JP5004505B2 - Oral composition - Google Patents
Oral composition Download PDFInfo
- Publication number
- JP5004505B2 JP5004505B2 JP2006139485A JP2006139485A JP5004505B2 JP 5004505 B2 JP5004505 B2 JP 5004505B2 JP 2006139485 A JP2006139485 A JP 2006139485A JP 2006139485 A JP2006139485 A JP 2006139485A JP 5004505 B2 JP5004505 B2 JP 5004505B2
- Authority
- JP
- Japan
- Prior art keywords
- hydroxyapatite
- hyaluronic acid
- salt
- caries
- composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000000203 mixture Substances 0.000 title claims description 24
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 50
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims description 50
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 30
- 229920002674 hyaluronan Polymers 0.000 claims description 27
- 229960003160 hyaluronic acid Drugs 0.000 claims description 27
- 208000002925 dental caries Diseases 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 13
- 210000000214 mouth Anatomy 0.000 claims description 10
- 239000002324 mouth wash Substances 0.000 claims description 9
- 229940051866 mouthwash Drugs 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 7
- 239000000551 dentifrice Substances 0.000 claims description 5
- 230000000052 comparative effect Effects 0.000 description 17
- 238000012360 testing method Methods 0.000 description 16
- 210000003298 dental enamel Anatomy 0.000 description 14
- 239000002245 particle Substances 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- 229920002385 Sodium hyaluronate Polymers 0.000 description 9
- 229940010747 sodium hyaluronate Drugs 0.000 description 9
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 9
- 239000000606 toothpaste Substances 0.000 description 8
- 239000000306 component Substances 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 229940034610 toothpaste Drugs 0.000 description 6
- 239000001506 calcium phosphate Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 230000001737 promoting effect Effects 0.000 description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 210000000988 bone and bone Anatomy 0.000 description 4
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 4
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000001133 acceleration Effects 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 235000011010 calcium phosphates Nutrition 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
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- 241000251468 Actinopterygii Species 0.000 description 2
- 239000000120 Artificial Saliva Substances 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229920002683 Glycosaminoglycan Polymers 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 241000194017 Streptococcus Species 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 description 2
- FUWUEFKEXZQKKA-UHFFFAOYSA-N beta-thujaplicin Chemical compound CC(C)C=1C=CC=C(O)C(=O)C=1 FUWUEFKEXZQKKA-UHFFFAOYSA-N 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 238000013329 compounding Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 235000019688 fish Nutrition 0.000 description 2
- 239000004088 foaming agent Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical group [F-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 description 1
- CRBJBYGJVIBWIY-UHFFFAOYSA-N 2-isopropylphenol Chemical compound CC(C)C1=CC=CC=C1O CRBJBYGJVIBWIY-UHFFFAOYSA-N 0.000 description 1
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 238000004438 BET method Methods 0.000 description 1
- 229910014497 Ca10(PO4)6(OH)2 Inorganic materials 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- 208000006558 Dental Calculus Diseases 0.000 description 1
- 108010001682 Dextranase Proteins 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920001503 Glucan Polymers 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical class NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
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- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
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- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
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- 241000194019 Streptococcus mutans Species 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
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- XEFQLINVKFYRCS-UHFFFAOYSA-N Triclosan Chemical compound OC1=CC(Cl)=CC=C1OC1=CC=C(Cl)C=C1Cl XEFQLINVKFYRCS-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
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- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
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Description
本発明は、歯牙エナメル質の再石灰化促進による虫歯予防用の口腔用組成物に関する。 The present invention relates to an oral composition for preventing dental caries by promoting remineralization of tooth enamel.
歯のう蝕は、ストレプトコッカス・ミュータンス、ストレプトコッカス・ソブライナスなどの口腔内連鎖球菌(虫歯菌)が歯牙表面に付着し、これら細菌が不溶性グルカンを産生し、プラーク(歯垢)を形成することから始まる。そのプラーク中で、上記細菌が食物を代謝することにより生じた酸が、歯牙エナメル質を脱灰し、初期う蝕状態となる。
歯牙表面のエナメル質はハイドロキシアパタイト結晶からなり、このハイドロキシアパタイトはリン酸カルシウムから構成されていて、カルシウムやリン酸の供給源として有効と考えられている。それで、これまで、この脱灰部を再石灰化するため、フッ化物や歯牙の無機成分と類似の結晶構造を有するハイドロキシアパタイトの微粒子を配合した歯磨き剤などが開発されてきた。
しかしながら、フッ化物やハイドロキシアパタイトの使用だけでは再石灰化は十分ではなかった。
For dental caries, Streptococcus mutans, Streptococcus sobrinaus, and other oral streptococci (carious fungi) adhere to the tooth surface, and these bacteria produce insoluble glucan and form plaques. Begins. In the plaque, the acid produced by the bacteria metabolizing food demineralizes the tooth enamel and enters an initial caries state.
The enamel on the tooth surface is composed of hydroxyapatite crystals, and this hydroxyapatite is composed of calcium phosphate and is considered to be effective as a source of calcium and phosphate. So far, in order to remineralize the demineralized portion, a dentifrice containing a fine particle of hydroxyapatite having a crystal structure similar to that of fluoride or an inorganic component of a tooth has been developed.
However, remineralization was not sufficient only by the use of fluoride or hydroxyapatite.
そこで、ハイドロキシアパタイトについては、他の成分を配合することなどにより改善がなされてきた。配合されるものとしては、たとえば、水溶性セルロース(特許文献1)、温度感応性高分子化合物(特許文献2)、キシリトール(特許文献3)、イソフラボン(特許文献4)、トレハロース(特許文献5)、植物抽出タンパク質(特許文献6)、ローヤルゼリー(特許文献7)などがある。 Thus, hydroxyapatite has been improved by blending other components. For example, water-soluble cellulose (patent document 1), temperature-sensitive polymer compound (patent document 2), xylitol (patent document 3), isoflavone (patent document 4), trehalose (patent document 5). Plant extract protein (Patent Document 6), royal jelly (Patent Document 7), and the like.
一方、ヒアルロン酸はグリコサミノグリカンの一種であり、硝子体、関節液などに含まれる生体成分として知られている。このヒアルロン酸は医薬品、化粧品、食品などに用いられるほか、口腔用としても使用される。口腔用としては、たとえば、歯周疾患の予防のため抗酸化剤と併用するもの(特許文献8)、口腔粘膜への付着改善のため薬物、軟質無水ケイ酸、疎水性軟質基剤に配合するもの(特許文献9)、歯石防止、抗う蝕などのための亜鉛化合物を含有する口腔用組成物に渋み改善剤としてヒアルロン酸を配合するもの(特許文献10)などがある。 On the other hand, hyaluronic acid is a kind of glycosaminoglycan and is known as a biological component contained in vitreous, joint fluid and the like. This hyaluronic acid is used not only for pharmaceuticals, cosmetics and foods but also for oral use. For oral use, for example, it is used in combination with an antioxidant for prevention of periodontal disease (Patent Document 8), and is added to a drug, soft anhydrous silicic acid, a hydrophobic soft base for improving adhesion to the oral mucosa. (Patent Document 9), and a composition for oral cavity containing a zinc compound for preventing tartar, anti-caries, and the like (Patent Document 10) containing hyaluronic acid as an astringency improving agent.
これまで、ハイドロキシアパタイトとヒアルロン酸を配合した口腔内で用いる組成物としては、歯の代替材料あるいは骨修復材料としての用途が記載されたものがある(特許文献11,12)が、これらはいずれも粒径の大きいハイドロキシアパタイトを用い、ヒアルロン酸の配合量も多い組成物であり、欠損した歯を修正あるいは代替するためのものであって、歯磨き剤、洗口剤のような虫歯の予防用のものとは異なっていた。また、これらの文献には、ヒアルロン酸をハイドロキシアパタイトと配合して使用することにより、エナメル質の再石灰化の促進に効果のあることは記載されていなかった。 Until now, as compositions used in the oral cavity in which hydroxyapatite and hyaluronic acid are blended, there are those described as applications for tooth substitutes or bone repair materials (Patent Documents 11 and 12). Is a composition that uses hydroxyapatite with a large particle size and contains a large amount of hyaluronic acid, and is intended to correct or replace missing teeth. It is used to prevent caries such as toothpaste and mouthwash. It was different. In addition, these documents did not describe that hyaluronic acid was used in combination with hydroxyapatite and was effective in promoting remineralization of enamel.
本発明は、脱灰したエナメル質の再石灰化促進による虫歯予防に優れた口腔用組成物の提供を目的としたものである。 The object of the present invention is to provide an oral composition excellent in preventing dental caries by promoting remineralization of decalcified enamel.
本発明者らは、ヒアルロン酸あるいはヒアルロン酸ナトリウムと、ハイドロキシアパタイトを併用することにより、歯エナメル質の再石灰化が促進されることを見出し、本発明を完成するに至った。 The present inventors have found that remineralization of tooth enamel is promoted by using hyaluronic acid or sodium hyaluronate in combination with hydroxyapatite, and have completed the present invention.
すなわち、本発明は、(1)ヒアルロン酸またはその塩、及びハイドロキシアパタイトを含有する虫歯予防のための口腔用組成物、(2)ヒアルロン酸又はその塩を0.001〜5重量%、ハイドロキシアパタイトを0.001〜50重量%配合した上記(1)に記載の虫歯予防のための口腔用組成物である。
さらに、本発明は、(3)上記(1)又は(2)に記載の虫歯予防のための口腔用組成物を含有する歯磨き剤又は洗口剤である。
That is, the present invention comprises (1) a composition for oral cavity for preventing caries containing hyaluronic acid or a salt thereof and hydroxyapatite, and (2) 0.001 to 5% by weight of hyaluronic acid or a salt thereof, hydroxyapatite. Is a composition for oral cavity for preventing dental caries according to (1) above.
Furthermore, the present invention is (3) a dentifrice or mouthwash containing the composition for oral cavity prevention for caries as described in (1) or (2) above.
本発明の口腔用組成物は、再石灰化促進試験の結果から明らかなとおり、比較例であるヒアルロン酸ナトリウム単独、ハイドロキシアパタイト単独又はヒアルロン酸ナトリウムと他のリン酸カルシウムとを併用した場合と比して、歯牙のエナメル質の再石灰化率が顕著に異なることがわかった。このことから、ヒアルロン酸又はその塩とハイドロキシアパタイトを併用した本発明は、脱灰した歯牙のエナメル質の再石灰化を顕著に促進することができるため、う蝕を積極的に抑制するのに大変優れた効果を有する口腔内組成物を提供することが可能となった。 As is apparent from the results of the remineralization acceleration test, the oral composition of the present invention is a comparative example of sodium hyaluronate alone, hydroxyapatite alone or sodium hyaluronate and other calcium phosphates in combination. It was found that the remineralization rate of tooth enamel was significantly different. From this fact, the present invention using hyaluronic acid or a salt thereof and hydroxyapatite in combination can remarkably promote the remineralization of the demineralized tooth enamel, and thus actively suppresses caries. It has become possible to provide an oral composition having a very excellent effect.
本発明の虫歯予防のための口腔用組成物は、ヒアルロン酸あるいはその塩とハイドロキシアパタイトを含有し、練り歯磨き、粉歯磨き、液状歯磨き等の歯磨類、洗口剤などとして用いられる。 The composition for oral cavity prevention of caries of the present invention contains hyaluronic acid or a salt thereof and hydroxyapatite, and is used as a toothpaste such as toothpaste, toothpaste, liquid toothpaste, mouthwash, and the like.
(ハイドロキシアパタイト)
本発明において使用されるハイドロキシアパタイトは、リン酸カルシウムの1種であり、通常の方法で合成されるものの他、天然硬組織としてサケ等の食用魚の魚骨、豚骨、牛骨等から得られる。
通常、ハイドロキシアパタイトは、化学量論的にはCa10(PO4)6(OH)2からなる組成で示されるが、Ca/Pモル比が1.67にならない非化学量論的なものであっても、ハイドロキシアパタイトの性質を示すと共にアパタイト構造をとることができ、このような、例えば、Ca/Pモル比1.4〜1.8程度の合成ハイドロキシアパタイトも本発明におけるハイドロキシアパタイトに含まれる。
(Hydroxyapatite)
Hydroxyapatite used in the present invention is a kind of calcium phosphate, and is obtained from fish bones, pork bones, cow bones, etc. of edible fish such as salmon as natural hard tissues, in addition to those synthesized by ordinary methods.
Usually, hydroxyapatite is stoichiometrically represented by a composition composed of Ca 10 (PO 4 ) 6 (OH) 2 , but is non-stoichiometric with a Ca / P molar ratio of not 1.67. Even if it has the properties of hydroxyapatite, it can take an apatite structure, and such hydroxyapatite having a Ca / P molar ratio of about 1.4 to 1.8 is also included in the hydroxyapatite in the present invention. It is.
本発明のハイドロキシアパタイトは、結晶性、低結晶性、非晶質のいずれであってもよいが、う蝕予防効果の点から、低結晶性又は非晶質のハイドロキシアパタイトが好ましい(以下、低結晶性ハイドロキシアパタイト及び非晶質のハイドロキシアパタイトを「アモルファスハイドロキシアパタイト」と称する。)。なお、「低結晶性」とは、X線回折ピークが、高結晶性の粉体に比べてブロードな結晶質のものをいい、「非晶質」とは、X線回折パターンが幅広いハローを示し、結晶の特徴を示す回折パターンが得られないものをいう。このようなアモルファスハイドロキシアパタイトは、例えば、湿式合成法により合成したアパタイトを凍結乾燥若しくは100℃以下の温度で乾燥し、又は300℃程度以下の温度で焼成して得ることができる。 The hydroxyapatite of the present invention may be crystalline, low crystalline or amorphous, but is preferably low crystalline or amorphous hydroxyapatite from the viewpoint of caries prevention effect (hereinafter referred to as “low hydroxyapatite”). Crystalline hydroxyapatite and amorphous hydroxyapatite are referred to as “amorphous hydroxyapatite”). “Low crystallinity” means that the X-ray diffraction peak is broader than that of highly crystalline powder, and “amorphous” means that the X-ray diffraction pattern has a wide halo. The diffraction pattern showing the characteristics of the crystal cannot be obtained. Such amorphous hydroxyapatite can be obtained, for example, by freeze-drying apatite synthesized by a wet synthesis method, drying at a temperature of 100 ° C. or lower, or baking at about 300 ° C. or lower.
本発明のハイドロキシアパタイトとしては、通常粉末状か、水に懸濁状であり、レーザ回折・散乱法粒度分布測定装置(LS 130)(ベックマン・コールター(株)製)で測定した最大粒径が、好ましくは40μm以下、特に好ましくは1μm以下である。最大粒径の下限は、製造上0.08μmである。また、マイクロトラック7340UPA粒度分布計(日機装(株)製)で測定した平均粒径は、好ましくは0.01〜10μm、特に好ましくは0.02〜5μmである。
なお、通常用いられるハイドロキシアパタイトのBET法による比表面積は、100m2/g以下程度である。また、必要に応じて、粉末化後に、乾燥処理、多孔化処理、静電処理等を施してもよい。
本発明におけるハイドロキシアパタイトの配合量は、う蝕予防効果と製造コスト、使用感の観点から、好ましくは、組成物全体の0.001〜50重量%であり、特に好ましくは0.01〜30重量%である。
The hydroxyapatite of the present invention is usually in powder form or suspended in water, and has a maximum particle size measured with a laser diffraction / scattering particle size distribution analyzer (LS 130) (manufactured by Beckman Coulter, Inc.). , Preferably 40 μm or less, particularly preferably 1 μm or less. The lower limit of the maximum particle size is 0.08 μm in production. The average particle size measured with a Microtrac 7340UPA particle size distribution meter (manufactured by Nikkiso Co., Ltd.) is preferably 0.01 to 10 μm, particularly preferably 0.02 to 5 μm.
In addition, the specific surface area by the BET method of the hydroxyapatite used normally is about 100 m < 2 > / g or less. Moreover, you may give a drying process, a porous process, an electrostatic process, etc. after powdering as needed.
The compounding amount of hydroxyapatite in the present invention is preferably 0.001 to 50% by weight, particularly preferably 0.01 to 30% by weight, based on the caries prevention effect, production cost, and usability. %.
(ヒアルロン酸)
本発明において用いられるヒアルロン酸又はその塩は、グルクロン酸とN−アセチルグルコサミンが結合した二糖類を繰り返し単位とするムコ多糖類である。本発明で言うヒアルロン酸とは、遊離のヒアルロン酸及びその誘導体を包含する。
平均分子量としては、特に制限はないが、通常、1万から500万程度のものが使用され、特に50万〜350万の範囲のものが好適である。
起源についても、特に制限はなく、例えば臍帯、動物皮膚、眼球ガラス帯、ニワトリの鶏冠などから抽出された動物由来品、微生物由来品(例えばストレプトコッカス属細菌)、合成品のいずれであっても良い。また、天然起源の場合の抽出方法、精製処理方法についても特に制限はない。
(hyaluronic acid)
Hyaluronic acid or a salt thereof used in the present invention is a mucopolysaccharide having a disaccharide in which glucuronic acid and N-acetylglucosamine are bound as a repeating unit. As used herein, hyaluronic acid includes free hyaluronic acid and its derivatives.
Although there is no restriction | limiting in particular as an average molecular weight, Usually, the thing of about 10,000 to 5 million is used, and especially the thing of the range of 500,000-3,500,000 is suitable.
The origin is not particularly limited, and may be any animal-derived product, microbial-derived product (eg, Streptococcus spp.), Or synthetic product extracted from, for example, umbilical cord, animal skin, eyeglass band, chicken hen's crown, etc. . There are no particular restrictions on the extraction method and the purification treatment method in the case of natural origin.
ヒアルロン酸の誘導体としては、口腔内において使用可能なものであれば特に制限はなく、例えば、硫酸化されたヒアルロン酸(特開平10−195107号公報参照)、アセチル化されたヒアルロン酸(特開平8−53501号公報参照)、乳酸などの生体内有機酸で置換されたヒアルロン酸(特開平6−16702号公報参照)、架橋されたヒアルロン酸(特開平7−97401号公報参照)などがある。
ヒアルロン酸の塩としては、口腔内において使用可能なものであれば特に制限はなく、ナトリウム塩、カリウム塩、リチウム塩、マグネシウム塩、カルシウム塩などの金属塩類、リジン塩、アルギニン塩、ヒスチジン塩等の塩基性アミノ酸塩、アンモニウム塩、トリエタノールアミン塩、ジイソプロパノールアミン塩等が好適なヒアルロン酸の塩として挙げられる。特に好ましくは、ナトリウム塩である。
The derivative of hyaluronic acid is not particularly limited as long as it can be used in the oral cavity. For example, sulfated hyaluronic acid (see Japanese Patent Laid-Open No. 10-195107), acetylated hyaluronic acid (Japanese Patent Laid-Open No. 8-53501), hyaluronic acid substituted with an in vivo organic acid such as lactic acid (see JP-A-6-16702), and crosslinked hyaluronic acid (see JP-A-7-97401). .
The salt of hyaluronic acid is not particularly limited as long as it can be used in the oral cavity. Metal salts such as sodium salt, potassium salt, lithium salt, magnesium salt, calcium salt, lysine salt, arginine salt, histidine salt, etc. The basic amino acid salts, ammonium salts, triethanolamine salts, diisopropanolamine salts, and the like are suitable as hyaluronic acid salts. Particularly preferred is a sodium salt.
市販品としては、ヒアルロン酸 ナトリウムQ−5(キューピー(株))、バイオヒアルロン酸ナトリウム((株)資生堂)、バイオヒアルロン酸 (旭化成(株))、ヒアルロン酸 FCH(紀文フードケミファ(株))等、数多くあり、いずれも好適に使用することができる。
上記ヒアルロン酸 及び/又はその塩は、単独で使用することもできるし、二種以上を組み合わせて使用することもできる。
ヒアルロン酸又はその塩の配合量は、う蝕予防効果と使用感の観点から見て、組成物全体の0.001〜5重量%が好ましく、0.01〜3重量%が特に好ましい。
Commercially available products include sodium hyaluronate Q-5 (Cuppy), bio sodium hyaluronate (Shiseido Co., Ltd.), bio hyaluronic acid (Asahi Kasei Co., Ltd.), hyaluronic acid FCH (Kibun Food Chemifa Corporation) Etc., and any of them can be suitably used.
The said hyaluronic acid and / or its salt can also be used individually, and can also be used in combination of 2 or more type.
The amount of hyaluronic acid or a salt thereof is preferably 0.001 to 5% by weight, particularly preferably 0.01 to 3% by weight, based on the caries prevention effect and the feeling of use.
(その他の添加剤)
本発明の口腔用組成物は、前述の成分に加えて、口腔用組成物に通常使用される添加剤である研磨剤、湿潤剤、発泡剤、増粘剤、防腐剤、香料、甘味料及び各種薬効成分などを含有することができる。これらの成分の具体例を下記に示す。
研磨剤:炭酸カルシウム、リン酸水素カルシウム、ピロリン酸カルシウム、シリカ、珪酸アルミニウム、水酸化アルミニウム、アルミナ、ゼオライト、酸化チタン、珪酸ジルコニウム等。
湿潤剤:グリセリン、プロピレングリコール、ポリエチレングリコール、ソルビトール、キシリトール等。
発泡剤:ラウリル硫酸ナトリウム、N−ラウロイルサルコシンナトリウム、非イオン性界面活性剤等。
増粘剤:ヒドロキシエチルセルロース、カルボキシメチルセルロースナトリウム、カラギーナン、カルボキシビニルポリマー、キサンタンガム、ゼラチン、プルラン、アルギン酸ナトリウム等。
防腐剤:パラオキシ安息香酸エステル、塩酸アルキルジアミノエチルグリシン、メチルパラベン、エチルパラベン、安息香酸ナトリウム等。
香料:メントール、スペアミント油、レモン油、ユーカリ油等。
甘味剤:サッカリンナトリウム、ステビアエキス、アスパルテーム等。
その他薬効成分:アラントイン、酢酸トコフェロール、イソプロピルフェノール、β−グリチルレチン酸、トリクロサン、クロルヘキシジン、デキストラナーゼ、クロロフィル、フラボノイド、トラネキサム酸、ヒノキチオール等。
なお、これら任意成分の配合量は、本発明の効果を妨げず、薬剤学的に許容できる範囲で適宜使用される。
(Other additives)
The oral composition of the present invention comprises, in addition to the above-mentioned components, abrasives, wetting agents, foaming agents, thickeners, preservatives, fragrances, sweeteners and additives that are usually used in oral compositions. Various medicinal ingredients can be contained. Specific examples of these components are shown below.
Abrasive: calcium carbonate, calcium hydrogen phosphate, calcium pyrophosphate, silica, aluminum silicate, aluminum hydroxide, alumina, zeolite, titanium oxide, zirconium silicate and the like.
Wetting agent: glycerin, propylene glycol, polyethylene glycol, sorbitol, xylitol, etc.
Foaming agent: sodium lauryl sulfate, sodium N-lauroyl sarcosine, nonionic surfactant and the like.
Thickener: hydroxyethyl cellulose, sodium carboxymethyl cellulose, carrageenan, carboxyvinyl polymer, xanthan gum, gelatin, pullulan, sodium alginate and the like.
Preservatives: paraoxybenzoic acid ester, alkyldiaminoethylglycine hydrochloride, methylparaben, ethylparaben, sodium benzoate and the like.
Perfume: menthol, spearmint oil, lemon oil, eucalyptus oil, etc.
Sweetening agents: sodium saccharin, stevia extract, aspartame, etc.
Other medicinal ingredients: allantoin, tocopherol acetate, isopropylphenol, β-glycyrrhetinic acid, triclosan, chlorhexidine, dextranase, chlorophyll, flavonoid, tranexamic acid, hinokitiol and the like.
In addition, the compounding quantity of these arbitrary components is used suitably in the range accept | permitted pharmacologically, without preventing the effect of this invention.
(調製法)
本発明において、ヒアルロン酸又はその塩や、ハイドロキシアパタイトを組成物に添加せしめる方法としては、当該製品の製造過程のいかなる時に添加しても良く、また、如何なる時に残余の原料と混合しても良いが、ヒアルロン酸又はその塩とハイドロキシアパタイトを予め混合してから他原料と混合することが最も望ましい。
(Preparation method)
In the present invention, as a method of adding hyaluronic acid or a salt thereof or hydroxyapatite to the composition, it may be added at any time during the production process of the product, and may be mixed with the remaining raw materials at any time. However, it is most preferable that hyaluronic acid or a salt thereof and hydroxyapatite are mixed in advance and then mixed with other raw materials.
以下に本発明の実施例と試験例について説明するが、本発明の範囲がこれによって限定されるものではない。なお、「%」は、特に断りがない限り重量%を意味する。
(アモルファスハイドロキシアパタイトの調製)
撹拌している水酸化カルシウム溶液中に、リン酸塩溶液を滴下し、析出する生成物を採取し、100℃以下で送風乾燥することによりアモルファスハイドロキシアパタイトを得た。得られたアモルファスハイドロキシアパタイトは、最大粒径が約1μm、最小粒径が約0.01μm、平均粒径が約0.03μmであった。
(結晶性ハイドロキシアパタイトの調製)
上記で得られたアモルファスハイドロキシアパタイトの一部を空気中にて800℃、2時間焼成して、結晶性ハイドロキシアパタイトを得た。
得られた結晶性ハイドロキシアパタイトは、最大粒径が約40μm、最小粒径が約0.1μm、平均粒径が約3.7μmであった。
(ヒアルロン酸ナトリウム)
実施例及び比較例において、ヒアルロン酸ナトリウムは、(株)資生堂製バイオヒアルロン酸ナトリウム 1%水溶液(MP−PE)を使用した。
EXAMPLES Examples and test examples of the present invention will be described below, but the scope of the present invention is not limited thereby. “%” Means% by weight unless otherwise specified.
(Preparation of amorphous hydroxyapatite)
A phosphate solution was dropped into the stirring calcium hydroxide solution, and the precipitated product was collected and blown and dried at 100 ° C. or lower to obtain amorphous hydroxyapatite. The obtained amorphous hydroxyapatite had a maximum particle size of about 1 μm, a minimum particle size of about 0.01 μm, and an average particle size of about 0.03 μm.
(Preparation of crystalline hydroxyapatite)
A part of the amorphous hydroxyapatite obtained above was baked in air at 800 ° C. for 2 hours to obtain crystalline hydroxyapatite.
The obtained crystalline hydroxyapatite had a maximum particle size of about 40 μm, a minimum particle size of about 0.1 μm, and an average particle size of about 3.7 μm.
(Sodium hyaluronate)
In the examples and comparative examples, sodium hyaluronate 1% aqueous solution of biohyaluronate sodium (MP-PE) manufactured by Shiseido Co., Ltd. was used.
(実施例及び比較例の口腔内組成物の調製)
下記組成の練歯磨剤、及び洗口剤を常法に従って製造した。
実施例中、実施例1〜11は練り歯磨き剤、実施例12〜16は洗口剤である。このうち、実施例4は結晶性ハイドロキシアパタイトを使用し、その他の実施例はアモルファスハイドロキシアパタイトを使用した例である。また比較例中、比較例1〜11は練り歯磨き剤、比較例12及び13は洗口剤である。このうち、比較例1〜2、比較例4〜5はアモルファスハイドロキシアパタイト単独の例、比較例3は結晶性ハイドロキシアパタイト単独の例、比較例6はハイドロキシアパタイトに代えて炭酸カルシウムを使用した例、比較例7はハイドロキシアパタイトに代えて第2リン酸カルシウムを使用した例、比較例8はハイドロキシアパタイトに代えてリン酸三カルシウムを使用した例、比較例9〜11はヒアルロン酸ナトリウム単独の例、比較例12はハイドロキシアパタイト単独の例、及び比較例13はヒアルロン酸ナトリウム単独の例である。
(Preparation of oral compositions of Examples and Comparative Examples)
A toothpaste and a mouthwash having the following composition were produced according to a conventional method.
In Examples, Examples 1 to 11 are toothpastes, and Examples 12 to 16 are mouthwashes. Among these, Example 4 uses crystalline hydroxyapatite, and the other examples are examples using amorphous hydroxyapatite. In Comparative Examples, Comparative Examples 1 to 11 are toothpastes, and Comparative Examples 12 and 13 are mouthwashes. Among these, Comparative Examples 1-2 and Comparative Examples 4-5 are examples of amorphous hydroxyapatite alone, Comparative Example 3 is an example of crystalline hydroxyapatite alone, Comparative Example 6 is an example of using calcium carbonate instead of hydroxyapatite, Comparative Example 7 is an example using dicalcium phosphate instead of hydroxyapatite, Comparative Example 8 is an example using tricalcium phosphate instead of hydroxyapatite, Comparative Examples 9-11 are examples of sodium hyaluronate alone, Comparative Example 12 is an example of hydroxyapatite alone, and Comparative Example 13 is an example of sodium hyaluronate alone.
[再石灰化促進試験]
再石灰化促進試験において、図中の「コントロール面」とは、実施例及び比較例の「口腔用組成物」がどの程度再石灰化効果を有するかを比較対象とする為の部分であり、「人工初期う蝕」の状態を維持したものである。人工初期う蝕(3.5×3.0mmのウインドウ)領域のうち、半分の部分である。
図中の「処理面」(図1においては「試験面」)とは、実施例及び比較例の被検体を次のように作用させた部分である。
(1)被検物質の調整は、歯磨剤、洗口剤を人工唾液との懸濁溶液にしたものを試験溶液とした。
(2)再石灰化促進試験は、人工初期う蝕試験体を各々の試験用液に24時間浸漬した。
[Recalcification promotion test]
In the remineralization acceleration test, the “control surface” in the figure is a part for comparing the degree to which the “oral composition” in Examples and Comparative Examples has a remineralization effect, The state of “artificial initial caries” is maintained. It is a half of the artificial initial caries (3.5 × 3.0 mm window) region.
The “treated surface” (“test surface” in FIG. 1) in the figure is a portion where the specimens of the example and the comparative example are operated as follows.
(1) The test substance was prepared by preparing a dentifrice and mouthwash in suspension with artificial saliva.
(2) In the remineralization promotion test, the artificial initial caries test specimen was immersed in each test solution for 24 hours.
(再石灰化促進試験方法)
再石灰化の促進効果を確認する為に、予め作成した人工初期う蝕試験試料を用いた。
人工初期う蝕試験試料の作成は、歯科保存、補綴処置の施されていないヒトの抜去歯の歯冠部を用い、エナメル質表面の汚れや、沈着物を除去した後、エナメル質表面の試験対象部位をNail Enamel(メイベリン社製)で3.5×3.0mmのウインドウを作成し、0.1M乳酸緩衝液(pH4.5、3.0mm CaCl2、1.8mm KH2PO4、0.5% CMC)に37℃、7日間浸漬させて、人工初期う蝕を作成した。なお、試験のコントロールには、3.5×3.0mmのウインドウのうち、歯冠登頂部側の半分をさらにNail Enamel(メイベリン社製)でマスキングし、比較対象部位(コントロール)とした。
被検物質の調製は、歯磨剤、洗口剤を人工唾液との懸濁溶液にしたものを試験溶液とした。
(Recalcification promotion test method)
In order to confirm the effect of promoting remineralization, an artificial initial caries test sample prepared in advance was used.
Preparation of the artificial initial caries test sample is performed by removing the dirt and deposits on the enamel surface using the crown of a human extracted tooth that has not undergone dental preservation and prosthesis treatment, and then testing the enamel surface. A 3.5 × 3.0 mm window was created with Nail Enamel (Maybelin) as a target site, and 0.1 M lactate buffer (pH 4.5, 3.0 mm CaCl 2 , 1.8 mm KH 2 PO 4 , 0 .5% CMC) at 37 ° C. for 7 days to prepare artificial initial caries. For control of the test, a half of the top of the crown of the 3.5 × 3.0 mm window was further masked with Nail Enamel (manufactured by Maybelline) to obtain a comparison target site (control).
The test substance was prepared by using a dentifrice and mouthwash in suspension with artificial saliva as a test solution.
再石灰化促進試験は、上記で作成した人工初期う蝕試験体を各々の試験溶液に24時間浸漬した後、試験体をマイクロカッターにて歯軸に対して平行となるように約500μm厚に切断し、その後、この切片を練り砥石、及び天然砥石を用い、注水下にて約100μm厚の平行薄切片となるように研磨を行った。研磨後、歯の再石灰化効果の確認を行う為、コンタクトマイクロラジオグラム(CMR)撮影を行ない(図1と図2参照)、人工初期う蝕部位の再石灰化の効果について、コンピュータを用いて解析を行った。 In the remineralization acceleration test, the artificial initial caries test specimen prepared above was immersed in each test solution for 24 hours, and then the specimen was about 500 μm thick so as to be parallel to the tooth axis with a microcutter. After cutting, this piece was polished using a kneading stone and a natural whetstone so as to obtain a parallel thin piece having a thickness of about 100 μm under water injection. After polishing, contact microradiogram (CMR) imaging was performed to confirm the remineralization effect of the teeth (see FIGS. 1 and 2), and the effect of the remineralization of the artificial initial caries site using a computer Analysis.
コンピュータでの画像解析は、Angmerらの式(B.Angmer, D.Carlstrom and J.E..Glas : Studies on Ultrastructure of Dental Enemel IV : The Mineralization of normal Human Enamel, J. Ultrastructure.Res.8, 12-23, 1963)を基に再石灰化したミネラル量を算出し、Damatoらの方法(F.A. Damato, R.Stang and K.W.Stephen : Effect of Fluoride Concentration on Reminerelization of Carious Enamel : an in vitro pH-Cycling Study, Caries Res, 24, 174-180,1990)に従って、各切片のコントロール面と処理面のミネラル喪失量△Z(%volume mineral ・ μm)を算出した。なお、再石灰化率は、以下の式により算出した。 Computer image analysis was performed using the formula of Angmer et al. (B. Angmer, D. Carlstrom and JE. Glas: Studies on Ultrastructure of Dental Enemel IV: The Mineralization of normal Human Enamel, J. Ultrastructure. Res. 8, 12-23. , 1963) to calculate the amount of remineralized minerals, and the method of Damato et al. (FA Damato, R. Stang and KW Stephen: Effect of Fluoride Concentration on Reminerelization of Carious Enamel Res, 24, 174-180, 1990), the amount of mineral loss ΔZ (% volume mineral · μm) between the control surface and the treated surface of each section was calculated. In addition, the remineralization rate was computed by the following formula | equation.
(試験結果)
表6は、前記の再石灰化促進試験法により口腔組成物の再石灰化の促進効果を確認した結果を示す。
(Test results)
Table 6 shows the results of confirming the effect of promoting remineralization of the oral composition by the above-described remineralization promotion test method.
Claims (4)
A mouthwash containing the composition for oral cavity for preventing caries according to claim 1 or 2.
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