TNF-α production inhibitor and muscle degradation inhibitor

Abstract

To provide a TNF-α inhibitor and a muscle degradation inhibitor that exhibit enhanced effectiveness.SOLUTION: A TNF-α production inhibitor contains one or more selected from the group consisting of chamomile extract and Citrus junos extract. In addition, a muscle degradation inhibitor contains one or more selected from the group consisting of chamomile extract and Citrus junos extract.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a TNF-α production inhibitor, a muscle degradation inhibitor, and the like. [Background technology]

[0002] In the bodies of mammals, including humans, myoblasts differentiate into myotubes, which fuse to form muscle fibers, and connective tissue fills the spaces between these cells to form muscle bundles, which then assemble to form muscles. Muscles play an important role in energy metabolism, the uptake of sugars and other substances into the body, daily movements such as walking and maintaining posture, and physical activities such as exercise, but they are known to decrease with age.

[0003] The health of muscle tissue plays an important role in the progression of aging and various diseases. TNF-α (tumor necrosis factor alpha) causes muscle weakness and makes recovery difficult. Age-related muscle atrophy not only leads to a decline in physical function, but also to cosmetic problems such as sunken eyes and sagging skin due to weakening of facial muscles.

[0004] TNF-α is known to be involved not only in muscle weakness but also in immune diseases such as rheumatoid arthritis, Crohn's disease, psoriasis, and atopic dermatitis.

[0005] Currently, research and treatments specifically targeting TNF-α inhibition are limited, and new insights and therapeutic approaches are needed in this field.

[0006] Patent Document 1 (JP 2010-116348 A) discloses that extracts of purple mokwangju, phloxacinth, and russet mokwangju have anti-inflammatory and anti-aging effects that suppress the production of TNF-α. However, these effects are not sufficient, and there is a need to explore components with stronger effects in suppressing TNF-α production and muscle breakdown, as well as to develop topical and oral products that have the effects of suppressing TNF-α production and muscle breakdown. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] Patent Publication No. 2010-116348 Summary of the Invention [Problem to be solved by the invention]

[0008] An object of the present invention is to provide a more effective TNF-α inhibitor and a more effective muscle degradation inhibitor. [Means for solving the problem]

[0009] The present inventors have discovered that chamomilla extract and / or yuzu extract have the effect of suppressing TNF-α. They have also discovered that combining these ingredients produces a more effective effect than using each ingredient alone. The present invention is based on this finding and provides the following inventions.

[0010] [1] A TNF-α production inhibitor containing one or more extracts selected from the group consisting of chamomilla extract and yuzu extract. [2] A muscle degradation inhibitor containing one or more selected from the group consisting of chamomilla extract and yuzu extract. [3] An external preparation for preventing or improving hollows around the eyes, sagging cheeks, facial sagging, or facial thinning, containing one or more extracts selected from the group consisting of chamomile extract and yuzu extract. [4] An external preparation for preventing or ameliorating immune diseases, comprising one or more selected from the group consisting of chamomilla extract and yuzu extract. [5] The topical preparation according to [4], wherein the immune disease is atopic dermatitis and / or psoriasis. [6] The agent according to any one of [1] to [5], wherein the chamomilla extract is derived from chamomilla flowers. [7] The agent according to any one of [1] to [6], wherein the yuzu extract contains ceramide. [8] The agent according to any one of [1] to [7], wherein the content ratio of chamomilla extract to yuzu extract is 1:100 to 200:1. [Effects of the Invention]

[0011] According to the present invention, the use of chamomilla extract and / or yuzu extract contributes to the suppression of TNF-α production and muscle breakdown, thereby maintaining the health of muscle tissue and preventing or improving hollows around the eyes, sagging of the face, and the like.

[0012] According to the present invention, by using chamomilla extract and / or yuzu extract, it is possible to suppress the production of TNF-α and prevent or improve immune diseases such as rheumatoid arthritis, Crohn's disease, psoriasis, and atopic dermatitis. [Brief explanation of the drawings]

[0013] [Figure 1] 1 shows the results of a TNF-α production inhibition test in Test Example 1. DETAILED DESCRIPTION OF THE INVENTION

[0014] Hereinafter, embodiments of the present invention will be described in detail, but the present invention is not limited to the following embodiments.

[0015] In this specification, when the expression "X to Y" (X and Y are any numbers) is used, unless otherwise specified, it includes the meaning of "X or more and Y or less," as well as "preferably larger than X" or "preferably smaller than Y." Furthermore, in this specification, unless otherwise specified, "α and / or β" (α and β are optional structures or components) means three combinations: "α only," "β only," and "both α and β." In addition, in the present specification, with respect to the numerical ranges described in stages, the upper or lower limit of a certain stage can be arbitrarily combined with the upper or lower limit of another stage. Furthermore, in the numerical ranges described in this specification, the upper or lower limit of the numerical range can also be replaced with the values ​​shown in the examples or formulation examples.

[0016] [Application] The TNF-α production inhibitor of the present invention has an inhibitory effect on the production of TNF-α, an inflammatory cytokine. Therefore, in one embodiment, it can be used as a muscle inflammation inhibitor or muscle degradation inhibitor, thereby preventing muscle atrophy, degradation, and inflammation. Although not limited thereto, the muscle inflammation inhibitory effect and muscle degradation inhibitory effect of the present invention can lead to applications for the prevention and / or treatment of sarcopenia, locomotive syndrome, and physical frailty, particularly those associated with aging. Furthermore, although not limited thereto, the above effects of the present invention can lead to applications for suppressing subcutaneous muscle atrophy, preventing and / or improving hollows around the eyes, wrinkles and sagging skin, and loss of firmness and elasticity. In particular, with regard to the face, weakening of the orbicularis oculi and facial muscles associated with aging causes the skin to sink along the shape and hollows of the skull, creating shadows that give the impression of being older to those around, making these changes in appearance more noticeable. Therefore, in one embodiment, the present invention can be used to prevent and / or improve hollows in the eyelids, sagging and puffy under-eye bags and bags under the eyes, and wrinkles and sagging at the corners of the eyes. Although not limited thereto, the skin around the eyes is particularly thin, so significant effects in preventing and / or improving changes in appearance are expected. Although not limited thereto, the present invention, due to its muscle inflammation inhibitory effect, can lead to applications in preventing and / or improving muscle fatigue, muscle pain, muscle tiredness, and the like.

[0017] In another embodiment, the TNF-α production inhibitor of the present invention has an effect of suppressing the production of TNF-α, an inflammatory cytokine, and is expected to be highly effective in preventing and / or improving psoriasis by calming inflammation in the affected area and suppressing the excessive proliferation of keratinocytes. Psoriasis is known to be associated with abnormalities in immune function, and the present invention may also be effective against such immune diseases.

[0018] In another embodiment, the TNF-α production inhibitor of the present invention has an inhibitory effect on the production of TNF-α, an inflammatory cytokine, and is expected to be highly effective in preventing and / or ameliorating atopic dermatitis by suppressing inflammation in the affected area, improving the skin's barrier function, and suppressing itching. Atopic dermatitis is known to be associated with abnormalities in immune function, and the present invention can also be effective against such immune diseases.

[0019] <1. TNF-α production inhibitor, muscle breakdown inhibitor, topical agent> The TNF-α production inhibitor and muscle degradation inhibitor according to this embodiment contain one or more extracts selected from the group consisting of chamomilla extract and yuzu extract.

[0020] [Chamomilla extract] Chamomilla extract refers to an extract of chamomilla (also known as chamomile or camomile), a plant belonging to the Asteraceae family. In this specification, the parts of the plant from which the extract is derived may include, for example, leaves, flowers, nuts, roots, stems, bark, branches, fruits, pericarp, and seeds. Any part may be used, and one or more parts may be selected for use. Although not limited, the part extracted from chamomilla is preferably an extract of the flower. The extraction method and extraction solvent for chamomilla are not particularly limited, and known techniques can be used. The extract may be used as is, or may be dried into powder or granules, or a decomposition product obtained by treating the extract using known techniques such as enzymatic hydrolysis. Although not limited, an extract extracted with water, aqueous ethanol, or ethanol is preferred. Commercially available products can also be used. Examples of such products include "Chamomile Extract" and "Chamomile Extract BG-J" manufactured by Maruzen Pharmaceutical Co., Ltd. or Iwase Cosfa Co., Ltd., and "Chamomile Liquid" manufactured by Ichimaru Pharcos Co., Ltd. In addition to these, products marketed under the names Chamomile Extract (1) and Chamomile Water can also be used.

[0021] The content of chamomilla extract in the TNF-α production inhibitor and muscle degradation inhibitor according to this embodiment is not particularly limited as long as it is within a range that exhibits the TNF-α production inhibitory effect, and is set appropriately depending on the types and contents of other ingredients, the formulation form of the TNF-α production inhibitor, etc. From the perspective of more significantly exhibiting the effects of the present invention, the content of chamomilla extract can be, for example, 0.00001% by mass or more, 0.00005% by mass or more, 0.0001% by mass or more, 0.0005% by mass or more, 0.001% by mass or more, 0.005% by mass or more, 0.01% by mass or more, 0.05% by mass or more, etc., relative to the total amount (100% by mass) of the formulation. The content of chamomilla extract may be, for example, 10% by mass or less, 7% by mass or less, 5% by mass or less, 4% by mass or less, 3% by mass or less, 2% by mass or less, 1% by mass or less, 0.5% by mass or less, 0.1% by mass or less, etc., relative to the total amount (100% by mass) of the formulation. In one embodiment, the content of chamomilla extract is, for example, preferably 0.00001 to 5% by mass, more preferably 0.00005 to 3% by mass, even more preferably 0.0001 to 1% by mass, and particularly preferably 0.0005 to 0.1% by mass, relative to the total amount (100% by mass) of the formulation.

[0022] From the viewpoint of more significantly achieving the effects of the present invention, the dosage of chamomilla extract to humans is, for example, preferably 0.001 to 2000 mg per day, more preferably 0.01 to 1000 mg, even more preferably 0.1 to 500 mg, and particularly preferably 1 to 300 mg.

[0023] [Yuzu extract] Yuzu extract refers to the fruit of the citrus fruit, which belongs to the Rutaceae family. The yuzu extraction method and extraction solvent are not particularly limited, and known techniques can be used. The extract may be used as is, or dried powder or granules may be used, or a hydrolyzed product obtained by treating the extract using known techniques such as enzymatic hydrolysis may also be used. Although not limited, extracts extracted with water or 1,3-butylene glycol are preferred. Commercially available products can also be used, such as "Yuzu Ceramide B" and "Falcorex Yuzu E" from Ichimaru Pharcos Co., Ltd., and "Waism (registered trademark) <Tosa Yuzu>" from Maruzen Pharmaceuticals. Other commercially available products include those marketed under the names yuzu fruit extract and yuzu ceramide.

[0024] The yuzu extract used in the present invention is not limited, but is preferably an extract containing ceramide, and more preferably contains the ceramide identified as C24-ceramide (CAS No. 34435-05-7).

[0025] The content of yuzu extract in the TNF-α production inhibitor and muscle degradation inhibitor according to this embodiment is not particularly limited as long as it is within a range that exhibits TNF-α production inhibitory activity, and is set appropriately depending on the types and contents of other formulated ingredients, the formulation form of the TNF-α production inhibitor, etc. From the perspective of more significantly exhibiting the effects of the present invention, the content of yuzu extract can be, for example, 0.000001% by mass or more, 0.000005% by mass or more, 0.00001% by mass or more, 0.00005% by mass or more, 0.0001% by mass or more, 0.0005% by mass or more, 0.001% by mass or more, 0.005% by mass or more, etc., relative to the total amount of the formulation (100% by mass). The content of the yuzu extract may be, for example, 10% by mass or less, 7% by mass or less, 5% by mass or less, 4% by mass or less, 3% by mass or less, 2% by mass or less, 1% by mass or less, 0.5% by mass or less, 0.1% by mass or less, 0.05% by mass or less, 0.01% by mass or less, etc., relative to the total amount (100% by mass) of the formulation. In one embodiment, the content of the yuzu extract is, for example, preferably 0.000001 to 5% by mass, more preferably 0.000005 to 1% by mass, even more preferably 0.00001 to 0.1% by mass, and particularly preferably 0.00005 to 0.01% by mass, relative to the total amount (100% by mass) of the formulation.

[0026] From the viewpoint of more significantly achieving the effects of the present invention, the dosage of yuzu extract to humans is, for example, preferably 0.001 to 2000 mg per day, more preferably 0.01 to 1000 mg, even more preferably 0.1 to 500 mg, and particularly preferably 1 to 300 mg.

[0027] In the TNF-α production inhibitor and muscle degradation inhibitor according to this embodiment, chamomilla extract and yuzu extract can be used in combination. The content ratio (mass %) of chamomilla extract to yuzu extract in the entire formulation is not limited, but can be, for example, 1:100 to 200:1, preferably 1:50 to 180:1, more preferably 1:10 to 150:1, even more preferably 1:5 to 120:1, and particularly preferably 1:1 to 100:1.

[0028] In addition, when various extracts are formulated in the form of a solution in this topical skin preparation, the content of each extract in this topical skin preparation means the pure content of the extract, and is calculated by multiplying the liquid volume of the solution by the concentration of the extract in that solution.

[0029] The TNF-α production inhibitor and muscle degradation inhibitor according to this embodiment may further contain additives such as excipients, thickeners, binders, disintegrants, dispersants, surfactants, suspending agents, emulsifiers, stabilizers, gelling agents, sweeteners, sour agents, umami agents, salty agents, bitter agents, colorants, UV protection agents, antioxidants, preservatives, antibacterial agents, pH adjusters, buffers, chelating agents, vitamins, flavorings, minerals, amino acids or salts thereof, sugars, moisturizers, organic acids or salts thereof, dietary fiber, plant extracts excluding chamomilla and yuzu, animal tissue extracts, etc. These may be appropriately selected from known substances and can be produced using conventional methods.

[0030] The dosage form of the TNF-α production inhibitor and muscle degradation inhibitor according to this embodiment is not limited to a specific product or property, and can be prepared as appropriate by known methods in any dosage form, such as liquid, gel, cream, paste, solid, aerosol, or patch. Examples of liquid forms include lotions, emulsions, serums, oral liquids, and syrups. Examples of solid forms include sticks, tablets, chewable preparations, granules, powders, capsules, and ointments. Furthermore, while the dosage form may be either an external or internal preparation, external preparations are preferred from the viewpoint of achieving the effects of the present invention. External preparations may be pharmaceuticals or cosmetics, and are not limited to these. These can be prepared using conventional methods.

[0031] <2. External products> The topical product according to this embodiment has the effect of inhibiting TNF-α production, and is expected to have the effects of inhibiting muscle breakdown and muscle atrophy, as well as the effects described above in the section "Uses." Therefore, one embodiment of the present invention provides an topical product for inhibiting TNF-α production and muscle breakdown, which contains one or more extracts selected from the group consisting of chamomilla extract and yuzu extract.

[0032] In this embodiment, the content of one or more selected from the group consisting of chamomilla extract and yuzu extract, the types and contents of other ingredients, the formulation and use of the external product, etc. are as explained in <1. TNF-α production inhibitor and muscle degradation inhibitor>.

[0033] <3.Food and beverage products〕> The food and beverage product according to this embodiment has the effects of inhibiting TNF-α production and muscle degradation, as well as the effects described above in the section "Uses." Therefore, one embodiment of the present invention provides a food and beverage product for inhibiting TNF-α production and muscle degradation, which contains one or more extracts selected from the group consisting of chamomilla extract and yuzu extract.

[0034] In this embodiment, the content of one or more selected from the group consisting of chamomilla extract and yuzu extract, the types and contents of other ingredients, the formulation and use of the external product, etc. are as explained in <1. TNF-α production inhibitor and muscle degradation inhibitor>. [Example]

[0035] The present invention will be specifically described below based on test examples, but the present invention is not limited to these. Furthermore, the amounts of ingredients in the following test examples are expressed in mass % unless otherwise specified. Furthermore, the test conditions, such as culture conditions, in each test example were the same except for the plant extract added, unless otherwise specified. Furthermore, a control without added plant extract was used in every test to accurately evaluate the effects of the plant extract of the present invention.

[0036] [Test Example 1: TNF-α production inhibition test] In this study, the following procedure was used to evaluate the TNF-α inhibitory effects of chamomilla extract and yuzu extract.

[0037] Raw264.7 cells were used in DMEM (Thermo Fisher Scientific) supplemented with 10% bovine serum (Thermo Fisher Scientific) and 1% antibiotics (Fujifilm Wako Pure Chemical Industries, Ltd.). 1.8 × 10 5 The cells were seeded into a 96-well plate at a density of 200 μl / well and cultured at 37°C in an atmosphere of 5% carbon dioxide and 95% air for 24 hours. The medium was then removed, and serial dilutions of chamomilla extract and yuzu extract were added to medium containing 0.2% bovine serum alone, and the cells were cultured for another 24 hours. Next, 0.05 ng / mL lipopolysaccharide (LPS; Fujifilm Wako Pure Chemical Industries, Ltd.) was added, and the cells were cultured for another 24 hours. After the culture, the culture supernatant was collected and used as a sample for TNF-α measurement.

[0038] TNF-α was measured based on the enzyme-linked immunosorbent assay (hereinafter referred to as ELISA) method using a TNF-α ELISA kit (manufactured by R&D Systems).

[0039] Next, we evaluated the inhibitory effects of chamomilla extract and yuzu extract on TNF-α production in the presence of LPS (0.05 ng / ml). Chamomilla extract and yuzu extract were added to RAW264.7 cells, and the amount of TNF-α produced was measured both alone and in combination. The results are shown in Figure 1.

[0040] As shown in Figure 1, compared to the LPS-only group, TNF-α production was suppressed when chamomilla extract or yuzu extract was added alone. Furthermore, when chamomilla extract and yuzu extract were used in combination, an even stronger inhibitory effect on TNF-α production was observed.

[0041] Specifically, if the TNF-α production rate in the control group was taken as 100%, it was suppressed to approximately 160% in the LPS-only group, approximately 80% in the chamomilla extract group, approximately 60% in the yuzu extract group, and approximately 50% in the group given a combination of chamomilla extract and yuzu extract.

[0042] These results suggest that the combined use of chamomilla extract and yuzu extract has the effect of suppressing LPS-induced inflammatory responses, and is expected to be useful as an anti-inflammatory agent.

[0043] In order to maintain and improve health and appearance, it is important to regulate the quantity and quality of muscles throughout the body, and it is also important to regulate the quantity and quality of muscles required for the proper functioning of each part of the body.

[0044] Appropriately suppressing inflammation in various parts of the body is important for preventing and improving immune diseases, as it can prevent immune dysfunction caused by prolonged inflammation.

[0045] Suppressing inflammation that occurs in the skin of various parts of the body is important for preventing and improving psoriasis and atopic dermatitis, as well as for preventing and / or improving unpleasant symptoms that interfere with daily life, such as body itching, and for improving the appearance of skin, such as scaling, desquamation, lichenification, and pigmentation.

[0046] According to the present invention, the production of TNF-α can be suppressed by one or more members selected from the group consisting of chamomilla extract and yuzu extract, thereby suppressing muscle atrophy, decomposition, and inflammation.

[0047] According to the present invention, the production of TNF-α can be suppressed by one or more selected from the group consisting of chamomilla extract and yuzu extract, and thus immune diseases can be prevented and / or improved. In particular, when applied to the skin, psoriasis and atopic dermatitis can be prevented and / or improved.

Claims

1. A TNF-α production inhibitor containing at least one extract selected from the group consisting of chamomilla extract and yuzu extract.

2. A muscle degradation inhibitor containing one or more extracts selected from the group consisting of chamomilla extract and yuzu extract.

3. The external preparation for preventing or improving hollows around the eyes, sagging cheeks, facial sagging, or facial thinning contains one or more selected from the group consisting of chamomile extract and yuzu extract.

4. An external preparation for preventing or ameliorating immune diseases, comprising one or more extracts selected from the group consisting of chamomilla extract and yuzu extract.

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