JP2022006753A - Blood vessel wall reinforcer - Google Patents

Abstract

To provide a blood vessel reinforcer.SOLUTION: A blood vessel wall reinforcer contains soybean protein and/or ergothioneine.SELECTED DRAWING: None

Description

The present invention relates to a blood vessel wall strengthening agent and a blood vessel wall strengthening product.

Blood vessels have a structure in which blood vessel parietal cells such as pericytes (pericytes) adhere to endothelial cells from the basement membrane side. Blood vessels with reduced pericytes that surround or line vascular endothelial cells are unstable in structure and fragile, resulting in poor control of blood vessel permeation, which is the movement of substances between blood and tissues, and blood flow. Defects are likely to occur. A blood vessel wall strengthening agent containing alktigenin as an active ingredient and increasing blood vessels coated with blood vessel parietal cells is known (Patent Document 1).

International release 2017/061559

An object of the present invention is to provide a blood vessel wall strengthening agent containing soy protein and / or ergothioneine as an active ingredient.

The present inventors have found that a composition containing soy protein and / or ergothioneine has a blood vessel wall strengthening effect and remarkably promotes blood vessel wall strengthening. It was also found that soy protein and / or ergothioneine can improve skin tone (blood flow, dark circles, dull skin). The present invention has been completed based on these findings.

That is, the present invention
[1] A blood vessel wall strengthening agent containing soy protein and / or ergothioneine as an active ingredient;
[2] The blood vessel wall strengthening agent according to [1], wherein the soybean protein is a soybean protein hydrolyzate;
[3] The blood vessel wall strengthening agent according to [1], which contains ergothioneine as an extract of Pleurotus cornucopiae;
[4] The blood vessel wall strengthening agent according to [1] to [3], wherein the blood vessel wall strengthening agent is a pericyte growth promoting agent;
[5] A skin tone improver containing soy protein and / or ergothioneine as an active ingredient;
[6] The skin tone improver according to [5], wherein the soybean protein is a soybean protein hydrolyzate;
[7] The skin tone improver according to [5], which contains ergothioneine as an extract of Pleurotus cornucopiae;
[8] The skin tone improver according to [5] to [7], wherein the skin tone improver is a blood flow improver and / or an eye dark circle improver;
[9] A cosmetological composition for promoting pericyte growth, which contains soy protein and / or ergothioneine as an active ingredient;
[10] The cosmetological composition for promoting pericyte growth according to [9], wherein the soybean protein is a soybean protein hydrolyzate;
[11] The cosmetological composition for promoting pericyte proliferation according to [9], which comprises ergothioneine as an extract of Pleurotus cornucopiae;
[12] The cosmetological composition for promoting pericyte proliferation according to [9] to [11], which is used for improving skin tone;
[13] A method for promoting pericyte growth, which comprises using soy protein and / or ergothioneine;
[14] A method for producing a pericyte growth promoter, which comprises using soy protein and / or ergothioneine;
[15] A method for producing a cosmetological composition for promoting pericyte growth, which comprises using soy protein and / or ergothioneine;
[16] The method for producing a cosmetological composition for promoting pericyte growth according to [15], wherein the soybean protein is a soybean protein hydrolyzate;
[17] The method for producing a cosmetological composition for promoting pericyte proliferation according to [15], which comprises ergothioneine as an extract of Pleurotus cornucopiae;
[18] A cosmetological method in which a composition containing soy protein and / or ergothioneine is applied to the skin to improve and / or prevent the condition caused by the disappearance of pericytes (excluding the method for treating human diseases);
Etc. are provided.

Since the vascular wall strengthening agent of the present invention contains soy protein and / or ergothioneine, it is possible to promote vascular wall strengthening. Further, since the blood vessel wall strengthening agent of the present invention contains soy protein and / or ergothioneine, it improves and / or prevents skin conditions (poor blood flow, dark circles, dull skin, etc.) caused by the disappearance of pericite. It is also excellent to do.

The result of the dark circle improvement of the eye in Test Example 2 is shown. The result of the dark circle improvement of the eye in Test Example 2 is shown. The result of the blood flow improvement in Test Example 3 is shown.

Hereinafter, embodiments for carrying out the present invention will be described in detail. However, the present invention is not limited to the following embodiments.

[1. Blood vessel wall strengthening agent]
The blood vessel wall strengthening agent according to this embodiment contains soy protein and / or ergothioneine.

The vascular parietal cells adhere from the basement membrane side so as to surround or line the endothelial cells, stabilize the structure of the blood vessel, and strengthen the blood vessel. Pericytes (pericytes) stabilize the structure of capillaries and venules as blood vessel wall cells, so that the movement of contraction and relaxation of capillaries is strengthened and blood flow can be appropriately regulated. In blood vessels with decreased pericytes, blood flow is blocked and congestion occurs, blood vessels dilate, and poor blood circulation is thought to cause angiogenesis. When blood flow decreases, the amount of reduced hemoglobin, which is blue to purple-red, increases. In such a state, the color of blood vessels is easily seen through, such as a part of the skin where the thickness of the skin is thin or a part of the skin where collagen and elastin are low, and the color looks darker than the appearance of normal skin. In particular, since the color of blood vessels is easily visible around the eyes, when the blood vessel structure is weakened, the appearance of the skin becomes dull and bears under the eyes are likely to occur, which tends to spoil the impression of the appearance. Therefore, if pericytes that strengthen the structure of capillaries and the like can be increased as blood vessel wall cells like the blood vessel wall strengthening agent of the present invention, the motility of blood vessels is improved, dilation and thickening are suppressed, and blood is suppressed. The flow is improved, the amount of reduced hemoglobin is improved, the dark circles of the eyes and the dullness of the skin are improved, and the effect of improving the skin tone can be exerted.

The soybean protein in the blood vessel wall strengthening agent according to the present embodiment is not particularly limited as long as it is derived from soybean of the leguminous family, and one or more of soybean plants may be selected and used. As the plant part used for soybean protein, any part may be used, and one or more kinds of parts may be selected and used. The method for extracting soybean protein and the extraction solvent are not particularly limited, and known techniques can be used. The extract may be used as it is, powder or granules obtained by drying the extract may be used, or a decomposition product obtained by treating the extract using a known technique such as enzymatic decomposition may be used. good. It is preferably an enzymatic degradation product, more preferably a proteolytic enzymatic degradation product such as trypsin, papain, thermolysin, and chymotrypsin, and particularly preferably a thermolysin degradation product. Soybean protein can be obtained by a known method, and commercially available soybean protein may be used. The content of soy protein in the blood vessel wall strengthening agent according to the present embodiment is not particularly limited as long as it has a blood vessel wall strengthening effect, and the type and content of other compounding components, the formulation form of the blood vessel wall strengthening agent, etc. It is set appropriately according to. From the viewpoint of exerting the effect of the present invention more remarkably, for example, it is preferably 0.00001 to 2% by mass, more preferably 0.0001 to 1.6% by mass, and 0.0005 to 1.2. It is more preferably by mass%, and particularly preferably 0.001 to 1% by mass. The dose to humans is preferably 0.001 to 100 mg, more preferably 0.01 to 80 mg, still more preferably 0.1 to 60 mg, and 1 to 50 mg per day. It is preferable to have.

As the ergothioneine in the blood vessel wall strengthening agent according to the present embodiment, one extracted, separated or purified from an organism may be used, or one obtained by chemical synthesis may be used. The pharmaceutically acceptable salt or isomer may be used. Ergothioneine may be contained as an extract of basidiomycetes, preferably an extract of basidiomycetes of the family Pleurotaceae, and more preferably selected from the group consisting of Pleurotus cornucopiae extract, Pleurotus cornucopiae extract, King trumpet mushroom extract and Pleurotus cornucopiae extract. One or more species, most preferably Pleurotus cornucopiae extract. Commercially available products can also be used. The content of ergothioneine in the blood vessel wall strengthening agent according to the present embodiment is not particularly limited as long as it has a blood vessel wall strengthening effect, and may vary depending on the type and content of other compounding components, the formulation form of the blood vessel wall strengthening agent, and the like. It is set as appropriate according to the situation. From the viewpoint of exerting the effect of the present invention more remarkably, for example, it is preferably 0.0000000015 to 0.00015% by mass, more preferably 0.0000000015 to 0.000015% by mass, and 0.0000000075 to 0. It is more preferably .0000075 mass%, and particularly preferably 0.0000015 to 0.0000015 mass%. The dose to humans is preferably 0.001 to 100 mg, more preferably 0.01 to 80 mg, still more preferably 0.1 to 60 mg, and 1 to 50 mg per day. It is preferable to have. The content of the extract of the basidiomycete of the family Pleurotaceae in the blood vessel wall strengthening agent according to the present embodiment is not particularly limited as long as it has a blood vessel wall strengthening action, and the type and content of other compounding components and the blood vessel wall. It is appropriately set according to the formulation form of the fortifier and the like. From the viewpoint of exerting the effect of the present invention more remarkably, for example, it is preferably 0.01 to 0.001% by mass, more preferably 0.001 to 0.0001% by mass, and 0.0005 to 0. It is more preferably 0.0005% by mass, and particularly preferably 0.0001 to 0.00001% by mass. The dose to humans is preferably 0.00000015 to 0.0015 mg, more preferably 0.000000015 to 0.0012 mg, and further preferably 0.0000015 to 0.0009 mg per day. It is preferably 0.000015 to 0.00075 mg.

The mass portion of ergothioneine with respect to 100 parts by mass of soybean protein in the blood vessel wall strengthening agent according to the present embodiment is not particularly limited, but is, for example, 0.0001 to 10 from the viewpoint of exerting the effect of the present invention more remarkably. It is preferably 0.001 to 20, more preferably 0.005 to 25, and particularly preferably 0.01 to 50. The mass portion of the extract of the basidiomycete of the family Pleurotaceae is not particularly limited with respect to 100 parts by mass of the soybean protein in the blood vessel wall strengthening agent according to the present embodiment, but from the viewpoint of more remarkable effect of the present invention, for example, 0. It is preferably 0.0001 to 0.5, more preferably 0.00001 to 0.1, further preferably 0.00005 to 0.05, and 0.0001 to 0.01. Is particularly preferable.

The blood vessel wall strengthening agent of the present invention is expected to have an effect of preventing and / or ameliorating a condition caused by disappearance of pericyte such as bear under the eyes, dull skin, and poor blood flow. As the pericyte disappears, the vascular structure becomes fragile, resulting in decreased vascular permeability, poor blood flow, changes in blood composition, etc., which may affect the appearance. In particular, in areas such as the face, neck, and hands where changes in appearance are likely to occur due to aging, or in areas where blood vessels are easily visible due to thin skin, bears under the eyes, dull skin, poor blood flow, etc. Expected to be effective in prevention and / or improvement. In particular, it is expected to have a great effect on the prevention and / or improvement of bears under the eyes.

The vascular wall strengthening agent according to the present embodiment further includes excipients, thickeners, binders, disintegrants, dispersants, surfactants, suspending agents, emulsifiers, stabilizers, gelling agents, sweeteners, and the like. Additives such as acidulants, tasting agents, salting agents, bitterness agents, coloring agents, ultraviolet inhibitors, antioxidants, preservatives, antibacterial agents, pH regulators, buffers, chelating agents, vitamins, fragrances, minerals, etc. It may contain amino acids or salts thereof, sugars, moisturizers, organic acids or salts thereof, dietary fibers, biological extracts (excluding plant extracts) and the like. These can be appropriately selected and used from known ones, and can be produced by a conventional method.

The dosage form of the blood vessel wall strengthening agent according to the present embodiment can be used without being limited to specific products and properties, such as liquid, gel, cream, paste, solid, aerosol or patch. , Any dosage form can be appropriately prepared by a known method. Examples of liquids include lotions, milky lotions, beauty essences, oral liquids, and syrups. Examples of solids include sticks, tablets, chewables, granules, powders, capsules, ointments and the like. The administration form may be an external preparation or an internal preparation, but is preferably an external preparation from the viewpoint of achieving the effects of the present invention. The external preparation is not limited to pharmaceuticals and cosmetics. These can be manufactured using a conventional method.

[2. Beauty composition for strengthening blood vessel wall]
The cosmetological product according to this embodiment has a blood vessel wall strengthening effect. Therefore, as an embodiment of the present invention, a cosmetological product for strengthening a blood vessel wall containing soy protein and / or ergothioneine is provided. Regarding the types and contents of other components such as the content of soybean protein and ergothioneine in the present embodiment, the formulation form and use of the cosmetological composition are described in [1. Blood vessel wall strengthening agent].

<Manufacturing method of beauty composition for strengthening blood vessel wall>
The method for producing the cosmetological composition for strengthening the blood vessel wall according to the present embodiment is not particularly limited, and the vascular wall strengthening agent of the present invention (a preparation characterized by containing soy protein and / or ergothioneine) is blended. It is a feature. The above-mentioned blood vessel wall strengthening agent (soy protein and / or ergothioneine) and other optional components (base or carrier, additive, etc.) may be appropriately selected, blended and mixed, and manufactured by a conventional method. can.

The beauty composition for strengthening the blood vessel wall of the present invention promotes the proliferation of pericytes by the blood vessel wall strengthening agent of the present invention, stabilizes the structure of blood vessels, and strengthens the blood vessels to improve blood flow and reduce blood flow. It can produce cosmetic effects such as reduction of hemoglobin amount, prevention and / or improvement of blood vessel dilation and thickening, prevention and / or improvement of bears under the eyes, prevention and / or improvement of dullness of skin. Therefore, the cosmetological composition for strengthening the blood vessel wall of the present invention is also effective in improving and improving the skin tone and whitening the skin. As described above, the beauty composition for strengthening the blood vessel wall of the present invention is, for example, a beauty essence, a lotion, a milky lotion, a cream, a gel cream, a beauty mask (face mask), a makeup base, a foundation, a sunscreen, a cleansing agent, and a cleaning agent. It can be suitably used as an external composition such as, and more preferably it can be used as a skin care product such as a beauty essence, a lotion, a milky lotion, a cream, and a gel cream. Further, the cosmetological composition for promoting exosome secretion of the present invention can be a food composition. This food composition can be suitably used as a health food, a dietary supplement (including a balanced nutritional food, a supplement, etc.). It is also suitable for foods with health claims (foods for specified health use (including disease risk reduction labeling and standard type)).

Examples of the administration method or application method of the blood vessel wall strengthening agent or the cosmetic composition for strengthening the blood vessel wall of the present invention include transdermal administration and oral administration, which are suitable depending on the type of disease or symptom and the purpose of use. The method may be selected as appropriate.

[3. Blood vessel wall strengthening beauty method]
The cosmetic method according to the present embodiment has a blood vessel wall strengthening effect. Therefore, as one embodiment of the present invention, a cosmetological method containing soy protein and / or ergothioneine is applied to the skin to improve and / or prevent the condition caused by the disappearance of pericite (however, for humans). Except for methods of treating the disease). As one embodiment of the present invention, a cosmetological method in which a cosmetological composition containing soy protein and / or ergothioneine is orally ingested to improve and / or prevent a condition caused by the disappearance of pericite (provided that a human disease is treated). Except for how to do) is provided.

Regarding the content of soy protein, ergothioneine, etc., the type and content of other components, the formulation form and use of the beauty product in this embodiment, [1. Blood vessel wall strengthening agent].

Hereinafter, the present invention will be specifically described based on test examples, but the present invention is not limited thereto. Further, the blending amount in the following examples and the like indicates mass% unless otherwise specified.

[Test Example 1: Evaluation of pericyte proliferation ability]
Frozen vials of pericyte (HBVP, manufactured by ScienCell) were put to sleep, seeded in 75 cm ² flasks at 5000 cells / cm ² , and cultured at 37 ° C. for 3 days under 5% CO ² conditions. After peeling the pericyte from the flask by trypsin treatment and collecting it, the pericyte was inoculated on a 96-well plate so as to have 4000 cells / 100 uL / well and cultured for 24 hours.
Pericyte Medium (PM, manufactured by ScienCell) containing 0.2% FBS containing the components shown in Table 1 was added to a 96-well plate after suction removal of the medium so as to be 200 uL / well, and cultured for 2 days. .. The final concentration of each component is as shown in Table 1. Soy protein is a thermolysin-degraded soy protein hydrolyzate. The test solution containing the Pleurotus cornucopiae extract contains 0.000015% by mass of ergothioneine. The control was a culture medium alone for 2 days without containing any components.
The medium was removed, 1000-fold diluted Hoechst 33342 (manufactured by Dojin Chemical Research Institute) was added, and the reaction was carried out in the dark for 15 minutes to stain the pericytes with nuclei. The stained nuclei were measured by ImageXpress, and the absorbance at 450 nm was measured by a microplate reader to obtain the number of cells.
The cell number of each test solution was calculated with respect to the control cell number of 100, and the value was used as the pericyte proliferation ability of each test solution and is shown in Table 1.

As shown in Table 1, the test solution 1 containing the soybean protein decomposition product and the test solution 2 containing the Pleurotus cornucopiae extract had higher pericyte proliferation ability than the control. The test solution 3 containing the soybean protein decomposition product and the Pleurotus cornucopiae extract further improved the pericyte proliferation ability.

[Test Example 2: Skin evaluation]
Formulation Example 1 was prepared using a known technique. The subject continued to apply Prescription Example 1 under the eyes twice a day (morning and evening) for 8 weeks. Before the start of application and 8 weeks after application, images were taken with a facial image analyzer (VISIA, canfield) or a digital camera. FIG. 1 shows the results taken by the face image analysis device, and FIG. 2 shows the results taken by the digital camera.

Prescription example 1
Pleurotus cornucopiae extract ^* 0.00025 (% by mass)
Hydrolyzed soy protein 0.1
1,3-butylene glycol 10.0
Caprilyl methicone 5.0
Cyclopentasiloxane 7.0
Dimethicone 10.0
Squalan 2.0
Diethoxyethyl succinate 2.0
Tocopherol 0.2
Sorbitan monostearate 2.0
Cetyl PEG / PPG-10 / 1 Dimethicone 2.0
Boron Nitride 3.0
Silicone treated titanium oxide coated mica 2.0
Dimethylstearylammonium hectorite 0.8
Tribehenin 0.1
Total remaining amount of purified water 100.0%
*; Indicates the net amount of extract.

As shown in FIGS. 1 and 2, the bear under the eyes became thinner 8 weeks after application (right figure) as compared with before the start of application (left figure). Furthermore, the dullness of the skin around the cheekbones improved during 8 weeks of application as compared with before the start of application. As a result, the entire skin became brighter, more transparent, and toned up.

[Test Example 3: Blood flow evaluation]
Formulation Example 1 was prepared using a known technique. The subject continued to apply Prescription Example 1 under the eyes twice a day (morning and evening) for 8 weeks. Blood flow was monitored at the application sites before the start of application and 8 weeks after application using a laser two-dimensional blood flow imaging device (Omega Zone OZ-1, Omega Wave). FIG. 3 shows the result of displaying the distribution of blood flow as a gray scale image. The higher the blood flow, the whiter (brighter) the display, and the lower the blood flow, the blacker (darker) the display. The dotted lines in FIGS. 3A and 3B show the upper and lower eyelashes with the eyes closed. Except for the dotted line, FIGS. 3 (a) and 3 (c) and FIGS. 3 (b) and 3 (d) are the same images.

As shown in FIG. 3, 8 weeks after the application (Fig. (D)) as compared with the time before the start of the application (Fig. (C)), there were many bright areas and the blood flow was significantly improved. Furthermore, since the entire coated area is bright, it can be seen that the blood flow has improved in a wide area. Therefore, at the site where Formulation Example 1 was applied, the blood flow was improved 8 weeks after the application as compared with that before the start of the application, and the blood flow improving ability was improved.
The subjects evaluated that the bears under the eyes became less noticeable 8 weeks after the application than before the start of the application, and evaluated that the bears felt that the bears gradually became thinner while the application was continued for 8 weeks.

A blood vessel strengthening agent was prepared for Formulation Example 2 using known techniques. Prescription Example 2 could be used without any problem.
Prescription example 2
Pleurotus cornucopiae extract ^* 0.00025 (% by mass)
Hydrolyzed soy protein 0.1
1,3-butylene glycol 7.0
Glycerin 3.0
Polyglyceryl monostearate 2.0
Glyceryl monostearate 1.5
Squalene 5.0
Glyceryl tri2-ethylhexanoate 3.0
Stearyl alcohol 0.3
Behenyl alcohol 0.1
Carboxyvinyl polymer 0.2
Triethanolamine Appropriate amount Purified water Total remaining amount 100.0%
*; Indicates the net amount of extract.

Claims (7)

A blood vessel wall strengthening agent containing soy protein and / or ergothioneine as an active ingredient. The blood vessel wall strengthening agent according to claim 1, wherein the soybean protein is a soybean protein hydrolyzate. The blood vessel wall strengthening agent according to claim 1, which comprises ergothioneine as an extract of Pleurotus cornucopiae. The blood vessel wall strengthening agent according to claim 1, wherein the blood vessel wall strengthening agent is a pericyte growth promoting agent. A skin tone improver containing soy protein and / or ergothioneine as an active ingredient. The skin tone improver according to claim 5, wherein the skin tone improver is a blood flow improver and / or an eye dark circle improver. A cosmetological composition for promoting pericyte growth, which contains soy protein and / or ergothioneine as an active ingredient.

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