WO2003022257A1

WO2003022257A1 - External preparations for the skin

Info

Publication number: WO2003022257A1
Application number: PCT/JP2002/009270
Authority: WO
Inventors: Atsushi Suzumatsu; Hikaru Sumida; Toshio Uesaka; Kimihiko Hori; Mami Nonomura
Original assignee: Kao Corporation
Priority date: 2001-09-11
Filing date: 2002-09-11
Publication date: 2003-03-20

Abstract

External preparations for the skin which contain the following components (A) and (B): (A) cedrol; and (B) an anionic surfactant. These preparations show improved percutaneous absorbability of cedrol and excellent antiinflammatory, antiallergic (regulating IL4 production) and irritation-relieving effects and give a favorable feel in using.

Description

Description Skin external preparation Technical field

The present invention relates to an external preparation for skin which has improved percutaneous absorbability of cedrol, and has excellent anti-inflammatory, anti-allergic (IL 4 production inhibition) and irritation-relieving effects. Background art

Drug administration methods include oral administration, mucosal administration, injection administration, and other methods of directly administering the drug into the body. Recently, topical preparations containing these drugs by transdermal administration have been developed because of their low side effects.

In general, the surface of the skin (epidermis) is covered by the stratum corneum and has a structure that prevents foreign substances from entering from outside the body. Simply applying an external preparation containing an active ingredient to the epidermis is sufficient for transdermal absorption You can't get to life. In order to improve the direct absorption from the epidermis, transdermal absorption enhancers such as dimethyl sulfoxide, dimethylformamide, and dimethylacetamide have been proposed (Japanese Patent Application Laid-Open No. Sho 61-331129). However, these transdermal absorption enhancers were not sufficient in terms of irritation, stability, and feeling of use. On the other hand, the present inventors have found that Sedokuru has an excellent anti-inflammatory and anti-allergic effect due to an excellent inhibitory effect on IL 4 production (Japanese Patent Application Laid-Open No. 2000-3099528). Since it is an insoluble substance, transdermal absorption of cedrol into the stratum corneum was often not sufficient.

An object of the present invention is to provide an external preparation for skin in which the transdermal absorbability of cedrol is improved and the effects of cedrol (anti-inflammatory action, anti-allergic action, irritation-relieving action) can be sufficiently exerted. Disclosure of the invention

The present inventor uses the softening action of the stratum corneum possessed by the a-on surfactant and the compatibility between the anionic surfactant and cedrol to efficiently store cedrol in the stratum corneum. It has been found that a skin external preparation with improved percutaneous absorption and biotransformation can be obtained. In addition, by using one or more anionic surfactants having a phosphate ester group or an acylamino group as anionic surfactants that are satisfactory in terms of safety and usability, the transdermal absorption of cedrol It has been found that an external preparation for skin can be obtained that further enhances the anti-inflammatory action, anti-allergic action (suppressing IL-4 production) and irritation-relieving action of cedrol itself.

The present invention comprises the following components (A) and (B):

(A) Sedronore,

(B) Anionic surfactant

And a skin external preparation containing the same. BEST MODE FOR CARRYING OUT THE INVENTION

Cedrol of component (A) used in the external preparation for skin of the present invention is a kind of sesquiterpene alcohol, and has an optical isomer, but is generally represented by the formula (1) (d) Exists in the body. Cedrol, which is an active ingredient having an antiallergic effect according to the present invention, is preferably the (d) isomer, but is an optical isomer of the (1) isomer or a mixture of the (d) isomer and the (1) isomer However, there is no problem in effectiveness.

Cedrol is generally known as a fragrance component contained in essential oils of plants such as Pinaceae, Cedars, Cypresses, Scorpiones, Prunus, etc. It can be obtained by purifying essential oils such as fern wood oil and hiba oil by distillation or the like, and can also be obtained by synthesis. As the cedrol used in the present invention, any of the above-mentioned essential oil products and synthetic products may be used, or a commercially available product may be used.

If cedrol is contained in the skin preparation for external use of the present invention in an amount of 0.01 to 10% by weight, particularly 0.1 to 5% by weight, the anti-inflammatory and anti-allergic effects can be effectively exhibited. preferable.

Examples of the anionic surfactant of the component (B) used in the skin external preparation of the present invention include those having a phosphate group, an acylamino group, a carboxylic acid group, a sulfonic acid group, a sulfate ester group, and the like, and salts thereof. No.

Those having a phosphate ester group include alkyl phosphates and alkyl ether phosphates; those having an acylamino group include acylsarcosine, acylglutamate, acylmethyltaurine, and acylalginate. Carboxylic acid groups, such as fatty acid salts, ether carboxylic acids or salts thereof; sulfonic acid groups, such as alkyl sulfonates, sulfosuccinates, and ester sulfonates. And alkylaryl sulfonates; examples of those having a sulfate group include sulfated oils, ester sulfates, alkyl sulfates, ether sulfates, and alkylaryl sulfates. Here, examples of the salt include alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, amino acid salts such as arginine, ammonium salt, monoethanolamine salt, and diethanolamine salt. Preferred are alkali metal salts. Further, among the above substituents containing an alkyl group and an acyl group, when used alone, the alkyl group preferably has 12 or more carbon atoms, and the acyl group preferably has 14 or more carbon atoms.

As the component (B), particularly, an ionic surfactant having a phosphate ester group and an anionic surfactant having an acylamino group having an acyl group having 14 or more carbon atoms have no skin irritation and a feeling of use. From the viewpoint, it is more preferable in terms of the transdermal absorption effect.

Mono- or di- (C _6- )

C ₂₄₎ alkyl or Narukenirurin ester salts, mono- or di (Poriokishechi Len _{(2~ 2 0) C 6 ~C} 24 alkyl or Aruke - Le) phosphoric acid ester salts like et be. Specific examples include sodium monolauryl phosphate, sodium isostearyl phosphate, 21-hexyl decyl phosphate arginine, 21-heptyl pentadecyl phosphate, polyoxyethylene (4 to 10) lauryl ether phosphorus Sodium acid, sodium monocetyl phosphate, monomyristinolelate anoreginine, sodium monooleate, polyoxyethylene (2 to 10) lauryl ether 02 09270 Potassium phosphate, sodium octyl phosphate and the like.

Examples of the anionic surfactant having an acylamino group having an acyl group having ₁₄ or more carbon atoms include N—C _{14 to} C ₂₄ acyl sarcosine salts, N—C _{14 to} C ₂₄ acyl methyl taurine salts, and N—C ₁₄ -C ₂₄ § sill glutamate, N- C _{14 ~C} ₂₄ § sills arginine salt, N_ C _{14 ~C} ₂₄ § sill methyl § La Nin salts. Specific examples include myristoyl methyl taurine sodium, palmitoyl methyl taurine sodium, stearoyl methyl phosphate sodium, sodium N-stearoyl glutamate, potassium N-palmitoyl glutamate, N-palmityl / 3-alanine arginine, palmitoyl Sarcosine sodium and the like.

In the skin external preparation of the present invention, two or more anionic surfactants may be used in combination. The anionic surfactant is preferably contained in the skin external preparation in an amount of 0.001 to 10% by weight, particularly 0.1 to 5% by weight, in view of the effect and stability.

In addition to the above-mentioned components (A) and (B), the skin external preparation of the present invention may be a component usually used in skin external preparations such as pharmaceuticals, quasi-drugs, and cosmetics, for example, whitening agents, humectants, Inhibitors, UV absorbers, nonionic surfactants (polyoxyethylene hydrogenated castor oil, etc.), oily components (scoulane, olive oil, higher alcohols, higher fatty acids, etc.), thickeners (hydroxyethyl cellulose, xanthan gum, carboxy) Vinyl alcohols), alcohols (glycerin, 1,3-butylendalcol, ethanol, etc.), organic acids (cunic acid, succinic acid, adipic acid, lactic acid), pH adjusters (sodium hydroxide) , Potassium hydroxide, etc.), powder components, coloring agents, aqueous components, preservatives, antioxidants, fragrances, chelating agents, water, various skin nutrition agents, crude drugs, extracts, It may be blended in accordance with oil or the like as required.

The external preparation for skin of the present invention can be produced according to a usual method, and can be in the form of, for example, a cream, an emulsion, a lotion, a jewel, and the like. Example

Example 1

A skin external preparation having the following composition was prepared by a conventional method, and evaluated for percutaneous absorption, irritation, and feeling upon use. Table 1 shows the results. 02 09270

(Composition): Cedrol 0.1 (% by weight)

Surfactants (Table 1)

Sonorebitan monostearate 1

Glycerin 5

Olive oil 1

1, 3-loops, polyethylene glycol 5

purified water

(Evaluation method)

(1) Percutaneous absorption:

A patch test patch having a hole diameter of 16 ram was applied to the upper arm of the panelists (10 persons), and 200 L of the sample was applied. After the application, the banso plaster was peeled off for 6 hours, and in the next step, the application portion was tape-striped 10 times with a velcro tape to measure the amount of cedrol in the stratum corneum adhered to the cellophane tape.

The quantitative determination of cedrol was performed by gas chromatography using ethanol extract from 10 cellophane tapes. The percutaneous absorption rate was determined by the following formula, and was determined according to the criteria.

Amount of cedrol in the stratum corneum in close contact with cellophane tape (average value of 10 persons) Percutaneous absorption (%): X 100

Amount of cedrol applied Percutaneous absorption criteria: 1; Percutaneous absorption less than 1%

2; Percutaneous absorption rate 1% or more and less than 2%

3; Percutaneous absorption 2. /. More than 3%

4; Percutaneous absorption rate 3% or more

(2) Irritation:

After washing the face with a stone test, sensitive skin panelists (10 persons) were applied with each skin external preparation, and the state of the skin one minute later was determined according to the following criteria. In the results in Table 1, the irritability in the case of cedrol is not shown.

Irritation criteria: A; Number of people who felt a little irritation 0 people

B: 1-2 people who felt a little irritation C: 3-5 people who felt a little irritation

D: Number of people who felt a little irritation 6-10

(3) Usability:

Beauty panelists (10 people) evaluated the feeling of use when using each skin external preparation according to the following evaluation criteria, and the evaluation criteria were used.

Evaluation criteria: 1; non-sticky

2; slightly sticky

3; sticky

4; markedly sticky

Usability judgment criteria: A; average evaluation point less than 1.5

B: Average score of 1.5 or more and less than 25

C: Average score 2.5 or more and less than 35

D: Average score of 3.5 or more

*: When Katsuko does not pick up cedrols. All of the products 1 to 4 of the present invention had improved percutaneous absorption, had no irritation, and were excellent in usability.

Example 2 (Emulsion) Cedrol 0. Polyoxyethylene (4) sodium lauryl ether phosphate 0.3 N-Stearoyl-N-methyltadulin sodium 1 Sorbitan monostearate 0.3 Olive oil 2.5

2.5 Cholesterol 0,2 Cholesteryl disostearate 0,14 Cetinorea noreco ^ "Nore 03 Stearyl alcohol 02 Glycerin 10 Carboxyvinyl polymer

(Carbopol 981, manufactured by BF GOODRICH) 0.2 Potassium hydroxide 0.07 Acid 0.01 Yurikuri extract

(Eucalyptus extract BG, manufactured by Ichimaru Fuarcos)

Ma-e extract

(Fanorecorex Maronnier B, manufactured by Ichimaru Fuarcos) 0.5 Rosemari Mono Oil 0.1 Paraoxybenzoate 0.2

Example 3 (Giel) Cedrol 0.1 Polyoxyethylene (10) Sodium Cetyl Ether Phosphate 0.2 Palmitoyl Sanolecosin Sodium 0.2 Polyoxyethylene (40) Hardened Castor Oil 0.2 Methyl Polysiloxane (50cs ) Five Glycerin 6

1,3-butylene glycolonole

Canoleboxybininole polymer

(Carbopol 980, manufactured by BF GOODRICH) 0.7 Azelaic acid 0.02 Potassium hydroxide 0.3 Paraoxybenzoic acid ester 0.3 Royal anolyzeri extract

(Royal jelly extract, manufactured by Ichimaru Fuarcos) 0.3 Cya extract (green tea liquid, manufactured by Maru Fuarcos) 0.1 Purified water

Example 4 (Lotion) Cedrol 0.005 Lauroylu Sodium β-alanine 0.2 Olive oil

Methyl polysiloxane (6cs) 2 Polyoxyethylene (60) Hardened castor oil 2 Glycerin 1 Trimethyldaricin 2 Acrylic acid. Alkyl methacrylate copolymer

(PEMULEN TR-1, manufactured by BF GOODRICH) 0.3 Potassium hydroxide 0.2

0.06 Edetic acid 2-sodium 0.02 Paroxybenzoic acid ester 0.5 Aloe extract

(Fanorecorex Aloe KB, manufactured by Ichimaru Fuarcos) 0.5 Yurikuri Oil 0.0 purified water

Example 5 (Cream) Sed, Mouth 0.5 Polyoxyethylene (8) Sodium Oleyl Ether Phosphate 0.2 Polyglyceryl Stearate 5 35 5 Sodium Palmitoyl Sarcosine 0 2 Cetinoleanorecoronole 15 15 Stearyl Alcohol 1

N-(3-hexadecyloxy-2-hydroxypropyl) 1 Ν ·

2-Hydrox-kisethyl hexademamide 4 Cholesterol 0.8 0.8 Cholesteryl disostearate 0.5 Olive oil 2.7 Methylpolysiloxane (50cs) 4 Glycerin 20 Co / oxalic acid 0 0 2 Sodium hydroxide 0 0 0 2 Paraoxybenzoic acid: 0 2 Horsetail extract 0 2

(Brown horse extract BG, manufactured by Maruzen Pharmaceutical Co., Ltd.) 0 2 Hamamelis extract

(Fanorecorex Hamamelis B, manufactured by Ichimaru Fuarcos) 0.1 Water

The skin external preparations of Examples 2 to 5 are excellent in percutaneous absorbability of cedrol, and are excellent in anti-inflammatory, anti-allergic (suppressing IL-4 production), stimulating alleviation, and feeling of use. Good. Industrial availability The external preparation for skin of the present invention improves the transdermal absorbability of cedrol, is excellent in anti-inflammatory action, anti-allergic (IL4 production inhibition) action, irritation relieving action, and has good feeling in use.

Claims

The scope of the claims

1. The following components (A) and (B):

(A) Cedrol,

(B) Anionic surfactant

An external preparation for skin containing.

2. The external preparation for skin according to claim 1, wherein the component (B) is an anionic surfactant having a phosphate group.

3. Component (B) is a mono- or di- (C ₆ -C ₂₄ ) alkyl or alkenyl phosphate ester salt, and a mono- or di- (polyoxyethylene (2-20) C ₆ -C ₂₄ alkyl or alkenyl 3. The external preparation for skin according to claim 2, which is selected from phosphoric acid ester salts.

4. The external preparation for skin according to claim 1, which is an anionic surfactant having an acylamino group having an acyl group having 14 or more carbon atoms as the component (B).

5. Component (B) is, N- C ₁₄ ~C ₂₄ Ashirusarukoshin salts, N_C ₁₄ -C ₂₄ Ashirumechi Ruturin salts, N- C ₁₄ ~C ₂₄ § sill glutamate, N- C ₁₄ ~C ₂₄ Ashiruarugi Nin salts, and N-C ₁₄ -C ₂₄ skin external preparation according to claim 4, wherein those selected from § sill methyl § La Nin salt.

6. The external preparation for skin according to any one of claims 1 to 5, comprising 0.001 to 10% by weight of the component (A) and 0.001 to 10% by weight of the component (B).