RU2092153C1 - Composition for remineralization of demineralized tooth part - Google Patents

Abstract

FIELD: stomatology. SUBSTANCE: teeth were treated with nonbinding composition containing at least 10-20% xylitol and at least one compound that represents fluoride ions taken at total dose to provide final concentration 150-1800. Sodium fluoride is used as prevailing part of fluoride ions. EFFECT: enhanced effectiveness of composition. 5 cl, 2 tbl

Description

 The invention relates to oral compositions in the form of toothpastes and mouth rinses, which provide an improvement in the effects of remineralization.

 In the oral cavity there is a natural balance, on the one hand, between hydroxyapatite, which is dissolved from tooth enamel, and, on the other hand, hydroxyapatite, which is formed on teeth or in teeth from substances naturally present in saliva. This balance is constantly shifting. Along with other factors, it is determined by diet and physical condition. If this equilibrium is such that said hydroxyapatite dissolves, then a karyogenic state arises, which is referred to as dimineralization. If the equilibrium is such that this hydroxyapatite is formed in demineralized enamel, then this condition is called remineralization. Through remineralization, preexisting tooth decay and caries can naturally be reduced or eliminated.

 It has long been known that fluoride-releasing compounds, even at low concentrations, contribute to the remineralization process and thereby suppress the previously carious state in the tooth structure.

 It has been described in patents and in the published literature that xylitol is used to treat tooth structure, to provide sweetened non-cariogenic compositions, to control tooth stains, to prevent the occurrence of carious conditions and / or remineralize pre-existing carious conditions. Bart's patent, 3932604 (USA) and US patent 3970747 isolated therefrom are devoted to toothpastes containing significant amounts of xylitol as a non-cariogenic sweetener / moisturizer. They describe and disclose formulations also containing sodium monofluorophosphate; no indication of remineralizing effect. Hoffman-Laroche's Irish Patent Application 307/76, filed February 16, 1976 and publicly available September 1, 1976 (based on Swiss patent application 2158/75), describes oral compositions containing xylitol, but without fluoride, for remineralization tooth decay. European Patent Publication No. 0138705, which appeared in Patent Bulletin 85/17, describes anti-caries compositions containing xylitol and mixtures of at least two fluoride salts, which provides a total fluoridion concentration of not less than 2,000 to 20,000 ppm. In the publication of Europatent N 0251146, which appeared on January 7, 1968 in Patent Bulletin 88/01, oral compositions are disclosed which are active in the prevention of tooth stains and, therefore, prevent caries. They contain a synergistic mixture of at least one fluoride compound of at least one compound releasing zinc ions (astringent) and xylitol.

 The aim of the invention is the provision of a new and improved method for remineralization of the demineralized part of the tooth structure. Another objective of the invention is the provision of such a method of achieving unobviously improved effects of demineralization.

 The achievement of one or more of the above objectives was made possible by the invention, which includes a method for remineralization of demineralized parts of the tooth structure, which consists in applying to such parts a non-astringent oral composition in the form of toothpaste or mouth rinse, which contains from about 10 to 20 wt. . xylitol and at least one compound supplying fluoride ion in an amount sufficient to ensure their concentration from 150 to 1800 ppm preferably 200 to 1200 ppm moreover, the predominant part of these fluoride ions is supplied by sodium fluoride.

 As indicated above, the compositions used in the invention are non-binders, i.e. they do not contain zinc salts, with which there are problems of sensation in the mouth and taste and which interfere with the target mechanism of remineralization, for example, by interaction, complexing, precipitation or other modification of significant xylitol and sodium fluoride in the compositions currently used.

 In the method of the invention, it was unexpectedly found that a certain combination of xylitol and compounds supplying fluoride ions, used within the indicated weight limits and in relative proportions or ratios determined in advance to achieve optimal remineralization effects, work together synergistically, providing significantly improved remineralization results, according to compared with those obtained for compositions containing individual xylitol and compounds that supply fluoridion.

 Compounds supplying fluoride ions and optionally present as such or in any mixtures in the compositions used in the invention in addition to the substantial sodium fluoride are well known as anti-caries agents. They can be completely or at least partially, but sufficiently soluble in water to provide the required amount of fluoride ions, organic or inorganic, and are characterized by their ability to release fluoride ions in water or saliva and by the absence of undesirable interaction with other components of oral compositions that are used here.

 Inorganic compounds providing fluoride ions include metal salts of alkali metals, alkaline earth metals and ammonium, such as potassium fluoride, acid ammonium fluoride, calcium fluoride, copper fluoride such as copper fluoride (1), zinc fluoride, barium fluoride, sodium fluorosilicate, ammonium fluorosilicate, sodium fluorozirconate, sodium monofluorophosphate, aluminum mono- and difluorophosphates, fluorinated sodium calcium pyrophosphate, tin fluoride, lithium fluoride, cesium fluoride, aluminum fluoride, copper fluoride, indium fluoride, ferric fluoride (III), nickel fluoride, palladium fluoride, silver fluoride, zirconium fluoride, etc. and mixtures thereof.

Organic compounds providing fluoride ions include hexylamine hydrofluoride, laurylamine hydrochloride, myristylamine hydrofluoride, decanolamine hydrofluoride, octadecenylamine hydrofluoride, myristoxyamine hydrofluoride, diethylaminoethylamine-diethylamine-di-aminolidene-aminolenido-aminolide-di-aminolide-aminolenido-aminolide-aminolide-di-aminolide-aminolide-aminolide-aminolide-aminolenido-aminolide-aminolide-aminolide-amide-aminolide-aminolide-aminolide-amide-aminolide 1-ethanol-2-hexadecylmidazoline dihydrofluoride, dodecyl ethyl dimethylammonium fluoride, octoylethanolamine hydrofluoride, octyltrimethylammonium fluoride, tetraethylammonium fluoride, dilauryl dimer ilammony fluoride, Δ ^8,9 -oktadetsenilbenzildimetilammony-fluoride, fluoride dioktildietilammony, tsiklogeksiltsetildimetilammony-fluoride, fluoride furfurillaurildimetilammony, fenoksietiltsetildimetilammony fluoride, N, N'-tetramethyl-N, N--dilauriletilendiammony difluoride, N-cetylpyridinium fluoride, N, N--dilaurilmorfoliny fluoride, N-myristyl-N-ethylmorpholine fluoride, N- (oktilaminokarboniletil) -N-benzyl-dimethylammonium fluoride, N- (borgidroksidodetsil) trimethylammonium fluoride, N-phenyl-N-geksadetsildietilammony fluoride , N-cyclohexyl-N-octadecyl-dimethylammonium-f toride, N - (2-carbomethoxyethyl) - N-benzyldimethylammonium fluoride, N - (2-carbocyclohexoxyethyl) -N-myristylammonium fluoride, N- (2-carbobenzyloxyethyl) -N-dodecyldimethylammonium fluoride, N- (2- - N, N'-dimethylaminocarbonyl) ethyl) -N-dodecyldiethylammonium fluoride, N-carboxymethyl-N-cyclosyldimethylammonium fluoride, sarcosine-tin (II) betaine hydrofluoride, alanine-tin (II) fluoride, potassium glycine fluoride fluoride -potassium, glycine hydrofluoride, lysine hydrofluoride, alanine hydrofluoride, betaine-zirconium fluoride, etc. and mixtures thereof.

 In some preferred forms of this invention, the oral composition may be substantially liquid in nature, such as a mouthwash or rinse. In such preparations, the usual carrier is a hydroalcoholic mixture, preferably comprising the humectant described below. In general, the weight ratio of water to alcohol ranges from about 1: 1 to 20: 1, preferably from 5: 1 to 18: 1 or more, preferably from about 10: 1 to 15: 1. The total amount of water-alcohol mixture in this type of preparation is usually in the range of about 50 to 99 wt. by weight of the drug, often in combination with about 5-40% of a moisturizer, part of which (or all) may be xylitol.

 The pH of such liquid and other preparations is usually in the range of about 4.5 to 10, and usually in the range of 5.5 to 9. The preferred pH is in the range of about 6 to 8.0. The pH value may be controlled by an acid (e.g., citric or benzoic acid) or a base (e.g., sodium hydroxide) or a buffer (such as sodium citrate, benzoate, sodium carbonate or bicarbonate, disodium hydrogen phosphate, sodium dihydrogen phosphate, etc.).

In some other desirable forms of this invention, the composition of the toothpaste may be solid or pasty in nature, such as tooth powder, tooth tablets, toothpaste (cream), or tooth jelly. The carrier of such solid or paste-like preparations for the teeth usually contains an acceptable polishing material for the oral cavity or teeth for use in combination with brushing the teeth. Examples of such polishing materials are water-insoluble sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, dihydrated calcium phosphate, anhydrous dicalcium phosphate, calcium pyrophosphate, magnesium orthophosphate, trimagnesium phosphate, calcium carbonate, aluminum silicate, zirconium silicate, silicon dioxide, b dioxide mixtures thereof. Other suitable polishing materials include granular thermosetting resins described in US Pat. No. 4,070,510 of December 15, 1962, such as melamine, phenol, and urea-formaldehyde resins and crosslinked polyepoxides and polyesters. Preferred polishing materials include crystalline silica having a particle size of up to about 5 microns, an average particle size of up to about 1.1 microns, and a surface area of about 50,000 cm ² / g silica gel or colloidal silicon dioxide and an amorphous alkali metal aluminosilicate.

 When a visually clear gel is desired, a polishing agent made of colloidal silicon dioxide, such as those sold under the trade name SILOID, such as Siloid 72 and Siloid 74, or under the trade name SANTOZEL, like Santocel 100, and alkali metal aluminosilicate complexes, are particularly suitable, since they are possess a refractive index close to that for thickening agent-liquid systems (including water and / or a moisturizer), which are commonly used in toothpastes.

 Many of the so-called "water-insoluble" polishing materials are anionic in nature and also include small amounts of soluble material. So, insoluble sodium metaphosphate can be formed in any suitable way, as illustrated in the Thorpe Dictionary of Applied Chemistry, Volume 9, 4th Edition, pp. 510-511. Such forms of insoluble sodium metaphosphate, known as the Madrell salt and the Currol salt, are further examples of suitable materials. These metaphosphate salts have only insignificant solubility in water and therefore they are usually referred to as insoluble metaphosphates (NMPs). They contain, as an admixture, a small amount of soluble phosphate material (usually a few percent, up to 4 wt.). This amount of insoluble phosphate material, which is believed to include soluble sodium trimetaphosphate in the case of insoluble metaphosphate, can be reduced or eliminated by washing with water, if desired. Insoluble alkali metal metaphosphate is usually used in the form of a powder with a particle size such that approximately no more than 1% of this material is larger than 37 microns.

 The polishing material is mainly present in solid or pasty compositions in weight concentrations of from about 10 to 99%. Preferably, it is present in an amount varying from about 10 to 75% in toothpaste or jelly and from 70 to 99% in tooth powder or tablets.

 In toothpaste, cream or jelly, the liquid carrier is usually water in concentrations of about 2 to 50%, and it is mixed with about 0.2-5 moisturizers per 1 part by weight of water. Active xylitol may act as part (or all) of the moisturizer. Examples of suitable humectants / carriers are glycerin, propylene glycol, sorbitol, propylene glycol and / or polyethylene glycol (e.g. 400 600). Liquid mixtures of water, glycerin and sorbitol are also beneficial. In transparent gels, in which an important factor is the refractive index, preferably about 3-30 wt. water, 0-80 wt. glycerol and 20-80 wt. sorbitol.

 Toothpastes (creams) and jellies typically contain a natural or synthetic binder, thickener or gelling agent in ratios of from about 0.1 to 10%, preferably from 0.5 to 5 wt. Suitable thickeners are synthetic hectorite, a synthetic colloidal complex of magnesium silicate and alkali metal with clay, available under the brand name, for example, Laponite (e.g. CP, SP 2002, D), supplied by Laporte Industries Limited. According to the analysis, Laponite D by weight contains approximately 58.00% silicon dioxide, 25.40% magnesium oxide, 3.05% sodium oxide, 0.98% lithium oxide and some water and trace metals. Its true specific gravity is 2.53, and the apparent bulk density (at 8% humidity) is 1.0 g / ml.

 Other suitable thickeners include Irish moss, tragacanate gum, starch, polyvinylpyrrolidone, hydroxyethylpropyl cellulose, hydroxybutyl methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose (e.g. available as Natrozole), sodium carboxymethyl sulfide, and carboxyloxymethylmethylcellulose;

 It can be understood that, as usual, oral formulations must be sold or distributed differently in packs with proper labels. So toothpaste, cream or gel can usually be in compressible tubes, usually aluminum, coated with lead or plastic, or in another squeezed, inflated or pressed dispenser for dispensing the contents, which has a label describing its substances in the form of toothpaste, jelly or tooth cream.

 The compositions of the invention use one or more organic surface-active agents to achieve improved hydration, foaming and prophylactic action, to help achieve thorough and complete dispersion of the composition throughout the oral cavity, which makes the present compositions more acceptable cosmetically. The organic surfactant is preferably anionic, non-ionic or ampholytic in nature, and it is preferable to use a detergent as a surfactant that imparts detergent and foaming properties to this composition. Suitable examples of anionic surfactants are water-soluble salts of higher monosulphates of fatty acid monoglycerides, such as sodium salt of monosulphonated coconut hydrogenated fatty acids monoglyceride, higher alkyl sulfates, such as sodium lauryl sulfate, alkylaryl sulfonates, such as sodium dodecylbenzenesulfonates acids of 1,2-dihydroxypropane sulfonates, and practically saturated higher aliphatic acylamides of lower aliphatic amines carboxylic acid compounds such as those having 12 to 16 carbon atoms in the fatty acid, alkyl or acyl radicals, and the like Examples of the latter amides mentioned are N-lauroylsarcosine and the sodium, potassium and ethanolamine salts of N-lauroyl, N-myristoyl or N-palmitoyl-sarcosine, which should be substantially free of soap or similar higher fatty acid material. The use of these sarcosinate compounds in the oral compositions of the invention is particularly advantageous since these materials have a prolonged and pronounced effect in inhibiting the formation of acids in the oral cavity, which is due to decay in addition to the manifestation of a decrease in the solubility of tooth enamel in acid solutions.

 Examples of water-soluble non-ionic surfactants are the condensation products of ethylene oxide with various reactive hydrogen-containing compounds having long hydrophobic chains (for example, aliphatic chains with 12-20 carbon atoms), and these condensation products ("ethoxamers") contain a hydrophilic polyoxyethylene function, such as condensation products of poly (ethylene oxide) with fatty acids, fatty alcohols, fatty amides, polyhydric alcohols (e.g. sorbitan monostearate) and olipropylene oxide (e.g. Pluronic materials).

 Various other materials may be incorporated into the oral formulations of this invention, such as whitening agents, preservatives, silicones, chlorophyll compounds, other anti-stone agents and / or ammonia-containing materials such as urea, diammonium phosphate and mixtures thereof. When such adjuvants are present, they are introduced into the preparations in amounts that should not have a noticeable worsening effect on the desired properties and characteristics. Significant amounts of zinc and other salts of metals and materials, usually soluble, that could form a complex with the active components of the invention should be avoided.

 In addition, any suitable perfumes or sweeteners may be used. Examples of suitable fragrance components are fragrance oils, for example, peppermint, peppermint, pear, sassafras, cloves, sage, eucalyptus, oregano, cinnamon, lemon and orange; and methyl salicylate. Suitable sweetening agents include sucrose, lactose, maltose, dextrose, levulose, sorbitol, o-tryptophan, dihydrochalcones, sodium cyclamate, perillartine, AFM (aspartylphenylalanine, methyl ether), saccharin, and the like. Active xylitol may form part (or all) of the sweetening agent. Accordingly, the fragrance and sweetening agents together can comprise from about 0.1 to 5% or more by weight of the preparation.

 In the practice of the invention, a specific composition in conventional amounts that are used for traditional oral compositions is preferably applied to the demineralized parts of the tooth structure in the oral cavity of a caries consumer by brushing in the case of toothpastes, creams, jellies and powders and through a “whirlpool” in the case of rinses for the mouth for about 1 to 5 minutes, 1-3 times a day, until the desired degree of remineralization is achieved. Typically, the composition is removed by washing with water after each use.

 The method of the invention can also be used professionally using compositions in the form of coherent thickened pastes or gels for topical, temporary application to demineralized parts of the tooth structure.

 The following examples further illustrate the nature of the invention, however, it should be understood that the invention is not limited to them. All quantities and ratios referred to herein and in the appended claims are by weight and temperatures are in degrees Celsius unless otherwise indicated.

Example 1. Composition for washing the mouth
Component Parts
Deionized Water 57.3824
Xylitol 20,000
Glycerin 7,500
Sorbitol (70% aqueous solution) 7,500
Ethanol 4.9964
Pluronic EF-108 ^* 0.9992
Pluronic EF-127 ^* 0.9992
Sodium benzoate 0.5000
Sodium Fluoride 0.0484 ^**
"F-Di and C" blue N 1 0,0400
"EFD &C" yellow N 5 0,0200
Benzoic acid 0.0100
Fragrance 0.0024
Total 100,0000
^* Polyoxyethylated polyoxypropylene, non-ionic block polymer surfactant
^** Provides 225 ppm feed fluoride ions
Example 2. The composition of example 1 for washing the mouth was tested by people for remineralization at the site of artificial caries damage using the methodology described by Mellberg et al. in J. Dent. Res. Volume 65, p. 1078-1083 (1983), the description of this article is incorporated herein by reference. The following test results were obtained:
Used composition remineralization,
a) Example 1 17.4
b) Example 1 without xylitol 11.3
c) Example 1 without fluoride -4.7
d) Placebo -1.7
These results show that when using the composition of example 1 for washing the mouth a) in the method of the invention unexpectedly significantly and significantly better remineralization is achieved than when using the same composition without xylitol (b), i.e. with one fluoride, or the same composition without fluoride (c), i.e. with one xylitol, or with a placebo (g).

Example 3. The composition of the euba paste
This toothpaste composition is obtained by sequentially mixing parts (1), 2), 3), 4) and 5) indicated in the table. one.

 Example 4. The toothpaste compositions of example 3 were tested on caries of living rats according to the method described by A. Gaffar et al. in Calcif. Jissue Res. volume 35, p. 562-565 (1983), the description of this article is incorporated herein by reference. The following results were obtained (see table. 2).

 These results show that when using the composition (B) of the toothpaste of example 3, the method of the invention unexpectedly obtained a significant and significantly (P less than 0:05) greater effectiveness against caries than when using the same composition without xylitol (A), i.e. e. with sodium fluoride alone, and with placebo (C).

 The invention may be described in accordance with certain preferred embodiments, it being understood that modifications and variations of the invention that are obvious to those skilled in the art should be included in spirit within the purview of this application and in the scope of protection of the appended claims.

Claims (5)

1. Composition for remineralization of the demineralized part of the teeth, having a pH of 4.5 to 10.0 and comprising a carrier containing well-known amounts of water and a humectant and other acceptable excipients, characterized in that it contains xylitol in an amount of 10 to 20 wt. 150 1800 ^-1 million of fluoride ions, with sodium fluoride providing 50 100% fluorine ions, but not containing significant amounts of astringent zinc salt.  2. The composition according to claim 1 in the form of a mouthwash, characterized in that it contains 50 to 99 wt. water-alcohol media in the ratio of water to alcohol 1 20: 1.  3. The composition according to claim 1 in the form of a toothpaste, characterized in that it contains 10 99 wt. polishing agent and 0.1 to 10.0 wt. a binding, thickening or gelling agent.  4. The composition according to PP.1 to 3, characterized in that the humectant is selected from the group consisting of glycerol, propylene glycol, sorbitol, polypropylene glycol, polyethylene glycol and mixtures thereof.  5. The composition according to claims 1 to 4, characterized in that the fluorine ions are mainly provided by sodium fluoride.

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