JP2007063140A - Bleaching agent and bleaching cosmetic containing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a bleaching cosmetic which has an epidermal cell melanocyte proliferation factor production-inhibiting effect and has an excellent bleaching action. <P>SOLUTION: This satisfiable bleaching effect/skin-bleaching effect-having bleaching cosmetic contains a monoalkyl glyceryl ether and a glycerol mono fatty acid ester as bleaching ingredients as the result of zealous researches. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a whitening agent and a whitening cosmetic containing the same. More specifically, it has a melanocyte growth factor production inhibitory effect, a whitening agent with an excellent whitening effect, and prevention and improvement of skin prevention such as pigmentation / stains / freckle / liver spots after sunburn, etc. The present invention relates to a whitening cosmetic that exhibits a whitening effect.

  Pigmentation such as skin spots and freckles is a result of excessive synthesis of melanin pigments caused by ultraviolet rays and other stimuli, and is a major cosmetic problem.

  This melanin pigment is produced in melanin-producing granules (melanosomes) in melanocytes (melanocytes) existing in the basal layer at the bottom of the epidermis, and the produced melanin diffuses to adjacent cells by osmotic action. The biochemical reaction in this melanocyte is considered as follows.

  That is, tyrosine, an essential amino acid, is converted to dopaquinone by the action of the enzyme tyrosinase, and this process changes from red and colorless pigments to black melanin pigments by enzymatic or non-enzymatic oxidation. is there.

  Conventionally, substances that suppress the production of melanin are used to prevent stains and freckles, such as L-ascorbic acid, L-ascorbic acid-2-magnesium phosphate, L-ascorbic acid glucoside, kojic acid, cysteine, A common method is to apply a whitening agent such as arbutin or glutathione to an ointment, cream, lotion or the like and apply it locally. In addition, a method of locally injecting a reducing amino acid such as glutathione is also performed. However, many of these whitening cosmetics are not effective enough, have problems with stability and safety, have a high whitening effect and a beautiful skin effect, have good stability, and are mild to the skin. And whitening agents that are easy to use.

On the other hand, in recent years, it has been reported that melanocytes are activated by factors released from epidermal cells due to ultraviolet rays, and the influence of these factors on pigmentation due to ultraviolet rays is large, and their importance is drawing attention. As this factor, α-melanocyte stimulating hormone (α-MSH), endothelin-1 (ET-1), prostaglandin E ₂ (PGE ₂ ), nitric oxide (NO), and the like have been reported. It is necessary to inhibit the release and action of these factors, and reduction of pigmentation due to ultraviolet rays can be expected. (Patent Documents 1, 2, and 3)

The monoalkyl glyceryl ether and glycerin mono fatty acid ester according to the present invention are known substances and have been widely used as an emulsion stabilizer, a W / O emulsifier, or an oil component in cosmetics. As a mild cosmetic base material that is less irritating to the skin, many cosmetics have been formulated as an irritation reducing agent. (Patent Documents 4 and 5) However, it is not known that monoalkyl glyceryl ether and glycerin mono fatty acid ester have a whitening action.
Japanese Patent Laid-Open No. 06-321755 JP 09-194344 A Japanese Patent No. 2511815 JP 2000-72618 A JP 2003-233831 A

  The present invention has been made in view of the above circumstances, and its purpose is to provide a highly safe whitening agent having an excellent whitening effect, and further to a whitening cosmetic product that exhibits an excellent whitening effect on the skin. It is to provide.

  As a result of earnest research to provide a whitening cosmetic having a satisfactory whitening effect and skin-beautifying effect, the present inventor has found that monoalkyl glyceryl ether and glycerin monofatty acid ester conventionally used as a cosmetic base material have been obtained. Finding that it has a whitening effect, and whitening cosmetics containing these have a safe and excellent whitening effect on the skin, such as prevention and improvement of pigmentation, stains, freckles, liver spots etc. after sunburn As a result, the present invention has been completed.

  That is, the present invention is a whitening agent comprising a monoalkyl glyceryl ether and / or a glycerin mono fatty acid ester.

  Moreover, this invention is a melanocyte growth factor production inhibitor consisting of monoalkyl glyceryl ether and / or glycerol mono fatty acid ester.

  Furthermore, the present invention is a whitening cosmetic containing one or more compounds of the monoalkyl glyceryl ether and / or glycerol mono fatty acid ester.

According to the present invention, monoalkyl glyceryl ether and glycerin monofatty acid ester enhance UVB tolerance, inhibit UVB-induced PGE ₂ release, inhibit UVB-induced IL-1α release, and inhibit production of UVB-induced epidermal cell-derived melanocyte growth factor. A safe whitening cosmetic that exhibits excellent whitening effects on the skin, such as prevention and improvement of pigmentation, stains, freckles, liver spots, etc. after sunburn by combining these substances. can get.

Hereinafter, the configuration of the present invention will be described in more detail.
The whitening agent used in the present invention is monoalkyl glyceryl ether or glycerin mono fatty acid ester.

The monoalkyl glyceryl ether used in the present invention exists in nature, and alkylyl 16 and 18 or alkenyl carbon 18 chimyl alcohol, batyl alcohol, and ceralkyl alcohol are components contained in shark liver oil and the like, and have a liquid crystal forming ability. It is known to have.
Monoalkyl glyceryl ethers can also be prepared synthetically and obtained by known methods such as condensation reaction of linear or branched alkyl halides or alkenyl halides (halogenated hydrocarbons) having 8 to 22 carbon atoms with glycerol alcoholate. be able to. The synthesis method may be in accordance with a known method, and it is obtained by preparing glycerin alcoholate in advance with glycerin and caustic soda or caustic potash, and further reacting with a halogenated hydrocarbon. The reaction temperature is suitably from 100 ° C to 200 ° C, and the reaction time is suitably from 1 hour to 5 hours. Since the obtained product usually contains an inorganic salt such as salt, it is purified by washing with water and further recrystallizing with methanol or ethanol. As another synthetic method, glycidyl ether is prepared from higher alcohols such as isooctanol, octanol, lauryl alcohol, oleyl alcohol, stearyl alcohol, behenyl alcohol, isostearyl alcohol and epichlorohydrin, and then their epoxy bonds are opened. It can also be obtained by ringing. Since the obtained product similarly contains inorganic salts such as sodium chloride, it is purified by washing with water and further recrystallizing with methanol or ethanol.

  As the monoalkyl glyceryl ether of the present invention, those having a linear or branched alkyl group or alkenyl group having 8 to 22 carbon atoms can be preferably used, more preferably batyl alcohol (alkyl group carbon number 18), Kimi. Examples include alcohols (alkyl group carbon number 16), ceralkyl alcohols (alkenyl group carbon number 18), isostearyl glyceryl ether (alkyl group carbon number 18), monobehenyl glyceryl ether (alkyl group carbon number 22), and the like. Particularly preferred are batyl alcohol, chimyl alcohol, and seraalkyl alcohol.

  Commercially available batyl alcohol, chimyl alcohol, and seraalkyl alcohol used in the present invention can be used. For example, batyl alcohol 100 or batyl alcohol EX manufactured by Nikko Chemicals Co., Ltd. can be used.

  The amount of monoalkyl glyceryl ether blended into the whitening cosmetic varies depending on the application, dosage form, blending purpose, etc. and is not particularly limited, but is generally 0.01-20.0% in the whitening cosmetic. % By mass is preferable, and more preferably 0.1 to 10.0% by mass.

  The glycerin monofatty acid ester used in the present invention is a glycerin monofatty acid ester having a fatty acid residue having 8 to 22 carbon atoms, such as glycerin monopalmitate, glycerin monomyristate, glycerin monostearate, glycerin. Examples include monooleic acid ester, glycerin monolinoleic acid ester, glycerin monoisopalmitic acid ester, glycerin monoisostearic acid ester, and glycerin monobehenic acid ester. Preferably, glycerol monopalmitate, glycerol monomyristate, glycerol monostearate, glycerol monooleate is used. More preferably, glycerol monostearate, glycerol monooleate, and glycerol monobehenate are used.

  The blending amount of the glycerin monofatty acid ester varies depending on the use, dosage form, blending purpose and the like, but generally 0.01 to 20.0% by mass in the whitening cosmetic is preferable, and more preferably 0.1 to 10%. 0.0% by mass.

  The whitening cosmetics of the present invention include L-ascorbic acid, L-ascorbic acid-2-phosphate sodium, L-ascorbic acid-2-phosphate, which are existing whitening agents, together with monoalkyl glyceryl ether or glycerin monofatty acid ester. Magnesium, L-ascorbic acid glucoside, ascorbyl tetrahexyldecanoate, kojic acid, cysteine, arbutin, glutathione and the like may be blended.

  In the whitening cosmetics of the present invention, hydrocarbons such as liquid paraffin, vegetable oils and fats, waxes, synthetic ester oils, silicones as ingredients to be blended in cosmetics, quasi-drugs and the like as long as the effects of the present invention are not impaired Oil phase components, fluorinated oil phase components, higher alcohols, fatty acids, thickeners, UV absorbers, powders, pigments, coloring materials, anionic surfactants, cationic surfactants, non- An ionic surfactant, an amphoteric surfactant, a polyhydric alcohol, a sugar, a polymer compound, a physiologically active ingredient, a transdermal absorption accelerator, a solvent, an antioxidant, a fragrance, an antiseptic, and the like can be blended.

The dosage form of the cosmetic according to the present invention is arbitrary, and can take any dosage form such as lotion, lotion, emulsion, cream, pack, ointment, dispersion, solid, mousse and the like. Moreover, as a use, it can use suitably for cosmetics, a skin external preparation, a pharmaceutical ointment, etc.
EXAMPLES The present invention will be specifically described below with reference to examples, but the technical scope of the present invention is not limited to these examples.

The following tests on the inhibitory action of UVB-induced epidermal cell-derived melanocyte growth factor, UVB-induced prostaglandin E ₂ (PGE ₂ ) and IL-1α release inhibitory action, UVB tolerance enhancing action and whitening effect of the compounds according to the present invention Went.

  (1) Evaluation of UVB-induced epidermal cell-derived melanocyte growth factor production inhibitory action

<Experiment method>
Normal human keratinocytes were cultured in a sample-containing medium for 24 hours, and then replaced with a sample-free Hank's gentle solution and irradiated with UVB. Furthermore, the medium was replaced with a new medium, and after 24 hours of culture, the culture supernatant (K-CM) was recovered. The recovered K-CM was treated with human normal melanocytes and cultured for 24 hours. After culturing, the medium was replaced with a medium containing 0.4 mg / mL MTT and cultured for 2 hours. After removing the medium, the amount of MTT reduction was determined by measuring the absorbance (OD = 550 nm) of the cell lysate dissolved by adding 2-propanol, and used as an index for melanocyte activation.

<Result>
As shown in Tables 1 and 2, batyl alcohol and chimyl alcohol were found to inhibit the production of melanocyte growth factor derived from UVB-induced epidermis.

(2) Evaluation of inhibitory action on UVB-induced PGE ₂ and IL-1α release

<Experiment method>
Normal human epidermal cells were seeded in a 96-well microplate so as to be almost confluent. The medium was replaced with a sample-containing medium 24 hours after sowing. After culturing for 24 hours, the solution was replaced with Hanks buffer (Ca ²⁺ , Mg ²⁺ not contained; HBS (−)) and irradiated with UVB. Control cells were covered with aluminum foil and shielded from UVB. After irradiation, HBS (−) was replaced with a sample-containing medium, and the cells were cultured for 24 hours. The amounts of PGE ₂ and IL-1α in the culture supernatant after 24 hours of culture were quantified using an EIA kit (PGE ₂ Express EIA Kit (Cayman), Human IL-1α Immunoassay (Quantikine)). At the same time, the amount of cellular protein was measured and calculated as the amount released per unit protein. In addition, statistical processing was performed with a significant difference test using a Student t test.

<Result>
As shown in Tables 3 and 4, batyl alcohol and chimyl alcohol were found to inhibit PGE ₂ and IL-1α release by UVB induction.

  (3) UVB cell damage alleviation action evaluation

<Experiment method>
Normal human epidermal cells were seeded in a 96-well microplate so as to be almost confluent. The sample-containing medium was replaced 24 hours after seeding. After culturing for 24 hours, the solution was replaced with Hanks buffer (Ca ²⁺ , Mg ²⁺ not contained; HBS (−)) and irradiated with UVB. Control cells were covered with aluminum foil and shielded from UVB. After irradiation, the HBS (−) was replaced with a new medium, and the cells were cultured for 24 hours. After culturing for 24 hours, the cells were cultured for 2 hours in KG2 containing 20 μg / mL neutral red (NR). The amount of NR taken up by viable cells was determined by measuring the absorbance at 550 nm of a cell lysate lysed using a 0.1N HCl solution containing 30% ethanol. The cell viability was expressed as a percentage where the absorbance of the control cells (UVB non-irradiated cells) was 100. For statistical processing, a significant difference test using a Student t test was performed.

<Result>
As shown in Tables 5 and 6, batyl alcohol, chimyl alcohol, ceralkyl alcohol and glycerin monostearic acid ester were found to alleviate cell damage caused by UVB.

  (4) Whitening effect test

<Test method>
1. Preparation of pigmentation by ultraviolet irradiation The test site is the inner left upper arm that is not easily exposed to sunlight in daily life. Irradiation with ultraviolet rays corresponding to 5 MED was performed to produce pigmentation with a diameter of 1 cm. As a light source, a multiport solar UV simulator model 601 (Solar Light Co. Inc.) is used with a wavelength range of 300 to 400 nm and a peak wavelength of 356 nm, and the irradiation intensity is measured using a multi-function measurement system model PMA2100 (Solar Light Co. Inc.). It was measured.
2. Test preparation A test preparation having the following formulation was used. A test preparation was obtained according to a conventional method for preparing an oil-in-water emulsion composition.

１．塗布方法および塗布期間
被験製剤はそれぞれの紫外線照射部位を含む２×２ｃｍ^２に約２０ｍｇを朝夕１日２回紫外線照射直後から３週間塗布した。
２．皮膚色測定および評価
観察日に、被験部位を分光測色計ＣＲ−１３（ミノルタ）を用いて測色した。測色パラメーターとしてはＬ＊を用い、色素沈着はΔＬ＊値（＝紫外線照射前のＬ＊値−紫外線照射後のＬ＊値）を用いて評価した。
美白効果の評価は以下の基準で行った
×：ΔＬ＊値がコントロールの値と同じ
△：ΔＬ＊値が（コントロールの値−１．０）以上
○：ΔＬ＊値が（コントロールの値−１．０）以内

1. Application Method and Application Period About 20 mg of the test preparation was applied twice a day in the morning and evening for 3 weeks to 2 × 2 cm ² including each ultraviolet irradiation site.
2. Skin color measurement and evaluation On the day of observation, the test site was measured using a spectrocolorimeter CR-13 (Minolta). L * was used as a colorimetric parameter, and pigmentation was evaluated using a ΔL * value (= L * value before ultraviolet irradiation−L * value after ultraviolet irradiation).
The whitening effect was evaluated according to the following criteria. X: ΔL * value is the same as control value Δ: ΔL * value is (control value −1.0) or more ○: ΔL * value is (control value−1) Within 0)

<Result>
As shown in Table 8, when 0.5% by mass of batyl alcohol was blended, a whitening effect equivalent to that of an existing whitening agent was shown, and when 3% by mass of batyl alcohol was blended, an excellent whitening effect was observed.

  Examples of whitening cosmetics containing the compound according to the present invention will be given below. A compounding quantity represents the mass%. The whitening cosmetics obtained in Examples 1 to 8 were all effective in the whitening effect test.

Cream 1
(Prescription) Mass%
Oil phase Kimyl alcohol 7.0
Squalane 3.0
Behenyl alcohol 4.0
Vaseline 3.0
Liquid paraffin 15.0
Aqueous phase POE (20) sorbitan monostearate
3.0
1,3-butylene glycol 3.0
Preservative Appropriate amount Fragrance Appropriate amount Purified water Remainder (Preparation method)
The oil-in-water emulsion composition was prepared according to a conventional method.

Essence (Prescription) Mass%
Kimyl alcohol 1.0
Squalane 1.0
Behenyl alcohol 4.0
Vaseline 3.0
Liquid paraffin 15.0
Decaglyceryl monolaurate 1.0
Monostearic acid POE (20) sorbitan
3.0
Xanthan gum 0.5
1,3-butylene glycol 10.0
Preservative Appropriate amount Fragrance Appropriate amount Purified water Remainder (Preparation method)
The oil-in-water emulsion composition was prepared according to a conventional method.

Lotion (Prescription) Mass%
Serakil alcohol 0.1
Squalane 0.2
Decaglyceryl monolaurate 2.0
Sodium hyaluronate 0.2
1,3-butylene glycol 3.0
Ethyl alcohol 10.0
Preservative Appropriate amount Fragrance Appropriate amount Purified water Remainder (Preparation method)
All ingredients were mixed and prepared at 50 ° C. until uniform.

Cream 2 (emollient type)
(Prescription) Mass%
Oil phase Seraquil alcohol 3.0
Squalane 10.0
Isocetyl myristate 6.0
Glyceryl tri-2-ethylhexanoate 3.0
Macadamia nut oil 1.0
Dimethylpolysiloxane (6cs) 0.2
Cetanol 5.0
POE (20) cetyl ether 1.0
Tetraoleic acid POE (40) Sorbit
0.5
Glyceryl monostearate 1.0
Aqueous phase Hydrogenated soybean lecithin 0.2
1,3-butylene glycol 5.0
Xanthan gum 0.1
Sodium hyaluronate 0.01
Citric acid 0.1
Sodium citrate 0.4
Preservative Appropriate amount Purified water The remainder (preparation method)
It was prepared according to a conventional method for producing an oil-in-water emulsion composition.

Beauty oil (prescription) Weight%
Serakil alcohol 1.0
Isocetyl myristate 10.0
Jojoba oil 5.0
Natural vitamin E 0.1
The remaining squalane (preparation method)
All ingredients were mixed and prepared at 50 ° C. until uniform.

Skin lotion (prescription)
Oil phase Seraquil alcohol 0.3
Tri (caprylic acid / capric acid) glyceryl
0.1
POP (4) POE (20) cetyl ether
0.6
Aqueous phase Propylene glycol 10.0
Sodium hyaluronate 0.1
Preservative Appropriate amount Purified water The remainder (preparation method)
It was prepared according to a conventional method for producing an oil-in-water emulsion composition.

Emulsion (prescription) mass%
Oil phase Batyl alcohol 1.0
d-δ-tocopherol 0.1
Squalane 5.0
Cetyl 2-ethylhexanoate 5.0
Dimethylpolysiloxane (100 cs) 0.5
Cetyl palmitate 0.5
Behenyl alcohol 1.5
Stearic acid 0.5
Lipophilic glyceryl monostearate
1.0
Monostearic acid POE (20) sorbitan
1.0
Tetraoleic acid POE (40) sorbitan
1.5
Aqueous phase Propylene glycol 7.0
Xanthan gum 0.1
Preservative Appropriate amount Purified water The remainder (preparation method)
It was prepared according to a conventional method for producing an oil-in-water emulsion composition.

Cream 3 (water-in-oil emollient type)
(Prescription) Mass%
Oil phase Batyl alcohol 4.0
Dimethicone copolyol 0.5
Decamethylcyclopentasiloxane 5.0
Tri (Capryl / Capric Acid) Glyceryl
15.0
Beeswax 2.0
Decaglyceryl pentahydroxy acid 2.0
Isostearic acid 1.0
Aqueous phase Glycerin 4.5
Sodium hyaluronate 0.01
Preservative Appropriate amount Purified water The remainder (preparation method)
An emulsified composition was prepared according to a conventional method for emulsifying water-in-oil emulsified compositions.

Sunscreen cream (prescription)
Oil phase Kimyl alcohol 2.5
Liquid paraffin 7.0
Decamethylcyclopentasiloxane 3.0
Cetyl alcohol 4.0
Condensed ricinoleic acid hexaglyceryl 0.5
POE (20) cetyl ether 1.0
Octyl paramethoxycinnamate 7.0
Powder phase Titanium oxide 3.0
Aqueous phase Sodium cetyl sulfate 1.0
Stearoyl methyl taurine sodium 0.3
1,3-butylene glycol 5.0
Xanthan gum 0.3
Preservative Appropriate amount Purified water The remainder (preparation method)
After the powder phase was added to the oil phase, an emulsion composition was prepared according to a conventional method for emulsifying water-in-oil emulsion compositions.

(Evaluation of whitening effect)
As a result of evaluating the whitening effect of the cosmetics of Examples 1 to 9 according to the whitening effect test method described above, the whitening effect was recognized in all the cosmetics.

  It is possible to provide a whitening cosmetic that is highly safe and has an excellent whitening effect due to its inhibitory effect on melanocyte growth factor production from epidermal cells.

Claims (10)

A whitening agent comprising monoalkyl glyceryl ether and / or glycerin mono fatty acid ester. A melanocyte growth factor production inhibitor comprising a monoalkyl glyceryl ether and / or a glycerin mono fatty acid ester. The whitening agent according to claim 1, wherein the monoalkyl glyceryl ether is selected from one or more of batyl alcohol, chimyl alcohol, and seraalkyl alcohol. The whitening agent according to claim 1, wherein the fatty acid group of the glycerin monofatty acid ester has 8 to 22 carbon atoms. 3. The melanocyte growth factor production inhibitor according to claim 2, wherein the monoalkyl glyceryl ether is selected from one or more of batyl alcohol, chimyl alcohol, and seraalkyl alcohol. The melanocyte growth factor production inhibitor according to claim 2, wherein the fatty acid group of the glycerin monofatty acid ester has 8 to 22 carbon atoms. Whitening cosmetics containing monoalkyl glyceryl ether as a whitening agent. Whitening cosmetics containing glycerin mono fatty acid ester as a whitening agent. Whitening cosmetics containing monoalkyl glyceryl ether as a melanocyte growth factor production inhibitor. Whitening cosmetics containing glycerin mono fatty acid ester as a melanocyte growth factor production inhibitor.