JP2005179235A - Composition for preventing, treating or ameliorating disorder of feeling comprising specific molecular weight fraction obtained from water-soluble fraction of royal jelly or treated royal jelly as active ingredient - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To develop a composition or a food having bioactivation action based on royal jelly or its component by identifying an active ingredient of bioactivation of royal jelly. <P>SOLUTION: The composition for preventing, treating or ameliorating disorder of feeling comprises a fraction having ≤10,000 molecular weight as an active ingredient which is obtaiend from a water-soluble fracton of royal jelly or treated royal jelly. The food for preventing, treating or ameliorating disorder of feeling comprises a fraction having ≤10,000 molecular weight as the active ingredient, obtaiend from the water-soluble fracton of royal jelly or treated royal jelly. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a composition or food for preventing, treating or improving mood disorders containing, as an active ingredient, a specific molecular weight fraction obtained from a water-soluble fraction of royal jelly or a processed product thereof.

  As the so-called stress society in the present day, people who have abnormal mental and behavioral aspects are becoming apparent reflecting the increase in various stresses. In particular, insomnia, fatigue, excessive emotion, depression, depression, etc. caused by persistent anxiety, tension, and agitation in daily life are classified as mood disorders (see Non-Patent Document 1), and are represented by technostress. It is constantly increasing against the background of changes in the workplace environment, increased social stress due to complex relationships, physical and mental overwork, and disruption of life rhythm. In addition, the decrease in sex hormones due to the decline of gonad function due to aging leads to physical or mental changes collectively called climacteric disorder, which also has a significant effect on the body's adaptation process to stress and impaired mood. Induced. These symptoms are accompanied by physical symptoms such as gastric ulcer, palpitations, arrhythmia, and hypertension due to abnormalities in the autonomic nervous system resulting from distortion of mental activity. If appropriate measures are not taken early, desperation and self-responsibility Transition to severe depression. Depression is known to cause about 10-15% of affected patients to attempt suicide attempts and commit suicide, and has become a major social problem throughout puberty, maturity, menopause, and old age.

  Conventionally, drugs such as tricyclic antidepressants, non-tricyclic antidepressants, and monoamine oxidase inhibitors have been used to treat mood disorders, but these drugs have adverse effects on cardiac function. Therefore, it is difficult to take for a long time, for elderly people, or for preventive use. In addition, hormone replacement therapy has been applied to mood disorders during menopause, but warnings are issued due to adverse effects such as abnormalities of the genital system, high carcinogenicity, and severe heart damage caused by long-term use ( The development of safe complementary and alternative medicine is awaited.

  In addition, since subjective complaints are mainly used for mood disorders, it is a treatment that has been confirmed to prevent its onset by self-care, to improve early, and to be safe for long-term use. Something is important. However, no supplemental alternative medicine has been developed in addition to drugs that have adverse effects even at normal doses, and mood disorders such as depression and depression may temporarily fall due to changes in the environment and the situation faced. Therefore, in general, it is often not recognized as a disease, and preventive measures and countermeasures are often not taken until behavioral abnormalities are manifested.

  On the other hand, royal jelly, also known as “Oyster Milk”, is a milky white substance that is secreted from worker bees and becomes the diet of queen bees, and is composed of proteins, carbohydrates, lipids, and unknown components. Traditionally used in traditional medicine and ethnology as a food effective for maintaining, promoting and restoring health, promoting growth (see Non-Patent Document 3), life-prolonging effect (See Non-Patent Document 4), anti-tumor action It is known to have many physiological activities such as (see Non-Patent Document 5) and depressive symptom improvement (see Non-Patent Document 6).

However, the scientific basis supporting these effects of royal jelly has been scarce, and it has not been possible to identify a component having pharmacological activity. In particular, scientific evaluation of which components of royal jelly are effective and identification of active ingredients have not been made, particularly for mental behavioral aspects such as mood disorders and improvement of indefinite complaints.
Saburo Takahashi, Hiroshi Ohno, Toshiyuki Someya, DSM-IV: Diagnosis / Statistics Manual for Mental Disorders, Medical School, June 1996 James V. Lacey, Jr. et al., JAMA, 2002, Vol.288, No.3 Ishio Ishiguro et al., 1963, Gifu Pharmaceutical University Bulletin 13: 17-21 Junnosuke Kawamura, 1961, Showa Medical Society Journal 20: 1465-1474 Tamura Toyoyuki et al., 1987, Japanese Pharmacological Journal 89: 73-80 Hiroyuki Yoshimura et al., 2002, Journal of Japanese Neuropsychopharmacology, 22: 299

  The inventor tried to scientifically evaluate the effectiveness of royal jelly for improving mental function, particularly the improvement of mood disorders such as depression and depression, and any component contained in royal jelly is the main body of action. As a result of repeated extraction and separation, the specific fraction obtained by purifying the water-soluble fraction of royal jelly or its processed product is effective in reducing mood disorders and being safe in an extremely small amount. The present invention has been completed through headings and further studies.

That is, the present invention relates to the following composition or food.

1. A composition for preventing, treating, or improving mood disorders containing, as an active ingredient, a fraction having a molecular weight of 10,000 or less obtained from a water-soluble fraction of royal jelly or a processed product thereof.

  Specifically, a composition for preventing, treating or improving mood disorders containing, as an active ingredient, a fraction having a molecular weight of 10,000 or less obtained by separating a water-soluble fraction of royal jelly or a processed product thereof with an ultrafiltration membrane Is mentioned.

2. A composition for preventing, treating, or improving mood disorders containing, as an active ingredient, a fraction having a molecular weight of 1500 or less obtained from a water-soluble fraction of royal jelly or a processed product thereof.

3. A composition for preventing, treating, or improving mood disorders containing, as an active ingredient, a fraction having a molecular weight of 300 or less obtained from a water-soluble fraction of royal jelly or a processed product thereof.

4). Item 4. The composition for preventing, treating, or improving mood disorders according to Item 1 to 3, wherein the processed product of royal jelly is any one selected from the group consisting of freeze-dried royal jelly, royal jelly enzymatic degradation product, and royal jelly ethanol aqueous solution precipitation residue.

5). Mood disorder is insomnia, malaise, excessive emotion, depressed mood, depression, irritability, weakness, fatigue, head feeling, depression, anxiety, irritability, indefinite complaints, anger, muscle tone, Item 5. The composition for prevention, treatment or amelioration of mood disorders according to item 1 to 4, which is at least one selected from the group consisting of loss of concentration.

6). Item 6. The composition for preventing, treating, or improving mood disorders according to Items 1 to 5, wherein the mood disorder is associated with peri-menopause or menopause.

7). A food for preventing, treating, or improving mood disorders containing, as an active ingredient, a fraction having a molecular weight of 10,000 or less obtained from a water-soluble fraction of royal jelly or a processed product thereof.

  Preferably, a food for preventing, treating or ameliorating mood disorders containing a fraction having a molecular weight of 1500 or less obtained from a water-soluble fraction of royal jelly or a processed product thereof as an active ingredient, more preferably a water-soluble solution of royal jelly or a processed product thereof. A food for preventing, treating, or improving mood disorders, comprising a fraction having a molecular weight of 300 or less obtained from a sex fraction as an active ingredient.

8). A food containing a fraction having a molecular weight of 10,000 or less obtained from a water-soluble fraction of royal jelly or a processed product thereof, which is displayed for prevention, treatment or improvement of mood disorders.

Preferably, a food containing a fraction having a molecular weight of 1500 or less obtained from a water-soluble fraction of royal jelly or a processed product thereof displayed for prevention, treatment or improvement of mood disorders, more preferably prevention of mood disorders A food containing a fraction having a molecular weight of 300 or less obtained from a water-soluble fraction of royal jelly or a processed product thereof, which is displayed for treatment or improvement.

  According to the present invention, by using a specific molecular weight fraction obtained from a water-soluble fraction of royal jelly or a processed product thereof as an active ingredient, a composition or food effective for preventing, treating or improving mood disorders is provided. The Rukoto.

  The composition and food of the present invention can effectively prevent, treat, or improve mood disorders at a lower volume than conventional royal jelly.

  By adding this component, it is possible to develop an RJ-related food with an enhanced action for effectively preventing, treating or improving mood disorders. More specifically, by adding a specific molecular weight fraction obtained from the water-soluble fraction of the royal jelly or a processed product thereof in the present invention, the royal jelly having an enhanced effect of effectively preventing, treating or improving mood disorders. Develop related foods.

  Moreover, the active ingredients of the compositions and foods of the present invention exhibit little adverse effects such as increased uterine weight and toxicity in an amount effective for the prevention, treatment or improvement of mood disorders. Further, royal jelly or a processed product thereof as a raw material of the active ingredient has been conventionally used as a food or the like and has almost no side effects or toxicity, so that it can be safely ingested even for a long period of time.

  As described above, the composition and food of the present invention are effective in the prevention, treatment or improvement of mood disorders, but have almost no harmful effects or toxicity and are safe and prevent, treat or improve mood disorders. It is usefully used in.

Hereinafter, the present invention will be described in more detail.

Specific molecular weight fraction obtained from water-soluble fraction of royal jelly or processed product thereof The composition and food of the present invention contain a specific molecular weight fraction obtained from the water-soluble fraction of royal jelly or processed product thereof as an active ingredient.

  The kind of the royal jelly or the processed product as a raw material of the active ingredient of the present invention is not particularly limited, and can be appropriately selected as desired.

  As the royal jelly, natural ones, specifically, those collected by bees secreted can be used. Moreover, what is generally marketed can also be used.

  The processed product of royal jelly is processed or processed natural royal jelly, and the type of treatment is not particularly limited, but specifically, freeze-dried royal jelly, royal jelly enzymatic degradation product, royal jelly ethanol aqueous solution precipitation residue, etc. Can be mentioned.

  The freeze-dried royal jelly is a product obtained by vacuum drying a royal jelly in a frozen state.

  The royal jelly enzymatic degradation product is a degradation composition obtained by degrading royal jelly with an enzyme. The type and origin of the enzyme are not particularly limited, and examples thereof include sugar chain degrading enzymes and proteolytic enzymes.

  Specific examples of the glycolytic enzyme include amylase, cellulase, avicelase, hemicellulase, glucosidase, mannanase, galactosidase, xylanase, and β-mannosidase.

  Specific examples of proteolytic enzymes include microorganisms-derived protease aspergillopeptidase A and animal-derived digestive enzymes pepsin, pancreatin, trypsin, chymotrypsin, and the like.

The said enzyme can also be used individually by 1 type, and may be used in combination of 2 or more type as appropriate. The purity of the enzyme used is not particularly specified, and for example, a microbial product producing the enzyme, a homogenate from a plant or an animal may be used.

  The royal jelly decomposition treatment with an enzyme can be appropriately performed according to a conventional method. For example, it can be carried out in an aqueous solvent at a temperature of about 15 ° C. to about 55 ° C., preferably about 20 ° C. to about 50 ° C. At this time, the liquidity of the reaction solution can be appropriately adjusted according to the type of enzyme used. The type of the reaction solvent is not particularly limited, and for example, water-containing alcohol can be used as appropriate.

  The royal jelly ethanol aqueous solution precipitation residue is a residue precipitated when royal jelly is treated with a hydrous ethanol solution.

  The water-soluble fraction of the royal jelly or a processed product thereof may be a fraction obtained by classifying the water-soluble component contained in the royal jelly or the processed product, and the method of sorting the fraction is not particularly limited.

  For example, an aqueous solution of royal jelly or a treated product thereof, or a water-soluble fraction obtained by extracting and purifying a suspension obtained by mixing royal jelly or a treated product thereof and water with an organic solvent such as ethyl acetate or butanol. Is mentioned.

Further, a water-soluble fraction obtained from the supernatant by standing and / or centrifuging a suspension obtained by mixing royal jelly and water can be used.

The specific molecular weight fraction obtained from the water-soluble fraction of royal jelly or a processed product thereof is a fraction obtained by dividing the water-soluble fraction into components having a specific molecular weight. The specific molecular weight is a fraction having a molecular weight of 10,000 or less, preferably a molecular weight of 1500 or less, and more preferably a molecular weight of 300 or less.

  The method or means for sorting a specific molecular weight fraction is not particularly limited. For example, a fraction obtained by separating a water-soluble fraction of royal jelly or a processed product thereof using an ultrafiltration membrane and / or gel filtration, etc. Is mentioned.

When the present inventor applied an ovariectomized mouse to which a specific molecular weight fraction obtained from a water-soluble fraction of royal jelly or a processed product thereof was administered to a forced swimming test, the immobilization state compared to a group to which they were not administered. It became clear that the floating time, i.e., immobility time, was significantly shortened. In addition, even when the amount that reduces the immobility time is administered to ovariectomized mice, the specific molecular weight fraction obtained from the water-soluble fraction of royal jelly or its processed product has an adverse effect on abnormally enlarged uterine weight. It was also revealed that it does not show. In addition, the amount of the specific molecular weight fraction required to shorten the immobilization time is significantly smaller than the amount that the water-soluble fraction of the original royal jelly or its processed product shortens the immobility time. It became clear. Specifically, the fraction with a molecular weight of 10,000 or less is 55% or less compared to the water-soluble fraction of the original royal jelly or its processed product, the fraction with a molecular weight of 1500 or less is 55% or less, and the molecular weight is 300 or less. It became clear that the immobility time was shortened by an amount of 1% or less in the fraction. As for the active ingredient in the fraction having a molecular weight of 10,000 or less, a substance having a molecular weight of 1500 or less is important, and a substance having a molecular weight of 300 or less is more important.

  The forced swimming test is widely used for preclinical evaluation of mood disorders such as antidepressant action. Clinically effective antidepressants are known to reduce immobility time (Porsort et al., Nature, 266: 730-732, 1977). Okada et al. (Okada et al., Jpn. J. Pharmacol., 73: 93-96, 1997)) and Yoshimura et al. [Yoshimura, Yamakawa, Brain Science, 22: 49-54, 2000] are female animals. When the ovary is removed and placed in an artificial menopausal state, the immobility time is found to be significantly prolonged, and it has been reported that it becomes a pathologic model reflecting depression or depression in the perimenopausal period.

  Furthermore, it has been reported that when the female hormone estrogen is administered to the ovariectomized female animal, the immobility time is shortened and returns to normal (Betsumiya, Yoshimura et al., Japanese Journal of Neuropsychopharmacology, 22: 298,2002) . This indicates that estrogen improves perimenopausal “depression”. However, it has also been found that when ovariectomized female mice are administered estrogen in an amount that reduces immobility time, uterine weight is significantly enlarged compared to female animals that have not had their ovaries removed. This means that at doses that improve the “depressed state”, estrogen develops adverse effects that abnormally enlarge uterine weight. This abnormal increase in estrogen uterine weight is considered to be a symptom corresponding to the adverse effects noted in human hormone replacement therapy.

  On the other hand, as described above, the specific molecular weight fraction obtained from the water-soluble fraction of the royal jelly or a processed product thereof in the present invention is an amount that shortens immobility time and does not show an adverse effect on uterine weight.

Therefore, a composition for preventing, treating, or improving a safe mood disorder having an excellent effect at a low volume by using a specific molecular weight fraction obtained from the water-soluble fraction of the royal jelly or a processed product thereof as an active ingredient Or food is provided.

Composition for preventing, treating or improving mood disorders The composition for preventing, treating or improving mood disorders according to the present invention comprises a specific molecular weight fraction obtained from the water-soluble fraction of the royal jelly or a processed product thereof as an active ingredient. Contained as.

  The manufacturing method of a composition is not specifically limited, It can manufacture using a well-known method suitably.

  Moreover, the composition of this invention can also mix another additive, as long as the desired effect of this invention is satisfy | filled. Other additives include, for example, water-soluble vitamins, xanthine derivatives, crude drugs, excipients, pH adjusters, cooling agents, suspending agents, antifoaming agents, thickening agents, solubilizing agents, disintegrating agents, Examples include binders, lubricants, antioxidants, coating agents, colorants, flavoring agents, surfactants, plasticizers, and fragrances.

  Moreover, the composition of this invention can be suitably formulated according to a well-known manufacturing method. For example, the composition of the present invention can be used in the form of a solid or liquid formulation suitable for oral administration.

  Examples of solid preparations include powders, granules, capsules, tablets, chewables, lozenges and the like.

  Liquid preparations include liquids, syrups, drinks and the like.

  In the case of producing a liquid preparation, water, glycerin, propylene glycol, simple syrup, ethanol, ethylene glycol, polyethylene glycol, sorbitol and the like can be used as an excipient.

Food for prevention, treatment or amelioration of mood disorder The food of the present invention contains a specific molecular weight fraction obtained from the water-soluble fraction of the above-mentioned royal jelly or processed product thereof, and prevents, treats or improves mood disorder. It can be used as a food. Specifically, it can be used as a health food, a functional food, a dietary supplement, a supplement or a food for specified health use.

  The type of the food of the present invention is not particularly limited. For example, beverages (soft drinks such as coffee, juice, tea drinks, milk drinks, lactic acid bacteria drinks, yogurt drinks, carbonated drinks, Japanese sake, western liquor, fruit seeds, honey Liquor like liquor); Spreads (such as custard cream); Pastes (such as fruit paste); Pastry (chocolate, donut, pie, cream puff, gum, jelly, candy, cookies, cake, pudding); Daifuku, salmon, buns, castella, anmitsu, mutton); ice confectionery (ice cream, popsicle, sherbet); foods (curry, beef bowl, miso soup, miso soup, soup, meat sauce, pasta, pickles, jam, honey, propolis ); Can be used as a raw material for seasonings (dressing, sprinkling, umami seasoning, soup base).

  Products that have been specially enhanced for the above purpose by adding a small amount or a specific amount of a specific molecular weight fraction obtained from the water-soluble fraction of royal jelly or its processed product to conventional royal jelly products (especially prevention, treatment or prevention of mood disorders) A food particularly suitable for improvement).

  The production method of the food of the present invention is not particularly limited, and can be appropriately followed by a known method. For example, a specific molecular weight fraction obtained from the water-soluble fraction of the royal jelly or a processed product thereof is mixed or sprayed with the intermediate product or the final product in the food production process as described above and used for the above purpose. Can be obtained.

Applicable object The mood disorder to which the composition and the food of the present invention are applied includes not only a case of being recognized as a disease but also a symptom based on a subjective complaint.

Specifically, mood disorders include insomnia, malaise, excessive emotion, depressed mood, depression, annoyance, weakness, fatigue, head feeling, depression, anxiety, agitation, indefinite complaints, easy Examples include anger, muscle tone, and loss of concentration.
In particular, the composition and food of the present invention are effectively used for the prevention, treatment or improvement of mood disorders associated with perimenopause or menopause.

  The intake of the composition of the present invention effective for prevention, treatment or improvement of mood disorders depends on the subject's symptoms, health condition, age, body type, constitution, administration method, combination with other drugs, etc. Usually, the specific molecular weight fraction obtained from the above-mentioned fraction, that is, the water-soluble fraction of royal jelly or a processed product thereof, is usually in a dose range of about 0.01 mg to 10 g per day for an adult weighing 60 kg. The dose range is preferably about 0.1 mg to 1 g.

  Even a person who needs to consume a large amount of conventional royal jelly, a small amount is sufficient when ingesting a specific fraction of the present invention, that is, a specific molecular weight fraction obtained from a water-soluble fraction of royal jelly or a processed product thereof. This will give a good effect.

  Hereinafter, although a test example and an example are given and explained, the present invention is not limited to these examples.

Test example 1
(1-1) Preparation of sample (i) Preparation of water-soluble fraction 1L of purified water was added to 109.41g of lyophilized royal jelly, stirred at 20 ° C for 30 minutes with ultrasound, and further stirred at room temperature for 2 hours with a three-one motor. , Using a centrifuge (Hitachi high-speed cooling centrifuge CR-21, rotor (R10A, approximately 400ml x 6), maximum rotation speed 10000rpm (maximum centrifugal acceleration 18780xg)) at 10000rpm x 10min, 20 ℃ And centrifuged.

  The supernatant was separated, 1 L of purified water was added to the precipitate, suspended, and stirred for 30 minutes at room temperature with a three-one motor, and then centrifuged at 10,000 rpm × 10 min at 20 ° C. with the above centrifuge.

  The supernatant was separated again, 1 L of purified water was added to the precipitate, suspended, and stirred for 30 minutes at room temperature with a three-one motor, and then centrifuged at 10,000 rpm × 10 min at 20 ° C. with the above centrifuge. . 300 ml of purified water was added to the obtained supernatant (about 3 L in total) and the precipitate, and the suspended product was lyophilized.

As a result, a water-soluble fraction (A1S 90.1 g) and an insoluble fraction (B1 20.5 g) were obtained.

(Ii) Preparation of specific molecular weight fraction 88.1 g was weighed from the water-soluble fraction (A1S) obtained in (i) and 1 L of purified water was added and dissolved. The lysate was fractionated using an ultrafiltration membrane (Millipore, Prep / Scale-TFF Cartridge PLGC10k 1ft ² , molecular weight cut off 10,000, material: cellulose type). This was freeze-dried to obtain a fraction (A2S 25.5 g) of MW (weight average molecular weight) 10,000 or more and a fraction (A3S 58.0 g) of MW 10,000 or less.

(1-2) Animal experiments (i) Preparation of test animals As test animals, ovariectomized model animals of ICR female mice (9 weeks old, body weight 29-33 g) were used. All mice were housed in groups of 10 cages, and the white flakes were exchanged once a week. Ovariectomy is performed under anesthesia of pentobarbital (65 mg / kg, ip) with a 5 mm incision in the dorsal abdomen of the mouse. After ligation, the ovaries were excised and removed. Thereafter, the tissue around the uterus and ovary was quickly returned to the abdominal cavity, and then the abdominal wall and skin were sutured. As a comparative control group, a sham operation group in which laparotomy was performed in the same manner as the operation group, but sutured without excision of the ovary, and a normal group (a group in which surgery and sham operation were not performed) were used.

(Ii) Administration of test substance Each sample was dissolved in water to prepare a suspension so that royal jelly was contained in an amount of about 2.5 g / 50 ml in terms of raw material. Each aqueous suspension was orally administered once a day for 2 weeks from the day of ovariectomy using an oral sonde at a rate of 0.1 ml per 10 g of mouse body weight.

As a control for the test substance, distilled water for injection was orally administered at a rate of 0.1 ml per 10 g of mouse body weight.

(Iii) Immobility time measurement test Two weeks after ovariectomy, a forced swimming test was performed as follows according to the method of Porsort. Water at 25 ° C. was poured into a transparent polycarbonate graduated cylinder (inner diameter 10 cm, height 25 cm), and the water surface was aligned at a position 10 cm from the bottom. Swim for 6 minutes, recorded with a high-sensitivity video system, and then operated the event recorder while observing the recording screen to measure the time of floating in an immobile state. Specifically, the immobilization time was measured from the second minute of the swimming time, and the immobility time was analyzed up to 4 minutes at the longest.

(Iv) Test for measuring uterine weight After completion of observation of immobility time, mice were brought to respiratory arrest by administration of an excessive amount of pentobarbital (100 mg / kg or more), sacrificed, opened, and the uterus was removed. The excised uterus was spread on a filter paper to remove the adhering capsule and blood vessels, and immediately, the wet weight was weighed with an analytical balance.

(1-3) Results The measurement results of immobility time are shown in FIG. 1. As shown in FIG. 1, immobility time is determined by the water-soluble fraction (A1S) of royal jelly (RJ) and the fraction (A3S) having a molecular weight of 10,000 or less. Was confirmed to shorten. The water-insoluble fraction (B1) and the fraction with a molecular weight of 10,000 or more (A2S) did not affect the immobility time.

The fraction (A3S) with a molecular weight of 10,000 or less separated by an ultrafiltration membrane was measured by TOFMASS. Specifically, the A3S fraction was made into a matrix (UFP) methanol suspension (200 μl) using a matrix-assisted laser desorption ionization time-of-flight mass spectrometer (Shimadzu / KRATOS mass spectrometer KOMPACT MALDIII tDE). After mixing a sample (A3S, 1 mg), a part was dried, and then laser ionization was performed with a MASS measuring apparatus to detect positive ions. The MASS measurement result for A3S is shown in FIG. As shown in FIG. 2, it was found that the components contained in A3S are substances having a molecular weight of 1500 or less. That is, it was found that a substance having a molecular weight of 1500 or less contained in the water-soluble fraction shortens the immobility time.

  The water-soluble fraction A1S accounted for about 82% of the lyophilized royal jelly, and the water-soluble fraction (A3S) of 10,000 or less accounted for about 54%. In the same way, the amount required to shorten the immobilization time is about 82% of the lyophilized royal jelly in the case of the water-soluble fraction A1S, and the fraction with a water-soluble fraction of 10,000 or less (A3S) This means that only 54% of the weight is required.

  The above numbers (about 82%, about 54%) were calculated as follows. For example, about 82% was calculated from 90.1 g (yield of A1S) ÷ 109.4 g (lyophilized RJ) = 0.82 (about 82%). For lyophilized RJ mice, lyophilized RJ was adjusted to 2.5 g / 50 ml. For A1S mice, A1S (2.5 g / 50 ml) x 0.82 was prepared. About 82%) has equivalent activity in lyophilized RJ and animal experiments. Similarly, about 54% was calculated from 2) 0.82 × [58.0 mg (A3S yield) ÷ 88.1 mg (A1S amount used to fractionate A3S)] = 0.54 (about 54%).

  Moreover, the measurement result of a uterine weight is shown in FIG.

  As shown in FIG. 3, no increase in uterine weight was observed in fractions (A1S, A3S) and RJ that shortened immobility time.

Test example 2
In order to further clarify the active ingredient, the following tests were further conducted.
(2-1) Sample preparation A3S (10 g) obtained in Test Example 1 was suspended in 50 ml of ion-exchanged water and stirred at room temperature. It was filtered, and the filtrate was applied to a gel filtration column (Toyopeal HW40F 2L) using UV210nm as an index at a flow rate of 8 ml / min, and fractionated as follows from the start of introduction every 96 ml. As an elution solvent, ion-exchanged water was used. The fractionated D1, D2, D3, and D4 were lyophilized to obtain fractions D1S (360 mg), D2S (8.0 g), D3S (120 mg), and D4S (130 mg).
Fr3-11: D1
Fr12-24: D2
Fr25-40: D3
Fr41-(until 4.5L elution): D4
A chart of the elution pattern is shown in FIG.

(2-2) Animal experiment The immobility time measurement test and the uterine weight measurement test were performed in the same manner as in (1-2) above.

(2-3) Result The measurement result of immobility time is shown in FIG.

  As shown in FIG. 5, it was confirmed that the administration of the water-soluble fraction of royal jelly (D4S) significantly shortened the immobilization time by ovariectomy and became the normal value (dotted line) of the sham operation group. It was. However, Vehicle and fractions D1S, D2S, and D3S did not affect immobility time.

The D4S fraction was measured by TOFMASS in the same manner as the A3S fraction. Specifically, using a matrix-assisted laser desorption / ionization time-of-flight mass spectrometer (Shimadzu / KRATOS mass spectrometer KOMPACT MALDIII tDE), a sample (D4S, 1 mg) in a methanol suspension (200 μl) of matrix (UFP) After mixing, a part was dried and then laser ionization was performed with a MASS measuring apparatus to detect positive ions.

  The MASS measurement result for D4S is shown in FIG. As shown in FIG. 6, it was found that the components contained in D4S were components having a molecular weight of 300 or less. Therefore, it was found that the water-soluble fraction (D4S) having a molecular weight of 300 or less shortens the immobility time.

  In addition, it was found that the amount of D4S required to shorten the immobility time was sufficient with a small amount of about 1% or less (about 0.8%) of lyophilized royal jelly showing the same shortening. The above numerical value (about 1% or less) was calculated as follows. As already explained, A3S accounts for 54% of freeze-dried RJ, and the proportion of D4S in A3S is 130mg (D4S) ÷ [360mg (D1S) + 8g (D2S) + 120mg (D3S) + 130mg (D4S)] = 0.015 = about 1.5%. That is, the ratio of D4S contained in the freeze-dried RJ is approximately 54% × 0.015 = 0.81% = 0.8% (that is, about 1% or less).

Moreover, the measurement result of uterine weight is shown in FIG.

  As shown in FIG. 7, no increase in uterine weight was observed even in the fraction (D4S) that shortened the immobility time.

From the results of Test Examples 1 and 2, the specific fraction obtained from the royal jelly of the present invention or a processed product thereof effectively improves immobility time and has a very low risk of adverse effects, and improves and prevents mood disorders. It became clear that it was a component more suitable for treatment.

Formulation Example Using the D4S fraction obtained in Test Example 2, the following composition and food were obtained.

Formulation Example 1 (Capsule)
D4S 10mg
Lactose 240mg
The above ingredients (per capsule) were uniformly mixed and filled into a No. 2 capsule to obtain a capsule with an inner volume of 250 mg.

Formulation Example 2 (tablet)
D4S 10mg
Lactose 230mg
Sucrose fatty acid ester 10mg
The above ingredients (per tablet) were uniformly mixed, and 250 mg tablets were obtained using a tableting machine.

Formulation Example 3 (Granule)
D4S 20mg
Cellulose 100mg
Dextrin 150mg
Lactose 700mg
The above ingredients (per packet) were uniformly mixed, granulated with an extrusion granulator, and dried to obtain granules.

Formulation Example 4 (Drink)
D4S 10mg
Ascorbic acid 300mg
Honey 10g
Lemon juice 10ml
Appropriate amount of water The above ingredients were mixed to obtain a drink containing a royal jelly extract of 50 ml in total.

6 is a graph showing measurement results of immobility time in the forced swimming test of Test Example 1. The vertical axis represents the immobility time. A dotted line is a line which shows the immobility time (normal value) of the sham operation group which has not removed the ovary. RJ indicates lyophilized royal jelly (processed royal jelly). Vehicle represents distilled water for injection used as a control. 4 is a drawing showing a MASS spectrum chart of A3S in Test Example 1. It is drawing which shows the measurement result of the influence which each fraction in Test Example 1 has on uterine weight. The dotted line is the uterine weight (normal value) of the mouse without ovariectomy. It is drawing which shows the chart of the elution pattern of each fraction fractionated with the gel filtration column in Test Example 2. FIG. 6 is a graph showing measurement results of immobility time by a forced swimming test of Test Example 2. The vertical axis represents the immobility time. A dotted line is a line which shows the immobility time (normal value) of the sham operation group which has not removed the ovary. Vehicle represents distilled water for injection used as a control. 5 is a drawing showing a D4S MASS spectrum chart in Test Example 2. FIG. 6 is a drawing showing the measurement results of the effect of each fraction in Test Example 2 on uterine weight. The vertical axis represents uterine weight. The dotted line is the uterine weight (normal value) of the sham operation group in which the ovaries have not been removed.

Claims (8)

A composition for preventing, treating, or improving mood disorders containing, as an active ingredient, a fraction having a molecular weight of 10,000 or less obtained from a water-soluble fraction of royal jelly or a processed product thereof. A composition for preventing, treating, or improving mood disorders containing, as an active ingredient, a fraction having a molecular weight of 1500 or less obtained from a water-soluble fraction of royal jelly or a processed product thereof. A composition for preventing, treating, or improving mood disorders containing, as an active ingredient, a fraction having a molecular weight of 300 or less obtained from a water-soluble fraction of royal jelly or a processed product thereof. The composition for preventing, treating or improving mood disorders according to claim 1, wherein the processed product of royal jelly is any one selected from the group consisting of freeze-dried royal jelly, royal jelly enzymatic degradation product and royal jelly ethanol aqueous solution precipitation residue. . Mood disorder is insomnia, malaise, excessive emotion, depressed mood, depression, irritability, weakness, fatigue, head feeling, depression, anxiety, irritability, indefinite complaints, anger, muscle tone, The composition for preventing, treating or improving mood disorders according to claim 1, wherein the composition is at least one selected from the group consisting of loss of concentration. The composition for preventing, treating, or improving mood disorders according to claim 1, wherein the mood disorder is associated with peri-menopause or menopause. A food for preventing, treating, or improving mood disorders containing, as an active ingredient, a fraction having a molecular weight of 10,000 or less obtained from a water-soluble fraction of royal jelly or a processed product thereof. A food containing a fraction having a molecular weight of 10,000 or less obtained from a water-soluble fraction of royal jelly or a processed product thereof, which is displayed for prevention, treatment or improvement of mood disorders.

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