Dentifrice Containing Antibacterial Material

1. Field of the Invention

This invention relates to improvements in a dentifrice (tooth paste or powder), and more particularly to the dentifrice having an antibacterial effect.

2. Description of the Prior Art

In general, a dentifrice (tooth paste or powder) includes abrasive powder, foaming agent, perfume and taste adjusting agents, lubricant, caking additive and medicative ingredients as main components. In recent years, a dentifrice provided with an antibacterial effect has been developed, in which organic substances such as parahydroxybenzoates, chlorhexidines, hinokitiol and protamine and inorganic substances such as salt are known and used as materials exhibiting an antibacterial effect.

However, such a dentifrice containing the antibacterial materials is problematic from view points of toxicity, stability and taste, owing to the character of the antibacterial materials. Particularly, almost all the conventional antibacterial materials are low in heat-resistance and soluble in water, and therefore difficult to be thermally processed and not durable to use for a long period of time.

In this connection, it is known that metals such as silver, copper and zinc and salts thereof exhibit a high antibacterial effect. However, these metals or the salts cannot be safely used in a dentifrice (tooth paste) because metal ions of the metal tend to be readily released thereby causing a toxicity.

It is an object of the present invention to provide an improved dentifrice (tooth paste or powder) which can overcome the drawbacks encountered in conventional dentifrices.

Another object of the present invention is to provide an improved dentifrice (tooth paste or powder) which is high in safety and stability, while maintaining a high antibacterial effect.

A further object of the present invention is to provide an improved dentifrice (tooth paste or powder) in which an antibacterial material is stably and firmly carded or supported by a carrier as a component of the dentifrice.

An aspect of the dentifrice (tooth paste or powder) of the present invention comprises a calcium compound, and an antibacterial metal carded by the calcium compound. Another aspect of the dentifrice of the present invention comprises a phosphate containing calcium, and an antibacterial metal carried in a metallic state by the calcium containing phosphate. Accordingly, the dentifrice exhibits a high antibacterial effect. The antibacterial metal carded by the calcium compound is highly stable, and therefore the toxicity due to the ion form of the metal is prevented while contributing to a medical treatment of teeth and further providing the dentifrice with a good preservability for a long period of time. Thus, the dentifrice of the present invention is highly effective for preventing occurrence of carious tooth and periodontal diseases such as alveolar blennorrhea.

A dentifrice (tooth paste: or powder) according to the present invention is comprised of a calcium compound, and an antibacterial metal carried by the calcium compound. More specifically, the dentifrice according to the present invention is comprised of a phosphate containing calcium (such as hydroxylapatite, tricalcium phosphate and calcium diphosphate), and the antibacterial metal carded in its metallic state by the calcium containing phosphate.

Examples of the calcium compound are calcium hydrogenphosphate CaHPO.sub.4 .multidot.0--2H.sub.2 O, tricalcium phosphate Ca.sub.3 (PO.sub.4).sub.2, calcium diphosphate Ca.sub.2 P.sub.2 O.sub.7, calcium carbonate CaCO.sub.3 and the like. Examples of the antibacterial metal are silver (Ag), zinc (Zn), copper (Cu) and the like. The antibacterial metal(s) are carried by or combined to the calcium compound under an ion exchange and/or adsorption, thereby forming an antibacterial calcium compound(s). The antibacterial calcium compound(s) is mixed in the dentifrice (tooth paste or powder). The use of the antibacterial metal adds the functions of preventing generation of carious tooth and periodontal diseases such as alveolar blennorrhea, to the dentifrice.

A method of production of an antibacterial calcium hydrogenphosphate will be discussed. First, metallic salt(s) such as silver nitrate or silver sulfate is added to an aqueous suspension of calcium hydrogenphosphate under agitation to promote the reaction between the metallic salt(s)and the calcium hydrogenphosphate, thereby forming a reaction product. Thereafter, the reaction product is rinsed, dehydrated and dried thereby to obtain the antibacterial calcium hydrogenphosphate. Besides, the antibacterial calcium hydrogenphosphate is obtained by firing the above-mentioned dehydrated and dried reaction product at a temperature of 800.degree. C. or higher, or by reducing the above-mentioned dehydrated and dried reaction product with hydrogen, in which the antibacterial metal(s) are carried in a metallic state (not in an ionic or salt state) on the calcium compound. In the process of the heating or the reduction with hydrogen, the antibacterial metal will be converted from its ionic state to its metallic state. It will be understood that antibacterial hydroxylapatite, antibacterial tricalcium phosphate, antibacterial calcium diphosphate, antibacterial calcium carbonate and the like can be obtained by the same production method as that of the antibacterial calcium hydrogenphosphate and the like in which the antibacterial metal is carried in its metallic state by the calcium hydrogenphosphate.

For example, an antibacterial phosphate containing calcium (such as hydroxylapatite, tricalcium phosphate and calcium diphosphate) is prepared by virtue of using a firing step as follows:

Hydroxylapatite in an amount of 1.0 kg is added to 10 liters of water together with 32 g of silver nitrate and 69 g of zinc nitrate, and then the whole was stirred to make a reaction. The solids are separated off to form a cake, then the cake is rinsed thoroughly with distilled water and dried. The washed cake is heated or fired at 1200.degree. C. and powdered to provide the antibacterial hydroxylapatite carrying about 2% by weight of silver in a metallic state and 1.5% by weight of zinc in a metallic state.

Tricalcium phosphate in an amount of 1.0 kg of tricalcium phosphate is added to 10 liters of distilled water together with 30 g of silver nitrate and 45 g of zinc nitrate, and the whole is stirred to make a reaction. The solids are separated off to form a cake, and then the cake is rinsed thoroughly with distilled water and dried. The dried cake is heated or fired at 1100.degree. C. and powdered to provide the antibacterial tricalcium phosphate carrying about 0.5% by weight of silver in a metallic state and about 1% by weight of zinc in a metallic state.

Otherwise, the antibacterial phosphate containing calcium carrying an antibacterial metal such as silver is prepared by virtue of using a reduction step as follows:

Metallic salt(s) such as silver nitrate and/or silver sulfate is added to an aqueous suspension of the calcium containing phosphate under agitation to promote the reaction between the metallic salt(s) and the phosphate, thereby forming a reaction product or solid in which metallic ion and/or the metallic salt is supported on the phosphate. Thereafter, the reaction product is rinsed, dehydrated and dried. The dried reaction product is put in a reaction tube and heated at a temperature of 350.degree. C. or higher in the stream of hydrogen so as to reduce the metallic ion and/or metallic salt, thereby obtaining the antibacterial phosphate carrying the antibacterial metal in a metallic state.

An antibacterial calcium hydrogenphosphate (carrying or containing 0.1 wt % of silver), an antibacterial tricalcium phosphate (carrying or containing 2 wt % of silver and 3 wt % of zinc), an antibacterial calcium diphosphate (containing or carrying 1 wt % of silver and 2 wt % of zinc), and an antibacterial calcium carbonate (containing or carrying 0.001 wt % of silver) will be used in Experiment 1 set forth below. It will be appreciated that these antibacterial materials were prepared by methods similar to those mentioned above for the antibacterial phosphate containing calcium, so that the antibacterial metal(s) is carried in a metallic state on the calcium compound in the antibacterial materials to be used in Experiment 1.

The amount of the antibacterial metal carried by the calcium compound is suitably selected according to the kind of the metallic salt to be used, the concentration and the temperature of the aqueous suspension of the calcium compound. The amount of the antibacterial metallic salt is preferably not more than 30% by weight, and more preferably 5 to 0.0001% by weight relative to the amount of the calcium compound such as calcium phosphate and calcium carbonate.

The thus obtained antibacterial calcium compound exhibits a sufficient antibacterial effect even upon addition of a small amount thereof to the dentifrice, maintaining the antibacterial effect for a long period of time. Additionally, the antibacterial calcium compound can be safely used since the amount of released metal to water is extremely small, i.e., less than several ppb.

The dentifrice of the pre, sent invention will be discussed further in detail with reference to experiments for Examples and Comparative Example.

[Preparation of Specimen Tooth Paste and Powder]

in this experiment, first specimen tooth pastes having compositions of Examples 1 to 4 and of Comparative Example 1 were prepared by mixing components listed below in each Example. It will be understood that the antibacterial calcium compound carrying the antibacterial metal(s) to be used in Examples 1 to 4 were previously prepared as discussed above.

[Antibacterial Test]

1 gram of each specimen tooth paste prepared in Examples 1 to 4 and Comparative Examples 1 and 2 was added to 10 ml of a liquid containing each of bacillus (streptococcus mutans type G and streptococcus sanguis as bacilluses or causatives for carious tooth, and actinobacillus actinomycetemcomitans Y4 and bacteroides gingivalis as bacillus or causatives for periodontal diseases) in a flask. The flask was shaked according to a so-called shake flask method in which the number of living bacillus was measured with lapse of time in order to evaluate an antibacterial. effect. The result of the antibacterial test is shown in Table 1.

As can be appreciated from Table 1, the specimen tooth pastes of Examples (according to the present invention) are considerably high in antibacterial effect to the bacillus for carious tooth and periodontal diseases such as alveolar blennorrhea, as compared with that of Comparative Example (a conventional tooth paste). Additionally, a released metal content test for the specimen tooth pastes were conducted, which revealed that no releasing of the antibacterial metal was recognized.

While only silver and zinc have been described as being used as the antibacterial metal in Examples, it will be appreciated that they may be replaced with other antibacterial metals.

The above-mentioned examples of the calcium compound includes apatite. In case of using apatite as the calcium compound of the present invention, the antibacterial metal such as silver (Ag), copper (Cu) and/or zinc (Zn) is carried by or combined with the apatite under ion exchange and/or adsorption thereby to form an antibacterial apatite. The thus formed antibacterial apatite takes the form of Ca.sub.10-x .multidot.M.sub.x (PO.sub.4).sub.5 (OH.sub.2, Ca.sub.10 (M.multidot.PO.sub.4).sub.5 (OH).sub.2 or the like, in which M is the antibacterial metal, and x is an integer or decimal larger than 0. The antibacterial apatite is mixed in the dentifrice (tooth paste). The antibacterial apatite is stable and heat-resistive, and good in mixability with the tooth paste since the apatite is in the state of powder.

The antibacterial apatite can be easily produced under coexistence of the metallic salt of the antibacterial metal(s) during synthesis of the apatite, or by reacting the metallic salt with the apatite. More specifically, according to the former method, a phosphoric acid aqueous solution is dropped to an aqueous solution containing calcium hydroxide and the metallic salt(s) of silver, copper, zinc and/or the like under stirring thereby synthesizing the antibacterial apatite. According to the latter method, fine powder of the apatite obtained under the conventional method is suspended in distilled water to form a suspension. To the suspension, a water-soluble metallic salt(s) of the antibacterial metal(s) is added and then stirred to promote the reaction between the apatite and the antibacterial metal(s) thereby to form a product. Thereafter, the product is rinsed, dried and pulverized thus obtaining the antibacterial apatite.

In the above production processes, there is the possibility that calcium salt remains in the resultant antibacterial apatite, the calcium salt being formed during the reaction process in which acidic roots, the metallic salts and metallic ions are replaced with calcium ions. Accordingly, it is preferable that the resultant antibacterial apatite is sufficiently rinsed with water in order to completely remove these foreign matters.

The amount of the antibacterial metal carried by the apatite is suitably selected according to the kind of the antibacterial metal to be used, and the concentration and the temperature of the aqueous solution containing the apatite or raw materials of the apatite. The amount of the antibacterial metal is preferably not more than 30% by weight, more preferably 5 to 0.0001% by weight relative to the apatite.

The thus obtained antibacterial apatite exhibits a sufficient antibacterial effect even upon addition of a small amount thereof to the dentifrice, maintaining the antibacterial effect for a long period of time. Additionally, the antibacterial apatite can be safely used since the amount of released metal to water is very small, i.e., less than several ppb.

The antibacterial apatite will be discussed further in detail with reference to experiments conducted to evaluate advantageous effects of the antibacterial apatite.

[Preparation of Specimen Tooth Paste]

Specimen tooth pastes having compositions of Examples 5 and 6 and Comparative Examples 2 and 3 were prepared. In Example 5, the antibacterial apatite was a hydroxylapatite carrying 2% by weight of silver and 3% by weight of zinc which were adsorbed to or combined (under ion exchange) with the apatite. The antibacterial hydroxylapatite obtained under the ion exchange seems to take the form of Ca.sub.10-x-y .multidot.Zn.sub.y .multidot.Ag.sub.x (PO.sub.4).sub.6 (OH).sub.2, Ca.sub.10-y .multidot.Zn.sub.y (Ag.multidot.PO.sub.4).sub.6 (OH).sub.2 or the like, in which x and y are respectively integers or decimals larger than 0. In Example 6, the antibacterial apatite was a hydroxylapatite carrying 0.1% wt weight of silver which had been absorbed to and carried (under ion exchange) by the hydroxylapatite. The antibacterial hydroxylapatite obtained under the ion exchange seems to take the form of Ca.sub.10-x .multidot.Ag.sub.x (PO.sub.4).sub.6 (OH).sub.2, Ca.sub.10 (Ag.multidot.PO.sub.4).sub.6 (OH).sub.2 or the like.

[Antibacterial Test (I)]

In case of Examples 5 and 6 and Comparative Example 2, 1 gram of each specimen tooth paste was sampled. In case of Reference Example 1, 0.001 gram of the powder of the antibacterial hydroxylapatite was sampled. Each of the thus sampled specimen tooth paste and the hydroxylapatite powder was added to 10 ml of a liquid containing each of bacillus (streptococcus mutans type G and streptococcus sanguis as bacillus or causatives for carious tooth, and actinobacillus actinomycetemcomitans Y4 and bacteroides gingivalis as bacillus or causatives for periodontal diseases) in a flask. The flask was shaked according to the shake flask method in which the number of living bacillus was measured with lapse of time in order to evaluate an antibacterial effect. The result of the antibacterial test is shown in Table 2.

As can be appreciated from the test result of Table 2, the composition of the tooth pastes of the above Examples exhibits a sufficient antibacterial effect against the bacillus which causes carious tooth and for periodontal diseases. Additionally, as a result of further tests conducted in which the content or blended ratio of the antibacterial hydroxylapatite was changed in the above specimen tooth paste of Examples 5 and 6, it was revealed that a sufficient antibacterial effect was exhibited if only 0.01% by weight of the antibacterial hydroxylapatite was added to the tooth paste.

[Antibacterial Test (II)]

In this test, the antibacterial effect of only the antibacterial hydroxylapatite was measured. The test was conducted on the antibacterial hydroxylapatites used in Examples 5 and 6 as follows: First, binder was added to and mixed with the antibacterial hydroxylapatite to form a mixture. The mixture was subjected to a compression-molding and then degreased at 500.degree. C. thereby to obtain a pellet (formed of the antibacterial hydroxylapatite 100%) having a diameter of 3 cm. Thereafter, escherichia coli (E. coli) was adhered to the pellet, upon which the change of the number of living bacillus with the lapse of time was observed. The test result is shown in Table 3.

In this test, the released amount of the carded antibacterial metal was measured for a first sample of the hydroxylapatite carrying 5% by weight of silver (Ag) as the antibacterial metal, and for a second sample of the hydroxylapatite carrying 5% by weight of zinc (Zn) as the antibacterial metal. The test was conducted as follows: First, 1 gram of each of the first and second sample hydroxylapatites was added to 100 cc of distilled water and stirred for a long period of time. Then, measurement was made on the concentration of the metal released from the hydroxylapatite to the aqueous solution. As a result, in case of the first sample, the concentration of the released metal was 0.01 ppm or less. In case of the second sample, the concentration was 0.2 ppm or less. Accordingly, it was confirmed that the antibacterial metal carded by the hydroxylapatite was not released at all to water. Additionally, it was also confirmed that no change occurred in the concentration of the released metal even upon lapse of time. This revealed that the antibacterial hydroxylapatite was highly stable as a molecule, which seemed to be caused because of the fact that the antibacterial metal was indeed firmly combined with or taken up into the fine pores of the molecule structure of the hydroxylapatite.

The antibacterial hydroxylapatite has functions to separate protein and to remove dental plaque as a source for producing carious tooth, and therefore has a further effect to preventing occurrence of the carious tooth in addition to the above-discussed antibacterial effect. Moreover, the antibacterial hydroxylapatite functions to be filled in fine grooves or depressions on the surface of teeth thereby accomplishing the restoration of the teeth.

As appreciated from the above, the antibacterial hydroxylapatite is stable in molecular structure and therefore is prevented from exhibition of toxicity due to the antibacterial metal, maintaining a good preservability for a long period of time. Thus, the dentifrice (tooth paste) containing the antibacterial hydroxylapatite, according to the present invention is very effective for preventing occurrence of carious tooth and periodontal diseases, suppressing occurrence of hyperesthesia due to the carious tooth and the periodontal diseases and other oral disorders in general.