Sarcopenia improving agent

Abstract

To provide sarcopenia improvers.SOLUTION: Provided is a sarcopenia improver containing royal jelly and / or propolis.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a sarcopenia improving agent. [Background technology]

[0002] In recent years, as the aging society advances, sarcopenia has become a major factor in reducing the quality of life (QOL) of the elderly. Sarcopenia refers to a condition in which skeletal muscle mass decreases with age. Sarcopenia is diagnosed using muscle mass, muscle strength (or grip strength), and walking speed as indicators.

[0003] The number of diabetes patients in Japan is rapidly increasing, and preventing the progression of sarcopenia, which is associated with diabetes, is a top priority issue for preventing patients from becoming bedridden, as it not only worsens life prognosis but also significantly reduces the patient's ADL / QOL, and is a problem that cannot be overlooked from the perspective of nursing care. In recent years, it has been thought that sarcopenic obesity, which causes a decrease in skeletal muscle mass in addition to an increase in body fat, is at the heart of the pathology of obesity associated with diabetes, but the detailed mechanism is unclear.

[0004] Obesity is a condition in which white adipose tissue increases excessively and accumulates. It is known that obesity increases the incidence of various diseases such as impaired glucose tolerance, dyslipidemia, cerebral infarction, hypertension, and hyperuricemia. Furthermore, sarcopenic obesity, which is characterized by a decrease in skeletal muscle mass, is not only accompanied by physical disabilities, but also by the progression of metabolic disorders and arteriosclerosis, and is considered to be a high cardiovascular risk.

[0005] Royal jelly is a milky substance synthesized in the salivary glands of honeybees and secreted from the Mandebraan glands in the head, which worker bees give to larval bees placed in a queen bee larvae cell in order to produce queen bees. Royal jelly is currently used widely around the world as health food, medicine, cosmetics, etc., and its reported effectiveness includes increasing blood flow, lowering blood pressure, promoting growth, acting like a sex hormone, antibacterial, antitumor, promoting wound healing, curing autonomic nervous system imbalance, anti-stress, promoting calcium absorption, lowering blood sugar levels, and antioxidant properties.

[0006] Propolis is a glue-like substance made by mixing tree sap, plant buds and exudates collected by honeybees with beeswax, and is known to have antibacterial, antioxidant, anti-inflammatory, anti-tumor, and anti-allergic effects.

[0007] Regarding the effects of propolis, Patent Document 1 describes that propolis extract suppresses the expression of genes involved in lipid synthesis, thereby reducing the activity of enzymes that synthesize triglycerides and cholesterol, thereby inhibiting the synthesis of these lipids, and that ingestion of propolis extract suppressed the accumulation of lipids in the body of mice.

[0008] Furthermore, Non-Patent Document 1 describes that in a study conducted on three groups of C57BL / 6N mice, a control group was given a high-fat diet ad libitum, and propolis extract was orally administered at 5 and 50 mg / kg twice a day for 10 days. Compared to the control group, the propolis extract group showed a decrease in body weight gain, visceral adipose tissue weight, liver and serum triglycerides, cholesterol, and non-esterified fatty acids, indicating that propolis reduced weight gain in obese mice.

[0009] However, Patent Document 1 and Non-Patent Document 1 do not include any studies targeting sarcopenia or sarcopenic obesity. [Prior art documents] [Patent documents]

[0010] [Patent Document 1] JP 2010-53122 A [Non-patent literature]

[0011] [Non-Patent Document 1] Biol. Pharm. Bull. 32(12) 2022-2028(2009) Summary of the Invention [Problem to be solved by the invention]

[0012] The present invention aims to provide a sarcopenia improving agent. [Means for solving the problem]

[0013] As a result of extensive research to achieve the above-mentioned objective, the inventors discovered that the loss of soleus muscle weight can be significantly suppressed by administering royal jelly or propolis to sarcopenic obese mouse model mice.

[0014] The present invention was completed based on these findings and through further investigation, and provides the following sarcopenia improving agents, etc.

[0015] Item 1. A sarcopenia improving agent comprising royal jelly and / or propolis. Item 2. A sarcopenia / obesity improving agent comprising royal jelly and / or propolis. Item 3. The agent according to Item 1 or 2, wherein the royal jelly is an enzyme-treated royal jelly. Item 4. The agent according to any one of Items 1 to 3, wherein the propolis is Brazilian propolis. Item 5. The agent according to any one of Items 1 to 4, which is a food or drink, a medicine, or a quasi-drug. Item 6. The agent according to Item 3, wherein the enzyme treatment is a protease treatment. Item 7. A composition for improving, preventing, or treating sarcopenia or sarcopenic obesity, comprising royal jelly and / or propolis. Effect of the Invention

[0016] Royal jelly and propolis have excellent inhibitory effects on the loss of muscle weight in sarcopenia (particularly sarcopenic obesity), and are therefore useful as active ingredients in sarcopenia improving agents (particularly sarcopenic obesity improving agents).

[0017] In addition, royal jelly and propolis are highly safe because they are naturally derived ingredients. [Brief description of the drawings]

[0018] [Figure 1] Graph showing the effect of royal jelly administration on soleus muscle weight in sarcopenic obese mouse models. Values ​​shown are mean ± standard deviation, ***: p<0.001, *: p<0.01 [Diagram 2] Graph showing the effect of propolis administration on soleus muscle weight in sarcopenic obese mouse models. Values ​​shown are mean ± standard deviation, ***: p<0.001, *: p<0.01 DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] Hereinafter, an embodiment of the present invention will be described in detail.

[0020] In this specification, the term "comprise" includes the meanings of "essentially consist of" and "consist only of."

[0021] The sarcopenia improving agent of the present invention is characterized by containing royal jelly and / or propolis.

[0022] In this specification, the term "sarcopenia improving agent" is used to include sarcopenia and obesity improving agents.

[0023] (Royal Jelly) Royal jelly is a milky white jelly-like substance produced by mixing secretions secreted from the hypopharyngeal gland and mandibular gland by 3-12-day-old worker bees among honeybees. Major physiologically active components in royal jelly include, for example, organic acids such as 10-hydroxy-2-decenoic acid (hereinafter referred to as "decenoic acid") that are specific to royal jelly, proteins, lipids, sugars, vitamin Bs, vitamins such as folic acid, nicotinic acid, and pantothenic acid, and various minerals. The royal jelly in the present invention includes raw royal jelly, dried royal jelly, dried royal jelly powder, enzyme-treated royal jelly, royal jelly extract, and royal jelly fermentation product. The royal jelly may be produced in any of European countries, Oceanian countries, America, Brazil, Japan, China, and other Asian countries.

[0024] Dried royal jelly powder is made by drying and powdering fresh royal jelly.

[0025] The enzyme-treated royal jelly is royal jelly treated with a protein-degrading enzyme (protease). Preferably, the enzyme-treated royal jelly is hypoallergenic, in which allergic reactions caused by the proteins contained in royal jelly are suppressed by peptidase treatment. Therefore, the components contained in the enzyme-treated royal jelly include organic acids such as the above-mentioned decenoic acid, lipids, sugars, vitamins, and various minerals, in addition to the protease decomposition products of the proteins contained in royal jelly.

[0026] The royal jelly used to produce the enzyme-treated royal jelly is not particularly limited, and examples thereof include raw royal jelly, royal jelly powder obtained by drying and powdering raw royal jelly, and raw royal jelly extracted with water or aqueous ethanol, etc.

[0027] Enzyme-treated royal jelly can be produced by treating royal jelly raw material with an enzyme having at least endopeptidase activity, an enzyme having at least exopeptidase activity, and / or an enzyme having both endopeptidase activity and exopeptidase activity.

[0028] Examples of proteolytic enzymes having at least endopeptidase activity include endopeptidases derived from animals (e.g., trypsin, chymotrypsin, etc.), plants (e.g., papain, etc.), and microorganisms (e.g., lactic acid bacteria, yeast, mold, Bacillus subtilis, actinomycetes, etc.).

[0029] Examples of proteolytic enzymes having at least exopeptidase activity include carboxypeptidase, aminopeptidase, exopeptidases derived from microorganisms (e.g., lactic acid bacteria, Aspergillus bacteria, Rhizopus bacteria, etc.), and pancreatin and pepsin which also have endopeptidase activity.

[0030] Among these various enzymes, preferred examples of the enzyme having both exopeptidase activity and endopeptidase activity include the peptidase produced by Streptomyces griseus (trade name: Actinase AS), the peptidase produced by Aspergillus oryzae (trade name: Protease A, Flavorzyme, Proteax), and the peptidase produced by Aspergillus melleus (trade name: Protease P). Preferred examples of the enzyme having exopeptidase activity include the peptidase produced by Aspergillus oryzae (trade name: Umamizyme G, Promod 192P, Promod 194P, Sumizyme FLAP), and the peptidase produced by Aspergillus sojae (trade name: Protease P). sojae (trade name: Sternzyme B15024), Aspergillus (trade name: Cocrase P), and Rhizopus oryzae (trade name: Peptidase R) can be used as peptidases. Further preferred examples of enzymes having endopeptidase activity include peptidase produced by Bacillus subtilis (trade name: Orientase 22BF, Nucleisin), peptidase produced by Bacillus licheniformis (trade name: Alcalase), peptidase produced by Bacillus stearothermophilus (trade name: Protease S), peptidase produced by Bacillus amyloliquefaciens (trade name: Neutrase), and peptidase produced by the genus Bacillus (trade name: Protamex).

[0031] Enzyme treatment to reduce the allergenicity of royal jelly can be carried out, for example, according to the description in JP-A-2007-295919 and JP-A-2007-295920.

[0032] Royal jelly extract is obtained by extracting royal jelly (including raw, dried and crushed royal jelly) with water or aqueous ethanol or the like.

[0033] The royal jelly fermented product can be produced by a conventional method using microorganisms such as yeast and lactic acid bacteria.

[0034] (Propolis) Propolis is a resinous or waxy substance that constitutes the wall of a beehive. In the present invention, the propolis may be derived from any place of origin or plant, for example, Brazil, China, European countries, Oceania, America, etc. Therefore, any propolis, such as Alecrin, Super Green, Eucalyptus, Ultra Green, etc., can be used.

[0035] The propolis in the present invention includes, for example, propolis original mass or residue, its pulverized product, supercritical extract, extract with water or hydrophilic organic solvent, powder obtained by powdering the extract, granule form obtained by granulating the powder, etc. Among them, hydrophilic organic solvent extract is preferable because it is an effective ingredient of propolis extracted efficiently and in a good balance in a short time, and does not require large-scale equipment when scaling up.

[0036] The hydrophilic organic solvent extractant may be lower alcohol such as ethanol, methanol, propanol, etc., and ethanol is particularly preferred. For extraction, propolis original mass or residue, alcohol-washed propolis original mass or residue, etc. may be used, and the extraction efficiency can be improved by using propolis original mass or residue cut or crushed to an appropriate size.

[0037] The content of royal jelly in the sarcopenia improving agent of the present invention is not particularly limited as long as the effects of the present invention can be obtained, and can be appropriately adjusted depending on the final form, etc., and can be, for example, 0.1% by mass or more, 0.5% by mass or more, 1% by mass or more, 3% by mass or more, 5% by mass or more, 7% by mass or more, 10% by mass or more, 15% by mass or more, 20% by mass or more, 30% by mass or more, 40% by mass or more, 50% by mass or more, 55% by mass or more, etc., based on the total solid content in the sarcopenia improving agent. % by mass or more, 57% by mass or more, 60% by mass or more, 70% by mass or more, 80% by mass or more, or 90% by mass or more, 100% by mass or less, 90% by mass or less, 80% by mass or less, 70% by mass or less, 60% by mass or less, 55% by mass The amount may be % or less, 50% by mass or less, 40% by mass or less, 30% by mass or less, 20% by mass or less, 15% by mass or less, 10% by mass or less, 7% by mass or less, 5% by mass or less, 3% by mass or less, 1% by mass or less, or 0.5% by mass or less.

[0038] In addition, royal jelly is preferably orally administered periodically for the improvement or prevention of sarcopenia (or sarcopenic obesity), and is particularly preferably orally administered several times a day. Although not particularly limited, it can be used at a dose of 10 mg to 15,000 mg per day for an adult weighing 60 kg, preferably at a dose of 100 mg to 10,000 mg, more preferably at a dose of 150 mg to 8,000 mg, even more preferably at a dose of 180 mg to 7,200 mg, even more preferably at a dose of 600 mg to 5,400 mg, and particularly preferably at a dose of 800 mg to 3,600 mg. The dose can be appropriately set within the above range depending on factors such as the health condition of the person to be administered, the administration method, and the combination with other agents.

[0039] The content of propolis in the sarcopenia improving agent of the present invention is not particularly limited as long as the effects of the present invention can be obtained, and can be appropriately adjusted depending on the final form, etc., and can be, for example, 0.01% by mass or more, 0.05% by mass or more, 0.1% by mass or more, 0.5% by mass or more, 0.8% by mass or more, 1% by mass or more, 1.5% by mass or more, 2% by mass or more, 3% by mass or more, 10% by mass or more, 15% by mass or more, 17% by mass or more, 20% by mass or more, 25% by mass or more, 30% by mass or more, 40% by mass or more, based on the total solid content in the sarcopenia improving agent. It may be 50% by mass or more, 60% by mass or more, 70% by mass or more, or 80% by mass or more, 100% by mass or less, 80% by mass or less, 70% by mass or less, 60% by mass or less, 50% by mass or less, 45% by mass or less, 40% by mass or less, 35% by mass or less, 30% by mass or less, 2 It may be 5% by mass or less, 20% by mass or less, 18% by mass or less, 15% by mass or less, 10% by mass or less, 3% by mass or less, 2% by mass or less, 1.5% by mass or less, 1% by mass or less, 0.8% by mass or less, 0.5% by mass or less, 0.1% by mass or less, or 0.005% by mass or less.

[0040] In addition, propolis is preferably orally administered periodically for the improvement or prevention of sarcopenia (or sarcopenic obesity), and is particularly preferably orally administered several times a day. Although not particularly limited, the active ingredient equivalent value can be used at a dose of 1 mg to 5000 mg per day for an adult weighing 60 kg, preferably at a dose of 5 mg to 2500 mg, more preferably at a dose of 10 mg to 1000 mg, even more preferably at a dose of 50 mg to 800 mg, even more preferably at a dose of 100 mg to 600 mg, and particularly preferably at a dose of 150 mg to 450 mg. The dose can be appropriately set within the above range depending on factors such as the health condition of the person to be administered, the administration method, and the combination with other agents.

[0041] The sarcopenia improving agent of the present invention can be used as a food or beverage (particularly a food or beverage intended for health, maintenance or promotion of health, etc. (e.g., health food, functional food, nutritional composition, nutritional supplement, supplement, health food, food for specified health use, nutritional functional food, or food with functional labeling)), quasi-drug, pharmaceutical, etc. The sarcopenia improving agent of the present invention also encompasses the meaning of an additive that imparts a sarcopenia improving effect. Furthermore, the sarcopenia obesity improving agent of the present invention also encompasses the meaning of an additive that imparts a sarcopenia obesity improving effect.

[0042] The above-mentioned royal jelly and propolis can be used as is in the above-mentioned foods and beverages, and if necessary, minerals, vitamins, flavonoids, quinones, polyphenols, amino acids, nucleic acids, essential fatty acids, cooling agents, binders, sweeteners, disintegrants, lubricants, colorants, fragrances, stabilizers, preservatives, sustained-release regulators, surfactants, solubilizers, humectants, etc. can also be blended therein.

[0043] Food and drink includes all foods and drinks that animals (including humans) can consume. The types of food and drink are not particularly limited, and examples thereof include dairy products, fermented foods (yogurt, etc.), beverages (soft drinks such as coffee, juice, and tea drinks, milk drinks, lactic acid bacteria drinks, drinks containing lactic acid bacteria, yogurt drinks, carbonated drinks, sake, Western liquor, and alcohol such as fruit wine, etc.), spreads (custard cream, etc.), pastes (fruit paste, etc.), Western confectionery (chocolate, donuts, pies, cream puffs, gum, jelly, candy, cookies, cakes, puddings, etc.), Japanese confectionery (daifuku, mochi, manju, castella, anmitsu, yokan, etc.), frozen desserts (ice cream, popsicle, sorbet, etc.), foods (curry, beef bowl, porridge, miso soup, soup, meat sauce, pasta, pickles, jam, etc.), and seasonings (dressing, furikake, umami seasoning, soup base, etc.).

[0044] The method for producing the food and drink of the present invention is not particularly limited, and can be any known method as appropriate.

[0045] The dosage unit form when used as a supplement is not particularly limited and can be selected appropriately. Examples include tablets, capsules, granules, liquids, powders, syrups, pastes, drinks, etc.

[0046] The above-mentioned royal jelly and propolis may be used alone in the above-mentioned pharmaceutical products, or may be used in combination with other medicinal ingredients such as vitamins and herbal medicines described in the Japanese Pharmacopoeia.

[0047] When the sarcopenia improving agent of the present invention is prepared as a pharmaceutical product, the royal jelly and propolis described above can be prepared together with pharmaceutical acceptable ingredients into the form of tablets (including plain tablets, sugar-coated tablets, effervescent tablets, film-coated tablets, chewable tablets, troches, etc.), capsules, pills, powders (dispersed medicines), fine granules, granules, liquids, suspensions, emulsions, syrups, pastes, etc. to form pharmaceutical preparations (for example, for oral use).

[0048] In addition to royal jelly and propolis, the pharmaceutical composition of the present invention may contain, as necessary, pharma- ceutically acceptable ingredients such as excipients, binders, disintegrants, lubricants, colorants, suspending agents, thickeners, antioxidants, absorption enhancers, pH regulators, preservatives, antiseptics, stabilizers, surfactants, sweeteners, flavorings, and fragrances.

[0049] The pharmaceutical product of the present invention also includes quasi-drugs.

[0050] The sarcopenia improving agent of the present invention described above is applied to mammals including humans (preferably humans). The target human is preferably an elderly human, and elderly means a human aged 65 years or older.

[0051] As shown in the examples below, royal jelly and propolis, which are contained as active ingredients in the sarcopenia improving agent of the present invention, have an excellent effect of suppressing a decrease in muscle weight in sarcopenic obesity model mice. Therefore, the sarcopenia improving agent (particularly the sarcopenic obesity improving agent) of the present invention has an excellent effect of improving, preventing or treating sarcopenia (particularly sarcopenic obesity).

[0052] In addition, the sarcopenia improving agent of the present invention is highly safe because it contains naturally derived ingredients as active ingredients. EXAMPLES

[0053] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

[0054] Test Example The effects of royal jelly and propolis on sarcopenic obesity were examined using a sarcopenic obesity model mouse (Db / Db mouse).

[0055] The enzyme-treated royal jelly was obtained by treating raw royal jelly with a peptidase having endopeptidase and exopeptidase activities. The propolis ethanol extract powder was obtained by freeze-drying and pulverizing the ethanol extract of Alecrin propolis raw block (produced in Minas Gerais, Brazil). These enzyme-treated royal jelly and propolis ethanol extract powder were used in the following tests.

[0056] Db / Db mice and Db / m mice (6 mice per group) were fed normal diet mixed with 5% royal jelly, normal diet mixed with 2% propolis, or normal diet. They were raised from 8 to 16 weeks of age and then sacrificed. The mouse soleus muscles were then harvested and weighed.

[0057] The results of administering royal jelly are shown in Figure 1, and the results of administering propolis are shown in Figure 2. The results of Figures 1 and 2 show that the administration of royal jelly and propolis significantly inhibited the decrease in soleus muscle weight in sarcopenic obesity model mice.

Claims

[Claim 1] A sarcopenia / obesity improvement agent containing propolis produced in Minas Gerais, Brazil (excluding those containing omega-3 polyunsaturated fatty acids or royal jelly).

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