JP2000239157A - Agent for external use for skin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject agent for external use excellent in percutaneous absorption of water soluble pharmacodynamically effective ingredients by including the water soluble pharmacodynamically effective ingredients in an internal water phase and a carboxylic acid ester in an oil phase of a W/O/W type emulsion consisting of the internal water phase, the oil phase and an external water phase. SOLUTION: In a W/O/W type emulsion consisting of an internal water phase, an oil phase and an external water phase, water soluble pharmacodynamically effective ingredients (e.g. antiinflammatory agents, circulation promoters, vitamins, hair growing ingredients, moisturizing agents, hormone preparations, amino acids, hydrolyzed proteins, peptides), are included in the internal water phase, and a carboxylic acid ester (usually an ester of an alcohol and a carboxylic acid, particularly lauryl lactate, isononyl isononanate, cetyl octanoate, ethyl oleate, isopropyl myristate, or the like) is included in the oil phase. The preferable contents of the ingredients are approximately 0.001-80 wt.% water soluble pharmacodynamically effective ingredients and approximately 0.001-60 wt.% of the carboxylic acid ester, respectively. As the agent for external use for skin, it is preferably a one for scalp.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an external preparation for skin. More specifically, the present invention relates to a skin external preparation having excellent transdermal absorbability of a medicinal ingredient.

[0002]

2. Description of the Related Art Hitherto, a medicinal ingredient which is applied externally to skin, scalp and the like to improve properties of skin, hair and the like has been studied. However, there is a problem that the water-soluble medicinal ingredient is hardly absorbed by the presence of sebum, and it is difficult to exert a sufficient effect.

[0003] Japanese Patent Application Laid-Open No. 56-12307 discloses a technique of blending a medicinal ingredient with a W / O / W emulsion in order to increase the transdermal absorbability of the medicinal ingredient. The publication discloses, as the oil component of the oil phase, vegetable oils and hydrocarbons commonly used as the oil component of the emulsion, and it is also possible to mix a water-soluble medicinal component in the outer aqueous phase. It has been disclosed. However, the percutaneous absorbability of the water-soluble medicinal component is not sufficiently improved even by such an emulsion, and a W / O / W emulsion exhibiting more excellent percutaneous absorbability has been demanded.

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to provide a W / O / W emulsion (multiple emulsion) having excellent transdermal absorption of a water-soluble medicinal ingredient.

[0005]

That is, the present invention provides the inventions described in the following items.

Item 1 W composed of an internal water phase, an oil phase and an external water phase
A topical skin preparation comprising a / O / W emulsion containing a water-soluble medicinal component in an inner aqueous phase and a carboxylic acid ester in an oil phase.

Item 2. The external preparation according to Item 1, which is an external preparation for the scalp.

Item 3 is a hair restorer, characterized in that it is a hair restorer
An external preparation according to item 1.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION The W / O / W emulsion of the present invention contains a water-soluble medicinal component in an inner aqueous phase, and is an outer aqueous phase which is a continuous phase of the W / O / W emulsion. Does not contain any medicinal ingredients.

The medicinal component contained in the inner aqueous phase is not particularly limited as long as it is a water-soluble medicinal component, and examples thereof include anti-inflammatory drugs such as dipotassium glycyrrhizinate, β-glycyrrhetinic acid, and mugwort extract. Agents: Assembly extract, blood circulation promoters such as benzyl nicotinate; Vitamins such as pyridoxine hydrochloride; Hair-growing components such as calendula extract, Rhododendron extract, β-glycyrrhetinic acid; Sodium hyaluronate, sodium pyrrolidonecarboxylate, mugwort extract, etc. Moisturizers; hormonal agents such as ethinyl estradiol; amino acids, hydrolyzed proteins, peptides and derivatives thereof (eg, cationized and esterified peptides).

These medicinal ingredients may be contained alone or in combination of two or more.

The content of the water-soluble medicinal ingredient is not particularly limited as long as the desired effect of the present invention can be obtained, but it is usually about 0.0001 to 80% by weight, preferably 0.1 to 80% by weight in the internal aqueous phase. About 001 to 50% by weight, particularly preferably 0.1 to 0.1% by weight.
About 01 to 30% by weight, more preferably 0.05 to 1%
It is about 0% by weight.

The oil phase of the W / O / W emulsion of the present invention contains a carboxylic acid ester.

The carboxylic acid ester is usually an ester of an alcohol and a carboxylic acid. The alcohol used as a raw material of the carboxylic acid ester of the present invention is not particularly limited, but has 1 to 30 carbon atoms, particularly 2 to 22 carbon atoms, and more preferably 2 to 1
Eight straight or branched alcohols are preferred.

[0015] Specific examples include ethanol, isopropanol, isononyl alcohol, dodecanol, isostearyl alcohol, octyl dodecanol, cetyl alcohol and the like.

The carboxylic acid is preferably a monocarboxylic acid such as a fatty acid or a hydroxy fatty acid, and has 1 to 2 carbon atoms.
0, especially 3-18 monocarboxylic acids are more preferred.

The fatty acid may be a linear or branched fatty acid, and may be saturated or unsaturated.

Specific examples of the carboxylic acid include octanoic acid, nonanoic acid, isononanoic acid, oleic acid, myristic acid, palmitic acid, lactic acid and the like.

The ester of the present invention is preferably an ester of an alcohol and a carboxylic acid as exemplified above, but an ester of octanoic acid, nonanoic acid, isononanoic acid, oleic acid, myristic acid, palmitic acid or lactic acid is preferred. It is more preferable because the skin absorbability is particularly excellent.

The ester of the alcohol and the carboxylic acid is preferably an ester having a total carbon number of the alcohol and the carboxylic acid of 5 to 50, particularly 8 to 40, and more preferably 12 to 30.

Specific examples of such an ester include lauryl lactate, isostearyl lactate, octyldodecyl lactate, isononyl isononanoate, isotridecyl isononanoate, cetyl octanoate, ethyl oleate, and isopropyl myristate.

The content of the carboxylic acid ester in the external preparation of the present invention can be appropriately set within a range in which the intended effect of the present invention can be achieved. 0.001 to 60% by weight, preferably about 0.01 to 50% by weight, particularly preferably about 0.1 to 40% by weight, more preferably 0.5 to 3% by weight.
It is about 0% by weight.

The external preparation for skin of the present invention can be used in various fields depending on the kind of the water-soluble medicinal component in the internal aqueous phase, and is applicable to various uses in the fields of pharmaceuticals, quasi-drugs, and cosmetics. can do.

The external preparation for skin of the present invention is applied, for example, by applying it to the skin (including the scalp; the same applies hereinafter), but is preferably an external preparation for the scalp. As an external preparation for the scalp, a skin external preparation containing a hair-growth component, a blood circulation promoter, a component that promotes hair growth such as vitamins as a medicinal component, that is, a hair-growth agent is preferable.

Further, the skin external preparation of the present invention includes a skin external preparation containing an anti-inflammatory agent (for example, a skin external preparation having a rough skin improving effect) and a skin external preparation containing a humectant (for example, a moisturizing skin external preparation). It can also be suitably used as such.

The external preparation of the present invention may be in any known form (for example, lotion,
External preparations such as emulsions, creams, ointments and the like).

More specifically, hair tonic, scalp lotion, hair milk, hair cream, milky lotion, foundation, massage cream, hand cream,
It can be in the form of a skin lotion, body lotion, body cream and the like.

The external preparation of the present invention can be prepared according to a conventional method for forming a W / O / W emulsion by using appropriate additives, bases, diluents and the like according to the form. It is.

Specific examples of the additives, bases, diluents and the like include diluents such as water and ethanol; hydroxyethyl cellulose, cationized cellulose, protein derivatives,
Polymers such as various hair setting resins; wetting agents such as polyethylene glycol, glycerin, 1,3-butylene glycol, propylene glycol, and dipropylene glycol; antioxidants such as dibutylhydroxytoluene; ultraviolet absorbers; Preservatives; chelating agents such as sodium ethylenediaminetetraacetate and sodium 1-hydroxyethane-1,1-diphosphonate; coloring agents;
And an adjusting agent.

In addition to the above-mentioned components, the oil phase includes oil-soluble medicinal components such as α-tocopherol; silicone oils (for the purpose of improving feel, etc.); oils such as olive oil and almond oil; liquid paraffin, squalane, etc. Hydrocarbons;
Components such as fatty acids such as oleic acid and stearic acid; and higher alcohols such as octyldodecanol and isostearyl alcohol can be blended within a range that does not impair the intended effects of the present invention.

A W / O / W emulsion is prepared by dispersing a liquid to be an internal water phase into a liquid or a fluid to be an oil phase, and
It can be produced by preparing a type emulsion and dispersing the emulsion in a liquid to be an external aqueous phase. As a method for producing such an emulsion, a commonly used method can be appropriately used, and examples thereof include an emulsification method using a high-pressure homogenizer, a high-speed stirrer, an ultrasonic emulsifier, or the like. When preparing an emulsion,
Heat may be applied as needed.

The oil phase contains a surfactant for preparing a W / O emulsion. Such a surfactant can be appropriately selected from commonly used anionic surfactants, cationic surfactants, amphoteric surfactants and nonionic surfactants.

The amount of the surfactant added to the oil phase is not particularly limited, but is usually about 0.0001 to 30% by weight, preferably about 0.0001 to 30% by weight, based on the total weight of the external preparation of the present invention.
The amount is about 1 to 10% by weight.

A surfactant is also incorporated in the external aqueous phase to prepare a W / O / W emulsion. As described above, commonly used anionic surfactants and cationic surfactants are used. The surfactant can be appropriately selected from surfactants, amphoteric surfactants and nonionic surfactants.

The amount of the surfactant in the external aqueous phase is not particularly limited, but is usually about 0.00001 to 20% by weight, preferably 0.0001 to 5% by weight based on the total weight of the external preparation of the present invention. The amount is such that it is about weight%.

In the W / O / W emulsion of the external preparation of the present invention, the weight ratio, volume ratio, and W of the internal aqueous phase, oil phase and external aqueous phase
The average particle size of the / O emulsion particles and the like can be appropriately set according to the form, the type of the water-soluble medicinal component contained, and the like.

The amount of the external preparation for skin of the present invention is not particularly limited, and is appropriately selected depending on the type and degree of the disease or symptom, the form of the external preparation, the age of the user, sex and other conditions. However, usually, the medicinal component is about 0.00001 to 1000 mg per adult per day, preferably about 0.1 to 0.1 mg.
The amount is preferably about 001 to 300 mg, and it can be used once a day or divided into 2 to 4 times.

[0038]

According to the external preparation for skin of the present invention, it becomes possible to enhance the absorbability of the water-soluble medicinal ingredient to the skin, and it can be expected that the medicinal ingredient exerts a sufficient effect.

[0039]

EXAMPLES Next, the present invention will be described in more detail with reference to Production Examples, Examples, Comparative Examples, Test Examples and Formulation Examples, but the present invention is not limited thereto.

Production Example 1 W /
Production of O / W Emulsion Using a high-pressure homogenizer, the emulsion was emulsified at 1,000 kg / cm ² to obtain a W / O emulsion in which (A) in Table 1 was dispersed in (B).

As the water extract of the pentagon, a pure substance having a solid content of about 2.7% by weight was used.

Next, the mixture was stirred at 3,000 rpm for 10 minutes using a high-speed stirrer to obtain a W / O / W emulsion in which the W / O emulsion obtained above was dispersed in (C).

Production Examples 2 to 6 In the same manner as in Production Example 1, W / O / W emulsions having the compositions shown in Table 1 were obtained.

Production Example 7 A water extract of Japanese gourd was mixed with a predetermined amount of purified water.

Test Example 1 The effect of the emulsions or aqueous solutions obtained in Production Examples 1 to 7 on hair regeneration in mice was tested (Production Examples 1, 2 and 3 were referred to as Examples 1, 2 and 3, respectively. 4,
5, 6, and 7 are Comparative Examples 1, 2, 3, and 4, respectively).

Using 8-week-old C3H male mice, one group
The test was performed with 0 animals. Once a day, 0.1 ml of the emulsion or aqueous solution obtained in the above Preparation Example was applied to the back of a mouse having an area of about 2 × 4 cm and shaved. Observation by photography over time, image processing,
The ratio of the hair regeneration area was defined as the hair regeneration rate (%), and was calculated by the following equation (1).

[0047]

(Equation 1)

The results are shown in Table 1 below.

[0049]

[Table 1]

The hair growth effect was evaluated according to the following criteria. Hair regeneration rate is 40% or more after 15 days of shaving and 80% or more after 17 days of shaving... ◎◎ Hair regeneration rate is 30% or more after 15 days of shaving and 70% or more after 17 days of shaving. The hair regeneration rate is 20% or more after 15 days of shaving and 60% or more after 17 days of shaving .... △ The hair regeneration rate is less than 20% after 15 days of shaving or less than 60% after 17 days of shaving. .

Examples 1 to 3 all showed an excellent hair growth effect as compared with Comparative Examples 1 to 4.

The liquid paraffin used as the oil component in Comparative Example 2 is that disclosed in JP-A-56-12307 as the oil component.

Further, Comparative Example 3 in which the pentagonal extract as a medicinal component was contained in the external aqueous phase had the same results as Comparative Example 1 in which no medicinal component was contained.

Production Example 8 W / O using mugwort extract
Production of / W Emulsion Using a high-pressure homogenizer, emulsification was performed at 1,000 kg / cm ² to obtain a W / O emulsion in which (A) in Table 2 was dispersed in (B).

The concentrated mugwort extract powder used had a pure content of about 95% by weight or more as a solid content.

Then, the mixture was stirred at 3,000 rpm for 10 minutes using a high-speed stirrer to obtain a W / O / W emulsion in which the W / O emulsion obtained above was dispersed in (C).

Production Examples 9 to 12 In the same manner as in Production Example 8, W / O / W emulsions having the compositions shown in Table 2 were obtained.

Production Example 13 A concentrated mugwort extract powder was dissolved in purified water to obtain an aqueous solution.

Test Example 2 In order to evaluate the anti-inflammatory properties of the emulsions or aqueous solutions obtained in Production Examples 8 to 13, the inhibitory effect on rat paw edema reaction was tested using Compound 48/80 (a histamine releasing agent) ( Those using the emulsions of Production Examples 8 and 9 are referred to as Examples 4 and 5, respectively, and those using the emulsions of Production Examples 10, 11, 12, and 13 are Comparative Examples 5, respectively.
6, 7, and 8).

The test was carried out using 6-week-old male Wister / ST rats in groups of 6 rats. The right hind limb volume of the rat was measured with a foot volume measurement device, and 0.1 ml of the emulsion or aqueous solution obtained in Production Examples 8 to 13 was immediately applied.
The application area was covered with a wrap film. After 4 hours, wipe the application area and use Compound48 / 80 saline solution (10μg / pa
w) was administered subcutaneously to the right hind footpad, and two hours later the right hind foot volume was measured. The edema rate with respect to the paw volume before Compound 48/80 administration was calculated by the following formula (2).

Edema rate (%) = (Va−Vb) / Vb × 100 (2) Va: Paw volume after administration of Compound 48/80 Vb: Paw volume before administration of Compound 48/80 The results are shown in Table 2.

[0062]

[Table 2]

The evaluation of rat paw edema inhibition was performed according to the following criteria. The edema rate is less than 20%... ◎ The edema rate is 20% or more and less than 30%... ○ The edema rate is 30% or more and less than 40%.

Examples 4 and 5 are different from Comparative Examples 5 to 8 in that:
All of them exhibited an excellent edema suppressing effect, that is, an anti-inflammatory effect.

Production Example 14 Production of W / O / W emulsion using sodium pyrrolidonecarboxylate Emulsification was carried out at 1,000 kg / cm ² using a high-pressure homogenizer, and (A) in Table 3 was dispersed in (B). The obtained W / O emulsion was obtained.

The aqueous sodium pyrrolidonecarboxylate solution used had a pure content of 50%.

Next, the mixture was stirred for 10 minutes at 3,000 rpm using a high-speed stirrer to obtain a W / O / W emulsion in which the W / O emulsion obtained above was dispersed in (C).

(D) was added to the obtained W / O / W emulsion to obtain a creamy W / O / W emulsion.

Production Example 15 W / O / W having the composition shown in Table 3 was produced in the same manner as in Production Example 14.
A type emulsion was obtained.

Production Example 16 (B) was added to (C), and 3,000 rpm was added using a high-speed stirrer.
For 10 minutes to obtain an O / W emulsion.

Next, (D) was added to the obtained O / W emulsion to obtain a creamy O / W emulsion.

Production Example 17 An aqueous sodium pyrrolidonecarboxylate solution and a carboxyvinyl polymer were dissolved in purified water to obtain an aqueous solution, and then (D) was added.

Test Example 3 In order to evaluate the moisture retention of the emulsions or aqueous solutions obtained in Production Examples 14 to 17, a moisture retention evaluation test was carried out on the inner part of the upper arm of a person (Production Example 14 was designated as Example 6). Production Examples 15, 16 and 17 were compared to Comparative Examples 9, 10 and 11, respectively.
And).

The water content of the stratum corneum of the epidermis at eight locations (4 locations each on the right and left, 1 area: 3 × 4 cm) of 10 right and left upper arm panels of 10 male and female panelists aged 27 to 36 years old was measured using a Corneometer CM820, Courage + Khazaka) five times at one location, and the average of the three values excluding the highest and lowest values is the initial stratum corneum water content (Wf)
And Next, 0.1 ml of the emulsion or aqueous solution obtained in Production Examples 14 to 17 was applied to the same site. Since one kind of emulsion or aqueous solution was applied one place per one arm, it means that each emulsion or aqueous solution was applied to two places per one panelist. After leaving for 1 hour, it was rinsed with running water. One hour later, the water content of the stratum corneum of the epidermis was measured again five times for one application site, and the average value of the three values excluding the highest value and the lowest value was taken as the water content (Wa) of the stratum corneum after treatment.

Using the moisture retention of the emulsions or aqueous solutions obtained in Production Examples 14 to 17 as the E value, the E value of each panel was determined by the following equation (3). Asked).

E (%) = 100 × Wa / Wf (3) The average value of E values (data number: 20) of 10 panelists was evaluated according to the following criteria. Table 3 shows the results.

E value (%) is 3 or more: E value (%) is 2 or more and less than 3 E value (%) is 1 or more and less than 2 E value (%) is less than 1 ×.

[0078]

[Table 3]

Example 6 showed an excellent moisturizing effect as compared with Comparative Examples 9 to 11.

The following is a formulation example of the external preparation of the present invention. The compounding amount indicates% by weight.

Formulation Example 1 W / O / W type skin cream (A) Sodium hyaluronate 0.01 Sodium pyrrolidonecarboxylate solution (50%) 2.0 Methyl paraben 0.03 Purified water 8.0 (B) Cetyl octanoate 10.0 Silicon oil 2.0 Decaglyceryl tristearate 3.0 (C) POE (20) sorbitan monooleate 3.0 Carboxyvinyl polymer 0.3 Triethanolamine 0.3 Glycerin 5.0 Methyl paraben 0.3 Perfume 0.1 Purified water Remaining A W / O emulsion was prepared using a high-pressure homogenizer with (A) dissolved by heating as a dispersed phase and (B) dissolved uniformly as a continuous phase. Next, a W / O / W type skin cream was prepared with a high-speed stirrer using the obtained W / O emulsion as a dispersion phase and heating and dissolving (C) as a continuous phase. The obtained skin cream was very excellent in moisturizing effect.

Formulation Example 2 W / O / W emulsion (A) β-glycyrrhetinic acid 0.01 Purified water 3.0 (B) Isotridecyl isononanoate 5.0 Olive oil 1.0 Glyceryl trioctanoate 0.5 Monooleic acid Sorbitan 2.0 (C) POE (60) sorbit tetraoleate 1.5 hydroxyethyl cellulose 0.2 1,3-butylene glycol 5.0 glycerin 3.0 methyl paraben 0.3 fragrance 0.1 purified water Remaining homogeneous dissolution A W / O emulsion was prepared using a high-pressure homogenizer using the obtained (A) as a dispersed phase and the homogeneously dissolved (B) as a continuous phase. Next, a W / O / W type emulsion was prepared using a high-speed stirrer with the obtained W / O emulsion as a dispersed phase and (C) obtained by heating and dissolving as a continuous phase. The obtained emulsion was very excellent in anti-inflammatory effect.

Formulation Example 3 W / O / W Type Scalp Proration (A) Artemisia Extract 3.0 Methylparaben 0.05 Purified Water 2.0 (B) Ethyl Oleate 3.0 Isopropyl Palmitate 3.0 POE (6) Sorbit Tetraoleate 2.0 (C) POE (60) Sorbit Tetraoleate 1.5 Ethanol 20.0 Fragrance 0.05 Purified Water Remaining Heat-dissolved (A) dispersed phase, homogeneously dissolved (B) As a continuous phase, a W / O emulsion was prepared using a high-pressure homogenizer. Next, using the obtained W / O emulsion as a dispersed phase and uniformly dissolving (C) as a continuous phase, a W / O / W type scalp lotion was prepared with a high-speed stirrer. The obtained scalp lotion was very excellent in the anti-itch effect on the scalp.

Claims (3)

[Claims] 1. W / O comprising an internal water phase, an oil phase and an external water phase
/ A skin external preparation characterized in that in a W-type emulsion, a water-soluble medicinal ingredient is contained in an inner aqueous phase and a carboxylic acid ester is contained in an oil phase. 2. The external preparation according to claim 1, which is an external preparation for the scalp. 3. A hair restorer according to claim 2.
An external preparation according to item 1.