JP4808580B2 - Whitening agent - Google Patents

Description

  The present invention relates to a whitening agent containing a triterpene characterized by having two or three hydroxyl groups in the side chain portion located at the 17th position of the lanostane skeleton.

  Ganodermanone diol, ganodermanone triol, lucidamol A and ganodeliol F are triterpenes contained in the fruit body of Ganoderma lucidum and are known to have an inhibitory action on specific proteases of HIV virus ( Non-patent document 1). On the other hand, it is known that the whitening action of triterpene derived from Mannentake is in ganoderol B and ergosterol derivatives (Patent Documents 1 to 3).

Byung-Sun Min et al, Chem. Pharm. Bull. 46 (10), 1607-1612 (1998) JP 2002-284690 A Japanese Patent Application Laid-Open No. 2002-114685 JP 2003-267873 A

  However, a more effective one is desired, and the ergosterol derivative is a peroxide, so that there is a problem in terms of stability.

  Accordingly, an object of the present invention is to provide a whitening agent which is excellent in whitening action and has high stability.

In view of such circumstances, as a result of intensive studies, a triterpene having two or three hydroxyl groups in the side chain portion located at the 17th position of the lanostane skeleton has an excellent whitening effect, and The inventors have found that the stability is high and have completed the present invention.
Examples of the triterpene having 2 or 3 hydroxyl groups in the side chain portion located at the 17th position of the lanostane skeleton include ganodermanone diol, ganodermanone triol, lucidamol A and ganoderiool F. .
Ganodermanone diol, ganodermanone triol, lucidamol A, ganodeliol F and the like used in the present invention can be extracted from the fruit bodies and spores of ganoderma. Ganoderma is a basidiomycete that circulates as a herbal medicine, and is a mushroom belonging to the family Ganodermaaceae and Ganoderma. Extraction and purification methods such as ganodermanone diol, ganodermanone triol, lucidamol A, and ganoderriol F are the methods of Fujita et al. (Journal of Natural Products, 49 (6), 1121-1125 (1986)) and the method of Min et al. Non-patent document 1) can be referred to. Ganodermanone diol (Chemical Formula 1), Ganodermanone Triol (Chemical Formula 2), Lucidamol A (Chemical Formula 3), Ganoderriol F (Chemical Formula 4) and the like used in the present invention are within the range that does not impair the effect. Coarse fractions containing may be used.

  For example, a dried product of a ganoderma fruit body is shredded, immersed in ethanol, methanol, hexane, chloroform, or the like, and extracted at room temperature or by heating. It can also be extracted with carbon dioxide in the supercritical state or in the vicinity thereof. The obtained extract is subjected to chromatography on silica gel, ODS gel, ion exchange resin, etc., and recrystallized as necessary to obtain ganodermanone diol, ganodermanone triol, lucidamol A, ganodeliol F, etc. be able to.

  The triterpene characterized by having two or three hydroxyl groups in the side chain moiety located at position 17 of the lanostane skeleton of the present invention can be used for any of cosmetics, quasi drugs, pharmaceuticals, and foods, As the dosage form, for example, lotion, cream, emulsion, gel, aerosol, essence, pack, cleaning agent, bath preparation, foundation, powder, lipstick, ointment, poultice, powder, emulsion, solution , Suspensions, syrups, beverages, tablets and the like.

  The triterpene having 2 or 3 hydroxyl groups in the side chain moiety located at the 17th position of the lanostane skeleton of the present invention is particularly preferably blended in a whitening agent that prevents and improves spots and freckles.

  When a triterpene having 2 or 3 hydroxyl groups in the side chain portion located at the 17th position of the lanostane skeleton of the present invention is added to the whitening agent, it is preferably 0.0001% by weight or more, preferably A blending ratio of 0.001 to 10% by weight is good. 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. The intake for internal use varies depending on the administration form, purpose of use, age, weight, etc., but is 1 to 5,000 mg / day, preferably 10 to 1,000 mg / day. In addition, the addition method may be added in advance or during the production, and may be appropriately selected in consideration of workability.

  The whitening agent containing a triterpene, which has two or three hydroxyl groups in the side chain portion located at the 17th position of the lanostane skeleton of the present invention, has a high whitening action and good stability.

  In order to describe the present invention in detail, examples of production of the extract used in the present invention, formulation examples of the present invention, and experimental examples are given as examples, but the present invention is not limited thereto. The part of the blending amount shown in the examples indicates part by weight.

Production Example 1
The dried product of the ganoderma fruit body was chopped, 40 L of ethanol was added to 4 kg of the dried product, and the extraction was started at room temperature. One week later, the residue was removed by filtration, and the obtained extract was evaporated under reduced pressure to obtain 50 g of an extract. The obtained extract was dissolved in chloroform, subjected to silica gel column chromatography and eluted with chloroform / methanol (10: 1), and the desired fraction was eluted with methanol. The obtained fraction was concentrated under reduced pressure, the components were separated by preparative chromatography using an ODS column, and ganodermanonediol, ganodermanone triol, lucidamol A and ganodeliol F were respectively 200 mg, 300 mg, 150 mg and 100 mg was obtained. In addition, ganoderic acid A, ganoderic acid DM, and ganoderol B were also isolated as comparative controls. Each compound was identified by measuring NMR and MS and comparing it with literature values.

Production Example 2
The dried product of the ganoderma fruit body was chopped, and 80 L of ethanol was added to 4 kg thereof, followed by extraction at 50 ° C. for 2 hours, followed by filtration to remove the residue. The obtained extract was evaporated under reduced pressure to obtain 45 g of an extract. The obtained extract was dissolved in a 40 v / v% aqueous ethanol solution to remove insolubles, then subjected to Diaion HP-20 and eluted with ethanol. The obtained fraction was concentrated under reduced pressure, the components were separated and recrystallized by preparative chromatography using an ODS column, and 300 mg each of ganodermanone diol, ganodermanone triol, lucidamol A and ganodeliol F were obtained. , 50 mg, 300 mg and 30 mg were obtained. Each compound was identified by measuring NMR and MS and comparing it with literature values.

Formulation Example 1 Cream Formulation Amount 1. Ganodermanone diol 1.0 part Squalane 5.5
3. Olive oil 3.0
4). Stearic acid 2.0
5. Beeswax 2.0
6). Octyldodecyl myristate 3.5
7). Polyoxyethylene cetyl ether (20E.O.) 3.0
8). Behenyl alcohol 1.5
9. Glycerol monostearate2.5
10. Fragrance 0.05
11.1,3-butylene glycol 8.5
12 Ethyl paraoxybenzoate 0.05
13. Methyl paraoxybenzoate 0.2
14 Purified water 67.2
[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 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. The component 10 is added at 45 ° C., and further cooled to 30 ° C. to obtain a product.

Comparative Example 1 Conventional Cream In Formulation Example 1, a conventional cream was prepared by replacing ganodermanone diol with purified water.

Formulation Example 2 Lotion Formulation Amount Ganodermanone diol 0.005 parts 2.1,3-butylene glycol 8.0
3. Glycerin 2.0
4). Xanthan gum 0.02
5. Citric acid 0.01
6). Sodium citrate 0.1
7). Ethanol 5.0
8). Methyl paraoxybenzoate 0.1
9. Polyoxyethylene hydrogenated castor oil (40E.O.) 0.1
10. Fragrance 0.1
11. Purified water 84.565
[Production method] Components 1 to 6 and 11 and components 7 to 10 are uniformly dissolved, and both are mixed and filtered to obtain a product.

Formulation Example 3 Emulsion Formulation Formulation 1. Ganodermanone diol 0.2 parts Gano Del Manon Trial 0.1
3. Lucida Mall A 0.1
4). Ganodeliol F 0.1
5. Squalane 5.0
6). Olive oil 5.0
7). Jojoba oil 5.0
8). Cetanol 1.5
9. Glycerol monostearate 2.0
10. Polyoxyethylene cetyl ether (20E.O.) 3.0
11. Polyoxyethylene sorbitan monooleate (20E.O.) 2.0
12 Fragrance 0.1
13. Propylene glycol 1.0
14 Glycerin 2.0
15. Methyl paraoxybenzoate 0.2
16. Purified water 72.7
[Manufacturing method] Components 5 to 11 are heated and dissolved and mixed, and kept at 70 ° C to obtain an oil phase. Ingredients 1 to 4 and 13 to 16 are dissolved by heating 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. The component 12 is added at 45 ° C., and further cooled to 30 ° C. to obtain a product.

Formulation Example 4 Gel formulation Formulation amount 1. Ganodermanone diol 0.1 part2. Ethanol 5.0
3. Methyl paraoxybenzoate 0.1
4). Polyoxyethylene hydrogenated castor oil (60 EO) 0.1
5. Fragrance 0.1
6.1,3-Butylene glycol 5.0
7). Glycerin 5.0
8). Xanthan gum 0.1
9. Carboxyvinyl polymer 0.2
10. Potassium hydroxide 0.2
11. Purified water 84.1
[Manufacturing method] Components 2 to 5 and components 1 and 6 to 11 are uniformly dissolved and mixed to obtain a product.

Formulation Example 5 Pack Formulation Formulation 1. Ganodermanone diol 0.2 parts Polyvinyl alcohol 12.0
3. Ethanol 5.0
4.1,3-Butylene glycol 8.0
5. Methyl paraoxybenzoate 0.2
6). Polyoxyethylene hydrogenated castor oil (20 EO) 0.5
7). Citric acid 0.1
8). Sodium citrate 0.3
9. Fragrance 0.1
10. Purified water 73.6
[Production method] Components 1 to 10 are uniformly dissolved to obtain a product.

Formulation Example 6 Foundation Formulation Amount 1. Ganodermanone diol 1.0 part Stearic acid 2.4
3. Polyoxyethylene sorbitan monostearate (20E.O.) 1.0
4). Polyoxyethylene cetyl ether (20E.O.) 2.0
5. Cetanol 1.0
6). Liquid lanolin 2.0
7). Liquid paraffin 3.0
8). Isopropyl myristate 6.5
9. Butyl paraoxybenzoate 0.1
10. Sodium carboxymethylcellulose 0.1
11. Bentonite 0.5
12 Propylene glycol 4.0
13. Triethanolamine 1.1
14 Methyl paraoxybenzoate 0.2
15. Titanium dioxide 8.0
16. Talc 4.0
17. Bengala 1.0
18. Yellow iron oxide 2.0
19. Fragrance 0.1
20. Purified water 60.0
[Manufacturing method] Components 2 to 9 are heated and dissolved and kept at 80 ° C to obtain an oil phase. Swell component 10 well with component 20, then add components 1 and 11-14 and mix uniformly. To this, components 15 to 18 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 oily phase is added to the aqueous phase with stirring, cooled, and component 19 is added at 45 ° C, and cooled to 30 ° C with stirring to give a product.

Formulation Example 7 Bath preparation formulation 1. Ganodermanone diol 1.0 part Sodium bicarbonate 50.0
3. Yellow No. 202 (1) Appropriate amount 4. Perfume appropriate amount 5. Anhydrous sodium sulfate 48.0
[Production method] Components 1 to 5 are uniformly mixed to obtain a product.

Formulation Example 8 Ointment Formulation Formulation 1. 1. Ganodermanone diol 1.0 part Polyoxyethylene cetyl ether (30E.O.) 2.0
3. Glycerol monostearate 10.0
4). Liquid paraffin 5.0
5. Cetanol 6.0
6). Methyl paraoxybenzoate 0.1
7). Propylene glycol 10.0
8). Purified water 65.9
[Manufacturing method] Components 2 to 5 are dissolved by heating and mixed, and kept at 70 ° C to obtain an oil phase. Ingredients 1 and 6 to 8 are dissolved by heating 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 to 30 ° C. with stirring to obtain a product.

Formulation Example 9 Granule formulation Formulation amount 1. Ganodermanonediol 5.0 parts Reduced maltose syrup 35.0
3. Microcrystalline cellulose 60.0
[Production Method] An appropriate amount of 70 w / w% ethanol is added to components 1 to 3, kneaded, extruded and granulated, and dried to obtain granules. The granules are used internally at 1 g per day.

Formulation Example 10 Cream Formulation Formulation 1. 1. Ganodermanon triol 1.0 part Squalane 5.5
3. Olive oil 3.0
4). Stearic acid 2.0
5. Beeswax 2.0
6). Octyldodecyl myristate 3.5
7). Polyoxyethylene cetyl ether (20E.O.) 3.0
8). Behenyl alcohol 1.5
9. Glycerol monostearate2.5
10. Fragrance 0.05
11.1,3-butylene glycol 8.5
12 Ethyl paraoxybenzoate 0.05
13. Methyl paraoxybenzoate 0.2
14 Purified water 67.2
[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 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. The component 10 is added at 45 ° C., and further cooled to 30 ° C. to obtain a product.

Formulation Example 11 Lotion Formulation Amount Ganodermanone triol 0.005 parts 2.1,3-butylene glycol 8.0
3. Glycerin 2.0
4). Xanthan gum 0.02
5. Citric acid 0.01
6). Sodium citrate 0.1
7). Ethanol 5.0
8). Methyl paraoxybenzoate 0.1
9. Polyoxyethylene hydrogenated castor oil (40E.O.) 0.1
10. Fragrance 0.1
11. Purified water 84.565
[Production method] Components 1 to 6 and 11 and components 7 to 10 are uniformly dissolved, and both are mixed and filtered to obtain a product.

Formulation Example 12 Emulsion Formulation Formulation 1. Ganodermanon triol 0.3 parts Lucida Mall A 0.1
3. Ganodeliol F 0.1
4). Squalane 5.0
5. Olive oil 5.0
6). Jojoba oil 5.0
7). Cetanol 1.5
8). Glycerol monostearate 2.0
9. Polyoxyethylene cetyl ether (20E.O.) 3.0
10. Polyoxyethylene sorbitan monooleate (20E.O.) 2.0
11. Fragrance 0.1
12 Propylene glycol 1.0
13. Glycerin 2.0
14 Methyl paraoxybenzoate 0.2
15. Purified water 72.7
[Manufacturing method] Components 4 to 10 are heated and dissolved, mixed, and kept at 70 ° C to obtain an oil phase. Ingredients 1 to 3 and 12 to 15 are dissolved by heating 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. The component 11 is added at 45 ° C., and further cooled to 30 ° C. to obtain a product.

Formulation Example 13 Gel formulation formulation Ganodermanon triol 0.1 part Ethanol 5.0
3. Methyl paraoxybenzoate 0.1
4). Polyoxyethylene hydrogenated castor oil (60 EO) 0.1
5. Fragrance 0.1
6.1,3-Butylene glycol 5.0
7). Glycerin 5.0
8). Xanthan gum 0.1
9. Carboxyvinyl polymer 0.2
10. Potassium hydroxide 0.2
11. Purified water 84.1
[Manufacturing method] Components 2 to 5 and components 1 and 6 to 11 are uniformly dissolved and mixed to obtain a product.

Formulation Example 14 Pack Formulation Formulation 1. Ganodermanon triol 0.2 part Polyvinyl alcohol 12.0
3. Ethanol 5.0
4.1,3-Butylene glycol 8.0
5. Methyl paraoxybenzoate 0.2
6). Polyoxyethylene hydrogenated castor oil (20 EO) 0.5
7). Citric acid 0.1
8). Sodium citrate 0.3
9. Fragrance 0.1
10. Purified water 73.6
[Production method] Components 1 to 10 are uniformly dissolved to obtain a product.

Formulation Example 15 Foundation Formulation Amount 1. Ganodermanon triol 1.0 part Stearic acid 2.4
3. Polyoxyethylene sorbitan monostearate (20E.O.) 1.0
4). Polyoxyethylene cetyl ether (20E.O.) 2.0
5. Cetanol 1.0
6). Liquid lanolin 2.0
7). Liquid paraffin 3.0
8). Isopropyl myristate 6.5
9. Butyl paraoxybenzoate 0.1
10. Sodium carboxymethylcellulose 0.1
11. Bentonite 0.5
12 Propylene glycol 4.0
13. Triethanolamine 1.1
14 Methyl paraoxybenzoate 0.2
15. Titanium dioxide 8.0
16. Talc 4.0
17. Bengala 1.0
18. Yellow iron oxide 2.0
19. Fragrance 0.1
20. Purified water 60.0
[Manufacturing method] Components 2 to 9 are dissolved by heating and kept at 80 ° C to obtain an oil phase. Swell component 10 well with component 20, then add components 1 and 11-14 and mix uniformly. To this, components 15 to 18 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 oily phase is added to the aqueous phase with stirring, cooled, and component 19 is added at 45 ° C, and cooled to 30 ° C with stirring to give a product.

Formulation Example 16 Bath preparation formulation 1. Ganodermanon triol 1.0 part Sodium bicarbonate 50.0
3. Yellow No. 202 (1) Appropriate amount 4. Perfume appropriate amount 5. Anhydrous sodium sulfate 48.0
[Production method] Components 1 to 5 are uniformly mixed to obtain a product.

Formulation Example 17 Ointment Formulation Formulation 1. 1. Ganodermanon triol 1.0 part Polyoxyethylene cetyl ether (30E.O.) 2.0
3. Glycerol monostearate 10.0
4). Liquid paraffin 5.0
5. Cetanol 6.0
6). Methyl paraoxybenzoate 0.1
7). Propylene glycol 10.0
8). Purified water 65.9
[Manufacturing method] Components 2 to 5 are dissolved by heating and mixed, and kept at 70 ° C to obtain an oil phase. Ingredients 1 and 6 to 8 are dissolved by heating 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 to 30 ° C. with stirring to obtain a product.

Formulation Example 18 Granule formulation Formulation amount Gano Del Manon Triol 5.0 parts Reduced maltose syrup 35.0
3. Microcrystalline cellulose 60.0
[Production Method] An appropriate amount of 70 w / w% ethanol is added to components 1 to 3, kneaded, extruded and granulated, and dried to obtain granules. The granules are used internally at 1 g per day.

Formulation Example 19 Cream Formulation Formulation 1. Lucida Mall A 1.0 part2. Squalane 5.5
3. Olive oil 3.0
4). Stearic acid 2.0
5. Beeswax 2.0
6). Octyldodecyl myristate 3.5
7). Polyoxyethylene cetyl ether (20E.O.) 3.0
8). Behenyl alcohol 1.5
9. Glycerol monostearate2.5
10. Fragrance 0.05
11.1,3-butylene glycol 8.5
12 Ethyl paraoxybenzoate 0.05
13. Methyl paraoxybenzoate 0.2
14 Purified water 67.2
[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 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. The component 10 is added at 45 ° C., and further cooled to 30 ° C. to obtain a product.

Formulation Example 20 Lotion Formulation Amount Lucidamol A 0.005 part 2.1,3-Butylene glycol 8.0
3. Glycerin 2.0
4). Xanthan gum 0.02
5. Citric acid 0.01
6). Sodium citrate 0.1
7). Ethanol 5.0
8). Methyl paraoxybenzoate 0.1
9. Polyoxyethylene hydrogenated castor oil (40E.O.) 0.1
10. Fragrance 0.1
11. Purified water 84.565
[Production method] Components 1 to 6 and 11 and components 7 to 10 are uniformly dissolved, and both are mixed and filtered to obtain a product.

Formulation Example 21 Emulsion Formulation Formulation Amount Lucida Mall A 0.3 part2. Ganodermanonediol 0.2
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 (20E.O.) 2.0
10. Fragrance 0.1
11. Propylene glycol 1.0
12 Glycerin 2.0
13. Methyl paraoxybenzoate 0.2
14 Purified water 72.7
[Manufacturing method] Components 3 to 9 are dissolved by heating and mixed, and kept at 70 ° C to obtain an oil phase. Ingredients 1, 2 and 11-14 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. The component 10 is added at 45 ° C., and further cooled to 30 ° C. to obtain a product.

Formulation Example 22 Gel formulation Formulation amount 1. Lucida Mall A 0.1 part 2. Ethanol 5.0
3. Methyl paraoxybenzoate 0.1
4). Polyoxyethylene hydrogenated castor oil (60 EO) 0.1
5. Fragrance 0.1
6.1,3-Butylene glycol 5.0
7). Glycerin 5.0
8). Xanthan gum 0.1
9. Carboxyvinyl polymer 0.2
10. Potassium hydroxide 0.2
11. Purified water 84.1
[Manufacturing method] Components 2 to 5 and components 1 and 6 to 11 are uniformly dissolved and mixed to obtain a product.

Formulation Example 23 Pack Formulation Amount 1. Lucida Mall A 0.2 part 2. Polyvinyl alcohol 12.0
3. Ethanol 5.0
4.1,3-Butylene glycol 8.0
5. Methyl paraoxybenzoate 0.2
6). Polyoxyethylene hydrogenated castor oil (20 EO) 0.5
7). Citric acid 0.1
8). Sodium citrate 0.3
9. Fragrance 0.1
10. Purified water 73.6
[Production method] Components 1 to 10 are uniformly dissolved to obtain a product.

Formulation Example 24 Foundation Formulation Amount Lucida Mall A 1.0 part2. Stearic acid 2.4
3. Polyoxyethylene sorbitan monostearate (20E.O.) 1.0
4). Polyoxyethylene cetyl ether (20E.O.) 2.0
5. Cetanol 1.0
6). Liquid lanolin 2.0
7). Liquid paraffin 3.0
8). Isopropyl myristate 6.5
9. Butyl paraoxybenzoate 0.1
10. Sodium carboxymethylcellulose 0.1
11. Bentonite 0.5
12 Propylene glycol 4.0
13. Triethanolamine 1.1
14 Methyl paraoxybenzoate 0.2
15. Titanium dioxide 8.0
16. Talc 4.0
17. Bengala 1.0
18. Yellow iron oxide 2.0
19. Fragrance 0.1
20. Purified water 60.0
[Manufacturing method] Components 2 to 9 are heated and dissolved and kept at 80 ° C to obtain an oil phase. Swell component 10 well with component 20, then add components 1 and 11-14 and mix uniformly. To this, components 15 to 18 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 oily phase is added to the aqueous phase with stirring, cooled, and component 19 is added at 45 ° C, and cooled to 30 ° C with stirring to give a product.

Formulation Example 25 Bath preparation formulation Lucida Mall A 1.0 part2. Sodium bicarbonate 50.0
3. Yellow No. 202 (1) Appropriate amount 4. Perfume appropriate amount 5. Anhydrous sodium sulfate 48.0
[Production method] Components 1 to 5 are uniformly mixed to obtain a product.

Formulation Example 26 Ointment Formulation Formulation 1. Lucida Mall A 1.0 part2. Polyoxyethylene cetyl ether (30E.O.) 2.0
3. Glycerol monostearate 10.0
4). Liquid paraffin 5.0
5. Cetanol 6.0
6). Methyl paraoxybenzoate 0.1
7). Propylene glycol 10.0
8). Purified water 65.9
[Manufacturing method] Components 2 to 5 are dissolved by heating and mixed, and kept at 70 ° C to obtain an oil phase. Ingredients 1 and 6 to 8 are dissolved by heating 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 to 30 ° C. with stirring to obtain a product.

Formulation Example 27 Granule formulation Formulation amount Lucida Mall A 5.0 parts Reduced maltose syrup 35.0
3. Microcrystalline cellulose 60.0
[Production Method] An appropriate amount of 70 w / w% ethanol is added to components 1 to 3, kneaded, extruded and granulated, and dried to obtain granules. The granules are used internally at 1 g per day.

Formulation Example 28 Cream Formulation Formulation 1. Ganodeliol F 1.0 part2. Squalane 5.5
3. Olive oil 3.0
4). Stearic acid 2.0
5. Beeswax 2.0
6). Octyldodecyl myristate 3.5
7). Polyoxyethylene cetyl ether (20E.O.) 3.0
8). Behenyl alcohol 1.5
9. Glycerol monostearate2.5
10. Fragrance 0.05
11.1,3-butylene glycol 8.5
12 Ethyl paraoxybenzoate 0.05
13. Methyl paraoxybenzoate 0.2
14 Purified water 67.2
[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 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. The component 10 is added at 45 ° C., and further cooled to 30 ° C. to obtain a product.

Formulation Example 29 Lotion Formulation Amount Ganoderiol F 0.005 part 2.1,3-butylene glycol 8.0
3. Glycerin 2.0
4). Xanthan gum 0.02
5. Citric acid 0.01
6). Sodium citrate 0.1
7). Ethanol 5.0
8). Methyl paraoxybenzoate 0.1
9. Polyoxyethylene hydrogenated castor oil (40E.O.) 0.1
10. Fragrance 0.1
11. Purified water 84.565
[Production method] Components 1 to 6 and 11 and components 7 to 10 are uniformly dissolved, and both are mixed and filtered to obtain a product.

Formulation Example 30 Emulsion Formulation Formulation 1. Ganodeliol F 0.1 part2. Gano Del Manon Triol 0.4
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 (20E.O.) 2.0
10. Fragrance 0.1
11. Propylene glycol 1.0
12 Glycerin 2.0
13. Methyl paraoxybenzoate 0.2
14 Purified water 72.7
[Manufacturing method] Components 3 to 9 are dissolved by heating and mixed, and kept at 70 ° C to obtain an oil phase. Ingredients 1, 2 and 11-14 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. The component 10 is added at 45 ° C., and further cooled to 30 ° C. to obtain a product.

Formulation Example 31 Gel formulation formulation Ganodeliol F 0.1 part2. Ethanol 5.0
3. Methyl paraoxybenzoate 0.1
4). Polyoxyethylene hydrogenated castor oil (60 EO) 0.1
5. Fragrance 0.1
6.1,3-Butylene glycol 5.0
7). Glycerin 5.0
8). Xanthan gum 0.1
9. Carboxyvinyl polymer 0.2
10. Potassium hydroxide 0.2
11. Purified water 84.1
[Manufacturing method] Components 2 to 5 and components 1 and 6 to 11 are uniformly dissolved and mixed to obtain a product.

Formulation Example 32 Pack Formulation Amount Ganodeliol F 0.2 part Polyvinyl alcohol 12.0
3. Ethanol 5.0
4.1,3-Butylene glycol 8.0
5. Methyl paraoxybenzoate 0.2
6). Polyoxyethylene hydrogenated castor oil (20 EO) 0.5
7). Citric acid 0.1
8). Sodium citrate 0.3
9. Fragrance 0.1
10. Purified water 73.6
[Production method] Components 1 to 10 are uniformly dissolved to obtain a product.

Formulation Example 33 Foundation Formulation Amount Ganodeliol F 1.0 part2. Stearic acid 2.4
3. Polyoxyethylene sorbitan monostearate (20E.O.) 1.0
4). Polyoxyethylene cetyl ether (20E.O.) 2.0
5. Cetanol 1.0
6). Liquid lanolin 2.0
7). Liquid paraffin 3.0
8). Isopropyl myristate 6.5
9. Butyl paraoxybenzoate 0.1
10. Sodium carboxymethylcellulose 0.1
11. Bentonite 0.5
12 Propylene glycol 4.0
13. Triethanolamine 1.1
14 Methyl paraoxybenzoate 0.2
15. Titanium dioxide 8.0
16. Talc 4.0
17. Bengala 1.0
18. Yellow iron oxide 2.0
19. Fragrance 0.1
20. Purified water 60.0
[Manufacturing method] Components 2 to 9 are heated and dissolved and kept at 80 ° C to obtain an oil phase. Swell component 10 well with component 20, then add components 1 and 11-14 and mix uniformly. To this, components 15 to 18 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 oily phase is added to the aqueous phase with stirring, cooled, and component 19 is added at 45 ° C, and cooled to 30 ° C with stirring to give a product.

Formulation Example 34 Bath preparation formulation Ganodeliol F 1.0 part2. Sodium bicarbonate 50.0
3. Yellow No. 202 (1) Appropriate amount 4. Perfume appropriate amount 5. Anhydrous sodium sulfate 48.0
[Production method] Components 1 to 5 are uniformly mixed to obtain a product.

Formulation Example 35 Ointment Formulation Formulation 1. Ganodeliol F 1.0 part2. Polyoxyethylene cetyl ether (30E.O.) 2.0
3. Glycerol monostearate 10.0
4). Liquid paraffin 5.0
5. Cetanol 6.0
6). Methyl paraoxybenzoate 0.1
7). Propylene glycol 10.0
8). Purified water 65.9
[Manufacturing method] Components 2 to 5 are dissolved by heating and mixed, and kept at 70 ° C to obtain an oil phase. Ingredients 1 and 6 to 8 are dissolved by heating 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 to 30 ° C. with stirring to obtain a product.

Formulation Example 36 Granule formulation Formulation amount Ganodeliol F 5.0 parts2. Reduced maltose syrup 35.0
3. Microcrystalline cellulose 60.0
[Production Method] An appropriate amount of 70 w / w% ethanol is added to components 1 to 3, kneaded, extruded and granulated, and dried to obtain granules. The granules are used internally at 1 g per day.

Experimental Example 1 Whitening Effect of the Present Invention A melanin production inhibition test using B16 mouse melanoma was performed.
A melanoma in the logarithmic growth phase is seeded with 3 × 10 ⁴ cells in a 60 mm petri dish, Eagles'MEM (containing 10% fetal bovine serum) containing samples of various concentrations is added, and 37 ° C., 5% CO ₂ is added. Cultured under conditions. After 5 days of culture, the cells were detached from the petri dish, and the cells were ultrasonically disrupted. Then, a 2N aqueous sodium hydroxide solution was added, and the mixture was treated at 60 ° C. for 2 hours. D. 475 nm was measured. In addition, the cell lysate after sonication was subjected to protein quantification by Lowry's method (J. Biol. Chem., 193, 265-275, 1951), and the amount of melanin per protein amount was compared, thereby suppressing melanin production. It was used as an index of action.

  The experimental results are shown in Table 1, Table 2, Table 3, and Table 4. As a result, ganodermanone diol, ganodermanone triol, lucidamol A and ganodeliol F of the present invention have superior melanin production inhibitory action compared to ganoderol B, lanosterol (commercially available), ganoderic acid A, and ganoderic acid DM. Indicated. That is, Ganoderma triterpene, which has 2 or 3 hydroxyl groups in the side chain moiety located at the 17th position of the lanostane skeleton, is markedly more melanin than components with 0 or 1 hydroxyl groups. It became clear that the production suppression effect was high.

Experimental Example 2 Use Test One month use test for 20 women suffering from spots and freckles using the creams of Formulation Example 1, Formulation Example 10, Formulation Example 19 and Formulation Example 28, and the conventional cream of Comparative Example 1. Went. After use, the effect of improving spots and freckles was judged by a questionnaire.

These test results are shown in Table 5, Table 6, Table 7, Table 8, Table 9, and Table 10. As a result, the cream containing ganodermanone diol, ganodermanone triol, lucidamol A and ganodeliol F according to the present invention showed an effect of improving skin spots and freckles as compared with conventional creams. During the test period, there was no skin problem and there was no problem with safety. Further, even after storage at 40 ° C. for 6 months, there was no problem with the deterioration of the prescription components without any decrease in the effect of improving spots and freckles.

  When other usage examples (external preparations) were tested in the same manner, they showed excellent stain and buckwheat improving effects and good stability.

Experimental Example 3 Stability test 1,3-butylene glycol containing 0.1% each of ganodermanone diol, ganodermanone triol, lucidamol A and ganodeliol F was stored at 40 ° C. for 6 months, and then subjected to HPLC analysis. Each component was quantified. HPLC conditions were as described in Chem. Pharm. Bull. 52 (6), 688-695 (2004). As a result, almost no decomposition was observed in all four components (residual rate of 99.0% or more), which revealed that the components were very stable.

  The whitening agent containing a triterpene, which has two or three hydroxyl groups in the side chain portion located at the 17th position of the lanostane skeleton of the present invention, exhibits an excellent whitening action and also has good stability. It can be applied to cosmetics, quasi drugs, pharmaceuticals, foods, etc.

Claims (1)

A melanin production inhibitor consisting of one or more selected from ganodermanone diol, ganodermanone triol, lucidamol A, and ganodeliol F derived from ganoderma.