JP2007153807A - Iron absorption promoter - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an iron absorption-promoting composition having iron absorption-promoting action, an iron agent and an iron-enriched food or beverage as a food or a beverage, a health food or a medicine for improving anaemia and the like and to provide a method for producing the iron-enriched food or beverage. <P>SOLUTION: The present invention provides an oral iron absorption-promoting composition containing nicotianamine as an active ingredient, and a food or beverage and a medicines each containing a chelate substance of nicotianamine-iron compound or a mixture of nicotianamine with an iron compound as an active ingredient and each having iron absorption-promoting action and provides a method for producing those and applies them for improvement of symptom of anaemia, etc., and as an oral iron absorption promoter and an oral iron agent after blood donation, after operation and after delivery. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to an iron absorption promoting composition containing nicotianamine as an active ingredient, an iron agent having a good absorbency formed by simply mixing nicotianamine and an iron compound, or chelating these, and an iron-reinforced food or drink. .

  In the case of iron deficiency, it is recommended to take heme iron contained in liver or the like, or to take foods with many components that promote absorption of iron such as vitamin C and cysteine. Iron is a trace element that is difficult to solubilize at the pH in the environment of the digestive tract and difficult to be absorbed from the digestive tract. Therefore, even if a large amount of iron is ingested orally, most of the ingested iron component remains as it is outside the body. Since it is discharged, a material that promotes absorption of iron from the digestive tract has been desired. Moreover, although it is thought that a female woman needs more iron components than an adult man, it is thought that the amount of iron components ingested by women is lower than that required for men. Therefore, it has been desired to develop iron-enriched foods and beverages and iron absorption promoters that have good absorbability as health foods and drugs for improving anemia.

  On the other hand, nicotianamine is known to have a blood pressure lowering action because it has an angiotensin converting enzyme inhibitory action. It is known that nicotianamine is widely distributed in the plant kingdom such as tobacco, rice, wolfberry, beech, kidney beans, soybean, noni, and can be obtained from this plant (for example, see Non-patent Document 1 and Patent Document 1).

  As for nicotianamine present in kidney beans and soybeans, a method of purifying a liquid obtained by extracting the nicotianamine with water or hot water using a synthetic resin is known (for example, see Patent Document 2). In addition, a method is known in which a precipitate is produced by adding an organic solvent to soybean aqueous extract or soybean whey produced as a by-product in the production of separated soybean protein, and nicotianamine is obtained at a high concentration from the precipitate ( For example, see Patent Document 3 and Patent Document 4). In addition, methods for obtaining nicotianamine from rice roots, noni, and the like are known (see, for example, Patent Document 5 and Patent Document 6). A method for producing nicotianamine by a synthetic method has also been developed (see, for example, Patent Document 7).

Tetrahedron Lett. , No. 22, 2017-2020 (1971) JP 63-87990 A JP-A-5-246865 JP 2002-179647 A JP 2003-231675 A JP-A-2005-51519 JP 2003-55248 A JP 2004-277317 A

  The present invention provides an iron absorption promoting composition having an iron absorption promoting effect, an iron preparation, an iron-reinforced food and drink, and a method for producing an iron-reinforced food and drink as foods and drinks, health foods and pharmaceuticals for improving anemia. It is what.

  As a result of intensive studies to solve the above problems, the present inventor has found that nicotianamine has an excellent iron absorption promoting action, and a mixture of nicotianamine and an iron compound, and a nicotianamine-iron compound chelate with blood iron The effect of increasing the concentration was found and the present invention was completed.

Therefore, the present invention
(1) Iron absorption promoting composition containing nicotianamine as an active ingredient (2) Iron agent containing nicotianamine and iron compound (3) Iron compound is iron chloride, ferrous sulfate, ferrous citrate, ammonium iron citrate Succinic acid, sodium iron citrate, iron lactate, chondroitin iron sulfate, ferrous fumarate, and iron pyrophosphate, the iron agent according to (2) above, wherein the iron agent is nicotianamine And the iron agent according to any one of the above (2) or (3), which is formed by simply mixing the iron compound and the iron compound (5) above (2) to (4) Iron-enriched food or drink containing the iron agent according to any one of (6) In the method for producing an iron-enhanced food or drink in which an iron compound is added to the food or drink, nicotianamine and an iron compound are chelate-bonded A method for producing an iron-reinforced food or drink characterized by using (7) A method for producing an iron-reinforced food or drink obtained by adding an iron compound to a food or drink, wherein nicotianamine and an iron compound are added to the food or drink, The present invention relates to a method for producing an iron-reinforced food or drink characterized in that a chelate of iron compound is produced.

  The present invention relates to an iron absorption promoting composition comprising nicotianamine as an active ingredient, and a pharmaceutical, food and drink having an iron absorption promoting action containing a mixture of nicotianamine and an iron compound, or a chelate of nicotianamine-iron compound as an active ingredient, and the same The present invention provides a production method, and exhibits effects such as improvement of symptoms such as anemia, and an iron absorption promoter or iron agent after blood donation, post-surgery and postpartum. Since the iron absorption promoting composition and iron preparation of the present invention can remarkably improve iron absorbability, they are suitable as foods, drinks, health foods, and pharmaceuticals for improving anemia.

(1) Manufacturing method of nicotianamine The nicotianamine used in the present invention includes, for example, JP-A-5-246865, JP-A-2002-179647, JP-A-2003-231675, JP-A-2003-55248, JP-A-2004-277317. In accordance with conventional methods, separation and purification from extracts extracted from natural products such as beans such as soybeans and kidney beans, tomatoes, noni, buckwheat and other relatively nicotianamine extracted materials. It may be synthesized, chemically or enzymatically synthesized, or produced by a microorganism.

  As long as it has an iron absorption promoting action, as the nicotianamine used in the present invention, a nicotianamine-containing product can be used in addition to a highly purified product. For example, soybean processed foods such as soy sauce, miso, tofu, natto, and soy milk produced using soybean as a raw material, and water or heat of soybeans produced as a by-product in a large amount in the manufacturing process of the processed soybean food and discarded as waste liquid A significant amount of nicotianamine is contained in the immersion waste liquid and the steaming waste liquid (Japanese Patent Laid-Open No. 5-246865).

  As a method for extracting and concentrating nicotianamine from food and waste liquid containing nicotianamine, for example, soy be immersed in 2 to 20 times the amount of water and allowed to stand for 1 hour to 2 days while warming at room temperature to 80 ° C. Water may be distilled off after stirring and circulation as necessary. Conditions such as the amount of water during extraction, extraction temperature / time, distillation temperature / decompression degree, etc. are affected by the type of raw soybean, the presence or absence of defatting, the liquidity of water, etc., so the amount of nicotianamine extracted from the extract And the purity may be selected as appropriate. The concentrated liquid obtained after the distillation can be further distilled off to obtain a dried product, or may be pulverized using a known method such as spray drying or freeze drying. In that case, excipient | fillers, such as dextrin, can also be added as needed.

  For the resulting nicotianamine-containing material, column chromatography using ion exchange resin, Sephadex, polyamide, silica gel, ODS, activated carbon, membrane separation using cellulose membrane, etc., precipitation treatment using water-ethanol, etc. If a known purification / separation / decolorization operation such as the above is performed, a nicotianamine-containing product with higher purity can be obtained. Nicotianamine can be measured by a general biological fluid amino acid analysis method.

  Furthermore, since nicotianamine is excellent in water solubility, it can be added to various foods and drinks. Moreover, the nicotianamine of the present invention may be an acid addition salt, and these can be used alone or in combination. Preferred acid addition salts include pharmaceutically acceptable salts such as hydrochloride, sulfate, nitrate, succinate, citrate, and tartrate.

(2) Iron absorption promoting composition The iron absorption promoting composition of the present invention is characterized by containing nicotianamine as an active ingredient and exhibits an action orally or parenterally. The iron absorption promoting composition of the present invention can be used as a pharmaceutical or added to a food or drink.

  When the iron absorption enhancing composition of the present invention is used as an iron absorption enhancing agent, the dosage form may be any dosage form that can be conveniently administered orally or parenterally, for example, Examples include injections, infusions, powders, granules, tablets, capsules, intestinal solvents, suppositories, ointments, inhalants, troches, etc., which are used alone or in combination depending on the symptoms. be able to. These various preparations are prepared by using known adjuvants that can be usually used in the pharmaceutical preparation technical field such as excipients, binders, disintegrants, lubricants, and corrigents according to the purpose according to conventional methods. Can be

  The dose of nicotianamine varies depending on the administration route, dosage form, symptom, age, body weight, etc., but usually when administered orally to an adult, the total amount of nicotianamine of the present invention is 1 mg to 250 mg / day, preferably 6 mg to 180 mg. / Day, more preferably 20 mg to 100 mg / day, but is not particularly limited.

  When using the iron absorption promoting composition of the present invention in the form of an iron absorption promoting food or drink, the required amount of nicotianamine used in the present invention, or an extract based on these alone, or a food or drink raw material, In particular, it can be processed and produced by a general production method in addition to food and drink raw materials that do not substantially contain nicotianamine. The blending amount varies depending on the dosage form and the morphological properties of the food, but the amount of nicotianamine in a general beverage is 0.0005 to 0.125% (W / V) per 200 ml, preferably 0.003 to 0.09% (W / V), more preferably 0.01 to 0.05% (W / V) is preferable, but not particularly limited.

  After blood donation and surgery, for the purpose of promoting iron absorption after delivery, under the management of a dietitian based on a doctor's meal, add the iron absorption promoting food and drink of the present invention to any food during cooking for hospital meals, It can also be given to patients in the form of functional food adjusted on the spot. Moreover, it can also use in combination with other iron absorption metabolism promoters (patent 3167402), such as a trace element, vitamin C, and a peptide, in the iron absorption promotion food-drinks of this invention. The iron absorption enhancer and iron absorption promoting food and drink of the present invention are effective in preventing and improving various symptoms caused by insufficient use of iron and maintaining health, after blood donation, after surgery, and postpartum iron absorption. It is.

(3) Iron agent The iron agent of this invention contains a nicotianamine and an iron compound. Since nicotianamine forms a chelate with iron to promote iron absorption, the present invention provides an iron agent with improved iron absorption.

  Examples of the iron compound include, but are not limited to, iron chloride, ferrous sulfate, ferrous citrate, ammonium iron citrate, sodium iron citrate succinate, iron lactate, chondroitin iron sulfate, ferrous fumarate Iron pyrophosphate and other inorganic or organic iron compounds can be used as appropriate, and the blending amount can be the same as that of commercially available iron agents.

  The iron agent of the present invention can be expected to be non-specifically applied to various symptoms caused by insufficient use of iron such as anemia, headache, tinnitus, shortness of breath, dizziness, movement disorder, and malaise. It can also be applied as a postpartum iron preparation after blood donation, surgery.

  The iron preparation of the present invention can be used as a pharmaceutical or added to a food or drink. When used as a pharmaceutical, the dosage form may be any dosage form that can be conveniently administered orally or parenterally, such as injections, infusions, powders, granules, tablets, Capsule, enteric solvent, suppository, ointment, inhalant, troche and the like can be mentioned, and these can be used alone or in combination depending on the symptoms. These various preparations are prepared by using known adjuvants that can be usually used in the pharmaceutical preparation technical field such as excipients, binders, disintegrants, lubricants, and corrigents according to the purpose according to conventional methods. Can be

  The dose of the iron preparation of the present invention varies depending on the administration route, dosage form, symptom, age, body weight and the like. Usually, when administered orally to an adult, the total amount of nicotianamine of the present invention is 1 mg to 250 mg / day and iron ions. (Converted as iron amount) 0.18 mg to 46.1 mg / day, preferably 6 mg to 180 mg / day as total amount of nicotianamine and iron ion (converted as iron amount) to 1.1 mg to 33.2 mg / day, more preferably Is 20 mg to 100 mg / day as the total amount of nicotianamine and 3.7 mg to 18.5 mg / day as iron ions (converted as iron amount), but is not particularly limited. The blending ratio of nicotianamine and iron ions (iron ions are converted as iron content) in the iron agent is preferably 1: 0.001-1: 100 (W / W), and 1: 0.01-1: 10 (W / W). W) is more desirable, and 1: 0.1 to 1: 1 (W / W) is more desirable, but not particularly limited.

(4) Iron-enhanced food / beverage and its manufacturing method The iron-reinforced food / beverage of this invention contains said iron agent. As a form of iron-fortified food or drink, a product obtained by simply mixing nicotianamine and an iron compound, or a product obtained by chelating nicotianamine and an iron compound, a protein (a protein source having a high nutritional value with an amino acid balance) Proteins such as milk protein, soy and buckwheat protein, and egg albumin are most widely used. In addition to these degradation products, egg white oligopeptides, soy and buckwheat hydrolysates, a mixture of amino acids alone is also used) , Sugars, fats, etc., mixed with trace elements, vitamins, emulsifiers, fragrances, etc. to make natural liquid foods, semi-digested nutritional foods and component nutritional foods, or solid or liquid foods or luxury goods, for example, Agricultural foods such as bread, noodles, rice, confectionery (biscuits, cakes, candy, chocolate, Japanese confectionery), tofu and processed products thereof, Fermented foods such as liquor, medicinal liquor, mirin, vinegar, soy sauce, miso, dressing, yogurt, ham, bacon, sausage, mayonnaise, and other marine foods, kamaboko, fried tempura, marinated food such as hampen, fruit juice, soft drink Sports beverages, alcoholic beverages, milk, soy milk, tea and other beverages can be used.

  When used in the form of the iron-enriched food or drink according to the present invention, the blending amount varies depending on the dosage form and the form properties of the food, but 200 ml as the amount of nicotianamine and iron ions (converted as iron amount) in general beverages. Per nicotianamine 0.0005 to 0.125% (W / V) and iron ions (converted as iron) 0.000093 to 0.023% (W / V), preferably nicotianamine 0.003 to 0.09% ( W / V) and iron ion (converted as iron amount) 0.00055 to 0.017% (W / V), more preferably nicotianamine 0.01 to 0.05% (W / V) and iron ion (iron amount) Is preferably 0.0019 to 0.0093% (W / V), but is not particularly limited.

(5) Safety Since nicotianamine and trace elements of the present invention are substances originally present in the living body of plants, they have low toxicity and high safety. Therefore, the iron absorption promoting composition is also of great significance as an iron agent. .
For example, regarding the safety of soybean extract containing 2% nicotianamine, it was announced at the 2005 Agricultural Chemical Society of Japan (Sato et al., Sapporo) that there are no problems in acute toxicity tests and 28-day subacute toxicity tests. Yes.
EXAMPLES Hereinafter, although an Example demonstrates this invention, these do not restrict | limit this invention.

(1) Preparation of nicotianamine 250 liters of water was added to 20 kilograms of pulverized defatted soybean meal to adjust to pH 9. After soaking at 25 ° C. for 90 minutes, the defatted soybean meal was removed to obtain 235 liters of an aqueous extract. Next, the pH of the water extract was adjusted to 4.5, and centrifuged (7500 G, 30 minutes) to remove the resulting precipitate, thereby obtaining 225 liters of supernatant.

  To 225 liters of this soybean water extract (soybean whey), 7.5 kg of activated carbon (purified white lees produced by Takeda Pharmaceutical Co., Ltd.) was added and stirred at room temperature for 3 hours to adsorb impurities. This was mixed with 7.5 kg of diatomaceous earth filter aid (Radiolite 500). Suction filtration was performed on 2 filter papers to obtain a filtrate.

  The filtrate was treated with a hollow fiber type ultrafiltration module (prep scale UF cartridge PLAC type manufactured by Nihon Millipore) with a molecular weight cut off of 1,000, and the permeate was freeze-dried to obtain 1.5 kg of a white powder. It was. This contained 0.3% of nicotianamine. The obtained ultrafiltrate was applied to an anion exchange resin (Diaion PA318 manufactured by Mitsubishi Chemical Corporation) column (volume 50 liters, OH type), washed with 100 liters of distilled water, and further with 100 liters of 0.5 N hydrochloric acid. Eluted.

  Subsequently, this was applied to a cation exchange resin (Dow Chemical Co., Ltd., Dowex 50W × 2) column (volume: 50 liters; H type), washed with 100 liters of distilled water, and further eluted with a 0.5% aqueous ammonia solution. The 100th to 150th liters were collected and concentrated to 5 liters using a rotary evaporator. Finally, this was freeze-dried to obtain 5 g of white powder.

  This contained 40% nicotianamine. Further, the obtained nicotianamine-containing powder was dissolved in a small amount of water and subjected to a polyamide C-200 (manufactured by Wako Pure Chemical Industries) column (volume: 25 liters) previously equilibrated with 100% ethanol, and 100% ethanol, 90% Elution was performed sequentially using 50 liters of ethanol, 80% ethanol, 70% ethanol, 60% ethanol, and 50% ethanol.

  The elution fractions of 70% ethanol, 60% ethanol and 50% ethanol were concentrated, filtered and freeze-dried to obtain 2 g of white powder. This contained 80% nicotianamine.

  Further, the obtained nicotianamine-containing powder was dissolved in a small amount of water and subjected again to polyamide C-200, and the eluted fraction was treated with activated carbon, filtered, ethanol precipitated, filtered and freeze-dried. Obtained. This contained 100% nicotianamine.

(2) Effect of promoting the solubilization of iron by nicotianamine First, the effect of promoting the solubilization of iron was confirmed for nicotianamine used in the present invention. Iron is a trace element that is difficult to solubilize at the pH in the digestive tract and difficult to be absorbed from the digestive tract. Therefore, even if a large amount of iron compound is ingested, most of the ingested iron compound is excreted outside the body. Will be. The effect of promoting the solubilization of iron by nicotianamine can be expected to exert the effect of promoting the absorption of iron from the intestinal tract.

  That is, the nicotianamine according to the present invention was subjected to an iron solubilization test (based on phosphate buffer) at pH 7.5 on various iron samples. In addition, distilled water was used as a comparative control sample. For the measurement of iron, a serum iron measurement kit Fe C-Test Wako (catalog No. 432-27220) manufactured by Wako Pure Chemical Industries, Ltd. was used.

The test on the solubility of iron was performed as follows. First, 100 μl of a nicotianamine (0-3.6 mM) solution dissolved in water in 800 μl of pH 7.5 phosphate buffer and generally administered orally because it is difficult to dissolve in water as a treatment for anemia. 100 μl of a 3.6 mM aqueous solution of ferrous sulfate (FeSO ₄ ) which is difficult to dissolve or ferric chloride (FeCl ₃ ) used as a strengthening agent was added. Subsequently, the mixture was shaken overnight, and the supernatant was filtered through a 0.45 μm filter, and then the amount of iron was measured.

The iron solubilization rate was measured for two types of iron samples, ferric chloride (FeCl ₃ ) and ferrous sulfate (FeSO ₄ ) according to the above-described method, and the results are shown in Table 1.

  As is clear from the above results, the solubilization rate of iron in the solution increased greatly as nicotianamine was added, and it was proved that nicotianamine has an excellent iron solubilizing ability. That is, by allowing each iron compound and an equivalent amount of nicotianamine to coexist, it was possible to improve the solubility of iron in a neutral solution. It is thought that the iron absorption promoting effect is exhibited by the excellent iron solubilizing ability of nicotianamine. In particular, the improved solubility of ferric chloride and ferrous sulfate, which is difficult to dissolve in the vicinity of neutrality, is thought to expand the range of application to beverages and the like.

(3) Iron absorption promotion action of nicotianamine About nicotianamine, the iron absorption promotion action was examined using mice, and the iron absorption promotion effect was confirmed. Table 2 shows each test group.

  The specimens shown in Table 2 above were forcibly orally administered to 5-week-old ICR male mice (6 per group) that had been fasted for 16 hours using an orally administered sonde. Blood is collected from the orbital venous plexus at a predetermined time, and the amount of iron in the serum is measured using a serum iron measurement kit Fe C-Test Wako (catalog No. 432-27220) manufactured by Wako Pure Chemical Industries, Ltd. did. In addition, the mineral in nicotianamine powder (purity 100%) is 1 ppm or less, and even if nicotianamine (purity 100%) is added to the experimental sample, the value of iron content is almost the same. In addition, about A group to D group, it administered so that it might become 2 mg / kg (each solution: 10 ml / kg) as iron ion (converted as iron amount). The results are shown in Table 3.

The nicotianamine-Fe ³⁺ chelate (Group A) not only has a higher iron concentration in the serum than the group administered with ferric chloride (Group C) even at 2 hours and 5 hours, and is excellent in absorption, It was found to be absorbed continuously. Further, in the group (group B) administered immediately after dissolution after mixing nicotianamine and the iron compound (group B), the iron concentration in serum is higher than that in the group (group C) administered ferric chloride at 5 hours. It became clear. In addition, the amount of serum iron of ferric chloride and ferrous sulfate at 2 hours and 5 hours was almost the same. From the above results, it was revealed that nicotianamine promotes iron absorption.

(4) Iron absorption promoting effect of iron-enriched food and drink The effect of promoting iron absorption when ingesting soy sauce containing nicotianamine and iron was examined using mice. Table 4 shows each test group.

  The specimens shown in Table 4 below were forcibly orally administered to 5-week-old ICR male mice (6 mice per group) fasted for 16 hours using an orally administered sonde. Blood is collected from the orbital venous plexus at a predetermined time, and the amount of iron in the serum is measured using a serum iron measurement kit Fe C-Test Wako (catalog No. 432-27220) manufactured by Wako Pure Chemical Industries, Ltd. did. In addition, the mineral in nicotianamine powder is 1 ppm or less, and even if nicotianamine is added to the experimental sample, the value of iron content is almost the same. The results are shown in Table 5.

  Compared with the group in which ferric chloride was added to water (group E), the group in which ferric chloride was added to soy sauce (group B) showed an increase in iron absorption. Furthermore, the group (group A) in which ferric chloride and nicotianamine were added to soy sauce, the group (group D) in which ferric chloride and nicotianamine (purity 100%) were added to water, and ferric chloride were added to soy sauce It was revealed that iron absorption was promoted compared to the group (Group B). From the above results, it became clear that nicotianamine promotes iron absorption even when added to soy sauce. It has also been found that nicotianamine in soy sauce tends to promote iron absorption.

(5) Manufacture of iron agent An iron agent can be manufactured with the following mixing | blending (Table 6).

  This mixture can be compressed by a compression tableting machine to produce 10,000 iron tablets for oral use containing about 85.7 mg of nicotianamine and about 6.6 mg of iron ions (converted as iron amount) per tablet (0.3 g).

(6) Production of iron-enriched soymilk Iron-enriched soymilk can be produced by the following composition (Table 7).

  By sterilizing this mixed beverage, 100 soymilk containing about 39.2 mg of nicotianamine and about 7.4 mg / 200 g of iron ions (converted as iron amount) can be produced.

Claims (7)

An iron absorption promoting composition comprising nicotianamine as an active ingredient. An iron preparation containing nicotianamine and an iron compound. The group of iron compounds consisting of iron chloride, ferrous sulfate, ferrous citrate, ammonium iron citrate, sodium iron citrate succinate, iron lactate, chondroitin iron sulfate, ferrous fumarate, and iron pyrophosphate The iron agent according to claim 2, which is one or more selected from the group consisting of: The iron agent according to any one of claims 2 and 3, wherein the iron agent is obtained by simply mixing nicotianamine and an iron compound, or by chelating these. Iron-reinforced food or drink containing the iron preparation according to any one of claims 2 to 4. The manufacturing method of the iron reinforced food / beverage products which adds a chelate bond of nicotianamine and an iron compound in the manufacturing method of the iron reinforced food / beverage products which adds an iron compound to food / beverage products. In a method for producing an iron-reinforced food or drink obtained by adding an iron compound to a food or drink, iron-enriched food or drink is characterized by adding nicotianamine and an iron compound to the food or drink to produce a chelate of nicotianamine and an iron compound. Product manufacturing method.