JP2012126646A - Mineral-adjusted water - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide mineral-adjusted water capable of effectively suppressing or improving symptoms of atopic dermatitis when a person with atopic dermatitis drinks the mineral-adjusted water daily.SOLUTION: In the mineral-adjusted water, calcium ions and magnesium ions are contained so that a calcium ion concentration becomes less than 200 ng/ml while a magnesium concentration becomes 50 ng/ml or more and less than 2,500 ng/ml.

Description

  The present invention relates to mineral-adjusted water that can effectively suppress or improve atopic dermatitis.

  Water accounts for about 70% of the cell mass of the living body and is a main component constituting the living body. As is well known, water plays an important role in keeping the temperature of a living body constant because specific heat is the largest among substances. In addition, water has a large surface tension and has a function of spreading blood and body fluid to the periphery of the living body by capillary action. In addition, water dissolves proteins, nucleic acids, and sugars that are important for living organisms, and has an important role as a reaction solvent in in vivo chemical reactions for life support activities such as metabolism and energy generation of in vivo substances. ing. Thus, water is an indispensable component for a living body.

Humans take water directly or orally from various foods. The water that humans drink on a daily basis includes various mineral ions such as calcium ions (Ca ²⁺ ), magnesium ions (Mg ²⁺ ), sodium ions (Na ⁺ ), and potassium ions (K ⁺ ). ing. These mineral ion contents vary depending on the region from which the mineral ions are collected, topography, geology, or the preparation method after collection. Among the mineral ions contained in water, calcium ions and magnesium ions are said to have the greatest influence on the taste of water. For this reason, the content of these two mineral ions contained in water is the hardness shown below. Is displayed. Examples of water hardness display methods include German hardness, American hardness, French hardness, and British hardness. For example, German hardness indicates the total amount of calcium ions and magnesium ions contained in 100 ml of water by the corresponding oxidation. It is defined as the mass (mg) converted to the amount of calcium (CaO). The American hardness is defined as the mass (mg) obtained by converting the total amount of calcium ions and magnesium ions contained in 1 L of water into the corresponding amount of calcium carbonate (CaCO ₃ ). German hardness (unit: “° dH”) and American hardness (unit: “ppm”) have a relationship of 1 ° dH = 17.8 ppm. Hardness is an index for classifying water. For example, for classification of water based on American hardness, “Detergent / Washing Encyclopedia”, Motoki Minagawa, Fumiko Fujii, Katsumi Oya, published by Asakura Shoten Co., Ltd., 282- This is shown on page 284, January 10, 2004, the second print.

  In general, water having low hardness, that is, water containing calcium ions and magnesium ions and having a small total amount of these mineral ions is said to be refreshing over the throat, and in particular, water having a hardness of 10 to 100 ppm. Is called “delicious water”.

  It is known that calcium ions and magnesium ions contained in water not only affect the taste, but also have various effects on the living body. For example, many epidemiological survey results have been reported regarding the relationship between calcium ion and magnesium ion concentrations contained in drinking water and the onset of diseases, particularly ischemic heart diseases such as myocardial infarction. According to it, in general, there are some reports that mortality due to myocardial infarction is low in areas where water with high calcium ion and magnesium ion concentration (so-called water with high hardness) is ingested (Non-patent Document 1, 2). According to a report on calcium ion and magnesium ion concentrations in water and mortality due to myocardial infarction (see Non-Patent Document 3), magnesium mortality due to heart attack or cardiovascular disorder is highly negatively correlated. It is said to be ion concentration. In addition, in Japan and Europe, epidemiological findings have been reported that the incidence of atopic eczema increases when humans routinely use water with high calcium and magnesium ion concentrations (non-patent literature). 4, 5). According to Non-Patent Document 5, in the results of a survey conducted on children aged 6 to 12 years, the frequency of atopic eczema is higher in children who are taking water with high calcium ion and magnesium ion concentrations. It was reported that these were significantly higher than those of children taking water with low mineral ion content. Similar epidemiological findings have been reported by a British group (see Non-Patent Document 6). Although the cause and mechanism that water induces atopic eczema has not been elucidated, in areas where water with high calcium ion and magnesium ion concentration is used, soap foam is poor, so the amount used is increased, As a result, the amount of soap that comes into contact with or remains on the skin has increased, and it has been speculated that it may be due to irritation of the skin.

  Under such circumstances, in this field, it is considered that there is some relationship between water and atopic dermatitis, and water that can suppress or ameliorate atopic dermatitis through daily use by humans. It was a crane head.

S.J. Pocock et al., “British Medical Journal”, 280, 6226, 1243-1249 (1980) RF Racey et al., “International Journal of Epidemology”, Vol. 13, No. 1, pp. 18-24 (1984) “Encyclopedia of Minerals”, edited by Yoshinori Itokawa, published by Asakura Shoten Co., Ltd., 492-494 (2004) Juan Ferrandiz et al., “Environmental Health Perspectives”, Vol. 112, No. 9, pages 1037-1044 (2004) Miyake Yoshihiro et al., “Environmental Research”, 94, 33-37 (2004) KS Thomas et al., “British Journal of Dermatology”, Vol. 159, pages 561 to 566 (2008)

  This invention makes it a subject to provide the mineral adjustment water which can suppress or improve atopic dermatitis effectively.

  The inventors of the present invention have the mineral ion concentration that influences the hardness of naturally occurring water and various drinking water that is commercially available, that is, the calcium ion and magnesium ion concentrations contained in these drinking water, and atopic dermatitis. Focusing on the relationship of, we have studied earnestly. As a result, mineral-adjusted water containing calcium ions and magnesium ions so that the concentration falls within a predetermined range, in particular, calcium ions that do not contain calcium ions or less than a predetermined concentration, and magnesium ions within a predetermined concentration range. In addition, a mineral-adjusted water containing a predetermined amount of one or more selected from potassium ions, manganese ions, iron ions, and zinc ions as other mineral ions in total solves the above problem As a result, the present invention was completed.

  That is, the present invention solves the above problems by providing mineral-adjusted water that is contained so that the calcium ion concentration is less than 200 ng / ml and the magnesium ion concentration is 50 ng / ml or more and less than 2,500 ng / ml. To do.

  In a preferred embodiment, the mineral-adjusted water of the present invention further includes one or more mineral ions selected from potassium ion, manganese ion, iron ion, and zinc ion as other mineral ions in total. Mineral-adjusted water containing 50 ng / ml or more and less than 1,000 ng / ml.

  In one preferred embodiment, the mineral-adjusted water of the present invention contains magnesium or one or more kinds of water substantially free of mineral ions selected from distilled water, deionized water, and ultrapure water. Or it is mineral adjustment water obtained through the process of adding 1 type, or 2 or more types chosen from calcium, potassium, manganese, iron, zinc, and a yeast extract with magnesium.

  Furthermore, in one preferred embodiment, the mineral-adjusted water of the present invention is mineral-adjusted water for suppressing or improving atopic dermatitis, and can be suitably used on a daily basis as drinking water or skin external water. it can.

  The mineral adjustment water of the present invention is supplied to the market as river water, tap water, underground water, underground water, well water, spring water, mineral water, hot spring water, cold spring water, lake water, sea water, and commercial products that are around us. Compared with water such as natural water, natural mineral water, mineral water, bottled water, etc., both calcium ion and magnesium ion concentrations are significantly lower, a fraction of a few to a few hundred. is doing.

  The mineral-adjusted water of the present invention can effectively suppress or improve atopic dermatitis by daily use by humans. The mineral conditioned water of the present invention is different from tap water and commercially available drinking water, although it does not contain calcium ions that affect the taste of water, or even though the calcium ion concentration and the magnesium ion concentration are extremely low. It is a safe water that has a refreshing throat, is easy to drink, and does not easily induce abdominal pain or diarrhea even when humans drink a relatively large amount on a daily basis. Moreover, the mineral adjustment water of this invention can be used suitably also as cosmetic water, such as face washing water, skin moisturizing water, and hair water. Since the mineral-adjusted water of the present invention is sterile water, there is no fear of contamination with bacteria even when stored at room temperature. When the container is appropriately filled, sealed and stored at room temperature, it is usually 1 year or longer. Preferably, the water is excellent in storage stability, maintaining the quality immediately after production for more than 2 years.

FIG. 1 is a graph showing the amount of interleukin-2 (IL-2) produced when spleen cells of test group A to J mice and control group K mice were stimulated with an anti-CD3 antibody. FIG. 2 is a diagram showing the amount of interleukin-4 (IL-4) produced when spleen cells of test group A to J mice and control group K mice were stimulated with an anti-CD3 antibody. FIG. 3 is a graph showing the amount of interferon-γ (IFN-γ) produced when spleen cells of test group A to J group mice and control group K group mice were stimulated with an anti-CD3 antibody. FIG. 4 is a graph showing the amount of interleukin-1β (IL-1β) produced when spleen cells of test group A to J mice and control group K mice were stimulated with LPS. FIG. 5 is a graph showing the amount of interleukin-6 (IL-6) produced when spleen cells of test group A to J mice and control group K mice were stimulated with LPS. FIG. 6 is a diagram showing interleukin-10 (IL-10) production when spleen cells of test group A to J mice and control group K mice were stimulated with LPS.

The mineral-adjusted water of the present invention does not contain impurities such as proteins, carbohydrates, and lipids, and does not substantially contain mineral ions, such as distilled water, deionized water, and ultrapure water (hereinafter collectively referred to as these). Prepared using 1 or 2 or more types of water selected from "water for raw materials" and 1 or 2 or more types selected from magnesium or other minerals other than magnesium and yeast extract together with magnesium or magnesium can do. The ultrapure water means water that is theoretically close to 100% pure water (H ₂ O). The raw material water used in the present invention is river water, tap water, underground water, underground water, well water, spring water, mineral water, hot spring water, cold spring water, lake water, seawater (including deep seawater), natural, which humans can drink. From water such as water, natural mineral water, mineral water, bottled water (hereinafter referred to as “raw water”), for example, distillation method, desalting method using H-type and OH-type ion exchange resins, RO membrane, etc. One or two or more known methods such as a membrane filtration method using can be used as appropriate. In the present invention, “substantially free of mineral ions” means means such as inductively coupled plasma emission spectrometry (ICP-AES) and inductively coupled plasma mass spectrometry (ICP-MS) that are usually used in the field. Means that the various mineral ion concentrations are below the detection limit.

  Among raw water, tap water meets the water quality standards stipulated in the “Ministerial Ordinance on Water Quality Standards” established based on the provisions of Article 4 Paragraph 2 of the Water Supply Law in Japan. It is safe water that can. Although details are omitted, according to the above water quality standard, for example, the calcium (Ca) concentration allowed as minerals contained in tap water is 300 mg / l (liter) or less, and the magnesium (Mg) concentration is 300 mg / l. Hereinafter, the sodium (Na) concentration is 200 mg / l or less, the manganese (Mn) concentration is 0.05 mg / l or less, the iron (Fe) concentration is 0.3 mg / l or less, and the zinc (Zn) concentration is 1.0 mg / l. Hereinafter, the copper (Cu) concentration is 1.0 mg / l or less, the chromium (Cr) concentration is 0.05 mg / l or less with respect to the amount of hexavalent chromium, and the selenium (Se) concentration is 0.01 mg / l or less. .

  In addition, although the mineral concentration contained in tap water in major cities in Japan varies from city to city, these tap waters contain more calcium and magnesium than other minerals. About 4-30 mg / l (= about 4,000-30,000 ng / ml), and about 1-8 mg / l (= about 1,000-8,000 ng / ml) (“Mineral Encyclopedia”, Edited by Yoshinori Itokawa, published by Asakura Shoten Co., Ltd., page 512 (2004)).

  In addition, in Japan, water such as natural water, natural mineral water, mineral water, and bottled water is regulated by the Food Sanitation Act in Japan. It is safe water that can be used, and in the present invention, it can be suitably used as a raw material (raw water) for preparing raw material water.

  The mineral-adjusted water of the present invention is, as raw material water, one or two or more kinds of water selected from distilled water, deionized water, and ultrapure water, together with magnesium or magnesium, and other minerals other than magnesium, In particular, it is mineral-adjusted water obtained through a step of adding a predetermined amount of one or more selected from calcium, potassium, manganese, iron, zinc and yeast extract, as described above. In addition, the calcium ion concentration and the magnesium ion concentration contained in the mineral-adjusted water of the present invention are remarkably low, such as a fraction of one to several hundreds of the calcium ion concentration and the magnesium ion concentration contained in the raw water around us. In that respect, the mineral conditioned water of the present invention is clearly different from the raw water around us. As far as the applicant knows, there is no raw water having the same mineral composition as the mineral-adjusted water of the present invention.

  Examples of the source of magnesium ions contained in the mineral-adjusted water of the present invention include magnesium hydroxide and salts (hydrochloride, nitrate, sulfate, bromate, carbonate, phosphate, acetate, tartrate) , Lactate, citrate, etc.), or one or more of raw water containing magnesium ions can be used as appropriate.

  Examples of mineral ions other than magnesium ions included in the mineral-adjusted water of the present invention include, for example, calcium, potassium, sodium, phosphorus, sulfur, manganese, iron, cobalt, nickel, copper, zinc, molybdenum, vanadium, silicon, Examples include ions (cations) of minerals such as tin, aluminum, rubidium, boron, lithium, chromium, and selenium. Examples of the source of mineral ions other than the magnesium ion include hydroxides and salts of the minerals (hydrochloride, nitrate, sulfate, bromate, carbonate, phosphate, acetate, tartrate, lactate) , Citrate, etc.), and raw water containing the mineral ions can be used.

  Moreover, among other mineral ions other than the above magnesium ions, calcium ions, potassium ions, manganese ions, iron ions, and zinc ions are all combined with magnesium ions that are essential components of the mineral adjustment water of the present invention. Preferred mineral ions. In the mineral-adjusted water of the present invention, the calcium ion concentration needs to be less than 200 ng / ml.

  The yeast extract used in the present invention is selected from sake yeast, wine yeast, alcohol yeast, brewer's yeast, baker's yeast, and mineral yeast such as manganese yeast, zinc yeast, copper yeast, chromium yeast, and selenium yeast. It means an extract (including a dry extract) obtained by appropriately extracting one or two or more of them with a solvent. More specifically, in terms of anhydride, 1 part by mass of the one or more yeasts is 5 to 500 parts by mass, preferably 10 to 100 parts by mass of a solvent mainly composed of raw material water or raw material water, More preferably, it is added to 30 to 70 parts by mass, dispersed, and extracted at a temperature of 80 to 150 ° C., preferably 100 to 130 ° C. for 5 minutes or more, preferably 10 to 300 minutes, Examples of liquid yeast extract obtained by using a centrifugal separation method, an ion exchange method, a gel filtration method, a membrane filtration method (for example, a membrane filtration method using a membrane having a pore size of 1 μm or less, and preferably a pore size of 0.5 μm or less) it can. Such a liquid yeast extract is optionally concentrated, dried and optionally used as a solid dry yeast extract. In preparing the mineral-adjusted water of the present invention, the yeast extract is usually added in the range of 0.001 to 500 g, preferably 0.01 to 100 g, with respect to 1 t (1,000 kg) of raw material water. The mineral yeasts such as manganese yeast, zinc yeast, copper yeast, chromium yeast, and selenium yeast are those obtained by incorporating a manganese compound, zinc compound, copper compound, chromium compound, and selenium compound into the yeast, respectively. . In the present invention, among yeast extracts prepared from the above yeasts, for example, manganese yeast extract and zinc yeast extract can be suitably used as a source of manganese ions and zinc ions, respectively.

  Hereinafter, a preferable embodiment is described concretely about the manufacturing method of the mineral adjustment water of this invention.

  First, as the raw material water used in the present invention, one or two kinds selected from distilled water, deionized water, and ultrapure water that do not contain impurities such as proteins, carbohydrates, and lipids and substantially do not contain mineral ions. Prepare more water. The raw material water used in the present invention is prepared by applying one or more known methods such as a distillation method, a desalting method, and a membrane filtration method using an RO membrane to raw water. As long as the requirements for the raw material water are satisfied, one or more kinds of water selected from commercially available distilled water, deionized water, and ultrapure water can be used as the raw material water.

  Next, the source water is made to contain a magnesium ion source so that the magnesium ion concentration is 50 ng / ml or more and less than 2,500 ng / ml, or together with the magnesium ion source, one or more other minerals An ion source is included so that the total concentration of other mineral ions is 50 ng / ml or more and less than 1,000 ng / ml. As the other mineral ions, calcium ions, potassium ions, manganese ions, iron ions, and zinc ions are most preferably used, and the source of these mineral ions is such that the total concentration of these mineral ions falls within the above concentration range. Is added to the raw material water and stirred and mixed uniformly. The above operation is usually performed at a temperature of 90 ° C. or lower, more preferably 90 to 50 ° C. When the magnesium ion, calcium ion, potassium ion, manganese ion, iron ion and / or zinc ion concentration exceeds the upper limit of the desired concentration range, it may be appropriately diluted with raw material water so as to be within the predetermined concentration range. On the other hand, when the lower limit is exceeded, one or more of magnesium ion source and / or other mineral ion source may be added and adjusted to be within a predetermined concentration range. In the process of producing the mineral-adjusted water of the present invention, when the magnesium ion concentration or the total of potassium ion, manganese ion, iron ion and / or zinc ion concentration is below the lower limit of the above concentration range, the preparation is in progress. It is also possible to concentrate the mineral-adjusted water under reduced pressure and adjust it to a predetermined concentration range. This operation is also desirably performed under the same conditions as described above.

  The mineral ion concentration contained in the mineral-adjusted water of the present invention is, as described above, means such as inductively coupled plasma emission spectrometry (ICP-AES) and inductively coupled plasma mass spectrometry (ICP-MS) widely used in the field. Can be measured. According to the above analysis method, various mineral ions can be measured with an accuracy of usually less than ± 5% (n = 3). The detection limit of the above analytical method is usually less than 5 ng / ml, although there are some differences depending on the type of mineral ion to be measured.

  When the mineral ion concentration in the mineral adjusted water of the present invention deviates from the predetermined concentration range, a part or all of the intended effects in the present invention are remarkably reduced or not exhibited. The intermediate product and final product mineral ion concentrations obtained in each process until mineral-adjusted water is obtained are accurately analyzed by means such as ICP-AES and ICP-MS, and based on the analysis results, It adjusts so that the mineral ion concentration in mineral adjustment water may become a predetermined range.

  When the mineral-adjusted water of the present invention is used as drinking water, for example, it is degassed, oxygen and / or hydrogen is dissolved, or carbon dioxide gas is added by a known method as necessary. It is optional to use carbonated water. The pH of the mineral-adjusted water of the present invention is usually from pH 3 to 11, preferably from pH 3. in consideration of taste when used as drinking water, affinity for skin and scalp when used as cosmetic water. The pH is preferably 5 to 9, more preferably pH 4.5 to 8.5, and even more preferably pH 5.0 to 7.5. The pH adjustment of the mineral-adjusted water of the present invention is performed within a range not departing from the object of the present invention by applying one or more known appropriate pH adjusters or one or more techniques such as electrolysis to a desired pH. Adjustments are also optional.

  Further, the mineral-adjusted water of the present invention is selected from organic acids, amino acids, vitamins, sugars, sweeteners, dietary fibers, pigments, fragrances, and the like as needed without departing from the intended purpose of the present invention. One or more components may be added at an appropriate concentration, preferably 0.001 to 50% by mass in total, more preferably 0.001 to 20% by mass, and still more preferably 0.001 to 5% by mass. % Does not interfere.

  The mineral-adjusted water of the present invention is usually known in the art in order to enhance its safety and storage stability, such as centrifugation, membrane filtration, microfiltration, ultraviolet sterilization, heat sterilization, radiation sterilization, After sterilization and sterilization by one or more known methods selected from autoclaving and autoclave sterilization, aseptically filling a container of an appropriate material, shape and capacity, and the present invention One or more methods selected from ultraviolet sterilization method, heat sterilization method, radiation sterilization method, autoclave sterilization method, and autoclave sterilization method It is optional to sterilize and sterilize. As the above-mentioned container, a transparent or light-shielding glass container, metal container, paper that does not substantially change the mineral ion composition, pH, or electrical conductivity of the mineral-adjusted water during the storage period Examples of such containers include plastic containers such as polyethylene containers, polyethylene terephthalate containers, and polypropylene containers, and pouch containers. The capacity of these containers is not limited, but for example, 1 ml or more, 50 ml or more, 0.1 to 2 liters, 5 to 25 liters, or 100 to 2,000 liters can be appropriately selected and used. Furthermore, when transporting a large amount of the mineral-adjusted water of the present invention, it is optional to appropriately fill a container, a tank lorry or the like of a volume, and further to fill and transport a tank provided in the tanker.

  The mineral-adjusted water of the present invention has a mineral ion composition that is clearly different from raw material water and raw water, and is water having an action of suppressing or improving atopic dermatitis as shown in the experimental examples described later. In addition, when using the mineral-adjusted water of the present invention as drinking water, the recommended dosage may vary depending on the age, sex, symptoms, etc. of the subject to be ingested, but is usually about 25 to 1 per day for an adult. 5,000 ml, preferably about 50 to 500 ml. The intended effect of the present invention can be effectively achieved by daily consumption of an amount in this range. The mineral-adjusted water of the present invention is not only liquid when used, but also in the form of droplets, sprays, sherbets, ice, etc., if necessary, and a thickener is used as appropriate. In addition, it can be administered in a jelly-like or paste-like form, not only orally and transdermally, but also by tube or nasal administration.

  The mineral-adjusted water of the present invention is safe for living organisms, manufactured at low cost and in large quantities, and using easily available raw materials, and is used in this field for its production. Since the liquid mixing container / device, the filtering device, the sterilizing device, the liquid filling device, and the like can be diverted, the mineral-adjusted water of the present invention has the practical advantage that it can be produced industrially at low cost, in large quantities, and easily. In addition, since the mineral adjusted water of the present invention is sterile water, there is no concern about contamination with bacteria even when stored at room temperature. When properly filled in a container, sealed and stored at room temperature, it is usually 1 year. As described above, it preferably has excellent storage stability that maintains the quality immediately after production for 2 years or longer.

  Hereinafter, the present invention will be described in more detail based on experimental examples.

<Experimental example: suppression or improvement test of atopic dermatitis>
1. Outline of Experiments Several types of test waters with different mineral ion compositions were prepared, and the effects of these test waters on atopic dermatitis were examined by animal experiments. That is, when raised on a special feed deficient in linoleic acid (trade name “HR-AD Feed” manufactured by Oriental Yeast Co., Ltd.), atopic dermatitis-like symptoms in humans (hereinafter referred to as “human atopic dermatitis-like symptoms”). HR-1 mice known to show), and the mice were bred for 10 weeks using the HR-AD feed and each of the above test waters, Human atopic dermatitis-like symptom is developed, the symptom is observed, and interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin- in spleen cells collected from mice 6 (IL-6), interleukin-10 (IL-10), and interferon-γ (IFN-γ) and other inflammatory, anti-inflammatory, and allergic hypercytokines We examined the production of emissions class. Furthermore, hip skin tissue of each group of mice was collected and analyzed histologically.

2. Preparation of test water In order to obtain the mineral ion composition shown in Table 1, calcium chloride dihydrate (sold by Tomita Pharmaceutical Co., Ltd., pharmaceutical grade, purity 96.7%) was added to ultrapure water substantially free of mineral ions. Above), Magnesium chloride hexahydrate (Tomita Pharmaceutical Co., Ltd., food additive grade, purity 93.0%), Potassium chloride (Ako Kasei Co., Ltd., Food additive grade, purity 98.8%), Chloride Manganese tetrahydrate (sold by Showa Chemical Co., Ltd., reagent grade, purity 99.0%), ferric chloride hexahydrate (sold by Tomita Pharmaceutical Co., Ltd., food additive grade, purity 94.5%), and 1 type or 2 or more types selected from zinc sulfate heptahydrate (Tonda Pharmaceutical Co., Ltd. sale, food additive grade, purity 98.0%) are added, and it stirs and mixes uniformly, melt | dissolves, and the obtained aqueous solution Is filtered through a membrane (0.22 μm) and 0.1N-hydroxylated To obtain a test water 1 to 7 was adjusted to pH7.3 with um aqueous or 0.1N- aqueous hydrochloric acid. As control water, tap water (pH 7.3) from Okayama City (hereinafter referred to as “control water”) was used. Samples were taken from each of test water 1 to 10 and control water, and their mineral ion composition was analyzed by inductively coupled plasma optical emission spectrometry (ICP-AES) using “Multi CCD-ICP emission spectrometer” (Spectro). . The results are shown in Table 2.

註：表２中、「同等」、「抑制傾向」、「低下傾向」、「増加傾向」、「有意に低下」及び「有意に増加」はいずれも、各評価項目における対照群であるＫ群マウスとの相対評価に基づく評価である。また、「０ｎｇ／ｍｌ」は、検出限界以下の濃度であることを意味する。

註: In Table 2, “equivalent”, “suppression tendency”, “decreasing tendency”, “increasing tendency”, “significantly decreasing”, and “significantly increasing” are all control groups in each evaluation item. The evaluation is based on relative evaluation with mice. Further, “0 ng / ml” means that the concentration is below the detection limit.

3. Onset of human atopic dermatitis-like symptoms and administration of test water 66 HR-1 female mice (6 weeks old) were purchased from Japan SLC Co., Ltd. Preliminary breeding was performed using “NMF” manufactured by Oriental Yeast Co., Ltd. As drinking water during the preliminary breeding period, the control water was ingested freely. After the preliminary breeding, the mice were randomly divided into 11 groups of A to K (6 animals in each group) and reared for 10 weeks using HR-AD diet to develop human atopic dermatitis-like symptoms. . Meanwhile, as drinking water, mice in groups A to J, which are test groups, freely received test water 1 to 10, respectively, and mice in group K, which was a control group, freely received control water. In the breeding test over 10 weeks, the body weight, feed intake, and drinking water intake were measured for each group of mice at regular intervals. The moisture content of the skin was measured with a skin surface horn layer moisture content measuring device (“SKICON (registered trademark) -200EX”, manufactured by IBS). In addition, after a 10-week rearing test, the presence or absence of human atopic dermatitis-like symptoms in each group of mice, and the observation and evaluation of the thickening of the epidermis observed when such symptoms appear were Went. In addition, after completion of the breeding test over 10 weeks, blood was collected from each group of mice, and the spleen and buttocks skin were removed. The hip skin was fixed by neutral buffered formalin by a conventional method, a pathological tissue section was prepared, and hematoxylin-eosin staining (HE staining) was performed for histological analysis.

4). Measurement of cytokine production inducing ability in spleen cells Spleen cells were collected from each spleen excised from each group of mice, and the concentration was 5 × 10 ⁶ cells / ml in a cell culture solution (RPMI1640 medium, pH 7.3). Suspended and dispensed into a 24-well microplate (trade name “MULTIEWELL ^™ 24 WELL” (Becton Dickinson Labware)), to which 2 μg / ml of anti-CD3 antibody (manufactured by Sedarene) or lipopolysaccharide (LPS ) (Manufactured by Sigma) was added at 5 μg / ml, and cultured in a 37 ° C., 5% (v / v) CO ₂ incubator for 2 days. Interleukin-1β (IL-1β) in the culture supernatant was use IL-1βEIA kit (trade name "ELISA · BD OptEIA ^TM", Nippon Becton Dickinson Co., Ltd.) It was measured Te. Interleukin-2 (IL-2) consists of rat anti-mouse IL-2 antibody and biotin-labeled rat anti-mouse IL-2 antibody (both manufactured by BD Fermidine), and horseradish peroxidase (HRPO) -labeled streptavidin (Amersham). ). Interleukin-4 (IL-4) is obtained by using rat anti-mouse IL-4 antibody, biotin-labeled rat anti-mouse IL-4 antibody (both manufactured by BD Fermidine), and HRPO-labeled streptavidin (manufactured by Amersham). It was measured. Interleukin-6 (IL-6) is obtained by using rat anti-mouse IL-6 antibody, biotin-labeled rat anti-mouse IL-6 antibody (both manufactured by BD Fermidine), and HRPO-labeled streptavidin (manufactured by Amersham). It was measured. Interleukin-10 (IL-10) is obtained by using rat anti-mouse IL-10 antibody, biotin-labeled rat anti-mouse IL-10 antibody (both manufactured by BD Fermidine), and HRPO-labeled streptavidin (manufactured by Amersham). It was measured. As interferon-γ (IFN-γ), rat anti-mouse IFN-γ antibody, biotin-labeled rat anti-mouse IL-10 antibody (both manufactured by BD Fermidine), and HRPO-labeled streptavidin (manufactured by Amersham) are used. Measured.

5. Statistical analysis Comparison between the control group and the test group was performed using commercially available statistical analysis software [“JMP Ver. 4 ”(manufactured by SAS Institute) was subjected to a multiple comparison test by the Dunnett method, and when p <0.05, it was determined that there was a significant difference.

6). Results and Discussion (1) Body Weight, Feed Intake, Drinking Water Intake, and Skin Water Content Drinking water in group K mice fed with control water and groups A through J fed test water 1-10 There was no significant difference in body weight, feed intake, drinking water intake, and skin moisture content due to the difference in the above.

(2) Onset of human atopic dermatitis-like symptom Human atopic dermatitis in any of group K mice fed with control water and group A to J mice fed any of test water 1 to 10 The following symptoms were observed. Group A, G or J mice that received test water 1, 7 or 10 were all treated with control water (such as the degree of infiltration of inflammatory cells into dry skin and dermis). All the symptoms of the B to F group, H group and I group mice that received the test water 2 to 6, 8 or 9 were “equivalent” to the mice, but the control group was ingested the K group There was a clear tendency to suppress compared to mice (see “Results” column in Table 2).

(3) Histological analysis of the buttock skin After the completion of the 10-week rearing test, the groin of group K mice fed with control water and the mice of groups A to J fed with any of test water 1 to 10 When histological analysis was performed on the skin, symptoms in the B to F group, H group, or I group mice that received test water 2 to 6, 8, or 9 (thickening of the epidermis layer = human atopic dermatitis-like) As the symptom progressed, the thickness increased) was clearly “suppressed” compared to the K group mice fed with control water (see “Results” column in Table 2).

(4) Production of cytokines in spleen cells Spleen cells prepared from spleens excised from mice A to K after the breeding test for 10 weeks were respectively stimulated with anti-CD3 antibody or LPS according to a conventional method. , IL-1β, IL-2, IL-4, IL-6, IL-10, or IFN-γ production was induced, and the amount of cytokines produced by spleen cells derived from each group of mice was measured.

  As a result, when spleen cells were stimulated with an anti-CD3 antibody, the production amount of IL-2, which is a T cell growth factor and involved in allergic diseases, was determined as follows. No significant difference was observed between mice A and J fed 10 (see FIG. 1).

  The production amount of IL-4 having an allergic effect is as follows: a group K mouse fed with control water, and a group A, group B, group G and J mice fed test water 1, 2, 7 or 10 There was no significant difference between the two. However, the amount of IL-4 produced by the group B mice fed with the test water 2 showed a “decrease tendency” compared to the group K mice fed with the control water. On the other hand, all of the B to F group, H group and I group mice fed with test water 3 to 6, 8 or 9 showed “significant” IL-4 production compared to the K group mice fed with control water. (Refer to the “Result” column in FIG. 2 and Table 2).

  The production of IFN-γ, an inflammatory cytokine, was significantly different between group K mice fed with control water and group A to J mice fed either test water 1 to 10. None (see FIG. 3).

  In addition, when spleen cells were stimulated with LPS, the production amounts of IL-1β and IL-6, which are inflammatory cytokines, were ingested in group K mice ingested with control water and test water 1, 2, 7 or 10. No significant difference was observed among the A group, B group, G group and J group mice. However, the production amounts of IL-1β and IL-6 of the B group mice fed with the test water 2 both showed a “decrease tendency” compared to the K group mice fed with the control water. On the other hand, the B to F group, the H group and the I group mice fed with the test water 3 to 6, 8 or 9 all had IL-1β and IL-6 compared to the K group mice fed the control water. All of the production amounts were “significantly reduced” (see the “Result” column in FIGS. 4 and 5 and Table 2).

  Furthermore, the production amount of IL-10, which is an anti-inflammatory cytokine, was measured in group K mice fed with control water, group A, group B, group G and group J fed test water 1, 2, 7 or 10. There was no significant difference between mice. However, the IL-10 production amount of the group B mice fed with the test water 2 showed an “increase tendency” compared to the group K mice fed with the control water. On the other hand, all of the B to F group, the H group and the I group mice fed with the test water 3 to 6, 8 or 9 had an IL-10 production amount as compared with the K group mice fed with the control water. “Significantly increased” (see FIG. 6 and the “Result” column in Table 2).

(5) Summary From the results shown in the above (1) to (4), in animal experiments using mice, test water 2 to 6, 8, or 9 is human atopic dermatitis-like symptoms and human atopic skin The action of inhibiting or improving the thickening of the epidermis layer, which was observed when flaky symptoms appeared, was observed. This inhibitory action is caused by the production amount of IL-4 having an allergic enhancing action, IL-, which is an inflammatory cytokine, in the B to F group, the H group and the I group mice fed with the test water 2 to 6, 8 or 9. Both 1β and IL-6 production were “decreasing” or “significantly decreased”, and IL-10 production, an anti-inflammatory cytokine, was “increased” or “significantly increased” Therefore, all of test water 2 to 6, 8 and 9 are dominant helper T (Th) 2 cells (known as cytokine producing cells such as IL-4) involved in the pathogenesis of human atopic dermatitis. It is judged that the immune response was improved and the result was achieved. Further, in view of the behavior of various cytokines in the B to F group, the H group and the I group mice fed with the test water 2 to 6, 8 or 9, the test waters 2 to 6, 8 and 9 are human atopic skin. It is judged to have an action of suppressing or improving not only the flame but also the inflammatory reaction caused by infection with bacteria and the like.

  From the results of this experiment, the mineral ion composition containing mineral ions such that the calcium ion concentration is less than 200 ng / ml and the magnesium ion concentration is 50 ng / ml or more and less than 2,500 ng / ml, especially calcium ions. The concentration is less than 200 ng / ml, the magnesium ion concentration is 50 ng / ml or more and less than 2,500 ng / ml, and the other mineral ion is one or two selected from potassium ion, manganese ion, iron ion, and zinc ion Mineral-adjusted water containing a total of 50 ng / ml or more and less than 1,000 ng / ml of mineral ions of at least species has an effect of effectively suppressing or improving human atopic dermatitis, and is caused by infection with bacteria, etc. Has the effect of suppressing or improving the inflammatory response It is determined to be.

  EXAMPLES Hereinafter, although this invention is demonstrated in detail based on an Example, this invention is not limited at all by these Examples.

<Mineral adjustment water>
To 1,000,000 parts by mass of ultrapure water substantially free of mineral ions prepared from tap water using RO membrane, magnesium chloride hexahydrate (sold by Tomita Pharmaceutical Co., Ltd., food additive grade, purity) 93.0%) 2.60 parts by mass, potassium chloride (Ako Kasei Co., Ltd., food additive grade, purity 98.8%) 0.21 parts by mass, manganese yeast (manganese content 5.03%, food additive 2.15 parts by mass, sold by Glow Co., Ltd., ammonium citrate (sold by Tomita Pharmaceutical Co., Ltd., food additive grade, iron content 17.4%) 0.48 parts by mass, and zinc yeast (zinc content 5.03%, food additive grade, sold by Glow Co., Ltd.) 1.24 parts by mass were added, stirred and mixed uniformly, heated and dissolved at 85 ° C., sterilized by membrane filtration (0.22 μm), Aseptically fill this into a 5L polyethylene container, To give a light mineral adjusted water (pH about 6).

  This product was sampled, and its mineral ion composition was analyzed by inductively coupled plasma emission spectrometry (ICP-AES) using “Multi CCD-ICP emission spectrometer” (Spectro), and the magnesium ion concentration was 300 ng / ml. The potassium ion concentration was 105 ng / ml, the manganese ion concentration was 101 ng / ml, the iron ion concentration was 100 ng / ml, and the zinc ion concentration was 60 ng / ml.

  If this product is used as it is or after being diluted with the above-mentioned ultrapure water by about 2 to 5 times (volume ratio), if a person with atopic dermatitis drinks on a daily basis, the symptoms should be effectively suppressed or improved. Can do. In addition, this product is used as a safe mineral adjustment water that does not easily induce abdominal pain or diarrhea even if humans drink a relatively large amount on a daily basis.Furthermore, facial cleansing water, skin moisturizing water, It can also be suitably used as cosmetic water such as hair water. Since this product is sterile water, there is no concern about contamination with bacteria even if it is stored at room temperature, and the mineral composition and pH immediately after production are kept stable for a long period of 1 year or longer.

<Mineral adjustment water>
To 1,000,000 parts by mass of ultrapure water substantially free of minerals prepared from tap water using RO membrane, magnesium chloride hexahydrate (sold by Tomita Pharmaceutical Co., Ltd., food additive grade, purity 93) 0.0%) 8.60 parts by mass, potassium chloride (Ako Kasei Co., Ltd., food additive grade, purity 98.8%) 0.25 parts by mass, manganese yeast (manganese content 5.03%, food additive) Grade, sold by Grow Inc.) 2.61 parts by mass, ammonium iron citrate (sold by Tomita Pharmaceutical Co., Ltd., food additive grade, iron content 17.4%) 0.61 parts by mass, and zinc yeast (zinc content 5 0.03%, food additive grade, sold by Glow Co., Ltd.) 2.70 parts by mass are added, mixed, dissolved by heating at 90 ° C., and sterilized by membrane filtration (0.22 μm). Aseptically filling a plastic bottle of the present invention, the mineral-adjusted water of the present invention pH to obtain about 6).

  This product was sampled and its mineral composition was analyzed by inductively coupled plasma optical emission spectrometry (ICP-AES) using "Multi CCD-ICP emission spectrometer" (Spectro). Magnesium ion concentration 993ng / ml, potassium The ion concentration was 125 ng / ml, the manganese ion concentration was 121 ng / ml, the iron ion concentration was 125 ng / ml, and the zinc ion concentration was 124 ng / ml.

  If this product is used as it is, or diluted about 2 to 6 times (volume ratio) with the above-mentioned ultrapure water and taken by a person with atopic dermatitis on a daily basis, the symptoms can be effectively suppressed or improved. it can. In addition, this product is used as a safe mineral adjustment water that does not easily induce abdominal pain or diarrhea even if humans drink a relatively large amount on a daily basis.Furthermore, facial cleansing water, skin moisturizing water, It can also be suitably used as cosmetic water such as hair water. Since this product is sterile water, there is no concern about contamination with bacteria even if it is stored at room temperature, and the mineral composition and pH immediately after production are kept stable for a long period of 1 year or longer.

<Mineral adjustment water>
To 1,000,000 parts by mass of ultrapure water substantially free of minerals prepared from tap water using RO membrane, magnesium chloride hexahydrate (sold by Tomita Pharmaceutical Co., Ltd., food additive grade, purity 93) 1.0%) 13.74 parts by mass, uniformly stirred and mixed, dissolved by heating at 80 ° C., sterilized by membrane filtration (0.22 μm), and aseptically put into a 1 L polyethylene container. The mineral-adjusted water of the present invention (pH about 6) was obtained.

  When this product was sampled and its mineral composition was analyzed by inductively coupled plasma emission spectrometry (ICP-AES) using “Multi CCD-ICP emission spectrometer” (Spectro), the magnesium ion concentration was 1,490 ng / ml.

  If this product is used as it is or diluted approximately 2 to 25 times (volume ratio) with the above-mentioned ultrapure water, and a person with atopic dermatitis drinks on a daily basis, the symptoms can be effectively suppressed or improved. it can. In addition, this product is used as a safe mineral adjustment water that does not easily induce abdominal pain or diarrhea even if humans drink a relatively large amount on a daily basis.Furthermore, facial cleansing water, skin moisturizing water, It can also be suitably used as cosmetic water such as hair water. Since this product is sterile water, there is no concern about contamination with bacteria even if it is stored at room temperature, and the mineral composition and pH immediately after production are kept stable for a long period of 1 year or longer.

<Mineral adjustment water>
To 1,000,000 parts by mass of ultrapure water substantially free of minerals prepared from tap water using an RO membrane, calcium chloride dihydrate (sold by Tomita Pharmaceutical Co., Ltd., pharmaceutical grade, purity 96.7) 0.40 part by mass) and magnesium chloride hexahydrate (sold by Tomita Pharmaceutical Co., Ltd., food additive grade, purity 93.0%) 9.62 parts by mass are added, and the mixture is stirred and mixed uniformly. It was dissolved by heating at 0 ° C., sterilized by membrane filtration (0.22 μm), and this was aseptically filled into a 1 L polyethylene container to obtain the mineral-adjusted water (pH about 6) of the present invention.

  This product was sampled and its mineral composition was analyzed by inductively coupled plasma optical emission spectrometry (ICP-AES) using “Multi CCD-ICP emission spectrometer” (Spectro), and the calcium ion concentration was 102 ng / ml. The magnesium ion concentration was 1,040 ng / ml.

  If this product is used as it is, or diluted about 2 to 15 times (volume ratio) with the above-mentioned ultrapure water, and a person with atopic dermatitis drinks on a daily basis, the symptoms can be effectively suppressed or improved. it can. In addition, this product is used as a safe mineral adjustment water that does not easily induce abdominal pain or diarrhea even if humans drink a relatively large amount on a daily basis.Furthermore, facial cleansing water, skin moisturizing water, It can also be suitably used as cosmetic water such as hair water. Since this product is sterile water, there is no concern about contamination with bacteria even if it is stored at room temperature, and the mineral composition and pH immediately after production are kept stable for a long period of 1 year or longer.

<Mineral adjustment water>
The operation of recrystallizing “Treha (registered trademark)” (Trehalose, purity 98% or more, sold by Hayashibara Shoji Co., Ltd.) in distilled water was performed a plurality of times in advance in the mineral-adjusted water of the present invention obtained in Example 1. Using trehalose with a purity of 99.9% or more prepared in this way, add it so that the trehalose concentration is 0.3% (w / w), stir and mix at 10 ° C., and filter through a membrane (0.22 μm). These were sterilized and aseptically filled into 500 ml PET bottles to obtain mineral-adjusted water (pH about 6) of the present invention.

  This product is directly or diluted 2 to 6 times (volume ratio) with the same ultrapure water used in Example 1, and effectively suppresses the symptoms when atopic dermatitis is drunk daily. Or it can be improved. In addition, this product is used as a safe mineral adjustment water that does not easily induce abdominal pain or diarrhea even if humans drink a relatively large amount on a daily basis.Furthermore, facial cleansing water, skin moisturizing water, It can also be suitably used as cosmetic water such as hair water. Since this product is sterile water, there is no concern about contamination with bacteria even if it is stored at room temperature, and the mineral composition and pH immediately after production are kept stable for a long period of 1 year or longer.

<Mineral adjustment water>
Re-crystallize “AA2G (registered trademark)” (L-ascorbic acid 2-glucoside, purity 98% or more, sold by Hayashibara Biochemical Laboratories, Inc.) in distilled water in advance in the mineral-adjusted water obtained in Example 2. Using L-ascorbic acid 2-glucoside having a purity of 99.9% or more prepared by performing the operation a plurality of times, the L-ascorbic acid 2-glucoside concentration was added to 0.2% (w / w). The mixture was stirred and mixed uniformly, sterilized by membrane filtration (0.22 μm), and this was aseptically filled into a 350 ml light-shielding PET bottle to obtain the mineral-adjusted water (pH about 4) of the present invention. .

  This product can effectively suppress or ameliorate the symptoms of atopic dermatitis when taken on a daily basis by humans. In addition, this product is used as a safe mineral adjustment water that does not easily induce abdominal pain or diarrhea even if humans drink a relatively large amount on a daily basis.Furthermore, facial cleansing water, skin moisturizing water, It can also be suitably used as cosmetic water such as hair water. Since this product is sterile water, there is no concern about contamination with bacteria even if it is stored at room temperature, and the mineral composition and pH immediately after production are kept stable for a long period of 1 year or longer.

<Mineral adjustment water>
1% (w / w) of purified pullulan previously desalted with “food additive pullulan” (sales by Hayashibara Shoji Co., Ltd.) in any of the mineral adjusted water obtained in Examples 1 to 6 v), uniformly stirred and mixed, sterilized by membrane filtration (0.22 μm), and aseptically filled into a 500 ml PET bottle, 5 kinds of mineral preparation of the present invention Got water.

  This product can effectively suppress or ameliorate the symptoms of atopic dermatitis when taken on a daily basis by humans. In addition, this product is used as a safe mineral adjustment water that does not easily induce abdominal pain or diarrhea even if humans drink a relatively large amount on a daily basis.Furthermore, facial cleansing water, skin moisturizing water, It can also be suitably used as cosmetic water such as hair water. Since this product is sterile water, there is no concern about contamination with bacteria even if it is stored at room temperature, and the mineral composition and pH immediately after production are kept stable for a long period of 1 year or longer.

<Mineral adjustment water>
“ΑG rutin P” (sugar transfer rutin powder, sold by Hayashibara Shoji Co., Ltd.) or “αG hesperidin” (sugar transfer hesperidin, sold by Toyo Seika Co., Ltd.) is added to any of the mineral-adjusted water obtained in Examples 1 to 6. Purified αG rutin P or purified αG hesperidin previously desalted is added to a concentration of 1% (w / v) per dry solid, stirred and mixed uniformly, and membrane filtration (0.22 μm And sterilized into a 350 ml light-shielding PET bottle to obtain 10 types of mineral-adjusted water of the present invention.

  When this product is drunk daily by humans with atopic dermatitis, it can effectively suppress or improve the symptoms together with the blood circulation promoting action by glycosylated rutin or glycosylated hesperidin. In addition, this product is used as a safe mineral adjustment water that does not easily induce abdominal pain or diarrhea even if humans drink a relatively large amount on a daily basis.Furthermore, facial cleansing water, skin moisturizing water, It can also be suitably used as cosmetic water such as hair water. Since this product is sterile water, there is no concern about contamination with bacteria even if it is stored at room temperature, and the mineral composition and pH immediately after production are kept stable for a long period of 1 year or longer.

<Mineral adjustment water>
One or more amino acids selected from alanine, glutamine, ornithine, valine, leucine and isoleucine are added to any one of the mineral-adjusted waters obtained in Examples 1 to 6 to a concentration of 1% (w / v). The mixture was stirred and mixed uniformly, sterilized by membrane filtration (0.22 μm), and this was aseptically filled into a 100 ml light-shielding PET bottle to obtain a plurality of types of mineral-adjusted water of the present invention.

  This product can effectively suppress or ameliorate the symptoms when combined with the blood circulation promoting action by amino acids when taken by humans with atopic dermatitis on a daily basis. In addition, this product is used as a safe mineral adjustment water that does not easily induce abdominal pain or diarrhea even if humans drink a relatively large amount on a daily basis.Furthermore, facial cleansing water, skin moisturizing water, It can also be suitably used as cosmetic water such as hair water. Since this product is sterile water, there is no concern about contamination with bacteria even if it is stored at room temperature, and the mineral composition and pH immediately after production are kept stable for a long period of 1 year or longer.

<Mineral adjustment water>
Either one of the mineral conditioned water obtained in Example 7, one of the mineral conditioned water obtained in Example 8, and one of the mineral conditioned water obtained in Example 9 is stirred and mixed uniformly in equal amounts. This was sterilized by filtration (0.22 μm), and this was aseptically filled into a 200 ml light-shielding PET bottle to obtain a plurality of types of mineral-adjusted water of the present invention.

  This product is excellent in taste and is a safe mineral preparation water that is unlikely to induce abdominal pain or diarrhea even if humans drink a relatively large amount on a daily basis. It can also be suitably used as cosmetic water such as moisturizing water for hair and water for hair. Since this product is sterile water, there is no concern about contamination with bacteria even if it is stored at room temperature, and the mineral composition and pH immediately after production are kept stable for a long period of 1 year or longer.

  As described above, the mineral-adjusted water of the present invention is water having an action of effectively suppressing or improving the symptoms when used daily by humans with atopic dermatitis. The mineral-adjusted water is safe water that has a throat that is easy for humans to drink and is unlikely to induce abdominal pain or diarrhea even if it is taken in a relatively large amount on a daily basis. Further, the mineral adjustment water can be suitably used as cosmetic water such as facial cleansing water for skin use, skin moisturizing water, and hair water. In addition, since the mineral adjustment water is sterile water, the quality immediately after production is maintained as it is for a long period of one year or more even at room temperature when it is properly filled in a container and stored tightly. Mineral-adjusted water with excellent storage stability. As described above, the mineral-adjusted water itself can be used not only as drinking water and cosmetic water for external use on the skin, but also as one of the water conventionally used for the production of foods, cosmetics, pharmaceuticals, quasi drugs and the like. It can be used in place of part or all.

  The present invention is an invention that exhibits such remarkable effects, and it is a very significant invention that contributes to this field.

Claims (5)

  Mineral-adjusted water that is contained so that the calcium ion concentration is less than 200 ng / ml and the magnesium ion concentration is 50 ng / ml or more and less than 2,500 ng / ml.   Furthermore, as other mineral ions, a total of 50 ng / ml or more and less than 1,000 ng / ml of one or more mineral ions selected from potassium ion, manganese ion, iron ion, and zinc ion is included. Item 1. Mineral-adjusted water according to item 1.   One or two or more kinds of water substantially free of mineral ions selected from distilled water, deionized water, and ultrapure water, together with magnesium or magnesium, calcium, potassium, manganese, iron, zinc, and The mineral-adjusted water according to claim 1 or 2, wherein the mineral-adjusted water is obtained through a step of adding one or more selected from yeast extracts.   The mineral-adjusted water according to any one of claims 1 to 3 for suppressing or improving atopic dermatitis.   The mineral adjustment water in any one of Claims 1 thru | or 3 as drinking water or skin external use water.

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