JP2010126510A - Composition for oral cavity and foodstuff containing calcium lactobionate - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a composition and foodstuff having recalcification effect more excellent than ever. <P>SOLUTION: There are provided the anticaries composition for oral cavity comprising (i) calcium lactobionate; or (ii) lactobionate salt excluding calcium lactobionate or a combination of lactobionic acid and a water soluble calcium salt excluding calcium lactobionate. There are provided the anticaries foodstuff comprising (i) calcium lactbionate; or (ii) a lactobionate salt excluding calcium lactobionate, or a combination of lactobionic acid and a water-soluble calcium salt excluding calcium lactobionate, and the foodstuff which retains at least 5 min in the oral cavity in eating time is also provided. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to an anti-cariogenic oral composition and food containing lactobionic acid or a salt thereof (for example, calcium lactobionate). More specifically, the present invention relates to an anti-caries oral composition and food that reduce the occurrence of dental caries due to remineralization of teeth.

  Caries are parenchymal defects caused by decalcification of the tooth by organic acids produced by oral bacteria present on the tooth surface, and are generally known as caries. In recent years, it has been found that a phenomenon called initial caries occurs before caries occurs. The initial caries means a state in which no substantial loss of the tooth has occurred and the surface of the tooth surface is retained, but calcium and phosphate are lost from under the surface layer of the tooth surface. When initial caries occurs, the tooth surface appears white due to the loss of calcium and phosphate, which changes the crystalline state of the teeth. Since caries is a real defect, it cannot be repaired naturally, and the defect cannot be filled without treatment by a dentist. On the other hand, initial caries takes time, but can be naturally restored. This is usually due to the occurrence of dental demineralization and remineralization in the oral cavity.

  In general, teeth are exposed to high concentrations of organic acids by preventing diffusion of organic acids produced by oral bacteria present on the tooth surface due to some obstacles, resulting in the formation of caries. In this sense, all oral bacteria having sugar-fermenting ability to produce organic acids by metabolism can cause caries. Convenient substrates for organic acid production are saccharides, which include monosaccharides and oligosaccharides such as glucose and sucrose, and polysaccharides such as starch which is a polymer of monosaccharides.

  Factors that impede the diffusion of organic acids can be broadly divided into the following two categories: (1) starch ingested by meals stays in the neck and roots; and (2) is susceptible to degradation of sucrose and the like Insoluble glucan produced by bacteria using sugar (ie, fermentable sugar) as a substrate is fixed to the tooth surface.

  The above factor (1) is considered to be caused by all bacteria having sugar-fermenting ability present in the oral cavity, such as lactobacilli. In this case, it is known that the progress of caries is generally slow.

  Since there are many sucrose-containing foods in modern foods, the above factor (2) is considered to be the main factor of modern caries. Streptococcus mutans and Streptococcus sobrinus are considered as causative bacteria for this factor (2). These bacteria are streptococci in a form in which spherical individual bacteria having a diameter of about 0.6 μm are linked in a bead shape. These bacteria actively produce water-insoluble α-glucan in the presence of sucrose. This glucan has the property of adhering very strongly to the tooth surface. These bacteria exhibit acid-producing ability by rapidly metabolizing sucrose. Since these bacteria have strong acid resistance, they can survive even under acid conditions where other bacteria cannot grow. Since water-insoluble α-glucan has strong adhesiveness, it can firmly bind bacteria to the tooth surface and the like. The organic acid produced by the bacteria is prevented from spreading by the water-insoluble glucan adhering to the tooth surface, and as a result, a high concentration of organic acid accumulates on the tooth surface, resulting in a high concentration of organic acid on the tooth surface. Exposed to. In this case, the progress of caries is faster than the factor (1).

In consideration of dental health, a new approach to dental caries prevention has been practiced from the microscopic level of tooth decalcification and remineralization (Non-patent Document 1). The tooth consists of a dentin part and an enamel part, and the enamel covers the dentin. About 97% of the enamel is composed of hydroxyapatite [Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ]. Hydroxyapatite is mainly a crystal structure of calcium and phosphoric acid. The enamel is the hardest part of the tooth. The organic acid produced by the bacteria in the plaque and the acid contained in the food cause the precious calcium or phosphate to dissolve (demineralize) from the inside of the enamel. Defending. The organic acid penetrates into the enamel through the inter-pillar space filled with moisture and dissolves hydroxyapatite by a process called decalcification. This loss of calcium and phosphate from the enamel tissue results in an initial caries beneath the enamel surface. The initial caries can be repaired, and calcium and phosphate ions can penetrate into the subsurface caries and restore the lost apatite by a process called remineralization.

  By eating or snacking, plaque (plaque) is formed in the oral cavity, organic acid is produced, pH is lowered, and enamel is dissolved. This is decalcification. The case where the degree of demineralization remains below the surface layer and the tooth surface remains is initial caries, and when demineralization progresses and depression of the tooth surface occurs, a cavity is formed and caries. The pH of the plaque becomes acidic every time when a food or drink containing fermentable carbohydrates is ingested, and exceeds the critical pH at which demineralization begins. This is due to the action of acid producing bacteria in the plaque. In addition to caries bacteria, caries involve various factors such as dentition and aging. Acidic foods and drinks also increase the risk of dental caries. Demineralization with acidic foods and drinks is non-bacterial and is called erosion. Erosion refers to a phenomenon in which the tooth surface is chemically dissolved by acid or chelation without involvement of caries bacteria. Erosion is also a type of caries. In recent years, attention has been focused on erosion caused by carbonated drinks and sports drinks mainly for infants and young people, and erosion caused by alcoholic drinks and health drinks mainly for adults and elderly people, as well as associated dental fracture and attrition. Collecting. The critical pH of enamel is 5.5, and the pH value of many commercially available drinks is lower than 5.5. Usually, saliva has a cleaning effect of washing away dirt on the tooth surface and an acid buffering effect of neutralizing acid. These two functions protect the enamel. However, if a drink having a low pH value is consumed frequently and excessively, these effects are not sufficiently exhibited. Moreover, the amount of saliva secreted decreases while sleeping. Therefore, after drinking a drink having a low pH value and sleeping without thoroughly washing the oral cavity, the time during which the oral cavity is exposed to an acidic environment becomes long, and erosion tends to occur.

  On the other hand, when the pH in the oral cavity rises to neutrality by receiving a buffering action of saliva at the initial caries stage, and calcium ions and phosphate ions are supplied, enamel is reformed. This is remineralization.

  Therefore, as a means of preventing and treating caries, it should not be a nutrient source for oral bacteria that cause caries and should not produce organic acids; it should not be a source of mutans bacteria that cause caries, Prevent water-insoluble glucans and organic acids from being generated; prevent the pH from being reduced by this organic acid so as not to exceed the pH at which demineralization begins (for example, have a buffering effect and prevent a decrease in pH) It is considered important to promote remineralization.

  Various studies have been conducted on oral compositions, foods, and the like for treating initial caries using remineralization.

  For example, Patent Document 1 discloses an oral composition containing a buffering agent such as a phosphorylated oligosaccharide, which is a composition for eating and drinking and an oral composition having an anti-cariogenic function.

  However, even if these conventional methods are used, the remineralization of the demineralized portion of the initial caries cannot be restored to a complete state, and its effect is limited.

  Moreover, patent document 2 is disclosing the dentifrice composition containing the specific aldobionamide which has (beta) -galactoside bond. In the invention described in Patent Document 2, a specific aldobionamide (for example, lactobionamide) containing a β-galactoside bond has an anti-plaque effect by disrupting the binding or action of bacteria as an antibacterial agent in the oral cavity. Based on the findings that were shown. In Table 1 and Table 2 of Patent Document 2, lactobionic acid is described as a comparative control. However, Table 1 shows the results of the bacterial co-aggregation test, and Table 2 shows the results for the inhibition of bacterial-latex bead aggregation, all indicating that lactobionic acid has no antibacterial function. It is.

Patent Document 3 discloses a method for producing a lactobionic acid-containing milk beverage. Patent Document 3 states in paragraph 0009 that "the lactobionic acid-containing milk drink is absorbed at the time of oral intake of foods and drinks containing minerals such as calcium and iron, or before and after that, to absorb minerals derived from foods and drinks. It can be promoted. " Patent Document 3 describes, in paragraph 0010, “The absorption efficiency of calcium contained in lactobionic acid-containing milk beverages itself is higher than that in normal milk because absorption is promoted by the presence of lactobionic acid”. is doing. However, Patent Document 3 does not disclose that lactobionic acid has an action of promoting tooth remineralization. Furthermore, although patent document 3 describes the manufacturing method of a milk drink in the Example, the Example which shows that absorption of calcium is accelerated | stimulated is not described.
JP 2002-325557 A JP-A-6-80543 Japanese Patent Laid-Open No. 2008-245587 Yoichi Iijima, Takashi Kumagai; Caries Control Mechanism of decalcification and remineralization, Ishiyaku Shuppan Publishing Co., Ltd., 1999, p. 21-51

  The present invention is intended to solve the above-described problems, and an object thereof is to provide an oral cavity composition and food for anti-caries.

  As a result of intensive studies to solve the above problems, the present inventors have found that calcium lactobionate has an action of promoting remineralization, and based on this, the present invention has been completed.

In order to achieve the above object, the present invention provides, for example, the following means:
(Item 1)
An anti-caries oral composition, the composition comprising:
A composition comprising (i) a lactobionic acid calcium salt; or (ii) a combination of a lactobionic acid salt or lactobionic acid other than the lactobionic acid calcium salt and a water-soluble calcium salt other than the lactobionic acid calcium salt.

(Item 2)
Item 2. The composition according to Item 1, comprising the calcium lactobionate salt.

(Item 3)
The calcium lactobionate content of the composition is such that when the composition is used in the oral cavity, the calcium concentration in the mixture of the composition in the oral cavity and saliva is 1.5 mM to 6 mM. 3. The composition according to item 1 or 2, which is an appropriate amount.

(Item 4)
Item 4. The composition according to any one of Items 1 to 3, further comprising a phosphate source compound.

(Item 5)
Item 5. The composition according to Item 4, wherein the phosphate source compound is selected from the group consisting of phosphoric acid, sodium phosphate, potassium phosphate, polyphosphoric acid, and cyclic phosphate.

(Item 6)
Item 6. The composition according to any one of Items 1 to 5, further comprising a fluoride.

(Item 7)
The fluorine content of the composition is an appropriate amount for the fluoride ion concentration in the mixture of the composition in the oral cavity and saliva when the composition is used in the oral cavity to be 50 ppm or less. Item 7. The composition according to Item 6.

(Item 8)
Item 8. The composition according to any one of items 1 to 7, which is used for treatment of initial caries.

(Item 9)
Item 8. The composition according to any one of Items 1 to 7, which is used for strengthening the tooth quality of a healthy person.

(Item 10)
Item 10. The composition according to any one of Items 1 to 9, which is a dentifrice, mouthwash, troche, or gel.

(Item 11)
An anti-cariogenic food, the food
(I) a lactobionic acid calcium salt; or (ii) a lactobionic acid salt or lactobionic acid other than a calcium lactobionic acid salt and a combination of a water-soluble calcium salt other than the lactobionic acid calcium salt, and the food is 5 minutes at the time of eating A food that stays in the mouth.

(Item 12)
12. The food according to item 11, which is a chewing gum, candy, tablet confectionery or frozen confectionery.

(Item 13)
Item 13. The food according to Item 11 or 12, comprising the calcium lactobionate salt.

(Item 14)
Item wherein the content of the calcium lactobionate salt of the food is an appropriate amount for the calcium concentration in the saliva in the oral cavity when the food is present in the oral cavity to be 1.5 to 6.0 mM. 13. The food according to 13.

(Item 15)
Item 15. The food according to any one of Items 11 to 14, further comprising a phosphate source compound.

(Item 16)
Item 16. The food according to item 15, wherein the phosphate source compound is selected from the group consisting of phosphoric acid, sodium phosphate, potassium phosphate, polyphosphoric acid and cyclic phosphate.

(Item 17)
The food according to any one of Items 11 to 16, further comprising a fluoride.

(Item 18)
Item 18. The food according to item 17, wherein the fluorine content of the food is an amount appropriate for the fluoride ion concentration in saliva in the oral cavity when the food is present in the oral cavity to be 50 ppm or less.

(Item 19)
19. The food according to any one of items 11 to 18, wherein the food is a chewing gum, and the weight of calcium lactobionate contained in a single intake is 1.2 mg to 4.8 mg as the weight of calcium. Food.

(Item 20)
Item 20. The food according to Item 19, wherein the chewing gums are eaten 1 to 3 g at a time.

Food and compositions of the present invention, for the treatment of early caries, i.e., is suitable for people with dentition before initial caries to be caries is evaluated as C ₁ -C _4.

  According to the present invention, the oral cavity has an excellent remineralization effect as in the past and has the further advantage that the possibility of caries is lower than before, there is no fear of Maillard reaction, and there is no taste and smell. Compositions and food products are provided.

Calcium lactobionate supplies calcium to the enamel in the oral cavity and promotes remineralization. The behavior of the calcium salt of lactobionic acid is characteristic unlike other calcium salts, that is, lactobionic acid calcium salt remains soluble without binding to insoluble inorganic phosphate under neutral conditions . In addition, calcium is not released under a normal environment, and calcium is released when reaching a place where hydroxyapatite exists (that is, a tooth surface). Furthermore, lactobionic acids other than calcium salts play a role of releasing calcium in an enamel-specific manner when present together with calcium ions. Therefore, when lactobionic acid and calcium ions are present, a large amount of calcium is provided to hydroxyapatite, and remineralization is significantly promoted. In other words, phosphorylated saccharide satisfies the following two points necessary for a remineralization promoting substance in initial caries:
(1) Prevent calcium-phosphate insolubilization under neutral pH conditions; and (2) Calcium ions and phosphate ions reach the affected area for remineralization.

  On the other hand, calcium salts such as, for example, calcium chloride release calcium very easily. Therefore, calcium is released before calcium chloride reaches the place where hydroxyapatite is present, and calcium cannot be provided to hydroxyapatite. Conversely, CPP (casein phosphopeptide) and calcium are strongly bound to calcium and do not readily release calcium. Therefore, even if it reaches the place where hydroxyapatite exists, only a small amount of calcium is provided to hydroxyapatite.

  Therefore, the combination of lactobionic acid and calcium ions has an excellent calcium-providing effect that is significantly different from other calcium compounds, as is the case with phosphorylated oligosaccharide calcium salts.

  Furthermore, lactobionic acid and its salts have properties superior to phosphorylated oligosaccharides. Phosphorylated oligosaccharides are usually S. cerevisiae among oral bacteria. Some mutans are hardly assimilated and do not cause caries. However, S. There are a variety of bacteria other than mutans, among which there may be bacteria that have or produce phosphatases. In that case, the phosphatase liberates the phosphate group portion of the phosphorylated oligosaccharide to produce an oligosaccharide. Oligosaccharides are often assimilated by oral bacteria and cause caries. For this reason, phosphorylated oligosaccharides have little risk of being utilized. On the other hand, lactobionic acid and its salts are hardly assimilated by oral bacteria and do not cause caries. Since the phosphate group is not bonded to lactobionic acid and its salt, there is no concern that the performance of lactobionic acid is reduced even if phosphatase is present. Thus, lactobionic acid and its salt are substances with extremely low risk of being utilized and causing caries even if phosphatase is present in the oral cavity.

  Moreover, since the phosphorylated oligosaccharide has a reducing end, it reacts with the protein by the Maillard reaction to cause browning. Since foods often contain protein, it is preferable that the Maillard reaction does not occur. On the other hand, lactobionic acid and its salt do not have a reducing end and do not cause Maillard reaction. Therefore, lactobionic acid and its salt can be blended without concern for browning even in foods containing protein.

  Furthermore, lactobionic acid and its salt have the advantage that there is no habit of taste and aroma. Therefore, when blended in various foods and oral compositions, the original taste and aroma are not impaired, that is, it is possible to easily obtain high-quality foods and oral compositions in terms of taste and aroma. It has the advantage of being able to.

  Hereinafter, the present invention will be described in detail.

(1. Definition)
In this specification, the anti-caries function includes both a caries prevention function and a caries treatment function. The caries treatment function refers to a function of repairing a part of a tooth once lost due to caries. In this specification, having an “anti-cariogenic function” means having one or more of the following properties: (1) having a pH buffering action and reducing pH by an acid produced by oral bacteria. (2) has the ability to suppress the formation of insoluble glucan produced by oral bacteria; (3) has the ability to promote recalcification of teeth in early caries. Preferably it has two of the above properties, most preferably all of the above properties.

  According to the composition and food of the present invention, phosphoric acid and calcium can be stably provided to a carious tooth. Teeth that have been provided with phosphate and calcium are remineralized so that some of the teeth lost due to caries can be restored.

  In particular, according to the present invention, since a buffering agent is added to the oral cavity, it is expected that a pH buffering action can be obtained in the oral cavity. Due to the pH buffer action in the oral cavity, phosphate and calcium present in the saliva and the like in the oral cavity are stably used for tooth remineralization. Accordingly, it is possible to repair a tooth that was conventionally considered difficult or impossible.

  Demineralized lesions, which are the initial symptoms of caries, are restored to a healthy state by replenishing calcium and phosphate (remineralization) in the demineralized enamel part when conditions in the oral cavity are in place. In order to maintain the healthy state of the teeth, it is necessary that minerals are supplied to the affected area of the demineralized lesion by the action of saliva and that demineralization and remineralization at the micro level are balanced. Generally, after eating and drinking, the pH in dental plaque tends to decrease, the balance relationship of “demineralization-remineralization” breaks down, and the lesion progresses when “demineralization> remineralization”. On the other hand, in the relationship of “remineralization> demineralization”, the demineralized lesion is restored and the teeth are remineralized. The balance between demineralization and remineralization plays an extremely important role in the oral environment, especially saliva and plaque, in the pH, calcium, and phosphate concentrations (Yoichi Iijima, Takashi Kumagai; The mechanism of ash and remineralization, Ishiyaku Shuppan Co., Ltd .; 21-51, 1999). According to the present invention, since the oral environment can be adjusted to an environment in which remineralization is likely to occur, caries can be prevented, decalcification lesions that are the initial symptoms of caries can be treated, and teeth can be healthy and durable. Can do.

(2. Materials used in the present invention)
In the present invention, lactobionic acid or a salt thereof is used. Other materials can also be used if desired.

(2a. Lactobionic acid and lactobionic acid salt)
Lactobionic acid used in the present invention is an acidic oligosaccharide obtained by oxidizing lactose and has the following structure:

As used herein, the term “salt of lactobionic acid” refers to any salt of lactobionic acid. As used herein, the term “lactobionic acid inorganic salt” refers to any inorganic salt of lactobionic acid. As used herein, the term “calcium lactobionic acid salt” refers to a calcium salt of lactobionic acid.

  Lactobionic acid is in the acid form (i.e., hydrogen is bonded to the carboxyl group). In the present invention, the ionized form of lactobionic acid (that is, the hydrogen of the carboxyl group is dissociated and separated into a carboxylate ion) may be used, or the salt form (that is, the positive ion of the carboxylate ion and the base). May be used). In certain embodiments, preferably an inorganic salt of lactobionic acid is used. The inorganic salt of lactobionic acid is preferably a calcium salt, magnesium salt, potassium salt, zinc salt, iron salt or sodium salt.

  As a lactobionic acid and its salt, a high purity thing may be used and a low purity thing may be used. For example, lactobionic acid and a salt thereof may be used as a mixture with a part of raw materials in the production thereof. In addition, when mentioning content of lactobionic acid and its salt in this specification, this content is calculated based on the quantity of pure lactobionic acid and its salt. Therefore, when a mixture containing a substance other than lactobionic acid and its salt is used, the content is calculated based on the amount of lactobionic acid and its salt in the mixture, not the total amount of the mixture.

  Commercially available lactobionic acid and lactobionic acid salt can be used. For example, calcium lactobionate is commercially available from Reliable Biopharmaceutical Corporation (St. Louis, USA) under the trade name CALCIUM LACTOBIONATE, and lactobionic acid is commercially available from the company under the trade name LACTOBIONIC ACID. Methods for producing lactobionic acid are known, for example, Yang, B. et al. Y. , Et al. , Carbohydrate Research, 340, 2698-2705 (2005).

(2b. Water-soluble calcium salt)
In certain embodiments of the invention, water soluble calcium salts are used. In the present specification, the “water-soluble calcium salt” refers to a calcium salt having a solubility in water of 20 ° C. of 1% by weight or more. The solubility of the water-soluble calcium salt used in the present invention in water at 20 ° C. is preferably about 2% by weight or more, more preferably about 3% by weight or more, and further preferably about 4% by weight or more. Particularly preferably, it is about 5% by weight or more. The definition of water-soluble calcium salt includes lactobionic acid calcium salt. Other examples of such water-soluble calcium salts include calcium chloride, organic acid calcium salts (for example, calcium lactate, calcium gluconate, calcium acetate, calcium glutamate, fermented calcium, calcium citrate, citric acid / malate calcium) , Calcium formate, calcium benzoate, calcium isobutyrate, calcium propionate, calcium salicylate, etc.), colloidal calcium carbonate, polyol calcium phosphate, calcium hydroxide, calcium carbonate, calcium hydrogen phosphate, calcium phosphate, whey calcium, casein phospho Peptide calcium, calcium fluoride and the like can be mentioned.

(2c. Phosphate source compound)
Hydroxyapatite (which is represented by Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ), which is the main component of tooth enamel, has a Ca / P ratio of about 1.67, and constitutes tooth enamel. In the composition, the Ca / P ratio is about 1.0 to about 1.67 (P / Ca ratio = 0.6 to 1.0). Accordingly, the Ca / P ratio is made to approach about 1.0 to about 1.67 (P / Ca ratio = 0.6 to 1.0), preferably about 1.67 (P / Ca ratio = 0.6). Further, remineralization of enamel can be promoted by supplying phosphate ions and calcium ions.

  In the present invention, when only calcium lactobionate is used or only lactobionate other than calcium salt or a combination of lactobionic acid and water-soluble calcium salt is used, only calcium ions are supplied. Phosphate ions are insufficient for calcification.

  It is known that a large amount of phosphoric acid is present in saliva. In a normal human body, the molar ratio of calcium: phosphate in saliva (hereinafter referred to as “Ca / P ratio”) is generally about 0.25 to about 0.67 (P / Ca = about 1.45). To about 3.9), and there is an excess of phosphoric acid (ie, approximately 3 moles phosphate to 2 moles calcium to 3.9 moles phosphorus to 1 mole calcium). Therefore, in the case of foods that are often chewed in the oral cavity, such as chewing gums, phosphoric acid is hardly deficient without adding phosphoric acid.

  However, in the case of foods that wash away saliva, such as juice, and compositions that are applied directly to the tooth surface, phosphate ions may be deficient for more efficient remineralization. Therefore, it is preferable to use a phosphate ion source at the same time in the composition and food of the present invention. In this specification, the source of phosphate ions is referred to as a phosphate source compound. A phosphoric acid source compound means a phosphoric acid compound.

  The phosphate source compound that can be used in the present invention can be any compound as long as it is a compound that releases phosphate ions when dissolved in water. The phosphate source compound is preferably a water-soluble phosphate or inorganic phosphoric acid. Examples of such phosphate source compounds include phosphoric acid, sodium phosphate, potassium phosphate, polyphosphoric acid and salts thereof, cyclic phosphoric acid and salts thereof, and the like. Examples of sodium phosphate include sodium metaphosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, trisodium phosphate, sodium pyrophosphate, sodium hydrogen pyrophosphate, and the like. Examples of potassium phosphate include potassium dihydrogen phosphate, dipotassium hydrogen phosphate, and tripotassium phosphate. Polyphosphoric acid is a compound formed by condensation of two or more phosphoric acids. The degree of polymerization in the polyphosphoric acid is arbitrary as long as it is 2 or more. For example, it is 2 or more and 10 or less. Examples of polyphosphoric acid include pyrophosphoric acid, triphosphoric acid, trimetaphosphoric acid, tetrametaphosphoric acid, and cyclopolyphosphoric acid. These polyphosphoric acid salts may also be used, preferably sodium, potassium or magnesium salts. Examples of cyclic phosphoric acid include hexametaphosphoric acid. These cyclic phosphate salts may also be used, preferably sodium, potassium or magnesium salts.

  This phosphate source compound has a Ca / P ratio of about 1.0 to about 1.67 (P / Ca ratio = about 0.6 to about 1.0), preferably about 1.67 (P / Ca ratio = It can be added to the compositions and food products of the present invention alone or in combination so as to approach about 0.6).

(2d. Fluoride)
In the present invention, fluoride can also be suitably used. Fluoride ions react with calcium ions and easily precipitate, but the presence of phosphorylated saccharide is known to maintain the state of calcium ions and fluoride ions (Patent Document 1 (Japanese Patent Laid-Open No. 2002-2002)). -325557))). In the present invention, it was found that calcium lactobionate also has the property of maintaining the state of calcium ions and fluoride ions, like phosphorylated saccharide. Therefore, recrystallization of the affected area of decalcification can be promoted by supplying fluoride together with calcium ions and phosphate ions. Furthermore, acquisition of acid resistance can be expected by incorporating fluoride ions into the crystal. In the present invention, it is preferable that the fluoride is designed to be released simultaneously with the water-soluble calcium salt or after the water-soluble calcium salt. In the present invention, it is preferable that the fluoride is designed to be released simultaneously with or after the lactobionic acid or a salt thereof.

  Conventionally, fluoride is often used at a high concentration of 1000 ppm or more. However, ingestion of high concentrations of fluoride may result in dental fluorosis and mildly white spots on the tooth surface, and severe cases may cause brown spots and stains. Toxicity may be a problem for toxicity. In the present invention, by using lactobionic acid at the same time as fluoride, a sufficient amount of fluoride ions can be secured even with a lower concentration of fluoride than in the prior art. An effect equivalent to or higher than the high concentration of can be obtained. According to the present invention, for example, a sufficient effect can be obtained even by adding fluoride of about 100 ppm or less, preferably using about 10 ppm or less. The fluoride concentration is preferably about 0.01 ppm or more, more preferably about 0.1 ppm, even more preferably about 0.5 ppm or more, and most preferably about 2 ppm or more. The concentration of fluoride is preferably about 100 ppm or less, more preferably about 50 ppm or less, still more preferably about 10 ppm or less, and most preferably about 5 ppm or less. The fluoride is preferably a compound that dissolves in water and releases fluoride ions. The fluoride is preferably a fluoride that is approved for incorporation into foods, pharmaceuticals or quasi drugs. Examples of such fluorides include sodium fluoride, potassium fluoride, monofluorophosphoric acid, calcium fluoride, cryolite, monofluoroacetic acid 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 a very high fluorine concentration and a very low tea polyphenol concentration may be used.

(2e. Other materials)
In the composition and food of the present invention, any material usually used in the intended composition and food can be used as long as it does not interfere with the action of lactobionic acid and calcium.

  When the food of the present invention is a chewing gum, for example, it may contain a gum base, sweetener, gelatin, flavor, brightener, colorant, thickener, acidulant, pH adjuster and the like. Examples of gum bases include chicle, vinyl acetate, ester gum, polyisobutylene and styrene butadiene rubber. The sweetener can be a sugar, a sugar alcohol, or a high intensity sweetener. The sweetener is preferably non-cariogenic to prevent caries. The sweetener is more preferably selected from maltitol, reduced palatinose, palatinose, lactitol, erythritol, sorbitol, xylitol, aspartame L-phenylalanine compound, trehalose and mannitol. The chewing gums can be blended according to blends known in the art.

  For example, when the food of the present invention is a candy, sugars such as sucrose and syrup, wheat flour, condensed milk, salt, agar, gelatin, nuts (such as peanuts), shortening, butter, acidulant, flavor, pH adjuster , Colorants and the like. The sugar can be a sugar, a sugar alcohol, or a high intensity sweetener. The saccharide is preferably a non-cariogenic saccharide in order to prevent caries. The saccharide is more preferably selected from maltitol, reduced palatinose, palatinose, lactitol, erythritol, sorbitol, xylitol, aspartame L-phenylalanine compound, trehalose and mannitol. The compounding of the candy can follow a compounding well-known in the said field | area.

  Tablet confectionery (also referred to as a tablet) refers to foods that are formed by compression molding powders or granules, and are gradually dissolved or disintegrated in the mouth and designed to work for a long time in the mouth. The time it takes for tablet confection to start melting in the oral cavity and to finish melting depends on the size and ingredients of the tablet confection. A person skilled in the art can arbitrarily design and manufacture a tablet confection suitable for achieving a desired time from when the tablet confection starts to melt until it finishes melting. Examples of raw materials used in tablet confectionery include the following: sugars, calcium carbonate, calcium phosphate, calcium sulfate, powdered cellulose, emulsifiers, acidulants, flavorings, pH adjusters and colorants. The saccharide is preferably a non-cariogenic saccharide in order to prevent caries. The sugar can be a sugar (sucrose, starch syrup, lactose, glucose, starch, etc.), a sugar alcohol or a high intensity sweetener. The saccharide is more preferably selected from maltitol, reduced palatinose, palatinose, lactitol, erythritol, sorbitol, xylitol, aspartame L-phenylalanine compound, trehalose and mannitol. The blending of tablet confectionery can be in accordance with a blend known in the art.

  On the other hand, caries is a disease caused by bacteria. Therefore, in the composition and food of the present invention, the combined use with an antibacterial agent or a plaque formation inhibitor is also effective. It is also known that hydroxyapatite adsorbs cariogenic bacteria. Examples of bactericides and antibacterial agents include benzalkonium chloride, cetylpyridinium chloride, parapenes, benzoic acid, alcohols such as ethanol, and the like. Examples of relatively safe substances include combinations with chitin chitosan, chitosan oligosaccharide, lactoferrin, polyphenol, and the like. In addition, measures to suppress inflammation caused by bacteria can be used in combination. Examples of main anti-inflammatory agents include flavonoids such as genistein and naringenin, polyamines, β-glucans, alkaloids, hesperidin, hesperetin, and sugar-transferred hesperidin. These various agents can be included as needed in the compositions and foods of the present invention.

  In certain embodiments, the compositions and foods of the present invention preferably do not include phosphorylated oligosaccharides or salts thereof and hydroxyapatite. This phosphorylated oligosaccharide and its salt are the phosphorylated oligosaccharide and its salt described in JP-A-8-104696.

(3. Food of the present invention)
In one embodiment, the food product of the present invention is an anti-cariogenic food product, the food product comprising:
(I) a lactobionic acid calcium salt; or (ii) a lactobionic acid salt or lactobionic acid other than a calcium lactobionic acid salt and a combination of a water-soluble calcium salt other than the lactobionic acid calcium salt, and the food is 5 minutes at the time of eating It stays in the oral cavity.

(3a. Method for producing food of the present invention)
The food of the present invention includes (i) lactobionic acid calcium salt; or (ii) lactobionic acid salt or lactobionic acid other than calcium lactobionic acid and a combination of water-soluble calcium salt other than calcium lactobionic acid, It can be produced by any method known in the art.

  In the case of (ii), it is preferable that the food of the present invention contains substantially uniformly a combination of lactobionate or lactobionic acid other than lactobionic acid calcium salt and water-soluble calcium salt other than lactobionic acid calcium salt. . A food containing these uniformly has the advantage of being easy to manufacture.

  In the case of (ii), a part containing lactobionate or lactobionic acid may be divided from a part containing a water-soluble calcium salt other than the lactobionic acid calcium salt. In this case, in the food of the present invention, the water-soluble calcium salt other than the lactobionic acid calcium salt is released from the food at the same time or after the lactobionic acid salt or lactobionic acid other than the lactobionic acid calcium salt is released. Should be designed to be. This is because when water-soluble calcium salts other than calcium lactobionic acid are released earlier than lactobionic acid or salts thereof, calcium ions are deposited randomly on the tooth surface, which is not preferable.

  In the food product of the present invention, fluoride may also be used, in which case the fluoride is designed to be released simultaneously with lactobionate or lactobionic acid or after lactobionate or lactobionic acid. Should.

  In the food product of the present invention, a phosphate source compound may also be used, in which case the phosphate source compound is released simultaneously with lactobionate or lactobionic acid or after lactobionate or lactobionic acid. It is preferable to be designed.

  These apply to all foods and compositions of the present invention.

(3b. Food of the present invention)
The food of the present invention includes any of (i) a lactobionic acid calcium salt; or (ii) a lactobionic acid salt or lactobionic acid other than a lactobionic acid calcium salt and a combination of a water-soluble calcium salt other than a lactobionic acid calcium salt. Can be food. In the case where the food of the present invention contains lactobionic acid calcium salt, the food of the present invention does not need to contain lactobionic acid or a salt thereof, but may contain it.

  The food of the present invention may contain fluoride as necessary. If the food product of the present invention contains fluoride, it should be designed so that the fluoride is released simultaneously with or after lactobionate or lactobionic acid. These apply to all food products of the present invention.

  Examples of the food of the present invention include, for example, chewing gums; candies; tablet confectionery; compound beverages; semi-fluid foods such as yogurt; baked confectionery such as biscuits and rice crackers; frozen confectionery such as ice cream; And noodles. Chewing gums, candies and tablet confections are suitable as foods of the present invention because active ingredients can be retained in the oral cavity for a long time. Stimulated saliva is known to contain calcium ions at a concentration of about 1 to 1.5 mM in advance, and it is desirable to consider it when designing products.

  When the food of the present invention is a chewing gum, the chewing gum can be a sugar-coated gum or a plate gum. As for the chewing gums, any part of (i) calcium lactobionate, or (ii) a combination of lactobionate or lactobionic acid other than calcium lactobionate and a water-soluble calcium salt other than calcium lactobionate It is preferable to contain. When the gum is a sugar-coating gum and contains a combination of lactobionic acid salt or lactobionic acid other than lactobionic acid calcium salt and a water-soluble calcium salt other than lactobionic acid calcium salt, the sugar-coated portion is lactobionic acid other than calcium lactobionic acid salt It is preferable that salt or lactobionic acid is contained and the gum part contains water-soluble calcium salt other than calcium lactobionic acid. When the chewing gum is a plate gum and includes a combination of lactobionic acid salt or lactobionic acid other than lactobionic acid calcium salt and a water-soluble calcium salt other than lactobionic acid calcium salt, the chewing gum includes microcapsules. Preferably, the gum part contains lactobionate or lactobionic acid other than lactobionic acid calcium salt, and the microcapsule contains a water-soluble calcium salt other than lactobionic acid calcium salt. In either case, lactobionic acid may be included in either the lactobionic acid-containing moiety, the calcium-containing moiety, or both.

  When the food of the present invention is a candy, the candy may be a single-layer candy or a multi-layer candy. Candy refers to a food produced by a method including a step of simmering sugars using sugars such as sucrose and starch syrup as main raw materials. Candy can be classified into soft candy and hard candy. Examples of soft candy include soft caramel, hard caramel, nougat and marshmallow. Examples of hard candies include drops, toffees and blits.

  When the food of the present invention is a single-layer candy, the candy is (i) calcium lactobionate or (ii) lactobionate or lactobionate other than calcium lactobionate and water-soluble other than lactobionate calcium salt. It is preferable that the combination with a calcium salt is included substantially uniformly. Single-layer candies have the advantage of being easier to manufacture than multi-layer candies.

  When the multi-layer candy is a candy composed of two layers of a center layer and a coating layer surrounding the candy, for example, (i) calcium lactobionate or (ii) calcium lactobionate other than both the center layer and the coating layer A combination of lactobionic acid salt or lactobionic acid and a water-soluble calcium salt other than calcium lactobionic acid may be included, or only one of the center layer and the coating layer may be included. In one embodiment, the center layer preferably contains lactobionate or lactobionic acid other than lactobionic acid calcium salt, and the coating layer preferably contains a water-soluble calcium salt other than lactobionic acid calcium salt. The center layer may be a hard candy, a soft candy, or a cream. The coating layer may be a hard candy, a soft candy, a sugar coating, or a powder layer. The candies of the present invention are not limited to single-layer candies and double-layer candies, and further layers may be provided.

  In one embodiment, the food of the present invention may be a confectionery (also referred to as sugar-coated candy gum) in which gum is wrapped with candy. In this case, for example, both candy and gum are (i) calcium lactobionate, or (ii) lactobionate or lactobionic acid other than lactobionic acid calcium, and a combination of water-soluble calcium salt other than lactobionic acid calcium salt. Or may be included only in one of the candy and gum. When the food of the present invention is a sugar-coated candy gum and (ii) a lactobionic acid salt other than calcium lactobionic acid or a combination of lactobionic acid and a water-soluble calcium salt other than lactobionic acid calcium salt, It is good also as a structure which contains lactobionate other than calcium lactobionate or lactobionic acid, and contains water-soluble calcium salt other than lactobionic acid calcium salt in a candy part.

  When the food of the present invention is tablet confectionery, the tablet confectionery may be a single layer tablet confectionery or a multi-layer tablet confectionery. When the food of the present invention is a single-layer tablet confectionery, the tablet confectionery contains (i) calcium lactobionate, or (ii) lactobionate or lactobionate other than lactobionate calcium and lactobionate calcium other than It is preferable that the combination with a water-soluble calcium salt is contained substantially uniformly. Single-layer tablet confections have the advantage of being easier to manufacture than multi-layer tablet confections.

  When the food of the present invention is a multi-layered tablet confectionery, for example, (i) calcium lactobionate or (ii) lactobionate or lactobionic acid other than lactobionic acid calcium and lactobionic acid calcium in all layers In combination with a water-soluble calcium salt, or only in one or two layers. When the food of the present invention is a three-layer tablet confection consisting of three layers (ii) including a combination of lactobionic acid salts or lactobionic acids other than lactobionic acid calcium salts and water-soluble calcium salts other than lactobionic acid calcium salts, The middle layer between the two layers contains water-soluble calcium salt other than calcium lactobionate, and the two layers sandwiching this layer contain lactobionate or lactobionic acid other than calcium lactobionate Preferably.

  When the food of the present invention is a frozen dessert such as ice cream, the food of the present invention includes (i) lactobionic acid calcium salt, or (ii) lactobionic acid salt or lactobionic acid other than lactobionic acid calcium salt, and lactobionic acid calcium salt. It is preferable that the combination with water-soluble calcium salts other than is included substantially uniformly.

  In another embodiment, the food product of the present invention may be a frozen dessert comprising a solid food product in the base frozen dessert. In this case, for example, both (i) calcium lactobionate or (ii) lactobionate or lactobionate other than lactobionate calcium and water-soluble calcium other than lactobionate calcium are used as both the base frozen dessert and the solid food. A combination with salt may be included, or only one of the base frozen dessert and the solid food may be included. A frozen dessert containing a solid food in the frozen dessert based on the food of the present invention, wherein (ii) a combination of lactobionic acid salt or lactobionic acid other than calcium lactobionic acid and a water-soluble calcium salt other than calcium lactobionic acid When it contains, lactobionate other than lactobionic acid calcium salt or lactobionic acid may be included in the base frozen dessert, and a water-soluble calcium salt other than lactobionic acid calcium salt may be included in the solid food.

  Examples of the frozen dessert of the present invention or such a base frozen dessert include ice cream, ice milk, lacto ice and ice confection. Such a solid food can be, for example, a gel. Examples of such a solid food include tapioca, nata de coco, agar, jelly, bavaroa, jam and the like. Such a solid food may be of any size, but preferably has a diameter of 2 mm or more, more preferably a diameter of 3 mm or more. The diameter of the solid food may be, for example, 4 mm or more, 5 mm or more, 6 mm or more, 7 mm or more, 8 mm or more, 9 mm or more, or 10 mm or more. The diameter of the solid food is preferably 15 mm or less, more preferably 14 mm or less, and still more preferably 13 mm or less. The diameter of the solid food may be, for example, 12 mm or less, 11 mm or less, 10 mm or less, 9 mm or less, 8 mm or less, 7 mm or less, 6 mm or less, or 5 mm or less.

  The weight of the food product of the present invention can be any weight. The weight of the food of the present invention is preferably about 0.05 g or more, more preferably about 0.1 g or more, and further preferably about 0.5 g or more. The weight of the food of the present invention is preferably about 5 g or less, more preferably about 4 g or less, and still more preferably about 3 g or less.

  When the food of the present invention is a chewing gum, the weight of the chewing gum is preferably about 0.05 g or more, more preferably about 0.1 g or more, and further preferably about 0.5 g or more. The weight of the chewing gums is preferably about 3 g or less, more preferably about 2 g or less, and still more preferably about 1 g or less.

  When the food of the present invention is a candy, the weight of the candy is preferably about 0.5 g or more, more preferably about 1 g or more, and further preferably about 1.5 g or more. The weight of the candy is preferably about 5 g or less, more preferably about 4 g or less, and still more preferably about 3 g or less.

  When the food of the present invention is tablet confectionery, the weight of tablet confectionery is preferably about 0.05 g to about 10 g, more preferably about 0.1 g to about 5 g, and further preferably about 0.2 g to about 3 g. It is.

  The food of the present invention can be in any shape. For example, when the food of the present invention is a chewing gum, candy, or tablet confectionery, it may be disc-shaped, spherical, rugby ball-shaped, heart-shaped, or the like. For example, when the food of the present invention is a compound beverage, yogurt or the like, there is no particular shape.

  In one embodiment, when the food of the present invention contains lactobionic acid or a salt thereof (excluding the calcium salt), the content of lactobionic acid and the salt in the food of the present invention can be arbitrarily set. For example, the content (total) of lactobionic acid and its salt in the food of the present invention is such that when the food is present in the oral cavity, its concentration in saliva in the oral cavity is converted to lactobionic acid, Preferably in an amount suitable for a concentration of about 1.0 mM or more, more preferably about 1.5 mM or more, more preferably about 2.0 mM or more, particularly preferably about 2.5 mM or more, most preferably about 3 mM or more. is there. For example, the content (total) of lactobionic acid and its salt in the food of the present invention is such that when the food is present in the oral cavity, its concentration in saliva in the oral cavity is converted to lactobionic acid, The amount is preferably about 10 mM or less, more preferably about 6 mM or less, further preferably about 5 mM or less, particularly preferably about 4.5 mM or less, and most preferably about 4 mM or less.

  As used herein with respect to food, “the content is such that when the food is present in the oral cavity, the concentration in the saliva in the oral cavity is such that its concentration is 1.0 mM or higher. "There is" means that the liquid produced in the oral cavity within 20 minutes after starting to eat the food of the present invention, and the concentration of the component in the liquid is measured to be 1.0 mM. An appropriate amount. For example, a method of collecting 20 times per minute is possible, and in this case, a combination of liquids collected 20 times can be used as a measurement sample. The food is preferably kept in the oral cavity for 20 minutes without being swallowed. Alternatively, food may be put in the mouth little by little during 20 minutes and chewed. Then, every time the eater feels that saliva has accumulated in the oral cavity, the saliva is exhaled, and a method of collecting the exhaled liquid is possible. However, be careful not to spit out food when spitting out saliva. The same is true for other concentrations. In this specification, the term “saliva” is not pure saliva secreted from the oral glands, but refers to fluid that accumulates in the oral cavity when food is chewed in the oral cavity. In this case, the liquid that accumulates in the oral cavity is a mixture of pure saliva, a liquid portion derived from food, and various solutes derived from food. The amount of each component added to the food varies depending on the weight and size of the food. When the single intake of food is large, it is blended so as to have a lower content than when the intake is small. For example, in order to achieve the same use amount, the amount (%) in 2 g of food is about 0.5 times the amount (%) in 1 g of food. About 20 mL of human saliva is secreted on average in 20 minutes. Therefore, the blending amount into the food is set in consideration of how much is eluted with respect to 20 mL of saliva. Such a blending amount can be easily set by those skilled in the art.

  When the food is a chewing gum containing lactobionic acid or a salt thereof, when the gum is chewed in the mouth for about 20 minutes, almost all the lactobionic acid and its salt contained in the gum are contained in the saliva within 20 minutes. Elute.

  When the food is a chewing gum containing a phosphate source compound, when the gum is chewed in the mouth for about 20 minutes, almost all the phosphate source compound contained in the gum is dissolved in saliva within 20 minutes. .

  When the food is a chewing gum containing fluoride, when the gum is chewed in the mouth for about 20 minutes, almost all the fluoride contained in the gum is dissolved in the saliva within 20 minutes.

  In one embodiment, when the food of the present invention contains lactobionic acid or a salt thereof (excluding calcium salt), the content of lactobionic acid and the salt thereof in the food of the present invention is determined by the form of food, feeding It can be arbitrarily set in consideration of the dilution rate at the time. For example, the content (total) of lactobionic acid and its salt in the food of the present invention is preferably about 1.0 mM or more, more preferably about 1.5 mM or more, and still more preferably about 2 in terms of lactobionic acid. The amount is appropriate to obtain a concentration of 0.0 mM or more, particularly preferably about 2.5 mM or more, and most preferably about 3 mM or more. For example, the content of lactobionic acid or a salt thereof in the food of the present invention, when used in the oral cavity, is preferably about 10 mM or less, more preferably about 6 mM or less, still more preferably about 10 mM or less in terms of calcium content. The amount is suitable for a concentration of 5 mM or less, particularly preferably 4.5 mM or less, and most preferably about 4 mM or less.

  In one embodiment, the content of the water-soluble calcium salt (including calcium lactobionate) in the food of the present invention can be arbitrarily set in consideration of the form of the food, the dilution rate during feeding, and the like. . For example, the content of the water-soluble calcium salt in the food of the present invention is such that the calcium concentration in the saliva in the oral cavity when the food is present in the oral cavity is preferably about 1.0 mM or more, more preferably about The amount is suitable to be 1.5 mM or more, more preferably about 2.0 mM or more, particularly preferably about 2.5 mM or more, and most preferably about 3 mM or more. For example, the content of the water-soluble calcium salt in the food of the present invention is such that the calcium concentration in the saliva in the oral cavity when the food is present in the oral cavity is preferably about 10 mM or less, more preferably about 6 mM or less. The amount is more preferably about 5 mM or less, particularly preferably 4.5 mM or less, and most preferably about 4 mM or less.

  In one embodiment, the content of the water-soluble calcium salt (including calcium lactobionate) in the food of the present invention can be arbitrarily set in consideration of the form of the food, the dilution rate during feeding, and the like. . For example, when a water-soluble calcium salt (including calcium lactobionate) is added to chewing gum, the amount of saliva that appears during chewing for 20 minutes is 20 mL, and the molecular weight of calcium is about 40. In order to adjust the calcium concentration in the saliva in the oral cavity when present to 1.5 mM to 6 mM, 1.2 mg to 4.8 mg of calcium may be included as a single intake (40 × 1.5 ( mM) x 0.002 (L) = 1.2 mg, 40 x 6 (mM) x 0.002 (L) = 4.8 mg). Therefore, if the weight of the gum is Xg and the blending amount (calculated as calcium) is Y%, Y (%) = {(1.2 to 4.8 (mg)) / (X (g) × 1000)} The blending amount is determined by × 100. For example, when the weight of the gum is 2 g, the blending amount as calcium is 0.06 to 0.24% by weight. For example, if the gum weight is 1 g, the blending amount as calcium is 0.12 to 0.48% by weight. If the gum weight is 10 g, the blending amount as calcium is 0.012 to 0. 0.048% by weight. The same calculation is performed when the weight of the gum is another weight. A similar design can be applied to foods other than gum.

  In one embodiment, when the food of the present invention contains fluoride, the content of fluoride in the food can be arbitrarily set in consideration of the form of the food, the dilution rate at the time of eating, and the like. . For example, the fluoride content in the food of the present invention is such that the fluorine concentration in the saliva in the oral cavity when the food is present in the oral cavity is preferably about 0.1 ppm or more, more preferably about 0.00. The amount is suitable to be 5 ppm or more, more preferably about 1 ppm or more, particularly preferably about 2 ppm or more. The fluoride content in the food of the present invention is such that the fluorine concentration in the saliva in the oral cavity when the food is present in the oral cavity is preferably about 100 ppm or less, more preferably about 50 ppm or less, and still more preferably. An amount suitable to be about 30 ppm or less, even more preferably about 10 ppm or less, particularly preferably about 5 ppm or less, and most preferably about 3 ppm or less.

In one embodiment, the content of fluoride in the food of the present invention can be arbitrarily set in consideration of the form of the food, the dilution rate at the time of eating, and the like. For example, when fluoride is added to chewing gum, the amount of saliva that appears during chewing for 20 minutes is 20 mL, so the concentration of fluorine in the saliva in the oral cavity when the food is present in the oral cavity is 50 ppm or less. To do so, it is sufficient to include 1 mg or less of fluorine as a single intake (20 (g) × 50 × 10 ⁻⁶ = 1 (mg)). Therefore, if the gum weight is Xg and the blending amount of fluoride (converted as fluorine) is Y%, the blending amount is Y (%) = {1 (mg) / (X (g) × 1000)} × 100. Is determined. For example, when the weight of the gum is 2 g, the blending amount as fluorine is 0.05% by weight or less. For example, when the weight of the gum is 1 g, the blending amount as fluorine is 0.1% by weight or less, and when the weight of the gum is 10 g, the blending amount as fluorine is 0.01% by weight or less. . The same calculation is performed when the weight of the gum is another weight. A similar design can be applied to foods other than gum.

  In one embodiment, when the food of the present invention contains a phosphate source compound, the content of the phosphate source compound in the food is arbitrary in consideration of the form of the food, the dilution rate at the time of eating, and the like. Can be set to For example, the content of the phosphate source compound in the food of the present invention is such that the phosphate concentration in the saliva in the oral cavity when the food is present in the oral cavity is preferably about 0.1 mM or more, more preferably The amount is suitable to be about 0.5 mM or more, more preferably about 1 mM or more, particularly preferably about 2 mM or more, and most preferably about 2.5 mM or more. For example, the content of the phosphate source compound in the food of the present invention is such that the phosphate concentration in the saliva in the oral cavity when the food is present in the oral cavity is preferably about 10 mM or less, more preferably about 8 mM. Hereinafter, the amount is more preferably about 6 mM or less, particularly preferably about 5 mM or less, and most preferably about 4 mM or less.

  In one embodiment, the content of the phosphate source compound in the food of the present invention can be arbitrarily set in consideration of the form of the food, the dilution rate at the time of eating, and the like. For example, when a phosphoric acid source compound is blended in chewing gum, the amount of saliva that appears during 20 minutes of chewing is 20 mL and the molecular weight of phosphoric acid is about 98, so the oral cavity when the food is present in the oral cavity In order to adjust the phosphate concentration in the saliva in the inside to 0.1 mM to 10 mM, 0.0196 mg to 1.96 mg of phosphate may be included as a single intake (98 × 0.1 (mM) × 0. 002 (L) = 0.0196 mg, 98 x 10 (mM) x 0.002 (L) = 1.96 mg). Therefore, assuming that the weight of the gum is Xg and the blending amount (converted as phosphoric acid) is Y%, Y (%) = {(0.0196 to 1.96 (mg)) / (X (g) × 1000) } × 100 determines the blending amount. For example, when the weight of the gum is 2 g, the blending amount as phosphoric acid is 0.00098 to 0.098% by weight. For example, if the gum weight is 1 g, the blending amount as phosphoric acid is 0.00196 to 0.0000196% by weight. If the gum weight is 10 g, the blending amount as phosphoric acid is 0.000196. ~ 0.00000196 wt%. The same calculation is performed when the weight of the gum is another weight. A similar design can be applied to foods other than gum.

(3c. Method for Eating Food of the Present Invention)
The food of the present invention can be used for any application. The food of the present invention can be used by both healthy people and those who need treatment for initial caries.

  There is no restriction | limiting in particular in the intake amount, intake frequency, and intake period of the foodstuff of this invention, It can ingest arbitrarily.

  The intake amount of the food of the present invention is preferably about 0.1 g or more, more preferably about 0.2 g or more, still more preferably about 0.5 g or more, and still more preferably about 0.1 g or more. 1 g or more. There is no particular upper limit on the intake of the food of the present invention, but for example, about 1000 g or less, about 750 g or less, about 500 g or less, about 250 g or less, about 100 g or less, about 50 g or less, about 40 g or less, about 30 g per serving. Hereinafter, about 20 g or less, about 10 g or less, about 7.5 g or less, about 5 g or less, about 4 g or less, about 3 g or less, about 2 g or less, about 1 g or less.

  The intake frequency of the food of the present invention can be set arbitrarily. For example, at least once a week, at least twice a week, at least 3 times a week, at least 4 times a week, at least 5 times a week, at least 6 times a week, at least 7 times a week It may be once a day or more, twice a day or more, three times a day or more. There is no upper limit to the intake frequency of the food of the present invention, for example, 3 times or less per day, 2 times or less per day, 1 time or less per day, 7 times or less per week, 6 times or less per week, 5 times per week Or less, 4 or less per week, 3 or less per week, 2 or less per week, 1 or less per week, or the like.

  The timing of intake of the food of the present invention may be before a meal, after a meal, or between meals, but is preferably after a meal. Pre-meal means from about immediately before meal to about 30 minutes before eating, post-meal means from immediately after meal to about 30 minutes after meal, and between meals is about 2 after eating. It means the time about two hours or more before the next meal after more than an hour.

  The intake period of the food of the present invention can be arbitrarily determined. The food of the present invention can be ingested preferably for about 1 day or more, more preferably for about 3 days or more, and most preferably for about 5 days or more. The intake period of the food of the present invention may be about 1 month or less, about 2 weeks or less, or about 10 days or less. Since demineralization in the oral cavity can occur on a daily basis, the food of the present invention is preferably ingested almost permanently.

  The food of the present invention is preferably retained in the oral cavity for a certain period of time without being swallowed during ingestion, that is, at the time of eating. The time for allowing the food of the present invention to stay in the oral cavity is preferably about 5 minutes or longer, more preferably about 10 minutes or longer, and even more preferably about 15 minutes or longer. There is no particular upper limit on the time for which the food of the present invention is retained in the oral cavity, and it may be, for example, about 1 hour or less, about 50 minutes or less, about 40 minutes or less, about 30 minutes or less, about 20 minutes or less. If the residence time is too short, it is difficult to obtain a remineralization effect.

  When the food of the present invention is a chewing gum, candy, tablet confectionery, etc., it may be taken one at a time, or a plurality (eg, 2 to 10) may be taken at a time. When ingesting a plurality at a time, a plurality may be ingested at once, or a plurality may be ingested one by one. When the food of the present invention is a chewing gum, it is preferable to continue chewing for a long time, and when the food of the present invention is a candy or a tablet confectionery, it is preferably licked to the end without chewing.

  The food of the present invention is usually packaged and sold. This packaging may be a commonly used packaging such as paper, plastic, cellophane and the like. This packaging contains instructions on the intake amount, timing of intake, and intake method of the food of the present invention (for example, in the case of gum, “it is preferable to continue to chew 2 capsules for about 20 minutes or more”). Is preferred. Alternatively, an instruction sheet in which such an instruction is described may be inserted.

(4. Oral composition for anti-caries of the present invention)
In one embodiment, the anti-caries oral composition of the present invention comprises (i) a calcium lactobionate salt; or (ii) a lactobionic acid salt or lactobionic acid other than a lactobionic acid calcium salt and a calcium lactobionic acid salt. It is a composition containing the combination with water-soluble calcium salt. In certain embodiments, the composition preferably contains neither hydroxyapatite fine particles nor phosphorylated sugar or a salt of phosphorylated sugar. This anti-caries oral composition can contain calcium phosphates other than hydroxyapatite (for example, calcium monohydrogen phosphate, calcium dihydrogen phosphate and tricalcium phosphate). The initial caries treatment composition of the present invention preferably further contains a fluoride or phosphate source compound. In one embodiment, the anti-caries oral cavity composition of the present invention is preferably an initial caries treatment composition.

  The composition for oral cavity for anti-caries of the present invention may be composed of only the above materials, but may contain other materials other than those described above. Examples of other materials that can be included in the anti-caries oral composition of the present invention include powdered cellulose, starch, water, antibacterial agents, and bactericides.

  When the anti-cariogenic oral cavity composition of the present invention is a powder, the composition comprises: (i) a powder of lactobionic acid calcium salt; or (ii) a lactobionic acid salt or lactobionic acid powder other than the calcium lactobionic acid salt; In addition, a combination with a powder of a water-soluble calcium salt other than lactobionic acid calcium salt can be produced by mixing with other conventionally known materials as required by a conventionally known method.

  When the oral composition for anti-caries of the present invention is a liquid, the composition comprises (i) a calcium lactobionate salt; or (ii) a lactobionic acid salt or lactobionic acid other than the lactobionic acid calcium salt and calcium lactobionic acid. It can be produced by adding a combination with a water-soluble calcium salt other than a salt to a conventionally known solvent and mixing by a conventionally known method.

  In one embodiment, the total content of lactobionic acid or a salt thereof in the anti-cariogenic oral composition of the present invention takes into account the form of the oral composition, the dilution rate in use, etc. It can be set arbitrarily. For example, the total content of lactobionic acid or a salt thereof (excluding calcium lactobionate) in the composition for oral cavity of the present invention is used in the oral cavity when the composition is used in the oral cavity. The lactobionic acid concentration in the mixture of the composition and saliva is preferably about 1.0 mM or higher, more preferably about 1.5 mM or higher, particularly preferably about 2.0 mM or higher, most preferably about 3 mM or higher. Appropriate amount. For example, the total content of lactobionic acid or a salt thereof in the oral cavity composition for anti-caries of the present invention is a mixture of the composition in the oral cavity and saliva when the composition is used in the oral cavity. In a suitable amount such that the concentration of lactobionic acid is preferably about 10 mM or less, more preferably about 6 mM or less, further preferably about 5 mM or less, particularly preferably about 4.5 mM or less, most preferably about 4 mM or less. is there.

  As used herein with respect to an oral composition, “the content of which is 1.0 mM in the mixture of the composition and saliva in the oral cavity when the composition is used in the oral cavity. "It is an amount suitable for achieving the above concentration" means that a liquid produced in the oral cavity is collected for 20 minutes after the use of the oral composition of the present invention, and the concentration of the component in the liquid is collected. Is an amount appropriate for a concentration of 1.0 mM. The same is true for other concentrations. The liquid that accumulates in the oral cavity is a mixture of pure saliva, a liquid portion derived from the oral composition, and various solutes derived from the oral composition.

  In one embodiment, the total content of lactobionic acid or a salt thereof in the anti-cariogenic oral composition of the present invention takes into account the form of the oral composition, the dilution rate in use, etc. It can be set arbitrarily. When the composition for oral cavity is used in a form that acts as it is without being diluted in the oral cavity, such as a dentifrice and mouthwash, the composition for oral cavity for anti-caries of the present invention The total content of lactobionic acid or a salt thereof (excluding calcium lactobionate) in the product is preferably about 1.0 mM or more, more preferably about 1.5 mM or more in terms of lactobionic acid, Particularly preferred is about 2.0 mM or more, and most preferred is about 3 mM or more. In this case, for example, the total content of lactobionic acid or a salt thereof in the composition for oral cavity of the present invention is preferably about 10 mM or less, more preferably about 10 mM, in terms of lactobionic acid. 6 mM or less, more preferably about 5 mM or less, particularly preferably about 4.5 mM or less, and most preferably about 4 mM or less. When the composition for oral cavity is a composition intended to be used diluted in the oral cavity, the ingredients are blended in consideration of the dilution ratio. For example, in the case of an oral composition intended to be diluted about 20 times, it is blended at a concentration of 20 times. In the present specification, in the case of such an oral composition which is hardly diluted, the mixture of the composition present in the oral cavity and a small amount of saliva is referred to as “when the composition is used in the oral cavity. It is regarded as “the saliva in the oral cavity”.

  In one embodiment, the content of the water-soluble calcium salt (including calcium lactobionate) in the anti-cariogenic oral composition of the present invention depends on the form of the oral composition, the dilution rate during use, and the like. It can be set arbitrarily in consideration. For example, the content of the water-soluble calcium salt in the oral cavity composition for anti-caries of the present invention is preferably such that the calcium concentration in the saliva in the oral cavity when the composition is used in the oral cavity is about 1 The amount is appropriate to be 0.0 mM or more, more preferably about 1.5 mM or more, particularly preferably about 2.0 mM or more, and most preferably about 3 mM or more. For example, the content of the water-soluble calcium salt in the oral cavity composition for anti-caries of the present invention is such that the calcium concentration in saliva in the oral cavity when the composition is used in the oral cavity is preferably about 10 mM. Hereinafter, it is an amount suitable to be about 6 mM or less, more preferably about 5 mM or less, particularly preferably about 4.5 mM or less, and most preferably about 4 mM or less.

  The content of the water-soluble calcium salt (including calcium lactobionate) in the anti-cariogenic oral composition of the present invention is arbitrarily determined in consideration of the form of the oral composition, the dilution rate during use, etc. Can be set. When the composition for oral cavity is used in a form that acts as it is without being diluted in the oral cavity, such as a dentifrice and mouthwash, the composition for oral cavity for anti-caries of the present invention The total content of water-soluble calcium salts in the product is preferably about 1.0 mM or more, more preferably about 1.5 mM or more, particularly preferably about 2.0 mM or more, in terms of calcium content. And most preferably about 3 mM or more. In this case, for example, the total content of the water-soluble calcium salt in the composition for oral cavity of the present invention is preferably about 10 mM or less, more preferably about 6 mM in terms of calcium content. Or less, more preferably about 5 mM or less, particularly preferably about 4.5 mM or less, and most preferably about 4 mM or less. When the composition for oral cavity is a composition intended to be used diluted in the oral cavity, the ingredients are blended in consideration of the dilution ratio. For example, in the case of an oral composition intended to be diluted about 20 times, it is blended at a concentration of 20 times.

  When the composition for oral cavity for anti-caries of the present invention contains fluoride, the content of fluoride in the composition for oral cavity takes into consideration the form of the composition for oral cavity, the dilution rate at the time of use, etc. Can be set arbitrarily. For example, the fluoride content in the oral composition of the present invention is such that the fluorine concentration in the saliva in the oral cavity when the composition is used in the oral cavity is preferably about 0.1 ppm or more, more preferably The amount is suitable to be about 0.5 ppm or more, more preferably about 1 ppm or more. The content of fluoride in the oral composition of the present invention is such that the fluorine concentration in the saliva in the oral cavity when the composition is used in the oral cavity is preferably about 100 ppm or less, more preferably about 50 ppm or less. The amount is more preferably about 30 ppm or less, even more preferably about 10 ppm or less, particularly preferably about 5 ppm or less, and most preferably about 3 ppm or less. These apply to all anti-caries oral compositions of the present invention.

  The content of the fluoride in the oral cavity composition for anti-caries of the present invention can be arbitrarily set in consideration of the form of the oral cavity composition, the dilution rate during use, and the like. When the composition for oral cavity is used in a form that acts as it is without being diluted in the oral cavity, such as a dentifrice and mouthwash, the composition for oral cavity for anti-caries of the present invention The content of fluoride in the product is preferably about 100 ppm or less, more preferably about 50 ppm or less, still more preferably about 30 ppm or less, even more preferably about 10 ppm or less, in terms of fluorine content. Particularly preferably about 5 ppm or less, and most preferably about 3 ppm or less. In this case, for example, the total content of fluoride in the oral cavity composition for anti-caries of the present invention is preferably about 100 ppm or less, more preferably about 50 ppm or less in terms of fluorine content. More preferably about 30 ppm or less, still more preferably about 10 ppm or less, particularly preferably about 5 ppm or less, and most preferably about 3 ppm or less. When the composition for oral cavity is a composition intended to be used diluted in the oral cavity, the ingredients are blended in consideration of the dilution ratio. For example, in the case of an oral composition intended to be diluted about 20 times, it is blended at a concentration of 20 times.

  In one embodiment, when the oral cavity composition for anti-caries of the present invention contains a phosphate source compound, the content of the phosphate source compound in the composition is in the form of the oral composition, in use. It can be arbitrarily set in consideration of the dilution ratio of For example, the content of the phosphate source compound in the composition for treating initial caries according to the present invention is such that the phosphate concentration in the saliva in the oral cavity when the composition is used in the oral cavity is preferably about 0.1 mM. Above, more preferably about 0.5 mM or more, further preferably about 1 mM or more, particularly preferably about 2 mM or more, most preferably about 2.5 mM or more. For example, the content of the phosphate source compound in the oral cavity composition for anti-caries of the present invention is preferably about 10 mM in the saliva concentration in the oral cavity when the composition is used in the oral cavity. Hereinafter, it is an amount suitable to be about 8 mM or less, more preferably about 6 mM or less, particularly preferably about 5 mM or less, and most preferably about 4 mM or less.

  When the oral cavity composition for anti-caries of the present invention contains a phosphate source compound, the content of the phosphate source compound in this composition takes into account the form of the oral composition, the dilution rate in use, etc. And can be set arbitrarily. When the composition for oral cavity is used in a form that acts as it is without being diluted in the oral cavity, such as a dentifrice and mouthwash, the composition for oral cavity for anti-caries of the present invention The content of the phosphate source compound in the product is preferably about 0.1 mM or more, more preferably about 0.5 mM or more, still more preferably about 1 mM or more, in terms of the phosphate content. Particularly preferred is about 2 mM or more, and most preferred is about 2.5 mM or more. In this case, the content of the phosphate source compound in the oral cavity composition for anti-caries of the present invention is preferably about 10 mM or less, more preferably about 8 mM or less in terms of phosphate content, More preferably, it is about 6 mM or less, Especially preferably, it is about 5 mM or less, Most preferably, it is about 4 mM or less.

  In another embodiment, the anti-cariogenic oral composition of the present invention can be used as follows. First, the anti-caries oral composition of the present invention is applied to a desired tooth surface (for example, an initial caries portion or a healthy portion). This composition is preferably applied to the tooth surface using a device such as a contra, a roller, a brush or the like. During and after application of the composition, it may be in contact with saliva and steps may be taken to reduce contact with saliva so that applied calcium and lactobionate ions do not flow out. In the case where measures are taken to reduce contact with saliva, the anti-caries oral composition of the present invention preferably contains a sufficient amount of a phosphate source compound. In this case, for example, it is preferable to remove saliva. The time taken to reduce the contact with saliva is preferably continued for about 5 minutes or more, more preferably about 10 minutes or more, most preferably about 15 minutes or more from the start of application of these compositions. preferable. There is no particular upper limit to the time for taking measures to reduce contact with saliva, for example, about 1 hour or less, about 45 minutes or less, about 30 minutes or less, about 25 minutes or less after starting to apply these compositions, Such as about 20 minutes or less. By taking measures to reduce contact with saliva, recalcification of the initial caries can be significantly promoted. It is preferable to use an organic substance removing agent before applying the oral cavity composition for anti-caries of the present invention to the tooth surface.

  Examples of oral compositions other than food include dentifrices, mouthwashes (also referred to as mouthwashes), troches, gels, etc. Examples of pharmaceutical compositions include tablets, rounds, and the like. Agents, powders, solutions, suspensions, emulsions, granules, capsules and the like. It is also possible to use a form such as a wiping cloth in which a nonwoven fabric or the like is impregnated with these liquid agents, or a form such as a cotton swab.

  The oral composition of the present invention is usually sold in a container or packaged. This container may be a commonly used container such as plastic. This packaging may be a commonly used packaging such as paper, plastic, cellophane and the like. In this container or package, instructions on the intake amount, intake timing, intake method of the oral composition of the present invention (for example, in the case of gum, “it is preferable to continue chewing two tablets for about 20 minutes or more”), etc. Preferably it is described. Alternatively, an instruction sheet in which such an instruction is described may be inserted.

(1. Calcium lactobionic acid salt and lactobionic acid used)
The lactobionic acid calcium salt and lactobionic acid used in the following experiments, examples and test examples are the same as the lactobionic acid calcium salt and the lactobionic acid calcium used in the test examples, as described in FFI Journal Vol. 211, no. What was prepared by the method according to the method published in 10,2006 874-881 was used.

(2. Subsurface demineralized lesion formation)
In the following experiments, examples and test examples, subsurface demineralized lesions were formed by the following method. An enamel block (10 mm × 10 mm) was cut from the crown of a bovine incisor and then the block was attached to the resin without an oral surface portion. The block was polished with wet abrasive paper (# 1000 and # 2000) to expose a new flat enamel surface. A portion of the enamel surface (1/3) was coated with nail varnish to protect it from subsequent decalcification. This part is a healthy part of the control. Method of layering 0.1 M lactic acid solution (pH 4.5) on methylcellulose gel (Lynch RJM, ten Cate JM: The effect of bases on bases on subsequents and remineralization 30: 200 535), a subsurface lesion of the enamel block was formed. In this way, bovine tooth pieces having a healthy part and a demineralized part were prepared.

(3. Method of TMR)
In the following experiments, examples and test examples, TMR was performed by the following method. After remineralization, thin parallel sections were cut from the enamel blocks using a water-cooled diamond saw. This thin slice was polished to a parallel horizontal plane to a thickness of 150 μm. The thin sections of enamel were X-rayed with Cu-Kα X-rays generated by 20 kV and 20 mA for 13 minutes using a high resolution plate, developed and microscopically analyzed (PW-3830, Philips, The. Netherlands). At the time of X-ray imaging, various known amounts of aluminum were used as a standard substance, and images were taken simultaneously to prepare a calibration curve for the amount of calcium. Mineral profiles were delineated from digital images observed under a microscope and mineral parameters (decalcification depth ld and mineral loss (ML)) were calculated by the software of Inspector Research Systems BV (The Netherlands). Mean values were calculated per sample and analyzed statistically.

(Experiment 1 and Experiment 2: Effect evaluation on remineralization of calcium lactobionate)
Conditions for promoting remineralization are the following two points:
(1) Prevent calcium-phosphate binding and insolubilization under neutral pH conditions;
(2) Supply calcium ions and phosphate ions to the affected area of decalcification, and contribute to the crystal growth of hydroxyapatite.

Calcium ions combine with phosphate ions and remineralize to form hydroxyapatite and hydrogen ions. This reaction is reversible as shown below:
10Ca ⁺ + 6HPO ₄ ⁻ + 2H ₂ O⇔Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ + 8H ⁺
Therefore, the remineralization reaction can be monitored by measuring the calcium ion concentration and pH. Furthermore, the promotion effect of the remineralization reaction can be evaluated by using the crystal nucleus of hydroxyapatite (Tanaka, T., et al., Caries Res. 41 (4), 327 (2007)).

In order to evaluate the effect of calcium lactobionate on remineralization, recalcification solution containing calcium lactobionate salt or remineralization solution containing phosphorylated oligosaccharide calcium salt (control 1) or remineralization solution containing CaCl ₂ (control) 2) The changes over time in pH and calcium ions were examined. Moreover, the time-dependent change of pH and calcium ion at the time of using the combination of sodium lactobionate and sodium chloride instead of calcium lactobionate was also investigated.

Specifically, calcium lactobionate-containing remineralization solution having the composition of Experiment 1 in Table 1, phosphorylated oligosaccharide calcium salt (POs-Ca) -containing remineralization solution having the composition of Comparative Experiment 1 in Table 1, Table 1 A CaCl ₂ -containing remineralization solution having the composition of Comparative Experiment 2 and a phosphorylated oligosaccharide sodium salt and CaCl ₂ -containing remineralization solution having the composition of Comparative Experiment 3 in Table 1 were prepared. All of these solutions contained a phosphate source compound (KH ₂ PO ₄ ). The source of calcium was calcium lactobionate in Experiment 1, POs-Ca in Comparative Experiment 1, and CaCl ₂ in Comparative Experiment 2 and Comparative Experiment 3. When preparing this solution, add a small amount of 1N hydrochloric acid solution and calcium source and phosphate source compound to 50 ml of water and mix, then add HEPES solution, which is a buffer solution, and finally add 1N potassium hydroxide solution. After neutralizing the pH, distilled water was added to the solution to 100 ml, and incubation was started at 37 ° C. and pH 6.5 ± 0.02.

During incubation, changes in pH and Ca concentration were measured every 5 minutes. The pH and Ca concentration at each time point were measured with an electrode.

  After the start of incubation, crystal nuclei (hydroxyapatite (Wako Pure Chemical Industries, Ltd., 100 mg)) were added to each solution at 60 minutes for each of Experiments 1-2 and Comparative Experiments 1 to 3, and then 120 minutes. Incubation and measurement were continued until this point. FIG. 1 shows the results of Experiment 1, FIG. 2 shows the results of Comparative Experiment 1, FIG. 3 shows the results of Comparative Experiment 2, FIG. 4 shows the results of Experiment 2, and FIG. 5 shows the results of Comparative Experiment 3.

  As shown in FIG. 1 (Experiment 1), in the case of a remineralized solution containing calcium lactobionate, when incubation is continued without adding crystal nuclei, the calcium concentration slightly increases but the pH hardly changes. The solubility of calcium ions was maintained. Then, it was found that when the crystal nucleus was added after 60 minutes, the calcium concentration and pH were rapidly lowered. 120 minutes after the start of the reaction, the pH value decreased by 0.32 compared to the time when the reaction was started, and calcium ions became insoluble by 22.5%. This indicates that the presence of crystal nuclei promotes calcium deposition and remineralization occurs. Thus, calcium lactobionate is considered to be a substance that promotes remineralization in the same manner as phosphorylated oligosaccharides.

  As shown in FIG. 2 (Comparative Experiment 1), in the case of a remineralized solution containing phosphorylated oligosaccharide calcium, if incubation is continued without adding crystal nuclei, the calcium concentration slightly decreases, but the pH changes little. The solubility of calcium ions was maintained. Then, it was found that when the crystal nucleus was added after 60 minutes, the calcium concentration and pH were rapidly lowered. 120 minutes after the start of the reaction, the pH value decreased by 0.25 compared to the start of the reaction, and calcium ions became insoluble by 32.2%. This indicates that the presence of crystal nuclei promotes calcium deposition and remineralization occurs.

  From the comparison between FIG. 1 and FIG. 2, it was found that lactobionic acid is superior to POsCa in the effect of calcium deposition in the presence of crystal nuclei.

  On the other hand, as shown in FIG. 3 (Comparative Experiment 2), in the case of a remineralized solution containing calcium chloride, if incubation is performed without adding crystal nuclei, the calcium concentration and pH decrease, and the bottom of the container The formation of precipitates was observed. After 60 minutes from the start of the reaction, the pH value decreased by 0.41 compared to the start of the reaction, and 23.4% of calcium ions were insolubilized. Even when crystal nuclei were added, there was no change in the trend of decreasing calcium concentration and pH. This indicates that calcium precipitates regardless of the crystal nuclei. From this, it was confirmed that calcium chloride hardly contributes to remineralization.

  That is, calcium chloride contains a large amount of calcium, but releases calcium in a place where hydroxyapatite does not exist, and cannot provide a large amount of calcium to hydroxyapatite. On the other hand, calcium lactobionate and phosphorylated oligosaccharide hold the calcium without releasing it in a place where hydroxyapatite does not exist, and release calcium for the first time in the place where hydroxyapatite exists. Therefore, calcium lactobionate and phosphorylated oligosaccharide can provide a large amount of calcium to hydroxyapatite.

As shown in FIG. 4 (Experiment 2), in the case of a remineralized solution containing sodium lactobionate and CaCl ₂ instead of calcium lactobionate, if the incubation is continued without adding crystal nuclei, the calcium concentration is slightly increased. The pH increased and the pH decreased slightly, but the solubility of calcium ions was maintained. Then, it was found that when the crystal nucleus was added after 60 minutes, the calcium concentration and pH were rapidly lowered. This was the same as when calcium lactobionate was used. 120 minutes after the start of the reaction, the pH value decreased by 0.33 compared to the time when the reaction was started, and calcium ions were insolubilized by 22.1%. This indicates that the presence of crystal nuclei promotes calcium deposition and remineralization occurs. It was also found that excellent remineralization can be obtained by using calcium lactobionate mineral salt other than calcium salt and water-soluble calcium salt instead of calcium lactobionate.

As shown in FIG. 5 (Comparative Experiment 3), in the case of a remineralized solution containing phosphorylated oligosaccharide sodium and CaCl ₂ , when incubation is continued without adding crystal nuclei, the calcium concentration slightly increases, but the pH Was hardly changed, and the solubility of calcium ions was maintained. And it turned out that a calcium concentration and pH fall by adding a crystal nucleus 60 minutes afterward. This decrease in the proportion of soluble calcium was less than when phosphorylated oligosaccharide calcium was used. 120 minutes after the start of the reaction, the pH value decreased by 0.197 as compared to the start of the reaction, and 26.5% of calcium ions became insoluble. This indicates that the presence of crystal nuclei promotes calcium deposition and remineralization occurs.

As described above, when only calcium lactobionate or a combination of sodium lactobionate and CaCl ₂ is used, a substantially constant pH is maintained before the addition of crystal nuclei, and the proportion of soluble calcium rapidly decreases due to the addition of crystal nuclei. did. This is similar to phosphorylated oligosaccharides, when lactobionic acid is present in the oral cavity, it has the ability to retain calcium ions before contact with the tooth surface, and releases calcium ions immediately upon contact with the tooth surface. This suggests that it promotes remineralization.

(Experiment 3: Confirmation of assimilation of calcium lactobionate by mutans streptococci)
As a result of examining with a simple evaluation system in Experiment 1 and Experiment 2, it was found that calcium lactobionate may have an effect of promoting remineralization. In this experiment, the utilization of calcium lactobionate by Streptococcus mutans was investigated to evaluate whether calcium lactobionate would cause decalcification.

  Streptococcus mutans MT8148 and Streptococcus sobrinus 6715 were used as strains.

  First, 4 ml of Brain Heart Infusion (BHI) liquid medium (manufactured by Difco) was inoculated twice from the stock solution of each strain (glycerol: BHI = 1: 1, stored at −80 ° C.) using a platinum loop. Static culture was performed overnight. Subsequently, main culture was performed using a culture solution having the composition described in Table 2 below. In the main culture, Heart Infusion (HI) liquid medium (manufactured by Difco) was used, a preculture was added, the test tube was tilted obliquely, and stationary culture was performed at 37 ° C. A 1% or 10% calcium lactobionate solution was prepared as a test sample, and added to the culture solution to a final concentration of 0.1% or 1%. A 20% sucrose solution was used as a control and added to the culture solution to a final concentration of 2%. Moreover, the liquid culture medium which does not contain saccharide | sugar as a blank was prepared.

After inoculation, static culture was performed at 37 ° C., and 800 μl of the reaction solution was sampled at 0, 4, 7, and 23 hours. The D570 value (turbidity) was measured.

(result)
In the control to which sucrose was added, S. mutans and S. For both Sobrinus, a decrease in pH and an increase in turbidity were observed, confirming significant bacterial growth and sucrose utilization (Tables 3 and 4). However, in the calcium lactobionate addition test group, a slight decrease in pH (Table 3) and an increase in turbidity (Table 4) were observed in the 1% addition group. When 0.1% of calcium lactobionate was added, the pH decrease and turbidity increase were almost the same as the blank (sterile water), and the pH decrease and turbidity increase were very small. In the calcium lactobionate addition test group, pH 6.0 or more was maintained after 23 hours of culture as in the case of the blank, so that no acid was produced at a level that caused tooth decalcification. Therefore, it is considered that calcium lactobionate is hardly assimilated by oral bacteria and hardly causes decalcification.

(Example 1 and Reference Example 1: Remineralization effect in bovine teeth by lactobionic acid calcium salt or phosphorylated oligosaccharide calcium salt)
From Experiments 1 and 2, it was considered that calcium lactobionate-containing remineralization solution was excellent in remineralization ability in the same manner as phosphorylated oligosaccharide calcium-containing remineralization solution. The following experiment was carried out using an artificially decalcified bovine tooth piece.

  According to “2. Subsurface demineralization lesion formation”, a subsurface demineralization lesion of bovine enamel teeth was formed. Was decalcified). Further, nail burnish was applied to one half of the demineralized part to preserve the demineralized part. This prepared bovine tooth pieces in which nail burnish was applied to 2/3 of the enamel surface. Next, the next remineralization treatment was performed. In the remineralization treatment, the decalcified bovine teeth were continuously immersed in the remineralization solution shown in Table 5 below at 37 ° C. for 24 hours. After soaking, the bovine tooth pieces are collected and the nail varnish is peeled off. Then, a cross-section slice (about 150 μm) of the teeth is cut out, and the remineralization degree of each remineralization composition is determined according to the above “2. Method of TMR”. Evaluated by transversal microradiography (TMR) analysis. The mineral profile obtained from the TMR analysis was also evaluated. That is, the degree of demineralization and remineralization was evaluated from the microradiograph and mineral profile of the tooth cross section.

FIG. 6 shows the results of TMR analysis (that is, micrographs of X-ray imaging results; microradiograph). 6 (A) and 6 (B) show the results when a calcium lactobionate-containing remineralization solution is used, and FIG. 6 (C) and (D) show phosphorylated oligosaccharide calcium salt-containing remineralization. The result when using a solution is shown. Each DEM shows the result after the demineralization treatment but before the remineralization treatment (the portion that was decalcified but was protected with nail polish during the remineralization treatment), and REM shows the remineralization treatment. The result of the latter (the part which received the demineralization process and then the remineralization process) is shown.

  The mineral profile calculated from the result of the TMR analysis of FIG. 6 is shown in FIGS. FIG. 7 shows the remineralization treatment using calcium lactobionate-containing remineralization solution (the portion that was decalcified but protected with nail polish during the remineralization treatment) and the remineralization treatment. The mineral profile obtained by calculating from the TMR analysis after the calcification treatment (the portion subjected to the decalcification treatment and then the remineralization treatment) is shown.

  FIG. 8 shows a remineralization treatment when using a phosphorylated oligosaccharide calcium salt-containing remineralization solution (the portion that was decalcified but protected with nail polish during the remineralization treatment). And the mineral profile obtained by calculating from the TMR analysis after the remineralization treatment (the portion subjected to the demineralization treatment and then the remineralization treatment) is shown.

  In FIG. 6, the black portion is the background, and the tooth surface layer is white on the upper side, the lower side is gray, and the lower side is white. The thickness of the tooth piece is uniform, and the more calcium, the more difficult it is to transmit X-rays. That is, the calcium content of the portion can be known from the color tone of this photograph. From the photographs of FIGS. 6A and 6C, it can be seen that in the tooth pieces after decalcification, calcium remains on the surface layer of the tooth surface, but calcium is missing from the lower layer.

  When the thin lines indicating the demineralization process before remineralization in FIG. 7 are viewed, all of them are mineral when the depth of demineralization (relation depth, which indicates the distance from the tooth surface, that is, the sample position) is 0. Mineral loss (vol.%) Is about 15-25%, mineral amount% is almost constant or decreased until the sample position is about 20 μm, from which the mineral amount% increases. At first, when Ld is about 100 μm, the mineral amount% increases to about 60% or more. Thereafter, as the sample position deepens, the mineral amount% gradually increases to about 80%.

  7 and 8 after the remineralization treatment, the mineral amount% increased to at least about 40% in both cases of treatment with calcium lactobionate and treatment with phosphorylated oligosaccharide calcium. This can also be confirmed visually from the REM in FIG. In the REM of FIG. 6, the lower part of the tooth surface layer is considerably white.

Based on the following formula, the amount of mineral loss is calculated based on the standard substance, the mineral loss amount is calculated, and the mineral loss in the demineralized portion is taken as 100% loss. Calculated:
[{(Amount of mineral loss in demineralized portion) − (Amount of mineral loss in remineralized portion)} / (Amount of mineral loss in demineralized portion)] × 100 = Recovery rate (%)
The recovery rate of the demineralization depth (Resion depth) of the recalcification part was calculated based on the following formula:
[{(Demineralization depth of demineralization part) − (demineralization depth of remineralization part)} / (demineralization depth of demineralization part)] × 100 = recovery rate (%)
As a result, regarding the calcium lactobionate, the recovery rate of the demineralization depth (μm) was 4.8%, and the recovery rate of the mineral loss (vol% .μm) was 29.8%. For the phosphorylated oligosaccharide calcium salt, the recovery rate of demineralization depth (μm) was 23.9%, and the recovery rate of mineral loss (vol% .μm) was 36.2%. For substances without remineralization capacity, the recovery rate is usually about 0%. From this, it was confirmed that calcium lactobionate also has an excellent remineralization effect in the same manner as phosphorylated oligosaccharide calcium. Thus, it was found that calcium lactobionate can be effectively used as a calcium source for remineralization and as a material for promoting remineralization.

(Example 2: Production of calcium lactobionate-containing gum)
A center gum is prepared by mixing the ingredients shown in Table 6 below in accordance with a method commonly used in the art. Furthermore, this center gum was sugar-coated with the weight of the center gum: the weight of the sugar coating = 7: 3, and coated with a brightener (shellac) to obtain a sugar-coated gum. Maltitol was used as a sugar coating. When it is assumed that 20 mL of saliva comes out after chewing 2 grains of the center gum, the content of calcium lactobionate in 20 mL of saliva is about 4.68 mM as the calcium concentration. The weight per center gum is about 1 g. The gum has a good taste and flavor, with no lingering taste, and the taste and flavor of xylitol and mint oil are felt intact.

(Example 3: Production of candy containing calcium lactobionate)
According to a method commonly used in the art, a 60:40 weight ratio mixture of paratinite and reduced water candy is boiled to a moisture value of 1.8% by weight to obtain a candy base. A sugarless candy is prepared by adding and mixing the lactobionic acid calcium salt, flavor, and colorant to the candy base in the formulation shown in Table 7 below. The weight per candy is about 3.6 g. Assuming that the amount of saliva secreted when this candy is dissolved in the oral cavity is 20 mL, the content of calcium lactobionate in 20 mL of saliva is about 4.6 mM as the calcium concentration.

(Example 4: Production of calcium lactobionate-containing tablet)
Tablets are prepared by mixing the ingredients shown in Table 8 below according to the methods commonly used in the art. The weight per tablet is about 1 g. When it is assumed that the amount of saliva secreted when one tablet is dissolved in the oral cavity is 20 mL, the content of calcium lactobionate in 20 mL of saliva is about 4.6 mM as the calcium concentration.

(Example 5: Production of toothpaste)
A toothpaste is produced by mixing the materials shown in Table 9 below according to a method commonly used in the art. The used weight of this dentifrice is about 1 to 3 g. When the amount of saliva secreted when 2 g of this dentifrice is dissolved in the oral cavity is assumed to be 10 mL by brushing for 5 minutes, the content of calcium lactobionate in 10 mL of saliva is about 5.1 mM as the calcium concentration. is there.

(Example 6: Remineralization effect by various concentrations of calcium lactobionate)
In this example, the range in which calcium ions derived from calcium lactobionate can be used for remineralization in the presence of phosphoric acid and fluorine in an ionized state was examined.

  The saliva in the oral cavity is neutral. When using conventional calcium materials, calcium phosphate precipitates are likely to form between calcium and phosphoric acid, and calcium fluoride precipitates are likely to be formed between fluorine and calcium under the saliva in the mouth. . Therefore, when a general calcium material (for example, calcium chloride) is used, a remineralization effect is hardly obtained, and a tooth quality improvement effect by fluorine is hardly obtained. However, calcium contained in calcium lactobionate can coexist with phosphoric acid in an ionized state under neutral conditions. In the above examples, we used 3.6 mM phosphoric acid normally contained in saliva to facilitate remineralization to hydroxyapatite, which is the main component of tooth enamel, and the composition ratio of hydroxyapatite (Ca / P = 1.67) It was confirmed that calcium lactobionate 6 mM was supplied so as to remineralize. In this example, it was examined in what concentration range calcium CaF and fluorine or phosphoric acid can coexist in an ionized state for ratios other than Ca / P = 1.67. In this example, an experiment was conducted in accordance with a simple remineralization test method described in JP-A-2002-325557.

experimental method:
(1) Solutions were prepared so that the calcium concentration, phosphoric acid concentration and fluorine concentration of Nos. 1 to 12 described in Table 12 below were obtained. Next, various solutions of the apatite non-addition group A and the apatite addition group B were prepared according to the composition of Table 11 using this solution.

  (2) Each of the solutions prepared in (1) was reacted at 37 ° C. for 24 hours.

  (3) After 24 hours of reaction, the sample was centrifuged at 12000 rpm for 3 minutes.

  (4) In each case, 100 μl of 1N hydrochloric acid was added to 900 μl of the supernatant and stirred to obtain a measurement mixture.

  (5) Using the measurement mixture obtained in (4) as a sample, the calcium concentration and the phosphoric acid concentration were measured. Calcium E test Wako was used for the measurement of calcium concentration. Phospha C-Test Wako was used for measuring the phosphoric acid concentration.

(6) By subtracting the calcium concentration (C _addition ) of the supernatant after the reaction of the test tube of the corresponding apatite addition group from the calcium concentration (C _addition ) of the supernatant after the reaction of the test tube of the apatite non-addition group, The calcium concentration (C _available ) that can be used for remineralization was determined (C _non-added- C _added = C _available (concentrated)). The ratio of calcium available for remineralization was determined by dividing the concentration of calcium available for remineralization by the calcium concentration of the supernatant after reaction of the test tube of the apatite non-addition group and multiplying by 100 ( {(C _{not added-} C _added ) / C _{not added} } × 100 = C _available (%)). The results are shown in Table 12 below and FIGS.

Generally, the phosphate concentration in saliva is 2-6 mM. Assuming that the phosphate concentration in saliva is 3.6 mM, the calcium concentration at which Ca / P = 1.67 close to the hydroxyapatite composition is 6 mM (Experiment Nos. 1 to 4). Experiment No. As a result of 1-4, it was confirmed that calcium, phosphoric acid and fluorine were liberated at a fluorine concentration of 0 to 50 mM under the condition of Ca / P = 1.67. Therefore, it was confirmed that these liberated ions can be effectively used for remineralization and tooth quality improvement. Similarly, when using phosphoric acid (2 to 3.6 mM) in saliva, calcium, phosphoric acid, and fluorine are free when Ca / P = 1.67-3 and fluorine is 0-50 ppm. Was confirmed. Therefore, it was confirmed that these liberated ions can be effectively used for remineralization and tooth quality improvement.

(Example 7: Remineralization effect by various concentrations of calcium lactobionate)
The remineralization effect when the calcium concentration was 1.5 mM was examined in the same manner except that the composition described in Table 13 below was used instead of the composition described in Table 12. The results are shown in Table 13 below and FIGS.

As a result, when the calcium concentration is 1.5 mM and the ratio of calcium to phosphoric acid (Ca / P) is 0.50 to 3.00, calcium ions when the fluorine concentration is 0 to 100 ppm, It was confirmed that phosphate ions and fluoride ions can coexist as free ions. Therefore, it was confirmed that these liberated ions can be effectively used for remineralization and tooth quality improvement.

  When the results of Examples 6 to 7 are summarized, it is preferable that the ratio of calcium to phosphoric acid (Ca / P) is 1 to 3, and the concentration of added calcium (Ca) is preferably 1 mM or more and 10 mM or less. More preferably, it is 5 mM or more and 6 mM or less. Furthermore, the phosphate ion is preferably 0 mM or more and 6 mM or less, more preferably 2 mM or more and 5 mM or less. The fluorine concentration (F) is preferably 0 ppm or more and less than 100 ppm, and more preferably 0.5 ppm or more and 50 ppm or less. If the concentration of these ions is within this range, calcium ions, phosphate ions and fluoride ions can coexist in a neutral solution such as saliva in the oral cavity. Therefore, it is considered that a high remineralization effect and a tooth quality improvement effect can be obtained.

  As mentioned above, although this invention has been illustrated using preferable embodiment of this invention, this invention should not be limited and limited to this embodiment. It is understood that the scope of the present invention should be construed only by the claims. It is understood that those skilled in the art can implement an equivalent range based on the description of the present invention and the common general technical knowledge from the description of specific preferred embodiments of the present invention. Patents, patent applications, and documents cited herein should be incorporated by reference in their entirety, as if the contents themselves were specifically described herein. Understood.

  According to the present invention, it is possible to obtain a level of remineralization that could not be obtained conventionally.

FIG. 1 shows the time course of pH and soluble calcium (%) in a remineralization solution containing calcium lactobionate and a phosphate source compound. Black triangles indicate the time of crystal nucleus addition. White circles indicate the percentage (%) of soluble calcium (Ca ions (%)), and black circles indicate pH. FIG. 2 shows the time course of pH and the percentage of soluble calcium in a remineralization solution containing phosphorylated oligosaccharide calcium and a phosphate source compound. Black triangles indicate the time of crystal nucleus addition. White circles indicate the percentage (%) of soluble calcium (Ca ions (%)), and black circles indicate pH. FIG. 3 shows the time course of pH and the percentage of soluble calcium in a remineralization solution containing CaCl ₂ and a phosphate source compound. Black triangles indicate the time of crystal nucleus addition. White circles indicate the percentage (%) of soluble calcium (Ca ions (%)), and black circles indicate pH. FIG. 4 shows the time course of pH and percentage of soluble calcium in a remineralization solution containing sodium lactobionate, CaCl ₂ and a phosphate source compound. Black triangles indicate the time of crystal nucleus addition. White circles indicate the percentage (%) of soluble calcium (Ca ions (%)), and black circles indicate pH. FIG. 5 shows the time course of the pH and the percentage of soluble calcium in a remineralization solution containing phosphorylated oligosaccharide sodium, CaCl ₂ and a phosphate source compound. Black triangles indicate the time of crystal nucleus addition. White circles indicate the percentage (%) of soluble calcium (Ca ions (%)), and black circles indicate pH. FIG. 6 shows the results of tooth fragment analysis by TMR of the remineralization treatment when using a calcium salt containing calcium lactobionate or a calcium salt containing phosphorylated oligosaccharide calcium. DEM shows a microradiograph after demineralization treatment but before remineralization treatment (the portion that has been demineralized but was protected with nail polish during remineralization treatment), and REM represents the remineralization treatment. The microradiograph of the back (the part which received the demineralization process and then received the remineralization process) is shown. FIG. 6 (A) is a DEM microradiograph when a calcium lactobionate-containing remineralization solution is used. FIG. 6 (B) is a REM microradiograph when a calcium lactobionate-containing remineralization solution is used. FIG. 6 (C) is a DEM microradiograph when a phosphorylated oligosaccharide sodium-containing remineralization solution is used. FIG. 6 (D) is a REM microradiograph when using a phosphorylated oligosaccharide-containing remineralization solution. FIG. 7 shows a mineral profile obtained by calculation from TMR analysis before remineralization treatment and after remineralization treatment when using a calcium lactobionate-containing remineralization solution. Before remineralization treatment, it is the result of the part that was demineralized but was protected with nail polish at the time of remineralization treatment. It is the result of the part which received the remineralization process. The mineral profile before the remineralization treatment is indicated by a thin line, and the mineral profile after the remineralization treatment is indicated by a thick line. FIG. 8 shows the mineral profile calculated from the TMR analysis before and after the remineralization treatment when using the phosphorylated oligosaccharide calcium salt-containing remineralization solution. Before remineralization treatment, it is the result of the part that was demineralized but was protected with nail polish at the time of remineralization treatment. It is the result of the part which received the remineralization process. The mineral profile before the remineralization treatment is indicated by a thin line, and the mineral profile after the remineralization treatment is indicated by a thick line. FIG. 9 is a graph showing the calcium concentration that can be used for remineralization when the concentration ratio (Ca / P) of calcium and phosphoric acid by calcium lactobionate is 1.67 and the fluorine concentration is 0 to 50 ppm. The added fluorine concentrations are 0 ppm, 0.5 ppm, 5 ppm, and 50 ppm from the left. FIG. 10 is a graph showing the calcium concentration that can be used for remineralization when the concentration ratio (Ca / P) of calcium and phosphoric acid by calcium lactobionate is 2.0 and the fluorine concentration is 0 to 50 ppm. The added fluorine concentrations are 0 ppm, 0.5 ppm, 5 ppm, and 50 ppm from the left. FIG. 11 is a graph showing the calcium concentration that can be used for remineralization when the concentration ratio of calcium and phosphoric acid by calcium lactobionate (Ca / P) is 3.0 and the fluorine concentration is 0 to 50 ppm. The added fluorine concentrations are 0 ppm, 0.5 ppm, 5 ppm, and 50 ppm from the left. FIG. 12 is a graph showing the calcium concentration that can be used for remineralization when the concentration ratio of calcium and phosphoric acid by calcium lactobionate (Ca / P) is 0.5 and the fluorine concentration is 0 to 100 ppm. The added fluorine concentrations are 0 ppm, 0.5 ppm, 5 ppm, 50 ppm, and 100 ppm from the left. FIG. 13 is a graph showing the calcium concentration that can be used for remineralization when the concentration ratio of calcium and phosphoric acid by calcium lactobionate (Ca / P) is 1.0 and the fluorine concentration is 0 to 100 ppm. The added fluorine concentrations are 0 ppm, 0.5 ppm, 5 ppm, 50 ppm, and 100 ppm from the left. FIG. 14 is a graph showing the calcium concentration that can be used for remineralization when the concentration ratio (Ca / P) of calcium to phosphoric acid by calcium lactobionate is 1.67 and the fluorine concentration is 0 to 100 ppm. The added fluorine concentrations are 0 ppm, 0.5 ppm, 5 ppm, 50 ppm, and 100 ppm from the left. FIG. 15 is a graph showing the calcium concentration that can be used for remineralization when the concentration ratio of calcium and phosphoric acid by calcium lactobionate (Ca / P) is 2.0 and the fluorine concentration is 0 to 100 ppm. The added fluorine concentrations are 0 ppm, 0.5 ppm, 5 ppm, 50 ppm, and 100 ppm from the left. FIG. 16 is a graph showing the calcium concentration that can be used for remineralization when the concentration ratio of calcium and phosphoric acid by calcium lactobionate (Ca / P) is 3.0 and the fluorine concentration is 0 to 100 ppm. The added fluorine concentrations are 0 ppm, 0.5 ppm, 5 ppm, 50 ppm, and 100 ppm from the left.

Claims (20)

An anti-caries oral composition, the composition comprising:
A composition comprising (i) a lactobionic acid calcium salt; or (ii) a combination of a lactobionic acid salt or lactobionic acid other than the lactobionic acid calcium salt and a water-soluble calcium salt other than the lactobionic acid calcium salt.   The composition of claim 1 comprising the calcium lactobionic acid salt.   The calcium lactobionate content of the composition is such that when the composition is used in the oral cavity, the calcium concentration in the mixture of the composition in the oral cavity and saliva is 1.5 mM to 6 mM. 3. A composition according to claim 1 or 2 in an appropriate amount.   The composition according to any one of claims 1 to 3, further comprising a phosphate source compound.   The composition according to claim 4, wherein the phosphate source compound is selected from the group consisting of phosphoric acid, sodium phosphate, potassium phosphate, polyphosphoric acid and cyclic phosphate.   The composition according to any one of claims 1 to 5, further comprising a fluoride.   The fluorine content of the composition is an appropriate amount for the fluoride ion concentration in the mixture of the composition in the oral cavity and saliva when the composition is used in the oral cavity to be 50 ppm or less. The composition according to claim 6.   The composition according to any one of claims 1 to 7, which is used for treatment of initial caries.   The composition according to any one of claims 1 to 7, which is used for strengthening the tooth quality of a healthy person.   The composition according to any one of claims 1 to 9, which is a dentifrice, mouthwash, troche, or gel. An anti-cariogenic food, the food
(I) a lactobionic acid calcium salt; or (ii) a lactobionic acid salt or lactobionic acid other than a calcium lactobionic acid salt and a combination of a water-soluble calcium salt other than the lactobionic acid calcium salt, and the food is 5 minutes at the time of eating A food that stays in the mouth.   The food according to claim 11, which is a chewing gum, candy, tablet confectionery or frozen confectionery.   The food according to claim 11 or 12, comprising the calcium lactobionate salt.   The calcium lactobionate salt content of the food product is an amount suitable for the calcium concentration in the saliva in the oral cavity to be 1.5 mM to 6 mM when the food product is present in the oral cavity. Food described in.   The food according to any one of claims 11 to 14, further comprising a phosphate source compound.   16. The food product according to claim 15, wherein the phosphate source compound is selected from the group consisting of phosphoric acid, sodium phosphate, potassium phosphate, polyphosphoric acid and cyclic phosphate.   The food according to any one of claims 11 to 16, further comprising a fluoride.   The food according to claim 17, wherein the fluorine content of the food is an amount appropriate for the fluoride ion concentration in saliva in the oral cavity when the food is present in the oral cavity to be 50 ppm or less.   19. The food according to claim 11, wherein the food is chewing gum, and the weight of calcium lactobionate contained in a single intake is 1.2 mg to 4.8 mg as the weight of calcium. Food.   The food according to any one of claims 11 to 19, wherein the chewing gums are eaten 1 to 3 g at a time.