JP5586713B2 - Mineral solubilizer - Google Patents

Description

  The present invention relates to a composition comprising, as an active ingredient, maltobionic acid represented by the general formula of 4-O-α-D-glucopyranosyl-D-gluconic acid composed of glucose and gluconic acid, a salt thereof, or maltobiono delta lactone. Regarding functions and uses.

  Gluconic acid is a monosaccharide and has functionality such as bifidobacteria growth selectivity. It is contained in about 0.3% of honey and brewed vinegar and has a mild acidity of about 1/3 of citric acid. Have. Gluconic acid or its salts are widely used for salty taste replacement, masking effect, pH adjustment, shelf life improvement and the like. However, the solution stability is poor, and there is a drawback that it precipitates when stored at a high concentration.

  In addition, lactobionic acid, which is an aldonic acid disaccharide, is a disaccharide in which galactose and gluconic acid are combined. ) Is reported to have an effect of promoting mineral absorption, and can be produced from lactose as a raw material by chemical synthesis or oxidase.

  However, it is necessary to purify lactose as a raw material from whey discharged during the production of dairy products. In recent years, only countries that have been called advanced countries such as China and Southeast Asia, the former Eastern Europe, Central and South America, and the Middle East. In addition, the demand for dairy products from other regions has been increasing rapidly, so the demand for whey, a by-product that has been available at low prices, has been very strong. For this reason, it is not easy to secure lactose in Japan, which relies on imports, and it is difficult to stably and inexpensively supply it to general consumers.

  On the other hand, calcium is the fifth most abundant element in the human body, and it has physiologically important actions such as the formation of teeth and bones, blood coagulation, neuromuscular excitement, and enzyme activity in the body, and these are insufficient. It is widely known that it causes serious diseases such as osteoporosis, hypertension, and colon cancer. According to a report from the Ministry of Health, Labor and Welfare regarding Japanese nutrition surveys, calsim is the only essential nutrient that is less than the required amount. Therefore, various calcium agents have been developed.

  As calcium preparations used for the purpose of strengthening calcium, natural materials such as eggshell powder, coral powder, bone powder, and shell powder, and chemically synthesized products such as calcium carbonate and calcium chloride are known. Problems include low solubility and adverse effects on taste. As a technique for partially solving these problems, organic acid calcium salts such as calcium gluconate and calcium lactate are used as a highly soluble calcium material, but the solubility in water is not so high as to be satisfactory. In addition, the problem is that the dissolution rate in water is slow and the workability is poor. As typical examples of improving the solubility and dissolution rate of these calcium salts, the complex of calcium citrate and calcium malate described in JP-A-56-97248 (Patent Document 3), and Japanese Patent No. 2906215. There is a method of making a complex of calcium lactate and calcium gluconate described in the gazette (Patent Document 4), and this improved the solubility by about 3 to 5 times. However, the stability in the solution is not satisfactory, and precipitates when stored refrigerated. Therefore, there is a problem that it can be used only in a low concentration solution.

  In addition, calcium ascorbate is a highly soluble calcium material, but calcium ascorbate has a problem that urinary calculus is induced by excessive intake because the ascorbic acid portion is absorbed.

  In order to solve such a problem, a material with high solubility and high safety of calcium components contained in foods has been desired.

  Regarding maltobionic acid, there are several reports on the production method, such as microbial conversion and a method using a catalyst, but regarding the use, there is a taste described in JP-A-47-20372 (Patent Document 5). It is only about improvement, and there is no report about other uses and physiological functions of maltobionic acid and its salts.

  Furthermore, in recent years, lifestyle-related diseases such as hypertension, arteriosclerosis, and diabetes have become a national problem due to diversification of eating habits, and preventing obesity considered as one of these causes is a major issue. It has become. Since fat is greatly involved in this obesity, a food material that suppresses the rise of lipid in the blood is required.

  Traditionally, it has been known that dietary fibers such as pectin have an effect of improving lipid metabolism, but because of its high molecular weight, it has poor solubility and high viscosity, and its workability is poor, and its texture and flavor have changed. I had many shortcomings. As an improvement measure, there is a method disclosed in Japanese Patent Application Laid-Open No. 6-256198 (Patent Document 6) in which the viscosity is reduced by lowering the molecular weight of pectin. An inexpensive material that has little effect on feeling was desired.

  An object of the present invention is to provide a material capable of promoting the growth of useful bacteria in the intestine and suppressing the growth of harmful bacteria.

  Moreover, the objective of this invention is providing the raw material which can accelerate | stimulate absorption of minerals, such as calcium.

  In addition, the present invention provides a novel calcium agent and calcium liquid agent or substance that is superior in solubility (dissolution rate, storage stability) than conventional calcium agents and is expected to improve absorption in the body, and is easy to drink. It aims at providing the calcium supplement containing, a calcium fortifier, and a calcium drink.

  Furthermore, another object of the present invention is to provide a material that has good workability during food processing, has little effect on the texture, and can suppress an increase in blood lipids.

  On the other hand, in order to achieve these objects, an object of the present invention is to provide a material that is easily available and can be stably and inexpensively supplied to general consumers.

  Specifically, the present invention comprises a composition containing maltobionic acid, a salt thereof or maltobiono delta lactone as an active ingredient, an action for improving the intestinal environment of humans and other animals, a calcium absorption promoting action, The object is to provide foods and drinks, pharmaceuticals, quasi-drugs, health foods, feeds, feeds, and the like having functions such as an action of absorbing calcium koji and an effect of improving lipid metabolism.

  The present inventors searched for a substance having an intestinal environment improvement promoting activity, and as a result of intensive research, maltobionic acid represented by the general formula of 4-O-α-D-glucopyranosyl-D-gluconic acid, The salt or maltobiono delta lactone promotes the growth of useful bacteria such as bifidobacteria and lactic acid bacteria in the intestine, and also promotes the improvement of the intestinal environment by inhibiting the growth of harmful bacteria such as Clostridium bacteria. I found out. Further, the present inventors have found that salts such as calcium maltobionate have high solubility, promote mineral absorption, and have an action of improving lipid metabolism, thereby completing the present invention.

  Furthermore, the present inventors have obtained a calcium agent or liquid agent in which calcium maltobionate is immediately soluble and excellent in solubility, and does not precipitate even when stored refrigerated in a high-concentration solution, and is easy to drink. The present invention has been completed.

  On the other hand, maltobionic acid represented by the general formula of 4-O-α-D-glucopyranosyl-D-gluconic acid, which is an aldonic acid disaccharide like lactobionic acid, is maltose produced in Japan in large quantities. Since it is a raw material, it is inexpensive and very easy to obtain, so it can be stably and inexpensively provided to general consumers.

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

  First, intestinal environment characterized by containing maltobionic acid represented by the general formula of 4-O-α-D-glucopyranosyl-D-gluconic acid, a salt thereof or maltobiono delta lactone as an active ingredient It is an improving agent.

  Second, the maltobionate is at least one selected from sodium maltobionate, calcium maltobionate, magnesium maltobionate, potassium maltobionate, copper maltobionate, iron maltobionate, and zinc maltobionate. The intestinal environment improving agent described in 1.

  Third, mineral absorption promotion characterized by containing maltobionic acid represented by the general formula of 4-O-α-D-glucopyranosyl-D-gluconic acid, a salt thereof or maltobiono delta lactone as an active ingredient It is an agent.

  Fourth, the third maltobionate is at least one selected from sodium maltobionate, calcium maltobionate, magnesium maltobionate, potassium maltobionate, copper maltobionate, iron maltobionate and zinc maltobionate. Is a mineral absorption promoter.

  Fifth, calcium absorption promotion characterized by containing maltobionic acid represented by the general formula of 4-O-α-D-glucopyranosyl-D-gluconic acid, a salt thereof or maltobiono delta lactone as an active ingredient It is an agent.

  Sixth, the fifth maltobionate is at least one selected from sodium maltobionate, calcium maltobionate, magnesium maltobionate, potassium maltobionate, copper maltobionate, iron maltobionate and zinc maltobionate. Is a calcium absorption promoter.

  Seventh, it is a calcium absorption promoter characterized by using the composition according to the fifth or sixth above and one or more kinds of inorganic calcium or organic calcium salt in combination.

  Eighth, it is an easily absorbable calcium agent containing calcium maltobionate as an active ingredient.

  Ninth, it is an easily absorbable calcium agent containing calcium maltobionate and sugar or sugar alcohol.

  Tenth, improvement in lipid metabolism, comprising as an active ingredient maltobionic acid represented by the general formula of 4-O-α-D-glucopyranosyl-D-gluconic acid, a salt thereof or maltobiono delta lactone It is an agent.

  Eleventh, the maltobionate is at least one selected from sodium maltobionate, calcium maltobionate, magnesium maltobionate, potassium maltobionate, copper maltobionate, iron maltobionate and zinc maltobionate, 10. A lipid metabolism improving agent according to 10.

  Examples of the method for producing maltobionic acid or a salt thereof or a lactone thereof as an active ingredient of the present invention include a maltose oxidation method by a chemical oxidation reaction, a method of causing a microorganism having maltose oxidation ability or an oxidase to act, soluble starch or malto-oligo It can be produced by a transfer reaction with α-glucosidase or cyclodextrin synthase having high transfer ability to a substrate composed of sugar and gluconic acid.

  As a chemical oxidation reaction, a method is known which is obtained by catalytic oxidation of maltose and oxygen in an alkaline atmosphere in the presence of an oxidation catalyst in which palladium, platinum or bismuth is supported on activated carbon.

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

  As a production method by an enzymatic reaction, soluble starch is used by extracting oxidase from the microorganism having the oxidation ability, using cyclodextrin synthase having high transfer ability derived from Bacillus stearothermophilus or Thermoanaerobacter genus. Alternatively, it can be produced by a transfer reaction from a substrate composed of maltooligosaccharide and gluconic acid.

  Examples of the salt of maltobionic acid include alkali metal salts such as sodium salt and calcium salt, alkaline earth metal salts such as magnesium salt, and metal salts such as copper salt, iron salt and zinc salt.

  If an example of the manufacturing method by a chemical oxidation reaction is given, first, 3 g of 5% platinum carbon catalyst is added to 100 ml of 20% maltose solution kept at 50 ° C., and stirred at 600 rpm while blowing oxygen at 100 mL / min. The reaction pH is maintained at 9.0 by dropwise addition of 10N sodium hydroxide solution. After completion of the oxidation reaction, the catalyst can be removed by centrifugation and membrane filter filtration to obtain a sodium maltobionate solution.

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

  Maltobionate can be prepared by adding various salts to maltobionic acid, and maltobiono delta lactone can also be prepared by dehydration. In addition, maltobiono delta lactone quickly becomes maltobionic acid when dissolved in water.

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

  Calcium maltobionate is stable without being precipitated even in a solution state, and a powder product can be easily prepared by freeze-drying or spray-drying. If necessary, a crystallized powder can be prepared.

  The maltobionic acid represented by the general formula of 4-O-α-D-glucopyranosyl-D-gluconic acid prepared as described above, a salt thereof or maltobiono delta lactone has the following properties.

(1) Calcium maltobionate has a room temperature dissolution stability 30 times or more that of calcium gluconate.

(2) Maltobionic acid, a salt thereof, or maltobiono delta lactone has the ability to enhance the dissolution stability of a sparingly soluble inorganic salt or organic salt.

(3) Maltobionic acid, a salt thereof or maltobiono delta lactone is indigestible and difficult to digest with in vivo enzymes.

(4) Maltobionic acid, a salt thereof or maltobiono delta lactone has intestinal bacterial growth selection ability and has an intestinal environment improvement promoting activity.

(5) Maltobionic acid, a salt thereof or maltobiono delta lactone has an effect of improving lipid metabolism.

(6) The calcium maltobionate solution maintains a stable solution state without precipitation even when stored in a refrigerator at a concentration of 70%.

(7) Calcium maltobionate has a significantly faster dissolution rate than calcium gluconate.

(8) Calcium maltobionate has a weaker bitter taste than calcium gluconate.

(9) Calcium maltobionate has high heat stability and pH stability.

  Maltobionic acid represented by the general formula of 4-O-α-D-glucopyranosyl-D-gluconic acid of the present invention, a salt thereof or maltobiono delta lactone is hardly absorbed in the digestive tract by oral ingestion, most of which Reaches the large intestine, proliferates useful bacteria such as bifidobacteria and lactic acid bacteria in the intestinal bacterial phase, and selectively inhibits harmful bacteria such as Clostridium.

  In addition, selective growth of enteric bacteria produces organic acids such as acetic acid, butyric acid, and propionic acid to lower the pH in the large intestine and selectively inhibit harmful bacteria such as Clostridium.

  Furthermore, since the maltobionic acid salt or maltobiono delta lactone of the present invention is indigestible, after reaching the large intestine like indigestible oligosaccharides such as fructooligosaccharides, it is affected by intestinal bacterial feces. By tilting the pH of the large intestine to the acidic side, it increases the solubility of easily deficient minerals such as calcium, magnesium, iron, and zinc in the large intestine region and promotes their absorption, so it is also effective as a mineral absorption promoter. is there.

  Maltobionate has higher solubility in water than gluconate. For example, since calcium maltobionate has a room temperature solubility 30 times or more that of calcium gluconate, the calcium absorption rate is increased in the small intestine, which is the main absorption site of calcium. Therefore, it can be used more advantageously as a calcium easy-absorbing agent, and is expected to contribute to the prevention and improvement of serious diseases such as osteoporosis, hypertension, and colon cancer.

  Similarly, maltobionates such as iron, magnesium, and zinc are more soluble in water than gluconate, so they can be used more advantageously as easy absorbants, contributing to hormone regulation, cardiovascular disease prevention, and anemia prevention. Is expected to do.

  In addition, due to such room temperature solubility of calcium maltobionate, it does not precipitate even when refrigerated and stored at a concentration of 70%, so that it can be distributed as a calcium high-concentration solution that could not be produced conventionally.

  On the other hand, even in a powder state, the solubility is higher and the dissolution rate is faster than calcium materials such as calcium gluconate, so that it can be put into the solution without worrying about powdering or solution temperature.

  Other maltobionic acid and calcium maltobionate that have low solubility and poor storage stability Calcium carbonate, calcium chloride, whey calcium, calcium lactate, calcium gluconate, calcium citrate, calcium acetate, calcium fluoride, monobasic calcium phosphate By using in combination with dicalcium phosphate, tricalcium phosphate, calcium pyrophosphate and the like, the dissolution stability thereof is maintained.

  The calcium may be added in the form of natural products containing, for example, livestock such as cattle bones, pork bones and chicken bones, poultry bone meal, eggshells, shells, salmon and whey.

  The maltobionic acid represented by the general formula of 4-O-α-D-glucopyranosyl-D-gluconic acid of the present invention, a salt thereof or maltobiono delta lactone does not affect HDL cholesterol which is a good blood. It has the effect of improving lipid metabolism, which lowers the bad LDL cholesterol and VLDL cholesterol concentrations, and is expected to have the effect of preventing, treating or improving hyperlipidemia, obesity and the like. It is also expected to contribute to the prevention and improvement of complications associated therewith, such as cardiovascular system such as arteriosclerosis and hypertension, lifestyle-related diseases such as breast cancer and colon cancer.

  Therefore, maltobionic acid represented by the general formula of 4-O-α-D-glucopyranosyl-D-gluconic acid of the present invention, its salt or maltobiono delta lactone is maintained for beauty and health regardless of gender. It can be effectively used for promotion, adult disease prevention, during and after the disease, promotion of recovery after illness, treatment and prevention of osteoporosis and the like.

  It is also effective in domestic animals such as pigs and cattle, birds such as chickens and ostriches, fish such as eel and Thailand, and is used for the purpose of preventing infection, promoting fattening, suppressing malodor of faeces, and promoting mineral absorption. Is possible.

  The various properties of maltobionic acid represented by the general formula of 4-O-α-D-glucopyranosyl-D-gluconic acid of the present invention, salts thereof, or maltobiono delta lactone are: It can be advantageously used in various compositions such as external products, health foods, feeds, and feeds. In particular, it is possible to produce various compositions by containing these together with one or more components selected from syrup, sugar alcohol, mineral and sucrose.

  For example, the various properties of the calcium maltobionate of the present invention can be advantageously used in various compositions such as foods and drinks, taste products, pharmaceuticals, quasi drugs, health foods, feeds, and feeds. One or more of these selected from sweeteners and minerals such as glucose, maltose, trehalose, fructose, isomerized sugar, flour, honey, maple sugar, sorbitol, maltitol, lactitol, stevioside, sucralose, acesulfame K, etc. It is also possible to produce various compositions by containing them together with the components. If necessary, it can be mixed with a bulking agent such as dextrin, starch, lactose and the like.

  Since maltobionic acid represented by the general formula of 4-O-α-D-glucopyranosyl-D-gluconic acid of the present invention exhibits about half the acidity of gluconic acid, it can also be used effectively as an acidulant. . In addition, it blends well with various other substances with other tastes such as sweet taste, salty taste, astringency, umami taste, and bitter taste, and has high heat resistance and acid resistance, so acidification, taste improvement and quality improvement of general food and drink It is possible to use it.

  In addition, the calcium maltobionate of the present invention has less bitterness than other calcium materials, and has high heat stability and pH stability and low Maillard properties. It is possible to use.

  The food and beverage composition of the present invention is a generic term for human food, animal or fish feed, and pet food. In other words, beverages such as Japanese tea, oolong tea, tea, coffee, tea, juice, processed milk, sports drinks, bakery items such as bread, pizza, pie, confectionery items such as cookies, crackers, biscuits, cakes, castella, udon Noodles such as soba and ramen, pasta such as spaghetti and macaroni, snacks such as rice cake, potato chips and snacks, confectionery such as hard candy, soft candy, caramel, gum and chocolate, frozen confectionery such as ice cream and sorbet Dairy products such as cream, cheese, mousse, powdered milk, condensed milk, milk beverages, Western confectionery such as jelly, pudding, mousse, yogurt, butter cream, custard cream, fertilizer, uirou, mochi, rice cake, dorayaki Kind, jam, marmalé Processed fruits and vegetables such as pickles, syrup, sugar cane, pastes such as flower paste, fruit paste, peanut paste, pickles such as raccoon pickles, Fukujin pickles, kimchi, soy sauce, sauce, sauce, noodle soup, Compound seasonings such as soup stock, soup base, stew base, soup base, curry base, mayonnaise, ketchup and other retort or canned food such as curry, stew, soup, ham, sausage, Includes frozen and refrigerated foods such as bacon, hamburger, meatballs, croquettes, dumplings, pilaf, rice balls, seafood processed foods such as chikuwa and kamaboko, and cooked rice such as risotto and sushi. Furthermore, infant milk, baby food, baby food, pet food, pet gum, animal feed, sports food, nutritional supplement, health food, and the like are also included.

  The composition of the present invention may be formulated into an appropriate dosage form and used. For example, it can be used in preparations such as tablets, powders, granules, capsules, troches, chewables, solutions, syrups, enteral nutrients, swallows and the like.

  More specifically, the maltobionic acid of the present invention, a salt thereof or maltobiono delta lactone is mixed with a bulking agent, an excipient, a binder and the like to form granules, spheres, short bars, plates, legislature, It can be used in various shapes such as tablets, capsules, troches, chewables.

The figure showing the time-dependent change of blood calcium concentration.

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

[Preparation Example 1]
Preparation of maltobionic acid

  9 g of 5% palladium carbon (manufactured by Kawaken Fine Chemical Co., Ltd.) was added to 1000 ml of 30% maltose solution (manufactured by Sanei Saccharification Co., Ltd.). After maintaining this solution at 40 ° C., the reaction was started at 1.0 L / min air and a rotation speed of 600 rpm. A 20% sodium hydroxide solution was continuously added to maintain the reaction pH at 9.0. Six hours after the reaction, the reaction solution containing the catalyst was centrifuged and filtered through a 0.2 μm membrane filter to obtain a sodium maltobionate solution. This solution was desalted by passing it through a column filled with 2 L of a strongly acidic cation exchange resin (manufactured by Dow Chemical Co., Ltd., trade name “DOWEX-88”). Next, a column packed with 200 ml of a mixed resin of 200 ml of weakly basic anion exchange resin (trade name “WA30” manufactured by Mitsubishi Chemical Co., Ltd.) and 200 ml of strongly acidic cation exchange resin (trade name “DOWEX-88” manufactured by Dow Chemical Co., Ltd.) Subsequently, after passing through a column filled with 200 ml of granular activated carbon (manufactured by Takeda Pharmaceutical Co., Ltd., granular white rice cake) in order, decolorization was performed, and then 285 g of maltobionic acid powder was obtained by vacuum concentration and lyophilization.

[Preparation Example 2]
Preparation of calcium maltobionate, zinc maltobionate, magnesium maltobionate, copper maltobionate

  After dissolving 30 g of maltobionic acid powder obtained in Preparation Example 1 in 100 ml of distilled water, calcium carbonate, zinc oxide, magnesium oxide and copper carbonate were added to the maltobionic acid in a molar ratio of 2: 1, The mixture was stirred at 50 ° C. for 2 hours. The solution after completion of the reaction was filtered through a 0.2 μm filter and freeze-dried to obtain calcium maltobionate, zinc maltobionate, magnesium maltobionate, and copper maltobionate powder samples.

[Preparation Example 3]
Preparation of sodium maltobionate and potassium maltobionate

  After dissolving 30 g of maltobionic acid powder obtained in Preparation Example 1 in 100 ml of distilled water, sodium hydroxide and potassium hydroxide were respectively added so as to have a molar weight ratio of 1: 1 with respect to maltobionic acid. Stir for hours. The solution after completion of the reaction was filtered with a 0.2 μm filter and freeze-dried to obtain sodium maltobionate and potassium maltobionate powder samples.

[Preparation Example 4]
Preparation of maltobiono delta lactone

  100 ml of acetone was added to 5 g of the maltobionic acid powder obtained in Preparation Example 1, and concentration was performed using an evaporator. By repeating this operation several times, dehydration was performed to obtain about 4 g of maltobiono delta lactone.

  Digestion test

  The in vitro tests shown below were performed by partially modifying the method reported by Okada et al. In the Journal of the Japan Society for Nutrition and Food, Vol. 43, No. 1, pages 23-29 (1990). The degree of digestion of calcium maltobionate and sodium maltobionate prepared in Preparation Examples 2 and 3 was evaluated by measuring the amount of maltobionate remaining by HPLC analysis. Moreover, it tested similarly using the maltose and maltitol as a comparative example, the sodium maltotrionate prepared by the method similar to the preparation examples 1 and 3, sodium maltotetraonate, and sodium maltopentanoate.

(1) Digestibility by human salivary α-amylase

  1 ml of human saliva α-amylase (40 units / ml) was added to 5 ml of 10% sample (50 mM maleate buffer containing 1 mM calcium chloride, pH 6.0), and reacted at 37 ° C. for 30 minutes.

(2) Digestibility by artificial gastric juice

  2 ml of 50 mM HCl-KCl buffer (pH 2.0) was added to 4 ml of 2.2% sample and reacted at 37 ° C. for 100 minutes.

(3) Digestibility by porcine pancreatic α-amylase

  To 5 ml of 1% sample (50 mM maleate buffer containing 1 mM calcium chloride, pH 6.6), 0.5 ml of porcine pancreatic α-amylase (20 units / ml) was added and reacted at 37 ° C. for 6 hours.

(4) Digestibility by rat small intestinal mucosal enzyme

  1 ml of rat small intestinal mucosal enzyme (3.8 units / ml) (manufactured by Sigma) was added to 5 ml of 1% sample (50 mM maleate buffer, pH 6.6), and reacted at 37 ° C. for 3 hours.

  As is apparent from the results in Table 1, sodium maltotrionate and sodium maltotetraonate were well degraded by small intestinal mucosal enzymes, and the degradation products were glucose and maltobionic acid. On the other hand, the maltobionic acid of the present invention is only slightly degraded by small intestinal mucosal enzymes like maltitol, which is an indigestible saccharide, so that most of it will reach the large intestine when taken orally. It is done.

  Assimilation test by intestinal bacteria

  Using the maltobionic acid, calcium maltobionate and sodium maltobionate obtained in Preparation Examples 1 to 3, the assimilation property of intestinal bacteria was evaluated. In the preculture, each of the bacteria shown in Table 2 was precultured overnight in GAM bouillon (Nissui Pharmaceutical). The main culture is a medium containing 0.5% of each sugar sample (1.0% polypeptone (manufactured by Nippon Pharmaceutical), 0.5% meat bouillon (manufactured by Kyokuto Pharmaceutical), 0.5% yeast extract (manufactured by Asahi Breweries), After autoclaving 0.3% dipotassium hydrogen phosphate (manufactured by Kanto Chemical Co., Ltd., 0.1% Tween 80 (manufactured by Kanto Chemical Co.) at 121 ° C. for 20 minutes, 1% sodium ascorbate (manufactured by Kanto Chemical Co., Ltd.) as a reducing agent, 10 μl of the preculture solution was inoculated into 2 ml of a medium supplemented with 0.05% L-cysteine hydrochloride solution (manufactured by Wako Pure Chemical Industries), and anaerobic culture was performed at 37 ° C. for 3 days. The turbidity of the post-culture liquid was determined by subtracting the turbidity of the culture liquid when cultivated without adding a sugar sample from the absorbance at 660 nm, and the degree of intestinal bacterial growth was determined. .

  Moreover, glucose, maltose, maltitol, gluconic acid, sodium gluconate, and calcium gluconate were used as comparative examples.

  As apparent from the results in Table 2, maltobionic acid and its salts showed high growth selectivity for other saccharides. In other words, it has been found that it promotes the growth of useful bacteria such as bifidobacteria and lactic acid bacteria, and at the same time hardly or hardly assimilates to Bacteroides and Eubacterium, which are the most dominant bacterial groups in the adult intestine, and Clostridium, which is a harmful bacteria.

  Effects on mouse intestinal feces and cecal contents

  Using the calcium maltobionate obtained in Preparation Example 2, the effect on the intestinal feces and cecum contents of mice was evaluated. The purified feed based on the AIN93G feed composition was used as a control, and the feed obtained by replacing the pregelatinized corn starch of this feed composition with calcium maltobionate (5% w / w per feed solid content) was added to mice (BALB / c, 5 weeks old, (♀, Japan SLC) 2 groups 6 animals were ingested freely. Two weeks after the start of administration, the blood was lethal to death, and then the cecum containing the contents was collected. DNA was extracted from the cecum contents, and the numbers of lactic acid bacteria and bifidobacteria were counted by real-time PCR. Furthermore, the organic acid composition in the cecal contents was analyzed using HPLC.

  As a result, as is apparent from Table 3, the administration of calcium maltobionate increases the cecal content and the weight of the cecal wall compared to the case where calcium maltobionate is not administered, and thus acetic acid, butyric acid, and propionic acid affect the bioregulatory function. An increase in was observed. A significant increase in bifidobacteria and lactic acid bacteria in feces was also observed.

  From the above results, it was found that the intestinal environment was significantly improved by administration of calcium maltobionate.

  Effects on lipid metabolism in mice

  Using maltobionic acid obtained in Preparation Example 1 and calcium maltobionate obtained in Preparation Example 2, the effect on lipid metabolism in mice was evaluated.

  As in Example 3, a purified feed based on the AIN 93G feed composition was used as a control, and a feed obtained by replacing the pregelatinized corn starch of this feed composition with maltobionic acid and calcium maltobionate (5% w / w per feed solid) was added. Two groups of 6 mice (BALB / c, 5 weeks old, rabbit, Japan SLC) were allowed to ad libitum. Two weeks after the start of administration, blood was collected from the jugular vein under ether anesthesia, and total cholesterol in serum was cholesterol E-test Wako (manufactured by Wako Pure Chemical Industries), and HDL cholesterol was HDL-cholesterol E-test Wako (manufactured by Wako Pure Chemical Industries, Ltd.). ) And the amounts of HDL and LDL + VLDL were calculated.

  As a result, as is apparent from Table 4, HDL, which is a good cholesterol in the group with maltobionic acid and calcium maltobionate, hardly changes from the control group, whereas it is significantly suppressed with LDL + VLDL, which is a bad cholesterol. It was revealed.

  Solubility test of calcium maltobionate

  The water solubility was evaluated using calcium maltobionate obtained in Preparation Example 2.

  Calcium maltobionate was added to 100 ml of distilled water maintained at 20 ° C. and stirred with a magnetic stirrer to determine the limit solubility. For comparison, calcium carbonate (manufactured by Wako Pure Chemical Industries), calcium citrate (manufactured by Fuso Yakuhin Kogyo), calcium gluconate monohydrate (manufactured by Fuso Yakuhin Kogyo), and calcium lactate pentahydrate (manufactured by Fuso Yakuhin Kogyo) Using.

  As a result, in the case of calcium maltobionate, 130 g / 100 ml or more, 34 times or more of calcium gluconate, 300 times or more of calcium citrate, a high solubility was obtained.

  Calcium maltobionate dissolution rate test

  The dissolution rate was evaluated using the calcium maltobionate obtained in Preparation Example 2.

  1 g of calcium maltobionate was added to 100 ml of distilled water at 25 ° C. and stirred with a magnetic stirrer to determine the dissolution rate. For comparison, calcium lactate pentahydrate (manufactured by Fuso Yakuhin Kogyo) and calcium gluconate monohydrate (manufactured by Fuso Yakuhin Kogyo) were used.

  As a result, calcium maltobionate was completely dissolved about 130 times faster than calcium gluconate.

  Calcium maltobionate solution refrigerated storage stability test

  Using the calcium maltobionate obtained in Preparation Example 2, the refrigerated storage stability of the solution was evaluated.

  The state of the solution when the calcium maltobionate solution prepared to each concentration was stored refrigerated was observed. For comparison, calcium lactate pentahydrate (manufactured by Fuso Yakuhin Kogyo) and calcium gluconate monohydrate (manufactured by Fuso Yakuhin Kogyo) were used.

  As a result, calcium gluconate and calcium lactate used for comparison were precipitated, whereas calcium maltobionate maintained the solution state without precipitation even at a concentration of 70%.

  Calcium maltobionate solution stability test

  Solution stability was evaluated using calcium maltobionate obtained in Preparation Example 2.

  Various samples were weighed into a 2.0 ml microtube according to the formulation shown in Table 8, and 25 ° C. distilled water was added to make 1 ml, followed by stirring for 5 minutes with a VORTEX mixer. After confirming the solubility at this time, the solution was heated and dissolved in a boiling liquid for 10 minutes. The dissolution stability when stored at 4 ° C. was visually evaluated. For comparison, calcium lactate pentahydrate (manufactured by Fuso Yakuhin Kogyo) and calcium gluconate monohydrate (manufactured by Fuso Yakuhin Kogyo) were used.

  As a result, the solubility at room temperature was 50 mg / ml for calcium gluconate and 100 mg / ml for calcium lactate, whereas calcium maltobionate rapidly dissolved even at 500 mg / ml.

  Moreover, compared with the calcium lactate and calcium gluconate mixed product, the result with higher maltobionic acid and calcium lactate or calcium gluconate mixed product was obtained in both dissolution rate and solubility.

  As for refrigerated storage stability after heating and dissolving, both calcium maltobionate alone and calcium lactate or calcium gluconate mixture maintained a transparent solution state without precipitation. On the other hand, precipitation was observed from about 100 mg / ml in calcium gluconate and calcium lactate, and precipitation was also observed in these mixed products.

  From the above results, it can be said that calcium maltobionate is a material having very excellent solution stability compared to other calcium materials.

  Calcium solubility test of maltobionic acid and maltobiono delta lactone

  Calcium solubility was evaluated using the maltobionic acid and maltobiono delta lactone obtained in Preparation Examples 1 and 4.

  To a 2.0 ml microtube, 500 μl of a 10 mM calcium carbonate solution was added to 500 μl of a 5% (w / w) sample solution (maltobionic acid, maltobiono delta lactone, maltose) and shaken at 37 ° C. for 1 hour at 130 rpm. After filtering this with a 0.2 μm filter, the amount of calcium solubilized in the solution was measured with Calcium C-Test Wako (manufactured by Wako Pure Chemical Industries). For comparison, maltose was used.

  As a result, calcium carbonate was 9.5% soluble in maltose solution, whereas maltobionic acid and maltobiono delta lactone were 100% solubilized.

  Calcium solubility test of maltobionates

  The solubility of calcium materials was evaluated using the calcium maltobionate, zinc maltobionate, magnesium maltobionate, copper maltobionate, sodium maltobionate, and potassium maltobionate obtained in Preparation Examples 2 and 3.

  A 100 ml solution was prepared in a 200 ml beaker at the blending ratio shown in Table 10, and then stirred at 37 ° C. for 30 minutes with a magnetic stirrer. The supernatant was removed by centrifugation, and the precipitate was freeze-dried to determine the solubilization rate.

  As a result, compared with calcium gluconate alone, the solubilization amount of calcium increased by about 20% by adding maltobionates.

  From these results, it was found that maltobionates have the effect of increasing the solubility of other calcium materials.

  Effects on calcium absorption in mice

  The effects of maltobionic acid and calcium maltobionate obtained in Preparation Examples 1 and 2 on calcium absorption in mice were evaluated.

  For the experiment, 6-week-old ddY female mice (Japan SLC) were fasted overnight and used. Only deionized water was given during the test period. The mice were divided into 3 groups of 5 per group, 5 mmol / kg body weight calcium maltobionate for group I, 5 mmol / kg body weight maltobionic acid and 5 mmol / kg body weight calcium carbonate for group II, III Each group was orally administered 5 mmol / kg body weight of calcium carbonate. Blood was collected from the tail vein before administration and at 15, 30, 60, and 120 minutes after administration. The calcium concentration in the blood was measured using Calcium C-Test Wako (manufactured by Wako Pure Chemical Industries). A t-test was used to compare the mean values between the two groups, and a case where p <0.05 was determined to be significant.

  FIG. 1 shows the time course of blood calcium concentration in both groups. The blood calcium concentration tended to be higher at 30 minutes after administration in the calcium maltobionate administration group and the group to which maltobionic acid and calcium carbonate were administered at the same time, and showed a significantly higher value after 60 minutes. . Further, in the area under the time curve shown in Table 11, the calcium maltobionate administration group and the maltobionic acid and calcium carbonate administration group showed significantly higher values than the calcium carbonate administration group.

  Dissolution stability and taste test of calcium maltobionate

  Calcium-fortified beverages were prepared at the blending ratios shown in Table 12, and the solubility at room temperature was confirmed. The sample solution was evaluated for precipitation after storage at 4 ° C. for 1 week after dissolution by heating. Moreover, about taste quality, 4-step evaluation was performed by the sensory test by 10 panelists.

  As a result, in the calcium maltobionate addition section of the present invention 1-5, all dissolved rapidly at room temperature, and maintained a transparent solution state even after refrigerated storage. On the other hand, in Comparative Examples 6 to 10 using calcium gluconate and calcium lactate, none was dissolved at room temperature. In addition, when calcium gluconate was added to a calcium content of 1%, precipitation was observed during refrigerated storage, and refrigerated storage was stable up to a calcium content of 1.5% due to complexation with calcium lactate. In 2%, precipitation was observed.

  As for the taste quality, all of the beverages of Comparative Examples 6 to 10 in which calcium lactate and calcium gluconate were blended felt strong bitterness, but almost no bitterness was felt in the calcium maltobionate-added beverage.

  From the above results, it was found that calcium maltobionate can be contained in a high amount of calcium without affecting the taste quality as compared with existing organic acid calcium materials.

Japanese Patent No. 3559063 Japanese Patent No. 3501237 JP-A-56-97248 Japanese Patent No. 2906215 JP 47-20372 A JP-A-6-256198

Claims (3)

  A mineral-solubilizing stabilizer comprising, as an active ingredient, maltobionic acid represented by a general formula of 4-O-α-D-glucopyranosyl-D-gluconic acid, a salt thereof, or maltobiono delta lactone.   The mineral according to claim 1, wherein the maltobionate is at least one selected from sodium maltobionate, calcium maltobionate, magnesium maltobionate, potassium maltobionate, copper maltobionate, iron maltobionate and zinc maltobionate. Solubilizing stabilizer. The mineral solubilization stabilizer according to claim 1 or 2, wherein the mineral is calcium .

Images