JP2018008895A - Cognitive decline inhibitor or preventive agent - Google Patents

Abstract

[Problem] The present invention aims to provide an agent capable of suppressing or preventing cognitive decline, or a composition containing the same. [Solution] The present invention provides an agent for suppressing or preventing cognitive decline, containing at least one active ingredient selected from the group consisting of fucoxanthinol-containing eggs, at least a portion thereof, and processed products thereof, and a food composition for suppressing or preventing cognitive decline, containing the same. [Selected Figure] None

Description

  The present invention relates to a cognitive function decrease inhibitor or preventive agent.

  It is said that the number of patients with dementia will increase to about 4.6 million in 2012 and 7 million in 2025. This is an extremely large social problem in Japan, which is facing an aging society. Although there are several treatments for dementia, there is currently no fundamental cure. Therefore, the development of an active ingredient that suppresses the onset and progression of dementia is awaited.

  Patent Documents 1 and 2 describe the effects of fucoxanthin on dementia and related symptoms. Fucoxanthin is known to be absorbed in the body as fucoxanthinol, but fucoxanthinol itself is unstable to light and heat and is known to decompose in a few days. Yes.

  Non-Patent Document 1 describes that when a feed in which seaweed lipids containing fucoxanthin were added to a chicken was fed, fucoxanthinol was detected in the egg yolk.

JP 2008-239505 A JP 2014-009214 A

News from Kitamizu trial (2009) 77, 22-25.

  However, fucoxanthin and fucoxanthinol are difficult to formulate because they are fat-soluble substances, and there has been a problem in using them for various purposes. In addition, the use of chicken eggs containing fucoxanthinol has not been known. An object of this invention is to provide the agent which can fully exhibit the cognitive ability improvement or prevention effect of fucoxanthinol in the body.

  The inventors prepared egg yolk powder from chicken eggs fed with fucoxanthin. Fucoxanthin ingested by chickens is contained in egg yolk in the form of fucoxanthinol. This chicken egg powder was ingested by SAMP8 mice to evaluate the cognitive function, and the cognitive function lowering inhibitory effect was confirmed. On the other hand, when fucoxanthin is added to normal chicken egg powder that does not contain fucoxanthinol and fed, fucoxanthin is ingested by the body as fucoxanthinol, but there is no effect on cognitive function It was. Although it is presumed that it exists in egg yolk or its presence state contributes to the cognitive function reduction inhibitory effect, details are unknown.

The present invention provides the following [1] to [5].
[1] An agent for suppressing or preventing cognitive function deterioration comprising a fucoxanthinol-containing raw egg as an active ingredient.
[2] An agent for suppressing or preventing cognitive decline, comprising fucoxanthinol-containing egg yolk as an active ingredient.
[3] An agent for suppressing or preventing cognitive function deterioration comprising fucoxanthinol-containing egg yolk powder as an active ingredient.
[4] A cognitive function reduction inhibitor or preventive agent comprising fucoxanthinol-containing egg yolk oil as an active ingredient.
[5] A food composition for suppressing or preventing cognitive decline, comprising the agent according to any one of [1] to [4].

  ADVANTAGE OF THE INVENTION According to this invention, the cognitive function fall suppression or prevention agent which can exhibit favorable cognitive function fall suppression or a preventive action is provided.

FIG. 1 is a diagram showing the results (Experiment 1) of the passive avoidance test of the example. FIG. 2 is a diagram showing the results (Experiment 2) of the passive avoidance test of the example. FIG. 3 is a diagram illustrating a result (Experiment 3) of the passive avoidance test of the example.

  In the present invention, the fucoxanthinol-containing egg is an egg containing fucoxanthinol transferred from the bird's body in the yolk. The content of fucoxanthinol in the yolk powder of fucoxanthinol-containing eggs is usually 0.01 ppm or more, preferably 0.1 ppm or more, more preferably 1.0 ppm or more, and further preferably 3 ppm or more. The upper limit is usually 30 ppm or less, preferably 20 ppm or less, more preferably 9.8 ppm or less.

  Although the manufacturing method of a fucoxanthinol containing egg yolk powder is not specifically limited, For example, the method of manufacturing by pulverizing the yolk of the egg which the bird which ingested fucoxanthin or fucoxanthinol spawned is mentioned.

  The bird is not particularly limited as long as it is a female bird, and examples thereof include poultry such as chicken, turkey, quail, duck, and goose. The age of the bird is not particularly limited, but is not particularly limited as long as it has the ability to lay eggs.

  The method (administration method) for ingesting fucoxanthin or fucoxanthinol to a bird is not particularly limited, and for example, oral administration (for example, oral administration, sublingual administration, etc.), parenteral administration (intravenous administration, muscle) Internal administration, subcutaneous administration, transdermal administration, nasal administration, transpulmonary administration, etc.). Among these, a less invasive dosage form is preferable, and oral administration is usually used.

  The origin of fucoxanthin and fucoxanthinol is not particularly limited, and may be derived from natural products (for example, seaweeds such as dry algae, microalgae), or may be chemically synthesized. In the case of being derived from a natural product, the degree of extraction is not particularly limited, and any of a crude extract, an extract and a purified product may be used.

  In the case of oral administration, fucoxanthin or fucoxanthinol is preferably mixed with the feed. The content of fucoxanthin or fucoxanthinol in the feed is usually 0.0006% by mass or more, preferably 0.003% by mass or more, and more preferably 0.006% by mass or more. The upper limit is usually 0.15% by mass or less, preferably 0.03% by mass or less, and more preferably 0.018% by mass or less.

  The feed may contain other components in addition to fucoxanthin and / or fucoxanthinol. Other components are not particularly limited as long as they are components that are usually contained in avian feed.

  The feed needs only to contain or be able to contain fucoxanthin or fucoxanthinol, and the dosage form is not particularly limited, but liquid (liquid), syrup (syrup), tablet (tablet, tablet), capsule (Capsule, hard capsule), powder (granule, fine particle), soft capsule (soft capsule), usually powder. The feed may contain the components contained in a normal blended feed.

  The daily intake of avian fucoxanthin or fucoxanthinol is not particularly limited because it depends on the intake period, type of bird, health condition, etc., but is usually 0.2 ng / g body weight or more, preferably 0.6 ng / Body weight g or more, more preferably 1.2 ng / body weight g or more. The upper limit is usually 500 ng / body weight g or less, preferably 300 ng / body weight g or less, more preferably 100 ng / body weight g or less.

  The period during which the bird takes fucoxanthin or fucoxanthinol is not particularly limited because it depends on the amount of intake, type of bird, health condition, etc., but is usually 10 days or longer, preferably 20 days or longer, more preferably 29 More than a day. The upper limit is usually 60 days or less, preferably 50 days or less, more preferably 40 days or less.

  In the present invention, fucoxanthinol-containing eggs are themselves (raw eggs), at least a part (preferably egg yolk), or a group consisting of fucoxanthinol-containing eggs and / or at least part of processed products thereof. One or more types selected may be used. Examples of the processed product include powder, oil, and solution, and egg yolk powder, egg yolk oil, and egg yolk liquid are preferable. The processing method is not particularly limited. Egg yolk powder can be produced by lyophilization. Egg yolk oil can be produced by heating egg yolk to remove solids. The egg yolk liquid can be produced by adding an appropriate amount of water or saline to the egg yolk.

  A fucoxanthinol-containing egg can exert a cognitive function-suppressing or preventing effect when ingested by a living body. Daily intake (total amount in the case of a combination of two or more) of fucoxanthinol-containing eggs in an adult is preferably 0.1 g or more, more preferably 0.2 g or more in the case of egg yolk powder. More preferably, it is 0.3 g or more. An upper limit becomes like this. Preferably it is 26 g or less, More preferably, it is 12 g or less, More preferably, it is 5.25 g or less.

  Fucoxanthinol-containing eggs can be used as agents alone or in combination with other components. As described above, fucoxanthinol-containing eggs have a cognitive function lowering inhibitory or preventive action, and therefore, agents containing fucoxanthinol-containing eggs can be used as cognitive function lowering inhibitory or preventive agents.

  Cognitive functions include judgment (execution function, task processing, etc.), calculation, memory (working memory, learning memory, social cognition, etc.), understanding, learning (language learning, visual learning, etc.), thinking (logical thinking, Problem solving ability), and at least one function selected from languages. Suppressing or preventing cognitive function deterioration means suppressing or preventing cognitive function deterioration or regression, or maintaining normal cognitive function. Suppression and prevention of cognitive decline is caused by dementia (eg, Alzheimer type dementia (including juvenile and familial)), Lewy body dementia, cerebrovascular dementia, frontotemporal dementia, juvenile cognition. Disease, alcoholic dementia, normal pressure hydrocephalus, mottled dementia, microinfarct dementia, drug-related dementia), mild cognitive impairment, memory impairment, schizophrenia, attention deficit disorder, prevention of ADHD and other diseases Since it is useful for suppression, the agent of the present invention is also useful as an agent for preventing or suppressing these diseases.

  Representative definitions of dementia include ICD-10 (International Disease Classification 10th Edition) and DSM-IV (American Psychiatric Association Psychiatric Diagnostic Statistics Handbook 4th Edition). Although there are some differences, conceptually, the intellectual function that has been achieved normally has been continuously reduced by acquired organic disorders, causing problems in daily life and social life. What is seen when there is no disturbance of consciousness is called dementia.

That is, dementia can be diagnosed with a condition that satisfies the following conditions (1) to (6) (from the Dementia Textbook / Chugaku Medical Co., Ltd.).
(1) The core of dementia is impairment of intellectual functions such as memory impairment, and there are also several impairments of intellectual functions such as aphasia, apraxia, agnosia and executive dysfunction.
(2) Since these intellectual disabilities are acquired disabilities, there is a state in which the intelligence once developed has declined.
(3) There is a change in the organic nature of the brain, which is based on material abnormalities in the brain.
(4) It is necessary to continue for a certain period of time, and ICD-10 says that it will last for "at least 6 months".
(5) As a result of intellectual disability, social life and daily activities are hindered.
(6) The above-mentioned condition is also seen when there is no consciousness disorder, not acute or temporary.

  Mild cognitive impairment (MCI) is a precursor state of dementia, a state in which cognitive function is lower than expected in normal physiological aging processes. That is, dementia is not diagnosed, and the cognitive function is normal, but amyloid β is accumulated in the brain.

  The agent of the present invention only needs to contain at least one fucoxanthinol-containing egg, and may contain a combination of two or more fucoxanthinol-containing eggs having different production methods and compositions.

  The agent of this invention should just use the fucoxanthinol containing egg as an active ingredient, and may contain another component as needed. There is no restriction | limiting in particular as long as the effect of this invention is not impaired as another component, For example, the support | carrier accept | permitted pharmacologically is mentioned.

  The pharmacologically acceptable carrier may be appropriately selected depending on the dosage form, and examples thereof include ethanol, water, and starch.

  In the present invention, other components may be contained in addition to the fucoxanthinol-containing egg and the pharmacologically acceptable carrier. Examples of other components include oily components, excipients, disintegrants, binders, lubricants, coating agents, colorants, color formers, flavoring agents, flavoring agents, antioxidants, preservatives, and tastes. Ingredients, sour agents, sweeteners, fortifiers, swelling agents, thickeners, surfactants, fucoxanthinol-containing eggs, and components having an inhibitory or preventive effect on cognitive decline other than pharmacologically acceptable carriers Can be mentioned. The optional component may be selected according to the dosage form, type, etc. of the food composition, and may be one type or a combination of two or more types.

  Examples of the oil component include fatty acid esters, hydrocarbons, higher fatty acids, higher alcohols, and the like.

  Examples of the excipient include cellulose such as hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, crystalline cellulose, ethylcellulose, low-substituted hydroxypropylcellulose, and pharmacologically acceptable derivatives thereof, polyvinylpyrrolidone, and partially saponified polyvinyl alcohol. Synthetic polymers such as gelatin, gum arabic powder, pullulan, agar, alginic acid, sodium alginate, chitansan gum and other starches, corn starch, potato starch, pregelatinized starch, hydroxypropyl starch and other pharmacologically acceptable Derivatives, lactose, fructose, glucose, sucrose, trehalose, palatinose, mannitol, sorbitol, erythritol, xylitol, reduced palatinose, powder Based maltose syrup, sugars and sugar alcohols such as maltitol, light anhydrous silicic acid, particulate silicon oxide, particulate silicon dioxide, titanium oxide, and inorganic excipients such as aluminum hydroxide gel. The content of the excipient with respect to the total amount of the agent is preferably 0.01% by mass or more. The upper limit is preferably 70% by mass or less.

  Examples of the disintegrant include crospovidone, carmellose calcium, croscarmellose sodium, low-substituted hydroxypropyl cellulose, carboxymethyl cellulose, carboxymethyl starch sodium, hydroxypropyl starch, and partially pregelatinized starch.

  Examples of the binder include hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, ethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, gelatin, dextrin, starch, pregelatinized starch and the like.

  Examples of the lubricant include calcium stearate, magnesium stearate, sucrose fatty acid ester, light anhydrous silicic acid, sodium stearyl fumarate, polyethylene glycol, talc, stearic acid and the like. The content of the lubricant with respect to the total amount of the agent is preferably 0.01% by mass or more. The upper limit is preferably 25% by mass or less.

  The dosage form of fucoxanthinol-containing eggs and agents containing the same are not particularly limited. For example, oral administration (eg, oral administration, sublingual administration, etc.), parenteral administration (intravenous administration, intramuscular administration, subcutaneous administration, transdermal administration, nasal administration, pulmonary administration, etc.) and the like can be mentioned. Among these, a less invasive dosage form is preferable, and oral administration (internal use) is more preferable.

  Examples of the dosage form of the oral administration agent (internal use) or the composition for oral administration (composition for internal use) include, for example, liquid (solution), syrup (syrup), tablet (tablet, tablet), capsule (capsule) Agent), powder (granule, fine granule), soft capsule (soft capsule), solid, semi-liquid, cream, and paste.

  The dosage of the fucoxanthinol-containing egg in the preparation may be appropriately determined with reference to the above-mentioned guideline for the intake of the fucoxanthin-containing egg.

  The administration target of the fucoxanthinol-containing egg and the agent containing the same may be an animal including a human, and is usually a human. The subject of administration may be a healthy person, but may be a patient with the above-mentioned dementia, cognitive impairment or the like.

  The subject is not limited to humans, and may be animals other than humans (for example, mammals such as mice, rats, hamsters, dogs, cats, sheep, goats, cows, pigs, monkeys).

  Fucoxanthinol-containing eggs and agents containing them can be used as food compositions, pharmaceuticals, and quasi drugs as they are or in combination with other ingredients. Examples of food compositions include beverages (soft drinks, carbonated drinks, nutritional drinks, powdered drinks, fruit drinks, milk drinks, jelly drinks, etc.), confectionery (cookies, cakes, gums, candies, tablets, gummies, buns, sheep candy) , Pudding, jelly, ice cream, sherbet, etc.), processed fishery products (kamaboko, chikuwa, hanpen, etc.), processed livestock products (hamburg, ham, sausage, winner, cheese, butter, yogurt, fresh cream, cheese, margarine, fermentation Milk, etc.), soup (powder soup, liquid soup, etc.), staple foods (rice, noodles (dried noodles, raw noodles), bread, cereals, etc.), seasonings (mayonnaise, shortening, dressing, sauce, sauce, soy sauce, etc.) ).

  Examples of food compositions include health foods, functional foods, health supplements (supplements), nutritional supplements, foods for specified health use, medical foods, sick foods, infant foods, nursing foods, and elderly use Foods etc. are also mentioned.

  The administration time of the fucoxanthinol-containing egg and the agent containing the same is not particularly limited, but is preferably non-fasting and more preferably after a meal. In general, lipid-based components are more easily absorbed when food is present in the intestinal tract. Therefore, absorption can be promoted when the administration time is the above time.

  Examples of the method for confirming the inhibitory or preventive effect on the cognitive function lowering of the agent containing a fucoxanthinol-containing egg and the composition containing the same include a method using a dementia model animal, as shown in the Examples. As a method for evaluating with a dementia model animal, for example, there is a method of carrying out a passive avoidance test of an animal after breeding for a certain period while feeding the dementia model animal with a diet prepared by mixing a sample with a normal diet. Examples of dementia model animals include SAMP8 mice. Commercial products such as CE-2 (Nippon Claire Co., Ltd.) may be used as the normal food. The breeding period of the dementia model animal is not particularly limited and may be appropriately selected according to the purpose.

  The manufacturing method of the agent containing a fucoxanthinol-containing egg is not particularly limited, and may be manufactured by any method depending on the dosage form, composition, and the like.

  Hereinafter, the present invention will be described in detail with reference to examples. The following examples are for explaining the present invention preferably, and the present invention is not limited to the following examples.

[Production Example 1] Production of fucoxanthinol-containing egg yolk powder The fucoxanthinol-containing egg yolk powder used in the examples was produced by the following procedure.
A 5% fucoxanthin solution (manufactured by Oriza Oil Co., Ltd.) was mixed with chicken food to a concentration of 0.1% and ingested for 4 weeks. The egg yolk of chicken eggs born in the meantime was pulverized according to a standard method. The fucoxanthinol concentration in the egg yolk powder was 6 ppm.

  The concentration of fucoxanthinol in the egg yolk powder was confirmed by high performance liquid chromatography. The measurement conditions were as follows.

  Egg yolk powder (500 mg) was placed in a 15 mL tube, ethanol (5 mL) was added, and the mixture was extracted at room temperature while stirring with a high-speed shaker (Cutemixer, EYELA) for 20 minutes. After centrifugation at 1500 rpm for 5 minutes, the supernatant was collected. The above steps were repeated until the supernatant became transparent (usually 3 times), and the collected supernatant was distilled off.

  The volume was made up to 5 mL with isopropyl alcohol, and high performance liquid chromatography analysis was performed under the following conditions.

HPLC conditions / column: Inertsil ODS-3 (GL Science, 4.6 × 150 mm)
Mobile phase: MeOH / H ₂ O = 85/15, flow rate: 1 mL / min
-Column oven: 40 ° C

[Production Example 2] Production of kombu-derived fucoxanthin Kombu-derived fucoxanthin (Fx) used in the comparative example was produced by the following procedure.
1) Extraction process (preparation of crude fucoxanthin)
In a separatory funnel, 500 g of fucoxanthin 1% oil (manufactured by South Product Co., Ltd., derived from Kombu), 500 g of hexane, 500 g of methanol and 50 g of saturated brine are mixed for 1 minute and then allowed to stand for 10 minutes. ) Was recovered. To the remaining upper layer (dark green), 250 g of methanol and 25 g of saturated brine were added and the same operation was performed to recover the lower layer. These recovered lower layers and 250 g of hexane were mixed in a separatory funnel and allowed to stand for 10 minutes, and then the lower layers were recovered and concentrated to dryness with an evaporator to obtain a solid content. The obtained solid content was dissolved in 250 g of diethyl ether, put into a separatory funnel, mixed with 100 g of water, and allowed to stand for 10 minutes. The upper layer (dark red) was collected, dried over sodium sulfate, filtered through filter paper, and the resulting filtrate was concentrated to dryness with an evaporator to obtain crude fucoxanthin (17 g, fucoxanthin purity: 28%, fucoxanthin recovery rate) : 95%). Crude fucoxanthin was subjected to the following two steps.

2) Chromatographic purification process (preparation of purified fucoxanthin)
Crude fucoxanthin (9 g) was dissolved in 50 mL of hexane / acetone = 50/50 (v / v) and purified by silica gel chromatography (φ50 mm × H500 mm). Development started with a hexane / acetone ratio = 70/30 and a final ratio of 50/50. The dark red fractions were collected and concentrated to dryness with an evaporator to obtain purified fucoxanthin (3.5 g, fucoxanthin purity: 65%, fucoxanthin recovery rate: 92%). Purified fucoxanthin was subjected to the following three steps.

3) Recrystallization process (Preparation of high purity fucoxanthin)
Purified fucoxanthin (3.5 g) was dissolved in a minimum amount of acetone, an appropriate amount of water was added, and acetone was distilled off using an evaporator to the extent that crystals did not precipitate. Thereafter, the solution was cooled on ice and allowed to stand until crystals were formed. Suction filtration was performed using hexane as a washing liquid, and the crystals were collected and dried to obtain high-purity fucoxanthin (2 g, fucoxanthin purity: 99%, fucoxanthin recovery rate: 83%).

  The purity of fucoxanthin in the result of each step was confirmed by high performance liquid chromatography under the following conditions.

HPLC conditions / sample: 20 mg was precisely weighed, and 10 μL of a solution obtained by diluting to 50 mL with ethanol was introduced.
Column: Inertsil ODS-3 (5 μm, 4.6 mm (ID) × 150 mm)
-Mobile phase: methanol / water = 85/15 (0 minutes to), 100/0 (8 minutes to), 100/0 (35 minutes to)
・ Flow rate: 1.0 mL / min
・ Oven: 60 ℃
-Detector: UV-VIS (440 nm)

  The recovery rate of fucoxanthin in each step was calculated by the following formula:

  Recovery rate = fucoxanthin weight in the result of each step / fucoxanthin weight in the sample before treatment in each step

  The fucoxanthin weight was calculated by multiplying the weight of the sample by the purity of fucoxanthin measured as described above. In addition, the sample before a process in each refinement | purification process is 1% fucoxanthin oil, crude fucoxanthin, and refined fucoxanthin, respectively.

Experiments 1-3 (Examples 1-2 and Comparative Examples 1-3)
[animal]
A male SAMP8 mouse (Japan SLC, Inc.) was used as the animal. The SAMP8 mouse is one of the lines of Sense-Accelerated Mouse (SAM). SAM is the degree of aging in the pathology section of the Research Institute for Tuberculosis and Thoracic Diseases of Kyoto University (currently, Regenerative Medicine Chemistry Research Institute). It is a mouse strain established with an age-dependent rapid increase in scores as an index. There are two strains of SAM: P strain (SAMP) showing accelerated aging and short life, and R strain (SAMR) showing normal aging, each of which is further subdivided, and SAMP8 mice are one of the P strains. . SAMP8 mice are known to exhibit learning / memory impairment, immune dysfunction, and circadian rhythm abnormalities. Beginning to show minor learning / memory impairment at 3 months of age, the disorder becomes prominent at 5 months of age or older (aging model mouse (SAM) Research Council homepage (http://www.samrc.jp/ (Some modifications from SAMmouse.htm)

[Dosage substance]
The administration substances to be tested are as follows.
-Fucoxanthin (Fx): produced in Production Example 2-Egg yolk powder (control egg): obtained from Pharma Foods, Inc.-Fucoxanthinol-containing egg yolk powder (Fxol egg): produced in Production Example 1, containing 6 ppm Fxol, Obtained from Pharma Foods ・ Low-capacity fucoxanthinol-containing egg yolk powder (low Fxol egg): 0.975 ppm Fxol contained, obtained from Pharma Foods

[Group setting]
The animals were divided into the following groups, and each dosed substance was given under the following conditions.
-CE-2 group (Comparative Examples 1 and 1 '): CE-2 powder feed (Japan Clare Co., Ltd.) administered at 6 g / day-Fx group (Comparative Example 2): Fx 20 mg / kg / day Administration and control egg group solubilized in drinking water (Comparative Examples 3 and 3 ′): Fxol-free egg yolk powder was mixed with CE-2 powder to 10% w / w and administered at 6 g / day. Egg group (Example 1): Fxol-containing egg yolk powder was mixed with CE-2 powder food to 10% w / w and administered at 6 g / day. Low Fxol egg group (Example 2): egg yolk containing low Fxol Powder is mixed with CE-2 powder food to 10% w / w and administered at 6 g / day.

[Dose period]
The administration period in each group was 3 months from 7 weeks of age. After the administration period, the following passive avoidance test was performed.

[Passive avoidance test]
A step-through passive avoidance test was performed on SAMP8 mice at 20 weeks of age. Analysis was performed using the software ShutAvoid (PanLab). Preliminary learning on the first day sets the time to enter the dark room (light room stay time) to a maximum of 2 minutes, opens the shielding door after acclimatization to the light room for 1 minute, closes the door after moving to the dark room, and then stimulates 0.4 mA For 2 seconds. After electrical stimulation, the mouse was immediately returned to the home cage. In the main test on the second day, the upper limit of staying time in the bright room was set to 5 minutes, and the time spent in the bright room was measured. The measured value of the individual who remained in the light room for 5 minutes on the second day was calculated as 5 minutes, and the light room stay time on the second day was averaged for each group (Table 1, FIGS. 1 to 3). The number of individuals per group is 9 for both the control group and the Fx egg group.

[Footnotes in Table 1]
* Based on the fact that the conversion efficiency from Fx to Fxol in the body is about 80% (Sugawara et al., Nutrient Metabolism, 2002, 132: 946-951), the Fx dose is 20 mg / kg / day (the mouse body weight is 30 g Then, the amount after conversion from 600 ng / day to Fxol in the body is converted.

  In the passive avoidance test, the stay in the bright room was significantly increased in the Fxol egg group compared to the control egg group. On the other hand, no significant difference was detected in the bright room stay time between the CE-2 group and the Fx mixed CE-2 group. That the staying time in the bright room on the second day is high means that the electrical stimulation on the first day is stored. It is known that SAMP8 mice have a reduced cognitive ability at the age of this study, that is, the duration of stay in the light room on the second day is low in this study (Sawano E et al., J Neurosci Res, 2013). , 91 (3): 382-92, Alterations in Local Thyroid Hormone Signaling in the Hippocampus of the SAMP8 Mouse at YoungAge, I understand that.

  Fx effective dose (Fx alone) in Fx cognitive function suppression inhibitory evaluation using rodents is 0.001-20 mg / day (special table 2013-540110), and this is converted to Fxnol dose Since the conversion efficiency of Fx to Fxol in the body is about 80% (Sugawara et al., Nutrient Metabolism, 2002, 132: 946-951), it is considered that the conversion efficiency is 800 ng / day to 16 mg / day. The Fxol dosage in the Fxol egg group of the examples is approximately 36 ng / day. From this, it was clarified that by administering Fxol eggs, the cognitive function reduction inhibitory effect can be obtained even at a dose of Fxol far lower than the effective dose of Fx alone.

  The Fx dose of the Fx group of the comparative example is 20 mg / kg / day (600 ng / day when the mouse body weight is 30 g). When this is converted into the Fxnol dose, the conversion efficiency to Fxol in the body is about 80%. It is presumed that it is about 480 ng / day from certain (Sugawara et al., Nutrient Metabolism, 2002, 132: 946-951). In contrast, the Fxol intake in the Fxol egg group of the example is approximately 36 ng / day, which is much smaller than the Fx dose in the Fx group. From this, it was clarified that cognitive function lowering suppression or prevention effect can be obtained only by administering Fx not directly but through an egg.

Formulation Example 1 (tablet)
Tablets were produced according to a conventional method with the following composition.
Egg yolk powder containing fucoxanthinol 40% by mass
Calcium stearate 5% by mass
Crystalline cellulose 10% by mass
Lactose 43% by mass
Fine silicon dioxide 2% by mass

Formulation example 2 (soft capsule)
Soft capsules were produced according to a conventional method with the following composition.
[Solid formulation / 1 unit]
-Outer layer-
Gelatin ... 130mg
Glycerin ... 70mg
Ethyl paraoxybenzoate 0.5 mg
-Inner layer-
Egg yolk oil containing fucoxanthinol ... 100mg

Claims (5)

  A preventive or preventive agent for cognitive decline, comprising a fucoxanthinol-containing raw egg as an active ingredient.   An agent for inhibiting or preventing cognitive decline, comprising fucoxanthinol-containing egg yolk as an active ingredient.   A preventive or preventive agent for cognitive decline, comprising fucoxanthinol-containing egg yolk powder as an active ingredient.   An agent for inhibiting or preventing cognitive decline, comprising fucoxanthinol-containing egg yolk oil as an active ingredient.   The food composition for cognitive function fall suppression or prevention containing the agent of any one of Claims 1-4.