JPWO2014038630A1 - Cesium excretion agent, hazardous metal excretion agent, food and drink, feed and medicine - Google Patents

Abstract

To provide a cesium excretion agent, a toxic metal excretion agent, a food and drink, a feed and a medicine that suppress the absorption of cesium and toxic metals into the body or promote the discharge of cesium and toxic metals to the outside of the body. A cesium excretion agent, a toxic metal excretion agent, a food and drink, a feed and a medicine containing the cesium excretion agent or the toxic metal excretion agent containing calcium alginate as an active ingredient.

Description

  The present invention relates to a cesium excretion agent, a toxic metal excretion agent, a food and drink, a feed, and a medicine that suppress the absorption of cesium and toxic metals into the body or promote the discharge of cesium and toxic metals out of the body.

  Alginic acid is a natural polysaccharide contained in brown algae such as kombu and wakame. Alginic acid, alginates, and derivatives thereof are used in the food field as thickeners, stabilizers, gelling agents, and the like, and are also used in a wide range of applications such as pharmaceuticals, cosmetics, and textile processing. Alginic acid is a kind of dietary fiber, and alginates such as sodium alginate are effective in reducing blood cholesterol and improving bowel movement (see, for example, Non-Patent Documents 1 and 2).

  Alginate can change its physical properties by ion exchange. For example, sodium alginate, which is a monovalent metal salt, is soluble in water, but is relatively easily ion-exchanged by bringing it into contact with divalent metal ions such as calcium, thereby forming a network of alginic acid and calcium. Is strengthened and further gelled to calcium alginate which is almost insoluble in water. Many studies have been conducted on the removal of radioactive substances taken into the body and methods for promoting excretion by utilizing this ion exchange capacity. In particular, since strontium is the same divalent metal ion as calcium and has an ionic radius close to that of calcium, it can be easily analogized that alginic acid adsorbs strontium like calcium. In vitro removal of strontium has already been studied, and it has been reported that the amount of residual strontium in humans is about 1/8 compared to the case where radiostrontium is administered after oral administration of alginic acid to humans. (Non-patent Document 3). In animal experiments, it has been confirmed that the same effect is obtained. When 10% alginic acid is added to the feed and rats are bred for a certain period of time, oral administration of radioactive strontium results in a survival rate in the body compared to the control group. It has been reported to decrease to about 1/4 (Non-patent Document 4).

  On the other hand, the excretion effect of alginic acid against radioactive cesium has not been confirmed. Cesium is a monovalent metal ion unlike calcium, and alginic acid adsorbs cesium even though it has a different ionic radius, which is a phenomenon that cannot be easily predicted. Moreover, the excretion effect of alginic acid with respect to a toxic metal has not been confirmed.

Tsutomu Asaoka et al., “Effect of low molecular weight sodium alginate on serum total cholesterol levels in healthy men”, Nutrition-Evaluation and Treatment, 1996, Vol. 13, No. 4, p. 86-91 Oku Tsuneyuki et al., “Improvement of stool volume and stool properties of low molecular weight sodium alginate-containing corn potage”, Progress in Medicine, 2000, Volume 20, No. 10, p. 181-189 R. Hesp et al., “Effect of sodium alginate in inhibiting uptake of radiostrontium by the human body”, Nature, 1965, 208, p. 1341-1342 G.E.Harrison et al., Science, 1966, 152, p. 655

  An object of the present invention is to provide a cesium excretion agent, a toxic metal excretion agent, a food and drink, a feed, and a medicine that suppress the absorption of cesium and a toxic metal into the body or promote the discharge of cesium and a toxic metal to the outside of the body. There is.

  The present invention is a cesium excretion agent containing calcium alginate as an active ingredient.

  The present invention is intended to adsorb cesium ingested by a human or an animal, suppress absorption of cesium into the human or animal body, or promote excretion of cesium from the human or animal body to the outside of the body. It is a cesium excretion agent that is used and contains calcium alginate as an active ingredient.

  The present invention is a food or drink containing the cesium excretion agent.

  The present invention is a feed containing the cesium excretory agent.

  The present invention is a pharmaceutical product containing the cesium excretory agent.

  The present invention is a harmful metal excretion agent containing calcium alginate as an active ingredient.

  The present invention adsorbs harmful metals ingested by humans or animals, suppresses the absorption of harmful metals into the human or animal body, or promotes the discharge of harmful metals from the human or animal body to the outside of the body. It is a harmful metal excretion agent that contains calcium alginate as an active ingredient.

  The present invention is a food or drink containing the harmful metal excretion agent.

  The present invention is a feed containing the harmful metal excretion agent.

  The present invention is a pharmaceutical product containing the harmful metal excretion agent.

  In the present invention, by containing calcium alginate as an active ingredient, the absorption of cesium and harmful metals into the body is suppressed, or the excretion of cesium and harmful metals to the outside of the body is promoted. Food and drink, feed and medicines can be provided.

In an Example, it is a figure which shows the result of the absorption inhibitory effect by comparing the transition of plasma cesium density | concentration when a rat is orally ingested cesium chloride. In an Example, it is a figure which shows the result of the absorption inhibitory effect by comparing the maximum plasma cesium density | concentration when a rat is orally ingested cesium chloride. In an Example, it is a figure which shows the result of the absorption inhibitory effect by comparing the area under the plasma cesium plasma concentration-time curve when a rat was orally ingested cesium chloride. In an Example, it compares the cesium density | concentration in the plasma of a rat, and is a figure which shows the result of an elimination promotion effect. It is a figure which shows the result of the histopathological observation of the control | contrast rat in an Example. (A-2) is an enlarged view of a square part in (a-1). It is a figure which shows the result of the histopathological observation of the rat which gave the sodium alginate diet in an Example. (B-2) is an enlarged view of the left square part in (b-1), and (b-3) is an enlarged view of the right square part in (b-1).

  Embodiments of the present invention will be described below. This embodiment is an example for carrying out the present invention, and the present invention is not limited to this embodiment.

  The cesium excretion agent according to the embodiment of the present invention contains calcium alginate as an active ingredient. Further, the cesium excretion agent according to the present embodiment adsorbs cesium ingested by humans or animals, suppresses absorption of cesium into the human or animal body, or releases cesium from the human or animal body to the outside of the body. Used to promote excretion and contains calcium alginate as an active ingredient.

  The present inventors examined the excretion effect of alginic acid and various alginate on radioactive cesium. By using calcium alginate instead of alginic acid or sodium alginate as an active ingredient, it was administered orally or force maternally to humans or animals. The present inventors have found a new solution that suppresses the absorption of cesium ingested into the body or promotes the discharge of the cesium from the human or animal body to the outside of the body. The cesium excretion agent according to the present embodiment contains calcium alginate that adsorbs cesium as an active ingredient. Therefore, for example, by ingesting orally, cesium that is ingested or accumulated in the body of a human or animal is contained. It can be quickly excreted outside the body.

  Alginic acid is a biodegradable polymeric polysaccharide and is a polymer in which two types of uronic acids, D-mannuronic acid (M) and L-guluronic acid (G), are polymerized in a straight chain. More specifically, homopolymer fraction of D-mannuronic acid (MM fraction), homopolymer fraction of L-guluronic acid (GG fraction), and D-mannuronic acid and L-guluronic acid are randomly arranged This is a block copolymer in which the fractions (MG fraction) are bound arbitrarily. The composition ratio (M / G ratio) of D-mannuronic acid and L-guluronic acid of alginic acid varies mainly depending on the type of organism from which seaweed and the like are derived. The M / G ratio of calcium alginate used in the present embodiment is not particularly limited, but may contain 1.0 or less. More preferably 0.8 or less, more preferably 0.6 or less.

  Calcium alginate, which is an active ingredient, is preferably ingested in an amount of 1.5 to 4 g for humans, taking 1 to 3 times per day as a guide. Moreover, it is more preferable if it is ingested habitually in order to cope with cesium taken forcefully through the digestive tract or the like.

  The cesium excretion agent according to the present embodiment contains calcium alginate as an active ingredient, and uses known pharmaceutically acceptable carriers, excipients, and other additives, tablets, powders, fine granules, capsules , Pills, granules, sustained-release preparations, oral jelly preparations, oral liquid preparations and the like. Moreover, you may contain auxiliary additives, such as a well-known stabilizer, a thickener, a bulking agent, a coloring agent, and a fragrance | flavor.

  A pharmaceutical product intended to remove cesium according to an embodiment of the present invention contains calcium alginate as an active ingredient, adsorbs cesium taken by a human or an animal, and absorbs cesium into the human or animal body. It is used to suppress or promote the discharge of cesium from the human or animal body to the outside of the body.

  Moreover, the harmful metal excretion agent which concerns on embodiment of this invention contains calcium alginate as an active ingredient. Further, the harmful metal excretion agent according to the present embodiment contains calcium alginate as an active ingredient, adsorbs harmful metals taken by humans or animals, and suppresses the absorption of harmful metals into the human or animal body, or It is used to promote the discharge of harmful metals from the human or animal body.

  By using calcium alginate instead of alginic acid or sodium alginate as an active ingredient, the absorption of harmful metals taken orally or forcefully into humans or animals is suppressed, or the harmful metals are treated by humans. Or the discharge | emission from the body of an animal outside a body can be accelerated | stimulated. The harmful metal excretion agent according to the present embodiment contains calcium alginate that adsorbs harmful metals as an active ingredient, so that it is taken or accumulated in the body of a human or animal by taking it orally, for example. Harmful metals can be rapidly excreted outside the body.

  Examples of harmful metals include cadmium, mercury, lead, arsenic, chromium (hexavalent), silver (radioactive silver), thallium, polonium, selenium, copper, antimony, bismuth, cobalt, nickel, and the like. Among these, the harmful metal excretion agent according to the present embodiment is cadmium, mercury, lead, arsenic, chromium (hexavalent), silver (radioactive silver), thallium, polonium from the point of being toxicologically useful. It can be suitably applied to absorption suppression and the like and excretion outside the body.

  A pharmaceutical product intended to remove harmful metals according to an embodiment of the present invention contains calcium alginate as an active ingredient, adsorbs harmful metals taken by humans or animals, and is harmful to humans or animals. Used to suppress metal absorption or to promote the release of harmful metals from the human or animal body.

  In general, pharmaceuticals intended to remove cesium and pharmaceuticals intended to remove toxic metals according to the present embodiment use known pharmaceutically acceptable carriers, excipients, and other additives. In the form of preparations such as tablets, powders, fine granules, capsules, pills, granules, sustained-release preparations and the like. In addition, the pharmaceutical product according to the present embodiment may contain auxiliary additives such as known stabilizers, thickeners, extenders, colorants, and fragrances. The pharmaceutical according to this embodiment may be administered to humans or animals by oral, topical, parenteral, inhalation, spraying, transdermal administration, or the like, or may be administered by other means.

  Here, “pharmaceuticals” include medical drugs that can be ingested containing calcium alginate, health foods developed for medical use, and veterinary drugs developed for animals other than humans.

  Furthermore, by blending the above calcium alginate into foods and drinks, cesium ingested by humans can be adsorbed, absorption of cesium into the human body can be suppressed, or excretion of cesium from the human body to the outside of the body can be promoted. Therefore, the food and drink intended for removing cesium can be used. In addition, by blending the above calcium alginate into the feed, the cesium ingested by the animal can be adsorbed, the absorption of cesium into the animal's body can be suppressed, or the release of cesium from the body of the animal to the outside of the animal can be promoted. The feed for the purpose of removing cesium can be used.

  In addition, by blending the above calcium alginate into foods and drinks, it adsorbs harmful metals ingested by humans, suppresses the absorption of harmful metals into the human body, or discharges harmful metals from the human body to the outside of the body. It can be set as the food-drinks aiming at removing the harmful metal used for promoting. In addition, by blending the above calcium alginate into the feed, the harmful metals ingested by the animals can be adsorbed to suppress the absorption of the harmful metals into the animal's body, or the harmful metals can be discharged from the animal's body to the outside of the body. The feed can be used for the purpose of removing harmful metals used for promotion.

  There are no particular restrictions on the food and drink to be blended, such as beverages, baked goods, frozen sweets, tablet confectionery, candy, gummi, jelly, caramel, jam, chocolate, gum, Japanese confectionery, soups, bread, various retort foods, side dishes, Examples include seafood products, ham, sausages, seasonings, and supplements. Moreover, there is no restriction | limiting in particular also in the feed to mix | blend, Livestock raising of a chicken, a cow, a pig, etc., the feed for aquaculture of fish, etc. are mentioned.

  The mixing ratio of the calcium alginate in the food or drink or feed is not particularly limited as long as it does not affect the main purpose of the food or drink or feed, and a wide range of usage modes is selected according to the product form. can do. Specifically, it is preferably 0.025 to 10% by mass or more when blended in soups, beverages, or feeds as a blending ratio per solid content of food or drink or feed, and blended in cookies or breads. When it does, it is preferable that it is 30-60 mass% or more. When blended in capsules or tablets, the content is preferably 60 to 100% by mass. In addition, if the calcium alginate is used as a powder as it is or as a tablet, the food or drink or feed according to this embodiment can be used as a more natural food or drink or feed containing no additives. preferable.

  Hereinafter, although an example and a comparative example are given and the present invention is explained more concretely in detail, the present invention is not limited to the following examples.

<Example 1>
(Preparation of calcium alginate feed)
It was prepared by mixing 10% by mass of calcium alginate with rat feed.

<Comparative Example 1>
(Preparation of sodium alginate feed)
It was prepared by mixing 10% by mass sodium alginate with the rat feed.

<Test Example 1>
(Cesium absorption suppression effect)
The cesium absorption inhibitory effect of the calcium alginate feed prepared in Example 1 was compared with other alginates. That is, it compared with the sodium alginate feed prepared in Comparative Example 1.

  First, rats are fed with each test substance for 2 weeks and reared. Next, 5 mg of 0.4 mg / ml cesium chloride aqueous solution was orally administered to 1 kg of rat body weight, and the change in plasma cesium concentration after administration was measured. The results are shown in FIG. 1, FIG. 2, FIG. 3 and Table 1. As a control, the change in plasma cesium concentration was also measured for a rat feed (Comparative Example 2) to which no test substance was added. The time 0 in FIG. 1 indicates the plasma cesium concentration before administration of the aqueous cesium chloride solution.

  As a result, calcium alginate prepared in Example 1 from the maximum plasma cesium concentration (Cmax) and the area under the drug blood concentration-time curve (AUC) of each cesium shown in FIG. 1, FIG. 2, FIG. It was revealed that the feed can significantly suppress the absorption of cesium for 1 hour after cesium administration. On the other hand, the sodium alginate diet of Comparative Example 1 showed almost the same cesium concentration transition as that of the control of Comparative Example 2 for 1 hour after cesium administration, and it was not found that the cesium concentration in plasma was decreased. Further, when Cmax in the control of Comparative Example 2 was regarded as 100%, no significant difference was observed in the sodium alginate diet, whereas it decreased to 61% in the calcium alginate diet, and calcium alginate was another test substance. It was revealed that the cesium absorption inhibitory effect was significantly higher than that of.

<Test Example 2>
(Cesium excretion promoting effect)
The cesium excretion promoting effect of the calcium alginate diet prepared in Example 1 was compared with a rat diet to which no test substance was added (Comparative Example 2) as a control.

  Each test substance was given for 2 weeks and the rats were bred and the change in plasma cesium concentration after administration was measured. Also, no cesium chloride aqueous solution was given during the breeding period. The result is shown in FIG. Day 0 indicates the time before ingestion of alginic acid, and the cesium concentration in plasma at that time is defined as the initial concentration, which is indicated as 100%.

  As a result, as shown in FIG. 4, the calcium alginate diet prepared in Example 1 had a plasma cesium concentration reduced after 7 days compared with the control of Comparative Example 2, but no significant difference was observed. After the day, it became clear that the increase of plasma cesium concentration could be suppressed and cesium excretion could be promoted.

  As described in the background art, it is easily imagined that alginic acid can adsorb divalent metal ions such as strontium, and it has been already studied. Surprisingly, however, cesium is a monovalent metal ion. Was also found to have an adsorption effect and promote excretion. This is expected to facilitate the excretion of various metal ions, particularly toxic metals, and can be an effective extracorporeal agent when a large amount of toxic metals are ingested.

  In addition, when histopathological observation was performed after feeding each test substance for 2 weeks, mineral deposition in the renal pelvic epithelium was observed in rats fed with sodium alginate diet. Epithelial hyperplasia was observed around the deposit. Mineral deposits were also observed in the renal medulla or papillary epithelium (FIG. 6 (↓: renal pelvis epithelium, ↓↓: papillary epithelium), see Table 2). Abnormalities were not observed in other tissues. No obvious abnormalities were observed in rats fed the control and calcium alginate diet (see FIG. 5 (*: papillary epithelium, **: renal pelvic epithelium), Table 2). These are thought to be due to the sodium content. When the sodium content of 1 g of sodium alginate is converted to sodium chloride, it becomes 0.3 g, and if the rat ingests 100 g of a diet containing 10% sodium alginate, it means that 3 g of sodium salt has been consumed, resulting in excessive intake of sodium. I think that the. Therefore, this indicates that calcium alginate has less burden on the kidney than sodium alginate.

Claims (10)

  A cesium excretion agent comprising calcium alginate as an active ingredient.   It is used to adsorb cesium ingested by humans or animals, suppress the absorption of cesium into the human or animal body, or promote the discharge of cesium from the human body or animal body to the outside. A cesium excretory agent characterized by containing calcium as an active ingredient.   A food or drink comprising the cesium excretory agent according to claim 1 or 2.   A feed comprising the cesium excretory agent according to claim 1 or 2.   A pharmaceutical comprising the cesium excretory agent according to claim 1 or 2.   A harmful metal excretion agent comprising calcium alginate as an active ingredient.   Used to adsorb harmful metals ingested by humans or animals, suppress the absorption of harmful metals into the human or animal body, or promote the discharge of harmful metals from the human or animal body to the outside of the body A noxious metal excretion agent characterized by containing calcium alginate as an active ingredient.   A food or drink comprising the harmful metal excretory agent according to claim 6 or 7.   A feed comprising the harmful metal excretion agent according to claim 6 or 7.   A pharmaceutical comprising the harmful metal excretory agent according to claim 6 or 7.

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