JP5976866B2 - Caries preventive agent - Google Patents

Description

The present invention relates to a dental caries preventive agent, and more specifically, inhibits dentin collagen degradation in dental caries generated on the root surface and further suppresses dentin mineral elution (decalcification). And a dental caries preventive agent characterized by promoting remineralization of dentin.

The caries is that the microorganisms (especially Streptococcus mutans) in the plaque on the tooth surface metabolize the sugar in food and drink to produce an acid, which erodes and erodes the tooth mineral. Caused by.

The techniques for preventing this dental caries include the prevention of plaque adhesion to the tooth surface, the removal of plaque adhering to the tooth surface (brushing), and the killing of microorganisms in the plaque by antibacterial and antibacterial agents. Or, prevention of dental caries focusing on prevention of tooth mineral elution by microorganisms such as intake regulation of sugar or intake of alternative sugar has become mainstream.

However, such caries prevention is generally performed for caries that occur in tooth enamel, and is not necessarily the same for caries that occur in dentin on the root surface (root surface caries). It will not be effective.

This is because the caries that occur in the dentin on the root surface is not only the dissolution of minerals by the acid produced by the microorganisms in the oral cavity, but also the decomposition of collagen, which is an organic substance contained in a large amount in this dentin. Is considered to be the cause of the progression (Non-Patent Documents 1 and 2), which is basically different from caries generated in tooth enamel containing almost no organic matter. In fact, there are also reports that the activity of collagenase was actually confirmed from the dentin on the root surface (Non-patent Documents 3 to 5).

As a result, even if the dissolution of dentin mineral is simply prevented, the caries on the root surface is further deteriorated if the dentin collagen is further decomposed. If this collagen is decomposed, the scaffolding material when the mineral is deposited will also be lost, so that remineralization is less likely to occur, which is very disadvantageous in the healing or recovery of caries.

Therefore, in order to prevent caries generated in the dentin on the root surface, it is necessary to suppress the degradation of dentin collagen, and further suppress the elution (decalcification) of minerals, and the minerals It is necessary to promote reabsorption (remineralization).

From this point of view, there has been little research on prevention of dental root caries. To date, dental caries targeted for dental root caries include, for example, water-soluble aluminum compounds, fluorides and water-soluble calcium compounds. The composition for oral cavity to mix | blend is mentioned (patent documents 1, 2). However, these suppress dentin hypersensitivity caused by the exposure of the root surface, and at the same time suppress caries by the effect of fluoride, and no description is given on collagen degradation of dentin.

As for collagen degradation inhibition in the oral cavity, for example, tetracycline antibiotics such as doxycycline have been shown as having an effect of matrix metalloprotease (MMPs) inhibition (Non-patent Document 6). However, these are said to be useful for the treatment or prevention of periodontal diseases such as periodontitis and gingivitis. Regarding the effects on decalcification and remineralization and the effectiveness of root surface caries It is not specifically shown. Furthermore, considering the side effects peculiar to tetracycline antibiotics that are synthetic substances and the risk of appearance of resistant bacteria in the body, it is not preferable to apply these antibiotics to the oral cavity for a long period of time.

On the other hand, as for MMPs inhibitors derived from natural products, such as hinokitiol (patent document 3), abietic acid (patent document 4), histidine (patent document 5), flavones or anthocyanidins (patent document 6). However, all of these have only been shown to have an effect on periodontal tissue, and any description or proposal has been made regarding the suppression of dentin mineral elution due to caries on the root surface. No.

Journalof Oral Medicine 42, 40-8, 1987 Journalof Oral Pathology & Medicine 18, 146-56, 1989 Acta Odontologica Scandinavica 65, 1-13, 2007 Journalof Dental Research 86, 436-40, 2007 Archivesof Oral Biology 52, 121-127, 2007 Journalof Periodontal Research 28, 379-385, 1993

JP-A-5-155745 JP-A-5-155746 JP2007-91686A JP-A-2005-132768 JP2007-246436 JP-A-8-104628

The present invention is characterized by inhibiting dentin collagen degradation in dental caries generated on the root surface, further suppressing dentine mineral elution (decalcification), and promoting remineralization. An object of the present invention is to provide a dental caries preventive agent and an oral composition containing the same.

As a result of intensive studies to solve the above-mentioned problems, the present inventors have effectively applied collagen degradation of dental dentin by caries on the root surface by applying flavanones and / or glycosides thereof. In addition, it was found that dentin mineral elution (decalcification) was synergistically suppressed and remineralization was promoted, and the present invention was completed as a dental caries preventive agent.

That is, the present invention includes the following aspects. Item 1. A dental caries preventive agent comprising flavanones and / or glycosides thereof. Item 2. Item 2. The root caries preventive agent according to Item 1, wherein the flavanone and / or glycoside thereof is hesperidin. Item 3. Item 3. A composition for oral cavity comprising the root caries preventive agent according to Item 1 or 2. Item 4. Item 4. The oral composition according to Item 3, which is a coating agent.

The root caries preventive agent of the present invention inhibits dentin collagen degradation in caries generated in the root surface dentin by using flavanones and / or glycosides thereof as active ingredients, and dentine It is possible to suppress decalcification of quality and promote remineralization. Furthermore, it becomes possible to provide the composition for oral cavity prevention for root surface caries prevention in the oral cavity field by mix | blending the root caries prevention agent which concerns on this invention.

FIG. 1 is a microradiograph showing the remineralization effect on the bovine root dentin block under each condition. FIG. 2 is a mineral profile obtained from image analysis of a microradiograph in the case of remineralizing a bovine tooth root dentin block of “collagenase”. FIG. 3 is a mineral profile obtained from microradiographic image analysis in the case of remineralizing a “collagenase + HPN” bovine root dentin block. FIG. 4 is a mineral profile obtained from microradiographic image analysis when a “collagenase + phytic acid” bovine root dentin block is remineralized.

The present invention will be described in further detail.

The root surface caries preventive agent according to the present invention is used for prevention of caries occurring in the dentin on the root surface. The root surface is generally the surface of the root portion (tooth root) of the tooth embedded in the gingiva and indicates the portion not covered with enamel. Tooth root caries refers to caries that intensively occurs on the root surface, and is often said to occur frequently when the root surface is exposed due to gingival retraction such as periodontal disease. Further, root caries are also called dentin caries because they occur in dentin that is not covered with enamel.

The flavanones and / or glycosides thereof used in the present invention have a 2-phenylchromanone skeleton as the basic skeleton of their chemical structure, and are not particularly limited, and can be obtained as a synthetic product or a product derived from a natural product. Anything can be used. About this, hesperidin, hesperetin, neohesperidin, eriocitrin, neoeriocitrin, aromadendrin, taxifolin, ampelopsin, astilbine, pinobankin, angelitin, pinocembrin, nariltin, naringin, naringenin, saliprpine, sakuranin, sakurane, sakurane, Examples include eriodictyol, mattisinol, silybin, and isosiribine, and examples of these glycosides, optical isomers, methoxy groups, and methyl groups. Among them, hesperidin and hesperetin are preferable, and hesperidin is particularly preferable among them. Moreover, flavanone and / or its glycoside can be used individually by 1 type or in combination of 2 or more types as appropriate.

In the present invention, hesperidin means that rutinose (L-rhamnosyl- (α1 → 6) -D-glucose) is β at the hydroxyl group at position 7 of hesperetin (5,7,3′-trihydroxy-4′-methoxyflavanone). It is a combination. This hesperidin is a kind of flavonoid among flavanones, and it can be extracted and isolated from citrus crusts such as Citrus unshiu and orange (Citrus aurantium L). It can be used for pharmaceuticals, cosmetics, etc. as vitamin P having physiological effects such as enhancement of sex, prevention of bleeding, and blood pressure adjustment, and as a substance having an anti-inflammatory / analgesic action or an action to improve arteriosclerosis, hypertension and the like. In addition, hesperidin is considered to have little direct effect on the cell itself because hesperidin hardly suppresses degranulation of basophil cells and weakly affects colon cell function compared to other flavonoids. Therefore, there is no worry about side effects. Hesperidin used in the present invention is commercially available from Wako Pure Chemical Industries, Ltd. (trade name “Hesperidin”) and the like.

This hesperidin is composed of a glycoside in which hesperetin is aglycon and a sugar is bound to this, and hesperidin sugar adducts to which sugars such as glucose, maltose, fructose, rhamnose, and lactose are further bound. These hesperidin sugar adducts can also be used. This hesperidin sugar adduct is commercially available from Toyo Seika Co., Ltd. (trade name “αG-Hesperidin PA-T”) and the like.

In the present invention, inositol phosphates can also be used. The inositol phosphates used in the present invention are not particularly limited. For example, inositol 1-phosphate, inositol 2-phosphate, inositol 3-phosphate, inositol 4-phosphate, inositol 5-phosphate, inositol 6-phosphate (phytin) Acid) and the like. Of these, phytic acid is particularly preferred. Inositol phosphates can be used alone or in combination of two or more.

The phytic acid of the present invention is not particularly limited as long as it is a phytic acid compound containing phytic acid itself, and those obtained by neutralizing the free acid group with a base or those esterified can also be used. Specific phytic acid compounds include, for example, phytic acid, sodium phytate, potassium phytate, lithium phytate, magnesium phytate, calcium phytate, ammonium phytate, ethanolamine neutralized phytic acid, and phytic acid. Examples include alcohol esters.

  In the present invention, steroids can also be used. Steroids used in the present invention are not particularly limited. For example, hydrocortisone, triamcinolone, dexamethasone, prednisolone, triamcinolone acetonide, fluocinolone acetonide, hydrocortisone acetate, prednisolone acetate, methylprednisolone, dexamethasone acetate, betamethasone, Betamethasone herbate, flumethasone, fluorometholone, beclomethasone propionate, fluocinolone, amsinonide, prednisolone acetate valerate, dexamethasone valerate, cortisone acetate, diflorazone acetate, difluprednate, betamethasone dipropionate, desoxymethasone, halcinonide, flucinonide , Prednisolone farnesylate, budesonide, mometasone furanate, fluocinonide, Cold Loki Shikoru tides, acetate fluocinolone acetonide, alclometasone propionate, clobetasol propionate, dexamethasone propionate, deprodone propionate, betamethasone butyrate propionate, methyl prednisolone, and the like. Among these, hydrocortisone, triamcinolone, dexamethasone, prednisolone, triamcinolone acetonide, fluocinolone acetonide, hydrocortisone acetate, prednisolone acetate, methylprednisolone, dexamethasone acetate, betamethasone, betamethasone valerate, flumetasone, fluorometholone, and beclomethasone propionate are preferred. Of these, hydrocortisone and hydrocortisone acetate are particularly preferred. Moreover, these steroids can be used individually by 1 type or in combination of 2 or more types as appropriate.

In the present invention, a biguanide drug can also be used. The biguanide drug used in the present invention is not particularly limited. Examples of the biguanide drug include chlorhexidines such as chlorhexidine, chlorhexidine gluconate, chlorhexidine acetate, and chlorhexidine hydrochloride. Among these, chlorhexidine, chlorhexidine gluconate, chlorhexidine acetate, and chlorhexidine hydrochloride are preferable, and chlorhexidine gluconate is particularly preferable. Moreover, these gluconates can be used individually by 1 type or in combination of 2 or more types as appropriate.

In the present invention, cysteine derivatives can also be used. The cysteine derivative used in the present invention does not include cysteine itself and is not particularly limited. For example, N-acetyl-L-cysteine, DL-homocysteine, L-cysteine methyl ester, L-cysteine ethyl ester N-carbamoylcysteine, cysteamine, cystine which is a dimer of cysteine, and salts thereof such as hydrochloride thereof. Of these, ethylcysteine and methylcysteine or their salts are particularly preferred. Moreover, these cysteine derivatives can be used individually by 1 type or in combination of 2 or more types as appropriate.

In the present invention, grape seed extract can also be used. The grape seed extract used in the present invention can be used without particular limitation as long as the desired effect of the present invention can be obtained. For example, it can be obtained by extraction or the like using seeds of European grape (Vitis vinifera) as a raw material. Examples of the extraction solvent for extracting the grape seed extract include water; alcohols such as methanol, ethanol, propanol and butanol; lower alkyl esters such as ethyl acetate; hydrocarbons such as benzene and hexane; other ethyl ethers, acetone, A known solvent such as acetic acid can be mentioned. These solvents may be used alone, or may be used in combination of two or more, and a known extraction method that is usually used can be employed.

In the grape seed extract of the present invention, the extract may be used as it is, or may be concentrated or dried by a usual means such as drying under reduced pressure or freeze drying. In addition, the extract can be used after being purified using a countercurrent distribution method, liquid chromatography, or the like. The grape seed extract used in the present invention is commercially available from Kikkoman Corporation (trade name “Gravinol”), Indina Corporation (trade name “Leuco Select”), and the like.

Naphthoquinones can also be used in the present invention. The naphthoquinones used in the present invention are not particularly limited, and examples thereof include juglone, lawson, phylloquinone, menaquinone, menadione, plumbagin, futhiocol, echinochrome A, alkanine, and shikonin. Of these, juglone is particularly preferred. Moreover, these naphthoquinones can be used individually by 1 type or in combination of 2 or more types as appropriate.

These root surface caries preventive agents used in the present invention are colored, discolored, and altered not only to dentin but also to enamel in consideration of the aesthetics of teeth or the effect on the healing and recovery of caries. It is preferable that it does not cause modification or the like.

In the present invention, these root caries preventive agents can be used alone or in combination. These are blended with various known ingredients as required by methods known per se, and are used as a coating agent, varnish agent, ointment, pasta agent, gel agent, patch dispersion paste external preparation, liquid external preparation, washing agent. It can be provided as an external preparation composition such as a mouthpiece, a mouthwash, etc., and can also be used as a powder, fine granule, granule, powder, tablet, capsule, liquid, syrup, dry syrup, inhalant, orally disintegrating agent, lozenge, It can also be provided as an internal composition such as a troche or drop. These external preparation compositions and internal use compositions can be produced by ordinary production methods, and are particularly preferably used for the oral cavity.

Among these compositions, it is a composition for oral cavity that can be used as a topical external preparation, considering the effective dosage form with a high amount of drug reaching the affected area for local diseases such as dental caries on the root surface. In particular, a coating agent-like coating agent that is not easily washed away by saliva or the like in the oral cavity is preferable. In addition, when using the root caries preventive agent of the present invention as an oral composition, a dentifrice (toothpaste, liquid dentifrice, liquid dentifrice, etc.), mouthwash, oral gel, spray formulation, etc. This form can also be provided. In addition, the preventive agent for root surface caries according to the present invention is effectively added to 0.0001 to 10% by weight, preferably 0.001 to 5% by weight, based on the total amount of the composition. Decomposition can be suppressed and mineral elution (decalcification) can also be prevented. When the amount of the dental caries preventive agent is less than 0.0001% by weight, a satisfactory effect cannot be obtained, while when it is more than 10% by weight, it is disadvantageous in terms of preparation or cost. Such oral compositions are also within the scope of the present invention.

When using the root caries preventive agent of the present invention as a coating agent, shellac, methacrylic acid copolymer, ethyl acrylate / methyl methacrylate copolymer dispersion, aminoalkyl methacrylate copolymer contained in the coating base , Hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose, zein, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, methylcellulose, ethylcellulose, hydroxyethylcellulose, polyvinylacetal diethylaminoacetate, fumaric acid, stearin Acid, polyvinyl acetal, diethylaminoacetate, hydroxypropi 2910 mixture, can be used a carboxyl vinyl polymer. Although these compounding quantities can be set suitably, normally about 0.0001-70 weight% can be mix | blended based on the composition whole quantity.

Furthermore, when using the tooth root surface caries preventive agent of the present invention as a coating agent, a brush, brush, sponge, roller, syringe, spray, spray, wiping material using ultrafine fibers, and a dentifrice component were impregnated. A rod-shaped cleaning tool or sheet, a tape-shaped cleaning tool, a dentifrice to be brushed by chewing, a pen-type applicator, or the like can be used.

Moreover, when it is set as a coating agent, other components can be mix | blended other than said component, for example, a thickener, surfactant, a sweetening agent, a flavoring agent, etc. do not impair the effect of this invention. It can mix | blend suitably in the range.

For example, as the thickening agent, ethanol, glycerin, sorbit, ethylene glycol, propylene glycol, 1,3-butylene glycol, polyethylene glycol, polypropylene glycol, xylitol, maltitol, lactitol, palatinit and the like can be used alone or in combination. It can mix | blend combining a seed | species or more suitably.

Examples of the surfactant include surfactants such as sodium lauryl sulfate, sodium myristyl sulfate, sucrose fatty acid ester, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monostearate, polyoxyethylene hydrogenated castor oil. These surfactants can be blended singly or in appropriate combination of two or more.

As the sweetener, saccharin sodium, stevioside, glycyrrhizin, xylit, sucralose, xylitol, palatinose, palatinit, erythritol, maltitol and the like can be blended. These sweeteners can be blended singly or in appropriate combination of two or more.

Examples of the flavoring agent include menthol, anethole, eugenol, limonene, peppermint oil, spearmint oil, cionel, thymol, citronellol and the like. These flavoring agents can be blended alone or in combination of two or more.

Other fluorine compounds such as sodium fluoride and sodium monofluorophosphate; enzymes such as dextranase, mutanase and amylase; vitamins such as acetic acid-dl-α-tocopherol, ascorbic acid and salts thereof; tranexamic acid, ε- Other active ingredients such as aminocaproic acid, allantoin, glycyrrhizic acids, glycyrrhetinic acid, chlorhexidine salts, triclosan, cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, preservatives such as parabens, coloring agents, pH adjusters, etc. 1 type can be mix | blended individually by 1 type or in combination of 2 or more types as appropriate. The blending amount of these components can also be a normal amount as long as the effects of the present invention are not hindered.

EXAMPLES Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated concretely, this invention is not limited to the following Example. In addition, the compounding quantity in each example shows weight%, unless there is a prescription | regulation.

<Measurement of Inhibitory Effect on Dentin Collagen Degradation and Inhibition Effect on Dentin Demineralization> A refrigerated bovine root was used as a sample for measurement, and this was cut and embedded in a dental resin. The tooth surface was polished with abrasive paper, stirred with 1.0 mM phosphoric acid for 10 seconds and rinsed well with tap water. The tooth surface was exposed to a certain area, and water drops were dropped so that the tooth surface could not be completely dried, and this was used as a bovine tooth root dentin block.

The bovine root dentin block was immersed in a decalcification solution (calcium chloride: 1.5 mM, potassium dihydrogen phosphate: 0.9 mM, acetic acid: 50 mM, pH 5.0) at 37 ° C. for 16 hours, and then remineralized solution (Calcium chloride: 1.5 mM, potassium dihydrogen phosphate: 0.9 mM, potassium chloride: 130 mM, HEPES: 20 mM, pH 7.0) was immersed for 8 hours at 37 ° C., and this was repeated for 8 days. Collagenase was added to the remineralization solution to 5.5 μg / mL, and various test compounds were added to 2 mg / mL.

In order to investigate the effect of various test compounds on the inhibition of dentin collagen degradation, the amount of collagen contained in the remineralized solution after 8 days obtained by the above operation was determined by using hydroxyproline contained in a certain amount of collagen as an index. It measured using the analyzer (DIONEX amino acid analysis system DXA-500). The collagen degradation inhibition rate (%) was obtained by dividing various measured values by the collagen amount measured value of the remineralized liquid (control) to which no test compound was added, and subtracting this from 100%. . The evaluation criteria were as follows.
5: Collagen degradation inhibition rate is 75% or more 4: Collagen degradation inhibition rate is 60% or more and less than 75% 3: Collagen degradation inhibition rate is 45% or more and less than 60% 2: Collagen degradation inhibition rate is 30% or more and less than 45% 1 : Collagen degradation inhibition rate is less than 30%

Furthermore, in order to investigate the effect of various test compounds on the suppression of dentin decalcification, the amount of calcium (decalcification amount) contained in the demineralization liquid after 8 days obtained by the above operation was measured using an atomic absorption photometer (Shimadzu Corporation) It was measured using an absorptiometer (AA-6300). As a measurement of the decalcification inhibitory effect, in order to correct the difference in the demineralization amount among bovine root dentin block individuals, the relative value of the decalcification amount after 8 days with reference to the decalcification amount measurement value on the first day Was calculated. Evaluation of this decalcification inhibitory effect is based on the relative value of decalcification amount (a) in various test compounds, the relative value of decalcification amount (b) when no test compound was added (control 1), and the test compound Using the decalcification amount relative value (c) when no collagenase was added (control 2), the following criteria were used.
5: (ba) / (bc) is 1 or more 4: (ba) / (bc) is 0.75 or more and less than 1 3: (ba) / (bc) is 0.5 or more and less than 0.75 2: (ba) / (bc) is 0.25 or more and less than 0.5 1: (ba) / (bc) is 0 or more and less than 0.25 0: (ba) / (bc) is less than 0

Moreover, in addition to the evaluation of the dentin collagen degradation inhibitory effect and the demineralization inhibitory effect, the presence or absence of coloration was examined by visual inspection of the bovine tooth root dentin block after 8 days obtained by the above operation. . Then, the following criteria were set for comprehensive evaluation. The results obtained are shown in Table 1 below.
◎: Collagen degradation inhibition and demineralization suppression were both “5”, and there was no coloration. ○: One of collagen degradation inhibition and demineralization suppression was “5” and the other was “3” or “4”. Yes, no coloring Δ: One of collagen degradation inhibition and demineralization suppression is “5” and the other is “3” or more, but colored ×: “◎”, “◯”, or Items that do not fall under “△”

As shown in Table 1, among the test compounds, hesperidin (Example 1), phytic acid (Example 2), hydrocortisone acetate (Example 3), and chlorhexidine hydrochloride (Example 4) inhibit collagen degradation and release. Both of the ash suppression showed the highest effect, and the coloring of the bovine root root dentin block was not observed. In addition, dexamethasone (Example 5), ethylcysteine hydrochloride (Example 6), and methylcysteine hydrochloride (Example 7) also showed high effects on collagen degradation inhibition and decalcification suppression, and no coloring was observed. However, although the grape seed extract (Example 8) and juglone (Example 9) were both highly effective in inhibiting collagen degradation and suppressing decalcification, coloring of the bovine root root dentin block was observed. In addition, none of the test compounds according to the comparative examples showed high effects in both collagen degradation inhibition and decalcification inhibition. Among these, although L-histidine (Comparative Example 5) and glutathione (Comparative Example 6) have a high collagen degradation inhibitory effect, no decalcification inhibitory effect is observed. On the contrary, tranexamic acid (Comparative Example 8) It was shown that the ash suppression effect is high but the collagen degradation inhibitory effect is low.

<Measurement of Remineralization Effect of Dentin on Collagen with Addition of Various Test Compounds> A bovine tooth root dentin block after the above test was used as a measurement sample. That is, the root dentin block of the bovine tooth root obtained by performing the test under the condition that “the test compound was not added to the remineralization solution but only collagenase (5.5 μg / mL) was contained” was referred to as “collagenase”. , The root dentin block of the bovine tooth root obtained by conducting the above test under the condition that “the remineralization solution contains hesperidin (2 mg / mL) and collagenase (5.5 μg / mL)” is referred to as “collagenase + HPN”. , The bovine tooth root dentin block obtained by carrying out the above test under the condition of “containing phytic acid (2 mg / mL) and collagenase (5.5 μg / mL) in the remineralized solution” is “collagenase + phytic acid” As a result, it was subjected to the following test.

Each bovine root dentin block is remineralized (calcium chloride: 1.5 mM, potassium dihydrogen phosphate: 0.9 mM, potassium chloride: 130 mM, HEPES: 20 mM, NaF: 2 ppm, pH 7.0). It was immersed for 2 weeks at 37 ° C. and recalcified. At that time, in order to make it easy to contrast the remineralization state, the half of the dentin surface exposed on the surface is coated with nail enamel (Beauty Max Nail Base & Top Coat: Max Factor Co., Ltd.). Avoid contact with remineralization liquid.

After the remineralization treatment, various bovine tooth root dentin blocks were cut to a thickness of 100 μm perpendicular to the dentin surface. The obtained 100 μm thin section sample was evaluated by a transverse microradiography (TMR) method using an X-ray imaging apparatus (soft X-ray imaging apparatus HB-50: Hitex Co., Ltd.). The thin slice sample to be evaluated was pressed against a high-resolution film and irradiated with X-rays, and the remineralization state was observed from the obtained microradiograph. The obtained results are shown in FIG. Moreover, the mineral profile was obtained by image analysis. The obtained results are shown in FIGS.

As shown in FIG. 1, the thin slice sample only treated with collagenase has already undergone organic decay at the site where remineralization has been performed, there is no room for remineralization, and the mineral layer after remineralization Was found to remain below the healthy dentin.

On the other hand, among the test compounds, the thin slice sample treated with hesperidin (Example 1) is significantly remineralized compared with the portion not subjected to remineralization treatment, and healthy dentin. It was observed that the mineral layer had recovered to the same level as. As can be seen from the graph of FIG. 3, the distance until the mineral density is 80% or more is 7 μm, which is clearly improved from the 21 μm of the collagenase-treated group of FIG. is there. From the above results, it was confirmed that hesperidin exhibits collagen degradation inhibition and demineralization suppression effects without inhibiting remineralization.

In addition, as with hesperidin, a thin slice sample treated with phytic acid (Example 2), which showed high effects on both collagen degradation inhibition and decalcification inhibition, was recalcified despite remineralization treatment. No mineralization was observed (FIG. 1), and the mineral density remained low (FIG. 4).

From this, it is clear that it not only has an effect of inhibiting collagen degradation and demineralization, but also does not inhibit its action even in remineralization, and hesperidin is a very expensive root caries preventive agent I can say that.

Hereinafter, although the composition for oral cavity using the root surface caries preventive agent of this invention is demonstrated, this invention is not limited to the following Example. Unless otherwise specified, the blending amount is% by weight.

Example 10 Coating agent

Ingredients Amount <br/> Shellac 10.0
Ethyl alcohol 40.0
Hesperidin 1.0
Sodium fluoride 0.2
Fragrance 1.5
Sodium hydroxide
Purified water balance <br/> Total 100.0

Example 11 Toothpaste

Ingredient Blending amount Dicalcium phosphate 30.0
Glycerin 10.0
Sorbitol 20.0
Sodium carboxymethylcellulose 1.0
Sodium lauryl sulfate 1.5
Carrageenan 0.5
Saccharin sodium 0.1
Fragrance 1.0
Sodium benzoate 0.3
Hesperidin 1.0
Vitamin E 0.05
Oil-soluble licorice extract 0.05
Purified water balance <br/> Total 100.0

Example 12 Liquid dentifrice

Ingredient Blending amount Sorbite 10.0
Polyoxyethylene hydrogenated castor oil (60) 5.0
Fragrance 0.05
Saccharin sodium 0.01
Chlorhexidine gluconate 0.05
Sodium citrate 0.05
Hesperidin 1.0
Tocopherol acetate 0.02
Sodium fluoride 0.05
Undecalactone 0.05
Purified water balance <br/> Total 100.0

Example 13 Mouthwash

Ingredient Blending amount Ethanol 10.0
Glycerin 5.0
Citric acid 0.01
Sodium citrate 0.1
Polyoxyethylene hydrogenated castor oil (60) 0.5
Methyl paraoxybenzoate 0.1
Fragrance 0.2
Hesperidin 1.0
Vitamin E 0.05
Vitamin C 0.01
Purified water balance <br/> Total 100.0

Example 14 Oral Gel

Ingredient Blending amount Carboxymethylcellulose 0.2
Glycerin 40.0
Hesperidin 1.0
Vitamin E 0.05
Purified water balance <br/> Total 100.0

Example 15 Mouse Spray

Ingredient Blending amount Glycerin 15.0
Ethanol 10.0
Cetylpyridinium chloride 0.3
Stevia extract 0.1
Hesperidin 1.0
Citric acid appropriate amount Sodium citrate appropriate amount 1-menthol 2.0
Fragrance 0.1
Purified water balance <br/> Total 100.0

Claims (3)

Root surface caries preventive / improving agent for root surface caries prevention / improvement used in dentures of root surfaces, containing hesperidin dental root caries preventive agent and coating agent (excluding "urea"). (Excluding “dentifrice composition”) Coating agent is shellac, methacrylic acid copolymer, ethyl acrylate / methyl methacrylate copolymer dispersion, aminoalkyl methacrylate copolymer, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose, zein, hydroxypropyl Cellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, methylcellulose, ethylcellulose, hydroxyethylcellulose, polyvinylacetal diethylaminoacetate, fumaric acid / stearic acid / polyvinylacetal diethylaminoacetate / hydroxypropylmethylcellulose 2910 mixture, carboxyl vinyl polymer Root surface localized coating agent for root surfaces caries prophylaxis or improvement of claim 1 is at least one selected. The root surface area local coating agent for preventing or improving caries surface according to any one of claims 1 and 2, wherein the pen type applicator is filled.

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