JPS61112030A - Preventive for dental caries - Google Patents

Abstract

PURPOSE:A preventive for dental caries having an inhibitory action on formation of bacterial plaque for a long period, obtained by immunizing an animal against the whole mold a mold component of Streptococcus mutans to give an antibody, and blending a preventive for dental caries with it and aluminum hydroxide. CONSTITUTION:An animal is immunized against the whole mold or a mold component (e.g., cell wall fraction, or fibrous structure fraction) of Streptococcus mutans, preferably a strain or a mutant (e.g., K-Dp strain, or KH2 strain) of human type Streptococcus mutans whose serum type is c, d, e, f, or g type, as an antigen to give an antibody. A preventive for dental caries is blended with the antibody and aluminum hydroxide. The antibody has an inhibitory action on formation of bacterial plaque, preventing effect on dental caries, and addition of aluminum hydroxide keeps stable the antibody in the preventive for dental caries for a long period. An amount of the aluminum hydroxide is 5-70wt% based on the total amounts of the preventive for dental caries.

Description

[Detailed Description of the Invention] 0. Field of Application The present invention can suppress the formation of dental plaque and prevent dental caries by immunizing animals with whole bacterial cells or bacterial cell components of Streptococcus mutans and incorporating antibodies that are absorbed into the stomach. The present invention relates to a dental caries preventive agent, and more specifically, relates to a dental caries preventive agent that can stably hold antibodies for a long period of time, and therefore can reliably exhibit the effects of the antibodies over a long period of time.
゛Dental plaque that adheres to the surface of teeth using the conventional technology is 70% scraped, approximately 20% polysaccharide formed by bacteria, and approximately 10% food residue, and is firmly stuck to the tooth surface. . It is said that the acid stored inside the tooth demineralizes the enamel and causes dental caries, and plaque is attracting attention as a cause of dental caries.

The formation of this dental plaque is promoted by the synthesis of polysaccharide from sucrose by oral bacteria, mainly Streptococcus mutans. That is, Streptococcus
Mutans produces GTF (glucosyltransferase, dextran synthase), which synthesizes sticky polysaccharides such as dextran and mutan from sucrose. This synthesized polysaccharide is then produced by Streptococcus
Streptococcus mutans and other bacteria (pathogens),
Forms dental plaque with a certain bacterial flora. Furthermore, bacteria such as Streptococcus mycotans use various sugars to produce acids, and this acid stays in the polysaccharides and blank walls, thereby demineralizing the enamel surface.

Therefore, in order to prevent dental caries, it is necessary to suppress the number of Streptococcus mutans, which is considered to be a major cause of caries.
It is desired to suppress and inhibit the formation of dental plaque.

Conventionally, as a method of suppressing colonization of the oral cavity by Streptococcus mutans, a method using breast milk obtained by immunizing cows with whole Streptococcus mutans cells has been known (UK Patent No. 1505).
513 Specification).

The present inventors also investigated antibodies that inhibit colonization of the oral cavity by Streptococcus mutans among antibodies against various antigens derived from Streptococcus mutans. As a result, Streptococcus mutans, the blank cell wall fraction, the fibrous structure fraction of the bacterium,
Antiserum and antibodies in milk obtained by immunizing mammals with the pili component fraction, the empty glucosyltransferase fraction, the empty protein antigen fraction, etc. of the bacterium have an inhibitory effect on dental plaque formation. However, there is a problem that these antibodies are not necessarily retained sufficiently stably and deeply in caries preventive agents, and are particularly susceptible to deactivation due to the presence of anionic surfactants such as sodium lauryl sulfate. Therefore, in order to exhibit the effects of the antibodies well over a long period of time, it is necessary to stably incorporate these antibodies into caries preventive agents.

1"2"1 In view of the above circumstances, the present inventors have discovered that Streptococcus spp.
As a result of extensive research into stably incorporating antibodies obtained by immunizing the original cells with whole cells or cell components of S. mutans into anti-caries agents, we found that when these antibodies are used in combination with aluminum hydroxide. , antibodies can be stably retained in the caries preventive agent for a long period of time, and even if anionic surfactants such as sodium lauryl sulfate, which are particularly likely to deactivate antibodies, are included, the presence of aluminum hydroxide It has been found that the deactivation of the antibody can be prevented as much as possible and the effect of the antibody can be effectively exerted even after long-term storage. Therefore, for example, when a caries preventive agent is manufactured in the form of toothpaste by WA. If aluminum hydroxide is used as the main abrasive, the antibody can be stably incorporated into toothpaste,
The inventors have discovered that antibodies can be effectively used as active ingredients for toothpaste, leading to the present invention.

The present invention will be explained in more detail below.

11" As mentioned above, the caries preventive agent of the present invention uses whole bacterial cells or bacterial cell components of Streptococcus mutans as an antigen, and contains antibodies that can be raised by immunizing the first organism with this antigen. This is what has been done.

Here, the Strea 1 Hecotucus mutans bacterium used as the antigen is one that has been cultured and pretreated in a known manner, such as using a dialysate solution of BHr medium as a culture medium, and washing and treating the grown bacteria with formalin. I would like to use it.

In this case, the Streptococcus mutans bacteria is preferably a strain or mutant strain of human Streptococcus mutans isolated from the human oral cavity with serotypes c, d, e, f, or q. Those belonging to serotype C, which is abundant in the human oral cavity, are preferable. As such Streptococcus mutans bacteria,
NCTCl 0449, lngbritt.

OMZ70. JC-2, etc., and mutant strains include -Dp strain (FERM-BP317) and KH2 strain (FERM-BP317).
FERM-P7166), strainable (FeRM-P7166)
No. 14) etc. are preferably used.

Antigens for obtaining antibodies used in the present invention include the above-mentioned whole cells or cell components of Streptococcus mutans, particularly cell wall fractions and Il#-like structure fractions of Streptococcus mutans. A fimbriae component fraction, a glucosyltransferase (GTF) fraction, and a protein antigen fraction are used.

In this case, the cell wall fraction of Streptococcus mutans is 3. Method LJ of Ieiweis et al.

3acterio1. , 88.1198-1200゜1
964), the cells were disrupted using a Braun cell disrupter using glass beads with a diameter of 0.17 to 0.18 nm, and the resulting cell walls were treated with trypsin to remove proteins mixed in the cell walls. , those prepared by washing with distilled water and freeze-drying, etc. can be used. The fibrous (pili-like or fimbrial) structure fraction is J.

The method of van Hoate et al. (Arch, 0r
al, Bio,.

1131-1141.1971>, add 5% sucrose to BHI dialysis medium, culture under anaerobic conditions, add 3 times the amount of ethanol to the centrifuged culture supernatant, and collect the precipitate. Those prepared by □ etc. can be used. In addition, the method of Shimizu et al. (Japanese Journal of Bacteriology) was used as the pili component 1 fraction.

13-(1) 471.1983), the pure structural fraction is prepared from cultured bacteria by conventional cell wall extraction methods using a solvent such as a phosphate buffered solution containing 1 M NaCl. . Specifically, for example, after culturing a Streptococcus mutans mutant strain as a pili component fraction of the -Dp strain in liquid, this culture solution is injected with lii! Ammonium chloride was added to achieve 33% saturation, the supernatant was removed, and 1M sodium chloride-added phosphate buffer (PH 7,0) was added to the precipitate, stirred at 4°C for 3 days, and then centrifuged. After removing the bacterial cells and adding til to the supernatant to achieve 60% saturation, the precipitated portion was dialyzed against phosphate buffer, and the sucrose density was reduced to 8 to 80% by sucrose density gradient ultracentrifugation fractionation. The fimbriae component fraction obtained by dialyzing the fraction around 15% again against a phosphate buffer is used. Furthermore, the GTF fraction was determined using the method of Inoue et al. (M 1c
robial A 5pects of denta
l caries Vol, m, 665-68
2゜I D 76 [Information Re
trieval ] nc, ] ), 81-
1. Streptococcus mutans was inoculated into analysis medium, after growth, the bacterial cells were removed by centrifugation, ammonium sulfate was added to the supernatant, and the precipitate of the 40% ammonium sulfate fraction was dialyzed against 50 mM phosphate buffer. Those prepared by a method of using a concentrated liquid, etc. can be used. In addition, the protein antigen fraction was determined by the method of Lehner et al. (J.

General Microbiology, 1
22.217-225.1981) k: Therefore, the supernatant obtained by culturing in BHI dialysis medium and centrifugation was fractionated using 75% ammonium sulfate, the precipitate was collected, and the precipitate was purified in the presence of 6M urea. The protein antigen fraction used was prepared by performing DE-52 column chromatography, dissolving the protein antigen fraction in physiological saline, and after dialysis, performing gel 3 filtration with Sepharose CL 6B to obtain both fractions. It is possible.

Conventional methods can be used to immunize animals with the antigen. In addition, animals to be immunized include +X7 animals, sheep,
Mammals such as horses, cows and rabbits are effectively used.

As described above, the present invention uses the antiserum obtained by immunizing a mammal with the anti-1 East and antibodies in milk as active ingredients. Milk may be used, and antiserum and antibodies separated and purified from milk may be used. Furthermore, one type of these may be used alone or two or more types may be used in combination.

Note that the antibody (antiserum or protein fraction in milk) can be separated from the antiserum or milk according to a normal antibody purification method. Examples of antibody purification methods include salting-out method, gel 3 filtration method, ion-exchange O-mography, and affinity chromatography, among which salting-out method using ammonium sulfate is preferred. The salting-out method involves saturating the antiserum and milk with ammonium sulfate, preferably at a concentration not more than 40%, purifying the precipitate, and subsequently salting out the precipitate with physiological saline to obtain the purified precipitate as the antibody.

Preferred antibodies are horse antisera, bovine antisera and those obtained from milk.

The dosage of the antibody is preferably 0.0001 to 50 t/ha/day, in which case the antibody accounts for 0.0002 to 10% (wt%, same hereinafter) of the entire dosage form containing the antibody, particularly 0.
．． It is preferable to use the compound in an amount of 0.002 to 5% and at the above dosage.

The caries preventive agent of the present invention contains aluminum hydroxide as a stabilizer for the antibody in addition to the above antibody, and thereby can effectively prevent the deactivation of the antibody. Even if an anionic activator or the like that easily deactivates antibodies is included, antibodies can be stably maintained for a long period of time.

Here, as aluminum hydroxide, ordinary commercial products can be suitably used, but modified aluminum hydroxide obtained by treating aluminum hydroxide with an acid such as phosphoric acid or a salt thereof is used. You can also do that. The average particle size of aluminum hydroxide is not particularly limited, but
It is preferable to set it as 1-50 micrometers.

The amount of aluminum hydroxide added is 5 to 50% of the total caries prevention agent.
It is preferably 70%, particularly 10 to 55%.

In the caries preventive agent of the present invention, in addition to the above-mentioned antibodies, one or more synergists selected from fluorine compounds, chlorhexidines, lytic enzymes, bacteriocins, glucosyltransphenylase inhibitors, proteases, and dextranases are added. They can be used in combination, and as a result, colonization of Streptococcus mutans is further inhibited, the plaque formation inhibiting effect is significantly enhanced, and the caries preventive effect can be enhanced.

In this case, the fluorine compounds include monofluorophosphates such as sodium monofluorophosphate, potassium monofluorophosphate, sodium monofluorohydrogenphosphate, and ammonium monofluorophosphate, sodium fluoride, and fluorine. Alkali metal fluorides such as potassium chloride, lithium fluoride, ammonium fluoride, potassium hexafluorozirconate, potassium hexafluorotitanate, cesium fluoride, nickel fluoride, zirconium fluoride, silver fluoride, hexylamine hydro Fluoride, laurylamine hydrofluoride, cetylamine hydrofluoride, glycine hydrofluoride, lysine hydrofluoride, alanine hydrofluoride, etc. are used. Among these, monofluorophosphates such as sodium monofluorophosphate, potassium monofluorophosphate, alkali metal fluorides such as sodium fluoride, potassium fluoride, ammonium fluoride, and difluoride. Although stannous fluorides such as tin and stannous fluoride chloride can be preferably used, sodium monofluorophosphate, sodium fluoride, and stannous fluoride are particularly preferably used.

Chlorhexidines include chlorhexidine hydrochloride,
O-rhexidine gluconate and the like are used.

As a lytic enzyme, Streptomyccs gr
iseus.

Streptomyces diastatoch
romagenes.

5treptomyces farinosus,
Chalaropsis.

Flavobacterium, Myxobac
ter.

S taphylococcus epidermi
dis, M1crococcus.

P seudomonas aetuginosa,
A eromonas.

Streptomyccs albus, 3
Bacteriocins derived from treptomyces globiBorus etc. can be used, and bacteriocins such as Ente
robactor cloacae.

Escherichia coli, Prote
us m1abilis.

p 5eudoIIlonas aeruginos
a, Streptococcus mutans,
3taphylococcus 5taphylol
Those derived from P. yticus etc. can be used.

As a GTF inhibitor, A rthritul
sp,, Fusarinus sp,, Mac
rophominasp, , Micromonos
pora sp,, Gnomoniellasp,
, Nodulisporium Sp, ,
Those derived from Δspergillus sp0 etc. can be preferably used, specifically those described in JP-A-56-103193, JP-A-57-28097, JP-A-57-98215, and JP-A-57-146587. can be used.

As a protease, Aspergillus s
p.

Dextranase derived from 3 acillus sp, etc. can be suitably used, and as the dextranase, (:, hae
tolurasp, , 3treptomyce
s sp, , 3acillus3
Those derived from Coryneba aterruva and the like can be suitably used.

In addition, in the present invention, one of these synergist components
A species may be used alone, or two or more species may be used 1n. Further, 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 into separate dosage forms, and both may be used together at the time of use. It's okay.

In the case of fluorine compounds, the dosage of these synergist ingredients is 0.0001 to 1 in terms of fluorine. /kg/day, in the case of chlorhexidine, 0.0 as chlorhexidine
001 to 1')/9/day, and 0.0001 to 10 for bacteriolytic enzymes and bacteriocins. /ka/day, glucosyl transphenylase inhibitor/day, protease, dextranase IiIejj
can be 0.0001 to 59/ka/day, respectively. In the case of fluorine compounds, these synergist ingredients have a fluorine conversion ratio of 0.0001 to the entire dosage form containing them.
~0.1%, especially 0.0001~o. ooi%, in the case of chlorhexidine, 0.1 to chlorhexidine
1000 ppm, especially 10-100 ppm, respectively o. oooi~10
%, especially 0,001 to 5%, in the case of glucosyl transphenylase inhibitors 0.0001 to 10%, especially 0.001 to 5%, in the case of proteases 0,0001
-10%, especially 0.001-5%, in the case of dextranase, 0.0001-10%, especially 0.001-5%, and can be applied intraorally at the above dosages.

The dental caries prevention agent according to the present invention is suitably used as a toothpaste such as toothpaste, toothpaste, liquid toothpaste, etc., and can also be prepared in various forms for application in the oral cavity. As other components of the prophylactic agent, appropriate components are used depending on the purpose of use, mode of use, etc.

For example, I! [For 1 polishing vI 4%l, it is preferable to use aluminum hydroxide as the main polishing agent as mentioned above, but in addition to aluminum hydroxide, dibasic calcium phosphate dihydrate, dibasic calcium phosphate anhydrous , monobasic calcium phosphate, tribasic calcium phosphate, calcium carbonate, birocalcium phosphate, insoluble sodium metaphosphate, amorphous silica, crystalline silica, aluminosilicate, aluminum oxide, tribasic magnesium phosphate, magnesium carbonate, magnesium sulfate, titanium oxide, and An abrasive such as resin can be blended.

For the preparation of pasty compositions such as toothpaste, sodium carboxymethylcellulose, methylcellulose, sodium carboxymethylhydroxyethylcellulose, hydroxyethylcellulose, sodium alginate, carrageenan, gum arabic, xanthan gum, gum tragacanth, gum karaya, sodium polyvinylalcoholate, carboxylic Binders such as vinyl polymers and polyvinyl bi-Olidone are usually incorporated at concentrations of 0.3 to 5%. Here, the use of carrageenan can further improve the stability of the antibody. In addition, for the preparation of a paste composition, polyethylene glycol, ethylene glycol, sorbitol, glycerin, propylene glycol, 1.

Thickeners such as 3-butylene glycol, xylit, maltite, and lufftite are usually blended in amounts of 10 to 70%.

In addition, the caries preventive agent of the present invention contains an anionic, nonionic, cationic, and zwitterionic surfactant in an amount of 0.1 to 6
%, especially 0.3 to 3%. In this case, in the present invention, as described above, by blending aluminum hydroxide, the deactivation of antibodies can be effectively prevented even if an anionic surfactant that easily deactivates antibodies is blended. surfactants, such as sodium lauryl acid and sodium myristyl sulfate, which have 8 or more carbon atoms.
Water-soluble higher fatty acids whose fatty acid group has 10 to 18 carbon atoms, such as water-soluble salts of alkyl sulfate esters of No. 18, sodium lauryl monoglyceride, sodium coconut oil monoglyceride sulfate, and higher fatty acid monoglyceride monosulfuric acid. Monoglyceride sulfate, a-olefin sulfonate, paraffin sulfonate, sodium salt of N-methyl-N-balmitoyl tauride, N-
Sodium lauroyl sarcosinate, N-lauroyl-
Water-soluble salts of alkyl sulfate esters such as β-alanine sodium salt can be effectively incorporated.

In addition, examples of nonionic surfactants include fatty acid alkanolamides such as lauric acid jetanolamide.

Sucrose fatty acid L esters such as sucrose mono- and dilaurate, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid ester, 149 polyoxyethylene hydrogenated castor oils, lactose fatty acid ester, lactitol fatty acid ester, maltitol fatty acid ester, polyoxy Examples include ethylene polyoxypropylene block copolymer, etc., and one or more of these may be used, and the stability of the antibody can be further enhanced by incorporating these nonionic activators.

Furthermore, the caries preventive agent of the present invention may optionally contain;
Essential oils such as permint and spearmint, omenthol,
Flavoring materials such as carvone, eugenol, and anethole, sweeteners such as saccharin sodium, stevioside, neohesberidyl dihydrochalcone, glycyrrhizin, perillartine, and p-methoxycinnamic aldehyde, and preservatives are appropriately blended, as well as gelatin,
peptone.

Proteins such as casein, collagen, albumin, etc.
It is also possible to mix oi to 10%, and the stability of the antibody can be further enhanced by blending these proteins. In addition,
In the present invention, mutanase, sorbic acid, alexidine, hinokitiol, cetylpyridinium chloride, alkylglycine, alkyldiaminoethylglycine salt, allantoin, ε-aminocaproic acid, tranexamic acid, azulene, vitamin E1 water-soluble primary or secondary phosphorus ffjl, Active ingredients such as quaternary ammonium compounds, sodium chloride, crude drug extracts, etc. can also be blended.

In addition, in the case of other types of compositions, 5. Select appropriate components that are normally used, mix them in the usual manner, and use W.
Made by I.

Here, ... of the caries preventive agent of the present invention is not necessarily limited, but r414 to 10. More preferably 5 to 9, especially 5.
It is preferable to set it as 5-7.5.

The caries preventive agent of the present invention is stored and stored in an appropriate container before use. 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 gold R1a container such as an aluminum tube. In this case, the antibody is relatively easily deactivated in the metal container, but by incorporating aluminum hydroxide, the deactivation of the antibody in the metal container can be effectively prevented. In this case, a metal container such as an aluminum tube can be effectively used.

"Tetyogan" The caries prevention agent of the present invention is applied to the oral cavity in an appropriate manner depending on its dosage form, etc.
By immunizing animals with whole cells or components of Streptococcus mutans, the resulting antibodies inhibit the colonization of Streptococcus mutans in the oral cavity and suppress the formation of dental plaque, thereby preventing dental caries. However, according to the present invention, by using aluminum hydroxide in combination with this antibody, deactivation of the antibody is prevented, and the effect of the antibody is effectively exerted even after long-term storage. It's something you get.

EXAMPLES Hereinafter, the present invention will be specifically explained by showing experimental examples and examples.

In addition, production examples of antiserum, breast milk, and antibodies used in the following experimental examples and examples are shown below.

[Production Example] Using the following antigen, its antiserum and breast milk were obtained by the following method.

(1) Antigen Streptococcus muns BHI medium dialyzed external solution was used as a medium, and after washing the grown bacteria, formalin treatment was used.

The method of Q Ieiweis et al.
iol,.

88.1198-1200.1964) ￥14
I used something from vJ.

J. Van Hoate et al.'s method (Arch.

0ral,Bio,, 16.1131-1141.1
971) was used.

Inoue et al.'s method (M 1crobial A 5pec
ts of dental caries Vol.
, N, 665-682.1976 [Infor
OnRetrieval Enc, 1)
Use the one prepared according to the following.

The method of Lehner et al. (J, GeneralMi
crobiology, 122.217-225゜1981).

Streptococcus myco9ns The method of Tsurumi et al. (Japanese Journal of Bacteriology).

38 (1), 471.1983).

(2) Antiserum, breast milk and antibody W4 manufacturing method 50-100μ
The 9/11 antigen was mixed with an equal amount of Freund's complete adjuvant and immunized by subcutaneously injecting 0.3 g/g of pregnant goats, horses, cows, or rabbits into the back of pregnant goats, horses, cows, or rabbits.
The mice were immunized three times every four weeks with a mixture of antigen and incomplete Freund's adjuvant, and colostrum was collected after birth.

Furthermore, the antiserum was sampled after four immunizations in the same manner as described above, coagulated, and the centrifuged supernatant was used as a sample.

Next, an equal volume of 0.9% saline was added to the colostrum sample, and after centrifugation at 15,000 rpm for 60 minutes, the upper layer of fat and sediment was removed to collect the middle liquid component, which was then added with concentrated hydrochloric acid. was added to adjust to -14.

Further, centrifugation was performed at 5000 rpm for 30 minutes, and the supernatant was dissolved in tris-hydroxyaminomethane ([1]), and ammonium sulfate was added to achieve 75% saturation. The antibody component (internal fluid) of breast milk was obtained by dialysis with liquid.

In addition, ammonium 1jilate was added to the above antiserum to
The resulting precipitate was dialyzed with phosphate buffer to obtain an antiserum antibody (internal solution).

[Experiment example j A toothpaste with the following formulation was prepared.

Abrasives Age 60% shown in Table 1
Sorbitol liquid 35% propylene glycol 3゜0 carrageenan
1.0 gelatin 0.
3 Satucalin sodium 0. 1 incense
Fee 1
, 0.76 Methylparaben 0.2 Butylparaben 0.01 Sodium lauryl phosphate 0.8 Lauric acid jetanolamide
1.0 rabbit anti-S, S. mutans strain III cell wall serum 0.5 water

Total 100.0% Next, the above toothpaste was stored at 40°C for 2'iM, and its antibody activity was measured by the method described below to examine the antibody residual rate.

The results are shown in Table 1, and the results are expressed as relative activity when the antibody activity after storing the toothpaste containing aluminum hydroxide as an abrasive at 40° C. at 2:ill is set as 100.

III14L1 Teeth! Phosphate III81 (0
, 1M, State 7) to dissolve the soluble components in the toothpaste in the phosphate buffer, centrifugation is performed, and the sterilized solution is collected.

The activity of the antibody component in this supernatant was determined by Streptococcus.
mutans mutant strain using -Dp strain cells as an antigen.
ISA method (Eng wallE, et al, J
, IIILnol, , 109: 129
-135.1972).

The activity of the antibody component was determined using the aluminum hydroxide compound that showed the maximum absorbance when the absorbance at 405 nl was used as an indicator.
s was set as 100%.

Table 1 Examples are shown below.

[Example 1] Toothpaste propylene glycol
3.0% Sodium Alginate
0.9 methylparaben
0.1 Butylparaben
0.01 Sodium benzoate
0.260% sorbitol liquid
15.085% glycerin solution
10.0 Sodium saccharin 0.15 Sodium monofluorophosphate
0.76 dextranase (2 million units/l)
0.1 gelatin
0.3 Sodium lauryl sulfate
1.0 Lauric acid diethalamide
1.0 fragrance
0.6 aluminum hydroxide 45.
0 horse anti-S, mutans strain 10449 fimbriae component antibody
0.05 Purified water total 1
00.0% [Example 21 Toothpaste Propylene Glycol
3.0% carboxymethylcellulose sodium
1.2 Methylparaben
0.1 Butylparaben
0.01 Sodium benzoate 0
・260% sorbitol liquid
35.0 Satucalin Sodium
0.157)Stannic chloride
0.41 Chlorhexidine hydrochloride 0.
01 Peptone 0.2 Casein 0.1 Sodium lauryl acid
0.8 sucrose monolaurate
1.0 fragrance
0.6 aluminum hydroxide 45.0
Bovine anti-S, mutans OMZ175 cell wall antibody
0.02 Purified water Total 100
．． 0% [Implementation If43] Toothpaste propylene glycol
2.5% carrageenan
0.8 methylparaben
. , 1 butylparaben
0.01 Sodium benzhonzoate
0.285% glycerin solution
21.0 Satucalin Sodium
0.157 Sodium fluoride 0.21 Collagen
0.2 Fulbumin
0.2 Liumium lauryl sulfate
0.8 polyoxyethylene (20
Mol) 0.8 Sorbitan Monostearate Flavor
0.6 aluminum hydroxide
45.0 goat anti-S, mutans MT
3940 strain GTF antibody 0.5I Seisui
゛Total ioo
, o% [Example 4] Toothpaste propylene glycol
2.5% carrageenan
1.0 Methylparaben
0.1 Butylparaben
0.01 Sodium acrylic acid 0
．． 260% sorbitol liquid
30.0 Satucalin Sodium
0.15 Sodium heptanofluorophosphate o, 76 Sodium hydrochloride o Rhexidine 0.0
1 Sodium lauryl sulfate
0.8 Rau Oyl Sodium Sarcosinate
0.2 Polyoxyethylene (60 mol) Hydrogenated castor oil 0.8 Fragrance
0.6 aluminum hydroxide
45. .

Horse anti-S, S. mutans strain 10449 GTF antibody. , 1 water
Remaining amount total
100.0% Procedural Amendment FIN (side March 26, 1985 1, Indication of the case 1988 Patent Application No. 232354 2, Title of the invention: Anti-caries agent 3, Person making the amendment Relationship to the case Patent Applicant 11 Address: 1-3-78, Honjo, 5Il, T'a-ku, Tokyo Name (676) Line Δ Co., Ltd. Representative: Maki Kobayashi 4, Agent: 104 Address: 3-11, Ginza, 5A Chuo, Tokyo No. 14 Daba Create Building 5th floor Story M<545) 64547, Contents of amendment (1) Meill1g1, page 8, lines 4 to 6 [3
method of leiweis et al. - 1964') J
There is a certain thing called "B Ieiweis"
(Journal of Bacteriology <J.

13 acteriol, > , Dan 8.119
8-1200°1964) Corrected as J.

(2) Page 8, lines 112 to 14, “J.

van...-1971)J is replaced with "The method of Jay Vanhote <J, Van loate> et al. (Archives of Oral Biology <Arc
h.

0ral, [3io, >, Engineering 6, 1131-114
1°1971) Corrected as J.

(3) Page 9, lines 16 to 18 r <Mtc
robial--・-Retrieval Inc.
, ] ) J is ``(Micro Vial Aspect A7-Dintal Caries < fyJ 1cr
obial A 5 pects of dental
caries>Vol, m, 665-682゜1976 [Information Retrieval Inc.
rieVal I nc, > ] ) J and correction.

(4) Page 10, line 5 to line 711 rL ehn
er et al. old...1981) J [Lehner<
Lehner et al.'s method (digital male
General Microbiology<J.

Qeneral Microbiology
>, 12 2. 2 1 7 -225.198
1) Correct it as J.

(5) From page 14, line 13 to page 15, line 10 [
As a lytic enzyme... Aspergillus
Correct the text "so" and "J" according to the legal text.

"As a lytic enzyme, Streptomyces glycicose < 3 treptomyces griseu
s>.

Streptomyces diastertochromazien<
StreptoIlyces diastatoc
hromagenas〉, Streptomyces) 7 linosas〉 3 treptomyces fari
nosus>, Charalobushis<Cha
l a r Op S I S >, Flavobacterium genus < F Iavobacterium + >,
Myxobacter genus <Myxobacter>,
Staphylococcus evidelmidis < S ta
phylococcuspidermidis>,
Miku On] Crococcus ζM tcrococcus>
, Pseudomonas aeruginosa
nas aetuginosa>
A0rOIllOnaS>, Streptomyces alpus<3 treptomyces alb
us >, Streptomyces glopisporus <
S treptomycesglobisporus
> etc. can be used, and the bacteriocins derived from Enterobacter cloaceae < Enterobacter
ctor cloacae >
, Proteus miabilis
m1abi I +S>.

Pseudomonas aeruginosa < Pseudomon
asaerugtnosa>, Streptococcus Φ
mutans < 3 treptococcus 5
utans>, Staphylococcus<3 taphylococcus 5taphy
Lolyticus > etc. can be used.

As a G-F inhibitor, Erythrinum <A
rthrintllll Sp, >, Fusarium <r: usartnum sp, >, Microphomina <lvlacrophomina sp
, >, Micromonospora H< Micromono
spora sp, > , Nomonilla 〆Qnomo
niella sp, ＞, Tour 1 Lisborium < N 0dlJljSpOriull Sp, ＞
, Aspergillus bottom < A spergillus
sp, > J(6), page 15, lines 15 to 16
Row [Aspergillus sp,, Bici
llus sp, J [Aspergillus bottom <A spergillus sp.

〉, Bacillus sp.
Correct it with J.

(7) Page 15, lines 17 to 19, “Chae
jomiun+ -・----(', oryneba
cterium J [Chaetomium genus <Cha
etoniUI Sp,>, Streptomyces<
3 Treptomyces sp, >, Bacillus sp, :] Linebacterium Coryncbacter+um
Correct it with J.

(8) From page 23, line 20 to page 24, line 1 [1
3 Leiweis et al.'s method (1964) J.

Bactcriol, > , Dan 8.1198-12
00°1964) Corrected as J.

(9th page 24th line 5th to 7th tr UJ.

van...1971) J is 1.
The method of Van Hoate et al.
rch.

Qral, Bio, >, 1 History, 1131-11
41°1971) Corrected as J.

(10) Page 24, lines 11 to 14 “(~1
icrobial-=・l'(etrieval l
nc, ] ) j [(Microvial aspect male dental caries < M 1c
robialA 5pccts of denta
l caries> V of, DI.

665-682.1976 [Information Retrieval, Inc.
r nc, > ] ) Correct it as l. .

(11) l1jl page 24 line 18 I″J↑No. 20
Line FL ehner et al. (1981) J is the method of Lehner et al.
J.

General Microbiology >,
122, 217 = 225.1981) Corrected as J.

(12) rEng, page 27, lines 18 to 19
vall E, at al, J, 1mmu
No. 1.1 [Ink Pal E, etc., Journal of Immunology <Eng wall
l:,t! jal, J, l mmunol,
> Correct as J.

Below

Claims (1)

[Claims] 1. It contains an antibody obtained by immunizing an animal with whole cells or cell components of Streptococcus mutans, and also contains aluminum hydroxide. Characteristic caries preventive agent. 2. Streptococcus mutans is a human type of Streptococcus mutans with serotypes c, d,
The caries preventive agent according to claim 1, which is an e, f or g type strain or mutant strain. 3. The caries preventive agent according to claim 2, wherein the mutant strain is a Streptococcus mutans mutant K-Dp strain, KH2 strain, or K-III strain. 4. Claims 1 to 3, wherein the bacterial cell component is a cell wall fraction, fibrous structure fraction, pilus component fraction, glucosyltransferase fraction, or protein antigen fraction of Streptococcus mutans. The caries preventive agent according to any of the above. 5. The caries preventive agent according to any one of claims 1 to 4, which contains antiserum or milk containing this antibody as the antibody. 6. The caries preventive agent according to any one of claims 1 to 4, which contains an antiserum containing the antibody or one isolated from milk as the antibody. 7. The caries preventive agent according to any one of claims 1 to 6, wherein the amount of the antibody is 0.0002 to 10% by weight of the entire preventive agent. 8. The amount of aluminum hydroxide is 5 to 7 of the total preventive agent.
The caries preventive agent according to any one of claims 1 to 7, which has a content of 0% by weight. 9. The caries preventive agent according to any one of claims 1 to 8, which is prepared as a toothpaste and uses aluminum hydroxide as the main abrasive.