WO2006068001A1

WO2006068001A1 - Hydrolyzed-silk-containing composition for oral cavity

Info

Publication number: WO2006068001A1
Application number: PCT/JP2005/022831
Authority: WO
Inventors: Yasushi Fukuda; Kouichi Saito
Original assignee: Lion Corporation
Priority date: 2004-12-22
Filing date: 2005-12-13
Publication date: 2006-06-29
Also published as: KR20070091622A; JP4826790B2; KR101293893B1; CN101098676B; CN101098676A; JPWO2006068001A1

Abstract

A composition for the oral cavity characterized by containing: a hydrolyzed silk having a number-average molecular weight, as calculated from total nitrogen amount and the amount of amino-form nitrogen, of 200-6,000; and a fluorine compound.

Description

Specification

Oral composition containing hydrolyzed silk

Technical field

[0001] The present invention coats teeth with hydrolyzed silk having a high ability to adsorb teeth to dentin, thereby effectively protecting the teeth from fungal acid, enzymes, etc. that cause caries. The present invention also relates to a composition for oral cavity in which the retention of fluorine and antibacterial agents is improved, and the dental caries preventive effect is dramatically improved by remarkably preventing dissolution and decomposition of the dentin. . Background art

Conventionally, as means for causing an active ingredient to act on teeth, means such as dentifrices, mouthwashes, jewels, tablets, gummi, gums and the like have been taken. However, in the case of dentifrices and mouthwashes, the amount of active ingredient in the oral cavity is insufficient after vomiting, and cream gel is painful for solid inserts with poor usability. When I was accompanied, there was a problem. In both cases, the concentration of the active ingredient is lowered due to the cleaning action by saliva, and the effect is lowered.

[0003] On the other hand, dentin has a structure that is more porous and rich in organic matter than enamel, and most of the organic matter is type I collagen. The onset mechanism of dentin caries is as follows. First, plaque adheres to the dentin surface, and sugars are metabolized by bacteria in the plaque to produce acid. The acid elutes (mineralizes) dentin minerals, exposing collagen. Furthermore, collagen is degraded by collagenase derived from bacteria and saliva to form an axilla (dent). Dentin caries progress to deeper depth and caries by repeated decalcification and collagen decomposition. For these reasons, it is important to effectively suppress both demineralization and collagen degradation in order to improve the effect of preventing dentin caries.

[0004] On the other hand, a technique for protecting tooth quality has been proposed. For example, a technology that improves the appearance of a composition by combining a natural or synthetic cationized peptide / protein with a nonionic or amphoteric active agent (JP-A-6-9354) incorporates a tooth surface of fluorine. The power of cationized peptides and proteins can be applied for 1 hour. I can't say that the effect is sufficient in that it is effective in long-term treatment. Mouthwash containing collagen or gelatin (JP-A-2003-119157) exhibits high adsorbability to type II collagen contained in the vitreous body and cartilage of the eye, while dentin, bone, and oral mucosa Adsorption of the composition to the teeth has a big problem because it has a small adsorption ability for type I collagen contained in the tooth. The tooth surface coating agent containing fatty acid salt (Japanese Patent Laid-Open No. 2000-103726) has a surface active action of the fatty acid salt itself, and the active ingredient flows out of the oral cavity due to gargle after the drug treatment. There are still significant issues regarding the surface coating effect and the retention of the effective tooth surface. In addition, tooth acid resistance enhancing composition (Japanese Patent Laid-Open No. 6-298632) composed of tea polyphenol, fluorine and aluminum salt has a bad taste and can be effective in the acidic region. Under normal use, such as a mouthwash, an insoluble precipitate is formed between fluorine and aluminum ions in the vicinity of neutral pH, and in the case of a dentifrice, and also with an abrasive. The effect of improving the incorporation into the tooth is not expected.

Furthermore, as a technique using Synolec, a stress inhibitor containing a silk protein degradation product (Japanese Patent Publication No. 2003-81868) and a bioactive composition derived from a silk protein hydrolyzate (Japanese Patent Laid-Open No. 11139986) However, these are not designed as oral compositions such as dentifrices and mouthwashes, and their effects are unclear. In addition, there is a scrubbing agent composed of silk fiber mouth (Japanese Patent Laid-Open No. 2003-113072), but when it is used in the oral cavity, a scrubbing effect is recognized, but a protective effect on the tooth quality is not recognized. Furthermore, the composition for oral cavity composed of sinoretafive mouth-in (Japanese Patent Laid-Open No. 2001-226242) is not hydrolyzed silk as in Japanese Patent Laid-Open No. 2003-113072, so the number average molecular weight of fibrin is about 350 Although it has excellent film-forming protection effects on mucous membranes such as 舌 000, which have a large tongue, the effect on the tooth surface is inferior because of its low adsorption effect on hard teeth. In general, naturally-occurring polypeptide compounds are more permeable and more adsorbable as the molecular weight is smaller, while the lower the film-forming property and the larger the molecular weight, the lower the adsorptivity and permeability, while the film-forming performance is improved. It is said. For example, according to Seiwa Kasei's product catalog (Promois (registered trademark)), the adsorptivity and penetrability of collagen polypeptides to hair are molecular weight, and the higher the molecular weight, the greater the film-forming property. While improving the adsorptive 'permeability There is a decline.

As described above, all known techniques are effective in adsorbing and protecting teeth on dentin in a short time, retention of tooth surfaces of active ingredients such as fluorine and antibacterial agents, stability in preparations, There is a big problem with the flavor.

[0006] In order to solve these problems, effective adsorption ability of teeth to dentin in a short time treatment, retention function of tooth surfaces of active ingredients such as fluorine and antibacterial agents, stability in preparations A composition having both sexiness and flavor is desired.

Disclosure of the invention

Problems to be solved by the invention

[0007] An object of the present invention is to solve the above-mentioned problems and to provide a composition for oral cavity having a high effect of preventing dentine caries in a short time treatment.

Means for solving the problem

[0008] As a result of intensive studies to achieve the above object, the inventors of the present invention have developed a peptide complex obtained by further hydrolyzing a sinoretive mouth-in obtained by refining silk yarn with an acid, an alkali, an enzyme, and the like. In combination with compounds, we have found excellent collagen degradation-inhibiting and demineralization-inhibiting properties for dentin containing organic substances mainly composed of type I collagen. Furthermore, it has been found that the ability to inhibit collagen degradation and the ability to suppress decalcification are further improved by providing a poorly water-soluble nonionic antibacterial agent, and the present invention has been completed.

Therefore, the present invention

[I] An oral composition comprising hydrolyzed silk having a number average molecular weight of 200 to 6,000 calculated based on the total nitrogen content and amino nitrogen content, and a fluorine compound,

[II] Hydrolyzed synolec is obtained by phosphoric acid hydrolysis, The composition for oral cavity according to [I],

[III] The amount of hydrolyzed silk is 0.:! To 10% by mass of the entire composition, and the amount of fluorinated compound is 0.02 to 3% by mass of the entire composition [I] or [ II] oral cavity composition,

[IV] The oral composition according to any one of [I] to [III], further comprising a slightly water-soluble nonionic antibacterial agent, a surfactant and Z or an alcohol. , [V] The poorly water-soluble nonionic antibacterial agent is triclosan or isopropylmethylphenol, and the surfactant is polyoxyethylene hydrogenated castor oil or alkyl sulfate ester salt having an average added mole number of 5 to 100. The composition for oral cavity according to [IV], wherein the alcohol is propylene glycol, polyethylene glycolate (# 200 to 6000), ethylene glycolanol, glycerin, sorbitol or ethanol,

[VI] The amount of the poorly water-soluble nonionic antibacterial agent is 0.0 :! to 2% by mass of the whole composition, and the amount of the surfactant is 0.0.% To 5% by mass of the whole composition The composition for oral cavity according to [IV] or [V] is provided, wherein the blending amount of alcohol is 0.:! To 50% by mass of the entire composition.

The invention's effect

[0009] According to the present invention, by using hydrolyzed silk having a specific number average molecular weight and a fluorine compound, collagen degradation and decalcification of dentin can be remarkably suppressed. Furthermore, by adding a hardly water-soluble nonionic antibacterial agent and a surfactant and / or alcohol to solubilize it, both the collagen degradation inhibitory effect and the demineralization inhibitory effect of dentin are improved. Thus, it is possible to provide a composition for oral cavity in which the effect of preventing dentin caries has been dramatically improved.

BEST MODE FOR CARRYING OUT THE INVENTION

[0010] The composition for oral cavity of the present invention is characterized by containing hydrolyzed synolec.

Here, the hydrolyzed silk can be obtained by hydrolyzing silk fibroin obtained by refining the silk thread spun from the silkworm with an acid, alkali, enzyme or the like. A silk thread has a five mouth-in in the center and sericin in the periphery.

= 70-80%: It is known that it is 20-30% (mass percentage).

As for silk thread, first, silkworms produced by a sericulture farmer are dried and boiled to produce raw silk, and then raw silk is scoured to obtain silk thread or silk fabric. The most common method of boiling is a method of boiling in an aqueous solution containing alkaline sodium salt gypsum (alkaline stone koji), which removes sericin on the outside of the silk thread, Purified by mouth-in only. Hydrolyzed silk can be obtained by hydrolyzing this hive mouth-in (average molecular weight: about 350,000) with acid 'alkali, enzyme, etc., but depending on the degree of hydrolysis, Various molecular weights can be prepared. In the case of the present invention, hydrolyzed silk obtained by phosphoric acid hydrolysis is particularly preferred.

The hydrolyzed silk used in the present invention has a number average molecular weight of 200 to 6,000, preferably a f of 500 to 5,000, more preferably a clay of 500 to 1,000. If the number average molecular weight is less than 200, there is adsorptivity to teeth, but the film-forming property is extremely low, and if it exceeds 6,000, the film-forming property is high, but the adsorptivity decreases. The effect is reduced. Hydrolyzed synolec is available from various companies in grades with various number average molecular weights, and they can be used as needed. Commercially available products include silk レク -Ρ (manufactured by NDC Co., Ltd., number average molecular weight 500) as hydrolysis synolec by phosphoric acid hydrolysis, and silk peptide Μ_500 ( Cosmo Foods Co., Ltd., number average molecular weight 500), and other hydrolyzed silks produced by Promose (registered trademark) Synolec ΙΟΟΟρ (manufactured by Seiwa Kasei Co., Ltd., number average molecular weight 1,000), Synolecpe Examples include Peptide 5 (manufactured by Kanebo Co., Ltd., number average molecular weight 1,500), Silk Powder FD (manufactured by Kanebo Co., Ltd., number average molecular weight 5,000), and the like. The hydrolyzed silk of the present invention is ineffective thionic or nonionic.

[0011] The number average molecular weight can generally be calculated by gel filtration chromatography (GPC) and calculation of analytical nitrogen value. For this invention, a polypeptide such as hydrolyzed silk can be used. The latter is often used for compounds. More specifically, the number average molecular weight of the hydrolyzed silk of the present invention is calculated by the following formula (1) based on the total nitrogen amount in the molecule, the amino nitrogen amount, and the average molecular weight of the constituent amino acids.

[Number 1]

(Average molecular weight of constituent amino acids 1 8) X total nitrogen content

Number average molecular weight = 10 ₁₈ (1)

Amino nitrogen content

In the above formula (1), the average molecular weight of the constituent amino acids is obtained by multiplying the abundance ratio (%) of constituent amino acids obtained by ordinary amino acid analysis by the molecular weight of each amino acid, and the total nitrogen amount is In addition, the first nitrogen determination method of the cosmetic raw material standard general test method or gas chromatography (GC), the amount of amino nitrogen can be measured by a formol titration method.

[0013] The amount of the hydrolyzed synolec is not particularly limited. 0.1 to 10% (percentage by mass, the same shall apply hereinafter) is preferable, and 0.5 to 5% is particularly desirable. When the content is lower than 0.1%, the effect of the present invention cannot be sufficiently obtained. When the content exceeds 10%, the taste and feeling of use may be deteriorated.

[0014] The oral composition of the present invention contains a fluorine compound. Examples of the fluorinated compound used in the present invention include sodium fluoride, sodium monofluorophosphate, stannous fluoride and the like, and sodium fluoride and sodium monofluorophosphate are particularly preferred. From the viewpoint of caries prevention, it is preferable to add these fluorine compounds in an amount of 0.02 to 3% of the whole composition, particularly in the case of Futsui sodium, more preferably 0.0 to 1% of the whole composition. Is 0.02 to 0.7%, and in the case of sodium monofluorophosphate, it is preferably 0.05 to 3%, more preferably 0.07 to 2.5% of the total composition.

[0015] In the present invention, it is preferable to further blend a poorly water-soluble nonionic antibacterial agent. Difficult water-soluble nonionic antibacterial agents include triclosan (water solubility; 0.001 g / l00 mL (20 ° C), the value listed on the Ministry of the Environment website), isopropylmethylphenol (same; 0 · 015 g / 10 0 mL (25 ° C), Osaka Kasei Co., Ltd. catalog value), thymol (same; 0 · 098g / 100mL (25 ° C), Osaka Kasei Co., Ltd. catalog value), etc., to water at 20-25 ° C Examples include nonionic antibacterial agents having a solubility of 0 · lg / lOOmL or less, among which triclosan and isopropylmethylphenol are preferable. In the present invention, one or two or more of the poorly water-soluble nonionic antibacterial agents can be used in combination. The blending amount is preferably 0.001 to 2% force S of the whole composition, more preferably 0.01 to 1%. If it is less than 001%, the sufficient bactericidal effect may not be exhibited, and if it exceeds 2%, solubilization in the preparation may be difficult, and the taste and usability may be deteriorated.

[0016] Furthermore, a surfactant can be added to the oral composition of the present invention in order to improve the solubility of the poorly water-soluble nonionic antibacterial agent and oil-soluble fragrance. As surfactants, polyoxyethylene hydrogenated castor oil and alkyl sulfate esters are preferred. Polyoxyethylene hydrogenated castor oil has an average added mole number of ethylene oxide of 5 to 100. Especially, 5 to 20 for dentifrice and 40 to 100 for mouthwash are preferred. ,. If the average number of added moles is less than 5, oil solubility increases and foaming power decreases, and if it exceeds 100, stability of the poorly water-soluble nonionic antibacterial agent may decrease. Polyoxyethylene curing The amount of castor oil blended is preferably 0.1-5% of the composition, especially 0.5-2.5% for dentifrice and 0.2-2% for mouthwash. is there. If it is less than 1%, the stabilizing effect of the poorly water-soluble nonionic antibacterial agent cannot be obtained sufficiently, and if it exceeds 5%, sufficient foaming power may not be obtained.

[0017] Examples of the alkyl sulfate ester salts include alkali metal salts such as sodium, potassium, lithium and the like such as octyl sulfate, decyl sulfate, lauryl sulfate, myristyl sulfate, palmityl sulfate, stearyl sulfate, etc. Sodium lauryl sulfate is most preferred. The blending amount of the alkyl sulfate ester salt is preferably 0.05 to 5%, and more preferably 0.5 to 2.5 for a dentifrice. / _0, in the case of mouthwashes is preferably 0.:!～ 0.5%. If it is less than 0.05%, sufficient foaming property cannot be obtained, and if it exceeds 5%, foaming property is strong and the feeling of use may be lowered.

[0018] Alternatively, alcohols can be blended in place of the surfactant or together with the surfactant. As the alcohol, one or more of propylene glycol, polyethylene glycol (# 200 to 6000), ethylene glycol, glycerin, sonorebitol, ethanol and the like can be used, and the blending amount is 0.:! To 50 of the entire composition. % Is more preferably 1 to 40%. When the content is less than 0.1%, a poorly water-soluble nonionic antibacterial agent may not be stably blended, and when it exceeds 50%, the taste and usability may be deteriorated.

[0019] Furthermore, as other caries-preventing ingredients, known effective drugs can be used. Inorganic calcium compounds such as calcium chloride, calcium nitrate, calcium sulfate, calcium glycephosphate, calcium hydroxide, and calcium lactate Used in combination with organic calcium compounds such as calcium acetate, calcium malonate, calcium citrate, calcium dalconate, calcium glycerate, calcium tartrate, calcium phytate, and enzyme agents such as dextranase, mutanase, and lysozyme can do. The blending amount of these drugs is preferably in the range of 0.005 to 10% of the whole composition, particularly preferably in the range of 0.05 to 5%. If it is less than 0.005%, no effect is exhibited, and if it exceeds 10%, there may be a problem in taste and usability.

[0020] The composition for oral cavity of the present invention is in the form of toothpaste such as toothpaste, toothpaste, liquid toothpaste, mouthwash, mouth freshener, gargle tablet, denture cleaner, chewing gum and the like. It is possible, Each composition can be prepared by a conventional method using other components within the range not impairing the effects of the present invention, depending on the characteristics. In this case, in the case of dentifrice, abrasives, wetting agents, binders and the like are usually blended.

[0021] As the abrasive, precipitated silica, silica gel, aluminosilicate, zeolite, dinoreconosilicate, dicalcium phosphate dihydrate and anhydride, calcium pyrophosphate, calcium carbonate, aluminum hydroxide, alumina, magnesium carbonate, (3) Magnesium phosphate, insoluble sodium metaphosphate, insoluble potassium metaphosphate, titanium oxide, hydrated hydroxyapatite, synthetic resin-based abrasives, etc. (blending amount: usually 5-50% of the total composition) .

[0022] Examples of the wetting agent include polyhydric alcohols and the like among the above alcohols (mixing amount; usually 10 to 50% based on the entire composition).

[0023] Examples of the binder include carrageenan, hydroxyethyl cellulose sodium, carboxymethylenosolerose sodium, hydroxyethylenosenolellose, hydroxypropinoresenellose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, alginic acid. Propylene glycol ester, polyacrylic acid, sodium polyacrylate, xanthan gum, tara gum, guar gum, locust bean gum, gelatin gum, gelatin, cardan, gum arabic, agar, pectin, polyvinyl alcohol, polyvinyl pyrrolidone, punoreran, etc. (Blending amount; usually 0.1 to 5% based on the entire composition).

[0024] Further, if necessary, an anionic surfactant other than the above-mentioned surfactant, a cationic surfactant, a nonionic surfactant, and the like can be blended, for example, α-talifine sodium sulfin sulfonate,ァ Acylglutamate, 2-alkyl Ν-Carboxymethyl- Ν- Hydroxyethyl imidazolinium betaine, Ν Acyl taurate, Sucrose fatty acid ester ester, Alkyrol amide, Polyglycerol fatty acid ester, Polyoxyethylenepolyoxypropylene glycol, Polyoxyethylene sorbitan monostearate, lauroylole sarcosine sodium, alkylpolydarcoside, polyoxyethylene alkyl ether sulfosuccinate and the like may be added in an amount of 0 to 5% based on the entire composition.

[0025] In the case of a liquid oral composition such as a mouthwash, it is possible to combine the above thickener and other surfactants. [0026] Furthermore, the oral composition of the present invention is blended with sweeteners such as saccharin and xylitol, as well as other preservatives, fragrances, colorants, pH adjusters, excipients, various medicinal ingredients, and the like as necessary. That power S.

[0027] The pH of the composition of the present invention is not particularly limited as long as it is within the range of safety in the oral cavity and human body, but is preferably pH 4 to 10, and more preferably pH 5. 5-9. If the pH is less than 4, there is a concern of decalcification depending on the application time, and if it exceeds pHIO, the usability and taste may deteriorate. As pH adjusters, acetic acid, hydrochloric acid, sulfuric acid, nitric acid, citrate, phosphoric acid, sodium hydroxide, potassium hydroxide, sodium acetate, sodium carbonate, sodium citrate, sodium hydrogen citrate, sodium phosphate, phosphoric acid An appropriate amount of sodium hydride or the like can be blended.

Example

Hereinafter, the present invention will be specifically described with reference to examples and comparative examples, but the present invention is not limited to the following examples. In addition, all% in each example is a mass percentage. In the following examples, the number average molecular weight is the number average molecular weight calculated by the formula (1).

[0029] Experiment 1: Inhibition of collagen degradation in early demineralized ivory

[Example:! To 21, Comparative example:! To 6]

(1) Preparation of model dentifrice (Example:! ~ 7)

A model dentifrice was prepared according to the prescription in Table 1 below. Silk BN-P made by NDC Co., Ltd. with a number average molecular weight of 500 was used as the hydrolyzed silk by the phosphoric acid hydrolysis method. Silk peptide M-500 (Cosmo Foods Co., Ltd., number average molecular weight 500), Promois (registered trademark) Silk ΙΟΟΟρ (Seiwa Kasei Co., Ltd., number average molecular weight) as hydrolyzed silk other than phosphoric acid hydrolysis method 1, 000), Synolec peptide 5 (manufactured by Kanebo Co., Ltd., number average molecular weight 1,500), Synolec powder FD (manufactured by Kanebo Co., Ltd., number average molecular weight 5,000) were used. Further, a 7% silk-five mouth-in aqueous solution was prepared by referring to Reference Example 1 <Production Method of Five-Mouth-in Aqueous Solution> of JP-A-2001-226242. What was prepared with reference to Example 1 of Japanese Patent No. 113072 was used. Furthermore, pork skin collagen is NMP collagen PS manufactured by Nippon Ham Co., Ltd., and cationized silk is 20% higher alkyl cationized silk peptide solution (Promois (registered trader) manufactured by Seiwa Kasei Co., Ltd.). Standard) S—CAQ) was used.

As a method for preparing a dentifrice, A phase was prepared by mixing and dissolving water-soluble components (sodium fluoride, sodium monofluorophosphate, hydrolyzed synolec, cation synolect, pork skin collagen, etc.) in purified water at room temperature. In addition, sodium fluoride and sodium monofluorophosphate have a content approved in Japan of 1, OOOppm or less as fluorine ions, so in the examples sodium fluoride is 0.21% and sodium monofluorophosphate is 0. 73% was compounded mainly. On the other hand, B phase was prepared by dispersing sodium polyacrylate (Rheozic 250H, manufactured by Nippon Pure Chemical Co., Ltd.) in purified water at room temperature. The B phase was added and mixed in the A phase being stirred, and the sodium polyacrylate was swollen to prepare the C phase. In addition, mix ingredients such as other ingredients (silk five mouth inscrubbing agent, polyoxyethylene (20 mol) hydrogenated castor oil), etc. in phase C using a 1.5 L kneader (manufactured by Ishiyama Machine Co., Ltd.) at room temperature. The pressure was reduced to 4 kPa and defoamed to obtain 1.0 kg of a dentifrice.

The number average molecular weights of hydrolyzed silk, silk fiber mouth-in, and pig skin collagen were determined by measuring the total nitrogen amount, the first nitrogen determination method of the cosmetic raw material standard general test method, and the amino nitrogen amount by the formol titration method. Calculated by the equation (1).

(2) Preparation of dentifrice (Examples 8 to 19)

A phase was prepared by mixing and dissolving water-soluble components (hydrolyzed silk, sodium fluoride, sodium monofluorophosphate, sodium saccharin, xylitol, 70% sorbite, etc.) in purified water at room temperature. As for the hydrolyzed silk, as in (1) above, silk BN-P manufactured by NDC Co., Ltd. having a number average molecular weight of 500 was used as the hydrolyzed silk by the phosphoric acid hydrolysis method. Silk peptide M-500 (Cosmo Foods Co., Ltd., number average molecular weight 500), Promois (registered trademark) Synolec ΙΟΟΟρ (Seiwa Kasei Co., Ltd., number average molecular weight) as hydrolyzed silk other than the phosphate hydrolysis method 1, 000), Synolecpeptide 5 (manufactured by Kanebo Co., Ltd., number average molecular weight 1,500), and silk powder FD (manufactured by Kanebo Co., Ltd., number average molecular weight 5,000) were used. In addition, sodium fluoride and sodium monofluorophosphate have a content approved in Japan of 1, OOOppm or less as fluorine ions. Therefore, in the examples, sodium fluoride is 0.21% and sodium monofluorophosphate is 0.73%. It mix | blended focusing on%. On the other hand, triclosan, isopropylmethylphenol, thymol, and polyacrylic acid in propylene glycol. Phase B was prepared by dissolving and dispersing thorium (Rheology 250H, manufactured by Nippon Pure Chemicals Co., Ltd.), xanthan gum, sodium carboxymethylcellulose and the like at room temperature. Next, the B phase was added and mixed into the A phase being stirred, and the C phase was prepared by adding and mixing the examples in which polyoxyethylene hydrogenated castor oil was blended. In Phase C, fragrance, anhydrous carboxylic acid, and other ingredients (dextranase, sodium lauryl sulfate, etc.) are mixed at room temperature using a 1.5 L kneader (manufactured by Ishiyama Kogyo Co., Ltd.), depressurized to 4 kPa and removed. Foaming was performed to obtain a dentifrice 1. Okg.

[0031] (3) Preparation of mouthwash (Examples 20 and 21)

A specified amount of purified water was charged into a stainless steel container equipped with a three-one motor and a stirrer having rotating blades, and water-soluble components such as hydrolyzed silk among the blended components were charged and dissolved. On the other hand, in a separate stainless steel container equipped with a three-one motor and a stirrer with rotating blades, a specified amount of an organic solvent such as ethanol was added, and the oil-soluble component of the blended components was added and dissolved while stirring. . Furthermore, the oil-soluble component was added to a container in which the water-soluble component was dissolved, and the mixture was stirred for 1 to 30 minutes to obtain a uniform solution to obtain a mouthwash.

[0032] (4) Dentin collagen degradation inhibition experiment

Bovine ivory with reference to JM, Ten Cate et al. (The influence of the organic matrix on de mineralization of bovine root dentin in vitro, Journal of Dental Research 73 (9): pl 523-1529, September, 1994) A collagen collagen degradation test was conducted.

Specifically, the root dentin of the incisor extracted from a healthy ushi was cut out, and a dentin block measuring 5 mm in length, 5 mm in width, and 3 mm in height was produced. In addition, one surface of the block is mirror-polished with # 4000 water-resistant abrasive paper, except for the 2mm X 2mm portion of the surface, a commercial nail burnish is applied to all surfaces, and the test is 2mm X 2mm in size. Surface (window) was made. This test surface was decalcified with 0.1 M acetic acid (pH 5.0) for 2 days to obtain a demineralized layer having a depth of about 300 × m, that is, a collagen layer.

[0033] Examples:! To 19 and comparative examples:! To 6 model dentifrice 'dentifrice is diluted 3 times with distilled water in consideration of the usage capacity under human use, and the diluted solution is treated liquid. It was. For the mouth washes of Examples 20 and 21, the stock solution was used as the treatment solution. The test surface of the bovine dentin block is immersed in the treatment solution of each example and comparative example for 3 minutes at room temperature, and the dentifrice is rinsed thoroughly with distilled water in consideration of the usage volume, and then used as a mouthwash. Then, it was not rinsed with distilled water, but treated with a collagenase (Type VII, Sigma) solution (400 units ZmL 50 mM HEPES, pH 7.8) derived from Clostridium histolyticum for 18 hours. After repeating this treatment three times, a section with a thickness of about 200 μm was cut out in a direction perpendicular to the test surface with a microcutter (MC_201, manufactured by Marto Co., Ltd.) to prepare a wet preparation. .

Finally, images of the collagen degradation layer of each section were acquired with a polarizing microscope (BH_2, Olympus Optical Co., Ltd.), and the collagen decomposition depth was obtained with an image analyzer (PIAS_V, Pierce Co., Ltd.). (Μm) was obtained. Furthermore, the collagen degradation inhibition rate of each Example and Comparative Example was calculated based on the average collagen degradation depth of samples subjected to only collagen degradation treatment (the following formula (2)). A series of experimental operations were performed with N = 3 for each of the examples and comparative examples, and the average value was shown. The evaluation criteria for the dentin collagen degradation inhibitory effect were as follows.

[0034] [Equation 2]

Dentin collagen inhibition rate =

(Collaboration depth of untreated group) I (Example · tt ^ Collagen depth of example)

X 1 0 0 Untreated group collagen arc depth

(2) Evaluation criteria: Dentin collagen degradation inhibition rate is

◎: 80% or more

○ ~ ◎: 60% or more, less than 80%

〇: 40% or more and less than 60%

△: 20% or more and less than 40%

X: Less than 20%

[0035] Experiment 2: Experiments on suppression of healthy ivory decalcification using artificial plaque

[Example:! -21, Comparative example:! -6]

In this experiment, the causative bacteria are adsorbed on the dentin surface, the acid production by the sugar metabolism of the causative bacteria, the cause This was to evaluate the comprehensive demineralization phenomenon due to the production of various enzymes of the fungus, and was conducted as an evaluation experiment closer to the actual human oral environment. In the same manner as in Experiment 1, the root surface dentin of the incisor extracted from a healthy ushi was cut out to produce a dentin block 5 mm long x 5 mm wide x 3 mm high. Furthermore, one surface of the block is mirror-polished with # 4000 water-resistant abrasive paper, except for the 2mm X 2mm portion of the surface, and a commercial nail burnish is applied to all sides, and the size is 2mm X 2mm. A test surface (window portion) was prepared. This sample was sterilized by irradiation with cobalt 60 gamma rays at a dose of 10.4 kj / kg.

The model dentifrice, dentifrice, and mouthwash prepared in Experiment 1 were used as they were. Examples:! To 19 and comparative examples:! To 6 model dentifrices and dentifrices were diluted three-fold with distilled water, and centrifuge (Hitachi 05PR_22, manufactured by Hitachi Eki Co., Ltd.) 3, The supernatant obtained by centrifugation at OOOrpm and room temperature for 10 minutes was further sterilized by filtration through a filter having a pore size of 0.22 zm (Millex-GS, manufactured by Nihon Millipore Co., Ltd.), and this was used as a treatment solution. In Examples 20 and 21, since the mouthwash was used, a solution obtained by sterilizing the stock solution by filtration was used.

Next, after immersing the test surface of the bovine dentin block in the treatment solution of each Example and Comparative Example for 3 minutes at room temperature and rinsing well with sterilized distilled water, the mutans bacteria that are caries-causing bacteria THB (Todd Hewitt Broth, Difco) medium containing (Stre ptococcus mutans ATCC25175) 1. Add to 5 mL and incubate at 37 ° C for 1 day under anaerobic conditions to form artificial plaque on the surface of dentin block I let you. In this case, Examples 20 and 21 were not rinsed with sterilized distilled water because of the mouthwash. Thereafter, the dentin block was taken out, and the treatment solution of each Example and Comparative Example was again immersed in the test surface on which the human plaque was formed for 3 minutes at room temperature, rinsed well with sterile distilled water, and then 1% THB medium containing sucrose was added to 1.5 mL and cultured at 37 ° C for 1 day under anaerobic conditions. Also in this case, Examples 20 and 21 were not rinsed with sterilized distilled water because of the mouthwash. This treatment was repeated once a day for a total of 4 days. In addition, the culture medium immersed after chemical | medical agent treatment used the new thing each time. After that, carefully remove the artificial plaque on the test surface with a brush, and use a microcutter (MC-201, manufactured by Manoleto Co., Ltd.) to make the test plate approximately 200 μm thick so that it is perpendicular to the test surface. Sections were carefully cut under running water. Furthermore, with a soft X-ray generator (CMRII, manufactured by Softex Co., Ltd.) in a wet state, 2.8 mA, 18 on the soft X-ray film (SO-343, manufactured by Kodak). Irradiated with kVp for 60 minutes, a TMR (Transverse Micro Radiography) image of each section was obtained.

Finally, the demineralization degree of each section was drawn from the TMR images of 15 aluminum step wedges taken together with the sections, and the mineral profile for each TMR image was drawn using an image analyzer (PIAS_V, manufactured by Pierce Co., Ltd.). The amount of loss Δ Ζ (decalcification amount) was calculated. Furthermore, the delta dentin demineralization suppression rate of each Example and the comparative example was calculated by using the average ΔZ of the sample without treatment with the drug as the reference decalcification amount (the following formula (3)). In the series of experimental operations, N = 3 for each example and comparative example, and the average value was shown. The evaluation criteria were as follows.

[0037] [Equation 3]

Dentin demineralization inhibition rate (%) =

(Average of untreated group ^ Ζ)-(Average Z of Examples and Comparative Examples)

X 1 0 0 (3) Average of untreated group

Evaluation criteria: Dentin demineralization inhibition rate is

: 70% or more

○: 50% or more and less than 70%

△: 30% or more and less than 50%

X: Less than 30%

The evaluation results of Examples:! To 7 and Comparative Examples:! To 6 are summarized in Table 1. Examples 8-2

The evaluation results for 1 are summarized in Table 2.

[0039] [Table 1]

Ratio Ratio Ratio Ratio Ratio Application Application Comparison Comparison Example Example Example Example

1 2 3 4 I D 7 1 2 3 4 f 6 Hydrolyzed silk * 1

1 2 1.5 1

(Number average molecular weight 500)

Hydrolyzed silta * 2

1

(Number average molecular weight 500)

Karo water splitting /

1

(Number average molecular weight 1,000)

Karo water splitting silk

1

(Number average molecular weight 1,500)

DTK decomposition silk

1

(Number average molecular weight 5,000)

7% silk hive π in ί night

20

(Number average molecular weight 350,000)

Silk Fif 'Mouth Inn

2

(Scrub agent)

Pork skin

1.5

(Number average molecular weight 400,000)

Vitalized silk 7.5 Sodium fluoride 0.21 0.21 0.21 0.21 0.21 0,21 0.21 0,21 0.21 0.21 0.21 Monoful ti sodium phosphate 0.73

Hori's old xylene

0.7 (20 mol) hydrogenated castor oil

Polyacrylic needle thorium 0.9 0.9 0.9 0.9 0.9 0.9 0,9 0.9 0.9 0.9 0.9 0,9 0.9 0.9 Purified water Residue Residue Residue Residue Residual Residual Residue Residual Residual Residue Residue ^ 100 100 100 100 100 100 100 100 100 100 100 100 100 Elephant a¾ Collagen

o ~ ® 〇〇〇〇 ~ © 〇 ~ © X Δ Δ X

^ 军 Suppressive effect △ △ Quality control effect ○ ○ o ○ ○ o ○ △ X △ △ △ △

* 1 Silk BN—P by phosphoric acid hydrolysis method

* 2 Silk peptide M_ 500 by enzymatic hydrolysis method

As in Examples 1 to 7, those containing hydrolyzed silk and fluorine compounds having a number average molecular weight of 500 to 5,000 showed excellent dentin collagen degradation inhibitory effect and demineralization inhibitory effect. . Among them, especially those containing hydrolyzed synolec having a number average molecular weight of 500 to 1,000 and a fluorine compound showed a high inhibitory effect on dentin collagen degradation. In addition, when the effects of hydrolyzed silk having the same number average molecular weight are compared, the hydrolyzed silk that has been hydrolyzed with phosphoric acid and the fluorine compound are particularly those containing hydrolyzed silk that has not been hydrolyzed with phosphoric acid and fluorine. Dentin collagen higher than that containing the compound Degradation inhibitory effect was shown. This is presumably because hydrolyzed silk that had been hydrolyzed with phosphoric acid had a higher peptide content. On the other hand, when only hydrolyzed silk or only fluorine compounds are used as in the comparative examples, or when cationized silk or a silk fiber mouth-in or collagen having a considerably large number average molecular weight is contained, the dentin collagen degradation inhibitory effect or The decalcification inhibitory effect was not sufficient.

[0041] [Example 8] Dentifrice

Caustic anhydride 15.0

Futsui Sodium 0.21

Hydrolyzed silk (Number average molecular weight: 500) 1.0

(Silk BN_P, NDC)

Sodium lauryl sulfate 0.1

Sodium polyacrylate 0.8

Xanthan gum 0.3

Fragrance 0. 1

purified water

Total 100.0%

[Example 9] Dentifrice

Caustic anhydride 15.0

Futsui Sodium 0.21

Hydrolyzed silk (Number average molecular weight: 500) 1.0

(Synolecpeptide M-500, manufactured by Cosmo Foods Co., Ltd.)

Sodium lauryl sulfate 0.1

Sodium polyacrylate 0.8

Xanthan gum 0.3

Fragrance 0. 1

Cum m

Total 100.0%

[0043] [Example 10] Dentifrice Caustic anhydride 15.0 Sodium fluoride 0.21 Hydrolyzed silk (number average molecular weight: 5,000) 1.0 (Sinorek powder FD, Kanebo Co., Ltd.)

Sodium lauryl sulfate 0.1 Sodium polyacrylate 0.8 Xanthan gum 0.8 8 Saccharin sodium 0.02 Fragrance 0.1 Purified water m Total 100.0%

[0044] [Example 11] Dentifrice

Caustic anhydride 15. 0 Sodium fluoride 0 · 21 Hydrolyzed silk (Number average molecular weight: 1, 000) 1.0 (Promois® silk 1 OOOp, manufactured by Seiwa Kasei Co., Ltd.) Sodium lauryl sulfate 0 · 1 Sodium polyacrylate 0 · 5 Sodium carboxymethylcellulose 0 · 3 Xanthan gum 0 · 5 Xylitol 9.0 Sodium citrate 0.3 Fragrance 0.1 Purified water m Total 100.0%

[0045] [Example 12] Dentifrice

Caustic anhydride 15.0 Sodium fluoride 0.21 Hydrolyzed silk (Number average molecular weight: 1,500) 1.0 (Silk peptide ⁵ , manufactured by Kanebo Corporation)

Sodium lauryl sulfate 0.1 Poly sodium acrylate 0.3 Sodium carboxymethyl cellulose 0.5 Xanthan gum 0.8 Xylitol 2.0 Dextranase 0.3 Fragrance 0.1

Purified water m Total 100. 0%

[0046] [Example 13] Dentifrice

Sodium fluoride 0 · 21 Hydrolyzed silk (Number average molecular weight: 500) 1.0 (Silk BN—P, manufactured by NDC)

卜 Lique mouth sun 0. 05 Polyoxyethylene (20 mol) hydrogenated castor oil 1.4 Sodium lauryl sulfate 1 · 0

70% Sonorebit 40.0 Propylene glycol 5.0 Sodium polyacrylate 0.8 Sodium carboxymethylcellulose 0.4 Xanthan gum 0.4 Perfume 0.5

Purified water m Total 100. 0%

[0047] [Example 14] Dentifrice

Sodium fluoride 0.21 Hydrolyzed silk (Number average molecular weight: 500) 1.0 (Silk BN—P, manufactured by NDC)

Isopropylmethylphenol 0, 05 Polyoxyethylene (20 mol) hydrogenated castor oil 1.4 Sodium lauryl sulfate 1.0

70% Sonorebit 40.0 Propylene Glycolol 5.0 Sodium Polyacrylate 0.4 Sodium Carboxymethyl Cellulose 0.2 Xanthan Gum 0.2 Fragrance 0.5

B

Total 100. 0% [Example 15] Dentifrice

Caustic anhydride 15. 0 Sodium fluoride 0.21 Hydrolyzed silk (Number average molecular weight: 500) 1.0 (Silk BN—P, manufactured by NDC)

Thymol 0. 05 Polyoxyethylene (20 mol) hydrogenated castor oil 1 · 4 Sodium lauryl sulfate 1.0

70% Sorbit 40.0 Propylene Glycolol 5.0 Sodium Polyacrylate 0.5 Xanthan Gum 0.8 Xylitoleol 9.0 Perfume 0.5

B Total 100.0%

[0049] [Example 16] Dentifrice

Sodium fluoride 0.21 Hydrolyzed silk (Number average molecular weight: 500) 1.0 (Silk BN_P, manufactured by NDC)

卜 Lique mouth sun 0.05 Alcohol methylphenol 0.05 Alcohol (20 mol) hydrogenated castor oil 1.4 Sodium lauryl sulfate 1.0

70% sorbit 40.0 propylene glycol 5.0 sodium polyacrylate 0.8 sodium carboxymethyl cellulose 0.8 sodium hydroxide 0.3 sodium saccharin 0.05 xylitol 9.0 perfume 0.5

purified water

Total 100.0%

[0050] [Example 17] Dentifrice

Dicalcium phosphate 15. 0 Sodium monofluorophosphate 0.73 Hydrolyzed silk (Number average molecular weight: 500) 1.0 (Silk BN—P, manufactured by NDC)

卜 Lique mouth sun 0.03 Polyoxyethylene (20 mol) hydrogenated castor oil 1.2 Sodium lauryl sulfate 0.8

70% Sonorbit 40. 0 Propylene glycol 5.0 Sodium polyacrylate 0.5 Sodium sodium canoleoxymethyl senorelose 0.5 Sodium hydroxide 0.3 Sodium saccharin 0.5 05 Xylitol 9.0 Fragrance 0.5 Total semen 100. 0%

[0051] [Example 18] Dentifrice

Sodium fluoride 0.4 Hydrolyzed silk (Number average molecular weight: 500) 0.5 (Silk BN—P, manufactured by NDC)

Isopropylmethylphenol 0.05 0.05 Polyoxyethylene (20 mol) hydrogenated castor oil 1 · 4 Sodium lauryl sulfate 0 · 5

70% Sonorbit 30.0 Propylene glycol 5. 0 Sodium polyacrylate 0.5 Sodium hydroxide 0.3 Sodium saccharin 0.05 Dextranase 0. 3 Fragrance 0.5 0.5 Total m 100.0%

[0052] [Example 19] Dentifrice

Caustic anhydride 15.0 Sodium fluoride 0.21 Hydrolyzed silk (Number average molecular weight: 500) 2.0 (Silk BN—P, manufactured by NDC)

卜 Likuguchi Sun 0.1 Polyoxyethylene (10 mol) hydrogenated castor oil 0.8 Sodium lauryl sulfate 1.0

70% Sonorebit 40.0 Propylene glycol 5. 0 Sodium polyacrylate 0. 8 Sodium carboxymethylcellulose 0. 5 Xanthan gum 0. 3 Sodium hydroxide 0. 3 Sodium saccharin 0. 05 Fragrance 0. 5

purified water

Total 100.0%

[Example 20] Mouthwash

Hydrolyzed silk (Number average molecular weight: 500) 1.5 (Silk BN—P, manufactured by NDC)

Futsui Sodium 0.5.5 Kikuchi Sun San 0.02 Polyoxyethylene (60 mol) hydrogenated castor oil 0.3 Ethanol Nore 10.0 Cenoic acid 0.01 Nacreate 30.3 Sodium saccharin 0.1 0.1 Xylitol 5.0

0. 1% Green No. 3 0. 8 Fragrance 0. 3 Purified water m

Total 100.0%

[0054] [Example 21] Mouthwash

Hydrolyzed silk (number average molecular weight: 1,000) 2.0

(Promois (registered trademark) Silk 1000p, Seiwa Kasei Co., Ltd.)

Futsui sodium 0. 05

Isopropyl methyl phenol 0. 08

卜 Rikuguchi Sun 0. 05

Polyoxyethylene (60 mol) hydrogenated castor oil 0.3

Ethanore 10. 0

Quenic acid 0. 01

Cenoic acid trisodium 0.3

Saccharin sodium 0 · 1

Dextranase 3 · 0

0. 1% green No. 3 0. 8

Fragrance 0.3

purified water

Total 100.0%

[0055] [Table 2]

From Table 2, the dentin collagen degradation inhibitory effect and the demineralization inhibitory effect were excellent for those containing hydrolyzed silk having a number average molecular weight of 500 to 5,000 and a fluorine compound. Among them, in particular, hydrolyzed silk having a number average molecular weight of 500 to 1,000, fluorine compound, The one containing a high dentin collagen degradation inhibitory effect. In addition, when comparing the effects of hydrolyzed silk of the same number average molecular weight, especially those containing phosphoric acid hydrolyzed synolec and fluorine compounds, hydrolyzed with phosphoric acid, hydrolyzed with phosphoric acid, It showed a higher inhibitory effect on dentin collagen degradation than that containing antisynolec and fluorine compounds. This was presumed to be due to the higher peptide content of hydrolyzed silk that had been hydrolyzed with phosphoric acid as described above. Furthermore, the combined use of a poorly water-soluble nonionic antibacterial agent and a surfactant and / or alcohol for solubilizing it further improves the collagen degradation inhibitory effect and decalcification inhibitory effect of the dentin. It was suggested that the quality of caries prevention could be improved dramatically.

From the above experimental examples, Examples:! To 21 protected the dentin in a short time treatment and effectively suppressed the degradation of the dentin collagen, compared with the comparative examples:! Furthermore, it has been speculated that the retention of fluorinated compounds and antibacterial agents on the tooth surface has been greatly improved, resulting in a synergistic high deashing suppression effect.

Therefore, according to the present invention, collagen degradation and decalcification of dentin can be remarkably suppressed by using hydrolyzed silk and a fluorine compound having a specific number average molecular weight. Furthermore, by adding a poorly water-soluble nonionic antibacterial agent and a surfactant and / or alcohol to solubilize it, both the collagen degradation inhibitory effect and the demineralization inhibitory effect of dentin are improved. Thus, it is possible to provide a composition for oral cavity in which the effect of preventing dentin caries has been dramatically improved.

Claims

The scope of the claims

[1] An oral composition comprising hydrolyzed silk having a number average molecular weight of 200 to 6,000 calculated based on the total nitrogen content and amino nitrogen content, and a fluorine compound.

[2] The composition for oral cavity according to claim 1, wherein the hydrolyzed silk is obtained by phosphoric acid hydrolysis.

[3] The amount of hydrolyzed synolec is 0.1 to 10% by mass of the entire composition, and the amount of fluorine compound is 0.02 to 3% by mass of the entire composition. Oral composition

[4] The composition for oral cavity according to any one of claims 1 to 3, further comprising a slightly water-soluble nonionic antibacterial agent, a surfactant and / or an alcohol.

[5] The poorly water-soluble nonionic antibacterial agent is triclosan or isopropylmethylphenol, and the surfactant is polyoxyethylene hydrogenated castor oil or alkyl sulfate salt having an average addition mole number of 5 to 100. The composition for oral cavity according to claim 4, wherein the alcohol is propylene glycol, polyethylene glycol mononole (# 200 to 6000), ethylene glycol, glycerin, sorbitol or ethanol.

[6] The amount of the poorly water-soluble nonionic antibacterial agent is 0.0 :! to 2% by mass of the whole composition, and the amount of the surfactant is 0.:! To 5% of the whole composition. The composition for oral cavity according to claim 4 or 5, wherein the blending amount of alcohol is 0.:! To 50% by mass of the whole composition.