JPH072630B2 - Caries preventive agent - Google Patents

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention contains an antibody obtained by immunizing an animal with whole cells of Streptococcus mutans or components of cells to prevent dental caries and prevent dental caries. More specifically, the present invention relates to a caries preventive agent capable of stably retaining an antibody for a long period of time and thus reliably exerting the effect of the antibody for a long period of time.

[0002]

BACKGROUND OF THE INVENTION Plaque on the surface of teeth is about 70% bacteria, about 20% polysaccharides formed by bacteria, and about 10% food residues.
It sticks tightly to the tooth surface. It is said that the acid stored therein decalcifies enamel and causes caries, and dental plaque is attracting attention as a cause of caries.

The formation of this dental plaque is promoted mainly by the synthesis of polysaccharides from sucrose by oral bacteria, mainly Streptococcus mutans. That is, Streptococcus mutans produces GTF (glucosyl transferase, dextran synthase), which synthesizes adhesive polysaccharides such as dextran and mutan from sucrose. Then, the synthesized polysaccharide is involved in other bacteria (pathogenic bacteria) including Streptococcus mutans and forms dental plaque having a certain bacterial lawn. Also,
Bacteria, such as Streptococcus mutans, utilize various sugars to produce an acid, and the acid retains in the polysaccharide and the wall of the bacteria to decalcify the enamel surface.

Therefore, in order to prevent dental caries, it is desired to suppress the number of Streptococcus mutans and the formation and formation of dental plaque, which are the major causes.

Conventionally, as a method for suppressing colonization of Streptococcus mutans in the oral cavity, a method using breast milk obtained by immunizing cows with whole Streptococcus mutans cells is known (UK Patent No. 1505513).

[0006] The present inventors also examined antibodies that inhibit the colonization of Streptococcus mutans bacteria in the oral cavity among antibodies against various antigens derived from Streptococcus mutans bacteria. As a result, Streptococcus mutans, cell wall fraction of the bacterium, fibrous structure fraction of the bacterium, pili component fraction of the bacterium, glucosyl transferase race fraction of the bacterium, protein antigen fraction of the bacterium It was found that the antibodies in antisera and milk obtained by immunizing mammals with the components of the above have a plaque formation-inhibiting effect, but these antibodies are not always sufficiently and stably retained in caries preventive agents. In particular, there is a problem that it is easily deactivated due to the presence of an anionic surfactant such as sodium lauryl sulfate. Therefore, in order to exert the effect of the antibody well for a long period of time, it is necessary to stably mix these antibodies with a caries preventive agent.

[0007]

Means and Actions for Solving the Problems The present inventors have
In view of the above circumstances, as a result of earnest research on stable incorporation of an antibody obtained by immunizing an animal with whole cells or components of Streptococcus mutans into a caries preventive agent, these antibodies When used in combination with carrageenan, the antibody can be stably retained in the caries preventive agent for a long period of time, and particularly if an anionic surfactant such as sodium lauryl sulfate that easily inactivates the antibody is blended, The present inventors have completed the present invention by finding that the presence of carrageenan can prevent the inactivation of the antibody as much as possible, and that the effect of the antibody can be effectively exhibited even after long-term storage.

The present invention will be described in more detail below.
As described above, the dental caries preventive agent of the present invention contains whole cells or cell components of Streptococcus mutans as an antigen, and an antibody obtained by immunizing an animal with this antigen is mixed. is there.

Here, Streptococcus mutans used as an antigen is one that has been subjected to known culture and pretreatment, for example, using the dialyzed external solution of BHI medium as a medium and washing the grown bacteria with formalin after washing. Can be used. In this case, the Streptococcus mutans bacterium is preferably a strain of human Streptococcus mutans serotype c, d, e, f or g which is isolated from the human oral cavity, or a mutant strain, particularly Those belonging to the serotype classification c, which is abundant in the human oral cavity, are preferred. Such Streptococcus mutans bacteria include NCTC 10449, Ingbritt, OM.
Z70, JC-2, etc., and K-Dp strain (FERM-BP317) and KH2 strain (FE
RM-P7166), K-III strain (Ministry of Engineering, Microbiology Co., Ltd. 63
No. 14) and the like are preferably used.

As the antigen for obtaining the antibody used in the present invention, the whole cells or cell components of Streptococcus mutans described above, particularly the cell wall fraction, the fibrous structure fraction of Streptococcus mutans, Pili component fraction, glucosyl transferase (GTF) fraction,
A protein antigen fraction is used.

[0011] In this case, the cell wall fraction of Streptococcus mutans is Bleweise.
s> et al. (Journal of Bacteriology <J. Bacteriol.>, 88 , 1198-12).
00, 1964), a Brown cell disruptor was used to perform disruption treatment using glass beads having a diameter of 0.17 to 0.18 mm, and the resulting cell wall was treated with trypsin to remove proteins mixed in the cell wall. Those which are prepared by a method such as removing, washing with distilled water and freeze-drying can be used. Fibrous (pili-like or fimbri
al-like) structure fractions are described by J. Van Horte <J. Va
n Hoate> et al. (Archives of Oral Biology <Arch. Oral. Bio.>,
16 , 1131-1141, 1971).
Add 5% sucrose to the dialysis medium and culture under anaerobic conditions,
What was prepared by a method of adding a 3-fold amount of ethanol to the centrifugation supernatant of the culture solution to collect the precipitate, and the like can be used.

As the pili component fraction, culture was carried out according to the method of Tsurumizu et al. (Journal of Bacteriology, 38 (1) 471, 1983) using a solvent such as a phosphate buffer solution containing 1 M sodium chloride. The pure structural fraction prepared from bacteria by the usual cell wall extraction method is used. Specifically, for example, Streptococcus mutans mutant strain K
As a pili component fraction of the Dp strain, the strain was liquid-cultured, and ammonium sulfate was added to the culture solution to reach 33% saturation. After removing the supernatant, the precipitate was added with 1 M sodium chloride-containing phosphate buffer. (PH 7.0) was added and the mixture was stirred at 4 ° C. for 3 days, then the cells were removed by centrifugation, ammonium sulfate was added to the supernatant to make it 60% saturated, and the sedimented portion was dialyzed against phosphate buffer, A pilose component fraction obtained by obtaining a fraction having a sucrose density of about 8 to 15% by a sucrose density gradient ultracentrifugation fractionation method and performing dialysis again with a phosphate buffer is used.

Further, the GTF fraction is obtained by the method of Inoue et al. (Microvial Aspects of Dental Caries <Microbial Aspects of Den.
talcarries> Vol. III, 665-68
2,1976 [Information Retrial Incorporation <Informatin Retr
ieval Inc. >)), Inoculate Streptococcus mutans into a BHI dialysis medium, remove the cells by centrifugation after growth, add ammonium sulfate to the supernatant, and precipitate the 40% ammonium sulfate fraction with a 50 mM phosphate buffer solution. It is possible to use those prepared by a method such as dialysis with and using a concentrated solution.

Further, the protein antigen fraction is a Leener <L
ehner> et al.'s method (Journal of General Microbiology <J. General Mic
robology>, 122 , 217-225, 19
81), culturing in a BHI dialysis medium and centrifuging the resulting supernatant and fractionating with 75% ammonium sulfate,
A precipitate was collected, and the precipitate was added to DE-52 in the presence of 6M urea.
Column chromatography was performed, the protein antigen fraction was dissolved in physiological saline, and after dialysis, Sepharose CL6 was used.
Those prepared by the method of performing gel filtration in B to obtain a fraction can be used.

As a method of immunizing an animal with the antigen, a usual method can be adopted. In addition, as an animal to be immunized, goat,
Mammals such as sheep, horses, cows and rabbits are effectively used.

The present invention uses an antiserum obtained by immunizing a mammal with the above-mentioned antigen as described above, and an antibody in milk as an active ingredient. In the present invention, an antiserum containing this antibody is used. And milk may be used, or antiserum and antibody separated and purified from milk may be used.
Furthermore, these 1 type may be used individually or in mixture of 2 or more types.

The antibody (antiserum or protein fraction in milk) can be separated from antiserum or milk according to a conventional antibody purification method. Examples of the antibody purification method include salting out method, gel filtration method, ion exchange chromatography, affinity chromatography and the like. Among them, the salting out method using ammonium sulfate is preferable. The salting out method is
The antiserum and milk are saturated with ammonium sulphate, preferably at a concentration of not more than 40%, the precipitate is purified and the precipitate is subsequently salted out with physiological saline to obtain a purified precipitate as an antibody. Preferred antibodies are those obtained from horse antiserum, bovine antiserum and milk.

The dose of the antibody is 0.0001 to 50 g /
The dose is preferably kg / day, and in this case, the amount of the antibody is 0.0002 to 10% (weight%, the same applies hereinafter), particularly 0.002 to 5% of the total dosage form containing the antibody, and Preference is given to using.

The caries preventive agent of the present invention comprises carrageenan as a stabilizer of the antibody in addition to the above-mentioned antibody, whereby the inactivation of the antibody can be effectively prevented, and particularly the antibody The antibody can be stably retained for a long period of time even if an anionic activator or the like that easily deactivates is mixed.

Here, as carrageenan, ι, κ,
A single type or a mixture of each type of λ may preferably be used.

The content of carrageenan is preferably 0.001 to 10%, more preferably 0.05 to 5% of the total caries preventive agent.

In the caries preventive agent of the present invention, in addition to the above-mentioned antibody, one or more selected from fluorine compounds, chlorhexidines, lytic enzymes, bacteriocins, glucosyl transferase inhibitors, proteases and dextranases. A synergist can be used in combination, which further suppresses the establishment of Streptococcus mutans, significantly increases the plaque formation suppressing effect, and can improve the caries preventing effect.

In this case, as the fluorine compound, monofluorophosphate salts such as sodium monofluorophosphate, potassium monofluorophosphate, sodium hydrogen monofluorophosphate, ammonium monofluorophosphate, and fluorinated compounds are used. Alkali metal fluorides such as sodium, potassium fluoride, lithium fluoride and ammonium fluoride, potassium hexafluorozirconate, potassium hexafluorotitanate, cesium fluoride, nickel fluoride, zirconium fluoride, silver fluoride, Hexylamine hydrofluoride, laurylamine hydrofluoride, cetylamine hydrofluoride, glycine hydrofluoride, lysine hydrofluoride, alanine hydrofluoride and the like are used. Among these, monofluorophosphate salts such as sodium monofluorophosphate, potassium monofluorophosphate, alkali metal fluorides such as sodium fluoride, potassium fluoride, ammonium fluoride, and fluoride fluorides. Stannous fluorides such as stannous tin and stannous fluorochloride can be preferably used, but sodium monofluorophosphate, sodium fluoride and stannous fluoride are particularly preferably used.

As chlorhexidines, chlorhexidine hydrochloride, chlorhexidine gluconate and the like are used.

As the lytic enzyme, Streptomyces
Grisse <Streptomyces grise
us>, Streptomyces diasterocromagen <Streptomyces diastatoc
romagenes>, Streptomyces farinos
us>, Chararopsis genus <Charaaropsi>
s>, Flavobacterium <Flavobacter
ium>, Myxobacter genus <Myxobacte
r>, Staphylococcus epidermidis <St
aphylococcus epidermidi
s>, Micrococcus genus,
Pseudomonas <Pseudomonas
aetuginosa>, genus Aeromonas <Aerom
onas>, Streptomyces arbus <Stre
ptomyces albus>, Streptomyces glo
Those derived from bisporus, etc. can be used, and as bacteriocin, Enterobacter croace <En
terrobacterium cloacae, Escherichia coli, Proteus miabili
s>, Pseudomonas arginosa <Pseudomo
nas aeruginosa>, Streptococcus mutans
ns>, Staphylococcus staphylol
yticus> and the like can be used.

Examples of GTF inhibitors include Erythrinum sp. >, Fusarium sp. <Fusarinum sp. >, The genus Microphomina spp. >, Genus Micromonospora <Micromonospora sp. >, Nomonilla sp. <Gnomoniella sp. >, Genus Noturisporium
p. >, Aspergillus <Aspergillus
sp. > And the like can be preferably used, and specifically, JP-A-56-103193 and 57-2809.
No. 7, JP-A-57-98215, and JP-A-57-146.
Those described in Japanese Patent No. 587 can be used.

As the protease, Aspergillus sp. >, Bacillus <B
acillus sp. >, Etc., can be preferably used, and as the dextranase, the genus Ketomium <Ch
aetium sp. >, Streptomyces sp. And the like can be preferably used.

In the present invention, one type of these synergist components may be used alone, or two or more types may be used in combination. Alternatively, the antibody and the synergist component may be mixed together to prepare a predetermined dosage form, or the antibody and the synergist component may be prepared in separate dosage forms, and both may be used together when used. May be.

The dose of these synergist components is 0.0001 to 1 g / k in terms of fluorine in the case of a fluorine compound.
g / day, 0.0001 to 1 g / kg / day as chlorhexidine for chlorhexidines, 0.0001 to 10 g / kg / day for lytic enzymes and bacteriocins
Day, 0.0001 to 10 g / kg / day for glucosyl transferase inhibitor, 0.0001 to 5 g / day for protease and dextranase, respectively
It can be kg / day. In the case of a fluorine compound, these synergist components are 0.0001 to 0.1% in terms of fluorine, particularly 0.0001 to
0.001%, in the case of chlorhexidines, as chlorhexidine, 0.1 to 1000 ppm, especially 10 to 10
0 ppm, 0.0001-10% in the case of lytic enzyme and bacteriocin, especially 0.001-5%, 0.0 in the case of glucosyl transferase inhibitor
001 to 10%, especially 0.001 to 5%, in the case of protease 0.0001 to 10%, especially 0.001 to 5%
%, In the case of dextranase 0.0001 to 10%,
In particular, the compounding amount of 0.001 to 5% can be applied in the oral cavity at the above dose.

The caries preventive agent according to the present invention is a toothpaste such as toothpaste, powder toothpaste, liquid toothpaste, mouthwash, oral pasta, gum massage cream, tablets such as effervescent tablets for gargling, troches, chewing gum, ice cream. It is prepared and used in various modes such as cream and whipped cream that are applied to the oral cavity, and as other components of the caries preventive agent of the present invention, suitable components according to the purpose of use and the mode of use are used. Used.

For example, for the preparation of toothpaste, dibasic calcium phosphate dihydrate, dibasic calcium phosphate anhydrous, monobasic calcium phosphate, tribasic calcium phosphate, calcium carbonate, calcium pyrophosphate, insoluble sodium metaphosphate, amorphous silica. Abrasives such as crystalline silica, aluminosilicate, aluminum oxide, aluminum hydroxide, tribasic magnesium phosphate, magnesium carbonate, magnesium sulfate, titanium oxide and resin are usually 5 to 95.
%, Preferably 15-60%.

A binder is mixed in the preparation of a paste-like composition such as toothpaste, and carrageenan is used as a binder in the present invention. In this case, other binder may be used in combination with carrageenan. Here, as other binders, sodium carboxymethyl cellulose, methyl cellulose, sodium carboxymethyl hydroxyethyl cellulose, hydroxyethyl cellulose, sodium alginate, gum arabic, xanthan gum, tragacanth gum, karaya gum, polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer and Examples thereof include polyvinylpyrrolidone. The content of the binder can be usually 0.3 to 5%.

For the preparation of paste-like and liquid oral compositions such as toothpaste and mouthwash, polyethylene glycol, ethylene glycol, sorbitol, glycerin, propylene glycol, 1,3-butylene glycol, xylit, maltite, lactit, etc. The thickening agent is usually added in an amount of 10 to 70%.

Further, the caries preventive agent of the present invention contains 0.1 to 6%, particularly 0.3 to 3% of anionic surfactants, and further nonionic, cationic and zwitterionic surfactants. can do. In this case, in the present invention, the carrageenan as described above can effectively prevent the deactivation of the antibody even if the anionic surfactant that easily deactivates the antibody is mixed, as described above. Activator,
For example, water-soluble salts of alkyl sulfates having 8 to 18 carbon atoms such as sodium lauryl sulfate and sodium myristyl sulfate, and fatty acid groups such as sodium lauryl monoglyceride sulfate, sodium coconut oil fatty acid monoglyceride sulfate, and higher fatty acid monoglyceride sodium sulfate 1
0-18 water-soluble higher fatty acid monoglyceride sulfate, α-olefin sulfonate, paraffin sulfonate, sodium salt of N-methyl-N-palmityl taurate, sodium N-lauroyl sarcosinate, N
A water-soluble salt of an alkyl sulfate, such as -lauroyl-β-alanine sodium salt, can be effectively added.

As the nonionic activator, fatty acid alkanolamides such as lauric acid diethanolamide,
Sucrose fatty acid ester such as sucrose mono and dilaurate, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid ester, polyoxyethylene hydrogenated castor oil derivative, lactose fatty acid ester, lactitol fatty acid ester, maltitol fatty acid ester, polyoxyethylene poly Oxypropylene block copolymers and the like can be mentioned, and one or more of these are used, and the stability of the antibody can be further enhanced by blending these nonionic activators.

Further, in the caries preventive agent of the present invention, if necessary, essential oils such as peppermint and spearmint, perfumes such as 1-menthol, carvone, eugenol, anethole and other perfume materials, sodium saccharin, stevioside,
Neohesperidyl dihydrochalcone, glycyrrhizin,
Sweeteners such as perillartine and p-methoxycinnamic aldehyde, preservatives and the like are appropriately added. In the present invention, mutanase, sorbic acid, alexidine, hinokitiol, cetylpyridinium chloride,
Effective for alkylglycine, alkyldiaminoethylglycine salts, allantoin, ε-aminocaproic acid, tranexamic acid, azulene, vitamin E, water-soluble primary or secondary phosphates, quaternary ammonium compounds, sodium chloride, crude drug extracts, etc. Ingredients can also be included.

Also in the case of other types of compositions, suitable components which are usually used are selected and mixed by a usual method.

Here, when the agent for preventing dental caries of the present invention is formed into a liquid or paste, its pH is not necessarily limited, but pH 4 to 10, more preferably 5 to 9, and especially 5.
It is preferably set to 5 to 7.5.

The dental caries preventive agent of the present invention is put in an appropriate container, stored, and then used. For example, in the case of toothpaste, it can be stored in a plastic container such as a plastic tube or an aluminum foil laminated plastic tube, or a metal container such as an aluminum tube. In this case, the antibody is relatively easy to deactivate in a metal container, but by adding carrageenan, it is possible to favorably prevent the deactivation of the antibody in the metal container. , A metal container such as an aluminum tube can be effectively used.

[0040]

The caries preventive agent of the present invention is applied to the oral cavity in an appropriate mode depending on the dosage form thereof, etc., and the whole cells or cell components of Streptococcus mutans are used to treat animals. The antibody obtained by immunization inhibits the colonization of Streptococcus mutans bacteria in the oral cavity and suppresses the formation of dental plaque, thereby preventing dental caries. By using carrageenan together, the inactivation of the antibody is prevented, and the effect of the antibody can be effectively exhibited even after long-term storage.

[0041]

EXAMPLES The present invention will be described in detail below by showing experimental examples and examples. The production examples of antisera, breast milk and antibodies used in the following experimental examples and examples are shown below.

[Production Example] Using the following antigen, the antiserum and breast milk were obtained by the following method. (1) Antigen Streptococcus mutans BHI medium was dialyzed with an external solution used as a medium, and the grown bacteria were washed and then formalin-treated. Cell Wall Fraction of Streptococcus mutans The method of Bleweise <J. Bacteriology <J.
l. >, 88 , 1198-1200, 1964). Fibrous structure fraction of Streptococcus mutans J. van Horte <J. Van Hoate> et al. (Archives of Oral Biology <A
rch. Oral. Bio. >, 16 , 1131-111
41, 1971). Glucosyl tran of Streptococcus mutans
Spherase fraction method of Inoue et al. ( Microvial Aspect of
Dental Caries <Microbial Aspec
ts of dental carriers> Vol. I
II, 665-682, 1976 [Information Retrial Incorporation <Information
atin Retrieval Inc. >))) Was used. Protein antigen fraction of Streptococcus mutans
Min. Lehner's method (Journal of General Microbiology <J. Gener
al Microbiology>, 122 , 217-.
225, 1981). Pili component fraction of Streptococcus mutans Method of Tsurumizu et al. (Journal of Japanese Bacteriology, 38 (1) 471, 1
Use the one prepared according to 983).

(2) Method for preparing antiserum, breast milk and antibody 50 to 100 μg / ml of antigen was mixed with an equal amount of Freund's complete adjuvant, and the subcutaneous dose was applied to the back of pregnant goats, horses, cattle or rabbits at a dose of 0. Immunization was performed by injecting 3 ml, and thereafter, immunization was repeated 3 times with a mixture of an antigen and Freund's incomplete adjuvant every 2 to 4 weeks, and colostrum was collected after delivery. As for the antiserum, blood was collected after immunization 4 times and coagulated as described above, and the centrifuged supernatant was used as a sample.

Next, an equal amount of 0.9% was added to the colostrum sample.
After adding saline and centrifuging at 15,000 rpm for 60 minutes, the upper layer fat and sediment were removed to collect an intermediate liquid component, and concentrated hydrochloric acid was added thereto to adjust the pH to 4. Furthermore, 5
After centrifugation at 000 rpm for 30 minutes, the supernatant was neutralized with trishydroxyaminomethane, ammonium sulfate was added to 75% saturation, and the obtained precipitate was collected and dialyzed against phosphate buffer. , An antibody component (internal solution) of breast milk was obtained.

Ammonium sulfate was added to the above antiserum to make it 50% saturated, and the resulting precipitate was dialyzed against a phosphate buffer to obtain an antiserum antibody (internal solution).

Experimental Example 1 A toothpaste having the following formulation was prepared. Aluminum hydroxide 43% 60% Solbit liquid 35 Propylene glycol 3.0 Binder 1.0 Gelatin 0.3 Saccharin sodium 0.1 Perfume 1.0 Sodium monofluorophosphate 0.76 Methylparaben 0.2 Butylparaben 0. 01 Sodium lauryl sulfate 0.8 Lauric acid diethanolamide 1.0 Horse anti-S. Mutans 10449 strain pili component serum 0.5 water remainder Total 100.0%

Next, the toothpaste was stored at 40 ° C. for 2 weeks, and the antibody activity thereof was measured by the following method to examine the antibody residual rate. The results are shown in Table 1. The results are shown by the relative activity when the antibody activity after storing a toothpaste using carrageenan as a binder at 40 ° C. for 2 weeks is 100.

Antibody activity measuring method To 1 g of toothpaste, 4 ml of phosphate buffer (0.1 M, p
H7) is added and the soluble components in the toothpaste are dissolved in phosphate buffer, followed by centrifugation to collect the supernatant. The activity of the antibody component in this supernatant was determined by the ELISA method using the bacterial cells of the Streptococcus mutans mutant K-Dp strain as an antigen (Ingval E. et al., Journal of Immunology <Eng vall E. et al.,. J.I
mmunol. >, 109: 129-135,179
Measure in 2).

Regarding the activity of the antibody component, the heptone-containing dentifrice showing the maximum absorbance when the absorbance at 405 nm was used as an index was set to 100%.

[0050]

[Table 1]

Examples will be shown below. [Example 1] Toothpaste Propylene glycol 2.5% Carrageenan 1.0 Methylparaben 0.1 Butylparaben 0.01 Sodium benzoate 0.2 60% Sorbit solution 30.0 Sodium saccharin 0.15 Sodium monofluorophosphate 0. 76 Chlorhexidine hydrochloride 0.01 Sodium lauryl sulfate 0.8 Sodium lauroyl sarcosinate 0.2 Polyoxyethylene (40 mol) hydrogenated castor oil 0.8 Perfume 0.6 Abrasive silica 35.0 Horse anti-S. Mutans JC2 strain whole cell antibody 0.01 Lysozyme 0.01 Purified water balance Total 100.0%

[Example 2] Mouthwash Polyoxyethylene (40 mol) sorbitan monostearate 3.0% Carrageenan 0.01 Disodium phosphate 1.25 Citric acid 0.88 Chlorhexidine gluconate 0.01 Monoflu Sodium Orthophosphate 3.8 Horse Anti-S. Dilute 10-fold with water after use mutans 10449 strain whole cell antibodies 0.1 Sorbitol 15.0 Perfume 0.8 Sodium saccharin 0.2 Purified water balance Total 100.0%.

Claims (10)

[Claims] 1. A caries preventive agent comprising an antibody obtained by immunizing an animal with whole cells or components of Streptococcus mutans, and carrageenan. . 2. The method according to claim 1, wherein the Streptococcus mutans is a human Streptococcus mutans and the serotype is a strain of c, d, e, f or g or a mutant strain. Anti-corrosion agent. 3. The caries preventive agent according to claim 2, wherein the mutant strain is a Streptococcus mutans mutant strain K-Dp strain, KH2 strain or K-III strain. 4. The cell component of Streptococcus mutans, which is a cell wall fraction, a fibrous structure fraction, a pilus component fraction, a glucosyltransferase race fraction, or a protein antigen fraction. Item 4. A caries preventive agent according to any one of items 3 to 3. 5. The caries preventive agent according to any one of claims 1 to 4, wherein an antiserum or milk containing this antibody is mixed as an antibody. 6. The dental caries preventive agent according to any one of claims 1 to 4, wherein an antibody separated from antiserum or milk containing the antibody is blended as an antibody. 7. The compounding amount of the antibody is 0.000 of the whole preventive agent.
The caries preventive agent according to any one of claims 1 to 6, which is 2 to 10% by weight. 8. The caries preventive agent according to any one of claims 1 to 7, wherein the content of carrageenan is 0.001 to 10% by weight of the total preventive agent. 9. The caries preventive agent according to claim 1, wherein the pH of the caries preventive agent is in the range of 4 to 10. 10. The caries preventive agent according to claim 9, wherein the pH of the caries preventive agent is in the range of 5 to 9.