JP2022022617A - Muscle synthesis promoter - Google Patents

Abstract

To provide an internal medicine capable of promoting muscle synthesis ability based on the action of promoting IGF-1 production.SOLUTION: A muscle synthesis promoter comprises a Kamishimotsuto extract and is capable of promoting muscle synthesis ability based on the action of promoting IGF-1 production.SELECTED DRAWING: None

Description

The present invention relates to a muscle synthesis ability promoter.

Muscle function declines with aging and / or chronic lack of exercise. Although muscle dysfunction is not immediately life-threatening, it is observed extremely frequently, resulting in poor quality of life and a great impact on life prognosis. Therefore, efforts to prevent or improve muscle dysfunction are important in extending healthy life expectancy. The Ministry of Health, Labor and Welfare recommends that elderly people take a sufficient amount of protein in order to suppress muscle dysfunction, and the specific recommended amount of protein intake is for men aged 65 and over. 60 g or more per day for women and 50 g or more per day for women (Non-Patent Document 1).

IGF (insulin-like growth factor) is a single-stranded polypeptide consisting of 70 amino acids whose amino acid composition and biological action are similar to those of insulin, and is synthesized in tissues such as central nerves and muscles (Patent Document 1). ). In addition, IGF-1, which is a type of IGF, is one of the important growth factors that suppresses apoptosis and has a cell differentiation and proliferation effect. , It is known to show actions such as inflammation suppression, cognitive function improvement, hair growth, and immune function activation. It is also known that the IGF-1 signal, particularly in muscle tissue, promotes muscle protein synthesis (Non-Patent Document 2).

Walking is the most common activity to deal with leg weakness with the recent increase in awareness of efforts to prevent and improve muscle function. In fact, walking is said to bring various effects to the mind and body, and one of them is known to increase muscle storage, specifically red muscle (Non-Patent Document 3). On the other hand, it is also known that the amount of IGF-1 does not change by endurance training such as walking (Non-Patent Document 4).

Japanese Dietary Intake Standards (2020 Edition), Ministry of Health, Labor and Welfare IGF Signal and Skeletal Muscle Aging, Shuichi Machida, Basic Aging Research, Vol. 30, No. 1, 23-30, 2006 Benefits and attractiveness of walking that energizes people and society, Japan Walking Association, Fig. 1-1-1 (1) Benefits that walking brings to mind and body Proliferation and movement of skeletal muscle from the viewpoint of activation of muscle satellite cells, Katsumasa Goto, Physical Fitness Science, 2014, Vol. 63, No. 1, p. 42

Therefore, if IGF-1 production can be promoted in the body, an effect of promoting muscle synthesis ability based on the effect of promoting IGF-1 production can be expected.

An object of the present invention is to provide an internal medicine capable of promoting muscle synthesis ability based on the action of promoting IGF-1 production.

As a result of diligent studies, the present inventors have found that an extract of a Chinese herbal medicine containing a predetermined crude drug has an IGF-1 production promoting action. The present invention has been completed by further studies based on this finding.

That is, the present invention provides the inventions of the following aspects.
Item 1. A muscle synthesis-promoting agent containing an extract of Chinese herbal medicine containing Toki, Kawakyu, Peony and Rehmannia glutinosa as constituent crude drugs.
Item 2. Item 2. The muscle synthesis promoting agent according to Item 1, wherein the Chinese herbal medicine is Shimotsuto.
Item 3. Item 2. The muscle synthesis promoting agent according to Item 1, wherein the Chinese herbal medicine is Kami Shimotsuto.
Item 4. Item 6. The muscle synthesis ability promoter according to any one of Items 1 to 3, which promotes the synthesis ability of soleus muscle and / or gastrocnemius muscle.
Item 5. Item 6. The muscle synthesis ability promoter according to any one of Items 1 to 4, which is used for a subject who is not physically weak.
Item 6. Item 6. The muscle synthesis promoting agent according to any one of Items 1 to 5, which is used for people who are deficient in IGF-1.

According to the present invention, an internal medicine capable of promoting muscle synthesis ability based on the action of promoting IGF-1 production is provided.

The muscle synthesis ability promoter of the present invention is characterized by containing an extract of a Chinese herbal medicine containing a predetermined crude drug. Hereinafter, the muscle synthesis ability promoter of the present invention will be described in detail.

Active Ingredient The muscle synthesis promoter of the present invention contains an extract of Chinese herbal medicine containing Toki, Kawakyu, Peony and Rehmannia glutinosa as constituent crude drugs. Here, Toki is the root of Angelica acutiloba in the Umbelliferae family; Kawakyu is the root of the Umbelliferae peony that has been boiled; Is.

Specific examples of the Chinese herbal medicine used in the present invention include Shimotsuto, Kami Shimotsuto, Inoriyu Go Shimotsuto, Kyukigyoto, Shichimotsukokato, Onsei-drink, Renju-drink, and Juzendai. Hot water, Toki-drinking child, Shichimotsukokato, Shimotsuto blood-retaining hot water, Shichimotsukoka-to, Kamiyoyosan Kagawa Kyuji Huang, Saiko Seikoku-to, Daibofu-to, Keigairengyo-to, Sokei-katsu-to, Shimotsuto Meimeyu is mentioned. These Chinese herbs may be used alone or in combination of two or more.

In the present invention, among the above-mentioned Chinese herbs, preferably Kami-shimotsuto is mentioned. Kami Shimotsuto is described in the medical book "Man's Disease Rejuvenation" in the Ming Dynasty of China. It is a mixed crude drug containing mother and Tochu. Among the crude drugs contained in Kami-shimotsuto, Atractylodes japonicum may be replaced with or used in combination with Atractylodes japonicum (Rhizome of Atractylodes japonicum).

In the present invention, when Shimotsuto is used as a Chinese herbal medicine, the mixing ratio of Toki, Kawakyu, Peony and Rehmannia glutinosa constituting Shimotsuto is as described above, and preferably 1 part by weight of Toki and 1 part of Kawakyu. Examples include 1 part by weight of peony, 1 part by weight of peony, and 1 part by weight of rehmannia glutinosa.

In the present invention, when Kami-shimonoto is used as a Chinese herbal medicine, the mixing ratio of the raw medicines constituting Kami-shimonoto is not particularly limited, but is usually 1 to 2 parts by weight, preferably 1.25 to 1. 5 parts by weight; 0.75 to 2 parts by weight of Kawakyu, preferably 1 to 1.5 parts by weight; 0.75 to 2 parts by weight of sardine, preferably 1 to 1.5 parts by weight; 1.2 to 4. 25 parts by weight, preferably 1.5 to 4 parts by weight; 1 to 2 parts by weight, preferably 1.5 parts by weight (in the case of white, 1 to 1.5 parts by weight, preferably 1.25 parts by weight); Wheat Mon Winter 1-3 parts by weight, preferably 1.25 to 2.5 parts by weight; 0.5 to 1.5 parts by weight of carrots, preferably 0.75 to 1.25 parts by weight; 0.25 to cow knees 1.5 parts by weight, preferably 0.5 to 1.25 parts by weight; 0.5 to 1 part by weight of Huangqiao, preferably 0.75 parts by weight; 0.25 to 1 part by weight of Gomiko, preferably 0.5 to 1 part by weight. 0.75 parts by weight; 0.5 to 1 part by weight of Huangren, preferably 0.75 parts by weight; 0.25 to 1 part by weight of Chimo, preferably 0.5 to 0.75 parts by weight; and Tonaka 0. 5 to 1.5 parts by weight, preferably 0.75 to 1 part by weight.

Suitable examples of the crude drug formulation used in the production of the Kami-shimotsuto extract used in the present invention include 1.5 parts by weight of Toki, 1.5 parts by weight of Kawakyu, and 1.5 parts by weight of sardine. 1.5 parts by weight of ground yellow, 1.5 parts by weight of soy sauce, 2.5 parts by weight of bakumondoto, 1.2 parts by weight of carrots, 1.25 parts by weight of cow knee, 0.75 parts by weight of yellow kashiwa, 0.75 parts by weight of herbal medicine , 0.75 parts by weight of Huangren, 0.75 parts by weight of Chimo, and 0.75 parts by weight of Tochu.

The form of the extract of the Chinese herbal medicine may be either a liquid extract such as a flow extract or a soft extract, or a solid dry extract powder.

The liquid extract of Chinese herbal medicine can be obtained by extracting and treating a mixed crude drug according to each Chinese herbal medicine and concentrating the obtained extract as necessary. The extraction solvent used in the extraction treatment is not particularly limited, and examples thereof include water and hydrous ethanol. Further, the dried extract powder of Chinese herbal medicine can be obtained by drying a liquid extract. The method of the drying treatment is not particularly limited, and for example, a spray-drying method, a method of adding an appropriate adsorbent (for example, anhydrous silicic acid, starch, etc.) to a soft extract having an increased concentration of the extract to obtain an adsorbed powder, and the like are used. Can be mentioned.

In the present invention, as the Chinese herbal medicine extract, an extract prepared by the above-mentioned method may be used, or a commercially available extract may be used. For example, the dry extract powder of Shimotsuto is Shimotsuto Extract-M (manufactured by Nippon Powder Chemicals Co., Ltd.), and the dry extract powder of Kami Shimotsuto is Kami Shimotsuto Dry Extract (Nippon Powder Chemicals Co., Ltd.). (Made by the company) etc. are known as products and can also be obtained commercially.

In the muscle synthesis ability promoter of the present invention, the content of the Chinese herbal extract is not particularly limited as long as the effect of the present invention is exhibited, but it is usually 10 to 100% by weight, preferably 10 to 100% by weight, in terms of the dry extract powder amount of the Chinese herbal extract. 20 to 90% by weight, more preferably 40 to 80% by weight, still more preferably 60 to 70% by weight. In the present invention, the dry extract powder amount conversion of Chinese herbal medicine is the amount itself when the dry extract powder of Chinese herbal medicine is used, and when the liquid extract of Chinese herbal medicine is used, the residue after removing the solvent. It is an amount converted into an amount. When the dried extract powder of Chinese herbal medicine contains an additive such as an adsorbent added at the time of production, the amount is the amount excluding the additive.

Other Ingredients The muscle synthesis ability-promoting agent of the present invention may consist of the above-mentioned extract of the above-mentioned Chinese herbal medicine alone, or may contain additives and bases according to the pharmaceutical form. Such additives and bases are not particularly limited as long as they are pharmaceutically acceptable, but for example, excipients, binders, disintegrants, lubricants, tonicity agents, plasticizers, etc. Dispersants, emulsifiers, solubilizers, wetting agents, stabilizers, suspending agents, pressure-sensitive agents, coating agents, brighteners, water, fats and oils, waxes, hydrocarbons, fatty acids, higher alcohols , Esters, water-soluble polymers, surfactants, metal soaps, lower alcohols, polyhydric alcohols, pH regulators, buffers, antioxidants, UV inhibitors, preservatives, emulsifiers, fragrances, powders, Examples include thickeners, pigments, chelating agents and the like. These additives may be used alone or in combination of two or more. In addition, the content of these additives and bases is appropriately set according to the types of additives and bases to be used, the formulation form of the muscle synthesis ability-promoting agent, and the like.

Further, the muscle synthesis ability-promoting agent of the present invention may contain other nutritional components and pharmacological components, if necessary, in addition to the above-mentioned extract of the predetermined Chinese herbal medicine. Such nutritional components and pharmacological components are not particularly limited as long as they are pharmaceutically acceptable, but for example, antacids, stomachic agents, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, and astringents. Agents, antiemetics, antitussives, sputum, anti-inflammatory enzyme agents, sedative hypnotics, antihistamines, caffeines, cardiotonic diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, crude drug extracts, vitamins, menthol Kind and the like. These nutritional components and pharmacological components may be used alone or in combination of two or more. Further, the content of these components is appropriately set according to the type of the component to be used and the like.

Formulation form The formulation form of the muscle synthesis ability-promoting agent of the present invention is not particularly limited as long as it can be orally administered, and for example, powders, fine granules, granules, tablets, troches, chewable agents, etc. Solid formulations such as capsules (soft capsules and hard capsules) and rounds; semi-solid formulations such as jelly; liquid formulations such as liquids, suspensions and syrups, preferably granules. Can be mentioned.

Production method The method for producing the muscle synthesis ability-promoting agent of the present invention may be formulated by using the above-mentioned components according to a usual formulation method adopted in the pharmaceutical field.

Uses The muscle synthesis ability promoter of the present invention is used for the purpose of promoting muscle synthesis ability. Since the muscle synthesis ability promoter of the present invention promotes muscle synthesis ability by utilizing the action of promoting the expression of IGF-1, more specifically, the muscle synthesis ability promoter of the present invention is IGF-1. Can be used for objects that lack. IGF-1 decreases with age, and even those who are doing endurance training such as walking in their daily lives are deficient in IGF-1. The present invention is preferably applied to those who are deficient in such IGF-1.

In addition, the white muscle (fast muscle) is particularly mentioned as a muscle that declines with aging, and the gastrocnemius muscle is mentioned among the muscles of the lower limbs. Since the gastrocnemius muscle is a structure that extends from the top of the knee joint to the Achilles tendon, it is closely related to the movement of bending the knee, so people with a lack of gastrocnemius muscle tend to have difficulty bending the knee, that is, having difficulty raising the leg. It is in. The muscle synthesis ability promoter of the present invention can be used for the purpose of promoting the synthesis ability of the gastrocnemius muscle. The muscle synthesis ability promoter of the present invention can also be used for the purpose of promoting the synthesis ability of soleus muscle.

In addition, extracts of Chinese herbs such as Kami Shimotsuto have been applied to people with physical weakness, but the muscle synthesis ability promoter of the present invention is intended for subjects who are not physically weak, that is, healthy people, especially for physically weak people. It is also preferably applied to people aged 65 and over, that is, healthy elderly people. In addition, physical weakness is clear as a constitution to which Chinese herbal medicine is indicated.

Until now, when ingesting ingredients aimed at preventing or ameliorating muscle weakness, it has been a major premise to ingest a sufficient amount of protein (amino acid), which is a component of muscle, in order to obtain the effect. rice field. Specifically, the recommended amount of protein intake should be 60 g or more per day for men and 50 g or more per day for females in the case of 65 years or older. However, since the muscle synthesis ability promoter of the present invention enables efficient muscle synthesis by utilizing the action of promoting the expression of IGF-1, it is efficient from nutrition even if the protein intake is relatively low. Can build muscle. Therefore, the muscle synthesis promoter of the present invention is suitable for men aged 65 years or older and having a protein intake of less than 60 g per day, preferably 52 g or less, and women having a daily protein intake of less than 50 g, preferably 44 g or less. It is also preferably applied.

Dosage and Usage The muscle synthesis promoter of the present invention is used by oral administration. The dose of the muscle synthesis ability-promoting agent of the present invention is appropriately set according to the type of the Chinese herbal medicine, the age, constitution, degree of symptoms, etc. of the administration subject, and for example, the extract of the Chinese herbal medicine per day for humans. The amount of the extract powder is about 1000 to 10000 mg.

In the present invention, when Kami-shimotsuto is used as a herbal medicine, the dose of the muscle synthesis ability promoter is about 1500 to 8500 mg, preferably about 2000 to 6500 mg, more preferably about 2000 to 6500 mg in terms of the dry extract powder amount of the Kami-shimotsuto extract. An amount of about 2400 to 4500 mg, or an amount of about 6000 to 34000 mg, preferably about 8000 to 26000 mg, more preferably about 9600 to 18000 mg in terms of crude drug, 1 to 3 times a day, preferably 2 or 3 It should be taken as often as once. The timing of administration is not particularly limited and may be before meals, after meals, or between meals, but it is preferably before meals (30 minutes before meals) or between meals (2 hours after meals).

Further, since the effect of promoting the muscle synthesis ability by the muscle synthesis ability promoter of the present invention is exerted by continuous administration, the muscle synthesis ability promoter of the present invention is continuously taken (specifically,). It is preferable to take the drug continuously for 1 week or longer, preferably 2 weeks or longer).

Hereinafter, the present invention will be specifically described with reference to Examples, but the present invention is not limited to these Examples.

(1) Preparation of muscle synthesis ability promoter As raw material crude drugs, 1.5 parts by weight of Toki, 1.5 parts by weight of Kawakyu, 1.5 parts by weight of sardine, 1.5 parts by weight of ground yellow, 1.5 parts by weight of blue. , Wheat Mon Winter 2.5 parts by weight, Ginseng 1.2 parts by weight, Cow knee 1.25 parts by weight, Huang Kashiwa 0.75 parts by weight, Gomiko 0.75 parts by weight, Huangren 0.75 parts by weight, Chimo 0 Using .75 parts by weight and 0.75 parts by weight of Tochu, these were chopped and then extracted at about 100 ° C. for 1 hour using 10 times the weight of water and centrifuged to obtain an extract. Excipients were appropriately added to the extract, concentrated under reduced pressure, and dried using a spray dryer to obtain Kami-shimotsuto extract powder. The drying with a spray dryer was carried out by dropping the extract onto an atomizer having a rotation speed of 10000 rpm and supplying hot air with air at 150 ° C.

(2) Animal experiments Using aged model mice (C57BL / 6J mice, 72 weeks old, male, 6 per group), the control group was bred by freely feeding a diet with a protein content of 21.9% by weight every day. It was bred for 2 weeks. In addition to the normal diet, 1980 / kg of Kami-shimotsuto extract was orally administered daily to the Kami-shimotsuto extract-administered group and bred for 2 weeks. Normally, when examining the effect of promoting muscle synthesis in young mice, the protein content in the diet is adjusted to be 25% by weight or more so that sufficient protein intake can be obtained. The recommended protein intake in humans (males) is 65 g / day for ages 15-64 years, while the recommended protein intake for elderly people aged 65 years and older is 60 g / day, which is about 8% less. The protein amount of 21.9% by weight in the diet set in this test example is a low protein that is 12% or more less than the 25% by weight that is fed to normal young mice, and is a recommended protein for males aged 65 years or older. It corresponds to an amount less than 60 g / day.

After breeding for 2 weeks, the soleus muscle and gastrocnemius muscle were excised, the expression level of IGF-1 was analyzed, and the average value was used to set the expression level of IGF-1 in the control group to 100. Relative values were calculated. The results are shown in Tables 1 and 2.

As shown in Tables 1 and 2, a remarkable improvement in the expression level of IGF-1 was observed in the Kami-shimotsuto administration group, although the protein intake was not sufficient.

Claims (7)

A muscle synthesis promoter containing an extract of Chinese herbal medicine containing Toki, Kawakyu, Peony and Rehmannia glutinosa as constituent crude drugs. The muscle synthesis promoting agent according to claim 1, wherein the Chinese herbal medicine is Shimotsuto. The muscle synthesis ability promoter according to claim 1, wherein the Chinese herbal medicine is Kami Shimotsuto. The muscle synthesis ability promoter according to any one of claims 1 to 3, which promotes the synthesis ability of soleus muscle and / or gastrocnemius muscle. The muscle synthesis ability promoter according to any one of claims 1 to 4, which is used for a subject who is not physically weak. The muscle synthesis ability promoter according to any one of claims 1 to 5, which is used for a subject deficient in IGF-1. The muscle synthesis promoter according to any one of claims 1 to 6, which is used for a person aged 65 years or older and having a protein intake of less than 60 g per day for men and less than 50 g per day for females.