JP5886534B2 - Whitening agent and external preparation for skin containing the same - Google Patents

Description

  The present invention relates to a skin external preparation excellent in whitening and having an effect excellent in whitening. In particular, it relates to the synergistic effect of inhibiting the process of melanin migration to epidermal cells (keratinocytes).

Α-melanocyte stimulating hormone (α-MSH), endothelin-1 (ET-1), nitric oxide (NO), basic fibroblast growth factor (bFGF), accompanied by inflammation when stimulated by ultraviolet rays or the like, Signal transduction systems such as granulocytes, macrophages, colony stimulating factor (GM-CSF) are activated, thereby increasing the production of tyrosinase, and the production of melanin from tyrosine via dopa is activated and accumulated in melanocytes. The melanocyte extends a branch-like projection called a dendrite toward the keratinocyte, and the keratinocyte takes in the melanin together with the dendrite and completes a reaction that protects the keratinocyte from stimulation such as ultraviolet rays. After that, it falls off the skin surface by turnover and finishes its role.
The skin appears black because keratinocytes have a lot of melanin and are present for a long time.
Until now, many whitening agents that suppress the production of melanin such as tyrosinase activity inhibition have been used. However, in recent years, substances that suppress information transmission systems such as α-MSH and endothelin, and keratinocytes suppress the uptake of melanin. Substances are being used. (See Patent Document 1)
Thus, regarding whitening, a more excellent whitening effect can be obtained by suppressing various stages.
However, as for substances that suppress the process of melanin incorporation into keratinocytes, there has been no substance that can fully meet the requirements.

JP 2006-347926 A

  An object of the present invention is to find a substance that suppresses the process of melanin incorporation into keratinocytes (hereinafter referred to as keratinocyte phagocytosis inhibition), and to obtain a highly effective whitening agent.

As a result of intensive studies, the present inventors have found a strong keratinocyte phagocytosis inhibitor by combining an enzyme-decomposed product of Prunus pulp and a daisy flower extract.
Details are described below.
Prunus is a deciduous small tree of scientific name, Prunus domestica, Rosaceae, and is a plant that is said to originate from the Caspian Sea coast. Prunes are foods that dry their fruits.
The enzymatic degradation product of prune which is the product of the present invention can be obtained by treating the prune pulp as it is, or after pressing, pulverizing, crushing, grinding or the like, and then treating with a fibrinolytic enzyme. When using dried fruits, they are used for enzymatic degradation as they are or by swelling them with an aqueous solvent such as water.
Cellulase, hemicellulase, pectinase and the like can be used as the fibrinolytic enzyme, but cellulase is preferably used. The decomposition conditions are not particularly limited, but it is preferable to select various enzyme activity temperatures. After enzymatic degradation, the enzyme is deactivated by heat treatment or the like, and then filtered with or without adding an appropriate amount of aqueous solvent.
Examples of aqueous solvents include water, methanol, ethanol, propyl alcohol, isopropyl alcohol, butanol, isobutanol and other lower alcohols or hydrous lower alcohols, propylene glycol, 1,3-butylene glycol, 1,2-butylene glycol, 1,4 -Polyhydric alcohols such as butylene glycol, 1,5-pentanediol, 1,2-pentanediol, 1,3-pentanediol, 1,4-pentanediol, 1,3,5-pentanetriol, or hydrous polyhydric alcohols One or more selected from phenoxyethanol, paraben, ethylparaben, methylparaben, propylparaben and the like can be used.

The enzyme degradation product may be subjected to purification treatment by activated carbon treatment, adsorption resin treatment, ion exchange resin treatment, or the like as long as it does not cause a significant decrease in action. Furthermore, arbitrary auxiliary agents, for example, various excipients such as starch and lactose can be added. Furthermore, the aqueous solvent can be appropriately added to the obtained enzyme degradation product.
Enzyme degradation products of Prunus edulis have already been used as raw materials for cosmetics, and it has been known that they have an effect of improving keratinocyte phagocytosis as well as improving skin texture and moisturizing.

Daisy is the scientific name Bellis perennis L., and the Japanese names are perennial plants, which are also called daisies (chicks), enmeis (long life chrysanthemum), butterflies (long lifes). Western countries have long used daisies such as young leaves, buds and florets in addition to salads.
The roots were also used as a medicinal agent for the treatment of rheumatism and wounds, and expectorants.
An extract obtained by extracting the flower part of daisy with water, a lower aliphatic alcohol or a hydrated product of a lower aliphatic alcohol is used.
Daisy flower extracts contain saponins, polyphenols and polysaccharides.
Daisy flower extract is already used as a raw material for cosmetics, and is effective in various functions related to whitening such as endothelin production inhibition, α-MSH binding inhibition, tyrosinase production inhibition, and melanin production inhibition. The inhibitory effect of keratinocyte phagocytosis was also known, as was the enzyme degradation product of pulp.

Both of the above two substances were known to have an inhibitory effect on keratinocyte phagocytosis, but no synergistic action was known. In addition, since the whitening action is stronger and has a synergistic action, it is considered that the whitening action as a whole is enhanced by exhibiting a synergistic effect other than the keratinocyte phagocytosis inhibitory effect.
As a compounding quantity of the enzyme degradation product of a peach fruit pulp and a daisy flower extract, 0.00001 to 10%, preferably 0.0001 to 1%, respectively, is blended as a solid content. (Note that “%” means “% by weight,” and “%” means “% by weight”.)

It is necessary to add a substance having a whitening effect in addition to the enzymatically decomposed product of Prunus pulp and daisy flower extract in order to enhance the whitening effect, and information on the production of melanin such as α-MSH and endothelin A substance that suppresses actions other than the suppression of keratinocyte phagocytosis such as a substance that suppresses the transmission system, tyrosinase activity inhibition, tyrosinase production inhibition, and the like is added.
As a result of intensive studies by the present inventors, it has been found that good results can be obtained when at least one selected from arbutin and ascorbic acids is blended.
Arbutin is a phenolic glycoside contained in plants such as cowberry, pear and walrus. It is said to act directly on tyrosinase involved in melanin synthesis and inhibit melanin synthesis. There are β type and α type, but both can be used.
It is also possible to use plant extracts such as cowberry, pear, and walnut containing arbutin.
Alcorbic acid refers to alcorbic acid, a derivative of alcorbic acid or a salt thereof, and ascorbic acid derivatives include, for example, sodium L-ascorbate-2-phosphate, magnesium L-ascorbate-2-phosphate, L-ascorbic acid-2-sulfate sodium, L-ascorbic acid-2-sulfate magnesium salt such as magnesium, L-ascorbic acid-2-glucoside (2-O-α-D-glucopyranosyl-L-ascorbine Acid), ascorbic acid sugar derivatives such as L-ascorbic acid-5-glucoside (5-O-α-D-glucopyranosyl-L-ascorbic acid), and 6-position acylated products of these ascorbic acid sugar derivatives (acyl group is hexanoyl Group, octanoyl group, decanoyl group L-ascorbic acid tetraisopalmitate, L-ascorbic acid tetralaurate, L-ascorbic acid tetrafatty acid esters, 3-O-ethylascorbic acid, L-ascorbic acid-2-phosphate- Examples include sodium 6-O-palmitate.

Furthermore, the inventors have found that the whitening effect is enhanced by adding an anti-inflammatory agent.
Examples of the anti-inflammatory agent include allantoin, lysozyme chloride, guaiazulene, γ oryzanol, glycyrrhetinic acid, stearyl glycyrrhetinate, glycyrrhizic acid and its salt, tranexamic acid and its derivative, epsilon aminocaproic acid and the like.
In addition, plant extracts having anti-inflammatory activity, such as chamomile, peonies, lysins, tea, toki, peach, amacha, asunaro, arnica, ginkgo, inchinkou, turmeric, lauren, hypericum, Dutch mustard, kumazasa, gentian, kojisou, Comfrey, Salvia, Hawthorn, Salamander, Perilla, Zirconia, Achillea millefolium, Atlantic mint, Persian baboon, Thyme, Clover, Parsley, Hamelis, Biwa, Butcher bloom, Bodaiju, Mannenrou, Buttonpi, Cornflower, Lavender, Roman chamomile In addition, an extract such as Dokudami can also be used. As these plant extracts, one or more types of extracts or commercial products extracted from each plant by a conventional method can be used.
Among these anti-inflammatory agents, it is preferable to blend at least one selected from glycyrrhetinic acid, stearyl glycyrrhetinate, glycyrrhizic acid and salts thereof, and visabolol.
Furthermore, it has been found that the whitening effect is the highest when one or more selected from glycyrrhetinic acid, stearyl glycyrrhetinate, glycyrrhizic acid, and salts thereof and visabolol are blended.

In addition to these components, a raw material other than those described above is added for formulation in order to formulate or to impart other effectiveness.
There is no limitation in the kind of formulation, Arbitrary dosage forms, such as a liquid agent, an emulsion, a cream, an ointment, a patch, can be selected.

  Although an Example is described below, it is not limited to this. Numerical values represent parts by weight.

Whitening liquid 1
7.8 g of enzyme decomposition product (freeze-dried product) of plum fruit was mixed with 5.0 g of daisy flower extract (freeze-dried product) and made up to 100 ml with purified water.
Enzymatic degradation product of Prunus pulp and daisy flower extract used in this whitening agent were prepared as follows.
Enzyme degradation product (freeze-dried product)
Grind 1.0 kg of Prunus domestica pulp with a mixer, adjust the crushed liquid to about 60 ° C., and add cellulase and hemicellulase. After the enzyme reaction, the enzyme was inactivated by heating and then freeze-dried.
Daisy flower extract (freeze-dried)
100 g of daisy (Bellis perennis L.) flowers (dried product) was pulverized, 800 g of purified water was added, and the mixture was extracted at 40 ° C. for 30 hours. This was filtered and the filtrate was lyophilized.
The enzyme-decomposed solution of citrus pulp, which will be described later, is obtained by making 7.8 g of enzyme-decomposed product (freeze-dried product) of citrus pulp into 100 ml with purified water. Extract (lyophilized product) 5.0 g made up to 100 ml with purified water

Confirmation of the effect of the whitening agent Keratinocytes were seeded at 4.8 × 10 ³ cell / well in a Labtech 2 chamber slide system and cultured for 3 days. After culture, fluorescent beads (Tetra speck microspheres, 0.5 μm, fluorescent) were added to 2.0 × 10 ⁴ paticles / well, and at the same time, a test product diluted to a specified concentration was added and cultured for 3 days.
Then, it fixed with 10% neutral buffer formalin, and observed with the fluorescence microscope.
The image captured with the fluorescence microscope was analyzed with ImageJ, and the luminance value for one cell was calculated. The calculated luminance value was used as the amount of fluorescent beads taken up by keratinocytes, and the amounts taken up were compared.
The results are shown in Table 1.

Tables 2 and 3 show external preparations for skin containing the above whitening agents and comparative examples.

20 women were actually used. The method divided the face into left and right, and asked one to use Example 1 for the other and Comparative Examples 1 to 3 for one month to confirm the whitening effect.
In addition, the evaluation standard was quantified as follows as the standard of Example 1, and the average was shown.
3: It was more effective than Example 1.
2: More effective than Example 1.
1: Slightly more effective than Example 1.
0: Same as Example 1.
-1: The effect was slightly inferior to that of Example 1.
-2: The effect was inferior to Example 1.
-3: The effect was considerably inferior to that of Example 1.

  As a result, Comparative Example 1 was −1.6, Comparative Example 2-1.8 was −2.3, and Comparative Example 3 was −2.3.

Claims (2)

  A whitening agent that contains an enzyme degradation product of citrus pulp and daisy flower extract. Whitening skin external preparation containing a combination of a whitening agent of claim 1.