JP2009298724A - Collagen production promoter and external preparation for skin - Google Patents

Abstract

【Task】
A topical skin preparation that promotes collagen production, prevents and improves age-related changes in skin such as wrinkles and sagging due to a decrease in collagen, and is effective in the process of inflammation and wound healing. The purpose is to provide.
[Solution]
Collagen production comprising 0.00001% to 2.0% by weight of β-Tyapricin as an active ingredient, and blending various ingredients generally used in cosmetics, quasi drugs, pharmaceuticals, etc. as necessary Accelerator.
[Selection] Figure 2

Description

  The present invention relates to a collagen production promoter that promotes the production of collagen, and prevention of skin aging such as wrinkles and sagging due to a decrease in skin elasticity and elasticity, and wound healing that prevents and improves skin irritation and skin inflammation caused by ultraviolet rays. The present invention relates to an external preparation for skin particularly useful for promotion.

  Collagen plays an important role in maintaining the structure of the body, such as supporting, reinforcing, and bonding our entire body or organs. About one third of the total protein amount of the body is also called collagen, and is present in large quantities particularly in skin, bone, cartilage, tendon, blood vessel wall, and the like. About 40% of the total collagen is in the skin, 10-20% is in bone and cartilage, and 7-8% is in blood vessels.

  At the cellular level, collagen exists between cells and plays an important physiological role such as cell protection and cell adhesion. In addition, when tissues are damaged, it has been reported that the production of fiber components such as collagen in dermal fibroblasts plays an important role in inflammation and wound healing processes.

  However, it has been reported that collagen, which has an important role in the living body as described above, decreases due to ultraviolet rays, stress, and deterioration of metabolism due to aging, and causes various disorders. In particular, collagen accounts for 70% of the dry weight of the skin, and with the decrease in collagen, the reduction in the elasticity and elasticity is remarkable, and as a result, the skin undergoes age-related changes such as wrinkles and sagging.

  Under such circumstances, vitamin A (retinoid), which is known to have a collagen production promoting action in recent years, has attracted attention as a drug for preventing and improving aging changes in the skin, and retinoic acid and retinol, which are types of vitamin A, are used in the skin. It came to be used as an external preparation. However, since retinoic acid has very side effects such as inflammation, exfoliation, and irritation when applied to the skin, it is currently in a state where it cannot be used unless directed by a doctor. The other retinol is known to have side effects although not as much as retinoic acid. In addition, retinoic acid and retinol are substances that are easily destabilized by heat and oxygen.

  In recent years, substances other than vitamin A that have a significant collagen production promoting effect have been strongly desired. Therefore, in the present invention, collagen production is promoted, and skin age-related changes such as wrinkles and sagging are prevented and improved as a result of collagen reduction, and in addition, inflammation and wound healing processes. Another object of the present invention is to provide a skin external preparation containing a novel useful substance that is also effective.

  In addition, since this invention concerns a novel active ingredient, there is nothing which should be mentioned especially as related prior art document information.

  In order to achieve the above-mentioned object, the present inventors have conducted intensive research to obtain a substance that exhibits a collagen production promoting effect from substances having excellent safety, and as a result, conventionally, cell activators and preservatives have been obtained. As a result, it has been found that tsuyaprisin known only as a product has a remarkable collagen production-promoting effect, and the present invention has been completed.

  That is, the present invention provides a collagen production promoter containing tsuyapricin as an active ingredient. Hereinafter, the configuration of the present invention will be described in detail.

  Tsuyaprisin used in the present invention is a tropolone compound, which is a component naturally extracted from essential oils of Aomori Hiba and Taiwan Hinoki. As tsuyaprisin, isomers such as α-tyaprisin, β-tyaprisin, and γ-tyaprisin are known. In particular, β-tsuyapricin is also called hinokitiol, and is a compound that is widely used as a bactericidal agent, cell activator, etc. in the fields of pharmaceuticals, cosmetics, etc., regardless of nature or synthesis. Tsuyaprisin or a derivative thereof is particularly preferred.

  The blending amount of the collagen production promoter of the present invention when blended with an external preparation for skin can be adjusted according to the use of the external preparation for skin, but is not limited in terms of stability, safety, etc. 0.0001% by weight to 2.0% by weight is preferable, and 0.0001% by weight to 0.5% by weight is more preferable.

  In addition to the essential components described above, the external preparation for skin containing the collagen production promoter of the present invention is generally used in cosmetics, quasi drugs, pharmaceuticals, etc. as long as the effects of the present invention are not impaired. Various components used, aqueous components, humectants, thickeners, ultraviolet absorbers, ultraviolet scattering agents, preservatives, antioxidants, fragrances, colorants, drugs, crude drugs and the like can be blended. Further, the dosage form of the external preparation for skin containing the collagen production promoter of the present invention is arbitrary, for example, a solubilizing system such as lotion, an emulsifying system such as a milky lotion or cream, or an ointment, a powder dispersion system, or a water-oil. A dosage form such as a two-layer system or a water-oil-powder three-layer system may be used.

  Examples of the present invention will be described below, but these examples do not limit the present invention.

Evaluation of collagen production promoting effect of tsuyaprisin-containing external preparation using three-dimensional cultured human skin model (1) Test Example 1
[examined goods]
Hinokitiol aqueous solution (hinokitiol purity 98 (W / W)% or more): 60.9 μmol / L
Positive control Vitamin A palmitate aqueous solution (1.7 million units / g as vitamin A): 1700 IU / g
Negative target additive-free The above test products were each added to a three-dimensional cultured human skin model. The concentration of the positive control vitamin A palmitate was a relatively high concentration among the concentrations normally used as quasi drugs.

[Three-dimensional cultured human skin model]
The three-dimensional cultured human skin model is widely used for safety evaluation and usefulness evaluation as a human skin model. TESTSKIN LSE-d (Toyobo) was used as the three-dimensional cultured human skin model.

[Evaluation of collagen production promotion effect]
Collagen in the medium after culturing for 24 hours and 48 hours was quantified by enzyme immunoassay (ELISA method) using a commercially available collagen quantification kit (human collagen type 1 ELISA manufactured by ACBio).

表１に示したように、本発明のツヤプリシンの１つであるヒノキチオールは、４８時間の培養後、コラーゲン産生促進効果を有することがすでに報告されているビタミンＡパルミテート（非特許文献１）の３倍、無添加対照の３．６倍と、コラーゲン産生が著しく促進されていた。
「Ｆｒａｇｒａｎｃｅ Ｊｏｕｒｎａｌ，臨時増刊号 Ｎｏ．１５」、フレグランスジャーナル社、１９９６年、ｐ．１５４−１６２

As shown in Table 1, hinokitiol, which is one of the tsuyaprisin of the present invention, is a vitamin A palmitate (non-patent document 1) 3 that has already been reported to have a collagen production promoting effect after 48 hours of culture. Collagen production was remarkably promoted twice as much as that of the non-added control (3.6 times).
“Fragrance Journal, Special Issue No. 15”, Fragrance Journal, 1996, p. 154-162

(2) Test example 2
Hinokitiol aqueous solution: <1> 6.09, <2> 60.9 μmol / L
Positive control Vitamin A palmitate aqueous solution: 1530 IU / g
Collagenase inhibitor Aluminum sulfate aqueous solution: 75.03 μmol / L
Negative control No additive The above test products were each added to a three-dimensional cultured human skin model.

[Evaluation of cell activation effect]
Cell activation (cell viability) of cultured cells after 48 hours of culture was measured using the MTT (3- [4,5-dimethylthiazol-2-yl] -2,5-diphenyltetrazole bromide) method.

表２に示したように、本発明のツヤプリシンの１つであるヒノキチオールは、４８時間の培養後、濃度依存的にコラーゲン産生促進効果を高めることが明らかとなった。さらに、コラゲナーゼ阻害剤として知られているアルミニウム（非特許文献２）を添加しても、ヒノキチオールが配合されていない場合には、２４−４８時間後にコラーゲン産生量がわずかに増えたのみであった。従って、本発明のコラーゲン産生促進効果はコラゲナーゼの阻害作用では説明できない別の機能であることが明らかとなった。

As shown in Table 2, it was revealed that hinokitiol, which is one of the tsuyaprisin of the present invention, enhances the collagen production promoting effect in a concentration-dependent manner after 48 hours of culture. Furthermore, even when aluminum known as a collagenase inhibitor (Non-patent Document 2) was added, when hinokitiol was not added, collagen production was only slightly increased after 24-48 hours. . Therefore, it was revealed that the collagen production promoting effect of the present invention is another function that cannot be explained by the inhibitory action of collagenase.

“American Journal of Pathology” (USA), American Society for Research Pathology, December 2001, Vol. 159, No. 6, p. 1981-1986

さらに、表３に示したように、本発明のツヤプリシンの１つであるヒノキチオール（β−ツヤプリシン）のコラーゲン産生促進効果は、細胞賦活作用との相関もなく、このことから、単に細胞賦活効果及び代謝促進によりコラーゲン産生が促進されたわけでないことが明らかとなった。

Furthermore, as shown in Table 3, the collagen production promoting effect of hinokitiol (β-tyaprisin), which is one of the tyaprisin of the present invention, has no correlation with the cell activation action, and from this, the cell activation effect and It became clear that collagen production was not promoted by metabolism promotion.

  Next, the formulation of the composition shown in Table 4 (Example 1, Comparative Example 1) was adjusted by a conventional method, and an actual use test was conducted for 2 months. As panelists, 20 women in their late 30's to 50's who had marked symptoms such as dry skin, wrinkles and sagging were used. These compositions are used twice a day in the morning and evening for 2 months, and the skin condition is “improved”, “slightly improved”, and “no change” before the start of the use test and after the end of the use test. Evaluated. The results of the test are shown in Table 5 as the number of panelists that obtained each evaluation.

表５に示されるように、皮膚の乾燥、はり・弾力の低下、しわ・たるみ等の改善状況については、実施例の本発明は比較例のものに比べて優れた改善効果を有していることが認められた。また、実施例使用群において、皮膚刺激性反応や皮膚感作性反応を示したパネラーも存在しなかった。

As shown in Table 5, the present invention of the example has an improvement effect superior to that of the comparative example with respect to the improvement of dryness of the skin, reduction of elasticity / elasticity, wrinkle / sag, etc. It was recognized that In addition, there was no panel exhibiting a skin irritation reaction or a skin sensitization reaction in the example use group.

  Below, the various prescription examples using the collagen production promoter of this invention are shown. The preparation method for each preparation was adjusted by stirring and dissolving each component for skin lotion, and for each of emulsion, cream, and cosmetic liquids, each component was measured and then heated to about 80 ° C. An oil phase heated to the same temperature was added to the phase, emulsified with stirring, and cooled to room temperature for adjustment.

Formulation Example 1 Lotion
Hinokitiol 0.001 (wt%)
Dipotassium glycyrrhizinate 0.5
Hydrogenated soybean phospholipid 1.0
Ezoukogi Extract 2.0
Hydroxyethyl cellulose 0.5
1,3-butylene glycol 3.0
Paraben 0.2
Polyoxyethylene hydrogenated castor oil 0.3
Alcohol 5.0
Perfume 0.03
Purified water balance

Formulation Example 2 Latex
Hinokitiol 0.01 (wt%)
Retinol palmitate 0.1
Phosphatidylethanolamine 1.0
Ceramide 0.1
Licorice extract 1.0
Carboxyvinyl polymer 0.3
1,3-butylene glycol 5.0
Paraben 0.2
Polyoxyethylene hydrogenated castor oil 0.1
Polyglycerin fatty acid ester 1.0
Polyoxyethylene sorbitan fatty acid ester 0.3
Liquid paraffin 3.0
Potassium hydroxide 0.07
Perfume 0.03
Purified water balance

Formulation Example 3 Cream
Hinokitiol 0.1 (wt%)
Stearyl glycyrrhetinate 0.2
Retinol acetate 0.1
Tocopherol nicotinate 0.2
Cholesterol 1.0
Rhizophosphatidylcholine 1.0
Olive oil 5.0
Glycerin 15.0
Paraben 0.2
Carboxyvinyl polymer 0.3
Polyoxyethylene hydrogenated castor oil 0.1
Monoglycerin fatty acid ester 5.0
Propylene glycol fatty acid ester 5.0
Polyethylene glycol fatty acid ester 0.5
Squalane 10.0
Behenyl alcohol 3.0
Stearic acid 1.0
Plant extract 2.0
Perfume 0.03
Purified water balance

Formulation Example 4 Essence
Hinokitiol 0.5 (wt%)
Tocopherol acetate 0.5
Safflower oil 1.0
Hydroxyethyl cellulose 0.6
Dipropylene glycol 10.0
Paraben 0.2
Polyoxyethylene hydrogenated castor oil 0.1
Polyglycerin fatty acid ester 2.0
Polyoxyethylene sorbitan fatty acid ester 0.5
Squalane 5.0
Stearic acid 1.0
Plant extract 2.0
Perfume 0.03
Purified water balance

  As described above in detail, the collagen production promoter of the present invention prevents and ameliorates skin age-related changes such as a decrease in elasticity and elasticity due to a decrease in collagen, and wrinkles and sagging. It also has an effective effect on the healing process of, and has great industrial value.

The collagen production promotion effect shown by Table 1 is illustrated. The collagen production promotion effect shown by Table 2 is illustrated.

Claims (3)

Collagen production promoter containing tsuyaprisin as an active ingredient. An external preparation for skin containing tsuyaprisin as a collagen production promoter and having an effect of preventing skin aging and promoting wound healing. The collagen production promoter according to claim 1 or the external preparation for skin according to claim 2, wherein the lusterprisin is β-japrisin.

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