JP7372656B2 - Nutrient transport enhancer - Google Patents

Description

TECHNICAL FIELD The present invention relates to a nutrient transport promoter characterized by containing C. chinensis.

In order to maintain life activities, nutrients such as sugar and amino acids are transported from the intestinal tract into the body and further to all organs such as the brain, liver, and muscles. On the other hand, undernutrition, a state in which nutrients necessary to maintain bodily functions are lacking, increases the risk of developing pressure ulcers due to a decrease in subcutaneous fat, anemia, osteoporosis, muscle atrophy, fatigue, and weakness. (Non-patent document 1). Additionally, in the brain, cognitive function declines due to a lack of energy and neurotransmitters due to malnutrition. All cells that make up the body transport nutrients through solute carrier transporters (SLCs), and increasing the expression of solute transporters is extremely important in terms of promoting nutrient transport. It is.

Typical solute transporters include SLC2A1 and SLC2A3, which are responsible for glucose transport, SLC38A1, which is responsible for glutamine transport, SLC38A2, which is responsible for amino acid transport, SLC27A1, which is responsible for long-chain fatty acid transport, and SLC6A6, which is responsible for transporting taurine and β-alanine. . These solute transporters, which transport glucose and fatty acids as energy sources and amino acids necessary for protein synthesis, are extremely important for living organisms.

In the intestinal tract, dietary nutrients can be absorbed into the body by transporting nutrients such as sugars and amino acids via solute transporters expressed in intestinal epithelial cells. Nutrient transport in the intestinal tract is closely related to the nutritional status of the whole organism, and the function of solute transporters is very important in maintaining the bodily functions of the organism.

The brain has a mechanism called the blood-brain barrier that controls the transport of substances between blood and the brain. The blood-brain barrier is composed of vascular endothelial cells and the like, and solute transporters present in the vascular endothelial cells play a role in transporting nutrients from the blood into the brain. Cognitive function is maintained by the uptake of sugar, the brain's energy source, and amino acids, which are used in neurotransmitter synthesis, into the brain. The functions of the blood-brain barrier related to other cognitive functions include physical protection by tight junctions composed of occludin (OCLN) and claudin (CLDN), and unnecessary and foreign substances by ATP-binding cassette transporters (ABC transporters). excretion, drug metabolism by cytochrome P450 (CYP) and glutathione S-transferase (GST), etc. Furthermore, it has been revealed that dysfunction of the blood-brain barrier is involved in a decline in cognitive function (Non-Patent Document 2).

As methods for promoting nutrient transport, there are inventions such as polyphenol absorption enhancers (Patent Document 1) and calcium absorption enhancers (Patent Document 2). However, these inventions relate only to the transportation of specific nutrients, and are insufficient as inventions that assist in the transportation of nutrients obtained from meals on a daily basis. In addition, there is no knowledge whatsoever regarding nutrient transport in C. chinensis, and there is still no invention related to this.

JP2016-193845

JP2017-171594

Journal of the Geriatrics Society. 48(6):659-661

Clinical neurology. 57(3):96-109

The present invention relates to a nutrient transport enhancer, a cognitive function improver, and a malnutrition improver, which are characterized by containing C. chinensis.

As a result of intensive research, the present inventors found that C. chinensis has the effect of promoting nutrient transport, improving cognitive function, and improving malnutrition.

The Ganoderma used in the present invention is a mushroom belonging to the Basidiomycete Family Ganodermataceae and the genus Ganoderma. ), black reishi (black reishi), purple reishi (purple grass), blue reishi (qingzhi), yellow reishi (yellow reishi) and white reishi (white reishi) are known. In the present invention, all mushrooms belonging to the family Stonenaceae can be used, but red reishi, black reishi, purple reishi, blue reishi, yellow reishi, and white reishi are more preferred, and red reishi are more preferred. It is preferable to use Ganoderma lucidum or Ganoderma sinensis (Ganoderma atrum). Furthermore, it is also possible to use a combination of Ganoderma mushrooms, and it is preferable to combine red Reishi mushrooms and black Reishi mushrooms.

The mushroom used in the present invention can be used regardless of its fruiting body, spore, mycelium, natural product, cultivated product, cultured product, etc., and those widely distributed in the Chinese and Japanese markets can be used. . Further, if necessary, the raw material, crushed material, dried material, subcritical water-treated material, etc. can be appropriately selected and subjected to the extraction operation. Further, methods for obtaining broken wall spores include atomization treatment, roll press treatment, grinding treatment, ultra-high pressure microsteam treatment, and other mechanical methods commonly used in industry.

The subcritical water treatment used in the present invention is to bring water brought into a subcritical state under conditions of a predetermined temperature and pressure into contact with the object to be treated (Salmon mushroom in the present invention). For example, when water is raised to a pressure of 22.12 MPa and a temperature of 374.15° C., it becomes neither liquid nor gas. This point is called the critical point of water, and hot water with a temperature and pressure lower than the critical point is called subcritical water. This subcritical water has excellent component extraction and hydrolysis effects due to its lower dielectric constant and increased ionic product. Note that the water supplied to subcritical water treatment can be used in either a liquid state or a gas state. That is, to the treatment tank for subcritical water treatment, steam may be supplied, water may be supplied, or both may be supplied. When treating subcritical water, it is preferable to use water that has been forced into a liquid state in a closed container because the reaction progresses more easily in a liquid state than in a gaseous state as a desired reaction field. More specifically, a pressure-resistant container made of metal or ceramics, etc. is filled with rock mushrooms and water as a treatment agent, sealed, and the water is subcritical (temperature: 100°C or higher, pressure: saturated vapor pressure or higher). A treated product obtained by contacting the two for a certain period of time or more can be a subcritical water treated product.

The subcritical water-treated product of Stonecroceum used in the present invention is obtained by treating Stonecroceum with water in a subcritical state, and includes a mixture of Stonecroceum and an aqueous solution (such as an aqueous solution) or a dried product thereof. It also includes a filtrate obtained by filtering the above mixture or a dried product thereof. Furthermore, it is also possible to treat a plurality of types of Cinderella with subcritical water in the same treatment tank, or to use a combination of different subcritically treated Cinderella in subsequent treatments.

The temperature for the subcritical water treatment of C. chinensis is preferably between 100 and 300°C, and is preferably between 120 and 230° C., because the effective ingredients contained in the subcritical water treatment product of C. chinensis or its extract can be easily obtained efficiently. The temperature is more preferably between 140 and 180°C. When the temperature is less than 100°C, the amount of active ingredients tends to decrease. Moreover, when the temperature of subcritical water treatment exceeds 300° C., over-decomposition of the active ingredient is likely to occur.

The pressure for subcritical water treatment of Cinnamon mushrooms may be equal to or higher than the saturated vapor pressure at each temperature, more preferably between 0.1 and 3.0 MPa, and even more preferably between 0.26 and 2.0 MPa. When the pressure is less than 0.1 MPa, the amount of active ingredient tends to decrease. In addition, excessive pressurization in which the pressure of subcritical water treatment greatly exceeds the saturated vapor pressure requires the addition of a separate pressurization device and improvement of the pressure resistance of the equipment, which deteriorates the economic efficiency of extraction.

The time for the subcritical water treatment of Cinnamon mushrooms is preferably 5 to 90 minutes, more preferably 10 to 30 minutes. When the time is less than 5 minutes, the amount of active ingredient tends to decrease. Furthermore, if the time for subcritical water treatment exceeds 90 minutes, over-decomposition of the active ingredient is likely to occur.

That is, as the conditions for subcritical water treatment of Cinnamon mushroom, it is preferable that the temperature is 100 to 300°C, the pressure is 0.1 to 3.0 MPa, and the time is 5 to 90 minutes.

The extraction solvent used in the present invention includes water, lower alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.), and liquid polyhydric alcohols (1,3-butanol, etc.). butylene glycol, propylene glycol, glycerin, etc.), ketones (acetone, methyl ethyl ketone, etc.), acetonitrile, esters (ethyl acetate, butyl acetate, etc.), hydrocarbons (hexane, heptane, petroleum ether, etc.), ethers (ethyl ether, etc.) , tetrahydrofuran, propyl ether, etc.). These solvents may be used alone or in combination of two or more. Examples of extraction methods include continuous extraction, immersion extraction, supercritical extraction, and subcritical water extraction. In the present invention, it is particularly preferable to use a hot water extract of Stone Manga extracted with water at 95 to 100°C.

The subcritical water-treated material used in the present invention can be one that has been treated at a treatment temperature of 100 to 300°C, a treatment pressure of 0.1 to 3.0 MPa, and a treatment time of 5 to 90 minutes. In addition, an extract of the subcritical water-treated material of C. chinensis is obtained by extracting this subcritical water-treated material of C. monocytogenes with water, lower alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.). can be used. In the present invention, a subcritical water-treated material of C. chinensis processed under conditions of a treatment temperature of 100 to 300 °C, a treatment pressure of 0.1 to 3.0 MPa, and a treatment time of 5 to 90 minutes is extracted with water at a temperature of 95 to 100 °C. It is preferable to use a hot water extract of a subcritical water-treated material of C. chinensis.

The intake amount of C. chinensis used in the present invention varies depending on the dosage form, purpose of use, age, body weight, etc., but in terms of dry matter, it is 1 to 20,000 mg/day, preferably 10 to 10,000 mg/day, and more preferably 50 to 5,000 mg. It can be administered orally once to several times per day. In some cases, it may be sufficient to use an amount smaller than the above-mentioned dosage range, and in other cases, it may be necessary to administer more than the above range. Furthermore, the method of adding medicinal ingredients during formulation may be added in advance or during production, and may be selected as appropriate in consideration of workability.

The nutrient transport promoter of the present invention can be used in any food, quasi-drug, or pharmaceutical product. The dosage forms include powders, granules, tablets, sugar-coated tablets, capsules, syrups, pills, suspensions, solutions, and emulsions for oral use. It can also be made into injections, suppositories, etc. for parenteral use.

The nutrient transport enhancer of the present invention may be used as is, and if necessary, excipients and stabilizers used in ordinary pharmaceuticals, quasi-drugs, or foods may be added to the extent that the effect is not impaired. It may also contain components such as preservatives, binders, disintegrants, hydrocarbons, fatty acids, alcohols, esters, pH adjusters, preservatives, and fragrances.

Nutrients in the nutrient transport promoter of the present invention include sugars such as glucose, monoglycerides, fatty acids, glycerol, cholesterol, amino acids, dipeptides, tripeptides, vitamins, iron, calcium, water, zinc, bile acids, minerals, and the like.

Cognitive functions in the present invention refer to general intellectual abilities such as memory, thinking, understanding, calculation, learning, language, and judgment. In addition, the cognitive function improving agent can also be used to improve diseases such as memory impairment, aphasia, apraxia, agnosia, and executive dysfunction caused by decline in cognitive function, as well as dementia and Alzheimer's disease.

Malnutrition in the present invention refers to a state in which nutrients necessary for maintaining bodily functions are lacking. In addition, the malnutrition improving agent can also target the improvement of symptoms caused by malnutrition (occurrence of bedsores due to decrease in subcutaneous fat, anemia, osteoporosis, muscle atrophy, feeling of fatigue, weakness, decline in cognitive function, etc.).

The nutrient transport promoter of the present invention, which is characterized by containing C. chinensis, has a nutrient transport promoting effect, a cognitive function improving effect, and an undernutrition improving effect.

The following examples are provided for illustrative purposes only, and the claims of the present invention are not limited in any way by these examples.

Production Example 1 Red Reishi Subcritical Water Treated Product (Processing Conditions 1) and its Hot Water Extract 45 g of Red Reishi as a raw material for Ganoderma was put into a subcritical water treatment can, and the processing conditions 1 (processing temperature: 140°C, processing Subcritical water treatment was performed at a pressure of 0.37 MPa and a treatment time of 30 minutes. After the subcritical water treatment was completed, the treated product in the processing can was freeze-dried to obtain 43.8 g of Red Reishi subcritical water treated product. 200 mL of purified water was added to 10 g of the obtained Red Reishi subcritical water treated product and extracted at 95 to 100°C for 2 hours. After filtration, the filtrate was concentrated and freeze-dried to obtain 0.6 g of a hot water extract of subcritical water-treated Red Reishi.

Production Example 2 Red Reishi Subcritical Water Treated Product (Processing Condition 2) and its Hot Water Extract 45 g of Red Reishi was put into a subcritical water treatment can as a raw material for Ganoderma lucidum. Subcritical water treatment was performed at a pressure of 0.63 MPa and a treatment time of 20 minutes. After the subcritical water treatment was completed, the treated product in the processing can was freeze-dried to obtain 45.4 g of Red Reishi subcritical water treated product. 200 mL of purified water was added to 10 g of the obtained Red Reishi subcritical water treated product and extracted at 95 to 100°C for 2 hours. After filtration, the filtrate was concentrated and freeze-dried to obtain 0.8 g of a hot water extract of subcritical water-treated Red Ganoderma.

Production Example 3 Red Reishi Subcritical Water Treated Product (Processing Condition 3) and its Hot Water Extract 45 g of Red Reishi was put into a subcritical water treatment can as a raw material for Ganoderma lucidum, and the treatment condition 3 (processing temperature: 180°C, treatment Subcritical water treatment was performed at a pressure of 1.01 MPa and a treatment time of 30 minutes. After the subcritical water treatment was completed, the treated product in the processing can was freeze-dried to obtain 39.8 g of Red Reishi subcritical water treated product. 200 mL of purified water was added to 10 g of the obtained Red Reishi subcritical water treated product and extracted at 95 to 100°C for 2 hours. After filtration, the filtrate was concentrated and freeze-dried to obtain 2.6 g of a hot water extract of subcritical water-treated Red Reishi.

Production Example 4 Black Reishi Subcritical Water Treated Product (Processing Condition 1) and its Hot Water Extract 45 g of Black Reishi was put into a subcritical water treatment can as a raw material for Ganoderma lucidum. Subcritical water treatment was performed at a pressure of 0.37 MPa and a treatment time of 30 minutes. After the subcritical water treatment was completed, the treated product in the processing can was freeze-dried to obtain 41.7 g of black reishi subcritical water treated product. 200 mL of purified water was added to 10 g of the obtained black reishi treated with subcritical water and extracted at 95 to 100°C for 2 hours. After filtration, the filtrate was concentrated and freeze-dried to obtain 0.6 g of a hot water extract of the subcritical water-treated black reishi.

Production Example 5 Black Reishi Subcritical Water Treated Product (Processing Conditions 2) and Its Hot Water Extract 45 g of Black Reishi was put into a subcritical water treatment can as a raw material for Ganoderma lucidum. Subcritical water treatment was performed at a pressure of 0.63 MPa and a treatment time of 20 minutes. After the subcritical water treatment was completed, the treated product in the processing can was freeze-dried to obtain 40.3 g of black reishi subcritical water treated product. 200 mL of purified water was added to 10 g of the obtained black reishi treated with subcritical water and extracted at 95 to 100°C for 2 hours. After filtration, the filtrate was concentrated and freeze-dried to obtain 1.0 g of a hot water extract of the subcritical water-treated black reishi.

Production Example 6 Black Reishi Subcritical Water Treated Product (Processing Condition 3) and its Hot Water Extract 45 g of Black Reishi was put into a subcritical water treatment can as a raw material for Ganoderma, and treatment condition 3 (processing temperature: 180°C, Subcritical water treatment was performed at a pressure of 1.01 MPa and a treatment time of 30 minutes. After the subcritical water treatment was completed, the treated product in the processing can was freeze-dried to obtain 34.2 g of black reishi subcritical water treated product. 200 mL of purified water was added to 10 g of the obtained black reishi treated with subcritical water and extracted at 95 to 100°C for 2 hours. After filtration, the filtrate was concentrated and freeze-dried to obtain 2.4 g of a hot water extract of the subcritical water-treated black reishi.

Production Example 7 Mixture of hot water extract of the subcritical water-treated Red Reishi mushroom of Production Example 3 and the subcritical black Reishi of Production Example 6 2 g of the hot water extract of the water-treated product (processing conditions 3) was mixed uniformly to obtain 4 g of a mixture of the hot water extract of the subcritical water-treated material of C. chinensis.

Production Example 8 Hot Water Extract of Red Reishi 2 L of purified water was added to 100 g of Red Reishi and extracted at 95 to 100°C for 2 hours. After filtration, the filtrate was concentrated and freeze-dried to obtain 4.4 g of hot water extract of Red Ganoderma.

Production Example 9 Hot Water Extract of Black Reishi 2 L of purified water was added to 100 g of Black Reishi and extracted at 95 to 100°C for 2 hours. After filtration, the filtrate was concentrated and freeze-dried to obtain 4.2 g of a hot water extract of Black Ganoderma.

Production Example 10 Mixture of hot water extract of C. chinensis 2 g of the hot water extract of red reishi of Production Example 8 and 2 g of hot water extract of black reishi of production example 9 were mixed uniformly, 4 g of a mixture of hot water extracts was obtained.

Prescription example 1 Soft capsule <Formulation>
Component Content (%)
1. Mixture of hot water extract of subcritical water treated material of C. mantis (Manufacturing Example 7) 1.0
2. Red Reishi hot water extract (Production Example 8) 15.0
3. Hot water extract of black reishi (manufacturing example 9) 4.0
4. Rice germ oil 70.0
5. Beeswax 7.0
6. Vitamin E 3.0
<Manufacturing method>
Ingredients 1 to 6 are mixed, 350 mg is filled into a coating composed of gelatin, glycerin, and caramel color, and after drying, soft capsules are obtained.
<Usage>
Take 3 tablets per day.

Prescription example 2 Hard capsule <Formulation>
Component Content (%)
1. Hot water extract of red reishi subcritical water treated product (processing conditions 3) (manufacturing example 3) 5.0
2. Cornstarch 87.0
3. Sucrose fatty acid ester 8.0
<Manufacturing method>
Components 1 to 3 are mixed and 250 mg is filled into No. 2 hard capsules to obtain capsules.
<Usage>
Take 4 tablets per day.

Prescription example 3 Beverage <prescription>
Component Content (%)
1. Mixture of hot water extract of subcritical water treated material of C. mantis (Manufacturing Example 7) 0.05
2. Red Reishi hot water extract (Production Example 8) 0.30
3. Hot water extract of black reishi (manufacturing example 9) 0.05
4. Citric acid 6.00
5. Sucrose 10.60
6. Fragrance 1.00
7. Wednesday 82.00
<Manufacturing method>
Components 1 to 6 are dissolved in a portion of the water of component 7 with stirring. Next, the remaining water from component 7 is added and mixed to sterilize the mixture and use it as a beverage.
<Usage>
Take 50mL per day.

Prescription example 4 Granule <Prescription>
Component Content (%)
1. Hot water extract of black reishi subcritical water treated product (processing conditions 3) (manufacturing example 6) 0.5
2. Lactose 85.0
3. Cellulose 14.5
<Manufacturing method>
Ingredients 1 to 3 are granulated by a dry method to obtain granules.
<Usage>
Take 1g per day.

Prescription example 5 Tablet <prescription>
Component Content (%)
1. Red Reishi hot water extract (Production Example 8) 10.0
2. Lactose 60.0
3. Reduced maltose starch syrup 25.0
4. Sucrose fatty acid ester 5.0
<Manufacturing method>
Ingredients 1 to 4 are mixed and compressed to obtain 0.5 g tablets.
<Usage>
Take 2 tablets per day.

Prescription example 6 Jelly <Prescription>
Component Content (%)
1. Mixture of hot water extract of Subcritical Water Treated Mantis mushroom (Production Example 7) 2.0
2. carrageenan 2.0
3. gelatin 1.0
4. Sugar 27.0
5. Purified water 68.0
<Manufacturing method>
Mix ingredients 1 to 5, boil while heating, pour into a jelly mold, and cool.
<Usage>
Take 1 piece (100g) per day.

Comparative Example 1 Conventional Soft Capsules In the soft capsules of Formulation Example 1, a mixture of hot water extracts of subcritical water-treated Mandarin mushrooms (Production Example 7), hot water extracts of Red Reishi (Production Example 8), Conventional soft capsules were prepared by replacing the hot water extract of Black Reishi (Production Example 9) with rice germ oil.

Comparative Example 2 In the conventional beverage formulation example 3, a mixture of hot water extracts of subcritical water-treated L. lucidum (Production Example 7), hot water extracts of Red Reishi (Production Example 8), and black Reishi A conventional beverage was prepared by replacing the hot water extract (Production Example 9) with water.

Test Example 1 Effect of Promoting Nutrient Transport by Stonefish Hot water extract of treatment condition 3) (Production Example 6), mixture of hot water extract of subcritical water-treated Manchuria mushroom (Production Example 7), hot water extract of Red Ganoderma (Production Example 8), Kuroreishi A mixture of a hydrothermal extract of grass (Production Example 9) and a mixture of a hydrothermal extract of Stonecrop (Preparation Example 10) were added at the same concentration, and gene expression analysis of solute transporters was performed by real-time PCR.

Primer set for SLC2A1 GTCGTGTCGCTGTTTGTG (SEQ ID NO: 1)
ATGCTCAGATAGGACATCCA (SEQ ID NO: 2)
Primer set for SLC2A3 TGTGGCCGAACTCTTCAG (SEQ ID NO: 3)
CCTAAAATAGTGAGCAGCGG (SEQ ID NO: 4)
Primer set for SLC38A1 TTGGAGTCGTAGGAGTTACATCTGC (SEQ ID NO: 5)
ATGCTGACCAAGGAGAACAACA (SEQ ID NO: 6)
Primer set CGATTGTGGGCAGTGGAA for SLC38A2 (SEQ ID NO: 7)
GGAGATGAACAGAATACAGGGAAA (SEQ ID NO: 8)
Primer set CCCAACGCGATATACCAGGA (SEQ ID NO: 9) for SLC27A1
CTTGAAGGTGCCTGTGGTG (SEQ ID NO: 10)
Primer set CCCTTGGTCATCGTCATCC for SLC6A6 (SEQ ID NO: 11)
GGTGCGAGAGTTGTAAGGTGTG (SEQ ID NO: 12)
Primer set for OCLN TCCAATGGCAAAGTGAATGA (SEQ ID NO: 13)
AAGTCATCCACAGGCGAAGT (SEQ ID NO: 14)
Primer set CAGAGCACCGGGCAGATC for CLDN1 (SEQ ID NO: 15)
TTGCAATGTGCTGCTCAGATT (SEQ ID NO: 16)
Primer set GAGAAGAAGTACACGGCCAC for CLDN3 (SEQ ID NO: 17)
TCTGTCCCTTAGACGTAGTCC (SEQ ID NO: 18)
Primer set TAGCAAGAACAGAGTCCACCC (SEQ ID NO: 19) for CLDN4
CAGGCAGATCCCAAAGTCAG (SEQ ID NO: 20)
Primer set for CLDN7 CAACATTAAGTATGAGTTTGGCCC (SEQ ID NO: 21)
TTGGACTTAGGGTAAGAGCGG (SEQ ID NO: 22)
Primer set ACATTCTGGCCGGTATCTG for CLDN15 (SEQ ID NO: 23)
AGCTCGTACTTGGTTCCG (SEQ ID NO: 24)
Primer set for ABCB1 TGTGTTTATGATGGTCTGTTGG (SEQ ID NO: 25)
GATTGTTTCCTGTTGCATTGAG (SEQ ID NO: 26)
Primer set for ABCG2 TGTGTTTATGATGGTCTGTTGG (SEQ ID NO: 27)
GATTGTTTCCTGTTGCATTGAG (SEQ ID NO: 28)
Primer set for ABCC1 TGTGTTTATGATGGTCTGTTGG (SEQ ID NO: 29)
GATTGTTTCCTGTTGCATTGAG (SEQ ID NO: 30)
Primer set for ABCC3 CTGCTTCCAGAACTCCCT (SEQ ID NO: 31)
CACCCAGGACCATCTTGAG (SEQ ID NO: 32)
Primer set for ABCC4 TGTGTTTATGATGGTCTGTTGG (SEQ ID NO: 33)
GATTGTTTCCTGTTGCATTGAG (SEQ ID NO: 34)
Primer set AGTCACAACTGCTATCTCCTG for CYP1A1 (SEQ ID NO: 35)
AATCACTGTGTCTAGCTCCTC (SEQ ID NO: 36)
Primer set AGAGACCCAGAAGTGTTCC for CYP2R1 (SEQ ID NO: 37)
GACAATGTCTTCTTCCTAGGGA (SEQ ID NO: 38)
Primer set for CYP2S1 CCCAACATCTTCAAAGCACC (SEQ ID NO: 39)
GACACGCTTCCCTAAGGAG (SEQ ID NO: 40)
Primer set for GSTP1 CAGGGAGGCAAGACCTTCATT (SEQ ID NO: 41)
CCTCATGGATCAGCAGCAAGT (SEQ ID NO: 42)

The results of Test Example 1 are shown in Table 1. Hot water extract (Production Example 3) of Red Reishi subcritical water treated product (Processing conditions 3), Hot water extract (Production example 6) of Black Reishi subcritical water treated product (Processing conditions 3), Mixture of hot water extract of critical water treated product (Production Example 7), Hot water extract of Red Reishi (Production Example 8), Hot water extract of Black Reishi (Production Example 9), Hot water extract of Stone Manga The mixture of substances (Production Example 10) promoted gene expression of solute transporters (SLC2A1, SLC2A3, SLC38A1, SLC38A2, SLC6A6). This indicates that the nutrient transport promoting effect of Cinnamon mushrooms was demonstrated.

SLC2A1 and SLC2A3 are responsible for glucose transport, SLC38A1 is responsible for glutamine transport, SLC38A2 is responsible for amino acid transport, and SLC6A6 is responsible for transporting taurine and β-alanine. Transport-promoting effects and β-alanine transport-promoting effects were shown.

Here, when comparing the mixture of the hot water extract of the subcritical water-treated product of Mandarin mushroom in Production Example 7 and the mixture of the hot water extract of Mandarin mushroom in Production Example 10, it is found that for SLC2A3, SLC38A1, and SLC38A2, Production Example 10 Production Example 7 showed extremely excellent effects. Since SLC2A3 plays a role in glucose transport, SLC38A1 plays a role in glutamine transport, and SLC38A2 plays a role in amino acid transport, the substance treated with subcritical water of C. chinensis was shown to have extremely excellent glucose transport-promoting action, glutamine transport-promoting action, and amino acid transport-promoting action.

In addition, since Test Example 1 uses intestinal epithelial cells, it is thought to have an effect of promoting nutrient transport in the intestinal tract, and it can be said that C. chinensis has an excellent effect of improving malnutrition.

Furthermore, Caco-2 used in Test Example 1 is also used as a blood-brain barrier model cell. Therefore, in addition to solute transporters, tight junctions (OCLN, CLDN1, CLDN3, CLDN4, CLDN7, CLDN15), efflux transporters (ABCB1, ABCG2, ABCC1, ABCC3, ABCC4), and drug-metabolizing enzymes (CYP1A1) involved in the blood-brain barrier function are considered. , CYP2R1, CYP2S1, GSTP1) gene expression is shown in Table 1. The results showed that in addition to solute transporters, C. chinensis promoted the gene expression of tight junctions, efflux transporters, and drug-metabolizing enzymes. This indicates that Cinnamon mushroom has an effect on improving cognitive function.

Here, when comparing the mixture of the hot water extract of the subcritical water-treated product of Mandarin mushroom in Production Example 7 and the mixture of the hot water extract of Mandarin mushroom in Production Example 10, OCLN, CLDN4, CLDN7, ABCB1, ABCC1, ABCC3 Regarding this, Production Example 7 exhibited extremely superior effects compared to Production Example 10.

Furthermore, regarding ABCC1, a hot water extract of the red reishi subcritical water treated product of Production Example 3, a hot water extract of the black reishi subcritical water treated product of Production Example 6, and a hot water extract of the Black Reishi subcritical water treated product of Production Example 7. Comparing the mixtures of hot water extracts (mixtures of Production Example 3 and Production Example 6), it is found that the hot water extract of Red Reishi subcritical water-treated product and the hot water extract of Black Reishi subcritical water-treated product In combination, an extremely excellent effect on promoting efflux transporters was observed.

In addition, regarding the mixture of hot water extracts (Production Example 7) of the subcritical water-treated product of Ganoderma lucidum, the hot water extracts (Production Example 3) of the red reishi subcritical water-treated product and the mixture of the hot water extract of the subcritical water-treated product of Red Reishi mushroom (Production example 3) A similar effect was observed even when the hot water extract (Production Example 6) was mixed at an arbitrary ratio within the range of 9:1 to 1:9.

Test Example 2 Effect of promoting blood-brain barrier function by ICR mice. Brain tissue was collected after 30 days of ingesting a mixture of hot water extracts (manufacturing example 7) of subcritical water treatment of C. chinensis, and gene analysis was performed using real-time PCR. Expression analysis was performed.

Primer set for SLC2A1 GTCGTGTCGCTGTTTGTG (SEQ ID NO: 43)
ATGCTCAGATAGGACATCCA (SEQ ID NO: 44)
Primer set for SLC38A2 TGTGGCCGAACTCTTCAG (SEQ ID NO: 45)
CCTAAAATAGTGAGCAGCGG (SEQ ID NO: 46)
Primer set for SLC6A6 TTGGAGTCGTAGGAGTTACATCTGC (SEQ ID NO: 47)
ATGCTGACCAAGGAGAACAACA (SEQ ID NO: 48)
Primer set CGATTGTGGGCAGTGGAA for OCLN (SEQ ID NO: 49)
GGAGATGAACAGAATACAGGGAAA (SEQ ID NO: 50)
Primer set for ABCB1 CCCAACGCGATATACCAGGA (SEQ ID NO: 51)
CTTGAAGGTGCCTGTGGTG (SEQ ID NO: 52)
Primer set CCCTTGGTCATCGTCATCC for ABCC1 (SEQ ID NO: 53)
GGTGCGAGAGTTGTAAGGTGTG (SEQ ID NO: 54)
Primer set TCCAATGGCAAAGTGAATGA for ABCC4 (SEQ ID NO: 55)
AAGTCATCCACAGGCGAAGT (SEQ ID NO: 56)
Primer set CAGAGCACCGGGCAGATC for CYP2S1 (SEQ ID NO: 57)
TTGCAATGTGCTGCTCAGATT (SEQ ID NO: 58)
Primer set GAGAAGAAGTACACGGCCAC for GSTP1 (SEQ ID NO: 59)
TCTGTCCCTTTAGACGTAGTCC (SEQ ID NO: 60)

The results of Test Example 2 are shown in Table 2. The mixture of hot water extracts of subcritical water-treated M. chinensis (Manufacturing Example 7) contains solute transporters (SLC2A1, SLC38A2, SLC6A6), tight junctions (OCLN), and efflux transporters (ABCB1) that are deeply involved in the function of the blood-brain barrier. , ABCC1, ABCC4) and drug-metabolizing enzymes (CYP2S1, GSTP1). Therefore, it was demonstrated that Cinnamon mushroom has an effect on improving cognitive function.

In addition, regarding the mixture of hot water extracts (Production Example 7) of the subcritical water-treated product of Ganoderma lucidum, the hot water extracts (Production Example 3) of the red reishi subcritical water-treated product and the mixture of the hot water extract of the subcritical water-treated product of Red Reishi mushroom (Production example 3) A similar effect was observed even when the hot water extract (Production Example 6) was mixed at an arbitrary ratio within the range of 9:1 to 1:9.

Test Example 3 Cognitive Function Improving Effect by Stone Clover ICR mice were allowed to ingest a mixture of hot water extracts of subcritical water-treated C. chinensis (Manufacturing Example 7) and a hot water extract of Red Reishi (Manufacturing Example 8) for 30 days. Afterwards, a novel object recognition test was conducted. Preference Index (PI) was calculated 1 hour and 24 hours after sample recognition.

The results of Test Example 3 are shown in Table 3. The PI in the novel object recognition test was increased by ingesting a mixture of hot water extracts of subcritical water treated material of C. chinensis (Manufacturing Example 7) and a hot water extract of Red Reishi (Manufacturing Example 8). Therefore, it was demonstrated that Cinnamon mushroom has an effect on improving cognitive function.

In addition, regarding the mixture of hot water extracts (Production Example 7) of the subcritical water-treated product of Ganoderma lucidum, the hot water extracts (Production Example 3) of the red reishi subcritical water-treated product and the mixture of the hot water extract of the subcritical water-treated product of Red Reishi mushroom (Production example 3) A similar effect was observed even when the hot water extract (Production Example 6) was mixed at an arbitrary ratio within the range of 9:1 to 1:9.

Test Example 4 Cognitive function improvement effect of human intake of C. chinensis 40 men and women (32 to 60 years old) were divided into 2 groups of 20 to evaluate soft capsules containing C. chinensis (prescription example 1) and conventional soft capsules (comparison). Example 1) was used to drink 3 tablets once a day for 3 months. As an evaluation of cognitive function, we performed calculation tasks using the Kraepelin Test Form and compared the number of correct answers.

The results of Test Example 4 are shown in Table 4. The number of correct answers increased by drinking the soft capsules (Formulation Example 1) containing Rockfish. Therefore, it was demonstrated that Cinnamon mushroom has an effect on improving cognitive function.

In addition, when replacing the soft capsules containing C. chinensis (Formulation Example 1) with a beverage (Formulation Example 3) containing C. chinensis, and replacing the conventional soft capsules (Comparative Example 1) with a conventional beverage (Comparative Example 2). A similar effect was confirmed in .

The above results demonstrate that the nutrient transport promoting effect, cognitive function improving effect, and malnutrition correcting effect of Cinnamon mushroom are shown.

The nutrient transport promoter of the present invention exhibited excellent nutrient transport promoting action. Therefore, it is useful for use as a food, a drug, or a quasi-drug that has an excellent nutrient transport promoting effect.

Claims (7)

An agent for promoting the expression of SLC38A1 in intestinal epithelial cells, characterized by containing a hot water extract of red reishi mushroom and/or a hot water extract of black reishi mushroom. An agent for promoting the expression of SLC38A2 in intestinal epithelial cells, characterized by containing a hot water extract of red reishi mushroom and/or a hot water extract of black reishi mushroom. An agent for promoting the expression of SLC6A6 in intestinal epithelial cells, characterized by containing a hot water extract of red reishi mushroom and/or a hot water extract of black reishi mushroom. An agent for promoting the expression of SLC38A1 in intestinal epithelial cells, characterized by containing a hot water extract of a red reishi mushroom treated with subcritical water and/or a hot water extract of a black reishi mushroom treated with subcritical water. An agent for promoting the expression of SLC38A2 in intestinal epithelial cells, comprising a hot water extract of a red reishi mushroom treated with subcritical water and/or a hot water extract of a black reishi mushroom treated with subcritical water. An agent for promoting the expression of SLC6A6 in intestinal epithelial cells, characterized by containing a hot water extract of a red reishi mushroom treated with subcritical water and/or a hot water extract of a black reishi mushroom treated with subcritical water. For promoting the expression of SLC38A1, for promoting the expression of SLC38A2, or for promoting the expression of SLC38A2, characterized by containing the expression promoter of SLC38A1, the expression promoter of SLC38A2, or the expression promoter of SLC6A6 according to any one of claims 1 to 6. A food composition for promoting the expression of SLC6A6.