JPS58109408A - Oral composition - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] The present invention relates to an oral cavity composition containing an anti-calculus agent.

Tartar is a hard mineral body that forms on the surface of teeth.

Regular brushing prevents these rapid build-ups, but is not sufficient to remove all of the tartar on the teeth.

Dental calculus is caused by calcium phosphate crystals depositing within the thin film of dental plaque and extracellular membranes.
They form aggregates and resist deformation (2) on the surface of the teeth.

There is no complete consensus on the route by which calcium and orthophosphate ultimately form a crystalline product called human "roxyanomotite (HAP)."

However, at high saturations, ie, values above the critical saturation value, it is generally said that the precursor of crystalline hydroxyavatite is fine quality calcium phosphate.

“Amorphous calcium phosphate 1 is related to hydroxyapatite but differs in atomic structure, particle morphology, and stoichiometry. The non-toxic anti-calculus agent of the present invention inhibits tartar formation because the nucleating agent is able to penetrate into the matrix system of the oral cavity at physiological pH and temperature. It has been proposed that this involves binding amino groups and cross-linking proteins.

,' For example, bisubig T nide compounds and quaternary ammonium compounds, such as benzethonium chloride 9, motilbi+1
A significant number of different types of compounds and compositions are available for use as antibacterial, antiplaque, and anticalcin agents, including cationic substances such as dinium chloride (3) (disclosed in U.S. Pat. No. 4,090,441). has been developed. However, these cationic substances tend to cause tooth staining with continued use.

A first object of the present invention is to provide an improved anti-calculus oral composition that has relatively little or no tendency to stain teeth.
[An object of the present invention is to provide an oral composition that prevents the transformation of amorphous calcium phosphate into a crystal structure.]

A sixth objective is to provide an improved method for inhibiting tartar formation.

Other objects and advantages will be apparent from the description herein.

In one embodiment, the present invention provides an orally acceptable vehicle (free of antibacterial and antiplaque agents) that does not cause tooth staining and an anticalculus effective amount of at least one C2J aliphatic dicarboxylic acid. Substantially anhydrous oral composition (4) consisting of a bis(0-carboxyphenyl) ester of.

The free acid form of the anti-calculus agent of the present invention can be represented by the following formula.

(Preferably, R is individually H or C1j alkyl, preferably H, and n is an integer from 0 to 6, preferably 2.) Preferred anti-calculus agents are therefore bis(0-carboxyphenyl) succinate ( BooS).

The -+CRR)- group in oxalic acid bisester is a single bond if Kn is 0, and any CIJ alkylkylene alkylene group, i.e., true chain or branched, saturated or unsaturated, cleaved at 0 or S chain. and may be substituted with C8J-rukoxy.

When -CRR is part of an ethylene group, one or both of H's may be zero, that is, a bond. The following bis(0-carboxyphenyl)(5) esters of aliphatic dicarboxylic acids are exemplary of anti-calculus agents of the present invention.

Oxalic acid (ethanniic acid) Maron i! iI (prononodiic acid) 1g of amber! (Butani#) Glutaric acid (-'-!l'Ntanni#l) Adivic acid (
Hexanilic acid) Pimelic acid (Hexanilic acid) Maleic acid (1,2-ethylenedicarboxylic acid F (OOC)
CH:CH-COOf() itaconic acid (methylenesuccinic acid HOOCCi: CH,)OH, -COOH) isosuccinic acid (2-methylpronoe:/211) mucon*(2
,4-hexadienic acid HOOCCH: CHCH: (3H-COOH)dihydro A coy acid (HOOCiCH,OH,OH:C
In addition, one or both phenyl moieties of this agent may contain one or more methyl, alkoxy, alkoxy, alkoxy, or !, Br, I or F may be substituted with a halo.

A suitable method for preparing these anti-tartar agents is disclosed in the above-mentioned U.S. Pat.
Publication No. 41 has been published extensively. Another improved manufacturing method is described in Example A below. It is.

The free acid forms of these anti-tartar agents are treated with alkali metals (e.g. Na
. It is clear that they can be used in place of their equivalent salts by treatment with a base containing an acceptable cation.

The anti-calculus agents of the present invention are anti-cough-forming agents, and the oral compositions of the present invention containing them are effective in reducing dental calculus formation without excessive π-demineralization of tooth enamel. In contrast to bacterial, anti-plaque, and anti-tartar agents, they have been found to have little to no tendency to stain teeth and, furthermore, to effectively reduce or prevent gingivitis.

(7) The concentration of these anti-calculus agents in oral compositions can vary widely, but is typically about 0.01% by weight or higher, and is considered a There is no usage limit.

Generally, by weight, about 0.1 to 10%, preferably about 0.
0.05 to 8.0%, more preferably about 0.1 to 4%. Since oral compositions are likely to be accidentally ingested under normal usage conditions, a concentration of less than 1 mil/l within the above range is preferred.

The water solubility of these anti-calculus agents varies depending on their molecular weight, the substance and properties of salt-forming cations, but even at the low concentrations used in the present invention, they are sufficiently soluble in aqueous media, such as in the oral cavity, so that the degree of It can be called bathing property3.
However, it has been unexpectedly discovered that oral compositions containing such agents in an aqueous medium undergo significant hydrolysis or other degradation during storage. In certain embodiments of the invention, it is preferred to provide a substantially anhydrous oral composition (e.g., containing from about 0 to less than 0.2 moles of water per mole of anti-calculus agent).

(8) When the oral composition of the present invention is in the form of a liquid, paste, or cream such as a mouthwash, rinse, toothpaste, or dental cream, it is water-miscible (preferably water-soluble) and organic. The use of normally liquid orally acceptable vehicles is preferred. Typically such vehicles include water-soluble "tJ-valent, polyhydric alkanes and their C8~.

Alkyl ethers, such as ethanol, ethylene glycol, their methyl, ethyl, butyl ethers (methyl, ethyl, phthyl), propylene glycol, tetramethylene glycol and glycerin, aqueous poly(ethylene glycol), such as diethylene glycol, their methyl, Ethyl, diethyl, butyl ether (methyl, ethyl, diethyl, butylcarpitol)
, Ml ethylene glycol, low molecular weight t+n lyethylene glycol (eg, 400,600), and mixtures thereof. The polyhydric compounds in the group mentioned herein, particularly propylene glycol, glycerin, and low molecular weight polyethylene glycols, also generally serve as humectants, which are desired components of the oral compositions of the present invention.

(9) Many types of such water-miscible liquid vehicles that can be used include dimethylformamide, sulfoxide, N-
Polar neutral solvents such as methylpyrrolidone, sulfolane, tramethylsulfone, and diacetonitrile are preferred, with ethylene carbonate and propylene carbonate being preferred.

Essentially water-immiscible organic liquid vehicles may also be used;
Typical examples are hydrocarbons, fatty acid and fatty acid ester oils,
For example, mineral oil, tetradecane, takuntan, caproic acid,
These include enantylic acid, caproic acid, methyl ester of lauric acid, and ethylene glycol caprilate.

Of course, mixtures of the same and/or other types of liquid vehicles may also be employed.

The proportion of the liquid vehicle used in these oral compositions obviously depends in large part on the degree of fluidity or viscosity desired.
-2. In either case, it can be easily determined by conventional means.

Typically, by weight, liquid compositions such as mouthwashes, rinses, etc.
0-999%, toothpaste and dental cream about 10-8
Contains 0% of such liquid (10) vehicle, of which approximately 10-100% is humectant. Usually solid humectants such as sorbitol can also be included.

The oral compositions of the present invention are typically prepared in an aqueous medium, such as in the oral cavity, with a 20% aqueous slurry in the form of a solution of about 3%.
5-8, preferably about A-7, more preferably about 4-6
It has a pH of . Such PI (is the required amount of acidic substances (e.g., phosphoric acid, benzoic acid), basic substances (e.g., NaOH)
Stones can be controlled by the inclusion of &/or buffers (e.g. citric acid, benzoic acid, bicarbonate, Na salt of carbonate, disodium hydrogen phosphate, 11 um sodium dihydrogen phosphate) or mixtures thereof.

The vehicle in solid or pasty compositions such as tooth powders, tablets, toothpastes, tental creams, etc. generally contains an abrasive. An example is water-insoluble sodium metaphosphate <r
:pAp), 11 um metaphosphate, tricalcium phosphate, anhydrous, □-water, dihydrated calcium phosphate or nicalcium, birocalcium phosphate, magnesium orthophosphate, trimagnesium phosphate, magnesium carbonate or sulfate or ( 11) Calcium salts, alumina, alumina, aluminum silicate, alkali metal or alkaline earth metal salts of aluminosilicate, zirconium silicate, silica, indonite and mixtures thereof. Preferred abrasives include crystalline or colloidal silica, silica gel, composite amorphous aluminosilicate alkali metal salts, water-containing alumina, IMF, and the like.

Alumina content 64.9% by weight; silica content 0.008
%; ferric oxide 0.003%; water content 0.37% (11
specific gravity 2.42; particle size: 100% of the particles are less than 50 microns, 84% of the particles are less than 20 microns; It is effective for

When using gels that are clear to the naked eye, colloidal silica-based abrasives such as 5YLOID 72, 74.244 and 17, YLOID, or 5ANTOCEL may be used.
Particularly useful are those sold under the trademark 5ANTOCEL. This is because it has a refractive index close to that of the gelling agent-dispersion system commonly used for toothpaste. .

(12) Many of the so-called n-water non-renewable abrasives are anionic and also contain small amounts of soluble materials. For example, insoluble sodium metaphosphate is described in Thorpe's Dictionary of
Applied Chemistry, Volume 9, No. 4
A suitable subdivision is the form of insoluble sodium metaphosphate IJr'7, also known as Madrell's salt or Kroll's salt, which can be formed by any suitable method as exemplified in J.D., pp. 510-511. These metaphosphates exhibit little water solubility and are therefore commonly referred to as insoluble natalates. □A small amount (usually up to 4 W%) of soluble phosphate material is present as an impurity. , the amount of soluble phosphate material (believed to include soluble sodium trimetaphosphate in the case of insoluble metaphosphates) can be reduced by precipitation if desired. The insoluble alkali metal metaphosphate salt is typically used in powder form with a particle size of less than about 1% or greater than about 37 microns.

Abrasive materials are generally present in an amount of about 20-99 VV% of the oral formulation. About 20-75% for toothpaste, about 7% for toothpaste
0 to 99% is preferred.

(13) In the production of toothpaste, it is sufficient to mechanically mix, for example, by cross-mixing, various solid components in appropriate amounts and particle sizes, and then pulverize.

Toothpastes, creams, gels (in which liquids and solids are typically suitable for extrusion from pressurized containers or collapsible tubes to form creamy or gel-like masses)
Thickening to a suitable desired viscosity or fluidity is typically done with natural or synthetic gums, typically iris moss, zorlonik, carboxymethyl cellulose or carboxyethyl cellulose. Sodium salt of methylcellulose, human 90xyethylcellulose, human 90xypropylcellulose, hydroxypropylmethylcellulose, hydroxybutylmethylcellulose, Laponite CP or 5P
(synthetic hectorite from Laporte Industries), viscarin, gelatin, glucose, sucrose, Cart>opol (e.g. 964.94
0.941), karaya gum, gum arabic, tricanth gum, polyvinylvicaritone, poly(14) vinyl alcohol, starch, etc. Usually present alone or in amounts up to about 10 W%, preferably about 0.5 to 5 W%. 3, preferred gelling agents are Pluronic and hydroxypropyl cellulose. Pluronics such as F2O3 and F127 are polyoxypropylene polyoxyethylene block I which also act as 77 anionic active 1.
This is P Rimmer.

In the oral compositions of the present invention, is generally about 0.05 to 10,
Preferably at a concentration of about 0.5 to 5 W%, a water-soluble organic anion or 5. The world of nonion (ii
It is also possible to include additives to enhance wetting, cleaning, and foaming properties. In US Patent No. JR141149,
Appropriate anionic surfactants are disclosed in column 4, lines 61-38, and appropriate nonionic surfactants are disclosed in column 8, lines 60-68 and column 9, lines 1-12. .

In certain embodiments of the invention...the portal feeding compound is present in the oral formulation. These compounds may be only slightly water-soluble or only slightly water-bathable. It is characterized by being able to release fluoride ions into water (15) and by not substantially reacting with fine compounds in oral preparations.

These substances include inorganic fluoride salts, such as soluble alkali metal, alkaline earth metal, and heavy metal salts, such as sodium fluoride, potassium fluoride, ammonium fluoride, calcium fluoride, and cupric fluoride. Copper fluoride, zinc fluoride, tin fluorides such as stannic fluoride and stannic chlorofluoride, barium fluoride, sodium fluorosilicate, ammonium fluorosilicate, sodium fluorozirconate, monofluorophosphoric acid sodium, mono- or difluoroaluminum phosphate, fluorinated calcium sodium birophosphate, and the like. Alkali metal and tin fluorides such as sodium fluoride, stannous fluoride, sodium monofluorophosphate and mixtures thereof are preferred.

The amount of the fluorine-providing compound 'I2I depends to some extent on the type of compound, its solubility, and the type of oral preparation, but must be a non-toxic amount.1. For thickened or solid oral formulations such as toothpastes and tooth powders, (16) amounts that release up to about 1 W% of the nucleating agent are preferred.

Although such compounds may be used in any suitable minimum amount, it is preferred to use the compounds in an amount sufficient to release about 0.005 to 1%, preferably about 0.1%, of fluorine ions. Typically, in the case of the alkali metal fluoride, stannous fluoride, this component is present in an amount of up to about 2% by weight of the nucleating agent, preferably from about 0.05 to 1% by weight. In the case of sodium, this compound can be present in amounts up to 7.6 W%, typically about 0.5-1 W%.

In liquid mouthwash formulations, such as mouthwashes, the fluoride-providing compound typically comprises about 0.000.5-0.2%, preferably about 0.001-0.1%, more preferably about 0.00
It is present in an amount sufficient to release 13% of fluorine ions.

The oral preparation of the present invention includes whitening agents, preservatives, silicones, chlorophyll compounds, other anti-calculus agents, anti-bacterial anti-plaque agents and/or ammonia substances such as urea, diammonium phosphate and mixtures thereof. Various other substances can also be blended.

(17) Any suitable flavoring or sweetening agent may be used.

Examples of suitable flavoring ingredients are flavored oils, such as mint, peppermint, sassafras, clove, sage, eucalyptus, marjoram, etc. Cinnamon, lemon, orange, menthol, eugenol, cineole oil, and methyl salicylate. Suitable sweeteners include sucrose, fructose, rydose, maltose, Tsurupi 1, xylitol, sodium silamate, perilartine,
These include APM (aspartyl phenylalanine methyl ester) and saccharin. Suitably, the flavoring agents and sweeteners account for about 0.01 to 5% or more of the core.

In preparing the oral formulations of the present invention, it is preferred, but not essential, that the anti-calculus agent be added after mixing or contacting the other ingredients (with the exception of some of the water) to avoid the tendency of the nucleating agent to settle.

Like conventional products, the oral preparations of the present invention are distributed in the form of packages with appropriate labels attached. For example, mouthrinds are packaged in jars with labels stating that the contents are mouth rinses or mouth rinses (18) and have instructions for use, and toothpastes are usually packaged in jars with labels that state that the contents are mouth rinses or mouth rinses (18), and have instructions for use. Collapsible tubes (typically made of aluminium, lined lead or plastic) or other squeeze-type portions for dispensing the contents with a label stating ``dental cream'' are placed in the device. ing.

In the practice of the present invention, the oral composition of the present invention, such as a mouth rinse or toothpaste, containing the anti-tartar agent effective in inhibiting tartar on the tooth surface is applied to the oral cavity, particularly tooth enamel, preferably once a day. ~6
Apply times regularly.

Example A Bis(0-carboxyphenyl) succinate 0.4% salicylic acid (55.2 g) 0.4 mole pyridine (31
,2m1) 0.2 mol of succinyl chloride (31,0II
) Salicylic acid and pyridine were dissolved in 77 tons of 90 TILl. 90 ml of the resulting clear solution VC of succinyl chloride in acetone was added under stirring at a rate to maintain reflux of the acetone for 60 minutes. During this addition the desired (19)BOC8 product began to separate and the mixture turned black-purple. The reaction slurry was stirred for 60 minutes after the total succinyl chloride addition. Then 200 ml of water was added, the acetone was evaporated from the slurry on a rotary evaporator at 35° C., and the desired BCIS product was collected on a suction filter, washed with water, and washed with water.
It was vacuum dried at 0°C.

Yield: 66.5193%), mp: 177-177, 5
℃;, neutralization t: 179.9, ken t: 186.8.
Calculated value "18H110g).

The following examples are further illustrative of the present invention, and are not intended to limit the present invention.11 In the present specification, unless otherwise specified, -C is an amount, a proportion is a weight, and a temperature is a unit of °C.

Example 1 The following formulation is illustrative of a toothpaste of the present invention that is effective in inhibiting tartar.

Parts by weight Propylene 42.0 Hydroxypropyl cellulose 1.0 Polyethylene glycol 600 10.0 (20) Sodium saccharin 'D, 2T io,
0.4IMF
2B, 0 Shiroi)'(
Syloid) 244 12.0 Sodium lauryl sulfate 1.5 Flavoring agent
t 0BOC85,0 The following formulation is illustrative of the mouthwash of the present invention that is effective in inhibiting tartar. .

Example 64 Flavoring agent 0.22 0.22 0.
22 Ethanol 15.0 15.0 1
5.0 Pullo=yp F 10B 3.0
3.0 3.0 Glycerin 10.0
10.0 10.0 Satucalin Sodium 0.
03 0.03 0.03BOGS
O,050,501,0 Even when BOC8 used in the formulations of Examples 2 to 5 was substituted with an equivalent amount of the following bisester compounds, formulations effective in inhibiting tartar were obtained.

(21) Practical inversion Bisester compound 5 Bis(2-carboxy-4-butoxyphenyl) oxalate 6 Bis(2-carboxy-4-furopyru-6-chlorophenyl) glutarate 7 Bis(2-carboxy-4-methoxy-adipate) 6-Bromophenyl) 8 Hissperate (2-carboxy-4-iodo-
6-nitoxyphenyl) 9 Bis(2-carboxyphenyl) piperate 10 His(2-carboxy-5-methoxyphenyl) malonate 11 His(2-carboxy-6-butylphenyl) maleate 12 Bis(2-carboxyphenyl) itaconate phenyl) 13 Bis(2-carboxy-4-fluorophenyl) muconate (22) Example 14 In this experiment using 24 rats, 13 bis(2-carboxy-4-fluorophenyl) muconate was used in water as the bracebo and dimethyl sulfoxide as the test anti-calculus mouthwash. The anti-calculus formation efficacy of B OCS 0.1% solution (PH7, sum) was evaluated for 30 days. Consenting Mature Osbo
rne-Mendel rats were used.

Strep-muta- in the oral cavity on the 21st and 22nd days
nce and Acti'nomyces viscsou
Inoculated with excreta from Osborne-Mendel rats with s and tartar activity, t2, Na2PO, 0.2%
P supplemented with 580FVr, a meal that tends to cause tartar,
Placebo and test mouthrinses were applied to the teeth of each group of 12 such rats twice a day from Monday to Friday and once a day on Saturday and Sunday for 60 days.

Rats were weighed at the beginning and end of the experiment to ensure that they were otherwise normal. Finally, the tartar formation was evaluated in a routine manner and the results were obtained. .

Bracepo (Wed) 12 1281117.9 (23
) Mouth rinse 12 135g 14.8 α
<0.01 (0.1% BOO8) Hata Indicates the average number of surfaces on which tartar was formed among 20 teeth [I (20 units)].

The above results establish that topical application of 0.1% amount of BOC8 is significantly effective (±99%) in reducing tartar formation.

Although the invention has been described with reference to its preferred embodiments, variations and modifications thereof that are obvious to those skilled in the art are within the spirit and scope of the invention.

Patent applicant: Colgate-Palmolive Company (
24) 57-

Claims (1)

[Scope of Claims] Item 1: A substantially anhydrous oral composition comprising: a tooth stain-inducing antibacterial/antiplaque agent, an orally acceptable vehicle, and an effective amount as an anticalculus agent; At least one C2-8 aliphatic dicarboxylic acid bis(
0-carboxyphenyl) ester. (2) The composition according to claim 1, wherein the tartar agent is bis(0-carboxyphenyl) succinate. 6. The composition of claim 2, comprising about 0.01 to 10% by weight of said tartar agent. (1) Item 4: The composition according to claim 1 or 2, comprising about 0.05 to 5% by weight of the anti-calculus agent. Item 5 includes a liquid vehicle and has a pH of about 6.5 to 8 in an aqueous medium
Composition 1 according to claim 1 or 2, which is a mouthwash, comprising a liquid vehicle, a gelling agent, a dentally acceptable abrasive, in an aqueous medium. 3. The composition of claim 1 or 2, which is a toothpaste having a pH of about 6.5-8.