Sodium ion absorption inhibitor into bloodstream containing calcium alginate powder, and orally ingested product therewith

Abstract

To provide a sodium ion absorption suppressor into blood stream capable of being mixed with food or drinking and taken directly, capable of suppressing the absorption of sodium ions into the bloodstream, or furthermore of rapidly and efficiently excreting sodium ions from the body, less in a side effect and high in in vivo safety even when ingested, and capable of mass-producing or acquiring in mass, and an orally ingestive product therewith.SOLUTION: Sodium ion absorption inhibitors into the bloodstream contain calcium alginate powder as an active ingredient. The calcium alginate powder has a particle size that passes through an 80 mesh size or smaller, preferably a particle size that passes through a 270 mesh size or smaller.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a sodium ion absorption inhibitor for blood that contains calcium alginate powder, suppresses the absorption of sodium ions into the blood, reduces sodium ions in the body, and causes them to be excreted, and an oral intake product that uses the same to suppress the absorption of sodium ions into the blood and reduces and excretes sodium ions in the body when orally ingested.

Background Art

[0002] Alginic acid is a linear molecule composed of β-1,4 bonds of D-mannuronic acid and / or α-1,4 bonds of L-guluronic acid, and is a polysaccharide mainly contained in brown algae and the like. Alginic acid is used as a food additive as a free acid or as a sodium salt, potassium salt, calcium salt or ammonium salt, and is a general-purpose agent used to increase the viscosity of viscous foods such as mayonnaise, cheese, tomato ketchup, ice cream, sherbet, syrup, and rice flour, stabilize the emulsion structure, or gel. In addition, as alginates, alginate is used in dental impression materials, alginic acid is used in surgical sutures as a fibrous gel, alginate is used in wound dressings, sodium alginate is used as a binder for toothpaste, alginate is used as a binder for seedling cultivation soil, and sodium alginate powder or aqueous solution is used for gastrointestinal hemostasis. It is used 40,000 tons per year for food, medical and cosmetic, industrial and agricultural purposes. Therefore, alginic acid and its salts are substances that have been sufficiently confirmed to be safe.

[0003] In recent years, various medicinal effects of alginates have been discovered. For example, Patent Document 1 discloses a cholesterol-lowering agent in the body containing calcium alginate as an active ingredient, and food products, feeds, and pharmaceuticals containing the same. Patent Document 2 discloses a neutral fat-lowering agent for reducing neutral fat in the body, which contains calcium alginate as an active ingredient, and 0.15 g or more of calcium alginate is orally administered to humans or animals 1 to 3 times a day for at least 1 day, and food products, feeds, and pharmaceuticals containing the same. Patent Document 3 discloses a blood purine metabolite-lowering agent for reducing blood purine metabolites, which contains calcium alginate as an active ingredient, and food products, feeds, and pharmaceuticals containing the same.

[0004] Also, Patent Document 4 discloses a calcium alginate gel-forming treatment in which udon dough obtained by kneading a noodle-making raw material containing wheat flour and alginate is made into noodles, the obtained noodle strands are boiled, and then immersed in a calcium solution. After that, a frozen udon with improved viscoelasticity is obtained by performing a freezing treatment or a heat sterilization treatment after film filling. The udon dough obtained by kneading only the wheat flour and salt as raw materials and kneading them into a dough state equivalent to that of the frozen udon with improved viscoelasticity is made into noodles of the same shape by the same method, boiled under atmospheric pressure to adjust to the same moisture content, and compared with a control udon stored in the same distribution temperature range. The viscoelasticity is improved so that the compression depth indicating the breaking stress when the noodle strands returned to the edible state are cut by a rheometer is larger. The means for improving such viscoelasticity is that the wheat flour as a noodle-making raw material is medium-gluten flour, and in addition to medium-gluten flour, active gluten, and alginate, a starch blend with a higher pasting viscosity than wheat flour is used. A frozen udon with improved viscoelasticity that can suppress the increase in blood glucose level after ingestion is disclosed.

[0005] By the way, excessive salt intake causes lifestyle-related diseases, particularly hypertension. When salt is excessively ingested, almost all of the sodium ions in the salt are absorbed, which raises their blood concentration. In an attempt to return the concentration to its original level, the body retains water, increasing the amount of water in the blood and the volume of circulating blood. As a result, the force with which the blood presses against the blood vessels increases, leading to elevated blood pressure. Therefore, dietary therapies that actively involve consuming soy products, dairy products, bananas, avocados, broccoli, carrots, almonds, sardines, dried whitebait, etc., which are rich in potassium and magnesium that promote the excretion of sodium ions, and drug therapies that administer diuretics to promote the excretion of water and sodium in urine are being carried out.

[0006] To excrete sodium ions only through the components contained in food, one has to consume that food every day, which is troublesome. Long-term use of diuretics may cause dehydration, dizziness, weakness, low blood pressure, and electrolyte imbalance.

[0007] In the process of examining various medicinal effects of calcium alginate, the inventors of the present invention discovered the efficacy of calcium alginate powder in excreting sodium ions and completed the present invention.

Prior Art Documents

Patent Documents

[0008]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Summary of the Invention

Problems to be Solved by the Invention

[0009] The present invention has been made to solve the above problems, can be incorporated into foods and drinks, etc. or directly ingested, can suppress the absorption of sodium ions into the blood, or can further efficiently and rapidly excrete sodium ions in the body, has few side effects even when ingested, has high in vivo safety, and aims to provide a sodium ion absorption inhibitor into the blood that can be mass-produced or obtained in large quantities, an oral ingestion product using the same, and a method for measuring the ability to inhibit sodium ion absorption into the blood for examining its effectiveness.

Means for Solving the Problems

[0010] The sodium ion absorption inhibitor into the blood made to achieve the above object is characterized by containing calcium alginate powder as an active ingredient.

[0011] For this sodium ion absorption inhibitor into the blood, it is preferable that the calcium alginate powder has a particle size not exceeding a particle size passing through 80 mesh. Even finer is more preferable. It is even more preferable that the particle size does not exceed a particle size passing through 150 mesh.

[0012] For this sodium ion absorption inhibitor into the blood, it is even more preferable that the calcium alginate powder has a particle size not exceeding a particle size passing through 270 mesh.

[0013] This sodium ion absorption inhibitor into the blood is, for example, for single administration or repeated administration.

[0014] This sodium ion absorption inhibitor into the blood may be for single administration and may have an action of inhibiting the absorption of sodium ions into the blood and an action of inhibiting the increase of sodium ions in the blood.

[0015] This sodium ion absorption inhibitor in the blood, for example, contains the calcium alginate powder as the active ingredient in an amount of 0.006 g / kg to 2 g / kg per single administration based on the body weight of a human or an animal. Specifically, based on the results of rats in single administration and repeated administration, it is 0.006 g / kg to 0.3 g / kg in terms of the body surface area ratio when extrapolated to humans, and 0.04 g / kg to 2 g / kg in terms of the body weight ratio conversion when extrapolated to humans.

[0016] This sodium ion absorption inhibitor in the blood is for the repeated administration and may further have an action of promoting the excretion of sodium ions into feces.

[0017] This sodium ion absorption inhibitor in the blood, for example, contains the calcium alginate powder as the active ingredient in an amount of 0.006 g / kg to 2 g / kg per day based on the body weight of a human or an animal.

[0018] The oral intake product made to achieve the above object contains the sodium ion absorption inhibitor in the blood and is characterized by being any one selected from food and drink products, feeds, and pharmaceuticals.

[0019] This oral intake product is, for example, for single intake or repeated intake.

[0020] This oral intake product for single intake may have an action of inhibiting the absorption of sodium ions into the blood and an action of inhibiting the increase of sodium ions in the blood.

[0021] This oral intake product, for example, contains the calcium alginate powder as the active ingredient in an amount of 0.006 g / kg to 2 g / kg per single administration based on the body weight of a human or an animal.

[0022] This oral intake product may be for repeated intake and may also have an effect of promoting the excretion of sodium ions into feces.

[0023] This oral intake product may be for repeated intake and may also have an effect of suppressing blood pressure elevation.

[0024] This oral intake product contains, for example, the calcium alginate powder as the active ingredient in an amount of 0.006 g / kg to 2 g / kg per day based on the body weight of a human or an animal.

[0025] The method for measuring the ability to suppress sodium ion absorption into the blood, which is made to achieve the above object, is a method for measuring the ability to suppress sodium ion absorption into the blood by administering a sodium ion absorption inhibitor containing calcium alginate powder as an active ingredient, or an oral intake product selected from foods and drinks, feeds, and pharmaceuticals containing the same, to a subject or a test animal, measuring the blood sodium ion concentration over time, and measuring and calculating the ability to suppress sodium ion absorption into the blood based on at least any one of the maximum elevated blood sodium ion concentration among the elevated or decreased blood sodium ion concentrations from the control, the time to reach the maximum elevated blood sodium ion concentration, and the integrated value of the elevated or decreased blood sodium ion concentration.

[0026] In this method for measuring the ability to suppress sodium ion absorption into the blood, for example, the test animal is a rat, and the aqueous solution containing sodium chloride is 0.3% saline.

Effects of the Invention

[0027] The sodium ion absorption inhibitor of the present invention can be formulated in food and drink products, etc. or directly ingested orally, and contains calcium alginate powder as an active ingredient for inhibiting sodium ion absorption into the blood or suppressing an increase in sodium ions in the blood. The sodium ion absorption inhibitor into the blood may further have the ability to excrete sodium ions into feces.

[0028] Since the sodium ion absorption inhibitor into the blood can efficiently and promptly excrete sodium ions in the body, before the onset of lifestyle-related diseases, especially hypertension, or cerebral infarction / hemorrhage, myocardial infarction / angina pectoris, chronic renal failure such as nephrosclerosis, aortic aneurysm / obstructive arteriosclerosis, and diabetes, it can lower the blood salt concentration and suppress the onset and progression of lifestyle-related diseases or prevent them.

[0029] In the sodium ion absorption inhibitor into the blood, calcium alginate powder, which is an active ingredient for sodium ion excretion, is already industrially and commercially contained as an additive in a wide variety of orally ingested products for food, medical, cosmetic, industrial, and agricultural uses and has already been put into practical use. Therefore, it has high safety in the living body and there is almost no concern about side effects.

[0030] Oral ingestion products such as food and drink products, feeds, and pharmaceuticals containing this sodium ion absorption inhibitor into the blood can suppress the absorption of sodium ions into the blood and then excrete them from feces, and can adjust to an appropriate blood concentration even if there is an excessive intake of salt. Therefore, through normal eating habits of ingesting such oral ingestion products, the blood sodium ion concentration can be adjusted without difficulty.

[0031] This sodium ion absorption inhibitor into the blood may be administered repeatedly, for example, 1 to 3 times a day for consecutive days or 1 to 6 days a week, but the inhibitory effect on sodium ion absorption into the blood can be sufficiently achieved even by single administration. In particular, when it is formulated in staple foods such as rice, noodles, and bread, it can be ingested without difficulty without being noticed, and thus has the same effect as a low-salt diet.

[0032] The sodium ion absorption inhibitor in blood is a general-purpose product in which the active ingredient, calcium alginate powder, has already been distributed, and it can be mass-produced or obtained in large quantities.

[0033] Therefore, the oral intake products of the present invention, such as food and drink, feed, and pharmaceuticals containing this sodium ion absorption inhibitor in blood, can be easily manufactured at low cost and high quality.

[0034] Moreover, since calcium alginate powder is relatively stable to heat, even if it is heated during the manufacture of oral intake products, it does not cause a decrease in quality or a reduction in efficacy.

[0035] According to the method for measuring the ability to inhibit sodium ion absorption in blood of the present invention, by measuring the subtle fluctuations in sodium ion concentration in blood during excessive salt intake, the ability to excrete sodium ions by administering a sodium ion absorption inhibitor in blood can be accurately and easily measured.

Brief Description of the Drawings

[0036]

Figure 1

Figure 2

Figure 3

Modes for Carrying Out the Invention

[0037] Hereinafter, the modes for carrying out the present invention will be described in detail, but the scope of the present invention is not limited to these modes.

[0038] The sodium ion absorption inhibitor of the present invention contains calcium alginate (hereinafter, may be abbreviated as Ca-Alg) powder as an active ingredient, and may consist only of calcium alginate powder or may contain excipients and other additives, and the dosage form may be a powder, fine granule, or granule.

[0039] The particle size of the calcium alginate powder in this sodium ion absorption inhibitor significantly contributes to the sodium ion excretion ability. When the particle size of the calcium alginate powder is shown as the particle size passed through a sieve with the maximum particle size in mesh (ASTM mesh or Tyler mesh), it is preferably the particle size passed through a sieve with 80 mesh (aperture 177 μm), that is, a particle size of 80 mesh or less (hereinafter, also referred to as the maximum particle size being 80 mesh or less). Among them, it may be the one with the maximum particle size passed through a sieve with 150 mesh (aperture 104 μm), that is, a particle size of 150 mesh or less (hereinafter, also referred to as the maximum particle size being 150 mesh or less), and it is even more preferable that the maximum particle size is the particle size passed through a sieve with 270 mesh (aperture 53 μm), that is, a particle size of 270 mesh or less (hereinafter, also referred to as the maximum particle size being 270 mesh or less).

[0040] Examples of the calcium alginate powder include Kimica Alginate Grade CAW-SF20 (270 mesh or less), CAW-150 (150 mesh or less), and CAW-80 (80 mesh or less) (all are trade names of products manufactured by Kimica Corporation).

[0041] Although the details of the reason why the particle size of the calcium alginate powder significantly contributes to the sodium ion excretion ability are not necessarily clear, since calcium alginate powder is insoluble in water and the finer it is, the better the efficacy and effect, it is presumed that the larger the specific surface area of the powder, the better the efficacy and effect.

[0042] Therefore, when administered or ingested by humans, based on the results in rats for single-dose or repeated-dose administration once a day or multiple times a day, it is 0.006 g / kg to 0.3 g / kg in terms of the body surface area ratio when extrapolated to humans, and 0.04 g / kg to 2 g / kg in terms of the body weight ratio conversion when extrapolated to humans.

[0043] That is, since this sodium ion absorption inhibitor in the blood showed an inhibitory effect on sodium ion absorption in the blood with a single dose of 8 mg per rat (about 200 g), simply converting to an adult body weight of 60 kg, it is 300 times the body weight of the rat. Therefore, it can be estimated that it is effective at 2.4 g / adult (about 60 kg), that is, 0.04 g / kg. However, since the body surface area of a rat and that of a human are calculated to be about 1: about 45 - 50, although they are not proportional to their respective body weights, they are considered to be proportional to their respective intestinal surface areas. Therefore, it is estimated that calculating based on a ratio 45 - 50 times the body surface area of an adult to that of a single rat is closer to the approximate value than calculating based on a 300-fold ratio of the adult body weight (about 60 kg) to the body weight of a single rat. From this, it can be extrapolated that it is sufficiently effective at 8 mg × 45 = 0.36 g / adult (about 60 kg), that is, 0.006 g / kg.

[0044] On the other hand, since this sodium ion absorption inhibitor in the blood showed an inhibitory effect on sodium ion absorption in the blood and a promoting effect on sodium ion excretion in feces with repeated administration of up to 400 mg per rat (about 200 g), simply converting to an adult of 60 kg, it can be estimated that it is effective at 120 g / adult (about 60 kg), that is, 2 g / kg. However, from the human-rat body surface area ratio, it can be extrapolated that it is sufficiently effective at 400 mg × 45 = 18 g / adult (about 60 kg), that is, 0.3 g / kg. Accordingly, it is preferable to formulate this sodium ion absorption inhibitor in oral ingestion products containing the same, such as food and drink products, feeds, and pharmaceuticals, so that it falls within this range in terms of adult conversion.

[0045] For example, when it is set to 2.4 g / 60 kg (adult) to 120 / 60 kg (adult), as the blending ratio per solid content of food and drink products for adults who may develop lifestyle-related diseases, when blending into soup, beverages, etc. per 200 mL for one meal a day, the sodium ion absorption inhibitor in the blood becomes 1.2 to 60 w / w%, but considering the case of blending into soup, beverages, etc. per 200 mL for three meals a day, it may be set to about 1 / 3 of that. Also, as the blending ratio per solid content of food and drink products, when blending per 150 g of udon, bread, rice, or one side dish for one meal a day, it becomes 0.9 to 45 w / w% in proportion, but considering the case of blending per 150 g of udon, bread, rice, or one side dish for three meals a day, it may be set to about 1 / 3 of that. Also, as the blending ratio per solid content of food and drink products, when blending per one piece of confectionery, jelly, or ice cream for about one meal a day, it becomes 0.6 to 30 w / w% in proportion. Since it has high safety, it is preferable to administer / ingest it to children while appropriately adjusting the dosage and intake according to their weight and age. Or when blending into animal feed, in the case of rats (about 200 g / individual), when calculating proportionally according to a daily diet amount of 15 to 30 g, it will be mixed at most about 3 w / w%.

[0046] Within this range, even with a single administration, the sodium ion absorption inhibitory effect and sodium ion excretion effect from the blood can be sufficiently achieved. However, with repeated administration, for example, 1 to 6 times a day, preferably 1 to 3 times each before, during, after meals, or between meals, and administered for 1 to 6 days continuously or per week, the sodium ion absorption inhibitory effect in the blood and the promoting effect of sodium ion excretion into feces will be sufficiently shown.

[0047] This sodium ion absorption inhibitor in the blood may be administered orally as it is, or it may be used in oral intake products containing the sodium ion absorption inhibitor in the blood, such as food and drink products, feed, and pharmaceuticals.

[0048] Food and drink products include beverages such as juice and milk, dairy products such as ice cream, frozen yogurt, and jelly, confectioneries such as Japanese and Western sweets, baked products such as bread and cakes, noodles such as udon, soba, spaghetti, and ramen, and cooked rice. Calcium alginate powder is insoluble in water (equivalent to "hardly soluble" in the expression according to the Japanese Pharmacopoeia General Rules, that is, "the amount of solvent, which is water, required to dissolve 1 g of solute is 10,000 mL or more"), so it can remain in powder form even after administration or ingestion. It is preferable that food and drink products contain an appropriate amount of calcium alginate powder per product so that it can be ingested at 0.006 g / kg to 2 g / kg per single dose and / or repeatedly at 0.006 g / kg to 2 g / kg per day with respect to the total amount ingested per meal or per time. For example, it may be used by mixing calcium alginate powder into the flour such as wheat flour, buckwheat flour, and rice flour, which are raw materials for confectioneries, baked products, and noodles, to prepare the dough. It may also be used by mixing calcium alginate powder into the cooked rice.

[0049] As feed, it includes concentrated feeds such as seeds like wheat and oats, bran, oilseed meal such as oilseed extraction residues, and animal feeds such as fish meal, and roughages such as fresh grass like pasture, root vegetables like turnips and beets, silages obtained by lactic acid fermentation of fresh grass, hay obtained by drying pasture, straws such as crop straws, mineral feeds such as oyster shells and mineral salts, and feed additives such as vitamins. Since feeds are mostly in powder, granule, or solid form, they are prepared by mixing and kneading the aforementioned predetermined amount of calcium alginate powder.

[0050] As pharmaceuticals, they may contain excipients and other additives, and may be in the form of powders, fine granules, granules, tablets, or capsules, and may be administered to humans or animals such as livestock as a hypertension preventive or antihypertensive agent, or as a preventive agent for lifestyle-related diseases. Pharmaceuticals are prepared by mixing and kneading the aforementioned predetermined amount of calcium alginate powder.

[0051] The method for measuring sodium ion excretion ability of the present invention is made in view of the fact that even if excessive intake of salt is taken from food and drink, the blood sodium ion concentration fluctuates greatly depending on the intake time and duration of food and drink, and it is not easy to evaluate the excretion of sodium ions. It can simply and accurately measure the sodium ion excretion ability by administering a sodium ion absorption inhibitor containing calcium alginate powder as an active ingredient into the blood.

[0052] In the method for measuring sodium ion excretion ability of the present invention, a test subject or a test animal, preferably a rat, is simultaneously administered with an aqueous solution containing salt, for example, 0.3% saline diluted from miso soup (salt concentration of about 1%), and an oral intake product selected from a sodium ion absorption inhibitor into the blood or a food, drink, feed, and pharmaceutical containing the same. Blood is sampled at regular intervals, and the blood sodium ion concentration is measured over time with an ion selective analyzer. As a control, the blood sodium ion concentration (average value C cont,av : for example, the unit is mmol / L) and the difference between the blood sodium ion concentration (C) over time, that is, the maximum blood sodium ion concentration (ΔC max : for example, the unit is mmol / L), the time (T max : the unit is minutes) when the maximum blood sodium ion concentration is reached after administration, and the integrated value (ΔAUC: the unit is, for example, mmol·min / L) of the rising or falling blood sodium ion concentration (ΔC). That is, in a graph with the elapsed time after administration on the horizontal axis and the blood sodium ion concentration on the vertical axis, the area of the blood sodium ion concentration exceeding the average value C cont,av The sodium ion excretion ability is measured and calculated by at least any one of them. In addition, the positive control that administers only 0.3% saline without administering the sodium ion absorption inhibitor and the values obtained by administering both 0.3% saline and the sodium ion absorption inhibitor into the blood are compared with their respective ΔC max Or, if there is a significant difference when compared with ΔAUC, the effect of the sodium ion absorption inhibitor is recognized.

[0053] As a control, the blood sodium ion concentration (average value C cont,av ) in the group not administered with the sodium ion absorption inhibitor into the blood and not administered with the aqueous solution containing sodium chloride (negative control group) is replaced with 、 The blood sodium ion concentration at the time of administration of the sodium ion absorption inhibitor into the blood and the aqueous solution containing sodium chloride, or immediately before or after the administration of the sodium ion absorption inhibitor into the blood by the administration of the aqueous solution containing sodium chloride may be used.

Example

[0054] Hereinafter, an example in which a rat was administered with a sodium ion absorption inhibitor into the blood containing calcium alginate powder as an active ingredient and a feed containing the same to which the present invention is applied, and a comparative example in which a rat was administered with a feed not containing or not administered with a sodium ion absorption inhibitor into the blood to which the present invention is not applied will be described in detail.

[0055] (Example 1: Sodium ion excretion effect confirmation test by single administration of a sodium ion absorption inhibitor into the blood composed of calcium alginate having different particle sizes) Rats were orally administered once with a dilute saline solution and a sodium ion absorption inhibitor into the blood composed of calcium alginate having different particle sizes, and the difference in the sodium ion absorption inhibitory and excretion promoting effects was examined.

[0056] As test animals, 8-week-old male Wistar rats (manufactured by Nippon SLC Co., Ltd.) were used. As the sodium ion absorption inhibitor into the blood, calcium alginate powders having a particle size passing through 80 mesh or less, 150 mesh or less, and 270 mesh or less, namely, Kimica Alginate Grade CAW-80, CAW-150, and CAW-SF20 (all manufactured by Kimica Corporation; trade name) were used. Further, 0.3 w / v% saline was prepared from sodium chloride and ion-exchanged water.

[0057] Four groups of rats with n = 3 - 4 were prepared for each group. First, under anesthesia, 100 μL of blood was collected from the jugular vein. As test groups 1 - 3, 5 mL / kg of 0.3 w / v% saline and 8 mg of calcium alginate powder with particle sizes below 80 mesh, below 150 mesh, and below 270 mesh, respectively, were orally administered simultaneously while the rats were awake. As control group 1, no sodium ion absorption inhibitor was administered to the blood, and 5 mL / kg of 0.3 w / v% saline was orally administered while the rats were awake. In each case, blood was collected in the same manner at 5 minutes, 15 minutes, 30 minutes, 60 minutes, 120 minutes, and 180 minutes after administration. Immediately after blood collection, the sodium ion concentration was measured using an electrolyte Na, K dedicated measuring instrument Fingraph (manufactured by Otsuka Pharmaceutical Co., Ltd.; trade name. Registered trademark), which is a general medical device ion selective analyzer.

[0058] As a control, the difference between the average blood sodium ion concentration (C cont,av : unit is mmol / L) in control group 1 until 180 minutes after administration and the blood sodium ion concentration (C) over time, that is, the rising or falling blood sodium ion concentration (ΔC: unit is mmol / L), the maximum rising blood sodium ion concentration (ΔC max : for example, the unit is mmol / L) was calculated. The results of the rising or falling blood sodium ion concentration (ΔC) over time are shown in Fig. 1(a). Also, the achievement time (T max : unit is minutes) from administration to the maximum rising blood sodium ion concentration was calculated. Furthermore, the integrated value (ΔAUC: unit is, for example, mmol·min / L. That is, it corresponds to the area of the rising or falling blood sodium ion concentration (ΔC) in Fig. 1(a)) of the rising or falling blood sodium ion concentration (ΔC) was calculated. The results are shown in Table 1 below, as well as in Figs. 1(b) and 1(c).

[0059]

Table 1

[0060] As is clear from Table 1 and Figure 1, when 5 mL / kg of 0.3 w / v% saline and 8 mg / body of calcium alginate powder with different particle sizes were administered, a significant decrease in ΔAUC and a tendency for a decrease in ΔCmax were observed when the particle size of the calcium alginate powder was below the particle size passing through 270 mesh (ultrafine particles). From this, it can be seen that the absorption of sodium ions into the blood is suppressed by the calcium alginate powder. Also, it was shown that the ability to excrete sodium ions changes according to the particle size of the calcium alginate powder, and the finer the powder, the better the ability to excrete sodium ions.

[0061] (Example 2: Confirmation test of sodium ion excretion effect by repeated administration of a sodium ion absorption inhibitor composed of calcium alginate) While allowing rats to freely ingest a diet containing salt and calcium alginate with different particle sizes for about 5 weeks, the differences in the inhibitory effect on sodium ion absorption and the promoting effect on sodium ion excretion were examined.

[0062] As test animals, 7-week-old male Wistar rats (manufactured by Japan SLC Inc.) were used. As the diet, normal diet CE-2 (trade name, manufactured by Japan Clea Inc.) was used. This normal feed contains 3.2 g / kg of sodium ions.

[0063] Three groups of rats with n = 3 - 6 were prepared for each group. One group was fed a normal diet containing 1.5 w / w% calcium alginate with a particle size below the particle size passing through 270 mesh as the diet, one group was fed a normal diet containing 3.0 w / w% calcium alginate with a particle size below the particle size passing through 270 mesh as the diet, and the remaining one group was fed only the normal diet as a control. At 3 weeks, 4 weeks, and 5 weeks after the start of breeding, each rat was bred for 2 days using a metabolic cage for rats, Metabólica·MC (trade name, manufactured by Natsume Seisakusho Co., Ltd.), and feces and urine were separately collected.

[0064] The feces collected at the time point when two days had passed for each were freeze-dried, the feces volume was measured, 1 / 10 of the feces volume was suspended in 25 mL of a 0.5 W / V% calcium chloride aqueous solution, centrifuged at 10,600×g for 15 minutes, and the supernatant was measured for sodium ion concentration with a compact sodium ion meter LAQUAtwin (trade name, manufactured by Horiba, Ltd.). On the other hand, the urine collected at the time when two days had passed for each was measured for mass, then diluted 100-fold with a 0.5 W / V calcium chloride aqueous solution, and the sodium ion concentration was measured with LAQUAtwin.

[0065] The fecal excretion rate and the urinary excretion rate were determined as follows. Since the measured values of the ion meter are expressed in ppm, they were divided by 1000 and converted to mg / mL. The amount of Na in feces was obtained by multiplying that value by 25 and then further by 10. Since the urine was diluted 100-fold, the amount of Na in urine was obtained by multiplying that value by 100 and then multiplying by the urine volume. Specifically, the measured value of the sodium ion concentration in feces is A ppm. A ppm = A mg / L = (A / 1000) mg / mL. That is, in 25 mL of a 0.5 W / V% calcium chloride aqueous solution, it becomes (A / 1000×25) mg in 1 / 10 of the feces volume. Therefore, in the collected feces, it becomes (A / 1000×25×10) mg. Let F = (A / 1000×25×10) mg. On the other hand, let the measured value of the sodium ion concentration in urine be B ppm. B ppm = B mg / L = (B / 1000) mg / mL. That is, since it was diluted 100-fold with a 0.5 W / V calcium chloride aqueous solution, it becomes (B / 1000×100) mg. Therefore, in the collected urine, it becomes (B / 1000×100×urine volume) mg. Let N = (B / 1000×100×urine volume) mg. Then, the fecal excretion rate (%) is expressed as F / (F + N)×100. On the other hand, the urinary excretion rate (%) is expressed as N / (F + N)×100.

[0066] The results are shown in Table 2 and Figures 2(a) to (c) (in Table 2 and Figure 2, Ca-Alg is calcium alginate).

[0067]

Table 2

[0068] As is clear from FIG. 2 and Table 1, in rats, when rats were allowed to freely consume a diet containing 3.0% of a sodium ion absorption inhibitor containing calcium alginate powder for 5 weeks, it was confirmed that the excretion of sodium ions into feces was promoted.

[0069] As a result of repeated administration, assuming that the daily food intake of rats is 20 g, there is a significant difference at 13 weeks of age after 5 weeks of a diet containing 3% Na. So, 20×3÷100 = 0.6 g = 600 mg. However, since the body weight of rats at 13 weeks of age is about 300 g, when converted to 200 g, it is 400 mg / body.

[0070] From these results, it was shown that the sodium ion absorption inhibitor of the present invention and the oral intake product containing the same suppress the absorption of sodium ions and promote the excretion.

[0071] (Example 3: Confirmation test of blood pressure increase inhibitory effect by repeated administration of sodium ion absorption inhibitor composed of calcium alginate) As test animals, Wistar rats (manufactured by Nippon SLC Inc.) that did not show hypertension symptoms and were given a normal diet during a one-week breeding environment adaptation period, and spontaneously hypertensive SHR rats (Nippon SLC Inc.) that were separated from the Wistar Kyoto (WKY) rat strain and spontaneously developed hypertension with aging without any artificial treatment were used. Diet CE-2 (manufactured by Nippon Clea Inc.; trade name) containing 1.5% by mass or 3.0% by mass of calcium alginate with a particle size of 270 mesh or less or a normal diet CE-2 was given to each group of 5 rats per group as shown in Table 3. During the 15-week breeding period, blood pressure was measured almost weekly while allowing free feeding. Blood pressure measurement was performed non-invasively from the caudal artery of rats placed in a dark pocket using a non-invasive blood pressure measurement device BP-98AL (manufactured by Softron Inc.; trade name) for mice and rats.

[0072]

Table 3

[0073] The results are shown in Fig. 3. As is clear from Fig. 3, in the normotensive Wistar rats fed with the normal diet, the blood pressure hardly changed during the 15-week test period. On the other hand, the blood pressure of the spontaneously hypertensive SHR rats fed with the normal diet was high from the beginning of the test, and gradually increased with breeding. However, in the spontaneously hypertensive SHR rats fed with a powder diet containing 1.5% calcium alginate with a particle size below 270 mesh in the normal diet CE-2, the increase in blood pressure was slightly suppressed compared with those fed with the normal diet. Furthermore, in the spontaneously hypertensive SHR rats fed with a powder diet containing 3.0% calcium alginate with a particle size below 270 mesh in the normal diet CE-2, the increase in blood pressure was suppressed by about 10 - 15% from the 1st week to the 15th week compared with those fed with the normal diet or the powder diet containing 1.5% calcium alginate. In particular, when the Williams test (one-sided) was performed on the spontaneously hypertensive SHR rats fed with the powder diet containing 3.0% calcium alginate after the 10th week, there was a significant difference (** indicates a p-value of ≤ 1%, * indicates a p-value of ≤ 5%). From this, it was considered that calcium alginate is effective in suppressing the increase in blood pressure by repeated administration and treating hypertension. The mechanism is presumed to prevent the increase in blood volume and subsequent hypertension caused by excessive intake of salt (sodium chloride) by suppressing the transfer of sodium ions into the blood and promoting their excretion into feces, thereby adjusting the amounts of sodium and water in the body.

[0074] Thus, since repeated administration of calcium alginate can be expected to treat hypertension, there is a possibility of preventing diseases such as heart failure, myocardial infarction, cerebral infarction, and chronic kidney disease caused by heart hypertrophy due to persistent hypertension.

[0075] (Example 4: Safety evaluation test 1 of a sodium ion absorption inhibitor composed of calcium alginate by repeated administration; biochemical parameters) As test animals, 5-week-old SHR rats (manufactured by Japan SLC, Inc.) that were given normal diet during a one-week breeding environment adaptation period were fed powder diet CE-2 (manufactured by Japan CLEA, Inc.; trade name) containing 0% by mass, 1.5% by mass, and 3% by mass of calcium alginate with a particle size of 270 mesh or less, respectively, to 5 rats in each group. During the 15-week breeding period, while allowing free feeding, blood was collected at the 15th week to measure the biochemical parameters of the rats. The parameters were GLU (blood glucose level), which is an index of endocrine diseases such as diabetes and thyroid diseases, CREA (creatinine concentration), which is an index of renal function, PHOS (inorganic phosphorus concentration), which is an index of renal function and parathyroid function, Ca (calcium concentration), which is an index of endocrine diseases and bone metabolism disorders, ALT (alanine aminotransferase concentration) and AST (aspartate aminotransferase concentration), which are indexes of liver diseases and liver function, ALP (alkaline phosphatase concentration), which is an index of liver and biliary tract disorders and bone diseases, TRIG (triglyceride concentration), which can cause arteriosclerosis, myocardial infarction, and cerebral infarction, Na (sodium concentration), which is an index for maintaining the body's water balance and dysfunction of the kidneys, adrenal glands, nerves, etc., K (potassium concentration), which is an index for evaluating the body balance because it is involved in neurotransmission, muscle contraction, and renal function disorders, and CL (chloride concentration), which is an index of water metabolism disorders and acid-base balance status were measured. For comparison, biochemical parameters were measured in the same manner for Wistar rats, except that they were fed powder diet CE-2 without calcium alginate ad libitum. The results are summarized in Table 4.

[0076] [Table 4]

[0077] As is clear from Table 4, no significant difference was observed in biochemical parameters between SHR fed a normal diet without calcium alginate and SHR fed a diet containing calcium alginate, indicating that there is no problem with safety even after repeated administration. Although the absorption of sodium ions into the blood should be suppressed by ingesting calcium alginate, the blood Na concentration did not change. This is presumably because homeostasis is functioning in the living body, and excessive sodium ions are not absorbed into the blood but excreted in feces, while maintaining the concentration of sodium ions necessary for the living body in the blood to maintain homeostasis.

[0078] (Example 5: Safety evaluation test 2 by repeated administration of a sodium ion absorption inhibitor composed of calcium alginate; organ mass relative to rat body weight) As test animals, 5-week-old SHR rats (manufactured by Nippon SLC Co., Ltd.) were given a normal diet during a one-week acclimation period to the breeding environment, and then CE-2 powder diet (manufactured by Nippon Clea Co., Ltd.; trade name) containing 0 mass%, 1.5 mass%, and 3 mass% of calcium alginate with a particle size below 270 mesh was freely fed to 5 rats in each group for a 15-week breeding period. At the 15th week, after measuring the body weight, all blood was collected and each organ was removed and its mass was measured. For comparison, the mass of each organ was measured in the same manner for Wistar rats, except that they were freely fed a CE-2 diet without calcium alginate. The results are summarized in Table 5.

[0079]

Table 5

[0080] As is clear from Table 5, no significant difference was observed in the mass of each organ between SHR fed a normal diet without calcium alginate and SHR fed a diet containing calcium alginate. Therefore, it was shown that there is no problem with safety to each organ even after repeated administration of calcium alginate.

[0081] As is clear from these results, the sodium ion absorption inhibitor of the present invention containing calcium alginate powder as an active ingredient can suppress the absorption of sodium ions into the blood even with a single administration. However, for the prevention of lifestyle-related diseases and also for the improvement and treatment of lifestyle-related diseases, it was confirmed that the increase in blood pressure associated with the continuous suppression of sodium ion absorption was suppressed by repeated administration.

Industrial Applicability

[0082] The sodium ion absorption inhibitor of the present invention and the orally ingestible product containing the same exhibit the effects of suppressing the absorption and promoting the excretion of sodium ions. Therefore, before the onset of lifestyle-related diseases caused by excessive intake of salt, particularly hypertension, or chronic renal failure such as cerebral infarction, cerebral hemorrhage, myocardial infarction, angina pectoris, and renal sclerosis induced by hypertension, aortic aneurysm, obstructive arteriosclerosis, and diabetes, it is possible to lower the blood salt concentration, suppress the onset and progression of lifestyle-related diseases, prevent them, and contribute to the reduction of medical expenses.

[0083] In addition, according to the sodium ion excretion ability measurement method of the present invention, the efficacy of the sodium ion absorption inhibitor into the blood containing calcium alginate powder as an active ingredient can be accurately and simply measured.

Claims

1. 1. An agent for inhibiting sodium ion absorption into the blood, comprising calcium alginate powder as an active ingredient.

2. 2. The sodium ion absorption inhibitor according to claim 1, wherein the calcium alginate powder has a particle size that is equal to or smaller than a particle size that passes through an 80 mesh.

3. 2. The sodium ion absorption inhibitor according to claim 1, wherein the calcium alginate powder has a particle size that is equal to or smaller than a particle size that passes through a 270 mesh.

4. 2. The sodium ion absorption inhibitor into blood according to claim 1, which is for single or repeated administration.

5. 5. The sodium ion absorption inhibitor into the blood according to claim 4, which is for single-dose administration and has an effect of inhibiting sodium ion absorption into the blood and an effect of inhibiting an increase in sodium ions in the blood.

6. The sodium ion absorption inhibitor into the blood according to claim 5, characterized in that the calcium alginate powder is contained as the active ingredient in an amount of 0.006 g / kg to 2 g / kg of human or animal body weight per single dose.

7. 5. The sodium ion absorption inhibitor into the blood according to claim 4, which is for repeated administration and further has the effect of promoting excretion of sodium ions into feces.

8. The sodium ion absorption inhibitor into the blood according to claim 7, characterized in that the calcium alginate powder is contained as the active ingredient in an amount of 0.006 g / kg to 2 g / kg of human or animal body weight per day.

9. 13. An orally ingested product comprising the agent for inhibiting sodium ion absorption into blood as described in claim 1, the product being any one selected from the group consisting of food and drink, feed, and medicine.

10. 10. The orally ingested product according to claim 9, which is for single or repeated ingestion.

11. 11. The orally ingested product according to claim 10, which is for single-dose ingestion and has the effect of inhibiting sodium ion absorption into the blood and the effect of inhibiting an increase in sodium ions in the blood.

12. The orally ingested product according to claim 11, characterized in that the calcium alginate powder is contained as the active ingredient in an amount of 0.006 g / kg to 2 g / kg of body weight of a human or animal per single dose.

13. 11. The orally ingested product according to claim 10, which is for repeated ingestion and further has the effect of promoting excretion of sodium ions into feces.

14. 11. The orally ingested product according to claim 10, which is for repeated ingestion and further has an effect of suppressing elevation of blood pressure.

15. An orally ingested product as described in any one of claims 13 to 14, characterized in that the calcium alginate powder is contained as the active ingredient in an amount of 0.006 g / kg to 2 g / kg of human or animal body weight per day.

16. A method for measuring the ability to inhibit sodium ion absorption into the blood by administering an inhibitor of sodium ion absorption into the blood containing calcium alginate powder as an active ingredient, or an orally ingested product containing the same and selected from food, beverages, feed, and pharmaceuticals, characterized in that a salt-containing aqueous solution and the inhibitor of sodium ion absorption into the blood or the orally ingested product are administered to a subject or test animal, blood sodium ion concentration is measured over time, and the ability to inhibit sodium ion absorption into the blood is measured and calculated from at least one of the maximum increased blood sodium ion concentration among the increasing or decreasing blood sodium ion concentrations from a control, the time to reach the maximum increased blood sodium ion concentration, and the integrated value of the increasing or decreasing blood sodium ion concentrations.

17. 17. The method for measuring the ability to inhibit sodium ion absorption into blood according to claim 16, wherein the test animal is a rat, and the salt-containing aqueous solution is 0.3% saline.

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