CN1320879C - Oral preparation system - Google Patents
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- CN1320879C CN1320879C CNB2003801077763A CN200380107776A CN1320879C CN 1320879 C CN1320879 C CN 1320879C CN B2003801077763 A CNB2003801077763 A CN B2003801077763A CN 200380107776 A CN200380107776 A CN 200380107776A CN 1320879 C CN1320879 C CN 1320879C
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Abstract
An oral preparation of the present invention contains a multi-composition system including a calcium ion supplying compound; a fluoride ion supplying compound;a polyolphosphate ion supplying compound; and a monofluorophosphate ion supplying compound, wherein the calcium ion supplying compound and the fluoride ion supplying compound are separated within the oral preparation.
Description
Technical field
The present invention relates to oral preparation system, it contains chemical compound that calcium ion is provided and the chemical compound that fluoride ion is provided.
Background technology
Adamantine key component is a hydroxyapatite, usually in mouth phosphate anion or calcium ion from tooth loss (being demineralized) and the crystallization (being remineralization) of calcium phosphate or hydroxyapatite be in a kind of poised state.Fluoride ion can be by suppressing replenishing and crystallization of demineralized and promotion calcium ion and phosphate anion, and promptly the remineralization of tooth prevents dental caries.
Yet when fluoride ion and calcium ion were blended in the identical compositions, calcium fluoride precipitated in said composition.This preformed calcium fluoride is a kind of powdered substance (particle mean size: several microns), when it is used for the oral cavity, because granularity is too big, is adsorbed onto hardly on the tooth, therefore is difficult to the effect that performance promotes remineralization of teeth.
Based on this point, proposed a kind of oral preparation, wherein calcium ion source and fluoride ion source are made independent compositions, and these two compositionss are mixed in the oral cavity mutually then, immediately mixed before perhaps in importing the oral cavity, thereby form calcium fluoride in the oral cavity.For example, a kind of dental health product (spy opens clear 58-219107 and the flat 10-511956 of Te Kai) that contains calcium ion source, fluoride ion source and calcium screening agent is arranged.Yet, because this dental health product contains the calcium screening agent, so this dental health product problem of existing tooth that the absorption of fluorine is suppressed by the calcium screening agent on the contrary.
In addition, also propose to contain calcium fluoride with the preformed compositions of colloid form (spy opens flat 3-72415).Yet, this colloidal stability decreases when its problem is long preservation, like this its effect with regard to deficiency so that the calcium fluoride particle deposit at dental surface.
The spy opens the rapid precipitation that clear 63-101312 discloses calcium fluoride and can be induced.Yet,, also can not control the aggregation rate of post precipitation calcium fluoride particle (primary particle), so that after forming primary particle, identical aggregation (homo-aggregation) is carried out fast, thereby forms secondary particle even like this.Be that this granularity is looked too big for the problem of the secondary particle of the calcium fluoride of Xing Chenging like this, reduced the adsorbance on the tooth.
Here should be noted that this primary particle is the calcium fluoride crystalline particle that is formed by fluoride ion and calcium ion, this secondary particle is by gathering, for example the particle of the identical gathering formation of primary particle.
In addition, the spy opens the formation that discloses control fluoride in collutory, dentifrice and the gel among the flat 10-511956.That is, in order to control the formation of calcium fluoride, propose to contain a kind of calcium fluoride inhibitor, it causes the calcium fluoride precipitation to postpone about at least 5 seconds after calcium ion and fluoride ion mixing.
Contain the calcium fluoride inhibitor and get the delay that the result is the gathering (promptly forming secondary particle) that realized calcium fluoride.Yet the existence of this inhibitor has also suppressed the formation reaction (being the formation of primary particle) of calcium fluoride, and this can cause the problem as the formation amount reduction of the calcium fluoride of primary particle.
Therefore, more effectively promote remineralization in order to reach, the speed of expectation calcium fluoride gathering (formation of secondary particle) can be controlled, forms (formation of primary particle) and do not influence calcium fluoride.
Summary of the invention
The invention provides the oral preparation system that contains following component:
(A) provide the chemical compound of calcium ion;
(B) provide fluoride ion but the chemical compound of single fluorophosphoric acid radical ion is not provided;
(C) provide the chemical compound of polyhydroxy phosphate anion (polyolphosphate ion); With
(D) provide the chemical compound of single fluorophosphoric acid radical ion (monofluorophosphate ion),
Component (A) and (B) in this oral preparation system, separate wherein.
The present invention also provides a kind of multicomponent oral preparation system, it is characterized in that comprising following component:
(B) provide fluoride ion but the chemical compound of single fluorophosphoric acid radical ion be not provided,
(D) provide the chemical compound of single fluorophosphoric acid radical ion,
(E) Polyhydric calcium phosphate
Component (B) and (E) in described oral preparation system, separate wherein.
The present invention also provides a kind of oral preparation that contains the many composition systems that comprise compositions (X) and compositions (Y), it is characterized in that component (C) is blended in described many composition systems:
(X) contain (A) and first compositions (D);
(Y) second compositions that contains (B);
(A) provide the chemical compound of calcium ion;
(B) provide the chemical compound of fluoride ion;
(C) provide the chemical compound of polyhydroxy phosphate anion; With
(D) provide the chemical compound of single fluorophosphoric acid radical ion.
Brief Description Of Drawings
Fig. 1 is presented at the variation of solution turbidity behind blend compositions X and Y among an embodiment and the comparative example.
Fig. 2 is presented at the adsorbed state on the HAP powder among the embodiment 1.
Fig. 3 is presented at the adsorbed state on the HAP powder among the comparative example 1.
Fig. 4 is presented at the adsorbed state on the HAP powder among the comparative example 3.
Fig. 5 shows the result that calcium fluoride crystal size X-ray diffraction method is measured.
Fig. 6 is presented at the pH that the HAP titration causes among an embodiment and the comparative example to be changed.
Fig. 7 shows a pulsating state of incipient dental caries.
Fig. 8 (a) shows CMR (soft X-ray) photo of this section tooth.
Fig. 8 (b) shows the mineral recovery rate (recoveryratio) of an embodiment and comparing embodiment.
The specific embodiment
The invention provides a kind of oral preparation system, it can form the calcium fluoride primary particle, and can control the speed that calcium fluoride is assembled (being the formation of secondary particle), therefore and allow that the absorption on tooth etc. of calcium fluoride microgranule is more, suppressing the tooth demineralized and promoting effect excellence on the remineralization thus.
The inventor finds to be reduced to a less size by the size with the calcium fluoride primary particle, with the gathering (formation of secondary particle) that suppresses primary particle, the polyhydroxy phosphate anion can be controlled the granularity of calcium fluoride secondary particle (calcium fluoride aggregation), obtains benefit of the present invention thus.
That is to say, the inventor has prepared a kind of oral preparation system, it can promote primary particle to form and can control secondary particle to form, therefore by using this oral preparation system, show the excellent results that suppresses the tooth demineralized and promote remineralization, this oral preparation system is as a kind of oral preparation, be to contain (A) chemical compound of calcium ion is provided and (B) fluoride ion is provided but many composition systems of the compositions of single fluorophosphoric acid radical ion are not provided, component (A) and (B) separate wherein, in other words, they do not contact in this oral preparation system each other.These many composition systems further contain the chemical compound that (C) provides the chemical compound of polyhydroxy phosphate anion and single fluorophosphoric acid radical ion (D) is provided, they are included in the compositions that contains component (A) or component (B) as component, or in the compositions that contains component (A) with contain in the compositions of component (B) and all have, perhaps in another independent compositions.
And the inventor makes quick generation calcium fluoride microgranule (primary particle) become possibility by mutual blending ingredients (A), component (B), component (C) and component (D), such as in many composition systems, preparing following any one combination:
(1) contains component (A), (C) and compositions (D) and contain the combination of the independent compositions of component (B);
(2) contain the compositions of component (A) and contain the combination of component (B), (C) and independent compositions (D);
(3) contain component (A) and compositions (C) and the combination that contains component (B) and independent compositions (D);
(4) contain component (A) and compositions (D) and contain the combination of component (B) and independent compositions (C);
(5) contain component (A) and compositions (D) and contain the independent compositions of (B) and contain the combination of the independent compositions of (C);
(6) contain component (A) and compositions (C), contain the independent compositions of component (B) and contain the combination of the independent compositions of component (D);
(7) contain component (B) and compositions (D), contain the independent compositions of component (A) and contain the combination of the independent compositions of component (C);
(8) contain component (B) and compositions (C), contain the independent compositions of component (A) and contain the combination of the independent compositions of component (D); And
(9) contain the compositions of component (A), contain the independent compositions of component (B), contain the independent compositions of component (C) and contain the combination of the independent compositions of component (D).
The primary particle size of this calcium fluoride microgranule is preferably 0.3 to 15nm (nanometer), and more preferably 0.3 to 12nm, and more preferably 0.3 to 9nm.
Secondary particle as the calcium fluoride particle aggregate can contain mono-fluor phosphate.The content range of mono-fluor phosphate is preferably 0.05 to 20wt.% (percetage by weight) of aggregation, and more preferably 0.1 of aggregation to 15wt.%, and more preferably 0.5 of aggregation to 10wt.%.
The secondary particle of this calcium fluoride microgranule also can contain polyhydroxy phosphate.The phosphatic content range of polyhydroxy be preferably aggregation 0.05 to 20wt.%, more preferably 0.1 of aggregation to 15wt.%, more preferably 0.5 of aggregation to 10wt.%.
Further, the secondary particle of this calcium fluoride microgranule can contain mono-fluor phosphate and polyhydroxy phosphate simultaneously, and it can be mono-fluor phosphate and the phosphatic compound particle of polyhydroxy.The phosphatic total content scope of mono-fluor phosphate and polyhydroxy be preferably compound particle 0.1 to 40wt.%, more preferably 0.2 of compound particle to 30wt.%, more preferably 1 of compound particle to 20wt.%.
About using oral preparation system of the present invention, owing to can form more calcium fluoride primary particle, can control the speed that calcium fluoride is assembled (secondary particle formations), it is more that the calcium fluoride microgranule is adsorbed on tooth etc.So oral preparation system provided by the invention has such as adsorbable ability good on surfaces such as intraoral tooth and suppresses demineralized and promote the excellent results of remineralization of teeth.
In addition, use the oral preparation system that contains polyhydroxy phosphate as a component of these many composition systems of the present invention, when the calcium fluoride secondary particle formed, calcium fluoride microgranule and polyhydroxy phosphate were easy to form compound particle and are present in this secondary particle.This oral preparation system is by being contained in the reduction (particularly, the remaining dental plaque after brushing teeth) that the phosphatic pH buffer capacity of polyhydroxy in the described compound particle can suppress remaining dental plaque pH, thus the dental caries that causes owing to the reduction of dental plaque pH in advance.Further, in one embodiment, calcium fluoride microgranule and mono-fluor phosphate form compound particle, so then compound particle is present in the secondary particle, the effect of this mono-fluor phosphate is improved in this secondary particle, that is, strengthen the effect that suppresses the tooth demineralized and promote remineralization of teeth.These effects are similar to the advantage of caries prevention.
When using oral preparation system of the present invention, this calcium fluoride can be adsorbed on the tooth effectively by control calcium fluoride granularity, the excellent results that obtains to suppress demineralized thus and promote remineralization of teeth.
Further, in one embodiment, calcium fluoride microgranule, mono-fluor phosphate and polyhydroxy phosphate form compound particle, this compound particle is present in the secondary particle then, by the synergism between them, the pH of remaining dental plaque reduction is inhibited, and the demineralized of tooth is suppressed, remineralization more effectively promoted, therefore caries prevention more effectively.
The example that can be used as the chemical compound that calcium ion is provided of component (A) in the present invention comprises Polyhydric calcium phosphate, calcium hydroxide, calcium chloride, calcium acetate, calcium formate, calcium lactate, lime nitrate, calcium gluconate, calcium benzoate, isopropylformic acid. calcium, calcium propionate, calcium salicylate, calcium carbonate, calcium hydrogen phosphate, calcium phosphate, hydroxyapatite and composition thereof.The example of Polyhydric calcium phosphate (component (E)) comprises calcium glycerophosphate, Cori ester calcium and G-6-P calcium.In order to improve the taste of this oral preparation system, the example that the chemical compound of calcium ion preferably is provided is calcium lactate and calcium glycerophosphate.
In order in the oral cavity, to form calcium fluoride effectively, provide the chemical compound of calcium ion preferably to provide the said composition that contains component (A) 10 to 16000ppm calcium ions in the component (A), more preferably 50 to 12000ppm calcium ions, more preferably 200 to 8000ppm calcium ions.As can be used for the chemical compound that calcium ion is provided of the present invention, preferred use can ionizablely provide the chemical compound of calcium.The compositions that contains component (A) equates on weight with the use amount that contains the compositions of component (B), this amount that the chemical compound of calcium ion is provided in the compositions of component (A) of containing is preferably 0.25 to 400 μ mol/g (micromole's/g) scope, the more preferably scope of 1.25 to 300 μ mol/g, the more preferably scope of 5 to 200 μ mol/g.
The example that can be used as the chemical compound that fluoride ion is provided of component (B) in the present invention comprises sodium fluoride, stannous fluoride, potassium fluoride, zinc fluoride, betanin fluoride, alanine stannous fluoride, prodan, hexylamine fluoride and composition thereof.The example that the chemical compound of fluoride ion preferably is provided is sodium fluoride and stannous fluoride.
In order in the oral cavity, to form calcium fluoride effectively, provide the chemical compound of fluoride ion that this compositions that contains component (B) 5 to 4000ppm fluoride ions preferably are provided in the component (B), more preferably 25 to 2000ppm, and more preferably 100 to 1000ppm.In order to make fluoride ion concentration in above-mentioned scope, equate on weight as fruit component (A) and component (B), it is for example this in the compositions that contains component (B) that the preferred amount scope of chemical compound of fluoride ion is provided is 0.065 to 210 μ mol/g, more preferably 0.325 to 158 μ mol/g, more preferably 2.6 to 105 μ mol/g.
Calcium ion and fluoride ion form calcium fluoride with the ratio reaction of 1: 2 (mol ratio).In order in use effectively to form calcium fluoride, the chemical compound (representing with calcium) of calcium ion is provided in oral preparation system of the present invention and provides the content of the chemical compound (representing) of fluoride ion to be preferably 1: 8 to 4: 1 than (mol ratio) scope, more preferably 1: 4 to 2: 1 with fluorine.
The examples of compounds that single fluorophosphoric acid radical ion is provided that can be used as component (D) in the present invention comprises sodium monofluorophosphate, single fluorophosphoric acid potassium, single magnesium fluorophosphate, single calcium monofluorophosphate..The chemical compound that single fluorophosphoric acid radical ion preferably is provided is a sodium monofluorophosphate.Single fluorophosphoric acid radical ion is retained in the oral cavity, particularly in dental plaque etc., is decomposed gradually by the phosphatase in saliva or the dental plaque etc., therefore continues to provide the dental fluoride ion.Only be contained in the compositions that contains component (A) as fruit component (D), and the compositions that contains component (A) equates on weight with the use amount that contains the compositions of component (B), single fluorophosphoric acid radical ion is preferably 0.065 to 210 μ mol/g in the compositions that contains component (A), more preferably 0.325 to 158 μ mol/g, the more preferably amount of 2.6 to 105 μ mol/g.
The chemical compound that single fluorophosphoric acid radical ion is provided as component (D) can be included in the compositions that contains said components (A) or said components (B), can be included in the compositions that contains component (A), be included in simultaneously in the both compositions of component (B), perhaps can be used as the 3rd component and be independent of in the compositions that contains component (A) and component (B), perhaps be included in the 3rd compositions as a component.
The example that can be used as the chemical compound that the polyhydroxy phosphate anion is provided of component (C) in the present invention comprising: contain 3 to 10 carbon atoms, the monosaccharide that has one or more phosphate groups on the per molecule, by 2 to 6 oligosaccharide that such monosaccharide is formed with contain 3 to 10 carbon atoms, the polyhydric alcohol that has one or more phosphate groups on the per molecule.Provide the object lesson of the chemical compound of polyhydroxy phosphate anion to comprise phosphoglycerol, glyceraldehyde 3-phosphate, erythrose 4-phosphate, ribose 5-phosphate, glucose 1-phosphate, glucose 6-phosphate, inositol monophosphate salt, phytate, fructose-1-phosphate salt, fructose 6-phosphate, fructose 1,6-diphosphate, ascorbic acid 2-phosphate, phosphorylation maltotriose, phosphorylation maltotetraose and their salt are such as sodium, potassium, calcium or magnesium salt.In the middle of them, the sodium salt of phosphoglycerol or calcium salt, glucose 1-phosphate, perhaps glucose 6-phosphate is preferred.As mentioned above, containing Polyhydric calcium phosphate (component (E)), such as the situation of calcium glycerophosphate, Cori ester calcium and G-6-P calcium, it also can serve as the chemical compound (component (A)) that calcium ion is provided.
Providing the chemical compound of polyhydroxy phosphate anion to be included in as component (C) contains in the compositions of said components (A) or said components (B), can be included in the compositions that contains component (A), be included in simultaneously in the both compositions of component (B), perhaps can be used as the 3rd component and be independent of in the compositions that contains component (A) and component (B), perhaps be included in the 3rd compositions as a component.
In oral preparation system of the present invention, provide the amount of the chemical compound of polyhydroxy phosphate anion to be preferably 0.125 to 200 μ mol/g (micromole/g), more preferably 0.625 to 150 μ mol/g, more preferably 2.5 to 100 μ mol/g as component (C).Be included in the compositions that contains component (A) as component (C) at the chemical compound that the polyhydroxy phosphate anion is provided, and the use amount that contains the said composition of component (A) and the compositions that contains component (B) is under situation about equating on the weight, this amount of the chemical compound of polyhydroxy phosphate anion that provides is preferably 0.25 to 400 μ mol/g in the said composition that contains component (A), more preferably 1.25 to 300 μ mol/g, more preferably 5 to 200 μ mol/g.
When Polyhydric calcium phosphate (component (E)) is used as the chemical compound that the polyhydroxy phosphate anion is provided simultaneously and the chemical compound of calcium ion is provided, and the use amount that contains the said composition of component (E) and contain the compositions of component (B) on weight be equate the time, this Polyhydric calcium phosphate amount is preferably 0.25 to 400 μ mol/g (micromole/g) in the said composition that contains component (E), more preferably 1.25 to 300 μ mol/g, more preferably 5 to 200 μ mol/g.
Oral preparation system of the present invention preferably in this mixture working concentration be 10 to 70wt.% sugar alcohol.The example of sugar alcohol comprises lactose, hydroxyl isomaltulose, maltotriitol, isomaltotriitol, panitol, isomaltotetraitol, erithritol, 1,2,3,4,5-pentanepentol, ribitol, xylitol, Sorbitol, mannitol, maltose alcohol etc.Such sugar alcohol can be D or L configuration, perhaps their mixture.
In addition, this sugar alcohol preferably contains xylitol, and the content of xylitol is preferably 1 to 40wt.% in sugar alcohol, and more preferably 2 to 20wt.%.
In oral preparation system of the present invention, component (A) and component (B) are preferably put into a container or a plurality of container, so that component (A) do not contact mutually with component (B), and mixes them in the oral cavity, perhaps mix immediately before importing the oral cavity.
In addition, preferably a kind of many composition systems of oral preparation system of the present invention, this is to be a kind of contactless state by the compositions that keeps component (A) and component (B) and contain component (A) with the compositions that contains component (B), up to use or just before use.
In order to form this many composition systems, component (A) can each component be put into different containers with component (B), and perhaps component (A) and component (B) can be put into a container with contactless state.The example of the container of putting into contactless state comprises a kind of inner pipe of opening with a separator lined, another pipe insertion a kind of pipe wherein with by being connected the container that independent pipe is made so that at the opening part of this container in conjunction with content.
Oral preparation system of the present invention can mix the anion surfactant that generally uses in oral preparation system, for example, the ester salt of alkyl sulfate is such as the salt of sodium lauryl sulphate, N-acylamino acid, such as the N-acyl sarcosinates etc.In addition, composition commonly used in oral preparation can join in the oral preparation system of the present invention, and the example of this composition comprises: grinding agent, such as silicic acid anhydride, calcium hydrogen phosphate and calcium carbonate; Wetting agent is such as glycerol and Polyethylene Glycol; Foaming agent; Binding agent is such as sodium carboxymethyl cellulose and antler glue; Sweeting agent is such as sodium sucrate; Coloring agent; Antiseptic is such as the methyl P-hydroxybenzoic acid; Antibacterial is such as benzene rope chloramines, triclosan and isopropyl cresol; Antiinflammatory is such as β-glycyrrhizin acid and tocopherol; Spice etc.These compositions can and contain in the compositions of component (B) in the compositions that contains component (A) all to be had, perhaps in the compositions that contains component (A) or contain in the compositions of component (B) and have.
Oral preparation system of the present invention can be used as, as dentifrice, lubricated dentifrice, toothpaste, liquid dentifrice, collutory etc.
Embodiment
The following examples embodiment of the present invention that further describe and demonstrate.The embodiment that provides only is in order to illustrate, is not to limit the present invention.
1. collutory
(1) preparation of collutory
In each embodiment and comparative example, two components, promptly component (X) and component (Y) they are according to the preparation of compositions shown in the table 1.Then, each in them is put into the isolated container of each component with identical weight.
(2) assay method
A. about the observation of the absorption situation of microgranule on hydroxyapatite (HAP)
Compositions (X) among each embodiment shown in the table 1 and the comparative example and compositions (Y) are with mixed in equal amounts.10gHAP powder (available from Wako Pure Chemical Industries company) was handled 3 minutes in the mixture that 1L prepares, and used deionized water wash then, and carried out drying by vacuum drying, obtained a kind of powder like this.The situation of calcium fluoride absorption is observed by scanning electron microscope (SEM) on the HAP powder that reclaims.
Calcium fluoride is adsorbed superincumbent HAP powder sample well and is evaluated as " zero ", and the HAP powder sample that calcium fluoride is adsorbed some is evaluated as " △ " and calcium fluoride and seldom or not adsorbs superincumbent HAP powder sample and be evaluated as " * ".
Table 1
| Component | Compositions (wt.%) | ||||||||||
| Embodiment | The comparative example | ||||||||||
| 1 | 2 | 1 | 2 | 3 | |||||||
| X | Y | X | Y | X | Y | X | Y | X | Y | ||
| Calcium glycerophosphate | A，C (＝E) | 1 | - | 0.5 | - | - | - | 1 | - | - | - |
| Calcium lactate | A | - | - | 0.5 | - | 1 | - | - | - | - | - |
| Sodium monofluorophosphate | D | 0.7 | - | 0.7 | - | - | - | - | - | 0.7 | - |
| Sodium fluoride | B | - | 0.2 | - | 0.2 | - | 0.2 | - | 0.2 | - | 0.2 |
| Pure water | *1 | *1 | *1 | *1 | *1 | *1 | *1 | *1 | *1 | *1 | |
| Add up to | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | |
| Situation about particle absorption | ○ | ○ | △ | △ | × | ||||||
| Adsorbance (the mg/m of fluorine 2) | 33 | 28 | 20 | 14 | 2 | ||||||
*1: balance
B. the quantitative assay of fluorine adsorbance on the HAP spherolite
In each embodiment and comparative example, HAP spherolite (APP-100; 10 * 10 * 2mm, PENTAX, Japan) in l0ml compositions (X), handled 30 seconds, in 10ml compositions (Y), handled 30 seconds then.These processing hocketed 3 minutes.Be adsorbed on the calcium fluoride particle hcl as extraction agent of HAP pellet surface by such processing.The amount that is adsorbed on the fluorine of HAP pellet surface is used extract, measures by a kind of ion analyzer (Expandable ion AnalyzerEA940, ORION makes) that has fluoride ion selective electrode (inplus-Fluoride ORION manufacturing).
C. constant-current titration
0.1g HAP powder (contrast) and accurately weigh by the HAP powder that embodiment shown in the table 11 and comparative example's 1 compositions is handled respectively adds the 40ml deionized water in them, thereby prepares the slurry of suspended state.Use automatical potentiometric titrimeter AT-300 (manufacturing of Kyoto Electronics Manufacturing company), 0.1N hydrochloric acid be added dropwise in this suspension with 0.5ml, 0.5ml, use the agitator continuous stirring simultaneously, measured pH after dripping each time 5 minutes, obtain titration curve.
D. the mensuration of calcium fluoride primary particle size
For HAP powder (contrast) and the HAP powder sample handled respectively by embodiment shown in the table 11 and comparative example's 1 compositions, 2-theta (2 θ) degree is measured (instrument: RINT2500VPC (being made by Riguka Corporation) by the powder x-ray diffraction method in 2.5 to 75 scope, Cu K-α, 40Kv, 120mA, divergent slit: 1 degree, disperse vertical constraints slit (divergence vertical restriction slit): 10mm, diffraction slit: 1.25mm, collector slit: 0.3mm, sweep speed: 1.000 degree/minute).
E. the component analysis of calcium fluoride secondary particle
The HAP powder sample of the compositions-treated by the embodiment shown in the table 11 stands deposition processes by Pt-Pd, as the measuring samples of EDS.Under the condition of the measurement (instrument: S-4000 (manufacturings of Hitachi company) is in electron beam 10kV/EMAX-3770 (manufacturing of HORIBA company)) of SEM-EDS (energy disperse x-ray analysis method), the existence of the sample by UTW mode checking processing is carried out.
In addition, for each the HAP powder sample in embodiment 1 and comparative example's 1 compositions-treated, fluorine (19F) detects (instrument: TPD (manufacturing of BEL JAPAN company), 0.1g sample by mass spectrum with temperature programming desorption method (TPD), vacuum, 10 ℃/minute of program rates).
Further, each component of the HAP powder sample of the compositions-treated by embodiment 1 is identified and quantitative assay by chromatography of ions.The preparation of this sample is carried out by this way, promptly accurately takes by weighing the HAP powder sample of 0.1g in beaker, and the past 40ml ultra-pure water of wherein pouring into, and the hydrochloric acid of the 0.01mol/l of adding 0.5ml stirred 1 hour then.This slurry is the membrane filter filtration of 0.45 μ m by pore size.The initial filtered solution of 5ml abandons, and filtered solution is as the solution of chromatography of ions measurement subsequently.This chromatography of ions is measured by DX320 (being equipped with EG-40) (manufacturing of Dionex Corporation company), and in measurement, mono-fluor phosphate and glycerophosphate are identified by the time of staying and the reference material that compare them, and are measured from peak area quantification by the standard curve method.
The condition of the quantitative analysis of mono-fluor phosphate and glycerophosphate is as follows, detached dowel: IonPacAS-16 (Dionex Corporation manufacturing); Guard column: Ionpac AG-16 (DionexCorporation manufacturing); Eluting solvent: KOH (using EG-40); Flow velocity: 1.0ml/min; Gradient: 10mmol/l to 70mmol/l (0 to 20min.); Suppressor: ASRS (200mA); And detector: electric conductivity detector.
(3) result
The adsorbance of fluorine and situation on the a.HAP spherolite
Fluorine adsorbance on the HAP spherolite of compositions (X) among the embodiment 1 as shown in table 1 and compositions (Y) alternate treatment is 33mg/m
2, wherein compositions (X) contains calcium glycerophosphate and sodium monofluorophosphate, and compositions (Y) contains sodium fluoride.
This that is to say, under the situation of embodiment 1, this calcium fluoride microgranule (primary particle) that forms by sodium monofluorophosphate is because the existence of calcium glycerophosphate, suppress to form secondary particle, therefore this calcium fluoride microgranule of primary particle form can be adsorbed on the HAP spherolite effectively, and the adsorbance of the fluorine on the HAP spherolite is 33mg/m thus
2
In addition, under the situation of the embodiment 2 that contains component (A), wherein component (A) contains calcium glycerophosphate, calcium lactate and sodium monofluorophosphate, and the adsorbance of fluorine is 28mg/m on the HAP spherolite of compositions (X) and compositions (Y) alternate treatment
2
Embodiment 1 and embodiment 2 can both be confirmed with observe calcium fluoride good adsorption situation by SEM, and they are cited as " zero " (table 1).
On the contrary, under the situation of the comparing embodiment 1 that comprises the compositions (X) that contains calcium lactate, the adsorbance of fluorine is 20mg/m on the HAP spherolite of compositions (X) and compositions (Y) alternate treatment
2
Here, though have only the calcium lactate of 0.5wt.% to be included in the compositions (X), the adsorbance of fluorine is 28mg/m on the HAP spherolite in embodiment 2
2, on the contrary, the adsorbance of fluorine is 20mg/m on the HAP spherolite of compositions (X) by containing the 1wt.% calcium lactate and compositions (Y) alternate treatment in comparative example 1
2, so its adsorbance is lower than the adsorbance among the embodiment 2.
This is because this calcium fluoride microgranule (primary particle) that calcium lactate by in compositions (X) and the sodium fluoride in compositions (Y) form, and is implemented the glycerophosphate that contains 0.5wt.% in the situation of example 2 and suppresses to form secondary particle.Because glycerophosphate suppresses the effect that secondary particle forms, exist in a large number as the calcium fluoride microgranule of primary particle, and this microgranule (primary particle) is adsorbed on the HAP spherolite effectively, the adsorbance that obtains fluorine thus is up to 28mg/m
2Level.
On the contrary, in comparative example 1, because compositions (X) only contains calcium lactate, the calcium fluoride microgranule (primary particle) that calcium lactate in the use compositions (X) and the sodium fluoride alternate treatment in the compositions (Y) form, and the gathering of carrying out thereafter is too fast and lost control, forms the secondary particle of coarsegrain.The absorption of the secondary particle of this coarsegrain on the HAP spherolite is enough ineffective, and the result is that the adsorbance of fluorine becomes 20mg/m
2, comparing with embodiment 2 is a lower value.
In addition, in the compositions that only contains calcium glycerophosphate (X) with contain under compositions (Y) the alternate treatment situation of sodium fluoride, such as the situation of comparing embodiment 2, the slow (see figure 1) of the formation of calcium fluoride primary particle, the adsorbance of result's fluorine on the HAP spherolite becomes 14mg/m
2
In comparing embodiment 3, only contain the compositions (X) of sodium monofluorophosphate and contain under the situation of compositions (Y) alternate treatment of sodium fluoride, do not find the formation of calcium fluoride primary fine particles.
Adsorbed state by the observed calcium fluoride of SEM is presented in the table 1.In comparing embodiment 1 and comparing embodiment 2, the situation that calcium fluoride partly adsorbs can confirm, and is chosen as " △ ".In comparative example 3, the situation that calcium fluoride seldom adsorbs can confirm, and be cited as " *.
B. the calcium fluoride microgranule situation of on the HAP powder, adsorbing
Fig. 2 is the SEM photo of calcium fluoride microgranule absorption situation by compositions (X) in embodiment 1 and on the HAP powder of (Y) handling.In Fig. 2, can confirm that granule is adsorbed on the bar-shaped HAP powder.This granule is the calcium fluoride microgranule, and they mainly are secondary particles.
Fig. 3 shows by compositions (X) in comparative example 1 and (Y) the absorption situation of calcium fluoride microgranule on the HAP powder of processing.In Fig. 3, secondary microgranule bigger than embodiment 1 (Fig. 2) on bar-shaped HAP powder can be confirmed.
The generation of large scale secondary particle is owing to there is not the existence of glycerophosphate, and is uncontrollable or do not stop that secondary is accumulative to carry out fast.
The absorption situation of calcium fluoride microgranule is presented among Fig. 4 by compositions (X) among the comparative example 3 and on the HAP powder of (Y) handling.As shown in Figure 4, in comparative example 3, can not confirm that almost the calcium fluoride microgranule is on the HAP powder.Because in the compositions that only contains sodium monofluorophosphate (X) (seeing Table 1) with contain in the situation that the compositions (Y) of sodium fluoride handles, the calcium fluoride microgranule forms hardly.
C. the variation of turbidity after blend compositions (X) and compositions (Y)
Mix two compositionss (X) and (Y) variation of turbidity afterwards be presented among Fig. 1.Here, turbidity (in the absorption of 600nm) has reflected the formation situation of calcium fluoride microgranule (secondary particle).As shown in Figure 1, under the situation of embodiment 1, mix back absorption rising fast immediately, descend gradually then in compositions (X) and compositions (Y).This means that granularity is controlled after the calcium fluoride microgranule forms fast.
On the contrary, in the turbidity after blend compositions in comparing embodiment 1 (X) and the compositions (Y), absorption is presented at and mixes the trend that increases in time in back 10 seconds.This shows the normal formation behavior of calcium fluoride microgranule.In addition, in comparing embodiment 2 (spy opens the compositions of flat 10-511956), in the almost not confirmation of raising of blend compositions (X) and the absorption in about 10 seconds of compositions (Y) back.The formation that this means the calcium fluoride microgranule is suppressed.
D.X-x ray diffraction analysis x calcium fluoride primary particle (crystal particles) size
CaF
2Existence can pass through CaF
2(PDF#35-0816) diffraction maximum d=3.1546 (111), d=2.7314 (200) and d=1.9316 (220) confirm.Only the spectrum near d=3.1546 is presented among Fig. 5.Attention is at CaF
2The scope of d=3.1546 (111) is the easiest separately, not with the peak overlapping of hydroxyapatite, mensuration respectively in 2 θ, 26.0 to the 31.0 degree scopes that do not coexist of intensity between the diffraction maximum of the diffraction maximum of the HAP powder of handling through the different disposal method and untreated HAP powder (contrast).Has only CaF then
2Peak separately (S1 among Fig. 5 and S2).With this detached peaks (CaF
2) the angle of diffraction and half width (width at half place of peak height), this crystal size (: dust) pass through Scherrer ' s equation (D=K λ/Bcos θ) and calculate, COEFFICIENT K=0.9 wherein, CuK α λ=1.54056 dusts, B: the half width at peak (width at half place of peak height (rad)), θ is the angle of diffraction (position of summit).
As a result, crystalline size is 4nm among the embodiment 1, and crystalline size is 13nm in comparative example 1.
E. the component analysis of calcium fluoride secondary particle
In the HAP powder sample by the compositions-treated of embodiment 1, carbon detects from the SEM-EDS measurement result, and can confirm that it derives from the carbon that is adsorbed on the glycerophosphate on the HAP powder sample.
In the HAP powder sample by the compositions-treated of embodiment 1, the desorbing peak of fluorine derives near the decomposition more than 400 ℃, and this is from the measurement result of the mass spectrum by temperature programming desorption method (TPD) at 19F.On the other hand, in the HAP of the compositions-treated in comparative example 1 powder sample, the parsing peak that derives from the fluorine of decomposition does not obtain more than 400 ℃ nearly.In other words, can confirm that through the HAP powder sample of the compositions-treated among the comparative example 1 calcium fluoride is stable, can not decompose, and can confirm that the detected fluorine of HAP powder sample in the compositions-treated of passing through embodiment 1 is to derive from mono-fluor phosphate.
From above analysis result, can confirm that glycerophosphate and mono-fluor phosphate all are adsorbed on the HAP sample powder of the compositions-treated of embodiment 1, and be 1.0wt.% mono-fluor phosphate and 2.9wt.% glycerophosphate by the value of chromatography of ions quantitative assay.
F. the effect that suppresses demineralized
The result of constant-current titration is presented among Fig. 6.If phosphate anion or calcium ion run off from tooth (being demineralized), in the solution phosphate anion or calcium ion concentration will increase, and the variation that adds fashionable pH when hydrochloric acid will reduce.If the loss from tooth of phosphate anion or calcium ion is inhibited, in the solution phosphate anion or calcium ion concentration will reduce, and great variation can take place by adding hydrochloric acid in the pH value of this solution.Estimate the effect that collutory suppresses demineralized based on this principle.
As shown in Figure 6, during untreated HAP powder dissolution pH be lower than about 5.5, but pH is lower than approximately 4.5 during the HAP powder dissolution in embodiment 1, and pH is lower than about 5.1 during the HAP powder dissolution in comparing embodiment 1.The processing that this means compositions in embodiment 1 is better than the inhibition demineralized effect of the compositions-treated among the embodiment 1 frequently.
2. dentifrice
(1) preparation of dentifrice
Two kinds of compositionss promptly contain the compositions (X of calcium glycerophosphate and sodium monofluorophosphate
1) and contain the compositions (Y of sodium fluoride
1) prepare respectively according to the compositions shown in table 2 and 3.Each compositions for preparing is put into each marker space of dentifrice container then, and this container is to be made of the pipe that open by a separator lined a kind of inside, and every component is assigned in the independent marker space with the amount that equates.
Table 2
| Compositions (X 1) | (wt.％) |
| Sodium monofluorophosphate | 0.72 |
| Calcium glycerophosphate | 1 |
| Sorbitol solution (70wt.% solution) | 40 |
| Calcium carbonate *2 | 15 |
| Macrogol 600 | 4 |
| Citric acid | 0.1 |
| Sodium sucrate | 0.1 |
| Sodium lauryl sulphate | 1.2 |
| Silicic acid anhydride | 7 |
| Sodium carboxymethyl cellulose | 1 |
| Flavoring agent | 1 |
| Pure water | Balance |
| Amount to | 100 |
*2: particle mean size is 150 microns
Table 3
| Compositions (Y 1) | (wt.％) |
| Sodium fluoride | 0.21 |
| Xylitol | 9 |
| Sorbitol solution (70wt.% solution) | 32 |
| Macrogol 600 | 4 |
| Sodium sucrate | 0.1 |
| Sodium lauryl sulphate | 1.2 |
| Silicic acid anhydride | 20 |
| Sodium carboxymethyl cellulose | 1.5 |
| Flavoring agent | 1 |
| Pure water | Balance |
| Amount to | 100 |
Two kinds of compositionss promptly contain the compositions (X of calcium glycerophosphate and sodium monofluorophosphate
2) and contain the compositions (Y of sodium fluoride
2) prepare respectively according to the compositions shown in table 4 and 5.The compositions of each preparation is put into each marker space of dentifrice container then, and this container is to be made of the pipe that open by a separator lined a kind of inside, and every component is assigned in the independent marker space with the amount that equates.
Table 4
| Compositions (X 2) | (wt.％) |
| Sodium monofluorophosphate | 0.72 |
| Calcium glycerophosphate | 0.7 |
| Sorbitol solution (70wt.% solution) | 35 |
| Calcium lactate | 0.5 |
| Lactic acid | 0.3 |
| Macrogol 600 | 4 |
| Xylitol | 6 |
| Sodium sucrate | 0.1 |
| Sodium lauryl sulphate | 1.2 |
| Silicic acid anhydride | 17 |
| Sodium carboxymethyl cellulose | 0.9 |
| Antler glue | 0.2 |
| Xanthan gum | 0.2 |
| Flavoring agent | 1 |
| Pure water | Balance |
| Amount to | 100 |
Table 5
| Compositions (Y 2) | (wt.％) |
| Sodium fluoride | 0.21 |
| Xylitol | 6 |
| Sorbitol solution (70wt.% solution) | 35 |
| Macrogol 600 | 4 |
| Sodium sucrate | 0.1 |
| Sodium lauryl sulphate | 1.2 |
| Silicic acid anhydride | 17 |
| Sodium carboxymethyl cellulose | 0.9 |
| Antler glue | 0.2 |
| Xanthan gum | 0.2 |
| Flavoring agent | 1 |
| Pure water | Balance |
| Amount to | 100 |
(2) review of oral preparation system
＜1〉effect of remineralization
A. material and method
1) preparation of demineralized tooth
People's molar of extracting is as tooth samples.There are the enamel part 37 ℃ of immersions in the lactate buffer (pH:4.5) of 0.1M that are of a size of this tooth samples in 3mm * 3mm hole to form demineralized damage under the artificial surface in three days above.
2) remineralization of tooth treatment in people's oral cavity
The support (stents) that described demineralized tooth is made by resin also assembles in 30 to 40 years old adult examinate's the oral cavity of 0 health of an oral cavity mandibular bone dental arch stuck-at-.
(i) be used for the dentifrice that remineralization of teeth is treated
The dentifrice that is used for the remineralization of teeth treatment is as follows: at the dentifrice of embodiment 3 as two dosage form dentifrices, wherein contain the compositions (X of calcium glycerophosphate and sodium monofluorophosphate
1) and contain the compositions (Y of sodium fluoride
1) put into a bonded container, this internal tank becomes two marker spaces by a separator lined, so that distribute each component in each marker space with 1: 1 amount ratio; Dentifrice among the comparative example 5, the wherein compositions (X in the table 2 only
1) put into the container of single marker space; Dentifrice in comparative example 4, the wherein compositions (Y in table 3
1) put into another container of single marker space.
The (ii) use of dentifrice
Dentifrice among embodiment 3, comparative example 4 and the comparative example 5 is used by the examinate respectively.
As shown in Figure 7, support is connected to examinate's oral cavity 24 hours, and dentifrice was used 3 times in usual mode by the examinate in one day.Thereafter, support is removed from the oral cavity, and the sample separation segment.In same examinate, according to said method, 24 days one group repeat three times.
3) measure remineralization of teeth by contact microradiography (Contact Microradiography (CMR))
After the remineralization treatment, cut each sample segment, and form the about 150 microns polishing segment of thickness, and take a picture with CMR.The CMR image that obtains (soft X-ray photo) is analyzed by graphical analysis, measures the loss amount (△ Z) of mineral.Here, should be understood that △ Z be demineralized part concentration and from the surface the product (vol% micron) of the demineralized degree of depth.
In addition, this group is calculated by following formula with the mineral recovery rate (%) of each dentifrice:
{ (the △ Z after the △ Z (baseline) before the remineralization treatment-remineralization treatment)/before the remineralization treatment △ Z (baseline) } * 100
The high value of mineral recovery rate means the higher level of remineralization.
B. result
Fig. 8 (a) has shown the micrographic photo of X ray of tooth section.In Fig. 8 (a), can recognize between the surperficial and adamantine depths of tooth has a gray part.This grayish part means the better situation that mineral recover in tooth.In Fig. 8 (a), can confirm that the tone at embodiment 3 mellow lime color parts is the lightest in three.The remineralization effect of this explanation in embodiment 3 is higher with respect to comparative example 4 and comparative example 5.
Shown in Fig. 8 (b), in all groups of the dentifrice that uses comparative example 4, comparative example 5 and embodiment 3, can confirm that with respect to the demineralized tooth, △ Z greatly reduces (the carrying out of remineralization).In the group of the dentifrice that uses comparative example 4, the mineral recovery rate of calculating from △ Z (%) is 22%, is 12% in the group of the dentifrice that uses comparative example 5, and is 41% in the group of the dentifrice that uses embodiment 3.This can confirm oral preparation system of the present invention, is used to use the group of the dentifrice of embodiment 3, obtains promoting the highest effect of remineralization.
＜2〉suppress because the effect that the pH that remaining dental plaque causes reduces
A. material and method
Being used to estimate the dentifrice that suppresses pH reduction effect is prepared as follows.As the dentifrice in embodiment 4, use to combine the compositions (X that contains calcium glycerophosphate
2) and contain the compositions (Y of sodium fluoride
2) two dosage form dentifrices, wherein sodium monofluorophosphate further is included in compositions (X
2) in.As the dentifrice in comparative example 6, only use the compositions (Y that only contains sodium fluoride
2).
Approximately the dentifrice of 1g embodiment 4 was used 1 minute by the examinate, and this examinate's oral cavity cleaning has interrupted 2 days.Collect dental plaque afterwards immediately.The dental plaque that 30mg collects joins in 5% sucrose solution of 1ml suspension, and keeps 10 minutes at 37 ℃.Afterwards, the variation of pH value was with 10 minutes interval repeated measure.Dentifrice among the comparative example 6 is used by the examinate in aforementioned identical mode, uses the variation of the dental plaque measurement pH that collects according to above method.
B. result
The pH of dental plaque changes to pH6.4 from pH6.8 after through 10 minutes behind the dentifrice that uses implementation column 4, and the pH of dental plaque changes to pH5.4 from pH6.8 behind use comparative example's 6 the dentifrice after through 10 minutes.That is, can confirm that the pH of remaining dental plaque after using the dentifrice of embodiment 4 changes less than comparative example 6, and the dentifrice that pH that should the remnants dental plaque reduces by using embodiment 4 is suppressed.Can infer, because the glycerophosphate with pH buffer capacity that derives from embodiment 4 dentifrices has been mixed into the secondary particle of calcium fluoride when forming calcium fluoride, so the effect that the remaining dental plaque pH that is inhibited reduces.
Claims (12)
1. compositions oral preparation system more than a kind is characterized in that comprising following component:
(A) provide the chemical compound of calcium ion,
(B) provide fluoride ion but the chemical compound of single fluorophosphoric acid radical ion be not provided,
(C) provide the polyhydroxy phosphate anion chemical compound and
(D) provide the chemical compound of single fluorophosphoric acid radical ion,
Component (A) and (B) in described oral preparation system, separate wherein.
2. oral preparation system according to claim 1 is characterized in that component (A), (B), (C) and (D) mixes in the oral cavity, perhaps mixes immediately before importing the oral cavity.
3. oral preparation system according to claim 2 is characterized in that the calcium fluoride microgranule forms when all components mixes.
4. oral preparation system according to claim 1 is characterized in that described system has any one in the following combination:
Contain the system that comprises component (A), (C) and compositions (D) and contain the independent compositions of component (B);
Contain the compositions that comprises component (A) and contain the system of component (C), (D) and independent compositions (B);
Contain compositions that comprises component (A) and component (C) and the system that contains component (B) and independent compositions (D);
Contain the system that comprises component (A) and compositions (D) and contain component (B) and independent compositions (C);
Contain and comprise component (A) and compositions (D), contain the independent compositions of component (B) and the system that another kind contains the independent compositions of component (C);
Contain and comprise component (A) and compositions (C), contain the independent compositions of component (B) and the system that another kind contains the independent compositions of component (D);
Contain and comprise component (B) and compositions (D), contain the independent compositions of component (A) and the system that another kind contains the independent compositions of component (C);
Contain and comprise component (B) and compositions (C), contain the independent compositions of component (A) and the system that another kind contains the independent compositions of component (D); With
Contain the compositions that comprises component (A), contain the independent compositions of component (B), contain the independent compositions of component (C) and contain the system of the independent compositions of component (D).
5. oral preparation system according to claim 3, the primary size that it is characterized in that described calcium fluoride microgranule are 0.3 to 15nm.
6. oral preparation system according to claim 3 is characterized in that forming secondary particle from the aggregation of described calcium fluoride microgranule, and wherein said secondary particle comprises mono-fluor phosphate and/or polyhydroxy phosphate.
7. oral preparation system according to claim 6, the content range that it is characterized in that described mono-fluor phosphate be secondary particle 0.05 to 20wt.%, the phosphatic content range of described polyhydroxy be secondary particle 0.05 to 20wt.%.
8. oral preparation system according to claim 1 is characterized in that component (A) and component (B) are in the different spaces before mixing.
9. oral preparation system according to claim 1 is characterized in that described the chemical compound of calcium ion is provided is at least a Polyhydric calcium phosphate that is selected from calcium glycerophosphate, Cori ester calcium and the G-6-P calcium.
10. oral preparation system according to claim 1 is characterized in that described the chemical compound of polyhydroxy phosphate anion is provided is at least a Polyhydric calcium phosphate that is selected from calcium glycerophosphate, Cori ester calcium and the G-6-P calcium.
11. a multicomponent oral preparation system is characterized in that comprising following component:
(B) provide fluoride ion but the chemical compound of single fluorophosphoric acid radical ion be not provided,
(D) provide the chemical compound of single fluorophosphoric acid radical ion,
(E) Polyhydric calcium phosphate
Component (B) and (E) in described oral preparation system, separate wherein.
12. an oral preparation that contains the many composition systems that comprise compositions (X) and compositions (Y) is characterized in that component (C) is blended in described many composition systems:
(X) contain (A) and first compositions (D);
(Y) second compositions that contains (B);
(A) provide the chemical compound of calcium ion;
(B) provide the chemical compound of fluoride ion;
(C) provide the chemical compound of polyhydroxy phosphate anion; With
(D) provide the chemical compound of single fluorophosphoric acid radical ion.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP381820/2002 | 2002-12-27 | ||
| JP2002381820 | 2002-12-27 | ||
| JP327681/2003 | 2003-09-19 |
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| Publication Number | Publication Date |
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| CN1731971A CN1731971A (en) | 2006-02-08 |
| CN1320879C true CN1320879C (en) | 2007-06-13 |
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| JP6417319B2 (en) * | 2013-03-26 | 2018-11-07 | クラレノリタケデンタル株式会社 | Dental curable composition |
| KR20170100580A (en) * | 2014-12-24 | 2017-09-04 | 더 유니버시티 오브 멜버른 | Mineralized fluoride composition |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4080440A (en) * | 1974-12-13 | 1978-03-21 | The Procter & Gamble Company | Method for remineralizing tooth enamel |
| US4397837A (en) * | 1972-02-02 | 1983-08-09 | Blendax-Werke R. Schneider Gmbh & Co. | Process and composition for the remineralization and prevention of demineralization of animal teeth including humans |
| US4565691A (en) * | 1982-04-20 | 1986-01-21 | Beecham Group P.L.C. | Oral hygiene compositions |
| US5045305A (en) * | 1986-10-02 | 1991-09-03 | Chesebrough-Pond's Usa Co., Division Of Conopco, Inc. | Oral hygiene composition |
| CN1311657A (en) * | 1998-07-30 | 2001-09-05 | 亨克尔两合股份公司 | Anti-inflammatory dental care agents |
-
2003
- 2003-12-26 CN CNB2003801077763A patent/CN1320879C/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4397837A (en) * | 1972-02-02 | 1983-08-09 | Blendax-Werke R. Schneider Gmbh & Co. | Process and composition for the remineralization and prevention of demineralization of animal teeth including humans |
| US4080440A (en) * | 1974-12-13 | 1978-03-21 | The Procter & Gamble Company | Method for remineralizing tooth enamel |
| US4565691A (en) * | 1982-04-20 | 1986-01-21 | Beecham Group P.L.C. | Oral hygiene compositions |
| US5045305A (en) * | 1986-10-02 | 1991-09-03 | Chesebrough-Pond's Usa Co., Division Of Conopco, Inc. | Oral hygiene composition |
| CN1311657A (en) * | 1998-07-30 | 2001-09-05 | 亨克尔两合股份公司 | Anti-inflammatory dental care agents |
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