JP2018177702A - Skin aging inhibitor containing hydrangea paniculata siebold extract as active ingredient and skin external preparation containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a skin aging inhibitor having pleiotropic effects such as anti-inflammatory, anti-glycation, and moisture retention properties, and a skin external preparation containing the same.SOLUTION: The inventors have completed the invention such that: a skin aging inhibitor contains an inflammation inhibitor or a saccharification inhibitor containing Hydrangea paniculata siebold extract as an active ingredient; and a skin external preparation contains the skin aging inhibitor.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a skin anti-aging agent, in particular, an extract containing Hydrangea paniculata siebold as an active ingredient, the efficacy of which is based on the improvement of anti-inflammatory function and anti-glycation function, The present invention relates to a skin external preparation containing a skin anti-aging agent.

  Since the skin is located on the outermost layer of the living body, it is an organ that is constantly exposed to environmental stress. Among environmental stress, dryness and ultraviolet rays are known to cause skin inflammation. In addition, when the skin barrier function is reduced, inflammation due to the entry of foreign substances is likely to be caused. Skin inflammation not only causes skin diseases or skin cancer, but also causes rough skin.

  In epidermal keratinocytes stimulated with UV and inflammation-inducing factors such as microorganisms, various signal transduction pathways are activated and nuclear factor-kappa B (NF-κB), one of the transcription factors, is activated. Ru. Activated NF-κB induces an inflammatory response by inducing gene expression of inflammatory cytokines such as Interleukin and tumor necrosis factor-alpha. It is considered that suppressing the activation of NF-κB and the expression of inflammatory cytokines is an effective means for suppressing the inflammatory response.

  The saccharification reaction (Maillard reaction) that starts with the reaction between reducing sugars and proteins was discovered as a reaction in food, but was later revealed to be a reaction that also occurs in vivo. The glycation reaction is roughly divided into a pre-reaction until the formation of an Amadori transferred product and a post-reaction which is followed by oxidation, dehydration and condensation to produce Advanced Glycation End products (AGEs) which are final glycation products. Proteins modified by AGEs cause structural changes or functional changes associated therewith, which adversely affect living organisms. In addition, it is also known that inflammatory signals are triggered by binding of AGEs to RAGE which is an AGEs receptor. The presence of AGEs is also found in the skin, and is considered to be a cause of the skin's reduced elasticity and yellowing. From these facts, it can be said that inhibiting the accumulation of AGEs is important in preventing skin aging. Approaches to inhibit the accumulation of AGEs include (1) inhibiting the formation of AGEs and (2) degrading the generated AGEs.

  Nori-utsugi is a deciduous shrub of the family Anchovyaceae Hydrangea and has a conical inflorescence consisting of decorative flowers that attracts insects and bisexual flowers that pollinate. As the name says Noriutsugi (glued sky wood), the bark contains a large amount of mucus, so it is used before the war as a paste for making Japanese paper, and it is still used to disperse fibers evenly. There is. Since the inside of the stem of the apricot tree is hollow, it can be used as a pipe. While other hydrangea species prefer semi-shaded areas in the mountains, this species is not only found on forest edges, but also on wild sunny and sunny fields and can be found throughout Japan.

  Patent Document 1 describes a technology for blending one or two or more kinds of plant extracts of a group including Nori-utsuji or alkali-treated products thereof as a whitening cosmetic which is excellent in melanin production suppressive action and excellent in improving stains and buckwheat. It is done.

  Patent Document 2 describes that an extract of a plant of the family Citrusaceae has a whitening effect, and hydrangea is described as the plant.

  Non-Patent Document 1 discloses the physical properties of a red pigment extracted from Noriutsugi under specific conditions, and is reported to have a carbohydrate protecting action.

  Non-Patent Document 2 reports that the polysaccharide was isolated from a mucous composition extracted from the bark of Noriutsugi and its physical properties.

  Non-Patent Document 3 reports that the coumarin glucoside derived from Noriutsugi and the iridoid glucoside have a neuroprotective action.

  However, none of these describes or suggests the anti-inflammatory function, the anti-glycation function, the moisturizing function of Nori-utsugi extract and the application to skin anti-aging agents based on their effectiveness.

  On the other hand, those skilled in the art have proposed skin care and makeup cosmetic compositions which are a kind of external preparations for skin of various types based on the combination of various raw materials, not limited to plant extracts. (Non-patent document 4)

  However, likewise, nothing has been described or suggested as to the presence of the anti-inflammatory function, anti-glycation function, moisturizing function of the Nori-utsugi extract.

  In addition, those described or suggested about the applicability of anti-inflammatory agents, anti-glycation agents, moisturizers, and skin anti-aging agents and external preparations for skins comprising these extracts containing Nori-utsugi extract having these functions as an active ingredient There is also no.

Japanese Patent Application Laid-Open No. 04-346911 Patent document 1: JP-A-2001-206819

Dongbei Linye Daxue Xuebao 39: 5: 62-63, 71 (2011) Chem Pharm Bull 24: 2: 230-234 (1976) Planta Med 78: 17: 1844-1850 (2012) "Knowledge Technologies 2012 in the field of cosmetics (published on March 16, 2012)" (edited by the Japan Cosmetic Industry Association Patent Committee)

  Provided are a skin anti-aging agent having multiple effects such as anti-inflammatory property, anti-glycation property and moisturizing property, and a skin external preparation containing the same.

  The inventors focused on the unknown usefulness of Noriutsugi and proceeded with the search and study on its effect, and surprisingly, it has excellent anti-inflammatory properties, anti-glycation properties, moisturizing properties, and skin barrier effects. Found out and completed the invention. In addition, as a skin external preparation exemplified in Non-patent Document 4, it succeeded in finding more optimal conditions for forming into various dosage forms, and completed a further invention.

  Since the present invention can provide a skin anti-aging agent comprising an extract of Noriuchigi having multifaceted excellent effects such as anti-inflammatory property, anti-glycation property, moisturizing property, the effect on a single factor is confirmed It is possible to provide a skin external preparation that can respond to various factors of skin aging more broadly than existing anti-aging agents, or does not necessarily require a plurality of anti-aging agents.

Noriutsugi (flower) photo Noriutsugi (All grass) photo

  Although it is possible to use the extract alone, it can be prepared as various forms of external preparations (regardless of classification on medicines, quasi-drugs, cosmetics, etc.) to improve the convenience of the user. In particular, for preparation of a skin external preparation, for example, the preparation example introduced in Non-patent Document 4 can be used.

[Preparation of Noritsugi Extract]
General methods for preparing extracts from plant material can be employed as appropriate, but solvent extraction is preferred. For solvent extraction, it is desirable to use a polar solvent such as water and ethanol, and it is more desirable to use water and other polar solvents simultaneously. Furthermore, the extract can be separated and purified by activated carbon treatment, liquid-liquid distribution, column chromatography, liquid chromatography, gel filtration and the like to extract an active fraction (component).
Moreover, although the extraction site can also use whole grass, it is desirable to use especially flowers and fruits from the viewpoint of compounding efficiency.

[Preparation of external preparation]
For external use, for example, when prepared as a cosmetic, powder, powder foundation such as powder foundation, soap, solid body such as lipstick, cream, emulsion, emulsion such as milky lotion, cream foundation, liquid such as lotion, cosmetic liquid etc. It can be prepared in the form of Moreover, it may be a shampoo, a treatment, and a skin external preparation for scalp.

In this case, as other components that can be blended, components generally used for the purpose of imparting base or additive components of external preparations such as cosmetics and pharmaceuticals, or functionality, such as liquid oil, solid oil, various Surfactants, metal soaps, moisturizers, gelling agents, water-soluble polymers, lower alcohols, polyhydric alcohols, saccharides, UV absorbers, film-forming agents, resins, inclusion compounds, deodorants, amino acids, vitamins , Drugs, extracts from plants, animals and microorganisms, organic acids, organic amines, sequestering agents, antioxidants, antibacterial agents, preservatives, pH adjusters, fresheners, fragrances, emollients, dyes, whitening , Anti-wrinkle agent, anti-aging agent, anti-inflammatory agent, hair growth agent, hair growth promoting agent, active oxygen removing agent, blood circulation promoting agent, astringent agent, keratolytic agent, components such as proteolytic enzyme, and efficacy of external medicine As an ingredient Anti-inflammatory agents including non-steroidal agents, immunosuppressive agents, analgesic / anti-inflammatory agents, antibacterial agents, anti-fungal agents, anti-viral agents, anti-tumor agents, anti-ulcers, anti-ulcer agents, wound covering agents, circulation improving agents, stop There may be mentioned lozenges, local anesthetics, anti-sickness agents, nicotinic agents, female hormone agents and the like. In the preparation, it is possible to use a conventional method (for example, the preparation example of Non-Patent Document 4) according to the compounding amount of the Nori-tsutii extract of the present invention and the type of the intended external preparation.

According to the following procedure, Nori-utsugi extract was prepared as a 30% ethanol solution, and with respect to anti-inflammatory action and anti-glycation action, purified water was used as a comparative example to verify the effects as described later.
As for the extraction site of Nori-utsugi to be used, one obtained by removing a site other than flowers and fruits from the whole plant collected was used.
In addition, unless otherwise indicated, percentage means weight percentage, and so on.

<Preparation method of Noriutsugi extract (30% ethanol solution)>
1. One hundred grams of dried ginseng was ground and 500 g of 95% ethanol was added.
2. Extracted with stirring at 40 ° C. for 120 minutes.
3. After 500 g of water was further added, a 5% aqueous solution of sodium hydroxide was added to adjust to pH 13-14.
After heating to 4.70 ° C., 10% lactic acid was added to adjust to pH 6.5.
5. After slowing down to room temperature, the solution was hydrolyzed to a 30% ethanol solution to obtain a Japanese apricot extract (30% ethanol solution).

[Verification of anti-inflammatory effect]
The inflammatory cytokine production inhibitory action of Nori-utsugi extract was investigated using gene expression of interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) as an index.
The test was performed as follows.
0.2% of a cultured normal human epidermal keratinocytes (NHEK) containing 0.2% of a 0.2% extract as an extract by hydrolyzing a 0.2% extract from a Japanese rosewood extract (30% ethanol solution). Processed for 24 hours.
Thereafter, the cells were further treated with 2 μg / ml lipopolysaccharide (LPS; cell wall component of gram negative bacteria to cause inflammation) and 0.2% prickly pear extract for 6 hours.
RNA was extracted from the treated cells, and gene expression of IL-8 and TNF-α was examined by RT-PCR method using EcoTM Real time PCR system (illumina).

As described above, it was confirmed that Nori-utsugi extract suppresses the increase in gene expression of IL-8 and TNF-α by LPS.

The NF-κB activation inhibitory action of the Japanese apricot extract was examined using the nuclear level of p65, which is one of the subunits of NF-κB, as an indicator.
The test was performed as follows. The cultured NHEK was treated for 24 hours with 0.2% water lily extract. After that, it was further treated with 2 μg / ml LPS and 0.2% Sesium extract for 1 hour.
Nuclear proteins were extracted from the treated cells, and the expression level of p65 was examined by Western blotting.

As described above, it was confirmed that the extract of Noriuchigi has a function to suppress the increase of nuclear p65 level by LPS.

  From the above, it can be seen that Nori-utsugi extract is an excellent anti-inflammatory agent having an effect of suppressing the production of the expression gene of inflammatory cytokines.

[Verification of antiglycation effect]
The anti-glycation activity of Nori-utsuji extract was examined using AGEs formed by the glycation inducer glyoxal as an indicator.
The test was performed as follows.
Cultured normal human dermal fibroblasts (NB1 RGB) were treated for 24 hours with glyoxal and 0.2% Sesium extract.
Protein was extracted from the treated cells, and the formation level of AGEs was examined by dot blotting using Bio-Dot Microfiltration Apparatus (Bio-RAD).

As a result of analyzing the obtained dot-blotting, it was confirmed that AGE formation was suppressed as described above.

The anti-glycation activity of the Nori-tsugi extract was confirmed using the degradation of AGEs formed by glyoxal as an indicator. The test was performed as follows.
The cultured NHEK was treated with glyoxal for 24 hours.
After treatment, the glyoxal was removed and treated with 0.2% water lily extract for 24 hours.
Proteins were extracted from the treated cells, and degradation of AGEs was examined by dot blotting using Bio-Dot Microfiltration Apparatus (Bio-RAD).

As a result of analyzing the obtained dot-blotting, it was confirmed that AGEs were decomposed as described above.

From the above, it can be seen that the Nori-utsugi extract is an excellent anti-glycation agent having both the AGEs suppressing effect and the degrading effect.

  The following cosmetics were prepared as a preparation example of the skin external preparation which mix | blended the rosewood extract.

[Tooth water]
The following components were prepared in a conventional manner using the extract of Example 1 (30% ethanol solution). (The Nori-utsugi extract in the table refers to this Nori-tsutii extract (30% ethanol solution). The same shall apply hereinafter.)
Further, as a comparative example, a product in which Noriuchigi extract (30% ethanol solution) was replaced with purified water was prepared.

[lotion]
The following components were prepared in a conventional manner using the extract of Example 1 (30% ethanol solution).
In addition, as a comparative example, a product in which a part of Noriuchigi extract (30% ethanol solution) was replaced with purified water was prepared.

[Cream agent]
The following components were prepared in a conventional manner using the extract of Example 1 (30% ethanol solution).
In addition, as a comparative example, a product in which a part of Noriuchigi extract (30% ethanol solution) was replaced with purified water was prepared.

[Pack agent]
The following components were prepared in a conventional manner using the extract of Example 1 (30% ethanol solution).
In addition, as a comparative example, a product in which a part of Noriuchigi extract (30% ethanol solution) was replaced with purified water was prepared.

Below, the effect verification result in monitor sensory evaluation is shown for Examples 2 to 5 and a corresponding comparative example.
In addition, in verification, three monitors having healthy skin selected from a female employee are caused to use the lotion of Example 2 a plurality of times, and are required for cosmetics, particularly skin care cosmetics, and also for skin aging. We evaluated the "water,""smoothness,""softness,""gloss,""transparency,""harry," and "overall evaluation," which are considered to be indicators. At this time, the average value of what was judged in five steps of "1. not feel, 2. not felt much, 3. neither can say 4. somewhat feel, 5. feel" was adopted and verified.

As described above, anti-skin aging effects of the skin anti-aging agent of Nori-utsugi extract and cosmetics containing the same were observed.

The cosmetic composition of the present invention can be used not only as a base for makeup cosmetics and skin care cosmetics (functional cosmetics) as external cosmetics but also as functional cosmetics having a moisturizing effect by a water evaporation suppressing function. In addition, by providing various standards and requirements on pharmaceutical matters, it can be used for quasi drugs and medicines.

Claims (5)

Anti-inflammatory agent comprising an extract of Hydrangea paniculata siebold as an active ingredient An anti-glycation agent comprising an extract of hydrangea paniculata siebold as an active ingredient A skin anti-aging agent comprising the anti-inflammatory agent according to claim 1 A skin anti-aging agent comprising the anti-glycation agent according to claim 2 A skin external preparation characterized by containing any one or more of the skin anti-aging agents according to claim 3 or 4