JP3135292B2 - External preparation for skin - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a skin external preparation,
More specifically, it relates to a skin external preparation having a high skin cell proliferation effect. The external preparation for skin is suitably applied to cosmetics such as lotions, creams, emulsions, packs, cosmetics for scalp, and pharmaceuticals such as wound treatments and anti-inflammatory ointments.

[0002]

2. Description of the Related Art Psychosaponins extracted from plants such as Saiko have the effects of healing wounds on the skin, preventing and improving skin roughness, and preventing aging that prevents sagging and disappearance of the skin. It is blended.

Further, the extracted saikosaponin is separated into saikosaponin a, saikosaponin b ₁ , saikosaponin b ₂ , saikosaponin c, and saikosaponin d,
A technique in which the above effects are enhanced by using each component alone has been proposed (JP-A-61-7216).

However, an external preparation containing psychosaponin b ₁ and saikosaponin b ₂ becomes unstable when left for a long period of time, and the above-mentioned effects are reduced. Therefore, a skin external preparation that is stable over time is desired. ing.

[0005]

Among the above conditions [0006] The present invention is to stabilize the system comprising saikosaponins b ₁ and b _2, the excellent cell growth-promoting effects have the saikosaponins b ₁ and b ₂ An object of the present invention is to provide a skin external preparation that can be maintained for a long period of time.

[0006]

The first aspect of the present invention resides in an external preparation for skin characterized by containing at least one of saikosaponins b ₁ and b ₂ and an ester of a polyhydric alcohol.

A second aspect is the first aspect, wherein at least one of saikosaponins b ₁ and b ₂ is 0.0001
About 20% by weight. A third aspect is the skin external preparation according to the first or second aspect, characterized in that the polyhydric alcohol ester is contained in an amount of 0.01 to 10% by weight.

Hereinafter, the present invention will be described in detail.

The external preparation for skin of the present invention contains at least _{one of} saikosaponin b ₁ and saikosaponin b ₂ . The compounding amount is 0.0001 in the total amount of the external preparation for skin.
-20% by weight is preferable, and 0.001-10% by weight is more preferable. When the content is 0.001% by weight or more, the effect of improving skin roughness is further improved. On the other hand, when the content is 10% by weight or less, effects such as loss of stickiness and irritation are produced.

The polyhydric alcohol moiety of the polyhydric alcohol ester of the present invention includes, for example, trihydric alcohols such as glycerin, trimethylolpropane and 1,2,6-hexanetriol, tetrahydric alcohols such as pentaerythritol, xylitol and the like. Pentahydric alcohols, hexahydric alcohols such as sorbitol and mannitol, and polyhydric alcohols such as diethylene glycol, dipropylene glycol, triethylene glycol, polypropylene glycol, tetraethylene glycol, diglycerin, polyethylene glycol, triglycerin, tetraglycerin, and polyglycerin Polymer, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, ethylene glycol monophenyl ether Dihydric alcohols such as ethylene glycol monohexyl ether, ethylene glycol mono 2-methylhexyl ether, ethylene glycol isoamyl ether, ethylene glycol benzyl ether, ethylene glycol isopropyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, and ethylene glycol dibutyl ether Alkyl ethers, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, diethylene glycol dibutyl ether, diethylene glycol methyl ethyl ether, triethylene glycol monomethyl ether Le, triethylene glycol Moe methyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monobutyl ether, propylene glycol isopropyl ether,
Dihydric alcohol alkyl ethers such as dipropylene glycol methyl ether, dipropylene glycol ethyl ether, and dipropylene glycol butyl ether;
Glycerin monoalkyl ethers such as xyl alcohol, serachyl alcohol, and batyl alcohol, sorbitol, maltitol, maltotriose, mannitol,
Sucrose, erythritol, glucose, fructose,
Sugar alcohols such as starch-decomposed sugar, maltose, xylitol, and starch-decomposed sugar-reducing alcohol, glysolid, tetrahydrofurfuryl alcohol, POE (polyoxyethylene) tetrahydrofurfuryl alcohol, POP (polyoxypropylene) butyl ether;
POP POE butyl ether, tripolyoxypropylene glycerin ether, POP glycerin ether,
POP glycerin ether phosphate, POP POE pentane erythritol ether and the like.

On the other hand, examples of the acid to be ester-bonded include lower and higher fatty acids having 2 to 30 carbon atoms, such as acetic acid, butyric acid, palmitic acid, myristic acid, and stearic acid.

In the present invention, at least one of the above-mentioned esters of polyhydric alcohol and acid is blended. These blending amounts are 0.05 to 10% by weight based on the total amount of the external preparation for skin.
Is preferable, and 0.5 to 8% by weight is more preferable. 0.5
In the range of ８8% by weight, the stability of the system is further improved, and the skin cell proliferation effect of saikosaponins b ₁ and b2 is maintained for a long period of time.

The external preparation for skin of the present invention may contain, in addition to the above-mentioned essential components, components used in cosmetics and pharmaceuticals, such as aqueous components, powder components, oil components, surfactants, as long as the effects of the present invention are not impaired. An agent, a humectant, a thickener, a preservative, an antioxidant, a fragrance, a coloring agent, a drug and the like can be compounded.

[0014]

EXAMPLES Next, the present invention will be described in detail with reference to examples, but it goes without saying that the technical scope of the present invention is not limited to these examples.

First, the ester of polyhydric alcohol is blended with saikosaponins b ₁ and b ₂ to maintain the effects of wound healing of the skin, prevention and improvement of skin roughening, anti-aging which prevents sagging and loss of skin, and the like. to indicate that is improved by, to prepare an aqueous solution containing (1) saikosaponins b ₁ or b ₂ in aqueous solution and (2) saikosaponins b ₁ or b ₂ and polyhydric alcohol esters, skin cell proliferation The following tests were conducted for the promoting effect and the wound healing effect, and the changes over time in these effects were examined.

[0016] An aqueous solution containing 0.01% ester (dermal cell growth promoting action) (1) 0.01% aqueous solution of saikosaponins b ₁ and (2) saikosaponins b ₁ 0.01% with polyhydric alcohols prepared And left at room temperature.

On the other hand, human skin tissue is sliced and attached to the bottom of a cell culture dish, and Dulbecco's MEM culture solution (1
After culturing for 2 weeks in 0% fetal calf serum, the bottom of the Petri dish is almost completely filled with fibroblasts. The fibroblasts are treated with a 0.1% trypsin solution to make single cells, and a culture solution of 1000 cells / ml is prepared. 1 ml of this solution was collected per petri dish and added to Dulbecco's MEM.
Aqueous solution was added to the culture medium and saikosaponins concentration so becomes 20 ppm (1) or (2), CO ₂ - and cultured for 2 weeks in an incubator. Thereafter, the cells were fixed and stained, and the number of cell colonies was counted. Figure 1 shows the results
Shown in

The solid line in FIG. 1 is the result when the aqueous solution of (1) is added to the culture solution, and the broken line is the result when the aqueous solution of (2) is added. In the broken line, glycerin monoethyl ether diacetate was used as the ester of the polyhydric alcohol.

The cell growth rates in the figures are (1) and (2)
Was expressed as a ratio based on the number of cells in a test performed immediately after the preparation of the aqueous solution.

As is clear from the figure, the addition of glycerin monoethyl ether diacetate (2) hardly reduces the cell growth effect even after 2,000 hours, indicating that the effect is maintained. Was. On the other hand, the cell proliferation effect of the compound (1) containing no polyhydric alcohol ester decreased over time.

[0021] The results, also saikosaponin b _2, was obtained in the same manner.

(Wound healing effect) (1) 200 mg of saikosaponin b ₁ or (2)
200 mg of saikosaponin b _{1 and} 200 mg of glycerin monoethyl ether diacetate in 1 ml of physiological saline
Was prepared and left at room temperature.

Five Wistar rats, 6 weeks old, were
Groups were cut and subjected to a test after shearing. The rat was anesthetized with Nemptal, and the back skin was incised about 2 cm along the midline. Immediately, the incision was sutured with a Mitsuheru, and the aqueous solutions of (1) and (2) were diluted to 1 / 1,000 with physiological saline. Was applied once a day for 2 weeks. Two weeks later, the suture needle was removed, and a skin section was prepared so as to have a cross section of 1 cm.
The cutting tension of this section was measured by Tensilon U manufactured by Toyo Sokki Co., Ltd.
It measured using TM-4.

When the physiological saline of (1) immediately after the preparation was applied, the average tension was 470 g / cm, whereas the average tension was 470 g / cm.
When a physiological saline solution left for 000 hours was applied, the average tension decreased to 270 g / cm. In contrast, (2)
In the case of a physiological saline solution, the weight of the sample after standing for 1000 hours was 460 g / cm, and the sample immediately after the preparation (470 g
/ Cm).

[0025] Similar results with respect to saikosaponins b ₂ was obtained.

(Example 1 and Comparative Example 1)
It was dissolved by adding saikosaponins b ₂ and perfume were prepared alcohol phase. On the other hand, an aqueous phase was prepared by adding propylene glycol monoacetate to ion-exchange water and heating and dissolving it at 70 ° C. The other components except the quince seed extract were mixed and dissolved by heating at 70 ° C. to prepare an oil phase.

In addition, the oil phase is added to the water phase to perform preliminary emulsification,
Subsequently, the mixture was uniformly emulsified with a homomixer. Add the alcohol phase and quince seed extract to the emulsion while stirring.
After cooling to 0 ° C., an emulsion having the following composition was prepared. As a comparative example, an emulsion without the addition of propylene glycol monoacetate was also prepared.

Emulsion Weight% Saikosaponin b ₂ 0.001 Fragrance 0.03 Ethanol 3.0 Stearic acid 1.5 Cetyl alcohol 0.5 Beeswax 2.0 Polyoxyethylene (10) monooleic acid 1.0 Ester Glycerin mono Stearic acid ester 1.0 Ethyl paraben 0.3 Propylene glycol monoacetate 8.0 Quinseed extract (5% aqueous solution) 20.0 Deionized water 62.669 The temporal stability of the emulsions of Example 1 and Comparative Example 1 was measured. In order to investigate, a skin roughness improvement effect test was performed on a human body panel immediately after the preparation and after leaving it in a constant temperature room at 50 ° C. for 6 months.

The method for testing the effect of improving skin roughness is as follows.

A replica of the skin of a healthy female subject is morphologically observed by a replica method using a millisin resin and observed with a microscope. The emulsions of Example 1 and Comparative Example 1 were applied to the left and right half of the face of 25 panels evaluated as having a rough skin state “1” or “2” based on the criteria in Table 1 based on the state of the skin pattern and the peeled state of the stratum corneum. It was applied once a day for 2 weeks.

After two weeks, the condition of the skin was observed again by the replica method described above, and the condition of the skin was evaluated according to the criteria shown in Table 2. Table 2 summarizes the results.

[0032]

[Table 1]

[0033]

[Table 2] As is clear from Table 2, the emulsion of the comparative example left in a constant temperature bath at 50 ° C. for 6 months greatly reduced the effect of improving skin roughness, whereas the emulsion of this example maintained a high effect of improving skin roughness, It was shown to be stable.

(Examples 2 to 6) The composition shown in each Example
External skin preparation prepared based on the method is compared with the conventional example, in both cases, high rough skin stability is enhanced on the improvement effect or wound healing effect, polyhydric esters of alcohols of saikosaponins b ₁ or b ₂ above effect Can be maintained stably.

(Example 2) Lotion by weight (alcohol phase) Saikosaponin b ₁ 0.05 Ethylene glycol disuccininate 4.1 Ethanol 7.0 Polyoxyethylene oleyl alcohol 0.5 Methyl paraben 0.05 Perfume 0 05 (aqueous phase) glycerin 4.0 citric acid 0.01 sodium citrate 0.1 ion-exchanged water 84.14 (production method) An aqueous phase and an alcohol phase were prepared, and after mixing and solubilizing them, filtration was performed. A lotion was prepared.

(Example 3) Cream wt% (oil phase) Saikosaponin b ₂ 1.0 Cetostearyl alcohol 3.5 Squalane 38.0 Beeswax 3.0 Reduced lanolin 5.0 Stearic acid monoglyceride 2.0 Polyoxyethylene (20) Sorbitan 2.0 Monopalmitate Ethylparaben 0.3 Fragrance 0.03 (Aqueous phase) 1,3-butylene glycol acetate 7.0 Glycerin 5.0 Ion-exchanged water 33.17 (Production method) Heat and melt to maintain at 75 ° C.
It was added to the aqueous phase heated to 5 ° C. with stirring. Next, the mixture was uniformly emulsified with a homomixer and then rapidly cooled with stirring to obtain a cream.

(Example 4) Pack weight% saikosaponin b ₁ 0.1 diethylene glycol monobutyl ether 7.0 acetate polyvinyl alcohol 15.0 polyethylene glycol 3.0 ethanol 10.0 methyl paraben 0.05 fragrance 0.05 ion-exchanged water 64.8 (Production method) Polyethylene glycol, propylene glycol, and methyl paraben were added to ion-exchanged water, and the mixture was stirred and dissolved. Next, add polyvinyl alcohol and heat and stir,
Psychosaponin b ₁ , diethylene glycol monobutyl ether acetate, and ethanol in which a fragrance was dissolved were added, and the mixture was stirred and dissolved to obtain a pack.

[0038] (Example 5) Scalp cosmetic wt% (A phase) saikosaponins b ₁ 0.5 1,3-butylene glycol diacetate 6.5 Polyethylene glycol 1500 5.0 Ethanol 5.5 Potassium hydroxide 0 .05 ion-exchanged water 46.95 (phase B) 2-hexyldecyl palmitate 10.0 squalane 5.0 butylparaben 0.2 vitamin E acetate 0.15 fragrance 0.05 (phase C) ion-exchanged water 19.9 Carboxyvinyl polymer 0.2 (Preparation method) A solution prepared by dissolving phase B at 75 ° C. is added to phase A heated to 75 ° C. while stirring, and phase C dissolved by stirring at room temperature is further cooled while stirring. To obtain a scalp cosmetic.

[0039] (Example 6) Ointment wt% saikosaponins b ₂ 5.0 glycerol monoethyl ether diacetate 3.0 Vaseline 40.0 Stearyl alcohol 15.0 Japan wax 20.0 Polyoxyethylene (10) monooleate 0 .25 ester glycerin monostearate 0.25 ion-exchanged water 16.5 (Preparation method) Add other components mixed and dissolved in ion-exchanged water at 70 ° C at 70 ° C, homogenize with a homomixer, cool after emulsification An ointment was obtained.

[0040]

Effect of the Invention] The present invention, namely by incorporating the ester of polyhydric alcohol saikosaponins b ₁ or saikosaponins b _2, the stability of the cell growth effect possessed by saikosaponins b ₁ or b ₂ is improved . As a result, it is possible to provide a skin external preparation that exhibits a high effect of preventing and improving rough skin, an effect of preventing skin aging or an effect of healing wounds stably over a long period of time.

[Brief description of the drawings]

1 is a graph showing the time course of cellular proliferative effects of saikosaponins b _1.

──────────────────────────────────────────────────続 き Continuation of front page (56) References JP-A-61-7216 (JP, A) JP-A-1-19014 (JP, A) JP-A-63-255212 (JP, A) JP-A-58-58 88333 (JP, A) JP-A-56-92208 (JP, A) JP-A-60-199807 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K 7/00-7 / 50 CA (STN) REGISTRY (STN)

Claims (2)

(57) [Claims] 1. Saikosaponin b ₁ and saikosaponin b ₂
Of a skin external preparation containing at least one ester of a polyhydric alcohol, less of the saikosaponins b ₁ and saikosaponins b ₂
An external preparation for skin characterized by containing 0.0001 to 20% by weight of at least one of them . 2. The method according to claim 2, wherein the ester of the polyhydric alcohol is 0.0
Skin external preparation according to claim 1, characterized in that it comprises 1 to 10 wt%.