WO2017119476A1 - Composition for preventing neurological diseases - Google Patents

Abstract

Provided are: a composition for preventing neurological diseases; use of a material for preventing neurological diseases; and a method for preventing neurological diseases. It has been discovered that a heat-treated product of an animal/plant-derived peptide is effective in preventing neurological diseases. The present invention provides a novel means for preventing neurological diseases such as dementia, schizophrenia, Alzheimer's disease, Parkinson's syndrome, amyotrophic lateral sclerosis, etc.

Description

Composition for preventing neurological diseases

The present invention relates to a composition for preventing neurological diseases. More specifically, a composition for preventing a neurological disease containing a heat-treated animal and plant peptide as an active ingredient, use of the heat-treated animal and plant peptide to prevent a neurological disease, and neurological properties using the heat-treated animal and plant peptide The present invention relates to a disease prevention method.

The increase in the number of patients with neurological diseases accompanying the arrival of an aging society is a serious problem in modern society. The neurological disease is a disease that occurs due to a decrease in function or death of a specific group of nerve cells present in the brain or spinal cord. Representative neurological diseases include dementia, schizophrenia, Alzheimer's disease, Parkinson's syndrome, amyotrophic lateral sclerosis and the like. It has been reported that the onset of these neurological diseases involves neuronal inflammation resulting from microglial cell activation (Non-patent Documents 1 and 2). For example, Non-Patent Documents 3 and 4 report that microglial cell activation is involved in the development of dementia and schizophrenia. Non-patent documents 5 and 6 report that neuronal inflammation caused by nitric oxide and inflammatory cytokines secreted with microglial cell activation is involved in the development of Alzheimer's disease and Parkinson's syndrome. Yes. Furthermore, it has been reported that microglia cells are involved in amyotrophic lateral sclerosis (Non-patent Document 7).

Since the above-mentioned neurological diseases have such characteristics that they have a long incubation period and are difficult to treat after onset, prevention before onset is important. On the other hand, taking an artificially synthesized compound for a long period before the onset of a neurological disease is not preferable because of the possibility of unexpected side effects. Therefore, development of an active ingredient that is safe and can be taken for a long time is desired.

Cell, 140 (6), 918-934 (2010) Fukuoka Medical Journal, 100 (7), 243-247 (2009) Chronic inflammation and schizophrenia, molecular psychiatry, Vol.14, No.1 (2014) Evidence-Based Complementary and Alternative Medicine, Vol.2015, Article ID 768049 (2015) Journal of Alzheimer ’s Disease, 42, 587-605 (2014) Journal of Agricultural and Food Chemistry, 63, 3472-3480 (2015) Biochemistry, 85, No.1, p.1 (2013)

An object of the present invention is to provide a composition for preventing neurological diseases, use of a material for preventing neurological diseases, and a method for preventing neurological diseases.

As a result of intensive studies in view of the above problems, the present inventors have found that a heat-treated product of animal and plant peptides has a preventive effect on neurological diseases. In addition, the heat-treated product of animal and vegetable peptides has an inhibitory effect on the secretion of nitric oxide from microglia cells. As a result, the heat-treated product of animal and plant peptides has an inhibitory effect on microglial cell activation and an inhibitory effect on neuronal inflammation. The present invention has been completed.

That is, the present invention relates to the following, but is not limited thereto.
(1) A composition for preventing neurological diseases, comprising a heat-treated product of animal and plant peptides as an active ingredient.
(2) The composition for preventing neurological diseases according to (1), wherein the heat-treated animal and plant peptide product is a high-temperature and high-pressure processed product of animal or plant peptide.
(3) The composition for preventing neurological diseases according to (1) or (2), wherein the high-temperature and high-pressure treated product is obtained by high-temperature and high-pressure treatment at 100 ° C. or higher and 0.101 MPa or higher.
(4) The composition for preventing neurological diseases according to any one of (1) to (3), wherein the animal or plant peptide is soybean peptide or whey peptide.
(5) The composition for preventing neurological disease according to any one of (1) to (4), which has an action of suppressing inflammation of nerve cells.
(6) The composition for preventing neurological disease according to any one of (1) to (5), which has an action of suppressing secretion of nitric oxide from microglia cells.
(7) The composition for preventing a neurological disease according to any one of (1) to (6), which has an action of suppressing activation of microglia cells.
(8) The composition for preventing neurological disease according to any one of (1) to (7), which has an effect of preventing dementia.
(9) The composition for preventing neurological disease according to any one of (1) to (7), which has a preventive effect on schizophrenia.
(10) The composition for preventing neurological disease according to any one of (1) to (7), which has an effect of preventing Alzheimer's disease.
(11) The composition for preventing neurological disease according to any one of (1) to (7), which has a preventive effect on Parkinson's syndrome.
(12) The composition for preventing neurological disease according to any one of (1) to (7), which has an effect of preventing amyotrophic lateral sclerosis.
(13) The composition for preventing a neurological disease according to any one of (1) to (12), which is labeled with a function related to the prevention of the neurological disease,
Function indications are `` reducing the risk of developing neurological disease '', `` reducing the risk of developing dementia '', `` reducing the risk of developing Alzheimer's disease '', `` reducing the risk of developing Parkinson's syndrome '', `` schizophrenia The composition for preventing neurological disease, which is selected from the group consisting of “reducing the onset risk of” and “reducing the onset risk of amyotrophic lateral sclerosis”.
(14) Use of a heat-treated animal or plant peptide for preventing neurological diseases.
(15) A method for preventing a neurological disease using a heat-treated product of animal and plant peptides as an active ingredient.

According to the present invention, a composition having a preventive effect on neurological diseases can be provided. Since the heat-treated animal and vegetable peptide contained in the composition of the present invention has high safety, it can be said that the composition of the present invention has a high utility value in the market. Further, by ingesting the composition of the present invention, an effect of suppressing secretion of nitric oxide from microglia cells, an effect of suppressing activation of microglia cells, an effect of suppressing inflammation of nerve cells, and the like are obtained, thereby preventing dementia. The effect of preventing schizophrenia, the effect of preventing Alzheimer's disease, the effect of preventing Parkinson's syndrome, the effect of preventing amyotrophic lateral sclerosis and the like are exhibited.

FIG. 1 shows the amount of nitric oxide metabolites secreted from BV2 microglia cells (distilled water added) under the simultaneous addition of heat-treated soybean peptide (final concentration 1 mg / mL) and LPS (final concentration 100 ng / mL). It shows the production amount) ^- NO ₂ in the case of the production of the group is 100. FIG. 2 shows the production amount of nitric oxide metabolites secreted from BV2 microglia cells (addition of distilled water) under the simultaneous addition of heat-treated soybean peptide (final concentration 5 mg / mL) and LPS (final concentration 100 ng / mL). It shows the production amount) ^- NO ₂ in the case of the production of the group is 100. FIG. 3 shows the amount of nitric oxide metabolite secreted from BV2 microglia cells (added with distilled water) under the simultaneous addition of heat-treated whey peptide (final concentration 1 mg / mL) and LPS (final concentration 100 ng / mL). It shows the production amount) ^- NO ₂ in the case of the production of the group is 100. FIG. 4 shows the amount of nitric oxide metabolites secreted from BV2 microglia cells (added with distilled water) under the simultaneous addition of heat-treated whey peptide (final concentration 5 mg / mL) and LPS (final concentration 100 ng / mL). It shows the production amount) ^- NO ₂ in the case of the production of the group is 100.

One aspect of the present invention is a composition for preventing neurological diseases comprising a heat-treated animal or plant peptide as an active ingredient.

1. Animal and Plant Peptide In the present specification, the “animal and plant peptide” may be an animal peptide or a plant peptide. In this specification, unless otherwise specified, “animal peptide” refers to animal-derived protein or an animal body containing protein known decomposition treatment (decomposition treatment with heat or pressure, decomposition treatment with acid or alkali, enzyme decomposition It means a peptide produced by processing to reduce the molecular weight. In the present specification, unless otherwise specified, the “vegetable peptide” means an animal-derived protein or an animal body containing a protein known in the degradation treatment (decomposition treatment by heat or pressure, degradation treatment by acid or alkali, enzyme It means a peptide produced by reducing the molecular weight by subjecting it to a degradation treatment. In this specification, “animal and plant” includes “animal” and “plant”.

The animal and plant peptide of the present invention may be a single peptide obtained from an animal or plant derived protein or an animal or plant containing a protein, or a mixture of two or more peptides. The number of amino acids constituting the animal or vegetable peptide is not particularly limited, but is preferably 2 to several tens, more preferably 2 to several (that is, oligopeptide).

In the present invention, the animal and plant peptides are preferably those having a high ratio of peptides having a molecular weight of 5000 or less, more preferably those having a high ratio of peptides having a molecular weight of 3000 or less, and high ratios of peptides having a molecular weight of 1000 or less. It is particularly preferable to use one. Here, “the ratio of peptides is high” means a state in which at least 50% of the whole animal and plant peptides correspond to the peptide. The molecular weight can be measured using a method and apparatus (such as HPLC) well known to those skilled in the art.

The animal and plant peptides of the present invention are not particularly limited, but peptides derived from plants such as beans, seeds and moss, and peptides derived from animals such as whey, placenta and collagen are preferably used. Examples of beans include soybeans, red beans, and black beans. Examples of seeds include barley, wheat (including wheat germ), malt, sesame and rice. Examples of moss include sweet potatoes and potatoes. Among these, soybean and whey are preferable in the present invention. In addition, in this specification, description of "derived" may be abbreviate | omitted about the animal and plant peptide derived from a specific animal and plant. For example, in the case of “soybean-derived peptide”, this may be referred to as “soybean peptide”. At this time, both are used interchangeably.

The animal and plant peptide can be obtained by decomposing a plant or animal derived protein or plant or animal body containing the protein by a conventionally known method. Examples of such decomposition treatment include decomposition treatment with heat or pressure, decomposition treatment with acid or alkali, and decomposition treatment with an enzyme. In any treatment, water, ethanol or the like can be used as a solvent. For example, in the case of a decomposition treatment by heating, a condition of 30 minutes to several hours at a temperature of 100 ° C. or higher is indicated. In addition, this heat treatment can be performed simultaneously with the heat treatment of the heat-treated animal and plant peptide. Moreover, if it is a decomposition process by an enzyme, various proteolytic enzymes (protease) can be used suitably according to the objective.

The animal and plant peptides may be those prepared by themselves using a known method, or commercially available products may be used. Examples of commercially available plant peptides include soy peptides such as High Newt AM, High Newt DC, and High Newt HK (above, manufactured by Fuji Seiyaku Co., Ltd.), rice peptides such as Oriza Peptide-P60 (manufactured by Oriza Yuka Co., Ltd.), Examples thereof include wheat peptides such as glutamine peptide GP-1N and glutamine peptide GP-N (manufactured by Nisshin Pharma), and sesame peptides such as sesame peptide KM-20 (manufactured by KISCO). Examples of commercially available animal peptides include whey peptides such as whey peptide HW-3 (manufactured by Snow Brand Megmilk), whey peptide PeptigenIF-3090 (manufactured by Arraughs), casein peptide CU2500A manufactured by Morinaga Milk Industry, and manufactured by Health Support Examples thereof include placenta peptide and collagen peptide manufactured by Nitta Gelatin.

2. Heat treated animal and plant peptide Peptide heat treated animal and plant peptide can be obtained by heat-treating animal and plant peptide in a liquid at high temperature. The high-temperature heat treatment is not particularly limited, but treatment under conditions including not only high-temperature conditions but also high-pressure conditions is preferable. Pure water can be suitably used as the liquid in the high-temperature heat treatment and the high-temperature and high-pressure treatment, but an organic solvent such as ethanol can be appropriately contained therein. Moreover, hardness can also be suitably adjusted by adding a mineral part to an extraction solvent.

In this specification, “high temperature heat treatment” means that the treatment is performed for a certain period of time at a temperature of 100 ° C. or higher and a pressure exceeding atmospheric pressure. As the high-temperature and high-pressure treatment device, a pressure-resistant extraction device, a pressure cooker, an autoclave, or the like can be used according to conditions.

The temperature in the high-temperature heat treatment is not particularly limited as long as it is 100 ° C. or higher, but is preferably 105 ° C. or higher, 110 ° C. or higher, 115 ° C. or higher, 120 ° C. or higher, 125 ° C. or higher, 130 ° C. or higher, or 135 ° C. or higher. . The temperature is preferably 170 ° C. or lower, 165 ° C. or lower, 160 ° C. or lower, 155 ° C. or lower, 150 ° C. or lower, 145 ° C. or lower, or 140 ° C. or lower. Typically, the temperature is 100 ° C to 170 ° C, preferably 110 ° C to 150 ° C, more preferably 120 ° C to 140 ° C. In addition, this temperature shows the value which measured the exit temperature of an extraction column, when using a pressure-resistant extraction apparatus as a heating apparatus, and when using an autoclave as a heating apparatus, it is the temperature of the center temperature in a pressure vessel. The measured value is shown.

The high-temperature and high-pressure is not particularly limited as long as it exceeds atmospheric pressure, but is preferably 0.101 MPa or more, 0.15 MPa or more, 0.2 MPa or more, 0.25 MPa or more, or 0.3 MPa or more. The pressure is preferably 0.79 MPa or less, 0.75 MPa or less, 0.7 MPa or less, 0.65 MPa or less, 0.6 MPa or less, 0.55 MPa or less, 0.5 MPa or less, or 0.48 MPa or less. Typically, the pressure is 0.101 MPa to 0.79 MPa, preferably 0.101 MPa to 0.60 MPa, more preferably 0.101 MPa to 0.48 MPa.

The high temperature heat treatment time is not particularly limited as long as a desired processed product is obtained, but is preferably about 15 minutes to 600 minutes, more preferably about 30 minutes to 500 minutes, and even more preferably about 60 minutes to 300 minutes. .

In the present invention, more suitable high-temperature treatment conditions for obtaining a heat-treated product of animal and plant peptides include, for example, a coordinate system (i) in a coordinate system in which the horizontal axis is time (min.) And the vertical axis is temperature (° C.). ) To (vi) is a high temperature treatment held within a range of time and temperature. (I) (170 ℃, 30min.), (Ii) (150 ℃, 30min.), (Iii) (115 ℃, 180min.), (Iv) (105 ℃, 480min.), (V) (135 ℃ , 480min.), (Vi) (150 ℃, 180min.)
The treatment conditions relating to the temperature, pressure and time of the animal and plant peptide for obtaining the heat treated animal and plant peptide are not particularly limited, and can be set as follows, for example:
(Temperature, pressure, time) =
(105 ° C to 170 ° C, 0.101 MPa to 0.79 MPa, 15 minutes to 600 minutes),
(105 ° C to 170 ° C, 0.101 MPa to 0.79 MPa, 30 minutes to 500 minutes),
(105 ° C to 170 ° C, 0.101 MPa to 0.79 MPa, 60 minutes to 300 minutes),
(105 ° C to 170 ° C, 0.15 MPa to 0.48 MPa, 15 minutes to 600 minutes),
(105 ° C to 170 ° C, 0.15 MPa to 0.48 MPa, 30 minutes to 500 minutes),
(105 ° C to 170 ° C, 0.15 MPa to 0.48 MPa, 60 minutes to 300 minutes),
(110 ° C. to 150 ° C., 0.101 MPa to 0.79 MPa, 15 minutes to 600 minutes),
(110 ° C. to 150 ° C., 0.101 MPa to 0.79 MPa, 30 minutes to 500 minutes),
(110 ° C. to 150 ° C., 0.101 MPa to 0.79 MPa, 60 minutes to 300 minutes),
(110 ° C. to 150 ° C., 0.15 MPa to 0.48 MPa, 15 minutes to 600 minutes),
(110 ° C. to 150 ° C., 0.15 MPa to 0.48 MPa, 30 minutes to 500 minutes),
(110 ° C. to 150 ° C., 0.15 MPa to 0.48 MPa, 60 minutes to 300 minutes),
(120 ° C. to 140 ° C., 0.101 MPa to 0.79 MPa, 15 minutes to 600 minutes),
(120 ° C. to 140 ° C., 0.101 MPa to 0.79 MPa, 30 minutes to 500 minutes),
(120 ° C. to 140 ° C., 0.101 MPa to 0.79 MPa, 60 minutes to 300 minutes),
(120 ° C. to 140 ° C., 0.15 MPa to 0.48 MPa, 15 minutes to 600 minutes),
(120 ° C. to 140 ° C., 0.15 MPa to 0.48 MPa, 30 minutes to 500 minutes),
(120 ° C. to 140 ° C., 0.15 MPa to 0.48 MPa, 60 minutes to 300 minutes) and the like.

In the present invention, the heat-treated animal and plant peptide product can be prepared using an apparatus that can provide the above-described treatment conditions. Examples of such a device include, but are not limited to, a pressure-resistant extraction device, a pressure cooker, and an autoclave that are well known to those skilled in the art. Moreover, the animal and plant peptide heat-treated product may be subjected to solid-liquid separation before and / or after the heat treatment. By performing the solid-liquid separation process, the liquid part can be recovered, and it can be handled only by the solid. For solid-liquid separation, means such as filtrate and / or centrifugation are used. Moreover, the animal and plant peptide heat-treated product may be subjected to a purification treatment after the heat treatment. By performing the purification treatment, specific components contained in the heat-treated animal and vegetable peptide product can be concentrated. Purification of the heat-treated animal and plant peptide product can be performed using a known method and apparatus. Moreover, the animal and plant peptide heat-treated product may further be subjected to a clarification treatment before and / or after the heat treatment. The clarification treatment can be carried out using a known method and apparatus, and the degree of freedom in designing the composition to which the heat-treated animal and plant peptide product is added can be increased by the treatment. Further, the heat-treated animal and plant peptide may be lyophilized or powdered using a known method and apparatus. In addition, the manufacturing method of the heat-processed animal and vegetable peptide in this invention can refer to the method of international publication 2014/200000.

3. The cyclic dipeptide or its salt heat-treated animal or vegetable peptide can be obtained by subjecting an animal or vegetable peptide to high-temperature heat treatment or high-temperature and high-pressure treatment, but a large amount of cyclic dipeptide or its salt is included in the heat-treated animal or plant peptide. It becomes like this. That is, in the present invention, the heat-treated animal and vegetable peptide contains a cyclic dipeptide or a salt thereof as one of its characteristics. Although not wishing to be bound by a specific theory, since the heat-treated animal and plant peptide contains a large amount of cyclic dipeptide or a salt thereof, the cyclic dipeptide or a salt thereof is not included in the composition for preventing neurological diseases. It can be an active ingredient. In the present specification, a cyclic dipeptide or a salt thereof may be collectively referred to simply as a cyclic dipeptide.

As used herein, a cyclic dipeptide refers to a dipeptide having a diketopiperazine structure produced by dehydration condensation of an amino group and a carboxyl group of an amino acid. Therefore, the cyclic dipeptide is distinguished from the chain dipeptide.

Cyclic dipeptide salts include any pharmacologically acceptable salt (including inorganic and organic salts). Examples of such salts include sodium salt, potassium salt, calcium salt, magnesium salt, ammonium salt, hydrochloride, sulfate, nitrate, phosphate, organic acid salt (acetate, citrate, maleate, Malate, oxalate, lactate, succinate, fumarate, propionate, formate, benzoate, picrate, benzenesulfonate, trifluoroacetate, etc.) However, it is not limited to these.

The amount of the cyclic dipeptide or the salt thereof contained in the heat-treated animal / vegetable peptide product varies depending on the type of the heat-treated animal / vegetable peptide product, and is not particularly limited. For example, per brix (Bx) in the heat-treated animal / vegetable peptide product. The total amount of the cyclic dipeptide or a salt thereof is preferably 20000 μg / 100 g / Bx or more, 25000 μg / 100 g / Bx or more, 30000 μg / 100 g / Bx or more, more preferably 35000 μg / 100 g / Bx or more. The total amount is preferably 10,000 mg / 100 g / Bx or less, 5000 mg / 100 g / Bx or less, 2000 mg / 100 g / Bx or less, more preferably 1000 mg / 100 g / Bx or less. Typically, the total amount of the cyclic dipeptide or a salt thereof contained in the heat-treated animal and plant peptide according to the present invention is preferably 20000 μg / 100 g / Bx to 10,000 mg / 100 g / Bx, more preferably 30000 μg / 100 g / Bx to 5000 mg / 5000. 100 g / Bx, even more preferably 35000 μg / 100 g / Bx to 1000 mg / 100 g / Bx.
When the cyclic dipeptide is in the form of a salt, the content is calculated after conversion to a free form (free form).

Favorable embodiments of the heat-treated animal and plant peptide product of the present invention include a malt peptide heat-treated product and a whey peptide heat-treated product. Hereinafter, the cyclic dipeptide in these heat-treated products will be described in detail.

3-1. Soybeans (scientific name: Glycine max), which is a raw material for heat-treated soybean peptide, can be used without limitation of varieties and production areas, and can also be used in processed products such as pulverized products. It is said that protein in soybeans accounts for about 30%. Soy protein does not have much water-insoluble protein like tea leaf protein, so pretreatment for removing water-soluble protein is not essential, and may be performed as needed. When there is no pretreatment for removing the water-soluble protein, a soybean peptide heat-treated product containing a cyclic dipeptide at a high concentration can be more easily produced by a one-pot reaction.

In the present invention, the soybean peptide heat-treated product is a cyclic dipeptide that was not included in the conventional soybean protein degradation product (soy peptide), Cyclo (Ala-Gln), Cyclo (Ala-Ala), Cyclo (Ser-Tyr) , Cyclo (Gly-Trp), Cyclo (Val-Val), Cyclo (Trp-Tyr), Cyclo (Leu-Trp) and Cyclo (Phe-Phe) with a content per Bx of 10 μg / 100 g / Contains at least Bx.

The heat-treated soybean peptide in the present invention is Cyclo (Ala-Gln), Cyclo (His-Pro), Cyclo (Ala-Ala), Cyclo (Gly-Pro), Cyclo (Ser-Tyr), Cyclo (Pro- Thr), Cyclo (His-Phe), Cyclo (Ala-Pro), Cyclo (Phe-Ser), Cyclo (Gly-Leu), Cyclo (Gly-Phe), Cyclo (Gly-Trp), Cyclo (Asp-Phe ), Cyclo (Val-Pro), Cyclo (Pro-Tyr), Cyclo (Met-Pro), Cyclo (Val-Val), Cyclo (Leu-Pro), Cyclo (Trp-Tyr), Cyclo (Phe-Pro) , Cyclo (Leu-Trp), Cyclo (Leu-Phe), Cyclo (Leu-Leu) and Cyclo (Phe-Phe) are each contained at a concentration of 0.1 ppm / Bx (10 μg / 100 g / Bx) or more. Preferably, each cyclic dipeptide is 0.5 ppm / Bx or more, more preferably 0.7 ppm / Bx or more, still more preferably 0.9 ppm / Bx or more, particularly preferably 1.0 ppm / Bx or more, and particularly preferably 1. It is a soybean peptide heat-treated product containing at a concentration of 2 ppm / Bx or more. Furthermore, Cyclo (Leu-Leu), Cyclo (Leu-Phe), Cyclo (Ser-Tyr) and Cyclo (Pro-Thr) are each 0.1 ppm / Bx (10 μg / 100 g / Bx) or more, preferably 0. It can be contained at a concentration of 2 ppm / Bx or more, more preferably 0.3 ppm / Bx or more.

This heat-treated product of soybean peptide (especially heat-treated product obtained from soybean or a pulverized product thereof) is known as Cyclo (Leu-Pro), Cyclo (Phe-Pro) and Cyclo (Leu Despite containing -Trp), its bitterness is reduced. When an aqueous solution containing the same concentration of Cyclo (Leu-Pro) and Cyclo (Phe-Pro) was prepared, strong bitterness was felt.Therefore, other cyclic dipeptides and components derived from soybeans were added together. It is considered that the bitter taste of Cyclo (Leu-Pro), and Cyclo (Phe-Pro) and Cyclo (Leu-Trp) is moderately or synergistically. In particular, the total amount of cyclic dipeptides Cyclo (Leu-Pro), Cyclo (Phe-Pro) and Cyclo (Leu-Trp) having a bitter taste relative to the total amount (A) of Cyclo (Leu-Leu) and Cyclo (Leu-Phe) (B ) Ratio [(B) / (A)] is 1.0 or less (preferably 0.8 or less, more preferably 0.6 or less, particularly preferably 0.5 or less), It is a cyclic dipeptide-containing heat-treated product with significantly reduced bitterness and can be applied orally.

The total amount of cyclic dipeptide or salt thereof per Bx in the soybean peptide heat-treated product in the present invention is preferably 20000 μg / 100 g / Bx or more, 25000 μg / 100 g / Bx or more, 30000 μg / 100 g / Bx or more, more preferably 35000 μg / 100 g. / Bx or more. The total amount is preferably 10,000 mg / 100 g / Bx or less, 5000 mg / 100 g / Bx or less, 2000 mg / 100 g / Bx or less, more preferably 1000 mg / 100 g / Bx or less. Typically, the total amount of cyclic dipeptide or salt thereof per Bx in the heat-treated soybean peptide in the present invention is preferably 20000 μg / 100 g / Bx to 10,000 mg / 100 g / Bx, more preferably 30000 μg / 100 g / Bx to 5000 mg. / 100 g / Bx, still more preferably 35000 μg / 100 g / Bx to 1000 mg / 100 g / Bx.

The soybean peptide heat-treated product in the present invention preferably contains Cyclo (Leu-Leu), Cyclo (Leu-Phe), Cyclo (Ser-Tyr) and Cyclo (Pro-Thr) in a high concentration. Specifically, Cyclo (Leu-Leu) is 8% or more (weight basis), Cyclo (Leu-Phe) is 8% or more, and Cyclo (Ser-Tyr) based on the total amount of cyclic dipeptide in the soybean peptide heat-treated product. Is a heat-treated product with 6% or more. In the soybean peptide heat-treated product, these concentrations are each 0.1 ppm / Bx (10 μg / 100 g / Bx), preferably 5.0 ppm / Bx or more, more preferably 6.0 ppm / Bx or more, and even more preferably 7.0 ppm. / Bx or more. In particular, the content of Cyclo (Leu-Leu) and Cyclo (Leu-Phe) is 10.0 ppm / Bx or more, preferably 12.0 ppm / Bx or more. Although these upper limits are not specifically limited, Preferably they are 500 ppm / Bx or less, 400 ppm / Bx or less, More preferably, it is about 350 ppm / Bx or less, More preferably, it is about 300 ppm / Bx or less.

3-2. The raw material of the whey peptide heat-treated product is not particularly limited, and examples thereof include WPC (whey protein concentrate) and WPI (whey protein isolate) which are whey proteins. The whey peptide is a product obtained by degrading these whey proteins with an enzyme or the like. There are various degrees of decomposition, but when the degree of decomposition is low, the milky odor becomes strong and the liquidity after dissolution tends to be opaque (white turbidity). On the other hand, when the degree of decomposition is high, the liquidity at the time of dissolution becomes transparent, but it tends to increase bitterness and astringency.

The heat-treated product of whey peptide is obtained by subjecting the whey peptide to a high-temperature heat treatment or a high-temperature / high-pressure treatment. By this treatment, a large amount of cyclic dipeptide or a salt thereof is included in the heat-treated product of whey peptide. That is, in the present invention, the whey peptide heat-treated product contains a cyclic dipeptide or a salt thereof as one of its features.

In addition, the heat-treated product of whey peptide in the present invention is Cyclo (Arg-Leu), Cyclo (Leu-Lys), Cyclo (Ala-Leu), Cyclo (Glu-Pro), Cyclo (Ile-Pro), Cyclo (Val- Phe), Cyclo (Asp-Glu), Cyclo (Thr-Lys), Cyclo (Lys-Lys), Cyclo (Lys-Phe), and Cyclo (Thr-Tyr), 0.1 ppm / Bx (10 μg / 100 g / Bx). Preferably, each of the above cyclic dipeptides or salts thereof is 0.5 ppm / Bx or more, more preferably 0.7 ppm / Bx or more, still more preferably 0.9 ppm / Bx or more, particularly preferably 1.0 ppm / Bx or more, particularly A heat-treated whey peptide containing a concentration of 1.2 ppm / Bx or more is preferable.

The total amount of cyclic dipeptide or salt thereof per Bx in the heat-treated product of whey peptide in the present invention is preferably 20000 μg / 100 g / Bx or more, 25000 μg / 100 g / Bx or more, 30000 μg / 100 g / Bx or more, more preferably 35000 μg / 100 g. / Bx or more. The total amount is preferably 10,000 mg / 100 g / Bx or less, 5000 mg / 100 g / Bx or less, 2000 mg / 100 g / Bx or less, more preferably 1000 mg / 100 g / Bx or less. Typically, the total amount of cyclic dipeptide or salt thereof per Bx in the heat treated whey peptide in the present invention is preferably 20000 μg / 100 g / Bx to 10000 mg / 100 g / Bx, more preferably 30000 μg / 100 g / Bx to 5000 mg. / 100 g / Bx, still more preferably 35000 μg / 100 g / Bx to 1000 mg / 100 g / Bx.

The heat-treated product of the whey peptide in the present invention is preferably Cyclo (Arg-Leu), Cyclo (Leu-Lys), Cyclo (Ala-Leu), Cyclo (Glu-Pro), Cyclo (Ile-Pro), Cyclo (Val -Phe), Cyclo (Asp-Glu), and Cyclo (Thr-Lys) are contained in high concentrations. In the whey peptide heat-treated product, these concentrations are each 0.1 ppm / Bx (10 μg / 100 g / Bx) or more, preferably 5.0 ppm / Bx or more, more preferably 6.0 ppm / Bx or more, and even more preferably 7. 0 ppm / Bx or more. Although these upper limits are not specifically limited, Preferably they are 500 ppm / Bx or less, 400 ppm / Bx or less, More preferably, it is about 350 ppm / Bx or less, More preferably, it is about 300 ppm / Bx or less.

4). One aspect of the neurological disease prophylactic composition the present invention contains a plant and animal peptide thermal treatment as an active ingredient, a neurological disease prevention composition.

The content of the heat-treated animal and plant peptide in the composition of the present invention is not particularly limited as long as the desired effect of the present invention is obtained in consideration of its administration form, administration method and the like. Absent. For example, the content of the heat-treated animal and vegetable peptide is 0.10% by weight or more, preferably 0.20% by weight or more, more preferably 0.40% by weight or more based on the total weight of the composition of the present invention. . The content of the heat-treated animal and plant peptide is 50% by weight or less, preferably 10% by weight or less, more preferably 5.0% by weight or less based on the total weight of the composition of the present invention. Typically, the content of the heat-treated animal and vegetable peptide is 0.10% to 50% by weight, preferably 0.20% to 10% by weight, more preferably based on the total weight of the composition of the present invention. Is 0.4 wt% to 5.0 wt%. Unless otherwise specified, “wt%” used in the present specification means weight / weight (w / w).

4-1. Mechanism of action Microglial cells are present in the brain as one of the constituent cells of the central nervous system, and are responsible for immune defense in the brain through functions such as cleaning the brain damage site and providing antigens. When activated by various stimuli, the microglial cells release humoral factors such as inflammatory cytokines, nitric oxide, and active oxygen, and cause inflammation of nerve cells existing in the brain. In addition, neuronal inflammation promotes the onset of neurological diseases such as dementia, schizophrenia, Alzheimer's disease, Parkinson's syndrome, and amyotrophic lateral sclerosis. Therefore, if the activation of microglia cells and the release of humoral factors such as inflammatory cytokines, nitric oxide, and active oxygen from microglia cells can be suppressed, inflammation of nerve cells can also be suppressed. As a result, dementia, schizophrenia Effects of neurological diseases such as symptom, Alzheimer's disease, Parkinson's syndrome, and amyotrophic lateral sclerosis.

4-2. Other Components The composition for preventing neurological diseases of the present invention can contain any additive and any commonly used component in addition to the heat-treated animal and plant peptide according to the form. Examples of these additives and / or ingredients include vitamins such as vitamin E and vitamin C, bioactive ingredients such as minerals, nutritional ingredients, and fragrances, as well as excipients and binders incorporated in the formulation. , Emulsifiers, tonicity agents (isotonic agents), buffers, solubilizers, preservatives, stabilizers, antioxidants, colorants, coagulants, or coating agents, but are not limited thereto. It is not something.

4-3. Use The composition for preventing neurological diseases of the present invention contains the above heat-treated animal and plant peptide as an active ingredient, thereby releasing humoral factors such as inflammatory cytokines, nitric oxide and active oxygen from microglia cells. In particular, the release of nitric oxide can be suppressed. Thereby, the inhibitory effect of the inflammation of the nerve cell in a brain is exhibited. Therefore, by ingesting the composition of the present invention, diseases caused by neuronal inflammatory disorders such as dementia, Alzheimer's disease, Parkinson's syndrome, schizophrenia, amyotrophic lateral sclerosis, etc. Disease prevention effects can be obtained.

The composition for preventing neurological diseases of the present invention includes, for example, a raw material containing a heat-treated product of animal and plant peptides, and optionally a solvent, a dispersant, an emulsifier, a buffer, a stabilizer, an excipient, a binder, a disintegrant, Or, add a lubricant, etc., and formulate it into a solid agent such as a tablet, granule, powder, powder, or capsule, or a liquid agent such as a normal solution, suspension, or emulsion according to a known method. be able to. These compositions can be taken with water or the like as it is. Moreover, after preparing the form (for example, powder form and granule form) which can be mix | blended easily, it can use, for example as a raw material of a pharmaceutical.

The present invention can be provided in the form of an agent as an example, but is not limited to this form. The agent can be provided as a composition as it is or as a composition containing the agent. As an example, it can be provided in the form of a medicine or the like, but is not limited to this form. Examples of the composition of the present invention include, but are not limited to, a pharmaceutical composition, a food / beverage product composition, a food composition, a beverage composition, a cosmetic composition, and the like. Non-limiting examples of food compositions include functional foods, health supplements, functional nutrition foods, special foods, foods for specified health use, dietary supplements, diet foods, health foods, supplements, food additives, etc. Can be mentioned.

The composition for preventing neurological diseases of the present invention can be applied to any therapeutic use (medical use) or non-therapeutic use (non-medical use). Specific examples include use as pharmaceuticals, quasi-drugs, cosmetics, and the like, and they do not belong to these under the Pharmaceutical Affairs Law, but prevent neurological diseases, prevent dementia, prevent Alzheimer's disease, Examples thereof include use as a composition that explicitly or implicitly appeals to preventive effect on Parkinson's syndrome, preventive effect on schizophrenia, preventive effect on amyotrophic lateral sclerosis, and the like.

In another aspect, the present invention relates to the composition for preventing a neurological disease, which is labeled with a function related to the prevention of the neurological disease. Such indications or functional indications are not particularly limited. For example, “Preventing neurological diseases”, “Reducing the risk of developing neurological diseases”, “Preventing dementia”, “Preventing the risk of developing dementia” Reduce, "Prevent Alzheimer's disease," "Reduce the risk of developing Alzheimer's disease," "Prevent Parkinson's syndrome," "Reduce the risk of developing Parkinson's syndrome," "Prevent schizophrenia," "Integration “Reduce the risk of developing ataxia”, “Prevent amyotrophic lateral sclerosis”, or “Reduce the risk of developing amyotrophic lateral sclerosis”. In the present specification, such indications and indications such as function indications may be attached to the composition itself, or may be attached to the container or packaging of the composition.

The composition for preventing neurological diseases of the present invention can be taken by an appropriate method according to the form. Examples of ingestion methods include internal (oral), external, and injection methods, but the method is not particularly limited as long as the desired effect of the present invention is exhibited. In the present specification, “ingestion” is used to include all aspects of ingestion, taking, drinking, and the like.

The application amount of the composition for preventing a neurological disease of the present invention is set in a timely manner according to the form, administration method, purpose of use, and age, weight, and symptom of the subject patient or animal, and is not constant. The effective human intake of the heat treated animal and plant peptide according to the present invention is not constant, but is preferably 500 mg or more, more preferably 1000 mg or more, per day for a human body weight of 50 kg. Further, administration may be performed once or several times within one day within a desired dose range. The administration period is also arbitrary. The effective human intake of the heat-treated animal and plant peptide product means the intake amount of the heat-treated animal and plant peptide exhibiting an effective effect in humans.

The subject of application of the composition for preventing neurological disease of the present invention is preferably a human, but domestic animals such as cattle, horses and goats, pet animals such as dogs, cats and rabbits, or mice, rats, guinea pigs, It may be a laboratory animal such as a monkey. When a non-human animal is administered to a subject, the amount used per day for about 20 g per mouse is the content of the active ingredient in the composition, the state of the subject, weight, sex, age, etc. Usually, the dosage of the heat-treated animal and plant peptide is preferably 100 mg / kg or more, more preferably 1000 mg / kg.

5). Use of Heat Treated Animal and Plant Peptide for Preventing Neurological Disease One aspect of the present invention is the use of a heat treated product of animal and plant peptide for preventing neurological disease.

Use of the heat-treated animal and plant peptide of the present invention includes, for example, use for preventing dementia, Alzheimer's disease, Parkinson's syndrome, schizophrenia, amyotrophic lateral sclerosis, etc. Is not to be done. In addition, the use is a use in a human or non-human animal, and may be a therapeutic use or a non-therapeutic use. Here, “non-therapeutic” is a concept that does not include a medical act, that is, a treatment act on the human body by treatment.

6). Method for Preventing Neurological Disease One embodiment of the present invention prevents a neurological disease, comprising administering a therapeutically effective amount of a heat-treated animal or plant peptide to a subject in need of neurological disease prevention as an active ingredient. A method is provided. The subject in need of neurological disease prevention is the same as the administration subject of the composition for preventing neurological disease of the present invention.

In the present specification, the therapeutically effective amount refers to an amount capable of preventing a neurological disease when the subject is ingested with the heat-treated animal or plant peptide of the present invention as compared with a subject who has not been ingested. It is. The specific effective amount is appropriately set depending on the administration form, administration method, purpose of use, age, weight, symptom, etc. of the subject and is not constant.

In the method of the present invention, the heat-treated animal or plant peptide may be administered as it is or as a composition containing the heat-treated animal or plant peptide so that the therapeutically effective amount is obtained.

According to the method of the present invention, it becomes possible to prevent neurological diseases without causing side effects.

Hereinafter, the present invention will be described in more detail with reference to examples, but the scope of the present invention is not limited thereby. Those skilled in the art can use the method of the present invention with various changes and modifications, and these are also included in the scope of the present invention.

Example 1: Preparation of heat-treated soybean peptide Heat-treated soybean peptide was produced by using soybean peptide as a vegetable peptide and subjecting it to high-temperature and high-pressure treatment in a liquid. Specifically, 15 ml of distilled water is added to 3 g of soybean peptide (Hi-New AM, manufactured by Fuji Oil Co., Ltd.), placed in an autoclave (produced by Tommy Seiko Co., Ltd.), and treated at 135 ° C., 0.31 MPa for 3 hours at high temperature and pressure Was added. Moreover, the soybean peptide non-heating thing which does not perform a high temperature / high pressure process using the same peptide was prepared as a comparative example.

Example 2: Preparation of heat-treated product of whey peptide A whey peptide heat-treated product was produced by using a whey peptide as an animal peptide and subjecting it to high-temperature and high-pressure treatment in a liquid. Specifically, 30 ml of distilled water is added to 3 g of whey peptide Peptigen IF-3090 (manufactured by Arraughs, average molecular weight 300 to 400), whey peptide having an average molecular weight of 440, or casein peptide CU2500A (manufactured by Morinaga Milk Industry Co., Ltd., average molecular weight 375). Was added to an autoclave (manufactured by Tommy Seiko Co., Ltd.), and high-temperature and high-pressure treatment was added at 135 ° C., 0.31 MPa for 3 hours. As a comparative example, a non-heated whey peptide was prepared using the same peptide and not subjected to high-temperature and high-pressure treatment. The whey peptide non-heated product 3 and the heat-treated product 3 shown in FIGS. 3 and 4 are derived from the whey peptide Peptigen IF-3090, and the whey peptide non-heated product 5 and the heat-treated product 5 are derived from the whey peptide having an average molecular weight of 440. The whey peptide non-heated product 7 and the heat-treated product 7 are derived from the casein peptide CU2500A.

Example 3: Evaluation of the production amount of nitric oxide (NO) derived from microglia cells (heat added to soybean or whey peptide and LPS)
The inhibitory effect of nitric oxide produced from LPS-stimulated BV2 microglia cells was evaluated under the conditions of addition of soybean or whey peptide heat-treated product. A 96-well plate was seeded with 100 μL of BV2 microglia cells adjusted to a concentration of 2.0 × 10 ⁵ cells / mL with 10% FBS-added DMEM medium. 24 hours after sowing, LPS (final concentration 100 ng / mL) and cyclic dipeptide (final concentration 5 mg / mL) were added simultaneously. After 24 hours, the culture supernatant was collected, and the amount of nitric oxide metabolite (NO ₂ ⁻ ) was measured by Griess assay (n = 2). Griess assay was performed using Griess Reagent System (same composition as Promega cat. # G2930).

The results are shown in FIGS. As a result of the experiment, as shown in FIG. 1 and FIG. 2, by simultaneously adding the soybean peptide heat-treated product and LPS, production of nitric oxide metabolite (NO ₂ ⁻ ) from BV2 microglia cells caused by LPS stimulation It was revealed that the soybean peptide heat-treated product was suppressed depending on the concentration. Furthermore, it is also clear that the degree of inhibition of nitric oxide metabolite (NO ₂ ⁻ ) production from BV2 microglial cells caused by LPS stimulation is higher compared to the non-heated soy peptide product by adding heat-treated soybean peptide. It became.

Further, as shown in FIGS. 3 and 4, by simultaneously adding the heat-treated whey peptide and LPS, the production of nitric oxide metabolites (NO ₂ ⁻ ) from BV2 microglia cells caused by LPS stimulation is It was clarified that it was suppressed depending on the concentration of the heat-treated peptide. On the other hand, when the whey peptide non-heated product and LPS were added simultaneously, the production inhibitory effect of the nitric oxide metabolite (NO ₂ ⁻ ) from the BV2 microglia cells caused by LPS stimulation was not observed.

Therefore, it has been clarified that the heat-treated soybean or whey peptide significantly suppresses nitric oxide production from BV2 microglia cells caused by LPS stimulation.

The present invention provides a composition for preventing neurological diseases comprising a heat-treated product of animal and plant peptides as an active ingredient. Therefore, the present invention provides a new means for the prevention of neurological diseases such as dementia, schizophrenia, Alzheimer's disease, Parkinson's syndrome, amyotrophic lateral sclerosis, etc. High nature.

Claims (15)

A composition for the prevention of neurological diseases, comprising a heat-treated animal and plant peptide as an active ingredient. The composition for preventing neurological diseases according to claim 1, wherein the heat-treated product of animal and plant peptides is a high-temperature and high-pressure processed product of animal and plant peptides. The composition for preventing neurological diseases according to claim 1 or 2, wherein the high-temperature and high-pressure treated product is obtained by high-temperature and high-pressure treatment at 100 ° C or higher and 0.101 MPa or higher. The composition for preventing neurological diseases according to any one of claims 1 to 3, wherein the animal or plant peptide is a soybean peptide or a whey peptide. The composition for preventing a neurological disease according to any one of claims 1 to 4, which has an action of suppressing inflammation of nerve cells. The composition for preventing neurological disease according to any one of claims 1 to 5, which has an action of inhibiting secretion of nitric oxide from microglia cells. The composition for preventing a neurological disease according to any one of claims 1 to 6, which has an activity of suppressing activation of microglia cells. The composition for preventing a neurological disease according to any one of claims 1 to 7, which has a dementia-preventing effect. The composition for preventing a neurological disease according to any one of claims 1 to 7, which has a preventive effect on schizophrenia. The composition for preventing a neurological disease according to any one of claims 1 to 7, which has a preventive effect against Alzheimer's disease. The composition for preventing a neurological disease according to any one of claims 1 to 7, which has a preventive effect on Parkinson's syndrome. The composition for preventing neurological disease according to any one of claims 1 to 7, which has a preventive effect on amyotrophic lateral sclerosis. A composition for preventing a neurological disease according to any one of claims 1 to 12, which is labeled with a function related to the prevention of the neurological disease,
Function indications are `` reducing the risk of developing neurological disease '', `` reducing the risk of developing dementia '', `` reducing the risk of developing Alzheimer's disease '', `` reducing the risk of developing Parkinson's syndrome '', `` schizophrenia The composition for preventing neurological disease, which is selected from the group consisting of “reducing the onset risk of” and “reducing the onset risk of amyotrophic lateral sclerosis”. 使用 Use of heat treated animal and plant peptides to prevent neurological diseases. A method for preventing neurological diseases, wherein a heat-treated animal or plant peptide is used as an active ingredient.

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