JPWO2016167254A1 - Nourishing tonic containing bees - Google Patents

Abstract

Disclosed are tonic tonic containing bees, sexual function improving agents including bees, male menopausal symptoms improving agents including bees, and anti-fatigue agents including bees.

Description

  The present invention relates to tonic tonics, sexual function improving agents, male menopausal symptoms improving agents and anti-fatigue agents.

  One of the aging problems faced by men is the onset of menopause. It is estimated that about 40% of men in their 40s and 60s experience some degree of male menopause.

  In menopause, various symptoms (e.g. depression, discouragement, irritation, anxiety, irritability, fatigue, loss of vitality, myositis, arthritis, muscle weakness, hot flashes, sweating, memory loss, sleep disorders, poor concentration) , Physical exhaustion, erectile dysfunction (ED), decreased libido, loss of ejaculation, etc.) are strongly expressed. As a method for confirming whether or not it is male climacteric disorder, there are a method of measuring blood testosterone concentration by blood test and a method of questionnaire. It has been pointed out that the onset of male climacteric disorders is greatly influenced by various stresses at work and homes of active men, and in recent years middle-aged men suspected of having climacteric disorders are increasing.

  Male climacteric disorder, with the background of age-related androgen decline, shows autonomic ataxia and neuropsychiatric symptoms similar to those of female climacteric disorder, and in most cases is associated with a decline in male function (Akihiko Okuyama Book, Men's Menopause LOH Syndrome I What is Men's Menopause D. From the perspective of psychosomatic medicine, page 24 (Nanzando Co., Ltd. 2007)). On the other hand, the secretion of sex hormones including testosterone is regulated through negative feedback through hormones including testosterone via the hypothalamus-pituitary-testis system (Akihiko Okuyama, Male Climacteric Disorder LOH Syndrome) II Diagnosis of male climacteric disorder C. Hormone measurement and evaluation 65 pages (Nanzando Co., Ltd. 2007.). For this reason, it is difficult to judge male climacteric disorder based on testosterone measurements alone.

  In general, subjects who are aware of decreased vitality and have a tendency to decrease free testosterone in the blood are diagnosed with age-related male hypogonadism syndrome (LOH syndrome), and androgen replacement therapy to maintain QOL Can be adapted. However, while hormone replacement therapy in women is widespread internationally, treatment for men is not a medical target other than the spread of PDE5 inhibitors and the like for ED.

  For example, Patent Documents 1 to 3 report various components that increase testosterone.

  In Patent Document 1, it has been reported that Tangshenosides, Lancemaside-A and Syringin contained in a plant of the genus Cultivation have an action of suppressing a decrease in blood testosterone.

  Patent Document 2 reports that geranylgeraniol has a testosterone enhancing action.

  In Patent Document 3, it is reported that a black vinegar-related material and a combination of the material and a specific material significantly promote testosterone secretion.

  However, androgen replacement therapy may also have side effects, and attention must be paid especially to prostate-specific antigen (PSA), which is a prostatic tumor marker, and therefore there is a need for a climacteric symptom-relieving agent that does not have an androgenic effect.

  In addition, “sildenafil”, a PDE5 inhibitor, is used as an ED therapeutic agent. However, side effects and drug interactions have been reported for sildenafil, albeit transiently. For example, sildenafil works in an accelerated manner against the blood pressure lowering effect of nitrates such as nitroglycerin, so it is contraindicated in combination with them. Red eye disease etc. are recognized.

  By the way, bees have been eaten as a nutrient source for proteins and the like in various countries and regions since ancient times. In recent years, health foods made from powders obtained by drying and pulverizing bees have been known. This health food contains abundant proteins, amino acids, vitamins and minerals of bees. As disclosed in Patent Document 4, bee pups are known to have an antioxidative effect, but other actions are often unknown.

JP 2006-306889 A Japanese Patent No. 5382512 JP 2013-181031 A Japanese Patent No. 5405067

  An object of the present invention is to provide a highly safe tonic agent, sexual function improving agent, male climacteric symptom improving agent, and anti-fatigue agent that do not increase androgen.

  As a result of intensive research to achieve the above object, the present inventors have a tonicity effect, sexual function improvement effect, male menopausal symptom improvement effect and anti-fatigue effect. It was found that the child did not raise androgen and was highly safe.

  The present invention has been completed based on these findings and has been completed. The present invention provides the following tonic tonic, sexual function improving agent, male menopausal symptom improving agent, anti-fatigue agent and the like.

Item 1. Tonic tonic containing bee pups.
Item 2. Sexual function improving agent containing bee pups.
Item 3. Men's menopausal symptoms-improving agent including bee pups.
Item 4. Anti-fatigue agent including bee cubs.
Item 5. A vitality improver containing a bee.
Item 6. Item 5. The tonic tonic preparation according to Item 1, the sexual function improving agent according to Item 2, the male climacteric symptom improving agent according to Item 3, and the male climacteric symptom improving agent according to Item 4. 6. An anti-fatigue agent or a vitality improver according to Item 5.
Item 7. A composition for tonic use, including bee pups, for improving sexual function, for improving menopausal symptoms, for anti-fatigue and / or for improving vitality.
Item 8. A food composition for tonic use, including bee pups, for improving sexual function, for improving menopausal symptoms, for anti-fatigue and / or for improving vitality.
Item 9. Item 9. The composition according to Item 7 or 8, wherein the bee is treated with a protein hydrolase.
Item 10. A tonicity method, a sexual function improvement method, a male climacteric symptom improvement method, a fatigue improvement method, or a vitality improvement method, comprising a step of administering an effective amount of a bee pup to a mammal.
Item 11. Item 11. The method according to Item 10, wherein the bee is treated with a protein hydrolase.
Item 12. Use of bees in the manufacture of tonic tonics, sexual function improvers, male menopausal symptoms improvers, anti-fatigue agents, or vitality enhancers.
Item 13. Item 13. The use according to Item 12, wherein the bee is treated with a protein hydrolase.

  Since the bee has a tonic tonic effect improving action, sexual function improving action, male climacteric symptoms and anti-fatigue action, it is an active ingredient of tonic tonic, sexual function improving agent, male climacteric symptom improving agent and anti-fatigue agent Useful as. In addition, bees are safe because they do not raise androgens.

It is a graph which shows (a) AMS score (total) before and after test food intake, (b) AMS score (sexual factor), (c) AMS score (physical factor). Mean ± SE ^* p <0.05 ^** p <0.01 It is a graph which shows IIEF5 before and after test food intake. Mean ± SE ^* p <0.05 ^** p <0.01 It is a graph which shows the number of early morning erections before and after taking test food. Mean ± SE ^* p <0.05 ^** p <0.01 It is a graph which shows the fatigue feeling VAS before and behind test food intake. Mean ± SE ^* p <0.05 ^** p <0.01 It is a graph which shows SDS before and after test food intake. Mean ± SE ^* p <0.05 ^** p <0.01 It is a graph which shows (a) TT before and behind test food intake, (b) FT. Mean ± SE ^* p <0.05 ^** p <0.01

  Hereinafter, the present invention will be described in detail.

  The tonic composition, the sexual function improving agent, the male menopausal symptom improving agent and the anti-fatigue agent of the present invention are characterized by containing a bee.

  The tonicity enhancing agent, sexual function improving agent, male menopausal symptom improving agent and anti-fatigue agent of the present invention are highly safe because they do not increase androgen.

  Androgen is a generic name for steroid hormones, also called male hormones, and includes, in addition to typical testosterone, dihydrotestosterone, dehydroepiandrosterone, androsterone, androstenedione, and epiandrosterone.

  Here, the bee kid means bee larvae and pupae. The kind of bee is not particularly limited, and known bees such as honey bees such as Japanese honey bees and western honey bees, African bee honey bees, wasps (including cross wasps), wasps and bumble bees can be widely used. A bee is preferable, and a western bee is more preferable because of availability. It should be noted that males and females are not necessarily distinguished and are preferably males.

  Larva and pupa are not particularly limited as long as they are hatched from eggs. Among them, bee larvae and pupae that have passed 16 to 23 days after hatching are preferred, and bee larvae and pupae that have passed 18 to 21 days after hatching are more preferred.

  A bee cub accumulates nutrients in the body. In particular, bee males have long been used as traditional Chinese herbal medicines and contain a variety of amino acids including essential amino acids in a well-balanced manner, as well as vitamins such as proteins, lipids, sugars, vitamin Bs, folic acid, nicotinic acid, and pantothenic acid. And rich in minerals such as zinc and selenium. As the physiological activity and pharmacological action of bee pupae, antibacterial action, anti-inflammatory action, antiviral action, antiprotozoal action, tinnitus elimination action and the like are known.

  In the present invention, a bee is used in a state in which a raw bee and a raw bee are processed. Specifically, processed bees were pulverized bees (raw or dried), dried bees (raw or crushed), bees (raw, dried) Or pulverized product), and those obtained by extracting honeybees with water, hydrous ethanol, or the like. Preferable examples include dried powder of bees prepared by drying and then pulverizing the bees (raw).

  The term `` bee '' in the present invention, unless otherwise specified, in addition to a raw bee, a processed product obtained by subjecting the bee to drying, pulverization, or heating, a bee ( (Including raw, dried and pulverized products) extracted with water, hydrous ethanol, and the like, and bees and processed products thereof treated with proteolytic enzymes (peptidases).

  As a drying method, a known method employed in general food processing, such as natural drying such as ventilation drying, sun drying, forced drying by heating with electricity or the like, freeze drying, and the like can be used. Preferably, it is freeze-dried. The drying time is not particularly limited. For example, in the case of natural drying such as ventilation and sun drying, about 3 days, and in the case of forced drying by heating with electricity, etc., about 50 ° C. for 1 to 3 days. The degree can be mentioned. Usually, drying is preferably performed so that the water content is 10% by mass or less, preferably 5% by mass or less. In addition, when it is difficult to reduce the water content to 10% by mass or less as in the case of natural drying such as ventilation and sun drying, a treatment for further reducing the water content can be performed with a freeze dryer.

  The pulverization treatment (powdering treatment) can be performed using a known method such as a pulverization method using a pulverizer (mill) or a mortar grinding method.

  The method for heating the bee kid is not particularly limited, and a method of heat treatment at 70 to 120 ° C. can be mentioned. In order to avoid elution of active ingredients such as various vitamins and amino acids as much as possible, it is possible to simply heat bees (including raw, dried and pulverized products) in boiling water. As the heat treatment, a method of steaming a bee with steam is preferably used.

  The extraction method is to add water, hydrous ethanol, etc. to bees (including raw, dried and crushed), stir and then obtain the supernatant by centrifugation, filter with filter paper, The method of obtaining is used.

  The bees and their processed products are treated with proteolytic enzymes to reduce the molecular weight of the protein contained in the bees and their processed products, so that allergic reactions caused by the proteins are suppressed ( It is expected that a product with reduced allergenase will be obtained.

  Peptidase can be preferably mentioned as a proteolytic enzyme used for enzymatic treatment of bees and processed products thereof. The peptidase used may have at least one of an endopeptidase action and an exopeptidase action.

  Proteolytic enzymes having at least endopeptidase activity are derived from animals (eg, trypsin, chymotrypsin, etc.), plants (eg, papain, etc.), microorganisms (eg, lactic acid bacteria, yeast, mold, Bacillus subtilis, actinomycetes, etc.) And endopeptidase.

  As a proteolytic enzyme having at least exopeptidase activity, carboxypeptidase, aminopeptidase, exopeptidase derived from microorganisms (e.g., lactic acid bacteria, Aspergillus sp., Rhizopus sp., Etc.), pancreatin, pepsin, etc. that also have endopeptidase activity Is mentioned.

  Among these various enzymes, preferable examples of enzymes having both exopeptidase activity and endopeptidase activity include Streptomyces griseus-produced peptidase (trade name: Actinase AS), Aspergillus oryzae (Aspergillus oryzae) orizae) -produced peptidase (trade name: Protease A, flavorzyme), Aspergillus melleus-produced peptidase (trade name: Protease P), and the like.

  Further, preferable examples of the enzyme having an exoprotease action include Aspergillus oryzae-produced peptidase (trade name: Umamizyme G, Promod 192P, Promod 194P, Sumiteam FLAP), Aspergillus sojae-produced peptidase ( Product name: Sternzyme B15024), Aspergillus genus peptidase (trade name: cochlase P), Rhizopus oryzae production peptidase (product name: peptidase R), and the like.

  Furthermore, preferable examples of the enzyme having endoprotease action include Bacillus subtilis producing peptidase (trade name: orientase 22BF, nucleicin), Bacillus licheniformis producing peptidase (trade name: Alkalase), Bacillus stearothermophilus-produced peptidase (Product name: Protease S), Bacillus amyloliquefaciens-produced peptidase (Product name: Neutase), Bacillus genus-produced peptidase (Product) Name: Protamex).

  The enzyme treatment for reducing the allergenicity of bees and their processed products can be performed, for example, according to the description in JP-A-2009-159997.

  The tonic tonic, sexual function improving agent, male climacteric symptom improving agent and anti-fatigue agent of the present invention may contain additional components as long as the effects of the present invention are not hindered. In the case of including such an additional component, the proportion of bees in tonic tonic, sexual function improving agent, male climacteric symptom improving agent and anti-fatigue agent is 0.01-99% by mass, preferably 1-80% by mass, more Preferably 10-70 mass%, More preferably, 20-50 mass% can be illustrated.

  The tonic tonic, sexual function improving agent, male menopausal symptom improving agent and anti-fatigue agent of the present invention are not particularly limited in form, for example, powder, granule, tablet, capsule, liquid, suspension, It may have a pharmaceutical form such as an emulsion.

  The tonicity enhancing agent, sexual function improving agent, male menopausal symptom improving agent and anti-fatigue agent of the present invention can be suitably used as ingredients of food compositions, quasi drugs and pharmaceuticals (especially oral drugs).

  The tonic tonic, sexual function improving agent, male menopausal symptom improving agent and anti-fatigue agent of the present invention are foods and beverages (e.g., health food, functional food, nutritional composition (nutritional) composition), nutritional supplements, supplements, foods for health use, foods for specified health use, nutritional functional foods, or functional labeling foods), quasi-drugs and pharmaceuticals (especially oral medicines). In addition, the tonic tonic, sexual function improving agent, male menopausal symptom improving agent and anti-fatigue agent of the present invention impart tonic tonicity action, sexual function improving action, male menopausal symptom improving action, anti-fatigue action and vitality improving action. The meaning of the additive is also included.

  In the above food and drink, as necessary, excipients, brighteners, minerals, vitamins, flavonoids, quinones, polyphenols, amino acids, nucleic acids, essential fatty acids, cooling agents, binders, sweeteners, Disintegrating agents, lubricants, colorants, fragrances, stabilizers, preservatives, sustained release regulators, surfactants, solubilizers, wetting agents and the like can be blended.

  The types of the above-mentioned food and drink are not particularly limited. For example, beverages (soft drinks such as coffee, juice, tea drinks, milk drinks, lactic acid bacteria drinks, yogurt drinks, carbonated drinks, sake, Western liquor, fruit seeds, etc. Spreads (such as custard cream); pastes (such as fruit paste); pastries (chocolate, donuts, pies, cream puffs, gum, jelly, candy, cookies, cakes, puddings, etc.); Japanese confectionery (Daifuku) , Salmon, buns, castella, anmitsu, mutton etc.); ice confectionery (ice cream, popsicle, sherbet, etc.); foods (curry, beef bowl, miso soup, soup, meat sauce, pasta, pickles, jam etc.); Seasonings (dressing, sprinkles, umami seasonings, soup ingredients, etc.) are included.

  The dosage unit form for use as a supplement is not particularly limited and can be appropriately selected. Examples thereof include tablets, capsules, granules, liquids, and powders.

  The proportion of bees contained in the food and drink is, for example, 0.01 to 99% by mass, preferably 1 to 80% by mass, more preferably 10 to 70% by mass, and still more preferably 20 to 50% by mass. Can be mentioned.

  The intake of the above food and drink can be appropriately set according to various conditions such as the body weight, age, sex, and symptoms of the user.

  When the tonic tonic, sexual function improving agent, male menopausal symptom improving agent and anti-fatigue agent of the present invention are prepared as a quasi-drug or a pharmaceutical product, they can be referred to as a bee-child preparation. For quasi-drugs or medicines, the above-mentioned bees can be used alone or in combination with other pharmaceutical ingredients such as vitamins and herbal medicines described in the Japanese Pharmacopoeia.

  When preparing the tonic agent, sexual function improving agent, male menopausal symptom improving agent and anti-fatigue agent of the present invention as a quasi-drug or pharmaceutical product, the bee is a non-toxic carrier or diluent acceptable in the pharmaceutical product. Or with excipients, tablets (including plain tablets, sugar-coated tablets, effervescent tablets, film-coated tablets, chewable tablets, troches, etc.), capsules, pills, powders (powder), fine granules, granules, liquids It can be prepared in the form of suspensions, emulsions, syrups, pastes, and the like to make oral preparations.

  The dosage of the above-mentioned quasi-drug or pharmaceutical can be appropriately determined according to various conditions such as the patient's body weight, age, sex, and symptoms, and 0.5 g or more, preferably 0.7 g of bees per day. Above, more preferably 1 g or more is desirable.

  The proportion of bees contained in the quasi-drug or pharmaceutical is not particularly limited as long as the effect of the present invention is exhibited, and is, for example, 0.01 to 99% by mass, preferably 1 to 80% by mass, more preferably 10%. The concentration can be -70% by mass, more preferably 20-50% by mass.

  The tonic tonic, sexual function improving agent, male climacteric symptom improving agent and anti-fatigue agent of the present invention described above are applied to mammals including humans (preferably humans, particularly males).

  The food / beverage products, quasi-drugs and pharmaceuticals of the present invention have tonicity, sexual function improvement, male menopausal symptoms, anti-fatigue, and vitality improvement. Moreover, since the food / beverage products, quasi-drugs, and pharmaceuticals of the present invention do not increase androgen, they are highly safe.

  Hereinafter, the present invention will be described in detail with reference to examples. However, the present invention is not limited to these examples.

[Test example]
<Subject>
Conduct questionnaires and examinations (physical examinations, doctors' interviews, blood tests, questionnaires, etc.), and (1) males aged 35 to 60 years old, (2) 27 to 49 in the menopause questionnaire (AMS) The subjects were (3) free testosterone of 8.5 pg / mL or more and less than 11.8 pg / mL, and (4) 11 married or heterosexual partners.

<Test method>
Eleven subjects ingested 6 capsules of soft capsule-shaped food containing 180 mg of bees per capsule every day for 12 weeks. The following table shows the nutritional components per capsule of the test food.

  From the week before the start of the study until the end of intake, the subjects recorded subjective symptoms including daily erections and daily life information in a diary.

  At the start of the study and at the 12th week after ingestion, a doctor's examination, questionnaire survey, physical examination, blood test and urinalysis are performed, and total testosterone (TT), free testosterone (FT), and aging male symptoms survey Votes (hereinafter referred to as AMS), Self-rating depression scale (hereinafter referred to as SDS), simplified international erection function score (hereinafter referred to as IIEF5) and fatigue VAS were evaluated. The number of early erections during the test was also evaluated.

  AMS score is a self-filled questionnaire widely used for symptom inquiry of LOH syndrome. Psychological factors are 5 items (25 points), physical factors are 7 items (35 points), and sexual function factors are 5 items. It consists of a total of 17 items (25 points) (85 points). Each item is rated on a five-point scale: “No”, “Light”, “Medium”, “Heavy”, “Very heavy”, with a score of 1 to 5 each. The higher the score, the more severe the symptoms.

  SDS is an index indicating the degree of depression, and consists of 20 question items that ask about depressive symptoms. The higher the score, the more severe the symptoms.

  IIEF5 is a simplified version of the IIEF International Index of Erectile Function, which is an international index used for screening ED and determining the effectiveness of treatment. The lower the score, the more severe the symptoms.

  The feeling of fatigue follows the VAS method, and the left end of the 10 cm straight line is “the best sensation that you have never experienced, never experienced fatigue”, and the right end is anything that you have never experienced before. As the worst sense of exhaustion that cannot be done, the location on the straight line is recorded with a cross, and the distance from the left end to the recorded location is quantified.

<Statistical analysis>
For each data, an average value and a standard deviation were obtained for each group, and AMS score, IIEF5, SDS, number of early erections, and fatigue VAS were subjected to Wilcoxon sign rank sum test.

  TT, FT, physical examination, hematology examination and blood biochemistry examination performed corresponding t-test.

  All statistical analysis methods were two-sided tests, and the risk rate was 5% and 1%.

<Result>
1 Effectiveness evaluation items 1) AMS
The AMS score is significantly lower at the end of ingestion in the “total” (FIG. 1-a), “sexual factors” (FIG. 1-b), and “physical factors” (FIG. 1-c) than at the start of ingestion. It was seen.

2) IIEF5
In comparison between before and after taking the test food, IIEF5 showed a significant increase at the end of ingestion (FIG. 2).

3) Number of erections in the morning In the comparison between before and after taking the test food, the number of erections in the early morning significantly increased at the end of the intake (Fig. 3).

4) Fatigue VAS
In comparison between before and after taking the test food, fatigue decreased significantly at the end of ingestion (FIG. 4).

5) SDS
In comparison between before and after taking the test food, the depressive symptoms showed a significant decrease at the end of the intake (FIG. 5).

2 Safety evaluation items
When TT and FT (FIG. 6), physical examination, hematological examination, blood biochemical examination, and urinalysis were confirmed for each subject, no clinically relevant fluctuation was found.

  No subjective symptoms were observed in the subjects during the study period. In addition, there were no adverse events that were observed during the intake period.

<Conclusion>
When 11 males aged 35 to 60 years old who are dissatisfied with vitality in daily life take 6 capsules of soft capsules containing bee pups a day for 12 weeks, there is a significant decrease in AMS, IIEF 5 and number of early erections There was a significant increase and a significant decrease in the VAS and SDS questionnaires for fatigue assessment. On the other hand, there was no change in total and free testosterone values. In other words, the bee pups were found to have improved menopausal symptoms, anti-fatigue effects, and anti-stress effects without increasing testosterone levels.

Formulation Example Hereinafter, a formulation example of the present invention will be shown.

Formulation Example 1 Soft capsule
Edible fats and oils, beeswax, and soybean-derived plant lecithin were added to 1080 mg of 1/6 amount of bees and filled into soft capsules containing gelatin and caramel pigment to obtain a soft capsule formulation.

Formulation Example 2 Soft capsule
Mix edible oil, γ-aminobutyric acid, glycerin, soybean-derived plant lecithin, beeswax, vitamin B2, and vitamin B12 into 180 mg of bees and fill into soft capsules containing gelatin and caramel pigment to obtain a soft capsule formulation It was.

Formulation Example 3 Soft capsule
Soft capsules containing gelatin and cacao pigments mixed with 100 mg bee edible edible fat, maca extract powder, tonkat ant extract powder, cordyceps mycelium powder, zinc-containing yeast, baboon extract powder, beeswax, and soybean-derived plant lecithin To obtain a soft capsule preparation.

Claims (4)

  Tonic tonic containing bee pups.   Sexual function improving agent containing bee pups.   Men's menopausal symptoms-improving agent including bees   Anti-fatigue agent including bee cubs.

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