JP6381284B2 - Composition for prevention and / or treatment of memory impairment - Google Patents

Description

  The present invention relates to uses of a yam enzyme-treated product such as a pharmaceutical or a functional food.

  A kind of yam, Tedokoro (scientific name: Dioscorea esculenta) is also called a potato, and is cultivated mainly in the south of Kyushu. Recently, it has been clarified that Tedokoro has an anti-fatigue action, an endurance enhancing action, a nourishing tonic action, and a muscle enhancing action (Patent Document 1). In addition, Tedokoro is known to be a species having a particularly high diosgenin glycoside content among yams, and health-oriented foods focusing on this point have also been developed (Patent Document 2). Furthermore, in recent years, it has been revealed that a composition containing an enzyme-treated product of rhododendron rhizome is effective for anti-fatigue, endurance enhancement, nutrition tonic and body fat reduction (Patent Document 3).

  Alzheimer's disease is a disease that involves pathological findings such as senile plaques, Alzheimer's fibrillary changes, etc., accompanied by clinical problems such as developmental disorders, nest symptoms, ankylosing limbs, epileptiform seizures, etc. It is a type. There has been an increasing trend in the aging society in recent years, and significant social attention has been paid, but no method for improving or treating these symptoms has been found. Moreover, no symptom improvement or treatment has been found for juvenile Alzheimer's disease. Alzheimer's disease is thought to be one of the causes of degeneration and loss of acetylcholinergic nerves (the nerves that produce and release acetylcholine). It protects acetylcholinergic nerves from degeneration and loss of acetylcholinergic nerves. It is considered as one of the symptom improvement methods to activate acetylcholine to promote the release of acetylcholine and to inhibit the degradation of acetylcholine.

  In recent years, intraperitoneal administration of diosgenin (aglycone) has been reported to reduce memory impairment in Alzheimer's disease model mice (Non-Patent Documents 1 and 2). In this report, in the diosgenin administration group, amyloid deposition in the cerebral cortex and hippocampus of model mice was reduced, and a decrease in the amount of fibrotic tau protein was also observed. From this, the target of diosgenin was considered to be 1,25D3-MARRS. However, in the said report, the effect expression by the oral administration of diosgenin is made into the subject.

International Publication No. 2008/123417 Pamphlet JP 2007-274985 A JP 2011-37822 A

Scientific Reports, Volume 2, Issue 535 (2012) Scientific Reports, Vol. 3, No. 3395 (2013)

  An object of the present invention is to provide a diosgenin-containing composition that has a sufficient effect in oral administration with reduced memory impairment.

  1st invention of this invention is related with the composition for the prevention and / or treatment of the memory disorder which contains a yam enzyme processed material as an active ingredient. The composition of the first invention of the present invention is a composition containing an enzyme-treated product obtained by treating yam with an enzyme agent containing a sugar hydrolase and / or a microorganism producing a sugar hydrolase. However, after treating yam with an enzyme containing saccharide hydrolase and / or a microorganism that produces saccharide hydrolase, water-insoluble enzyme-treated product obtained by removing water-soluble substances is effective. The composition may be contained as a component. Further, the composition of the first invention of the present invention may be a composition for oral consumption. Furthermore, the composition of the first invention of the present invention may be a composition for preventing and / or treating memory impairment caused by Alzheimer's disease.

  The second invention of the present invention relates to the use of a yam enzyme-treated product in the manufacture of a composition for oral administration to a human or animal with memory impairment.

  A third invention of the present invention relates to a method for suppressing memory impairment in humans, characterized by orally administering a yam enzyme-treated product to a human in need of prevention and / or treatment of memory impairment.

  The fourth invention of the present invention relates to a food containing the composition of the first invention of the present invention for the prevention and / or treatment of memory impairment.

  The fifth invention of the present invention relates to a prophylactic or therapeutic agent for oral administration containing the composition of the first invention of the present invention for the prevention and / or treatment of memory impairment.

  In the present invention, the processed product of yam is preferably a processed product of Togekokoro.

  The inventors of the present application have a composition containing, as an active ingredient, a water-insoluble enzyme-treated product obtained by treating a yam, for example, rhododendron rhizome, with an enzyme agent having a carbohydrate hydrolyzing activity and / or a microorganism producing a carbohydrate hydrolase. It was found for the first time that an object has the effect of improving the symptoms of memory impairment. Furthermore, this enzyme-treated product was found to have the above-mentioned effect more than an extract containing the same amount of diosgenin glycoside, thereby completing the present invention. According to the present invention, there is provided a composition for preventing or treating memory impairment, comprising a yam enzyme-treated product as an active ingredient. Since the composition of the present invention is a composition that can be taken orally, it is very useful in the prevention or treatment of memory impairment. Moreover, since the composition of this invention can be made into forms, such as a foodstuff, feed, and a pharmaceutical, it can be provided for oral administration.

In Example 2, it is a figure which shows the memory disorder inhibitory effect by the composition of this invention. In Example 3, it is a figure which shows the memory disorder improvement effect by the composition of this invention.

(1) Enzyme-treated product of the present invention and method for producing the same The composition of the present invention is characterized by containing an enzyme-treated product prepared from yam. The yam used as a raw material for the enzyme-treated product (hereinafter referred to as the enzyme-treated product of the present invention) is an enzyme-treated product produced by the method described below that improves or improves learning / memory ability by oral administration. The kind is not particularly limited as long as it can exhibit a memory disorder preventive action or an anti-memory disorder action. Each of the physiological actions can be confirmed according to a method using Alzheimer's disease model mouse 5XFAD as in Example 2 or Example 3 described later, for example. Although the present invention is not particularly limited, todokoro, yellow guinea yam, white guinea yam, Mexican yam and wild yam having a high diosgenin content are suitable for the present invention.

  The enzyme-treated product of the present invention is obtained by treating the yam with an enzyme agent having a carbohydrate hydrolyzing activity and / or a microorganism that produces a sugar hydrolase. In the following, details will be described with reference to rhododendron rhizomes, but the present invention is not limited to those using rhododendron as a raw material. For example, when an enzyme agent or gonococcus having saccharide hydrolyzing activity is allowed to act on rhododendron rhizomes, the structure of the diosgenin glycoside is not hydrolyzed, but the polysaccharide constituting the cell walls of rhododendron rhizomes. Undergoes hydrolysis to lower the molecular weight. In addition, when gonococcus is used or when the lipase or protease is contained in the enzyme agent, proteins and lipids contained in the rhizomes are further decomposed. As a result, many of the constituents of the rhododendron rhizomes other than the diosgenin glycoside are soluble in water. Since the diosgenin glycoside is sparingly soluble in water, a composition that is sparingly soluble in water, obtained by treating rhododendron rhizomes with an enzyme agent having saccharide hydrolyzing activity or a microorganism that produces saccharide hydrolase, Contains a high concentration of diosgenin glycosides. Therefore, after treatment of rhododendron rhizomes with an enzyme agent having saccharide-hydrolyzing activity and / or a microorganism producing saccharide-hydrolyzing enzyme, the solid layer is separated by solid-liquid separation, thereby enriching diosgenin glycosides. Can be collected.

  The rhizome rhizome used as the raw material of the enzyme-treated product of the present invention may be, for example, harvested as it is, and preferably, for example, a ground product, a pulverized product, a crushed product or a mixture thereof, more preferably a dried product thereof. Processed products such as powder can be used.

  In the present specification, the pulverized product and the crushed material refer to, for example, a plant body that has been cut or crushed after being dried, and generally a large particle size is referred to as a crushed material, A small one is called a pulverized product. In the present specification, the dry powder refers to a dry product having a particle size smaller than that of the pulverized product or crushed product. As a method for producing such a dry powder, for example, dried rhododendron rhizomes are pulverized. A method of obtaining a dry pulverized product of powdered spiny rhizomes by pulverizing using a machine.

  Togekokoro rhizome may be subjected to hydrolysis treatment with an enzyme agent having saccharide hydrolyzing activity as it is or fermentation treatment using a microorganism that produces saccharide hydrolase, and this method is also encompassed by the present invention. It is preferable to use these treatments after mixing with an aqueous liquid. Examples of the aqueous liquid include water, for example, tap water, deionized water, distilled water, and the like, and the water may contain an inorganic salt (such as salt) or an organic salt. Moreover, you may use the water to which the other component (The substance which enhances the activity of the enzyme agent which has a carbohydrate hydrolysis activity, the nutrient source for the growth promotion of a koji mold, etc.) was added if desired. In addition, when mixing a rhododendron rhizome and an aqueous liquid, you may adjust pH to pH suitable for the subsequent sugar hydrolysis process and the fermentation process by a koji mold. Such pH is not particularly limited as long as it is suitable for the present invention, but is preferably pH 2 to 10, more preferably pH 3 to 9, and still more preferably pH 3.5 to 8.

  Before the sterilization of rhododendron rhizomes or the mixture of rhizobial rhizomes and aqueous liquids, they must be sterilized before being hydrolyzed with an enzyme that has saccharide-hydrolyzing activity or fermented with microorganisms that produce saccharide-hydrolyzing enzymes. Heat treatment may be performed. The conditions for the heat treatment may be any conditions that are suitable for the subsequent hydrolysis treatment of rhododendron rhizomes with an enzyme agent and / or fermentation treatment of rhododendron rhizomes with Aspergillus, and the temperature condition is preferably, for example, 70 ° C to 130 ° C. It is preferably 80 ° C to 120 ° C, more preferably 90 ° C to 110 ° C. Although the present invention is not particularly limited, the heat treatment time is preferably 5 minutes to 10 hours, preferably 10 minutes to 5 hours, and more preferably 15 minutes to 1 hour.

  In the present specification, the enzyme agent having a saccharide hydrolyzing activity refers to a composition containing an enzyme having a saccharide hydrolase activity (an activity to hydrolyze a glycosidic bond), for example, pectinase, xylanase. And an enzyme composition containing at least one sugar hydrolase selected from the group consisting of hemicellulase, mannanase, amylase, glucoamylase, glucanase, glucosidase, and cellulase. Moreover, the said enzyme agent may contain protease and lipase further. The organisms derived from the sugar hydrolyzing enzymes exemplified here are not particularly limited to the present invention, but include Aspergillus kawachii, Aspergillus awamori, Aspergillus sasperis, Aspergillus sasperis, Aspergillus usamii, Aspergillus usamii Mutant Shirosamii (Aspergillus usamii mut. Shiro-usamii), Aspergillus oryzae, Aspergillus oryzae Bacillus s btillis), Bacillus amyloliquefaciens (Bacillus amyloliquefaciens) Gram-positive bacteria, and the like, as well as Rhizopus sp. (Rhizopus sp.) And filamentous fungi such as Trichoderma reesei. As an enzyme agent that can be used in the present invention, those prepared by a known method from the above organisms and those commercially available can be used. Examples of commercially available products include sucrase (registered trademark, Mitsubishi Chemical Foods), cochlase (registered trademark, Mitsubishi Chemical Foods), glutase (HIBI), cellulosin (HIBI), gluc gin (Amano Enzyme). An enzyme agent for food processing such as Uniase (registered trademark, Yakult Pharmaceutical Co., Ltd.) is exemplified. Among these, Sucrase (registered trademark) A (Mitsubishi Chemical Foods), which is an enzyme agent for fruit juice clarification, includes pectinase, xylanase, protease, lipase and amylase derived from Aspergillus oryzae. Sucrase (registered trademark) X (Mitsubishi Chemical Foods) includes xylanase, cellulase, pectinase and glucanase derived from Trichoderma filamentous fungi.

  In the present invention, for example, Neisseria gonorrhoeae can be used as a microorganism that produces a saccharide hydrolase. Aspergillus oryzae that can be used for the production of the composition of the present invention include Aspergillus awamori, Aspergillus cytoii, Aspergillus osamii, etc. And Aspergillus sojae which is a white mutant thereof. These koji molds produce enzymes such as pectinase, xylanase, hemicellulase, mannanase, amylase, glucoamylase, glucanase, glucosidase, and cellulase. The koji mold used for the fermentation of the rhododendron rhizome is not particularly limited, but black koji mold or white koji mold is preferable, and Aspergillus kawachi and Aspergillus awamori can be preferably used.

  In the production of the enzyme-treated product of the present invention, only an enzyme agent having a saccharide hydrolyzing activity, only a microorganism producing a saccharide hydrolase, or a hydrolysis using the above enzyme agent is used. You may use together a decomposition process and the fermentation process using the said microorganisms.

  In the case of treating the rhizome rhizome with an enzyme agent having saccharide hydrolyzing activity, the amount of enzyme agent added, reaction conditions, etc. are not particularly limited as long as a composition containing a high concentration of diosgenin glycoside is obtained. And can be appropriately determined in consideration of the properties of the enzyme agent used. For example, an enzyme treatment condition is suitable for the present invention so that 10 to 20 kg of a water-insoluble enzyme-treated product can be obtained from a dry weight of 100 kg of spiny rhizome or a treated product thereof. Although not particularly limited, for example, when sucrase (registered trademark) A and sucrase (registered trademark) X are used as enzyme agents as in the method described in Example 1, 0.1 to 20% by weight with respect to the raw material What is necessary is just to use the enzyme agent of a weight%, and what is necessary is just to react about 1 hour-3 days in the temperature range of room temperature-50 degreeC. After the treatment with the enzyme agent for rhizomes, treatment (such as heat treatment) for inactivating the enzyme may be performed as necessary.

  When fermenting rhododendron rhizomes with Aspergillus oryzae, even if the Aspergillus rhizomes are directly inoculated with Aspergillus spores, pre-prepared solid koji or liquid koji (Koji mold culture solution) is added to the mixture of rhododendron rhizomes or rhododendron rhizomes and aqueous liquids May be. The solid koji can be produced by a known method used for liquor production. As raw materials for solid koji, rice, wheat, koji, beans, millet, etc. can be used, and it is not always necessary to use rhododendron rhizomes. The liquid koji can be produced by inoculating a liquid medium with koji mold spores or precultured koji mold hyphae.

  There are no particular limitations on the conditions for the fermentation of rhododendron rhizomes by Aspergillus as long as a composition containing a high concentration of diosgenin glycoside is obtained, but the temperature condition is preferably 5 ° C to 40 ° C, and 15 ° C. ~ 30 ° C is more preferred. The fermentation time is not particularly limited, but is preferably 1 day to 30 days, and more preferably 1 day to 7 days. A sterilization treatment may be performed as necessary after the fermentation treatment of Aspergillus rhizomes by Aspergillus.

  When treating rhododendron rhizomes in combination with fermentation treatment with koji mold and hydrolysis treatment with an enzyme agent having saccharide hydrolyzing activity, either treatment may be performed first, and treatment with koji mold and enzyme You may perform the process by an agent simultaneously.

  In the method for producing an enzyme-treated product of the present invention, there may be a step of collecting as a water-insoluble fraction. Although not particularly limited, the solid-liquid material after the enzyme treatment can be recovered as a water-insoluble material by solid-liquid separation by an existing method as it is or after the enzyme inactivation treatment such as heat treatment. Existing methods include filter press filtration, centrifugation, and the like.

  In addition, the fraction obtained by fractionating the enzyme-treated product by a known method also has an effect of improving or improving learning / memory ability, a memory disorder preventing action, or an anti-memory disorder action. It may be used as an enzyme-treated product. In a preferred embodiment, the water-insoluble fraction itself obtained from the enzyme-treated yam is used as the enzyme-treated product of the present invention. Examples of the fractionation means include extraction, fractional precipitation, column chromatography, thin layer chromatography and the like. These fractions can be used alone or in admixture of two or more. Further, in the present invention, processed products obtained under the same enzyme treatment conditions from the same yam, for example, Tedokoro, can be used alone or in admixture of two or more.

(2) Composition of the present invention The composition of the present invention means a composition containing the enzyme-treated product of the present invention. The enzyme-treated product is mixed with known ingredients that can be taken orally, such as excipients or carriers, and formulated by a method known per se. Any excipient and carrier may be used as long as they are pharmacologically acceptable. For example, water, alcohols or soybean oil, peanut oil, sesame oil, mineral oil, or other animal or vegetable oils or synthetic oils may be used as the liquid carrier. Oil is used. Solid carriers include sugars such as lactose, maltose, sucrose, carboxymethylcellulose, corn starch, amino acids, cellulose derivatives such as hydroxypropylcellulose, organic acid salts such as magnesium stearate, dextran, dextran sulfate, chondroitin sulfate, heparin, gelatin Etc. are used. These solid carriers or liquid carriers can be used to produce any shape.
As an example of the composition of the present invention, a composition containing 100 μg to 500 mg of the enzyme-treated product per gram of the dry weight of the composition and having a high content of diosgenin glycoside can be provided.

  The composition of the present invention can be used as a medicine to be described later by itself or as an active ingredient of a medicine or food.

(3) Pharmaceutical for oral administration containing the composition of the present invention The active ingredient according to the present invention can exert an effect on the prevention or treatment of memory impairment safely and appropriately. Therefore, the medicament of the present invention comprising the active ingredient is extremely effective as a preventive or therapeutic agent for memory impairment.

  In this specification, the term “active ingredient” means the active ingredient itself. Specifically, for example, an enzyme-treated product as an active ingredient may be used as a mixture in actual use. However, the “enzyme-treated product” does not mean the mixture, but means the treated product of the staghorn enzyme in the mixture, and therefore, the treated product of the stalked enzyme as an active ingredient itself. (That is, a dried product etc. of the processed product of the toggedokoro itself). Moreover, a living individual or an individual refers to a living organism such as a human or a farmed animal described later.

  The pharmaceutical agent of the present invention can effectively exhibit the preventive or therapeutic action of memory impairment of the pharmaceutical agent of the present invention by setting the administration method to oral administration. That is, the medicament of the present invention exerts these actions, thereby causing memory impairment and its peripheral symptoms, such as memory loss, amnesia, aphasia, aphasia, aphasia, dementia exhibiting executive dysfunction, Alzheimer's disease, etc. It is useful as a therapeutic or prophylactic agent. These actions are also exhibited in the food or feed of the present invention described later.

  The medicament of the present invention is formulated by a method known per se, with the enzyme-treated product of the present invention alone or mixed with an excipient or carrier. As the excipient and carrier, those described above can be used. Further, the composition of the present invention may be further mixed with an excipient or carrier to prepare a formulation. The medicament of the present invention can be made into dosage forms for oral administration such as tablets, capsules, powders, granules, solutions, dry syrups, microspheres and the like. In addition, an acid, an alkali, or an appropriate amount of a buffer may be added to the medicament of the present invention for the purpose of adjusting pH. Furthermore, a surfactant such as sodium laurate or glycocholic acid or β-cyclodextrin may be added to the medicament of the present invention in order to enhance oral absorption. In addition, in order to promote uptake from the gastrointestinal mucosa and enhance absorbability, a biodegradable lactic acid polymer, a lactic acid-glycolic acid copolymer, etc. are used to make a microsphere preparation, and optionally a wetting agent. Addition of adjuvants such as suspending agents, sweetening agents, flavoring agents, preservatives, etc. is also acceptable. In addition, solid formulations may be coated with a sugar coating or a film of gastric or enteric material.

  The content of the treated product of the stalked enzyme in the composition for oral administration of the present invention varies depending on the dosage form, but is usually 0.1 to 100% by weight, preferably 1 to 98% by weight. In general, tablets, capsules, powders and granules contain 5 to 100% by weight, preferably 25 to 98% by weight, of the active ingredient.

  The medicament of the present invention may contain other active ingredients effective for memory impairment and its peripheral diseases.

  Each of the above-mentioned various preparations can be produced by conventional methods. In addition, the content of the active ingredient in such a preparation is not particularly limited as long as it is an amount that allows the active ingredient to be administered within the dosage range described below, taking into consideration its administration form and the like. In general, the content of the active ingredient in the medicament of the present invention is not particularly limited as long as the active ingredient can be administered within the dosage range described below, preferably in consideration of its administration form. Absent.

  The dosage as a medicament of the present invention is appropriately set depending on the preparation form, administration method, purpose of use, and age, weight, and symptoms of an individual to whom the medicament is administered, and is not constant. In general, the dosage of the active ingredient contained in the preparation is preferably 10 mg to 10 g per day, more preferably 100 mg to 1 g, for humans (for example, adults) per day.

  Since the dose of the active ingredient varies depending on various conditions, an amount smaller than the above dose may be sufficient or may be necessary beyond the range. Administration may be performed once or divided into several times within one day within a desired dose range. The administration period is also arbitrary. Moreover, the medicament of the present invention can be orally administered as it is, or can be added to any food or drink and taken on a daily basis.

  The use of the enzyme-treated product of the present invention in the production of a composition for oral administration to a patient with memory impairment is also one aspect of the present invention.

(4) Memory disorder suppression method using the prophylactic and / or therapeutic agent for oral administration of the present invention No particular toxicity is observed in the active ingredient according to the present invention. Therefore, the effect can be exhibited safely and appropriately for the prevention or treatment of memory impairment. Therefore, the medicament of the present invention comprising the active ingredient can be used in a method for suppressing memory impairment.

(5) Food and feed of the present invention The composition of the present invention can be used for foods and beverages. The method for producing the food of the present invention is not particularly limited. For example, blending, cooking, processing and the like may be in accordance with those of general foods, and can be produced by those production methods. What is necessary is just to contain the composition of this invention. Here, “containing” means containing, adding and / or diluting, and “containing” refers to an embodiment in which the active ingredient of the present invention is contained in food, beverage or feed, and “adding” refers to food, beverage or feed. The aspect in which the active ingredient of the present invention is added to the raw material and the dilution refers to the aspect in which the raw material of food, beverage or feed is added to the active ingredient of the present invention.

  There is no particular limitation on the type of food, for example, processed cereal products, processed oil products, processed soybean products, processed meat products, processed fish products, dairy products, processed vegetables and fruits, containing the composition of the present invention. Agricultural and forestry processed products such as products, confectionery, alcoholic beverages, taste beverages, seasonings and spices, processed livestock products and processed fishery products. The food may be in liquid form. That is, the food of the present invention includes a beverage.

  Moreover, you may combine the foodstuff of this invention with the well-known component which has the same effect as the composition of this invention.

  The content of the active ingredient in the food of the present invention is not particularly limited and can be appropriately selected from the viewpoint of its functionality and activity expression. For example, the active ingredient of the present invention is preferably 0.01% by weight or more in the food. , More preferably 1 to 100% by weight, still more preferably 10 to 90% by weight, for example, preferably 0.001% by weight or more, more preferably 0.1 to 100% by weight, even more preferably in the beverage. Is 1 to 90% by weight. The food of the present invention has an active ingredient of the present invention that is preferably 0.001 to 100 g / kg body weight, particularly preferably 0.01 to 10 g / kg body weight per day for humans (for example, adults). You can ingest it.

  By ingesting the food of the present invention described above, the action of improving or improving the learning / memory ability of the active ingredient, the action of preventing memory impairment, or the action of anti-memory disorder are exhibited. Therefore, the food of the present invention is useful for prevention or treatment of memory impairment.

  In addition, the food of the present invention may be administered to pets or industrial animals for preventing or treating memory impairment. Examples of the animals include farm animals, pet animals, etc., and farm animals include domestic animals such as horses, cows, pigs, sheep, goats, camels, llamas, laboratory animals such as mice, rats, guinea pigs, rabbits, Poultry such as chickens, ducks, turkeys and eagle birds, and pet animals include dogs and cats.

  The active ingredient used in the present invention does not show toxicity even if it is orally administered in an effective amount for the expression of its action. For example, even if a composition of the present invention is orally administered to mice at a dose of 2 g / kg body weight, no adverse events occur and no deaths are observed.

  The food of the present invention contains one or more of the above-mentioned active ingredients, is added and / or diluted, and is limited to its shape as long as it contains a necessary amount for the prevention and treatment of memory impairment. It also includes orally ingestible forms such as tablets, granules and capsules.

  The pharmaceutical agent of the present invention can effectively exhibit the preventive or therapeutic action of memory impairment of the pharmaceutical agent of the present invention by setting the administration method to oral administration. That is, the medicament of the present invention exerts these actions, thereby causing memory impairment and its peripheral symptoms, such as memory loss, amnesia, aphasia, aphasia, aphasia, dementia exhibiting executive dysfunction, Alzheimer's disease, etc. It can be used as a therapeutic or preventive agent for memory impairment. Moreover, the use as a memory disorder | damage | failure suppression method is possible similarly in the foodstuff of the above-mentioned this invention.

  EXAMPLES The present invention will be described in more detail with reference to examples below, but the present invention is not limited to the following examples.

Example 1 Preparation of Enzyme-treated Togedokoro Powder 20 kg of dried powder of rhododendron rhizome was added to 200 L of distilled water and mixed, and then heat sterilized at 95 ° C. for 30 minutes. After cooling, 200 g each of sucrase A and sucrase X (Mitsubishi Chemical Foods) was added and reacted at 45 ° C. for 24 hours. Thereafter, the reaction solution was heated at 95 ° C. for 20 minutes to deactivate the enzyme. After cooling, solid-liquid separation was performed by filter press filtration. 1 kg of dextrin (trade name: Paindex # 100, manufactured by Matsutani Chemical Co., Ltd.) was added to 3 kg of the collected solid and freeze-dried to obtain 4 kg of enzyme-treated Togedokoro powder. The content of diosgenin glycoside in the enzyme-treated togekodoro powder was 0.73% as a result of quantification by HPLC using a standard substance of dioscin and dioscinin.

Example 2 Evaluation of preventive effect of enzyme-treated Togedokoro powder on memory impairment 5XFAD mouse (Charles River Japan, 17-18 weeks old) before onset of memory impairment was powdered with the enzyme-treated Togedokoro powder prepared in Example 1 (CE-2, manufactured by Clea Japan Co., Ltd.) was mixed with 10% and allowed to eat freely. An object recognition test was performed according to a report by Higashida et al. [Scientific Reports, Vol. 3, No. 3395 (2013)] before administration (during training) and on the 33rd day of administration. This test is to confirm whether or not an experimental animal can detect a change to a new object when the object recognized during training is replaced with a new object during the test. As a comparison, a group in which the powder diet was administered to wild-type mice (mating breed of 5XFAD mouse and normal mouse (B6 SJL), 18 weeks old) (normal group), a group in which the powder diet was administered to 5XFAD mice (control) Group). The results are shown in FIG.

  That is, FIG. 1 is a graph showing the memory impairment suppressing effect of the composition of the present invention, wherein the vertical axis shows the ratio (%) of the number of searches for new objects to the total number of searches as a search directivity index, and the horizontal axis Indicates each experimental group and the time of training and testing of the experimental group. As shown in FIG. 1, the onset of memory impairment was clearly suppressed or prevented by administration of the composition of the present invention.

Example 3 Evaluation of Memory Impairment Effect of Enzyme-treated Togedokoro Powder 10% of 5XFAD mice (29-30 weeks of age) that developed memory impairment were treated with the enzyme-treated toggedokoro powder prepared in Example 1 in a powder bait (CE-2). Mixed and allowed to eat freely. An object recognition test was performed before administration (during training) and on the 32nd day of administration. For comparison, a group (normal group) in which the powder diet was administered to wild-type mice (29 weeks old) and a group (control group) in which the powder diet was administered to 5XFAD mice were set. The result is shown in FIG.

  That is, FIG. 2 is a graph showing the memory impairment improving effect of the composition of the present invention, wherein the vertical axis shows the search orientation index, and the horizontal axis shows each experimental group and the time of training and testing of the experimental group. As shown in FIG. 2, administration of the composition of the present invention clearly improved memory impairment.

Example 4 Preparation of Togedokoro Extract Powder Ten times the amount of 60% ethanol was added to the enzyme-treated toggedokoro powder prepared in Example 1, and extracted at room temperature for 2 hours, followed by solid-liquid separation by centrifugation. Eight times the amount of 60% ethanol was added to the extraction residue and extracted in the same manner. The extracts were mixed and concentrated using an evaporator. Next, the synthetic adsorbent Sepabead SP207 (manufactured by Mitsubishi Chemical Corporation) was filled in the open column, and after applying the concentrated solution, each was washed with 3 times the amount of water and 2 times the amount of 50% ethanol. Finally, 3 times the amount of acetone as the resin was applied, and the eluate was collected. The obtained eluate was concentrated with an evaporator and freeze-dried to obtain a powdered Tedokoro extract. The content of diosgenin glycoside in this powdered extract was 21%.

Example 5 Evaluation of memory disorder improving action of Togekokoro extract powder To 5XFAD mice (20 to 22 weeks old) who developed memory disorder, the powder of Togedocoro extract powder prepared in Example 4 was added to powder feed (CE-2). .5%, 1% mixed and allowed to eat freely. An object recognition test was performed before administration (during training) and on the 40th day after administration. For comparison, a group (normal group) in which the powder diet was administered to wild type mice (20 to 22 weeks of age) (control group) in which the powder diet was administered to 5XFAD mice was set. As a result, memory was maintained in the normal group, but administration of Togedocoro extract powder did not show an effect of improving memory impairment. In addition, the content of the diosgenin glycoside in the powder bait is higher in the powder bait of this example than in the powder bait used in Examples 2 and 3. From the above, it was confirmed that the enzyme-treated Togedocoro powder tested in Examples 2 and 3 had a remarkable effect on memory impairment.

  According to the present invention, there is provided a composition for preventing or treating memory impairment, comprising a yam enzyme-treated product as an active ingredient. Since the composition of the present invention is a composition that can be taken orally, it is very useful in the prevention or treatment of memory impairment.

Claims (7)

The yam, pectinase, xylanase, amylase, cellulase, glucanase, protease, and obtained by treating with an enzyme composition containing lipase, as an active ingredient an enzymatic treatment of water-insoluble mainly containing diosgenin glycoside A composition for preventing and / or treating memory impairment.   The composition of claim 1 for oral consumption.   The composition according to claim 1 for the prevention and / or treatment of memory impairment due to Alzheimer's disease. In the manufacture of a composition for oral administration to a human or animal with memory impairment,
The yam, pectinase, xylanase, amylase, cellulase, glucanase, protease, and obtained by treating with an enzyme composition containing lipase, use of enzyme-treated water-insoluble mainly containing diosgenin glycosides. For pets or industrial animals that require prevention and / or treatment of memory impairment
The yam, pectinase, xylanase, amylase, cellulase, glucanase, protease, and obtained by treating with an enzyme composition containing lipase, an enzyme-treated water-insoluble mainly containing diosgenin glycoside administered orally A method for suppressing memory impairment in pets or industrial animals.   A food comprising the composition according to claim 1 for the prevention and / or treatment of memory impairment.   A prophylactic or therapeutic agent for oral administration comprising the composition according to claim 1 for the prevention and / or treatment of memory impairment.

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