JPS62234006A - External drug for skin - Google Patents

Abstract

PURPOSE:To provide an external drug for skin, containing alpha-cyperone, alpha-cyperol, isocyperol and/or cyperenone and having excellent effect for the remedy of the burning sensation of sunburnt skin, chapped skin and inflammation caused by razor or acne, etc. CONSTITUTION:The objective external drug for skin having stable odor and quality and excellent effect as a remedy for inflammation can be produced by using one or more compounds selected from alpha-cyperone, alpha-cyperol, isocyperol and/or cyperenone expressed by formulas I-IV or an extract of KOBUSHI (bulb of Cyperus rotundus) containing said compounds, preferably purified extract of KOBUSHI as an active component. The amount of the active component is 0.005-20wt%, preferably 0.01$15wt% (dry basis) when the above extract is used as it is or 0.0005-10wt%, preferably 0.001-5wt% (dry basis) when the purified extract is used as the active component.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to an external skin preparation that is highly effective in treating hot flashes after sunburn, rough skin, razor burn, inflammation caused by acne, and the like.

[Prior Art] Kofuji has been used as a herbal medicine and a folk medicine, but its effect on the skin was not clear. While studying α-, β-unsaturated carbonyl- or allyl alcohol-containing compounds such as α-siberone, α-siberol, civerenone, isosiberol, etc. contained in this extract, the present inventors found that these compounds It has been found that it is effective in treating inflammation caused by hot flashes, rough skin, shaving, acne, etc.

[Problem to be Solved by the Invention 1] The present inventors have conducted intensive research on extracts of the natural product such as Kofuzi, with the aim of obtaining a truly effective skin preparation without deterioration or odor. As a result,
In addition to the above findings, external skin preparations containing α,β unsaturated carbonyl or furyl alcohol-containing compounds such as α-siberone, α-siverol, civerenone, and isosiverol do not cause odor or deterioration, and are excellent anti-inflammatory agents. The present inventors have discovered that the present invention can be used, and have completed the present invention.

[Means for Solving the Problems] That is, the present invention is an external skin preparation characterized by containing one or more of the following compounds.

Page Gron Extract R Roll Isosil R Roll Siylenone The structure of the present invention will be explained in detail below.

The α-, β-unsaturated carbonyl or furyl alcohol-containing compound such as α-siberone, α-siverol, civerenone, isosyperol, etc. represented by the above formula may be obtained by any method.

An example of the manufacturing method is shown below.

Although the above-mentioned compound can be obtained by artificial synthesis, it is most preferable to obtain it from a natural product such as Kofuji.

That is, xiangfuzi is mixed with a hydrocarbon such as hexane, benzene, toluene, petroleum ether, liquid paraffin, etc.
Esters such as ethyl acetate, butyl acetate, propyl acetate, and amyl acetate, ketones such as acetone, methyl ethyl ketone, and acetylacetone, ethers such as diethyl ether and dimethyl ether, and halogenated hydrocarbons such as chloroform and trichlene. The extract obtained by heating under reflux and filtration with one or more organic solvents such as alcohols such as ethanol and methanol may be concentrated and purified, or the powdered Kofushi may be purified as it is. May be used. At this time, it is preferable to wash it with hot water to remove dust and bacteria. By this method, a Xiangfuzi extract containing α-cyperone, α-siberol, ciberenone, and isosiverol is obtained.

For α-, β-unsaturated carbonyl or furyl alcohol-containing compounds such as α-siberone, α-siberol, civelenone, and isosiberol, the extract is roughly subjected to silica gel chromatography and eluted with a solvent such as hexane/ethyl acetate. It can be obtained by fractionation.

The compound used in the present invention may be a crude product as extracted as described above, but it is most preferable to use a compound that has been sufficiently purified in this way.

When using the extract as it is, the blending amount is from 0.005 to 20% by weight, preferably from 0.01 to 15% by weight as a dry product, based on the total amount of the skin external preparation.

If it is less than 0.005% by weight, the effect of the present invention cannot be fully exhibited, and if it is more than 20% by weight, it is uneconomical and undesirable.

When using purified α, β unsaturated carbonyl or furyl alcohol-containing compounds such as α-sibene a, α-siverol, civerenone, isosyperol, etc., the blending amount is o,ooos~10 as dry matter in the total amount of the skin external preparation. weight%
, preferably 0.001 to 5% by weight.

If it is less than o, oos weight %, the effect of the present invention cannot be fully exhibited, and if it is more than 10 weight %, it is uneconomical and undesirable.

In addition to the above-mentioned essential ingredients, the external skin preparation of the present invention may optionally include various ingredients commonly used in cosmetics, quasi-drugs, pharmaceuticals, etc., i.e., aqueous ingredients, within the range that does not impair the effects of the present invention. Powder ingredients, oil, surfactants, humectants,
Thickeners, preservatives, antioxidants, fragrances, coloring agents, drugs, etc. can be added.

Further, the dosage form of the cosmetic of the present invention is arbitrary, and can be, for example, a solubilized system such as a lotion, an emulsified system such as a milky lotion or a cream, or a dosage form such as a foundation, a dispersion, or an ointment.

[Effects of the Invention] Compounds containing α, β unsaturated carbonyl or furyl alcohol, such as α-cyperone, α-siberol, cyperenone, and isosyperol, were produced and their effects were studied.

(Manufacturing Example 1) Extract 1 kg of α-Siberon production side with ether, concentrate the extract, apply it to silica gel column chromatography, and elute with a mixed solvent of hexane and acetic acid ethyl ester. , hexane/ethyl acetate mixing ratio 99:1-97
The eluate of the mixed solvent of :3 was concentrated to obtain about 1 g of α-siberone.

The physical properties of α-Cyberone produced as described above were published in the Journal of the Chemical Society (J, Che+s
, Soc, ) 1955.525-8, and was free of deterioration, turbidity, odor, and precipitates.

(Production Example 2) Production of α-Siberol Extract 1 kg of Side Banfuji with acetone, concentrate it, apply the obtained extract to silica gel column chromatography, and elute with a mixed solvent of hexane and acetic acid ethyl ester. , hexane/ethyl acetate mixing ratio 90:10
The eluate of the mixed solvent of ~85:15 was concentrated to obtain about 800 mg of α-siberol.

The structure of α-siberol thus obtained was confirmed by reducing α-siberone with NaBH+.

The extract obtained according to the present invention and α-cyperone, α-cyperol, ciberenone, isosiverol, etc.
, β-unsaturated carbonyl or furyl alcohol-containing compounds did not cause precipitation or turbidity even when incorporated into external skin preparations.

(Anti-inflammatory effect test using ultraviolet erythema method) Next, the effects of α-, β-unsaturated carbonyl or allyl alcohol-containing compounds such as α-cyperone, α-cyperol, cyperenone, isosyperol, etc. applied to the skin will be described.

The ultraviolet erythema method is suitable as a test to measure the anti-inflammatory effect of drugs applied to the skin. That is, the dorsal skin of a Hartley type alpino guinea pig was pricked, and a rubber plate was used on the dorsal skin symmetrically about the midline to 1.41 x 1.
41c+*2 sections are provided, and medium wavelength ultraviolet rays (λ11ax
= 305 nm) to 2. Erythema was created by OJ/am2 irradiation. After UV irradiation, a drug was applied to one compartment, and the formation of erythema was determined over time. The erythema (El) at the drug application site and the erythema (Eo) at the unapplied control site were determined, and the ultraviolet erythema suppression rate was calculated using the following formula, which was taken as the anti-inflammatory activity of the drug. The drug sample was prepared by dissolving the dried residue in ethanol.

Es　E.

Ultraviolet erythema suppression rate = -X 100 (parallels) E.

Measured values 3 hours after drug application are shown in Table 2 as an example.

The determination method is as follows.

Judgment 10: Ultraviolet erythema suppression rate 50% or more 0: Ultraviolet erythema suppression rate 35~sorΔ: Ultraviolet erythema suppression rate
20-35%×: Ultraviolet erythema suppression rate 20 or less Table 2 Ultraviolet erythema suppression rate Strong ultraviolet erythema suppression for compounds containing α, β unsaturated carbonyl or furyl alcohol such as α-siberone, α-siberol, cyperenone, and isosyberol. The effect was observed.

(Actual usage test) The effects of sunburn on hot flashes, rough skin, and razor burn in actual usage tests are shown below.

- Test method - A total of 10 groups were tested, each consisting of 20 healthy female subjects who suffered from hot flashes and rough skin after sunburn, and a lotion containing the formula shown in Table 3 was applied to the face. Comprehensive evaluation was made by evaluating skin irritation and rough skin after one week.

In addition, the test was conducted in a total of 10 groups, with 20 male subjects who suffer from razor burn, and each time after shaving,
One coat of roller containing the formulation shown in was applied to examine the effect on razor sharpness.

-Sample- A lotion containing the formulation shown in Table 3 was used as a sample.

The blending amount is in weight%.

Table-3 Test lotion prescription “Formulation example 1゜1) Glycerin 4.0!2) 1.3
-Butylene glycol 4.0X3) Ethanol
7.0 pieces 4) Polyoxyethylene oleyl alcohol (20 mol) 0.5χ 5) Xiangfuzi hexane extract 0.36) Purified water Remaining "Formulation Example 2゜1) Glycerin 4.0!2) 1.3
-Butylene glycol 4.0%3) Ethanol
7.0 pieces 4) Polyoxyethylene oleyl alcohol (20 mol) 0.5χ 5) α-Ciberone 0.3z6) Purified water Remaining “Formulation Example 3” 1) Glycerin 4.0z2) 1.3
-Butylene glycol 4.0z3) Ethanol
７．０
-Butylene glycol 4. O$3) Ethanol
7.0$ 4) Polyoxyethylene oleyl alcohol (20 mol) 0.5 liters 5) Cyperenone 0.3χ 6) Purified water Remaining formulation example 5 liters) Glycerin 4.0 liters 2) 1.3
-Butylene glycol 4.0%3) Ethanol
7.0$4) Polyoxyethylene oleyl alcohol (20 mol) 0.5 cup 5) Isosyperol 0.3 cup 6) Purified water Remaining - Slight sunburn, hot flashes,
Judgment criteria for rough skin - Significant effect: Hot flashes after sunburn, and 1
After a week, the rough skin was hardly noticeable.

Effective second-day tanning resulted in significantly less hot flashes and rough skin after one week.

Slightly effective second-day tanning resulted in slightly less hot flashes and rough skin after one week.

There was no change in hot flashes or rough skin after 1 week of ineffective second tanning.

Judgment criteria for one razor- Significant effect: Razor stickiness after hair pricking was significantly improved.

Effective: Razor compatibility after hair pricking has been greatly improved.

Slightly effective: Slightly improved razor compatibility after hair pricking.

Invalid: There is no change in the razor blade after hair pricking.

- Judgment for hot flashes after sunburn, rough skin test, and razor dryness test - 0: The test subject's rate of effective and effective results (effective rate) is 6
If it is 0% or more, O: If the test subject's percentage of effective response (effective rate) is 40 to 60% or more △: The test subject's percentage of excellent response or effective response (effective rate) is 2
0 to 40% or more
In the case of 0x or less, Comparative Example 1 in Table 4 used the same formulation as Test Example 1 except that the Xiangfuzi extract was excluded.

As is clear from Table 4, the extract containing α-siberone, α-cyperol, civerenone, isosyberol, and the α-, β-unsaturated carbonyl or furyl alcohol containing α-siberone, α-siberol, civerenone, isosyperol, etc. Formulation Examples 1 to 5 in which the compound was blended had very good improvement effects on hot flashes after sunburn, rough skin after sunburn, and razor burn.

[Example] Next, the present invention will be explained in detail with reference to Examples. Note that the present invention is not limited to this.

The blending amount is in weight%.

Example 1 Lotion (1) Kofuji ethanol extract 0.15 (2)
Glycerin 4.0 (3) 1,
3-Butylene glycol 4.0(4) Ethanol
7.0 (5) Polyoxyethylene oleyl alcohol 0.5 (6) Methyl paraben 0.05 (7)
Citric acid 0.01(8) Sodium citrate 0.1(9) Flavoring
0.05 (10) Purified water
Remaining (11) Sodium hyaluronate
O, OS (manufacturing method) Purified water with citric acid, sodium citrate, glycerin, 1.
Dissolve 3-butylene glycol and sodium hyaluronate. Separately, polyoxyethylene oleyl alcohol, fragrance, methyl paraben, and Kofuji extract were dissolved in ethanol, and this was added to the purified aqueous solution described above to solubilize.
A lotion was obtained by filtration.

Example 2 Cream (1) Cetostearyl alcohol 3.5 (2
) Squalane 40.0 (3)
Beeswax 3.0 (4) Reduced lanolin 5.0 (5) Ethylparaben 0.3 (6) Polyoxyethylene (20) Sorbitan monopalmitate ester
2.0(7) Stearic acid monoglyceride 2
．． 0(8) α-Siberone 1.0
(9) Fragrance 0.03 (
10) 1.3-butylene glycol 5.0
(11) Glycerin 5.0 (1
2) Purified water remainder (manufacturing method) (1) (2) (3) (4) (5) (6) (
7) Dissolve (8) and (9) by heating and keep at 75°C and add to (10), (11) and (12) heated to 75°C with stirring. After processing with a homomixer to make emulsified particles fine, the mixture was rapidly cooled while stirring to obtain cream. Example 3 Emulsion (1) α-Siberol 0.05 (
2) Stearic acid 1.5 (3)
Cetyl alcohol 0.5 (4) Beeswax 2.0 (5) Polyoxyethylene (10) Monooleate 1.0 (6) Glycerin monostearate 1.0 (7) Quince seed extract (5 units water soluble) i) 20.
0(8) Propylene glycol 5.0(
9) Ethanol 3.0 (10
) Ethylparaben 0.3 (11)
Fragrance 0.03 (12)
Purified water Residue (manufacturing method) Add fragrance and α-siberol to ethanol and dissolve (alcohol phase). Add propylene glycol to purified water, dissolve by heating, and keep at 70°C (aqueous phase). Mix other ingredients except quince seed extract, heat and dissolve at 70°C.
(oil phase). Pre-emulsify by adding the oil phase to the water phase and homogeneously emulsify using a homomixer. While stirring, add the alcohol phase and quince seed extract. Thereafter, the mixture was cooled to 30°C while stirring to obtain a milky lotion.

Example 4 Back (1) Siberenone 0.5 (2) Polyvinyl alcohol 15.0 (3) Polyethylene glycol 3.0 (4) Propylene glycol 7.0 (5) Ethanol
10.0(6) Methylparaben 0
．． 05 (7) Fragrance 0.05
(8) Purified water remainder (manufacturing method) Add polyethylene glycol, propylene glycol, and methylparaben to purified water and dissolve with stirring. Next, polyvinyl alcohol was added and stirred with heating, and ethanol and cyperenone in which the fragrance had been dissolved were added and dissolved with stirring to obtain a pack.

Example 5 Solid white powder (1) Talc 85.4
(2) Stearic acid 1.5 (
3) Lanolin 5.0 (4
) Squalane 5.0 (5)
Sorbitan sesquioleate 2.0 (6) Triethanolamine 1.0 (7) Isosiberol 0.1 (8) Pigment
Appropriate amount (9) Fragrance
Appropriate amount (manufacturing method) Thoroughly stir talc and pigment in a kneader (powder part).

Add triethanolamine to 50% equivalent amount of purified water7
Keep at 0°C (aqueous phase). Other ingredients except the fragrance are mixed, heated and dissolved and kept at 70°C (oil phase). The oil phase is added to the water phase and homogeneously emulsified using a homomixer, and this is added to the powder portion and kneaded using a kneader, after which water is evaporated and the mixture is processed using a pulverizer. While stirring the mixture well, spray the fragrance evenly and compression mold.

Example 6 Ointment (1) α-Ciberone 3.0 (
2) Stearyl alcohol 18.0 (3
)Mokurou 20.0(4)
Polyoxyethylene (10) monooleate ester
0.25 (5) Glycerin monostearate 0.25 (6) Vaseline 40.0 (
7) Purified water Remaining (8) Sodium hyaluronate 0°5 (9>Collagen hydrolyzate 0.1 (manufacturing method) Keep purified water at 70°C (water phase). Mix and dissolve other ingredients at 70°C. (Oil phase) The oil phase was added to the water phase, uniformly emulsified with a homomixer, and then cooled to obtain an ointment.

The cosmetics obtained from Examples 1 to 6 were excellent in effectiveness against inflammation caused by hot flashes, rough skin, razor burn, acne, and the like.

Claims (1)

[Scope of Claims] A skin preparation for external use, characterized by containing one or more of the following compounds. ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ α-Cyperone ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ α-Cyperol ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ Isosyperol ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ Cyperenone