JP2006062991A - Skin whitening agent for external use - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a skin care preparation for external use, suppressing melanization of B16 melanoma cells by suppressing autoxidation of dopaquinone as one factor of the melanization by using extracts of papaya whose effect as a whitening agent is conventionally unknown. <P>SOLUTION: The extracts of papaya suppress melanization in melanocytes of cutaneous epidermal tissue by dominantly inhibiting autoxidation of dopaquinone as one factor of melanization. Several skin troubles such as skin blotch, skin somberness and skin roughening are found to be improved by compounding the extracts, with one or more of specific agents of humectants, cell activators, antiphlogistics, antioxidants, skin whitening agents, antiplasmin agents, active oxygen-suppressing agents and antihistaminic agents. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

The product of the present invention has an extract extracted from a specific plant that promotes the whitening of melanocytes in the skin epidermis tissue, thereby suppressing skin spots and freckles, and a moisturizer, cell activator, anti-inflammatory. Skin external preparations that improve various skin problems such as dull skin and rough skin by combining combinations of specified agents such as anti-oxidants, antioxidants, whitening agents, anti-plasmin agents, active oxygen inhibitors, and antihistamines .

  Papaya is a fruit native to tropical America that is popular for its ripe, soft fruit and moderate sweetness. So far, papaya has been known as a proteolytic enzyme and a moisturizing effect, and has been disclosed as a cosmetic composition (JP H15-081751, JP H15-155213, JP H13-039823, JP H13- 226219). However, its use as a whitening agent is not known.

Melanocytes are present in the basal layer of the skin epidermis and have melanosomes responsible for melanin production in the cells.
When the melanocytes receive various danger signals that indicate an abnormality for the living body, the number increases and melanin continues to be produced. There are various danger signals such as excessive ultraviolet rays, stress, air pollutants contained in the outside environment, active oxygen, inflammatory signal transmitters generated during inflammation such as acne and wounds, and hormones. When these melanin production signals enter melanocytes, a series of melanogenesis reactions occur. That is, it is metabolized from tyrosine to dopa, from dopa to dopaquinone, and from dopaquinone to melanin having a black color by automatic oxidation by the action of tyrosinase, an enzyme in melanosomes.
Melanosomes saturated with melanin and matured are engulfed by the surrounding keratinocytes from the tip of the dendrite. Keratinocytes containing melanin are pushed up to the surface of the skin as keratinization progresses, forming a stratum corneum, and finally peeling off. However, when the skin function becomes abnormal due to various factors such as aging and ultraviolet irradiation, this cycle is delayed. Such proliferation of melanocytes, abnormal formation of melanin, and colonization of the stratum corneum appear as visible pigmentation, i.e., spots and faintness, which is one of the skin troubles.
Japanese Patent Laid-Open No. 13-039823 Japanese Patent Laid-Open No. 13-226219 Japanese Patent Laid-Open No. 15-081751 Japanese Patent Laid-Open No. 15-155213

The object of the present invention is to find a skin external preparation effective as a whitening agent so far.

In order to achieve the above-mentioned object, the present inventors have intensively studied and found that the effect of papaya extract is high. Furthermore, by adding specific agents (humectants, cell activators, anti-inflammatory agents, antioxidants, whitening agents, antiplasmin agents, active oxygen inhibitors, antihistamines, etc.), not only stains / freckle but also dullness and rough skin It has been found to improve various skin problems.

The form of the papaya extract is not limited in any way, but preferably, the papaya is shade-dried, pulverized, then immersed in an extraction solvent (for example, alcohol such as ethanol, water, or a mixture thereof) for 3 days or 100 degrees for 1 hour. Use the solution heated, cooled, and filtered in.

Test Example 1: B-16 melanoma cell whitening test The mouse-derived B-16 melanoma cell whitening test was used to examine the melanin production inhibitory action of the papaya extract. Using Eagle's MEM containing 10% FBS as a medium, B-16 was planted on a 24-well microplate at 2 × 103 cells / well and cultured for 24 hours. After 24 hours, a test product was prepared and added in the same medium as described above, and cultured for 3 days. Three days later, the medium was changed with the medium containing the test product, and further cultured for 2 days. On the fifth day after planting, the cells were detached with EDTA and collected as a floating cell population, and the color and amount of the pellet were visually determined.
<Criteria for visual inspection>
1. Cytotoxicity (cell count)
Non-toxic; comparable to control (approximately 80%)
Weak toxicity; about 70-80% of control
Addictive; about 40-60% of control
Strong toxicity; about 30% or less of control 2. Whiteness-: Same as control ±; Slight whitening tendency +; Whitening tendency ++; Clear whitening (based on positive control 1 mM kojic acid)
+++; Strong whitening /; Indeterminate (due to cytotoxicity)
The test products are shown below, and the test results are shown in Tables 1 to 3.
Papaya E: Papaya immature fruit (dried product) (20 g) ethanol (100 ml) extract Papaya EW: Papaya immature fruit (dried product) ((20 g) 50% ethanol-water (100 ml) extract Papaya W: Papaya W Unripe fruit (dried) ((20g) hot water (100ml) extract

  The papaya extract is preferably blended at 0.000001 to 10% by weight in terms of dry matter.

Based on the above results, when a specific drug (humectant, cell activator, anti-inflammatory agent, antioxidant, whitening agent, antiplasmin agent, active oxygen inhibitor, antihistamine, etc.) is added to the papaya extract, It was found to improve various skin problems such as freckles, dullness, and rough skin.
Listed particularly effective are the whole grass of morning glory, Asam wood, Adhatoda vasica wood, yellow ranch wood, Ixcate (Hippocratea celastroides) bark, Ibonashi shiraji branch, Indian salsa root, bark of neem, Woodfordia fruticosa flowers and leaves, lumberwood, lagerstroemia speciosa leaves, CASCA-DOCE (CASCA-DOCE) (scientific name Pradosia lactescens or Lucumaglyciphloea Or Chrysophyllum buranhem), wig material, Kapoor material, stalk and branch of swordfish, genus Kawaraketsume (Kemeko, Senna, Wangjiang South, Mountain pea, Nambansaikachi), whole plant of spinach, cinnamon flower, Cuachalalate (Cuachalalate) Juliania adstringens Schl) bark, guava leaf, Quercus pidankrate Quercus pedunculate fruit, cumin seeds, cubraco heartwood, coustigaya rhizome, costillas (Acalypha diversifolia Jacq.) Trunk and branch, bark of melanoleuca leucadendron, Gordolobo (Gnaphalium) sphacellatum), saffron pistil, Saraka indica bark, JEQUITIBA (Carinianabrasiliensis or Couratari legalis or Pyxidaria macrocarpa) bark, Shimoniro whole grass, Jatoba (Hymenaea couba) Bark of Eugenia jambolana, seeds of white dwarf morning glory, whole plant of Sphaeranthus indicus, bark of spruce, root of Smilax zeylanica, scepter wood, bark of barb tree, chaba Pepper root, Desmodium gangeticm Whole grass, Terminalia horrida fruit, Tragia involucrata whole grass, Nigella sativa seed, Scots grass whole plant, Hierba del sapo (Eryngium comosum) whole plant, Hijat root, Whole plant of Pirul (Schinus molle), whole plant of Phyllanthus nuriri, whole plant of Fusenkazura, PUCA (Cissus antiparaliticus), root of vetiver, Hedesalum austrobilis (Hedysarum) austrosibiricus root, Herpestris monnies whole grass, VERONICA (Veronica officinalis) bark, Borrelia hispida root and stem, Pongamia glabra root, Mizuki bark , Mimusops elengi whole plant, Murraya koenigii shoot, Munronia Whole plant of mira, wood of melapie, bark of magnoliaceae genus genus, mountain cherry, lumbo, rumex cyprius leaf, wattle bark, aitamago, one root, fateless, fossil grass , Shellfish mother, intruder, Iwaben Kei root, Paeonia anomala root, chestnut butter, chestnut leaf, chicken blood wisteria, Saya, messenger, small gold crab, cinnamon bark, red spicy, Saiheyanagi, Ishirenko , Stone persimmon skin, stone persimmon bark, sanctuary grass, pierced stone, persimmon, valley essence, Chinese white birch, iron wrapping, winter lion, persimmon leaves, Hishimi, Kashio grass, Ryo Wang, lotus leaf , Eggplant, cormorant sea, toothpick, coconut tree, samurai, sea urchin, seaweed of Ishigeaceae; pearl powder, conchiolin, conchyolin hydrolyzate, conchiolin hydrolyzate treated with succinic anhydride, shellfish Substances obtained by hydrolyzing mucus, sterols obtained from shellfish meat, acidic polysaccharides obtained from shellfish meat Collagen obtained from shellfish meat, glycogen obtained from shellfish meat, phospholipid obtained from shellfish meat, deoxyribonucleic acid obtained from shellfish meat, thiosalicylic acid and its salt, magnolol, honokiol, 1- (4 -Hydroxyphenthio) -2-propanol, 2- (4-hydroxyphenyl) -1,3-dithiane, 2- (4-acetoxyphenyl) -1,3-dithiane, 2,5-dihydroxybenzamide, 2,6 -Dihydroxybenzamide, 4-aminophenol, 4-hydroxythiophenol, 4-hydroxybenzamide, 5-hydroxyindole, 6-dihydroxy) -dihydrobenzofuran-3-yl- (3'4'-dihydroxy) -phenyl ketone, stilbengalo Ile glycoside, citracin C, ethylenediamine derivative, carahanaenone derivative, cashew nut shell oil, carda A peptide containing the sequence of nord, cardol, anacardic acid, sennoside, α-arbutin, Glu-Glu-Met-Gln-Arg-Arg, or the terminal of the carboxyl group of this peptide is converted to an amide or / and the amino group is acylated Peptides converted into isomers can be mentioned.
Examples of ethylenediamine derivatives include N-phenyl-N- (2,3,3 trimethyl-1-cyclopentene-1-ethyl) -N ′, N′-dimethylethanediamine, N-2-pyridyl-N- (3 , 7-Dimethyl-6-octen-1-yl) -N ', N'-dimethylethanediamine, N-2-pyridyl-N- (2-pinen-10-yl) -N', N'-dimethylethane Mention may be made of diamines, N-2-pyridyl-N- (1,8-p-menthadien-7-yl) -N ', N'-dimethylethanediamine.
For example, N-p-hydroxyphenyl-3,3,6-trimethyl-5-cycloheptan-2-one-1-carboxamide, 2-hydroxy-Np-hydroxyphenyl-3,3 , 6-trimethyl-5-cycloheptene-1-carboxamide. Examples of stilbene galloyl glycosides include 3,5,4'-trihydroxystilbene 4'-0-β-D- (6 "galloyl) glucopyranoside, 3,5,4'-trihydroxystilbene 4'- Mention may be made of 0-β-D- (2 ″ galloyl) glucopyranoside.

Furthermore, it has also been found that the effect can be further obtained by blending one or more of polyhydric alcohols containing two or more hydroxyl groups, lower alcohols, surfactants, and low molecular betaines.

The polyhydric alcohol that can be used is not particularly limited, and examples thereof include glycerin, 1,3 butylene glycol, propylene glycol, isoprene glycol, sorbitol, trehalose, maltose and the like. These are blended in an amount of 0.1 to 80% by weight, preferably 1 to 30% by weight. Needless to say, the blending amount varies depending on the type of polyhydric alcohol, and a plurality of polyhydric alcohols can be used.

Absorbability improves by mix | blending a lower alcohol. Although there are various kinds of lower alcohols, ethanol is usually used. The blending amount is not particularly limited but is preferably 2 to 70% by weight.
It is also effective to combine a surfactant with a combination of polyhydric alcohols containing a pomegranate (Punica granatum) flower extract, and it is also effective to combine the lower alcohol.
There is no particular limitation on the surfactant, and the type and amount may be selected depending on the application and dosage form.
Surfactants are used for emulsification and solubilization of oils, etc., and are anionic (alkyl carboxylates, alkyl sulfonates, alkyl sulfate esters, alkyl phosphate esters), nonionic (ether type) Nonionic surfactant, ether ester type nonionic surfactant, ester type nonionic surfactant, block polymer type nonionic surfactant, nitrogen-containing type nonionic surfactant) and amphoteric (carboxylic acid type amphoteric surfactant) Agents (amino type, betaine type), sulfate ester type amphoteric surfactant, sulfonic acid type amphoteric surfactant, phosphate ester type amphoteric surfactant) and other surfactants (natural surfactants, protein hydrolysates) Derivatives, polymer surfactants, surfactants containing titanium and silicon, and fluorocarbon surfactants) can be used as appropriate.

Low molecular weight betaine is also one of the raw materials to be selected, and by blending this, the effect is further improved and the feeling of application is improved, and the effectiveness as an external preparation for skin is increased.
Low molecular weight betaines that can be utilized may include those that form zwitterions with internal salts such as quaternary ammonium bases, sulfonium bases, phosphonium bases and the like having a molecular weight of 200 or less. Examples include trimethylglycine, N, N, N-trimethylalanine, N, N, N-trimethylglutamic acid, triethylglycine, and the like, with trimethylglycine being preferred.
Those having a molecular weight of 200 or more have a surface-active ability, which is different from the effect of low molecular betaine. As described above, the use of a surfactant enhances the effect of the present invention, but the effect of low molecular betaine is Is different.

  The external preparation for skin of the present invention can be prepared by blending with various forms of base materials known as normal external preparations for skin according to conventional methods.

It does not specifically limit as a form of an external preparation, For example, arbitrary dosage forms, such as a milky lotion, cream, aqueous solution, a pack, can be selected.

In the external preparation for skin of the present invention, in addition to the above-mentioned essential components, components that are blended in normal external preparations, such as oils, powders, purified water, polymer compounds, gelling agents, UV absorbers, UV scattering Agents, antioxidants, pigments, preservatives, fragrances, and cosmetic ingredients can be appropriately selected and used within a range not impairing the effects of the present invention.

EXAMPLES Next, although an Example is given and this invention is demonstrated further in detail, this invention is not restrict | limited at all. Moreover, the extraction method about the extract of the used chemical | medical agent is not limited at all.
The formulations of the examples are shown in Tables 4 to 6. The preparation method was performed by a conventional method. Table 4 is a lotion, Table 5 is a cosmetic liquid, Table 6 is a cream formulation, and the amount is shown in parts by weight.

(Note 1) Papaya extract 1 was prepared by adding 200 ml of purified water to 10 g of papaya fruit (dried product) and boiling for 1 hour, followed by filtration.
(Note 2) Papaya extract 2 was prepared by adding 100 ml of purified water and 100 ml of ethanol to 10 g of papaya fruit (dried product) and allowing to stand for 10 days, followed by filtration.
(Note 3) Papaya extract 3 was obtained by adding 200 ml of ethanol to 10 g of papaya fruit (dried product) and allowing it to stand for 10 days, followed by filtration. (
(Note 4) The hydrolyzed conchiolin solution used was a hydrolyzed conchyolin that had a molecular weight of 1000 or less.
(Note 5) As the tablinus extract, a Matils extract [manufactured by Maruzen Pharmaceutical Co., Ltd.] was used.
(Note 6) Falco Rex Honoki E [Ichimaru Falcos Co., Ltd.] was used as the honoki extract.
(Note 7) As the guava extract, 300 ml of ethanol was added to 10 g of guava leaves and allowed to stand for 5 days, and then the filtered extract was used.
(Note 8) Nishi-Haruyanagi extract used Nishi-Haruyanagi extract [Nippon Seika Co., Ltd.].
(Note 9) Marine purge [manufactured by Ichimaru Falcos Co., Ltd.] was used as the seaweed extract.
(Note 10) As the acacia bark extract, 300 ml of ethanol was added to 10 g of bark and left for 5 days, and then the filtered extract was used.
(Note 11) Murayako Engii extract was used as an extract from Murayako Engui [Yamakawa Trading Co., Ltd.].
(Note 12) The giant crape myrtle extract used was the greater crested weevil extract [manufactured by Yamakawa Trading Co., Ltd.].

The whitening effect tests of Examples 1 to 12 and Comparative Examples 1 to 3 described in Tables 4 to 6 were performed. The test method consisted of 20 females aged 25 to 55 years old, and a suitable amount of a topical preparation was applied to the face after washing the face twice a day in the morning and night for 12 weeks. Table 7 shows the results of the skin trouble improving effect by application.

Claims (4)

Papaya (Carica papaya L. An external preparation for skin whitening characterized by containing an extract. Contains one or more of papaya (Carica papaya L.) extract and moisturizer, cell activator, anti-inflammatory agent, antioxidant, whitening agent, antiplasmin agent, active oxygen inhibitor, antihistamine The whitening skin external preparation of Claim 1 characterized by the above-mentioned. Moisturizers, cell activators, anti-inflammatory agents, anti-oxidants, whitening agents, anti-plasmin agents, active oxygen suppressors, anti-histamine agents are whole grasses of Asagakarakakusa, materials of Asam, materials of Adhatoda vasica, materials of yellow ume Lunch lumber Ixcate (Hippocratea celastroides) bark, Ibonashi ヅ rafuji branch, Indian salsa root, Neem bark, Woodfordia fruticosa flower and leaf, Woodpecker lumber lagerstroemia speciosa) leaves, CASCA-DOCE (scientific names Pradosia lactescens or Lucumaglyciphloea or Chrysophyllum buranhem) Peas, peanuts, whole spinach, cinnabar flower, Cuachalalat e) bark of (Juliania adstringens Schl), guava leaves, berries of Quercus pedunculate, seeds of cumin, heartwood of quebraco, rhizomes of Coustigaya (Costillas) (Acalypha diversifolia Jacq.), trunks and branches, Bark of black-breasted tree (Melaleuca leucadendron), whole plant of Gordolobo (Gnaphalium sphacellatum), bark of saffron, bark of Saraka indica (JEQUITIBA) (Carinianabrasiliensis macrocarpaxarial or Carpayarisma) Bark, Whole Shimoniro grass, JATOBA (Hymenaea coubaril) peel, Eugenia jambolana bark, White Spodoptera seeds, Sphaeranthus indicus whole grass, Spruce bark, Smilax Zelamonica (Smilax zeylanica) root, scepter wood, tablin Bark, root of Chaba pepper, whole plant of Desmodium gangeticm, fruit of Terminalia horrida, whole plant of Tragia involucrata, seeds of Nigella sativa, whole plant of Habibissa del sapo) (Eryngium comosum), baboon root, Pirul (Schinus molle), Phyllanthus nuriri, Fusenkazura, PUCA (Cissus antiparaliticus) ) Fruit, vetiver root, Hedysarum austrosibiricus root, herpestris monnies whole bark, VERONICA (Veronica officinalis) bark, Borrelia hispida root and stem, Pongamia Pongamia glabra root, dogwood bark, earthworm bark, mimsops erenghi ( Mimusops elengi whole plant, Murraya koenigii shoot, Munronia pumila whole plant, merapie wood, magnoliaceae bark, mountain cherry wood, lambo wood, Rumex cyprius Leaf, bark of wattle, aitamako, ichisone root, impregnated king, fossil grass, shellfish, intruder, root of paiwania anomala, root of chestnut, chestnut leaf, chestnut leaf, chicken blood wisteria, sasa, Ambassador, small gold cocoon, husk, bonito, saikawa willow, stone lotus, stalagmite rind, sarcophagus bark, sengaku bark, sengakuso, drilling stone, cocoon, valley essence, Chinese white birch, iron wrapping, winter cocoon Child, bamboo leaf, Hishimi, Kashio grass, Ryoo Wang, lotus leaf, coconut tree, 海 大海, 茘 枝, 訶子, Saito, 鵝 食 、, seaweed of Ishigeaceae; pearl powder, conchiolin, Conchiolin hydrolyzate, conquiolin hydrolyzate treated with succinic anhydride, shellfish mucus Substances obtained by hydrolysis of sterols, sterols obtained from shellfish meat, acidic polysaccharides obtained from shellfish meat, collagen obtained from shellfish meat, glycogen obtained from shellfish meat, phosphorus obtained from shellfish meat Lipid, deoxyribonucleic acid obtained from shellfish, thiosalicylic acid and its salts, magnolol, honokiol, 1- (4-hydroxyphenthio) -2-propanol, 2- (4-hydroxyphenyl) -1,3- Dithiane, 2- (4-acetoxyphenyl) -1,3-dithiane, 2,5-dihydroxybenzamide, 2,6-dihydroxybenzamide, 4-aminophenol, 4-hydroxythiophenol, 4-hydroxybenzamide, 5-hydroxy Indole, 6-dihydroxy) -dihydrobenzofuran-3-yl- (3'4'-dihydroxy) -phenyl ketone, stilbengaloyl glycoside , Citracin C, ethylenediamine derivative, caranahanaone derivative, cashew nut shell oil, cardanol, cardol, anacardic acid, sennoside, α-arbutin, Glu-Glu-Met-Gln-Arg-Arg peptide or carboxyl group of this peptide The whitening skin external preparation according to claim 2, which is a peptide having a terminal converted to an amide form and / or an amino group terminal converted to an acylated form. The whitening skin external preparation according to any one of claims 1 to 3, further comprising one or more of polyhydric alcohols, lower alcohols, surfactants, and low-molecular-weight betaines containing two or more hydroxyl groups.