obtained, it is crushed if necessary and finished as a product. [Action] The antibacterial apatite according to the present invention is Ca ^{++ in} apatite.
Alternatively, it is a metal-substituted apatite carrying Mg ⁺⁺ and a metal ion having a bactericidal action such as Ag ⁺ , Cu ⁺⁺ , Zn ⁺⁺ by ion exchange or the like, and has excellent antibacterial activity. That is, this antibacterial apatite shows a broad antibacterial spectrum not only for various bacteria but also for fungi. Although the mechanism of such antibacterial action is unknown, it is difficult to effectively take up microorganisms due to the affinity of apatite for proteins and the presence of antibacterial metal ions such as silver carried on it as active phosphate. Probably sterilized. Furthermore, the antibacterial apatite according to the present invention has significantly improved light stability,
No blackening when exposed to sunlight or artificial light,
The whiteness of apatite can be substantially maintained over a long period of time. The mechanism of such blackening suppression is also unknown, but it is presumed that zinc and / or copper coexisting with silver suppress the precipitation of Ag ₃ PO ₄ and maintain white color.

This property is not only awarded as an indispensable physical property for use in the medical, food and hygiene fields, but also enables vivid coloring with pigments, pigments, etc., and promotes commercial value.

[Example] Example An aqueous mixed metal salt solution having the formulation shown in Table 1 was prepared. Calcium hydroxyapatite slurry [manufactured by Nippon Chemical Industry Co., Ltd., solid concentration 10
%, Trade name Supertight-10], and add 3 g at room temperature.
Stirred for hours. After that, the cake was repulped with 5 times the amount of water of the cake and dried at 70 ° C. for 3 hours.

Table 2 shows the amount of the supported antibacterial apatite on the metal (% by weight), and Table 3 shows the test results.

Antimicrobial activity test 0.5 g of sample prepared in Examples 1 to 7 and Comparative Examples 1 to 5
Was added to 50 ml of previously prepared bacteria-contaminated water (Note 1) or mold dilution water (Note 2), and the mixture was slowly stirred with a magnetic stirrer for 10 minutes. This solution was used for easy microbial measurement equipment EasyCart-TTC [for testing aerobic bacteria, fungi, and yeasts: a product of Sanai Sekiyu KK] and EasyCult-M [Fungi,
For yeast inspection: Sanai Oil Co., Ltd. product], a culture test (Note 3) was performed. The results are shown in Table 3.

(Note 1): The river water was diluted with sterile water, for the number of bacteria · Total bacteria test which was 10 ⁵ (2): · fungus test that the black fungus occurred plaster 1g was diluted in sterile water 100ml (Note 3): Cultivation was performed in an incubator at 27-30 ° C for 2 days (total bacteria) or 4 days (fungi). Color hue test of powder. Put it in, and exposed to sunlight for 5 days, and visually checked the surface layer and the hue of the inside. The bag was placed at a position of 30 cm under a fluorescent lamp (30 W), exposed for 50 hours, and evaluated in the same manner as above. Note 4: The evaluation of the total bacterial count was performed based on the relationship between the degree of colony generation and the bacterial count roughly determined in advance. 0 indicates that no colonies were generated.

Note 5: The degree of fungal contamination was determined by a four-step method.-: No contamination, + Mild contamination, ++: Medium contamination, +++: Strong contamination.

The blanks in Table 3 represent unsubstituted apatite.

[Effect of the Invention] The antibacterial apatite according to the present invention is obtained by adding Ca ^{++ in} apatite.
Or an inorganic antibacterial agent that carries Mg ⁺⁺ with a bactericidal metal ion, especially Ag ⁺ by ion exchange, etc., which not only has a broad antibacterial spectrum but also suppresses photosensitivity (blackening) caused by Ag ⁺ , Can maintain white color for a long time.

Apatite, as is well known in recent bioceramics, is not only a compound that is safe for humans, but also a food additive.

Therefore, an antibacterial agent relating to apatite carrying Ag in particular can be said to be an antibacterial agent safe for humans and animals.

In addition, since apatite has very fine primary particles, this antibacterial agent can be widely used in various fields requiring sterilization, such as industrial use, agricultural use, and food use. For example, when added to rubber or plastic, an antibacterial rubber or plastic is obtained, and when filled in a film, a blocking action can be imparted simultaneously with the antibacterial film.

Furthermore, extremely effective uses such as toothpastes, dental fillers, and powders for skin for preventing dental caries can be expected. In these uses, the light-stable antibacterial apatite according to the present invention can be used as a commercial product. This is extremely important, and the antibacterial apatite of the present invention has a great effect on this application.

Continuation of the front page (51) Int.Cl. ⁶ Identification symbol FI // A61K 6/033 A61K 6/033 (56) References JP-A-1-238508 (JP, A) JP-A-1-164721 (JP, A) (58) Field surveyed (Int.Cl. ⁶ , DB name) A01N 61/00 A01N 59/16-59/20 A01N 25/08 A61K 6/033 WPI / L (QUESTEL)

Claims (3)

(57) [Claims] An apatite carrying antibacterial metal ions of silver, zinc and / or copper, the amount of which is (Zn + Cu) / Ag is 0.5 or more and the silver ion is Ag Antibacterial apatite, characterized by being at least 0.2% by weight per total weight. 2. The antibacterial apatite according to claim 1, wherein the apatite is a hydroxyapatite having a composition of Me / P (Me represents Ca or Mg) in a molar ratio of 1.4 to 1.8. 3. The antibacterial apatite according to claim 1, wherein the supported amount of the antibacterial metal ion is in the range of 0.5 to 60% by weight in terms of MeO in the apatite.