CN1736388B - Compositions having anti-dental caries function - Google Patents
Compositions having anti-dental caries function Download PDFInfo
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- CN1736388B CN1736388B CN 200510082015 CN200510082015A CN1736388B CN 1736388 B CN1736388 B CN 1736388B CN 200510082015 CN200510082015 CN 200510082015 CN 200510082015 A CN200510082015 A CN 200510082015A CN 1736388 B CN1736388 B CN 1736388B
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Abstract
The present invention relates to dietary compositions and oral compositions having an anti-dental caries function. The present invention provides dietary compositions and oral compositions having an anti-dental caries function which contain a buffering agent having a pH buffering action in the oral cavity.
Description
The application be that August 28, application number in 2003 are 02805648.5 the applying date, denomination of invention divides an application for the application for a patent for invention of " compositions with anti-dental caries function ".
Technical field
The present invention relates to have the dietary composition and the oral cavity composition of anti-dental caries function.More specifically, the present invention relates to have the dietary composition and the oral cavity composition of anti-dental caries function, for example give the tooth Remineralization to reduce the generation of dental caries.
Background technology
Dental caries is a kind of demineraliting by the bacterial dental surface that is present in dental surface in the oral cavity.Specifically, because the organic acid that some obstacles produce oral cavity bacterium can not spread, tooth is exposed to the organic acid of high concentration, so dental surface is by demineraliting.In this definition, any oral cavity bacterium that has by metabolism sugar fermentation generation organic acid ability can both cause dental caries.The substrate that is fit to organic acid production is a saccharide, comprises the polymer polysaccharide (as starch) of monosaccharide and oligosaccharide (for example, dextrose plus saccharose) and monosaccharide.
In general, the starch that organic acid can not disperse to absorb from diet owing to (1) is detained at neck and root of the tooth, (2) undissolved glucosan sticks on the tooth, and this is to use the sugar that is easy to degrade, for example sucrose (i.e. Fa Jiao sugar) as substrate by bacteriogenic.
For factor (1), think any oral cavity bacterium with sugar fermentation ability, for example lactobacillus is the reason that causes dental caries.In this case, the progress of known dental caries normally slowly.Passive factor is depended in the development that produces high concentration organic acid environment.
In today that the food that contains sucrose can extensively obtain, factor (2) is the main cause of dental caries.In this case, think that Streptococcus mutans (Streptococcus mutans) and Streptococcus sobrinus (s.sobrinus) are the reasons that causes dental caries.These two kinds of antibacterials all are streptococcic types that takes place with chain, and each cell has the circle of about 0.6 μ m diameter.In the presence of sucrose, these two kinds of antibacterials enliven real estate and give birth to water-fast alpha-glucans.This glucosan has the fine characteristic that adheres to dental surface.The rapid metabolism sucrose of antibacterial is brought into play acidic ability.This antibacterial itself has strong acid-resisting and can survive in the sour environment that other antibacterial can not grow.The adhesiveness of water-fast glucosan makes antibacterial adhere to places such as dental surface securely.Water-fast glucosan is adsorbed in dental surface, makes by bacteriogenic organic acid to spread, and causes dental surface to be exposed in the high concentration organic acid environment.Think and compare that the activity factor of antibacterial is depended in the formation that produces high concentration organic acid environment with factor (1).In this case, the development of dental caries than factor (1) cause very fast.
There is a new method to come caries prevention, i.e. the demineraliting of dentine and Remineralization (Yoichi Iijima, Takashi Kumagaya by on microscopic scale, considering tooth health; The mechanism of Kariesu Kontororu Dakkai-toSaisekkaike-no-Mekanizumu[dental caries control-demineraliting and Remineralization (Caries Control-Mechanism of Demineralization and Remineralization)], Ishiyaku Shuppan K.K.; 21-51,1999).Dental surface is by calcium and phosphate crystal hydroxyapatite [Ca
10(PO
4)
6(OH)
2] make, and be called enamel.Enamel is the hardest part of tooth, and prevents because enamel important calcium or the phosphate down that contained acid etc. causes in the bacteriogenic organic acid, food in the dental plaque dissolves (demineraliting).
Organic acid permeates enamel by the gap between the water-filled enamel fiber, and by being called the process dissolving hydroxyapatite of demineraliting.Calcium and phosphate lose the generation that causes dental caries initial under the enamel top layer from the enamel tissue.As hereinafter described, according to the present invention, the dental caries in above-mentioned stage can be repaired.Calcium and phosphate ion can be by being called the course recovery of Remineralization through the loss of part of the dental caries under the enamel surfaces and apatite.
Whenever absorption contains the food of the carbohydrate of fermentation, the pH of dental plaque becomes acid and surpasses critical pH, and demineraliting begins.This is because the effect of acidic antibacterial in the dental plaque.When dental plaque was cushioned by saliva, it is neutral that the pH of dental plaque recovers, and calcium in the saliva and phosphate ion enter dentine (this process is called as Remineralization) by dental plaque again.
Therefore, the method for prevention and treatment dental caries should not be to cause that dental caries makes antibacterial produce the nutrient of organic acid oral cavity bacterium; Should not to cause that dental caries makes antibacterial produce the nutrient of water-fast glucosan and organic acid Streptococcus mutans; Should prevent because organic acid pH drops to the pH following (for example, should have buffer capacity descends to prevent pH) that demineraliting begins; Should promote Remineralization or the like.
The medicament of known various dental caries up to now.
Dental caries begins when using sucrose to produce water-fast glucosan as nutrient and glycosyl transferase as the enzyme variant streptococcus.This glucosan covers dental surface, produces dental plaque.When Streptococcus mutans carried out acid fermentation in dental plaque, tooth is dissolved to be fallen and forms odontoptosis.
About the saccharide of dental caries, the nutraceutical oligosaccharide that some are not Streptococcus mutans (S.Hamada etc., J.Jpn.Soc.Starch Sci., 31 volumes, 83-91 page or leaf, 1984) has been proposed.An example of the saccharide of these dental caries is palatinit (Japanese public publication 2000-281550 numbers).When palatinit combines with fluorine or zinc, promote the Remineralization of tooth.(Japanese public publication 2000-247852 number).But, the sweet taste difference of palatinit and be not suitable for food.And, need be for the effect of palatinit Remineralization up to the concentration of about 1-20wt%.
Also known sugar alcohol (specifically being xylitol) is a kind of medicament (for example, Japanese public publication 2000-128752 number and Japanese public publication 2000-53549 number) of dental caries.Japan's public publication discloses a kind of oral cavity composition that comprises one or more sugar alcohols that are selected from xylitol, mannitol, galactitol and inositol for 11-12143 number.Japan's public publication is described these sugar alcohols for 11-12143 number and can be promoted the tooth Remineralization, but does not suppress the growth of antibacterial.Though sugar alcohol is only effective when high concentration, known huge uptake sugar alcohol causes loose stool.Described in embodiment hereinafter, do not confirm the effect of xylitol in fact.
In addition, reported and utilized the medicament (S.Sakanaka etc., Fragrance Journal, 11 volumes, 42-49 page or leaf, 1990) of a kind of composition polyphenol of Folium Camelliae sinensis as dental caries.But the use of polyphenol also causes the problem of the sense of taste and therefore is restricted.
At present, it is said that fluorine is the most effective for the effect of Remineralization.Fluorine can be brought into play enough effectiveness when about 2ppm.About the effectiveness of fluorine, clarified following 2 points: (1) promotes Remineralization; (2) fluorine mixes the hydroxyapatite crystal, and then the hydroxyapatite crystal changes into the hard crystal structure (using fluorine is desired effects (2) rather than (1)) of anti-demineraliting.Recently, the fluorine with this specific character has added in the various oral cavity compositions.For example, Japanese public publication 11-130643 number a kind of oral cavity composition that contains calcium carbonate and soluble fluoride is disclosed.The ability in conjunction with the additional tooth mineral nitrogen of enhancing fluorine of known fluoride ion and sugar alcohol (for example, Japanese public publication 11-21217 number, Japanese public publication 2000-72638 number and Japanese public publication 2000-154127 number).Japan's public publication discloses a kind of compositions that contains variant enzyme (mutanase) and fluoride for 8-12541 number, and its enhancing dentine also promotes Remineralization and prevents dental caries effectively.
The supply of calcium phosphate known in the art promotes tooth Remineralization (for example, Japanese public publication 11-228369 number and Japanese public publication 10-310513 number).
Japan's public publication discloses a kind of oral cavity composition that contains calcium carbonate and alginate for 11-29454 number.Said composition strengthens calcium carbonate adheres to and is retained in ability on the tooth, therefore obtains the neutralization of gratifying pH and promotes replenishing of mineral nitrogen, produces the effect of fabulous caries prevention.
Japan's public publication has been described precipitation and the crystallization (being calcification) that wherein disclosed phosphorylation oligosaccharide suppresses calcium and phosphorus for 8-104696 number, the phosphorylation oligosaccharide is not the nutrient that causes the Streptococcus mutans of dental caries, therefore do not produce water-fast glucosan, and the phosphorylation oligosaccharide has buffer capacity and has the effect that prevents that pH from descending.Above-described characteristic prevents the generation of dental caries and dental plaque and the acid fermentation that is caused by Streptococcus mutans.It also discloses the phosphorylation oligosaccharide that is contained in a kind of dietary composition or the oral cavity composition has and prevents that because the effect that the pH that causes of lactic acid descends, lactic acid is the product of fermentation in the dental plaque, and to not influence of fragrance.Yet, the effect of not pointing out above-mentioned phosphorylation oligosaccharide can when low concentration, have Remineralization as described herein Japanese public publication 8-104696 number.
Content of the present invention
Therefore, the present invention relates to have the material of anti-dental caries function.Specifically, the purpose of this invention is to provide dietary composition and oral cavity composition, these compositionss are by the generation of minimizing dental caries such as tooth Remineralization.
The inventor has critically studied the technology of caries prevention by using various materials.As a result, the inventor has found a kind of tooth to be had the buffer agent of Remineralization effect, and has finished the present invention.
According to an aspect of the present invention, a kind of dietary composition has anti-dental caries function.Said composition comprises a kind of buffer agent that has the pH cushioning effect in the oral cavity.
In one embodiment of the invention, this buffer agent is phosphorylation oligosaccharide or its sugar alcohol.
In one embodiment of the invention, this buffer agent is selected from: phosphorylation oligosaccharide or its sugar alcohol, wherein middle phosphorylation oligosaccharide is by having α-1, the 3-5 of 4 keys the glucosan that glucose is formed, one of them phosphate group is connected with glucosan, perhaps by the glucosan of 2-8 glucose composition with α-1,4 key, wherein two phosphate groups are connected with glucosan; Chondroitin sulfate; The chondroitin sulfate oligosaccharide; G-6-P; Few galacturonic acid; And tartaric acid.
In one embodiment of the invention, this buffer agent is phosphorylation oligosaccharide or its sugar alcohol.This phosphorylation oligosaccharide is the glucosan of being made up of 3-5 glucose with α-1,4 key, and one of them phosphate group is connected with glucosan, or by the glucosan of 2-8 glucose composition with α-1,4 key, wherein two phosphate groups are connected with glucosan.
In one embodiment of the invention, this buffer agent is that form with alkaline metal salt, alkali salt and iron salt exists.
In one embodiment of the invention, this buffer agent is that form with sodium salt or calcium salt exists.
In one embodiment of the invention, this dietary composition further comprises the fluorine of effective dose or contains the fluorine of the material of dental caries.
According to another aspect of the present invention, a kind of dietary composition has the function of dental caries.Said composition comprises a kind of buffer agent that has the pH cushioning effect in the oral cavity, a kind of phosphorus-calcium compensation, a kind of phosphorus preparation, and/or a kind of calcium preparation.
In one embodiment of the invention, this buffer agent is phosphorylation oligosaccharide or its sugar alcohol.
In one embodiment of the invention, this buffer agent is selected from: phosphorylation oligosaccharide or its sugar alcohol, wherein the phosphorylation oligosaccharide is by having α-1, the 3-5 of 4 keys the glucosan that glucose is formed, one of them phosphate group is connected with glucosan, perhaps by the glucosan of 2-8 glucose composition with α-1,4 key, wherein two phosphate groups are connected with glucosan; Chondroitin sulfate; The chondroitin sulfate oligosaccharide; G-6-P; Few galacturonic acid; And tartaric acid.
In one embodiment of the invention, this buffer agent is phosphorylation oligosaccharide or its sugar alcohol.This phosphorylation oligosaccharide is the glucosan of being made up of 3-5 glucose with α-1,4 key, and one of them phosphate group is connected with glucosan, or by the glucosan of 2-8 glucose composition with α-1,4 key, wherein two phosphate groups are connected with glucosan.
In one embodiment of the invention, this buffer agent is that form with alkaline metal salt, alkali salt and iron salt exists.
In one embodiment of the invention, this buffer agent is that form with sodium salt or calcium salt exists.
In one embodiment of the invention, this dietary composition further comprises the fluorine of effective dose or contains the fluorine of the material of dental caries.
According to another aspect of the present invention, a kind of oral cavity composition has the function of dental caries.Said composition is included in the buffer agent that has the pH cushioning effect in the oral cavity.
In one embodiment of the invention, this buffer agent is phosphorylation oligosaccharide or its sugar alcohol.
In one embodiment of the invention, this buffer agent is selected from: phosphorylation oligosaccharide or its sugar alcohol, wherein the phosphorylation oligosaccharide is by having α-1, the 3-5 of 4 keys the glucosan that glucose is formed, one of them phosphate group is connected with glucosan, perhaps by the glucosan of 2-8 glucose composition with α-1,4 key, wherein two phosphate groups are connected with glucosan; Chondroitin sulfate; The chondroitin sulfate oligosaccharide; G-6-P; Few galacturonic acid; And tartaric acid.
In one embodiment of the invention, this buffer agent is phosphorylation oligosaccharide or its sugar alcohol.This phosphorylation oligosaccharide is the glucosan of being made up of 3-5 glucose with α-1,4 key, and one of them phosphate group is connected with glucosan, or by the glucosan of 2-8 glucose composition with α-1,4 key, wherein two phosphate groups are connected with glucosan.
In one embodiment of the invention, this buffer agent is with alkaline metal salt, alkali salt, and the form of zinc salt and iron salt exists.
In one embodiment of the invention, this buffer agent is that form with sodium salt, calcium salt or zinc salt exists.
In one embodiment of the invention, this oral cavity composition further comprises the fluorine of effective dose or contains the fluorine of the material of dental caries.
According to another aspect of the present invention, a kind of oral cavity composition has the function of dental caries.Said composition comprises a kind of buffer agent that has the pH cushioning effect in the oral cavity, a kind of phosphorus-calcium compensation, a kind of phosphorus preparation, and/or a kind of calcium preparation.
In one embodiment of the invention, this buffer agent is phosphorylation oligosaccharide or its sugar alcohol.
In one embodiment of the invention, this buffer agent is selected from: phosphorylation oligosaccharide or its sugar alcohol, wherein the phosphorylation oligosaccharide is by having α-1, the 3-5 of 4 keys the glucosan that glucose is formed, one of them phosphate group is connected with glucosan, perhaps by the glucosan of 2-8 glucose composition with α-1,4 key, wherein two phosphate groups are connected with glucosan; Chondroitin sulfate; The chondroitin sulfate oligosaccharide; G-6-P; Few galacturonic acid; And tartaric acid.
In one embodiment of the invention, this buffer agent is phosphorylation oligosaccharide or its sugar alcohol.This phosphorylation oligosaccharide is the glucosan of being made up of 3-5 glucose with α-1,4 key, and one of them phosphate group is connected with glucosan, or by the glucosan of 2-8 glucose composition with α-1,4 key, wherein two phosphate groups are connected with glucosan.
In one embodiment of the invention, this buffer agent is with alkaline metal salt, alkali salt, and the form of zinc salt or iron salt exists.
In one embodiment of the invention, this buffer agent is that form with sodium salt, calcium salt or zinc salt exists.
In one embodiment of the invention, this oral cavity composition further comprises the fluorine of effective dose or contains the fluorine of the material of dental caries.
According to another aspect of the present invention, a kind ofly be used to study expection has the sample of dental caries effect to tooth the method for Remineralization effect, the method comprising the steps of: (A) having under the situation of sample, making the solution that contains phosphorus, calcium and tooth composition carry out the calcium deposit reaction; (B) after the precipitation, measure the concentration of calcium in the solution or the quantity of sedimentary calcium; (C) make the solution that does not contain sample carry out the calcium deposit reaction; (D) after the precipitation, measure the concentration of calcium in the solution or the quantity of sedimentary calcium; (E) the relatively concentration of calcium or the quantity of sedimentary calcium in the solution in step (B) and (D).
In one embodiment of the invention, this solution contains hydroxyapatite, buffer, KH
2PO
4And CaCl
2
The accompanying drawing summary
Fig. 1 shows that the tooth slice that uses cattle causes the figure of mineral loss value owing to dental caries in the pilot system of Remineralization.
Fig. 2 is the figure that shows dental disk lesion depths in the pilot system of Remineralization of using cattle.
Fig. 3 is the figure that is presented among the embodiment 4 result who uses phosphorylation oligosaccharide sodium salt Remineralization in the simple pilot system.
Fig. 4 is the figure that is presented among the embodiment 4 result who uses phosphorylation oligosaccharide calcium salt Remineralization in the simple pilot system.
Fig. 5 shows that the phosphorylation oligosaccharide is to the figure of the influence of Remineralization when P/Ca is 0.6.
Fig. 6 A is presented under the situation that does not have the phosphorylation oligosaccharide, and the variation of P/Ca concentration ratio is to the figure of the influence of Remineralization.Fig. 6 B is presented under the situation of phosphorylation oligosaccharide sodium salt, and the variation of P/Ca concentration ratio is to the figure of the influence of Remineralization.Fig. 6 C is presented under the situation of phosphorylation oligosaccharide calcium salt, and the variation of P/Ca concentration ratio is to the figure of the influence of Remineralization.
Fig. 7 A is the figure that is presented at the effect of phosphorylation oligosaccharide calcium salt and phosphorylation oligosaccharide sodium salt Remineralization among the embodiment 5.Fig. 7 B is the figure that shows xylitol and the effect of xylose Remineralization.Fig. 7 C is the figure that shows the Remineralization effect of palatinit and isomaltulose (palatinose).
Fig. 8 is the photo that shows TLC analysis result among the embodiment 7.
Fig. 9 shows that phosphorylation oligosaccharide and fluorine are to the synergistic figure of Remineralization among the embodiment 7.
Figure 10 is the photo that shows the TLC analysis result of the phosphorylation oligosaccharide that has concentration of standard solution among the embodiment 8.
Figure 11 is the photo that shows the TLC analysis result, this presentation of results in embodiment 8 when eating when containing the phosphorylation oligosaccharide of chewing gum the amount of elution in time.
Figure 12 is the figure that shows the effect of various substance supplement mineral nitrogens among the embodiment 12.
Figure 13 is the figure that shows the effect of various substance supplement mineral nitrogens among the embodiment 13.
Figure 14 is the figure that shows among the embodiment 14 that the pH in the artificial oral means changes.
Figure 15 shows among the embodiment 16 figure of the amount of saliva when chewing chewing gum that contains POs Ca or the chewing gum that does not contain POs Ca.
Figure 16 shows among the embodiment 16 figure of the pH of saliva when chewing chewing gum that contains POs Ca or the chewing gum that does not contain POs Ca.
Figure 17 shows among the embodiment 16 figure of the P content of saliva when chewing chewing gum that contains POs Ca or the chewing gum that does not contain POs Ca.
Figure 18 shows among the embodiment 16 figure of the Ca content of saliva when chewing chewing gum that contains POs Ca or the chewing gum that does not contain POs Ca.
Figure 19 is the figure that shows the variation of Ca/P ratio when chewing chewing gum that contains POs Ca or the chewing gum that does not contain POs Ca among the embodiment 16.
Figure 20 A shows among the embodiment 16 figure of lesion depths in the tooth of each processing.Figure 20 B is the figure that shows among the embodiment 16 in the tooth mineral loss value of each processing.
Figure 21 is the figure that shows Remineralization ratio among the embodiment 17.
Figure 22 shows among the embodiment 18 figure of the pH of excretory saliva when eating the confection that contains POs Ca.
Figure 23 shows among the embodiment 18 figure of the amount of excretory saliva when eating the crystal sugar that contains POs Ca.
Figure 24 shows among the embodiment 18 Ca of excretory saliva and the figure of P content when eating the confection that contains POs Ca.
Figure 25 is the figure that shows the result of the test of the soft sweet Remineralization of utilizing the confection that contains POs Ca and containing POs Ca.
Figure 26 is the figure that shows the chemical structural formula of representational phosphorylation oligosaccharide.
Implement optimal mode of the present invention
Hereinafter the present invention will be described in more detail.
Term used herein " anti-dental caries function " is meant the function of caries prevention and treatment dental caries.The function of treatment dental caries is meant the function of the part of the tooth that reparation was once lost owing to dental caries.Term used herein " anti-dental caries function " is meant one or more following characteristics: (1) prevents because the pH buffer capacity that the pH that the acid that oral cavity bacterium produces causes descends; (2) prevent that oral cavity bacterium from producing the ability of insoluble glucosan; (3) in the ability of the early stage promotion tooth Remineralization of dental caries.Preferably, this anti-dental caries function has two above-mentioned characteristics, has whole above-mentioned characteristics best.
Compositions of the present invention can stably provide phosphate and calcium to corrosive tooth.The tooth that phosphate and calcium are provided is by Remineralization, and therefore the dental part owing to the dental caries loss can be repaired.
Therefore according to the present invention, a kind of buffer agent joins in the oral cavity, stably uses phosphate and calcium in the saliva that is present in the oral cavity etc. in the tooth Remineralization.Therefore, can realize that routine is thought is difficult to or the reparation of impossible tooth.
If under suitable condition, calcium or phosphate are offered the enamel part (Remineralization) of demineraliting, can repair demineralized lesion and reach serviceable condition.In order to keep the serviceable condition of tooth, need provide the damage of mineral by saliva to demineraliting so that on microscopic scale balance demineraliting and Remineralization.Usually, the pH after eating or getting something to drink in the dental plaque often reduces, and the balance between demineraliting and the Remineralization is changed.When demineraliting>Remineralization, damage takes place.On the contrary, when Remineralization>demineraliting, because the Remineralization of tooth, the damage of demineraliting is repaired.Balance between demineraliting and the Remineralization depends on oral environment (specifically, the pH in saliva and the dental plaque, calcium and phosphatic concentration) to a great extent.The invention provides the oral environment that as if a kind of Remineralization can take place, thus caries prevention and treatment demineralized lesion (commitment of the dental caries) tooth firm to secure good health.
Term used herein " buffer agent " is meant the reagent that shows the pH cushioning effect in the oral cavity.Specifically, this buffer agent is a kind of water soluble salt that obtains from the anion and the cation of for example buffer agent.The existence of buffer agent can be stablized the pH in the oral cavity in the oral cavity.This buffer agent is stablized phosphate ion and the calcium ion in the saliva.Therefore, specifically, preferred a kind of reagent that under the situation that phosphate ion and calcium ion are arranged, has good pH cushioning effect.More preferably, when buffer agent adds in the aqueous solution that contains phosphate ion and calcium ion, the stability of phosphate ion and calcium ion is not cushioned agent and suppresses.As if in other words, can react and form sedimentary buffer agent with phosphate ion and calcium ion be worthless.
In addition, in the present invention, preferably in dental plaque, obtain the pH buffering effect.If show the pH cushioning effect in saliva, the cushioning effect of pH typically is shown in the dental plaque so.Therefore, the buffer agent that shows the pH cushioning effect in saliva can be used for showing the pH cushioning effect in the dental plaque.A responsive field-effect transistor electrode of hydrion (PH-6010: produced by Nihon Kohden company) can be placed on the interval of tooth part that an enamel section is gone up and mixed the partial denture of lower jaw.After this, the pH in the dental plaque that forms on the electrode sensitive part can be according to (the Japanese tooth reparation journal Journal of the Japan Prosthodontic Society of association, 40 volume special issues such as YoshizumiTamasawa, 147 pages, 1996), Kazuhiko Abe (DENTAL OUTLOOK, 90 (3), 650-654,1997), Takahashi-Abbe, (Oral Microbiol.Immunol. such as S, 16,94-99 page or leaf, 2001) the middle method mensuration of describing.PH in the dental plaque is preferably 6 or more, and better is 7 or more.When because cushioning effect when causing that pH in the dental plaque returns to neutrality, the phosphate ion and the calcium ion that are present in the saliva of buccal cavity are supplied to dental surface, cause the dentine Remineralization.The upper limit of pH is not specifically limited in the dental plaque, but does not want a high alkali condition for the organism of a reality.PH in the dental plaque is preferably 10 or still less, and better is 8 or still less.
Buffer agent typically uses with the form of salt, can randomly use with the form of free acid.Even buffer agent form with free acid in the oral cavity gives,, we can say that basically the salt of free acid offers the oral cavity owing to can be present in the oral cavity with the salifiable alkalinous metal of free acid shape etc.
Can be used for preferable buffer agent of the present invention can easily select by simple test.Specifically, various known pH buffer agents add in the neutral aqueous solution that contains phosphate ion and calcium ion (for example aqueous solution of pH 6-8).Observe sedimentary appearance or do not occur.Not forming sedimentary pH buffer agent in this test can be satisfactorily as the buffer agent that joins in the anticaries compositions of the present invention.
When buffer agent does not exist, because the organic acid effect oral cavity that oral cavity bacterium produces can be by acidification (being that saliva or dental plaque become acidity).When saliva or dental plaque during by acidification, the calcium of tooth and phosphorus by eluting, cause the generation of dental caries as Ca and P ion.In this case, if buffer agent exists, the pH of saliva and dental plaque is stabilized in about neutral pH in the oral cavity, as if the formation of dental caries can not take place thus.
Usually the pH of saliva is about neutrality.Therefore, to have the buffer agent of good cushioning effect be preferred to the pH about neutrality.
Preferably, this buffer agent be a kind of not with saliva in phosphate reaction and form sedimentary reagent.
Preferably, this buffer agent be a kind of not with saliva in calcium reaction and form sedimentary reagent.
Preferably, this buffer agent is a kind of acidic functionality.
Preferably, this buffer agent has any phosphate, carboxyl and sulfate.
Preferably, this buffer agent has three or acidic functionality still less in its molecule, more preferably two or acidic functionality still less.As if when having excessive acidic functionality in the molecule, its ability from calcium to hydroxyapatite that supply with phosphorus and reduces.For example, the phosphorylation oligosaccharide that has one or two phosphate in their molecule has the function of the dental caries treatment of improvement, surpasses to have the function of the phytic acid of 6 phosphates in its molecule.Therefore, preferably use buffer agent rather than a kind of material of phytic acid for example.
Have that fabulous to provide the buffer agent of the ability of phosphorus and calcium to hydroxyapatite be preferred.Buffer agent provides the ability of phosphorus and calcium to measure easily by the pilot system method of simple Remineralization described as follows to hydroxyapatite.
The example of buffer agent comprises phosphorylation oligosaccharide and sugar alcohol thereof.Term used herein " phosphorylation oligosaccharide " is meant the oligosaccharide that has at least one phosphate group in its molecule, preferably three or phosphate group still less, more preferably two or phosphate group still less.Term used herein " neutral oligosaccharides " is meant does not have the connected oligosaccharide of phosphate group.For example, this phosphorylation oligosaccharide can be the glucosan of being made up of 3-5 the glucose that α-1,4 key connects, and one of them phosphate group is connected with glucosan.In addition, the phosphorylation oligosaccharide can be the glucosan of being made up of 2-8 glucose with α-1,4 key, and wherein two phosphate groups are connected with glucosan.The example of buffer agent comprises, but (for example be not limited to acid saccharide and sugar alcohol thereof, few galacturonic acid, chondroitin sulfate, chondroitin sulfate oligosaccharide, G-6-P), the sugar alcohol of organic acid (for example tartaric acid, citric acid, malic acid, lactic acid, Fumaric acid and maleic acid), nucleic acid (phosphate ester of for example various nucleoside or nucleotide), aminoacid and above-mentioned phosphorylation oligosaccharide.
Above-mentioned buffer agent can be the form of salt, and slaine for example is so that buffer agent is effective.The example that is used to form the metal of this slaine comprises alkalinous metal, alkaline-earth metal, zinc, ferrum, chromium and lead.For example, comprise potassium, sodium, calcium and magnesium.As the slaine of the buffer agent that is contained in dietary composition of the present invention, calcium salt and sodium salt are preferred.As the slaine of the buffer agent that is contained in oral cavity composition of the present invention, calcium salt, sodium salt and zinc salt are preferred.Though zinc salt is not used in F﹠B, known zinc salt has the effect of prevention halitosis and treatment periodontal disease.Therefore, the slaine zinc salt that comprises as oral cavity composition is preferred.In addition, buffer agent can be the form of ammonium salt or quaternary ammonium salt.
Contain a sulfate group between general per two sugar of chondroitin sulfate allusion quotation.Sulfate group is connected in the 6-position of N-acetyl-D-galactosamine in the 4-position of N-acetyl-D-galactosamine in the chondroitin sulfate A and the chondroitin sulfate C.Chondroitin sulfate B (being called dermatan sulfate at large) has the unitary repetitive structure of disaccharidase of N-acetyl-D-galactosamine-4-sulphuric acid and L-iduronic acid.Chondroitin sulfate can be become the disaccharidase that has the oligosaccharide of unsaturated hexuronic acid at non-reduced end by chondroitin sulfate degrading enzyme.For example, chondroitin sulfate can not be degraded into the unsaturated disaccharidase that has hexosamine in their reduction end by chondroitinase abc (derived from P. vulgaris), chondroitinase ACI (derived from the heparin Flavobacterium) or chondroitinase ACII (derived from golden yellow arthrobacterium) (back two kinds of enzymes do not work to dermatan sulfate).Chondroitin sulfate and the effect that has Remineralization by the unsaturated oligosaccharide (preferably disaccharidase and tetrose) that obtains with this kind of enzyme degraded chondroitin sulfate.
Few galacturonic acid is a kind of oligosaccharide of polymeric galacturonic acid, and this oligosaccharide is known as the composition sugar of pectin.Few galacturonic acid preferably comprises 2 or more sugar, and more preferably 3 or more, even more preferably 4 or more, and preferably 10 or still less, more preferably 8 or still less, even more preferably 6 or still less.
Term used herein " sugar alcohol " is meant the sugar that its reduction end is reduced.For example, the sugar alcohol of phosphorylation oligosaccharide can add the hydrogen generation by the reduction end to the phosphorylation oligosaccharide.The adding of hydrogen can use the known any method of person skilled in the art to carry out.For example, can pass through the weak caustic solution of the 1N sodium hydrate aqueous solution of preparation pH 8, in this weak caustic solution of 100ml, add the 3% boron hydroxide sodium solution of 30ml, and make this mixture place 1 hour reduction oligosaccharide at 40 ℃.Can be by using the typical method commercial production sugar alcohol of the known Raney nickel of person skilled in the art.
Because buffer agent is contained in dietary composition of the present invention and the oral cavity composition, preferred phosphorylation oligosaccharide is by passing through α-1, the link coupled 3-5 of 4 keys the glucosan that glucose is formed, one of them phosphate group is connected with glucosan, or the phosphorylation oligosaccharide is by passing through α-1, the link coupled 2-8 of 4 keys the glucosan that glucose is formed, wherein two phosphate groups are connected with glucosan.
This phosphorylation oligosaccharide can preferably prepare from the starch with many phosphate groups from common natural plant starch preparation.The example of initial plant that is used for the starch of production phosphorylation oligosaccharide comprises Rhizoma Solani tuber osi, Rhizoma Dioscoreae esculentae, Maninot esculenta crantz., corn, Semen Tritici aestivi, Oryza sativa L., Oryza glutinosa, Glutinous Semen Maydis, Waxy wheat, glutinous Rhizoma Solani tuber osi, Herba Gelsemii Elegantis, Rhizoma Dioscoreae, Bulbus Lilii and Semen Castaneae.In these materials, subterraneous stem, Oryza sativa L., Semen Tritici aestivi etc. contain the phosphate group of many connections, and are the materials that is suitable for preparing the phosphorylation oligosaccharide.For example, in potato starch, the phosphate group relatively normally 3-position by ester bond and glucose or 6-position combines a component as starch.Phosphate group mainly is present in the amylopectin.When starch is used for production phosphorylation oligosaccharide, also can preferably use the starch of chemical modification.The starch of chemical modification obtains by connecting phosphorus and aforesaid native starch.For example, take from the starch of corn, Glutinous Semen Maydis etc. and phosphorus chemistry coupling with preparation phosphorylation oligosaccharide.
The above-mentioned phosphorylation oligosaccharide that is contained in dietary composition of the present invention and the oral cavity composition can followingly be produced.
For enzymolysis starch etc., make at least a amylolytic enzyme for example α-Dian Fenmei (EC 3.2.1.1), beta amylase (EC 3.2.1.2), glucoamylase (CE 3.2.1.3), isoamylase (EC 3.2.1.68), amylopectase (EC3.2.1.41) and the new amylopectase (Kuriki etc. of being selected from, Journal ofBacteriology, 170 volumes, the 1554-1559 page or leaf, 1988); With glycosyl transferase cyclodextrin glucanotrasferase enzyme (EC 2.4.1.19 for example; Hereinafter be called CGTase) starch is worked.In addition, at least a above-mentioned enzyme is used in combination with alpha-Glucosidase.
The phosphorylation saccharide that does not have branched structure can be by obtaining with α-1, the 6 branched structure degradable starch in isoamylase and the amylopectase cutting starch.If do not use isoamylase and amylopectase, can obtain to have the phosphorylation saccharide of α-1,6 branched structure.By using glucose starch enzymatic degradation phosphorylation saccharide, the non-phosphorylating glucose that is connected with the non-reduced end of phosphorylation saccharide can successfully discharge.Handle with this kind of enzyme, the quantity of the phosphate group of the purifying phosphoric acid saccharide of per unit molecular weight can increase or reduce.
Degraded by the enzyme of most of kinds can be carried out simultaneously by making enzyme and starch reaction.In brief, starch as material dissolution in water or have in the buffer of pH of adjusting and make enzyme can act on starch.The α-Dian Fenmei of liquefaction, amylopectase, glucoamylase etc. add in the reaction solution simultaneously, and make the solution reaction when heating that obtains.In this way,, can discharge neutral saccharide, can discharge and the bonded non-phosphorylating glucose of the non-reduced end of phosphorylation saccharide, maybe can cut deutero-α-1,6 branched structure from phosphorylation carbohydrate structure material when starch during by gelation.This method makes the phosphorylation saccharide that obtains to have the phosphorus acid content of increase by single step reaction become possibility, rather than two-step reaction.
Acting on respectively in each step by the enzyme that makes most of kinds under the situation that starch comprises two steps or the more rapid enzyme reaction of multistep, the order of using enzyme is not limited to concrete order.Yet if the concentration height of starch, preferably starch is at first handled with the diastatic enzyme that comprises liquefaction.If make isoamylase or amylopectase act on starch, amylose content increases.Amylose is compared with amylopectin and may be worn out and precipitate, so age of starch and precipitation.Thereby other enzyme no longer acts on starch.
Origin for employed starch degrading enzyme, glycosyl transferase, alpha-Glucosidase does not have concrete restriction.For example, α-Dian Fenmei is preferably derived from the antibacterial of bacillus or the starch degradation enzyme preparation of aspergillus.But the reaction condition of enzyme is any temperature and the pH of enzyme functionating.For example, the preferred temperature of using is in 25 ℃ to 70 ℃ scope, and pH is in 4 to 8 scope.
At first, in water or have in the buffer solution of pH of adjusting, enzyme can act on starch like this as the starch dissolution of raw material.The α-Dian Fenmei of liquefaction adds in the solution that obtains, and makes it reaction, starch liquefacation when by gelation whereby when heating.After this, the starch of liquefaction keeps suitable a period of time 20-80 ℃ temperature.As long as it can liquefying starch can use the α-Dian Fenmei of the liquefaction of any amount.The amount of preferable liquefaction α-Dian Fenmei is 20-50,000U.As long as starch liquefacation is to the non-ageing degree of starch in step process subsequently, this retention time without limits.Preferably, it is 30 minutes 20-80 ℃ of retention time.
After liquefaction is finished, do not need the deactivation of enzyme especially, but enzyme can promptly keep 10 minutes at 100 ℃ by normally used method deactivation.In addition, for example centrifugal or membrane filtration of available normally used method separates and removes undissolved material.After this, the saccharide of phosphorylation can be by fractional distillation.When needs have the phosphorylation saccharide of phosphorus acid content of increase, carry out following other step.
In brief, after raw material was liquefied, glucoamylase, isoamylase, amylopectase and alpha-Glucosidase added the raw material of liquefaction simultaneously or with suitable order so that the raw material saccharifying.The raw material that for example makes saccharifying was 40-60 ℃ thermotonus 30 minutes to 40 hours, neutral whereby sugar can discharge from raw material with the non-phosphorylating glucose that is connected with the non-reduced end of phosphorylation saccharide, and can be cut derived from α-1,6 branched structure in the phosphorylation carbohydrate structure of raw material.When glucoamylase, isoamylase and amylopectase were used in combination, the order of this combination and interpolation without limits.The amount of the enzyme that adds and the time of maintenance can be depending on the phosphorus acid content of required phosphorylation saccharide and determine.Preferably, can add glucoamylase 500-700U, isoamylase 2-100U, amylopectase 2-100U and alpha-Glucosidase 50-700U.Preferably can use immobilized enzyme.
After finishing with the reaction of each enzyme, do not need the deactivation of enzyme especially, but available normally used method inactivator kept 10 minutes at 100 ℃ promptly.In addition, for example centrifugal or membrane filtration separates and removes insoluble material with normally used method.
For purifying phosphoric acid oligosaccharide from the carbohydrate admixture that contains the phosphorylation oligosaccharide, be ionic species because do not resemble neutral saccharide phosphorylation saccharide, so can use anion exchange resin.Type for resin does not have concrete restriction.The preferable example of resin comprises that Chitopearl BCW 2500 types are (by Fuji Spinning Co., Ltd. produce), Anberlite IRA type is (by Japan Organo Co., Ltd produces), DEAE-cellulose (producing) by Whatman, DEAE-Sephadex and QAE-Sephadex (producing), and QAE-CELLULOSE (producing) by BioRad by Pharmacia.By the buffer balance resin that uses its pH suitably to regulate.For example, the about 10-50mM acetate buffer of preferential use.The equilibrated resin post of packing into, and pack into and contain the sugar mixture of phosphorylation oligosaccharide.Remove neutral saccharide by washing, absorb phosphorylation oligosaccharide on the post then with alkaline solution or saline solution elution.
Increased in use under the situation of eluant elution phosphorylation oligosaccharide of ionic strength, the kind of employed salt has been not specifically limited.The preferable example of salt comprises sodium chloride, ammonium bicarbonate, potassium chloride, sodium sulfate and ammonium sulfate.
Using pH to change under the situation of eluant elution phosphorylation oligosaccharide of alkalescence, be not specifically limited for the kind of the alkaline reagent that uses.For example, can use ammonium, sodium carbonate or sodium hydroxide.Yet, under the highly basic condition, phosphate group from sugar, discharge or sugar reduction end oxidized.Therefore, the phosphorylation oligosaccharide is elution in weak acid arrives weakly alkaline pH scope preferably, and more preferably the pH scope is 3-8.
In these cases, by using gradually or increasing the salinity or the pH elution phosphorylation sugar of eluant with the substep form, phosphorylation sugar can be dependent on the quantity of a bonded phosphate group of phosphorylation glycan molecule and carries out fractional distillation.
Active carbon also can be used to replace anion exchange resin with purifying phosphoric acid oligosaccharide from the sugar mixture that contains the phosphorylation oligosaccharide.Kind for the active carbon that uses is not specifically limited, but preferably uses the granular active carbon of the post of can packing into.Use buffer, acid, alkali, saline solution and distilled water to prepare active carbon, obtain the ability of the neutral saccharide of absorption except that glucose like this.For example, preferably can use the post and with the active carbon of the degassing with consistent particle diameter of distilled water wash of having packed into.By being added to sample on the post and neutral saccharide being adsorbed onto on the post, the phosphorylation oligosaccharide can be used as the part of passing through and obtains.
In addition, the alcohol that has 1-3 carbon atom by adding precipitates the phosphorylation oligosaccharide, with purifying phosphoric acid oligosaccharide from the sugar mixture that contains the phosphorylation oligosaccharide.In brief, in sample solution, add alcohol and only make phosphorylation oligosaccharide precipitation.Expectation be, in the sample solution of a volume, to add the alcohol of 3 parts or more volumes if sample solution has 10% or bigger sugared concentration.
At slaine, be preferably under the condition that calcium salt or iron salt add that alcohol exists, the phosphorylation oligosaccharide forms phosphorylation sugar slaine and may precipitate.For this reason, having under the situation of slaine, even use a spot of alcohol and the situation of only using alcohol to compare the easier recovery of phosphorylation oligosaccharide.Preferably, phosphorylation oligosaccharide precipitation under alkali condition.Kind to the salt that uses does not have concrete restriction.For example, preferably can use calcium chloride, magnesium chloride or ferrous chloride, because they have fine solubility.Carry out for example decant, filtration and centrifugal with normally used method by sedimentary the collecting that adds the alcohol generation.
The phosphorylation oligosaccharide can produce by remove slaine from phosphorylation oligosaccharide slaine, and this phosphorylation oligosaccharide slaine is by adding metal salt precipitate.Can carry out the removal (desalination) of slaine by normally used method.Desalination can use for example desk-top desalination microacilyzer G3 (being produced by Asahi Chemical Industry Co.Ltd) easily to carry out.
The phosphorylation sugar juice that obtains, phosphorylation sugar or phosphorylated sugar deriative can use used drying means usually, and for example hot-air dry, fluid bed drying and vacuum drying etc. concentrate or levigation.If desired, by removing the phosphorylation sugar that alcohol can obtain can be used for meals or oral application.
In potato starch, phosphate group relatively normally is connected a component as starch with the 3-position of ester bond and glucose or 6-position.Therefore, the phosphorylation oligosaccharide that uses various amylase to make from potato starch may be the bonded oligosaccharide in 3-position or 6-position of the main and glucose of its phosphate group.For example, if phosphate group is incorporated into by making glucoamylase act on the 6-position of the glucose in the phosphorylation oligosaccharide that potato starch obtains, this starch can (in a non-reduced terminal side) be cut before its 6-position has the glucose of phosphate group at once.Therefore, the phosphorylation oligosaccharide is the oligosaccharide with glucose, the 6-position of this glucose combines with phosphate group or this glucose has a kind of structure at non-reduced end, combines with phosphate group from least the second its 6-position of glucose of non-reduced terminal beginning in this structure.If phosphate group combines with the 3-position of glucose in the phosphorylation oligosaccharide, combine with phosphate group from the 3-position of second glucose of non-reduced terminal beginning.Shown representational example among Figure 26 by the phosphorylation oligosaccharide that uses various amylase hydrolysis potato starch acquisitions.Certainly, the phosphorylation oligosaccharide with said structure is not limited to the oligosaccharide produced through various amylase hydrolysis potato starch.Phosphorylation oligosaccharide with analog structure has similar anti-dental caries function.
Term used herein " sugar alcohol of phosphorylation oligosaccharide " is meant the chemical compound by the reduction end acquisition of reduction phosphorylation oligosaccharide.The sugar alcohol of above-mentioned phosphorylation oligosaccharide can add hydrogen production by the reduction end to the phosphorylation oligosaccharide.Can use the known any method of person skilled in the art to carry out the adding of hydrogen.For example, can pass through the weak caustic solution of the 1N sodium hydrate aqueous solution of preparation pH 8, add the 3% boron hydroxide sodium solution of 30ml, and make mixture place 1 hour reduction oligosaccharide at 40 ℃.Can be by using the typical method commercial production sugar alcohol of the known Raney nickel of person skilled in the art.
Above-mentioned phosphorylation oligosaccharide or its sugar alcohol can be the form of salt, for example slaine.The example that is used to form the metal of this slaine comprises alkalinous metal, alkaline-earth metal, zinc, ferrum, chromium and lead.For example, comprise potassium, sodium, calcium and magnesium.As the slaine that is contained in the phosphorylation oligosaccharide in the dietary composition of the present invention, calcium salt and sodium salt are preferred.As the slaine that is contained in the phosphorylation oligosaccharide in the oral cavity composition of the present invention, calcium salt, sodium salt and zinc salt are preferred.Though zinc salt is not used in F﹠B, known zinc salt has the effect of prevention halitosis and treatment periodontal disease.Therefore, the slaine zinc salt that comprises as oral cavity composition is preferred.In addition, the phosphorylation oligosaccharide can be the form of ammonium salt or quaternary ammonium salt.
This slaine can followingly be produced.The chemical compound phosphorylation oligosaccharide salt of phosphorylation oligosaccharide and slaine can be by precipitating as above-mentioned alcohol.If desired, the precipitation of recovery can be dissolved in water or the suitable solution again, adds alcohol subsequently.Can repeat this operation.Use this operation, can remove as neutral sugar and excessive impurity such as salt.Can use ultrafilter membrane to remove as impurity such as salt.
Known above-mentioned phosphorylation oligosaccharide has following characteristic: (1) is not utilized (being Streptococcus mutans and Streptococcus sobrinus) by pathogenic bacteria of decayed tooth; (2) suppress owing to the reduction among the pH that utilizes the sucrose generation by these antibacterials with the form of concentration dependent; (3) this inhibition depends on the buffer capacity (seeing Japanese public publication 8-104696 number) of phosphorylation oligosaccharide.According to the present invention, find that further the phosphorylation oligosaccharide of salt form and sugar alcohol thereof have the effect that promotes the tooth Remineralization in low-down concentration.By utilizing this specific character of phosphorylation oligosaccharide, can obtain to have the dietary composition and the oral cavity composition of anti-dental caries function.Specifically, the fact that obtains the Remineralization effect sufficiently at low concentration is very favorable for joining in the food.
Dietary composition of the present invention and oral cavity composition contain a certain amount of buffer agent, and buffer agent shows the function of dental caries effectively in the oral cavity like this.For example, with regard to phosphorylation oligosaccharide sodium salt, its amount can the concentration of salt be 0.01-20% in the oral cavity, is preferably 0.03-1%.For example, with regard to phosphorylation oligosaccharide calcium salt, its amount can the concentration of salt be 0.01-20% in the oral cavity, is preferably 0.03-1%.For example, with regard to phosphorylation oligosaccharide zinc salt, its amount can the concentration of salt be 0.01-20% in the oral cavity, is preferably 0.03-1%.For all phosphorylation oligosaccharide sodium salts, phosphorylation oligosaccharide calcium salt and phosphorylation oligosaccharide zinc salt, best, their concentration in the oral cavity is about 0.2%, and wherein the concentration of inorganic calcium and phosphorus is about 1.5mM and 0.9mM in the oral cavity.
Determine the amount of these additives by considering in the oral cavity retention time of dietary composition of the present invention and oral cavity composition.The behavior of dietary composition chew to(for) needs will provide a kind of purpose.For example, just contain the chewing gum of the 20% phosphorylation oligosaccharide of having an appointment, the elution from dietary composition of phosphorylation oligosaccharide, and can there be about 10 minutes in the phosphorylation oligosaccharide of relative high concentration (about 1% to about 5%) after chewing.After about 20 minutes to 30 minutes, have only 0.25% or phosphorylation oligosaccharide still less be present in the oral cavity.Therefore, in the oral cavity concentration of phosphorylation oligosaccharide be diluted as concentration in the food 1/4 or still less.Therefore, with regard to this food, buffer agent can be expected in the oral cavity four times or fewer concentration and add in the food (for example, one to four times).On the other hand, about the compositions (for example beverage) that does not need the behavior of chewing, the retention time in the oral cavity is in 1 minute.This compositions is not dilution fully in the oral cavity.Therefore, the phosphorylation oligosaccharide mixes compositions to be substantially equal to expect in the oral cavity concentration (for example, 0.1% to 5%).Dietary composition of the present invention and oral cavity composition can contain independent or bonded above-mentioned buffer agent, can keep above-mentioned dosage like this in the oral cavity.
On the other hand, dietary composition of the present invention and oral cavity composition further contain any phosphorus-calcium compensation, phosphorus preparation and calcium preparation or one or more combination except that above-mentioned buffer agent in addition.Specifically, when compositions comprised calcium salt, excessive calcium discharged from calcium salt, so that calcium-phosphorus ratio changes in the compositions.And the buffer agent of adding can be influential to elution calcium from tooth.In this case, if compensated by the ratio of phosphorus calcium concentration in the saliva of buccal cavity of buffer agent change, the tooth Remineralization can be more effective.For the normal person, the mol ratio of calcium phosphorus in the saliva (hereinafter being called " Ca/P ") is generally 0.25-0.67 (P/Ca=1.45-3.9), and therefore, the phosphorus of existence is than calcium many (that is, similar 3 moles of phosphorus than 2 moles of calcium to 3.9 mole phosphorus than 1 mole of calcium).The component hydroxyapatite of tooth (is expressed as Ca
10(PO
4)
6(OH)
2)) have 1.67 Ca/P than (P/Ca=0.6).The composition of forming dental enamel has the Ca/P of 1.0-1.67 than (P/Ca=0.6-1.0).Therefore, by providing phosphorus and/or calcium to make Ca/P near 1.0-1.67 (P/Ca=0.6-1.0) together with buffer agent, preferably 1.67 ((P/Ca=0.6), it may promote these substance crystallizations to enter hydroxyapatite.
The reagent that can compensate Ca/P is called " phosphorus-calcium compensation " here.The example of this phosphorus-calcium compensation comprises univalent calcium phosphate (Ca (H
2PO
4)
2H
2O), the calcium phosphate (CaHPO of bivalence
42H
2O), calcium of tervalent calcium phosphate, calcium pyrophosphate, hydroxyapatite powder, amorphous calcium phosphate, Os Bovis seu Bubali calcium, eggshell calcium, coral calcium, Margarita calcium, fish and shellfish and tervalent alpha-calcium phosphate.Compensate Ca/P herein and be meant that maintenance Ca/P is basically in the scope of 1.0-1.67 (P/Ca=0.6-1.0).In this case, Ca/P does not need strictly to be limited in 1.0-1.67 (P/Ca=0.6-1.0).As long as Ca/P can be basically near about 1.0-1.67 (P/Ca=0.6-1.0), Ca/P can drop to outside the scope of 1.0-1.67 (P/Ca=0.6-1.0).The amount that compensates required compensation changes with the kind of buffer agent and compensation, but if desired, the scope of this amount can simply be tested definite by the person skilled in the art.With regard to phosphorus-calcium compensation, for a buffer agent that adds, its suitable mole is 1/20 part to 20 parts, preferably 1/2 part to 2 parts.
Since phosphorus is excessive in saliva, can use the Ca preparation to adjust Ca/P to 1.0-1.67 (P/Ca=0.6-1.0).In people's saliva, phosphorus concentration is 3-3.5mM, and calcium concentration is 0.9-2mM.Therefore, preferably add the calcium of about 4-5mM to improve calcium concentration.Therefore, can use calcium salt (buffer agent) as phosphorus-calcium compensation.With regard to the phosphorylation oligosaccharide that contains 3% calcium, it is suitable adding about 0.7% phosphorylation oligosaccharide calcium.The preferable example of calcium preparation includes, but are not limited to calcium carbonate, calcium chloride, calcium lactate, calcium gluconate, whey calcium, calcium of organic acid, colloid calcium carbonate, casein phosphopeptides calcium and calcium fluoride.
Dietary composition of the present invention and oral cavity composition further contain the phosphorus preparation.Term used herein " phosphorus preparation " is meant phosphate compounds.The example of phosphate compounds comprises sodium phosphate, dibastic sodium phosphate, potassium phosphate and potassium hydrogen phosphate.
Above-mentioned phosphorus-calcium compensation, phosphorus preparation or calcium preparation can be separately or in conjunction with adding dietary composition of the present invention and oral cavity composition so that Ca/P near 1.0-1.67 (P/Ca=0.6-1.0), and preferably is 1.67 (P/Ca=0.6).
Term used herein " dietary composition " is people's the feedstuff of food, letting animals feed or fish and the general name of pet food.Particularly, dietary composition of the present invention comprises liquid and powder drink such as coffee, tea, green tea, oolong tea, fruit juice, processed milk and sports drink; Bake food for example bread, pizza and pie; Bake sweet food for example cookie, cracknel, cookies and cake; Pasta such as spaghetti and macaroni; Noodles are Semen Tritici aestivi noodles, noodle prepared from buckwheat and Chinese style noodles for example; Sweets is confection, soft sweet, chewing gum and chocolate for example; Snack is puffed rice and potato block for example; Frozen sweet is ice cream and sherbert for example; Milk product is butter, cheese, milk powder, condensed milk and milk beverage for example; The confection class dessert that does not cure in the west is fruit jelly, pudding, mousse and clabber for example; Japan's sweet food is butter roundlet bread, uirou (by add sugar, the square-cut new year cake that steaming and decocting subsequently obtains in flour), new year cake and ohagi (with the rice group of parcels such as bean sauce) for example; Flavoring agent is soy sauce, the sauce that dips in, noodle soup, chilli bean sauce, natural juice meat soup, stewed domestic animal, soup, blended flavoring agent, curry powder, mayonnaise and tomato sauce for example; Tinned or sterilize packed food for example curry, fricassee, soup and rice; It is freezing that for example Petaso, hamburger, meatball, Deep-fried meatballs, Chinese style dumplings, fried rice and rice are rolled into a ball with chilled food; The sea converted products is tikuwa (tubulose alec) and kamaboko (alec cake) for example; With metric system product for example rice and the sushi of open-air lunch.In addition, because dietary composition of the present invention has the ability that makes calcium be easy to absorb, so it comprises Infants'feeding milk, ablactation food, baby food, pet food, animal feed, motion food, tonic food and the health product of preparation.
In a preferred embodiment, F﹠B is the kind that need chew in a large number when edible, for example chewing gum.With regard to the F﹠B of being chewed in a large number, buffer agent easily spreads in the oral cavity, produces the good result of dental caries.With regard to the F﹠B of being chewed in a large number, the weight ratio that buffer agent can 0.1-50% preferably, the weight ratio of 0.5-20% more preferably, even the weight ratio of 0.5-10% more preferably, particularly preferably the weight ratio of 0.5-5% adds in the food.Particularly, for example, this food is the chewing gum of buffer agent that contains the weight ratio of 0.1-50%, or contains the lamellar confectionery, confection, soft sweet etc. of buffer agent of the weight ratio of 0.1-50%.
In another preferred embodiment, F﹠B is not need the kind of chewing when edible, for example beverage (as fruit juice or fresh water).Do not need food or the beverage chewed when edible, the weight ratio that buffer agent can 0.1-70% preferably, the weight ratio of 0.1-50% more preferably, even more preferably the weight ratio of 0.2-5% is mixed in the food.Specifically, for example, this food is to contain the fruit juice that weight ratio is the buffer agent of 1-30%.Preferably, this food is to contain vegetable juice, natural fruit juice, milk beverage, milk, bean milk, sports drink, nearly water beverage, nutritious drink, coffee beverage or the cocoa that weight ratio is the buffer agent of 0.1-10%.
In another preferred embodiment, F﹠B is to chew as many kind with usual staple food when edible.Preferably, this F﹠B is staple food and beverage.For example, this food is rice.With regard to staple food, since with the edible food of enough amounts, even add the remarkable and secular effect that a spot of buffer agent has advantageously provided caries prevention.Just chew as many food with usual main fresh food, the weight ratio that buffer agent can 0.01-20% preferably, the weight ratio of 0.02-10% more preferably, even the weight ratio of 0.03-5% more preferably, particularly preferably the weight ratio of 0.05-3% adds in the food.Specifically, this food is, for example contains the rice that weight ratio is the buffer agent of 0.02-10%, and containing weight ratio is bread of 0.01-20% phosphorylation oligosaccharide etc.
Certainly, the present invention can be used for except the F﹠B described in the above-mentioned preferred embodiment those.Particularly, the present invention can be used for, for example, contain the Chinese noodle that weight ratio is the buffer agent of 0.1-20%, containing weight ratio is the Semen Tritici aestivi noodles of the buffer agent of 0.1-20%, contain the new year cake that weight ratio is the buffer agent of 0.1-20%, contain the pretzel that weight ratio is the buffer agent of 0.1-20%, contain the agar that weight ratio is the buffer agent of 0.1-20%, contain the fruit jelly that weight ratio is the buffer agent of 0.1-20%, contain the clabber that weight ratio is the buffer agent of 0.1-20%, contain the cookie that weight ratio is the buffer agent of 0.1-20%, containing weight ratio is the lamellar sweet food of the buffer agent of 0.1-20%, contain the bean curd that weight ratio is the buffer agent of 0.1-20%, contain the chocolate that weight ratio is the buffer agent of 0.1-20%, containing weight ratio is the metric system sweet food of the buffer agent of 0.1-20%, contain weight ratio and be 0.1-20% buffer agent Chinese dumplings and contain the Petaso that weight ratio is the buffer agent of 0.1-20%.
Term used herein " oral cavity composition " is meant any compositions that is different from F﹠B, and said composition can be introduced the oral cavity and can contact with tooth.Oral cavity composition can be medicine or quasi drug or other chemical compound.For example, should " oral cavity composition " further comprise cosmetics (more particularly, have caries prevention, whitening teeth, remove dental plaque, cleaning oral cavity, prevention halitosis, remove tar, the dentifrice (it is the cosmetics of admitting under Japanese medicine method Japanese Pharmaceutical Affairs Law (calendar year 2001 revision)) of effects such as prevention tartar deposition.Particularly, oral cavity composition of the present invention comprises, for example, and dentifrice, collut, lozenge, gargarism, gingival massage cream, lozenge, artificial saliva etc.
In a preferred embodiment, oral cavity composition of the present invention be preferably contain weight ratio be 0.01-20%, more preferably weight ratio be 0.02-10% in addition more preferably weight ratio be 0.03-5% and particularly preferably weight ratio be the dentifrice of the buffer agent of 0.05-3%.
In a preferred embodiment, oral cavity composition of the present invention be preferably contain weight ratio be 0.01-20%, more preferably weight ratio be 0.02-10% in addition more preferably weight ratio be 0.03-5% and particularly preferably weight ratio be the rinse medicine of the buffer agent of 0.05-3%.
In a preferred embodiment, oral cavity composition of the present invention be preferably contain weight ratio be 0.01-20%, more preferably weight ratio be 0.02-10% in addition more preferably weight ratio be 0.03-5% and particularly preferably weight ratio be the oral cavity ointment of the buffer agent of 0.05-3%.
Preferably, oral cavity composition of the present invention is to contain dentifrice that weight ratio is the buffer agent of 0.01-20%, mouth-wash, lozenge, gargarism, artificial saliva etc.
Used artificial saliva to improve xerostomia.This artificial saliva contains the component substantially the same with people's saliva, for example mineral.Contain the artificial saliva of above-mentioned buffer agent can not only moistening tongue and the larynx mucosa tongue and larynx mucosa are smoothly moved, can also prevent and treat dental caries.
Dietary composition of the present invention and oral cavity composition also randomly contain fluorine.Dietary composition of the present invention and oral cavity composition are included in 1000ppm or still less, preferably 0.1-500ppm and more preferably in the scope of 0.1-300ppm.In order to improve the usefulness of 100ppm or more fluorine, buffer agent is applicable to medicine, accurate medicine and cosmetics.Meals of the present invention and oral cavity composition can be by further containing the effect that fluorine has the tooth Remineralization of higher level.Here, " fluorine " comprises fluorion.Term " fluorine-containing material " is meant any material that fluorion is provided, and preferably contains the chemical compound (for example, sodium monofluorophosphate, sodium fluoride, potassium fluoride, ammonium fluoride, amine salt fluoride and stannic fluoride) of fluorion.Preferably use sodium monofluorophosphate and sodium fluoride.
Only use fluorine or fluorine-containing material to cause low-level tooth Remineralization.Particularly, fluorine and fluorine-containing material may not dissolve at 100ppm or higher concentration, cause usefulness obviously to descend.Yet, in the present invention, find that buffer agent uses the raising that causes usefulness with fluorine or fluorine-containing material.For food, tea that contains a large amount of fluorine (200-300ppm) etc. is preferred.Fluorine or fluorine-containing material mix the tooth crystal to produce antacid firm crystal.Therefore, dietary composition of the present invention and oral cavity composition relate to crystalline production of firm tooth and tooth Remineralization, thereby reduce the generation of dental caries.
Dietary composition of the present invention and oral cavity composition can further comprise known other material with anti-dental caries function of person skilled in the art.This examples of substances comprises various oligosaccharide (panose (6
2-glucityl-maltose), dextrinosan, isomaltulose (6-O-α-glucose pyrans glycosyl-D-fructofuranose), trehalose (O-α-D-glucose pyrans glycosyl (1-1)-α-D-pyranglucoside), Fructus Hordei Germinatus oligose, lactosucrose
TM(4
G-β-D-galactosyl sucrose), furan oligosaccharide, coupling sugar, xylosylfructoside, cyclodextrin etc.); Sugar alcohol (xylitol, erythritol, palatinit, sorbitol, maltose alcohol, mannitol etc.); Folium Camelliae sinensis extract (fluorine, polyphenol, catechin etc.); Medical herbs (for example Herba Menthae, Oleum menthae, Chamomile, Salvia japonica Thunb., Rhizoma Zingiberis Recens, the perfume (or spice) etc. that changes are seen Shibuya etc., spice magazine special issue FRAGRANCEJOURNAL SPECIAL ISSUE, 12,150-155 page or leaf, 1992); Enzyme (for example, glucanase, mutase etc.); And vaccine (for example immunoglobulin A of excretory Antivariant streptococcus).Sugar alcohol is preferred.Xylitol is preferred.Dietary composition of the present invention and oral cavity composition are by containing the reinforced effects that above-mentioned substance can have caries prevention.
Can use known method to detect the effect of the Remineralization of buffer agent, pilot system of using the Remineralization of baurodont tooth section for example, it is described in Inaba.D etc., Eur.J.Sci.105:74-80,1997; Inaba.D etc., J.Dent.Health.47:67-74,1997; With Iijima.Y etc., Dental Caries Research.33:206-213,1999.
In order to measure the effect of the Remineralization that is contained in the buffer agent in dietary composition of the present invention and the oral cavity composition, inventor of the present invention has developed the simple pilot system of comparing with above-mentioned Remineralization pilot system.For example, the incidental condition of Remineralization is as follows: the contact surface to dental surface (hydroxyapatite) provides calcium and phosphorus fast, and they are mixed tooth composition (hydroxyapatite); In comprising the system of dental surface, keep higher calcium and phosphorus concentration; Zone except that dental surface does not have the deposition or the loss of calcium and phosphorus.These are used for the condition of easy Remineralization following simplification: be provided for crystalline calcium and phosphorus and reduce soluble calcium in the system that comprises hydroxyapatite; With in the system that does not comprise hydroxyapatite, phosphorus and calcium do not deposit and keep its higher dissolubility.Therefore, compare the size of the dissolubility of calcium in these two systems to detect the effect of Remineralization.These simple pilot systems will be described below.TMR (laterally microradiography) method has been used for a large amount of research to demineraliting and Remineralization as a kind of standard method that is used for measuring in quantitative mode the distribution of dentine mineral concentration.For this method, following restriction is arranged: need assess for a long time; Need high-caliber experimental technique etc.Therefore, need one can catch the simple evaluation system that the dentine mineral concentration changes rapidly.Consider exploitation Remineralization in the early stage caries damage of dental enamel by following two steps:
(i) part that component calcium (Ca) ion and phosphorus (P) ion of enamel offered demineraliting; With
Ca ion that (ii) provides and P ion are used for the crystal growth of the part enamel of demineraliting.
In view of above-mentioned two steps, a kind of have the material that promotes the Remineralization effect be considered to a kind of not dissolving and precipitate but not suppressing the material of the crystal growth of hydroxyapatite of Ca and P of suppressing under neutral pH.
These pilot systems are relevant with the conventional system of above-mentioned use baurodont tooth, and set up a simple and fabulous method.
In one aspect of the invention, the present invention relates to study expection and have the method for the sample of dental caries effect the effect of tooth Remineralization.This method comprises the steps: that (A) having under the situation of sample precipitated calcium in the solution that contains phosphorus, calcium and tooth composition; (B) post precipitation is measured the concentration of calcium in the solution or the amount of sedimentary calcium; (C) precipitated calcium in the solution that does not contain sample; (D) post precipitation is measured the concentration of calcium in the solution or the amount of sedimentary calcium; (E) comparison step (B) and (D) in the concentration of calcium or the amount of sedimentary calcium.In a preferred embodiment, above-mentioned solution can comprise hydroxyapatite, buffer, K
2HPO
4And CaCl
2" the tooth composition " that is contained in above-mentioned solution is because Remineralization precipitates phosphorus and calcium to produce any material of hydroxyapatite.The use of hydroxyapatite is preferred.In addition, can use as mammiferous tooth and its section or fractions such as cattle.When preparation was used for the solution of calcium deposit, the order that adds above-mentioned phosphorus, calcium and other tooth composition without limits.Preferably, adding with preparation solution with following order, at first is sample, is phosphorus, calcium chloride solution and tooth ingredient suspension or deionized water then.Preferably, add K
2HPO
4The pH of solution is adjusted in the back.Generally produced calcium deposit (preferably 10 hours to 7 days, more preferably 18 hours to 42 hours) in tens hours to several days by at room temperature cultivating.Can use the known any method of person skilled in the art to measure the calcium dissolubility of solution.The calcium dissolubility of solution can be measured (using " the Calcium Ctest Wako " that produced by Wako Pure Chemicals) by the OCPC method.In addition, can measure the amount of sedimentary calcium in the solution.Can use the known any method of person skilled in the art to measure the amount of sedimentary calcium in the solution.The calcium dissolubility of solution can use the known any method of person skilled in the art to measure.The example of this method comprises ICP method (the link coupled plasma method of inductivity), atomic absorption analysis and ion electrode method.
In order to measure the function of dental caries, a kind of artificial mouth equipment is used to obtain the enamel (seeing for example Jpn.J.Oral Biol.20:288-291,1984) of real as far as possible demineraliting.For example, this equipment can comprise an electrode, attached to the instrument of the section of the enamel around the electrode and Streptococcus mutans cell suspending liquid, culture fluid and the sugar juice that drips.Use this equipment, the Streptococcus mutans of synthetic water-fast glucosan forms an artificial plaque attached to electrode surface, thereby produces low pH.And an artificial plaque similarly forms on the enamel part, causes the remarkable decline of enamel hardness.
(embodiment)
Hereinafter, will describe the present invention in detail in the mode of embodiment.These embodiment will limit the present invention.Material, reagent that is used for embodiment etc. is commerce unless otherwise mentioned and buys.
(embodiment 1)
At first, when being dissolved in the 5ml solution of the calcium chloride that contains 6mM sodium chloride and 2mM, 1% potato starch solution is heated to 100 ℃ rapidly with gelation.After this, make the α-Dian Fenmei (Fukutamirase) of producing by Hankyu Bioindustry Ltd. of 35U act on the mixture of gelation, and kept 30 minutes at 50 ℃.A spot of reactant liquor is used to prepare 0.2% sugar juice.The Wagner's reagent of 1/10 part 0.01M adds in a sugar juice.Confirm that in iodometry the mixture that produces is negative.After this, make the amylopectase (producing) of 2U and the glucoamylase (by Toyobo Co., Ltd. produces) of 6U act on mixture 20 hours simultaneously at 40 ℃ by Hayashibara Biochemical Lab..Cessation reaction, centrifugal subsequently.Supernatant is applied to 20mM acetate buffer (pH 4.5) equilibrated anion-exchange resin column (Chitopearl BCW 2501; By FujiSpinning Co., Ltd produces).This post thoroughly washs to remove neutral saccharide with acetate buffer, subsequently with the acetate buffer elution that contains 0.5M sodium chloride.The part of each elution with vaporizer concentrate, desalination and lyophilizing, obtain the phosphorylation oligosaccharide thus.
The phosphorylation oligosaccharide of Huo Deing is used for the equilibrated anion-exchange resin column of 20mM acetate buffer (pH 4.5) (Chitopearl BCW 2501) once more like this.This post thoroughly washs to remove neutral saccharide with acetate buffer.Make this post with containing the acetate buffer of 0.15M sodium chloride and using the acetate buffer elution that contains 0.5M sodium chloride then.Partially desalted and the lyophilizing of collecting.According to these parts of methods analyst that are used for determining structure mentioned above, show in the phosphorylation sugar that (PO-1 part) obtains from the part of 0.15M sodium chloride elution phosphate group and glucosan combination with 3-5 glucose of the α of containing-1,4 key; And in the phosphorylation sugar that (PO-2 part) obtains from the part of 0.5M sodium chloride elution, two or more phosphate groups and glucosan combination with 2-8 glucose of the α of containing-1,4 key.
The structural analysis of above-mentioned phosphorylation oligosaccharide is following to be carried out.
At first, from the phosphorylation oligosaccharide, remove phosphate group.100 μ l, 3% phosphorylation oligosaccharide solution mix with the 60mM sodium carbonate buffer (pH 9.4) that 100 μ l contain 10mM magnesium chloride, 0.3mM zinc chloride and 0.05% sodium azide.100 μ l, 30U/ml alkali phosphatase (EC.3.1.3.1; Produce by SIGMA derived from escherichia coli) add mixture, make it then 40 ℃ of reactions 18 hours.By using ultrafilter membrane to remove the alkali phosphatase cessation reaction, obtain to contain the reactant liquor (hereinafter being called reactant liquor A) of the sugar (dephosphorylation sugar hereinafter referred to as) of removing phosphate group thus.
The beta amylase that the reactant liquor A that obtains to 10 μ l adds the 5000U/ml of the 200mM acetate buffer (pH 4.8) that is dissolved in 10 μ l (produces from Rhizoma Dioscoreae esculentae; Produce by SIGMA), the mixture that obtains keeps 2 hours (liquid that obtains is called reactant liquor B) at 37 ℃.Similarly, be dissolved in the saccharogenic amylase of 300U/ml of 60mM acetate buffer (pH4.5) of 10 μ l (derived from Rhizopus; By Totobo Co., Ltd. produces) add the reactant liquor A of 10 μ l, the mixture that obtains keeps 18 hours (liquid that hereinafter obtains is called reaction liquid C) at 35 ℃.
Analytical reactions liquid A-C is to confirm product wherein.By using anion-exchange resin column, CarboPacPA-100 (Ф 4 * 250mm, produce by Dionex Corp.) high performance liquid chromatography or use these liquid of thin layer chromatography analysis of silica gel to confirm product in these reactant liquors, and analysis result and the product with standard Fructus Hordei Germinatus oligose of the various degree of polymerization are made comparisons.Use high performance liquid chromatography elution dephosphorylation sugar by using the 100mM sodium hydroxide, improve the concentration of the sodium acetate of 1M and carry out as base soln.The detection of dephosphorylation sugar uses pulse current detector (being produced by Dionex Corp.) to carry out.Use thin layer chromatography analysis dephosphorylation sugar to spray sulphuric acid/methanol solution (=1/1), and carried out in 3 minutes 130 ℃ of reservations by with acetonitrile/water (80/20) multiple spreading dephosphorylation sugar.
Analytical reactions liquid A is so that determine the chain length of phosphorylation oligosaccharide.When analytical reactions liquid B, only detect maltose and maltotriose (with a spot of glucose).Therefore, confirm that dephosphorylation sugar is glucosan, wherein glucose is interconnection by α-1,4 key.And, when analytical reactions liquid C, only detect glucose.Therefore confirm that dephosphorylation sugar is made up of the glucose that α-key connects.
The average chain length of sugar (hereinafter, by DP representative, using glucose as a unit) obtains from the sugared content of dephosphorylation saccharide with various degree of polymerization.The total sugar content of whole phosphorylation saccharide uses the phenolsulfuric acid method to measure.The quantity conduct of the phosphate group that connects is by making dephosphorylation saccharide wet ashing (the saccharide test method relevant with starch, " biochemical test method " (Biochemistry experimental method) 19, M.Nakamura etc., 31 pages, 1986, JSSP Tokyo) inorganic phosphate that obtains is determined.According to following formula, use the amount of the inorganic phosphate of determining after the wet ashing of dephosphorylation saccharide and the quantity that DP calculates the bonded phosphate group of per molecule:
(embodiment 2)
Contain per molecule have a phosphate group the phosphorylation oligosaccharide PO-1 part and contain each 10g of PO-2 part that per molecule has the phosphorylation oligosaccharide of two phosphate groups and be dissolved in the distilled water of 100ml.Use electrodialysis instrument (Micro acilyzer) G3, AC210-400 film: by Asahi Kasei Co., Ltd production) remove the salinity in these aqueous solutions, use strong cation-exchanging resin (Dowex 50w 20-50MESH then, H-type: produce) carries out ion exchange, obtain the sugar juice of pH2.7 thus by NisshinKasei.With the solution that 1N sodium hydroxide or aqua calcis neutralization obtain, lyophilizing subsequently makes phosphorylation oligosaccharide sodium salt or calcium salt thus.
The phosphorylation saccharide of Shi Yonging (with the form of sodium salt or calcium salt) is to contain 80% or the phosphorylation carbohydrate admixture of the residue of the phosphorylation sugar of more above-mentioned PO-1 part and PO-2 phosphorylation sugar partly in the following embodiments.
(embodiment 3)
In embodiment 3, use the system of baurodont tooth part to be used to clarify of the effect of phosphorylation oligosaccharide for the early stage caries Remineralization.
The carrying out of this test is basically according to Inaba.D etc., Eur.J.Sci.105:74-80,1997; Inaba.D etc., J.Dent.Helth.47:67-74,1997; With Iijima.Y etc., Caries Research.33:206-213,1999.
The tooth part of Shi Yonging is prepared as follows in test: the cubical baurodont tooth part of placing every limit 3mm is so that its enamel surfaces makes progress.Remove enamel surface external synthetic resin and cover part.Handle enamel with wet grinding sand paper.Demineraliting is following to carry out: the tooth part is immersed in 3 weeks in the 1% lactic acid gel (pH5.0) that contains 6% carboxymethyl cellulose gel at 37 ℃.Remineralization is following carries out: at 37 ℃, the tooth part of demineraliting is immersed in and contains 1.5mMCaCl
2With 0.9mM KH
2PO
420mM 2-[4-(2-ethoxy)]-1-piperazine esilate (HEPES) buffer (pH7.0) in a week.
Be prepared as follows 8 test group: (1) is demineraliting (blank only; " blank " among Fig. 1 and 2); (2) Remineralization (negative control only; " contrast " among Fig. 1 and 2); (3) Remineralization solution+2ppm fluorine (F) (positive control; " 2ppm F " among Fig. 1 and 2); (4) Remineralization solution+4.0% phosphorylation oligosaccharide sodium salt (" POsNa 4% " among Fig. 1 and 2); (5) Remineralization solution+1.0% phosphorylation oligosaccharide sodium salt (" POs Na 1% " among Fig. 1 and 2); (6) Remineralization solution+0.2% phosphorylation oligosaccharide sodium salt (" POs Na 0.2% " among Fig. 1 and 2); (7) Remineralization solution+0.2% phosphorylation oligosaccharide calcium salt (" POs Ca 0.2% " among Fig. 1 and 2); (8) Remineralization solution+0.07% phosphorylation oligosaccharide calcium salt (" POs Ca 0.07% " among Fig. 1 and 2).
After each processing, preparation 200 μ m slabs are analyzed the distribution of its mineral concentration from microradiographic visual (not shown) from the tooth part of each processing.When tooth part during by demineraliting, mineral is from tooth part eluting and run off, and wherein produces cavity (dental caries outbreak) successively.Fig. 1 shows the figure (vertical axis shows mineral loss value) according to this mineral concentration assaying matter loss value.Fig. 2 shows the degree of depth [vertical axis shows lesion depths (μ m)] of demineraliting.According to Fig. 1, for phosphorylation oligosaccharide sodium and phosphorylation oligosaccharide calcium, on the least concentration level of test concentrations, mineral loss is minimum.This mineral loss is less than the loss of (2) positive control.With regard to phosphorylation oligosaccharide sodium and phosphorylation oligosaccharide calcium, obtain shallow lesion depths (Fig. 2).This shows that cavity passes through Remineralization and fills.What is interesting is that about having (2) positive control of fluorine, lesion depths does not change.
After each processing, also analyzed calcium and phosphorus concentration in the solution after the Remineralization.Solution is 10, centrifugal 2 minutes of 000g, and clear liquid analytically.Use the molybdic acid method to measure phosphorus concentration (" Shin-ban Bunseki KagakuJikken " new edition Experiment of Analytical Chemistry " (New Edition Analyical Chemistry Experiment) (front page); 313-314 page or leaf; publish), and (produces by Wako Pure Chemicals: mensuration calcium concentration use " calcium C test Wako " kit measurement) with the OCPC method by Kagaku Dojin K.K..The results are shown in the table 1.
Table 1
According to table 1, find that by adding the phosphorylation oligosaccharide concentration that is dissolved in calcium in the solution and phosphorus is still high.
Therefore, CAL shows by adding the phosphorylation oligosaccharide, and the concentration that is dissolved in calcium in the solution and phosphorus is still high, the result, and these dissolved phosphorus and calcium can offer the dental caries part and be used for Remineralization.This phenomenon is considered to occur in people's the oral cavity.
(embodiment 4)
In embodiment 4, a kind of simple experiment system of Remineralization is used to clarify the effect of phosphorylation oligosaccharide to the early stage caries Remineralization.
(step of Remineralization pilot system)
In order to detect the Remineralization phenomenon in simple more mode, the condition that more easily produces Remineralization is simplified.In a system that comprises hydroxyapatite, supply with calcium and phosphorus is used for crystallization and soluble calcium is reduced.On the contrary, in a system that does not comprise hydroxyapatite, calcium and phosphorus do not precipitate, so that its dissolubility remains on high level.Based on these facts, design following pilot system.
By mixing the solution that following material prepares 500 μ l: the 200mM HEPES buffer (pH7.0) of (1) 50 μ l with following order; The deionized water of (2) 200 μ l or sample; The 18mM KH of (3) 50 μ l
2PO
4Solution; The 30mM calcium chloride solution of (4) 50 μ l; (5) hydroxyapatite suspension (5mg/ml) or deionized water.After adding (3), use the pH of 0.1N potassium hydroxide solution regulator solution.The solution that stirring obtains was also cultivated 1-7 days at 37 ℃.After this, solution is 12, centrifugal 3 minutes of 000rpm.The calcium concentration of the supernatant that obtains uses the OCPC method to measure (as above-mentioned).For this reason, use Calcium test C Wako (numbering: 272-21801) measure absorbance at the 570-nm place.The percentage ratio of soluble calcium obtains by multiply by 100 with the concentration of the calcium that adds divided by the calcium concentration of supernatant.The percentage ratio of the difference acquisition Remineralization between the value that obtains when calculating the value that obtains by deionized water and in (5), adding hydroxyapatite.
(having of the influence of the phosphorylation oligosaccharide of various concentration) to Remineralization
Above-mentioned simple experiment system is used for having the phosphorylation oligosaccharide sodium salt of various concentration and phosphorylation oligosaccharide calcium salt 18 hours or 42 hours 37 ℃ of cultivations.The result of phosphorylation oligosaccharide sodium salt and phosphorylation oligosaccharide calcium salt Remineralization is shown in respectively in Fig. 3 and 4 that (in Fig. 3 and 4, vertical axis is represented the ratio (%) of Remineralization, and trunnion axis is represented sample (%), and the contrast expression does not add sample; For each sample concentration, the bar on the left side is represented processing in 18 hours, and the bar on the right is represented processing in 42 hours).Even phosphorylation oligosaccharide sodium salt has also improved the ability (Fig. 3) of the calcium of dissolving adding under low concentration.Phosphorylation oligosaccharide calcium salt has the ability of the outside calcium salt that adds of low dissolving, and discharges extra calcium on the contrary to change the calcium/phosphorus ratio in the solution, so that therefore the easier precipitation of calcium also can not keep high calcium concentration (Fig. 4).
Therefore, phosphorylation oligosaccharide sodium salt can show dissolution and calcium/phosphorus ratio in the not change system.With regard to phosphorylation oligosaccharide calcium salt, think that need supply with to keep the Ca/P ratio simultaneously with phosphorus (phosphate, phosphorus compound etc.) be 1.67 (P/Ca is than=0.6).In addition, the concentration of the phosphorylation oligosaccharide calcium salt of adding needs almost not influence of reduced value.
(the phosphorylation oligosaccharide of Ca/P concentration ratio=1.67 (P/Ca concentration ratio=0.6) is to the influence of Remineralization effect)
When using phosphorylation oligosaccharide calcium salt, calcium is set at 1.67 (P/Ca concentration ratio=0.6) with the ratio of phosphorus concentration, sets concentration to obtain calcium from the phosphorylation oligosaccharide.Setting sodium salt is complementary with the concentration with the phosphorylation oligosaccharide.Concentration is set and is shown in the following table 2.
Table 2
In above-mentioned simple experiment system, cultivated 15 hours for 37 ℃.The results are shown in that (vertical axis is represented the ratio (%) of Remineralization among Fig. 5, trunnion axis is represented Ca concentration (mM), the contrast of the not phosphorous acidify oligosaccharide of the square representative salt of filling, rhombus is represented phosphorylation oligosaccharide sodium salt (POs Na), the circular phosphorylation oligosaccharide calcium salt (POs Ca) of representing).As shown in Figure 5, when concentration constant when Ca/P concentration ratio=1.67 (P/Ca concentration ratio=0.6) and the calcium that adds improves, between phosphorylation oligosaccharide sodium salt and phosphorylation oligosaccharide calcium salt, obtain similar result.When the calcium salt that adds is 6mM or more for a long time, the effect of the phosphorylation oligosaccharide of interpolation reduces.
(the phosphorylation oligosaccharide of various Ca/P ratios is to the influence of Remineralization effect)
17.5 hours or 1 weeks are cultivated at 37 ℃ by above-mentioned simple experiment system, during the change of calcium and phosphorus concentration ratio be shown in (table 3 uses P/Ca) in the table 3.
Table 3
This results are shown in Fig. 6 A (vertical axis is represented the ratio (%) of Remineralization, and trunnion axis is represented P/Ca) in 6C.Fig. 6 A has shown the result of the contrast of not phosphorous acidify oligosaccharide.On behalf of a week, 17.5 hours processing of square representative, the rhombus of filling handle.Fig. 6 B shows the result of phosphorylation oligosaccharide sodium salt.Triangle is represented processing in 17.5 hours, and on behalf of a week, the triangle of filling handle.Fig. 6 C shows the result of phosphorylation oligosaccharide sodium salt.On behalf of processing in 17.5 hours, the circle of filling, circle represent a week to handle.As Fig. 6 A to shown in the 6C, when Ca be fixed to 1.5mM and phosphorus concentration change and change P/Ca than the time, think that phosphorylation oligosaccharide sodium salt and phosphorylation calcium salt cause relative Remineralization effectively.According to this result, even think that calcium salt is more stable under the situation of high concentration phosphorus.
(embodiment 5)
Embodiment 5 shows that phosphorylation oligosaccharide and other dental caries medicament are in the active comparison of Remineralization.As the medicament of dental caries, use xylose, xylitol, isomaltulose and palatinit.Use the effect of the single system detection Remineralization of embodiment 3.In this single system, cultivated 8 days for 37 ℃.The results are shown in Fig. 7 A (vertical axis is represented the ratio (%) of Remineralization, and trunnion axis is represented sample concentration (%)) in 7C.Fig. 7 A shows the result of phosphorylation oligosaccharide salt, and wherein the triangle of Tian Chonging is represented calcium salt, and empty triangle is represented sodium salt.Fig. 7 B shows the result of xylitol, and wherein the circle of Tian Chonging is represented xylitol, and empty circle is represented xylose.Fig. 7 C shows the result of palatinit, the square palatinit that represents of Tian Chonging wherein, the square representative isomaltulose of sky.According to Fig. 7 A to 7C, concentration is low to moderate the effect that about 0.1% phosphorylation oligosaccharide has shown high Remineralization, and the medicament of other dental caries (xylitol, isomaltulose and palatinit) is reported as former, in concentration is the effect (Japanese public publication 2000-128752 number, Japanese public publication 2000-247852 number etc.) of 20% o'clock demonstration Remineralization.For xylose, all low at the percentage ratio of any concentration Remineralization.
(embodiment 6)
In embodiment 6, detected the effect of phosphorylation oligosaccharide inhibition demineralized.
The demineralized solution that preparation has following component: 6.0mM calcium chloride solution; 3.6mM potassium dihydrogen phosphate; 2% lactate solution; With 5mg/ml hydroxyapatite solution, pH 5.0.The final concentration that has of the demineralized solution of 125 μ l and 125 μ l is that 0.2% and 2% phosphorylation oligosaccharide sodium salt solution mixes and stirring, cultivates 2 days at 37 ℃ subsequently.After this, mixture is 12, centrifugal 3 minutes of 000rpm.Use the OCPC method to measure the calcium concentration of the supernatant that obtains.The concentration of calcium concentration that adds and processing back calcium.If having under the situation of test sample, the difference between the concentration of the calcium concentration of adding and processing back calcium is compared little with contrast (sample that does not contain detection), think that test sample has the effect that suppresses demineralized.Compare with the contrast (5mM) of not phosphorous acidify oligosaccharide, 0.2% and 2% phosphorylation oligosaccharide sodium salt solution has little difference (3mM and 2mM).Therefore, think that phosphorylation oligosaccharide sodium salt has the effect that suppresses demineralized.
(embodiment 7)
Embodiment 7 has shown the collaborative influence for the Remineralization effect of phosphorylation oligosaccharide and fluorine.
Below the compositions described in the table 4 be used to detect the phosphorylation oligosaccharide exist or non-existent situation under the effect of Remineralization.
Table 4
Single system among the embodiment is used to detect the effect of Remineralization.In single system, cultivated 5 days at 37 ℃.After this, use the OCPC method to measure the amount of soluble calcium.(TLC) confirms the phosphorylation oligosaccharide qualitatively by thin layer chromatography.The condition that is used for the TLC analysis is as follows: silica gel plate (being produced by Merck); Ethanol/deionized water/acetic acid (=70/30/2); Launch once in room temperature; The sample that adds 5 μ l; 1% the maltotriose of the 1% phosphorylation oligosaccharide of 1 μ l and 1 μ l serves as a mark.
What TLC analyzed the results are shown in the table 8.In Fig. 8, each swimming lane shows the fluorine with various concentration (ppm), and the point of top is represented maltotriose, and the point of below is represented the phosphorylation oligosaccharide.Fig. 9 shows that (vertical axis is represented the ratio (%) of Remineralization, and trunnion axis is represented the concentration (ppm) of fluorine to the synergism of Remineralization effect for phosphorylation oligosaccharide and fluorine; In each value, the bar on the left side is represented the contrast of not phosphorous acidify oligosaccharide, and the bar on the right belongs to the group of 0.2% phosphorylation oligosaccharide).Fluorine is highly active halogen.Detected the quantitative effect of fluorine to phosphorylation oligosaccharide and calcium.Under experimental condition, the influence seemingly inappreciable (Fig. 8) that fluorine adds.The adding of fluorine has changed the balance of the concentration ratio of Ga/P, so that indissolubility descends.Therefore, because the decline of the ratio of the raising Remineralization of fluorine concentration.Yet when adding 0.2% phosphorylation oligosaccharide sodium salt, the effect of Remineralization is tending towards improving, therefore, and the significant synergism of susceptible of proof (Fig. 9).
(embodiment 8)
Embodiment 8 demonstrations and the blended phosphorylation oligosaccharide of chewing gum and the elution that enters the phosphorylation oligosaccharide of human mouth.
Preparation is shown in the tablet gum that contains phosphorylation oligosaccharide calcium salt (dull and stereotyped sample chewing gum) (calcium content is 3.2%) (tablet gum has the weight of about 3.2g) in the table 5.
Table 5
3.2g/ tablet gum
When chew gum, elution in time enters the amount of the calcium salt in oral cavity and analyzes by thin layer chromatography (TLC).The condition that is used for TLC is as follows: launching flat board is a silica gel plate; Launching eluant is ethanol/deionized water/acetic acid=70/30/2; Launching temperature is room temperature, launches to carry out once; The amount of point sample is 3 μ l; Detect by spraying detection solution (sulphuric acid/ethanol=1: 1), handled 3 minutes at 130 ℃ subsequently, show color whereby to flat board.
Figure 10 shows the TLC analysis result of the phosphorylation oligosaccharide with concentration of standard solution.Each swimming lane shows the elution (the expression left side is that 1% xylitol is 1% maltotriose (G3) with the right in contrast) of the phosphorylation oligosaccharide with various concentration.The point of below is represented the phosphorylation oligosaccharide, and the point of top is represented xylitol and maltotriose.Figure 11 shows when chewing the chewing gum of phosphorous acidify oligosaccharide elution amount in time.The logical expression of each swimming with the elution of the time of chewing (the expression left side be 1% phosphorylation oligosaccharide in contrast, the right is 1% xylitol and maltotriose (G3).The point of below is represented the phosphorylation oligosaccharide, and the point of top is represented xylitol and maltotriose.The ptyalin enzyme hydrolysis of no use of phosphorylation oligosaccharide.According to these figure, understanding was chewed the beginning back about 10 minutes, the high concentrations of phosphoric acid oligosaccharide is present in the oral cavity relatively, and after 20 minutes, the phosphorylation oligosaccharide keeps about 0.25% concentration.
(embodiment 9)
Embodiment 9 shows the influence of phosphorylation oligosaccharide to the sucrose fermentation.
Mutants streptococcus strain 8148 is incubated at 1 at 37 ℃, the brain-heart infusion medium of 000ml (being produced by DIFCOCorporation) 14 hours.After this, by 6,000rpm collected antibacterial in centrifugal 20 minutes.(PBS pH7.2) washs, and be suspended into 40% (v/v) in identical PBS antibacterial with phosphate buffered saline(PBS).In order to measure pH, reactant mixture (250 μ l) is made up of the 40% bacterial cell suspension of 125 μ l, the 80mM sucrose of 62.5 μ l and the aqueous solution that contains various oligosaccharide (5% phosphorylation oligosaccharide sodium salt and phosphorylation oligosaccharide calcium salt) of 62.5 μ l.When cultivating for 37 ℃, the pH of reactant mixture pH instrument (producing) METHOD FOR CONTINUOUS DETERMINATION by Toa Denpa.
When 0.684% sucrose or 0.684% glucose add the 20% bacterial cell suspension that contains Streptococcus mutans 8158 bacterial strains, the pH of 5 minutes internal reaction liquid drops to below 5.0, drops to 4.0 after 10 minutes.When 5% phosphorylation oligosaccharide (PO-1 and PO-2) when existing simultaneously, the decline of pH is obviously suppressed (data not shown) in both cases.When adding 5% phosphorylation oligosaccharide sodium salt or phosphorylation oligosaccharide calcium salt,, the pH that the fermentation of 0.684% sucrose causes effectively suppressed (data not shown) because descending.
(embodiment 10)
In embodiment 10, the sugar alcohol of preparation phosphorylation oligosaccharide.
10g contains that per molecule has the PO-1 part of phosphorylation oligosaccharide of a phosphate group and the PO-2 with phosphorylation oligosaccharide of 2 phosphate groups is partially dissolved in the distilled water of 100ml.With the 1N sodium hydroxide solution solution is adjusted into weak caustic solution (about pH8).The 3% boron hydroxide sodium solution that adds 30ml to the solution of 100ml acquisition.Mixture was placed 1 hour so that the reduction of phosphorylation oligosaccharide at 40 ℃.Like this, hydrogen is added into the reduction end of phosphorylation oligosaccharide.Regulate the solution of adding hydrogen to pH7.5 with the 1N hydrochloric acid solution.Behind the reaction terminating, solution uses 0.22 μ m film to dialyse.The solution that obtains uses electrodialysis instrument (Micro acilyser) G3, AC210-400 film: produce) desalination by AsahiKasei Corporation, use strong cation-exchanging resin (Dowex 50w 20-50MESH then, H-type: produce) carries out ion exchange, obtain the sugar juice of pH 2.7 thus by Nisshin Kasei.The solution that obtains neutralizes with 1N sodium hydroxide solution or aqua calcis, lyophilizing subsequently, thereby preparation phosphorylation oligosaccharide sodium or calcium salt.
(embodiment 11)
In embodiment 11, preparation chondroitin sulfate oligosaccharide (unsaturated disaccharidase (dimer)).
4.8g sodium chondroitin sulfate (C type: by Katayama Kagaku produce) be dissolved in the distilled water of 500ml (pH6.0).15U chondroitinase ACII (derived from golden yellow arthrobacterium, being produced by Seikagaku Kogyo) adds the solution that obtains and makes it 37 ℃ of reactions 23 hours.Cessation reaction in boiling water bath is subsequently as the desalination described in the embodiment 10.Like this, chondroitin sulfate oligosaccharide sodium or calcium salt have been prepared.
(embodiment 12)
In embodiment 12, detected the effect of various substance supplement mineral nitrogens.
Use the simple Remineralization pilot system of embodiment 4.About sample, use the material that is shown in the following table 6.The preparation all substances are 0.1% final concentration.
Table 6
In above-mentioned table 6, the POs Na of numbering 1 represents phosphorylation oligosaccharide (PO-1 part) sodium salt, the PO-2Na of numbering 2 represents phosphorylation oligosaccharide (PO-2 part) sodium salt, the POsH Na of numbering 3 represents phosphorylation oligosaccharide (PO-1 part) sugar alcohol sodium salt, the PO-2H Na of numbering 4 represents phosphorylation oligosaccharide (PO-2 part) sugar alcohol sodium salt, the G3 of numbering 5 represents maltotriose (glucose trisaccharide), the Glc-6-P of numbering 6 represents G-6-P, the Ser-P of numbering 7 represents phosphoserine, numbering 8 expression chondroitin sulfate Cs, numbering 9 expression oligomeric galactose aldehydic acid, the unsaturated disaccharidase of numbering 10 expression chondroitin sulfate is (in table 6 and Figure 12, dimer sodium) and number 11 D.W. and represent deionized water.
The results are shown in (vertical axis is represented the ratio (%) of Remineralization, and trunnion axis is represented sample material) among Figure 12.Among the figure, have the material higher and be determined effect with Remineralization than the ratio of deionized water Remineralization.The unsaturated disaccharidase sodium salt of phosphorylation oligosaccharide sodium alkoxide, G-6-P, chondroitin sulfate C sodium salt and chondroitin sulfate shows the effect of Remineralization, and its effect is the same with phosphorylation oligosaccharide sodium salt good or be better than phosphorylation oligosaccharide sodium salt.
(embodiment 13)
In embodiment 13, detected the effect of various substance supplement mineral nitrogens.
Use the simple Remineralization pilot system of embodiment 4.About sample, use the material that is shown in the table 7.
Table 7
In the table 7, the POs Na of numbering 1 represents phosphorylation oligosaccharide (PO-1 part) sodium salt (0.2% final concentration), the POs Na of numbering 2 represents phosphorylation oligosaccharide (PO-1 part) sodium salt (2.0% final concentration), numbering 3 expression isomaltulose (20% final concentration), numbering 4 expression isomaltulose (20% final concentrations, numbering 5 expression xylitol (Wako 244-0052) (2.0% final concentration), numbering 6 expression xylitol (Wako 244-0052) (20% final concentration), numbering 7 expression trehaloses (Wako 02252) (2% final concentration), numbering 8 expression trehaloses (Wako 02252) (20% final concentration), numbering 9 expression sorbitol (Katayama 28-4770) (2% final concentration), numbering 10 expression sorbitol (Katayama 28-4770) (20% final concentration), the G3 of numbering 11 represents maltotriose (2% final concentration), the D.W. of numbering 12 represents deionized water (contrast), numbering 13 expression organic acid (tartaric acid) (2% final concentration), numbering 14 is represented organic acid (tartaric acid) (1.4% final concentration) and is numbered 15 expression dextran sulfates (0.2% final concentration).
The results are shown in (vertical axis is represented Remineralization ratio (%), and trunnion axis is represented sample material) among Figure 13.In comprising 20% interpolation group of xylitol, isomaltulose and sorbitol, confirm the effect and consistent (as above-mentioned) reported in the past of Remineralization.And, similar to chondroitin sulfate, confirm the effect that dermatan sulfate has Remineralization.Organic acid is similar to the phosphorylation oligosaccharide also to be effective.
(embodiment 14)
In embodiment 14, in artificial oral-cavity device, detect the effect of caries prevention.
Streptococcus sobrinus bacterial strain 6715 cultures (being incubated at brain-heart infusion medium (producing) in advance) by DIFCO Corporation, heart infusion medium (producing) by DIFCO Corporation, and sample solution (each sample cools off in testing process), offer the baurodont tooth (about 5 * 5mm) that is stored in constant temperature bath (37 ℃) respectively with the speed of 6ml/ hour/pipe.Measure the pH of dental surface in time.The results are shown in that (vertical axis is represented the change of pH, and trunnion axis is represented time lag among Figure 14; Only 1% sugar (GF) is added in circular representative, and 1%GF+5% phosphorylation oligosaccharide calcium salt (POs Ca) is added in the triangle representative of filling).After 16 hours, dental plaque scrapes off from tooth, measures turbidity at the 500nm place.And, the amount of the water-insoluble glucosan (WIG) that measure to form by the phenolsulfuric acid method.Use durometer to measure the hardness of tooth.Obtain the difference (Δ H) between the hardness of this hardness and untreated tooth.The results are shown in the table 8.
Table 8
Clearly under the situation of 1%GF (sugar), produce organic acid, after about 10 minutes, pH is 5.6 or still less, this organic acid remains in the dental plaque.Dental plaque forms fully, and tooth suffers demineraliting and becomes fragile.On the contrary, in the solution that contains 1%GF and 5% phosphorylation oligosaccharide, do not form dental plaque, and pH does not reduce.That is, prevented dental caries antibacterial intrusion tooth, prevented so that dental plaque forms, and suppressed the demineralized of tooth.Therefore, the hardness of tooth does not change.According to this result, find that clearly the phosphorylation oligosaccharide has the effect of caries prevention.Think that this phenomenon betides in people's the oral cavity similarly.
(embodiment 15)
In embodiment 15, preparation phosphorylation oligosaccharide from various starch.
The starch that is used for present embodiment is taken from Oryza sativa L., starch (brand name Better Friend
TM: produce by ShimadaKagaku) and tapioca (Sanwa Cornstarch Co., Ltd.).
The starch powder of 100g adds in the 800-1000ml water.In the solution that obtains, add the starch liquefacation α-Dian Fenmei (BLA) of 50 μ l derived from the 5000U/ml of antibacterial Bacillus licheniformis (available from Fukutamirase, from Hankyu Industries, 1%).The gelation 48 hours in 50 ℃ of water-baths of this solution.In addition, 5000U/mlBLA (the Fukutamirase of 50 μ l, from Hankyu Industries, 1%), the 200U/ml amylopectase of 50 μ l (Promozyme: produced by Novo Nordisk) and the glucoamylase (416U/ml) (available from Toyobo) of 50 μ l join in the starch of gelation, cultivated 48 hours at 50 ℃ subsequently.The mixture that obtains is 8, centrifugal 20 minutes of 000rpm.Supernatant is applied to the equilibrated anion exchange resin of 10mM acetate buffer (pH4.5) (Chitopearl BCW 2501: by Fuji Spinning Co., Ltd. produces).To remove neutral saccharide, use the same buffer elution that contains 0.5M sodium chloride with the thorough column scrubber of identical buffer subsequently.The part of each elution concentrates with vaporizer, desalts subsequently and lyophilizing.Obtain the phosphorylation oligosaccharide thus.
The phosphorylation oligosaccharide of Huo Deing is used for once more by the equilibrated anion-exchange resin column of 20mM acetate buffer (pH4.5) (Chitopearl BCW2501) like this.With the thorough column scrubber of identical buffer to remove neutral saccharide.At first, then, collect part thus with the same buffer elution that contains 0.5M sodium chloride with the same buffer elution post that contains 0.15M sodium chloride.The part of collecting desalts and lyophilizing.According to above-mentioned these parts of methods analyst that are used for determining structure, show the phosphorylation oligosaccharide that the part (PO-1 part) from the elution of 0.15m sodium chloride obtains the glucosan connection of phosphate group and 3-5 the glucose that contains α-1,4 key; In the phosphorylation oligosaccharide that from the part (PO-2 part) of 0.5M sodium chloride elution, obtains, two or more phosphate groups and the glucosan combination that contains 2-8 glucose of α-1,4 key.The carrying out of describing among the structural analysis of phosphorylation oligosaccharide such as the embodiment 1.
(embodiment 16)
Embodiment 16 shows that the chewing gum that contains the phosphorylation oligosaccharide has the effect that promotes enamel Remineralization in the early stage caries.
Produce two kinds of tablet gums (about 1.5g/ sheet) with normally used method: contain derived from the sugar-free chewing gum (containing 45% xylitol) of the POs Ca of 2.5% (average content) of potato starch and do not contain the sugar-free chewing gum (containing 47.5% xylitol) of POs Ca.All test reagents all are guarantee reagents.The content of each material is the ratio about the chewing gum gross weight.
About dental material, use the hat enamel of baurodont tooth.Use rhombus saw (producing) that enamel is cut into and have normal size lateral (7 * 7 * 3mm) by LUXO.These enamel pieces (6 samples) are embedded in the resin of autohemagglutination, and (UNIFAST Trad is produced by GC), it is that 15 * 50mm and thickness are the flat board of 7mm that formation has size.After this, with the surface of moistening grinding sand paper (granularity 800) grinding flat plate to expose smooth and fresh enamel.On the other hand, the dentine side of tooth is embedded in die cream (being produced by GC) in advance.Each enamel piece embedding flat board for preparing like this (6wt% carboxymethyl cellulose, pH5.0) 4 weeks produces dental caries thus artificially at 37 ℃ of 0.1M lactic acid gels that are immersed in 100ml.
The person under inspection of 17 health has participated in a test, and the person under inspection chews two kinds of chewing-gum particles (3.0g) 20 minutes that contain the chewing gum of POs Ca or do not contain POs Ca in the test.In the test, do not inform the kind of person under inspection's chewing gum.Chewing-gum chewing begin the back by 1 minute after, after 1 minute by 3 minutes after, after 3 minutes by 6 minutes after, after 6 minutes by 10 minutes after, and after 10 minutes in the time phase after 20 minutes, use plastic funnel to collect saliva to the plastic test tube of 10ml from the person under inspection.Measure the amount and the pH of saliva after the collection immediately.With distilled water diluting saliva supernatant 10 times, subsequently use 0.45 μ m filter (by Millipore produce) filter thereafter.Use OCPC method (Calcium Ctest Wako; Produce by Wake Pure Chemicals) and the quantitative filtrate of molybdic acid method in the content of Ca and inorganic P.
The person under inspection of 12 health has participated in a test, and the person under inspection chews the chewing gum of the two kinds of flaky POs of containing Ca or do not contain the chewing gum (3.0g) 20 minutes of POs Ca in the test.In the test, do not inform the kind of person under inspection's chewing gum.Use plastic funnel to put into the 50ml plastic test tube from the saliva that the person under inspection is collected in (saliva B) in (saliva A) first process of 10 minutes of chewing in 20 minutes and second 10 minutes the process.Measure the amount and the pH of saliva after the collection immediately.After the mensuration, immediately the saliva impouring plastic containers of 7ml (in 10 * 30 * 60mm), are placed the bag enamel piece embedding flat board with artificial dental caries in advance in this container.This amount is that enamel piece embedding flat board can fully be immersed in the amount in the saliva.Flat board was immersed among the saliva A after 10 minutes, and this flat board was immersed among the saliva B 10 minutes.After this, remove flat board, thoroughly wash planar surface with distilled water.This submergence operation is to carry out at 37 ℃, and one day repeats 4 times continuously.The enamel piece embedding dull and stereotyped daily humidity that is stored in operation back is in 100% the nice and cool environment.People's saliva of using collect every day was tested in continuous 4 days.For the saliva of using in the test, use the part of supernatant and, use 0.45 μ m filter (producing) to filter subsequently by Millipore with 10 times of distilled water dilutings.Use said method to measure the Ca and the inorganic P of filtrate every day.
After the submergence, (Isomet, Buhler USA) are cut into each dental enamel the section with about 500 μ m thickness to use the hard tissues sickle in people's saliva.Grind each about 200 μ m thickness of cutting into slices with moistening grinding sand paper (granularity 800).Microradiography (PW-1830, Philips, Holland) is carried out in each section.Being used for microradiographic condition is that tube voltage is 25kv; Electric current is 25mA; Distance between pipe and the person under inspection is 370mm.After this, use the visual quantitative approach (Eur.J.Oral.Sci.105:74-84,1997) of Inaba etc. to measure lesion depths (Ld, μ m) and mineral loss value Δ Z (volume % μ m).
The person under inspection of 17 health chews 2 kinds of chewing-gum particles (3.0g) 20 minutes that contain the chewing gum of POs Ca or do not contain POs Ca.In this case, (Figure 16: trunnion axis is represented the chewing-gum chewing time to the pH of the amount of saliva (Figure 15: on behalf of chewing-gum chewing time vertical axis, trunnion axis represent saliva amount (ml)), saliva, vertical axis is represented pH), in the saliva Ca content (Figure 18: trunnion axis is represented the chewing-gum chewing time, vertical axis is represented Ca amount (mg)), (Figure 17: trunnion axis is represented the chewing-gum chewing time with P content in the saliva, vertical axis is represented phosphorus amount (mg)) measure in time, wherein numerical value is from beginning by integrating value representation.And, the variation (Figure 19: trunnion axis is represented the chewing-gum chewing time, and vertical axis is represented the Ca/P ratio) of calculating the Ca/P ratio of saliva.In each figure, the chewing gum (POs Ca chewing gum) that contains the chewing gum (+POs Ca chewing gum) of POs Ca and do not contain POs Ca is represented by square and rhombus respectively.
As a result, the variation (Figure 17) of the amount of excretory saliva (Figure 15), pH variation (Figure 16) and P content does not change to the significant level on the statistics in the chewing gum type.In 20 minutes chewing-gum chewing, the saliva of the about 30ml of secretion, 7.0 the when pH of saliva is from the beginning chew gum after 5 minutes brings up to 7.5.By the about 5mg of content of P in the excretory saliva of chewing-gum chewing, comparing it with calcium content is enough to be used in Remineralization.On the contrary, clearly find under the situation of the chewing gum that contains POs Ca, chew beginning be dissolved in after 20 minutes Ca in the saliva measure about 4 times to the situation of chewing the chewing gum that does not contain POs Ca (Figure 18).Because a certain amount of P was present in (Figure 16) in the saliva originally, containing under the chewing gum situation of POs Ca, Ca/P ratio also obvious high (p<0.001) is (Figure 19).In above-mentioned analysis result, between women and male person under inspection, do not find notable difference.
Fig. 9 has shown from chewing two kinds and has contained the chewing gum of POs Ca or do not contain the saliva A that collects 12 healthy subject of 20 minutes of chewing-gum particle (3.0g) of POs Ca and the analysis result of saliva B.
The comparison of table 9 saliva volume, pH and content of mineral substances
Mean+SD,
*P<0.05,
*P<0.001, n=12
In two kinds of chewing gum, the amount of saliva A doubles the amount of saliva B approximately.In saliva A, do not contain the chewing gum of POs Ca and contain that Ca content has notable difference between the chewing gum of POs Ca.Yet, in saliva B, this species diversity.For P content, do not differentiating difference between two kinds of chewing gum and between saliva A and B.Therefore, in saliva A, when chewing the chewing gum that contains POs Ca, its Ca/P than about 4 times to the ratio of the Ca/P when chewing the chewing gum that does not contain POs Ca.
Then, assessment result for the Remineralization facilitation effect of 12 person under inspections' processed tooth is shown in Figure 20 A (vertical axis is represented lesion depths (Ld, μ m)) and Figure 20 B (vertical axis is represented mineral loss value Δ Z (v% μ m)) with lesion depths and mineral loss value.In two figure, trunnion axis is represented with order blank, that contain the chewing gum of POs Ca and do not contain the chewing gum of POs Ca.According to lesion depths (Ld) and mineral loss value (Δ Z), observe under the situation of the chewing gum that contains POs Ca than the situation of the chewing gum that does not contain POs Ca under the recovery of dental enamel of demineraliting obvious.That is,, obtained the facilitation effect (p<0.001) of Remineralization chewing in the group of the chewing gum that contains POs Ca.
(embodiment 17)
Embodiment 17 is presented in people's the oral cavity, contains the facilitation effect of the chewing gum of phosphorylation oligosaccharide to the Remineralization of enamel.
Similar to embodiment 13, prepared two kinds of flaky chewing gum (about 1.5g/ sheet), promptly contain POs Ca chewing gum and do not contain POs Ca sugar-free chewing gum.The test reagent of all uses is guarantee reagents.
Partly prepare enamel sheet (diameter 5mm from the enamel of the tooth crown of cattle incisor; Thickness 1.5mm).The head surface of buccal surface polishes to expose fresh enamel planer with moistening grinding sand paper (granularity 800).Like this Zhi Bei enamel sheet 37 ℃ of 0.1M lactic acid solutions (pH5.0) that are immersed in 100ml 3 days to produce artificial dental caries.Behind the demineraliting, three enamel sheets are attached to the upper right of a palate plate palate district of grinding one's teeth in sleep movably.
The person under inspection of 12 health (6 male and 6 women; Mean age=21 year old) once chew 2 chewing gum that contain the chewing gum of POsCa, do not contain POs Ca, or (1: about 1.5g) 20 minutes of sucrose chewing gum (containing 62% sucrose).In this test, each person under inspection chews a kind of chewing gum one day 4 times wherein.Do not inform the people of responsible this test and the type of the chewing gum that the person under inspection is chewing.For each chewing gum, this test was carried out for 2 weeks always.The blanking time that one week was arranged between each test.In the process of chewing-gum chewing or afterwards, palate plate is attached 20 minutes.At test period, the person under inspection does not use fluorine agent and isolating palate plate to store under 100% humidity, avoids dry.
1, after 2 and 4 weeks, the tooth that adheres to of test is removed from each person under inspection's palate plate.Cut the section that thickness is about 200 μ m from each enamel.Microradiography (PW-1830, Philips, Holland) is carried out in each section.Microradiographic condition is as follows: tube voltage 25kV; Tube current 25mA; Distance between pipe and the person under inspection is 370mm.After this, measure lesion depths (ld, μ m) (Eur.J.Oral.Sci.105:74-84,1997) with the visual quantitative approach of Inaba etc.The value of Ld as determining to the distance the damage position from the tooth head surface, reaches 95% level of health tissues content of mineral substances according to the mineral scattergram at the position mineral content of damage.The ratio of Remineralization is calculated as the reduction gear ratio of the ld value relevant with initial ld value behind the demineraliting.Remineralization the results are shown in Figure 21.In Figure 21, trunnion axis with week 1, week 2 and week 4 order represent sucrose chewing gum group (Suc), do not contain the chewing gum group (Xyl) of POs Ca and contain the chewing gum group (POs) of POs Ca.Vertical axis is represented the ratio (%) of Remineralization.
In containing the chewing gum group (POs) of POs Ca, the ratio of week 1, week 2 and all 4 o'clock Remineralization is respectively 67%, 54% and 76%.The chewing gum group (Xyl) that does not contain POs Ca is 12 to 23%, and this value is lower than the chewing gum group that contains POsCa.Sucrose chewing gum group (Suc) shows the ratio of positive Remineralization by the end of week 2, and finally reaches negative value by the end of week 4, shows demineraliting.
Assess under the situation that is presented at the chewing gum that contains POs Ca than under the situation of chewing gum that does not contain POs Ca and sucrose chewing gum, having higher Remineralization facilitation effect in people's the oral cavity.Specifically, 12 all persons under inspection chew each two week of various chewing gum and obtain significant result under the situations of the chewing gum that contains POs Ca.Therefore, confirm in chewing gum, to add POs Ca by assessment in people's the oral cavity and cause high-caliber Remineralization facilitation effect.Simultaneously, in the oral cavity, also confirm to strengthen the effect of early stage caries Remineralization, therefore effectively prevent very much dental caries by the edible chewing gum product that contains POs Ca on the basis of every day basically.
(embodiment 18)
In embodiment 18, analyzed the composition of saliva when taking in the confection that contains the phosphorylation oligosaccharide.
Preparation contains the confection just like the composition of describing among Figure 10.
Table 10
The adult person under inspection Candy for food (4.7g) of 4 health is also collected excretory saliva.Confection is put into the mouth back and was stopped about 10 minutes in the oral cavity.Collect saliva in following 4 time periods: (i) 0-1 minute; (ii) 1-3 minute; (iii) 3-6 minute; (iv) 6-10 minute.Collect the test tube that excretory saliva enters 15ml by funnel.After the collection, stir excretory saliva immediately, and measure the pH and the content of saliva.The results are shown in Figure 22 and 23.In Figure 22, trunnion axis is represented the absorption time (min), and vertical axis is represented pH.In the oral cavity pH of saliva constant be 7.Among Figure 23, trunnion axis is represented the absorption time (min), and vertical axis is represented the amount (ml/min) of saliva.The amount of excretory saliva is substantial constant in taking in time course.
Then, the saliva of 1800 μ l is put into 4 centrifuge tubes.The 1N HCl solution of 200 μ l adds in each pipe.Mixed liquor fully mixes, and centrifugal 3 minutes subsequently at 10,000 * g, and make it by 0.5 μ m film.The supernatant of measuring 10 μ l acquisition with the OCPC method is to determine calcium content.Use the molybdenum method to measure the supernatant of 50 μ l to determine phosphorus content.Calcium and phosphorus content are shown among Figure 24.In Figure 24, trunnion axis is represented the absorption time (min), and the vertical axis on the left side is represented calcium or phosphorus content (mM), and the vertical axis on the right is represented the Ca/P ratio.In taking in time course, calcium and phosphorus content substantially constant (being maintained at about 0.6).
(embodiment 19)
Among the embodiment 19, preparation contains the confection of phosphorylation oligosaccharide and soft sweet to determine the Remineralization facilitation effect.
Prepare confection that contains these compositions shown in the table 11 (4.7g/ grain) and soft sweet (4.0g/ grain) according to normally used method.
Table 11
The 10ml distilled water adds in each above-mentioned confection or the soft sweet, and dissolves in boiling water bath.Use the minisize pH instrument to measure the pH of the extraction solution that obtains.After this, extract solution centrifugal 3 minutes of 10,000 * g and by 0.5 μ m film.The supernatant of measuring 10 μ l acquisition with the OCPC method is to determine calcium concentration.Use vanadium molybdic acid method to measure the supernatant soln of 50 μ l to determine inorganic phosphorus concentration.The results are shown in the table 12.
The content of mineral substances of Ca and P in the extract of table 12 soft sweet and confection
And based on the interpretation of result of table 12, the content that the extracting solution of 2 times and 10 times dilutions of adjustment has calcium and phosphorus is shown in the table 13.After this, assessment is to the Remineralization facilitation effect of hydroxyapatite.
Table 13 is used to promote the evaluating system of Remineralization effect
The results are shown among Figure 24.In Figure 24, trunnion axis is represented the absorption time (min), and the vertical axis on the left side is represented calcium or phosphorus content (mM), and the vertical axis on the right is represented the Ca/P ratio.
In confection or soft sweet, the solution of 10 times of dilutions has shown high-caliber Remineralization facilitation effect.
(embodiment 20)
Contain the dentifrice that is shown in the compositions in the table 14 with normally used method preparation.
Table 14
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol Sorbitol xylitol sodium lauryl sulphate antiseptic flavoring agent saccharide sodium fluoride POs Ca hydrogen sulfate disodium water | 15.00 1.50 3.00 10.00 10.00 1.50 0.10 1.00 traces, 0.15 4.00 3.75 residue |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 21)
Contain the dentifrice that is shown in the compositions in the table 15 with normally used method preparation.
Table 15
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol glycerol sodium lauryl sulphate antiseptic flavoring agent saccharide sodium fluoride POs Ca cetyl pyridinium drone chloride water | 15.00 1.50 3.00 20.00 5.00 1.50 0.10 1.00 0.10 0.20 4.00 0.25 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 22)
Contain the dentifrice that is shown in the compositions in the table 16 with normally used method preparation.
Table 16
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol glycerol sodium lauryl sulphate antiseptic flavoring agent tetrasodium pyrophosphate sodium fluoride POs Ca glucanase water | 15.00 1.50 3.00 20.00 5.00 1.50 0.10 1.00 0.50 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 23)
Contain the dentifrice that is shown in the compositions in the table 17 with normally used method preparation.
Table 17
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate sodium fluoride POs Na sucralose TMWater | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 24)
Contain the dentifrice that is shown in the compositions in the table 18 with normally used method preparation.
Table 18
Composition | % by weight |
The addition polymers xylitol sodium lauryl sulphate titanium dioxide flavoring agent triclosan (Triclosan) of silicon dioxide carboxymethyl cellulose sodium polyacrylate polypropylene glycol and oxirane is right-hydroxy benzoate POs Ca sodium monofluorophosphate Radix Betae chrysanthemum (stevia) extract water | 16.00 1.50 2.00 1.00 20.00 1.50 0.50 1.00 0.50 0.10 5.00 0.80 1.50 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 25)
Contain the dentifrice that is shown in the compositions in the table 19 with normally used method preparation.
Table 19
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate sodium fluoride POs Na Radix Betae chrysanthemum water | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 26)
Contain the dentifrice that is shown in the compositions in the table 20 with normally used method preparation.
Table 20
Composition | % by weight |
The Radix Betae chrysanthemum water that silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate zinc chloride POs Na enzyme is handled | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 27)
Contain the dentifrice that is shown in the compositions in the table 21 with normally used method preparation.Except that 1N zinc hydroxide solution is used for neutralization, POs Zn with embodiment 2 in identical mode prepare.
Table 21
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate sodium fluoride POs Zn water | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 1.00 residues |
Composition | % by weight |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 28)
Contain the dentifrice that is shown in the compositions in the table 22 with normally used method preparation.
Table 22
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent sodium tripolyphosphate POs Ca water | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 2.00 4.00 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 29)
Contain the collutory that is shown in the compositions in the table 23 with normally used method preparation.
Table 23
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol POs Ca cetyl pyridinium drone chloride water | 10.00 1.50 10.00 1.00 17.00 5.00 0.25 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 30)
Contain the collutory that is shown in the compositions in the table 24 with normally used method preparation.
Table 24
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol POs Ca sodium hydrogen phosphate water | 10.00 1.50 10.00 1.00 17.00 5.00 3.75 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 31)
Contain the collutory that is shown in the compositions in the table 25 with normally used method preparation.
Table 25
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol POs Ca sodium fluoride water | 10.00 1.50 10.00 1.00 17.00 5.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 32)
Contain the collutory that is shown in the compositions in the table 26 with normally used method preparation.
Table 26
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol POs Na α-tertiary calcium phosphate sodium hydrogen phosphate water | 10.00 1.50 10.00 1.00 17.00 5.00 4.00 3.75 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 33)
Contain the collutory that is shown in the compositions in the table 27 with normally used method preparation.Except that 1N zinc hydroxide solution is used for neutralization, POs Zn with embodiment 2 in identical mode prepare.
Table 27
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol POs Z n cetyl pyridinium drone chloride α-tertiary calcium phosphate water | 10.00 1.50 10.00 1.00 17.00 5.00 0.25 4.00 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 34)
The oral cavity ointment that contains the compositions that is shown in the table 28 with normally used method preparation.
Table 28
Composition | % by weight |
Liquid paraffin fragdecin sodium white vaseline silicone oil carboxymethyl cellulose pectin flavoring agent sodium fluoride POs Ca sodium hydrogen phosphate | 25.00 1.00 25.00 4.00 25.00 10.00 1.05 0.20 5.00 3.75 |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 35)
The oral cavity ointment that contains the compositions that is shown in the table 29 with normally used method preparation.
Table 29
Composition | % by weight |
Liquid paraffin fragdecin sodium white vaseline silicone oil carboxymethyl cellulose xylitol flavoring agent sodium fluoride POs Ca sodium hydrogen phosphate | 25.00 1.00 25.00 4.00 25.00 10.00 1.05 0.20 5.00 3.75 |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 36)
Contain the dentifrice that is shown in the compositions in the table 30 with normally used method preparation.
Table 30
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol sorbitol xylitol sodium lauryl sulphate antiseptic flavoring agent saccharide sodium fluoride chondroitin sulfate sodium hydrogen phosphate water | 15.00 1.50 3.00 10.00 10.00 1.50 0.10 1.00 traces, 0.15 4.00 3.75 residue |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 37)
Contain the dentifrice that is shown in the compositions in the table 31 with normally used method preparation.
Table 31
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol glycerol sodium lauryl sulphate antiseptic flavoring agent saccharide sodium fluoride chondroitin sulfate cetyl pyridinium drone chloride water | 15.00 1.50 3.00 20.00 5.00 1.50 0.10 1.00 0.10 0.20 4.00 0.25 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 38)
Contain the dentifrice that is shown in the compositions in the table 32 with normally used method preparation.
Table 32
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol glycerol sodium lauryl sulphate antiseptic flavoring agent tetrasodium pyrophosphate sodium fluoride chondroitin sulfate glucanase water | 15.00 1.50 3.00 20.00 5.00 1.50 0.10 1.00 0.50 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 39)
Contain the dentifrice that is shown in the compositions in the table 32 with normally used method preparation.
Table 33
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate sodium fluoride chondroitin sulfate sucralose TMWater | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 40)
Contain the dentifrice that is shown in the compositions in the table 34 with normally used method preparation.
Table 34
Composition | % by weight |
The addition polymers xylitol sodium lauryl sulphate titanium dioxide flavoring agent Triclosan of silicon dioxide carboxymethyl cellulose sodium polyacrylate polypropylene glycol and oxirane is right-hydroxy benzoate chondroitin sulfate sodium monofluorophosphate Radix Betae chrysanthemum extract water | 16.00 1.50 2.00 1.00 20.00 1.50 0.50 1.00 0.50 0.10 5.00 0.80 1.50 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 41)
Contain the dentifrice that is shown in the compositions in the table 35 with normally used method preparation.
Table 35
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate sodium fluoride chondroitin sulfate Radix Betae chrysanthemum water | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 42)
Contain the dentifrice that is shown in the compositions in the table 36 with normally used method preparation.
Table 36
Composition | % by weight |
The Radix Betae chrysanthemum water that silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate zinc chloride chondrosulphatase is handled | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 43)
Contain the dentifrice that is shown in the compositions in the table 37 with normally used method preparation.
Table 37
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate sodium fluoride chondroitin sulfate water | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 1.00 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 44)
Contain the dentifrice that is shown in the compositions in the table 38 with normally used method preparation.
Table 38
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent sodium tripolyphosphate chondroitin sulfate water | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 2.00 4.00 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 45)
Contain the collutory that is shown in the compositions in the table 39 with normally used method preparation.
Table 39
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol chondroitin sulfate cetyl pyridinium drone chloride water | 10.00 1.50 10.00 1.00 17.00 5.00 0.25 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 46)
Contain the collutory that is shown in the compositions in the table 40 with normally used method preparation.
Table 40
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol chondroitin sulfate sodium hydrogen phosphate water | 10.00 1.50 10.00 1.00 17.00 5.00 3.75 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 47)
Contain the collutory that is shown in the compositions in the table 41 with normally used method preparation.
Table 41
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol chondroitin sulfate sodium fluoride water | 10.00 1.50 10.00 1.00 17.00 5.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 48)
Contain the collutory that is shown in the compositions in the table 42 with normally used method preparation.
Table 42
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol chondroitin sulfate α-tertiary calcium phosphate sodium hydrogen phosphate water | 10.00 1.50 10.00 1.00 17.00 5.00 4.00 3.75 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 49)
Contain the collutory that is shown in the compositions in the table 43 with normally used method preparation.
Table 43
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol chondroitin sulfate cetyl pyridinium drone chloride α-tertiary calcium phosphate water | 10.00 1.50 10.00 1.00 17.00 5.00 0.25 4.00 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 50)
The oral cavity ointment that contains the compositions that is shown in the table 44 with normally used method preparation.
Table 44
Composition | % by weight |
Liquid paraffin fragdecin sodium white vaseline silicone oil carboxymethyl cellulose pectin flavoring agent sodium fluoride chondroitin sulfate sodium hydrogen phosphate | 25.00 1.00 25.00 4.00 25.00 10.00 1.05 0.20 5.00 3.75 |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 51)
The oral cavity ointment that contains the compositions that is shown in the table 45 with normally used method preparation.
Table 45
Composition | % by weight |
Liquid paraffin fragdecin sodium white vaseline silicone oil carboxymethyl cellulose xylitol flavoring agent sodium fluoride chondroitin sulfate sodium hydrogen phosphate | 25.00 1.00 25.00 4.00 25.00 10.00 1.05 0.20 5.00 3.75 |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 52)
Contain the dentifrice that is shown in the compositions in the table 46 with normally used method preparation.
Table 46
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol sorbitol xylitol sodium lauryl sulphate antiseptic flavoring agent saccharide sodium fluoride chondroitin sulfate dimer sodium hydrogen phosphate water | 15.00 1.50 3.00 10.00 10.00 1.50 0.10 1.00 traces, 0.15 4.00 3.75 residue |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 53)
Contain the dentifrice that is shown in the compositions in the table 47 with normally used method preparation.
Table 47
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol glycerol sodium lauryl sulphate antiseptic flavoring agent saccharide sodium fluoride chondroitin sulfate dimer cetyl pyridinium drone chloride water | 15.00 1.50 3.00 20.00 5.00 1.50 0.10 1.00 0.10 0.20 4.00 0.25 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 54)
Contain the dentifrice that is shown in the compositions in the table 48 with normally used method preparation.
Table 48
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol glycerol sodium lauryl sulphate antiseptic flavoring agent tetrasodium pyrophosphate sodium fluoride chondroitin sulfate dimer glucanase water | 15.00 1.50 3.00 20.00 5.00 1.50 0.10 1.00 0.50 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 55)
Contain the dentifrice that is shown in the compositions in the table 49 with normally used method preparation.
Table 49
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate sodium fluoride chondroitin sulfate dimer sucralose TMWater | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 56)
Contain the dentifrice that is shown in the compositions in the table 50 with normally used method preparation.
Table 50
Composition | % by weight |
The addition polymers xylitol sodium lauryl sulphate titanium dioxide flavoring agent triclosan (Triclosan) of silicon dioxide carboxymethyl cellulose sodium polyacrylate polypropylene glycol and oxirane is right-hydroxy benzoate chondroitin sulfate dimer sodium monofluorophosphate Radix Betae chrysanthemum extract water | 16.00 1.50 2.00 1.00 20.00 1.50 0.50 1.00 0.50 0.10 5.00 0.80 1.50 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 57)
Contain the dentifrice that is shown in the compositions in the table 51 with normally used method preparation.
Table 51
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate sodium fluoride chondroitin sulfate dimer Radix Betae chrysanthemum water | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 58)
Contain the dentifrice that is shown in the compositions in the table 52 with normally used method preparation.
Table 52
Composition | % by weight |
The Radix Betae chrysanthemum water that silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate zinc chloride chondroitin sulfate dimer enzyme is handled | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 59)
Contain the dentifrice that is shown in the compositions in the table 53 with normally used method preparation.
Table 53
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate sodium fluoride chondroitin sulfate dimer water | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 1.00 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 60)
Contain the dentifrice that is shown in the compositions in the table 54 with normally used method preparation.
Table 54
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent sodium tripolyphosphate chondroitin sulfate dimer water | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 2.00 4.00 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 61)
Contain the collutory that is shown in the compositions in the table 55 with normally used method preparation.
Table 55
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol chondroitin sulfate dimer cetyl pyridinium drone chloride water | 10.00 1.50 10.00 1.00 17.00 5.00 0.25 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 62)
Contain the collutory that is shown in the compositions in the table 56 with normally used method preparation.
Table 56
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol chondroitin sulfate dimer sodium hydrogen phosphate water | 10.00 1.50 10.00 1.00 17.00 5.00 3.75 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 63)
Contain the collutory that is shown in the compositions in the table 57 with normally used method preparation.
Table 57
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol chondroitin sulfate dimer sodium fluoride water | 10.00 1.50 10.00 1.00 17.00 5.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 64)
Contain the collutory that is shown in the compositions in the table 58 with normally used method preparation.
Table 58
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol chondroitin sulfate dimer α-tertiary calcium phosphate sodium hydrogen phosphate water | 10.00 1.50 10.00 1.00 17.00 5.00 4.00 3.75 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 65)
Contain the collutory that is shown in the compositions in the table 59 with normally used method preparation.
Table 59
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol chondroitin sulfate dimer cetyl pyridinium drone chloride α-tertiary calcium phosphate water | 10.00 1.50 10.00 1.00 17.00 5.00 0.25 4.00 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 66)
The oral cavity ointment that contains the compositions that is shown in the table 60 with normally used method preparation.
Table 60
Composition | % by weight |
Liquid paraffin fragdecin sodium white vaseline silicone oil carboxymethyl cellulose pectin flavoring agent sodium fluoride chondroitin sulfate dimer sodium hydrogen phosphate | 25.00 1.00 25.00 4.00 25.00 10.00 1.05 0.20 5.00 3.75 |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 67)
The oral cavity ointment that contains the compositions that is shown in the table 61 with normally used method preparation.
Table 61
Composition | % by weight |
Liquid paraffin fragdecin sodium white vaseline silicone oil carboxymethyl cellulose xylitol flavoring agent sodium fluoride chondroitin sulfate dimer sodium hydrogen phosphate | 25.00 1.00 25.00 4.00 25.00 10.00 1.05 0.20 5.00 3.75 |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 68)
Contain the dentifrice that is shown in the compositions in the table 62 with normally used method preparation.
Table 62
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol sorbitol xylitol sodium lauryl sulphate antiseptic flavoring agent saccharide sodium fluoride G-6-P sodium hydrogen phosphate water | 15.00 1.50 3.00 10.00 10.00 1.50 0.10 1.00 traces, 0.15 4.00 3.75 residue |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 69)
Contain the dentifrice that is shown in the compositions in the table 63 with normally used method preparation.
Table 63
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol glycerol sodium lauryl sulphate antiseptic flavoring agent saccharide sodium fluoride G-6-P cetyl pyridinium drone chloride water | 15.00 1.50 3.00 20.00 5.00 1.50 0.10 1.00 0.10 0.20 4.00 0.25 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 70)
Contain the dentifrice that is shown in the compositions in the table 64 with normally used method preparation.
Table 64
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol glycerol sodium lauryl sulphate antiseptic flavoring agent tetrasodium pyrophosphate sodium fluoride G-6-P glucanase water | 15.00 1.50 3.00 20.00 5.00 1.50 0.10 1.00 0.50 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 71)
Contain the dentifrice that is shown in the compositions in the table 65 with normally used method preparation.
Table 65
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate sodium fluoride G-6-P sucralose TMWater | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 72)
Contain the dentifrice that is shown in the compositions in the table 66 with normally used method preparation.
Table 66
Composition | % by weight |
The addition polymers xylitol sodium lauryl sulphate titanium dioxide flavoring agent triclosan of silicon dioxide carboxymethyl cellulose sodium polyacrylate polypropylene glycol and oxirane is right-hydroxy benzoate G-6-P sodium monofluorophosphate Radix Betae chrysanthemum extract water | 16.00 1.50 2.00 1.00 20.00 1.50 0.50 1.00 0.50 0.10 5.00 0.80 1.50 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 73)
Contain the dentifrice that is shown in the compositions in the table 67 with normally used method preparation.
Table 67
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate sodium fluoride glucose sugar-6-phosphoric acid Radix Betae chrysanthemum water | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 74)
Contain the dentifrice that is shown in the compositions in the table 68 with normally used method preparation.
Table 68
Composition | % by weight |
The Radix Betae chrysanthemum water that silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate zinc chloride G-6-Pase is handled | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 75)
Contain the dentifrice that is shown in the compositions in the table 69 with normally used method preparation.
Table 69
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate sodium fluoride G-6-P water | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 1.00 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 76)
Contain the dentifrice that is shown in the compositions in the table 70 with normally used method preparation.
Table 70
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent sodium tripolyphosphate G-6-P water | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 2.00 4.00 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 77)
Contain the collutory that is shown in the compositions in the table 71 with normally used method preparation.
Table 71
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol G-6-P cetyl pyridinium drone chloride water | 10.00 1.50 10.00 1.00 17.00 5.00 0.25 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 78)
Contain the collutory that is shown in the compositions in the table 72 with normally used method preparation.
Table 72
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol G-6-P sodium hydrogen phosphate water | 10.00 1.50 10.00 1.00 17.00 5.00 3.75 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 79)
Contain the collutory that is shown in the compositions in the table 73 with normally used method preparation.
Table 73
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol G-6-P sodium fluoride water | 10.00 1.50 10.00 1.00 17.00 5.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 80)
Contain the collutory that is shown in the compositions in the table 74 with normally used method preparation.
Table 74
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol G-6-P α-tertiary calcium phosphate sodium hydrogen phosphate water | 10.00 1.50 10.00 1.00 17.00 5.00 4.00 3.75 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 81)
Contain the collutory that is shown in the compositions in the table 75 with normally used method preparation.
Table 75
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol G-6-P cetyl pyridinium drone chloride α-tertiary calcium phosphate water | 10.00 1.50 10.00 1.00 17.00 5.00 0.25 4.00 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 82)
The oral cavity ointment that contains the compositions that is shown in the table 76 with normally used method preparation.
Table 76
Composition | % by weight |
Liquid paraffin fragdecin sodium white vaseline silicone oil carboxymethyl cellulose pectin flavoring agent sodium fluoride G-6-P sodium hydrogen phosphate | 25.00 1.00 25.00 4.00 25.00 10.00 1.05 0.20 5.00 3.75 |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 83)
The oral cavity ointment that contains the compositions that is shown in the table 77 with normally used method preparation.
Table 77
Composition | % by weight |
Liquid paraffin fragdecin sodium white vaseline silicone oil carboxymethyl cellulose xylitol flavoring agent sodium fluoride G-6-P sodium hydrogen phosphate | 25.00 1.00 25.00 4.00 25.00 10.00 1.05 0.20 5.00 3.75 |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 84)
Contain the dentifrice that is shown in the compositions in the table 78 with normally used method preparation.
Table 78
Composition | % by weight |
The few galacturonic acid sodium hydrogen phosphate of silicon dioxide carboxymethyl cellulose Polyethylene Glycol sorbitol xylitol sodium lauryl sulphate antiseptic flavoring agent saccharide sodium fluoride water | 15.00 1.50 3.00 10.00 10.00 1.50 0.10 1.00 traces, 0.15 4.00 3.75 residue |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 85)
Contain the dentifrice that is shown in the compositions in the table 79 with normally used method preparation.
Table 79
Composition | % by weight |
The few galacturonic acid cetyl pyridinium of silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol glycerol sodium lauryl sulphate antiseptic flavoring agent saccharide sodium fluoride drone chloride water | 15.00 1.50 3.00 20.00 5.00 1.50 0.10 1.00 0.10 0.20 4.00 0.25 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 86)
Contain the dentifrice that is shown in the compositions in the table 80 with normally used method preparation.
Table 80
Composition | % by weight |
The few galacturonic acid glucanase of silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol glycerol sodium lauryl sulphate antiseptic flavoring agent tetrasodium pyrophosphate sodium fluoride water | 15.00 1.50 3.00 20.00 5.00 1.50 0.10 1.00 0.50 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 87)
Contain the dentifrice that is shown in the compositions in the table 81 with normally used method preparation.
Table 81
Composition | % by weight |
The few galacturonic acid sucralose of silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate sodium fluoride TMWater | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 88)
Contain the dentifrice that is shown in the compositions in the table 82 with normally used method preparation.
Table 82
Composition | % by weight |
The addition polymers xylitol sodium lauryl sulphate titanium dioxide flavoring agent triclosan of silicon dioxide carboxymethyl cellulose sodium polyacrylate polypropylene glycol and oxirane is right-the few galacturonic acid sodium monofluorophosphate of hydroxy benzoate Radix Betae chrysanthemum extract water | 16.00 1.50 2.00 1.00 20.00 1.50 0.50 1.00 0.50 0.10 5.00 0.80 1.50 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 89)
Contain the dentifrice that is shown in the compositions in the table 83 with normally used method preparation.
Table 83
Composition | % by weight |
The few galacturonic acid Radix Betae of silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate sodium fluoride chrysanthemum water | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 90)
Contain the dentifrice that is shown in the compositions in the table 84 with normally used method preparation.
Table 84
Composition | % by weight |
The Radix Betae chrysanthemum water that the few galacturonic acid enzyme of silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate zinc chloride is handled | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 91)
Contain the dentifrice that is shown in the compositions in the table 85 with normally used method preparation.
Table 85
Composition | % by weight |
The few galacturonic acid sour water of silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate sodium fluoride | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 1.00 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 92)
Contain the dentifrice that is shown in the compositions in the table 86 with normally used method preparation.
Table 86
Composition | % by weight |
The few galacturonic acid sour water of silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent sodium tripolyphosphate | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 2.00 4.00 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 93)
Contain the collutory that is shown in the compositions in the table 87 with normally used method preparation.
Table 87
Composition | % by weight |
The few galacturonic acid cetyl pyridinium of ethanol sodium lauryl sulphate glycerol menthol xylitol drone chloride water | 10.00 1.50 10.00 1.00 17.00 5.00 0.25 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 94)
Contain the collutory that is shown in the compositions in the table 88 with normally used method preparation.
Table 88
Composition | % by weight |
The few galacturonic acid sodium hydrogen phosphate of ethanol sodium lauryl sulphate glycerol menthol xylitol water | 10.00 1.50 10.00 1.00 17.00 5.00 3.75 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 95)
Contain the collutory that is shown in the compositions in the table 89 with normally used method preparation.
Table 89
Composition | % by weight |
The few galacturonic acid sodium fluoride of ethanol sodium lauryl sulphate glycerol menthol xylitol water | 10.00 1.50 10.00 1.00 17.00 5.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 96)
Contain the collutory that is shown in the compositions in the table 90 with normally used method preparation.
Table 90
Composition | % by weight |
The few galacturonic acid α of ethanol sodium lauryl sulphate glycerol menthol xylitol-tertiary calcium phosphate sodium hydrogen phosphate water | 10.00 1.50 10.00 1.00 17.00 5.00 4.00 3.75 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 97)
Contain the collutory that is shown in the compositions in the table 91 with normally used method preparation.
Table 91
Composition | % by weight |
The few galacturonic acid cetyl pyridinium of ethanol sodium lauryl sulphate glycerol menthol xylitol drone chloride α-tertiary calcium phosphate water | 10.00 1.50 10.00 1.00 17.00 5.00 0.25 4.00 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 98)
The oral cavity ointment that contains the compositions that is shown in the table 92 with normally used method preparation.
Table 92
Composition | % by weight |
The few galacturonic acid sodium hydrogen phosphate of liquid paraffin fragdecin sodium white vaseline silicone oil carboxymethyl cellulose pectin flavoring agent sodium fluoride | 25.00 1.00 25.00 4.00 25.00 10.00 1.05 0.20 5.00 3.75 |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 99)
The oral cavity ointment that contains the compositions that is shown in the table 93 with normally used method preparation.
Table 93
Composition | % by weight |
The few galacturonic acid sodium hydrogen phosphate of liquid paraffin fragdecin sodium white vaseline silicone oil carboxymethyl cellulose xylitol flavoring agent sodium fluoride | 25.00 1.00 25.00 4.00 25.00 10.00 1.05 0.20 5.00 3.75 |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 100)
Contain the dentifrice that is shown in the compositions in the table 94 with normally used method preparation.
Table 94
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol sorbitol xylitol sodium lauryl sulphate antiseptic flavoring agent saccharide sodium fluoride tartaric acid sodium hydrogen phosphate water | 15.00 1.50 3.00 10.00 10.00 1.50 0.10 1.00 traces, 0.15 4.00 3.75 residue |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 101)
Contain the dentifrice that is shown in the compositions in the table 95 with normally used method preparation.
Table 95
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol glycerol sodium lauryl sulphate antiseptic flavoring agent saccharide sodium fluoride tartaric acid cetyl pyridinium drone chloride water | 15.00 1.50 3.00 20.00 5.00 1.50 0.10 1.00 0.10 0.20 4.00 0.25 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 102)
Contain the dentifrice that is shown in the compositions in the table 96 with normally used method preparation.
Table 96
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol glycerol sodium lauryl sulphate antiseptic flavoring agent tetrasodium pyrophosphate sodium fluoride tartaric acid glucanase water | 15.00 1.50 3.00 20.00 5.00 1.50 0.10 1.00 0.50 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 103)
Contain the dentifrice that is shown in the compositions in the table 97 with normally used method preparation.
Table 97
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate sodium fluoride tartaric acid sucralose TMWater | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 104)
Contain the dentifrice that is shown in the compositions in the table 98 with normally used method preparation.
Table 98
Composition | % by weight |
The addition polymers xylitol sodium lauryl sulphate titanium dioxide flavoring agent Triclosan of silicon dioxide carboxymethyl cellulose sodium polyacrylate polypropylene glycol and oxirane is right-hydroxy benzoate tartaric acid sodium monofluorophosphate Radix Betae chrysanthemum extract water | 16.00 1.50 2.00 1.00 20.00 1.50 0.50 1.00 0.50 0.10 5.00 0.80 1.50 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 105)
Contain the dentifrice that is shown in the compositions in the table 99 with normally used method preparation.
Table 99
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate sodium fluoride tartaric acid Radix Betae chrysanthemum water | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 106)
Contain the dentifrice that is shown in the compositions in the table 100 with normally used method preparation.
Table 100
Composition | % by weight |
The Radix Betae chrysanthemum water that silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate zinc chloride tartaric acid enzyme is handled | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 4.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 107)
Contain the dentifrice that is shown in the compositions in the table 101 with normally used method preparation.
Table 101
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent α-tertiary calcium phosphate sodium fluoride winestone sour water | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 4.00 0.20 1.00 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 108)
Contain the dentifrice that is shown in the compositions in the table 102 with normally used method preparation.
Table 102
Composition | % by weight |
Silicon dioxide carboxymethyl cellulose Polyethylene Glycol xylitol sodium lauryl sulphate antiseptic flavoring agent sodium tripolyphosphate winestone sour water | 15.00 1.50 3.00 20.00 1.50 0.10 1.00 2.00 4.00 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 109)
Contain the collutory that is shown in the compositions in the table 103 with normally used method preparation.
Table 103
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol tartaric acid cetyl pyridinium drone chloride water | 10.00 1.50 10.00 1.00 17.00 5.00 0.25 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 110)
Contain the collutory that is shown in the compositions in the table 104 with normally used method preparation.
Table 104
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol tartaric acid sodium hydrogen phosphate water | 10.00 1.50 10.00 1.00 17.00 5.00 3.75 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 111)
Contain the collutory that is shown in the compositions in the table 105 with normally used method preparation.
Table 105
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol tartaric acid sodium fluoride water | 10.00 1.50 10.00 1.00 17.00 5.00 0.20 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 112)
Contain the collutory that is shown in the compositions in the table 106 with normally used method preparation.
Table 106
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol tartaric acid α-tertiary calcium phosphate sodium hydrogen phosphate water | 10.00 1.50 10.00 1.00 17.00 5.00 4.00 3.75 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 113)
Contain the collutory that is shown in the compositions in the table 107 with normally used method preparation.
Table 107
Composition | % by weight |
Ethanol sodium lauryl sulphate glycerol menthol xylitol tartaric acid cetyl pyridinium drone chloride α-tertiary calcium phosphate water | 10.00 1.50 10.00 1.00 17.00 5.00 0.25 4.00 residues |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 114)
The oral cavity ointment that contains the compositions that is shown in the table 108 with normally used method preparation.
Table 108
Composition | % by weight |
Liquid paraffin fragdecin sodium white vaseline silicone oil carboxymethyl cellulose pectin flavoring agent sodium fluoride tartaric acid sodium hydrogen phosphate | 25.00 1.00 25.00 4.00 25.00 10.00 1.05 0.20 5.00 3.75 |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 115)
The oral cavity ointment that contains the compositions that is shown in the table 109 with normally used method preparation.
Table 109
Composition | % by weight |
Liquid paraffin fragdecin sodium white vaseline silicone oil carboxymethyl cellulose xylitol flavoring agent sodium fluoride tartaric acid sodium hydrogen phosphate | 25.00 1.00 25.00 4.00 25.00 10.00 1.05 0.20 5.00 3.75 |
100.00 |
Use this compositions can obtain satisfied anti-dental caries function.
(embodiment 116)
Contain the artificial saliva who is shown in the compositions in the table 110 with normally used method preparation.
Table 110
This artificial saliva has fabulous Remineralization facilitation effect and makes the pH in the oral cavity return to neutral ability.
(embodiment 117)
Contain the artificial saliva who is shown in the compositions in the table 111 with normally used method preparation.
Table 111
This artificial saliva has fabulous Remineralization facilitation effect and makes the pH in the oral cavity return to neutral ability.
The artificial saliva can be similarly by adding the buffer agent preparation except that POs Ca and POs Na.
Industrial usability
As mentioned above, the invention provides dietary composition and the oral cavity composition that reduces the generation of carious tooth by tooth increased remineralization etc.
Claims (9)
1. the compositions with additional mineral function is characterized in that, described compositions comprises the chondroitin sulfate oligosaccharide.
2. have the compositions of additional mineral function according to claim 1, it is characterized in that, the chondroitin sulfate oligosaccharide is the form that is alkali metal salt, alkali salt or iron salt.
3. as having the compositions of additional mineral function as described in the claim 2, it is characterized in that the chondroitin sulfate oligosaccharide is the form that is sodium salt or calcium salt.
4. the compositions that has additional mineral function according to claim 1, it is characterized in that, also comprise phosphorylation oligosaccharide or its sugar alcohol, wherein the phosphorylation oligosaccharide is by having α-1, the 3-5 of 4 keys the glucosan that glucose is formed, one of them phosphate group is connected with glucosan, or by having α-1, the 2-8 of 4 keys the glucosan that glucose is formed, wherein two phosphate groups are connected with glucosan.
5. as having the compositions of additional mineral function as described in the claim 4, it is characterized in that described phosphorylation oligosaccharide or its sugar alcohol are the forms that is alkali metal salt, alkali salt or iron salt.
6. according to the described compositions of claim 5, it is characterized in that described phosphorylation oligosaccharide or its sugar alcohol are the forms that is sodium salt or calcium salt with additional mineral function.
7. as having the compositions of additional mineral function as described in claim 1 or 4, it is characterized in that, described compositions further comprises the chemical compound of fluorion or fluoride ion, and the chemical compound of described fluoride ion is for being selected from sodium monofluorophosphate, sodium fluoride, potassium fluoride, ammonium fluoride, amine salt fluoride and stannic fluoride.
8. according to claim 1 or 4 described compositionss, it is characterized in that described compositions also comprises phosphorus-calcium compensation, phosphorus preparation and/or calcium preparation with additional mineral function.
9. as having the compositions of additional mineral function as described in claim 1 or 4, it is characterized in that described compositions is dietary composition or oral cavity composition.
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
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JP2001056011 | 2001-02-28 | ||
JP2001056010 | 2001-02-28 | ||
JP2001-056010 | 2001-02-28 | ||
JP2001056011 | 2001-02-28 | ||
JP2001056010 | 2001-02-28 | ||
JP2001-056011 | 2001-02-28 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB028056485A Division CN1230145C (en) | 2001-02-28 | 2002-02-28 | Compositions having anti-dental caries function |
Publications (2)
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CN1736388A CN1736388A (en) | 2006-02-22 |
CN1736388B true CN1736388B (en) | 2010-04-14 |
Family
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CN 200510082015 Expired - Lifetime CN1736388B (en) | 2001-02-28 | 2002-02-28 | Compositions having anti-dental caries function |
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JP (4) | JP2002325557A (en) |
CN (1) | CN1736388B (en) |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
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JP4729332B2 (en) * | 2004-04-21 | 2011-07-20 | 王子コーンスターチ株式会社 | Deashing inhibiting composition and food and drink containing the same |
JP4683988B2 (en) * | 2004-04-21 | 2011-05-18 | 王子コーンスターチ株式会社 | Liquid oral composition having remineralization action |
JP4566096B2 (en) * | 2005-09-05 | 2010-10-20 | 王子コーンスターチ株式会社 | PH adjuster using phosphorylated saccharide and / or salt thereof |
US8147807B2 (en) | 2006-07-20 | 2012-04-03 | National University Corporation Okayama University | Oral composition for dental purposes |
WO2009091052A1 (en) * | 2008-01-17 | 2009-07-23 | Ezaki Glico Co., Ltd. | Food having therapeutic effect on decay at the early stage and therapeutic kit for decay at the early stage |
JP5241249B2 (en) * | 2008-01-17 | 2013-07-17 | 正治 加藤 | Caries treatment kit |
JP5301214B2 (en) * | 2008-08-08 | 2013-09-25 | 花王株式会社 | Method for producing coffee composition |
WO2010061932A1 (en) * | 2008-11-28 | 2010-06-03 | 江崎グリコ株式会社 | Food and composition each comprising phosphorylated sccharide, polyphenol and fluorine |
BR112012017991A2 (en) * | 2010-01-29 | 2018-08-14 | Colgate Palmolive Co | oral care product for sensitive enamel care. |
JP2011177037A (en) * | 2010-02-26 | 2011-09-15 | Kishu Hosokawa:Kk | Method for neutralizing organic acid |
EP2648650A1 (en) * | 2010-12-07 | 2013-10-16 | Colgate-Palmolive Company | Apparatus for conducting oral care experiments and method of forming and using the same |
JP2014073989A (en) * | 2012-10-04 | 2014-04-24 | Sangi Co Ltd | Dentifrice composition |
JP6256770B2 (en) * | 2015-05-07 | 2018-01-10 | ジャパンモード株式会社 | Oral care composition, tablets, granular drugs |
JP5924604B1 (en) * | 2015-04-27 | 2016-05-25 | ジャパンモード株式会社 | Oral care composition |
WO2016174861A1 (en) * | 2015-04-27 | 2016-11-03 | ジャパンモード株式会社 | Oral care composition |
JP6570112B2 (en) * | 2015-06-18 | 2019-09-04 | ジャパンモード株式会社 | Pharmaceutical manufacturing method |
WO2016189846A1 (en) * | 2015-05-26 | 2016-12-01 | 株式会社サンギ | Composition for oral cavity and food product, or beverage |
WO2018168997A1 (en) | 2017-03-16 | 2018-09-20 | 江崎グリコ株式会社 | Oral composition capable of promoting teeth remineralization |
JP2019137645A (en) * | 2018-02-14 | 2019-08-22 | 王子ホールディングス株式会社 | Calcium dissolution promoter |
JP7076748B2 (en) * | 2018-05-29 | 2022-05-30 | 日本ゼトック株式会社 | Oral composition |
CN108434017A (en) * | 2018-06-13 | 2018-08-24 | 长沙小如信息科技有限公司 | A kind of tooth whitening liquid and preparation method thereof |
Family Cites Families (6)
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JP3014128B2 (en) * | 1990-08-17 | 2000-02-28 | サントリー株式会社 | Method for producing anti-cariogenic agent and anti-cariogenic substance |
JP3240102B2 (en) * | 1994-08-11 | 2001-12-17 | 江崎グリコ株式会社 | Phosphorylated sugar and method for producing the same |
JP4278118B2 (en) * | 1997-08-08 | 2009-06-10 | 江崎グリコ株式会社 | Phosphorylated sugar and method for producing the same |
JP3719874B2 (en) * | 1998-04-24 | 2005-11-24 | サンスター株式会社 | Oral composition |
JP2000154127A (en) * | 1998-11-18 | 2000-06-06 | Lion Corp | Composition for oral cavity |
JP3556849B2 (en) * | 1998-12-25 | 2004-08-25 | 花王株式会社 | Oral composition |
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2002
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- 2002-02-28 CN CN 200510082015 patent/CN1736388B/en not_active Expired - Lifetime
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- 2006-07-25 JP JP2006202637A patent/JP2006321812A/en not_active Withdrawn
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2009
- 2009-05-08 JP JP2009113894A patent/JP2009179631A/en active Pending
- 2009-05-08 JP JP2009113893A patent/JP2009258112A/en active Pending
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JP2009258112A (en) | 2009-11-05 |
JP2006321812A (en) | 2006-11-30 |
CN1736388A (en) | 2006-02-22 |
JP2002325557A (en) | 2002-11-12 |
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