JP5064714B2 - Anti-stress composition - Google Patents

Description

  The present invention relates to an anti-stress composition characterized by containing a royal jelly enzyme-treated product and a maca extract, and a pharmaceutical and a food containing the same. More specifically, the present invention relates to a composition that has an effect of suppressing an increase in blood glucocorticoid concentration due to stress and is intended to prevent or ameliorate various symptoms associated with stress.

  Stress refers to distortion or modulation that the body exhibits as a result of some stimulus being applied to the body. The types of stress include physical things such as noise, temperature changes, lack of oxygen, hunger and overwork, and mental things such as anxiety, tension and anger. In particular, in modern society, there is an advanced competitive society in schools and companies, significant changes in technology due to the spread of mechanization and computers, overpopulation in urban areas, nuclear families, and problems of aging society. Regardless of the exposure to various stresses.

  When a living body receives stress stimulation, ACTH (adrenocorticotropic hormone) is secreted by the hypothalamus acting on the pituitary gland, and ACTH stimulates the adrenal cortex to cause glucocorticoids such as cortisol, corticosterone, and cortisone. Secreted. Glucocorticoids are essential hormones for maintaining homeostasis and protecting yourself from stress, and are responsible for promoting glucose metabolism, regulating fat metabolism, and anti-inflammatory effects. However, when stress continues chronically, secretion of glucocorticoid becomes excessive, causing serious symptoms such as impaired immune function, memory impairment, diabetes, obesity, and chronic fatigue.

  Synthetic agents such as tranquilizers, anti-anxiety agents, and sleeping pills are used to relieve mental and physical symptoms caused by stress. However, these drugs have problems of habits and side effects and are not preferable for long-term use. Therefore, a safe anti-stress agent that can be used on a daily basis is required, and has been developed in various fields.

  For example, an anti-stress agent containing a tripeptide as an active ingredient and a functional food (see Patent Document 1), an anti-stress agent containing a lactoferrin as an active ingredient (see Patent Document 2), and an anti-stress agent containing a pine bark extract (See Patent Document 3) and the like. However, the effects of these antistress agents were not sufficient.

  Royal jelly is a milky white substance secreted from worker bees and is composed of proteins, carbohydrates, lipids, etc., and may have physiological activities such as antibacterial action, immune enhancement action, antitumor action, anti-inflammatory action, blood pressure regulation action, etc. Are known. Since most of the protein of royal jelly is insoluble, when it is added to a liquid food, a white precipitate is formed, which is not preferable in appearance. Therefore, a soluble royal jelly by enzyme treatment has been developed (see Patent Document 4). . In addition, royal jelly has been reported to have effects on environmental temperature alternation stress using rats. However, the royal jelly reported here is not an enzyme-treated product (Non-patent Document 1).

Japanese Patent Application Laid-Open No. 11-100348 Japanese Patent Laid-Open No. 2001-354583 Japanese Laid-Open Patent Publication No. 2003-95964 Japanese Patent No. 2623044 Sasazuka et al. Pharmacology and Treatment 1996 Vol. 24 No. 7 p1469-1473

  An object of the present invention is to provide a novel anti-stress agent that can effectively prevent or ameliorate various symptoms associated with stress and has high safety, and a pharmaceutical and food containing the same.

  As a result of intensive studies to solve the above-mentioned problems, the present inventor combined enzyme-treated royal jelly and maca extract, when used alone or in combination with untreated royal jelly and maca extract. As a result, it was found that glucocorticoid secretion is remarkably suppressed as compared with the case of the present invention, and the present invention has been completed.

  As the royal jelly in the present invention, a raw royal jelly secreted by a worker bee can be used, and a commercially available product, a frozen product, a freeze-dried product, or the like can be optionally used as necessary.

  The royal jelly enzyme-treated product used in the present invention may be any product obtained by enzymatic treatment of royal jelly. The enzyme may be any enzyme capable of degrading royal jelly, and examples of such enzymes include proteolytic enzymes, glycolytic enzymes, lipases, etc. Proteolytic enzymes are preferable for sufficiently degrading royal jelly, for example Furthermore, proteases and peptidases derived from microorganisms and plants, proteases such as pepsin, trypsin and pancreatin derived from mammals can be used.

  The above enzymes can be used alone or in combination of two or more. The enzyme treatment can be performed by a general method according to each enzyme used. For example, it can be carried out by treating at 20 to 60 ° C. At this time, the pH of the reaction solution and the reaction solvent can be appropriately selected according to the type of enzyme used.

  Maca (Lepidium meyenii) is a cruciferous plant native to the highlands of Peru, South America. It has been cultivated in the Andes region for over 2000 years, and its roots have been used for food.

  Maca in the present invention may use any part such as whole grass, flowers, fruits, leaves, stems, roots, etc., but the root is the most preferable part. As the maca extract used in the present invention, each part may be dried and pulverized and used as it is, but preferably with water or a hydrophilic organic solvent such as methanol, ethanol, propanol or acetone, or a mixed solvent thereof. It is better to use an extract obtained by extraction.

  The said extract may be used with the extracted solution as it is, and may be used by concentrating, diluting, and filtering as needed. Further, the extracted solution may be subjected to a treatment such as concentration to dryness, spray drying, freeze drying, etc. and used as a dried product.

  The anti-stress composition of the present invention can be used for either food or medicine. For example, capsules, tablets, granules, powders, beverages, gums, chocolates, strawberries, noodles, breads, cakes, biscuits, canned foods, retort foods, livestock meat products, marine products, margarine, butter, mayonnaise, etc. Pharmaceutical and food forms can be employed. Of these, capsules, tablets, granules, beverages and the like that allow easy adjustment of the intake are preferred.

  The intake amount of the composition used in the present invention varies depending on the administration form, purpose of use, age, body weight and the like, but is usually 0.001% by weight or more, preferably 0.01 to in terms of solid content in the total amount of the preparation. 50.0% by weight is good. In addition, the method for adding medicinal ingredients in the formulation may be added in advance or during production, and may be appropriately selected in consideration of workability. The daily dosage is 0.001 to 20 g, preferably 0.1 to 10 g, more preferably 0.5 to 4 g in terms of royal jelly converted to royal jelly. The maca extract is 0.001 to 20 g, preferably 0.1 to 10 g, more preferably 0.5 to 4 g in terms of dried maca. Since the administration method and dosage vary depending on various conditions, an amount smaller than the above-mentioned administration range may be sufficient, or it may be necessary to administer beyond the range.

  The royal jelly enzyme-treated product and maca extract of the present invention suppress glucocorticoid secretion and are effective in preventing and improving mental and physical symptoms caused by stress.

  In order to describe the present invention in detail, examples of producing enzyme-treated products and extracts used in the present invention, formulation examples and experimental examples of the present invention will be given as examples, but the present invention is not limited thereto. In the examples,% indicates% by weight.

Production Example 1 Pepsin-treated product of royal jelly 10 g of raw royal jelly was dissolved in 100 mL of purified water and stirred. To this solution was added 10% sodium citrate solution to adjust the pH to 4.0. To this solution, 0.1 g of pepsin derived from porcine gastric mucosa was added and subjected to enzyme treatment at 45 ° C. for 6 hours. After completion of the enzyme treatment, 10% sodium citrate solution was added to adjust the pH to 6.0, and then freeze-dried to obtain 3.0 g of a royal jelly pepsin-treated product.

Production Example 2 Protease-treated product of royal jelly 10 g of raw royal jelly was dissolved in 100 mL of purified water and stirred. The pH was adjusted to 7.0 using 10% sodium hydroxide solution. Aspergillus into this solution
0.1 g of oryzae-derived protease was added, and the enzyme treatment was performed at 50 ° C. for 6 hours. After completion of the enzyme treatment, the product was freeze-dried to obtain 3.3 g of a royal jelly protease-treated product.

Production Example 3 Maca Hot Water Extract 100 g of purified water was added to 10 g of dry powder of maca root, extracted at 95-100 ° C. for 2 hours, filtered, the filtrate was concentrated, freeze-dried and extracted with hot water 2.5 g of product was obtained.

Production Example 4 Maca 50% ethanol extract 50 g of ethanol and 50 mL of purified water were added to 10 g of dry powder of maca root, extracted at room temperature for 3 days, filtered, and the filtrate was concentrated and lyophilized to 50% 2.0 g of ethanol extract was obtained.

Formulation Example 1 Capsule <Prescription> Formulation amount (%)
1. Royal jelly treated with pepsin (Production Example 1) 20.0
2. Maca hot water extract (Production Example 3) 20.0
3. Cornstarch 57.0
4). Sucrose fatty acid ester 3.0
<Manufacturing method>
Ingredients 1-4 are mixed and 250 mg is filled into No. 2 hard capsule to obtain a capsule. By taking 6 capsules per day, the capsule can ingest a maca extract equivalent to 1.0 g / day of royal jelly and 1.2 g / day in terms of dried maca.

Formulation Example 2 Tablet <Prescription> Formulation amount (%)
1. Royal jelly protease processed product (Production Example 2) 20.0
2. Maca hot water extract (Production Example 3) 10.0
3. Lactose 41.0
4). Reduced maltose starch syrup 25.0
5. Sucrose fatty acid ester 4.0
<Manufacturing method>
An appropriate amount of 70% ethanol is added to components 1 to 4, kneaded, extruded and granulated, and dried to obtain granules. Ingredient 5 is added and tableting is performed to obtain 0.5 g of a tablet. By ingesting 6 tablets per day, the maca extract corresponding to 1.8 g / day of royal jelly and 1.2 g / day in terms of dried maca can be ingested.

Formulation Example 3 Granules <Prescription> Blending amount (%)
1. Royal jelly treated with pepsin (Production Example 1) 6.0
2. Maca 50% ethanol extract (Production Example 4) 6.0
3. Lactose 58.0
4). Cellulose 30.0
<Manufacturing method>
An appropriate amount of 70% ethanol is added to components 1 to 4, kneaded, extruded and granulated, and dried to obtain granules. The granule can be ingested 2 g at a time 3 times a day to obtain a maca extract equivalent to 1.2 g / day of royal jelly and 1.8 g / day in terms of dried maca.

Formulation Example 4 Beverage <Prescription> Blending amount (%)
1. Royal Jelly Protease Treated Product (Production Example 2) 2.0
2. Maca 50% ethanol extract (Production Example 4) 1.4
3. Sucrose 10.0
4). Citric acid 0.7
5. Perfume appropriate amount 6. Bring the total amount to 100 with purified water.
<Manufacturing method>
Add ingredients 1-5 to ingredient 6, stir and dissolve, filter, heat sterilize and fill into a 30 mL glass bottle. The beverage can ingest a maca extract corresponding to 2.1 g / day in terms of 1.8 g / day of royal jelly and converted to a dry product of maca by ingesting one a day.

Comparative example

Comparative Example 1 Conventional Beverage In the beverage of Formulation Example 4, a product obtained by replacing the protease-treated royal jelly and 50% ethanol extract of maca with water was used as a conventional beverage.

Experimental example 1
Effect of inhibiting blood glucocorticoid secretion during overcrowding stress using mice Six groups of 8 ICR male mice per group were preliminarily raised under normal breeding conditions. That is, using a normal mouse breeding cage (height 13 cm, bottom area 460 cm 2), the animals were raised for 7 days under the condition of 4 animals per cage. All groups were given regular chow during the experimental period, and water was freely consumed. Thereafter, while keeping under normal breeding conditions, the following samples were each orally administered for 7 days after diluting with 10 mL / kg of distilled water in an amount of 1 g / kg per day in terms of royal jelly and dried maca. did. 10 mL / kg distilled water was orally administered to the control group and the first group.
Control group; distilled water group 1; distilled water group 2; royal jelly (untreated)
Group 3: treated with royal jelly protease (Production Example 2)
Group 4: Maca extract (Production Example 4)
Group 5: Royal jelly (untreated) + Maca extract (Production Example 4)
Group 6: Royal jelly protease treated product (Production Example 2) + Maca extract (Production Example 4)

  After 7 days of feed administration, the control group was bred under normal conditions using a normal mouse breeding cage (height 13 cm, bottom area 460 cm 2). The first, second, third, fourth, fifth and sixth groups were reared for 72 hours under overcrowded rearing conditions. That is, breeding was carried out for 72 hours under the usual 8 times overcrowding condition of 8 animals in one section (height 13 cm, bottom area 115 cm 2) divided into four normal mouse breeding cages. The sample was orally administered once a day during the overcrowded period. After the breeding, serum corticosterone level was quantified using serum obtained by heart blood sampling. Corticosterone is the main glucocorticoid in mice, and the quantification of corticosterone was measured using AssayMax Corsosterone ELISA Kit (Assay Pro). Table 1 shows the amount of serum corticosterone in each group. From Table 1, the first group administered with distilled water in overcrowded breeding showed a marked increase in serum corticosterone level compared to the control group administered with distilled water in regular breeding. In addition, the second group administered with royal jelly (untreated) in overcrowded breeding and the third group administered with a royal jelly protease-treated product suppressed the increase in serum corticosterone concentration compared to the first group, but the effect Was slight. However, when these are combined with maca extract, the amount of serum corticosterone in the sixth group combined with the royal jelly protease treated product is higher than that in the first group than in the fifth group combined with the royal jelly (untreated). As a result, the inhibitory effect was synergistically recognized even when compared with the inhibitory effect of each compound alone.

Experimental Example 2 Use Test Forty females (25 to 50 years old) who feel daily stress are divided into a test group and a control group by 20 people, the test group contains the beverage of prescription example 4, and the control group contains comparative example 1. The conventional beverage was taken once a day for 3 months, and the stress-derived symptoms at the start and end of the test were determined by a questionnaire. 0 points if almost no symptoms are observed for each of the following symptoms, 1 point if symptoms are rare, 2 points if symptoms are occasionally seen, 3 points if symptoms are often seen, When the symptom was always observed, a score was assigned as 4 points, and the average value of 20 people at the start and end of the test was compared using the total score as a stress index.

Symptoms (1) Heavy head (2) Pain in stomach (3) Stiff shoulders and neck (4) Palpitation and shortness of breath (5) Vertigo (6) Tired eyes (7) No appetite (8 ) Constipation (9) Diarrhea (10) Poor sleep (11) Poor sleep (12) Irritated (13) Unwillingness (14) Unable to concentrate on things (15) Dullness (16) No fatigue

  The test results are shown in Table 2. As a result, the beverage of Formulation Example 4 containing the royal jelly protease-treated product and the maca extract alleviated stress-derived symptoms as compared with conventional beverages. During the test period, there was no subject who was unwell, and there was no problem with safety. There was also no problem with the deterioration of the prescription ingredients.

Anti-stress composition characterized by containing royal jelly enzyme-treated product and maca extract has the effect of suppressing glucocorticoid secretion due to stress. It is effective for prevention and improvement of mental and physical symptoms.

Claims (1)

A blood glucocorticoid concentration increase inhibitor comprising a royal jelly proteolytic enzyme-treated product and a maca extract.