JPWO2006033412A1 - Radiation damage reducing agent - Google Patents

Abstract

An object of the present invention is to provide a radiation injury reducing agent that is safe even when administered to a living body and a composition containing the radiation injury reducing agent, and α-D-glucopyranosyl- (1 → 2) -L-ascorbine. The problem is solved by providing a radiation damage reducing agent containing an acid as an active ingredient and a composition containing the radiation damage reducing agent.

Description

  INDUSTRIAL APPLICABILITY The present invention effectively uses a novel radiation damage reducing agent and its use, more specifically, α-D-glucopyranosyl- (1 → 2) -L-ascorbic acid (hereinafter referred to as “ascorbic acid 2-glucoside”). The present invention relates to a novel radiation damage reducing agent as a component and its use.

  Usually, people living on the earth have few opportunities to be exposed to radiation. However, people engaged in radiation work, such as nuclear power plant workers and X-ray engineers, are exposed to a greater amount of radiation than ordinary people. Moreover, even if it is a general person, although it is said that there is no influence on a human body, it is exposed by the radiation from a cosmic ray and a crust, ie, natural radiation. In recent years, radiation doses are gradually increasing in the general population due to an increase in the cosmic dose that reaches the ground due to the generation of ozone holes, medical examinations using X-rays and γ-rays, and treatment of cancer. Has been. Also, the risk of accidental exposure to large amounts of radiation has increased due to accidents at nuclear power plants. Exposure to large amounts of radiation causes cell dysfunction and death, and as a result, in the human body, hematopoiesis suppression, immunity decline, nerve tissue death, gastrointestinal bleeding, and reproductive function decline. It is said to cause organ failure, hair loss, skin erosion, organ fibrosis, and skin atrophy. In addition, even a relatively small amount of radiation exposure that does not cause such radiation damage is accumulated to promote aging, increase the incidence of cancer, and genetics to offspring. It has been pointed out that this leads to an impact.

  Although various radiation damage protective agents have been proposed for the purpose of reducing radiation damage (see, for example, JP-A-6-145557 or JP-A-10-72356), many have not been put into practical use. Even if it is put into practical use, there are many problems in terms of safety and effectiveness. Therefore, further development of an effective and safe radiation damage reducing agent is strongly desired. Apart from these, the present inventors have disclosed that ascorbic acid 2-glucoside exhibits excellent stability against heat and oxidation (for example, see Japanese Patent No. 2833848). The patent document does not describe or suggest that ascorbic acid 2-glucoside has an action of reducing radiation damage.

  An object of the present invention is to provide a radiation damage reducing agent that is safe even when administered to a living body and its use for the purpose of reducing various radiation damages.

  As a result of conducting various studies for the purpose of solving the above problems, the present inventors have newly found that ascorbic acid 2-glucoside is excellent in the effect of reducing radiation damage. Moreover, it came to complete this invention by confirming that the effect which reduces a radiation damage is exhibited also about the composition which mix | blended it. That is, this invention solves the said subject by providing the radiation injury reducing agent which contains ascorbic acid 2-glucoside as an active ingredient, and its use.

  Ascorbic acid 2-glucoside used in the present invention is one in which one molecule of glucose is bonded to the second carbon position of ascorbic acid, and its origin and production method are not limited. Fermentation method, enzyme method, organic synthesis method It is also optional to purchase and use commercially available ascorbic acid 2-glucoside. As a method for producing ascorbic acid 2-glucoside, for example, as disclosed in Japanese Patent No. 2833848, an α-type such as cyclomaltodextrin glucanotransferase is added to a mixed solution of ascorbic acid and starch such as dextrin. It can be produced by allowing glycosyl glycosyltransferase to act to glycosylate ascorbic acid and further act on glucoamylase. Moreover, this is refine | purified using an ion exchange resin etc., Ascorbic acid and dextrin which coexist can be removed, and highly purified ascorbic acid 2-glucoside can be prepared. Ascorbic acid 2-glucoside used in the radiation damage reducing agent of the present invention is preferably 90% by mass (hereinafter referred to as “% by mass” unless otherwise specified) in terms of solid matter. Is simply referred to as “%”.) Those containing at least 95% are used, more preferably 95% or more, and particularly preferably 97% or more. It also contains high-concentration active ingredients that are highly reactive with ascorbic acid such as vitamins, as well as quasi-drugs and pharmaceuticals, and ingredients that easily cause Maillard reactions such as amino acids and proteins. When blended in food or drink, a crystalline product having a purity of ascorbic acid 2-glucoside of 98% or more is particularly desirable.

  About the compounding quantity to the composition of the radiation injury reducing agent of this invention, when the said composition is ingestion thru | or administration (Hereinafter, ingestion or administration may be called "administration" collectively), a radiation disorder reduction effect | action is carried out. There is no particular limitation as long as it can be exerted, and usually, ascorbic acid 2-glucoside is usually contained in the composition in an amount of 0.01 to 100 w / w%, preferably 0.1 to 100 w / w%, more preferably 1. To 100w / w%.

  In addition, the radiation damage reducing agent of the present invention may be used in combination with other components having a radiation damage reducing action. Such components include terpenes such as vitamin E and vitamin A or derivatives thereof, catechins such as catechin and epigallocatechin or derivatives thereof, and radical scavenger effects such as flavonoids such as rutin, hesperidin and naringin or derivatives thereof. The component which has these is mentioned, The 1 type (s) or 2 or more types can also be used in combination. As terpenes, catechins and / or flavonoids, plant bodies containing these components or plant extracts using water, alcohol, organic solvents, propolis containing these components, etc. are used. It is also optional.

  In the present invention, the radiation damage reducing agent to be blended in the radiation damage reducing composition may be of any shape, such as liquid, syrup, mass kit, paste, powder, solid, semi-solid, granule, tablet, etc. It may be in any shape, and mixed with a bulking agent, excipient, binder, etc., if necessary, solution, emulsion, suspension, syrup, paste, granule, powder, tablet, etc. It is optional to use in various dosage forms.

  The radiation damage reducing agent of the present invention may be contained in the process until the intended composition is completed or in the finished product. Specific methods thereof include, for example, mixing, kneading, and dissolution. , Melting, dispersion, suspension, emulsification, infiltration, crystallization, spraying, application, adhesion, spraying, coating (coating), pouring, dipping, solidifying, reverse micellization, etc. It is chosen appropriately.

  The radiation damage reducing agent of the present invention or a composition containing the radiation damage is mainly used for humans who may be exposed to radiation in daily life, especially for medical facilities that handle radiation and industrial purposes. X-ray workers, nuclear power plants, nuclear waste treatment facilities and ships equipped with nuclear reactors, other workers with facilities and equipment with radiation sources, and workers nearby. Medical examination recipients, patients undergoing radiation therapy due to cancer, occupants and passengers in aircraft, mishandling of radiation sources, accidental ingestion of radioactive materials, nuclear accidents, nuclear explosions, use of depleted uranium bullets, etc. It can be used advantageously for the purpose of preventing or mitigating radiation damage such as nuclear accidents, experiments and war victims. It can also be used for non-human animals such as livestock, poultry, pets, fish, molluscs, and crustaceans. In addition, the radiation damage reducing agent of the present invention or a composition containing the same may be any method as long as it can be ingested or administered ascorbic acid 2-glucoside, which is an active ingredient, into a human or animal body. It may be administered by a method, for example, subcutaneously, intradermally, intramuscularly, intraperitoneally or intravascularly (including infusion or perfusion) and / or intramuscularly, orally, transgastric or enteral It is possible to appropriately select a parenteral administration method such as transnasal, pulmonary, transrectal, transvaginal, transmucosal, ophthalmic, and external (transdermal).

  Therefore, the radiation damage reducing agent of the present invention is an ascorbic acid, which is an active ingredient, according to the usage and dosage, for example, by a method according to a known pharmaceutical manufacturing method (13th revised Japanese Pharmacopoeia, USP24, etc.). 2-glucoside, alone or in addition, pharmaceutically and pharmacologically acceptable pharmaceutical carriers, excipients, diluents for pharmaceuticals, quasi-drugs, or skin external preparations, Binder, disintegrant, colorant, stabilizer, extender, wetting agent, surfactant, lubricant, dispersant, buffering agent, flavoring agent, flavoring agent, flavoring agent, preservative, solubilizing agent, solvent, Used with additives such as coatings and sugar coatings. Also, reducing sugars such as glucose and maltose, α, α-trehalose, α, α-trehalose, α-glucosyl α, α-trehalose and α-maltosyl α, α-trehalose carbohydrate derivatives, international Non-reducing carbohydrates such as cyclic tetrasaccharides, cyclodextrins, sugar alcohols such as xylitol, maltitol, high-intensity sweeteners, high-solubility sweeteners described in published WO 02/10361 or Japanese Patent Application No. 2004-174880 It is optional to use in combination with one or more selected from polysaccharides, inorganic acids, organic acids, salts, emulsifiers, erythorbic acid, chlorogenic acid or derivatives thereof. In addition, if necessary, known coloring agents, flavoring agents, preservatives, acidulants, flavourants, sweeteners, stabilizers, bulking agents, alcohols, water-soluble polymers, chelating agents, antioxidants, browning It can be used in the form of a composition using a mixture prepared by mixing an appropriate amount of one or two or more of an inhibitor, a taste / odour odor inhibitor and the like. It is also optional to use a pharmaceutically acceptable inert single substance or a mixture with a diluent and / or other pharmacological agent, a form encapsulated in liposomes, or a dosage unit form.

  The composition containing the radiation damage reducing agent of the present invention will be specifically described. When the composition is a solution, it is a water-soluble preparation such as distilled water, physiological saline or Ringer's solution, or sesame oil, corn oil, olive oil. It is prepared by conventional means using an oily solvent such as

  In this case, if desired, a solubilizing agent such as sodium salicylate and sodium acetate; a buffering agent such as sodium citrate; a humectant such as glycerin; a tonicity agent such as glucose; a stabilizer such as human serum albumin and polyethylene glycol; Preservatives such as benzyl alcohol and phenol; additives such as a soothing agent such as benzalkonium chloride and procaine acetate can also be used.

  When used as a parenteral administration agent, the radiation injury reducing agent of the present invention may be sterilized by an appropriate sterilization method, made isotonic with blood, or pyrogen-free as necessary.

  Examples of compositions for oral administration further include tablets, pills, granules, powders, capsules, syrups, emulsions, suspensions, sprays and the like. Such a composition itself is produced by a known method, and lactose, mannitol, starch, cellulose, magnesium stearate and the like are used as a carrier or an excipient.

  For parenteral administration, it is used as, for example, injections, suppositories, patches, eye drops, and external preparations. The injection is usually filled in a suitable ampoule. Examples of suppositories include rectal suppositories and vaginal suppositories, and examples of external preparations include ointments, nasal administration agents, and transdermal administration agents.

  When used as an external preparation, the composition of the present invention can be made into a solid, semi-solid or liquid external preparation according to a known method. For example, as the solid state, the composition of the present invention is used as it is, or powdered by adding and mixing excipients, thickeners (eg, natural gums, cellulose derivatives, acrylic polymers, etc.), etc. The composition is as follows. When used as a liquid, it should be an oily or aqueous suspension. In the case of a semi-solid form, an aqueous or oily gel or ointment is desirable.

  In addition, any of these external preparations may be added with a pH adjusting solution such as carbonic acid, phosphoric acid, citric acid, hydrochloric acid, and sodium hydroxide, and a preservative such as paraoxybenzoic acid esters, chlorobutanol, and benzalkonium chloride. Also good. When used as a suppository, the composition of the present invention can be advantageously made into an oily or aqueous solid, semi-solid, or liquid form according to a known method.

  In addition, when the composition containing the radiation damage reducing agent of the present invention is a cosmetic or quasi-drug, it is usually blended with the above ingredients and other ingredients used in cosmetics and quasi-drugs. It can be used as an external preparation for skin, such as lotion, milky lotion, gel, and haptic agent. When ascorbic acid 2-glucoside is added to cosmetics, when it is used in combination with a polymer substance and a neutralizing agent, oli, coloring and / or off-flavor may be generated. In such a case, glycerin, 1,3- One type or two types such as butylene glycol, 1,2-pentanediol, polyethylene glycol-60 hydrogenated castor oil may be blended. In addition, polymer substances used in combination with ascorbic acid 2-glucoside include anionic polymers such as xanthan gum, sodium alginate and sodium carboxymethylcellulose, nonionic polymers such as hydroxymethylcellulose and hydroxypropylmethylcellulose, acrylic acid / acrylic acid Any one or more of alkylated carboxyvinyl polymers including synthetic polymers such as alkyl copolymers and polymers such as vinylpyrrolidone / styrene copolymers are desirable. In addition, by using a chelating agent such as trisodium ethylenediaminetetraacetate, citrate buffer, ethanolamine, sodium hydroxide, potassium hydroxide, L-arginine and other neutralizing agents, cosmetics containing ascorbic acid 2-glucoside Stabilization of quasi drugs and suppression of coloring can be achieved.

  When the composition containing the radiation damage reducing agent of the present invention is a food, drink, feed, feed, or pet food, a necessary amount of the present invention is added to a normal food, drink, feed, feed, or pet food. What is necessary is just to mix | blend a radiation injury reducing agent.

  The dosage and administration method of these compositions are appropriately adjusted according to the weight, age, symptoms, dosage form, dosage form, administration period, exposure status, etc. of the subject human or animal, but usually per adult Desirably, it is desirable to carry out 0.01 to 100 g, more preferably 0.1 to 5 g ascorbic acid 2-glucoside at a rate of 1 to several times / day. As for the period of administration, ascorbic acid 2-glucoside is a safe substance that is enzymatically decomposed into ascorbic acid and glucose when administered to a living body, and thus continues every day or 1 to several days / week. You may use it. In addition, it is necessary to preliminarily expose more radiation than daily radiation exposure in a short time, such as boarding an aircraft, X-ray inspection during medical examinations and pathological examinations, and radiotherapy such as cancer. If it is known, high effects can be expected if it is administered immediately before receiving irradiation. The radiation damage reducing agent of the present invention can be expected to have a radiation damage reducing effect in any case administered before and / or after radiation exposure, but when administered immediately after exposure to radiation, the highest reduction effect is obtained. be able to. In addition, when a large amount of radiation is exposed due to an accident or an operation error of the apparatus, it is possible to obtain a higher therapeutic effect by applying it to the skin or administering it intravascularly or intramuscularly than oral administration. .

  Hereinafter, the present invention will be described in more detail with reference to experimental examples, but these do not limit the scope of the present invention.

<Experiment>
Mice irradiated with X-rays of a certain dose or more may have cell dysfunction or death, and hematopoiesis suppression or immunity decline may progress, resulting in multiple organ failure or infection such as bleeding from the digestive tract. It is known to lead to death. Therefore, the effect of ascorbic acid 2-glucoside on the X-ray exposure of this mouse was examined by the following method. That is, ascorbic acid 2-glucoside (reagent grade, sold by Hayashibara Biochemical Laboratories Co., Ltd.) is dissolved in physiological saline (sold by Otsuka Pharmaceutical Co., Ltd.) to prepare a test solution containing 100 mg / ml ascorbic acid 2-glucoside. Saline was used as a control solution. In each experiment, 10 females (body weight 22 to 25 g) of 10-week-old C3H mice were used per group. 0.2 ml of the test solution or control solution was administered intraperitoneally to the mouse. For X-ray irradiation, a medical X-ray irradiation apparatus was used.

<Experiment 1>
Pre-administration group of test solution (administration of test solution 120 minutes before X-ray irradiation and administration of control solution 10 minutes after irradiation), and pre- and post-administration groups of test solution (120 minutes before and 10 minutes after X-ray irradiation) Administration) and control solution administration groups (control solution administered 120 minutes before and 10 minutes after X-ray irradiation), and 7 Gy X-rays were irradiated. After the first X-ray irradiation, X-ray irradiation and administration of the test solution or control solution are performed on the 30th and 60th day under the same conditions, and then the survival every 10th day from the first X-ray irradiation until the 30th day. The number of mice (animals) was counted and the results are shown in Table 1.

  As is apparent from Table 1, the test solution administration group containing ascorbic acid 2-glucoside had a significantly higher survival rate than the control solution administration group to which physiological saline was administered. -Radiation damage mitigating action of glucoside was shown. Moreover, it was confirmed that the survival rate of the test solution administration group administered before and after the X-ray irradiation was higher than that of the test solution administration group.

<Experiment 2>
An experiment for examining the effect of ascorbic acid 2-glucoside on hematopoietic suppression, which is one of the causes of death of mice exposed to X-rays, was performed as follows using colony forming ability of spleen cells of mice as an index. That is, the pre-administration group of the test liquid (administer the test liquid 120 minutes before X-ray irradiation and administer the control liquid 10 minutes after the irradiation), the post-administration group of the test liquid (administer the control liquid 120 minutes before the X-ray irradiation) The test solution was administered 10 minutes after irradiation), before and after the test solution administration group (test solution was administered 120 minutes before and 10 minutes after X-ray irradiation), and the control solution administration group (120 minutes before and 10 minutes after X-ray irradiation). Later, the control solution was administered) and irradiated with X-rays (5 Gy). 9 days later, the abdomen was opened and the radiation damage-reducing effect of the test solution on the stem cells was determined by the colony method using splenocytes (Radiation Biology Practice Editing Committee, Radiation Biology Practice, pages 116-118, Kodansha Scientific) Fick). The results are shown in Table 2, in which the number of spleen colonies formed in each group was counted, and the spleen colony formation rate (%) was determined as a relative value with the average value of the number of spleen colonies of mice in the control solution administration group as 100. .

  As is apparent from Table 2, the test liquid administration group containing ascorbic acid 2-glucoside has an increased splenic colony formation rate compared to the control solution administration group to which physiological saline was administered, and the ascorbic acid 2-glucoside The effect of reducing radiation damage on spleen cells (stem cells) was confirmed. When compared between the test solution administration groups, the spleen colony formation rate of the test solution administration group was the highest, followed by the test solution administration group was the highest, and the test solution administration group was the lowest.

  From the above experimental results, ascorbic acid 2-glucoside is a multi-organ failure such as cell dysfunction and death caused by radiation exposure, progression of hematopoiesis suppression and immunity decline, and bleeding from the digestive tract. It was found to be effective in the prevention and treatment of radiation damage.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated in more detail, it cannot be overemphasized that this invention is not limited to these Examples.

Example 1 <Radiation injury reducing agent>
Ascorbic acid 2-glucoside (reagent grade, sold by Hayashibara Biochemical Laboratories Co., Ltd.) and 5 parts by mass of hydrous crystal α, α-trehalose (medicine, sold by Hayashibara Biochemical Laboratories Co., Ltd.) Dissolve in 90 parts by mass of 05M phosphate buffered saline, adjust pH to 7.2 by conventional method, disinfect with membrane and enclose 5ml each in ampule to prepare pyrogen-free injection for reducing radiation damage did.

Example 2 <Tablet for reducing radiation damage>
After mixing ascorbic acid 2-glucoside (reagent grade, Hayashibara Biochemical Laboratories Inc.) 20 mass, lactose 10 mass parts, calcium lactate 10 mass parts, magnesium stearate 25 mass parts, calcium carbonate 5 mass parts, always According to the method, tablets with a tableting machine were produced to produce tablets for reducing radiation damage having a diameter of about 8 mm and a weight of about 200 mg.

Example 3 <Granule for reducing radiation damage>
Ascorbic acid 2-glucoside (reagent grade, sold by Hayashibara Biochemical Laboratories Co., Ltd.) 20 parts, hydrous crystal α, α-trehalose 5 parts by mass (for pharmaceutical use, sold by Hayashibara Biochemical Laboratories Inc.) 10 parts by weight, calcium lactate After mixing 10 parts by mass, 25 parts by mass of magnesium stearate, and 5 parts by mass of calcium carbonate, 25 to 50 mesh granules for reducing radiation damage were produced using a spray granulation method.

Example 4 <Capsules for reducing radiation damage>
Ascorbic acid 2-glucoside (reagent grade, sold by Hayashibara Biochemical Laboratories Co., Ltd.) 50 mass, calcium lactate 20 mass parts, magnesium stearate 20 mass parts, calcium carbonate 10 mass parts, glucosyl rutin (Hayashibara Biochemical Laboratories, Inc.) 5 parts by weight of a commercial product (trade name “alpha glucosyl rutin”) was mixed, and 0.5 g each was enclosed in a gelatin capsule to produce a capsule for reducing radiation damage.

Example 5 <Ointment for reducing radiation damage>
200 parts by mass of hydrous crystal α, α-trehalose (Hayashibara Shoji Co., Ltd., trade name “Treha”) and 300 parts by mass of maltose are mixed, and 50 parts by mass of methanol in which 3 parts by mass of iodine are dissolved is mixed. Furthermore, 200 parts by mass of a 10% (W / V) aqueous solution of pullulan was added and mixed to obtain an ointment. This product is an ointment for reducing radiation damage that has moderate elongation and adhesion, and is excellent in the feeling of use.

Example 6 <cosmetic cream for reducing radiation damage>
1.2 parts by weight of decaglyceryl monostearate, 1.8 parts by weight of decaglyceryl monomyristate, 0.5 parts by weight of stearyl alcohol, 3 parts by weight of behenyl alcohol, 1 part by weight of batyl alcohol, 1 part by weight of cetyl palmitate, stearic acid 1.8 parts by mass of glyceryl, 2 parts by mass of fatty acid (C10-30) (cholesteryl / lanosteryl), 4 parts by mass of isopropyl palmitate, 5 parts by mass of squalane, 5 parts by mass of octyldodecyl myristate, 0.5 mass of macadamian nut oil Parts, 1.8 parts by weight of trioctanoin, 0.3 parts by weight of dimethicone, 6 parts by weight of butylene glycol, 2.5 parts by weight of pentylene glycol, 12 parts by weight of concentrated glycerin, and polyquaternium-51. 25 parts by mass, 1 part by mass of citric acid (1% aqueous solution), International Publication WO 1 part by mass of cyclic tetrasaccharide 5 hydrous crystal described in the specification of No. 02/10361, 5 parts by mass of ascorbic acid 2-glucoside (trade name “AA2G”, sold by Hayashibara Biochemical Co., Ltd.), 43.5 parts by mass of purified water And a mixture of 1 part by weight of glucosyl rutin (trade name “alpha glucosyl rutin” sold by Hayashibara Biochemical Laboratories Co., Ltd.) in 5 parts by weight of purified water, A cosmetic cream was prepared. This product can be used as a cosmetic cream for reducing radiation damage with an indication that it is used to reduce radiation damage.

Example 7 <Hap Agent for Reducing Radiation Damage>
Carboxymethylcellulose 4 parts by weight, sodium polyacrylate 5 parts by weight, glycerin 22 parts by weight, kaolin 10 parts by weight, Nicazole TS-620 (Nippon Carbite Sales) 6 parts by weight, peppermint oil 0.3 parts by weight, Cefsol (Nikko) (Made by Chemicals) 0.3 parts by mass, ascorbic acid 2-glucoside (trade name “AA2G”, sold by Hayashibara Biochemical Laboratories, Inc.), 39.4 parts by mass and 49.4 parts by mass of purified water are mixed in a conventional manner. A haptic agent was prepared. This product can be used as a radiation injury-reducing haptic with a label indicating that it is used to reduce radiation injury.

Example 8 <Pan for Radiation Damage Reduction>
French bread flour 100 parts by weight, frozen yeast 5 parts by weight, α, α-trehalose saccharide derivative-containing syrup (Hayashibara Shoji Co., Ltd., trade name "Hellodex") 3 parts by weight, ascorbic acid 2-glucoside ( Hayashibara Shoji Co., Ltd., trade name “ASCO Fresh”) 1 part by weight, salt 2 parts by weight, malt extract 0.3 part by weight, yeast food 0.1 part by weight, a small amount of emulsifier, water 65 parts by weight, Subdivided into rolls. This was fermented at 28 ° C. and 75% humidity for 80 minutes and then baked for 20 minutes to produce French bread. This product is a delicious bread that can be used to reduce radiation damage with an indication that it is used to reduce radiation damage.

Example 9 <Cookies for reducing radiation damage>
45 parts by weight of flour, 8 parts by weight of vegetable protein, 6 parts by weight of margarine, 6 parts by weight of corn starch, 0.7 parts by weight of swelling agent, 0.3 parts by weight of emulsifier, 25 parts by weight of water, ascorbic acid 2-glucoside Hayashibara Shoji, trade name “ASCO Fresh”) 3 parts by weight, 5 parts by weight of sugar, appropriate amounts of vitamins and minerals were added to make a total amount of 100 parts by weight, and cookies were prepared by a conventional method. This product is a delicious cookie that can be used to reduce radiation damage with an indication that it is used to reduce radiation damage.

Example 10 <Chocolate for reducing radiation damage>
15 parts by mass of cacao mass, 21 parts by mass of cacao butter, hydrous crystals α, α-trehalose (Hayashibara is a commercial sale, trade name “Treha”) 44 parts by mass, lecithin 1 part by mass, ascorbic acid 2-glucoside (Hayashibara Co., Ltd.) Commercial sales, trade name “ASCOFRESH”) 1 part by weight, 19 parts by weight of whole milk powder milk, according to the usual method, first cacao mass, cocoa butter, α, α-trehalose, lecithin, whole milk powder, ascorbic acid 2 -Glucosides were mixed in a mixer and homogenized in the tempering step after refining and conching. Then, the plate chocolate was produced through the casting and cooling process. This product is a delicious chocolate that can be used to reduce radiation damage with an indication that it is used to reduce radiation damage.

Example 11 <Gum for Radiation Damage Reduction>
20 parts by weight of gum base, 55 parts by weight of sugar, 12 parts by weight of glucose, 5 parts by weight of hydrous crystal α, α-trehalose (Hayashibara Shoji Co., Ltd., trade name “Treha”), 5 parts by weight of starch syrup, 2-glucoside ascorbic acid ( Hayashibara Shoji Co., Ltd., trade name "ASCO Fresh") 2 parts by weight, 1 part by weight of softener, trace amount of pigment, 2 parts of perfume, put gum base into kneader and dissolve at about 120 ° C using conventional methods The mixture was stirred and the temperature was lowered to 50 ° C., and then charged into the mixer. The above ingredients were added in the order of sugar, glucose, α, α-trehalose, starch syrup, ascorbic acid 2-glucoside, softener, pigment, and fragrance to the gum base transferred to the mixer, and stirred at the same temperature for 45 minutes. After mixing well, it was put into an injection molding machine, extruded into a block shape, gradually rolled on a roll, and chopped with a cutter. This product is a delicious gum that can be used to reduce radiation damage with an indication that it is used to reduce radiation damage.

Example 12 <Resistance for reducing radiation damage>
17 parts by weight of starch syrup, 60 parts by weight of water, 20 parts by weight of sugar, 1 part by weight of condensed milk, 2 parts by weight of butter, 2 parts by weight of ascorbic acid 2-glucoside (Hayashibara Shoji Co., Ltd., trade name “ASCO Fresh”), appropriate amount of vanilla essence Then, sugar, starch syrup and water were added to the pan and boiled. After the boiling temperature reached 125 ° C., condensed milk and ascorbic acid 2-glucoside were added with stirring. Thereafter, the mixture was further boiled with stirring, and butter was added after the boiling temperature reached 130 ° C. Subsequently, the mixture was boiled, and after the temperature reached 130 ° C., it was removed from the fire and vanilla essence was added. Thereafter, the mixture was stirred and poured into a cooling plate. After the temperature was lowered to about 80 ° C., it was cut into an appropriate length in a rod shape. This product is a delicious candy that can be used to reduce radiation damage with an indication that it is used to reduce radiation damage.

Example 13 <Radiation injury reducing beverage>
3 parts by weight of glucose fructose liquid sugar, 4 parts by weight of water-containing crystal α, α-trehalose (trade name “Trehha” sold by Hayashibara Corporation), ascorbic acid 2-glucoside (sold by Hayashibara Corporation, trade name “ASCO Fresh”) ) 4 parts by weight, glycosyl hesperidin (trade name “alpha glucosyl hesperidin” sold by Hayashibara Biochemical Laboratories, Inc.), 1 part by weight, mineral / seasoning proper amount, 2 parts by weight acidulant, proper flavoring, 92 parts by weight water 300 ml of purified water was heated to 70 ° C., and a small amount of minerals, seasonings and acids were added thereto and stirred and mixed. Trehalose, glucose fructose liquid sugar, ascorbic acid 2-glucoside and 1500 ml purified water were added to this and stirred and dissolved. The mixture was filtered through a filter having a pore size of 1 μm, and an appropriate amount of purified water was added to adjust the liquid volume to about 3000 ml of the final product, and a small amount of flavor was added and stirred. Bricks and acidity were adjusted in the intermediate tank, heated until reaching 85 ° C., and filled into cans or bottles at 80 ° C. This product is a delicious beverage that can be used to reduce radiation damage with an indication that it is used to reduce radiation damage.

Example 14 <Nutritional drink for reducing radiation damage>
As an amino acid mixture, isoleucine 4 parts by mass, leucine 6 parts by mass, lysine 8 parts by mass, phenylalanine 8 parts by mass, tyrosine 1 part by mass, tryptophan 12 parts by mass, valine 8 parts by mass, aspartic acid 1 part by mass, serine 1 part by mass, A mixture of 8 parts by weight of aminoacetic acid, 8 parts by weight of alanine, 2 parts by weight of histidine, 8 parts by weight of arginine, 2 parts by weight of threonine and 1 part by weight of methionine was prepared and dissolved in water to prepare a 1% solution. 2% by weight of orange fruit juice, syrup containing saccharide derivative of α, α-trehalose (sold by Hayashibara Shoji Co., Ltd., trade name “Hellodex”), 2-glucoside ascorbic acid (sold by Hayashibara Shoji Co., Ltd., trade name “ Asco Fresh ") An energy drink with 2 parts by mass added was prepared. This product is a tasty nutrition drink that can be used to reduce radiation damage with an indication that it is used to reduce radiation damage.

Industrial applicability

The radiation damage reducing agent of the present invention comprising ascorbic acid 2-glucoside as an active ingredient, in which equimolar glucose is bonded to ascorbic acid, is burned due to radiation exposure by oral or parenteral administration to a living body. Cellular dysfunction and death, suppression of hematopoiesis, decreased immune capacity Multiorgan failure including nerve tissue death and gastrointestinal bleeding, hair loss, skin erosion, organ fibrosis, genetic effects In addition, radiation damage such as skin atrophy, promotion of aging, and occurrence of cancer can be effectively reduced. It can also improve various clinical symptoms such as diarrhea, nausea, vomiting, loss of appetite, and fever associated with these radiation disorders.

Claims (6)

  A radiation injury reducing agent comprising α-D-glucopyranosyl- (1 → 2) -L-ascorbic acid as an active ingredient.   The radiation injury reducing agent according to claim 1, further comprising one or more radical scavengers.   The radiation injury reducing agent according to claim 1 or 2, further comprising one or more pharmaceutically acceptable additives.   A radiation damage reducing composition comprising the radiation damage reducing agent according to any one of claims 1 to 3.   The composition for reducing radiation damage according to claim 4, which is any one of a pharmaceutical, a quasi-drug, a cosmetic, a food and drink, a feed, a feed, and a pet food.   The composition for reducing radiation damage according to claim 4 or 5, characterized in that it has an action of reducing radiation damage, and is labeled as being used to reduce radiation damage. .