WO2006033412A1

WO2006033412A1 - Alleviator for radiation disorder

Info

Publication number: WO2006033412A1
Application number: PCT/JP2005/017526
Authority: WO
Inventors: Hiroto Chaen; Toshio Miyake
Original assignee: Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo
Priority date: 2004-09-24
Filing date: 2005-09-22
Publication date: 2006-03-30
Also published as: JPWO2006033412A1; JP2012121914A; JP5498521B2

Abstract

An alleviator for radiation disorders which is safe even when administered to the living body; and a composition containing the alleviator for radiation disorders. The alleviator for radiation disorders contains α-D-glucopyranosyl-(1→2)-L-ascorbic acid as an active ingredient.

Description

Specification

Radiation damage reducing agent

Technical field

[0001] The present invention relates to a novel radiation damage reducing agent and use thereof, more specifically, a-D-darcopyranosyl mono (1 → 2) -L-ascorbic acid (hereinafter referred to as "ascorbic acid 2-darcoside"). ) Related to a novel radiation damage reducing agent and its use.

Background art

[0002] 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 more radiation than ordinary people. Even ordinary people are said to have no effect on the human body, but they are exposed to radiation from cosmic rays and the crust, that is, natural radiation. In recent years, radiation doses have gradually increased 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 treatments for cancer, etc. I am worried. There is also an increased risk of accidental exposure to large amounts of radiation due to accidents at nuclear power plants. Exposure to large amounts of radiation can cause cell dysfunction and death, resulting in suppression of hematopoiesis, decreased immune capacity, death of nerve tissue, bleeding of the digestive tract, and decreased reproductive function in the human body. It is said to cause multiple organ failure, as well as 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 can be accumulated to promote aging, increase the incidence of cancer, and inheritance to offspring. It has been pointed out that this leads to a positive impact.

[0003] For the purpose of reducing radiation damage, various radiation protection agents have been proposed.

(For example, see JP-A-6-145057 or JP-A-10-72356), many are not put into practical use, and even if put into practical use, there are problems in terms of safety and effectiveness. There are many things. Therefore, further development of effective and safe radiation damage reducing agents It is strongly desired. Apart from these, the present inventors have disclosed that ascorbic acid 2-darcoside exhibits excellent stability against heat and oxidation (see, for example, Japanese Patent No. 2833848), In these patent documents, it has been described or suggested that ascorbic acid 2-darcoside has an action of reducing radiation damage!

[0004] 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.

Disclosure of the invention

[0005] As a result of various studies conducted by the present inventors for the purpose of solving the above-mentioned problems, it has been newly found that ascorbic acid 2-darcoside has an excellent effect of reducing radiation damage! I found it. In addition, the present invention was completed by confirming that the effect of reducing the radiation damage was exhibited for the composition containing the same. That is, the present invention solves the above-mentioned problems by providing a radiation injury reducing agent containing ascorbic acid 2-darcoside as an active ingredient and its use.

BEST MODE FOR CARRYING OUT THE INVENTION

[0006] Ascorbic acid 2-darcoside used in the present invention is one in which one molecule of glucose is bonded to the carbon position of ascorbic acid at the 2-position, and its origin and production method are not limited. It may be produced by a synthesis method or the like, and it is optional to purchase and use commercially available ascorbic acid 2-darcoside. As a method for producing ascorbic acid 2-glycoside, for example, as disclosed in Japanese Patent No. 2833848, a mixed solution of ascorbic acid and starch such as dextrin is mixed with cyclomaltodextricancyltransferase or the like. It can be produced by reacting a-glycosyl glycosyltransferase, glycosylated ascorbic acid, and further acting dalcamylase. In addition, it can be purified using ion exchange resin and the like to remove coexisting ascorbic acid and dextrin to prepare highly pure ascorbic acid 2-darcoside. Ascorbic acid 2-darcoside used in the radiation damage reducing agent of the present invention is preferably 90% by mass of ascorbic acid 2-dalcoside in terms of solids (hereinafter referred to as “mass% unless otherwise specified”). "Is simply expressed as"% ".) Those containing more than 95% are used, more preferably 95% or more, and more preferably 97% or more. Also, High reactivity with ascorbic acid such as vitamins like quasi drugs and pharmaceuticals

Crystals with ascorbic acid 2-glycoside purity of 98% or higher when incorporated in foods and drinks that contain active ingredients in high concentrations or ingredients that easily cause a Maillard reaction such as amino acids and proteins. Product is particularly desirable.

[0007] Regarding the blending amount of the radiation damage reducing agent of the present invention into the composition, the composition is ingested or administered (hereinafter, ingested or! May be collectively referred to as "administration"!). In this case, ascorbic acid 2-darcoside is usually contained in the composition in an amount of 0.01 to 100 wZw%, preferably 0.1 to 1 OOw /. W%, more preferably 1 to 100 wZw% is blended.

[0008] 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 epicarocatechin or derivatives thereof, and radivones such as flavonoids such as rutin, hesperidin and naringin or derivatives thereof. The component which has these is mentioned, It can also be used combining those 1 type (s) or 2 or more types. In addition, as terpenes, catechins, and Z or flavonoids, plants containing these components or extracts of plants using water, alcohol, organic solvents, propolis containing these components, etc. It is also optional to use.

[0009] In the present invention, the radiation damage reducing agent to be blended in the composition for reducing radiation damage is not limited in shape, for example, liquid, syrup, mass kit, paste, powder, solid, semi-solid. , Granules, tablets, etc. As necessary, mixed with fillers, excipients, binders, etc., liquids, emulsions, suspensions, syrups, pastes, granules It is also optional to use in various dosage forms such as powders and tablets.

[0010] The radiation damage reducing agent of the present invention may be contained in a process until the target composition is completed or in a finished product. One or more methods such as kneading, dissolving, melting, dispersing, suspending, emulsifying, penetrating, crystallization, spraying, applying, adhering, spraying, coating (coating), pouring, dipping, solidifying, reverse micelle A combination of these is selected as appropriate.

[0011] The radiation injury reducing agent of the present invention or a composition containing the radiation injury is mainly used in daily life. Used for humans who may be exposed to radiation, especially in medical facilities that handle radiation, facilities that use radiation for industrial purposes, nuclear power plants, nuclear waste treatment facilities and reactors Workers of facilities with facilities and equipment with other radiation sources, workers nearby, workers undergoing medical examinations using X-rays, patients receiving radiation therapy due to cancer, aircraft crew , Passengers, and sarayoko are responsible for radiation hazards such as mishandling of radiation sources, accidental ingestion of radioactive materials, nuclear accidents, nuclear accidents such as nuclear explosions and the use of depleted uranium bombs, victims of experiments and wars, etc. It can be used advantageously for prevention and mitigation purposes. It can also be used for non-human animals such as livestock, poultry, pets, fish, mollusks, 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 ascorbic acid 2-darcoside, which is an active ingredient, can be ingested or administered into a living body of a human animal. For example, subcutaneous, intradermal, intramuscular, intraperitoneal or intravascular (including infusion or perfusion) and Z or intramuscular administration, or oral or transgastric A parenteral administration method such as transnasal, pulmonary, transrectal, transvaginal and other transmucosal, eye drops, and external (transdermal) can be appropriately selected.

Therefore, the radiation damage reducing agent of the present invention is an ascorbic acid which is an active ingredient, depending on the usage and dosage, for example, by a method according to a known pharmaceutical manufacturing method (13th revised Japanese Pharmacopoeia, USP24, etc.). 2-Dalcoside alone or in addition, pharmaceutically and pharmacologically acceptable pharmaceutical carriers, excipients, diluents for pharmaceuticals, quasi drugs or topical skin preparations, Binder, disintegrant, colorant, stabilizer, extender, wetting agent, surfactant, lubricant, dispersant, buffering agent, flavoring agent, flavoring agent, fragrance, preservative, solubilizer, solvent It is used with additives such as coating agents and sugar coatings. In addition, reducing sugars such as glucose and maltose, and α, α-trehalose and other carbohydrates such as α, α-trehalose, α-darcosyl α, α-trehalose and α-maltosyl α, α-trehalose Conductors, international publications WO 02Z10361 or Japanese Patent Application No. 2004-174880, cyclic tetrasaccharides, non-reducing carbohydrates such as cyclodextrins, sugar alcohols such as xylitol and maltitol, high-intensity sweeteners, It is optional to use in combination with one or more selected from water-soluble polysaccharides, inorganic acids, organic acids, salts, emulsifiers, erythorbic acid, chlorogenic acid or derivatives thereof. Further, if necessary, known colorants and flavors 1 type of additives such as additives, preservatives, acidulants, umami, sweeteners, stabilizers, extenders, alcohols, water-soluble polymers, chelating agents, antioxidants, browning inhibitors, and off-flavors. Or, it can be used in the form of a composition by mixing two or more kinds in an appropriate amount and formulating them. In addition, it is optional to use a pharmaceutically acceptable inert substance or diluent and a mixture with Z or other pharmacologically active substance, or a form encapsulated in ribosome or a dosage unit form.

[0013] 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, Ringer's solution, sesame oil, corn It is prepared by conventional means using an oily solvent such as oil or olive oil.

[0014] At this time, if desired, solubilizing agents such as sodium salicylate and sodium acetate; buffers such as sodium citrate; humectants such as glycerin; isotonic agents such as glucose; human serum albumin, polyethylene glycol, etc. Stabilizers such as benzyl alcohol and phenol; and additives such as soothing agents such as salt benzalcohol and acetate.

[0015] When used as a parenteral agent, the radiation damage reducing agent of the present invention can be sterilized by an appropriate sterilization method, made isotonic with blood, or pyrogen-free as necessary. Yo! /

[0016] The composition for oral administration further includes tablets, pills, granules, powders, capsules, syrups, emulsions, suspensions, sprays and the like. The composition itself is produced by a known method, and lactose, mannitol, starch, cellulose, magnesium stearate and the like are used as a carrier or excipient.

[0017] 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.

[0018] 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, the solid state The above composition is used as it is, or an excipient, a thickener (for example, natural gums, cellulose derivatives, acrylic polymers, etc.) and the like are added and mixed to obtain a powdery composition. When used as a liquid, use an oily or aqueous suspension. In the case of a semi-solid form, a water-based or oil-based gel, or an ointment is desired.

[0019] In addition, these external preparations are!, And all of them are pH adjusting solutions such as carbonic acid, phosphoric acid, citrate, hydrochloric acid, sodium hydroxide, parabenzoate, chlorobutanol, benzalco-chloride. You may order antiseptics such as When used as a suppository, according to a known method, the composition of the present invention can be made into an oily or aqueous solid, semi-solid, or liquid form, and can be carried out.

[0020] When the composition containing the radiation damage reducing agent of the present invention is a cosmetic or quasi-drug, it is usually combined with the above ingredients and other raw materials used for cosmetics and quasi-drugs. Then, it can be used as a skin external preparation such as cream, lotion, milky lotion, jewel, nose, and poultice. In addition, when ascorbic acid 2-darcoside is added to cosmetics, when it is used in combination with a high molecular weight substance and a neutralizing agent, orientation, coloring and Z or off-flavor may occur. , 3 Butylene glycol, 1,2 pentanediol, polyethylene glycol 60 hydrogenated castor oil, etc. may be blended. In addition, polymer substances to be used in combination with ascorbic acid 2-darcoside include ion-on polymers such as xanthan gum, sodium alginate and sodium carboxymethylcellulose, nonionic polymers such as hydroxymethylcellulose and hydroxypropylmethylcellulose, Desirably, one or two or more kinds of polymers such as alkylated carboxybule polymer such as acrylic acid Z alkyl acrylate copolymer and alkylated carboxybulle polymer and bullypyrrolidone Z styrene copolymer are desirable. In addition, ascorbic acid 2-darcoside is added by using a chelating agent such as ethylenediamintetraacetic acid 3 sodium salt, citrate buffer, ethanolamine, sodium hydroxide, potassium hydroxide and L-arginine. It is possible to stabilize the cosmetics and quasi drugs and suppress coloring.

[0021] 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 usual food, drink, feed, feed, or pet food. If the radiation damage reducing agent of the present invention is blended, [0022] The dosage and administration method of these compositions are appropriately adjusted depending on the body weight, age, symptoms, dosage form, dosage form, administration period, exposure situation, etc. of the subject human animal, but are usually adults Desirably, ascorbic acid 2-darcoside is preferably 0.01 to: LOOg, more preferably 0.1 to 5 g at a rate of Z days once to several times. As for the period of administration, ascorbic acid 2-dalcoside is a safe substance that is enzymatically decomposed into ascorbic acid and glucose when administered to a living body. You may continue to use. In addition, it is possible to expose more radiation than daily radiation exposure in a short period of time, such as boarding an aircraft, X-ray inspection during medical examinations and pathological examinations, and radiation therapy for cancer, etc. If you are strikingly powerful, you can expect a high effect if you administer it just before receiving radiation. Although the radiation damage reducing agent of the present invention can be expected to reduce the radiation damage in any case administered before and after exposure to radiation, or after Z, the highest reduction effect is obtained when administered immediately after exposure to radiation. be able to. In addition, when a large amount of radiation is exposed due to an accident or an operation error of the device, it is more effective to apply it to the skin or administer intravascularly or intramuscularly than oral administration. I'll do it.

[0023] 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.

[0024] <Experiment>

Mice irradiated with X-rays of a certain dose or more will have cell dysfunction and death, and hematopoiesis suppression and immune function decline will progress, resulting in multiple organ failure and infectious diseases such as gastrointestinal bleeding. Is known to lead to death. Therefore, the effect of ascorbic acid 2-darcoside on X-ray exposure in mice was examined by the following method. Specifically, ascorbic acid 2-dalcoside (reagent grade, sold by Hayashibara Biochemical Laboratories Co., Ltd.) is dissolved in physiological saline (sales sold by Otsuka Pharmaceutical Co., Ltd.) to prepare a test solution containing ascorbic acid 2-darcoside (lOOmgZml). Saline was used as a control solution. In each experiment, 10 females (body weight 22 to 25 g) of 10-week-old C3H mice per group were used. 0.2 ml of the test solution or control solution was intraperitoneally administered to the mice. For X-ray irradiation, a medical X-ray irradiation apparatus was used. [0025] <Experiment 1>

Pre-administration group of test solution (test solution was administered 120 minutes before X-ray irradiation, and control solution was administered 10 minutes after irradiation), and pre- and post-administration groups of test solution (test solution 120 minutes before and 10 minutes after X-ray irradiation) Administration) was divided into control solution administration groups (control solution was administered 120 minutes before and 10 minutes after X-ray irradiation), and 7 Gy X-rays were irradiated. On the 30th and 60th day after the first X-ray irradiation, X-ray irradiation and test solution or control solution are administered under the same conditions, and then until the 30th day, every 10th day after the first X-ray irradiation. The number of surviving mice (units) was counted and the results are shown in Table 1.

[0026] [Table 1]

[0027] As is apparent from Table 1, the test liquid administration group containing ascorbic acid 2-darcoside had a significantly higher survival rate and a life-prolonging effect compared to the control solution administration group administered with physiological saline. Ascorbic acid 2-dalcoside was shown to reduce radiation damage. In addition, it was confirmed that the survival rate was higher in the group before and after the test solution administered with the test solution before and after the X-ray irradiation than in the group pre-administered with the test solution.

[0028] <Experiment 2>

An experiment to investigate the effect of ascorbic acid 2-dalcoside on hematopoietic suppression, which is one of the causes of death in mice exposed to X-rays, was performed as follows using the colony-forming ability of mouse splenocytes as an index. That is, the pre-administration group of the test solution (administer the test solution 120 minutes before X-ray irradiation and administer the control solution 10 minutes after irradiation), and the post-administration group of the test solution (administer the control solution 120 minutes before X-ray irradiation) The test solution was administered 10 minutes after irradiation), the test solution before and after administration (test solution was administered 120 minutes before and 10 minutes before X-ray irradiation), and the control solution administration group (120 minutes before and after X-ray irradiation and Ten minutes 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 Sai (Entity). The results are shown in Table 2. 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 number of spleen colonies of mice in the control solution administration group being 100. .

[0029] [Table 2]

[0030] As is apparent from Table 2, the test liquid administration group containing ascorbic acid 2-darcoside has an increased spleen colony formation rate as compared to the control solution administration group to which physiological saline was administered. The effect of acid 2-darcoside on reducing spleen cells (stem cells) was confirmed. Compared between the test solution administration groups, the spleen colony formation rate was highest in the groups before and after the test solution, followed by the test solution pre-administration group, which was the highest after the test solution administration group, and the lowest.

[0031] From the above experimental results, ascorbic acid 2 dalcoside has been shown to increase in cell dysfunction and death due to exposure to radiation, progression of hematopoiesis suppression and immunity decline, and many other factors including bleeding from the digestive tract. It was judged to be effective in the prevention and treatment of radiation damage because of its ability to reduce radiation damage such as organ failure and onset of infections.

[0032] Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples.

Example 1 <Radiation injury reducing agent>

Ascorbic acid 2-Dalcoside (reagent grade, sold by Hayashibara Biochemical Laboratories Co., Ltd.) 5 parts by mass and hydrated crystals (X, a trehalose 5 parts by weight (for pharmaceutical use, sold by Hayashibara Biochemical Laboratories Co., Ltd.) 0. Dissolve in 90 parts by mass of 05M phosphate buffered saline, adjust pH to 7.2 by the usual method, disinfect with membrane and enclose 5ml each in ampoules, pyrogen-free injection for reducing radiation damage Was prepared.

Example 2 <Tablet for reducing radiation damage> Ascorbic acid 2-Dalcoside (reagent grade, sold by Hayashibara Biochemicals Co., Ltd.) 20 mass, lactose 10 parts by mass, calcium lactate 10 parts by mass, magnesium stearate 25 parts by mass, calcium carbonate 5 parts by mass, According to a conventional method, the tablet was pressed with a tableting machine to produce a tablet for reducing radiation damage having a diameter of about 8 mm and a weight of about 200 mg.

[0035] Example 3 <Granules for reducing radiation damage>

Ascorbic acid 2-Dalcoside (reagent grade, sold by Hayashibara Biochemical Laboratories Co., Ltd.) 20 mass, hydrated crystals (, a 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, a granule for reducing radiation damage of 25 to 50 mesh was produced using a spray granulation method.

Example 4 <Capsules for reducing radiation damage>

Ascorbic acid 2-Dalcoside (reagent grade, sold by Hayashibara Biochemical Laboratories Co., Ltd.) 50 mass, calcium lactate 20 parts by mass, magnesium stearate 20 parts by mass, calcium carbonate 10 parts by mass, darcosylrutin (Hayashibara Biochemical Laboratories, Inc.) Sales and trade name “Alfadarcosilrutin”) 5 parts by mass were mixed and 0.5 g each was enclosed in a gelatin capsule to produce a capsule for reducing radiation damage.

[0037] Example 5 <Ointment for reducing radiation damage>

Hydrous crystals α, α Trehalose (Hayashibara Shoji Co., Ltd., trade name “Treha”) 200 parts by mass and maltose 300 parts by mass were mixed with 50 parts by mass of methanol in which 3 parts by mass of iodine was dissolved. Further, 200 parts by mass of a 10% (WZV) aqueous solution of pullulan was added and mixed to obtain an ointment. This product is a radiation damage-reducing ointment with moderate elongation and adherence, with excellent usability.

[0038] Example 6 <cosmetic cream for reducing radiation damage>

Decaglyceryl monostearate 1.2 parts by mass, decaglyceryl monomyristate 1. 8 parts by mass, 0.5 parts by mass of stearyl alcohol, 3 parts by mass of beryl alcohol, 1 part by mass of batyl alcohol, cetyl palmitate 1 Parts by mass, glyceryl stearate 1. 8 parts by mass, fatty acid (C10-30) (cholesteryl Z lanosteryl) 2 parts by mass, isopropyl palmitate 4 parts by mass, squalene 5 parts by mass, otatildodecyl myristate 5 parts by mass, ma force Demian 0.5 parts by weight of nut oil, 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, concentrated glycerin 1 2 Parts by mass, polyquatanumuum 51 0.25 parts by mass, quenate (1% aqueous solution) 1 part by mass, international publication WO 02Z10361, cyclic tetrasaccharide 5 hydrous crystals 1 part by mass, ascorbic acid 2—Dalcoside (trade name “AA2G” sold by Hayashibara Biochemical Laboratories Co., Ltd.) 5 parts by mass, purified water 43.5 parts by weight and darcosilrutin (trade name, Hayashibara Biochemical Laboratories Inc. A cosmetic cream was prepared by a conventional method by mixing 1 part by weight of “alpha darcosyl rutin”) with 5 parts by weight of purified water. This product can be used as a radiation damage-reducing cosmetic cream with an indication that it is used to reduce radiation damage.

[0039] Example 7 <Happens 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, Yucazole TS-620 (Sold by Nippon Carbide) 6 parts by weight, heart force oil

0.3 parts by mass, Cefsol (manufactured by Nikko Chemicals) 0.3 parts by mass, ascorbic acid 2-glucoside (sold by Hayashibara Biochemicals, Inc., trade name “AA2G”), 3 parts by weight, purified water 49.4 A mass part was mixed and a paste and a poultice were prepared by a conventional method. 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 <Radiation damage reducing pan>

100 parts by weight of French bread flour, 5 parts by weight of frozen yeast, syrup containing sugar derivatives of oc, _α —trehalose (trade name “Hello Dettas” sold by Hayashibara Corporation), 3 parts by weight, ascorbic acid 2-darcoside ( Hayashibara Shoji Co., Ltd., trade name "Ascofuresh") 1 part by weight, salt 2 parts by weight, malt extract 0.3 parts by weight, yeast food 0.1 parts 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. [0041] 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 part by weight of emulsifier, 25 parts by weight of water, ascorbic acid 2-darcoside ( Hayashibara Shoji Co., Ltd., 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 of 100 parts by weight. 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.

[0042] Example 10 Chocolate for reducing radiation damage>

15 parts by mass of cacao mass, 21 parts by mass of cacao butter, hydrated crystals a, a-trehalose (Hayashibara Co., Ltd. is a commercial sale, trade name “Treha”) 44 parts by mass, lecithin 1 part by mass, ascorbic acid 2-dalcoside Hayashibara Shoji Co., Ltd., trade name “Asco Fresh”) 1 part by weight, whole fat powdered milk 19 parts by weight, in accordance with the usual method, first cacao mass, cacao butter, a, hi-trehalose, lecithin, whole milk powder, Ascorbic acid 2-darcoside was mixed with a mixer, and after refining and conching, it was homogenized in a tempering process. Then, a plate chocolate was produced through a mold casting and cooling process. This product is delicious! /, A chocolate that can be used to reduce radiation damage with an indication that it is used to reduce radiation damage.

[0043] Example 11 <Gum for reducing radiation damage>

20 parts by weight of gum base, 55 parts by weight of sugar, 12 parts by weight of glucose, ex-hydrated crystals ex, a—Trehalose (trade name “Trehha”, Hayashibara Corporation), 5 parts by weight of starch syrup, 2 parts of ascorbic acid Dalcoside (Hayashibara Shoji Co., Ltd., trade name “ASCOFRESH”) 2 parts by weight, softener 1 part by weight, trace amount of pigment, 2 parts of fragrance, put gum base into the kneader according to a conventional method. After dissolving and stirring at 120 ° C, the temperature was lowered to 50 ° C and then charged into the mixer. The above ingredients are added to the gum base transferred to the mixer in the order of sugar, glucose, OC, hytretreose, starch syrup, ascorbic acid 2-darcoside, softener, pigment, and fragrance, and stirred at the same temperature for 45 minutes. did. After mixing well, it was put into an injection molding machine, extruded into a block shape, further rolled on a roll, and then chopped by a cutter. This product shall be used to reduce radiation damage with a label indicating that it is used to reduce radiation damage. Can be delicious and gum.

[0044] Example 12 <Resistance for reducing radiation damage>

17 parts by weight of water 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 of ascorbic acid 2-Dalcoside (Hayashibara Shoji Co., Ltd., trade name “Asco Fresh”) 2 parts by weight, vanilla An appropriate amount of essence, 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-darcoside were added. Thereafter, the mixture was further boiled with stirring, and butter was added after the boiling temperature reached 130 ° C. After boiling, the temperature reached 130 ° C, then removed from the fire and added with vanilla essence. 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>

Glucose fructose liquid sugar 3 parts by weight, hydrous crystals α, α-trehalose (Hayashibara Corporation sales, trade name "Treh") 4 parts by weight, ascorbic acid 2-Dalcoside (Hayashibara Corporation sales, trade name "a" Scofresh ”) 4 parts by mass, Glycosyl Hesperidin (sales from Hayashibara Biochemical Co., Ltd., trade name“ Alfadarcosyl Hesperidin ”) 1 part by weight, mineral“ condiment appropriate amount, acidulant 2 parts by weight, flavor perfume appropriate amount, water Using 92 parts by weight of the mixture, 300 ml of purified water was heated to 70 ° C., and a small amount of minerals, seasonings and acids were added and stirred. Trehalose, glucose fructose liquid sugar, ascorbic acid 2-darcoside and 1500 ml of purified water were added to this and stirred and dissolved. Pore size: Filtered with a filter of L m, added an appropriate amount of purified water to adjust the volume to about 3000 ml of the final product, added a small amount of perfume and stirred. Bricks and acidity were adjusted in an intermediate tank, heated to reach 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.

[0046] Example 14 Nutrition 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, parin 8 parts by mass A mixture of 1 part by weight of aspartic acid, 1 part by weight of serine, 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. 1% solution by dissolving in 2% by weight of orange juice, syrup containing sugar derivatives of a and a trehalose (trade name “Hello Dettas” sold by Hayashibara Corporation), ascorbic acid 2 —Dalcoside (trade name “Asco Fresh”, sold by Hayashibara Shoji Co., Ltd.) An energy drink containing 2 parts by mass was prepared. This product is a flavor and energy drink that can be used to reduce radiation damage with an indication that it is used to reduce radiation damage.

Industrial applicability

The radiation injury reducing agent of the present invention comprising ascorbic acid 2-darcoside, which has equimolar glucose bound to ascorbic acid, as an active ingredient can be administered to a living body by oral or parenteral administration. Caused by burns, dysfunction and death of cells, suppression of hematopoiesis, decreased immune capacity Multiple organ failure including death of nerve tissue and bleeding from the digestive tract, hair loss, skin erosion, organ fibrosis It can effectively reduce radiation damage such as genetic effects, skin atrophy, accelerated aging, and the development of cancer. It can also improve various clinical symptoms such as diarrhea, nausea, vomiting, loss of appetite and fever associated with these radiation disorders.

Claims

The scope of the claims

[1] a D Dalcoviranosyl (1 → 2) A radiation damage reducing agent containing L-ascorbic acid as an active ingredient.

[2] The radiation damage reducing agent according to item 1 of the claim, further comprising one or more radical scavengers.

[3] The radiation damage reducing agent according to claim 1 or 2, further comprising one or more pharmaceutically acceptable additives.

[4] A composition for reducing radiation damage comprising the radiation damage reducing agent according to any one of claims 1 to 3.

[5] The composition for reducing radiation damage according to claim 4, wherein the composition is any one of a pharmaceutical, a quasi-drug, a cosmetic, a food and drink, a feed, a feed, and a pet food.

[6] Characterized by reducing radiation damage, used for reducing radiation damage

V. The composition for reducing radiation damage according to claim 4 or 5, which is labeled as being able to be used.