JPH07277944A - Melanism inhibitor - Google Patents

Abstract

PURPOSE:To obtain a substance useful as a beautifying agent, having excellent inhibitory effect on melanism, high stability and safety. CONSTITUTION:This melanism inhibitor comprises a plant selected from Trachelospermum jasminoides Lemaire, Aftersmisia halodendron Turcz., Carthaums tinctorius L., Cassia tora L., Sparganium stoloniferum Buchham, Trichosantheskirilowii Maxim, Dipsacus asper Wall, Astoragatus membranaceus Bge., Typhaangustate Borg et Chaub, Polygonum lapidopsum Kataga, Rdina rubella Hance, Xanthium sibiricum Patr. ex Widd., Acanthopanax gracilistylus W.W.Smith, Cinnamonum cassiaBl., Elaeagnus angustiforia L., Ganoderma japonimum Iloyd., Clematis chineusis Osbeck., Euonymus forunei Turcz., Astragalus variabilis Bunge, Iris ensata Thomb, Oxytoropis glalora DC., Lalligonum mongilicum, Inula britannaica L., Pogonatun odoratun Mill., Tinospora capillipes Gagn., Sophora alopeuridsS L., Anemone altaia Fisch., Drynaria fortunei J., Achantherum splendens Nevski, Atractylodes ovata DC., Salsona collina Pail., Typha angustata B., Cassia tor L., Achranthesbidentate B and essence obtained by extracting the plant with a solvent as an active ingredient.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a melanin production inhibitory substance, more specifically, a stable and safe melanin production inhibitory substance or tyrosinase activity which is stable and safe by incorporating a plant and a plant solvent extract. It relates to suppressive substances.

Therefore, the substance according to the present invention is useful not only in the field of whitening cosmetics but also in the field of pharmaceuticals as a therapeutic agent for melasma, and can be used in an extremely wide industrial field.

[0003]

2. Description of the Related Art Although not all the pigmentation of the skin generally observed due to spots, freckles, sunburns, etc. has been clarified, tyrosine present in the skin generally becomes a melanin precursor by an enzymatic reaction. Since then, it is believed to be based on the production of melanin by autoxidation. Therefore, substances that suppress the production of melanin are mainly classified into two types. One is a type that directly suppresses the activity of the tyrosinase enzyme itself that affects melanin production, and the other is a type that does not directly suppress the activity of tyrosinase but suppresses melanin production in pigment cells. . There are also substances that have both types. At present, ascorbic acid, glutathione, hydroquinone and the like are generally known as melanin production-inhibiting substances, and various other natural plant-derived components, for example, water-soluble extract of plant herbal medicine (JP-A-61-50909).
Etc. have been proposed.

[0004]

However, ascorbic acids have a problem of stability, and they are unstable in an aqueous system and cause discoloration and odor. Thiol compounds such as glutathione have a problem that they have a strong offensive odor and are easily oxidized. Hydroquinone has a skin safety problem. The effect of kojic acid is extremely slow, and there is a problem with respect to stability such as discoloration. Arbutin has a serious bleaching effect, but has a serious drawback that it is highly cytotoxic. In addition, although the previously proposed mulberry bark and those derived from natural plants such as Toki are alleged to have the advantage of being less irritating, they are not yet satisfactory in terms of stability and effect. Absent. That is, the melanin production inhibitor and tyrosinase activity inhibitor known as the prior art, from the viewpoint of its effect, safety, stability, etc.
A substance that can satisfy all of them has not yet been found, and there is a demand for a synthetically useful melanin production inhibitor or tyrosinase activity inhibitor in pharmaceuticals and cosmetics.

[0005]

In view of the above-mentioned points, the present invention considers the above-mentioned points and uses many plants to treat the melanin production-inhibiting substance with the above-mentioned two types, that is, a substance which directly inhibits tyrosinase activity, and a pigment cell As a result of earnest research on a substance that suppresses melanin, it was found that many plants and plant solvent-extracted extracts have an effect of suppressing melanin, and the invention was completed based on this finding. In the melanin production inhibiting substance of the present invention, talc (T
rachelospermum jasminoides Lemaire) Sakou (Artemis
iahalodendron Turcz.) safflower (Carthamus tinctorius)
L.) Akiko Iku (Cassia tora L.) Sanryo (Sparganium stolo)
niferum BuchHam) Heaven pollen (Trichosanthes kirilowii)
Maxim) Interruption (Dipsacus asper Wall) Yellow Gi (Astoragatus
membranaceus Bge.) Guang Huang (Typhaangustate Borg et Cha
ub) Kusakawa Mura (Polygonum lapidopsum Kataga) Mizumeume (Rd
ina rubella Hance) Blue Ear (Xanthium sibiricum Patr.ex
Widd.) Acanthopanax gracilistylus WWSmi
th) Meat Katsura (Cinnamonum cassia Bl.) Saw (Elaeagnus a)
ngustiforia L.) Reishi (Ganoderma japonicum Iloyd.)
Clematis chineusis Osbeck.Euonymu
s fortunei Turcz.) is a plant that suppresses tyrosinase activity.
e) Horse phosphorus (Iris ensata Thomb) drunken grass (Oxytoropis gla
lora DC.) Mongolian fox tow (Lalligonum mongilicum) Safflower (Carthamus tinctorius L.) Inflorescence (Inula britannic
a L.) Tamambo (Pogonatun odoratun Mill.)
ospora capillipes Gagn.) Clematis chineusi
s Osbeck.) Bitter soybean (Sophora alopeurids SL.) Kumon iris (Anemone altaica Fisch.) Drynaria fortun
ei J.) Kyukyu (Achnatherum splendens Nevski)
White Jutsu (Atractylodes ovata DC.)
panax gracilistylus WWSmith) Sashina (Salsona col)
lina Pall.) Small incense (Typha angustata B.) Akiko Kousuke (Ca
ssia tora L.) A cow's knee (Achyranthes bidentate B.) is a plant that suppresses melanogenesis in pigment cells. That is, the present invention is a melanin production-inhibiting substance containing, as an active ingredient, a plant selected from one or two or more species of the group consisting of the above and a solvent-extracted extract of one or two or more species. The present invention will be described in detail below.

The plant in the present invention refers to the plant itself, but when it is used, it is practical to perform treatment such as mashing, squeezing or powder drying, if necessary, and the plant solvent extraction extract. (Hereinafter, referred to as a plant extract) means a solvent extract, a diluted solution, a concentrated solution, or a dried powder of the above plant obtained by the following method.

The plant extract is water or an organic solvent (hexane, ether, ethyl acetate, butanol, acetone, propanol, ethanol, methanol, propylene glycol, etc.) of the above plant, preferably dried powder.
1,3 butylene glycol) or a solvent prepared by mixing them in a fixed ratio, for example, aqueous alcohol, and usually obtained by extraction at 4 ° C to 100 ° C. The above-mentioned plants and plant extracts are selected according to the purpose of use, and are mixed as a whitening agent in a liquid, powder or pasty prescription system to prepare a whitening cosmetic, a dermatological external drug and a quasi drug. be able to. Generally, the blending amount is 0.001 to
The amount is 100% by weight, preferably 0.01 to 10% by weight. When using the material of the present invention for the above application,
It can be made more effective by specifically examining and selecting the most suitable material corresponding to the purpose and prescription.

[0008]

[Examples] Hereinafter, test examples relating to the melanin production inhibitory effect of plants and plant extracts according to the present invention will be shown, as well as prescription examples using the material as a whitening cosmetic agent for cosmetic purposes, and the present invention will be further detailed. However, the present invention is not limited to this.

[Example 1] Preparation of plant extract

As a raw material for the plant extract, 10 g of dried and powdered product of each plant was used. 10 g of the raw material
Put in a cylindrical filter paper, soak in 100 ml of deionized water, and
Heat extraction was performed at 0 ° C. for 8 hours to obtain a filtrate. This operation was repeated 4 times, and all the filtrates were combined and freeze-dried to obtain a water extract (dry powder) of the plant. Further, with respect to the 50% ethanol aqueous solution extract, a 50% ethanol aqueous solution was used in place of water in the operation in the water extract.
Extraction was performed under reflux conditions during the extraction operation. All the extracts were combined, and the concentrated extract after ethanol was distilled off as much as possible was lyophilized to obtain a 50% ethanol extract of a plant. Ethanol was used as the lower alcohol.
The plant ethanol extract was extracted with a Soxhlet extractor for 8 hours, the solvent was distilled off, and the extract was powdered to obtain an ethanol extract.

Experimental Example 2 Measurement of tyrosinase activity inhibition rate

(1) Preparation of sample solution The plant extract was treated with water or polyoxyethylene (20).
A sample solution is prepared by diluting to a concentration of 10 mg / 1 ml with an appropriate solvent such as a 1% aqueous solution of sorbitan monolaurate.

(2) Preparation of tyrosinase solution Mcllv of mushroom tyrosinase (manufactured by Sigma) was used.
It was prepared by diluting with ain Buffer (pH 6.8).

(3) Method for measuring tyrosinase activity inhibition rate (reference: K. Shimao, Biochem. Biophys. Acta., 62, 205)
-215, 1962)

L-tyrosine solution (0.
3 mg / ml) 1 ml and Mcllvain Buffer (pH 6.8) 1
Add 0.9 ml of the sample solution and blank test solution to each of these test tubes, and incubate at 37 ° C. for 10 minutes. 0.1 ml of the prepared tyrosinase solution is added thereto, the mixture is thoroughly stirred, and immediately, each reaction solution is set in a spectrophotometer, and the absorbance at 475 nm is measured with time. (The absorbance value at each time point is shown with a subscript ₀ immediately after the addition of the tyrosinase solution, and with a subscript _X after the incubation for X minutes after the addition)
Each absorbance value is substituted into the following equation to calculate the tyrosinase activity inhibition rate. In addition, the absorbance value 10 minutes after the addition of the tyrosinase solution is used for the calculation of the tyrosinase activity inhibition rate of the present invention.

[Equation 1]

The absorbance value is measured by the amount of dopachrome (a precursor of melanin) produced. Further, the tyrosinase activity inhibition rate was 0% in the control group, and the higher this value is, the higher the tyrosinase activity inhibition effect is.

Table 1 shows the results of the tyrosinase activity inhibition test.

As shown in Table 1, an extremely strong tyrosinase activity suppressing effect was recognized as compared with the control group.

[Table 1]

Experimental Example 3 Cell Melanin Production Inhibition Test

(1) Preparation of test solution The plant extract was added with CMF-PBS in an amount of 0.1 mg / ml.
A test solution was prepared by diluting to an appropriate concentration of 1 mg / ml and subjecting to autoclave treatment (121 ° C., 15 minutes treatment).

(2) Cell culture Mouse melanoma B-16 was placed in AUTOPOW MINIMUM ESSENTI
The cells were cultured in AL MEDIUM EAGLE (MODIFIED) (manufactured by Flow Laboratories) supplemented with 5% fetal bovine serum. In the test, a fixed amount of cells was placed in a sterile 12-well dish and cultured in the above medium, the above test solution was added on the second day of cell addition, and then the cells were cultured for 4 days.

(3) Cell Melanin Production Inhibition Test After culturing as described above, the medium in the 12-well dish is discarded, the cells are washed with CMF-PBS, and sodium hydroxide solution is added to lyse the cells. The amount of protein in this cell lysate is
It was measured with a ROTEIN ASSAY solution (manufactured by Bio-Rad), this value was taken as the cell growth rate, and this value was divided by the blank value to give the cell growth rate. The absorbance at 400 nm of the cell lysate is measured, and the absorbance at 400 nm divided by the amount of protein is taken as the amount of melanin. CMF-PBS was used as a blank for measuring the effect of the test substance. For the melanin production rate, use the following formula,
The calculation was performed by setting it to 00%.

[Equation 2]

The results of the cell melanin production inhibition test are shown in Table 2.

As shown in Table 2, the melanin production rate was decreased as compared with the control group. The cell growth rate is almost the same as that of the CMF-PBS group, and it is considered that the cells have no toxicity and are highly safe. All samples were autoclaved (121 ℃, 15
The sample was treated with high temperature and high pressure, and the effect of suppressing melanin production was observed even in the sample subjected to high temperature and high pressure treatment, and it is considered that these samples have considerably high stability.

[Table 2]

The prescription examples of the whitening cosmetic composition of the present invention are shown below. The mixing ratio is parts by weight.

[Formulation Example 1] Lotion <Composition> (wt%) Whitening cosmetic ───────────────────── 0.1 Glycerin ───── ──────────────── 5.0 Polyoxyethylene sorbitan monolaurate (20E. 0) ── 1.5 Ethanol ────────────── ──────── 10.0 Antiseptic / antioxidant ───────────────── Appropriate amount of fragrance ────────────── ────────── Appropriate amount of purified water ─────────────────────── Remainder

[Formulation Example 2] Cosmetic cream <Composition> (wt%) Whitening cosmetic agent ───────────────────── 0.1 Beeswax ──── ────────────────── 2.0 Stearyl alcohol ──────────────── 5.0 5.0 Stearic acid ────── ────────────── 8.0 Squalane ───────────────────── 10.0 Self-emulsifying glycerin monostearate ─ ─────── 3.0 Polyoxyethylene cetyl ether (20E.0) ──────── 1.0 Propylene glycol ───────────────── 5. 0 potassium hydroxide ─────────────────── 0.3 fragrance ──────────────────────── -Appropriate amount of preservative Antioxidants ───────────────── qs Purified water ─────────────────────── balance

[Formulation Example 3] Emulsion <Composition> (wt%) Whitening cosmetic agent ───────────────────── 0.1 Squalane ─────── ─────────────── 8.0 Vaseline ────────────────────── 2.0 Beeswah ───── ───────────────── 0.5 sorbitan sesquioleate ───────────── 0.8 polyoxyethylene oleyl ether (20E. 0) ────── 1.2 Carboxyvinyl polymer ────────────── 0.2 Propylene glycol ──────────────── 0.5 Potassium hydroxide ─────────────────── 0.1 Ethanol ───────────────────── 7.0 Perfume ────── ────────────────── Appropriate amount of preservatives / antioxidants ────────────────── Appropriate amount of purified water ───── ────────────────── Remainder

[Formulation Example 4] Packing agent <Composition> (wt%) Whitening cosmetic agent ───────────────────── 0.1 Vinyl acetate resin emulsion ── ─────────── 15.0 Polyvinyl alcohol ──────────────── 10.0 Olive oil ─────────────── ─────── 3.0 Glycerin ───────────────────── 5.0 Titanium oxide ────────────── ──────── 8.0 Kaolin ────────────────────── 7.0 Ethanol ──────────── ───────── 5.0 Fragrance ──────────────────────── Appropriate amount Preservative / antioxidant ────── ─────────── Appropriate amount of purified water ─── ─────────────────── balance

[0030]

[Effects of the Invention] Cosmetics and pharmaceuticals having a high whitening effect due to the excellent melanin purification-inhibiting effect of the above plant extract,
It has the effect of achieving the object of the invention, such as realizing a quasi drug.

Claims (3)

[Claims] 1. Trachelospermum jasminoides Lem
aire) Shako (Artemisia halodendron Turcz.) Safflower (C
arthamus tinctorius L.) Akiko Nagisa (Cassia tora L.)
Sanryo (Sparganium stoloniferum BuchHam) Heaven pollen (Tri
chosantheskirilowii Maxim) Interruption (Dipsacus asper Wal
l) Yellow ginger (Astoragatus membranaceus Bge.) Guang yellow (Typhaa
ngustate Borg et Chaub) Kusagawa Mura (Polygonum lapidops)
umKataga) Mizumeume (Rdina rubella Hance) Blue Ear (Xanthiu
m sibiricum Patr.ex Widd.) Acanthopanax gr
acilistylus WWSmith) Meat Katsura (Cinnamonum cassia Bl.)
Saw (Elaeagnus angustiforia L.) Reishi (Ganoderma
japonicum Iloyd.) Clematis chineusis Osbec
k.) Euonymus fortunei Turcz.
alus variabilis Bunge) Horse Lynn (Iris ensata Thomb)
Oxytoropis glalora DC. Mongolian fox tow (Lalli
gonum mongilicum) Overturned flower (Inula britannica L.)
(Pogonatun odoratun Mill.) Gold orchid (Tinospora cap
illipes Gagn.) Bitter soybean (Sophora alopeuridsS L.) Nine-section iris (Anemone altaica Fisch.) Drynaria fo
rtunei J.) Achnatherum splendens Nev
ski) White Jutsu (Atractylodes ovata DC.) Sashiho (Sal
sona collina Pall.) Small incense (Typha angustata B.) Akiko Nagisa (Cassia tora L.) Achyranthes bidentat
e B.) A melanin production-inhibiting substance containing as an active ingredient a plant selected from one or two or more species selected from the group consisting of e B.) and one or more plant solvent-extracted extract. 2. Trachelospermum jasminoides Lem
aire) Shako (Artemisia halodendron Turcz.) Safflower (C
arthamus tinctorius L.) Akiko Nagisa (Cassia tora L.)
Sanryo (Sparganium stoloniferum BuchHam) Heaven pollen (Tri
chosantheskirilowii Maxim) Interruption (Dipsacus asper Wal
l) Yellow ginger (Astoragatus membranaceus Bge.) Guang yellow (Typhaa
ngustate Borg et Chaub) Kusagawa Mura (Polygonum lapidops)
umKataga) Mizumeume (Rdina rubella Hance) Blue Ear (Xanthiu
m sibiricum Patr.ex Widd.) Acanthopanax gr
acilistylus WWSmith) Meat Katsura (Cinnamonum cassia Bl.)
Saw (Elaeagnus angustiforia L.) Reishi (Ganoderma
japonicum Iloyd.) Clematis chineusis Osbec
k.) Melanin production that suppresses tyrosinase activity using as an active ingredient a plant selected from one or more species of the group consisting of Euonymus fortunei Turcz. and one or more plant solvent-extracted extract It is an inhibitor. 3. Astragalus variabilis Bunge
Horse Rin (Iris ensata Thomb) Drunk horse grass (Oxytoropis glalor)
a DC.) Mongolian fox tow (Lalligonum mongilicum) safflower (C
arthamus tinctorius L.) Inflorescence (Inula britannica)
L.) Tamatake (Pogonatun odoratun Mill.)
pora capillipes Gagn.) Clematis chineusis
Osbeck.) Bitter soybean (Sophora alopeuridsS L.)
(Anemone altaica Fisch.) Bokuhokuboku (Drynaria fortunei
J.) Kyukyu (Achnatherum splendens Nevski)
White Jutu (Atractylodes ovata DC.)
nax gracilistylus WWSmith) Sashina (Salsona colli
na Pall.) Koukamaki (Typhaangustata B.) Akiko Iku (Cass
ia tora L.) A plant selected from one or two or more species of the group consisting of Ashinranthes bidentate B. and 1
It is a plant that suppresses melanin production in pigment cells, which contains a solvent-extracted extract of one or two or more plants as an active ingredient.