JP2005194240A - Ceramide synthesis promotor and skin care preparation for external use - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a ceramide synthesis promotor and to provide a skin care preparation for external use each containing an extract of Ganoderma lucidum or combinedly using the extract of Ganoderma lucidum with a ceramide. <P>SOLUTION: The extract of Ganoderma lucidum is excellent in ceramide synthesis-promoting effect and the effect is synergistically enhanced by combined use of ceramide. The skin care preparation for external use containing the extract is safe and excellent in effects of preventing and improving the chapped skin or the dried skin. The Ganoderma lucidum belongs to the genus Ganoderma of the family Ganodermataceae and includes Reishi (Ganoderma lucidum), Kuro-Reishi (Ganoderma japonicum, Ganoderma sinense, Ganoderma atrum), Murasaki-Reishi (Ganoderma japonicum, Ganoderma sinense) or Ganoderma neo-japonicum. The ceramide includes a yeast ceramide produced by utilizing a yeast, pseudo ceramide prepared by chemical synthesis or a plant ceramide obtained from a plant. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  TECHNICAL FIELD The present invention relates to a ceramide synthesis promoter and a skin external preparation excellent in the effect of preventing and improving rough skin and dry skin by using an extract of nanentake, or an extract of mannentake and ceramide in combination.

  Ceramide is produced by undergoing denaturation by glucocerebrosidase from glucocerebrosid or by sphingomyelinase from sphingomyelin when cells migrate from the basal layer to the stratum corneum of the skin. Ceramide is an important component of intercellular lipids, and is deeply involved in the stratum corneum barrier function and water retention. Causes of rough skin include dryness, contact with irritants, and skin irritation due to ultraviolet rays. It is said that promoting the production of ceramide is effective in restoring the barrier function that protects the skin from dryness and irritants. It has been confirmed that seven types of ceramide are present in human skin, and it is ideal to maintain the barrier function of the stratum corneum by supplementing all kinds of ceramides with the ratio existing in the stratum corneum.

Conventionally, ceramide has been blended into various skin external preparations as a cosmetic that is effective in preventing and improving rough skin and dry skin, but supplements all types of ceramide present in human skin at an appropriate ratio. That was technically difficult. Patent Literature 1 and Patent Literature 2 have been reported as ceramide synthesis promoters for promoting ceramide synthesis in vivo, but it was difficult to say that the effect was sufficient. In addition, there is no report on the effect of promoting the synthesis of ceramide in the case of Mannentake alone or in the combination of Mannentake and Ceramide.
JP-A-8-217658 JP 2001-220345 A

  From the above, a ceramide synthesis accelerator and a skin external preparation excellent in the effect of preventing and improving rough skin and dry skin are desired.

  Under these circumstances, as a result of intensive studies, the present inventors have found that the extract of Mannentake has an effect of promoting synthesis of ceramide, a rough skin, and an effect of preventing and improving dry skin. Furthermore, it has been found that the combined use of Mannentake extract and ceramide increases the effect of promoting ceramide synthesis, the effect of preventing rough skin and preventing dry skin, and the present invention has been completed.

  The garlic mushrooms used in the present invention belong to the genus Mushroom family and the genus Mungella mushroom, and are reishi (red ganoderma, scientific name: Ganoderma lucidum), black ganoderma (scientific name: G. japonicum, G. sinense, G. atrum), purple ganoderma. (Scientific name: G. japonicum, G. sincense), sagebrush (scientific name: G. neo-japonicum), and the like. Examples of the extract of the garlic mushroom of the present invention include extracts such as fruit bodies and mycelia, and these may be used alone or in combination. Moreover, you may use the extract of a nanentake together.

  Examples of the ceramide used in the present invention include yeast ceramide produced using yeast, pseudoceramide by chemical synthesis, plant ceramide obtained from plants, and the like. Examples of the pseudo ceramide include synthetic products such as ceramide 3 and ceramide 6, and examples of the plant ceramide include konjac ceramide, wheat ceramide, and rice ceramide. These can use a commercial item.

The method for extracting garlic mushroom of the present invention is not particularly limited, and for example, it may be extracted by heating, or may be extracted at normal temperature or low temperature.
Examples of the solvent to be extracted include water, lower alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.), liquid polyhydric alcohols (1,3-butylene glycol, propylene glycol). , Glycerin, etc.), ketones (acetone, methyl ethyl ketone, etc.), acetonitrile, esters (ethyl acetate, butyl acetate, etc.), hydrocarbons (hexane, heptane, liquid paraffin, etc.), ethers (ethyl ether, tetrahydrofuran, propyl ether) Etc.). Preferred are polar solvents such as water, lower alcohols and liquid polyhydric alcohols, and particularly preferred are water, ethanol, 1,3-butylene glycol and propylene glycol. These solvents may be used alone or in combination of two or more.

  The extract may be used as it is, or may be used after concentration, dilution, filtration, decolorization with activated carbon, deodorization, or the like, if necessary. Further, the extracted solution may be subjected to a treatment such as concentration to dryness, spray drying, freeze drying, etc. and used as a dried product, or the active ingredient may be concentrated or isolated by performing column purification or the like.

  In order to use the extract of garlic mushroom or ceramide of the present invention as a ceramide synthesis promoter for the purpose of improving rough skin, it is usually administered systemically or locally for internal or external use. The dose varies depending on the age, body weight, symptoms, therapeutic effect, administration method, treatment time, etc., but is usually 1 mg to 1 g per adult, preferably 20 mg to 200 mg, and once to several times a day. Be administered. Since the dosage varies depending on various conditions, an amount smaller than the above-mentioned administration range may be sufficient, or it may be necessary to administer beyond the range.

  Examples of the ceramide synthesis promoter for oral administration of the present invention include tablets, pills, powders, granules, capsules, emulsions, solutions, suspensions, syrups, and elixirs. The above extract may be used as it is, and the excipient, extender, binder, wetting agent, disintegrant, surfactant, lubricant, dispersant, buffer, as long as the effect of the extract is not impaired. Agents, fragrances, preservatives, solubilizers, solvents and the like can be used. Specifically, lactose, sucrose, sorbit, mannitol, starch, precipitated calcium carbonate, heavy magnesium oxide, talc, calcium stearate, magnesium stearate, cellulose or derivatives thereof, amylopectin, polyvinyl alcohol, gelatin, surface activity Agents, water, physiological saline, ethanol, glycerin, propylene glycol, cacao butter, lauric fat, petrolatum, paraffin, higher alcohol and the like.

  In the case of using the extract of garlic mushroom and ceramide used in the present invention as a skin external preparation, the total amount of the skin external preparation is 0.0001% by weight or more, preferably 0.001 to 10% by weight in terms of solids. Good formulation. If it is less than 0.0001% by weight, a sufficient effect is hardly expected. When it exceeds 10% by weight, the effect is hardly increased, which is uneconomical. In addition, the addition method may be added in advance or during the production, and may be appropriately selected in consideration of workability.

  The skin external preparation of the present invention can be used for any of cosmetics, quasi-drugs and pharmaceuticals. Examples of the dosage form include skin lotions, creams, emulsions, gels, aerosols, essences, packs, Examples of the cleaning agent, bath preparation, foundation, dusting powder, lipstick, ointment, and poultice applied to the skin. The above-mentioned extract may be used as it is, and the components used for the external preparation are within the range not impairing the effect of the extract, oils, waxes, hydrocarbons, fatty acids, alcohols, esters, interfaces Components such as activators, metal soaps, pH adjusters, preservatives, fragrances, moisturizers, powders, ultraviolet absorbers, thickeners, dyes, antioxidants, whitening agents, chelating agents, and the like can also be blended.

  The extract of the garlic mushroom of the present invention is excellent in the ceramide synthesis promoting effect and synergistically enhanced by using ceramide in combination. Moreover, the skin external preparation and internal preparation containing these extracts were safe and excellent in the effect of improving rough skin.

  Next, in order to describe the present invention in detail, examples of producing the extract used in the present invention, formulation examples and experimental examples of the present invention will be given as examples, but the present invention is not limited thereto. The part of the amount shown in the examples indicates part by weight, and% indicates% by weight.

Production Example 1 Black Ganoderma Hot Water Extract 400 g of purified water is added to 20 g of dried black ganoderma fruit bodies, extracted at 95-100 ° C. for 2 hours, filtered, and the filtrate is concentrated and freeze-dried. 1.4 g of hot water extract of black reishi was obtained.

Production Example 2 Black Ganoderma Ethanol Extract Add 2 liters of ethanol to 100 g of dried ganoderma fruit bodies, extract for 7 days at room temperature, filter, concentrate the filtrate to dryness, 1.6 g of extract was obtained.

Production Example 3 Black Ganoderma 50% 1,3-Butylene Glycol Aqueous Extract Extract After adding 1 L of purified water and 1 L of 1,3-butylene glycol to 100 g of a dried product of black ganoderma fruit, Filtration yielded 1.9 kg of a 50% 1,3-butylene glycol aqueous extract of black ganoderma.

Production Example 4 Hot Water Extract of Ganoderma (Red Ganoderma) 400 g of purified water was added to 20 g of dried ganoderma (red ganoderma) fruit body, extracted at 95-100 ° C. for 2 hours, filtered, The filtrate was concentrated and freeze-dried to obtain 2.0 g of a hot water extract of Ganoderma (red ganoderma).

Production Example 5 Ganoderma (red ganoderma) ethanol extract 2 g of dried ganoderma (red ganoderma) fruit body was added with 2 L of ethanol, extracted at room temperature for 7 days, filtered, and the filtrate was concentrated to dryness. Solidify to obtain 2.7 g of ethanol extract of Ganoderma (red ganoderma).

Production Example 6 50% 1,3-butylene glycol aqueous extract of Ganoderma lucidum (red ganoderma lucidum) Add 1 L of purified water and 1 L of 1,3-butylene glycol to 100 g of dried ginseng (red ganoderma) fruit body, Extraction was performed at room temperature for 7 days, followed by filtration to obtain 1.9 kg of a 50% 1,3-butylene glycol aqueous solution extract of Ganoderma lucidum (Agarashishiba).

Production Example 7 Hot water extract of pearl oyster 400 ml of purified water was added to 20 g of dried pearl oyster fruit body, extracted at 95-100 ° C. for 2 hours, filtered, and the filtrate was concentrated, freeze-dried and heated with potato potato. 2.2 g of water extract was obtained.

Manufacture example 8 Ethanol extract of pearl oyster 2 L of ethanol was added to 100 g of dried coconut fruit body, extracted at room temperature for 7 days, filtered, the filtrate was concentrated to dryness, 6 g was obtained.

Production Example 9 Extract of Magella's Mycelium Culture Magella's mycelia were cultured as follows using a jar fermenter. As the medium, 50 g of malt extract, 20 g of yeast extract and 20 g of glucose were mixed with 5 L of purified water and autoclaved at 121 ° C. for 30 minutes. After inoculating 150 mL of the seed mycelium culture of maggots that had been cultured with shaking in the same medium for 14 days at 25 ° C., the cells were cultured for 14 days at 25 ° C. with aeration of 3 L / min with stirring at 300 rpm. The obtained culture was filtered to obtain 2.0 kg (wet weight) of mycelia.
2 L of purified water was added to the separated mycelia and extracted at 95-100 ° C. for 2 hours, followed by filtration. The filtrate was concentrated and lyophilized to obtain 22 g of an extract of the fungus culture of maggot.

Formulation Example 1 Cream 1
Formulation Formulation 1. 1.0 part of hot water extract of Black Reishi (Production Example 1) Yeast Ceramide 1.0
3. Squalane 5.5
4). Olive oil 3.0
5). Stearic acid 2.0
6). Beeswax 2.0
7). Octyldodecyl myristate 3.5
8). Polyoxyethylene cetyl ether (20E.O.) 3.0
9. Behenyl alcohol 1.5
10. Glycerol monostearate2.5
11. Fragrance 0.1
12.1,3-Butylene glycol 8.5
13. Ethyl paraoxybenzoate 0.05
14 Methyl paraoxybenzoate 0.2
15. Purified water 66.15
[Manufacturing method] Components 2 to 10 are heated and dissolved and mixed, and kept at 70 ° C to obtain an oil phase. Ingredients 1 and 12 to 15 are dissolved by heating and mixed, and kept at 75 ° C. to form an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring.

Formulation Example 2 Cream 2
In Formulation Example 1, cream 2 was obtained by replacing the hot water extract of black ganoderma by the hot water extract (production example 4) of ganoderma (red ganoderma).

Formulation Example 3 Cream 3
In Formulation Example 1, cream 3 was obtained by replacing the hot water extract of black ganoderma biloba with an extract of mycelia fungus culture (Production Example 9).

Comparative Example 1 Conventional cream 1
In Formulation Example 1, a conventional cream 1 was obtained by replacing the hot water extract of black ganoderma with purified water.

Comparative Example 2 Conventional Cream 2
In Formulation Example 1, the conventional cream 2 was obtained by replacing yeast ceramide with squalane.

Formulation Example 4 Lotion Formulation Amount 10.0 parts of 50% 1,3-butylene glycol aqueous extract of black ganoderma (Production Example 3)
2. Synthetic ceramide 3 0.5
3. 1,3-butylene glycol 8.0
4). Glycerin 2.0
5). Xanthan gum 0.02
6). Citric acid 0.01
7). Sodium citrate 0.1
8). Ethanol 5.0
9. Methyl paraoxybenzoate 0.1
10. Polyoxyethylene hydrogenated castor oil (40E.O.) 0.1
11. Fragrance 0.1
12 Purified water 74.07
[Production method] Components 3-7 and 1, 12 and components 8-11 and 2 are uniformly dissolved, mixed and filtered to obtain a product.

Formulation Example 5 Latex 1
Formulation Formulation 1. Ethanol extract of black reishi (Production Example 2) 0.5 part Konjac Ceramide 0.5
3. Squalane 5.0
4). Olive oil 5.0
5). Jojoba oil 5.0
6). Cetanol 1.5
7). Glycerol monostearate 2.0
8). Polyoxyethylene cetyl ether (20E.O.) 3.0
9. Polyoxyethylene sorbitan monooleate 2.0
(20 EO)
10. Fragrance 0.1
11. Propylene glycol 1.0
12 Glycerin 2.0
13. Methyl paraoxybenzoate 0.2
14 Purified water 72.2
[Manufacturing method] Components 2 to 9 are heated and dissolved and mixed, and kept at 70 ° C to obtain an oil phase. Ingredients 1 and 11 to 14 are heated and dissolved and mixed, and kept at 75 ° C. to obtain an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled while stirring.

Formulation Example 6 Latex 2
In Formulation Example 5, 0.5 parts of black ganoderma ethanol extract was added to 0.25 parts of black ganoderma hot water extract (Production Example 1) and hot water extract of ganoderma (red ganoderma) (Production Example) 4) The emulsion 2 was replaced with 0.25 part.

Formulation Example 7 Gel formulation Formulation amount 1. 0.5 parts of 50% 1,3-butylene glycol aqueous extract of Ganoderma (Production Example 6)
2. Yeast ceramide 0.1
3. Ethanol 5.0
4). Methyl paraoxybenzoate 0.1
5). Polyoxyethylene hydrogenated castor oil (60 EO) 0.1
6). Fragrance 0.1
7.1,3-Butylene glycol 5.0
8). Glycerin 5.0
9. Xanthan gum 0.1
10. Carboxyvinyl polymer 0.2
11. Potassium hydroxide 0.2
12 Make the total amount 100 with purified water 83.6
[Production Method] Components 2 to 6 and Components 1 and 7 to 12 are uniformly dissolved, and both are mixed to obtain a product.

Formulation Example 8 Pack Formulation Amount Black Reishi hot water extract (Production Example 1) 0.1 part Yeast ceramide 0.1
3. Polyvinyl alcohol 12.0
4). Ethanol 5.0
5.1,3-butylene glycol 8.0
6). Methyl paraoxybenzoate 0.2
7). Polyoxyethylene hydrogenated castor oil (20 EO) 0.5
8). Citric acid 0.1
9. Sodium citrate 0.3
10. Fragrance 0.1
11. Purified water 73.6
[Production method] Components 1 to 11 are uniformly dissolved to obtain a product.

Formulation Example 9 Foundation Formulation Amount 1.0 part of 50% 1,3-butylene glycol aqueous extract of black reishi (Production Example 3)
2. Yeast Ceramide 1.0
3. Stearic acid 2.4
4). Polyoxyethylene sorbitan monostearate 1.0
(20 EO)
5). Polyoxyethylene cetyl ether (20E.O.) 2.0
6). Cetanol 1.0
7). Liquid lanolin 2.0
8). Liquid paraffin 3.0
9. Isopropyl myristate 6.5
10. Butyl paraoxybenzoate 0.1
11. Sodium carboxymethylcellulose 0.1
12 Bentonite 0.5
13. Propylene glycol 4.0
14 Triethanolamine 1.1
15. Methyl paraoxybenzoate 0.2
16. Titanium dioxide 8.0
17. Talc 4.0
18. Bengala 1.0
19. Yellow iron oxide 2.0
20. Fragrance 0.1
21. Purified water 59.0
[Manufacturing method] Components 2 to 10 are heated and dissolved and kept at 80 ° C to obtain an oil phase. Swell component 11 well in component 21, then add components 1 and 12-15 and mix uniformly. To this, components 16 to 19 pulverized and mixed with a pulverizer are added, and the mixture is stirred with a homomixer and kept at 75 ° C. to obtain an aqueous phase. The oil phase is added to this aqueous phase with stirring, cooled, component 20 is added at 45 ° C., and cooled to 30 ° C. with stirring to give a product.

Formulation Example 10 Ointment Formulation Amount 1. Black extract of Kuro Reishi (Production Example 2) 1.0 part Synthetic ceramide 3 0.5
3. Polyoxyethylene cetyl ether (30E.O.) 2.0
4). Glycerol monostearate 10.0
5). Liquid paraffin 5.0
6). Cetanol 6.0
7). Methyl paraoxybenzoate 0.1
8). Propylene glycol 10.0
9. Purified water 65.4
[Manufacturing method] Components 2 to 6 are dissolved by heating and mixed, and kept at 70 ° C to obtain an oil phase. Ingredients 1 and 7 to 9 are dissolved by heating and mixed, and kept at 75 ° C. to form an aqueous phase. The aqueous phase is added to the oil phase to emulsify, and the mixture is cooled to 30 ° C. with stirring to obtain a product.

Formulation Example 11 Tablet formulation Reishi hot water extract (Production Example 4) 4.0 parts Yeast Ceramide 1.0
3. Dried corn starch 25.0
4). Carboxymethylcellulose calcium 20.0
5). Microcrystalline cellulose 40.0
6). Polyvinylpyrrolidone 7.0
7). Talc 3.0
[Production method] Components 1 to 5 are mixed, and then an aqueous solution of component 6 is added as a binder to form granules. Ingredient 7 is added to the molded granules and compressed. One tablet is 0.52 g.

    Next, experimental examples will be given to explain the effects of the present invention in detail.

Experimental Example 1 Ceramide Synthesis Promotion Test 1 × 10 ⁵ Pam212 cells, a mouse keratinocyte-derived cell line, were seeded in a 6 cm dish and cultured for 4 days. Thereafter, the sample was added to a final concentration of 10 μg / mL, and the culture was further continued for 24 hours. Next, the cells were washed three times with PBS (−), collected by a rubber policeman, and lyophilized. Lipids were extracted from the cells with 1 mL of chloroform: methanol (2: 1), and the amount of ceramide therein was measured by the fluorescence method of Kisic et al. Specifically, the lipid was hydrolyzed with 0.15 mL of 3N hydrochloric acid at 100 ° C. for 2 hours, dried in a desiccator, and after removing hydrochloric acid, 2 mL of ethyl acetate and 1.25 mL of 0.1 M acetate buffer (pH 3.7) were added. In addition, stirred well. Next, 0.25 mL of a fluorescamine solution (7 mg / 25 mL acetone) was added and stirred well, then centrifuged, and the fluorescence intensity of the ethyl acetate layer was measured at Ex 410 nm and Em 490 nm. The rate of ceramide synthesis acceleration was determined by the ratio to the amount of ceramide produced by the control.

  The results of these experiments are shown in Table 1. As a result, the garlic mushroom extract and the mixture of the garlic mushroom extract and yeast ceramide exhibited a ceramide synthesis promoting effect superior to that of yeast ceramide alone. In addition, the Mannentake extract of other production examples showed the same excellent ceramide synthesis promoting effect when used alone or in combination with ceramide.

Experimental Example 2 Use Test A month-long use test for 30 women (19 to 48 years old) who suffer from rough skin and dryness using the creams of Formulation Examples 1 to 3 and the conventional creams of Comparative Examples 1 and 2. went. After use, the improvement effect of rough skin and dry skin was determined by questionnaire.

  The test results are shown in Table 2. As a result, the creams obtained in Formulation Examples 1 to 3 were superior in preventing rough skin and preventing dry skin than the creams obtained in Comparative Examples 1 and 2. During the test period, there was no skin problem and there was no problem with safety. There was also no problem with the deterioration of the prescription ingredients.

  When the usage test was similarly conducted on Formulation Examples 4 to 10, it was safe and excellent in preventing rough skin and preventing dry skin.

  The extract of the garlic mushroom of the present invention has an excellent ceramide synthesis promoting effect, and the effect is synergistically enhanced by the combined use of ceramide. Therefore, the preparation containing these extracts and ceramide can be effectively used as a skin external preparation for the purpose of preventing and improving rough skin and dry skin.

Claims (3)

A ceramide synthesis promoter characterized by containing an extract of Mannentake. A ceramide synthesis promoter characterized by containing an extract of mannentake and ceramide. An external preparation for skin, comprising an extract of Mannentake and ceramide.