KR101661694B1 - Low irritating composition for skin whitening comprising hydroquinone - Google Patents

Abstract

The present invention relates to a cosmetic composition comprising cetyl alcohol, stearic acid and stearyl alcohol as an oily component together with hydroquinone as an active ingredient so as to minimize irritation to the skin while maintaining high whitening activity of hydroquinone, hydroquinone 2 to 5 parts by weight; 1 to 5 parts by weight of cetyl alcohol; 1 to 5 parts by weight of stearic acid; And stearyl alcohol in an amount of 1 to 5 parts by weight based on the total weight of the composition.
The composition minimizes skin irritation as compared with conventional whitening agents, and thus can be widely used in external preparations for skin, cosmetic compositions and pharmaceutical compositions.

Description

[0001] The present invention relates to a hypo-irritating composition for skin whitening comprising hydroquinone,

The present invention relates to a composition for hypo-allergenic skin whitening comprising hydroquinone.

Melasma, which is one of the typical pigment deposits, such as spots and freckles, is a common acquired pigment disease in Asians. 0.25-4% of patients seeking dermatology have a stigma, which is especially common in middle-aged women aged 30 to 44 years. The ingredients of hydroquinone, tretinoin, kojic acid and azelaic acid are used as topical treatments for the treatment of vitiligo. Physical treatment is chemical peeling (glycolic acid) , Trichloroacetic acid), laser treatment, dermabrasion, etc. have been effectively used. [ Treatment of melasma . J Am Acad Dermatol, 2006; 54: S272-81].

Of the therapies recommended for the treatment of hyperpigmentation in the skin, phenolic derivatives, polyphenols, are one of the most effective active agents for decades. Therapeutic use of the formulation has been achieved as skin discoloration has been observed in rubber industry artisans, and some of these products have been used as antioxidants. Thereafter, a number of studies have confirmed its efficacy when used alone or in conjunction with other depigmenting agents (International Journal of Dermatology Jan-Feb 1982 Vol. 21, pp. 55-58].

Hydroquinone, one of the hydroxyphenols, inhibits the conversion of dopa into melanin by inhibiting the action of tyrosinase. Hydroquinone gradually reduces the degree of pigmentation at sites where the pigment is over-deposited. Three to three months must elapse before the color of the skin begins to change by these hydroquinones. Nonpresceiption product therapeutics , second edition, Shin-il book press, pp. 636-644, 2007]

In tests on guinea pigs, it has been shown that hydroquinone degrades melanocytes [The journal of investigative dermatology, 62: 436-449, 1974] and further confirms the results in human experiments. According to J Dermatol Treat (2000) 11: 173-179, 40% of patients treated with 4% hydroquinone compared with placebo showed improvement [ A double - blind , comparative , placebo- controlled study of the efficacy and tolerability of 4% hydroquinone as a depigmenting agent in melasma ], and other studies have reported that patients using 4% hydroquinone have improved by 76.9%. [ A Clinical , prospective , randomized, double - blind trial comparison skin whitening complex with hydroquinone vs. placebo in the treatment of melasma . Int J Dermatol 2003; 42: 153-6.]

However, while hydroquinone is effective in treating hypermotility, it has side effects. [Int J dermatol. For example, the main use range of hydroquinone is 2 to 5%, and when a high concentration product is used in a manner unsuitable for the dosage strength, the irritant contact There are side effects such as irritant dermatitis, contact dermatitis, postinflammatory pigmentation, and ochronosis. [ Treatment of melasma. J Am Acad Dermatol 2006; 54: S272-81].

One way to improve these side effects is to add an anti-inflammatory steroid component to reduce irritation. Corticosteroids are very effective for topical intermittent use, but serious adverse effects, including side effects such as nerve, mental, cardiovascular, and metabolism, and long-term skin contractions, (Korean Patent Laid-Open No. 10-2014-0019276 and [ Adverse effects of topical glucocorticosteroids , J Am Acad Dermatol: 54: 1-15).

As described above, there is an urgent need to study a preparation containing hydroquinone as an active ingredient, which is a therapeutic ingredient for improving schizophrenia, while alleviating side effects.

Under these circumstances, the inventors of the present invention, while intensively studying the whitening composition using hydroquinone, recognized that the amount and composition of the oily substance should be controlled in order to reduce the irritation of hydroquinone. It was confirmed that the skin irritancy was similarly reduced with the composition containing steroid, and the present invention was completed.

In order to solve the above problems, it is an object of the present invention to provide a composition for hypo-allergenic skin whitening comprising hydroquinone as an active ingredient.

According to the above-mentioned object, the present invention relates to a process for the preparation of a pharmaceutical composition, which comprises 2 to 5 parts by weight of hydroquinone, 1 to 5 parts by weight of cetyl alcohol; 1 to 5 parts by weight of stearic acid; And 1 to 5 parts by weight of stearyl alcohol.

The skin whitening composition of the present invention minimizes skin irritation as compared with conventional hydroquinone-containing whitening agents, and is highly safe for human body, and thus can be widely used in skin external preparations, cosmetic compositions and pharmaceutical compositions.

Fig. 1 is a graph of an experimental result of Test Example 1. Fig.
Fig. 2 is a graph of the experimental result of Test Example 2. Fig.
3 is a graph of the experimental result of Test Example 3;

The present invention is characterized in that it contains cetyl alcohol, stearic acid and stearyl alcohol as the oily components together with the active ingredient hydroquinone so as to minimize irritation to the skin while maintaining high whitening activity of hydroquinone, To a composition for polar skin whitening. Specifically, the present invention relates to a process for producing a curable composition comprising: 2 to 5 parts by weight of hydroquinone; 1 to 5 parts by weight of cetyl alcohol; 1 to 5 parts by weight of stearic acid; And 1 to 5 parts by weight of stearyl alcohol.

Hydroquinone contained in the whitening composition of the present invention is a compound having a structure represented by the following general formula (1), and is contained in an amount of 2 to 5 parts by weight per 100 parts by weight of the total composition according to the present invention.

[Chemical Formula 1]

Meanwhile, cetyl alcohol, stearic acid and stearyl alcohol contained in the whitening composition according to the present invention are oil-phase components, and the amount of cetyl alcohol contained in the composition is 1 to 5 parts by weight or 1.5 to 5 parts by weight, 4.5 parts by weight. The amount of stearic acid may be 1 to 5 parts by weight or 1 to 3.5 parts by weight based on 100 parts by weight of the total composition as described above. The amount of stearyl alcohol may be 1 to 5 parts by weight or 1.5 to 4.5 parts by weight based on 100 parts by weight of the total composition as described above. The total amount of the oily substances is preferably not more than 15 parts by weight based on 100 parts by weight of the total composition, but is not limited thereto.

In a preferred embodiment, the composition of the present invention may further comprise at least one additive selected from the group consisting of emulsifiers, oil stabilizers, water-soluble substances, water stabilizers and preservatives in addition to the hydroquinone and oily substances.

The emulsifier contained in the composition according to the present invention may increase the stimulation-relieving effect on the skin, but may include one or more selected from the group consisting of polyethylene glycol (PEG) 4000 and polyethylene glycol 1500, And 8 to 20 parts by weight based on 100 parts by weight of the total composition. When two or more kinds of emulsifiers are used in combination, the mixing ratio of the two or more kinds of emulsifiers is not limited and can be appropriately controlled within a range of 8 to 20 parts by weight, which is the total weight of the emulsifier.

In one specific embodiment, the composition according to the present invention may include polyethylene glycol 4000 and polyethylene glycol 1500 as emulsifiers, independently from 0.5 to 5 parts by weight or 1 to 4 parts by weight, relative to 100 parts by weight of the total composition, no.

In another specific embodiment of the present invention, in addition to the polyethylene glycol 4000 and the polyethylene glycol 1500 as the emulsifier, at least one selected from the group consisting of polysorbate 60 and self-emulsifying glyceryl monostearate may be further included .

At this time, the content ratios of polyethylene glycol 4000 and polyethylene glycol 1500 may independently be 0.5 to 5 parts by weight or 1 to 4 parts by weight based on 100 parts by weight of the total composition, but are not limited thereto.

Further, the amount of polysorbate 60 may be 3 to 7 parts by weight or 4 to 6 parts by weight based on 100 parts by weight of the total composition, and the amount of self-emulsifying glyceryl monostearate may be 2 to 5 parts by weight or 3 to 4 parts by weight But it is not limited thereto and can be suitably controlled within a range of 8 to 20 parts by weight, which is the total weight of the emulsifier.

In addition, the composition of the present invention may contain one or more compounds selected from the group consisting of concentrated glycerin, methylglucose-10, methylglucose-20 and methylglucose-20 benzoate together with butylene glycol or butylene glycol as the water- May be included. When the two or more kinds of water-based materials are used in combination, the mixing ratio of the water-based materials is not limited, and the weight of the entire water-based material And 13 to 19 parts by weight. In one preferred embodiment, when at least one water-based material is used together with butylene glycol, the butylene glycol may be used in an amount of 3 to 10 parts by weight, and 4 to 7 parts by weight, based on 100 parts by weight of the total composition.

The oil stabilizer contained in the composition according to the present invention may be at least one selected from the group consisting of butylhydroxytoluene and butylhydroxyanisole, but is not limited thereto, preferably butylhydroxytoluene, May be used in an amount of 0.01 to 0.1 parts by weight or 0.02 to 0.05 parts by weight based on 100 parts by weight.

The water stabilizer contained in the composition according to the present invention may be at least one member selected from the group consisting of ascorbic acid, sodium edetate, sodium pyrosulfite and sodium hydrogen sulfite, preferably sodium pyrosulfite, 0.01 to 0.3 parts by weight, and 0.1 to 0.3 parts by weight, relative to 100 parts by weight.

The preservative contained in the composition according to the present invention is selected from the group consisting of sorbic acid; Parabens such as methylparaben, propylparaben or ethylparaben; Benzoic acid; Benzyl alcohol; Imidazolidinyl urea; And diazolidinyl urea, but is not limited thereto. More specifically, at least one selected from the group consisting of methyl paraoxybenzoate and propyl paraoxybenzoate may be used. The amount thereof may be 0.05 to 0.3 parts by weight, or 0.1 to 0.25 parts by weight based on 100 parts by weight of the total composition, but is not limited thereto.

In one preferred embodiment, the composition according to the present invention may further comprise a stabilizer in addition to the above components. The stabilizer may be selected from the group consisting of sodium sulfite, potassium sulfite, ammonium sulfite, sodium hydrogensulfite, potassium hydrogensulfite, ammonium hydrogensulfite, sodium metabisulfite, potassium metabisulfite, formic acid, And a mixture thereof, and may be contained in an amount of 0.1 to 2.0 parts by weight based on 100 parts by weight of the total composition.

In the present invention, the composition may be a cosmetic composition or a pharmaceutical composition. When the composition is a cosmetic, the formulation is not particularly limited and may be appropriately selected according to the purpose. For example, skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisturizing lotion, nutrition lotion, massage cream, nutritional cream, moisturizing cream, hand cream, foundation, essence, nutrition essence, pack, soap, cleansing A cream, a gel, a foam, a cleansing lotion, a cleansing cream, a body lotion and a body cleanser, but it may be prepared in a paste, cream or gel form.

In addition, when the composition is a pharmaceutical composition, it may be formulated into various parenteral administration forms according to a conventional method. Preferably, the parenteral dosage form may be a transdermal dosage form, for example, but not limited to, lotions, ointments, gels, creams, patches or spray formulations.

Also, when the composition is used as a pharmaceutical composition for whitening, it can be effectively used for the treatment of melasma such as spots and freckles based on inhibition of tyrosinase action and melanin cell decomposition effect of hydroquinone.

The dosage of the active ingredient contained in the pharmaceutical composition is within the level of those skilled in the art. The daily dose of the drug depends on various factors such as the degree of disease progression, the onset of disease, age, However, when an adult is used as a standard, the composition may be divided into 1 to 50 mg / kg, preferably 1 to 200 mg / kg, 1 to 3 times a day, Is not intended to limit the scope of the invention in any way.

In another aspect, the present invention relates to an external preparation for skin comprising the composition, wherein the external preparation for skin is a generic term that may be applied to any external skin, and cosmetics and medicines of various formulations may be included therein .

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are intended to illustrate the contents of the present invention, but the scope of the present invention is not limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.

< Example  1 > hydroquinone-containing Cream  Produce

3 g of polyethylene glycol 4000 as an emulsifier, 3 g of polyethylene glycol, 5 g of polysorbate 60, 3.5 g of self-emulsifying glyceryl monostearate as the oil agent, 1.5 g of stearic acid, (0.04 g) was heated to 80 DEG C using a constant temperature water bath and dissolved by mechanical stirring (DAIHAN scientific Co. Ltd., product name: HT-50DX) at 500 rpm to dissolve.

4 g of the main component hydroquinone, 7 g of butylene glycol as a water-based substance, 4 g of concentrated glycerin and 5 g of methylglucose-10 were placed, and 0.18 g of methyl p-oxybenzoate, 0.02 g of propyl p-hydroxybenzoate and 0.2 g of sodium pyrophosphate And the total amount of purified water is adjusted to 100 g. The mixture was heated to 80 DEG C using a constant temperature water bath and dissolved by mechanical stirring (DAIHAN scientific Co. Ltd., product name: HT-50DX) at 700 rpm to dissolve.

When the two phases were completely dissolved, the oily dissolution tank was transferred to a water dissolution tank and stirred for 30 minutes at 40 to 60 ° C in a constant temperature water bath and at 5000 to 6000 rpm using a homogenizer (TOKUSHU KIKA, product name: Homo mixer mark II (model 2.5) .

< Example  2>

A cream formulation containing hydroquinone was prepared in the same manner as in Example 1 except that the content of butylene glycol was 5%.

< Example  3>

Except that hydroquinone was contained in the same composition and method except that 4% of cetyl alcohol, 3% of stearic acid, 4% of stearyl alcohol, 2% of polyethylene glycol 4000, 2% of polyethylene glycol 1500 and 5% of butylene glycol were used in Example 1 &Lt; / RTI &gt;

< Example  4>

Except that hydroquinone was contained in the same composition and method except that 4% of cetyl alcohol, 3% of stearic acid, 4% of stearyl alcohol, 1% of polyethylene glycol 4000, 1% of polyethylene glycol 1500 and 5% of butylene glycol were used in Example 1 &Lt; / RTI &gt;

< Comparative Example  1> Preparation of emulsifiers and emulsifiers modified in water content

In the same manner as in Example 1 except that 4% cetyl alcohol, 3% stearic acid and 4% stearyl alcohol were used and polyethylene glycol 4000, polyethylene glycol 1500 and butylene glycol were excluded from the composition, Cream formulations were prepared.

The component tables of Examples 1 to 4 and Comparative Example 1 are shown in Table 1 below.

purpose ingredient Example 1 Example 2 Example 3 Example 4 Comparative Example 1 Active ingredient Hydroquinone 4.00 4.00 4.00 4.00 4.00 Oil matter Cetyl alcohol 2.00 2.00 4.00 4.00 4.00 Stearic acid 1.50 1.50 3.00 3.00 3.00 Stearyl alcohol 2.00 2.00 4.00 4.00 4.00 Emulsifier Polyethylene glycol 4000 3.00 3.00 2.00 1.00 - Polyethylene glycol 1500 3.00 3.00 2.00 1.00 - Polysorbate 60 5.00 5.00 5.00 5.00 5.00 Self-emulsifying glyceryl monostearate 3.50 3.50 3.50 3.50 3.50 Oil stabilizer Butylated hydroxytoluene 0.04 0.04 0.04 0.04 0.04 Water-based material Butylene glycol 7.00 5.00 5.00 5.00 - Concentrated glycerin 4.00 4.00 4.00 4.00 4.00 Methylglucose-10 5.00 5.00 5.00 5.00 5.00 Water stabilizer Sodium pyrophosphate 0.20 0.20 0.20 0.20 0.20 antiseptic Methyl paraoxybenzoate 0.18 0.18 0.18 0.18 0.18 Propyl paraoxybenzoate 0.02 0.02 0.02 0.02 0.02 menstruum Purified water to make 100%

< Comparative Example  2> When the oil matter content is changed Creamy  Produce

As shown in Table 2 below, a cream formulation containing hydroquinone was prepared by the same composition and method except that the oily substance of Example 1 was changed as follows.

purpose Ingredients content (%) Active ingredient Hydroquinone 4.00 Oil matter Caprylic, capric triglyceride 3.00 Trioctanoin 2.00 Stearic acid 3.00 Cetearyl Alcohol / Ceteareth-20 2.00 Cetostearyl alcohol 2.00 Hydrogenated lecithin 1.00 Dimethicone 1.00 Sorbitan monostearate 1.00 Emulsifier Polyethylene glycol 4000 3.00 Polyethylene glycol 1500 3.00 Polysorbate 60 5.00 Self-emulsifying glyceryl monostearate 3.50 Oil stabilizer Butylated hydroxytoluene 0.04 Water-based material Butylene glycol 7.00 Concentrated glycerin 4.00 Methylglucose-10 5.00 Water stabilizer Sodium pyrophosphate 0.20 antiseptic Methyl paraoxybenzoate 0.18 Propyl paraoxybenzoate 0.02 menstruum Purified water to make 100%

&Lt; Comparative Example 3 > Preparation of cream formulations containing hydroquinone and tretinoin

According to the composition of Example 1 of Korean Patent Publication No. 2000-0073077, a cream formulation containing 4% of hydroquinone and 0.01% of tretinoin was prepared.

Ingredients % (w / w) Hydroquinone 4.00 Tretinoin 0.01 Methyl paraben 0.1 Propylparaben 0.05 Polyethylene glycol 1500 1.5 Polyethylene glycol 4000 1.5 Sodium edetate 0.5 Isopropyl myristate 5 Cetostearyl alcohol 3 Glycerol monostearate 3 Liquid paraffin 3 Sorbitan monostearate 1.5 Setomacrogol 1000 1.5 vaseline 5 Propylene glycol 0.5 Tocopherol 0.1 Butylhydroxytoluene 0.1 Purified water Suitable amount

< Comparative Example  4> hydroquinone, Tretinoin  And Steroid-containing Creamy  Produce

A cream formulation containing 4% of hydroquinone, 0.05% of tretinoin and 0.01% of fluorocinol acetonide (steroid) was prepared according to the composition disclosed in Korean Patent Laid-Open Publication No. 2006-0040755, Table 1.

ingredient % (w / w) Hydroquinone 4.00 Tretinoin 0.05 Fluorocinolone acetonide 0.01 Magnesium aluminum silicate 3.00 Butylated hydroxytoluene 0.04 Cetyl alcohol 4.00 Stearic acid 3.00 Stearyl alcohol 4.00 Methyl paraben 0.18 Propylparaben 0.02 Arlacel®165 3.50 Methylglucose-10 5.00 glycerin 4.00 Citric acid 0.05 Sodium metabisulfite 0.20 Purified water 68.95

< Test Example  1> Evaluation of skin irritation: Comparing stimulation reduction components and composition

In order to examine the degree of skin irritation of the cream agent according to the present invention, skin irritation tests were carried out on the cream agents described in Examples 1 to 4 and Comparative Example 1. In the test, 30 subjects were subjected to skin patch test on the back using Finn Chamber. People who are taking psoriasis, eczema, other skin lesions, pregnancy, breastfeeding or contraception, and antihistamines are excluded from this test. 30 parts of the prepared test subjects were wiped with 70% ethanol and then dried. Then, 25 占 퐇 of the cream preparations according to Examples 1 to 4 and Comparative Example 1 were dropped into Finn Chamber, . After applying the patch for 24 hours and removing the patch, the test area was marked with a marking pen, and the test site was observed after 30, 24 and 48 hours, respectively. The test was performed at 30 minutes, 24 hours, and 48 hours, and skin reactions were classified according to the criteria of the International Contact Dermatitis Research Group (ICDRG). The mean skin response was calculated according to the formula, and the degree of stimulation was considered to indicate a strong stimulus if the mean score was greater than 4.

The evaluation results are shown in Fig. As shown in FIG. 1, the formulation of the present invention contained butylene glycol in comparison with Comparative Example 1, and the stimulation level was remarkably decreased as polyethylene glycol 4000 and polyethylene glycol 1500 were included.

< Test Example  2> Evaluation of skin irritation: Comparison of total amount of oil matter

Skin irritation tests were conducted on the cream preparations according to Example 1 and Comparative Examples 1 and 2 in the same manner as in Test Example 1 in order to examine the degree of skin irritation according to the total amount of the oily substances, Respectively. Referring to FIG. 2, it can be seen that the irritation of the cream preparation of Comparative Example 2 was greatly increased as compared to Example 1 and Comparative Example 1. Thus, it was confirmed that when the total amount of the oily substances is 15% or more and the kinds thereof are eight or more, the stimulation increases and the degree of the stimulation is severe.

< Test Example  3> Skin irritation evaluation: comparison with commercial products

In order to compare the degree of skin irritation of the cream preparation according to the present invention with those of the commercial products, skin irritation tests were carried out on the cream preparations and commercial preparations according to Example 1, Comparative Examples 3 and 4 in the same manner as in Test Example 1 . Ultraquin, ultraquin plain, and ultraquin gel, which are commercially available products of Canderm Pharma Inc., were designated as marketed preparations A to C, respectively. As a result of examining the components of the commercial product before testing, it was confirmed that commercial products A to C contained five or more kinds of oil substances, and did not contain butylene glycol, polyethylene glycol 4000, and polyethylene glycol 1500. The test results are shown in Fig.

According to FIG. 3, in Comparative Example 3, the total amount of oily substances was not less than 15%, the number of the kinds of the oily substances was more than eight, and that of Comparative Example 4 included a steroid agent, . It was observed that the preparation of the present invention was remarkably reduced in stimulation level as compared with the commercially available products A to C of Canderm. In addition, it was confirmed that the degree of stimulation relaxation was similar to that of a preparation containing a steroid agent.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention as defined in the appended claims. will be. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (25)

Based on 100 parts by weight of the total composition,
2 to 5 parts by weight of hydroquinone as an active ingredient;
As the oily substance, 1 to 5 parts by weight of cetyl alcohol; 1 to 5 parts by weight of stearic acid; And 1 to 5 parts by weight of stearyl alcohol;
As the emulsifier, 8 to 20 parts by weight of a mixture of polyethylene glycol 4000 and polyethylene glycol 1500;
0.01 to 0.1 parts by weight of a liquid stabilizer;
13 to 19 parts by weight of butylene glycol as a water-based material; And
0.01 to 0.3 parts by weight of at least one selected from the group consisting of ascorbic acid, sodium edetate, sodium pyrosulfite, and sodium hydrogensulfite is contained as a water stabilizer,
Lt; RTI ID = 0.0 &gt; a &lt; / RTI &gt; steroid compound.
A cosmetic composition for hypoallergenic skin whitening.
The method according to claim 1,
Wherein the cosmetic composition further comprises 0.05 to 0.3 parts by weight of a preservative relative to 100 parts by weight of the total composition. delete delete The method according to claim 1,
Wherein the emulsifier further comprises at least one member selected from the group consisting of polysorbate 60 and self-emulsifying glyceryl monostearate. The method according to claim 1,
Wherein the water-based material further comprises at least one selected from the group consisting of concentrated glycerin, methylglucose-10, methylglucose-20, and methylglucose-20 benzoate. The method according to claim 1,
Wherein the oil stabilizer is at least one selected from the group consisting of butylated hydroxytoluene and butylhydroxyanisole. delete 3. The method of claim 2,
Wherein the preservative is selected from the group consisting of sorbic acid; Parabens selected from the group consisting of methylparaben, propylparaben and ethylparaben; Benzoic acid; Benzyl alcohol; Imidazolidinyl urea; And diazolidinyl urea. &Lt; / RTI &gt; The method according to claim 1,
Wherein the composition is selected from the group consisting of sodium sulfite, potassium sulfite, ammonium sulfite, sodium hydrogensulfite, potassium hydrogen sulphite, ammonium hydrogensulfite, sodium metabisulfite, potassium metabisulfite, formic acid, oxalic acid, &Lt; / RTI &gt; wherein the composition further comprises a stabilizing agent selected from the group consisting of &lt; RTI ID = 0.0 &gt; The cosmetic composition according to claim 10, wherein the stabilizer is included in an amount of 0.1 to 2.0 parts by weight based on 100 parts by weight of the total composition. On the basis of 100 parts by weight of the total composition
2 to 5 parts by weight of hydroquinone as an active ingredient;
As the oily substance, 1 to 5 parts by weight of cetyl alcohol; 1 to 5 parts by weight of stearic acid; And 1 to 5 parts by weight of stearyl alcohol;
As the emulsifier, 8 to 20 parts by weight of a mixture of polyethylene glycol 4000 and polyethylene glycol 1500;
0.01 to 0.1 parts by weight of a liquid stabilizer;
As the water-soluble substance, 13 to 19 parts by weight of butylene glycol; And
0.01 to 0.3 parts by weight of at least one selected from the group consisting of ascorbic acid, sodium edetate, sodium pyrosulfite, and sodium hydrogen sulfite is contained as a water stabilizer,
Lt; RTI ID = 0.0 &gt; a &lt; / RTI &gt; steroid compound.
A pharmaceutical composition for hypoallergenic skin whitening.
13. The method of claim 12,
Wherein the composition further comprises 0.05 to 0.3 wt% of a preservative relative to 100 wt% of the total composition. delete delete 13. The method of claim 12,
Wherein the emulsifier further comprises at least one member selected from the group consisting of polysorbate 60 and self-emulsifying glyceryl monostearate. 13. The method of claim 12,
Wherein the water-based material further comprises at least one selected from the group consisting of concentrated glycerin, methylglucose-10, methylglucose-20, and methylglucose-20 benzoate. 13. The method of claim 12,
Wherein the oil stabilizer is at least one selected from the group consisting of butylated hydroxytoluene and butylhydroxyanisole. delete 14. The method of claim 13,
Wherein the preservative is selected from the group consisting of sorbic acid; Parabens selected from the group consisting of methylparaben, propylparaben and ethylparaben; Benzoic acid; Benzyl alcohol; Imidazolidinyl urea; And diazolidinyl urea. &Lt; / RTI &gt; 13. The method of claim 12,
Wherein the composition is selected from the group consisting of sodium sulfite, potassium sulfite, ammonium sulfite, sodium hydrogensulfite, potassium hydrogen sulphite, ammonium hydrogensulfite, sodium metabisulfite, potassium metabisulfite, formic acid, oxalic acid, &Lt; / RTI &gt; further comprising a stabilizing agent selected from the group consisting of &lt; RTI ID = 0.0 &gt; 22. The composition according to claim 21, wherein the stabilizer is included in an amount of 0.1 to 2.0 parts by weight based on 100 parts by weight of the total composition. The cosmetic composition according to claim 1, wherein the composition is a paste, cream or gel formulation. 13. The composition of claim 12, wherein the composition is a lotion, ointment, gel, cream, patch or spray formulation. Based on 100 parts by weight of the total composition,
2 to 5 parts by weight of hydroquinone as an active ingredient;
As the oily substance, 1 to 5 parts by weight of cetyl alcohol; 1 to 5 parts by weight of stearic acid; And 1 to 5 parts by weight of stearyl alcohol;
As the emulsifier, 8 to 20 parts by weight of a mixture of polyethylene glycol 4000 and polyethylene glycol 1500;
0.01 to 0.1 parts by weight of a liquid stabilizer;
13 to 19 parts by weight of butylene glycol as a water-based material; And
0.01 to 0.3 parts by weight of at least one selected from the group consisting of ascorbic acid, sodium edetate, sodium pyrosulfite, and sodium hydrogensulfite is contained as a water stabilizer,
Lt; RTI ID = 0.0 &gt; a &lt; / RTI &gt; steroid compound.
A pharmaceutical composition for the treatment of schizophrenia.

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