CN1187117A - Processes and compositions for remineralization and prevention of demineralization of dental enamel - Google Patents
Processes and compositions for remineralization and prevention of demineralization of dental enamel Download PDFInfo
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- CN1187117A CN1187117A CN96194507A CN96194507A CN1187117A CN 1187117 A CN1187117 A CN 1187117A CN 96194507 A CN96194507 A CN 96194507A CN 96194507 A CN96194507 A CN 96194507A CN 1187117 A CN1187117 A CN 1187117A
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Abstract
The present invention relates to the problems of remineralization, without demineralization of dental enamel by applying to the teeth a composition which is present in two phases which do not react with one another until introduced into the oral cavity. One phase contains at least one water-soluble calcium compound and the other contains at least one water-soluble inorganic phosphate and at least one water-soluble fluorine compound. In this way the ions which effect remineralization can be absorbed by the dental enamel and their subsequent reaction causes rehardening of demineralized areas in the dental enamel.
Description
The present invention relates in order to rapid method and composition inferior top layer enamel Remineralization.More specifically, the present invention relates to for example saline solution of calcium and phosphoric acid salt of saline solution, cause the enamel Remineralization on time top layer and/or dential canaliculi mineralising to stop dental caries and/or allergy thereby this class saline solution can be applied in adamantine lesion.
Enamel in the tooth and Dentinal solvent are the calcium phosphate of calcareous hydroxyapatite type.This material is very insoluble under normal oral cavity pH.Yet, when the effect of various antibacterials causes the harm of the acid that produces of glycolysis of sugar in it is subjected to owing to the oral cavity, can form the dental caries sexually transmitted disease (STD) in the tooth and become.This is because the phosphoric acid salt of calcium is more diffluent in acid medium.
With regard to calcium and phosphate anion, saliva is oversaturated.Therefore, saliva helping, prevent the tooth demineralization and can make the tooth Remineralization gradually that has been lost mineral nitrogen by acid attack.The existence of well-known fluorion can be promoted this natural Remineralization process, and this is a toothpaste with fluoride and gargle washing liquid and can prevent one of generally acknowledged mechanism of dental caries.Because the concentration of calcium and phosphate radical is limited in the saliva, thereby makes toothpaste with fluoride and gargle washing liquid the effect of tooth Remineralization is restricted.It seems from prior art, obviously be starved of the calcium that increases in the oral cavity and the valid density of phosphate anion, to quicken the Remineralization process.Yet,, therefore, be difficult to realize adding the dissolved calcium and the phosphate anion of high concentration because the dissolubility of calcium phosphate is lower under the pH of saliva.
Existing people has carried out the interior and in vitro tests of body of enamel Remineralization.Some research concentrates on the Remineralization characteristic of saliva and the oversaturated synthetic solvent of hydroxyapatite.These researchs comprise United States Patent (USP) 3,679, the subject content of 360 (Rubin) and 4,097,935 (Jarcho).
Usually, being used for these patents, to be made for the supersaturated solution of Remineralization test or slurry all be by the calcium phosphate preparation of single form.When a kind of in adopting these supersaturated solutions flooded the lesion of dental caries, calcium and phosphate anion made the lesion Remineralization with sedimentary hydroxyapatite form.
Yet, owing to this class solution of some reasons is inapplicable.At first, it is too low to be used in the amount of the calcium of Remineralization and phosphate anion in these supersaturated solutions.It is reported, just need the usual supersaturated solution of about 10,000 unit volumes for the mineral that produces 1 unit volume.Therefore, adopt this method Remineralization not only to need excessive liquid but also the using of the too much number of times of needs.Because this supersaturated solution can not keep its hypersaturated state, thereby their application in this respect just are restricted inherently.When precipitation of hydroxyapatite is come out to reach solution and no longer is hypersaturated state, must add the supersaturated solution of new preparation, otherwise the Remineralization process will stop.
Another problem of single calcium phosphate slurry is that along with hydroxyapatite is separated out from solution, the pH of this solution changes.Unless exhausted solution is removed and is not contacted with dentine, thereby otherwise this solution can become and be very much acid or alkalescence infringement dental tissue.
United States Patent (USP) 4,080,440 (people such as Digiulio) disclose the calcium of a kind of low pH (2.5-4.0) and the meta solution of phosphate anion, and with this understanding, the dissolubility of calcium phosphate salt is higher.Infiltrate the enamel of demineralization at this solution after, when pH raises, owing to calcium phosphate salt precipitation produces Remineralization.Fluorion can be included in this meta solution.Adopt the remarkable shortcoming of meta solution to be, the low tissue that may make the enamel demineralization and/or injure other of the pH of this solution.
United States Patent (USP) 4,177,258 and 4,183,915 people such as () Gaffar provide a kind of calcium ion, phosphate anion and fluorine source of containing supersaturation concentration, and form for example solution of the stable Remineralization of diamidogen tetramethylene phosphonic acid of agent by adding anti-nucleus.Preferably this solution is adjusted to the neutral pH scope, it is said, the Remineralization to inferior top layer lesion is the most effective in this case.Even estimate that this anti-nucleus forms agent and can stablize this solution, but still find to be difficult to keep the balance and the variation of avoiding precipitation of hydroxyapatite and this pH value of solution of supersaturation concentration.
United States Patent (USP) 4,083,955 (people such as Grabenstetter) and 4,397,837 (people such as Raaf) provide solution that a kind of employing contains calcium ion and phosphate anion respectively sequentially to make the method for the enamel Remineralization of demineralization in the dental treatments surface.Can fluoride ion in the phosphoric acid salt solution of this method.Earlier unimportant with any ion solution dental treatments.By calcium and phosphate anion sequentially are applied on the dental surface, the ion of high concentration can infiltrate lesion with the solution form, when the ions diffusion of second kind of treatment liquid enters, they promptly with the calcium phosphate precipitation of calcium in lesion.Although it is successful coming this method outwardly, this method needs repeatedly sequentially to use, and this can make people feel to lose time very much.
Another problem of known Remineralization technology is since dental surface is outer field in or the outside accumulated the dental material of mineral nitrogenization, the Remineralization process was promptly stopped before the complete Remineralization of lesion.When the speed of Remineralization is too fast, hinders mineral to diffuse into the darker zone of pathological changes with regard to this accumulation occurring, thereby obstruct the sufficient Remineralization of tooth.
Therefore, need a kind of method to the enamel Remineralization, this method does not need excessive solution, long time or frequent frequency of exposure.
The purpose of this invention is to provide a kind of people's of being tooth Remineralization and prevent the method for its demineralization and particularly a kind of compositions, this method and composition can be attached to calcium ion, phosphate anion and fluorion in the enamel effectively, and said composition also is easy to use and at fragrance with there is no remarkable difference with the dentifrice of routine in appearance for the user.
According to the present invention, solved Remineralization and the problem of unlikely demineralization by on tooth, using compositions, said composition is up to being introduced into the oral cavity before with mutual nonreactive biphase the existence.Wherein one contain at least a water miscible calcium compounds mutually, another contains at least a water miscible inorganic phosphate and at least a water miscible fluorine compounds mutually.Like this, these ions that play the Remineralization effect can be absorbed by enamel, and its subsequent reaction can cause in the enamel position of demineralization to be rehardened.
Find that the solution or the preparation of the solubility salt of calcium, phosphate radical and fluorion by will containing high concentration directly merge, and can make the preparation of effective Remineralization, under moderate pH it are applied on the tooth then.Yet, must prevent calcium and phosphate anion or fluorion reaction before using up to facing.This can realize by being equipped with twin containers or two-tube system, wherein calcium ion is in the container or pipe different with phosphate radical or fluorion, or incorporate in the independent substrate by containing these ionic undissolved solubility salts, these ions physically separate in this substrate, for example can seal with capsule, or be insoluble in the described substrate at least a.
System for two parts, dimeric toothpaste, gel, special gel that use by the professional or that obtain by prescription, collutory etc. have been prepared, wherein part I contains 0.05% to about 15% the water-soluble Ca salt of having an appointment, and part II contains have an appointment 0.05% to 15% water-soluble phosphate and about 0.01% to 5% fluorine releasing agent, like this, when these two parts were mixed, its pH was about 4.5-10.0, is preferably about 5.5-7.0.This two parts mixing also is applied on the tooth to be treated immediately.Find that this compositions is carried out Remineralization rapidly in lesion, and make aspect the tooth Remineralization more effective than conventional toothpaste with fluoride.
Compare with prior art combinations, compositions of the present invention is to people's tooth Remineralization and prevent that its demineralization from having had significant improvement.
The present invention has realized inferior top layer Remineralization rather than surperficial Remineralization, thereby has overcome the shortcoming of prior art.Because dental caries when adamantine top layer demineralization, becomes because of this time top layer Remineralization can stop before tooth generation permanent structure damages and cure the dental caries sexually transmitted disease (STD).The present invention does not need enamel surface prepared and does not need to the tooth covering yet or remove corrosion product.In addition, the present invention is convenient to the public and is used, and does not change the custom of people to dental care basically.
The invention reside in discovery and can produce ionic solubility salt and can make the enamel Remineralization by using some, described ion can react and form the required precipitate of Remineralization.Described using comprise and use a kind of dimeric system simultaneously, and wherein first is reactive paste, gel or the solution that is applied to the soluble-salt of dental surface contact position.In this first kind of reactant part, selection can be diffused into the cation on the inferior top layer of demineralization by dental surface.In second portion, anionic reactive paste, gel or the solution that will contain selection are applied to and the dental surface contact position simultaneously.This anion can form and the bonded precipitate of tooth structure by the inferior top layer that dental surface is diffused into demineralization along with described cation.Consequently, when using this two parts system of effective dose, can make the inferior top layer Remineralization of tooth.
" effective dose of Remineralization system or preparation " refers to the consumption that can cause the tooth Remineralization with dental caries pathological changes when used according to the invention, or utilizes toothpaste, gel or the collutory of the various components with following content to make the consumption of normal dental mineralization to prevent that dental caries from forming.
The concentration of soluble-salt is about 0.05 to 15% or is the solubility limit of this salt.If desired, can contain excessive salt.Preferred concentration is about 0.10% to 10%.The concentration that contains required anionic soluble-salt is substantially the same with the concentration of the water soluble salt that contains required cationic.
Though many precipitations all belong to wide region of the present invention, can make the inferior top layer that has replenished mineral nitrogen than the more anti-demineralization of original enamel by the deposit precipitation lower than original adamantine dissolubility.Owing to have fluorion to exist, replenished the enamel of mineral nitrogen than the more anti-demineralization of original enamel.The concentration that contains the salt of fluorion in the solution can be about 0.01%-5.0%, yet preferably is about 0.02%-2.0%.
In order to realize adamantine Remineralization, must in the oral cavity, use the required cationic and the anion of effective dose.Infeed solution amount in the mouth and must contain the required cationic of 100ppm and the required anion of 250ppm at least, and preferably contain greater than 3 the required cationic of 000ppm and 3, the required anion of 000ppm.Preferably be about 20ppm to 5,000ppm from dentifrice or by the amount that the professional applies or the gel of writing out a prescription is supplied with the fluorion the oral cavity.
Although the persistent period that dissolved salt contacts with dental surface is not crucial, the persistent period must be long enough to make these ions to be diffused into the inferior top layer of demineralization by dental surface.The required time suggestion of above-mentioned diffusion was at least for 10 seconds, preferably should be greater than 30 seconds.
Before or after precipitation, the pH of various solution all should be about 4.5 to 10.0, preferably is about 5.5 to 7.0, and other conditions should be fit to oral environment.Although some precipitations may occur, yet should not make all ions chemical combination and form precipitation in solution prematurely, but these ions must be diffused into the zone, inferior top layer of demineralization and can form insoluble salt with the ion in other solution again by dental surface.
The toxicity of these solution and infusible precipitate must be in permissible range (that is, these specific ion must be nontoxic under the consumption in the Remineralization process).
In a preferred embodiment of the invention, the cationic solution used of Remineralization contains 0.05% to 15%, preferred about 0.10% to the 10% dissolved calcium salt that can produce calcium ion of having an appointment.The anion solutions that this Remineralization is used contain have an appointment 0.05% to 15%, preferred about 0.10% to the 10% dissolved phosphate that can produce phosphate anion, and about 0.01% to 5.0%, preferred about 0.02% to the 2.0% solubility villiaumite that can produce fluorion.
The precipitation of gained is Natural tooth Enamel component calcium phosphate or the hydroxyapatite that combines fluorion.This method not only can form the enamel that has replenished mineral nitrogen, and this enamel that has replenished mineral nitrogen can be than the more anti-demineralization subsequently of original enamel.
Harmless water-soluble calcium compound all can be used as calcium compounds in the preparation of the present invention on all toxicologies in principle.When a kind of chemical compound has at least 0.25 gram to be dissolved in 100 ml waters under 20 ℃, promptly think water miscible.
Suitable water-soluble calcium compound is the mixture of calcium chloride, lime nitrate, calcium acetate, calcium gluconate, calcium benzoate, calcium glycerophosphate, calcium formate, 2-Butenedioic acid (E)-, calcium salt, calcium lactate, calcium butyrate and isopropylformic acid. calcium, calcium malate, calcium maleate, calcium propionate, valeric acid calcium or water-soluble calcium compound for example.Lime nitrate is preferred.Compositions of the present invention being used for people's enamel Remineralization should contain the 100ppm calcium ion of having an appointment at least; Its upper limit is about 35, the 000ppm calcium ion.
Suitable water-soluble inorganic phosphate within the scope of the present invention is for example dalcium biphosphate, dipotassium hydrogen phosphate, Polymeric sodium metaphosphate., sodium dihydrogen phosphate and ortho-phosphoric alkali metal salt and ammonium salt, for example potassium orthophosphate, sodium orthophosphate or ammonium orthophosphate.Dalcium biphosphate and dipotassium hydrogen phosphate are preferred.The concentration of phosphate anion is preferably about 250-40,000ppm; Defined identical under dissolubility in the water and the calcium compounds situation.
If desired, can adopt the water soluble salt orthophosphoric acid calcium dihydrogen for example that can produce calcium ion and phosphate anion.Be used for people's tooth Remineralization or prevent that the compositions of the present invention of its demineralization from also containing water miscible fluorine compounds, the activity of its caries prevention has been considered to determine for a long time.Preferably these chemical compounds are included in contain phosphatic mutually in, to avoid forming sl. sol. calcium fluoride.
Suitable fluorine compounds be alkali-metal fluoride for example sodium fluoride, potassium fluoride, lithium fluoride or ammonium fluoride, stannic fluoride, indium, Zirconium tetrafluoride., copper fluoride, Nickel difluoride, fluoridize palladium, fluozirconate is sodium fluozirconate, potassium fluorozirconate or ammonium fluozirconate or Stannous Fluozirconate for example, fluosilicate, borofluoride, fluostannous acid salt.
The organic fluoride for example fluoride of known amine also is applicable to compositions of the present invention.
Can adopt water miscible alkali metal mono-fluor phosphate for example sodium monofluorophosphate, single lithium fluophosphate and single fluorophosphoric acid potassium, preferred sodium monofluorophosphate.In addition, can adopt other water-soluble mono fluorophosphates that comprise single fluorophosphoric acid ammonium, single fluorophosphoric acid aluminum etc.If with mono-fluor phosphate as the fluorine source, without departing from the invention, can be in the calcium cation be included in first kind of component with it.Yet this is not desirable, because the fluorine possible loss.
Suitable toothpaste and gel can be about 0.5% to 50% by using in the anion of this toothpaste and two parts of cation, preferably about abrasive material of 5% to 25%, about foaming agent of 0.2% to 5%, about binding agent of 0.1% to 5%, 0% to 50% wetting agent, all the other make as water and accessory constituent.
The pH that contains the ingredient of the toothpaste of active cation composition or gel is preferably greater than about 3.Yet the mixture that infeeds these two parts in oral cavity must have and is about 4.5 to about 10.0 pH, preferably is about 5.5 to 7.0.As long as be no more than above-mentioned parameter, can regulate the pH of cationic moiety and anionicsite.
Suitable abrasive material comprises silica xerogel.Other conventional dentifrice abrasives also can be used for compositions of the present invention, and these abrasive materials comprise β-phase calcium pyrophosphate, dicalcium phosphate dihydrate, anhydrous calcium phosphate, calcium carbonate, Zirconium orthosilicate. and thermosetting polymer resin.Can adopt for example insoluble Polymeric sodium metaphosphate. of aerosil and insoluble metaphosphate.Also can adopt the mixture of some abrasive materials.The silica xerogel abrasive material is preferred.
Suitable foaming agent is that stability is better and can form foamy foaming agent during whole using.The preferred anionic of no soap or the synthetic organic detergent of nonionic of adopting.The example of this class detergent be have in its alkyl 10-18 carbon atom alkyl sulfate water soluble salt for example sodium lauryl sulfate, have the water soluble salt C of monoglyceride sulfonates, taurine for example of sulfonation monoglyceride of the fatty acid of 10-18 carbon atom
10-C
18The salt of fatty acid amide is the C of N methyl taurine sodium, hydroxyethylsulfonic acid. for example
10-C
18The salt of fatty acid ester and the saturated substantially aliphatic amide with saturated mono amino carboxylic acid of 2-6 carbon atom, wherein this acyl group contains 12-16 carbon atom, for example N-lauryl sarcosine (sarcoside) sodium.Can adopt the mixture of two or more foaming agents.
Add the binding agent thickening so that compositions of the present invention obtains desirable denseness.Suitable thickening agent is water soluble salt for example sodium carboxymethyl cellulose, hydroxypropyl cellulose and the hydroxyethyl-cellulose of cellulose ethers.Also can adopt natural gum for example karaya, Radix Acaciae senegalis, carrageenin and gum tragacanth.Colloidal Magnesiumaluminumsilicate, aerosil, silica xerogel, fumed silica or other levigated silicon dioxide all can be used as the composition of thickening agent with further improvement architectural characteristic.Preferred thickening is an xanthan gum.
In toothpaste or gel, also need to comprise some wetting agent so that its unlikely sclerosis.Suitable wetting agent comprises glycerol, Sorbitol, Polyethylene Glycol, propylene glycol and other edible polyhydric alcohol and composition thereof.
Toothpaste or gel combination can also contain fumet for example wintergreen oil, Oleum menthae, Oleum Menthae Rotundifoliae, Sassafras oil and Oleum Caryophylli.Toothpaste or gel combination can also contain sweeting agent for example glucide, glucose, fructose, sodium cyclamate and aspartame.Sugar and the sweetener for example mixture of sucralose all were considered.
Certainly, also can produce be transparent gel form one mutually or biphase, used gellant comprises for example polyacrylic alkali metal salt of known thickening agent, and preferred size is that about 2 to 20 microns, specific surface area are about 200 to 900m
2The dehydrated silica gel of/g.
The form that the Remineralization system of this description also can be collutory provides.The cationic moiety of collutory and anionicsite all can make by the following method.Collutory generally includes the aqueous solution of ethanol and fumet.Ethanol can play antibacterial action, dissolving fumet and the mouthfeel of comfortable can be provided.Yet, do not have the collutory of alcohol and popularized gradually now.Collutory also can be chosen wantonly and contain other antibacterial and make wetting agent for example glycerol and the Sorbitol that wetness sensation is arranged in the mouth.
Usually, collutory contain have an appointment 0 to 30%, preferred about ethanol of 0 to 20%; About water of 30% to 90%; About glycerol of 0 to 20% or other wetting agent; About antibacterial of 0 to 0.1%; About 0 to 0.2% soluble fluoride source, about sweeting agent of 0.01% to 0.5%, about fumet of 0.01% to 2.0% and about emulsifying agent-surfactant of 0.1% to 1%.
The example of suitable fumet comprises garden heliotrope nitrile (heliotropyl nitrile), wintergreen oil (methyl salicylate), Oleum menthae, assia oil, Oleum Anisi Stellati, Oleum Cinnamomi and composition thereof.Suitable sweeting agent comprises glucide, glycerol, Sorbitol, fructose and 6-(trifluoromethyl)-tryptophan and aspartyl phenyalanine methyl ester.
A kind of product that is used to make the enamel Remineralization is provided in one embodiment of the invention, and this product comprises: the first kind of component that (i) comprises about 0.05% to 15.0%, preferred about water-soluble Ca salt of 0.10% to 10%; The second kind of component that (ii) comprises about 0.05% to 15.0%, preferred about water-soluble phosphate of 0.10% to 10% and about fluorine releasing agent of 0.01% to 10.0%, preferred about 0.02% to 5.0%; (iii) comprise at least two dispense container that the compartment of the port of export is respectively arranged, first compartment is deposited the first kind of component that comprises soluble calcium salt, and second compartment deposited the second kind of component that comprises soluble phosphate and fluorine source, (iv) in order to the closing device of sealing compartment and (v) wherein when these two kinds of components are mixed, its pH is about 4.5 to 10.0, preferably about 5.5 to 7.0.
In order to comprise respectively or to deposit these two kinds of components and provide effective distribution that it is sent in the oral cavity from this, can adopt multiple packing method.
Therefore, two kinds of components of this of toothpaste, gel, emulsifiable paste etc. can be distributed simultaneously from other flexible pipe of branch of preferably being made by plastics, plastics and metal level tabletting etc.For convenience with for for the purpose of helping to distribute equally basically these components, can be preferably together along its corresponding facies ventralis colligation or gluing with these pipes.
In another embodiment, two pipes can be processed into and have sidewall sections that adjoin, preferred flat.In the above-described embodiment, the mouth of these two pipes is sufficiently approaching usually, so that the toothpaste of q.s or the component of gel directly can be assigned on the toothbrush simultaneously after removing the pipe lid respectively.
Perhaps, another kind of packing method comprises each component of toothpaste or gel is packed in each compartment of the same compound flexible pipe that connects with the shared mouth of pipe.This multiple tube has the chamber that separates by dividing plate, and this dividing plate firmly is connected along the part of the sidewall diametrically contraposition of this pipe and the appropriate section of head construction basically.When producing this pipe, can be with sidewall and the head construction gluing or the welding of this dividing plate and pipe.This dividing plate preferably has outstanding part, the exit that this ledge extends to pipe until its edge with till the edge of outlet flushes basically.Like this, dividing plate is just substantially the same in order to store the compartment of cation and anionic group respectively with two volumes of sidewall formation.
In another adoptable packing method, these two pipes are " co-axial ".It is interior and parallel with outer tube that interior pipe is placed on outer tube.The outlet of two pipes abuts against on the same area.In outthrust or analog be inserted between pipe and the outer tube, so that make the component that is contained in the outer tube can obtain the interval of between the outlet of the outlet of outer tube and interior pipe, passing through.The closed shape of a this pipe in another pipe (can be tightened in interior pipe on the outer tube or straight by pressure fixing) can but also needn't assemble the inside outthrust that connects airtight with interior pipe mix prematurely in two kinds of components in pipe exit so that prevent.
The pipe of above-mentioned all embodiments fills from the bottom usually, adopts routine techniques that it is sealed subsequently.
Another kind of adoptable packaging scheme is made up of the pressurization container that is equipped with two compartments and two nozzles.Bottom at each compartment is the internal pressure that nitrogen keeps compartment with Compressed Gas.The unlatching mechanical switch can drive the valve of release compartment Chinese medicine and be expressed on the toothbrush by the component of nozzle with toothpaste or gel.
Collutory or gargle washing liquid and the mode of the embodiment of similar liquids when keeping being similar to toothpaste or gel and storing keeps various components separately, each other to avoid premature reaction.In a minute timing, these components are mixed to be incorporated in the oral cavity and are reacted to realize adamantine Remineralization.Therefore, these liquid components can be stored in the compartment of two chambers administrator separately.This administrator generally includes closed system, this system for example comprises the crown part that tilts, at least two upwardly extending filled nozzles of the upper surface from crown part and the firm lid of this crown part, this lid is furnished with closing device, and for example incidental (depending) stopper is to close this closed shape.The product spray orifice in nozzle, each filled nozzle preferred fit has blow vent.This spray orifice can be placed near hat, and all these help to realize to excessive filled control.Proved that transparent container is optimal.The transparency helps the people can be accurately and the preparation that controllably dispenses out relative equivalent from the administrator of two chambers.The container of transparent wall also can play form so that the liquid meter to leaving in the administrator.The wall of this container can groove or is demarcated to help to dispense out the product volume that Remineralization is accurately used.
Although the applicant does not wish that scope of the present invention is subjected to theoretic restriction, yet can think that calcium, phosphate radical and fluorion can be diffused into the inferior top layer of demineralization and in the inferior top layer of demineralization precipitation, give the tooth structure Remineralization at this place by dental surface.This is beyond thought, because enough calcium, phosphate radical and fluorion still keep solubility to be enough to make them to be diffused into adamantine demineralization time top layer in the regular hour.This can be accomplished by just before being administered to tooth these specific ion in the solution being mixed, the pH that this solution has is about 4.5 to 10, preferably be about 5.5 to 7, under this pH, enough calcium, phosphate radical and fluorion still keep solubility in enamel lesion Remineralization in the required time.As noted before, calcium and phosphate anion are stored respectively, to avoid the calcium phosphate premature precipitation.
Be at most 100 to 1, the first kind and second kind of solution and needn't on chemical equivalent concentration, equate as long as the mol ratio of calcium in this mixture and phosphate anion is about 0.01.Preferred this ratio is about 0.2 to 1, is at most 5 to 1, and most preferably this ratio is about 1.67 to 1, and this is the ratio of calcium and phosphate radical (hydroxyapatite) in the Natural tooth Enamel.
Although the present invention is aqueous solution completely preferably, yet also can use the nonaqueous solvent that cooperates with water.For example, Shi Yi nonaqueous solvent comprises ethanol, glycerol and propylene glycol.The dicyandiamide solution that can dissolve the used salt of the present invention and can be used for the oral cavity safely all is applicable to the present invention.
With regard to time that tooth contacts, must make the persistent period be long enough to allow the inferior top layer of these ions diffusion with regard to solution to demineralization.Above-mentioned diffusion needs about 10 seconds at least.The time that preferably this solution is applied to tooth was about for 10 seconds to about 5 minutes.After this solution was introduced the oral cavity, it is constant relatively that its pH still keeps.Calcium phosphate precipitates easily under this pH, but the most beyond thoughtly be, though may occur some precipitations immediately, even a spot of being settled out is applied to before the tooth now, but the calcium of q.s, phosphate radical and fluorion still are retained in the solution and diffuse into tooth, thereby are the enamel Remineralization of demineralization.Can think, when this solution is introduced the oral cavity at first, provide these ion solution the strongest, after this weaken gradually for the ability of Remineralization.
First kind and second kind of solution mixed with the gained mixture being applied to the interdental time should be no more than 1 minute, preferably less than 1 minute.When using toothpaste, gel etc. to brush teeth, on the surface of tooth, obtain mixing.Essence of the present invention is each component to be mixed and use gained solution rapidly and in time, and it can make calcium phosphate, calcium fluoride and calcium fluoro-apatite be deposited in the top layer adamantine time.Before this precipitation takes place, must rapidly the mixture that comprises this solution be applied on the tooth.Beyond thoughtly be, the pH that this solution has can be about 4.5 to 10, but preferred 5.5 to 7, to obtain above-mentioned effect.Be lower than at about 3 o'clock at pH, very fast generation demineralization.From the viewpoint of safety, it is 2.5 normally undesirable that pH is lower than.
The pH of various solution of the present invention can be adjusted to required pH by method well known in the art.Can pH be reduced by adding any acid that can be used for the oral cavity safely and under its consumption, can produce required pH.The example of suitable acid is acetic acid, phosphoric acid, hydrochloric acid, citric acid and malic acid.
The following example explanation the present invention: with the other places of this paper, except as otherwise noted, all umbers and percentage number average are by weight in these embodiments.
On baurodont enamel sheet surface, adopt carbopol Gel Treatment test specimen that demineralization uses 72 hours to be about 50 microns dark simulated lesions with formation.Measure the case hardness on pending surface then.
Endless form was included in the solution that the demineralization of standard uses demineralization 30 minutes, adopted then by the test products processing of 1 part of product and 2 parts of people's saliva dilution 5 minutes, and Yong Ren saliva Remineralization is 60 minutes again.Make on the test specimen every five circulations to keep one deck saliva and be stored in the low temperature chamber, placement is spent the night.Test has been carried out 3 days, always has demineralization 15 times: handle: the Remineralization circulation.
For cycle of treatment, the reagent of the Remineralization of two parts of this embodiment was blended together before facing dipping enamel test specimen respectively by 1 part of product and 2 parts of saliva dilution.
The preparation of oral cavity Remineralization that has prepared two parts is as follows:
Part A part B
Water 71 66.45
Lime nitrate 4 0.00
Dipotassium hydrogen phosphate 8.00
Sodium fluoride 0.55
Glycerol 25 25.00
After acetic acid mixes immediately with A and B
The pH regulator of mixture is 5.5
Owing to handle the increase of the hardness of bringing
(Vickers unit)
Embodiment 1 Crest placebo under pH5.5
11.2+1.720 circulation 48.2+2.8 of 11.8+1.410 circulation 23.6+1.4 of 5 circulation 17.0+1.9 of 1200ppm fluorine 3.9+0.715 circulation 34.8+2.8 of 13.0+3.6 13.7+2.3 17.5+2.2
Owing to handle the increase of the fluorine that brings
(microgram/centimetre
3)
Embodiment 1 Crest placebo under pH5.5
4,431 219620 circulations of 3,523 2,082 2,928 24415 circulations of 2,433 187910 circulations of 5 circulations of 1200ppm fluorine are 4,749 2964 these results show, when weighing with hardness value added and fluorion intake, because with the product treatment of embodiment 1, the effect of Remineralization is better than Crest, fluoride aqueous solution or placebo.
Embodiment 2,3 and 4
The preparation of oral cavity Remineralization that has prepared two parts is as follows:
Embodiment 2 embodiment 3 embodiment 4
Immediately will after will mixing immediately after will mixing immediately after A B A B A B water 73 66.45 74 66.45 73 66.45 calcium nitrate 2 0.00 1 0.00 2 0.00 dipotassium hydrogen phosphates 8.00 8.00 8.00 sodium fluorides 0.55 0.55 0.55 glycerine 25 25.00 25 25.00 25 25.00 acetic acid mix
The mixture A of A and B and the mixture A of B and the mixture of B
The pH regulator to 4.5 of pH regulator to 5.5 of pH regulator to 5.5 adopt with the same loop mode that is used for estimating embodiment 1 and estimate effectiveness with the Remineralization of Crest above-mentioned prescription relatively.In this research, adopt 15 circulations.
Because the hardness that processing brings and the increase of fluorine
Embodiment 2 embodiment 3 embodiment 4 Crest hardness increase these results of 45.1+2.9 37.6+2.4 32.7+2.5 14.2+1.8 fluorine intake 4677+219 5686+138 4495+343 2099+182 and show, when weighing with hardness value added and fluorion intake, because with the product treatment of embodiments of the invention 2,3 and 4, the effect of Remineralization is better than Crest.
Embodiment 5,6,7,8,9 and 10
The preparation of oral cavity Remineralization that has prepared two parts is as follows:
Embodiment 5 embodiment 6 embodiment 7
Immediately will after will mixing immediately after will mixing immediately after A B A B A B water 71.2 70.45 67.4 66.86 67.4 66.45 calcium nitrate 3.8 0.00 7.6 0.00 7.6 0.00 dipotassium hydrogen phosphates 4.00 8.00 8.00 sodium fluorides 0.55 0.14 0.55 glycerine 25.0 25.00 25.0 25.00 25.0 25.00 acetic acid mix
The mixture A of A and B and the mixture A of B and the mixture of B
The pH regulator to 4.5 of pH regulator to 5.5 of pH regulator to 5.5
Immediately will after will mixing immediately after will mixing immediately after embodiment 8 embodiment 9 embodiment 10 water 63.6 62.45 67.4 66.45 67.4 66.45 calcium nitrate 11.4 0.00 11.4 0.00 7.6 0.00 dipotassium hydrogen phosphates 12.00 8.00 8.00 sodium fluorides 0.55 0.55 0.55 glycerine 25.0 25.00 25.0 25.00 25.0 25.00 acetic acid mix
The mixture A of A and B and the mixture A of B and the mixture of B
The pH regulator to 4.5 of pH regulator to 5.5 of pH regulator to 5.5 adopt with the same loop mode that is used for estimating embodiment 1-4 and estimate effectiveness with the Remineralization of Crest embodiment 5-10 relatively.In this research, adopt 15 circulations.
Owing to handle the increase of the hardness of bringing
Vickers unit
The increase of hardness
Embodiment 5 97+6
Embodiment 6 97+6
Embodiment 7 95+2
Embodiment 8 84+5
Embodiment 9 83+5
Embodiment 10 82+3
Crest 20+2
These results show that when weighing with the hardness value added, owing to handle with the preparation of embodiments of the invention 5-10, the effect of Remineralization is better than Crest.Even embodiment 6 shows the fluorinion concentration that will supply with and only is reduced to Crest supplied with 27% (that is, the ratio of 275ppm and 1150ppm), still can obtain higher Remineralization level.
The different embodiments of the toothpaste preparation of embodiment 11-16 explanation Remineralization of the present invention, the result is as follows:
Embodiment 11 embodiment 12 embodiment 13
A B A B A B glycerine 10.0 10.0 5.0 4.0 6.0 6.0 D-sorbites 40.0 40.0 30.0 30.0 34.0 30.0 water 18.5 19.32 17.9 14.82 32.3 29.5 abrasive silica 15.0 15.0 0.0 0.0 10.0 5.0 silicon dioxide thickening agents 8.0 8.0 0.0 0.0 8.0 5.0DCPDH 0.0 0.0 40.0 0.0 0.0 0.0 calcium nitrate 5.0 0.0 3.5 0.0 6.0 0.0 sodium dihydrogen phosphates 0.0 3.7 0.0 6.5 0.0 10.0 sodium metaphosphates 0.0 0.0 0.0 40.0 0.0 10.0CMC 1.0 1.0 1.2 1.5 1.4 1.5 NaLSs 1.5 1.5 1.2 1.8 1.3 1.5 sodium fluorides 0.0 0.48 0.0 0.48 0.0 0.1 fumet 0.8 0.8 0.9 0.7 0.7 1.0 asccharin 0.2 0.2 0.3 0.2 0.3 0.4
Embodiment 14 embodiment 15 embodiment 16
A B A B A B glycerine 10.0 10.0 5.0 4.0 6.0 6.0 D-sorbites 40.0 40.0 30.0 30.0 34.0 30.0 water 18.5 19.32 17.9 14.82 32.3 29.5 abrasive silica 15.0 15.0 0.0 0.0 10.0 5.0 silicon dioxide thickening agents 8.0 8.0 0.0 0.0 8.0 5.0 DCPDH 0.0 0.0 40.0 0.0 0.0 0.0 calcium nitrate 5.0 0.0 3.5 0.0 6.0 0.0 sodium dihydrogen phosphates 0.0 3.7 0.0 6.5 0.0 10.0 sodium metaphosphates 0.0 0.0 1.2 1.5 1.4 1.5 NaLSs 1.5 1.5 1.2 1.8 1.3 1.5 sodium fluorides 0.0 1.81 0.0 0.0 0.0 0.0 sodium MFP 0.0 0.0 0.0 1.52 0.0 0.2 fumet 0.8 0.8 0.9 0.7 0.7 1.0 asccharin 0.2 0.2 0.3 0.2 0.3 0.4
The embodiment of the preparation of gargling that embodiment 17 explanation Remineralization are used is as follows:
Embodiment 17
Part A part B
Glycerol 10.000 10.0
Ethanol 20.000 20.0
Sodium fluoride 0.055 0.00
Lime nitrate 0.000 5.00
Dipotassium hydrogen phosphate 5.000 0.00
Potassium dihydrogen phosphate 0.000 0.00
Water is an amount of
Claims (35)
1. product that is used to make the enamel Remineralization, this product comprises:
(i) comprise first kind of independent component of about at least a water-soluble Ca salt of 0.05% to 15.0%;
(ii) comprise about 0.05% to 15.0% at least a water-soluble phosphate and at least a second kind of independent component that can produce the water solublity villiaumite of fluorion of about 0.01% to 5.0%; With
(iii) wherein when these two kinds of components are mixed, the pH of this mixture is about 4.5 to 10.0.
2. according to the product of claim 1, wherein this first kind of component comprises about 0.10% to 10.0% described calcium salt.
3. according to the product of claim 1, wherein this second kind of component comprises about 0.10% to 10.0% described phosphate.
4. according to the product of claim 1, wherein this second kind of component contains 0.02% to 2.0% the described villiaumite of having an appointment.
5. according to the product of claim 1, wherein when these two kinds of components were mixed, the pH of this mixture was about 5.5 to 7.0.
6. according to the product of claim 1, wherein the mol ratio of calcium and phosphate anion is about 0.01 to 1 in these two kinds of components, is at most 100.0 to 1.
7. according to the product of claim 6, wherein the mol ratio of calcium and phosphate anion is about 0.2 to 1 in these two kinds of components, is at most 5.0 to 1.
8. according to the product of claim 1, wherein each component is paste, gel or special gel.
9. according to the product of claim 1, wherein each component is the liquid collutory or gargles washing liquid.
10. according to the product of claim 1, wherein first kind of component contains the 100ppm to 35 that has an appointment, the calcium ion of 000ppm, and second kind of component contains the 250ppm to 40 that has an appointment, the phosphate anion of 000ppm and about 20ppm to 5, the fluorion of 000ppm.
11. a product that is used to make the enamel Remineralization, this product comprises:
(i) comprise first kind of independent component of about at least a water-soluble Ca salt of 0.05% to 15.0%;
(ii) comprise about 0.05% to 15.0% at least a water-soluble phosphate and at least a second kind of independent component that can produce the water solublity villiaumite of fluorion of about 0.01% to 5.0%;
(iii) comprise at least two dispense container that the independently divided chamber of mutually close outlet is respectively arranged, first compartment is deposited the first kind of component that comprises calcium salt, and second compartment deposited and comprised phosphatic second kind of component;
(iv) in order to seal the closing device of compartment; With
(v) wherein when the preparation in these two compartments is mixed, the pH of this mixture is about 4.5 to 10.0.
12. according to the product of claim 11, wherein this first kind of component comprises about 0.10% to 10.0% described calcium salt.
13. according to the product of claim 11, wherein this second kind of component comprises about 0.10% to 10.0% described phosphate.
14. according to the product of claim 11, wherein this second kind of component contains 0.02% to 2.0% the described villiaumite of having an appointment.
15. according to the product of claim 11, wherein when these two kinds of components were mixed, the pH of this mixture was about 5.5 to 7.0.
16. according to the product of claim 11, wherein the mol ratio of calcium and phosphate anion is about 0.01 to 1 in these two kinds of components, is at most 100.0 to 1.
17. according to the product of claim 16, wherein the mol ratio of calcium and phosphate anion is about 0.02 to 1 in these two kinds of components, is at most 5.0 to 1.
18. according to the product of claim 11, wherein each component is paste, gel or special gel.
19. according to the product of claim 11, wherein each component is the liquid collutory or gargles washing liquid.
20. according to the product of claim 11, wherein first kind of component contains the 100ppm to 35 that has an appointment, the calcium ion of 000ppm, and second kind of component contains the 250ppm to 40 that has an appointment, the phosphate anion of 000ppm and about 20ppm to 5, the fluorion of 000ppm.
21. a water-containing products that is used to make the enamel Remineralization, this product comprises:
(i) comprise first kind of independent liquid component of about 0.05% to 15.0% lysed calcium salt;
The second kind of independent liquid component that (ii) comprises about 0.05% to 15.0% lysed phosphate and about lysed villiaumite of 0.01% to 5.0%;
(iii) comprise at least two dispense container that the independently divided chamber of the port of export is respectively arranged, first compartment is deposited the first kind of component that comprises lysed calcium salt, and second compartment deposited and comprised lysed phosphatic second kind of component;
(iv) in order to seal the closing device of compartment; With
(v) wherein when these two kinds of components are mixed, its pH is about 4.5 to 10.0.
22. according to the product of claim 21, wherein each compartment contains the component that is about equivalent that is stored in wherein, this compartment can make first kind and second kind of closing device that component is approximately distributed from described compartment equally simultaneously in addition.
23. a method that is used for the enamel Remineralization, this method comprises:
(i) distribute the first kind of component that comprises about at least a water-soluble Ca salt of 0.05% to 15.0%;
Second kind of component of (ii) distributing at least a water solublity villiaumite comprise about 0.05% to 15.0% at least a water-soluble phosphate and about 0.01% to 5.0%;
(iii) described first kind of component and described second kind of component are mixed, wherein the pH of each component pH that the mixture that produced is had is about 4.5 to 10; With
The described mixture that (iv) will be the aqueous solution form is applied to time enough on the tooth so that the calcium and the phosphate anion that are produced by various salt are diffused into adamantine top layer of demineralization, thus then precipitation and form hydroxyapatite and make the enamel Remineralization.
24. according to the method for claim 23, wherein said first kind of component and second kind of component are paste, gel or special gel, and are expressed on the toothbrush simultaneously.
25., wherein after described each component being extruded and placed it on the toothbrush, brush teeth in about 1 minute according to the method for claim 23.
26. according to the method for claim 23, wherein the time that calcium and phosphate anion are applied on the tooth is to be at most 5 minutes about 10 seconds.
27. according to the method for claim 23, wherein this first kind of component comprises about 0.10% to 10.0% described calcium salt.
28. according to the method for claim 23, wherein this second kind of component comprises about 0.10% to 10.0% described phosphate.
29. according to the method for claim 30, wherein this second kind of component contains 0.02% to 2.0% the described water solublity villiaumite of having an appointment.
30. according to the method for claim 23, wherein the pH that has of the mixture that is produced is about 5.5 to 7.0.
31. according to the method for claim 23, wherein the mol ratio of calcium and phosphate anion is about 0.01 to 1 in these two kinds of components, is at most 100.0 to 1.
32. according to the product of claim 32, wherein the mol ratio of calcium and phosphate anion is about 0.2 to 1 in these two kinds of components, is at most 5.0 to 1.
33. according to the method for claim 23, wherein first kind of component contains the 100ppm to 35 that has an appointment, the calcium ion of 000ppm, and second kind of component contains the 250ppm to 40 that has an appointment, the phosphate anion of 000ppm and about 20ppm to 5, the fluorion of 000ppm.
34. a product that is used to make the enamel Remineralization, this product comprises:
(i) comprise first kind of independent component of at least a water-soluble alkali mono-fluor phosphate of about 0.05% to 15.0% at least a water-soluble Ca salt and about 0.01% to 5.0%;
The second kind of independent component that (ii) comprises about at least a water-soluble phosphate of 0.05% to 15.0%; With
(iii) wherein when these two kinds of components are mixed, the pH of this mixture is about 4.5 to 10.0.
35. according to the product of claim 34, wherein this alkali metal mono-fluor phosphate is a sodium monofluorophosphate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN96194507A CN1187117A (en) | 1995-06-06 | 1996-06-05 | Processes and compositions for remineralization and prevention of demineralization of dental enamel |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/465,875 | 1995-06-06 | ||
| CN96194507A CN1187117A (en) | 1995-06-06 | 1996-06-05 | Processes and compositions for remineralization and prevention of demineralization of dental enamel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1187117A true CN1187117A (en) | 1998-07-08 |
Family
ID=5128678
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN96194507A Pending CN1187117A (en) | 1995-06-06 | 1996-06-05 | Processes and compositions for remineralization and prevention of demineralization of dental enamel |
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| Country | Link |
|---|---|
| CN (1) | CN1187117A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100348164C (en) * | 2005-05-23 | 2007-11-14 | 西安理工大学 | Method of painting flourous delayed releasing matter onto denture to preventing demineralization of enamel |
| CN103230342A (en) * | 2013-04-16 | 2013-08-07 | 山东建筑大学 | Hydroxyfluorapatite membrane growing on enamel surface |
| CN106456466A (en) * | 2014-06-09 | 2017-02-22 | 荷兰联合利华有限公司 | Oral care compositions |
| CN110022840A (en) * | 2016-11-30 | 2019-07-16 | 荷兰联合利华有限公司 | Oral care composition |
| WO2021088327A1 (en) * | 2019-11-05 | 2021-05-14 | 浙江大学 | Tooth mineralization solution and mineralization method thereof |
| CN113509394A (en) * | 2021-07-14 | 2021-10-19 | 上海市第十人民医院 | Mineralized glycerin gel, preparation method and application |
| CN116023679A (en) * | 2022-12-01 | 2023-04-28 | 中山大学附属口腔医院 | Thermosensitive slow-release calcium-phosphorus antibacterial nano hydrogel and preparation method and application thereof |
-
1996
- 1996-06-05 CN CN96194507A patent/CN1187117A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100348164C (en) * | 2005-05-23 | 2007-11-14 | 西安理工大学 | Method of painting flourous delayed releasing matter onto denture to preventing demineralization of enamel |
| CN103230342A (en) * | 2013-04-16 | 2013-08-07 | 山东建筑大学 | Hydroxyfluorapatite membrane growing on enamel surface |
| CN106456466A (en) * | 2014-06-09 | 2017-02-22 | 荷兰联合利华有限公司 | Oral care compositions |
| CN114432165A (en) * | 2014-06-09 | 2022-05-06 | 联合利华知识产权控股有限公司 | Oral care compositions |
| CN110022840A (en) * | 2016-11-30 | 2019-07-16 | 荷兰联合利华有限公司 | Oral care composition |
| WO2021088327A1 (en) * | 2019-11-05 | 2021-05-14 | 浙江大学 | Tooth mineralization solution and mineralization method thereof |
| CN113509394A (en) * | 2021-07-14 | 2021-10-19 | 上海市第十人民医院 | Mineralized glycerin gel, preparation method and application |
| CN116023679A (en) * | 2022-12-01 | 2023-04-28 | 中山大学附属口腔医院 | Thermosensitive slow-release calcium-phosphorus antibacterial nano hydrogel and preparation method and application thereof |
| CN116023679B (en) * | 2022-12-01 | 2024-04-23 | 中山大学附属口腔医院 | Thermosensitive slow-release calcium-phosphorus antibacterial nano hydrogel and preparation method and application thereof |
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