TW201622696A - Ceramide-formulated external agent composition - Google Patents

Abstract

To provide a ceramide-containing external agent composition that has an improved barrier performance. The invention relates to an external agent composition comprising type I ceramide, type II ceramide, type III ceramide, and phytosterol. The formulation amount of type I ceramide is preferably 0.002 to 300 parts by weight per 100 parts by weight of type II ceramide.

Description

Mixture of neural amide

The present invention relates to a composition other than a blend of neural guanamine.

It is known that various environmental factors such as dryness and ultraviolet rays, and skin aging with age, or atopic skin lesions, can lower the barrier function of the stratum corneum of the skin, and produce symptoms such as dry and rough skin, and the barrier function is The layered structure composed of lipids and keratinocytes is maintained by keratinocytes.

The main component of the keratinocyte lipid is ceramide, and a neurolamine-containing external preparation having a purpose of repairing the stratum corneum barrier function is known (Patent Documents 1 and 2). However, since the nervous amine is expensive, it is not easily dissolved in the cosmetic substrate, and crystals are precipitated, it is not easy to increase the amount of the neuropterin blended in the external composition, and thus it is impossible to obtain the neurosteroid containing and has A topical agent composition that is fully barrier function.

On the other hand, lipids in keratinocytes contain cholesterol in addition to neuropterin, which is currently being reviewed and will be similar to cholesterol. The constructed phytosterol is used in an external composition for repairing the barrier function. However, since phytosterols are hardly soluble in fat and insoluble in water, it is not easy to use them in an external preparation composition, and thus an external preparation composition containing phytosterols and having a sufficient barrier function cannot be obtained.

[Previous Technical Document] [Patent Document]

[Patent Document 1] JP-A-2000-256188

[Patent Document 2] JP-A-2001-199872

The present invention has been made in an effort to provide a composition containing a neurolamine-containing agent which enhances the barrier function of the skin.

The inventors of the present invention have found that the barrier function of the skin can be effectively improved by containing a type I neuronamine, a type II neuropterin, a type III neuropterin, and a phytosterol, and the present invention has been completed.

That is, the present invention relates to a composition containing a type I neurosteroid, a type II neuropterin, a type III neurodecylamine, and a phytosterol.

The blending amount of type I neural guanamine relative to 100 parts by weight of II The neurosteroid amine is preferably 0.002 to 300 parts by weight.

The blending amount of the type III neuropterin is preferably 0.24 to 300 parts by weight based on 100 parts by weight of the type II neural steroid.

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

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

The composition for external use of the present invention can enhance the barrier function of the skin by containing type I neuronamine, type II neural steroid, type III ceramide, and phytosterol.

The composition for external use of the present invention contains type I neuronamine, type II neural amide, type III ceramide, and phytosterol.

There are seven kinds of free neuropterin (type I to type VII) and two kinds of membrane protein-bound neural amines (type A and type B) which constitute neuropeptides of keratinocyte intercellular lipids. These neuropteramines play an important role in forming a layered structure with a stable epidermis, maintaining moisture and preventing barrier function of skin such as foreign body invasion. The present invention particularly contains type I neuronamine, type II neural guanamine, and type III neural guanamine in the neurosteroids.

Type I neuropterin-based N-(ω-methoxy-indenyl) phytosphingosine and N-(ω-decyloxy-fluorenyl) sphingosine can be used from animals, plants, yeast, etc. Those who have been extracted and divided by each organization, and those who synthesize by chemical or enzyme methods. The type I neuropterin is preferably N-(ω-methoxy-indenyl) phytosphingosine. In addition, Among the fluorenyl fluorenyl groups, a sulfhydryl group bonded to phytosphingosine and sphingosine by direct guanamine bonding is preferably a linear chain having a carbon number of about 20 to 38 and saturated. More specifically, the carbon number of the sulfhydryl group is preferably from 20 to 34, preferably from 24 to 30, more preferably from 26 to 30, and most preferably from 27 to 30. Further, a thiol group bonded to a sphingosine or a sphingosine bond via an ester bond to the thiol group is preferably a carbon number of about 12 to 38 and preferably saturated, and a hydroxyl group is preferred. However, the linear chain is better. Further, the carbon number of the base is preferably 14 to 30, 16 to 28 is better, 16 to 20 is better, and 18 is the best.

Type II neural steroid amine N-mercapto sphingosine, or N-mercapto dihydrosphingosine, which can be extracted and divided using various tissues from animals and the like, and utilizes chemical properties. Or a combination of enzymes and other methods. Type II neuropterin is preferably N-mercaptodihydrosphingosine. Further, the sulfhydryl group is preferably a saturated or unsaturated group having a carbon number of about 12 to 38, and is preferably saturated and linear. Further, the fluorenyl group may be one having a hydroxyl group, but it is more preferably a group having no hydroxyl group. The carbon number of the thiol group is preferably 14~30, 16~28 is better, 16~24 is better, and 18 is the best.

The type III neuropterin-based sulfhydryl sphingosine can be synthesized by extraction and division from tissues such as animals, plants, and yeast, and synthesized by methods such as chemical or enzyme. The sulfhydryl group is preferably saturated or unsaturated with a carbon number of about 12 to 38, and saturated and linear is preferred. Further, the fluorenyl group may be one having a hydroxyl group, but it is more preferably a group having no hydroxyl group. The carbon number of the thiol group is preferably 14~30, 16~28 is better, 16~24 is better, and 18 is the best.

From the perspective of improving skin barrier function, type I neuropterin The blending amount is preferably 0.002 to 300 parts by weight, more preferably 0.0025 to 300 parts by weight, and most preferably 0.00495 to 100 parts by weight, per 100 parts by weight of the type II neural steroid.

From the viewpoint of improving the skin barrier function, the blending amount of the type III neuropterin is preferably 0.24 to 300 parts by weight based on 100 parts by weight of the type II neuropterin, more preferably 1.25 to 300 parts by weight, and 1.25 to 149.5 parts by weight. Very good.

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

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

From the viewpoint of improving the skin barrier function, the content of the type III neuropterin is preferably 0.0001 to 10% by weight, more preferably 0.01 to 8% by weight, more preferably 0.03 to 5% by weight, and most preferably 0.04 to 3% by weight.

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

Plant sterols can be found in small amounts of vegetable alcohols in vegetable oils such as corn, beans or other vegetable oils. Although plant sterols have a structure similar to cholesterol, the carbon chain of the side chain is different from cholesterol. The phytosterol in the external composition of the present invention is not limited, and examples thereof include β-sterol, rapeseed sterol, stigmasterol, and rapeseed sterol, and these may also be used. mixture.

The content of the phytosterol in the external preparation composition is preferably 0.001 to 60% by weight, more preferably 0.03 to 30% by weight, and most preferably 0.3 to 5% by weight. When it is less than 0.001% by weight, there is a tendency to form a layered structure. When it exceeds 60% by weight, there is a tendency that it is difficult to dissolve in the composition.

In addition, from the viewpoint of improving the skin barrier function, the amount of the plant sterol is 0.075 in the external composition with respect to 100 parts by weight of the total amount of the type I neuronamine, the type II neuropterin, and the type III neuropterin. ~60000 parts by weight is preferred, 0.75 to 1500 parts by weight is more preferred, 7.5 to 375 parts by weight is particularly preferred, and 35 to 150 parts by weight is most preferred.

It is preferred that the external composition contains water. Examples of the water include pure water, distilled water, sterilized water, physiological saline, deep ocean water, and the like.

The base of the external preparation composition may, for example, be water, a polyhydric alcohol, an ethanol, a polyoxygenated oil, a hydrocarbon oil, an ester oil, a vegetable oil, a higher alcohol, a higher fatty acid or the like.

The external preparation composition may contain an active ingredient and an additive as appropriate in addition to the type I neuronamine, the type II neuropterin, the type III neuropterin, and the phytosterol.

The active ingredient may, for example, be an ultraviolet preventive agent, a whitening agent, an anti-inflammatory agent, an anti-aging agent, a blood-suppressing agent, a fragrance, a sterilizing and disinfecting agent, a sweating agent, a deodorizing and deodorizing agent, a hair raising and hair raising agent, and a hair removing agent. , hair dye, perm, repellent, anti-inflammatory analgesic, etc.

The additive may, for example, be a sterol other than phytosterol, a fluorine-based fat or oil, a surfactant, a hydroxy acid, an anthracene derivative or a salt thereof, and may be formed. Film polymer, sugar, plant extract, antioxidant or singlet oxygen remover, sebum inhibiting agent, vitamin, gelling agent, powder, inorganic salt, pH adjuster, viscosity modifier, antioxidant, antiseptic Agent, metal ion chelating agent, cooling agent, pigment, solid and semi-solid oil, water-soluble polymer, oil-soluble polymer, biocompatible polymer, liposome preparation, capsule preparation, pearlescent agent, micro-nano Latex preparations, etc.

The external agent composition can be produced by a method generally used in the field. For example, type I neuronamine, type II neuropterin, type III neuropterin, and phytosterols, as well as other components as needed, are in type I neuronamine, type II neuropterin, type III neuropterin, and The blending amount of the plant sterol is added to the base in the above range, and is produced by mixing.

The composition for external use has the advantage of improving the skin barrier function, and the barrier function is particularly suitable for use in moisturizing the skin. Therefore, the external composition of the present invention can be used for a cosmetic applied to the skin, for example, as a cosmetic soap, a face wash, a makeup remover, an eye cream, an eye shadow, a cream, a lotion, a lotion, a perfume, a foundation, and honey. Powder, cosmetic oil, balm, powder, mask, suntan lotion, sunscreen lotion, sun lotion, sunscreen lotion, sun cream, sunscreen cream, hair removal cream, hair removal lotion, blush, eyelashes Cream, bath cosmetics, lipstick, lip balm, eyeliner, antiperspirant, bathing agent.

Further, the composition for external use can be used not only as a cosmetic suitable for the skin but also as a cosmetic for hair or nails. Examples of the cosmetic for hair include shampoo, conditioner, hair dye, hair conditioner, and hair growth. Agent, eyebrow pencil, etc. Examples of the cosmetic for nails include nail varnish, nail varnish, and glazing liquid.

The composition for external use can be used as a transdermal pharmaceutical composition or the like in addition to the cosmetic use. Examples of the percutaneous pharmaceutical composition include a sterilizing and disinfecting agent, a frostbite drug, a cracking drug, a suppurative disease drug, a topical analgesic drug, a topical analgesic drug, a topical astringent drug, a topical anti-inflammatory drug, a Hong Kong foot and a recalcitrant drug, and a skin softening. Medicine, hair medication, etc.

The composition of the external preparation can be formulated into a cream, an ointment, an emulsion, a gel, a latex or the like.

The barrier function of the external preparation composition can be measured by, for example, the method described in the examples. That is, type I neuronamine, type II neural amide, type III ceramide, and phytosterol were added to chloroform and dissolved to prepare a neural guanamine solution. Further, the neural guanamine solution was impregnated into a membrane filter (manufactured by Cellues, membrane pressure: 0.2 μm), and a ceramide membrane was produced by evaporating chloroform at room temperature. 1 mL of water was added to the ampoule and covered with the aforementioned neural guanamine film on the bottle mouth. The ampoules were maintained at 50 ° C for 3 days, and the amount of evapotranspiration of the water was calculated from the change in weight of the ampoule. The amount of moisture evapotranspiration when no neuropterin or phytosterol was used was used to calculate the barrier function by the following calculation formula.

Barrier function (%) = 100 - (moisture evapotranspiration (mg) of the sample / amount of water evapotranspiration (mg) when no neuropterin or phytosterol is used) × 100

[Examples]

The present invention is specifically described in the examples, but the present invention is not limited to the examples.

(Example 1 and Comparative Examples 1 to 2)

The concentration shown in Table 1 was added, and the following type I neuronamine, type II neural amide, type III ceramide, and phytosterol were added to chloroform and dissolved to prepare a ceramide solution.

Type I neuropterin: N-(27-stearyl alcoholoxyheptanyl) phytosphingosine (CERAMIDE I: Evonik Degussa Co., Ltd., Japan)

Type II neural guanamine: stearyl alcohol dihydrosphingosine (neuroguanamine TIC-001: Takasago Perfumery Industrial Co., Ltd.)

Type III neural guanamine: stearyl alcohol phytosphingosine (CERAMIDE III: Japan Evonik Degussa Co., Ltd.)

Plant sterols: phytosterols (plant sterols - SKP: TAMA Biochemical Co., Ltd.)

The neural guanamine solution was impregnated into a membrane filter (manufactured by Cellues, membrane pressure: 0.2 μm), and a ceramide membrane was prepared by evaporating chloroform at room temperature. 1 mL of water was added to the ampoule and covered with the aforementioned neural guanamine film on the bottle mouth. The ampoules were maintained at 50 ° C for 3 days, and the amount of evapotranspiration of the water was calculated from the change in weight of the ampoule. The barrier function was calculated by the following calculation formula in comparison with the amount of moisture evapotranspiration of Comparative Example 2 (no neuropterin). The results are shown in Table 1.

Barrier function (%) = 100 - (water vapor evapotranspiration (mg) of the sample / moisture evapotranspiration (mg) of Comparative Example 2) × 100

The neural guanamine solution of Example 1 has a high barrier function by containing type I neuronamine, type II neural amide, type III ceramide, and phytosterol. Since Comparative Example 1 did not contain phytosterol, Comparative Example 2 did not contain type I to III ceramide, and did not have a barrier function at all.

(Examples 2 to 5 and Comparative Examples 3 to 5)

The concentration of the neuropterin solution as described in Table 2 was adjusted, and the same operation as in Example 1 was carried out to calculate the barrier function. The results are shown in Table 2 together with the results of Example 1.

The neural guanamine solution of Examples 1 and 3 to 5 has a particularly high barrier function by containing 1.25 to 300 parts by weight of a type III neuropterin relative to 100 parts by weight of type II neural guanamine.

(Example 6 and Comparative Examples 6 to 8)

The concentration of the neurotamine solution as described in Table 3 was adjusted, and the same operation as in Example 1 was carried out to calculate the barrier function. The results are shown in Table 3 together with the results of Example 1 and Comparative Example 3.

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

(Examples 7 to 10 and Comparative Examples 9 to 12)

The concentration of the neurotamine solution as described in Table 4 was adjusted, and the same operation as in Example 1 was carried out to calculate the barrier function. As a result, with the example 1 The results are shown together in Table 4.

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

Hereinafter, based on the present invention, the composition for external use described in Tables 5 to 8 will be produced. Any of the external composition is an excellent barrier function by blending type I neuronamine, type II neural amide, type III ceramide, and phytosterol.

(Manufacturing Example 1)

A cream of the composition shown in Table 5 was produced. Specifically, A was dissolved at 80 ° C and B was heated at 80 ° C, and while B was stirred, B was added for emulsification. Thereafter, stirring was continued while adding C, and it was cooled. D, E were added at 40 ° C, stirring was continued and cooled to 35 ° C.

(Manufacturing Example 2)

An emulsion of the composition shown in Table 6 was produced. Specifically, A was dissolved at 80 ° C and B was heated at 80 ° C, and while stirring A with a homomixer, B was gradually added for emulsification. Further, while maintaining stirring, C was added and cooled to 35 °C.

(Manufacturing Example 3)

A moisturizing gel of the composition shown in Table 7 was produced. Specifically, A was dissolved by heating at 90 °C. While stirring A, B was gradually added to the temperature of 90 °C. A and B at 90 ° C were stirred to room temperature and added to C. Further, E is further added to D which is dissolved at room temperature, and then A to C is added. Finally add F and cool to room temperature.

(Manufacturing Example 4)

An emulsion of the composition shown in Table 8 was produced. Specifically, A was dissolved by heating at 90 °C. While stirring A, B was gradually added to the temperature of 90 °C. A and B at 90 ° C were stirred to room temperature and added to C. Further, E was further added to D which was dissolved at room temperature, and cooled to room temperature.

Claims (5)

An external composition comprising a type I neuronamine, a type II neuropterin, a type III neuropterin, and a phytosterol. A composition other than claim 1, wherein the blending amount of the type I neuronamine is 0.002 to 300 parts by weight based on 100 parts by weight of the type II neural amide. A composition other than claim 1 or 2, wherein the blending amount of the type III neuropterin is 0.24 to 300 parts by weight relative to 100 parts by weight of the type II neural steroid. The composition according to any one of claims 1 to 3, wherein the total content of the type I neuronamine, the type II neuropterin, and the type III neuropterin is 0.01 to 10% by weight. The composition of the composition other than any one of claims 1 to 4, wherein the phytosterol content is 0.001 to 60% by weight.