KR20220105360A - Composition for preventing or improving muscular strength reduction, sarcopenia comprising vitexin as an active ingredient - Google Patents

Abstract

The present invention relates to a composition for preventing, alleviating or treating muscle strength reduction or sarcopenia. Specifically, the present invention relates to a pharmaceutical composition for preventing, alleviating or treating muscle strength reduction or sarcopenia comprising vitexin as an active component or a food composition for preventing or alleviating muscle strength reduction or sarcopenia, which can effectively prevent and alleviate sarcopenia.

Description

Composition for preventing or improving muscular strength reduction or sarcopenia comprising vitexin as an active ingredient {Composition for preventing or improving muscular strength reduction, sarcopenia comprising vitexin as an active ingredient}

The present invention relates to a composition capable of preventing or improving muscle strength reduction or sarcopenia, and specifically, a pharmaceutical composition for preventing, improving or treating reduced muscle strength or sarcopenia comprising vitexin as an active ingredient, or reduced muscle strength or muscle weakness It relates to a food composition for preventing or improving hypothyroidism.

Skeletal muscle is the largest organ in the human body, accounting for 40-50% of the total body weight, and plays an important role in various metabolic functions in the body, including energy homeostasis and thermogenesis. Human muscle decreases by more than 1% every year from the age of 40, and at the age of 80, the level of 50% of the maximum muscle mass decreases. As aging progresses, it is recognized that body shape changes such as muscle and fat content and skeletal distortion. In the case of abnormal insulin secretion, the cells cannot properly supply energy, which can lead to muscle development disorders. In addition, muscle loss causes arthritis, back pain, and chronic pain to increase further, and can worsen urinary incontinence due to abdominal obesity. Sarcopenia is a major cause of lowering the quality of life associated with various diseases.

Sarcopenia is known to be closely related to geriatric chronic diseases such as osteoporosis, insulin resistance and arthritis, and it is possible to suppress the decrease in physical activity due to aging through the prevention or improvement of sarcopenia. The global progressive ataxia and muscle weakness treatment market was valued at about $14 billion in 2011, and after that, it is expected to grow at a compound annual growth rate of 9.4% to reach about $23.5 billion in 2017. As a treatment for sarcopenia, increased mitochondrial production, inhibition of muscle protein degradation, and anti-inflammatory drugs have been suggested, but there is no clear therapeutic agent. Recently, many people are choosing protein supplements as an alternative. Moreover, if you have kidney disease, you cannot eat a high-protein diet, and kidney function also decreases with aging.

On the other hand, Vitexin is also known as Apigenin-8-C-D glucopyranoside and apigenin flavone glucoside, and is known to have antibacterial effects against Staphylococcus aureus, Typhoid bacillus, Escherichia coli, and the like. In addition, it has strong antioxidant properties due to flavone chemicals, and is known to exhibit the effect of inhibiting inflammation and oxidative stress and promoting carbohydrate metabolism. However, the effect of reducing muscle strength and preventing or improving sarcopenia of vitexin is not known, and the present inventors have completed the present invention by confirming the effect of reducing muscle strength and preventing and improving sarcopenia of vitexin.

Registered Patent Publication No. 10-2087432 Laid-Open Patent Publication No. 10-2020-0114852

In order to solve the above problems, the present invention is to provide a pharmaceutical composition for the prevention, improvement or treatment of muscle weakness or sarcopenia, or a food composition for preventing or improving muscle strength reduction or sarcopenia, comprising vitexin as an active ingredient. .

In addition, an object of the present invention is to provide a method for preparing a pharmaceutical composition for preventing, improving or treating muscle weakness or sarcopenia, or a food composition for preventing or improving muscle strength reduction or sarcopenia, comprising vitexin as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing, improving or treating muscle weakness or sarcopenia, or a food composition for preventing or improving muscle strength reduction or sarcopenia, comprising vitaxin as an active ingredient.

In addition, there is provided a method for preparing a composition for preventing or improving muscle strength reduction and sarcopenia comprising vitexin as an active ingredient.

In the present invention, the Vitexin (Vitexin) is included in 0.5 to 10% by weight, preferably 1 to 8% by weight, more preferably 5 to 6% by weight relative to the total weight of the composition. If it is less than the above range, the effect of reducing muscle strength, preventing or improving sarcopenia is insignificant, and if it exceeds the above range, there is a risk of toxicity.

The composition may further include any one or more of agnuside and anethole as an active ingredient. In this case, the agnerside may be included in an amount of 1 to 5% by weight, preferably 2 to 3% by weight, based on the total weight of the composition. If it is less than the above range, the effect of reducing muscle strength, preventing or improving sarcopenia is insignificant, and if it exceeds the above range, there is a risk of toxicity.

The anetol may be included in an amount of 0.5 to 10% by weight, preferably 1 to 7% by weight, and more preferably 3 to 4% by weight based on the total weight of the composition. If it is less than the above range, the effect of reducing muscle strength, preventing or improving sarcopenia is insignificant, and if it exceeds the above range, there is a risk of toxicity.

The active ingredient is not limited, but preferably may be extracted from the fruit, leaf, flower, seed, root, stem, branch or bark of the chastity tree, more preferably, it may be extracted from the fruit of the chastity tree .

In addition, the composition may further include a chastity tree extract. The chastity tree extract may be included in an amount of 10 to 80% by weight based on the total weight of the composition, but is not limited thereto. When included below the above range, the effect of reducing muscle strength, preventing or improving sarcopenia is insignificant, and when it exceeds the above range, there is a risk of toxicity.

The chastity tree extract may be extracted from the fruit, leaf, flower, seed, root, stem, branch or bark of the chastity tree, and preferably may be extracted from the fruit of the chastity tree.

The extraction solvent of the chrysanthemum extract is not limited, but preferably 30 to 70% (v/v) ethanol, more preferably 50% (v/v) ethanol. When extracting with the solvent, it is economical and has the advantage of maximizing the extracted active ingredient.

In the present invention, the decrease in muscle strength means a state in which the strength of one or more muscles is reduced. The decrease in muscle strength may be limited to any one muscle, one side of the body, upper or lower extremities, or the like, or may appear throughout the body. In addition, subjective muscle weakness symptoms, including muscle fatigue and muscle pain, can be quantified objectively through physical examination.

The muscle weakness symptoms refer to all diseases that may occur due to muscle weakness, for example, sarcopenia, muscular atrophy, muscle dystrophy, or cardiac atrophy, but is not limited thereto.

In the present invention, sarcopenia refers to a gradual decrease in skeletal muscle mass with aging, which directly causes a decrease in muscle strength, and as a result, refers to a state that can cause a decrease in various bodily functions and disorders.

The composition for preventing or improving muscle strength reduction and sarcopenia according to the present invention is a food composition or a pharmaceutical composition, and the food composition is meant to include a health functional food composition.

The composition for preventing, improving or treating muscle weakness, sarcopenia according to the present invention is a pharmaceutically acceptable carrier, binder, lubricant, disintegrant, excipient, solubilizer, dispersing agent, stabilizing agent, suspending agent, etc. in addition to the above active ingredients. may further include, for example, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, malditol, starch, alginate, calcium phosphate, calcium silicate, maltodextrin, silicon dioxide, cellulose, Methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, etc., but is not limited thereto.

In addition, the pharmaceutical composition may be prepared in the form of tablets, capsules, sustained-release preparations, elixirs, suspensions, syrups, wafers, unit dose injection ampoules, suspensions, etc. by methods commonly used for formulation in the art.

The administration method of the pharmaceutical composition is oral administration, intravenous administration, intramuscular administration, intraarterial administration, intramedullary administration, intrathecal administration, intracardiac administration, transdermal administration, subcutaneous administration, intraperitoneal administration, intranasal administration, enteral administration It may be administered by methods such as topical administration, rectal administration, topical administration, dermal administration, mucosal administration, intravertebral administration, etc., including oral and sublingual administration, and preferably oral administration, but is not limited thereto. In addition, at the time of administration, it may be formulated and administered in a formulation appropriate for each administration method, and the formulation may be formulated by a method well known in the art.

The pharmaceutical composition may be appropriately selected according to the age, weight, health status, sex, administration time, administration route, excretion rate, content of active ingredient, severity of a specific disease to be prevented or treated, etc. of the subject to be administered, and the number of administration is 1 Administration may be performed once or twice a day, every other day, every other week, every other month, or the like.

In addition, the food composition may further include flavoring agents, flavoring agents, stabilizers, thickeners, preservatives, etc. commonly used in the art for preparing food, for example, lactose, dextrose, water Crose, sorbitol, mannitol, xylitol, erythritol, malditol, starch, alginate, calcium phosphate, calcium silicate, maltodextrin, silicon dioxide, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, methylhydroxybenzoate, It may be propylhydroxybenzoate, talc, magnesium stearate, etc., but is not limited thereto.

The food composition may be prepared in the form of beverages, gums, tea, vitamin complexes, powders, granules, tablets, capsules, confectionery, and the like.

The food composition may be appropriately selected according to the age, weight, health condition, sex, administration time, content of active ingredient, severity of disease, etc. of the ingestion target, and the number of intakes is once or twice a day, every other day, It can be taken every other week, every other month, etc.

The active ingredient of the composition for reducing muscle strength, preventing or improving sarcopenia according to the present invention may be a commercially available one, but it may be prepared by a method comprising the following steps when extracted from a chastity tree;

(a) extraction step;

(b) filtration and concentration steps;

The (a) extraction step is a step of extracting the active ingredient from the fruit, leaf, flower, seed, root, stem, branch or bark of the chastity tree as a raw material.

2 to 4 times, preferably 3 times the weight of the raw material can be extracted by adding an extraction solvent, and the extraction temperature is 85 to 95°C, preferably 90°C, and the extraction time is 1 to 4 hours, preferably 2 ~3 hours, the extraction steam pressure is 1 kg/cm ² or less, preferably 0.5 kg/cm ² or less can be extracted. When the extraction is less than the condition range, the active ingredient may not be well extracted, and when the extraction exceeds the condition range, the active ingredient may be destroyed or the impurities may be extracted together.

0.1 내지

3 ㎛, 바람직하게는

0.5 내지

1.5㎛일 수 있다. 필터 규격이 상기 범위 미만이면 불순물이 제대로 여과되지 않을 수 있고, 상기 범위를 초과하는 경우, 유효성분이 제대로 여과되지 않을 수 있다.In the (b) filtration and concentration step, the filtration is not limited, but a cartridge filter may be preferably used, and the filter specification is

0.1 to

3 μm, preferably

0.5 to

It may be 1.5 μm. If the filter specification is less than the above range, impurities may not be properly filtered, and if it exceeds the above range, the active ingredient may not be properly filtered.

The concentration is not limited, but preferably concentration under reduced pressure. The concentration temperature is 85 to 95 ℃, preferably 90 ℃, the pressure can be concentrated at 500 ± 30mmHg. If the above conditions are exceeded, the concentration may not be properly performed or the concentration may be over-concentrated.

When preparing a pharmaceutical composition or food composition for preventing or improving muscle strength reduction or sarcopenia by using the active ingredient obtained through the above step, the following steps may be further included;

(c) mixing an excipient;

(d) drying step.

The (c) excipient mixing step is a step of mixing excipients (including carriers, binders, lubricants, disintegrants, solubilizers, dispersants, stabilizers, suspending agents, etc.) with the prepared active ingredient.

The (d) drying step is a step of drying the mixture prepared by the step (c), and the drying method is not limited, but may preferably be a freeze-drying method, and the freezing temperature may be -18°C or less.

The composition prepared through the above step is a mixture of dry extract: dextrin in a weight ratio of 1: 0.5 to 3, preferably 1:1.

The present invention relates to a composition capable of preventing or improving muscle strength reduction or sarcopenia, and specifically, a pharmaceutical composition for preventing, improving or treating reduced muscle strength or sarcopenia comprising vitexin as an active ingredient, or reduced muscle strength or muscle weakness It is possible to provide a food composition for preventing or improving hypothyroidism.

Hereinafter, the present invention will be described in detail by way of Examples and Experimental Examples.

However, the following Examples and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following Examples and Experimental Examples.

<Production of Vitexin>

Vitaxin was extracted from the fruit of the chastity tree as a raw material. The specific method proceeded as follows;

0.5 내지

1.5㎛의 카트리지 필터를 사용하여 여과하였고, 90℃, 500 ± 30mmHg 압력 하에 감압농축시켜 최종적으로 바이텍신을 수득하였다. The chastity tree fruit was prepared and extracted using ethanol 50% (v/v) three times the weight of the chastity tree fruit as a solvent. The extraction temperature was 90° C., and the extraction time was 1 kg/cm ² or less under steam pressure for 2-3 hours. after

0.5 to

It was filtered using a cartridge filter of 1.5㎛, and concentrated under reduced pressure under a pressure of 90 ℃, 500 ± 30mmHg to finally obtain a vitaxin.

<Examples 1 to 5>

The vitaxin obtained as described above was prepared to contain 1, 3, 5, 7, and 10 wt%, respectively.

Vitexin content (% by weight) division One Example 1 3 Example 2 5 Example 3 7 Example 4 10 Example 5

<Experimental Example 1> Evaluation of sarcopenia improvement effect

The effects on myogenic activity were evaluated using Examples 1 to 5 above. For the evaluation method, muscle cells L6 myoblast (ATCC CRL-1458, Manassas, VA, USA) were mixed with Dulbecco's modified Eagle's media (DMEM; Hyclone) containing 10% fetal bovine serum (FBS; Hyclone, Logan, UT, USA) and Together, it was put in a 6-well plate so as to become 2 X ^{10 5} cell/ml. When the cell density reached about 80 to 85%, the medium in the well was removed and cells were treated with Examples 1 to 5 in DMEM (Hyclone) containing 2% horse serum (HS; Hyclone) to induce myotube differentiation. induced. At this time, the group treated with Schisandra extract, which was recognized as a functional raw material for improving muscle strength, instead of the sample was used as a control group. After differentiation was carried out for 6 days, the proteinase inhibitor cocktail was dissolved in NP-40 buffer (ELPIS-Biotech, Daejeon, Korea). The cells dissolved in the buffer were transferred to a 1.5 ml tube and centrifuged at 13,000 rpm for 10 minutes to take only the supernatant. The supernatant was quantified using the Bradford (Bradford, Bio-Rad Laboratories Inc., Hercules, CA, USA) method. After boiling for 5 minutes, the quantified protein was separated by electrophoresis using 10% SDS PAGE, and the separated proteins were transferred to a nitrocellulose membrane. The p-mTOR primary antibody (Cell signaling technology, Beverly, MA, USA) was diluted 1:1000 in 2.5% bovine serum albumin (BSA) and reacted with the protein transferred to the nitrocellulose membrane at room temperature for 20 hours. . After reacting with the primary antibody, the nitrocellulose membrane was washed 3 times for 10 minutes using Trisbuffer Saline Tween20 (TBST). After washing, an anti-rabbit secondary antibody conjugated with horseradish peroxidase that recognizes the primary antibody (Bethyl Laboratories, Inc., Montgomery, TA, USA) was diluted 1:5000 in 2.5% BSA to be mixed with a nitrocellulose membrane and 2 The reaction was carried out at room temperature for a period of time and washed three times for 10 minutes each using TBST. The protein band was developed using ECL western blotting detection reagents (Amersham, Tokyo, Japan), and the colored protein band was confirmed using the G;BOX EF imaging system (Syngene, Cambridge, UK). As a result, it was confirmed that the expression level of p-mTOR in L6 muscle cells was increased in the experimental group treated with Examples 2 to 4, and in particular, the expression level was significantly increased in the experimental group treated with Example 3. On the other hand, the expression level of the Schisandra extract treated group did not significantly increase.

<Experimental Example 2> Effect of muscle differentiation activity evaluation

After culturing L6 myoblast (ATCC), a muscle cell, in the same manner as in Experimental Example 1, Examples 1 to 5 were dissolved in DMEM (Hyclone) containing 2% HS (Hyclone) at a concentration of 10 μg/mL. Then, the cells were treated to induce myotube differentiation. At this time, the group treated with Schisandra extract, which was recognized as a functional raw material for improving muscle strength, instead of the sample was used as a control group. After differentiation was carried out for 6 days, RT-PCR was performed in the same manner as in Experimental Example 1. As a result, in the experimental group treated with Examples 2 to 4, the mRNA expression of MyoD and myogenin was increased in L6 muscle cells, and in particular, the expression level in Example 3 was high. On the other hand, the expression level of the Schisandra extract treated group did not significantly increase. This means that the composition comprising the vitaxin according to the present invention has an excellent ability to promote muscle differentiation in muscle cells.

Claims (9)

A composition for preventing or improving muscle strength reduction and sarcopenia comprising vitexin as an active ingredient. According to claim 1, wherein the vitaxin composition for the prevention or improvement of muscle strength loss, sarcopenia, characterized in that 0.5 to 10% by weight relative to the total weight of the composition is included. According to claim 1, wherein the composition further comprises any one or more of agnerside and anetol as an active ingredient, the composition for the prevention or improvement of muscle weakness, sarcopenia. The method according to claim 3, wherein the agnerside is contained in an amount of 1 to 5% by weight based on the total weight of the composition, and 1 to 7% by weight of the anetol based on the total weight of the composition. composition. According to claim 1, wherein the active ingredient is a composition for preventing or improving muscle strength, sarcopenia, characterized in that extracted from the fruit, leaf, flower, seed, root, stem, branch or bark of a chastity tree. According to claim 1, wherein the composition is a composition for preventing or improving muscle strength, sarcopenia, characterized in that it further comprises an extract of chrysanthemum tree additionally. The composition for preventing or improving muscle strength, sarcopenia, according to claim 6, wherein the chastity tree extract is included in an amount of 10 to 80% by weight. [Claim 7] The composition for the prevention or improvement of muscle weakness and sarcopenia according to claim 6, wherein the chastity tree extract is extracted with 30 to 70% (v/v) ethanol. According to claim 1, wherein the composition is a food composition or a pharmaceutical composition, characterized in that the composition for the prevention or improvement of muscle weakness, sarcopenia.