JPH09278643A - Preparation for external use for skin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prepare a preparation for external use for the skin having high safety and excellent in the percutaneous absorption of a biologically active substance. SOLUTION: This preparation is composed of 0.5-50 pts.wt. of a nonionic silicon-containing surfactant, 0.5-99 pts.wt. of an oil and a biologically active component as active components. The nonionic silicon-containing surfactant has a siloxane skeleton and a hydrophilic group, and the hydrophilic group is nonionic. As an example of the surfactant, a silicone having side chains modified with a trifluoropropyl group and a polyoxyethylene at the same time is cited. As example of the oil agent, one or more kinds selected from hydrocarbons, ester oils, and oil and fat are cited. As the biologically active substance, e.g. diisopropylamine dichloroacetate or vitamin C phosphoric acid ester can be used. The resultant composition can be formulated into a preparation for external use for the skin such as a hair tonic, a hair growing agent, a beautifying agent, a wrinkle-proofing agent, a bactericidal agent, a poultice, a skin fat suppressing agent or an improving agent for roughened skin.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a skin external preparation which is excellent in transdermal absorbability of a physiologically active ingredient by blending a nonionic silicone surfactant and an oil agent.

[0002]

BACKGROUND OF THE INVENTION The skin has excellent barrier properties that resist the ingress of external chemicals. Permeation resistance to external chemicals is strongest in the outer layer of the epidermis, the stratum corneum, and the underlying layer is relatively less resistant. Therefore, when compounding a physiologically active substance with an external preparation, it is most important to penetrate the stratum corneum.

Therefore, how to effectively permeate a physiologically active substance through the stratum corneum has been a subject of much research. As a solution to this problem, the use of a percutaneous absorption enhancer is considered, and many reports have been made. But,
Many of the conventional transdermal absorption enhancers, when applied to the skin,
Has the potential to form stimuli. It is thought that such a substance causes irritation by passing through the skin barrier and being transdermally absorbed (M. Suzuki: J. Soc. Cosmet.
Chem., 29, 265-282, 1978). Therefore, there is a relationship between transdermal absorbability and skin irritation, and the technology related to drug delivery systems has been widely practiced in recent years. is required.

Therefore, for the purpose of enhancing the permeability of the stratum corneum,
Transdermal absorption enhancers such as surfactants, lecithin and oleic acid have been investigated. Among these, the surfactants are attracting attention because they have the advantage that the barrier function of the stratum corneum is immediately restored when the administration is stopped because the action is transient. Among them, nonionic silicone-based surfactants have been found to have an effect of preventing skin irritation, which is considered to be due to inhibition of transdermal absorption. For example, JP-A-62-244431 describes that a polyether-modified silicone has low irritation and suppresses skin irritation of an oil agent. Further, the present inventor has also discovered a skin irritation alleviation effect which is considered to be due to a percutaneous absorption inhibitory effect of the fluoroalkyl / polyoxyalkylene co-modified silicone (Japanese Patent Application No. 6-2111756).

On the other hand, the present inventor recently found that glyceryl-modified silicone, which is the same nonionic silicone surfactant, has a percutaneous absorption accelerating property (Japanese Patent Application No. 7-300768).

[0006] Therefore, when the fluoroalkyl / polyoxyalkylene co-modified silicone and the polyether-modified silicone were examined again for their percutaneous absorption inhibitory properties, when these nonionic silicone surfactants were used alone. It often shows strong transdermal absorption inhibitory properties when used in combination with silicone oil or silicone oil, but exhibits transdermal absorption acceleration properties when used in combination with large amounts of oils such as ester oils and mineral oils. I found that there are cases.

[0007]

SUMMARY OF THE INVENTION It is an object of the present invention to obtain an external preparation for skin which is highly safe and promotes percutaneous absorption of a physiologically active substance.

[0008]

Therefore, as a result of intensive studies, the present inventor has found that by blending three components of a nonionic silicone-based surfactant, an oil agent and a physiologically active ingredient,
It was found that a skin external preparation having excellent transdermal absorbability of a physiologically active ingredient can be obtained.

That is, the present invention relates to a skin external preparation characterized by being excellent in transdermal absorbability of a physiologically active ingredient by blending a nonionic silicone surfactant, an oil agent and a physiologically active ingredient.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described in detail below.

The nonionic silicone surfactant referred to in the present invention is a surfactant having a siloxane skeleton and a hydrophilic group, and the hydrophilic group is nonionic. Examples of hydrophilic groups include polyoxyalkylene groups, polyhydric alcohols, sugars, hydroxyl groups, acryl groups and the like. Further, in addition to the hydrophilic group, a long chain alkyl group, a phenyl group, a fluoroalkyl group or the like may be introduced. Further, the hydrophilic group may be introduced as a side chain to the siloxane skeleton, or may be introduced as a block polymer in the main chain.

However, it has been reported by Nagase et al. That a silicone-based surfactant containing an ionic group such as an amino group, a phosphoric acid group and a sulfuric acid group may promote transdermal absorbability ( Makromol.Chem., Rapid Commun., 13,441-446,
(1992) may cause skin irritation if it contains ionic groups.

Examples of the nonionic silicone surfactant referred to in the present invention include, for example, polyoxyalkylene-modified silicone, alkyl-polyoxyalkylene co-modified silicone, glyceryl-modified silicone, sugar-modified silicone, fluoroalkyl-polyoxy. Examples thereof include alkylene co-modified silicone and acrylic modified silicone. The molecular weight of these silicones is not particularly limited, but in practice, those in the range of several thousand to several million are preferable.

Here, as the polyoxyalkylene co-modified silicone, for example, a silicone having a polyoxyethylene chain at a side chain or a terminal, or a polyoxyethylene / polyoxypropylene group and a dimethyl silicone chain are alternately block polymerized. The thing etc. are mentioned. The fluoroalkyl / polyoxyalkylene co-modified silicone has, for example, the structure shown in Chemical formula 1.

[0015]

Embedded image

(However, l, m, and n are integers, and l =
0 to 500, m = 1 to 500, n = 1 to 500,
R ¹ is the same or different unsubstituted or substituted C ¹ -C 1
20 alkyl groups or aryl groups, and R ² has 1 to 1 carbon atoms.
10 fluorine-substituted alkyl groups, wherein R ³ is —C _p H _2p
O a _{(C 2 H 4 O) a} (C 3 H 6 O) a polyoxyalkylene group represented by _b R ^5, R ⁴ is either R ¹ or R ² or R ^3, R ⁵ is hydrogen An atom or an alkyl group having 1 to 5 carbon atoms or an acetyl group, a,
b and p are integers, a = 0 to 100, b = 0 to 10
0 and a + b are 1 or more, and p = 2 to 6. )

The oil agent used in the present invention is preferably an oil agent excluding silicone oil, polyhydric alcohol, higher alcohol, and fluorine-based oil agent, and examples thereof include hydrocarbons, ester oils, fats and oils. These oil agents may be those conventionally used for external skin preparations such as cosmetics, for example, myristyl myristate, hexyl laurate, decyl oleate, isopropyl myristate,
Ester oils such as isocetyl myristate, hexyldecyl dimethyloctanoate, glyceryl monostearate, diethyl phthalate, ethylene glycol monostearate, octyl oxystearate, propylene glycol dicaprylate, carbonization of liquid paraffin, petrolatum, liquid isoparaffin, etc. Hydrogen may be mentioned.

Here, silicone oil or polyhydric alcohol,
The higher alcohols and the fluorinated oils are excluded because they work in the direction of inhibiting transdermal absorption when they are blended with a nonionic silicone surfactant. Since the purpose of the present invention is to promote percutaneous absorption, these oil agents are excluded from the external preparation for skin.

The oil agent used in the present invention can be used together with silicone oil, polyhydric alcohol, higher alcohol, fluorine-based oil agent and the like. However, in that case, since the effect of promoting transdermal absorption and the inhibitory effect are antagonized, it is necessary to confirm the effect according to the formulation of the product, but this method should be used to control the transdermal absorption by time. There is also an advantage that is possible.

Examples of the physiologically active ingredient used in the present invention include corticosteroids, non-steroids, antibiotics, vitamins, antihistamines, local anesthetics, bactericides, coronary vasodilators, anti-inflammatory agents, and tyrosinase. Known components include biological components such as activity inhibitors, blood circulation promoters, moisturizers, ceramides, hyaluronic acid, and collagen, cerebrosides, hair growth agents, and hair growth promoters.

The amount of the nonionic silicone-based surfactant, oil, and physiologically active ingredient used in the present invention is not particularly limited, but for example, the nonionic silicone-based surfactant is 0 per 100 parts by weight of the preparation. The amount is preferably 0.5 to 50 parts by weight, the oil agent is preferably 0.5 to 99 parts by weight, and the physiologically active ingredient is preferably used in the effective concentration range of each ingredient. For example, 0.2 to 0.7 parts by weight of dichloroacetic acid diisopropylamine and 3.0 parts by weight of vitamin C phosphate ester may be mentioned. In the external preparation for skin of the present invention, regarding the resin and the viscous agent, the influence is not generally clear, and the transdermal absorbability and the absorption inhibitory property are changed depending on the material, so that the object of the present invention is achieved. It is necessary to appropriately select the resin and the sticky agent.

In the external preparation for skin of the present invention, oils, powders (pigments, dyes, resins), fluorine compounds, resins, surfactants, adhesives, preservatives, fragrances, etc. which are usually used in cosmetics, etc.
Ultraviolet absorbers (including organic and inorganic ones, which may correspond to either UV-A or B), humectants, salts, solvents, antioxidants, chelating agents, neutralizing agents, pH adjusting agents Ingredients such as water and water can be blended simultaneously within the range where the object of the present invention is achieved.

Examples of the external preparation for skin of the present invention include a hair-growth agent, hair-growth agent, whitening agent, anti-wrinkle agent, bactericide, vap agent, sebum suppressor, and rough skin improving agent. In addition,
The external preparation for skin of the present invention may be in an emulsified state such as W / O or O / W, or may be non-aqueous, and may be in any form such as cream, gel, mousse, lotion, and solid. Absent.

[0024]

The present invention will be described in detail below with reference to examples and comparative examples. In addition, a method for evaluating the effect of promoting percutaneous absorption referred to in the present invention is shown below.

(Test Method) The preparations prepared in Examples and Comparative Examples were applied to the back skin of shaved rats at 2 mg / cm ² , and 1 hour after the application, the skin was stripped using cellophane tape, The obtained sample was extracted with ethanol, and the sample was analyzed for the amount of physiologically active components present in the skin by high performance liquid chromatography. The obtained results were evaluated according to the criteria shown in Table 1. In addition, from the B / A value when the transdermal absorption amount (control) of the physiologically active ingredient in the case of not using the oil agent is A and the results of Examples and Comparative Examples obtained by the same operation are B An evaluation was made.

[0026]

[Table 1]

Examples 1 to 3 and Comparative Examples 1 to 5 5 parts by weight of side chain (trifluoropropyl polyoxyethylene) co-modified silicone (HLB value 11.9) as a nonionic silicone surfactant, physiological activity 0.5 parts by weight of dichloroacetic acid diisopropylamine as a component,
Using 10 parts by weight of each component shown in Table 2 as an oil agent and 5 parts by weight of sodium lauryl sulfate, the remaining amount was supplemented with purified water to 100 parts by weight, and a transdermal absorbability test was conducted.

[0028]

[Table 2]

Examples 4 to 6 and Comparative Examples 4 to 6 5 parts by weight of a side chain polyoxyethylene-modified silicone (HLB value 10.0, manufactured by Shin-Etsu Chemical Co., Ltd., KF-6013) as a nonionic silicone surfactant. 0.5 parts by weight of dichloroacetic acid diisopropylamine as a physiologically active component, 10 parts by weight of each component shown in Table 3 as an oil agent, and 5 parts by weight of sodium lauryl sulfate were used, and the remaining amount was supplemented with purified water to 100 parts by weight. A transdermal absorbability test was conducted.

[0030]

[Table 3]

From the results of Tables 2 and 3, it is understood that the combination of the nonionic silicone surfactant, the oil agent and the physiologically active ingredient, which is an example of the present invention, promotes percutaneous absorption. On the other hand, in each of the comparative examples, it is found that the transdermal absorption was inhibited.

[0032]

From the above, it is clear that the present invention provides a skin external preparation having excellent transdermal absorbability.

Claims (3)

[Claims] 1. An external preparation for skin, which comprises a nonionic silicone-based surfactant, an oil and a physiologically active ingredient. 2. The external preparation for skin according to claim 1, wherein the nonionic silicone-based surfactant has a functional group selected from a polyoxyalkylene group, a sugar residue and a glyceryl group. 3. The oil agent is a hydrocarbon, an ester oil or a fat or oil.
The external preparation for skin according to claim 1 or 2, which is selected from two or more species.