JP2005179224A - Skin care preparation for external use - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a skin care preparation for external use, containing β-endorphin and/or a substance having promoting action on producing β-endorphin. <P>SOLUTION: Since βE (endorphin) is elucidated to exhibit cell activation action and bleaching action on the skin, the skin care preparation for external use comprises βE or a substance having promoting action on producing βE so as to prevent and ameliorate skin symptoms by cell activation action and bleaching action. Wrinkles, flabbiness, stains, drabness, dry skin, chapped skin, or the like, may be cited as the examples of skin symptoms to be prevented and ameliorated by this skin care preparation for external use. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to an external preparation for skin characterized by containing β-endorphin and / or a substance having an action of promoting the production of β-endorphin.

  β-endorphin (hereinafter abbreviated as βE) is contained in the brain, heart and other organs, and is a precursor protein common to the pituitary adrenocorticotropic hormone (ACTH) and melanocyte stimulating hormone (MSH). It is a kind of endogenous morphine-like peptide (opiotide peptide) biosynthesized from melanocortin (POMC), and is known as a brain pleasure substance because it has analgesic action and anti-stress action. It exists in the right brain and the limbic system, which are related to emotions, and plays an important role when feeling joy.

  Certain fragrance components have an effect of promoting βE release, and by smelling them, the body and spirit are relaxed and stress is relieved, so they may be used for aroma-related products.

  βE is particularly abundant in the pituitary midlobe and posterior lobe and is known to be secreted into the blood by noxious factors such as stress. However, recent studies have synthesized POMC in the skin, and the epidermis. It has been clarified that β-endorphin is released from keratinocytes (see Non-Patent Documents 1 and 2).

  However, there are still many unclear points regarding the physiological effects of βE in the skin, and no detailed study has been made yet. There is no example of using βE and / or a substance having an action of promoting βE production in an external preparation for skin, particularly cosmetics. Therefore, the present inventors have conducted various studies under the hypothesis that βE secreted by stress may exert some advantageous effect on the skin.

  As a result of these studies, the present inventors have found that βE exhibits cell activation and whitening effects in the skin.

Zenello S.B., Jackson D.M., Holick M.F. et.al., An immunocytochemical approach to the study of beta-endorphin production in human keratinocytes using confocal microscopy, Annals New York Academy of Sciences, 1999,885 (20), 85-99 Wintzen M., Zanello S.B., Holick M.F., Wiegant V.M., Burbach J.P., Vermeer B.J., Condition-dependent presence of beta-lipotropin-like peptide in human keratinocytes, Peptides, 2000,21 (5), 691-697

  Since it became clear that βE exerts cell activation and whitening effects in the skin, a skin external preparation containing βE in a skin external preparation or a substance having an action of promoting the production of βE It was shown that by promoting the production of βE, it is possible to prevent or improve skin symptoms due to cell activation or whitening. For this reason, the present inventors conducted various studies for the purpose of providing an external preparation for skin that can be applied to various skin symptoms using βE.

  Accordingly, an object of the present invention is to provide an external preparation for skin that can be applied to various skin symptoms using a substance having an action of promoting the production of βE and / or βE.

  In order to find an external preparation for skin that exhibits an excellent effect using a substance having an action of promoting the production of βE and / or βE, the present inventors examined βE. As a result, it has been found that βE has an effect of preventing or improving skin symptoms due to cell activation and whitening, and has completed the present invention.

  That is, the present invention relates to an external skin preparation characterized by containing βE and / or a substance having an action of promoting βE production, and having an effect of preventing or improving skin symptoms due to a cell activation action or a whitening action.

  ADVANTAGE OF THE INVENTION According to this invention, the skin external preparation containing the substance which has the effect | action which accelerates | stimulates production of (beta) E and / or (beta) E can be obtained. By applying βE and / or a substance that promotes the production of βE to the skin, the effect of βE can provide a relaxing effect on the skin and prevent or improve various skin symptoms caused by stress. Is possible. In particular, it is possible to prevent or improve skin symptoms based on cell activation and whitening effects. Examples of skin symptoms that can be prevented or ameliorated by the present invention include wrinkles, sagging, spots, dullness, dryness, and rough skin.

  The skin external preparation characterized by containing βE and / or a substance that promotes the production of βE of the present invention can prevent or improve skin symptoms based on cell activation or whitening. is there. These can contain only 1 type, and can also contain 2 or more types in combination. The content of βE in the external preparation for skin of the present invention is preferably 0.00001 to 0.1% by weight, more preferably 0.0001 to 0.05% by weight. The reason is that if the concentration is too high, it reaches a peak, and no further effect is exhibited. This is because the transdermal absorbability decreases at high concentrations. Conversely, if the concentration is low, the intended effectiveness cannot be exhibited. In the case of using a substance having an action of promoting the production of βE, the content is preferably 0.0001 to 75% by weight with respect to the total amount of the composition, more preferably, from the viewpoint of effectiveness and usability. It is 001-50 weight%, Most preferably, it is 0.01-25 weight.

  The dosage form of the external preparation for skin containing βE and / or a substance having an action of promoting the production of βE is arbitrary, but it is a solubilizing system such as lotion, an emulsifying system such as emulsion or cream, and a dispersion system such as calamine lotion. , Skin external preparations of various dosage forms can be provided as various dosage forms such as aerosols, ointments, powders and granules filled together with a propellant.

  In the range which does not impair the effect of the external preparation for skin containing βE and / or a substance having an action of promoting the production of βE of the present invention, it contains any component used in these external preparations for skin as needed. Can do. For example, oily ingredients, moisturizers, powders, pigments, emulsifiers, solubilizers, detergents for pharmaceuticals, quasi-drugs, skin cosmetics, hair cosmetics, hair restorations, bath preparations, detergents, etc. UV absorbers, thickeners, drugs, fragrances, resins, alcohols, and the like can be appropriately blended.

  The skin external preparation containing βE and / or a substance having an action of promoting βE production according to the present invention can prevent or improve various skin symptoms caused by stress. In particular, it is possible to prevent or improve skin symptoms based on cell activation and whitening effects, and examples include skin symptoms such as wrinkles, sagging, spots, dullness, dryness, and rough skin.

  Hereinafter, examination of the physiological action of βE in the skin, which has been clarified by the present inventors, will be described, but the technical scope of the present invention is not limited by this.

[Evaluation of epidermal cell activation by βE]
Evaluation was performed by the following procedure using human βE as a sample. Normal human epidermal cells were seeded in a 96-well microplate at 2.0 × 10 ⁴ cells per well. As a seeding medium, commercially available Humdia-KG2 manufactured by Kurabo Industries Co., Ltd. was used. After culturing for 24 hours, the culture medium was replaced with a test medium to which a sample having an arbitrary concentration was added, and further cultured for 24 hours. Next, the medium containing 100 μg / mL of 3- (4,5-dimethyl-2-thiazolyl) -2,5-diphenyltetrazolium bromide (MTT) was exchanged and cultured for 2 hours. Formazan generated by the opening of the tetrazolium ring was removed. Extraction was performed with 2-propanol, and absorbance at 550 nm was measured with a microplate reader. At the same time, the absorbance at 650 nm was measured as turbidity, and the cell activation effect was evaluated by the difference between the two measured values. The evaluation results are shown in Table 1 as relative values when the cell activation effect in the blank with no sample added is taken as 100. In addition, ** in the table indicates that a significant difference was recognized with a risk rate (P <0.01) having a significance probability of less than 1% with respect to the significance probability P value in the t-test.

  As is clear from Table 1, a significant epidermal cell activation effect was observed in the medium supplemented with βE. In particular, when βE was added at 0.125 to 0.5 ng / mL, a significant epidermal cell activation effect was observed at a risk rate of less than 1% compared to the blank. From this, it became clear that βE has an excellent epidermal cell activation effect.

[Evaluation of dermal fibroblast activation by βE]
Evaluation was performed by the following procedure using human βE as a sample. Normal human dermal fibroblasts were seeded in a 96-well microplate at 2.0 × 10 ⁴ cells per well. The seeding medium used was Dulbecco's modified Eagle medium (DMEM) supplemented with 1% fetal bovine serum. After culturing for 24 hours, the culture medium was replaced with a test medium to which a sample having an arbitrary concentration was added, and further cultured for 48 hours. Next, the medium containing 400 μg / mL of 3- (4,5-dimethyl-2-thiazolyl) -2,5-diphenyltetrazolium bromide (MTT) was exchanged and cultured for 2 hours. Formazan produced by the opening of the tetrazolium ring was removed. Extraction was performed with 2-propanol, and absorbance at 550 nm was measured with a microplate reader. At the same time, the absorbance at 650 nm was measured as turbidity, and the cell activation effect was evaluated by the difference between the two measured values. The evaluation results are shown in Table 2 as relative values with the cell activation effect in the blank with no sample added as 100. In addition, ** in the table represents a significance probability of less than 1% (P <0.01) with respect to the significance probability P value in the t test.

  As is clear from Table 2, a significant dermal fibroblast activation effect was observed in the medium supplemented with βE. In particular, when βE was added at 0.125 to 0.5 ng / mL, a significant dermal fibroblast activation effect was observed at a risk rate of less than 1% compared to the blank. From this, it became clear that βE has an excellent dermal fibroblast activation effect.

[Evaluation of Tyrosinase Activity Inhibitory Effect by βE]
Evaluation was performed by the following procedure using human βE as a sample. Normal human epidermal melanocytes were seeded in a 96-well microplate so as to be 3.0 × 10 ⁴ cells per well. As a seeding medium, Medium154S manufactured by Kurabo Industries Co., Ltd. was used. After 24 hours, the medium was replaced with a sample solution adjusted to each concentration by Medium154S, and further cultured for 48 hours. Next, it was replaced with 75 μL of 1 wt% Triton-X-containing phosphate buffer to completely lyse the cells. 50 μL of this was used as a crude enzyme solution, and 50 μL of 0.05 wt% L-dopa-containing phosphate buffer as a substrate was added thereto, and the mixture was allowed to stand at 37 ° C. for 2 hours. The absorbance at 405 nm immediately after the addition of the substrate and at the end of the reaction was measured with a microplate reader, and the amount of produced dopamelanin was measured. At the same time, the amount of protein in each sample was measured, and the amount of dopamelanin produced per amount of protein was calculated. As a tyrosinase activity inhibitory action, it shows in Table 3 by the relative value which set the production amount of dopamelanin per protein amount in the blank without a sample to 100. In addition, ** in the table represents a significance probability of less than 1% (P <0.01) with respect to the significance probability P value in the t test.

  As is apparent from Table 3, when a medium supplemented with βE was used, a significant tyrosinase activity inhibitory action was observed. In particular, when βE was added in an amount of 2.5 to 3.5 ng / mL, a significant tyrosinase activity inhibitory action was observed at a risk rate of less than 1% compared to the blank. From this, it has been clarified that βE has a tyrosinase activity inhibitory action and exhibits an excellent whitening action.

  From the above studies, it is clear that βE exerts cell activation and whitening effects in the skin, and βE and / or βE-containing cells can be obtained by applying βE and / or a substance that promotes the production of βE to the skin. It has been clarified that the skin effect such as wrinkles, sagging, spots, dullness, dryness and rough skin can be prevented or improved by the activation and whitening effects.

  Finally, Formulation Examples 1 and 2 show formulation examples of an external preparation for skin containing a substance having an action of promoting the production of βE and / or βE.

[Formulation Example 1] Cream (1) Squalane 10.0 (% by weight)
(2) Stearic acid 2.0
(3) Hydrogenated palm kernel oil 0.5
(4) Hydrogenated soybean phospholipid 0.1
(5) Cetanol 3.6
(6) Lipophilic glyceryl monostearate 2.0
(7) Glycerin 10.0
(8) Methyl paraoxybenzoate 0.1
(9) Arginine (20% by weight aqueous solution) 15.0
(10) Purified water 40.65
(11) Carboxyvinyl polymer (1% by weight aqueous solution) 15.0
(12) β-endorphin 0.05
Production method: The oil phase components (1) to (6) are heated and dissolved at 80 ° C. On the other hand, the aqueous phase components (7) to (10) are dissolved by heating at 80 ° C. The oil phase component is added to this while stirring and uniformly emulsified with a homogenizer. After the emulsification is completed, add (11), start cooling, add (12) at 40 ° C., and mix uniformly.

[Prescription Example 2] Whitening serum (1) Glyceryl tri-2-ethylhexanoate 7.0 (wt%)
(2) Hydrogenated soybean phospholipid 0.1
(3) Batyl alcohol 0.1
(4) Polyglyceryl distearate 3.0
(5) Purified water 71.585
(6) Glycerin 8.0
(7) 1,3-butylene glycol 2.0
(8) L-ascorbyl magnesium phosphate 3.0
(9) Xanthan gum 0.4
(10) Methyl paraoxybenzoate 0.1
(11) Ethanol 4.0
(12) Sodium citrate 0.5
(13) Lactic acid 0.005
(14) Fragrance 0.1
(15) β-endorphin 0.01
Production method: The oil phase components (1) to (4) are heated and dissolved at 80 ° C. On the other hand, the aqueous phase components (5) to (10) are dissolved by heating at 80 ° C. The oil phase component is added to this while stirring and uniformly emulsified with a homogenizer. After emulsification, cooling is started, and (11) to (15) are added at 50 ° C. and mixed uniformly.

Claims (2)

A topical skin preparation characterized by containing β-endorphin and / or a substance having an action of promoting the production of β-endorphin. The external preparation for skin according to claim 1, which is a cosmetic.