JP6057496B2 - Tooth enamel remineralization accelerator - Google Patents

Description

  The present invention relates to a tooth comprising a sugar carboxylic acid such as maltobionic acid and / or a calcium salt thereof as an active ingredient, wherein the aldehyde group on the reducing end side of a starch degradation product or transfer reaction product having a polymerization degree of 2 or more is oxidized. The present invention relates to an enamel remineralization accelerator, and further to an oral composition and food and drink produced by adding these remineralization accelerators.

The tooth consists of a dentin part and an enamel part, and the enamel covers the dentin. About 97% of the enamel is hydroxyapatite [Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ], which is a crystal structure mainly composed of phosphoric acid and calcium.

  In general, caries is a streptococcus mutans or Streptococcus sobrinas, such as oral streptococci (caries) that adhere to the tooth surface, and produces glucan by the action of these bacteria (glucosyltransferase), It begins with the formation of plaque. In the plaque, the acid produced by the bacteria metabolizing sugar, starch, etc. in the food residue decalcifies the tooth enamel, resulting in a so-called initial caries state.

  Calcium and phosphate are present in saliva, and these act to restore the teeth by restoring or remineralizing the demineralized portion. That is, on the tooth surface, a phenomenon that contradicts demineralization and remineralization always occurs, and the required balance is usually maintained. However, the balance tends to decalcify as dental plaque increases, and caries progresses.

  To prevent dental caries, a tooth adhesion inhibitor, an antibacterial agent, or a glucosyltransferase enzyme inhibitor that suppresses glucan formation of caries fungi (Patent No. 2859612, JP 2006-45154, JP, 2007-153788, A) and the like have been developed. However, for example, an antibacterial agent is not a specific material exhibiting an antibacterial action only against caries fungi, so there is a problem in safety, and a glucosyltransferase enzyme inhibitor has a problem that it is easily affected by saliva.

  In addition, there has been reported a technique for suppressing caries prevention / onset by using phosphorylated oligosaccharide as a substance that promotes remineralization (Japanese Patent Laid-Open No. 2002-325556, Japanese Patent No. 4402140). Phosphorylated oligosaccharides can be obtained from enzyme degradation products such as α-amylase using potato starch as a raw material. However, purification is complicated and the yield is about 1%, which is a very expensive material. Phosphoric acid starch obtained by mixing and roasting starch degradation products and phosphates can also be obtained from enzymatic degradation products such as α-amylase, but such a method is difficult to use as a food material. is there.

  In addition, there are calcium chloride and calcium gluconate among the water-soluble calcium already used for food materials. These substances are exemplified as comparative examples in the embodiments for carrying out the invention described later, but the presence of phosphate ions does not maintain the ionic state and precipitates immediately, so remineralization promoting effect is expected. Not.

  Accordingly, the object of the present invention is to prevent caries or to prevent initial caries by, for example, promoting re-mineralization of demineralized tooth enamel at a low cost without any problem in safety even when used in oral compositions and foods and drinks. It is in providing the remineralization promoter which can suppress a disease, the composition for oral cavity containing them, and food and drink.

  As a result of intensive studies to solve the above problems, the inventors of the present invention produce starch and / or starch degradation products by glycosyltransferase and / or amylolytic enzyme by a transfer reaction and / or a hydrolysis reaction. It is found that sugar carboxylic acid and / or calcium salt thereof, which is obtained by oxidizing the aldehyde group at the reducing end of a starch degradation product or transfer reaction product having a polymerization degree of 2 or more, has a good remineralization promoting action, Completed the invention.

  That is, the means for solving the problems of the present invention are as follows.

First, the present invention is a tooth characterized by comprising as an active ingredient a sugar carboxylic acid in which the aldehyde group at the reducing end of a starch degradation product or transfer reaction product having a polymerization degree of 2 or more and / or its calcium salt is oxidized. Enamel remineralization accelerator.
Second, in the present invention, the sugar carboxylic acid is maltobionic acid, isomaltobionic acid, maltotriionic acid, isomaltorionic acid, maltotetraionic acid, maltohexanoic acid, panose oxide, maltooligosaccharide oxide, Promotion of remineralization of tooth enamel according to the first aspect, characterized in that it is at least one selected from the group consisting of branched oligosaccharide oxide, starch syrup, powdered slag oxide, and dextrin oxide It is an agent.
3rdly, this invention is a remineralization promoter of the tooth enamel as described in said 1st or 2nd characterized by including at least 1 type of fluoride further.
Fourthly, the present invention is the tooth enamel remineralization promoter according to any one of the first to third aspects, further comprising at least one sugar alcohol.
Fifth, the present invention is an oral composition comprising the tooth enamel remineralization accelerator according to any one of the first to fourth aspects.
Sixth, the present invention is a food or drink comprising the tooth enamel remineralization accelerator according to any one of the first to fourth aspects.

  The present invention is described in detail below.

  In the present invention, the sugar carboxylic acid refers to a starch degradation product or transfer product having a degree of polymerization of 2 or more, which is produced by subjecting starch and / or starch degradation product to a glycosyltransferase and / or a starch degradation enzyme by a transfer reaction and / or hydrolysis reaction. This refers to a product in which the aldehyde group on the reducing end side of the reaction product is oxidized, and further includes these salt forms.

  Specific examples include maltobionic acid, isomaltobionic acid, maltotriionic acid, isomaltrionic acid, maltotetraionic acid, maltohexanoic acid, panose oxide, malto-oligosaccharide oxide, branched oligosaccharide oxide, and hydroxoxide. , Powdered oxide, dextrin oxide and the like.

  The sugar carboxylic acid used in the present invention is not limited in form, and may be liquid or powder, and may be in the form of not only a free acid but also a salt or lactone, or a combination thereof. Examples of the salt include calcium salts, magnesium salts, potassium salts, sodium salts, etc. Among these, the calcium salt forms are most preferable.

  Sugar carboxylic acid is produced by a method of oxidizing a starch decomposition product or transfer reaction product by a chemical oxidation reaction, or a reaction in which a microorganism or oxidase having an oligosaccharide oxidizing ability acts on the starch decomposition product or transfer reaction product. Can do.

  As a chemical oxidation reaction, a method is known which is obtained by catalytically oxidizing starch decomposition products or transfer products and oxygen in an alkaline atmosphere in the presence of an oxidation catalyst in which palladium, platinum or bismuth is supported on activated carbon. Yes.

  Further, as a method using a microorganism having an oligosaccharide oxidizing ability, a method obtained by a microorganism conversion / fermentation method such as Acinetobacter genus, Burkholderia genus, Acetobacter genus or Gluconobacter genus is known.

  As a production method by an enzyme reaction, it is possible to produce by a method of extracting an oxidase from the microorganism having the oxidation ability.

  If an example of the manufacturing method by a chemical oxidation reaction is given, first, 3 g of platinum-activated carbon catalysts will be added to 100 mL of 30% maltose solution maintained at 50 ° C., and stirred at 600 rpm while blowing oxygen at 100 mL / min. The reaction pH is maintained at 9.0 by dropwise addition of 10N sodium hydroxide solution. Then, after 5 hours of reaction, the catalyst is removed by centrifugation and membrane filter filtration to obtain a sodium maltobionate solution.

  The maltobionic acid solution can be obtained by desalting the sodium maltobionate solution obtained as described above by cation exchange resin or electrodialysis.

  Calcium maltobionate can be prepared by adding and dissolving a calcium source such as calcium carbonate in the maltobionic acid solution obtained by the above method so as to have a molar ratio of 2: 1. The calcium source used in the present invention may be edible calcium, for example, natural materials such as eggshell powder, coral powder, bone powder and shell powder, and chemically synthesized products such as calcium carbonate and calcium chloride. .

  In order for the sugar carboxylic acid according to the present invention to work effectively as a remineralization accelerator, a source of calcium and phosphate is required.

  Generally, the composition ratio of calcium and phosphorus in tooth enamel is about calcium / phosphorus = 1.0 to 1.67, so calcium and phosphoric acid are supplied to the oral cavity so that such a ratio is obtained. Is preferred.

  In a specific embodiment of the present invention, it is possible to blend a calcium material including the calcium salt of the sugar carboxylic acid. Available calcium materials include calcium carbonate, calcium chloride, calcium lactate, calcium gluconate, calcium citrate, calcium ascorbate, calcium malate, calcium citrate / malate, calcium acetate, calcium fluoride, and primary calcium phosphate. , Dicalcium phosphate, tricalcium phosphate, calcium formate, calcium benzoate, calcium isobutyrate, calcium propionate, calcium salicylate, calcium fluoride, stearoyl calcium lactate, calcium sulfate, calcium hydroxide, calcium pyrophosphate, whey calcium, eggshell Examples include calcium, seaweed calcium, shell calcium, fish bone powder, eggshell powder, coral powder, and shell powder.

  The phosphate source compound that can be used in the present invention may be a compound that releases phosphate ions when dissolved in water, and is preferably a water-soluble phosphate or inorganic phosphate. Examples of such phosphate source compounds include sodium metaphosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, trisodium phosphate, sodium pyrophosphate, sodium hydrogen pyrophosphate, potassium dihydrogen phosphate, phosphoric acid Examples include dipotassium hydrogen and tripotassium phosphate.

  In the present invention, it is also possible to use fluoride in combination as a remineralization promoting component. Fluoride is known to exhibit remineralization promotion, improved crystallinity, improved acid resistance, antibacterial and anti-enzyme action, and is used in dentifrices and the like.

  However, as a problem when applying fluoride, it is very responsive to calcium, so to prevent the fluoride from working with calcium and losing its effectiveness, dentifrices usually do not contain calcium-containing materials . On the other hand, in the present invention, it was found that the sugar carboxylic acid or its calcium salt can keep the fluoride in an ionic state even in the presence of calcium.

  The fluoride that can be used in the present invention is preferably a fluoride that is permitted to be incorporated into foods, pharmaceuticals, or quasi drugs, and examples of such fluorides include sodium fluoride and potassium fluoride. , Calcium fluoride, sodium monofluorophosphate, sodium monofluoroacetate, cryolite and the like. As the fluoride of the present invention, fluorine derived from tea, well water, seawater, seafood, seaweed and the like that can be used as food can also be used. For example, a tea extract having an extremely high fluorine concentration and an extremely low tea polyphenol concentration may be used.

  Moreover, in this invention, it is also possible to use sugar alcohol together as a remineralization acceleration | stimulation component. In this invention, it discovered that the amount of calcium ion which can be utilized for remineralization increases by stabilization of calcium ion increasing by adding sugar alcohol together with sugar carboxylic acid or its calcium salt.

  The sugar alcohol that can be used in the present invention is preferably xylitol, sorbitol, maltitol, reduced starch syrup, reduced starch saccharified product, palatinit, lactitol, erythritol, mannitol, galactitol, arabitol and the like.

  Examples of oral compositions containing the remineralization accelerator, i.e., sugar carboxylic acid and / or calcium salt thereof, or further fluoride or sugar alcohol, include toothpastes for toothpaste, toothpaste or liquid toothpaste, and mouthwashes. , Gingival massage cream, gargle or lozenge.

  In addition, as food and drink containing the remineralization accelerator according to the present invention, confectionery such as gum, candy, gummi, tablet confectionery, chocolate, baked confectionery such as cookies, biscuits, ice cream, ice confectionery, sherbet, etc. Frozen confectionery, green tea, oolong tea, tea, coffee, juice, sports drinks, processed milk and other beverages, Japanese confectionery such as buns, uirou, mochi, and hagi, confectionery such as jelly, pudding, and cake, cheese, yogurt, etc. Examples include dairy products, bakery products such as bread and hot cakes, livestock meat products such as ham and sausage, fish products such as kamaboko and chikuwa, and side dishes.

  The amount of sugar carboxylic acid and / or calcium salt thereof added to the oral composition or food or drink is difficult to determine in general depending on the type or form of the oral composition or food used, 0.01% to 100%, preferably 0.05% to 60%, and more preferably 0.1% to 40% with respect to the composition or food and drink.

  As one embodiment, it is generally known that about 20 mL of saliva is secreted by chewing for 20 minutes, such as gum, and the oral cavity composition has a concentration of 1 mM to 10 mM as the amount of calcium in the saliva in the oral cavity. Or when blending design to food and drink is carried out, in calcium maltobionate whose calcium content is 5.3%, 40 (calcium molecular weight) × (1.0 mM-10 mM) × 0.02 L (saliva) × [100% (Calcium maltobionate) /5.3% (calcium)] = 15 mg to 150 mg may be blended. When this is mix | blended with the gum 2g, the compounding quantity to the gum of calcium maltobionate will be (15 mg-150 mg) /2gx100=0.75%-7.5%. Moreover, when mix | blending dextrin calcium oxide with a calcium amount of 1.3%, since it will be about 60 mg-600 mg, it will mix | blend 3%-30% with 2g of gums.

  In addition, when the sugar carboxylic acid and / or calcium salt thereof and fluoride are added in combination, the amount of fluoride added is difficult to determine in general depending on the type and form of the oral composition or food and drink. These oral compositions or foods and drinks are preferably blended at 0.1 ppm to 1000 ppm, preferably 0.5 ppm to 100 ppm, more preferably 5 ppm to 50 ppm.

  Furthermore, when the sugar carboxylic acid and / or its calcium salt and sugar alcohol are added in combination, it is difficult to determine the amount of sugar alcohol depending on the type and form of the oral composition or food and drink. These oral compositions or foods and drinks are preferably blended at 0.1 ppm to 1000 ppm, preferably 1 ppm to 500 ppm, more preferably 10 ppm to 100 ppm.

  According to the present invention, a remineralization accelerator containing a sugar carboxylic acid in which the aldehyde group at the reducing end of a starch degradation product or a transfer reaction product having a polymerization degree of 2 or more and / or a calcium salt thereof is contained, or the like is contained. Ingestion of oral composition or food and drink that can promote remineralization of tooth enamel safely and inexpensively, and prevent dental caries or prevent primary disease by promoting remineralization sufficiently can do.

The figure which shows the result evaluated about the remineralization acceleration | stimulation effect | action using calcium maltobionate (calcium content 5.3%) based on this invention. The result of having evaluated the remineralization acceleration | stimulation effect | action using the calcium oxide salt (calcium content 3.8%) of the starch syrup of maltotriose content 56%, maltose content 22%, glucose content 5% based on this invention is shown. Figure. The figure which shows the result evaluated about the remineralization acceleration | stimulation effect | action using the oxide calcium salt (calcium content 2.2%) of the powdery meal of DE25 based on this invention. The figure which shows the result evaluated about the remineralization acceleration | stimulation effect | action using the calcium oxide salt (calcium content 1.6%) of the dextrin of DE19 based on this invention. The figure which shows the result evaluated about the remineralization acceleration | stimulation effect | action using calcium chloride (calcium content 36%) which is a soluble calcium raw material. The figure which shows the result evaluated about the remineralization promotion effect | action using maltobionic acid based on this invention, and calcium chloride (calcium content 36%) as a calcium source. The figure which shows the result evaluated about the remineralization acceleration | stimulation effect | action using the calcium gluconate monohydrate (calcium content 8.9%) which is a soluble calcium raw material. The figure which shows the result evaluated about the remineralization acceleration | stimulation effect | action using the calcium oxide salt (calcium content 3.5%, calcium gluconate 20% containing) of the branched oligosaccharide of DE44 based on this invention.

  Hereinafter, the present invention will be described in detail with specific examples, but the present invention is not limited to the following examples.

[Preparation Example]
(Preparation of sugar carboxylic acid and its calcium salt)

  9 g of 5% palladium carbon catalyst (manufactured by Kawaken Fine Chemical Co., Ltd.) was added to 1000 mL of 30% maltose solution (manufactured by Wako Pure Chemical Industries, Ltd.). After maintaining this solution at 40 ° C., the reaction was started at 1.0 L / min air and a rotation speed of 600 rpm. A 20% sodium hydroxide solution was continuously added to maintain the reaction pH at 9.0. Six hours after the reaction, the reaction solution containing the catalyst was centrifuged and filtered through a 0.2 μm membrane filter to obtain a sodium maltobionate solution. This solution was desalted by passing it through a column filled with 2 L of a strongly acidic cation exchange resin (manufactured by Dow Chemical Co., Ltd., trade name “DOWEX-88”). Next, a column packed with 200 mL of a mixed resin of 200 mL of a weakly basic anion exchange resin (trade name “WA30” manufactured by Mitsubishi Chemical Corporation) and 200 mL of a strongly acidic cation exchange resin (trade name “DOWEX-88” manufactured by Dow Chemical Co., Ltd.) Subsequently, after passing through a column packed with 200 mL of granular activated carbon (manufactured by Takeda Pharmaceutical Co., Ltd., granular white cocoon) in order, decolorization was performed, and concentrated to a maltobionic acid concentration of 40% by vacuum concentration. A calcium maltobionate was prepared by dissolving with stirring while adding calcium carbonate thereto. The reaction was terminated when the pH of the solution reached 7.0, and this solution was filtered through a 0.2 μm filter and freeze-dried to obtain a calcium maltobionate powder sample.

  Also, instead of maltose, starch syrup with a maltotriose content of 56%, maltose content of 22% and glucose content of 5% (trade name Pureatose P, manufactured by Sanei Saccharification Co., Ltd.), DE25 powder cake (trade name Nipodex 25, Sanei Saccharification Co., Ltd.) ), DE19 dextrin (trade name NSD700, manufactured by Sanei Saccharification Co., Ltd.) and DE44 branched oligosaccharide (trade name ISO, manufactured by Sanei Saccharification Co., Ltd.) were used as raw materials to prepare calcium sugar carboxylates in the same manner as described above.

  In addition, DE (dextrose equivalent) is a value that can be expressed by the formula [amount of direct reducing sugar (measured as glucose) / mass of total solids] × 100, and this DE value is the degree of hydrolysis of starch (decomposition) Index).

(Evaluation of remineralization promoting effect by calcium maltobionate)
Recalcification accelerating action was evaluated using calcium maltobionate (calcium content 5.3%) obtained in Preparation Example.

In a beaker for 200 mL to which 50 mL of distilled water was added, 6 mL of 100 mM calcium maltobionate solution (0.024 g as Ca amount, final concentration of 6 mM), 10 mL of 200 mM HEPES buffer (pH 7.0) (final concentration of 20 mM), 5 mL of 2 M KCl solution (Final concentration: 100 mM) and 3.6 mL of 100 mM K ₂ HPO ₄ solution (final concentration: 3.6 mM) were sequentially added and stirred, then 1M KOH solution was added dropwise to adjust to pH 6.8, so that the total volume becomes 100 mL. Distilled water was added. The reaction was started by magnetic stirrer in a 37 ° C. warm bath. After 60 minutes of reaction, 100 mg of hydroxyapatite (manufactured by Wako Pure Chemical Industries, Ltd.) was added, and the reaction was continued for 120 minutes. The time course of the reaction was evaluated by measuring pH and soluble calcium content every 10 minutes. The calcium concentration was measured using Calcium E Test Wako (manufactured by Wako Pure Chemical Industries).

  The evaluation results are shown in FIG.

  From the start of the reaction to 60 minutes, calcium remained solubilized even in the presence of phosphoric acid, and the pH did not change. When hydroxyapatite was added thereto, the solubilization rate of calcium decreased rapidly, and the pH also decreased rapidly. This is thought to be the result of hydroxyapatite becoming crystal nuclei, where calcium was deposited and remineralized. From this phenomenon, it was shown that calcium maltobionate is useful as a substance that promotes remineralization.

(Evaluation of remineralization promoting effect by hydrated calcium oxide salt)
Using the calcium oxide salt (calcium content 3.8%) of syrup (manufactured by Sanei Saccharification Co., Ltd., trade name Pureatose P) having a maltotriose content of 56%, a maltose content of 22%, and a glucose content of 5%. The calcification promoting action was evaluated.

To a 200 mL beaker containing 50 mL of distilled water was added 0.71 g of calcium hydroxide salt (0.024 g as Ca amount, final concentration 6 mM), dissolved by stirring, and then 10 mL of 200 mM HEPES buffer (pH 7.0) (final). Concentration 20 mM), 5 mL of 2 M KCl solution (final concentration 100 mM), 3.6 mL of 100 mM K ₂ HPO ₄ solution (final concentration 3.6 mM) were sequentially added and stirred, and then 1 M KOH solution was added dropwise so that the pH became 6.8. Adjusted and added distilled water to a total volume of 100 mL. The reaction was started by magnetic stirrer in a 37 ° C. warm bath. After 60 minutes of reaction, 100 mg of hydroxyapatite (manufactured by Wako Pure Chemical Industries, Ltd.) was added, and the reaction was continued for 120 minutes. The time course of the reaction was evaluated by measuring pH and soluble calcium content every 10 minutes. The calcium concentration was measured using Calcium E Test Wako (manufactured by Wako Pure Chemical Industries).

  The evaluation results are shown in FIG.

  From the start of the reaction to 60 minutes, calcium remained in a solubilized state even in the presence of phosphoric acid, and no significant change in pH was observed. When hydroxyapatite was added thereto, the solubilization rate of calcium decreased rapidly, and the pH also decreased rapidly. This is thought to be the result of hydroxyapatite becoming crystal nuclei, where calcium was deposited and remineralized. From this phenomenon, it was shown that the hydrated calcium oxide salt is useful as a substance that promotes remineralization.

(Evaluation of remineralization promoting effect by powdered calcium oxide salt)
The remineralization promoting action was evaluated using the oxide calcium salt (calcium content 2.2%) of the DE25 powder cake (trade name Nipodex 25, manufactured by Sanei Saccharification Co., Ltd.) obtained in the preparation example.

To a 200 mL beaker containing 50 mL of distilled water, 1.26 g of calcium oxide powder calcium salt (0.024 g of Ca, final concentration of 6 mM) was added and dissolved by stirring, and then 10 mL of 200 mM HEPES buffer (pH 7.0) ( Final concentration 20 mM), 5 mL of 2 M KCl solution (final concentration 100 mM), 3.6 mL of 100 mM K ₂ HPO ₄ solution (final concentration 3.6 mM) were sequentially added and stirred, and then 1 M KOH solution was added dropwise to reach pH 6.8. And distilled water was added so that the total volume was 100 mL. The reaction was started by magnetic stirrer in a 37 ° C. warm bath. After 60 minutes of reaction, 100 mg of hydroxyapatite (manufactured by Wako Pure Chemical Industries, Ltd.) was added, and the reaction was continued for 120 minutes. The time course of the reaction was evaluated by measuring pH and soluble calcium content every 10 minutes. The calcium concentration was measured using Calcium E Test Wako (manufactured by Wako Pure Chemical Industries).

  The evaluation results are shown in FIG.

  From the start of the reaction to 60 minutes, calcium remained in a solubilized state even in the presence of phosphoric acid, and no significant change in pH was observed. When hydroxyapatite was added thereto, the solubilization rate of calcium decreased rapidly, and the pH also decreased rapidly. This is thought to be the result of hydroxyapatite becoming crystal nuclei, where calcium was deposited and remineralized. From this phenomenon, it was shown that calcium oxide powder calcium salt is useful as a substance that promotes remineralization.

(Evaluation of remineralization promoting action by dextrin oxide calcium salt)
The remineralization promoting action was evaluated using the calcium oxide salt (calcium content 1.6%) of DE19 dextrin (manufactured by Sanei Saccharification, trade name NSD700) obtained in Preparation Example.

1.85 g of dextrin oxide calcium salt (0.024 g as Ca amount, final concentration 6 mM) was added to a 200 mL beaker containing 50 mL of distilled water, dissolved by stirring, and then 10 mL of 200 mM HEPES buffer (pH 7.0) (final). Concentration 20 mM), 5 mL of 2 M KCl solution (final concentration 100 mM), 3.6 mL of 100 mM K ₂ HPO ₄ solution (final concentration 3.6 mM) were sequentially added and stirred, and then 1 M KOH solution was added dropwise so that the pH became 6.8. Adjusted and added distilled water to a total volume of 100 mL. The reaction was started by magnetic stirrer in a 37 ° C. warm bath. After 60 minutes of reaction, 100 mg of hydroxyapatite (manufactured by Wako Pure Chemical Industries, Ltd.) was added, and the reaction was continued for 120 minutes. The time course of the reaction was evaluated by measuring pH and soluble calcium content every 10 minutes. The calcium concentration was measured using Calcium E Test Wako (manufactured by Wako Pure Chemical Industries).

  The evaluation results are shown in FIG.

  From the start of the reaction to 60 minutes, calcium remained in a solubilized state even in the presence of phosphoric acid, and no significant change in pH was observed. When hydroxyapatite was added thereto, the solubilization rate of calcium decreased rapidly, and the pH also decreased rapidly. This is thought to be the result of hydroxyapatite becoming crystal nuclei, where calcium was deposited and remineralized. From this phenomenon, it was shown that dextrin oxide calcium salt is useful as a substance that promotes remineralization.

[Comparative Example 1]
(Evaluation of remineralization promoting effect by calcium chloride)
Recalcification promoting action was evaluated using calcium chloride (manufactured by Wako Pure Chemicals, calcium content 36%) which is a soluble calcium material.

In a beaker for 200 mL to which 50 mL of distilled water was added, 6 mL of 100 mM calcium chloride solution (0.024 g as Ca amount, final concentration 6 mM), 10 mL of 200 mM HEPES buffer (pH 7.0) (final concentration 20 mM), 5 mL of 2 M KCl solution ( Final concentration of 100 mM) and 3.6 mL of 100 mM K ₂ HPO ₄ solution (final concentration of 3.6 mM) were sequentially added and stirred, and then 1M KOH solution was added dropwise to adjust the pH to 6.8 so that the total volume becomes 100 mL. Distilled water was added. The reaction was started by magnetic stirrer in a 37 ° C. warm bath. After 60 minutes of reaction, 100 mg of hydroxyapatite (manufactured by Wako Pure Chemical Industries, Ltd.) was added, and the reaction was continued for 120 minutes. The time course of the reaction was evaluated by measuring pH and soluble calcium content every 10 minutes. The calcium concentration was measured using Calcium E Test Wako (manufactured by Wako Pure Chemical Industries).

  The evaluation results are shown in FIG.

  Immediately after the start of the reaction, the solubilization rate of calcium decreased rapidly, and the pH also decreased rapidly. In addition, the formation of a precipitate was confirmed at the bottom of the reaction vessel. Further, even when hydroxyapatite was added 60 minutes after the reaction, no significant fluctuation was observed in the solubilization amount or pH of calcium. From this result, it is considered that calcium chloride cannot maintain the ionic state of calcium in the presence of phosphoric acid, and generates and precipitates calcium phosphate. From this result, it was shown that calcium chloride is not expected to promote remineralization.

(Evaluation of remineralization promoting action by maltobionic acid)
The remineralization promoting action was evaluated using maltobionic acid obtained in Preparation Example and calcium chloride (manufactured by Wako Pure Chemicals, calcium content 36%) as a calcium source.

In a beaker for 200 mL to which 44 mL of distilled water was added, 6 mL of 100 mM calcium chloride solution (0.024 g as Ca amount, final concentration of 6 mM), 6 mL of 100 mM maltobionic acid (final concentration of 6 mM), 10 mL of 200 mM HEPES buffer (pH 7.0) ( Final concentration 20 mM), 5 mL of 2 M KCl solution (final concentration 100 mM), 3.6 mL of 100 mM K ₂ HPO ₄ solution (final concentration 3.6 mM) were sequentially added and stirred, and then 1 M KOH solution was added dropwise to reach pH 6.8. And distilled water was added so that the total volume was 100 mL. The reaction was started by magnetic stirrer in a 37 ° C. warm bath. After 60 minutes of reaction, 100 mg of hydroxyapatite (manufactured by Wako Pure Chemical Industries, Ltd.) was added, and the reaction was continued for 120 minutes. The time course of the reaction was evaluated by measuring pH and soluble calcium content every 10 minutes. The calcium concentration was measured using Calcium E Test Wako (manufactured by Wako Pure Chemical Industries).

  The evaluation results are shown in FIG.

  From the start of the reaction to 60 minutes, calcium remained solubilized even in the presence of phosphoric acid, and the pH did not change. When hydroxyapatite was added thereto, the solubilization rate of calcium decreased rapidly, and the pH also decreased rapidly. This is thought to be the result of hydroxyapatite becoming crystal nuclei, where calcium was deposited and remineralized. In Comparative Example 1, no remineralization promoting effect was observed for calcium chloride, so it is considered that maltobionic acid worked usefully as a remineralization promoting substance. From this, it was shown that maltobionic acid is useful as a substance that promotes remineralization.

[Comparative Example 2]
(Evaluation of remineralization promoting effect by calcium gluconate)
Recalcification promoting action was evaluated using calcium gluconate monohydrate (manufactured by Kanto Chemical Co., Ltd., calcium content 8.9%) which is a soluble calcium material.

In a beaker for 200 mL to which 50 mL of distilled water was added, 6 mL of 100 mM calcium gluconate solution (0.024 g as Ca amount, final concentration 6 mM), 10 mL of 200 mM HEPES buffer (pH 7.0) (final concentration 20 mM), 5 mL of 2 M KCl solution (Final concentration: 100 mM) and 3.6 mL of 100 mM K ₂ HPO ₄ solution (final concentration: 3.6 mM) were sequentially added and stirred, then 1M KOH solution was added dropwise to adjust to pH 6.8, so that the total volume becomes 100 mL. Distilled water was added. The reaction was started by magnetic stirrer in a 37 ° C. warm bath. After 60 minutes of reaction, 100 mg of hydroxyapatite (manufactured by Wako Pure Chemical Industries, Ltd.) was added, and the reaction was continued for 120 minutes. The time course of the reaction was evaluated by measuring pH and soluble calcium content every 10 minutes. The calcium concentration was measured using Calcium E Test Wako (manufactured by Wako Pure Chemical Industries).

  The result of evaluation is shown in FIG.

  Immediately after the start of the reaction, the solubilization rate of calcium decreased, and the pH also decreased. In addition, the formation of a precipitate was confirmed at the bottom of the reaction vessel. In addition, even when hydroxyapatite was added 60 minutes after the reaction, no significant change was observed in the amount of calcium solubilized. From this result, it is considered that calcium gluconate was not able to maintain the calcium ion state in the presence of phosphoric acid, and precipitated as calcium phosphate. From these results, it was shown that calcium gluconate is not expected to promote remineralization.

  The recalcification promoting action was evaluated using the calcium oxide salt of DE44 branched oligosaccharide (trade name ISO, manufactured by Sanei Saccharification Co., Ltd., obtained in Preparation Example) (calcium content 3.5%, calcium gluconate 20%). .

1.85 g of branched oligosaccharide oxide calcium salt (0.024 g as Ca amount, final concentration of 6 mM) was added to a 200 mL beaker to which 50 mL of distilled water was added, dissolved by stirring, and then 10 mL of 200 mM HEPES buffer (pH 7.0). (Final concentration 20 mM), 2 M KCl solution 5 mL (final concentration 100 mM), 100 mM K ₂ HPO ₄ solution 3.6 mL (final concentration 3.6 mM) were added in order and stirred, and then 1 M KOH solution was added dropwise to reach pH 6.8. Distilled water was added so that the total amount would be 100 mL. The reaction was started by magnetic stirrer in a 37 ° C. warm bath. After 60 minutes of reaction, 100 mg of hydroxyapatite (manufactured by Wako Pure Chemical Industries, Ltd.) was added, and the reaction was continued for 120 minutes. The time course of the reaction was evaluated by measuring pH and soluble calcium content every 10 minutes. The calcium concentration was measured using Calcium E Test Wako (manufactured by Wako Pure Chemical Industries).

  The evaluation results are shown in FIG.

  From the start of the reaction to 60 minutes, calcium remained in a solubilized state even in the presence of phosphoric acid, and no significant change in pH was observed. When hydroxyapatite was added thereto, the solubilization rate of calcium decreased rapidly, and the pH also decreased rapidly. This is thought to be the result of hydroxyapatite becoming crystal nuclei, where calcium was deposited and remineralized. From this phenomenon, it was shown that the branched oligosaccharide oxide calcium salt is useful as a substance that promotes remineralization.

(Evaluation of remineralization promoting effect by combined use of fluoride)

To a microtube for 2 mL, 60 μL of 100 mM calcium maltobionate solution (final concentration 6 mM), 100 μL of 200 mM HEPES buffer (pH 7.0) (final concentration 20 mM), 50 μL of 2 M KCl solution (final concentration 100 mM), sodium fluoride (1 mg / ml) mL) 0 μL to 50 μL and 36 μL of 100 mM K ₂ HPO ₄ solution (final concentration 3.6 mM)) were added and mixed, and distilled water was added to a total volume of 800 μL. Two types of test solutions were prepared, one in which 200 μL of 5 mg / mL hydroxyapatite (manufactured by Wako Pure Chemical Industries) was added to the above solution and the other in which hydroxyapatite was not added (200 μL of distilled water was added). Shake at 160 rpm. After completion of the reaction, the calcium content of the centrifuged supernatant was measured with Calcium E Test Wako (manufactured by Wako Pure Chemical Industries), and the calcium solubilization rate and calcium deposition rate (calcium amount used for remineralization) ) Was calculated.

  Calcium solubilization rate (%) = [Soluble calcium amount in reaction completed solution (mg / mL) / Amount of calcium added to reaction solution (mg / mL)] × 100

  Calcium deposition rate (%) = [[soluble calcium amount in the reaction solution without addition of hydroxyapatite (mg / mL) −soluble calcium amount in the reaction solution with addition of hydroxyapatite (mg / mL)] / calcium amount added to the reaction solution (Mg / mL)] × 100

  The evaluation results are shown in Table 1.

  Since the calcium solubilization rate in the condition where hydroxyapatite was not added was maintained at around 95%, it was confirmed that calcium was kept in an ionic state without binding to fluorine or phosphorus. Moreover, since the solubilization rate of calcium is reduced to 12.9% to 52.1% by addition of hydroxyapatite, it is considered that calcium is deposited on the crystal nucleus (hydroxyapatite). Moreover, since the deposition rate of calcium increased depending on the sodium fluoride concentration, the synergistic effect of promoting remineralization by adding fluorine was confirmed.

[Comparative Example 3]
As a comparative test of Example 7, calcium chloride was used in place of calcium maltobionate, and the remineralization promoting effect by the combined addition of fluoride was evaluated.

  The evaluation results are shown in Table 2.

  The calcium solubilization rate under the condition where hydroxyapatite is not added is 50% or less, and the calcium solubilization rate is low depending on the added sodium fluoride concentration, so that calcium chloride contains fluorine and phosphoric acid. Below, it is considered that the calcium ion state could not be maintained, and calcium phosphate and calcium fluoride were generated and precipitated. From this result, it was shown that calcium chloride is not expected to promote remineralization by the combined use of fluoride.

(Evaluation of remineralization promoting effect by the combined use of sugar alcohol)

To a 2 mL microtube 100 mM calcium maltobionate solution (final concentration 6 mM), 200 mM HEPES buffer (pH 7.0) 100 μL (final concentration 20 mM), 2 M KCl solution 50 μL (final concentration 100 mM), sugar alcohol (xylitol, sorbitol) , Maltitol, or any one of palatinit) (500 mg / mL) 0 μL to 200 μL, and 36 μL of 100 mM K ₂ HPO ₄ solution (final concentration 3.6 mM) were added and mixed, and then distilled water was added to a total volume of 800 μL. It was. Two types of test solutions were prepared, one in which 200 μL of a 5 mg / mL hydroxyapatite solution (manufactured by Wako Pure Chemical Industries) was added to the above solution and the other in which hydroxyapatite was not added (200 μL of distilled water was added). Shake at 160 rpm. After completion of the reaction, the calcium content of the centrifuged supernatant was measured with Calcium E Test Wako (manufactured by Wako Pure Chemical Industries), and the calcium solubilization rate and calcium deposition rate (calcium amount used for remineralization) ) Was calculated.

  Calcium solubilization rate (%) = [Soluble calcium amount in reaction completed solution (mg / mL) / Amount of calcium added to reaction solution (mg / mL)] × 100

  Calcium deposition rate (%) = [[soluble calcium amount in the reaction solution without addition of hydroxyapatite (mg / mL) −soluble calcium amount in the reaction solution with addition of hydroxyapatite (mg / mL)] / calcium amount added to the reaction solution (Mg / mL)] × 100

  The results of evaluation are shown in Tables 3 to 6.

  Even if any sugar alcohol of xylitol, sorbitol, maltitol, and palatinit is used, since the deposition rate of calcium is increased depending on the sugar alcohol concentration, by adding sugar alcohol to maltobionic acid calcium salt, It is thought that the amount of calcium ions that can be used for remineralization has increased due to the increased stability of calcium ions. From these results, the synergistic effect of remineralization promotion by addition of sugar alcohol was confirmed.

Japanese Patent No. 2859612 JP 2006-45154 A JP 2007-153788 A JP 2002-325556 A Japanese Patent No. 4403140

Claims (4)

An active ingredient is a sugar carboxylic acid in which the aldehyde group at the reducing end of a starch decomposition product or a transfer reaction product having a polymerization degree of 2 or more is oxidized and / or its calcium salt, and the sugar carboxylic acid is maltobionic acid or isomaltobionic acid , Maltotriionic acid, isomaltotriionic acid, maltotetraionic acid, maltohexanoic acid, panose oxide, malto-oligosaccharide oxide, branched oligosaccharide oxide, starch oxalate, powdered oxide, dextrin oxide A remineralization promoter for tooth enamel, characterized in that it is at least one selected from the group consisting of: The tooth enamel remineralization accelerator according to claim 1, further comprising at least one fluoride. Furthermore, the remineralization promoter for tooth enamel according to claim 1 or 2 , further comprising at least one sugar alcohol. An oral composition comprising the tooth enamel remineralization accelerator according to any one of claims 1 to 3 .

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