JP6356457B2 - Ceramide-containing external preparation composition - Google Patents

Description

The present invention relates to a ceramide-containing external preparation composition.

It is known that the barrier function of the skin stratum corneum decreases due to various environmental factors such as dryness and ultraviolet rays, aging of the skin with aging, atopic lesions, etc., resulting in rough skin. It is maintained by a lamellar structure consisting of intercellular lipids and keratinocytes.

Ceramide is mentioned as a main component of the stratum corneum lipid, and an external preparation composition containing ceramide is known for the purpose of supplementing the barrier function of the skin stratum corneum (Patent Documents 1 and 2). However, it is not easy to increase the compounding amount of ceramide in an external preparation composition because ceramide is expensive, difficult to dissolve in a cosmetic base, and crystals precipitate. No external preparation composition containing ceramide and having a sufficient barrier function has been obtained.

On the other hand, the keratin intercellular lipid contains cholesterol in addition to ceramide, and the use of phytosterols having a structure similar to cholesterol in an external preparation composition for supplementing the barrier function has also been studied. However, phytosterol is hardly soluble in fat and insoluble in water, so it is not easy to use it in an external preparation composition, and it contains phytosterol and has a sufficient barrier function. An agent composition has not been obtained.

JP 2000-256188 A JP 2001-199872 A

This invention makes it a subject to provide the external preparation composition containing the ceramide which improves the barrier function of skin.

As a result of intensive studies, the present inventor has found that the inclusion of type I ceramide, type II ceramide, type III ceramide, and phytosterol effectively improves the skin barrier function, thereby completing the present invention.

That is, the present invention relates to an external preparation composition containing type I ceramide, type II ceramide, type III ceramide, and phytosterol.

The compounding amount of the type I ceramide is preferably 0.002 to 300 parts by weight with respect to 100 parts by weight of the type II ceramide.

The compounding amount of the type III ceramide is preferably 0.24 to 300 parts by weight with respect to 100 parts by weight of the type II ceramide.

The total content of type I ceramide, type II ceramide, and type III ceramide is preferably 0.01 to 10% by weight.

The phytosterol content is preferably 0.001 to 60% by weight.

The external preparation composition of the present invention can improve the skin barrier function by containing type I ceramide, type II ceramide, type III ceramide, and phytosterol.

The external preparation composition of the present invention contains type I ceramide, type II ceramide, type III ceramide, and phytosterol.

As ceramides constituting keratin intercellular lipids, seven types of free ceramides (types I to VII) and two types of membrane protein-bound ceramides (types A and B) are known. These ceramides play an important role in maintaining barrier functions such as formation and stability of the lamellar structure of the epidermis, retention of moisture, and prevention of foreign matter intrusion. In the present invention, among these ceramides, in particular, type I ceramide, type II ceramide, and type III ceramide are included.

Type I ceramide is N- (ω-acyloxy-acyl) phytosphingosine and N- (ω-acyloxy-acyl) sphingosine, which is obtained by extraction and fractionation from tissues such as animals, plants, and yeasts. Those synthesized by chemical or enzymatic methods can be used. As the type I ceramide, N- (ω-acyloxy-acyl) phytosphingosine is preferable. Of the acyloxyacyl groups, phytosphingosine or an acyl group directly amide-bonded to sphingosine is preferably a straight chain and saturated group having about 20 to 38 carbon atoms. More specifically, the acyl group preferably has 20 to 34 carbon atoms, more preferably 24 to 30 carbon atoms, still more preferably 26 to 30 carbon atoms, and particularly preferably 27 carbon atoms. preferable. Moreover, as an acyl group couple | bonded with phytosphingosine or a sphingosine through the ester bond with the said acyl group, a C12-38 saturated thing is preferable, and it may have a hydroxyl group, but it must be linear. More preferably, the acyl group has more preferably 14 to 30 carbon atoms, still more preferably 16 to 28, even more preferably 16 to 20, and particularly preferably 18.

Type II ceramide is N-acyl sphingosine or N-acyl dihydrosphingosine, which is obtained by extraction and fractionation from tissues such as animals, or those synthesized by chemical or enzymatic methods. it can. As type II ceramide, N-acyl dihydrosphingosine is preferred. Moreover, as an acyl group, a C12-C38 saturated or unsaturated thing is preferable, and a saturated and linear thing is more preferable. The acyl group may have a hydroxyl group, but preferably does not have a hydroxyl group. The number of carbon atoms of the acyl group is more preferably 14 to 30, further preferably 16 to 28, still more preferably 16 to 24, and particularly preferably 18.

Type III ceramide is N-acyl phytosphingosine, which can be extracted and fractionated from tissues such as animals, plants and yeasts, or synthesized by chemical or enzymatic methods. . The acyl group is preferably a saturated or unsaturated group having about 12 to 38 carbon atoms, and more preferably a saturated and straight chain group. Moreover, although the said acyl group may have a hydroxyl group, the thing which does not have a hydroxyl group is more preferable. The number of carbon atoms of the acyl group is more preferably 14 to 30, further preferably 16 to 28, still more preferably 16 to 24, and particularly preferably 18.

From the viewpoint of improving the barrier function of the skin, the amount of the type I ceramide is preferably 0.002 to 300 parts by weight, and preferably 0.0025 to 300 parts by weight with respect to 100 parts by weight of the type II ceramide. More preferably, the amount is 0.00495 to 100 parts by weight.

From the viewpoint of improving the skin barrier function, the compounding amount of the type III ceramide is preferably 0.24 to 300 parts by weight, and preferably 1.25 to 300 parts by weight with respect to 100 parts by weight of the type II ceramide. More preferably, the amount is 1.25 to 149.5 parts by weight.

From the viewpoint of improving the barrier function of the skin, the content of type I ceramide is preferably 0.00001 to 10% by weight, more preferably 0.00005 to 8% by weight, and 0.000075 to 5% by weight is more preferable, and 0.0001 to 2% by weight is even more preferable.

From the viewpoint of improving the barrier function of the skin, the content of the type II ceramide is preferably 0.0001 to 10% by weight, more preferably 0.5 to 8% by weight, and 1 to 5% by weight. % Is more preferable, and 2 to 5% by weight is even more preferable.

From the viewpoint of improving the barrier function of the skin, the content of the type III ceramide is preferably 0.0001 to 10% by weight, more preferably 0.01 to 8% by weight, 5% by weight is more preferable, and 0.04 to 3% by weight is even more preferable.

The total content of type I ceramide, type II ceramide, and type III ceramide is preferably 0.01 to 10% by weight, more preferably 2 to 8.5% by weight, and more preferably 3 to 5.1. More preferably, it is% by weight.

Phytosterols are plant sterols found in small amounts in vegetable oils such as corn, beans or other vegetable oils. Phytosterol has a structure similar to cholesterol, but the carbon skeleton of the side chain is different from cholesterol. In the external preparation composition of the present invention, phytosterol is not particularly limited, and examples thereof include β-sitosterol, campesterol, stigmasterol, and brassicasterol, and may be a mixture thereof.

In the external preparation composition, the content of phytosterol is preferably 0.001 to 60% by weight, more preferably 0.03 to 30% by weight, and 0.3 to 5% by weight. Further preferred. If it is less than 0.001% by weight, the ability to form a lamellar structure tends to be poor. If it exceeds 60% by weight, it tends to be difficult to dissolve in the composition.

From the viewpoint of improving the skin barrier function, in the external preparation composition, the content of phytosterol relative to 100 parts by weight of the total amount of type I ceramide, type II ceramide and type III ceramide is 0.075 to 60000 parts by weight. Preferably, it is 0.75 to 1500 parts by weight, more preferably 7.5 to 375 parts by weight, and even more preferably 35 to 150 parts by weight.

It is desirable that the external preparation composition contains water. Examples of water include purified water, distilled water, sterilized water, physiological saline, and deep sea water.

Examples of the base of the external preparation composition include water, polyol, alcohol, silicone oil, hydrocarbon oil, ester oil, vegetable oil, higher alcohol, and higher fatty acid.

The external preparation composition may appropriately contain an active ingredient and an additive depending on each application in addition to the type I ceramide, the type II ceramide, the type III ceramide, and the phytosterol.

Examples of active ingredients include UV protection agents, whitening agents, anti-inflammatory agents, anti-aging agents, blood circulation promoters, fragrances, bactericides / disinfectants, antiperspirants, deodorants / deodorants, hair growth / hair restorers, hair removers , Hair dyes, permanent wave agents, repellents, anti-inflammatory analgesics and the like.

Examples of additives include sterols other than phytosterols, fluorine oils, surfactants, hydroxy acids, guanidine derivatives or salts thereof, film-forming polymers, sugars, plant extracts, antioxidants or singlet oxygen scavengers, Sebum secretion suppressant, vitamin, gelling agent, powder, inorganic salt, pH adjuster, viscosity adjuster, antioxidant, preservative, sequestering agent, cooling agent, pigment, solid / semi-solid oil, water-soluble Include a water-soluble polymer, an oil-soluble polymer, a biocompatible polymer, a liposome preparation, a capsule preparation, a pearl luster imparting agent, and a micro / nanoemulsion preparation.

An external preparation composition can be manufactured by the method normally used in the said field | area. For example, the amount of type I ceramide, type II ceramide, type III ceramide, and phytosterol and other components as required, and the amount of type I ceramide, type II ceramide, type III ceramide, and phytosterol is within the above range. It can be manufactured by adding to the base and mixing.

The external preparation composition has the advantage of improving the skin barrier function, and can be suitably used for the purpose of moisturizing the skin among the barrier functions. Accordingly, the composition for external use is a cosmetic applied to the skin, for example, a cosmetic soap, a facial cleanser, a makeup remover, an eye cream, an eye shadow, a cream, an emulsion, a lotion, a perfume, a foundation, an interesting, a cosmetic oil, a kneading agent. Perfume, powder, pack, tanning oil, sunscreen oil, tanning lotion, sunscreen lotion, tanning cream, sunscreen cream, shaving cream, shaving lotion, blusher, mascara, bath cosmetic, lipstick, lip balm, eyeliner, It can be used as a deodorant agent and bathing agent.

The external preparation composition can be used not only as a cosmetic applied to the skin but also as a cosmetic for hair or nails. Examples of hair cosmetics include shampoos, rinses, hair dyes, hair nourishing agents, hair restoring agents, eyebrows, and the like. Examples of nail cosmetics include nail cream, beautiful nail enamel, and beautiful nail enamel remover.

The external preparation composition can be used as a transdermal pharmaceutical composition and the like in addition to cosmetic use. Examples of the transdermal pharmaceutical composition include bactericidal antiseptics, mosquitoes, redheads, purulent diseases, topical analgesics, topical antipruritics, topical astringents, topical antiphlogistics, wormworms, and insecticides. And emollients, hair drugs and the like.

The external preparation composition can take the form of cream, ointment, lotion, gel, emulsion and the like.

The barrier function of the external preparation composition can be measured, for example, by the method described in Examples. That is, type I ceramide, type II ceramide, type III ceramide, and phytosterol are added and dissolved in chloroform to prepare a ceramide solution. A ceramide membrane is produced by impregnating a ceramide solution into a membrane filter (made of cellulose, membrane pressure 0.2 μm) and evaporating chloroform at room temperature. 1 ml of water is put into a vial and the mouth of the bottle is closed with the ceramide membrane. The bottle is held at 50 ° C. for 3 days, and the amount of water transpiration is calculated from the change in the weight of the vial. Compared with the amount of water transpiration when ceramide or phytosterol is not used, the barrier function is calculated by the following formula.
Barrier function (%) = 100− (moisture transpiration amount of specimen (mg) / water transpiration amount when ceramide or phytosterol is not used (mg)) × 100

The present invention will be specifically described with reference to examples, but the present invention is not limited to these examples.

(Example 1 and Comparative Examples 1-2)
A ceramide solution was prepared by adding the following type I ceramide, type II ceramide, type III ceramide, and phytosterol to chloroform and dissolving them so that the concentrations shown in Table 1 were obtained.
Type I ceramide: N- (27-stearoyloxyheptacosanoyl) phytosphingosine (CERAMIDE I: Evonik Degussa Japan Co., Ltd.)
Type II ceramide: stearoyl dihydrosphingosine (ceramide TIC-001: Takasago International Corporation)
Type III ceramide: Stearoyl phytosphingosine (CERAMIDE III: Evonik Degussa Japan Co., Ltd.)
Phytosterol: Phytosterol (Phytosterol-SKP: Tama Seikagaku)

A ceramide membrane was prepared by impregnating a ceramide solution into a membrane filter (made of cellulose, membrane pressure 0.2 μm) and evaporating chloroform at room temperature. 1 ml of water was placed in the vial, and the mouth of the bottle was closed with the ceramide membrane. This bottle was kept at 50 ° C. for 3 days, and the amount of water transpiration was calculated from the change in the weight of the vial. The barrier function was calculated by the following calculation formula in comparison with the moisture transpiration amount of Comparative Example 2 (without ceramide). The results are shown in Table 1.
Barrier function (%) = 100− (moisture transpiration amount of specimen (mg) / moisture transpiration amount of comparative example 2 (mg)) × 100

The ceramide solution of Example 1 has a high barrier function by including type I ceramide, type II ceramide, type III ceramide, and phytosterol. Since Comparative Example 1 does not contain phytosterol and Comparative Example 2 does not contain I-III type ceramide, it does not have any barrier function.

(Examples 2-5 and Comparative Examples 3-5)
The ceramide solution was prepared so that it might become the density | concentration of Table 2, the same operation as Example 1 was performed, and the barrier function was computed. The results are shown in Table 2 together with the results of Example 1.

The ceramide solutions of Examples 1 and 3 to 5 have a particularly high barrier function by including 1.25 to 300 parts by weight of III type ceramide with respect to 100 parts by weight of type II ceramide.

(Example 6 and Comparative Examples 6-8)
The ceramide solution was prepared so that it might become the density | concentration of Table 3, and the same operation as Example 1 was performed, and the barrier function was computed. The results are shown in Table 3 together with the results of Example 1 and Comparative Example 3.

The ceramide solutions of Examples 1 and 6 have a high barrier function.

(Examples 7 to 10 and Comparative Examples 9 to 12)
The ceramide solution was prepared so that it might become the density | concentration of Table 4, and the same operation as Example 1 was performed, and the barrier function was computed. The results are shown in Table 4 together with the results of Example 1.

The ceramide solutions of Examples 1, 8 and 9 exhibited a particularly high barrier function by containing 3 to 5.1% by weight of the total of type I ceramide, type II ceramide, and type III ceramide.

Below, the external preparation composition of Tables 5-8 was manufactured based on this invention. Any of the external preparation compositions was excellent in the barrier function by blending type I ceramide, type II ceramide, type III ceramide, and phytosterol.

(Production Example 1)
A cream having the composition shown in Table 5 was produced. Specifically, A was heated and dissolved at 90 ° C. and B at 80 ° C., and while A was stirred, B was added to emulsify. C was then added with stirring and cooled. D and E were added at 40 ° C., and the mixture was cooled to 35 ° C. with stirring.

(Production Example 2)
An emulsion having the composition shown in Table 6 was produced. Specifically, A was heated and dissolved at 90 ° C. and B at 80 ° C., and B was gradually added and emulsified while A was stirred with a homomixer. C was further added with stirring, and the mixture was cooled to 35 ° C.

(Production Example 3)
Moisturizing gels having the compositions shown in Table 7 were produced. Specifically, A was heated and dissolved at 90 ° C. While stirring A, B heated to 90 ° C. was gradually added. 90 ° C. A and B were added to C at room temperature with stirring. Separately, E was added to D dissolved at room temperature, and then A to C were added. Finally, F was added and cooled to room temperature.

(Production Example 4)
Lotions with the compositions shown in Table 8 were produced. Specifically, A was heated and dissolved at 90 ° C. While stirring A, B heated to 90 ° C. was gradually added. 90 ° C. A and B were added to C at room temperature with stirring. Separately, E was added to D dissolved at room temperature, and cooled to room temperature.

Claims (5)

I ceramide, II ceramide, III ceramide, and phytosterols only contains, I ceramide, II ceramide, and the total content of type III ceramide is 2 wt% or more, external preparation composition. The external preparation composition of Claim 1 whose compounding quantity of a type I ceramide is 0.002-300 weight part with respect to 100 weight part of type II ceramide. The external preparation composition according to claim 1 or 2, wherein the amount of the type III ceramide is 0.24 to 300 parts by weight with respect to 100 parts by weight of the type II ceramide. The external preparation composition according to any one of claims 1 to 3, wherein the total content of type I ceramide, type II ceramide, and type III ceramide is 2 to 10 wt%. The external preparation composition in any one of Claims 1-4 whose content of a phytosterol is 0.001 to 60 weight%.