JPH08231368A - Light-aging preventing agent and skin cosmetic containing the agent - Google Patents

Abstract

PURPOSE: To provide a light-aging preventing agent having excellent stability and safety, exhibiting excellent light-aging preventing effect, effective for preventing and ameliorating wrinkles, sagging, etc., of the skin and useful for a skin cosmetic having excellent skin-beautifying effect. CONSTITUTION: This light-aging preventing agent contains hexahydrocurcumin of the formula as an active component. A skin cosmetic is produced by compounding the light-aging preventing agent in an amount of 0.001-10wt.%, preferably 0.01-1wt.% based on the total cosmetic. The hexahydrocurcumin can be produced e.g. by reducing curcumin with hydrogen. The cosmetic is preferably applied in the form of cream, milky lotion, oil, etc., from the viewpoint of percutaneous absorbability.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a photoaging agent and a skin cosmetic containing the same, and more specifically, to a photoaging agent containing hexahydrocurcumin as an active ingredient and wrinkles, tarmi and the like containing the same. The present invention relates to a skin cosmetic having an excellent skin-preventing effect to prevent and improve.

[0002]

2. Description of the Related Art In general, skin aging is a physiological phenomenon caused by the mutual effects of physiological aging associated with aging and photoaging due to exposure to sunlight (ultraviolet rays). The relationship between skin wrinkles, stains, and tarmi is drawing attention. UV-B for UV damage to the skin
(290-320 nm) -induced DNA damage and erythema,
Although many secondary blackenings have been reported, recently UV-A (320 to 400n) in the long wavelength region of ultraviolet rays has been reported.
There is also growing interest in the harm of m). UV-A
The amount of energy when reaching the ground is 10 times that of UV-B.
Because it doubles and reaches deep inside the dermis, large wrinkles on the skin,
This is because it has been found that it causes Talmi and the like (Bi
ssett, dlet.al: Photoaging of Skin by UVA, "Biolog
ical Responsesto Ultraviolet A Radiation "P181-18
8, Valdenmar Publishing Company, 1992).

Conventionally, in order to prevent the skin from being damaged by these ultraviolet rays, cosmetics containing various kinds of ultraviolet absorbing, scattering and shielding substances such as titanium oxide, zinc oxide, paramethoxycinnamic acid ester, paraaminobenzoic acid ester and the like. (Sunscreen, Sunprotect cosmetics) have been developed and are in use. However, even if these cosmetics are used, it is difficult to protect the skin from overwhelming sun exposure.

Therefore, in this way, the target cells are located around the cells from the ultraviolet rays that have not penetrated into the skin without being cut by the cosmetics present on the skin surface, and in particular from the UV-A that reaches deep inside the dermis. Drugs whose purpose is to protect or repair damaged cells,
For example, superoxide desmutase (SOD), β
-Carotene, vitamin C, etc. have also been developed. However, all of these drugs have poor stability, and even if incorporated into cosmetics, they are deteriorated or decomposed and the intended purpose cannot be sufficiently achieved.

On the other hand, it is known that hexahydrocurcumin can be obtained by extracting from curcuma which is a ginger family plant or by reducing curcumin contained in the root of turmeric. It is not known to have a photoaging inhibitory effect, and there is no report of a cosmetic for beautiful skin containing this hexahydrocurcumin as a photoaging inhibitor.

[0006]

The present invention has been made from the above viewpoints, and provides a photoaging agent having stability, good safety, and excellent antiaging effect, Further, it is an object of the present invention to provide a skin cosmetic which prevents and improves skin wrinkles and tarmi caused by photoaging and which is excellent in skin beautifying effect by blending this.

[0007]

Means for Solving the Problems As a result of intensive studies for solving the above problems, the present inventors have found that hexahydrocurcumin represented by the following general formula (I) is safe,
It has both stability and is found to be excellent in the effect of preventing photoaging, and further, a skin cosmetic containing hexahydrocurcumin as a photoaging inhibitor prevents skin wrinkles, tarmi, etc. due to photoaging, The present invention has been completed by finding that it is excellent in improving the beautiful skin effect.

That is, the present invention provides a photoaging inhibitor containing hexahydrocurcumin represented by the following general formula (I) as an active ingredient, and 0.001 to 10 of the photoaging inhibitor with respect to the total amount of cosmetics.
It is a skin cosmetic that contains wt%.

[0009]

Embedded image

The photoaging inhibitor and skin cosmetic of the present invention will be described in detail below. <1> Photoaging Agent of the Present Invention The photoaging agent of the present invention has a hexa structure having a chemical structure in which the double bond of curcumin and the keto group are reduced with hydrogen as represented by the above general formula (I). Although hydrocurcumin is used as an active ingredient, this hexahydrocurcumin can generally be produced by extracting from curcuma or reducing curcumin contained in the root of turmeric. Hexahydrocurcumin can also be produced by chemical synthesis, and its use in the present invention is not limited at all. In the present invention, an appropriate production method may be appropriately selected from among the several production methods of hexahydrocurcumin described above in consideration of economy, safety and the like.

As described above, there are various methods for producing hexahydrocurcumin applicable to the present invention. Among them, the method of subjecting curcumin to hydrogen reduction treatment to obtain hexahydrocurcumin as a target substance is simple and easy. The yield is also good and advantageous. In this case, the raw material curcumin itself is sold as a reagent, but it is not shown in Chem. Pha
rm. Bull. 35 (8) 3298-3304 (19
It is also possible to use the one extracted from turmeric by the method described in 87). A specific method for obtaining hexahydrocurcumin by hydrogen reduction treatment of curcumin will be described below.

Anhydrous methanol was placed in a three-necked flask purged with nitrogen to suspend platinum dioxide (PtO ₂ ). Hydrogen gas was blown into this suspension to activate platinum dioxide as a catalyst, and then an anhydrous methanol solution of curcumin was added,
Room temperature to 60 ° C while stirring with a magnetic stirrer
Then, the reaction is performed for about 2 to 12 hours. Then, the reaction solution is filtered and the filtrate is concentrated to dryness to obtain a crude hexahydrocurcumin product. As a purification method, for example, the above crude product is dissolved in chloroform or the like and subjected to silica gel column chromatography to obtain chloroform: methanol = 95:
A preferred method is to perform 5 as an elution solvent.

The hexahydrocurcumin applied to the photoaging inhibitor of the present invention thus obtained has excellent photoaging resistance and safety, is extremely stable, and discolors even when formulated. Since it does not cause a change with time such as a change in odor or decomposition and inactivation, it can be stably and easily compounded in various dosage forms.

The hexahydrocurcumin obtained as described above is used as a photoaging agent in a suitable dosage form by itself or by dissolving it in a solvent.

<2> Skin Cosmetic of the Present Invention The skin cosmetic of the present invention contains the above photoaging inhibitor in an amount of 0.001 to 10% by weight, preferably 0.0
It is compounded at 1 to 1% by weight. If the amount of the photo-aging agent is less than 0.001% by weight with respect to the skin cosmetic, the skin-improving effect for improving the skin condition such as wrinkles and tarmi may not be sufficiently obtained. %
Even if an amount exceeding the above is used, the effect commensurate with the increase may not be expected.

The dosage form of the cosmetic of the present invention is not particularly limited, and examples thereof include creams, emulsions, oils, lotions, packs, aqueous gels, oil gels and ointments. From the viewpoint, cream, milky lotion, oil and the like are more preferable dosage forms. These skin cosmetics can be produced by the same method as that for ordinary skin cosmetics except that the above photoaging agent is blended.

In addition to the above photoaging inhibitors, the skin cosmetics of the present invention are generally applied to skin cosmetics such as hydrocarbons such as liquid paraffin, petrolatum and squalane, isopropyl myristate (IPM). And synthetic gay wax, jojoba oil, carnauba wax, and other esters, olive oil, beef tallow, and other animal and vegetable oils, cetanol, stearyl alcohol, and other higher alcohols, stearic acid, oleic acid, and other higher fatty acids, sodium lauryl sulfate, alkyl sulfosuccinate Anionic surfactants such as acid esters, 4
Cationic surfactants such as primary alkylamine salts, fatty acid monoglycerides, nonionic surfactants such as pooxyethylene hydrogenated castor oil, surfactants such as amphoteric surfactants such as alkyl betaines, and polyvalent compounds such as glycerin and propylene glycol Alcohols, lower alcohols such as ethanol and propanol, preservatives such as parabens and chlorhexidine gluconate, antioxidants such as vitamin E and butylhydroxytoluene, thickeners such as gum arabic and carboxyvinyl polymer, polyethylene glycol Moisturizers such as citrate, acetate pH adjusting agents, titanium oxide, silica gel, powders such as talc, fragrances, pigments, hyaluronic acid, placenta extract, ginseng extract, sterol glycosides, etc. The medicinal components and the like according to various purposes are appropriately selected and mixed.

In addition to the above photoaging inhibitors, the skin cosmetic of the present invention protects the skin from UV absorbers such as paraaminobenzoic acid derivatives and benzophenone derivatives, and UV rays such as β-carotene and vitamin C. Alternatively, a drug or the like having a repairing effect on skin damaged by ultraviolet rays may be blended.

[0019]

EXAMPLES Examples of the present invention will be described below. First,
First, examples of the photoaging inhibitor of the present invention will be described.

[0020]

Example 1 was placed anhydrous methanol 10mL in a nitrogen-substituted three-neck flask, platinum dioxide (Pt0 ₂₎ 120 mg
Was suspended. Hydrogen gas was blown into this suspension at a rate of 100 mL / min to activate platinum dioxide as a catalyst.
Then, curcumin 200mg is added to anhydrous methanol 40m.
The solution dissolved in L was poured into the flask and reacted at room temperature for 2 hours while stirring with a magnetic stirrer.
After the reaction was completed, the reaction solution was filtered, and the obtained filtrate was concentrated to dryness. The obtained concentrated dry solid was dissolved in chloroform and purified by silica gel column chromatography using chloroform: methanol = 95: 5 (100 mL) as an elution solvent. After purification, the extraction solvent was removed to obtain 50 mg of the target hexahydrocurcumin. The NMR of the obtained hexahydrocurcumin was measured. ¹ H-NMR is shown in FIG. 1, and ¹³ C-NMR chart is shown in FIG. The hexahydrocurcumin thus obtained was used as it was as a photoaging inhibitor, and the following evaluations were carried out.

<Evaluation of Photoaging Agent of the Present Invention> Using the hexahydrocurcumin obtained in Example 1 above as a photoaging agent, the photoaging agent of the present invention suppresses the photo (ultraviolet) aging reaction, The UV erythema inhibitory effect and safety were evaluated.

(1) Light (ultraviolet) aging reaction inhibition test UV-A was applied to the back skin of three groups of hairless mice (9 to 10 weeks old, 5 females) in groups of 5 once a day, 5 times a week. For 6 months. UV light source is Toshiba BLB lamp
-A 7 mm thick glazing was attached between the animal and the lamp to cut B. Irradiation energy amount is 14-28
Although mJ / cm ² / day was set, the amount of energy was gradually increased every month. One hour before UV-A irradiation, 10 mg of hexahydrocurcumin obtained in Example 1 was dissolved in 1 mL of a diluting solvent (equal mixture of propylene glycol and ethanol, the same applies hereinafter) to one group of hairless mice. The resulting mixture (concentration: 1%) was added to the other group by adding 1 mg of the hexahydrocurcumin obtained in Example 1 to a dilution solvent of 1 m.
What was dissolved in L (concentration 0.1%), the remaining 1 group (control group), as a control, only the diluent solvent,
50 μL of each was uniformly applied to the entire back area. Six months after the start of the test, the photoaging reaction generated on the skin was visually evaluated according to the following criteria.

(Judgment Criteria) 0: The skin color is light milky pink and sewage is observed. 1: The skin color turned pale and Tajiwa disappeared. 2: The skin color was moderately pale, and Tajiwawa disappeared,
Weak nodules and large wrinkles and tarmi are observed. 3: The skin color was intensely pale, the white wrinkles disappeared, strong nodules, and strong wrinkles and tarmi were observed.

The average value of the scores of 5 animals was obtained, and the inhibition rate was calculated using the following formula. The results are shown in Table 1.

[0025]

## EQU1 ## Inhibition rate = 100 × (average value of control group−average value of sample administration group) / average value of control group

[0026]

[Table 1]

From these results, the photoaging inhibitor of the present invention comprising hexahydrocurcumin is concentration-dependent (Dose).
-Dependent), U of hairless mouse
It was found to have the effect of suppressing the VA photoaging reaction.

(2) UV Erythema Suppression Test 3 groups of 6 Hartley guinea pigs (weight 700-)
The back of a male (900 g, male) was previously removed and shaved. 1.5 × on a wide bandage so that UV rays do not hit the areas other than the irradiated area.
Six 1.5 cm small holes (three in parallel on the left and right) were opened, and the hair removal site was irradiated with ultraviolet rays. Toshiba FL30-SE was used as a light source. The irradiation energy amount was 768 mJ / cm ² . One time before irradiation of ultraviolet rays and three times every hour after irradiation, for 1 group of guinea pigs,
10 mg of hexahydrocurcumin obtained in Example 1
Was dissolved in 1 mL of a diluent solvent (equal mixture of propylene glycol and ethanol, the same applies hereinafter) (concentration 1%), and to the other group, 1 mg of hexahydrocurcumin obtained in Example 1 was added. What was dissolved in 1 mL of the diluent solvent (concentration 0.1%) was administered to the remaining 1 group (control group) as the control only with the diluent solvent. The single dose was 10 μL / site. After 24 hours of ultraviolet irradiation, a uniform erythema reaction was observed at the 6 sites. This erythema reaction was evaluated according to the following criteria.

(Judgment Criteria) 0: No skin reaction is observed. 1: Weak or erythema with unclear boundaries is observed. 2: Moderate erythema with unclear boundaries is observed. 3: Severely unclear erythema (sometimes accompanied by edema) is observed.

The average value of the scores of 6 animals was determined, and the inhibition rate of erythema of ultraviolet rays by each photoaging agent was determined in the same manner as in the above (1). Table 2 shows the results.

[0031]

[Table 2]

As is clear from the above results, the photo-aging agent of the present invention comprising hexahydrocurcumin has a remarkable inhibitory effect on the erythema of ultraviolet rays of Hartley guinea pigs with a concentration-dependent (Dose-dependent) effect. showed that.

(3) Safety test White petrolatum containing 1% by weight of hexahydrocurcumin obtained in Example 1 was used on the inside of the upper arm of 20 healthy men and women using a mini plaster for a torii patch test (Japan. (Pharmacopoeia) 4 types of specimens containing 5% by weight of white petrolatum, 10% by weight of white petrolatum, and white petrolatum alone were subjected to a closed patch for 24 hours to conduct a skin irritation test. Judgment is based on the following criteria by visual observation 30 minutes after removing the plaster (according to the criteria of the Japan Patch Research Group).
Made in.

(Criteria) −: No redness ±: Slight redness +: Minor redness ++: Clear redness ++++: Redness, papules, blisters ++++: Pustules, sores

The result is that all the subjects were judged as (-) in all the samples, no positive reaction was observed at all, and the photoaging inhibitor of the present invention comprising hexahydrocurcumin was
It was found to have high safety.

Next, examples of skin cosmetics containing the photoaging inhibitor (hexahydrocurcumin) of the present invention obtained in Example 1 above will be described. In addition, the compounding amounts shown below are all parts by weight.

[0037]

[Example 2] Lotion A component of Table 3 was mixed and dissolved at room temperature. On the other hand, the B component was also dissolved at room temperature, and this was added to the A component to be solubilized to obtain a lotion. Similarly, a lotion of Comparative Example containing no photoaging inhibitor of the present invention was produced.

[0038]

[Table 3]

[0039]

Example 3 Emulsion Component A in Table 4 was heated and mixed to 70 ° C. Separately from this, the component B was heated and mixed at 70 ° C., the above component A was added to this to emulsify, and the component C was added while cooling to prepare an emulsion. Similarly, a comparative emulsion containing no photoaging inhibitor of the present invention was produced.

[0040]

[Table 4]

[0041]

Example 4 Cream The components A in Table 5 were mixed by heating to 70 ° C. Separately from this, the component B was heated and mixed at 70 ° C., this was added to the above component A, emulsified and cooled to 35 ° C., and then the component C was further added to prepare a cream. Further, a cream of Comparative Example containing no photoaging inhibitor of the present invention was produced in the same manner.

[0042]

[Table 5]

[0043]

Example 5 Cream Component A in Table 6 was heated and mixed at 80 ° C. Aside from this,
The component B was heated to 80 ° C. The component B was added to the component A to emulsify with stirring, and then cooled to 35 ° C. to obtain a cream.

[0044]

[Table 6]

[0045]

Example 6 Emulsion The components A and B of Table 7 were dissolved at 70 ° C. with stirring. Add component A to component B and perform pre-emulsification, homogenize with a homomixer, then stir at 30 ° C.
To obtain an emulsion.

[0046]

[Table 7]

[0047]

Example 7 Toner Lotion Component A in Table 8 was mixed and dissolved at room temperature. On the other hand, the B component was also dissolved at room temperature, and this was added to the A component to be solubilized to obtain a lotion.

[0048]

[Table 8]

<Evaluation of the Skin Cosmetic of the Present Invention> A healthy adult female in Japan 20 having dry skin roughness, wrinkles, and tarmi on the face.
Named as panelists, 10 people were divided into 2 groups (A group, B group).
To the face, the lotion obtained in Example 2, the milky lotion obtained in Example 3 and the cream obtained in Example 4 were obtained, and for group B, the lotion obtained in Comparative Example 1 and the lotion obtained in Comparative Example 2. The obtained milky lotion and the cream obtained in Comparative Example 3 were continuously used for 3 months by the usual use method each day.

Three months after the start of use of each cosmetic, self-assessment was made according to the following evaluation criteria with respect to the evaluation state of makeup, rough skin, wrinkles, and tarmi on the improved state or the state of natural deterioration. Table 9 shows the number of people with each grade and the average of the grades for each group and each evaluation item.

(Evaluation Criteria) 3: Significant improvement 2: Significant improvement 1: Slight improvement 0: No change -1: Natural deterioration

[0052]

[Table 9]

From these results, the cosmetics of Examples containing the photoaging inhibitor of the present invention (hexahydrocurcumin) were compared to the cosmetics of Comparative Examples not containing the photoaging inhibitor of the present invention. It is clear that it improves skin roughness, wrinkles and tarmi.

[0054]

The photoaging agent of the present invention has high stability,
It has safety and an effective anti-aging effect. Further, the skin cosmetic of the present invention has an excellent skin-beautifying effect of preventing and improving wrinkles and tarmi due to photoaging, and can be safely used without any harmful effect on the skin.

[Brief description of drawings]

FIG. 1 is a diagram showing a ¹ H-NMR spectrum of hexahydrocurcumin obtained in Example 1.

FIG. 2 is a diagram showing a ¹³ C-NMR spectrum of hexahydrocurcumin obtained in Example 1.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification number Agency reference number FI Technical display location A61K 31/12 ADS A61K 31/12 ADS

Claims (2)

[Claims] 1. A photoaging agent containing hexahydrocurcumin represented by the following general formula (I) as an active ingredient. Embedded image 2. A skin cosmetic containing the photoaging inhibitor according to claim 1 in an amount of 0.001 to 10% by weight based on the total amount of the cosmetic.