JPH03279318A - External preparation of skin - Google Patents

Abstract

PURPOSE:To obtain an external preparation of skin having increased treating effects on pimple, remedying pimple in an early stage, having excellent stability and safety, containing a drug for pimple and a specific surfactant. CONSTITUTION:(A) A drug for pimple such as a compound (preferably salicylic acid, urea or resorcinol) having inhibitory action of excessive keratinization of conduit of sebaceous gland, one cause of pimple is blended with (B) a surfactant having an aliphatic alcohol residue containing one or more unsaturated bonds in the molecule, preferably oleic acid or oleyl alcohol, as a skeleton, especially POE oleyl ether in the ratio of 0.001-15wt.%, preferably 0.005-5wt.% component A and 0.01-5wt.%, preferably 0.1-2wt.% component B.

Description

[Detailed description of the invention] [Industrial application field] The present invention relates to an external skin preparation for treating acne.

[Conventional technology]

Acne is a skin disease that primarily occurs during adolescence, and is called acne vulgaris, and is clinically defined as ``chronic inflammatory changes that occur in the upper foramen, centering on the supragen sebaceous gland system.''

The etiology of acne is still unclear, and although it is a skin disease in which various factors are intricately intertwined, in general,
Excessive sebum secretion, epidermal hyperkeratosis, and epiphylactic bacteria are thought to play important roles.

Therefore, topical preparations for acne treatment include creams containing sebum secretion inhibitors and antibacterial substances depending on each factor;
Ointments are commonly used. However, most of the existing anti-acne drugs that combine various drugs do not always exhibit the expected therapeutic effects.

[Problem that the invention seeks to solve]

The inventors of the present invention have conducted intensive research to improve the therapeutic effects of conventional acne treatment drugs, and have found that by adding a specific surfactant to conventional acne treatment drugs, they can enhance the treatment effect of acne and facilitate early treatment. The present invention was completed based on the discovery that the same can be achieved.

That is, the present invention contains as active ingredients an acne drug and a surfactant having a backbone of an aliphatic alcohol residue or a fatty acid residue having one or more unsaturated bonds in the molecule. It is an external preparation for the skin.

The external skin preparation of the present invention is applied to the skin as a so-called external skin preparation, such as an ointment, or as a skin cosmetic, such as a cream lotion.

The anti-acne drugs used in the present invention include compounds that have the effect of suppressing hyperkeratinization of sebaceous gland ducts, which is one of the causes of acne, such as urea, benzoyl peroxide, resorcinol, salicylic acid, and vitamin A acid. However, salicylic acid, urea, and resorcinol are preferred. Furthermore, the most effective one is salicylic acid.

The amount of the acne drug of the present invention is 0.001-15% by weight, preferably 0.005-5% by weight. For the most preferred salicylic acid, 0.05 to 5% by weight is most preferred.

In the present invention, the aliphatic alcohol having one or more unsaturated bonds in the molecule preferably has 6 to 3 carbon atoms.
It is a straight chain or branched one having 6 double bonds,
Typical examples include 2-hexenol, 2-octenol, 2-dobcenol, 2-tetrazocenol, 2-
Examples include hexadecenol, 2-oftadecenol, palmitoleyl alcohol, oleyl alcohol, erucyl alcohol, lysyl alcohol, eleostearyl alcohol, lysyl alcohol, erucyl alcohol, geraniol, linalool, bisabolol, and the like. Among these, oleyl alcohol is most preferred.

In the present invention, the fatty acid having one or more unsaturated bonds in the molecule is preferably a linear or branched fatty acid having a double bond of 6 to 36 carbon atoms, and typical examples include , oleic acid, lanolin fatty acid, linoleic acid, ricinoleic acid, liluic acid, tall oil, undedylenic acid, decenoic acid, palmitoleic acid, erucic acid, myristoleic acid, and the like. Among these, oleic acid is most preferred.

Examples of substances added to the aliphatic alcohol or fatty acid of the present invention to use as a surfactant include polyhydric alcohols, sugars, alkylene oxides, etc. Among them, alkylene oxides typified by ethylene oxide are preferred. Examples of polyhydric alcohols include glycerin, ethylene glycol, propylene glycol, sorbitol, polyglycerene, and the like. Examples of sugars include sucrose, raffinose, and the like.

Specific examples of the above-mentioned surfactants of the present invention include the following.

Sorbitan monooleate, sorbitan sesquioleate, sorbitan trioleate, sorbitan monocastor oil fatty acid ester, P, 0. E, Gl! 0) Sorbitan monooleate, P, O, E, ■ Sorbitan trioleate, P, O, E, (6) Sorbitan monooleate, P, 0. E, (60) Sorbitan monooleate, P, O,E.

■Sorbitan castor oil fatty acid ester, glyceryl monooleate, glycerin castor oil fatty acid ester, glyceryl monooleate, P, O, E, (5) Glyceryl monooleate, P, 0. E, (1(1) Glyceryl monooleate, P, O, E, (15) Glyceryl monooleate, P, 0. E, ■ Glyceryl monooleate, P, 0. E.

00) Polyglycerin olive oil fatty acid ester, P, 0
゜E, (21 monooleate, P, 0.E, (6)
Monooleate, P, O, E, (10) Monooleate, P, O, E, (7) Oleyl ether, P,
O, E, (10) Oleyl ether, P, O, E
, (15) Oleyl ether, P, O, E, (2
0+oleyl ether, P, 0°E, (50) oleyl ether, P, 0. E, (2) Abethyl ether, P, O, E, (5) Abethyl ether, P,
0. E, (10) abiethyl ether, P, 0.
E, (20) abiethyl ether, P, O, E,
(10) Lanolin alcohol, P, 0. E, (to) lanolin alcohol, P, 0. E, (30) Lanolin alcohol, P, O, E, (5) Lanolin alcohol, P, 0. E, (10) lanolin alcohol, P, 0. E, @) Lanolin alcohol, P.

0, E, (40) Lanolin alcohol, P, O,
E, (3) Castor oil, P, O, E, OO) Castor oil, P, O, E, (20) l:- Castor oil, P, O, E
.

(40) Castor oil, P, O, E, (50) Castor oil, P, O, E, (60) Castor oil, P, O, E, 0
ω lanolin, P, 0. E, @) Lanolin, P, O
, E, (30) lanolin, P, O, E, (15) oleylamine, P, O, E, (5) oleic acid amide, P, O, E, (10) oleic acid amide.

Among these, surfactants having oleic acid or oleyl alcohol as a skeleton are preferred, and among them, P, O, E,
Most preferred is oleyl ether.

The HLB of the surfactant of the present invention can be arbitrarily selected, but is preferably 10 or more, preferably 10 to 18. Further, the blending amount is preferably selected in the range of 0.1 to 5% by weight, more preferably 0.1 to 2% by weight.

The skin external preparation of the present invention includes sebum secretion suppressants, gelling agents, stabilizers, thickeners, humectants such as polyhydric alcohols, astringents,
Commonly used auxiliary components such as pH adjusters, fragrances, pigments, alcohol, and water, as well as antibacterial agents and surfactants other than those of the present invention, may be appropriately blended within the range that does not impair the effects of the present invention.

Effects The skin external preparation of the present invention may be applied to the affected area in an amount of about 0.1 to 0.5 g, usually once to several times a day, depending on the symptoms. With this application method, mild acne usually disappears in a few days, and even severe acne disappears in 2 to 3 weeks. Furthermore, no side effects are observed even when this treatment method is applied.

Hereinafter, evaluation tests were conducted using Examples and Comparative Examples in order to clarify the excellent effects of the present invention. The blending amount is in weight%.

Test method - Method for measuring epidermal turnover rate using guinea pig skin.

Alpino guinea pigs were used in the evaluation with 8 animals per group. After pricking the abdominal skin of the guinea pig, apply 0% white petrolatum ointment containing 5% by weight of the fluorescent dye danzyl chloride.
Occlusive application was applied at 1 i/ctl for 24 hours. As for the test substances, Example 1 and Comparative Examples 1 to 3 were applied once a day at a rate of 0.3 to 100% on the area where danzyl chloride was applied, and the total skin turnover rate was determined by the number of days until danzyl chloride disappeared. evaluated.

As is clear from the results in Test Results Table 1, according to the evaluation using guinea pigs, Example 1 containing both salicylic acid and P OE (15) oleyl ether was superior to Comparative Examples 1 to 3.
It has been shown that the turnover of the epidermis is accelerated compared to the previous study.

Table 1: Effect measurement method: Total of 10 men and women aged 15 to 32 with facial acne
After thoroughly washing the face with cosmetic soap, the sample was applied only on the sebum 1 to 3 times a day.

The three symptoms of skin irritation, papules, and pus are observed, and the severity of each finding is graded into five levels: severe (4), moderate (3), mild (2), slight (1), and none (0). It was evaluated separately. Follow-up observation is before treatment, 1 week after treatment, 2 weeks after treatment,
After 3 weeks and 4 weeks, the degree of improvement in the symptoms of the sample used was compared to before use: markedly reduced (+++), slightly improved (++), slightly improved (+), unchanged (±), worsened. It was divided into 5 levels (-).

Extremely useful (◎) by comprehensively evaluating the above observation progress
, Very useful (○), Somewhat useful (△), Ineffective (×) 4
Comprehensive evaluation was performed in stages.

Table 2 Manufacturing method〉 ■~■ and ■~[phase] were heated and dissolved at 70°C, and a portion of ■, ■, and ■ that had been heated and melted at the same <70°C was added and mixed. and emulsify with a homomixer. To this, add ■ dissolved in the remainder of 0, then slowly add ■,
A milky lotion type cosmetic was obtained by processing with a homomixer.

As is clear from Table 2, the cosmetic composition according to the present invention has an excellent therapeutic effect on acne.Furthermore, the external preparation according to the present invention will be explained with reference to Examples. The blending amount is also expressed in weight %.

Example 3 Stearyl Alcohol 5.0 Stearic Acid 2.0 Hydrogenated Lanolin
2.0 squalane
6.0 Isopropyl myristate
4.0 Polyoxyethylene (25 mol) 3.0 Cetyl Alcohol Ether Monostearate Glycerin 2.0 POE (
10) Monooleate 0.3 salicylic acid
5.0 Propylene glycol
5.0 Butylparaben
0.2 dibutylhydroxytoluene 0
．． 05 Perfume 0.5 Ethinyl estradiol 0.1 Ion-exchanged water 64.85 A cream cosmetic was obtained by manufacturing the above prescription ingredients by a conventional method. The obtained cosmetic had excellent acne treatment effects.

Example 4 Pyridoxine hydrochloride 0.1 Precipitated sulfur 2.0 Alcohol
15.0 Methyl cellulose aqueous solution (1%) 5.0 Glycerin 5
．． 0 Polyoxyethylene (15 moles) 0.4 Oleyl alcohol ether salicylic acid 0.1 Hexachlorophene 0.05 Methyl paraben 0.1 Fragrance
0.1 ion exchange water
72.15 A lotion was obtained by manufacturing the above prescription ingredients by a conventional method. The obtained lotion had excellent acne treatment effects.

Example 5 (Production of emulsion) Component (A) Amount (wt%) Setanol 1.5 Stearic acid
1.0 palmitic acid
0.5 liquid lanolin
1.0 Squalane 2.
0 Isopropyl myristate 1.0 Glyceryl monostearate 1.5 Tween20
0.5 oleyl alcohol
3.0 EO (10 mol) adduct salicylic acid 0.5 Preservatives and fragrances Appropriate amount (B) component Propylene glycol 3.0 Polyethylene glycol 400 2.0 Triethanolamine 1.0 Purified water
81.5 Each component of (A) above was mixed to obtain a mixture.

Separately, a mixture (B) was obtained in the same manner. The mixture of (A) and the mixture of (B) were individually heated and dissolved at 70°C, and (
The mixture of A) was added to the mixture of (B) and emulsified using an emulsifier, followed by heat exchange and cooling to produce a milky lotion.

This emulsion showed remarkable efficacy in treating acne.

Example 6 (Manufacture of cream) Ingredients (A) Amount (wt%) Setanol 4.0 Stearic acid
2.0 Vaseline
4.0 liquid paraffin
10.0 Isopropyl myristate
5.0 Glyceryl monostearate 3.0
Oleyl alcohol 0.5EO (
15 mol) Adduct POE (10) Lanolin alcohol 0.1 Salicylic acid 1.0 Component of (B) Glycerin 5.0 Propylene glycol 5.0 Potassium hydroxide
0.2 Purified water
60.2 A cream was prepared in the same manner as in Example 5. This product also showed remarkable efficacy in treating acne.

Example 7 (Manufacture of cream) Ingredients (A) Amount (wt%) Setanol 4.0 Stearic acid
2.0 Vaseline
4.0 liquid paraffin
10.0 Isopropyl myristate
5.0 Glyceryl monostearate 3.0 Oleyl alcohol 0.1 EO (2
0 mol) Adduct polyglyceryl monooleate 0.1 Salicylic acid 1.5 Component of (B) Glycerin 5.0 Propylene glycol 5.0 Potassium hydroxide
0.2 Purified water
60.1 A cream was prepared in the same manner as in Example 5. This product also showed remarkable efficacy in treating acne.

Example 8 (soft ointment) Ingredients Amount (wt%) Solid paraffin 10.0 piece wax 10.0 squalane
10.0P OE (6) Sorbitan monooleate 1.0 Sorbitan monooleate 1.0 Salicylic acid 1.0 Fragrance
Appropriate amount of Vaseline
67.0 The above acid components were mixed, the mixture was heated and dissolved at 80°C, and then cooled with stirring to obtain an ointment. This product was highly effective in treating acne.

Examples 9 to 16 Dissolve 0.2 g of P OE (15) monooleate in 25.0 g of ethanol, add and dissolve 15.0 g of polyethylene glycol (PEG-600), then add 1.0 g of urea to 10.0 g of purified water. Add the solution dissolved in.

Then carboxyvinyl polymer (Carbopol 940
) 0.8g and hyaluronic acid 0.1g in purified water 20.
After adding 0 g of the solution and stirring and mixing, 27.7 g of purified water was further added and neutralized with 0.2 g of triethanolamine to obtain a gel-like external preparation.

Similarly, P OE (15) Monooleate 0.2-2
．． A gel ointment containing 0% was obtained. Their blending amounts are shown in the table as Examples 9 to 16.

(Hereinafter in the margin) [Effects of the Invention] The skin external preparation of the present invention has excellent acne treatment effects and good stability and safety.

Claims (1)

[Claims] (1) For external use on the skin, containing as active ingredients a drug for acne and a surfactant whose skeleton is an aliphatic alcohol residue or fatty acid residue having one or more unsaturated bonds in the molecule. agent.