JPS59104310A - Composition for oral cavity - Google Patents

Abstract

PURPOSE:A composition for oral cavity that contains an O-phosphoamino acid compound and a phosphate compound such as 2,3-diphosphoglyceric acid, thus inhibiting the crystal growth of hydroxyapatite and the formation of dental calculus. CONSTITUTION:A compound selected from O-phosphoamino acid compounds obtained by phosphating the hydroxyl in an aminoacid bearing a hydroxyl group and their salts such as O-phosphoserine, or O-phosphothreonine, 2,3-diphosphoglyceric acids of formula I and their salts further N,N-bisphosphonoalkyl compounds of formula II (R1-R3 are lower alkyl) and their salts such as N,N- bisphosphonoglycine is used to prepare the objective composition. The amount of the compound is more than 0.01, preferably 0.1-3wt% based on the total weight of the composition, especially when used in mouth wash, a liquid preparation or oral refreshing preparation which has a possibility of being swallowed, the content is preferably 0.1-1.5wt%.

Description

[Detailed Description of the Invention] The present invention... The present invention relates to an oral cavity composition that suppresses the formation of tartar.

Tartar is. It is a highly inorganic and hard deposit that forms on the six surfaces of the teeth, and is the cause of gingivitis and periodontitis, which leads to the formation of tartar. Suppressing periodontal disease is very effective in preventing and treating periodontal disease1. In this case, regular plunging of the teeth can prevent rapid accumulation of tartar, but Not enough to remove them all.

The formation of this dental calculus occurs when amorphous or microcrystalline calcium/umium phosphate is deposited on the bacterial membrane threads and interbacterial substances in the dental plaque, gradually becoming denser and turning into hydroxyapatite. Therefore, it is recognized that in order to suppress the formation of tartar, it is sufficient to inhibit the crystal growth of hydroxyapatite.

In view of the above circumstances, the present inventors have conducted extensive research on oral compositions that suppress the formation of tartar. Amino acid compound and its salt, the following (formula 11 (2,3-diphosphoglyceric acid and its salt shown in % formula %)
In addition, by blending one or more phosphoric acid compounds selected from the following (21 formula % formula % (2) (where R+, Rp, Rs ij: each represents a lower alkyl group)) It has been found that the above objective is effectively achieved.That is, the formation of dental calculus is caused by the formation of amorphous calcium/ium phosphate first, which is then converted into hydroquinoapatite. This is thought to result in hard and dense tartar, but the present inventors.

By blending the above-mentioned phosphoric acid compound into the oral composition, the amorphous 11-phosphate calcium/
The present invention was made based on the knowledge that the entire process of converting the molten metal into a hard and dense hydroxide into a tight one can be effectively prevented.

The present invention will be explained in detail below.

1] Compositions for traveling according to the present invention include toothpastes, toothpastes such as toothpastes, liquid toothpastes, mouthwashes, troches, and chewing gums. Gum Massage Cleano 1. Prepared as liquid mouth freshener, solid mouth freshener, etc.
Is it applicable to hydroxyl groups? O-phosphoamino)eta compound in which the hydroxyl group of an amino acid having a phosphoric acid ester and its i,2,3-diphosphoglycerin compound and the N,N-bisphosphonoalkyl compound represented by the above formula (21) 1 or 2 or more selected from compounds and their salts
It contains a tunic acid compound, which effectively suppresses the formation of tartar.

in this case. The above ML O-phosphor i) acid ratio compounds include serine, threonine, which are agonoic acids having a hydroxyl group,
Particularly preferably used are 0-phosphomonolone, 0-phosphothreonine, 0-phosphonaro/no, and O-phosphono\hydroki/burino, which are obtained by converting the hydroxyl groups of thyronone and hydroxyphenone into phosphoric acid esters.

Also, N. As an N-bisphosphonoalkyl compound.
N.N-bisphosphonomethylglycino compound in which R+ and & are each a methylene group in the formula (2) above. Among them, N,N-bisphosphonomethylglycino in which R2 is a methylene group is particularly preferred. used.

The amount of these phosphoric acid compounds is not particularly limited, but is usually 0.00% of the total composition. (11δ(cover amount Q2.

The same applies hereinafter), and the upper limit is not limited, but from a cost standpoint, it is preferable and desirable to set it to 0% or less. <KeO. It is preferable to set J-IO%, especially sail 1 to 3%. In addition, for items that may be swallowed during use, such as mouthwash and mouth fresheners, the amount should not exceed 2%. In particular, it is preferable to set the amount of Sail J to 1.5%.

As other components of the present invention, appropriate components commonly used may be blended depending on the type of oral composition, purpose of use, etc.

For example, in the case of toothpaste, dibasic calcium phosphate 2
Hydrates and anhydrides, monocalcium phosphate, tertiary calcium phosphate, calcium carbonate, carnoum pyrophosphate 5
Titanium oxide, alumina, hydrated aluminum, Noriyoku gel, colloidal Noriyoku, anhydrous alkali gold-striped silicate complex, aldanium silicate, insoluble sodium metaphosphate, insoluble potassium metaphosphate, tertiary phosphate magnet /um, magnesium carbonate, calcium/um sulfate, polymethyl methacrylate, bentonite, zirconium silicate, 5 synthetic resins, etc.
species or two or more species may be blended (compounding amount usually 10% to 99%)
%, 10% to 75% in the case of toothpaste) contains calcium pyrophosphate, acid f-hititanium, alumina, hydrated aluminum,
Norica gel, colloidal silica, and anhydrous alkali metal silicate complex salts are particularly preferred in that they effectively exhibit the ability to inhibit the crystallization of hydroxyapatite, the phosphoric acid compound.

In the case of paste-form oral compositions such as toothpaste, carrageenan, sodium carboxymethylcellulose, methylcellulose, and hydroquinoethylcellulose are used as binders. Cellulose derivatives such as sodium carboxymethyl hydroxyethyl cellulose, alkali metal alginates such as sodium alginate, propylene glycol alginate, gums such as xanothane gum, gum tragacanth, gum karaya, and gum arabic, polyvinyl alcohol, sodium polyacrylate,
Synthetic binders such as carboxyvinyl polymers and polyvinylpyrrolidone, and silica gel.

One or more inorganic binders such as argonium silica gel, Veegum, and Laponite may be blended (the blending amount is usually 5 to 5%).

Furthermore, in the production of dentifrices and other oral compositions,
Sorbit, glycerin as a thickening agent.

Ethylene glycol, propylene glycol.

1.3-phthylene gelicol, polyethylene glycol, polypropylene glycol, Kijilint.

It is also possible to blend one or more of Martent, Lactint, etc. (compounding amount usually JO~70%).

Water-bathable groups of higher alkyl sulfate esters whose alkyl group has carbon atoms of 8 to J8, such as sodium lauryl oxalate and sodium listyl oxalate; Higher fatty acid upper nocryceride mono Wf acid resistant.

Alkylaryl sulfonates such as sodium dodecylbenzenesulfonate, higher alkyl sulfonic acids tJi5
1. Lower aliphatic aminocarbons such as higher fatty acid esters of 2-hydroquine/propane sulfo/acid salts, sodium, potassium or ethanolamine salts of N-lauroyl, Ni-ristoyl or N-valmitoyl sarco7. Anion activators such as substantially saturated higher aliphatic asolamides of acid compounds, sucrose fatty acid esters in which the fatty acid group has 12 to 18 carbon atoms such as butyose mono- and dilaurates, lactose fatty acid esters, lacunatole fats, etc.
:c ster, maltitol I] 1lrlF [ester, stearin-based monoglyceride, polyoxy-7-ethylene rubitan monolaurate, polyoxy-7-enalene sorbitol/monostearate, polyoxy/ethylene (Jo, 2
0,40.60.80.100 mol) hard fIZ castor oil, polymer of ezalenoxide and probile/oxide, and polyenalenoxide such as polyquinoenalenopolyoquinobropyrenomonolauryl ester and fatty acid 1/4 → One or more surfactants such as nonionic surfactants such as fatty alcohols, polyhydric alcohols, and condensation products with polypropylene oxide, and amphoteric surfactants such as betaine type and amphoteric type (The amount of compounding is usually 0~
7 qb, preferably 0.5-5%).

The oral composition of the present invention further contains zankarin sodium, stevioside, neohesberidyl dihydrochalcone, glycyrrhizin, and perilartino.

Thaumateno, asparanal phenylalanine methyl ester, p-methocino/nadenqualdehyde, sucrose,
Flavoring agents (0 to 1%, preferably 0.01 to 0.5%) such as lactose, fructose, and zyklagone RI sodium, and if necessary, di-p-hydroxymenalbenzoisoquaside, p
- Preservatives such as hydroxyethyl benozoincanod, p-hydroxy 70 vir benozoinkuand, p-hydroquibuter benozoinkuand, sodium benzoate, lower fatty acid monoglyceride, wintergreen oil, spared oil, peppermit oil , Sansafras oil 0
Clove f1η, ingredients such as eucalyptus oil, gelatin, peptone, arginine hydrochloride, alpine, casein, 2CP
For example, in the case of a toothpaste, it can be produced by mixing the above-mentioned desired ingredients with an appropriate amount of water.

In addition, without producing other oral compositions, it is also possible to produce the composition 1' according to method 1' using appropriate commonly used ingredients.

Furthermore, in the present invention, gamma lantoins, ibusilone aminocabronoic acid, tranexamic acid, textlanase,
amylase, propease, mutanase. lysozyme,
Antibacterial enzymes, enzymes such as retenque enzymes, and sodium monofluorophosphate.

Alkali metal monofluorophosphate such as potassium monofluorophosphate, sodium fluoride.

Ammonium, fluoride No. JQI fluoride.

Chlorbeki/gin salts, dihydrocholesterol, glycyrrhetinic salts, glinarretinoic acid. Glyse 1 phosphate, chlorophyll, and cyclopeptide.

Contains one or two types of active ingredients such as water-based inorganic phosphoric acid compounds, vitamins, other anti-tartar agents, antibacterial agents, and plaque inhibitors.
- Can be blended.

Thus, in the oral composition of the present invention, the hydroxyl group of an amino acid having a hydroxyl group is replaced with a phosphoric acid ester.

- Phosphoamino compound and its salt, 2,3-diphosphoglyceric acid and its salt and the following (21 formula % formula % (
2) (However, R+ and I12.Rs each represent a lower alkyl group) One or more phosphoric acid compounds (dental calculus Preventive agent)? Due to the combination.

This effectively suppresses the crystal growth of amorphous calcium/mium phosphate into hydroxyapatite, thereby effectively suppressing the formation of dental calculus.

Next, the effects of the present invention will be specifically explained by skipping Experiment 1+11.

Example PI (By the stand method, the effect of inhibiting tartar formation of the phosphoric acid-based 111 compound was demonstrated. In this case, distilled water 22~'1
The tartar prevention agent according to the present invention (O-phosphoserine, 0-phosphothreonine, 2.3
-diphosphoglycerin]N,N-bisposponomethylcrisino)
2゜5XI 0-2PA/IJ) 1. The force was increased to 11 while continuously pumping sodium dihydrogen phosphate to Ornl and 0 under an N2 atmosphere. To this, U, 1MCaCJ
? ? Add 1alf of ♀ liquid to water, pHf 7.4 with NaOH
Train Joho 05.

This allows sodium dihydrogen phosphate and CraCe? reacts to produce secondary phosphate, and by continuing stirring, the secondary phosphate turns into hydroxyapatite, at which time OH- ions are consumed...
decreases, but 0. Add I N NaOH dropwise to adjust the pH.
l! ! Maintain at 77.4. 0 at this time. INNaO
H consumption of Toa Denpa PH stand H8S-10A
The generation time of hydroquinoapatite was determined by automatic recording using the mold. Show the results on the clothes. Here, Ca
The final concentrations of O'-phosphoserine, 0-phosphothreonino, 2,3-cyphosphoglyceric acid, and N,N-bisphosphotumenalglinone are 1×10 to 1×10 −3 M, respectively.

In addition, crystal growth of hydroxyapatite i 1111
The pH stand method is widely used as a method for screening active ingredients for the purpose of preventing tartar. Research has already shown that there is a good correlation with the ability to prevent damage.

Clothing Hydroquinoapatite Suppression Effect In the above experiment, when no tartar preventive agent was used (control), the production of hydroquinoapatite was demonstrated by a two-step reaction. The first rapid consumption of base (after 1-4 minutes) is caused by precipitation of amorphous calcium/ium phosphate, followed by a decline in consumption for 15-20 minutes before a second rapid consumption occurs; A second rapid consumption occurs due to crystal growth of amorphous calcium phosphate into hydroquinoapatite. Therefore.

The delay or complete absence of this second rapid consumption, which represents a disruption of hydroquinoapatite crystal growth, is a result of
It has been revealed that 0-phosphothreonino, 2,3-cyphosphoglyceric acid, and N,N-bisphosphonomethylglycino exhibit excellent growth-inhibiting effects on hydroquinapatite crystals.

Hereinafter, the present invention will be specifically explained with reference to Examples.

(Example 1) Mousewort stings 0.
2% ethanol 13
．． (+ Glycerin 10.0 Zancarinosodium 0.030・
-phosposthreonino 0.1-5.
0 lauryl pieces 1. Sodium acid 2.
0 water
Balance total 100
．． 0pH--7,2 (adjusted with NaOH) ←Example 2J Toothpaste paste strength (Zeodent IJ3)
31% Tsurupinto (7(,1% water bath liquid)
6.25 Glycerin
J8 Pluroninc F-JO83 Hydroxypropyl methylcellulose 1.50-
Phosphoserino disodium salt 2-1O Sankarin sodium 0.15 aroma
Fee 0.85 self Total 100.
0 (Example 3) Toothpaste Hydrated Alumina 3096 Nrubint (7
0% water broth) 6 glycerin
J8 Sodium lauryl sulfate
J, 5 carboxy/methylcellulose sodium
L20-phosphonaro/n
LO saccharin sodium
0゜J5 fragrance
0.85 water
Remaining amount total
100.0 (Example 4J Mouthwon/Yu Fragrance 0.2
% ethanol 13.
0 Glycerin 10.0 Satucalin Sodium 0.032.3
-Diphosphoglyceric acid 0. J~L5 Sodium lauryl sulfate 2.0 cups
Total 100.0pt
l --7,2 (adjusted with NaOH) [Example 5] Denture cup warping force (Zeodent month 3) 31% Tsurupinto (70% water M1g) fi, 25 Glycerin 18 Pluronic F
-JO83 Hydroxypropyl methylcellulose 1
．． 52.3-diphosphoglyceric acid disodium salt
2-3 saccharin sodium
0015 inspection fee
(1,85 water
Residue [Example 6J Toothpaste Oroalumina 30
% Turupinto (70q water bath solution) 6 Glycerin 18 Sodium lauryl sulfate 1.5 Sodium carboxymethyl cellulose J, 22.3-diphosphoglypeptaphosphate 1.0 Sodium zancarino 0.15 Flavor
0.85 total
100,0 [Example 7] Mousewonnoyu fragrance 0.2
%ethanol J3゜(
) Glycerin N1.0 Sankarin sodium 0.03N, N-bisphosphotumenalglinone 0.1-1.5 Sodium lauryl sulfate 2.0 Total
”00゜0’jbpH
= 7.2 (adjusted with NaOH) ゛(Example 8)
Toothpaste warping power (Zeodent JJ3) 3
1% sorbitol (70'?, water m liquid)
fi, 25 glycerin
J8 Pluroninc F-1083 Hydroxypropyl methylcellulose 1
．． 5N,N-bisphosphonomethylgritume e4 sodium salt 2-3 Zankarin sodium
(1, J5 fragrance
0.85 total
100.0 qh (Example 9) Toothpaste hydration aluminum 30
% Turupinto (70% water bath equivalent) 6 Glycerin J88 Sodium lauryl acid L5 Sodium carboxy/methyl heptralulose 1.2 N, N-bisphosphotumenalglinone 1.0 Sodium saccharin 0.15 Flavor
0.85 Above implementation 91
Oral compositions Nos. 0 to 9 all suppressed tartar formation well.

Applicant: Lion Corporation Daimisakito Patent attorney Takashi Kojima

Claims (1)

[Scope of Claims] 1 O-phosphoamino acid compound and salt thereof obtained by phosphoric acid esterification of the hydroxyl group of agonoic acid having a hydroxyl group, 2.3-
One or more phosphoric acid compounds selected from diphosphoglyceric acid and its salts, and N,N-bisphosphonoalkyl compounds represented by the following general formula and salts thereof? An oral composition characterized by comprising: N - & -COOH (wherein R1, R2, and R3 each represent a lower alkyl group) 2 The oral composition according to claim 1, wherein the tj-phosphoamino acid compound is 0-phosphoserine or 0-phosphothreonino. . 3.N. The N-bisphosphonoalkyl compound is an N compound in which R1 and R2 are each a methylene group in the above general formula.
．． The oral composition according to claim 1, which is an N-bisphosphonomethyl 16 compound. 4.N. The N-bisphosphonoalkyl compound is an N. Oral composition 9 of claim 3, which is N-bisphosphonoglycine. 5 Amount of phosphoric acid compound or 0.1 to 1 of the entire composition
The oral composition according to any one of claims 1 to 4, which has a 0M amount q6.