JPH10291929A - Wrinkle suppressive preparation for external use for skin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject preparation for external use useful for cosmetics and medicines by formulating rosmarinic acid thereto. SOLUTION: The rosmarinic acid-containing extract is obtained by immersing (a) terrestrial parts of labiate plants (preferably sage, rosemary, beefsteak plant, thyme or Isdon japonicus Hara) of raw material in (b) water and a lower alcohol (methyl alcohol and the like) in a/b (w/v) ratio of 1/500-1/2, preferably 1/50-1/5, at usually 5-100 deg.C for 1-4 hrs., if necessary under stirring and/or heating. The extract is, if necessary, further purified and then added to a preparation for external use for skin in an amount of 0.0001-2 wt.%, preferably 0.001-10 wt.% to give the subject high safe preparation for external use which inhibits collagenase and collagene crosslink polymerization.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a wrinkle formation-suppressing skin external preparation containing rosmarinic acid as an active ingredient, which has a strong collagenase inhibitory action and an action of inhibiting collagen crosslinking polymerization by ultraviolet rays.

[0002]

2. Description of the Related Art An aging phenomenon such as formation of wrinkles on the skin appears early in sun-exposed areas such as the face and hands, and progresses rapidly. It is well known that deep wrinkles are formed in field workers who have long exposure to the sun. Such a phenomenon is called a photoaging phenomenon, and the relationship with light, particularly ultraviolet light, has been studied. Recently, 320 ~
There have been many research reports on the effect of UVA having a wavelength region of 400 nm on skin. UVB with a wavelength range of 280 to 320 nm absorbs its energy in the epidermis despite its high energy content, while UVA reaches deep into the dermis and has a significant effect on wrinkle formation It has become.

[0003] Kligman et al. Observed a decrease in skin collagen during photoaging, suggesting collagen degradation by collagenase derived from inflammatory cells [J. Inves.
t. Dermatol., vol.93, 210-214, 1989]. Herrmann et al. Also reported that UVA increased the amount of collagenase mRNA transcribed and increased the amount of collagenase secreted in human dermal fibroblasts [Exp. Dermatol.,
vol.2, 92-97, 1993]. Have reported that UVA and hematoporphyrin generate singlet oxygen, forming a crosslinked polymer between collagen molecules [J. So
c. Cosmet. Chem. Jpn., vol. 28, 163-171, 1994]. In addition, Tanaka et al. Reported that superoxide anion, which is widely involved in inflammation, increased collagenase activity in human dermal fibroblasts [Koshokai, vol. 17, No.
4, 202-206, 1993]. These facts suggest that the degradation and cross-linking of collagen caused by ultraviolet light or inflammation has a significant effect on wrinkle formation. However, a substance that inhibits such collagenase and also inhibits collagen cross-linking polymerization has not been known.

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to search for a highly safe component which suppresses the degradation of collagen and the formation of wrinkles due to the cross-linking polymerization of collagen. Another object of the present invention is to provide a skin external preparation having an effect of suppressing wrinkle formation.

[0005]

Means for Solving the Problems The present inventors have widely sought in plants a highly safe active ingredient which inhibits collagenase and inhibits collagen crosslinking polymerization. As a result, they have found that rosmarinic acid contained in a specific plant has such an inhibitory action and is useful as an active ingredient of a skin external preparation for suppressing wrinkle formation. That is, the present invention provides a wrinkle formation-inhibiting skin external preparation containing, as an active ingredient, rosmarinic acid, which has an effect of inhibiting collagenase and inhibiting collagen cross-linking polymerization.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION Rosmarinic acid used in the present invention can be obtained from a plant containing rosmarinic acid through a solvent extraction and purification step by a method described in a document (German Patent DE 3,234,312). The literature [Synthesis, Ju
ne, 755-762, 1996]. Rosmarinic acid thus obtained is commercially available (E
XTRASYNTHESE, France).

Further, an extract containing rosmarinic acid from a plant containing rosmarinic acid can be used in the present invention. Plants containing rosmarinic acid include, for example, plants of the Labiatae family, the purple family, the Oleander family, the Apiaceae family, and the Genie family. It is preferred to use a rosmarinic acid-containing extract obtained by extraction of a Labiatae plant, such as sage, rosemary, perilla, thyme or diatomaceae. More preferably, a rosmarinic acid-containing extract obtained by sage extraction is used in the present invention.

[0008] The plant extract used in the present invention can be obtained by a usual method. The plant part used for the extraction is preferably the above-ground part (leaves and / or stems).
The plant may be used as it is after collection, or may be used after being subjected to a drying treatment such as sun drying. As the extraction solvent, water and one or more kinds of organic solvents such as lower alcohols (eg, methyl alcohol, ethyl alcohol or butanol), acetone or ethyl acetate can be used as appropriate. A preferred extraction solvent is water or a lower alcohol alone, or a mixture of water and a lower alcohol (the mixing ratio of water and lower alcohol may be arbitrary).

The extraction is carried out, for example, by immersing the plant material in the solvent and, if desired, stirring and / or heating. The ratio of plant material / extraction solvent (weight / volume) is
Preferably 1/500 to 1/2, more preferably 1 /
It is 50 to 1/5. The extraction temperature is usually 5-100
° C, preferably in the range of 5 to 50 ° C, and the extraction time is usually 1 to 48 hours. After the extract obtained by the above extraction is concentrated, the active ingredient can be further concentrated and purified by performing solvent replacement, column purification, activated carbon treatment and the like.

There is no particular limitation on the dosage form of the external preparation for suppressing wrinkle formation of the present invention, and it can be used by blending it into cosmetics, quasi-drugs, pharmaceuticals and the like. In particular, it is preferable to prepare and use it in the form of cosmetics. Examples of the form of cosmetics include face wash cream, lotion, milky lotion and the like.

The compounding ratio of rosmarinic acid or a rosmarinic acid-containing plant extract in the wrinkle formation-inhibiting skin external preparation of the present invention varies depending on the dosage form of the skin external preparation. 0.0001 to 2 in the preparation
0% by weight, preferably 0.001 to 10% by weight, more preferably 0.005 to 5% by weight.

The wrinkle formation-inhibiting skin external preparation of the present invention contains, in addition to its active ingredient, rosmarinic acid or a plant extract containing rosmarinic acid, various ingredients generally used in preparing the above-mentioned dosage form. I do. Other ingredients commonly used in preparing cosmetics are, for example, oils, surfactants, humectants, thickeners, preservatives, fragrances, colorings, drugs and the like.

The present invention will be described below with reference to Examples relating to the production of a rosmarinic acid-containing Lamiaceae plant extract used in the external preparation for skin of the present invention, the measurement of the effect of inhibiting the formation of collagen cross-links and the inhibitory effect of collagenase, and the production of various cosmetics. Although described in more detail, the present invention is not limited to these examples.

Example 1 Production of Lamiaceae Plant Extracts To 50 g of each Lamiaceae plant (sage, rosemary, perilla, thyme, or radish), 400 mL of ethanol was added, and the mixture was heated to reflux at 95 ° C. or higher for 2 hours. This mixture is
After allowing to cool to 0 ° C., the mixture was filtered to obtain 340 mL of an extract. The extract was concentrated under reduced pressure while heating at 60 ° C. and dried to dryness. 250 mL of water was added, and the mixture was allowed to stand at 4 ° C. for 48 hours. The generated insoluble precipitate was removed by filtration to obtain 248 mL of a Labiatae plant extract. Each extract thus prepared was concentrated by evaporating volatile components under a nitrogen stream. This concentrate was redissolved in water at a concentration of 1% by weight, and this was used as a Labiatae extract.

Example 2 Measurement of Collagen Crosslinking Inhibition Effect Rosmarinic acid (commercially available product EXTRASYNTHESE, France) and Labiatae extract (French) against the cross-linking reaction of collagen (Type I) by UVA (365 nm) irradiation in the presence of hematoporphyrin The suppression effect of (prepared in Example 1) was examined. 25
To bovine skin collagen Type I (manufactured by Sigma) dissolved in 50 mM Tris-HCl buffer (mM acetic acid), a sufficient amount of a 10% ETOH solution of hematoporphyrin adjusted to 0.2 mM was added. To this, add rosmarinic acid or Labiatae extract to each final concentration (control added the same volume of water)
Then, UVA (365 nm, 2.5 mW) was irradiated for 30 minutes.
After the completion of the reaction, each sample was electrophoresed on a 7.5% acrylamide gel and stained with silver. The amount of the protein thus separated was quantitatively analyzed using a densitometer, and the crosslinking inhibition rate was calculated. These results are shown in FIG. 1 and FIG. FIG.
Thus, it is clear that rosmarinic acid effectively suppresses photocrosslinking by UVA. From FIG. 2, it can be seen that among the extracts of the Labiatae plant, the sage extract is particularly effective in suppressing photocrosslinking by UVA.

Example 3 Measurement of Collagenase Inhibitory Effect Using a type I collagenase assay kit and human skin type I collagenase [Yagai Co., Ltd.], rosmarinic acid (commercially available EX
TRASYNTHESE, France) and the Labiatae extract (prepared in Example 1) were measured for collagenase inhibitory effect. After treating the kit substrate with a neutralizing buffer, rosmarinic acid or Labiatae extract was added to each final concentration (control was added with an equal volume of water), and then human skin type I collagenase was added. Allowed to react for hours. After completion of the reaction, the fluorescence-labeled peptide extracted by the kit extract was measured with a fluorometer (excitation wavelength: 495 nm, fluorescence wavelength: 520 nm), and the inhibition rate of each sample was determined. These results are shown in FIG. 3 and FIG. From FIG. 3, it is clear that rosmarinic acid effectively inhibits collagenase. From FIG. 4, it is clear that, among the Lamiaceae plant extracts, particularly the sage extract has a strong collagenase inhibitory action.

Example 4 Facial cleansing cream The sage extract (prepared in Example 1) is used as an active ingredient in the following facial cleansing cream formulation (100% by weight in total).

TABLE 1 Ingredient A wt% myristine 14.0 stearic acid 12.0 lauric acid 3.5 oleyl alcohol 1.5 coconut oil fatty acid amidopropyl betaine 10.5 component B wt% concentrated glycerin 18.0 potassium hydroxide 7. 0 Preservative (p-hydroxybenzoate) Appropriate amount of purified water Remaining component C weight% sage extract 0.5 Perfume 0.2 Component A is dissolved by heating and kept at 80 ° C. Separately, the component B heated and dissolved at 80 ° C. is added to the component A and mixed well. The mixture was cooled with stirring, and the component C was added at 50 ° C. to obtain a face wash cream.

Example 5 Lotion A sage extract (prepared in Example 1) is used as an active ingredient in the following lotion formulation (total 100% by weight).

TABLE 2 Ingredients % by weight concentrated glycerin 4.0 Sorbit solution (70% by weight aqueous solution) 4.0 Sodium citrate 0.3 Polyoxyethylene hydrogenated castor oil 0.5 Ethanol 15.0 Sage extract 0.1 Fragrance 0.05 Citric acid (pH adjusting agent) Appropriate amount of purified water All remaining components are stirred and mixed at room temperature to form a homogeneous solution.
The pH was adjusted to 5.5 to obtain a lotion.

Example 6 Emulsion Sage extract (prepared in Example 1) is used as an active ingredient in the following emulsion formulation (total 100% by weight).

[Table 3] Component A wt% sucrose fatty acid ester (Daiichi Kogyo Seiyaku S-160) 1.0 concentrated glycerin 6.0 carboxyvinyl polymer 0.06 potassium hydroxide 0.028 preservative (paraoxybenzoate) Purified water Remaining component B wt% olive oil 4.0 Jojoba oil 4.0 Lactic acid 2.0 Self-emulsifying glyceryl monostearate 1.5 Lipophilic glyceryl monostearate 1.5 Component C wt% sage extract 0.5 Flavor 0.2 Component A is dissolved by heating and kept at 80 ° C. Separately, the component B heated and dissolved at 80 ° C. is added to the component A and mixed well. The mixture was cooled with stirring, and the component C was added at 50 ° C. to obtain an emulsion.

Example 7 As a result of applying a cosmetic product such as a face wash cream, lotion, milky lotion and the like containing the sage extract as an active ingredient having an effect of suppressing wrinkle formation to a human as described above, the formation of wrinkles due to ultraviolet rays was suppressed. A remarkable inhibitory effect was observed. In addition, as a result of applying, to humans, various cosmetics containing other rosmarinic acid-containing plant extracts or rosmarinic acid according to the same prescription, the same effect of suppressing wrinkle formation was observed.

[Brief description of the drawings]

FIG. 1 is a graph showing the results of examining the effect of suppressing the formation of collagen cross-links by changing the concentration of rosmarinic acid.

FIG. 2 is a graph showing the results of examining the effect of various Lamiaceae plant extracts on inhibiting the formation of collagen crosslinks.

FIG. 3 is a graph showing the results of examining the collagenase inhibitory effect by changing the concentration of rosmarinic acid.

FIG. 4 is a graph showing the results of examining the collagenase inhibitory effects of various Labiatae plant extracts.

────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 35/78 AED A61K 35/78 AEDQ

Claims (5)

[Claims] 1. A wrinkle formation-inhibiting skin external preparation comprising rosmarinic acid as an active ingredient. 2. The external preparation for skin according to claim 1, comprising a rosmarinic acid-containing plant extract as an active ingredient. 3. The external preparation for skin according to claim 2, wherein the plant extract is an extract of a Labiatae plant. 4. The external preparation for skin according to claim 3, wherein the Lamiaceae plant is sage, rosemary, perilla, thyme, or diatomaceous. 5. The external preparation for skin according to claim 4, wherein the Labiatae plant is sage.