CN105534736B - Composition for oral cavity - Google Patents

Composition for oral cavity Download PDF

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Publication number
CN105534736B
CN105534736B CN201510960283.9A CN201510960283A CN105534736B CN 105534736 B CN105534736 B CN 105534736B CN 201510960283 A CN201510960283 A CN 201510960283A CN 105534736 B CN105534736 B CN 105534736B
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Prior art keywords
ingredient
composition
oral cavity
acid
salt
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CN201510960283.9A
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CN105534736A (en
Inventor
井上志磨子
藤川晴彦
朝熊弘树
鬼木隆行
福田康
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Lion Corp
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Lion Corp
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4913—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/20—Halogens; Compounds thereof
    • A61K8/21—Fluorides; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/24—Phosphorous; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/365—Hydroxycarboxylic acids; Ketocarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/731—Cellulose; Quaternized cellulose derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses

Abstract

The object of the present invention is to provide a kind of with separate constituent or 2 or more into the composition for oral cavity of subassembly, can play the inhibition of dentine dental caries, the inhibition of dentine acroesthesia or improvement, color spot forms and the functions such as inhibits or remove.The present invention provides a kind of composition for oral cavity, contains (A) ingredient: selected from the group being made of gamma-lactam skeleton, δ-lactams skeleton and ε-lactams skeleton more than one with lactams skeleton and with acidic-group compound and/or its salt.

Description

Composition for oral cavity
The application is the divisional application based on following Chinese patent application:
The original bill applying date: on 09 28th, 2012
Original bill application number: 201280047777.2 (PCT/JP2012/075223)
Original bill application title: composition for oral cavity
Technical field
The present invention relates to a kind of composition for oral cavity.
Background technique
Intraoral gum is easy atrophy with the aging of periodontosis or organism.If gingival atrophy does not have originally There is exposed root of the tooth (tooth root) that will expose.Root of the tooth exists in the state that dentine is not covered by enamel.Due to tooth Essence also more contains the organic horizon based on collagen, therefore its mine while with countless Minute Tubule Structures Material density is lower, is 50% or so, compared with mineral density is 97% or so enamel, physically, chemically all It is fragile.Therefore, if tooth root is caused to be exposed in oral cavity due to gingival atrophy, it is easy to happen dental caries (carious dentin Disease).The dentine dental caries using tooth root exposure as the root of the tooth started are referred to as cementum caries disease like this.
The pathogenesis of dentine dental caries (cementum caries disease) is as follows: firstly, being exposed to intraoral dentin surface's attachment The metabolism of sugar is occurred by the bacterium in plaque, produces acid for plaque.Thus acid causes the mineral composition of dentine molten (demineralization (Japanese: deliming)) out, the exposure of organic matter (collagen) layer.Further collagen layer physically chemically by It destroys, defect occurs in itself for the root of tooth.
All the time, the prevention method as dentine dental caries proposes several technologies for inhibiting demineralization and promotes mine again The technology (referring to patent document 1~4) of change.
In patent document 1, describes and inhibit the minerals of dentine to dissolve out using composition for oral cavity, the oral cavity group Closing object has the average grain diameter of hydrolysis silk (Japanese: hydrolyzable シ Le Network) and primary particle in 0.04~0.5 μ m Precipitated calcium carbonate ingredient.
In patent document 2, describe using dentin remineralization promotor to promote remineralization, the dentin remineralization promotes Monomer, (b) combined amount having containing phosphorus atoms for 5~200 weight %s relative to (a) ingredient of the agent with (a) with hydroxyl Acidic-group monomer.
It in patent document 3, describes using composition for oral cavity, prevents dentine dental caries, particularly cementum caries disease, the mouth The polyphenolic substance that there is chamber composition (A) zinc compound, (B) to extract from aldehyde based compound, phenol system compound and tea forms Group in at least one that selects.
In patent document 4, disclose using the Management of Root Surface Caries being made of flavanone and/or its glycosides (Japanese: glycocide) Sick prophylactic inhibits collagen decomposition and demineralization.
In addition, indicating in dentine dental caries (cementum caries disease), even if collagen layer exposure, becomes remineralization Foothold consumes calcium ion and phosphate ion in saliva, there is a possibility that depositing crystalline in exposed collagen layer.From And, it may be said that in the prevention of dentine dental caries, the decomposition for the collagen layer for inhibiting this to expose is necessary.
It as prevention of caries technology all the time, discloses centered on fluoride, with being used in combination for the metal ions such as calcium The fluoride of technology (patent document 5~7) etc. is sustained delay technology.Although these are possible to play certain to enamel dental caries Effect, but when dentine dental caries (cementum caries disease) occur, fluoride cannot fully protect exposed collagen layer, lead Collagen is caused to decompose.
On the other hand, as soverlay technique, although disclosing the facing coating technology (patent using phosphate or polymer Document 8 and 9), using dentine protection technique (patent document 10) of aluminium, fluoride and calcium etc., but to exposed collagen layer Coverage effect it is insufficient.
Polyphenol can cover exposed collagen layer.Polyphenol has the function of making the reduction of clostridiopetidase A enzymatic activity, as a result, There is the substance of the decomposition inhibitory effect of exposed collagen layer as expectation and is known.For example, it is more to disclose tea blend The acid resistance of the dentine of phenol fluoride aluminium salt enhances technology (patent document 11), and, utilize longan nuclear extract and fluorine The combination (patent document 12) of compound and sugar alcohol pays technology using the root face acid resistance of aurantiamarin (patent document 13).So And polyphenol has the shortcomings that be easy to produce discoloration and muddiness because of oxidation, pH variation, formation of complex etc., so in denfifrice, gargling It is difficult to keep stability in the dosage forms such as mouth agent.In addition validity of the polyphenol after preparation is made and saves reduces, after application preparation The collagen layer of exposure have the problem of extra coloring.Therefore, it is desirable to exploitation be made preparation save after can also inhibit tooth sheet The decomposition of the collagen of matter exposure, prevents the coloring to exposed collagen layer, moreover, showing preparation height when as preparation The effective component of stability.
[dentine acroesthesia]
If make dentine exposure as above-mentioned tooth root exposure, by being given in temperature to this dentine, chemistry Upper, external irritant mechanically can generate and be known as the transient very irritating of dentine acroesthesia Pain.
Caused by the reason of dentine acroesthesia, is considered that nerve is stimulated by dentinal tubule.
Inhibition and improvement (mitigation) as the dentine acroesthesia using oral hygienes products such as denfifrice is tactful, It can enumerate: the method for dentinal tubule being closed by aluctyl etc., makes neural paralysis by potassium nitrate etc. to make pain relief Method etc..
The known opening portion with blocking dentinal tubule of aluctyl, and improve the effect of dentine acroesthesia (specially Sharp document 14).But the effect for obtaining aluctyl needs the regular hour, there is the shortcomings that lacking prompt effect.Aluctyl it has also been found that There is the problem of distinctive astringent taste and metallic taste.
On the other hand, although potassium nitrate is passed through as neural paralysis ingredient frequently with (patent document 15), but while having Prompt effect, effect are also not easy to continue.In other words, the effect of potassium nitrate is limited.Potassium nitrate bitter taste is strong, companion sometimes when use There is discomfort.
[removal of color spot]
The coloring spot of tooth is referred to as color spot or color spot film, it is believed that is to be adsorbed onto the film of facing formation in sialoprotein On, the substance from the deposition such as polyphenol (tannic acid, chlorogenic acid etc.), metal ion, smoke tar of beverage/food and after colouring.Its In, the most frequent color spot being observed is known as moth patch, it is believed that with the polyphenolic substance phase in the beverage/foods such as tannic acid, chlorogenic acid It closes.
In the past, it is attached to the removal of the color spot on facing, it is main using by being mixed into composition for oral cavity such as denfifrice The technology of the mechanism of the grinding agent of conjunction.On the other hand, there is the toothpaste composition (patent document for proposing mixing pyrophosphate 16) color spot for, mixing sulfosuccinic acid system surfactant forms obstruction and is utilized with composition for oral cavity (patent document 17) etc. The removal technology of the color spot of chemical action, further the toothpaste containing papain (patent document 18), contain (A) lysozyme And/or the color spot of (B) lipase, dextranase, glucosidase, 1,3- dextranase and the enzyme for becoming one or more of dextranase Removal utilizes the removal technology of the color spot of enzyme effect with composition for oral cavity (patent document 19) etc..
On the other hand, it has been proposed that the technology for inhibiting teeth stains to be formed.For example, propose containing polyphosphoric acid or its salt and Acyl taurine salt makes to show the liquid oral composition (patent document 20) of regulation pH, containing (A) polyphosphoric acid or its salt and (B) liquid oral composition (patent document 21) of specific disaccharides and (C) malic acid, tartaric acid and its salt has tooth Coloring prevents effect.
However, if wanting to remove color spot by the mechanism of grinding agent, have because brushing teeth excessively make injury of teeth, There is the worry of color spot residual etc. at the position that the brush end of toothbrush cannot reach.
On the other hand, using the removal of the color spot of chemical action, have low from the taste difference and use feeling for removing ingredient Under problem.Using the removal of the color spot of enzyme effect, in the case where using papain, then there is papain that may act on In the intraoral soft tissue the problem of.In the case where using other enzymes, then also there is the ingredient of color spot to be not necessarily suitble to point of enzyme Solve matrix the problems such as point.
Above-mentioned color spot forms suppression technology, any one is all because containing polyphosphoric acids such as sodium tripolyphosphates, to fail gram It takes the distinctive taste of condensed phosphate and the problem of to the inadaptable sense of oral mucosa, therefore can not be said to be sufficient technology.
It is above-mentioned that color spot can be given full play to by, which not finding also, forms inhibitory effect and color spot removal effect in previous technology, Further play luster effect, and preparation use feeling also excellent technology.
It is such as above-mentioned, inquire into inhibition, dentine sense using previous various methods to dentine dental caries (cementum caries disease) The inhibition and improvement and the inhibition of color spot and removing of feel allergy.Therefore, status is to wait in expectation to provide to can be used as new tool Dentine dental caries (cementum caries disease) and dentine acroesthesia inhibition and improvement appropriate, the inhibition of color spot and removing Means.In particular, due to along with population aging, dentine dental caries (cementum caries disease) and dentine acroesthesia still have increasing Add tendency, therefore, these inhibit and improvement is the task of top priority.
All the time, 2-pyrrolidone-5-carboxylic acid and/or its salt, as being suitable for skin, scalp, hair, nail and/or viscous Film carries out the ingredient of the gelation topical compositions of cosmetic treatments and is known (patent document 22).But as oral cavity group The components uses for closing object are not known also.
Existing technical literature
Patent document
Patent document 1: Japanese Patent Laid-Open 2007-176862 bulletin
Patent document 2: Japanese Patent Laid-Open 2006-8596 bulletin
Patent document 3: Japanese Patent Laid-Open 11-228368 bulletin
Patent document 4: Japanese Patent Laid-Open 2009-256341 bulletin
Patent document 5: the flat 10-511104 bulletin of Japanese patent special table
Patent document 6: Japanese Patent Laid-Open 11-106322 bulletin
Patent document 7: Japanese Patent Laid-Open 2005-112841 bulletin
Patent document 8: Japanese Patent Laid-Open 5-320032 bulletin
Patent document 9: Japanese Patent Laid-Open 2005-200345 bulletin
Patent document 10: Japanese Patent Laid-Open 5-155746 bulletin
Patent document 11: Japanese Patent Laid-Open 6-298632 bulletin
Patent document 12: Japanese Patent Laid-Open 2011-168510 bulletin
Patent document 13: Japanese Patent Laid-Open 2009-256341 bulletin
Patent document 14: Japanese Patent Laid-Open 2010-222325 bulletin
Patent document 15: Japanese Patent Laid-Open 08-175943 bulletin
Patent document 16: Japanese Patent Laid-Open 10-182389 bulletin
Patent document 17: Japanese Patent Laid-Open 10-17443 bulletin
Patent document 18: the flat 1-503142 bulletin of Japanese patent special table
Patent document 19: Japanese Patent Laid-Open 2001-181163 bulletin
Patent document 20: Japanese Patent Laid-Open 2009-051734 bulletin
Patent document 21: Japanese Patent Laid-Open 2005-343794 bulletin
Patent document 22: Japanese Patent Laid-Open 9-202708 bulletin
Summary of the invention
Problems to be solved by the invention
The object of the present invention is to provide a kind of inhibition that can play dentine dental caries, the inhibition of dentine acroesthesia or The preparation or composition for oral cavity of each functions such as inhibition or removing that improvement, color spot are formed.Specifically, the purpose of the present invention 4 can be listed below.
1st purpose of the invention be to provide with dentine dental caries inhibitory effect, dentine acroesthesia inhibition or The composition for oral cavity of improvement, the inhibition of color spot or removal effect.
2nd purpose of the invention is to provide the decomposition and coloring for significantly inhibiting exposed collagen layer, and system is made When agent, the composition for oral cavity of high preparation stability is shown.
3rd purpose of the invention is to provide significant mitigation because of hypersensitive pain, while having good use feeling (taste Road) composition for oral cavity.For example, providing opening portion (the dentinal tubule early stage closing that can close dentinal tubule in early days Effect), the pain (pain relief effect) that patient feels can be mitigated, after use without or do not occur substantially astringent taste, metallic taste, The composition for oral cavity of peculiar smell etc. (good use feeling (taste)).
4th purpose of the invention, which is to provide, all simultaneously sufficiently there is color spot removal effect and color spot to form both inhibitory effects , luster effect is further played, preparation use feeling is also excellent, the composition for oral cavity useful to tooth whitening.
5th purpose of the invention is to provide the composition for oral cavity that collagen can be inhibited to colour.
The means solved the problems, such as
The present invention provides following (1)~(24).
(1) a kind of composition for oral cavity, wherein contain (A) ingredient: have gamma-lactam skeleton, δ-lactams skeleton or Any one lactams skeleton in ε-lactams skeleton and the lactam compound with acidic-group.
(2) composition for oral cavity as described in above-mentioned (1), wherein (A) ingredient is 2-pyrrolidone-5-carboxylic acid and/or its salt.
(3) composition for oral cavity as described in above-mentioned (1) or (2), wherein the content of (A) ingredient is 0.3~10 matter Measure %.
(4) composition for oral cavity as described in above-mentioned (1) or (2), wherein further contain (1-B) ingredient: fluorination is closed Object.
(5) composition for oral cavity as described in above-mentioned (4), wherein (B) ingredient is selected from sodium fluoride and sodium monofluorophosphate At least one selected.
(6) composition for oral cavity as described in above-mentioned (4) or (5), wherein (A) ingredient is relative in composition for oral cavity The mass ratio of fluorine amount is 1~250.
(7) such as the described in any item composition for oral cavity in above-mentioned (4)~(6), wherein further contain (1-C) ingredient: containing There is the protein of 1.0~6.0 mass % sulfur-containing amino acid residues.
(8) composition for oral cavity as described in above-mentioned (5), wherein (1-C) ingredient is casein.
(9) composition for oral cavity as described in above-mentioned (1) or (2), wherein further contain (2-B) ingredient: from by longan One selected in the group that nuclear extract, proanthocyanidin (Japanese: プ ロ ア Application ト シ ア ニ ジ Application), catechin and aurantiamarin form Kind or more polyphenolic substance.
(10) composition for oral cavity as described in above-mentioned (1) or (2), wherein further contain (3-B) ingredient: aluctyl.
(11) composition for oral cavity as described in above-mentioned (10), wherein further contain (3-C) ingredient: mono-fluor phosphate.
(12) composition for oral cavity as described in (10) or (11), wherein further contain (3-D) ingredient: water-soluble nothing Machine sylvite.
(13) composition for oral cavity as described in above-mentioned (1) or (2), wherein further contain (4-B) ingredient: water-soluble Inorganic potassium salt.
(14) composition for oral cavity as described in above-mentioned (13), wherein further contain (4-C) ingredient: water soluble fluoridized Close object.
(15) composition for oral cavity as described in above-mentioned (1) or (2), wherein further contain (5-B) ingredient: cation Cellulose.
(16) composition for oral cavity as described in above-mentioned (15), wherein (5-B) ingredient is hydroxyethyl cellulose dimethyl two Allyl ammonium chloride.
(17) composition for oral cavity as described in above-mentioned (1) or (2), wherein further contain (6-B) ingredient: polyphenol Close object.
(18) a kind of collagen coloration inhibitor, wherein using (A) ingredient as effective component, (A) ingredient are as follows: tool There is any one lactams skeleton in gamma-lactam skeleton, δ-lactams skeleton or ε-lactams skeleton and there is acidic-group Lactam compound.
(19) a kind of collagen decomposing inhibitor, wherein using (A) ingredient as effective component, (A) ingredient are as follows: tool There is any one lactams skeleton in gamma-lactam skeleton, δ-lactams skeleton or ε-lactams skeleton and there is acidic-group Lactam compound.
(20) a kind of dentinal tubule sealer, wherein using (A) ingredient as effective component, (A) ingredient are as follows: have Any one lactams skeleton in gamma-lactam skeleton, δ-lactams skeleton or ε-lactams skeleton and with acidic-group Lactam compound.
(21) a kind of dentine acroesthesia inhibition or improver, wherein described (A) using (A) ingredient as effective component Ingredient are as follows: with any one lactams skeleton in gamma-lactam skeleton, δ-lactams skeleton or ε-lactams skeleton and have There is the lactam compound of acidic-group.
(22) a kind of color spot remover, wherein using (A) ingredient as effective component, (A) ingredient are as follows: there is the interior acyl of γ- Any one lactams skeleton in amine skeleton, δ-lactams skeleton or ε-lactams skeleton and the lactams with acidic-group Compound.
(23) such as the described in any item preparations in above-mentioned (18)~(22), wherein (A) ingredient be 2-pyrrolidone-5-carboxylic acid and/or Its salt.
It (24) is dentine hyperesthesia such as above-mentioned (1), the described in any item composition for oral cavity in (2) and (9)~(14) Person's.
[composition for oral cavity]
Inhibition, collagen egg of the present inventor in order to obtain compared with previous composition for oral cavity, in collagen decomposition The inhibition of white coloring, the inhibition of dentine acroesthesia or improvement, color spot removal effect on excellent composition for oral cavity, Conscientiously research repeatedly is carried out.Finally, it is found that containing being that representative " has γ-using 2-pyrrolidone-5-carboxylic acid and/or its salt The lactams skeleton of any of lactams skeleton, δ-lactams skeleton or ε-lactams skeleton, and it is interior with acidic-group The composition for oral cavity of amide compound ", in inhibition, the inhibition of collagen coloring, dentine feeling that collagen decomposes Excellent effect can be obtained in the inhibition or improvement of allergy, the removal effect of color spot.
The present invention provides following composition for oral cavity (0-1)~(0-4).
A kind of (0-1) composition for oral cavity contains (A) ingredient: have gamma-lactam skeleton, δ-lactams skeleton or Any one lactams skeleton in ε-lactams skeleton and the lactam compound with acidic-group.
The composition for oral cavity of (0-2) as described in (0-1), wherein (A) ingredient is 2-pyrrolidone-5-carboxylic acid and/or its salt.
The composition for oral cavity of (0-3) as described in above-mentioned (0-1) or (0-2), the content of (A) ingredient is 0.3~10 matter Measure %.
(0-4) such as described in any item composition for oral cavity of above-mentioned (0-1)~(0-3) are that dentine hyperesthesia person uses 's.
[composition for oral cavity (1)]
The present inventor is excellent in dentine dental caries preventive effect in order to obtain compared with previous composition for oral cavity Composition for oral cavity has carried out conscientiously research repeatedly.In this research, be prepared for simultaneously with 2-pyrrolidone-5-carboxylic acid and/or its Salt be representative " the lactams skeleton with any of gamma-lactam skeleton, δ-lactams skeleton or ε-lactams skeleton, And the lactam compound with acidic-group " and the composition for oral cavity that is used as ingredient of fluorine compounds.This oral cavity is used Composition is used for dental caries sample, about its dentine dental caries inhibitory effect, with Transverse Microradiography (hereinafter, being slightly written as TMR method) is evaluated.
TMR method refers to the microradiogram (Japanese: マ イ Network ロ ラ ジ オ グ ラ Off) using tooth thin slice cross section, obtains The analysis of the tooth mineral quality to convert according to the brightness equivalent based on aluminium thickness is obtained as a result, to demineralization depth and mine The skill and technique that material damage amount measures is the putative method of reliability as the method for measurement dental caries degree.
With the evaluation assessment of the dentine dental caries inhibitory effect of above-mentioned TMR method evaluation as a result, finally discovery simultaneously with " the lactams skeleton with any of gamma-lactam skeleton, δ-lactams skeleton and ε-lactams skeleton, and there is acidity The composition for oral cavity (1) that the lactam compound of group " and " fluorine compounds " have as ingredient, shows to have played and is better than The dentine dental caries inhibitory effect of previous composition for oral cavity.
The present invention provides following composition for oral cavity (1).
(1-1) a kind of composition for oral cavity, it is characterised in that contain (A) ingredient: have interior from gamma-lactam skeleton, δ- More than one the lactams skeleton that is selected in amide backbone or ε-lactams skeleton composition group and interior with acidic-group Amide compound or its salt, and (1-B) ingredient: fluorine compounds.
The composition for oral cavity of (1-2) as described in above-mentioned (1-1), it is characterised in that (A) ingredient be 2-pyrrolidone-5-carboxylic acid and/ Or its salt.
The composition for oral cavity of (1-3) as described in above-mentioned (1-1) or (1-2), (1-B) ingredient are from sodium fluoride and single fluorine At least one selected in sodium phosphate.
(1-4) such as the described in any item composition for oral cavity of above-mentioned (1-1)~(1-3), wherein (A) ingredient is relative to mouth Chamber is 1~250 with the mass ratio of fluorine amount in composition.
(1-5) such as described in any item composition for oral cavity of above-mentioned (1-1)~(1-4), further contain (1-C) ingredient: Protein containing 1.0~6.0 mass % sulfur-containing amino acid residues.
The composition for oral cavity of (1-6) as described in above-mentioned (1-5), wherein (1-C) ingredient is casein.
[composition for oral cavity (2)]
The present inventor in order to achieve the above object, has carried out conscientiously research repeatedly.As a result, it has been found that defined polyphenol chemical combination The combination of object and defined lactam compound can inhibit the decomposition of the collagen layer of exposure compared with when being respectively used alone (dentin collagen protein breakdown inhibitory effect), and be made preparation save after its effect can also continue the (dentine after preservation Collagen decomposes inhibitory effect).It has also been found that above-mentioned lactam compound can inhibit to cause to be made because of above-mentioned polyphenolic substance The discoloration of preparation after agent preservation itself, also there is no problem on conformality (preparation stability), and can also inhibit for a long time Coloring (inhibitory effect of the dentin collagen albumen coloring after preservation) due to polyphenol to dentine.So as to complete this hair It is bright.
The present invention provides following composition for oral cavity (2).
A kind of (2-1) composition for oral cavity contains (A) ingredient: having from gamma-lactam skeleton, δ-lactams skeleton With more than one the lactams skeleton selected in ε-lactams skeleton composition group and with the lactams chemical combination of acidic-group Object or its salt, and (2-B) ingredient: one selected from the group that longan nuclear extract, proanthocyanidin, catechin and aurantiamarin form Kind or more polyphenolic substance.
The composition for oral cavity of (2-2) as described in above-mentioned (2-1), wherein (A) ingredient be 2-pyrrolidone-5-carboxylic acid and/or its Salt.
[composition for oral cavity (3)]
The present invention provides following composition for oral cavity (3).
A kind of (3-1) composition for oral cavity contains (A) ingredient: having from gamma-lactam skeleton, δ-lactams skeleton With more than one the lactams skeleton selected in the group of ε-lactams skeleton composition and the compound with acidic-group or its Salt, and (3-B) ingredient: aluctyl.
The composition for oral cavity of (3-2) as described in above-mentioned (3-1), wherein (A) ingredient be 2-pyrrolidone-5-carboxylic acid and/or its Salt.
The composition for oral cavity of (3-3) as described in above-mentioned (3-1) or (3-2) further contains (3-C) ingredient: single fluorine phosphorus Hydrochlorate.
(3-4) such as described in any item composition for oral cavity of above-mentioned (3-1)~(3-3), further contain (3-D) ingredient: Water-soluble inorganic sylvite.
(3-5) such as described in any item composition for oral cavity of above-mentioned (3-1)~(3-4) are that dentine hyperesthesia person uses 's.
[composition for oral cavity (4)]
The inventors discovered that containing specific lactam compound or its salt and water-soluble inorganic with acidic-group The composition for oral cavity of sylvite combination has good use feeling while pain caused by significant mitigate because of hyperesthesia (taste).
The present invention provides following composition for oral cavity (4).
A kind of (4-1) composition for oral cavity contains (A) ingredient: having from gamma-lactam skeleton, δ-lactams skeleton With more than one the lactams skeleton selected in ε-lactams skeleton composition group and with the lactams chemical combination of acidic-group Object or its salt, and (4-B) ingredient: water-soluble inorganic sylvite.
The composition for oral cavity of (4-2) as described in above-mentioned (4-1), wherein (A) ingredient is from 2-pyrrolidone-5-carboxylic acid, 6- oxygen Generation -2-piperidinecarboxylic acid, 3- (2- oxo -1- nitrogen heterocyclic heptyl) propionic acid and they salt form group in select more than one Compound.
The composition for oral cavity of (4-3) as described in above-mentioned (4-1) or (4-2) further contains (4-C) water-soluble fluorine chemical combination Object.
(4-4) such as described in any item composition for oral cavity of above-mentioned (4-1)~(4-3) are that dentine hyperesthesia person uses 's.
[composition for oral cavity (5)]
The present invention provides following composition for oral cavity (5).
A kind of (5-1) composition for oral cavity contains (A) ingredient: having from gamma-lactam skeleton, δ-lactams skeleton With more than one the lactams skeleton selected in ε-lactams skeleton composition group and with the lactams chemical combination of acidic-group Object or its salt, and (5-B) ingredient: cationic cellulose.
The composition for oral cavity of (5-2) as described in above-mentioned (5-1), (A) ingredient are 2-pyrrolidone-5-carboxylic acid and/or its salt.
The composition for oral cavity of (5-3) as described in above-mentioned (5-1) or (5-2), (5-B) ingredient is hydroxyethyl cellulose two Methyl diallyl ammonium chloride.
[composition for oral cavity (6)]
The present invention provides following composition for oral cavity (6).
A kind of (6-1) composition for oral cavity contains (A) ingredient: having from gamma-lactam skeleton, δ-lactams skeleton Or any one lactams skeleton in ε-lactams skeleton and the lactam compound with acidic-group, and (6-B) ingredient: Polyphenolic substance.
[preparation]
The present invention provides following various preparations.
A kind of (7-1) collagen coloration inhibitor, using (A) ingredient as effective component, (A) ingredient are as follows: have Any one lactams skeleton in gamma-lactam skeleton, δ-lactams skeleton or ε-lactams skeleton and with acidic-group Lactam compound.
A kind of (7-2) collagen decomposing inhibitor, using (A) ingredient as effective component, (A) ingredient are as follows: have Any one lactams skeleton in gamma-lactam skeleton, δ-lactams skeleton or ε-lactams skeleton and with acidic-group Lactam compound.
A kind of (7-3) dentinal tubule sealer, using (A) ingredient as effective component, (A) ingredient are as follows: there is γ- Any one lactams skeleton in lactams skeleton, δ-lactams skeleton or ε-lactams skeleton and interior with acidic-group Amide compound.
A kind of (7-4) dentine acroesthesia inhibits or improver, using (A) ingredient as effective component, (A) at It is divided into: with any one lactams skeleton in gamma-lactam skeleton, δ-lactams skeleton or ε-lactams skeleton and has The lactam compound of acidic-group.
A kind of (7-5) color spot remover, using (A) ingredient as effective component, (A) ingredient are as follows: there is gamma-lactam Any one lactams skeleton in skeleton, δ-lactams skeleton or ε-lactams skeleton and the lactamization with acidic-group Close object.
(7-6) such as the described in any item preparations of above-mentioned (7-1)~(7-5), wherein (A) ingredient be 2-pyrrolidone-5-carboxylic acid and/ Or its salt.
Invention effect
According to the present invention it is possible to provide the inhibition to dentine dental caries, the inhibition of dentine acroesthesia or improvement, color The useful composition for oral cavity and preparation such as the inhibition or removing of the formation of spot.
According to the present invention it is possible to provide, dentine dental caries inhibitory effect is excellent, preparation stability also excellent oral cavity group It closes object (1).Composition for oral cavity (1) is constituted by being allowed to be absorbed into intracorporal ingredient.Therefore, composition for oral cavity (1) can be with With the medicine part outer articles such as denfifrice, collutory (medicine part outer article), the food of chewing gum, candy, pressed candy (Japanese: ingot Fruit) etc. The form of the simplicity such as product provides excellent dentine dental caries preventive effect.
According to the present invention it is possible to provide the composition for oral cavity (2) for the decomposition that can significantly inhibit exposed collagen layer. Its effect can also be kept after preparation is made and saves.After composition for oral cavity (2) can also inhibit due to preparation preservation is made Discoloration and muddiness in the coloring and preparation to exposure collagen of polyphenolic substance.
According to the present invention it is possible to provide while pain caused by significant mitigate because of hyperesthesia, there is good make With the composition for oral cavity (3) of sense (taste) and (4).And composition for oral cavity (3) is on dentinal tubule sealing effect It is excellent.Composition for oral cavity (3) and (4) are the inhibition of dentine acroesthesia or improvement (mitigation) aspect is useful.
According to the present invention it is possible to provide the removal effect that can play color spot, the inhibitory effect that color spot is formed, luster effect With the composition for oral cavity (5) of excellent preparation use feeling.
According to the present invention it is possible to provide the composition for oral cavity (6) for showing the inhibitory effect of collagen coloring.
According to the present invention it is possible to provide the inhibitor for colouring (A) ingredient as the collagen of effective component, collagen egg White decomposing inhibitor, dentinal tubule sealer, acroesthesia inhibition or improver and color spot remover.
Specific embodiment
The present invention described further below.When in the following description, if not otherwise specified, " % " then indicates " matter Measure % ".
[(A) ingredient]
(A) ingredient has the group formed from gamma-lactam skeleton, δ-lactams skeleton and ε-lactams skeleton in the present invention More than one lactams skeleton of middle selection and with acidic-group compound (hereinafter referred to as lactam compound) and/ Or its salt.
Lactam compound or its salt, if it is with either one or two of above-mentioned specific 3 kinds of lactams skeletons and with acid If the lactam compound or its salt of property group, just it is not particularly limited.Also it can have two or more interior acyls in molecule Amine skeleton, it is possible to have two or more acidic-groups, it is possible to have two or more lactams skeleton and two or more Acidic-group.In a suitable embodiment, lactams skeleton is gamma-lactam skeleton.
As the acidic-group that lactam compound or its salt have, for example, phenolic hydroxyl group, carboxyl and sulfonic acid can be enumerated Base etc..It wherein, is preferably carboxyl as acidic-group.
As with gamma-lactam skeleton and with acidic-group lactam compound, for example, pyrrolidines can be enumerated Keto carboxylic acid, 4- (3- hydroxy phenyl) -4- aza-tricycle base (5.2.1.0 (2,6)) dodecyl -8- alkene -3,5- glycol (Japanese: 4- (3- ヒ De ロ キ シ Off ェ ニ Le) -4-Aza-tricyclo (5.2.1.0 (2,6)) Dec-8- エ Application -3,5- ジ オ Application), 2- (3,5- dioxo -4- aza-tricycle base (5.2.1.0 (2,6)) dodecyl -8- alkene -4- base) benzoic acid (Japanese: 2- (3,5- ジ オ キ ソ -4-Aza-tricyclo (5.2.1.0 (2,6)) Dec-8- エ Application -4-yl) benzoic Acid) and their salt, preferably 2-pyrrolidone-5-carboxylic acid and their salt.
As with δ-lactams skeleton and with acidic-group lactam compound, for example, 6- oxo-can be enumerated 2-piperidinecarboxylic acid, 4- (2- oxo -1- piperidyl) butyric acid, 1- ethyl -6- oxo-nipecotic acid and their salt, preferably For 6- oxo -2-piperidinecarboxylic acid.
As with ε-lactams skeleton and with acidic-group lactam compound, for example, 3- (2- oxygen can be enumerated Generation -1- nitrogen heterocyclic heptyl) propionic acid, 3- (the bromo- 5- hydroxy phenyl of 2-) -1- methyl -2- caprolactam and their salt, it is excellent It is selected as 3- (2- oxo -1- nitrogen heterocyclic heptyl) propionic acid.
The salt of lactam compound is not particularly limited if it is the salt pharmacologically allowed.As pharmacology The salt of upper permission, for example, acid-addition salts, base addition salts and amino-acid salt can be enumerated.As its concrete example, can enumerate hydrochloride, The inorganic acid salts such as hydrobromate, sulfate, hydriodate, nitrate, phosphate；Citrate, oxalates, acetate, formic acid Salt, propionate, benzoate, trifluoroacetate, maleate, tartrate, mesylate, benzene sulfonate, p-methyl benzenesulfonic acid The acylates such as salt；The inorganic base salts such as sodium salt, sylvite, calcium salt, magnesium salts, ammonium salt；Triethyl ammonium salt, tri ethanol ammonium salt, pyridiniujm, Organic alkali salt such as diisopropyl ammonium salt；The amino-acid salts such as arginine salt, aspartate, glutamate.
Lactam compound, preferably 2-pyrrolidone-5-carboxylic acid, 6- oxo -2-piperidinecarboxylic acid, 3- (2- oxo -1- azacyclo- Heptane base) propionic acid, more preferably 2-pyrrolidone-5-carboxylic acid or its salt.
Lactam compound and its salt can be synthesized according to well known scheme.Lactam compound and its salt can also make Use commercially available product.
As the commercially available product of the lactam compound (for example, 2-pyrrolidone-5-carboxylic acid) with gamma-lactam skeleton, for example, " AJIDEW A-100 (registered trademark) " sold by Ajincomoto Co., Inc can be enumerated.
As the commercially available product with δ-lactams skeleton lactam compound (for example, 6- oxo -2-piperidinecarboxylic acid), example Such as, it can enumerate by Sigma-Aldrich Amada Co., Ltd. (Japanese: シ グ マ ア Le De リ ッ チ ジ ャ パ Application Co., Ltd.) " (S) -6- oxo -2-piperidinecarboxylic acid (English: (S) -6-Oxo-2-piperidine carboxylic acid) (quotient of sale The name of an article) ".
As with ε-lactams skeleton lactam compound (for example, 3- (2- oxo -1- nitrogen heterocyclic heptyl) third Acid) commercially available product, for example, " 3- (the 2- oxo-azepine cycloheptyl sold by Sigma-Aldrich Amada Co., Ltd. can be enumerated Alkane -1- base) propionic acid (English: 3- (2-Oxoazepan-1-yl) propanoic acid) (trade name) ".
Composition can be independent one kind as the type of the lactam compound of (A) ingredient in the present invention, can also be with It is two or more combinations.
[(1-B) ingredient]
It is fluorine compounds in (1-B) ingredient of the invention.As fluorine compounds, for example, can enumerate sodium fluoride, potassium fluoride, Ammonium fluoride, tin fluoride, amine fluoride, sodium monofluorophosphate, single fluorophosphoric acid potassium, prodan and calcium fluosilicate.Fluorination preferably is closed Object is sodium fluoride and sodium monofluorophosphate.
Commercially available product also can be used in fluorine compounds.As the example of sodium fluoride commercially available product, can enumerate by Stella " sodium fluoride " of Chemifa company (Japanese: ス テ ラ ケ ミ Off ァ society) sale.It, can as the example of sodium monofluorophosphate commercially available product To enumerate " sodium monofluorophosphate " of Rhodia solar corona company (Japanese: ロ ー デ ィ ア solar corona society) sale.
[(1-C) ingredient]
(1-C) ingredient is the protein containing 1.0~6.0 mass % sulfur-containing amino acid residues in the present invention.
Sulfur-containing amino acid residue refers to from the meaning for removing residue obtained from more than one hydrogen in sulfur-containing amino acid.Sulfur-bearing Amino acid refers to the amino acid containing sulphur, for example, methionine, cysteine can be enumerated.
(1-C) ingredient, preferably comprises phosphate group.
In (1-C) ingredient, the number-average molecular weight of preferred protein is 1000~100,000, further preferably 10,000~10 Ten thousand.Number-average molecular weight can keep the compatibility with dentine, be not easy to be washed out by saliva, can sufficiently send out by being 1000 or more Wave dentine dental caries inhibitory effect.It on the other hand, is 100,000 by number-average molecular weight hereinafter, being able to maintain the adsorptivity to tooth, Dentine dental caries inhibitory effect can fully be obtained.
In (1-C) ingredient, the measuring method of the number-average molecular weight of protein is as follows.
The example of calculation method as number-average molecular weight, generally, can enumerate using gel filtration chromatography (GPC) to The method of calculating, and the method for the calculating according to the calculating for analyzing values of nitrogen might.The meter of the number-average molecular weight of protein, polypeptide compound It calculates, mostly uses the latter's method.The number-average molecular weight of the protein of (1-C) ingredient can also be measured with the method for the latter.
The number-average molecular weight of (1-C) ingredient, for example, can in molecule nitrogen pool, amino nitrogen amount, constituted amino acid Average molecular weight based on, pass through following formula (1-1) calculate.
[number 1]
Formula (1-1):
In formula (1), the average molecular weight of amino acid is constituted, is the composition amino acquired by common amino acid analysis Acid there are ratio (%) multiplied by each amino acid molecular weight calculating.Nitrogen pool can be tested by cosmetic material Standard General The first method of azotometry or gas chromatography (GC) of method measure.Amino nitrogen amount can be measured by formol titration.
As the protein of average molecular weight 1000~100,000 containing 1.0~6.0 mass % sulfur-containing amino acid residues, example Such as, lactoferrin, collagen decomposition product, casein can be enumerated.
Lactoferrin is the glycoprotein of the iron associativity of molecular weight widely distributed in animal body about 80,000.Newborn iron egg White source, autofrettage do not limit.For example, the colostrum of the mammality that can illustrate (such as people, ox, sheep, goat, horse etc.), mistake It crosses newborn, normal cream, late cream etc. or passes through usual method (for example, ion from the processed material (for example, skimmed milk, whey etc.) of these creams Exchange chromatography etc.) separation lactoferrin.Also the lactoferrin using the preparation of disclosed method can be used.As newborn iron egg It is white that it is preferable to use use the lactoferrin from ox.
Commercially available product also can be used as lactoferrin.As the example of the commercially available product from milk iron protein, can enumerate By " lactoferrin (Japanese: ラ Network ト Off ェ リ Application) (come from milk) (trade name) " of Wako Pure Chemical Industries, Ltd.'s sale, " MLF-1 " " MLF-EX " by MORINAGA MILK INDUSTRY Co., LTD.'s sale and the " lactoferrin by Nippon Shinyaku Co., Ltd.'s sale (Japanese: ラ Network ト Off ェ リ Application) ".As (1-C) ingredient, a kind of lactoferrin also can be used, it can also be by source or separation The different two or more lactoferrin compositions of condition use.
As the example of collagen decomposition product, it can enumerate and be manufactured by the collagen decomposition product of pigskin manufacture, by fish scale Collagen decomposition product, wherein the preferably collagen decomposition product that is manufactured by fish scale.In (1-B) ingredient, collagen Decomposition product can be one kind, be also possible to the combination of the different two or more collagen decomposition products of raw material.As collagen egg Commercially available product also can be used in white decomposition product.The example of commercially available product as the collagen decomposition product manufactured by fish scale can be enumerated It is decomposed by the collagen of the trade name " HACP-U2 " of JELLICE Co., Ltd. (Japanese: ゼ イ ラ ス Co., Ltd.) sale Object.
Casein contains in the dairy products such as milk, cheese, accounts for about 80 mass % of the lactoprotein contained in milk.Junket Albumen is the protein containing phosphate group, i.e. one kind of phosphoprotein (phosphorylating protein).Many phosphoric acid are integrated to composition On the serine residue of casein.In (1-B) ingredient, collagen decomposition product is also possible to one kind, is also possible to raw material not Same two or more collagen decomposition products combinations.Commercially available product also can be used as casein.As the junket from milk The example of albumen commercially available product can enumerate the trade name " casein (from milk) " by Wako Pure Chemical Industries, Ltd.'s sale.
The content of the sulfur-containing amino acid residue of protein is in (1-C) ingredient, every 1.0~6.0 matter of protein quality Measure %.By making 1.0% or more the content of sulfur-containing amino acid residue, the compatibility with dentine is improved, can sufficiently be obtained Dentine dental caries inhibitory effect.On the other hand, by making the content 6% of the sulfur-containing amino acid residue hereinafter, (1-C) ingredient exists The situation for just hindering fluffy degree higher without more generating stereochemical structure between other compositions, and can effectively prevent to dentine The reduction of the adsorptivity of (1-C) ingredient or other compositions can fully obtain dentine dental caries inhibitory effect.
[(2-B) ingredient]
(2-B) ingredient is the one kind selected from the group that longan nuclear extract, proanthocyanidin, catechin and aurantiamarin form Above polyphenolic substance.
Longan (Euphoria longana) is the plant for the Sapindaceae cultivated in tropical America and Southeast Asia.Longan Pulp is reused always as the Chinese medicine for the purpose of strong and is calm.Longan is also referred to as Longan (Japanese: ロ Application ガ Application).
Longan nuclear extract is the extract extracted from the core of longan.Containing polyphenol, (Japan is specially in longan nuclear extract Sharp special open 2003-327596 bulletin, The effect of Longan seed polyphenols on colorectal Carcinoma cells.Eur J Clin Invest. (2010,40 (8), p713-721), Identification and quantification of polyphenolic compounds in Longan(Euphoria longana Lam.) Fruit.J Agric Food Chem. (2005,53 (5), p1387-1392)).
The method extracted in the slave longan seed of longan nuclear extract is not particularly limited.It, can as the example of extracting method Longan seed is crushed by citing, with the method for well known extracting method, that is, solvent extraction.As solvent, water, one usually can be used First alcohol, polyalcohol, their mixture etc., as the example of solvent, can illustrate the rudimentary unitary such as water, methanol, ethyl alcohol, isopropanol The polyalcohols such as alcohol, ethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, 1,3-BDO.They can independent one kind or two Kind combination of the above uses.
As longan nuclear extract, solvent extractable matter can be directly used, also can be used and concentration is distilled off in solvent Obtained concentrate.Also it can be used and solvent extractable matter or concentrate removed into solvent by dry (such as: freeze-drying etc.) Obtained powder.Furthermore, it is also possible to which excipient etc. is added.Also the powder such as the freeze-drying product for making solvent extractable matter can be used again It is dissolved in solvent and adjusts the solution for arriving suitable concentration.Furthermore yield when extracting longan nuclear extract is not particularly limited.
As longan nuclear extract, commercially available product can be used.As commercially available product, for example, Chikkarin public affairs in piece storehouse can be enumerated The AGETECT (Japanese: エ イ ジ テ Network ト) of department's (Japanese: piece storehouse チ ッ カ リ Application society) manufacture, the longan seed of same company manufacture mention Take object powder SD etc..AGETECT is the freeze-drying object after extracting, being concentrated from longan seed crushed material, is dissolved with 1.0% concentration (the longan seed extract concentrations in AGETECT are the extract for the solution shape being prepared in 1,3-BDO and water 1.0%).Longan nuclear extract powder SD is similarly extracted, in the powder that freeze-drying obtains with above-mentioned, and addition is used as figuration The dextrin (Japanese: デ キ ス ト リ Application) of agent, being prepared into powdered extract, (longan seed in longan nuclear extract powder SD extracts 83%) object concentration is.
Proanthocyanidin is that have one kind whatever amount the polyphenol for the structure that the skeleton of theine combines.The source of proanthocyanidin does not have It is particularly limited to, may come from plant (for example, fruit class, wheat, beans etc.), be also possible to artificial composite.Wherein, excellent It is selected as the proanthocyanidin from plant, preferably from the proanthocyanidin of grape pip.Because rich in grape pip Proanthocyanidin.
In the case where being the proanthocyanidin from grape pip, then the method that proanthocyanidin is extracted from grape pip is not special Limitation.As extracting method, grape pip is crushed for example, can enumerate, with the method for well known extracting method, that is, solvent extraction.Make For solvent, can usually illustrate water, monohydric alcohol, polyalcohol or their mixture, for example, water, methanol, ethyl alcohol, isopropyl can be enumerated Polyalcohols such as the low-grade monobasic alcohols such as alcohol, ethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, 1,3-BDO etc..These solvents Can be individually a kind of, or be used in combination.
As proanthocyanidin, solvent extractable matter can be directly used, also can be used and solvent is distilled off, is concentrated to get Concentrate.It can be used by obtaining solvent extractable matter or concentrate dry (such as: freeze-drying etc.) to remove solvent The powder arrived, furthermore, it is also possible to which excipient etc. is added.Then, also can be used is re-dissolved in the powder of freeze-drying product etc. The solution of suitable concentration is adjusted in solvent.Furthermore yield when extracting proanthocyanidin is not particularly limited.
As proanthocyanidin, commercially available product can be used.It is, for example, possible to use Kikkoman company (Japanese: キ ッ コ ー マ Application Society) manufacture Gravinol-SL (Japanese: グ ラ ヴ ィ ノ ー Le-SL), same company manufacture Gravinol-N (Japanese: グ ラ ヴ ィ ノ ー Le-N) etc..Gravinol-SL is the Hydrolysis kinetics object of grape pip, is the dark brown of proanthocyanidin for main component The powder of color (the proanthocyanidin concentration in Gravinol-SL is 82%).Gravinol-N is similarly the extraction essence of grape pip Object processed is the powder of weak tea brown (the proanthocyanidin concentration in Gravinol-N is 38%).
Catechin is one kind (C of flavones15H14O6) and its derivative general name.As the example of catechin, can enumerate Theine, epicatechin, nutgall catechin, epigallocatechin, L-Epicatechin gallate, nutgall catechin are not eaten Sub- acid esters, Epigallo-catechin gallate (EGCG) etc..The catechin in (2-B) ingredient, can be one of they, or It can be two or more.The source of catechin is not particularly limited, and can be from plant (for example, tea etc.), is also possible to Synthetic artifact.Wherein, preferably from the catechin of plant, more preferably from the catechin of tea, further preferably For from the catechin of tealeaves.Because of catechin rich in tealeaves.
In the case where being the catechin from tealeaves, then it is not particularly limited from the extracting method of the catechin of tealeaves.Example Such as, it can be used and be crushed tealeaves, with well known extracting method using solvent extraction to the substance of preparation.As solvent, lead to Water, monohydric alcohol, polyalcohol or these mixtures can be often enumerated, for example, water, methanol, ethyl alcohol, isopropanol etc. rudimentary one can be enumerated Polyalcohols such as first alcohol, ethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, 1,3-BDO etc., they can be individually a kind of, or Person can be used in combination.
As catechin, solvent extractable matter can be directly used, also can be used and solvent is distilled off, is concentrated to get Concentrate.It can be used by obtaining solvent extractable matter or concentrate dry (such as: freeze-drying etc.) to remove solvent Powder, furthermore, it is also possible to which excipient etc. is added.Then, it also can be used that be re-dissolved in the powder of freeze-drying product etc. molten The solution of suitable concentration is adjusted in agent.Furthermore yield when extracting catechin is not particularly limited.
As catechin, commercially available product can be used.It is, for example, possible to use the Sunphenon (days of sun chemistry society manufacture Language: サ Application Off ェ ノ Application) EGCG, Sunphenon 90S etc..Sunphenon EGCG is the extraction product of green tea, be containing The white of the Epigallo-catechin gallate (EGCG) of high-purity~ash gray powder (do not eat by the table in Sunphenon EGCG 95%) sub- catechin and gallate concentration is.Sunphenon 90S is also the Hydrolysis kinetics object of green tea, is faint yellow~red The powder of brown (catechin concentration in Sunphenon 90S is (total concentration of various catechins) 70%).
Aurantiamarin is also known as the polyphenol of citrin.The source of aurantiamarin is not particularly limited, and can be from plant Object (for example, the citrus such as satsuma orange and eight north mandarin oranges), is also possible to Synthetic artifact.Wherein, preferably from plant Aurantiamarin, the aurantiamarin preferably from the aurantiamarin of citrus, more preferably from the pericarp of citrus.Because of mandarin orange Aurantiamarin rich in the pericarp of tangerine class.
If it is the aurantiamarin from pericarp, then it is not particularly limited from the method that pericarp extracts aurantiamarin.For example, can be with Using by peel crushing, pass through the substance prepared with well known extracting method solvent extraction.Solvent can usually enumerate water, unitary Alcohol, polyalcohol or their mixture, for example, the low-grade monobasic alcohols such as water, methanol, ethyl alcohol, isopropanol can be enumerated, ethylene glycol, gathered Polyalcohols such as ethylene glycol, propylene glycol, polypropylene glycol, 1,3-BDO etc., they can individually one kind or two or more combinations It uses.
As aurantiamarin, although the solvent extractable matter of solution shape can be used directly, it also can be used and remove solvent distillation Remove, be concentrated to the concentrate of suitable concentration.Also it can be used these by being obtained with the drying such as freeze-drying, removing solvent Powdered object, and directly can use or be added excipient etc. and use.Also the powder for making freeze-drying product etc. can be used End is re-dissolved in the solution that suitable concentration is adjusted in solvent.Furthermore yield when extracting aurantiamarin is not particularly limited.
As aurantiamarin, commercially available product can be used.It is, for example, possible to use the orange peels of Wako Pure Chemical Industries, Ltd.'s manufacture Glycosides, hesperidin methyl of Tokyo chemical conversion industry manufacture etc..Aurantiamarin is from the substance of pericarp crushed material Hydrolysis kinetics, is yellow Powder (aurantiamarin concentration is 92%).Hesperidin methyl is after aurantiamarin dimethyl sulfate methylates and keeps its water-soluble Substance, be faint yellow~orange powder (hesperidin methyl concentration be 90%).
(2-B) ingredient can be used more than one longan nuclear extract, more than one proanthocyanidin, more than one Catechin or more than one aurantiamarin or their multiple suitable combinations.As (2-B) ingredient, it is preferable to use Longan nuclear extract and/or proanthocyanidin further preferably use longan nuclear extract.
[(3-B) ingredient]
(3-B) ingredient is aluctyl in the present invention.
Commercially available product can be used as (3-B) ingredient.For example, the commercially available product as aluctyl, can enumerate and the pure medicine strain of light The trade name " aluctyl " of formula commercial firm manufacture.
In the case that aluctyl uses in the oral cavity, although there is the case where feeling astringent taste and/or metallic taste, because (A) ingredient is mixed simultaneously with (3-B) ingredient in composition for oral cavity (3), then can prevent the generation of astringent taste and metallic taste, can reach To the improvement of use feeling (taste).
[(3-C) ingredient]
(3-C) ingredient is mono-fluor phosphate.
It is that single fluorophosphoric acid ion, preferably water-soluble mono-fluor phosphate can be provided as mono-fluor phosphate.As Mono-fluor phosphate, the alkali metal salt for single fluorophosphoric acid that can illustrate, the alkali earth metal salt of single fluorophosphoric acid, ammonium salt of single fluorophosphoric acid etc., Wherein, preferably sodium monofluorophosphate, single fluorophosphoric acid potassium, single fluorophosphoric acid ammonium etc., more preferably sodium monofluorophosphate.
Commercially available product can be used as (3-C) ingredient.For example, the commercially available product as mono-fluor phosphate, can enumerate Rhodia " sodium monofluorophosphate " of solar corona company sale.
(3-C) ingredient can be a kind of mono-fluor phosphate, be also possible to the combination of two or more mono-fluor phosphates.
The mono-fluor phosphate of (3-C) ingredient, the fluorine in ingredient undertake main function.Composition for oral cavity contains in (3) Total amount of the total fluoro quantity relative to composition for oral cavity (3), preferably 0.01 mass % (100ppm) or more, more preferably 0.02 Quality % (200ppm) or more.The upper limit is preferably 1 mass % (10000ppm) hereinafter, more preferably 0.5 mass % (5000ppm) Below.The fluorine amount contained in composition for oral cavity (3) of the invention, preferably 0.01~1 mass % (100~10000ppm), More preferably 0.02~0.5 mass % (200~5000ppm).
[(3-D) ingredient and (4-B) ingredient]
(3-D) ingredient and (4-B) ingredient are water-soluble inorganic sylvite.
In the present invention, " water-soluble inorganic sylvite " refers to the inorganic potassium salt that 2g or more can be dissolved in 20 DEG C of water 100g.
As water-soluble inorganic sylvite, for example, can enumerate potassium nitrate, potassium chloride, potassium dihydrogen phosphate, potassium sulfate, potassium carbonate, With saleratus, alum etc..Wherein, effect and use feeling (taste) are significantly reduced to because of pain caused by hyperesthesia From the viewpoint of, preferably potassium nitrate, potassium chloride.These water-soluble inorganic sylvite can be used commercially available reagent (can from the pure medicine of light The suppliers such as Co., Ltd. obtain).
(3-D) ingredient and (4-B) ingredient may each be independent one kind, be also possible to two or more combinations.
There are the following problems for (4-B) ingredient: it is limited to the mitigation effect because of pain caused by hyperesthesia, bitter taste is had, And use feeling (taste) is bad.In (4-B) ingredient, although potassium nitrate to because pain relief caused by hyperesthesia have it is certain Effect, but bitter taste is strong, and use feeling (taste) is poor.In composition for oral cavity (4), used and with (4-B) at subassembly (A) ingredient, thus significantly improve (4-B) ingredient to because of hyperesthesia caused by pain mitigation effect while, inhibit It is derived from the bitter taste of (4-B) ingredient, the case where even with potassium nitrate, also can get good use feeling (taste).
[(4-C) ingredient]
In the present invention, (4-C) ingredient is aqueous fluorochemical dispersion." aqueous fluorochemical dispersion " refers to the water 100g at 20 DEG C The middle fluorine compounds that can dissolve 2g or more.
Aqueous fluorochemical dispersion is a kind of supply source as the fluoride ion for having remineralization effect dentulous etc., is From previous just for the known ingredient in composition for oral cavity, but the inventors discovered that, such soluble fluoride can be into one Step improves the effect (i.e. (B) ingredient significantly improving to the mitigation effect because of pain caused by hyperesthesia) of above-mentioned (A) ingredient.
It is suitble to the aqueous fluorochemical dispersion used as (4-C) ingredient, for example, sodium fluoride, potassium fluoride, fluorination can be enumerated Ammonium, tin fluoride, amine fluoride, sodium monofluorophosphate, single fluorophosphoric acid potassium, prodan and calcium fluosilicate.Wherein, from raising (A) ingredient From the perspective of effect, as aqueous fluorochemical dispersion preferred fluorinated sodium, sodium monofluorophosphate.These aqueous fluorochemical dispersions can make With commercially available reagent (for example, being obtained from suppliers such as Stella Chemifa company, Rhodia solar corona companies).
[(5-B) ingredient]
(5-B) ingredient is cationic cellulose.
As cationic cellulose, for example, the cellulose derivative etc. of cation group addition can be enumerated.As cation Group, for example, dimethyldiallylammonium (Japanese: ジ メ チ Le ジ ア リ Le ア Application モ ニ ウ system), 2- hydroxyl -3 can be enumerated (dimethylamino) propyl (Japanese: 2- ヒ De ロ キ シ -3 (ト リ メ チ Le ア Application モ ニ オ) プ ロ ピ Le) etc..As sun from The cellulose derivative of subbase group addition can enumerate hydroxyethyl cellulose dimethyl diallyl ammonium chloride, chlorination O- [2- hydroxyl Base -3- (dimethylamino) propyl] hydroxyethyl cellulose, their derivative etc..The preferred nitrogen content of cationic cellulose be 0.1~ The substance of 3 mass %.
(5-B) ingredient can be one kind, be also possible to two or more combinations.
As (5-B) ingredient, the color spot due to hydroxyethyl cellulose dimethyl diallyl ammonium chloride in tooth forms suppression Effect processed, the aspect of luster effect are excellent, thus are suitble to use.
[(6-B) ingredient]
(6-B) ingredient is polyphenolic substance.As polyphenolic substance, flavones, phenyl carboxylic acid, chlorogenic acid, the wooden phenol can be enumerated Each example of element, curcumin and above-mentioned (2-B) ingredient.
[composition or preparation of the invention]
Composition or preparation of the invention contains the lactam compound and/or its salt as (A) ingredient.Contain lactams Compound and/or its salt are as effective component.
(A) component content in composition or preparation of the invention is not particularly limited.
In the case that the effective component of composition of the invention is individually for (A) ingredient, then the content of (A) ingredient is relative to group Close object total amount, preferably 0.3 mass % or more, more preferably 0.5 mass % or more.It can be sufficiently obtained as a result, due to mixing Lactam compound and the effect obtained.(A) ingredient is with gamma-lactam skeleton and/or ε-lactams skeleton lactams In the case where compound, combined amount is more preferably 1 mass % or more.
If the effective component of composition of the invention is individually for (A) ingredient, the combined amount of (A) ingredient is relative to group The total amount of object is closed, preferably 10 mass % are hereinafter, more preferably 5 mass % or less.Because even a large amount of mixing, propose each effect High contribution is limited.
Total amount of the combined amount of (A) ingredient relative to composition in preparation of the invention, preferably 0.3~10 mass %, More preferably 0.5~5 mass %.
Preferred embodiment when being below composition for oral cavity to composition of the invention is illustrated.
[composition for oral cavity (1)]
Composition for oral cavity of the invention can contain (A) ingredient and (1-B) ingredient.(A) ingredient and (B-1) will be contained below The composition for oral cavity of ingredient is known as composition for oral cavity (1).
[content of (A) ingredient in composition for oral cavity (1)]
The content of (A) ingredient is not particularly limited in composition for oral cavity (1), but relative to composition for oral cavity (1) Total amount, preferably 0.1 mass % or more, more preferably 0.5 mass % or more, further preferably 1 mass % or more.(A) at If the content divided is more than 0.1 mass %, so that it may sufficiently obtain dentine dental caries inhibitory effect.
The upper limit of the content of (A) ingredient is preferably 10 mass % hereinafter, more preferably 5 matter in composition for oral cavity (1) Measure % or less.The gelatinization performance that can keep the tackifier in composition for oral cavity (1) as a result, can prevent through when caused by (A) precipitation of ingredient keeps good preparation stability.So as to keep dentine dental caries inhibitory effect.
(A) content of ingredient is preferably 0.1~10 mass % of composition for oral cavity (1) total amount, and more preferably 0.5~5 Quality %.(A) in the case that ingredient has δ-lactams skeleton and/or ε-lactams skeleton lactam compound, then (A) at The content divided is more preferably 1~5 mass %.
[content of (1-B) ingredient in composition for oral cavity (1)]
In composition for oral cavity (1) of the invention, as (1-B) ingredient of fluoride ion supply source and (A) in oral cavity Acting through addition, combining with being multiplied for both ingredients, has played in the past no excellent dentine dental caries preventive effect.
It, will since the effect of (1-B) ingredient used in the present invention is undertaken by the fluorine in (1-B) ingredient It is useful that the combined amount of (1-B) ingredient, which is scaled the fluorine content in composition for oral cavity (1) and carries out defined method,.So In following explanation, the content of (1-B) ingredient is replaced with the fluorine content in composition for oral cavity (1) in composition for oral cavity (1) To indicate.
The content of (1-B) ingredient is scaled in composition for oral cavity (1) contains relative to the fluorine of composition for oral cavity (1) total amount Amount, preferably 0.01 mass % (100ppm) or more, more preferably 0.02 mass % (200ppm) or more.It can be filled as a result, The dentine dental caries inhibitory effect divided.
On the other hand, the upper limit of the content of (1-B) ingredient is scaled relative to oral composition in composition for oral cavity (1) The fluorine content of object (1) total amount, preferably 1 mass % (10000ppm) hereinafter, more preferably 0.5 mass % (5000ppm) below. By making fluorine amount in 1 mass % (10000ppm) hereinafter, being able to maintain preparation stability.As keep preparation stability example, The example for preventing the gelatinization performance of tackifier in composition for oral cavity (1) from reducing can be enumerated.As other examples, if oral cavity With composition (1) be liquid preparation when, then can enumerate prevent precipitating occur example.
The content of (1-B) ingredient is scaled total relative to composition for oral cavity (1) in composition for oral cavity (1) of the invention The fluorine content of amount, preferably 0.01~1 mass % (100~10000ppm), more preferably 0.02~0.5 mass % (200~ 5000ppm)。
[(A) ingredient/(1-B) ingredient in composition for oral cavity (1)]
In the present invention, there is preferred range in the mixing ratio of (A) ingredient and (1-B) ingredient.In composition for oral cavity (1) (A) ingredient is relative to the mass ratio of (1-B) ingredient mass ratio " (A) ingredient/fluorine content " table of (A) ingredient relative to fluorine content Show." (A) ingredient/fluorine content " is preferably 1 or more, and more preferably 2 or more.As a result, due to relative to (A) ingredient fluoride ion Amount appropriateness, therefore prevent the precipitation of the fluoride ion in dentin surface, and sufficient dentine dental caries suppression can be obtained Effect processed.
(A) ingredient is preferably 250 hereinafter, more excellent relative to the upper limit of the mass ratio of fluorine content in composition for oral cavity (1) It is selected as 100 or less.As a result, due to fluoride ion relative to (A) ingredient amount appropriateness range, significant tooth sheet can be obtained Matter dental caries inhibitory effect.
(A) ingredient is preferably 1~250 relative to the mass ratio of fluorine content in composition for oral cavity (1), more preferably 2~ 100。
Composition for oral cavity (1) of the invention can further contain (1-C) ingredient.As a result, since mouth can be further increased The dentine dental caries preventive effect of chamber composition (1), thus preferably.
[content of (1-C) ingredient in composition for oral cavity (1)]
In the case that composition for oral cavity (1) contains (1-C) ingredient, then the content of (1-C) ingredient is not particularly limited, but It is preferably 0.1~10 mass %, further preferably 0.1~5 mass % relative to the total amount of composition for oral cavity (1).It is logical Crossing makes content more than 0.1 mass %, can sufficiently obtain dentine dental caries inhibitory effect.On the other hand, by 10 mass % Hereinafter, can prevent from changing colour, the use feeling for preventing the generation due to the basic strange smell from (1-C) ingredient and causing declines.
[(1-C) ingredient/(1-B) ingredient in composition for oral cavity (1)]
In the case that composition for oral cavity (1) contains (1-C) ingredient, then the mass ratio of (1-C) ingredient and (1-B) ingredient can Mass ratio with (1-C) ingredient relative to the fluorine content in composition for oral cavity (1), the i.e. quality/fluorine content of (1-C) ingredient come It indicates.
(1-C) ingredient relative to fluorine amount in composition for oral cavity (1) mass ratio [(1-C) ingredient/fluorine content] preferably 0.3~800, more preferably 0.5~80.By making mass ratio 0.3 or more, due to relative to (1-C) ingredient, fluoride ion Amount appropriateness, therefore the precipitation of fluoride ion in dentin surface can be prevented, sufficient dentine dental caries can be obtained and inhibit effect Fruit.On the other hand, by mass ratio 800 hereinafter, due to fluoride ion relative to (1-C) ingredient amount appropriateness model It encloses, therefore synergy can be obtained to dentine dental caries inhibitory effect.
[composition for oral cavity (2)]
Composition for oral cavity of the invention can also contain (A) ingredient and (2-B) ingredient.(A) ingredient and (B- will be contained below 2) composition for oral cavity of ingredient is referred to as composition for oral cavity (2).
[content of (A) ingredient in composition for oral cavity (2)]
The content of (A) ingredient is not particularly limited in composition for oral cavity (2), but relative to oral composition of the invention The total amount of object (2) is preferably 0.5% or more, and more preferably 1% or more.Pass through as a result, and with (2-B) ingredient, so that it may sufficiently hair Dentin collagen albumen coloring inhibitory effect after waving the dentin collagen protein breakdown inhibitory effect after saving and saving.Oral cavity The upper limit with (A) component content in composition (2) is preferably 10% hereinafter, more preferably 5% or less.It can give full play to as a result, Preparation stability, so that the dentin collagen protein breakdown inhibitory effect after saving can also be given full play to.(A) content of ingredient is excellent It is selected as 0.5~10%, more preferably 1~5%.
[content of (2-B) ingredient in composition for oral cavity (2)]
The content of (2-B) ingredient is not particularly limited in composition for oral cavity (2), but relative to composition for oral cavity (2) Total amount, preferably 0.001% or more, more preferably 0.01% or more.By making content 0.001% or more, and with (A) at Point, the dentin collagen protein breakdown after can giving full play to dentin collagen protein breakdown inhibitory effect simultaneously and saving inhibits effect Fruit.The upper limit of (2-B) component content is preferably 0.5% hereinafter, more preferably 0.2% or less.It can give full play to preservation as a result, The coloring inhibitory effect and preparation stability of dentin collagen albumen afterwards.The content of (2-B) ingredient is preferably 0.001~ 0.5%, more preferably 0.01~0.2%.
[(A) ingredient/(2-B) ingredient in composition for oral cavity (2)]
In composition for oral cavity (2), (A) ingredient does not limit especially relative to the mass ratio ((A)/(2-B)) of (2-B) ingredient It is fixed, but usually 5 or more, preferably 10 or more.The dentin collagen albumen coloring after saving can be given full play to as a result, inhibits effect Fruit and preparation stability.(A) ingredient relative to the mass ratio of (2-B) ingredient the upper limit usually 3000 hereinafter, preferably 300 with Under.Dentin collagen protein breakdown inhibitory effect can also be given full play to after being saved as a result,.In composition for oral cavity (2) (A) at Split-phase is preferably 5~3000 for the mass ratio ((A)/(2-B)) of (2-B) ingredient, and more preferably 10~300.
[composition for oral cavity (3)]
Composition for oral cavity of the invention can also contain (A) ingredient and (3-B) ingredient.(A) ingredient and (3- will be contained below B) composition for oral cavity of ingredient is known as composition for oral cavity (3).
[content of (A) ingredient in composition for oral cavity (3)]
The content of (A) ingredient is not particularly limited in composition for oral cavity (3), but relative to oral composition of the invention The total amount of object (3) is preferably 0.1 mass % or more, more preferably 0.5 mass % or more.It is small that dentine can sufficiently be obtained as a result, Pipe early stage sealing effect and pain relief effect.(A) ingredient is with gamma-lactam skeleton and with the compound of acidic-group And/or with ε-lactams skeleton and with acidic-group compound in the case where, then further preferably 1 mass % with On.(A) upper limit of the content of ingredient is preferably 10 mass % hereinafter, more preferably 5 mass % or less.Because even more than 10 matter Measure %, it is also possible to cannot get the raising of dentinal tubule early stage sealing effect.
(A) content of ingredient is preferably 0.1~10 mass %, more preferably 0.5~5 mass %.(A) ingredient be with Gamma-lactam skeleton and compound with acidic-group and/or with ε-lactams skeleton and with the chemical combination of acidic-group In the case where object, then the content of (A) ingredient is more preferably 1~5 mass %.
[content of (3-B) ingredient in composition for oral cavity (3)]
The content of (3-B) ingredient is not particularly limited in composition for oral cavity (3), but relative to oral cavity group of the invention Close the total amount of object (3), preferably 0.01 mass % or more, more preferably 0.1 mass % or more.Tooth can be sufficiently obtained as a result, Tubules early stage sealing effect and pain relief effect.The upper limit of (3-B) component content is preferably 10 mass % or less.It is more excellent It is selected as 5 mass % or less.It can keep well as a result, use feeling (taste), prevent the generation of astringent taste and metallic taste.(3-B) The content of ingredient is preferably 0.01~10 mass %, more preferably 0.1~5 mass %.
[(A) ingredient/(3-B) ingredient in composition for oral cavity (3)]
In composition for oral cavity (3), (A) ingredient is preferably 0.1 relative to the mass ratio [(A)/(3-B)] of (3-B) ingredient More than, more preferably 0.5 or more.The improvement of use feeling (taste) can be more given full play to as a result,.The upper limit is preferably 500 Hereinafter, more preferably 45 or less.The dentinal tubule sealing effect that (3-B) ingredient can be given full play to as a result, plays in which can dramatically (A) synergy of ingredient and (3-B) ingredient.(A) ingredient is preferably 0.1~500 relative to the mass ratio of (3-B) ingredient, more Preferably 0.5~45.
[content of (3-C) ingredient in composition for oral cavity (3)]
Composition for oral cavity (3) can also further contain (3-C) ingredient.
In the case that composition for oral cavity (3) contains (3-C) ingredient, then (C) ingredient contains in composition for oral cavity (3) Amount, i.e. total fluorine content fluorine amount contained in composition for oral cavity of the invention contained in composition for oral cavity (3), preferably 0.01~1 mass % (100~10000ppm), more preferably 0.02~0.5 mass % (200~5000ppm).
The content of (3-C) ingredient in composition for oral cavity (3), when if it is sodium monofluorophosphate, then preferably 0.076 matter Measure % or more, more preferably 0.15 mass % or more.Dentinal tubule early stage sealing effect and pain can be sufficiently obtained as a result, Mitigate effect.The upper limit of (3-C) component content in composition for oral cavity (3) is preferably 7.6 mass % hereinafter, more preferably 3.8 mass % or less.It can keep well as a result, use feeling (taste).The content of (3-C) ingredient is preferably 0.076~7.6 matter Measure %, more preferably 0.15~3.8 mass %.
[content of (3-D) ingredient in composition for oral cavity (3)]
Composition for oral cavity (3) can further contain (3-D) ingredient.
The content of (3-D) ingredient is not particularly limited in composition for oral cavity (3), but relative to oral cavity group of the invention The total amount for closing object (3) is preferably 0.005 mass % or more, more preferably 0.1 mass % or more.Pain can be sufficiently obtained as a result, Mitigate effect.The upper limit is preferably 10 mass %, more preferably 7 mass %.It can keep well as a result, use feeling (taste).(3- D) content of ingredient is preferably 0.005~10 mass %, more preferably 0.1~7 mass %.
[composition for oral cavity (4)]
Composition of the invention can contain (A) ingredient and (4-B) ingredient.(A) ingredient and (4-B) ingredient will be contained below Composition for oral cavity is referred to as composition for oral cavity (4).
[content of (A) ingredient in composition for oral cavity (4)]
The content of (A) ingredient in composition for oral cavity (4), to the effect significantly mitigated because of pain caused by hyperesthesia From the perspective of the improvement of fruit and use feeling (taste), preferably 0.1 mass % or more, more preferably 0.5 mass % with On.As (A) ingredient, δ-lactam compound with acidic-group, ε-lactam compound with acidic-group are used Or in the case where their salt, then in composition for oral cavity (A) ingredient content, shown to because of pain caused by hyperesthesia From the perspective of writing the effect mitigated, particularly preferably 1 mass % or more.
The upper limit of the content of (A) ingredient is not particularly limited in composition for oral cavity (4), even if but due to volume, to mentioning Height is limited because of the contribution for the effect of pain caused by hyperesthesia significantly mitigated, thus preferably generally 10 mass % with Under, more preferably 5 mass % or less.
In one embodiment, the content of (A) ingredient is relative to composition for oral cavity (4) in composition for oral cavity (4) Total amount is preferably 0.1~10 mass %, more preferably 0.5~5 mass %.The δ-with acidic-group is used as (A) ingredient In the case where lactam compound or ε-lactam compound with acidic-group, then (A) ingredient in composition for oral cavity Content is particularly preferably 1~5 mass %.
[content of (4-B) ingredient in composition for oral cavity (4)]
The content of (4-B) ingredient is to significantly mitigating because of pain caused by hyperesthesia in composition for oral cavity (4) From the perspective of effect, preferably 0.1 mass % or more, more preferably 1.0 mass % or more.
From the viewpoint of use feeling (taste), the content of (4-B) ingredient is preferably 10 matter in composition for oral cavity (4) % is measured hereinafter, more preferably 7 mass % or less.
In one embodiment, the content of (4-B) ingredient is preferably 0.1~10 mass % in composition for oral cavity (4), more Preferably 1.0~7 mass %.
[(A) ingredient/(4-B) ingredient in composition for oral cavity (4)]
In order to be taken into account at a high level simultaneously to the effect significantly mitigated because of pain caused by hyperesthesia and keep using Feel the improvement of (taste), the mass ratio of (A) ingredient and (4-B) ingredient has preferred scope in composition for oral cavity (4).That is, (A) ingredient is preferably 0.02 relative to the mass ratio " (A) ingredient/(4-B) ingredient " of (4-B) ingredient in composition for oral cavity (4) ~80, more preferably 0.1~10, further preferably 0.1~5.
[content of (C) ingredient in composition for oral cavity (4)]
Composition for oral cavity (4) can further contain (4-C) ingredient.
The effect of the aqueous fluorochemical dispersion as used in the present invention is undertaken by the fluorine in (4-C) ingredient, because It is useful that the fluorine content that the content of (4-C) ingredient is scaled in composition for oral cavity (4) is carried out regulation by this.Therefore, below Explanation in, the content of (4-C) ingredient with the fluorine content in composition for oral cavity (4) instead of.
The content of (4-C) ingredient is from the effect for further increasing above-mentioned (A) ingredient in composition for oral cavity (4), further Improve composition for oral cavity (4) to the effect significantly mitigated because of pain caused by hyperesthesia from the perspective of, be scaled The fluorine content of total amount relative to composition for oral cavity (4), preferably 0.01 mass % (100ppm) or more, more preferably 0.02 Quality % (200ppm) or more.
From the viewpoint of use feeling (taste), the content of (4-C) ingredient is in composition for oral cavity of the invention with fluorine amount It indicates, relative to the total amount of composition for oral cavity (4), preferably 1 mass % (10000ppm) is hereinafter, more preferably 0.5 matter Measure % (5000ppm) below.
In one embodiment, the content of (4-C) ingredient is scaled fluorine content in composition for oral cavity of the invention, relatively Total amount in composition for oral cavity (4), preferably 0.01~1 mass % (100~10000ppm), more preferably 0.02~0.5 Quality % (200~5000ppm).
[(4-C) ingredient/(A) ingredient in composition for oral cavity (4)]
In order to further increase the effect of (A) ingredient, further increase composition for oral cavity (4) to because hyperesthesia is led The mass ratio of the effect of the pain of cause significantly mitigated, (A) ingredient and (4-C) ingredient has preferred scope.That is, composition for oral cavity (4) in, (4-C) ingredient relative to the mass ratio " (4-C) ingredient/(A) ingredient " of (A) ingredient be preferably 0.002~5, more preferably For 0.005~0.5 (quality of (C) ingredient is fluorine content scaled value).
[composition for oral cavity (5)]
Composition of the invention can contain (A) ingredient and (5-B) ingredient.(A) ingredient and (5-B) ingredient will be contained below Composition for oral cavity is referred to as composition for oral cavity (5).
[content of (A) ingredient in composition for oral cavity (5)]
The content of (A) ingredient is not particularly limited in composition for oral cavity (5), but relative to oral composition of the invention The total amount of object (5) is preferably 0.1 mass % or more.Color spot removal effect can be sufficiently obtained as a result, and color spot forms inhibitory effect. The content of (A) ingredient is preferably 10 matter relative to the total amount of composition for oral cavity (5) of the invention in composition for oral cavity (5) Measure % or less.As a result, while obtaining good dissolubility and appearance, inadaptable sense can inhibit, improve use feeling.It uses in oral cavity The content of (A) ingredient is preferably 0.1~10 matter relative to the total amount of composition for oral cavity (5) of the invention in composition (5) Measure %, more preferably 0.5~5 mass %.
[content of (5-B) ingredient in composition for oral cavity (5)]
The content of (5-B) ingredient is preferably relative to the total amount of composition for oral cavity (5) in composition for oral cavity (5) 0.005 mass % or more.Color spot can be given full play to as a result, forms inhibitory effect and luster effect.In composition for oral cavity (5) Total amount of the content of (5-B) ingredient relative to composition for oral cavity (5), preferably 0.1 mass % or less.It can inhibit and as a result, From the inadaptable sense of cationic cellulose, good use feeling is kept.The content phase of (5-B) ingredient in composition for oral cavity (5) For the total amount of composition for oral cavity (5) of the invention, preferably 0.005~0.1 mass %, is formed and inhibited from the color spot of tooth The angle of effect and luster effect, more preferably 0.01~0.05 mass %.
[(A) ingredient/(5-B) ingredient in composition for oral cavity (5)]
In composition for oral cavity (5), (A) ingredient and the mass ratio ((A)/(5-B)) of (5-B) ingredient are not particularly limited, But usually 3 or more, preferably 15 or more.(A) mass ratio of ingredient and (5-B) ingredient is usually 600 hereinafter, preferably 300 Below.By making the ratio 3 or more, then it can give full play to color spot and form inhibitory effect and color spot removal effect.By 600 Hereinafter, forming inhibitory effect and luster effect in addition to color spot can be given full play to, good use feeling can be also kept.(A) ingredient with The ratio of (5-B) ingredient is preferably 3~600, and more preferably 15~300.
[effect of composition for oral cavity (5)]
Speculate that composition for oral cavity (5) by the effect below (A) ingredient and (5-B) ingredient, play color spot and form suppression Make use, color spot removal effect, luster effect and excellent preparation use feeling.
Color spot can be effectively suppressed in the attachment of enamel surface in (5-B) ingredient, assigns tooth gloss.On the other hand, (A) at Point with softening and the color spot of dissolution enamel surface attachment or be adsorbed in further calcification (Japanese: calcification) after attachment The effect of calcified material after color spot, and have the function of inhibiting color spot lamination.
By combination (A) ingredient and (5-B) ingredient, it can strongly inhibit color spot in the attachment and lamination of facing, as a result, Composition for oral cavity (5) can have color spot removal effect, color spot formation inhibitory effect and luster effect dentulous simultaneously.Due to (A) any of ingredient and (5-B) ingredient do not have condensed phosphoric acid, enzyme, the surfactant institute as conventional art completely Have to the inadaptable sense of oral mucosa and taste the problem of, therefore composition for oral cavity (5) can also play excellent preparation Use feeling.
[composition for oral cavity (6)]
Composition of the invention can contain (A) ingredient and (6-B) ingredient.(A) ingredient and (6-B) ingredient will be contained below Composition for oral cavity is referred to as composition for oral cavity (6).Furthermore due to (6-B) ingredient: polyphenolic substance, containing (3-B) ingredient Each compound, thus composition for oral cavity (6) be also said to be composition for oral cavity (3) upperseat concept, but the two is in effect Aspect is different.
[content of (A) ingredient in composition for oral cavity (6)]
The content of (A) ingredient is not particularly limited in composition for oral cavity (6), still, uses relative to oral cavity of the invention The total amount of composition (6) is preferably 0.3 mass % or more.Collagen coloring suppression can sufficiently be obtained by (6-B) ingredient as a result, Effect processed.The content of (A) ingredient is preferred relative to the total amount of composition for oral cavity (6) of the invention in composition for oral cavity (6) For 10 mass % or less.As a result, while obtaining good dissolubility and appearance, it can inhibit to be not suitable with sense, can improve makes With sense.The content of (A) ingredient is preferably relative to the total amount of composition for oral cavity (6) of the invention in composition for oral cavity (6) 0.3~10 mass %, more preferably 0.5~5 mass %.
[content of (6-B) ingredient in composition for oral cavity (6)]
The content of (6-B) ingredient is preferably relative to the total amount of composition for oral cavity (6) in composition for oral cavity (6) 0.001 mass % or more.The reason of (6-B) ingredient is collagen coloring as a result, by (A) ingredient and (6-B) ingredient and With can expect collagen colour inhibitory effect.The content of (6-B) ingredient is relative to oral cavity group in composition for oral cavity (6) The total amount for closing object (6) is preferably 5 mass % or less.The collagen coloring inhibitory effect based on (A) ingredient can be filled as a result, Ground is divided to play.Total amount of the content of (6-B) ingredient relative to composition for oral cavity (6) of the invention in composition for oral cavity (6) Preferably 0.001~5 mass %, more preferably 0.01~1 mass %.
[(A) ingredient/(6-B) ingredient in composition for oral cavity (6)]
In composition for oral cavity (5), the mass ratio ((A)/(6-B)) of (A) ingredient and (6-B) ingredient is although without special It limits, but usually 0.5 or more, preferably 3 or more.(A) mass ratio of ingredient and (6-B) ingredient is usually 1000 hereinafter, excellent It is selected as 200 or less.By the way that in this range, due to (A) ingredient, collagen coloring inhibitory effect can be played fully.(A) The ratio of ingredient and (6-B) ingredient is preferably 0.5~200, and more preferably 3~1000.
Furthermore in the present invention, the content of each ingredient in composition, with the addition of each ingredient when manufacturing composition Amount is used as standard.
Administration (Japanese: administration) form of composition of the invention, is not particularly limited.For example, oral administration can be enumerated (intravenous administration, subcutaneous administration, is percutaneously given intramuscular adminstration for (for example, oral administration, sublingual administration etc.), non-oral administration Medicine, nose administration, transpulmonary administration etc.) etc..The few form of medication of preferred invasion among these, more preferable oral administration.
The dosage form of composition of the invention can suitably be determined according to form of medication etc., be not particularly limited.As orally giving The example of dosage form when medicine can enumerate liquid (liquor), syrupy shape (syrup), piece (tablet, tablet), capsule shape (capsule Agent), powdered (particle, particulate), flexible glue cryptomere (soft capsule), solid-like, semi-solid (chewing gum etc.), membranaceous, half liquid Body shape, paste, paste, chewing gum etc..Wherein, preferably granular, capsule shape, powdered, flexible glue cryptomere, solid-like, more preferably For granular (tablet).The example of dosage form when as percutaneous dosing can enumerate aerosol, paste, emulsion form, spray form, post-chip Shape (Japanese: ス テ ィ ッ Network shape) etc..
In the case that composition of the invention is the dosage form of composition for oral cavity, then preferably liquid system (liquid, liquid, Paste), solid system (solid, solid-like, semi-solid, membranaceous).
[carrier (any ingredient) pharmacologically allowed]
, can be as needed other than above-mentioned each ingredient in composition for oral cavity of the invention, what mixing pharmacologically allowed Carrier (any ingredient).As any ingredient, such as surface can be mixed in the range for not damaging stability and demineralization inhibitory effect Activating agent, adhesive (Japanese: bonding drug), thickener (Japanese: sticky drug), sweetener, preservative, fragrance, acid, lubrication Agent, grinding agent, colorant, preservative agent, gloss agent, glidant, bonding agent (Japanese: in conjunction with drug), disintegrating agent, medicinal ingredient, water Equal solvent (solvent), excipient.The specific example of any ingredient is given below, but composition of the invention can be mixed and do not limited In this.
As grinding agent, for example, silicic acid anhydride, crystallinity silica, amorphism silica, silica can be enumerated The silica-based grinding agent such as gel, alumino-silicate, zeolite, calcium phosphate dibasic anhydrous, calcium phosphate dibasic dihydrate, calcium pyrophosphate, carbon Sour calcium, aluminium hydroxide, aluminium oxide, magnesium carbonate, tricresyl phosphate magnesium, zirconium silicate, tricalcium phosphate, hydroxyapatite, tetracalcium phosphate (day Language: the 4th リ Application acid カ Le シ ウ system), synthetic resin system grinding agent etc..
Grinding agent a kind of can be used alone or be used in combination.When mixed-abrasive, combined amount is cleaning one's teeth It is preferably 2~40%, more preferably the 5~20% of composition entirety in agent.In collutory be preferably composition it is whole 0~ 10%, more preferably 0~5%.
As adhesive, for example, tackifying silica, general Shandong indigo plant polysaccharide, gelatin, methylcellulose, hydroxyl second can be enumerated Base cellulose, hydroxypropyl cellulose, sodium carboxymethylcellulose, carrageenan, sodium alginate, xanthan gum, Sodium Polyacrylate, I Uncle's natural gum, guar gum, locust bean gum, polyvinyl alcohol, polyvinylpyrrolidone, carboxyl vinyl polymer etc..Adhesive can one Kind is used alone or is used in combination.Combined amount when using adhesive is usually relative to the total amount of composition 0.01~3%.
As thickener (wetting agent (Japanese: wet drug)), for example, D-sorbite, propylene glycol, butanediol, sweet can be enumerated Oil, polyethylene glycol etc..Thickener can be a kind of independent or be used in combination.If when using thickener, content It can be determined not harming in effective scope of the invention, but be 1~60% usually relative to the total amount of composition.
As surfactant, such as anionic surfactant, nonionic surfactant can be enumerated etc..
As anionic surfactant, for example, N- acyl amino hydrochlorate, alpha-alkene sulfonate, N- acyl group sulfonate, alkane Base sulfate, the sulfate of fatty acid glyceride, POE alkyl sulfo succinate, POE alkyl ether sulfate, POE alkyl ether phosphorus Hydrochlorate etc..Among these, in terms of the versatility, preferably N- acyl amino hydrochlorate, alpha-alkene sulfonate, alkyl sulfate Deng, in terms of the foaminess stability in hard water for, sodium lauroyl sarcosine, the carbon chain lengths of more preferable alkyl chain are carbon atom Alpha-olefin sodium sulfonate, sldium lauryl sulfate that number is 10~16 etc..
As nonionic surfactant, for example, polyoxyethylene alkyl ether, PULLRONIC F68 block can be enumerated Copolymer, Crodaret, the polyoxyethylene ether of glyceride, sucrose fatty ester, alkanolamide, glycerine fatty acid Ester etc..It among these, is suitable for using polyoxyethylene alkyl ether, Crodaret, alkanol in terms of the versatility Amide, sorbitan fatty acid ester etc..Polyoxyethylene alkyl ether, as the carbon chain length of alkyl chain, preferably carbon atom number is 14 ~18.The preferred ethylene oxide of polyoxyethylene alkyl ether be averaged addition molal quantity be 15~30.The oxygen of Crodaret Changing the ethylene addition molal quantity (be averaged addition EO) that be averaged is preferably 20~100.The preferred carbon of the carbon chain length of the alkyl chain of alkanolamide Atomicity is 12~14.Sorbitan fatty acid ester preferred fatty acid carbon atom number is 12~18.Polyoxyethylene sorbitol Acid anhydride aliphatic ester preferred fatty acid carbon atom number is 16~18.The preferred ethylene oxide of polyoxyethylene sorbitan fatty acid ester is flat Equal addition molal quantity is 10~40.
Surfactant can individually one or two kinds of combination of the above use.Content when using surfactant, usually Total amount relative to composition is 0~10%, preferably 0.01~5%.
As sweetener, for example, saccharin sodium, steviol glycoside, neohesperidin chalcone, glycyrrhizic acid, perillartine, right can be enumerated Methoxycinnamic aldehyde, Talin, palatinose, maltitol, xylitol, arabitol etc..Sweetener can independent one kind or two Kind combination of the above uses.When using sweetener, content can appropriate adjustment within the scope of the effect of the invention.
As preservative, for example, can enumerate sodium benzoate, methyl p-hydroxybenzoate, ethyl-para-hydroxybenzoate, to hydroxyl The p-hydroxybenzoates such as yl benzoic acid butyl ester, ethylenediamine base tetraacetate, benzalkonium chloride etc..Preservative can it is individually a kind of or It is used in combination.In the case where using preservative, content can be suitable for determining in the range for not damaging effect of the present invention.
As fragrance, for example, natural perfume material, synthetic perfume (single-item fragrance), compound perfume (grease fragrance (oil can be enumerated Property fragrance), powder perfume etc.).Fragrance can individually one or two kinds of combination of the above use.
As natural perfume material, for example, frankincense oil, parsley oil, fennel oil, eucalyptus oil, wintergreen, cassia oil, thin can be enumerated Lotus cerebrol (Japanese: メ ン ト ー Le oil), spearmint oil (Japanese: ス ペ ア ミ Application ト oil), oleum menthae piperitae (Japanese: ペ パ ー ミ Application ト Oil), lemon oil, coriander oil, orange oil, mandarin oil (Japanese: マ Application ダ リ Application oil), lime oil (Japanese: ラ イ system oil), lavender Oil, laurel berries oil (Japanese: ロ ー レ Le oil), oil of chamomile, cardamom oil (Japanese: カ Le ダ モ Application oil), caraway oil (day Language: キ ャ ラ ウ ェ イ oil), laurel (Japanese: ベ イ oil), lemongrass oil (Japanese: レ モ Application グ ラ ス oil), pine needle Oil, neroli oil, attar of rose, jasmine oil, iris flower essential oil, lavender essential oil, Rosa Damascana, flores aurantii essential oil (Japanese: オ レ Application ジ Off ラ ワ ー), tangerine oil, mixed fruit oil (Japanese: ミ ッ Network ス フ ル ー Star oil), arbusterol, cinnamon oil, caryophyllus oil, grape Oil, hundred inner careless oil, sage oil, peppermint oil (Japanese: Ha ッ カ is oily), rosemary oil, marjoram oil, origanum oil, oil of grapefruit, Platinum oil of grapefruit (Japanese: ス イ ー テ ィ ー oil), grape-fruit seed oil (Japanese: shaddock oil), perilla herb oil etc..
As single-item fragrance, for example, carvol (Japanese: カ Le ボ Application), anethole, gaultherolin, cortex cinnamomi can be enumerated Aldehyde, linalool, acetic acid virtue camphor tree ester, limonene, menthones, menthyl acetate, firpene, octanal, citral, pulegone, card must Alcohol acetate (Japanese: カ ル ビ ー Le ア セ テ ー ト), anisaldehyde, ethyl acetate, ethyl butyrate, allyl cyclohexyl propionate, Methyl anthranilate, methyl anthranilic acid ethyl ester, vanillic aldehyde, 11 carbon lactones, hexanal, ethyl alcohol (Japanese: エ チ ノ Application ア ル コ ー Le), propyl alcohol, butanol, isoamyl alcohol, hexenoic aldehyde, dimethyl suflfate (Japanese: ジ メ チ Le サ Le Off ェ イ De), Methyl cyclopentenyl ketone, furfural, trimethylpyrazine, ethyl lactate, ethyl acetate (Japanese: エ チ Le リ オ ア セ テ ー ト), eucalyptus Oily phenol, Eugenol, ocimenum, n-dodecanol, citronellol, alpha-terpineol etc..
Compound perfume refers to the fragrance concocting single-item fragrance and/or natural perfume material and making.For example, it is micro- to enumerate peppermint Powder, strawberry essence (Japanese: ス ト ロ ベ リ ー フ レ ー バ ー), flavoring apple essence, flavoring banana essence, flavoring pineapple essence, grape essence, awns Fruity essence, tropical fruit (tree) essence, butter flavor, milk flavour, yoghurt flavours, fruit mixing essence, draft Mint Essence (day Language: ハ ー Block ミ Application ト フ レ ー バ ー) etc..
The form of fragrance does not limit, and can be done by spraying for essential oil, extract, solids and to any of which Dry powder.It is preferable to use 0.000001~1% in preparation composition for above-mentioned spices material.Above-mentioned spices material is used Assigning fragrant fragrance, it is preferable to use 0.1~2.0% in preparation composition.
As medicinal ingredient, such as ingredient can be listed below: condensed phosphate, ethanehydroxy diphosphate (Japanese: エ タ Application ヒ De ロ キ シ ジ ホ ス Off ォ ネ ー ト) etc. calculus dentalis prophylactic；The astringents such as sodium chloride；Strontium chloride, strontium acetate, chlorination Hyperesthesia inhibitor such as zinc etc..Content when using medicinal ingredient can allow each medicinal ingredient in pharmacy Range is appropriately configured.
As colorant, for example, safflower red pigment, Gardenia Yellow, gardenia blue pigment, Perilla color, red yeast rice can be enumerated Pigment, deodorized red cabbage color, carrot pigment, rose of Sharon pigment, cacao color, spirulina blue color, tamarind pigment (Japanese: Network マ リ Application De pigment) etc. natural pigments, No. 3 red, No. 104 red, No. 105 red, No. 106 red, yellow 4, Sunset Yellow FCF, The regulations license such as green 3, blue 1 pigment, riboflavin, sodium copper chlorophyllin, titanium dioxide etc..If when containing colorant, Then total amount of its content relative to composition, preferably 0.00001~3%.
As gloss agent, for example, lacca wax, Brazil wax (Japanese: カ Le Na ウ バ ロ ウ), small candle tree can be enumerated The wax class such as cured, calcium stearate etc..When containing gloss agent, content is preferably 0.01~5% relative to the total amount of composition.
Composition of the invention is the pH (20 DEG C) in the case of composition for oral cavity, usually 6~10, preferably 7~9. As pH adjusting agent, for example, acetic acid, hydrochloric acid, sulfuric acid, nitric acid, citric acid, phosphoric acid, malic acid, gluconic acid, Malaysia can be enumerated Acid, succinic acid, glutamic acid, sodium hydroxide, potassium hydroxide, sodium acetate, sodium carbonate, sodium citrate, natrium hydrocitricum, sodium phosphate, The acid such as sodium dihydrogen phosphate, alkali, buffer.In the case where pH adjusting agent, content can be in the model for not damaging effect of the present invention It encloses and is suitably determined.
As solvent, for example, lower alcohol below of the carbon atom numbers such as water and ethyl alcohol, propyl alcohol 3 etc. can be enumerated.Solvent usually contains In the composition for oral cavity of liquid system.If contain water as solvent, content is excellent relative to the total amount of composition It is selected as 20~95%.In the case where containing lower alcohol as solvent, then its content relative to the total amount of composition be preferably 1~ 20%.
As excipient, for example, syrup, glucose, fructose, inverted sugar, dextrin, oligosaccharides etc. can be enumerated.Oral composition In the case that object is food formulation, then excipient is usually contained.In the case where containing excipient, then its content can not damage this The range of invention effect is suitably determined.
The pH (20 DEG C) of composition for oral cavity of the invention is usually 5~10, and preferably 6~10, more preferably 6~9, into One step is preferably 6~8 or 7~9.As pH adjusting agent, for example, can enumerate acetic acid, hydrochloric acid, sulfuric acid, nitric acid, citric acid, phosphoric acid, Malic acid, gluconic acid, maleic acid, succinic acid, glutamic acid, sodium hydroxide, potassium hydroxide, sodium acetate, sodium carbonate, citric acid The acid such as sodium, natrium hydrocitricum, sodium phosphate, sodium dihydrogen phosphate, alkali, buffer.If when containing pH adjusting agent, content can be The range for not damaging effect of the present invention is suitably determined.
[dosage form of composition for oral cavity of the invention]
Shape, the dosage form of composition for oral cavity of the invention are not particularly limited.For example, can be prepared into liquid system (liquid, Liquid, paste), the various shapes such as solid system (solid, solid-like).As the example of dosage form, toothpaste can be enumerated, liquid cleans one's teeth It is the dentifrice compositions such as agent, liquid denfifrice, tooth powder, mouthwash agent composition, inuncts composition, oral cavity ointment, clear in mouth Cool dose of composition, food form (such as chewing gum, pressed candy, candy, chewing gum, film, tablet (Japanese: ト ロ ー チ) Deng).In food form, no matter from time and place workable simplicity, Portability aspect, preferably pressed candy Any of fruit, candy, chewing gum, chewing gum and film.
As the example of candy, boiled goods such as the soft sweets such as caramel, nougat, fruit drops, taffy etc. can be enumerated, although It is not particularly limited, but from assigning from the point of view of high functionality experiences really, preferably boiled goods.The available usually side of boiled goods The method of method is manufactured, although being not particularly limited, for example, can be manufactured by the following method: in functional component and fragrance It is added water in raw material in addition, after high temperature (for example, 140~200 DEG C) boiling down, cooling (for example, to 70~130 DEG C) add function Energy ingredient and fragrance, further cooling, molding.It is more excellent in order to steadily be mixed in the state of keeping the activity of functional component It selects and water is added in the raw material other than functional component and fragrance, it is cooling (for example, to 70 after high temperature (140~200 DEG C) boiling down DEG C~100 DEG C), functional component and fragrance is added, further cooling, molding method is manufactured.
Chewing gum refers to using matrix and saccharic as the food for having chewing elasticity of main material, can there is sugar-coat.Chewing gum is available The manufacture of usual method, is not particularly limited.For example, can then mix the present invention containing (A) ingredient etc. when being plate chewing gum Effective component each ingredient, by molding manufactured.When being sugar-coat chewing gum, although then (A) ingredient etc. is of the invention Effective component can be contained in any of sugar-coat and matrix, or be contained in the two simultaneously, but be preferably contained in sugar-coat.Cause This, can be improved the storage stability of sugar-coat chewing gum.The manufacture of such sugar-coat chewing gum, such as can be fragrant as mouth by mixing Each raw material of sugared main body, after molding, by with the sugar-coat of the effective component of the invention containing (A) ingredient etc. be coated to Manufacture.The content of the effective component in the present invention such as (A) ingredient in sugarcoating layer when being sugar-coat chewing gum, then it is preferably opposite In the quality % of above-mentioned each ingredient of sugar-coat total amount.
As the matrix for being mixed into chewing gum main body, the matrix commonly used in chewing gum can be used.Matrix is for example, can enumerate It is mixed with selected from polyvinyl acetate resin (average degree of polymerization about 100~about 1000), natural resin class (tunny gum, jelutong Glue (Japanese: ジ ェ Le ト Application), rope horse glue (Japanese: ソ Le バ) etc.), polyisobutene, polybutene, the matrixs resin (base such as ester gum Plinth agent), emulsifier, calcium carbonate, calcium phosphate, filler (talcum powder etc.), lanolin, stearic acid, odium stearate, potassium stearate, The substance of the ingredient of the plasticizer such as triacetyl glycerine, glycerol or softening agent, native paraffin, pertroleum wax, paraffin etc..Matrix can be used Commercially available product, specifically, being suitble to make using Natural Base Co., Ltd. (Japanese: Na チ ュ ラ ル ベ ー ス Co., Ltd.) The matrix of the matrix, YOUTH Co., Ltd. (Japanese: ユ ー ス Co., Ltd.) manufacture made.Furthermore above-mentioned matrix can also contain Cape jasmine The natural pigment and titanium dioxide colorant of son, safflower, red yeast rice etc..
The content of matrix is preferably 10~50% relative to the total amount of composition, and particularly preferably 15~30%.
Pressed candy refers to using saccharic as main material, with the candy of the instruments compression forming such as tablet machine, can also there is sugar-coat.Pressure Piece candy can be manufactured with usual method, be not particularly limited, such as can be by mixing each ingredient, with the instruments pressure such as tablet machine Contracting (for example, pressure condition of 5~20kN) is to manufacture.
If enumerating composition for oral cavity of the invention to the example of the dosage of people, when being applicable in situation 3 times a day, 1 usage amount is 0.5~2g, appropriate in about 0.5~1g amount can preferably be adjusted.
The purposes of composition of the invention, although being not particularly limited, from the viewpoint of applicable position, for example, can Enumerate composition for oral cavity (also comprising beverage/food composition).As composition for oral cavity, for example, toothpaste, liquid can be enumerated The dentifrice composition of denfifrice, liquid denfifrice, tooth powder etc., mouthwash agent composition, coolant compositions, diet product group in mouth Close object.
As the other example of composition of the invention, collagen coloring composite inhibiting, collagen can be enumerated Decompose composite inhibiting, dentine dental caries composite inhibiting, dentinal tubule closed composite, because of pain caused by hyperesthesia Mitigate composition, color spot forms inhibition or color spot removal composition, facing gloss pay composition etc..
The applicable object of composition of the invention, is not particularly limited.Although not suffering from dentine sense for example, can enumerate Feel allergy sufferers, carious dentin patient, dentine hyperesthesia and dentine dental caries, or is not confirmed whether to suffer from, but think Prevent dentine hyperesthesia and the people of dentine dental caries etc..
Composition of the invention can be any of pharmaceuticals, medicine part outer article, cosmetics and diet product.
[collagen coloration inhibitor]
(A) lactam compound of ingredient or its salt are due to having the effect of coloring of the inhibition to collagen, so making Effective component for collagen coloration inhibitor is useful.
Collagen is present in the tissue of animal.The collagen of people is classified as tens of types, and main collagen is I Type.Although collagen coloration inhibitor of the invention is not particularly limited as the collagen of object, preferably contain I The collagen of collagen type.
The variation of collagen coloring being meant that from the original color of collagen to other colors.Collagen Coloration inhibitor is coloured as the collagen of object, the collagen coloring preferably generated in organism, more preferably The coloring of dentin collagen albumin layer.As the example of collagen coloring, can enumerate due to medicament, diet product, oral bacteria The coloring of caused dentin collagen albumin layer.When suffering from dentine dental caries, the coloring of the dentine as caused by oral bacteria, or In the treatment of dentine dental caries, by being applicable in for medicament, there is the case where generation coloring in dentin collagen albumin layer.In addition, Since the intake of diet product also has generation same the case where colouring.Inhibited by suitably being decomposed using collagen of the invention Agent can inhibit above-mentioned coloring.The prime example of the medicament of the reason of as collagen coloring is polyphenol.It, can as polyphenol Enumerate each example of flavones, phenyl carboxylic acid, chlorogenic acid, lignan (Japanese: リ グ Na Application), curcumin and above-mentioned (2-B) ingredient. In addition, the above-mentioned diet product (for example, black tea and green tea containing catechin, the coffee containing chlorogenic acid etc.) containing more polyphenol It is also possible to the reason of becoming coloring.
The form of medication of collagen coloration inhibitor of the invention, is not particularly limited.For example, oral administration can be enumerated (intravenous administration, subcutaneous administration, is percutaneously given intramuscular adminstration for (for example, oral administration, sublingual administration etc.), non-oral administration Medicine, nose administration, transpulmonary administration etc.) etc..Preferably aggressive few form of medication, more preferably oral administration or warp among these Skin administration.
The intake object of collagen coloration inhibitor of the invention can enumerate collagen coloring and fall ill and want to change Although the coloring of kind object, collagen does not fall ill but wants the object etc. of prevention.The medicine-feeding period of preparation of the invention, does not have There is special limitation.
[collagen decomposing inhibitor]
(A) lactam compound of ingredient or its salt are because there is collagen to decompose inhibitory effect, as collagen The effective component of protease inhibitors is useful.
The collagen of object as collagen decomposing inhibitor of the invention, is not particularly limited, preferably contains There is the collagen of I-type collagen.
In the collagen layer exposure of dentine dental caries dens in dente essence, if be destroyed due to clostridiopetidase A, tooth Foundation defect in itself.By the way that collagen decomposing inhibitor of the invention is suitable for tooth, because can inhibit or change Kind collagen decomposes, so can prevent dentine dental caries.
The collagen of periodontium is decomposed into the reason of periodontium problem such as gingival atrophy, absorption of alveolar bone.Cause Collagen can be inhibited to decompose for collagen decomposing inhibitor through the invention, so asking for periodontium can be prevented Topic.
The form of medication of collagen decomposing inhibitor of the invention, is not particularly limited.The example of form of medication and excellent Select example identical as the example and preference enumerated in the explanation of collagen coloration inhibitor.
Collagen of the invention decomposes the intake object of inhibition or improver, can enumerate being decomposed into collagen The symptom (for example, the problem of progress of dentine dental caries, periodontium (gingival atrophy, absorption of alveolar bone etc.)) of cause has been sent out Disease wants improved object, although these symptoms do not occur wanting object of prevention etc..When the administration of preparation of the invention Phase is not particularly limited.
[dentinal tubule sealer]
Because there is dentinal tubule early stage sealing effect as the lactam compound of (A) ingredient and/or its salt, It is useful as dentinal tubule sealer.
The form of medication of dentinal tubule sealer of the invention is not particularly limited.The example and preference of form of medication It is identical as the example and preference enumerated in the explanation of collagen decomposing inhibitor.
The intake object of dentinal tubule sealer of the invention can enumerate dentine acroesthesia and fall ill and think Dentinal tubule is carried out closed object, symptom there is no or cannot be confirmed whether occur and want prevention object Deng.The medicine-feeding period of preparation of the invention is not particularly limited.
[inhibition of dentine acroesthesia or improver]
Because there is dentinal tubule early stage sealing effect and pain as the lactam compound of (A) ingredient and/or its salt Pain mitigates effect, so the inhibition or improver as dentine acroesthesia are useful.
The inhibition of dentine acroesthesia or the form of medication of improver of the invention is not particularly limited.Form of medication Example and preference and the explanation of collagen decomposing inhibitor in the example enumerated and preference it is identical.
Dentine acroesthesia of the invention inhibits or the intake object of improver, can enumerate dentine hyperesthesia Although disease has been fallen ill and has wanted to improve the object of symptom, object of prevention etc. is not fallen ill but wanted to symptom.System of the invention The medicine-feeding period of agent is not particularly limited.
[color spot remover]
Because having the effect of removing the color spot as tooth spot as the lactam compound of (A) ingredient or its salt, So the effective component as color spot remover is useful.
The intake object of color spot remover of the invention can be enumerated and be attached with the color spot as tooth spot and want Except the object of spot.The medicine-feeding period and form of medication of preparation of the invention are not particularly limited, but can be with combinations of the above The form of medication of object is identical.
Embodiment
Below by embodiment, the present invention will be described in detail.Following each embodiment is for illustrating currently preferred embodiment party Formula is not intended to limit the present invention.% in following examples indicates quality percentage.
Embodiment 1-1~1-30 and comparative example 1-1~1-4
[primary raw material used]
[(A) ingredient]
(1) 2-pyrrolidone-5-carboxylic acid's (gamma-lactam compounds):
Ajincomoto Co., Inc's manufacture, trade name " AJIDEW A-100 (registered trademark) "
(2) 6- oxo -2-piperidinecarboxylic acid (δ-lactam compound):
Sigma-Aldrich Amada Co., Ltd. (Japanese: シ グ マ ア Le De リ ッ チ ジ ャ パ Application Co., Ltd.) system It makes, trade name " (S) -6- oxo -2-piperidinecarboxylic acid ((S) -6-Oxo-2-piperidine carboxylic acid) "
(3) 3- (2- oxo -1- nitrogen heterocyclic heptyl) propionic acid (ε-lactam compound):
The manufacture of Sigma-Aldrich Amada Co., Ltd., trade name " 3- (2- oxo aza ring hept- 1- yl) propionic acid (3- (2-Oxoazepan-1-yl)propanoic acid)”
[the comparison product of (A) ingredient]
(4) polyvinylpyrrolidone (lactam compound of no acidic group):
Wako Pure Chemical Industries, Ltd.'s manufacture, trade name " polyvinylpyrrolidone K25 (Japanese: Port リ ビ ニ Le ピ ロ リ ドンK25)”
(5) proline (cyclic amino acid):
Wako Pure Chemical Industries, Ltd.'s manufacture, trade name " DL-proline (Japanese: DL- プ ロ リ Application) "
[(1-B) ingredient]
(6) sodium fluoride:
The manufacture of Stella Chemifa company, trade name " sodium fluoride "
(7) sodium monofluorophosphate:
The manufacture of Rhodia solar corona company, trade name " sodium monofluorophosphate "
[(1-C) ingredient]
(8) casein:
Wako Pure Chemical Industries, Ltd.'s manufacture, trade name " casein (coming from milk) "
Sulfur-containing amino acid containing ratio (%): 3.0
Average molecular weight: 88000
Phosphate group: have
(9) lactoferrin:
Wako Pure Chemical Industries, Ltd.'s manufacture, trade name " lactoferrin (coming from milk) "
Sulfur-containing amino acid containing ratio (%): 5.4
Average molecular weight: 86000
Phosphate group: nothing
(10) Hydrolyzed Collagen:
The manufacture of JELLICE company, trade name " HACP-U2 "
Sulfur-containing amino acid containing ratio (%): 1.5
Average molecular weight: 1500
Phosphate group: nothing
(11) other adding ingredients other than above-mentioned effective component:
Sodium hydroxide (pH adjusting agent), citric acid (pH adjusting agent), D-sorbitol solution (thickener), saccharin sodium (sweet taste Agent), propylene glycol (thickener), Sodium Polyacrylate (adhesive), sodium carboxymethylcellulose (adhesive), silicic acid anhydride (grinding agent), NaLS (anionic surfactant), fragrance
[preparation of denfifrice]
Using above-mentioned effective component, according to mass ratio (mass parts) shown in aftermentioned table 1~9, by following usual The preparation method of denfifrice prepares denfifrice 1.0kg (100 mass parts).
(preparation method of denfifrice)
Following " effective components of (i) A phase " are mixed with " adding ingredient of (ii) A phase " in Purified Water under room temperature Dissolution prepares A phase.In addition, following " adding ingredients of (iii) B phase " are dissolved or dispersed at normal temperature in propylene glycol, system Standby B phase.Then, addition mixing B phase in the A phase in stirring, prepares C phase.Finally, using 1.5L kneader (tor work institute Manufacture), following " adding ingredients of (iv) C phase " are mixed in C phase under room temperature, are depressurized to 4kPa and are carried out deaeration, are cleaned one's teeth Agent 1.0kg (100 mass parts).The content of each ingredient is as shown in table 1~9.
(effective component mixed in A phase, B phase, C phase and other adding ingredients)
(i) effective component of A phase: 2-pyrrolidone-5-carboxylic acid, 6- oxo -2-piperidinecarboxylic acid, 3- (2- oxo -1- azacyclo- Heptane base) propionic acid, sodium fluoride, sodium monofluorophosphate, casein, lactoferrin, Hydrolyzed Collagen
(ii) adding ingredient of A phase: D-sorbitol solution, saccharin sodium, citric acid, sodium hydroxide
(iii) adding ingredient of B phase: propylene glycol, Sodium Polyacrylate, sodium carboxymethylcellulose
(iv) adding ingredient of C phase: silicic acid anhydride, NaLS, fragrance
Using each denfifrice obtained as described above, as follows to dentine dental caries inhibitory effect and preparation stability into Row evaluation.
(evaluation of dentine dental caries inhibitory effect)
(1) it is produced on the dentine area for implementing windowing on the surface of baurodont root, in the demineralization of acetic acid 100mmol/L, pH4.8 It is impregnated 6 hours for 37 DEG C in liquid, obtains saprodontia sample.
(2) each denfifrice is diluted 3 times with distilled water respectively, respectively obtained by denfifrice by saliva dilution when assuming to use Denfifrice treatment fluid.By saprodontia sample room temperature immersion 3 minutes in each denfifrice treatment fluid, denfifrice processing is then gently removed Liquid.
(3) preparation contains CaCl2: 1.5mmol/L, KH2PO4: 5.0mmol/L, acetic acid: 100mmol/L, NaCl: 100mmol/L, 1.0 units/mL come from the clostridiopetidase A (Type of clostridium histolyticum (Clostridium Histolyticum) 1A, Sigma manufacture) pH6.5 remineralization liquid.By above-mentioned (2) treated each saprodontia sample 37 DEG C of leachings in remineralization liquid Stain 18 hours.
(4) by above-mentioned (3) treated, each saprodontia sample impregnates 3 minutes in each denfifrice treatment fluid again at room temperature, Gently remove denfifrice treatment fluid.After being impregnated 6 hours at 37 DEG C in the demineralization liquid of acetic acid 100mmol/L, pH4.8, gently Remove demineralization liquid.
(5) processing 1 day each 1 time of above-mentioned (2)~(4) is repeated, is amounted to 3.
(6) after above-mentioned processing 3 days, each saprodontia sample is sufficiently rinsed with distilled water, focuses on being cut under flowing water with micro- Knife (manufacture of MARUTO Co., Ltd., " MC-201 (trade name) ") cuts thickness about in the vertical direction relative to sample window 200 μm of slice.
(7) sample sheet cut under hygrometric state is put into grenz ray film (Kodak's (Japanese: コダック society) system Make, " SO-343 (trade name) ") on, pass through grenz ray generator (SOFTEX Co., Ltd. (Japanese: ソ Off テ ッ Network on it ス (strain)) manufacture, " CMRII (trade name) ") irradiation grenz ray (2.8mA, 18kVp) 60 minutes, obtain each chip sample TMR (Transverse Micro Radiography) as.
(8) finally, confirming in accordance with the following methods to the demineralization degree of each chip sample.It is taken the photograph simultaneously from chip sample The TMR picture of 15 pieces of aluminium ladders (Japanese: ア Le ミ ニ ウ system ス テ ッ プ ウ ェ ッ ジ) of system uses portrait resolver (PIAS plants of formulas Commercial firm's (Japanese: ピ ア ス (strain)) manufacture, " PIAS-V (trade name) "), it is made the minerals distribution of each chip sample TMR picture (Japanese: ミ ネ ラ Le プ ロ Off ァ イ Le).From obtained each minerals distribution, calculate mineral loss amount Δ Z (demineralization amount).
The demineralization amount for the sample (untreated fish group) that the processing handled by denfifrice treatment fluid is not carried out is carried out similarly It calculates.
(9) above-mentioned a series of experimental implementation carries out each group (embodiment, comparative example and untreated fish group) respectively with N=3. The average value (average delta Z) that the groups of each individual of structure is found out to each group, respectively as " the average delta Z of untreated fish group ", " embodiment Average delta Z " and " the average delta Z " of comparative example." the average delta Z of untreated fish group " is used as standard demineralization amount, according to " embodiment Average delta Z " or " the average delta Z of comparative example ", dentine dental caries inhibiting rate is found out by following formula (1-2).
[number 2]
Formula (1-2)
Each embodiment and the dentine dental caries preventive effect of comparative example are evaluated according to the standard in following 5 stages.Such as The following evaluation scores of fruit are 3 or more, then it is believed that having good dentine dental caries preventive effect.
(evaluation criterion)
5 points: dentine dental caries inhibiting rate is 70% or more
4 points: dentine dental caries inhibiting rate is 50% more than and less than 70%
3 points: dentine dental caries inhibiting rate is 30% more than and less than 50%
2 points: dentine dental caries inhibiting rate is 10% more than and less than 30%
1 point: dentine dental caries inhibiting rate is less than 10%
(estimation of stability of preparation)
The denfifrice of each embodiment of visual valuation and comparative example just manufacture after appearance.To each embodiment and comparative example Fragrance after denfifrice just manufactures carries out sensory evaluation.Then, the sample that 1 month is saved under 50 DEG C of environment is carried out same Evaluation.
The following standards of Appreciation gist carry out.
(evaluation criterion)
A: precipitating without being precipitated, non-discolouring, the separation of no liquid separating layer.Do not have dulcet deterioration yet.
B: although visible seldom precipitation precipitates, changes colour, liquid separates, the whole only one in the deterioration of fragrance Point is put or any one, but belongs to the degree that there is no problem.
C: although just manufacture after there is no problem, after being saved 1 month under 50 DEG C of environment, be precipitated precipitating, change colour, The problem of significant deterioration occurs at least one in liquid separation, fragrance.
D: just starting after manufacture, at least one occurs significantly bad in precipitation precipitating, discoloration, liquid separation, fragrance The problem of change.
According to the dentine dental caries inhibitory effect of each embodiment and comparative example that above-mentioned evaluation method and evaluation criterion are evaluated It is documented in following table 1~9 simultaneously with preparation stability.
[table 1]
Table 1
In embodiment 1-1~1-5 shown in above-mentioned table 1, arbitrary effective component (1-C) ingredient is not added, uses pyrroles Alkanone carboxylic acid is used as (A) ingredient, uses sodium fluoride as (1-B) ingredient.
It is good if the evaluation of the dentine dental caries inhibitory effect of embodiment 1-1~1-5 is 3 or more.
It is well known that fluorine is used alone shown in the effective of inhibition but comparative example 1-1 as be described hereinafter of the fluorine compounds to dental caries The dentine dental caries inhibitory effect that compound obtains is evaluated as 2, it is practical it is upper not enough.
In this regard, using (A) ingredient and tooth of (1-B) ingredient as the composition for oral cavity of the embodiment of effective component simultaneously The evaluation of essential dental caries inhibitory effect is 3 or more, and wherein embodiment 1-1~1-3 is evaluated as 4.Therefore, it is known that by making simultaneously Use (A) ingredient and (1-B) ingredient as effective component, available (A) ingredient be added with (1-B) ingredient more than effect, i.e., Synergy.
[table 2]
Table 2
In embodiment 1-6 and 1-7 shown in above-mentioned table 2, do not add (1-C) ingredient, use sodium fluoride as (1-B) at Point.It uses 6- oxo -2-piperidinecarboxylic acid as (A) ingredient in embodiment 1-6,3- (2- oxo -1- nitrogen is used in embodiment 1-7 Trioxepane base) propionic acid conduct (A) ingredient.
The dentine dental caries inhibitory effect of embodiment 1-6 and 1-7 are evaluated as 3, are good.
[table 3]
Table 3
It is same as embodiment 1-1~1-5 of table 1 in embodiment 1-8~1-11 shown in above-mentioned table 3, do not add (1-C) Ingredient uses 2-pyrrolidone-5-carboxylic acid as (A) ingredient, uses sodium fluoride as (1-B) ingredient.
The evaluation of the dentine dental caries inhibitory effect of embodiment 1-8~1-11 is good 3 or more.Wherein embodiment 1-8 4 are evaluated as with 1-9.From these data it is found that having obtained the synergy of (A) ingredient Yu (1-B) ingredient.
[table 4]
Table 4
In embodiment 1-12~1-15 shown in table 4, do not add (1-C) ingredient, use 2-pyrrolidone-5-carboxylic acid as (A) at Point.It uses sodium monofluorophosphate as (1-B) ingredient in embodiment 1-12 and 1-13, fluorination is used in embodiment 1-14 and 1-15 Sodium.
The evaluation of the dentine dental caries inhibitory effect of embodiment 1-12~1-15 is good 3 or more.Wherein embodiment 1- 12 and 1-13's is evaluated as 4.It follows that having obtained the effect of (A) ingredient with (1-B) ingredient cooperateed with
[table 5]
Table 5
Embodiment 1-16~1-19 shown in table 5 uses casein as (1-C) ingredient, use 2-pyrrolidone-5-carboxylic acid as (A) ingredient uses sodium fluoride as (1-B) ingredient.
The dentine dental caries inhibitory effect of embodiment 1-16~1-19 is evaluated as 5.It follows that by (A) ingredient (1-C) ingredient, available good dentine dental caries inhibitory effect are added in (1-B) ingredient.
[table 6]
Table 6
Embodiment 1-20 and 1-21 shown in table 6 are added to (1-C) ingredient.Used in embodiment 1-20 lactoferrin as (1-C) ingredient uses Hydrolyzed Collagen as (1-C) ingredient in embodiment 1-21.Each embodiment uses pyrrolidones carboxylic Acid is used as (A) ingredient, uses sodium fluoride as (1-B) ingredient.
The dentine dental caries inhibitory effect of embodiment 1-20 and 1-21 are evaluated as 5.It follows that by (A) ingredient (1-C) ingredient, available good dentine dental caries inhibitory effect are added in (1-B) ingredient.
[table 7]
Table 7
In embodiment 1-22~1-26 shown in table 7 and use several compounds as effective component.
(δ-is interior for 2-piperidinecarboxylic acid in embodiment 1-22 and with 2-pyrrolidone-5-carboxylic acid's (gamma-lactam compounds) and 6- oxo- Amide compound) it is used as (A) ingredient.
In embodiment 1-23 and with 2-pyrrolidone-5-carboxylic acid's (gamma-lactam compounds) and 3- (2- oxo -1- azepan Base) propionic acid (ε-lactam compound) conduct (A) ingredient.
In embodiment 1-24 and with 6- oxo -2-piperidinecarboxylic acid (δ-lactam compound) and 3- (2- oxo -1- azacyclo- Heptane base) propionic acid (ε-lactam compound) conduct (A) ingredient.
In embodiment 1-25 and with 2-pyrrolidone-5-carboxylic acid's (gamma-lactam compounds), (δ-is interior for 2-piperidinecarboxylic acid for 6- oxo- Amide compound) and 3- (2- oxo -1- nitrogen heterocyclic heptyl) propionic acid (ε-lactam compound) conduct (A) ingredient.
It has used 2-pyrrolidone-5-carboxylic acid's (gamma-lactam compounds) as (A) ingredient in embodiment 1-26, and has used sodium fluoride (1-B) ingredient is used as with sodium monofluorophosphate.
[table 8]
Table 8
In embodiment 1-27~1-30 shown in table 8 and use several compounds as effective component.
In embodiment 1-27 and use casein and lactoferrin as (1-C) ingredient.
In embodiment 1-28 and use casein and Hydrolyzed Collagen as (1-C) ingredient.
In embodiment 1-29 and use lactoferrin and Hydrolyzed Collagen as (1-C) ingredient.
In embodiment 1-30 and use casein, lactoferrin and Hydrolyzed Collagen as (1-C) ingredient.
[table 9]
Table 9
Comparative example 1-1 does not use (A) ingredient, uses sodium fluoride as (1-B) ingredient.
Comparative example 1-2 and 1-3 use the analog of lactam compound and lactam compound as the comparison of (A) ingredient Product.Use polyvinylpyrrolidone as the comparison product of (A) ingredient in comparative example 1-2.Polyvinylpyrrolidone is that do not have acid The lactam compound of property group.Use proline as the comparison product of (A) ingredient in comparative example 1-3.Proline is ring-type ammonia Base acid.
Comparative example 1-4 does not use (1-B) ingredient, uses 2-pyrrolidone-5-carboxylic acid as (A).
Comparative example 1-1 does not use (A) ingredient, uses sodium fluoride as (1-B) ingredient.It is well known that fluorine compounds are to dental caries The inhibition of disease is effective.But the dentine dental caries inhibitory effect that this fluorine compounds obtains is used alone is evaluated as 2, it is practical on not It is enough.
In addition, in comparative example 1-4, although preparation stability is evaluated as zero, the evaluation of dentine dental caries inhibitory effect It is 1.
From the evaluation result of above-mentioned comparative example 1-1 and 1-4 and the evaluation result of embodiment above-mentioned, it will be clear that logical It crosses while using (A) ingredient and (1-B) ingredient as effective component, the effect more than effect of the addition of available each ingredient Fruit.
Two kinds of Formulation Examples of composition for oral cavity of the present invention are given below.Such Formulation Example can be obtained and above-described embodiment The same dentine dental caries preventive effect of composition for oral cavity.
[table 10]
10 Formulation Example 1-1 of table: collutory
Ingredient Combined amount (quality %)
Pyrrolidone sodium carboxylate 3
Sodium fluoride 0.22
Xylitol 3
Glycerol (AI=100) 2
Polyoxyethylene (60) rilanit special 0.5
Citric acid monohydrate closes object 0.1
Citrate trisodium dihydrate 0.3
Fragrance 0.2
Ethyl alcohol 8
Propylene glycol 3
Purified Water Balance
It is total 100
Dentine dental caries inhibitory effect 4 points
Preparation stability A
[table 11]
11 Formulation Example 1-2 of table: toothpaste
Ingredient Combined amount (quality %)
Pyrrolidone sodium carboxylate 3
Polyoxyethylene (10) cetyl ether 0.8
Polyoxyethylene (30) rilanit special 0.6
70% D-sorbitol solution 40
Propylene glycol 3
Sodium Polyacrylate 0.5
Xanthan gum 0.6
Sodium alginate 0.3
Saccharin sodium 0.2
Tin fluoride 0.39
NaLS 1.5
Silicic acid anhydride 22
Fragrance 1.2
Purified Water Balance
It is total 100
Dentine dental caries inhibitory effect 4 points
Preparation stability A
Embodiment 2-1~2-36 and comparative example 2-1~2-6
[primary raw material used]
[(A) ingredient]
(1) 2-pyrrolidone-5-carboxylic acid's (gamma-lactam compounds):
Ajincomoto Co., Inc's manufacture, trade name " AJIDEW A-100 (registered trademark) "
(2) 6- oxo -2-piperidinecarboxylic acid (δ-lactam compound):
The manufacture of Sigma-Aldrich Amada Co., Ltd., trade name " (S) -6- oxo -2-piperidinecarboxylic acid "
(3) 3- (2- oxo -1- nitrogen heterocyclic heptyl) propionic acid (ε-lactam compound):
The manufacture of Sigma-Aldrich Amada Co., Ltd., trade name " 3- (2- oxo aza ring hept- 1- yl) propionic acid "
[the comparison product of (A) ingredient]
(4) polyvinylpyrrolidone:
Wako Pure Chemical Industries, Ltd.'s manufacture, trade name " polyvinylpyrrolidone K25 "
[(2-B) ingredient]
(5) longan nuclear extract (other than embodiment 2-12 and 2-13 embodiment and comparative example in use):
Pian Cang Chikkarin Co., Ltd. (Japanese: piece storehouse チ ッ カ リ Application Co., Ltd.) manufacture, trade name " AGETECT (Japanese: エ イ ジ テ Network ト) "
Longan seed extractive content: 1%；
(6) longan nuclear extract (being used in embodiment 12 and 13):
The manufacture of Pian Cang Chikkarin Co., Ltd., trade name " longan nuclear extract powder SD "
Longan seed extractive content: 83%；
(7) proanthocyanidin:
Kikkoman Co., Ltd's (Japanese: キ ッ コ ー マ Application Co., Ltd.) manufacture, trade name " Gravinol-SL "
Proanthocyanidin content: 82%
(8) catechin:
Sun Chemical Co., Ltd.'s manufacture, trade name " Sunphenon EGCG "
Catechin content: 95%
(9) aurantiamarin:
Tokyo Chemical Industry Co., Ltd's manufacture, trade name " hesperidin methyl (Japanese: メ チ Le ヘ ス ペ リ ジ Application) "
Content of hesperidin: 90%
[the comparison product of (2-B) ingredient]
(10) rosemary extracting solution:
The kind manufacture medicine Co., Ltd. manufacture of ball, trade name " RKC-87 "
Rosemary extraction liquid hold-up: 1.5%
The composite rate of each polyphenolic substance shown in table 12~16 is that polyphenol contained in each commercially available product is former in each composition Shared composite rate in material.
The evaluation of experimental example 2-1 dentin collagen protein breakdown inhibitory effect
[preparation of denfifrice]
Prepare each composition for oral cavity formed shown in table 12~16.Preparation method is as follows.70% sorb will contained The A of water-soluble material (lactam compound, polyphenolic substance, disodium hydrogen phosphate, saccharin sodium) is mixed in the Purified Water of sugar alcohol Mutually with joined in propylene glycol sodium alginate, carrageenan, methyl p-hydroxybenzoate B phase mixed.It is pinched in 1.5L In conjunction machine (manufactured by limited commercial firm's tor work), silicic acid anhydride, fragrance, lauryl sulphur are mixed under room temperature in obtained mixture Sour sodium.Then, it is depressurized to 4kPa and carries out deaeration, continue to be mixed to get composition.Obtained composition is stored at room temperature 1 It is used within week, carries out following evaluations.
[collagen, which decomposes, inhibits evaluation]
Demineralization window to about 2mm width grinding baurodont root surface to remove cementum after, be cut into thickness with micro- cutter 250 μm of slice.In the part for removing cementum, about 1.5mm × 250 μm are used as demineralization window, rest part nail polish (Japanese: マ ニ キ ュ ア) covering.Nail polish is after drying at room temperature, the dipping in the aqueous acetic acid (pH4.5) of 0.1mol/L 50 hours, preparation was exposed to the cementum caries disease sample of collagen in window portion.Group of this sample in each embodiment and comparative example It closes in 3 times of water diluents of object room temperature immersion 5 minutes, after being cleaned with distilled water, is immersed in 37 DEG C of artificial saliva (CaCl2: 2.2mmol/L、KH2PO4: 2.2mmol/L, acetic acid: 0.1mol/L, clostridiopetidase A (Type 1A, Sigma from clostridium histolyticum Company's manufacture): in 1.0 units/mL, pH6.5).In the morning, afternoon and evening 3 times/day to composition implement dispose, remaining time be immersed in containing In the artificial saliva of clostridiopetidase A, amounts to and repeat 4.After experiment, micro- sem observation cementum caries disease sample, each sample measurement The depth of the exposure collagen at 3 positions, is averaged.Measurement is implemented with N=3, calculates average value.It is calculate by the following formula glue Former protein breakdown inhibiting rate, the standard shown in following are evaluated.In addition, embodiment or comparative example group refer to table in following formula Show the group of the disposition of the composition shown in embodiment or comparative example, control group refers to expression without shown in embodiment and comparative example Composition disposition group.Each embodiment and comparative example are similarly evaluated with N=3.These results are as shown in table 12~16.
[number 3]
Formula (2-1)
[evaluation criterion of dentin collagen protein breakdown inhibitory effect]
A: dentin collagen protein breakdown inhibiting rate is 70% more than and less than 90%
B: dentin collagen protein breakdown inhibiting rate is 50% more than and less than 70%
C: dentin collagen protein breakdown inhibiting rate is 20% more than and less than 50%
D: dentin collagen protein breakdown inhibiting rate is 0% more than and less than 20%
The evaluation of dentin collagen protein breakdown inhibitory effect after experimental example 2-2 preservation (after being saved 1 month at 50 DEG C)
[preparation of composition]
The composition for oral cavity of composition shown in table 12~16 is prepared as with experimental example 2-1, in 50 DEG C of high temperature slot Save carry out within 1 month using.
[evaluation of the dentin collagen protein breakdown inhibitory effect after preservation]
Using the composition of the product of preservation, implements the dentin collagen protein breakdown after saving and inhibit evaluation.Evaluation method, tooth Calculating method, the evaluation criterion that essential collagen decomposes inhibiting rate are same as experimental example 2-1.
The evaluation of dentin collagen albumen coloring inhibitory effect after experimental example 2-3 preservation (after 50 DEG C save 1 month)
[preparation of denfifrice]
The composition for oral cavity of composition shown in table 12~16 is prepared as with experimental example 2-1, in 50 DEG C of high temperature slot Save carry out within 1 month using.
[the dentin collagen albumen coloring after preservation inhibits evaluation]
After baurodont root is cut off on block, cementum is removed by lapped face.In the part for removing cementum, about 3.5mm × 3.5mm is used for demineralization window, and rest part is covered with nail polish.After nail polish is dried at room temperature for, 0.1mol/L's Dipping 72 hours in aqueous acetic acid (pH4.5), preparation window portion are exposed to the cementum caries disease sample of collagen.Initially as Initial value measures color difference (L*0、a*0、b*0).Then, this sample is diluted in 3 times of water of each embodiment and the composition of comparative example It is impregnated at room temperature in liquid 5 minutes, after being cleaned with distilled water, is immersed in 37 DEG C of artificial saliva (CaCl2: 2.2mmol/L, KH2PO4: 2.2mmol/L, acetic acid: 0.1MOL/L, the clostridiopetidase A (manufacture of Type 1A, Sigma company) from clostridium histolyticum: 0.1 unit/mL, pH6.5) in.3 times/day composition is implemented to dispose in the morning, afternoon and evening, remaining time is immersed in containing clostridiopetidase A In artificial saliva, amounts to and repeat 4.After experiment, color difference (L is implemented with N=3*1、a*1、b*1) it measures, calculates average value. Color difference uses spectrophotometer (manufacture of Konica Minolta (Japanese: U ニ カ ミ ノ Le タ (strain)) Co., Ltd., CM-2022) Measurement, coloring inhibitory effect are evaluated according to the △ E value calculated by following formula (2-2) based on following evaluation criterions.These knots Fruit is as shown in table 12~16.
△ E value=((L*1-L*0)2+(a*1-a*0)2+(b*1-b*0)2)1/2
[evaluation criterion]
A:0≤△ E < 2.0
B:2.0≤△ E < 4.0
C:4.0≤△ E < 6.0
D:6.0≤△ E < 8.0
The evaluation of experimental example 2-4 preparation stability (after being saved 1 month at 50 DEG C)
It is prepared as the denfifrice of composition shown in table 12~16 with experimental example 2-1,1 is saved in 50 DEG C of high temperature slot Month.Appearance after visual confirmation preservation carries out the evaluation of preparation stability (discoloration and conformality) according to following evaluation criterions.
[evaluation criterion]
A: it can't see the composition extracted from test tube and change colour, there is no problem on conformality
B: the composition extracted from test tube is in discoloration and conformality almost without problem
C: the composition extracted from test tube slightly problem in discoloration, and/or conformality
D: the composition extracted from test tube is quite problematic in discoloration, and/or conformality.
The result of experimental example 2-1~2-4 of the composition for oral cavity of each embodiment and comparative example is as shown in table 12~16.
[table 12]
Table 12
[table 13]
Table 13
[table 14]
Table 14
[table 15]
Table 15
[table 16]
Table 16
It was found from table 12~16: the preparation of the composition for oral cavity (embodiment 2-34~2-36) of (A) ingredient having been used to exist After being saved 1 hour at 50 DEG C, still persistently has and save preceding same excellent dentin collagen protein breakdown inhibitory effect.This Outside, the dentin collagen protein breakdown inhibitory effect ratio of the preparation of composition for oral cavity (embodiment 2-34~2-36) has used poly- The composition for oral cavity (comparative example 2-5) of vinylpyrrolidone is more excellent.It is mixed with the oral cavity of (A) ingredient He (2-B) ingredient With composition (embodiment) with it is having used individually (A) ingredient and (2-B) ingredient or used (A) ingredient and (2-B) The composition for oral cavity (comparative example) of the respective relatively product of ingredient is compared, and shows significantly high dentin collagen protein breakdown suppression Rate processed after saving preparation 1 month at 50 DEG C, remains to confirm constantly high dentin collagen protein breakdown inhibitory effect.This Outside, it is mixed with (A) ingredient or is mixed with the composition for oral cavity (embodiment) of (A) ingredient He (2-B) ingredient, pass through polyphenol component While significantly suppressing the coloring to dentin collagen albumen, also significantly suppresses and the discoloration after preparation saves is made.These The result shows that composition for oral cavity of the invention well-balanced, fully play dentin collagen protein breakdown inhibit effect Dentin collagen albumen coloring inhibitory effect and system after dentin collagen protein breakdown inhibitory effect, preservation after fruit, preservation Agent stability.These results also indicate that composition for oral cavity (2) is after dentin collagen protein breakdown inhibitory effect, preservation In dentin collagen albumen coloring inhibitory effect and preparation stability after dentin collagen protein breakdown inhibitory effect, preservation It shows significantly excellent.
Formulation Example is given further below.Effect same as above-described embodiment also can be obtained in such Formulation Example.
[table 17]
17 Formulation Example 2-1 (denfifrice) of table
[table 18]
18 Formulation Example 2-2 (denfifrice) of table
[table 19]
Table 19 (Formulation Example 2-3: denfifrice)
[table 20]
20 Formulation Example 2-4 (collutory) of table
[table 21]
21 Formulation Example 2-5 (collutory) of table
[table 22]
22 Formulation Example 2-6 (candy) of table
[table 23]
23 Formulation Example 2-7 (chewing gum) of table
< sugarcoating layer >
< chewing gum main body >
[table 24]
24 Formulation Example 2-8 (pressed candy) of table
Embodiment 3-1~3-26 and comparative example 3-1~3-3
[primary raw material used]
[(A) ingredient]
(1) 2-pyrrolidone-5-carboxylic acid's (gamma-lactam compounds):
Ajincomoto Co., Inc's manufacture, trade name " AJIDEW A-100 (registered trademark) "
(2) 6- oxo -2-piperidinecarboxylic acid (δ-lactam compound):
The manufacture of Sigma-Aldrich Amada Co., Ltd., trade name " (S) -6- oxo -2-piperidinecarboxylic acid "
(3) 3- (2- oxo -1- nitrogen heterocyclic heptyl) propionic acid (ε-lactam compound):
The manufacture of Sigma-Aldrich Amada Co., Ltd., trade name " 3- (2- oxo aza ring hept- 1- yl) propionic acid "
[the comparison product of (A) ingredient]
(4) polyvinylpyrrolidone:
Wako Pure Chemical Industries, Ltd.'s manufacture, trade name " polyvinylpyrrolidone K25 " and Wako Pure Chemical Industries strain formula meeting Society's manufacture
(5) proline:
Wako Pure Chemical Industries, Ltd.'s manufacture, trade name " DL-proline "
[(3-B) ingredient]
(6) aluctyl:
Wako Pure Chemical Industries, Ltd.'s manufacture, trade name " aluctyl "
[(3-C) ingredient]
(7) sodium monofluorophosphate:
It is bought from Rhodia solar corona company, trade name " sodium monofluorophosphate "
[(3-D) ingredient]
(8) potassium nitrate:
Wako Pure Chemical Industries, Ltd.'s manufacture, trade name " potassium nitrate "
Following " effective components of (i) A phase " are mixed with " adding ingredient of (ii) A phase " in Purified Water under room temperature Dissolution prepares A phase.In addition, following " adding ingredients of (iii) B phase " are dissolved or dispersed in propylene glycol under room temperature, preparation B phase.Then, addition mixing B phase in the A phase in stirring, prepares C phase.Finally, using 1.5L kneader (tor work under room temperature Manufactured by being used as) following " adding ingredients of (iv) C phase " are mixed in C phase, it is depressurized to 4kPa and carries out deaeration, obtain denfifrice 1.0kg (100 mass parts).The combined amount of each ingredient is as shown in table 25~29.(effective component that is mixed in A phase, B phase, C phase and Other adding ingredients)
(i) effective component of A phase: 2-pyrrolidone-5-carboxylic acid, 6- oxo -2-piperidinecarboxylic acid, 3- (2- oxo -1- azacyclo- Heptane base) propionic acid, aluctyl, sodium monofluorophosphate, potassium nitrate
(ii) adding ingredient of A phase: 70 mass % D-sorbites, saccharin sodium, sodium hydroxide
(iii) adding ingredient of B phase: propylene glycol, xanthan gum, sodium carboxymethylcellulose, methyl p-hydroxybenzoate
(iv) adding ingredient of C phase: silicic acid anhydride, NaLS, fragrance
Each denfifrice obtained as described above, dentinal tubule early stage sealing effect, pain relief effect and use feeling The evaluation of (taste) is carried out by experimental example 3-1~3-3 below.
The evaluation of (experimental example 3-1) dentinal tubule early stage sealing effect
Using the denfifrice prepared as described above, by the method for Pashley et al. (J.Dent.Res.57,187-193, 1978) passability of the liquid of political reform measurement dentinal tubule, evaluates the dentinal tubule early stage sealing effect of each denfifrice.
It is cut into the dentine piece of thickness 3mm from the tooth crown of people's molar, is ground with water-fast pouncing paper #2000, into one 37% phosphate aqueous solution acid etching is walked, makes the grinding of Dentinal tubules as sample.By each denfifrice 10g and containing suitable In the CaCl of 1.5mM2, be equivalent to the KH of 2.5mM2PO4, be equivalent to 0.1M NaCl, be equivalent to 0.1M acetic acid and 1.0 units/ The artificial saliva 20g of the pH7.0 of the acid phosphatase of mL is mixed, and obtains 3 times of dilutions, using this liquid as disposition liquid.In addition, dilute The reasons why releasing 3 times is as it is assumed that denfifrice is by saliva dilution at 3 times when brushing teeth.Sample, which is disposed herein in liquid, to be impregnated 3 minutes, is steamed Distilled water gently rinses, and removes extra disposition liquid, impregnates 15 hours at 37 DEG C in above-mentioned artificial saliva.Sample distilled water Sufficiently rinsing, after drained, is fixed on device, rushes distilled water under a certain pressure 5 minutes, and measurement passes through sample per unit The amount of time (5 minutes) distilled water calculates the passability inhibiting rate of each embodiment and comparative example for the throughput before disposition (formula (3-1)).Each embodiment and comparative example are evaluated with N=5, and the passability inhibition for constituting the sample of each embodiment is calculated The average value of rate, if average value at 60% or more, is evaluated as embodiment or comparative example and has dentinal tubule early stage Sealing effect.
[number 4]
Formula (3-1):
Footnote (*) in formula (3-1)
Throughput refers to 5 minutes amount of distilled water passed through (μ L).
The evaluation of (experimental example 3-2) pain relief effect
By 3 have brush teeth after gargle when feel transient pain tooth allergy symptom of feeling conduct by Examination person.Using the denfifrice prepared same as experimental example 3-1, brush teeth 2 times within subject 1 day.When to gargling immediately after brushing teeth after 2 days Pain degree given a mark according to (1~5 point) of following standards of grading, evaluate pain relief effect from the average value of 3 scores.This Outside, it is 1 point of following standards of grading that the pain degree before on-test, which is all subjects,.
(standards of grading of pain degree)
5 points: imperceptible pain
4 points: fundamental sensation is less than pain
3 points: only feeling some pain, but there is no problem
2 points: feeling a little pain
1 point: feeling suitable pain
(evaluation criterion of pain relief effect)
A: average value 5 divides
B: average value 4 divides more than and less than 5 points
C: average value 3 divides more than and less than 4 points
D: average value 2 divides more than and less than 3 points
E: average value is less than 2 points
The evaluation of (experimental example 3-3) use feeling (taste)
When carrying out the evaluation of pain relief effect to 3 subjects in experimental example 3-2, to combining the puckery of each denfifrice The use feeling (taste) of taste, metallic taste, peculiar smell etc. carries out questionnaire survey.In questionnaire, beaten according to following standards of grading (1~4 point) Point.From the score average of 3 subjects, the use feeling (taste) of each denfifrice is evaluated.
(standards of grading of use feeling (taste))
4 points: good
3 points: slightly good
2 points: slightly worse
1 point: poor
(evaluation criterion of use feeling (taste))
A: more than average value 3.5 divides
B: average value 3.0 divides more than and less than 3.5 points
C: average value 2.0 divides more than and less than 3.0 points
D: average value is less than 2.0 points
[table 25]
Table 25
[table 26]
Table 26
[table 27]
Table 27
[table 28]
Table 28
[table 29]
Table 29
It was found from the result of experimental example 3-1~3-3 shown in the table 25~29: the denfifrice that (A) ingredient is used alone (is implemented Example 3-26) dentinal tubule early stage sealing effect, pain relief effect, use feeling (taste) relatively used individually (3- B) ingredient or use (A) ingredient comparison product (polyvinylpyrrolidone or proline) denfifrice (comparative example 1~3) more It is excellent.The dentinal tubule early stage for being mixed with the denfifrice (embodiment 3-1~3-25) of (A) ingredient and (3-B) ingredient is closed It is that effect, pain relief effect, use feeling (taste) relatively use individually (A) ingredient and (3-B) ingredient or use (A) at The denfifrice (embodiment 3-26, comparative example 3-1~3-3) of the comparison product (polyvinylpyrrolidone or proline) divided is significant excellent It is different.In addition to (A) ingredient and (3-B) ingredient, also it is mixed in the denfifrice (embodiment 3-16~3-19) of (3-C) ingredient, tooth sheet Matter tubule early stage sealing effect is very excellent.In addition, being mixed in the denfifrice (embodiment 3-24 and 3-25) of (D) ingredient, ache It is very excellent that pain mitigates effect.Further, it is mixed with denfifrice (embodiment 3-20~3- of (3-C) ingredient He (3-D) ingredient 23) in, dentinal tubule early stage sealing effect and pain relief effect are very excellent.
These results indicate that composition for oral cavity of the invention is imitated in dentinal tubule early stage sealing effect, pain relief It is excellent in terms of fruit and use feeling (taste).These results are also shown that composition for oral cavity of the invention (3) in dentinal tubule morning It is significantly excellent in terms of phase sealing effect, pain relief effect and use feeling (taste).
Formulation Example is given further below.In such Formulation Example, available effect same as the above embodiments.
[table 30]
30 Formulation Example 3-1 (collutory) of table
(A)/(B)=3.0
[table 31]
31 Formulation Example 3-2 (collutory) of table
(A)/(B)=2.0
[table 32]
32 Formulation Example 3-3 (collutory) of table
(A)/(B)=1.0
Embodiment 4-1~4-22 and comparative example 4-1
[primary raw material used]
[(A) ingredient]
(A-1): 2-pyrrolidone-5-carboxylic acid
Ajincomoto Co., Inc's manufacture, " AJIDEW A-100 (registered trademark) "
(A-2): 6- oxo -2-piperidinecarboxylic acid
The manufacture of Sigma-Aldrich Amada Co., Ltd., trade name " (S) -6- oxo -2-piperidinecarboxylic acid "
(A-3): 3- (2- oxo -1- nitrogen heterocyclic heptyl) propionic acid
The manufacture of Sigma-Aldrich Amada Co., Ltd., trade name " 3- (2- oxo aza ring hept- 1- yl) propionic acid "
[(B) ingredient]
(B-1): potassium nitrate
Wako Pure Chemicals Co., Ltd. manufacture, special grade chemical
[(C) ingredient]
(C-1): sodium fluoride
The manufacture of Stella Chemifa company, trade name " sodium fluoride "
(C-2): sodium monofluorophosphate
The manufacture of Rhodia solar corona company, trade name " sodium monofluorophosphate "
[other adding ingredients]
Silicic acid anhydride (grinding agent), NaLS (anionic surfactant), propylene glycol (thickener), 70 mass % D-sorbite (thickener), sodium carboxymethylcellulose (adhesive), sodium hydroxide (pH adjusting agent), saccharin sodium (sweetener), perfume Material, methyl p-hydroxybenzoate (preservative), Purified Water (solvent)
Using above-mentioned ingredient, (mass parts) are matched according to shown in table 33~35, pass through following usual denfifrice Preparation method prepares denfifrice 1.0kg (100 mass parts).
(preparation method of denfifrice)
Following " effective components of (i) I phase " are mixed with " adding ingredient of (ii) I phase " in Purified Water under room temperature Dissolution prepares I phase.In addition, following " adding ingredients of (iii) II phase " are dissolved or dispersed in propylene glycol under room temperature, system Standby II phase.Then, addition mixing II phase in the I phase in stirring, prepares III phase.Finally, using 1.5L kneader under room temperature (manufactured by tor work) mixes following " adding ingredients of (iv) III phase " in III phase, is depressurized to 4kPa and carries out deaeration, Obtain denfifrice 1.0kg (100 mass parts).The combined amount of each ingredient is as shown in table 33~35.(I phase, II phase mix in III phase Effective component and other adding ingredients)
(i) effective component of I phase: 2-pyrrolidone-5-carboxylic acid, 6- oxo -2-piperidinecarboxylic acid, 3- (2- oxo -1- azacyclo- Heptane base) propionic acid, potassium nitrate, sodium fluoride
(ii) adding ingredient of I phase: 70 mass % D-sorbites, saccharin sodium, sodium hydroxide
(iii) adding ingredient of II phase: propylene glycol, sodium carboxymethylcellulose, methyl p-hydroxybenzoate
(iv) adding ingredient of III phase: silicic acid anhydride, NaLS, fragrance
To each denfifrice obtained as described above, evaluated as follows for the mitigation because of pain caused by hyperesthesia Effect and use feeling (taste).
(evaluation for the mitigation effect because of pain caused by hyperesthesia)
3 had the tooth that transient pain is felt when gargling after brushing teeth, allergy of feeling symptom conduct 1 Group, have 8 groups totally 24 be used as subject, 8 kinds of (" embodiment 4-1 "~" embodiment 4- in the 23 kinds of denfifrice prepared as described above 8 " denfifrice) each group is distributed to, it brushes teeth twice a day 3.After 4th day, all groups use from above-mentioned I phase remove effectively at Point and the placebo dentifrice for preparing, be carried out similarly brushing teeth twice a day.According to following standards of grading to from be switched to comfort The pain degree just brushed teeth when gargling later after agent denfifrice starts 1 week is given a mark (1~5 point), and calculating 3 by group has symptom The average value of scoring.
After being spaced apart about 3 weeks, to above-mentioned 8 groups totally 24 subjects, other 8 kinds of denfifrice (" embodiments of each group are distributed to 4-9 "~" embodiment 4-16 " denfifrice), carry out same evaluation test.
After being spaced apart 3 weeks again, to 7 groups in above-mentioned subject totally 21, other 7 kinds of denfifrice (" implementations of each group are distributed to The denfifrice of example 4-17 "~" embodiment 4-22 ", " comparative example 4-1 "), carry out same evaluation test.
From the grade average calculated each denfifrice, according to following evaluation criterions, to because of pain caused by hyperesthesia Mitigation effect evaluated.In addition, the pain degree before each evaluation test starts is full subject according to following standards of grading It is 1 point.
(standards of grading of pain degree)
5 points: imperceptible pain
4 points: fundamental sensation is less than pain
3 points: only feeling some pain, but there is no problem
2 points: feeling a little pain
1 point: feeling suitable pain
(to the evaluation criterion of the mitigation effect because of pain caused by hyperesthesia)
A: average value 4.5 divides above and 5.0 points or less
B: average value 4.0 divides more than and less than 4.5 points
C: average value 3 divides more than and less than 4 points
D: average value 2 divides more than and less than 3 points
E: average value is less than 2 points
(evaluation of use feeling (taste))
When the mitigation effect of pain caused by because of hyperesthesia carries out evaluation test, for each group subject, to comprehensive The use feeling (taste) for having closed astringent taste, metallic taste, peculiar smell of this denfifrice etc. carries out questionnaire, according to following standards of grading marking (1 ~4 points), calculate average value.According to following evaluation criterions, use feeling (taste) is evaluated from the grade average of calculating.
(standards of grading of use feeling (taste))
4 points: good
3 points: relatively good
2 points: poor
1 point: poor
(evaluation criterion of use feeling (taste))
A: more than average value 3.5 divides
B: average value 3.0 divides more than and less than 3.5 points
C: average value 2.0 divides more than and less than 3.0 points
D: average value is less than 2.0 points
Each embodiment and comparative example evaluated according to above-mentioned evaluation method and evaluation criterion, caused by because of hyperesthesia Mitigation effect and use feeling (taste) merging of pain are documented in table 33~35.
[table 35]
Table 35
*1Sodium hydroxide is the appropriate amount for adjusting the pH (20 DEG C) of denfifrice and using to 7
The denfifrice for the comparative example 4-1 for containing (4-B) ingredient without containing (A) ingredient is opened from placebo dentifrice is switched to After beginning 1 week when gargling after just brushing teeth, substantially not to the mitigation effect because of pain caused by hyperesthesia, use feeling (taste Road) bad (table 35).
Contain the denfifrice of the embodiment 4-22 of (A) ingredient and the Toothbrushing agent phase of comparative example 4-1 without containing (4-B) ingredient Than, since being switched to placebo dentifrice after 1 week when gargling after just brushing teeth to because of pain caused by hyperesthesia Mitigate effect and use feeling (taste) is excellent (table 35).
On the other hand, the denfifrice of embodiment 4-1~4-21 containing (4-B) ingredient and (A) ingredient is from being switched to comfort Agent denfifrice start 1 week after just brush teeth after gargle when, pain caused by effectively mitigating because of hyperesthesia, confirm to because Pain caused by hyperesthesia is significantly reduced effect (table 33 and 34).Further acknowledge the denfifrice of embodiment 4-1~4-21 With good use feeling (taste).
In addition to (A) ingredient, (4-B) ingredient also contain the denfifrice of the embodiment 4-16~4-21 of (4-C) ingredient from switching After starting 1 week for placebo dentifrice when gargling after just brushing teeth, because of pain relief caused by hyperesthesia to fundamental sensation Less than or the degree that totally can not feel, confirm by the way that containing (4-C) ingredient, the effect of (A) ingredient is more preferable, to because feeling The mitigation effect of pain caused by allergy is more significant (according to the comparison of embodiment 4-11 and embodiment 4-16~4-19 and in fact Apply the comparison of a 4-2 Yu embodiment 4-20,4-21).
In the following, providing 3 kinds of Formulation Examples of composition for oral cavity of the present invention.Such Formulation Example obtains and above-mentioned implementation The composition for oral cavity of example is similarly significantly reduced effect and good use feeling (taste to because of pain caused by hyperesthesia Road).
[table 36]
36 Formulation Example 4-1 (collutory) of table
*1Adjust the appropriate amount when pH (20 DEG C) to 7 of collutory
[table 37]
37 Formulation Example 4-2 (collutory) of table
*1It is scaled fluorine amount
*2Adjust the appropriate amount when pH (20 DEG C) to 7 of collutory
[table 38]
38 Formulation Example 4-3 (denfifrice) of table
*1It is scaled fluorine amount
*2Adjust the appropriate amount when pH (20 DEG C) to 7 of collutory
Embodiment 5-1~5-14 and comparative example 5-1~5-5 (denfifrice)
Prepare the denfifrice formed shown in table 39~41.That is, under room temperature in Purified Water by water-soluble composition (ingredient (A), at Divide (5-B), sodium fluoride, saccharin sodium, D-sorbite etc.) mixed dissolution, prepare A phase.On the other hand, make in propylene glycol under room temperature The dissolution such as the oil-soluble ingredients such as methyl p-hydroxybenzoate, the Sodium Polyacrylate as adhesive, sodium alginate or dispersion, preparation B phase.Then, addition mixing B phase in the A phase in stirring, prepares C phase.Perfume is mixed in C phase using 1.5L kneader under room temperature Material, silicic acid anhydride, other compositions (NaLS etc.) are depressurized to 4kPa and carry out deaeration, prepare each composition.In addition, table 39 The unit of each ingredient combined amount is quality % in~41.
[primary raw material used]
[(A) ingredient]
(1) 2-pyrrolidone-5-carboxylic acid:
Ajincomoto Co., Inc's manufacture, trade name " AJIDEW A-100 (registered trademark) "
(2) 6- oxo -2-piperidinecarboxylic acid:
The manufacture of Sigma-Aldrich Amada Co., Ltd., trade name " (S) -6- oxo -2-piperidinecarboxylic acid "
(3) 3- (2- oxo -1- nitrogen heterocyclic heptyl) propionic acid (ε-lactam compound):
The manufacture of Sigma-Aldrich Amada Co., Ltd., trade name " 3- (2- oxo aza ring hept- 1- yl) propionic acid "
[the comparison product of (A) ingredient]
(4) polyvinylpyrrolidone:
Wako Pure Chemical Industries, Ltd.'s manufacture, trade name " polyvinylpyrrolidone K25 "
(5) proline:
Wako Pure Chemical Industries, Ltd.'s manufacture, trade name " DL-proline "
[(5-B) ingredient]
(6) hydroxyethyl cellulose dimethyl diallyl ammonium chloride:
Japanese national starch Chemical Co., Ltd. (Japanese: Japanese エ ヌ エ ス シ ー Co., Ltd.) manufacture, trade name " CELQUAT L-200 (Japanese: セ ル コ ー ト L-200) "
(7) chlorination O- [2- hydroxyl -3- (dimethylamino) propyl] hydroxyethyl cellulose:
Lion Corporation's manufacture, trade name " LEOGARD GP (Japanese: レ オ ガ ー De GP) " (low viscosity product)
(8) chlorination O- [2- hydroxyl -3- (dimethylamino) propyl] hydroxyethyl cellulose:
The manufacture of flower king's Chemical Co., Ltd., trade name " POIZ C-150L (Japanese: Port イ ズ C-150L) " (high viscosity Product)
[the comparison product of (5-B) ingredient]
(9) cation guar gum:
Rhodia's manufacture, trade name " JAGUAR C-13S "
[other compositions]
(10) sodium fluoride:
The manufacture of Stella Chemifa company, trade name " sodium fluoride "
The denfifrice of each embodiment and comparative example is supplied in following experimental example 5-1~5-4.
The evaluation of experimental example 5-1. color spot formation inhibitory effect
1. the preparation of green tea extractive liquor
Green tea extractive liquor is prepared with the extracting method recorded in food composition analysis method.That is, about 90 DEG C of tap water 100mL It is middle to be added containing 3g green tea (the self-produced tea of tea grower 980 (Japanese: farmers' oneself go out tea 980), Ito En Ltd.'s system Make) tea bag, extract 2 minutes.
2. forming the evaluation of inhibitory effect using the color spot of hydroxyapatite (HA) piece
With spectrophotometer (CM2022, Konica Minolta Opto Inc. manufacture) to the face #1 that is put to the test, 500 sand paper Grind obtained HA piece (APP-735；Pentax Co., Ltd (Japanese: ペ Application タ ッ Network ス Co., Ltd.) manufacture) initial stage HA Color difference is measured.Then, 6 HA pieces are mounted on bite-block (Japanese: マ ウ ス ピ ー ス), are fixed on 11 volunteers' Lower jaw tongue side.Set time is 1 hour, stirs in distilled water after cleaning, is impregnated 5 minutes with green tea extractive liquor.Repeat this oral cavity Interior fixation and after impregnating 3 times in green tea extractive liquor, the denfifrice of each embodiment is diluted with 3 times of distilled water, is centrifuged supernatant at it Dipping these HA pieces 5 minutes in liquid (room temperature, 20 minutes, 10,000 turn).It is then gently rinsed, is drawn with filter paper more with distilled water Remaining moisture.In addition, the reasons why 3 times of dilutions of preparation, is because it is assumed that denfifrice is by saliva dilution when brushing teeth.With distilled water into The reasons why row rinsing, is because it is assumed that denfifrice is gargled after.Fixation in this oral cavity is carried out twice a day, in green tea extractive liquor It impregnates and in disposition liquid dipping, other times is immersed in physiological saline.This operation repeats 14, with spectrophotometric determination HA Color difference, use L*a*b*The b of color specification system*Value evaluation degree of staining.b*Value is calculated by following formula (5-0).
Formula (5-0):
(Δb*Value)=14 Time of Day disposition after b*Value-initial stage b*Value
[evaluation criterion of color spot formation inhibitory effect)
Each embodiment of a series of experimental implementation and comparative example are carried out respectively with N=3, calculate each Δ b*Value is averaged Value forms inhibitory effect with following evaluation criterion evaluation color spots.
A: Δ b*Value is less than 0.5
B: Δ b*Value is for 0.5 more than and less than 3.0
C: Δ b*Value is for 3.0 more than and less than 6.0
D: Δ b*Value is less than 6.0
The evaluation of experimental example 5-2. color spot removal effect
1. the preparation of dense black tea extracting solution
3 bags of black tea tea bags (day east black tea Daily Club (Japanese: day east black tea デ is put into the 200mL distilled water of boiling イ リ ー Network ラ Block), Mitsui Norin Co., Ltd. manufacture) investment, extract 10 minutes.Then, with filter paper (NO.5C, ADVANTEC Toyo Co., Ltd.'s (Japanese: ア De バ ンテック Toyo Co., Ltd.) manufacture) filtering extracting solution, as dense black tea extracting solution.
2. color spot model is made
HA (hydroxyapatite) piece (APP-735；HOYA Corp. manufacture) surface carry out asperities grinding with sandblasting after, This HA piece successively impregnates 20 minutes in 0.5 mass % albumin solution, soaks in the dense black tea extracting solution of above-mentioned project 1 preparation It stain 20 minutes, is impregnated 20 minutes in 0.3 mass % ferric chloride solution, is repeated 20 times altogether, prepares color spot model.
3. the removal test of color spot model
Initially, as standard value, color spot is measured with spectrophotometer (CM2022, Konica Minolta Opto Inc. manufacture) Model formed before HA piece coloration, with experiment 1 in the same manner as measure L*a*b*The L of color specification system*Value, as L*0.Then, it measures such as The coloration of the color spot model of the upper preparation, as coloration (L before cleaning*1)。
To the HA piece for forming this color spot model, in toothbrush (column of CLINICA toothbrush (Japanese: Network リ ニ カ Ha Block ラ シ) 4, lion The manufacture of king Co., Ltd.) brushhead be full of the denfifrice of each embodiment with 3 times of distilled water diluted liquid 1mL, brush teeth 3 points Clock.HA piece is gently rinsed with distilled water after brushing teeth, and extra moisture is drawn with filter paper.After HA piece is dry, coloration after measurement is brushed teeth (L*2).According to these measured values, color spot removal rate is found out by following formula (5-1).
[number 5]
Formula (5-1):
[evaluation criterion of color spot removal effect)
Each embodiment of a series of experimental implementation and comparative example are carried out with N=3, calculate being averaged for each color spot removal rate Value evaluates color spot removal effect with following evaluation criterions.
A: color spot removal rate is 80% or more
B: color spot removal rate is 60% more than and less than 80%
C: color spot removal rate is 30% more than and less than 60%
D: color spot removal rate is less than 30%
The evaluation of experimental example 5-3. luster effect
By test face #3,500 sand paper grinds HA piece (APP-735；Pentax Co., Ltd manufacture), each embodiment it is clean Tooth agent is diluted with 3 times of distilled water, these HA pieces 5 are impregnated in its centrifuged supernatant (room temperature, 20 minutes, 10,000 turn) and are divided.With It is gently rinsed with distilled water afterwards, extra moisture is drawn with filter paper.Then, in artificial saliva (CaCl2: 1.0mmol/L, KH2PO4: 3.0mmol/L, acetic acid: 100mmol/L, NaCl:100mmol/L, pH6.5) in 37 DEG C dipping.This is operated 3 times a day, It is co-continuous to carry out 3.
[evaluation criterion of luster effect)
HA piece is taken out after 3 days, is spontaneously dried after sufficiently being rinsed with distilled water, by 5 subjects with following estimators Standards of grading carry out luster effect evaluation.Furthermore.Each embodiment and comparative example is tested to carry out with N=3.Final calculate is commented The average value of valence person scoring evaluates luster effect with following average value standards.
(standards of grading of estimator)
3: whole faces are glossy
2: glossy in addition to a part
1: a part of glossy
0: lackluster (unchanged)
(the grade average standard of estimator)
A:2.5 points or more
B:1.6 points more than and less than 2.5 points
C:0.5 points more than and less than 1.6 points
D: less than 0.5 point
The evaluation of experimental example 5-4. preparation use feeling
5 group members suck disposition liquid 30 seconds after 3 times of each denfifrice distilled water dilutions.
(evaluation criterion of preparation use feeling)
With following standards of grading, the evaluation of the preparation use feeling after being disposed liquid use.Final calculating 5 is averaged Value, evaluates preparation use feeling with the standard of following average value.
(standards of grading of estimator)
3: good use feeling.
2: feeling the taste that slightly bitter taste is unhappy
1: can feel the unhappy taste of bitter taste
0: can feel the unhappy taste of strong bitterness
A:2.5 points or more
B:1.6 points more than and less than 2.5 points
C:0.5 points more than and less than 1.6 points
D: less than 0.5 point
[table 39]
Table 39
[table 40]
Table 40
[table 41]
Table 41
The color spot removal effect and preparation use feeling of the composition of embodiment 5-14 containing (A) ingredient are excellent (table 41). Color spot containing (A) ingredient and the composition of the embodiment 5-1~5-13 of (5-B) ingredient forms inhibitory effect, color spot removal effect Fruit, luster effect and preparation use feeling are well-balanced excellent (table 39 and 40).In contrast, lack the comparative example of (B) ingredient Composition in, do not entirely reach the composition (table 41) of aforementioned four effect.This result shows that, oral cavity group of the invention It closes object to pass through containing (A) ingredient and (5-B) ingredient, forms inhibitory effect, color spot removal effect, luster effect and preparation in color spot It is excellent in use feeling.
Embodiment 5-15~5-17 (collutory)
The embodiment of collutory is given below.
The stainless of blender with 31 motors (Japanese: ス リ ー ワ ン モ ー タ ー) and rotating vane is being installed In steel making container, the Purified Water of specified amount is put into, puts into (A) ingredient, (5- in the blending constituent of each embodiment while stirring B) the water soluble ingredients such as ingredient, D-sorbite are allowed to dissolve.On the other hand, it is being equipped with 31 motors and rotating vane Blender other stainless steel manufacture container in, put into the organic solvents such as the ethyl alcohol of specified amount, while stirring investment mixing The oil-soluble ingredients such as fragrance, methyl p-hydroxybenzoate in ingredient are allowed to dissolve.Further, dissolve water soluble ingredient Container in be added oil-soluble ingredients, stir 30 points, be prepared into the collutory of uniform solution.
[table 42]
The composition (collutory) of 42 Formulation Example 5-15 of table
[table 43]
The composition (collutory) of 43 Formulation Example 5-16 of table
[table 44]
The composition (collutory) of 44 Formulation Example 5-17 of table
Embodiment 6-1~6-14 and comparative example 6-1~6-2
In embodiment 5-1, other than it will form and replace with shown in table 45 and 46 and respectively to form, it is prepared as cleaning one's teeth Agent.The dentin collagen albumen coloring of each denfifrice inhibits evaluation to be evaluated with the following conditions.
[coloring of dentin collagen albumen inhibits evaluation]
Baurodont root is cut to block shape (Japanese: Block ロ ッ Network shape), cementum is removed by surface grinding.Remove cementum Part in, about 3.5mm × 3.5mm is covered as demineralization window, rest part with nail polish.Nail polish after drying at room temperature, Dipping 72 hours in the aqueous acetic acid (pH4.5) of 0.1mol/L prepare the cementum caries disease sample in window portion exposure collagen Product.Initially as initial value, color difference (L is measured*0、a*0、b*0).Then, composition of this sample in each embodiment and comparative example 3 times of water diluents in room temperature immersion 3 minutes, after being cleaned with distilled water, artificial saliva (CaCl at 37 DEG C2: 2.2mmol/ L、KH2PO4: 2.2mmol/L, acetic acid: 0.1mol/L, the clostridiopetidase A (manufacture of Type1A, Sigma company) from clostridium histolyticum: 0.2 unit/mL, pH6.5) middle dipping 5 hours.Then repeat leaching in 20 minutes in 0.2% bovine serum albumin(BSA) at 37 DEG C Dipping 5 times of 20 minutes in stain and 37 DEG C of coloring liquid (1) or (2).After experiment, color difference (L is implemented with N=3*1、a*1、b* 1) it measures, calculates average value.Color difference is measured using spectrophotometer (Konica Minolta Opto Inc.'s manufacture, CM-2022), Color inhibitory effect is stated evaluation criterion below the △ E value calculated by following formula (6-1) and is evaluated.These results such as table 45~46 It is shown.
Formula (6-1):
△ E value=((L*1-L*0)2+(a*1-a*0)2+(b*1-b*0)2)1/2
[coloring liquid]
Coloring liquid (1): 0.3% instant black tea (Kroger (registered trademark) instant tea (Instant Tea)) aqueous solution
Color liquid (2): 1.5% instant coffee (NESCAFE Excella: nest (Japanese: ネ ス レ) Amada Co., Ltd.)
Aqueous solution
[evaluation criterion]
A:0≤△ E < 2.0
B:2.0≤△ E < 4.0
C:4.0≤△ E < 6.0
D:6.0≤△ E < 8.0
[table 45]
Table 45
[table 46]
Table 46
In the composition of comparative example 6-1~6-2 without (A) ingredient, dentin collagen albumen coloring effect can't see, with This is opposite, the composition of embodiment 6-1~6-14 containing (A) ingredient, and it is excellent that dentin collagen albumen colours inhibitory effect. This result shows that, (A) ingredient is useful as the effective component of dentin collagen albumen coloration inhibitor.In addition, this result Show that composition for oral cavity (6) can play collagen coloring inhibitory effect.

Claims (6)

1. a kind of composition for oral cavity, wherein contain (A) ingredient: having gamma-lactam skeleton, δ-lactams skeleton or ε-interior Any one lactams skeleton in amide backbone and the lactam compound with acidic-group；And further contain
(B) ingredient: cationic cellulose；
The lactam compound be selected from 2-pyrrolidone-5-carboxylic acid, 4- (3- hydroxy phenyl) -4- aza-tricycle base (5.2.1.0 (2, 6)) dodecyl -8- alkene -3,5- glycol, 2- (3,5- dioxo -4- aza-tricycle base (5.2.1.0 (2,6)) dodecyl -8- alkene - 4- yl) benzoic acid and their salt, 6- oxo -2-piperidinecarboxylic acid, 4- (2- oxo -1- piperidyl) butyric acid, 1- ethyl -6- oxygen Generation-nipecotic acid and their salt, 3- (2- oxo -1- nitrogen heterocyclic heptyl) propionic acid, 3- (the bromo- 5- hydroxy phenyl of 2-) -1- One or more of methyl -2- caprolactam and their salt；Salt compound in the lactam compound is choosing Salt compound from the group that sodium salt, sylvite, magnesium salts, ammonium salt are formed,
The content of (A) ingredient is 0.1~10 mass %,
The content of (B) ingredient is 0.005~0.1 mass %.
2. composition for oral cavity as described in claim 1, wherein (A) ingredient is 2-pyrrolidone-5-carboxylic acid and/or selected from its sodium The salt compound in group that salt, sylvite, magnesium salts, ammonium salt are formed.
3. composition for oral cavity as claimed in claim 1 or 2, wherein the content of (A) ingredient is 0.5~5 mass %.
4. composition for oral cavity as claimed in claim 1 or 2, wherein (B) ingredient is two allyl of hydroxyethyl cellulose dimethyl Ammonium chloride.
5. a kind of color spot remover, wherein effective component be (A) ingredient: have gamma-lactam skeleton, δ-lactams skeleton or Any one lactams skeleton in ε-lactams skeleton and the lactam compound with acidic-group；And
(B) ingredient: cationic cellulose；
The lactam compound be selected from 2-pyrrolidone-5-carboxylic acid, 4- (3- hydroxy phenyl) -4- aza-tricycle base (5.2.1.0 (2, 6)) dodecyl -8- alkene -3,5- glycol, 2- (3,5- dioxo -4- aza-tricycle base (5.2.1.0 (2,6)) dodecyl -8- alkene - 4- yl) benzoic acid and their salt, 6- oxo -2-piperidinecarboxylic acid, 4- (2- oxo -1- piperidyl) butyric acid, 1- ethyl -6- oxygen Generation-nipecotic acid and their salt, 3- (2- oxo -1- nitrogen heterocyclic heptyl) propionic acid, 3- (the bromo- 5- hydroxy phenyl of 2-) -1- One or more of methyl -2- caprolactam and their salt；Salt compound in the lactam compound is choosing Salt compound from the group that sodium salt, sylvite, magnesium salts, ammonium salt are formed.
6. color spot remover as claimed in claim 5, wherein (A) ingredient is 2-pyrrolidone-5-carboxylic acid and/or its salt.
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