JP4523300B2 - Mushroom-derived composition - Google Patents

Description

  The present invention relates to a mushroom-derived composition. More specifically, the present invention relates to a mushroom fruit body extract, a mushroom culture mycelium culture liquid, or a mushroom culture mycelium extract. More specifically, Lepista nuda (Bull .: Fr) Cooke, Panellius serotinus (Pers .: Kuhn.), Daedalaex Dickinsi. (Fomes fomentarius (L .: Fr.) Kickx), Effvingia applanata (Pers.) Karst. ) Fr.), Ningyotakemodo Astragalus confluens (A. et S .: Fr.) Kotl. Et Pouz., Pleurotus ostreus (Jacq .: Fr.) Kummer, P. Pers .: Fr.) Karst.), Macrolepiota procera (Scop .: Fr.) Sing., Phythinaceae (Pers.) Sing. Extract of fruit body of Inonotus hispidus (Bull.:Fr.) Karst.), (Lycoperdon perlatum Pers .: Pers.), Lampteromyces japonicus (Kawam.) Sing., Lepista nuda (Bull .: Fr) ) Karst.), Mushroom (Panelus serotinus (Pers .: Fr.) Kuhn.), Daedarea dickinsii (Berk. Ex Cooke Yasuda), Osiroitake et Sing. ), Laiporus versisporus (Lloyd) Imaz., Coriulus hirususu (Wulf .: Fr.) Quel., F. fentarirus (F. applanata (Pers.) Karst.), Ganoderma neo-japonicum Imaz., Russula cyanoxantha (Schaeff.) Fr. .) KOtl. Et Pou ), Pleurotus ostreatus (Jacq .: Fr.) Kummer, Ryutes caperata (Pers .: Fr.) Karst., Karakasapuro (ce. Fr.) Sing.), Cultured mycelium of Psathyrella velutina (Pers.), Inotus hispidus (Bull .: Fr.) Karst. It relates to the whitening action, tyrosinase inhibition action, free radical scavenging action, anti-inflammatory action and moisturizing action of the mycelium extract.

  Mushroom mycelium grows using various organic substances in nature as nutrient sources. The mycelium gathers for breeding when the environment such as temperature is complete, forming a large fruit body. Since ancient times, humans have empirically selected effective foods from the fruit bodies of wild mushrooms. Some mushroom fruit bodies such as shiitake mushrooms and mushrooms are widely used as food after being artificially cultured. However, more than 1000 wild mushrooms grow natively in Japan alone, but most of them are not used industrially.

  On the other hand, mushrooms produce various physiologically active substances during growth. The components often differ not only in the type of mushrooms but also in the growth stages of mycelium and fruiting bodies. Focusing on the physiologically active function of mushrooms, it is an effective means for developing new products to obtain effective ingredients for skin preparations and functional foods. However, there are few examples where mushrooms are used in industries other than food. Examples of the industrial use of mushrooms include the use of white or jellyfish fruit bodies as a scrub agent disclosed in JP-A-61-260006, and the fruit body of kerosene disclosed in JP-A 63-126812. Use of the extract for whitening cosmetics, whitening action and antioxidation action containing extracts of fruit bodies of Ningyotake, Shogenji, Usura Sakihatsu and Usura Saki Houkitake disclosed in JP-A-2-49710 Use as cosmetics, Japanese urabei irogawari, ashibeniiguchi, irogawari, utsuiroirogawari, akakouji, madoritakemomodoki, dokuyamamadori, seiashibeiiguchi, koganemadori, koganemadori, disclosed in JP-A-9-227333 Kinokubori Iguchi, Shironumeiguchi, Numeritsu Chi, Hanaiguchi, Numeniguchi, Red-footed tiger, Kinchaamaiguchi, Yamaiuchi, Akebono-Awatake, Hoebishiiroiguchi, Niiguchii, Pokopuchii, Utsuroiguchi, Okinoboriguchi, Numerikougitake, Hannotakei Known as a whitening cosmetic or moisturizing cosmetic using a fruit body extract of Yashaiguchi or Kuroazaawatake, or as a whitening agent of a fruit body extract of Enokitake or Bunashimeji disclosed in JP-A-14-322044 It has been. However, these prior arts are extracts from certain mushroom fruiting bodies. On the other hand, it is difficult to artificially cultivate fruit bodies of mushrooms because a culture method corresponding to the type of mushrooms must be developed.

  The claim of Japanese Patent No. 3432940 includes a basidiomycete family selected from the group consisting of a basidiomycete family basidiomycete selected from the group consisting of Numetsubatatake, Matsuooji, Fuchidoritaketake, Murasakiximeji, and Nararatake, and from the group consisting of Shirametsumutake, Chanamemutake and Numerisugitake A basidiomycete family basidiomycete selected from the group consisting of Shiromaitake, Chakaigaratake, and Amanita mushroom, and a basidiomycete culture solution or fungus selected from the group consisting of Bunaharitake, Binohanatake, Shoro, Numerikojitake and Ohitake Although the skin external preparation characterized by mix | blending the 1 type (s) or 2 or more types of the melanin production suppression component of an extract group is disclosed, the kind is limited.

  On the other hand, it is well known that the expression product differs between the fruit body of a mushroom and an artificial culture. Moreover, although the said patent 3432940 mentions the mycelium, in the said prior art, it describes using the extract from a fruit body exclusively, and also the mycelium which inoculated and cultured the inoculum | spawn It is also disclosed that the body is not suitable for obtaining the desired components. Therefore, it is desired to establish a method for extracting an extract that can be used as an external preparation for skin, a whitening agent, a tyrosinase inhibitor, a free radical scavenger, an anti-inflammatory agent, and a moisturizer from a mushroom culture.

  In addition, when the active ingredients derived from mushrooms are found only in wild mushroom fruit bodies, the fruit bodies that form the material often occur every year in a similar place in the natural environment, so it is relatively easy to collect. it can. Furthermore, if a culture method up to the fruiting body is established, it is possible to stably supply the fruiting body as a raw material. However, if the components produced by the fruit body are different from the components produced by the mycelium, and the components produced by the mycelium exhibit a stronger physiological action, these may be overlooked. In addition, when it is difficult to culture up to fruiting bodies, the supply only relies on wild fruiting bodies, which is extremely unstable and is not industrially desirable.

  On the other hand, when the active ingredients derived from mushrooms are found only in cultured mycelia of wild mushrooms, the cultured mycelium used as the material can be cultured relatively easily indoors, and the amount of production can be freely adjusted according to market demand. It can also be adjusted. However, if the components produced by the cultured mycelium are different from the components produced by the fruit bodies and the components produced by the fruit bodies exhibit a stronger physiological action, these may be overlooked. In addition, if the fruiting body grows naturally in large quantities and there is no anxiety in terms of supply, it is disadvantageous to cultivate mycelium economically.

Therefore, even in view of the current situation that artificial cultivation of mushroom fruit bodies is difficult, it is suitable for extracting skin external preparations, whitening agents, tyrosinase inhibitors, free radical scavengers, anti-inflammatory agents, and moisturizers. It is very useful for industrial use of mushroom-derived compositions to find many types of fungi from mycelium and fruiting bodies of new mushroom candidates.
JP 61-260006 JP-A 63-126812 JP-A-2-49710 Japanese Patent No. 3432940 JP-A-9-227333 JP-A-14-322044 Kenjiro Kinugawa, Kei Ogawa "Mushroom Handbook" Asakura Shoten 2000 Tatsuyuki Sugawara “Mushroom Science” Asakura Shoten 1997

  The present invention seeks a component that exhibits a whitening action, a free radical scavenging action, an anti-inflammatory action, and a moisturizing action from the viewpoint of beautifying skin to wild mushrooms, and is a skin external preparation excellent in skin beautifying effects that contains ingredients derived from wild mushrooms. And to provide food.

  More specifically, it is an object of the present invention to find a mushroom capable of obtaining a component having the above action from cultured mycelia of mushrooms and to obtain a component having the above action. Further, it is an object of the present invention to find mushroom fruit bodies, which have not been known as a source of the above-mentioned components, as candidates capable of extracting the above-mentioned components and obtain the above-mentioned components.

  The present inventors have unexpectedly considered that mushrooms that have not been expected to contain components having excellent whitening action, tyrosinase inhibiting action, free radical scavenging action, anti-inflammatory action, and moisturizing action contain these ingredients. The present invention was completed.

Accordingly, the present invention provides the following.
1. Lepista nuda (Bull .: Fr) Cooke, Panellas serotinus (Pers .: Kuhn.), Daedala dickinsi (Bed.) Fomes formentarius (L .: Fr.) Kickx), Effvingia applanata (Pers.) Karst., Ganoderma neo-japonum (Ganoderma neo-japonum) .), Oyster mushroom (Pleurotus) strainus (Jacq .: Fr.) Kummer), Macrolepiota procera (Scop .: Fr.) Sing., Phythinaceae (Psathirella velutina) (Pers.) An extract of the fruiting body of Inonotus hispidus (Bull .: Fr.) Karst.
Pseudomonas (Lycoperdon perlatum Pers .: Pers.), Lamperomyces japonicus (Kawam.) Sing., U. Dickinsi (Berk. ex Cooke) Yasuda), Oyuroirotake (Tyromyces albellus (Peck) Bond. et Sing.), Hirafusbe (Laetiporus versisporus (Lloyd) Ima. .), Tsuriganetake (Form fomentarius (L .: Fr.) Kickx), Ganoderma neo-japonicum Imaz. et S.:Fr.) KOtl. et Pouz.), Pleurotus osteretus (Jacq .: Fr.) Kummer, Ryutes caperata (Pers., Kr.), Fr. Macrolepiota procera (Scop .: Fr.) Sing ), Extract of cultured mycelium of Psathyrella velutina (Pers.) Sing., And Inotus hispidus (Bull .: Fr.) Karst. A skin external preparation characterized by containing one or more selected from the group consisting of liquids.
2. The external preparation for skin according to item 1, which is powder, solid or liquid.
3. A method for preparing a skin external preparation, comprising:
1) Lepida nuda (Bull .: Fr) Cooke, Pancellus sertinus (Pers .: Kr.), Tachokinaceae as candidates for obtaining fruit body extracts (Dedarea dicchinsii (Berk. .), Ryusyu cyanoxantha (Schaeff.) Fr.) , Pleurotus ostreatus (Jacq .: Fr.) Kummer, Agaricaceae (Macropiota procera (Scop .: Fr.) Sing.), Musinatake (P. , And Tobacco spp. (Inonotus hispidus (Bull .: Fr.) Karst.), And
As candidates for obtaining a culture liquid of cultured mycelium or an extract of cultured mycelium, Lycoperdon perlatum Pers .: Pers., Lamperomyces japonicus (Kawam.) Sing. Panellus serotinus (Pers .: Fr.) Kuhn., Octopusaceae (Daedalea dickinsi (Berk. Ex Cooke et al.), L. s. versisporus (Lloyd) Imaz.), Coralius hirs Tus (Wulf .: Fr.) Quel.), Fomes formentarius (L .: Fr.) Kickx, Ganderma neo-japonicum Imaz. Fr.), Albatrollus confluens (A. et S .: Fr.) KOtl. Et Pouz., Pleurotus ostretus (Jacq .: mmr) Genji (Rozetes caperata (Pers .: Fr.) Karst.), Agaricaceae rolepiota procera (Scop .: Fr.) Sing.), Psathyrella velutina (Pers.) Sing., and Tobacco spp. Selecting one or more mushrooms from the mushrooms to be produced, and
2) A step of obtaining a fruit body extract, a cultured mycelium culture liquid or a cultured mycelium extract from the selected mushrooms,
Including the method.
4). The extraction is performed using a solvent selected from the group consisting of methanol, ethanol, hexane, benzene, acetone, ethyl acetate, chloroform, dichlorochloroform, diethyl ether, 1,3-butylene glycol, glycerin, propylene glycol, and water. 4. The method according to item 3, which is performed.
5). Lepista nuda (Bull .: Fr) Cooke, Panellas serotinus (Pers .: Kuhn.), Daedala dickinsi (Bed.) Fomes formentarius (L .: Fr.) Kickx), Effvingia applanata (Pers.) Karst., Ganoderma neo-japonum (Ganoderma neo-japonum) .), Oyster mushroom (Pleurotus) strainus (Jacq .: Fr.) Kummer), Macrolepiota procera (Scop .: Fr.) Sing., Phythinaceae (Psathirella velutina) (Pers.) An extract of the fruiting body of Inonotus hispidus (Bull .: Fr.) Karst.
Pseudomonas (Lycoperdon perlatum Pers .: Pers.), Lamperomyces japonicus (Kawam.) Sing., U. Dickinsi (Berk. ex Cooke) Yasuda), Oyuroirotake (Tyromyces albellus (Peck) Bond. et Sing.), Hirafusbe (Laetiporus versisporus (Lloyd) Ima. .), Tsuriganetake (Form fomentarius (L .: Fr.) Kickx), Ganoderma neo-japonicum Imaz. et S.:Fr.) KOtl. et Pouz.), Pleurotus ostreatus (Jacq .: Fr.) Kummer, Macrolepiota procera (Scop .: F.) Inotus hispidus (Bull .: Fr. Karst.) Culture of the culture mycelium, as well as
Lycoperdon perlatum Pers .: Pers., Lumpteromyces japonicus (Kawam.) Sing., P. leucomus, Peru. (Tyromyces albellus (Peck) Bond. Et Sing.), Coriolus hirsutus (Wulf .: Fr.) Quel., Formes mentarius (L .: kr. -Japonicum Imaz.), Agaricaceae (Russu) la cyanoxantha (Schaeff.) Fr.), Albatrellas confluens (A. et S .: Fr.) KOtl. et Poul. (Pleur. Pleur. Pleur) ), Rozites caperata (Pers .: Fr.) Karst., Macropiota procera (Scop .: Fr.) Sing., Ps. Sing.), And Inotus hispidus (Bu ll.:Fr.) A whitening agent comprising one or more selected from the group consisting of extracts of cultured mycelium of Karst.).
6). Item 6. The whitening agent according to Item 5, which is powder, solid or liquid.
7). A method for preparing a whitening agent comprising:
1) Lepida nuda (Bull .: Fr) Cooke, Pancellus sertinus (Pers .: Kr.), Tachokinaceae as candidates for obtaining fruit body extracts (Dedarea dicchinsii (Berk. .), Ryusyu cyanoxantha (Schaeff.) Fr.) , Pleurotus ostreatus (Jacq .: Fr.) Kummer, Agaricaceae (Macropiota procera (Scop .: Fr.) Sing.), Musinatake (P. , And Inotus hispidus (Bull .: Fr.) Karst.
As candidates for obtaining a culture solution of cultured mycelium, Lycoperdon perlatum Pers .: Pers., Lampteromyces japonicus (Kawam.) Sing., Musel : Fr.) Kuhn.), Daedalea dickinsii (Berk. Ex Cooke Yasuda), Tyromyces albellus (Peck) ord. Et Sing. , Coralius hirsutus (Wulf. Fr.) Quel.), Fomes formentarius (L .: Fr.) Kickx, Ganoderma neo-japonicum Imaz. Pleurotus ostretus (Jacq .: Fr.) Kummer, p. Sculpacea (S .: Fr.) KOtl. Et Pouz. .: Fr.) Sing.), And Tonotake (Inono) us hispidus (Bull.:Fr.) Karst.), as well as
As candidates for obtaining an extract of cultured mycelium, Lycoperdon perlatum Pers .: Lampteromyces japonicus (Kawam.) Sing., Musel : Fr.) Kuhn.), Tyromyces albellus (Peck) Bond. Et Sing., Coriolus hirstus (Wul.:fr.) Fent. : Fr.) Kickx), Ganoderma neo-japonicum Im az.), Russula cyanoxantha (Schaeff.) Fr., Albatrellas confluens (A. et S .: Fr.) KOtl. Ostreatus (Jacq.:Fr.) Kummer), Rozetes caperata (Pers .: Karst.), Agaricaceae (Macroleiota procera (Scop.), S .. Fr.) Of Psathyrella velutina (Pers.) Sing. Ke (Inonotus hispidus (Bull.:Fr.) Karst.) From mushrooms are selected from the group consisting of the steps of selecting one or more of mushrooms, and
2) A step of obtaining a fruit body extract, a cultured mycelium culture liquid or a cultured mycelium extract from the selected mushrooms,
Including the method.
8). The extraction is performed using a solvent selected from the group consisting of methanol, ethanol, hexane, benzene, acetone, ethyl acetate, chloroform, dichlorochloroform, diethyl ether, 1,3-butylene glycol, glycerin, propylene glycol, and water. 8. The method according to item 7, which is performed.
9. Lepista nuda (Bull .: Fr) Cooke, Panellas serotinus (Pers .: Kuhn.), Daedala dickinsi (Bed.) Fomes formentarius (L .: Fr.) Kickx), Effvingia applanata (Pers.) Karst., Ganoderma neo-japonum (Ganoderma neo-japonum) .), Oyster mushroom (Pleurotus) strainus (Jacq .: Fr.) Kummer), Macrolepiota procera (Scop .: Fr.) Sing., Phythinaceae (Psathirella velutina) (Pers.) An extract of the fruiting body of Inonotus hispidus (Bull .: Fr.) Karst.
Pseudomonas (Lycoperdon perlatum Pers .: Pers.), Lamperomyces japonicus (Kawam.) Sing., U. Dickinsi (Berk. ex Cooke) Yasuda), Oyuroirotake (Tyromyces albellus (Peck) Bond. et Sing.), Hirafusbe (Laetiporus versisporus (Lloyd) Ima. .), Tsuriganetake (Form fomentarius (L .: Fr.) Kickx), Ganoderma neo-japonicum Imaz. et S.:Fr.) KOtl. et Pouz.), Pleurotus ostreatus (Jacq .: Fr.) Kummer, Macrolepiota procera (Scop .: F.) Inotus hispidus (Bull .: Fr. Karst.) Culture of the culture mycelium, as well as
Lycoperdon perlatum Pers .: Pers., Lumpteromyces japonicus (Kawam.) Sing., P. leucomus, Peru. (Tyromyces albellus (Peck) Bond. Et Sing.), Coriolus hirsutus (Wulf .: Fr.) Quel., Formes mentarius (L .: kr. -Japonicum Imaz.), Agaricaceae (Russu) la cyanoxantha (Schaeff.) Fr.), Albatrellas confluens (A. et S .: Fr.) KOtl. et Poul. (Pleur. Pleur. Pleur) ), Rozites caperata (Pers .: Fr.) Karst., Macropiota procera (Scop .: Fr.) Sing., Ps. Sing.), And Inotus hispidus (Bu ll.:Fr.) A composition for inhibiting tyrosinase activity, comprising one or more selected from the group consisting of extracts of cultured mycelium of Karst.).
10. Lepista nuda (Bull .: Fr) Cooke, Panellas serotinus (Pers .: Kuhn.), Daedala dickinsi (Bed.) Fomes fomentarius (L.:Fr.) Kickx), Effvinia applanata (Pers.) Karst., Ganoderma neo-japonum ), Pleurotus o treatus (Jacq .: Fr.) Kummer), Macrolepiota procera (Scop .: Fr.) Sing., Psathyrella velutina (Pers.) An extract of the fruiting body of Inonotus hispidus (Bull .: Fr.) Karst.
(Lycoperdon perlatum Pers .: Pers.), Lamperomyces japonicus (Kawam.) Sing. : Fr.) Karst.), Muelleria serotinus (Pers .: Fr.) Kuhn., Daedarea dickinsii (Berk. Ex Cooke Yasuda), Otiroita et Sing.), Hirafusube (Laetiporus) versisporus (Lloyd) Imaz.), Corrius hirusutus (Wul .: Fr.) Quel. (F. forsentarius (L .: Fr.) Kickx) Karst., Ganoderma neo-japonicum Imaz., Russula cyanoxantha (Schaeff.) Fr., N. syrup (A. fus). Pouzu.), Pleurotus o tretus (Jacq .: Fr.) Kummer), Rozetes caperata (Pers .: Karst.), Agaricaceae (Macroleiota procera (Scop .: Fr.) S. From the culture mycelium or the extract of the mycelium of Psathyrella velutina (Pers.) Sing, and the fungus of the genus Tobacco mushroom (Inonotus hispidus (Bull .: Fr.) Karst.) A free radical scavenger comprising one or more selected from the group consisting of:
11. Item 11. The free radical scavenger of item 10, which is a powder, solid or liquid.
12 A method for preparing a free radical scavenger comprising:
1) Lepida nuda (Bull .: Fr) Cooke, Pancellus sertinus (Pers .: Kr.), Tachokinaceae as candidates for obtaining fruit body extracts (Dedarea dicchinsii (Berk. ), Rubusula cyanoxantha (Schaeff.) Fr.), Pleurotus ostreatus (Jacq .: Fr.) Kummer), Agaricaceae (Macropiota procera (Scop .: Fr.) Sing.), Mussunatake (Psa. And Tobacco spp. (Inonotus hispidus (Bull .: Fr.) Karst.) And
As candidates for obtaining a culture liquid of cultured mycelium or an extract of cultured mycelium, Lycoperdon perlatum Pers .: Pers., Lamperomyces japonicus (Kawam.) Sing. (Lepista nuda (Bull .: Fr) Cooke), Arillariella mellea (Vahl .: Fr.) Karst., Mudake (Panelus serotinus (Pers.) dicchinsiii (Berk. ex Cooke) Yasuda), Ooiroretake (Tyromyces albellus) k) Bond. et Sing.), Laetiporus versisporus (Lloyd) Imaz., Coriolus hirutus (Wul .: Fr.) Quel. (F.), (Elfvingia applanata (Pers.) Karst.), Scallop (Ganoderma neo-japonicum Imaz.), Ryusula cyno A. et S .: Fr.) KOt Et Pouz.), Pleurotus ostreatus (Jacq .: Fr.) Kummer, Ryutes caperata (Pers .: Karst.), M. Scop .: Fr.) Sing.), Psathyrella velutina (Pers.) Sing., And Tonoscus piste (Bull .: Fr.) Karst. Selecting one or more mushrooms from the mushrooms to be produced, and
2) A step of obtaining a fruit body extract, a cultured mycelium culture liquid or a cultured mycelium extract from the selected mushrooms,
Including the method.
13. The extraction is performed using a solvent selected from the group consisting of methanol, ethanol, hexane, benzene, acetone, ethyl acetate, chloroform, dichlorochloroform, diethyl ether, 1,3-butylene glycol, glycerin, propylene glycol, and water. 13. The method according to item 12, which is performed.
14 Lepista nuda (Bull .: Fr) Cooke, Dawdalea dickinsii (Berk. Ex Cooke Yasuda), Femme k. Ganoderma neo-japonicum Imaz., Russula cyanoxantha (Schaeff.) Fr., N. syrup, A. falcons. Pleurotus ostreatus (Jacq .: Fr Kummer), Rozites caperata (Pers .: Fr.) Karst., Macroleiota procera (Scop .: Fr.) Sing., P Pers.) Sing.), And extracts of fruiting bodies of Inonotus hispidus (Bull .: Fr.) Karst.
(Lampteromyces japonicus (Kawam.) Sing.), Panellus serotinus (Pers .: Fr.) Kuhn., Taedoexi Bokei Tyromyces albellus (Peck) Bond. Et Sing.), Laiporus versisporus (Lloyd) Imaz., Coriolus hirusus (Wul.), Qu.ent. Kickx) Noderma neo-japonicum Imaz.), Russula cyanoxantha (Schaeff.) F., Ningyotakeo et al. (Rozites caperata (Pers .: Fr.) Karst.), Macroleiota procera (Scop .: Fr.) Sing., (Psathyrella S.) And Inotus hispidus (Bull .: r.) Karst.) culture of the culture mycelium, as well as
(Lycoperdon perlatum Pers .: Pers.), Lamperomyces japonicus (Kawam.) Sing. : Fr.) Karst.), Muelleria serotinus (Pers .: Fr.) Kuhn., Daedarea dickinsii (Berk. Ex Cooke Yasuda), Otiroita et Sing.), Hirafusube (Laetiporus) versisporus (Lloyd) Imaz.), Corrius hirusutus (Wul .: Fr.) Quel. (F. forsentarius (L .: Fr.) Kickx) Karst., Ganoderma neo-japonicum Imaz., Russula cyanoxantha (Schaeff.) Fr., N. syrup (A. fus). Pouzu.), Pleurotus o tretus (Jacq .: Fr.) Kummer), Rozetes caperata (Pers .: Karst.), Agaricaceae (Macroleiota procera (Scop .: Fr.) S. 1 selected from the group consisting of extracts of cultured mycelium of Psathyrella velutina (Pers.) Singing, and Mushrooms of the Tobacco family (Inotus hispidus (Bull .: Fr.) Karst.) An anti-inflammatory agent comprising two or more kinds.
15. Item 15. The anti-inflammatory agent according to Item 14, which is a powder, a solid or a liquid.
16. A method for preparing an anti-inflammatory agent comprising:
1) Lepista nuda (Bull .: Fr) Cooke, Daedarea dickinsii (Berk. Ex Cooke) Yasuda, Tsukida family as candidates for obtaining fruit body extracts Fomes fomentarius (L .: Fr.) Kickx), Ganoderma neo-japonicum Iaz. Et S .: Fr.) Kotl. Et Pouz.), Pleur tus ostreatus (Jacq .: Fr.) Kummer), Rozites caperata (Pers .: Fr.) Karst., Macrolepiota procera (Scop. Psathyrella velutina (Pers.) Sing., And Tomotake mushroom (Inonotus hispidus (Bull .: Fr.) Karst.) And
As candidates for obtaining a culture solution of cultured mycelium, Lamperomyces japonicus (Kawam.) Sing., PanELLus serotinus (Pers .: Kr.), D Dickinsi (Berk. ex Cooke) Yasuda), Oyuroirotake (Tyromyces albellus (Peck) Bond. et Sing.), Hirafusbe (Laetiporus versisporus (Lloyd) Ima. .), Fomes formarius (L .: Fr.) Ki ckx), Ganoderma neo-japonicum Iz., Ryusyu cyanoxantha (Schaeff.) Fr., Alf. genus S. Et Pouz.), Rozites caperata (Pers .: Fr.) Karst., Macrolepiota procera (Scop .: Fr.) Sing. (Pers.) Sing.), Tonotake of Tobacco (Inono) tus hispidus (Bull .: Fr.) Karst.) and
As a candidate for obtaining an extract of cultured mycelium, a culture solution of cultured mycelium, Lycoperdon perlatum Pers .: Pers., Lamperomyces japonicus (Kawam.) Singyotake. ), Lepista nuda (Bull .: Fr) Cooke, Armillariella mellea (Vahl .: Fr.) Karst., Panlus serotinus (Pers. (Daedalea dicchinsii (Berk. Ex Cooke) Yasuda), Ooshiroitake (Tyromyces albellus ( eck) Bond. et Sing.), Laiporus versisporus (Lloyd) Imaz., Coriolus hirutus (Wul .: Fr.) Quent. (F.), F. (Elfvingia applanata (Pers.) Karst.), Scallop (Ganoderma neo-japonicum Imaz.), Ryusula cyno A. et S .: Fr.) K et Pouz.), Pleurotus ostereatus (Jacq .: Fr.) Kummer, Ryuzites caperata (Pers .: Karst. (Scop .: Fr.) Sing.), Psathyrella velutina (Pers.) Sing., And Tonotake hispidus (Bull .: Fr.) Karst. Selecting one or more mushrooms from the selected mushrooms, and
2) A step of obtaining a fruit body extract, a cultured mycelium culture liquid or a cultured mycelium extract from the selected mushrooms,
Including the method.
17. The extraction is performed using a solvent selected from the group consisting of methanol, ethanol, hexane, benzene, acetone, ethyl acetate, chloroform, dichlorochloroform, diethyl ether, 1,3-butylene glycol, glycerin, propylene glycol, and water. The method according to item 16, wherein the method is performed.
18. Lepista nuda (Bull .: Fr) Cooke, Panellas serotinus (Pers .: Kuhn.), Daedala dickinsi (Bed.) Fomes formentarius (L .: Fr.) Kickx), Effvingia applanata (Pers.) Karst., Ganoderma neo-japonum (Ganoderma neo-japonum) .), Ningyotake (Anyingaceae) (A lbatorellus confluens (A. et S .: Fr.) Kotl. et Pouz., Pleurotus ostereatus (Jacq .: Fr.) Kummer, P. ) Karst.), Macrolepiota procera (Scop .: Fr.) Sing., Psathyella verutina (Pers. Sing.), And H. urdus. .: Fr.) Karst.) Fruiting body extract, and
Pseudomonas (Lycoperdon perlatum Pers .: Pers.), Lamperomyces japonicus (Kawam.) Sing., U. Dickinsi (Berk. ex Cooke) Yasuda), Oyuroirotake (Tyromyces albellus (Peck) Bond. et Sing.), Hirafusbe (Laetiporus versisporus (Lloyd) Ima. .), Tsuriganetake (Form fomentarius (L .: Fr.) Kickx), Ganoderma neo-japonicum Imaz. et S.:Fr.) KOtl. et Pouz.), Pleurotus osteretus (Jacq .: Fr.) Kummer, Ryutes caperata (Pers., Kr.), Fr. Macrolepiota procera (Scop .: Fr.) Sing ), Extract of cultured mycelium of Psathyrella velutina (Pers.) Sing., And Inotus hispidus (Bull .: Fr.) Karst. A humectant comprising one or more selected from the group consisting of liquids.
19. Item 19. A humectant according to item 18, which is a powder, a solid or a liquid.
20. A method for preparing a humectant, comprising:
1) Lepida nuda (Bull .: Fr) Cooke, Pancellus sertinus (Pers .: Kr.), Tachokinaceae as candidates for obtaining fruit body extracts (Dedarea dicchinsii (Berk. .), Ryusyu cyanoxantha (Schaeff.) Fr.) , Glyceraceae (Albatrellus confluens (A. et S .: Fr.) Kotl. Et Pouz.), Pleurotus ostretus (Jacq .: Fr.) caperata (Pers .: Fr.) Karst.), Macrolepiota procera (Scop .: Fr.) Sing., Phythinaceae (Psathyrella velutina), Pers. (Inonotus hispidus (Bull .: Fr.) Karst.) And
As candidates for obtaining a culture liquid of cultured mycelium or an extract of cultured mycelium, Lycoperdon perlatum Pers .: Pers., Lamperomyces japonicus (Kawam.) Sing. Panellus serotinus (Pers .: Fr.) Kuhn., Octopusaceae (Daedalea dickinsi (Berk. Ex Cooke et al.), L. s. versisporus (Lloyd) Imaz.), Coralius hirs Tus (Wulf .: Fr.) Quel.), Fomes formentarius (L .: Fr.) Kickx, Ganderma neo-japonicum Imaz. Fr.), Albatrollus confluens (A. et S .: Fr.) KOtl. Et Pouz., Pleurotus ostretus (Jacq .: mmr) Genji (Rozetes caperata (Pers .: Fr.) Karst.), Agaricaceae from Rolepiota procera (Scop .: Fr.) Sing.), Psathyrella velutina (Pers.) Sing., and Tokuto Fistula (B.) from Intotus hispidus (Bul). Selecting one or more mushrooms from mushrooms selected from the group; and
2) A step of obtaining a fruit body extract, a cultured mycelium culture liquid or a cultured mycelium extract from the selected mushrooms,
Including the method.
21. The extraction is performed using a solvent selected from the group consisting of methanol, ethanol, hexane, benzene, acetone, ethyl acetate, chloroform, dichlorochloroform, diethyl ether, 1,3-butylene glycol, glycerin, propylene glycol, and water. The method according to item 20, wherein the method is performed.

  In the present invention, materials containing active ingredients were selected for the culture solution and extract of cultured mycelium derived from the fruit body of mushrooms collected in the wild, together with the extract of the fruit body of mushrooms collected in the wild. As a result, it is found that it is a kind of purple mullet, a kind of bamboo moth, an agaric moth, an agaric moth, a scallop, a scabbard, a scallop, a cypress, Karakasatake, Mudinatake of Toyotake department, Extract of the fruit body of Dendrobium of Tobacco sp. Aragekawaratake, Tricholoma, Prunus serrata, Prunus, Pleurotus, Pleurotus, Ningyotake, Pleurotus, Pleurotus Inhibition of tyrosinase activity or free radical scavenging action on cultured mycelium cultures or extracts of cultured mycelium of Ratake, Fusentaceae, Agaricaceae, Azalea, Mudinatake, Tobacco, Mushroom Or the anti-inflammatory effect or the moisturizing effect was found. Since this tyrosinase activity is an activity necessary for the synthesis of the precursor of melanin, melanin synthesis is inhibited by the action of inhibiting tyrosinase activity, resulting in a whitening action. The free radical scavenging action prevents skin aging and is effective in improving skin wrinkles and tarmi.

  That is, one or more kinds of fruit bodies or cultured mycelia culture solutions or cultured mycelium extracts or concentrated or diluted solutions selected from the above-mentioned mushrooms are added to the skin external preparation and food. Skin tyrosinase activity inhibitory action, whitening action, free radical scavenging action, anti-inflammatory action, skin external preparation excellent in moisturizing action, tyrosinase activity inhibitor, whitening agent, free radical scavenger, anti-inflammatory agent Moisturizer can be provided.

  Whitening action, tyrosinase activity inhibition action, free radical scavenging action, anti-inflammatory action, moisturizing action mushrooms (for example, purple mushrooms, mushrooms), octopus family mushrooms (for example, burrock mushrooms, mushrooms) Mushrooms (for example, Kofukisaru-no-Shokutake, Magojakushi), Amanita mushrooms (for example, Kawarihatsu), Ningyotake-no-Mushrooms (for example, Ningyotake), Amanita mushrooms (for example, Oyster mushrooms), Amanita mushrooms (for example) ), Agaric mushrooms (e.g. Caracasata), cypress mushrooms (e.g. Mujinata), tobacco mushroom mushrooms (e.g. mushrooms), or mushrooms (e.g. mushrooms) , Ki Medicinal mushrooms (for example, Tsukiyotake, Murasaki-meji, Nararatake, Mukitake), Octopus-like mushrooms (for example, Agaricus mushroom, Ooshiroitaketake, Hirafusube, Aragekawaratake, Tsuriganetake) Mushrooms of the family Amanita (for example, Kawarihatsu), mushrooms of the family Nymphalidae (for example Ningyotake), mushrooms of the mushroom family (e.g. oyster mushrooms), mushrooms of the family Mushrooms (e.g. ginger), mushrooms of the mushroom family (e.g. 1 type of cultured mycelium culture liquid extract or cultured mycelium extract solution or concentrated or diluted solution thereof of Karakasatake), Hitotake department mushroom (for example, Mudinatake), Tobacco mushroom family mushroom (for example, Yatakekotake) 2 or more By blending the skin external preparation or food, excellent external preparation for skin to skin softening or lightening agents, tyrosinase activity inhibitors, free radical scavengers, antiinflammatory agents, it is possible to provide a humectant.

  The present invention will be described below. Throughout this specification, it should be understood that the singular forms also include the plural concept unless specifically stated otherwise. Thus, it should be understood that singular articles (eg, “a”, “an”, “the”, etc. in the case of English) also include the plural concept unless otherwise stated. In addition, it is to be understood that the terms used in the present specification are used in the meaning normally used in the art unless otherwise specified. Thus, unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present specification, including definitions, will control.

(Definition of terms)
As used herein, the term “fruit body” is a reproductive body that produces a spore in a fungus and may be used interchangeably with the term “spore body”. Ascomycota and basidiomycetes refer to various forms of mycelial tissue such as ascomycetes and basidiomycetes.

  As used herein, the term “mycelium” is used interchangeably with the term “mycelium” and is a basic structure that constitutes the nutrients of filamentous fungi, and is multicellular and multinuclear. . Mycelium develops from the germ tube of the spore and extends by tip growth.

  Dust mushrooms of the department of Mushrooms used in the present invention, Azalea mushrooms of the Asteraceae department, Murasakimeji, Naratake, Mukitake, Agaricus mushrooms, Ooiroitaketake, Hirafusbe, Aragekawaratake, Azalea mushroom, Amanita mushroom The fruiting bodies of Ningyotake, Nymphalidae, Pleurotus, Pleurotus, Agaricaceae, Agaricaceae, Munatake, Tobaccoaceae, and Yakekogetake are grown naturally in Japan and around the world. In addition to the fruiting body, any artificially cultivated fruiting body may be used. Moreover, if it is a related species with these mushrooms, it can be used similarly.

  As the mycelium used for the cultured mycelium, those obtained by aseptically cultivating the mycelium from the above-mentioned fruiting bodies on a medium and using the mycelium can be used.

  The medium used for culturing the mycelium is a liquid such as potato dextrose agar medium, potato sucrose agar medium, peptone dextrose agar medium, potato dextrose medium excluding agar, potato sucrose medium, peptone dextrose medium, etc. In addition to the medium, any medium can be used as long as it can be used for culturing fungi. However, when the mycelium is induced from the fruit body or stored, an agar medium is used in the present invention. When obtaining the culture solution or extract of the mycelium to be used, it is easier in terms of operation to use a liquid medium. The mycelium culture conditions and the like are not particularly limited, but it is desirable to use a mycelium cultured on an agar medium and planted on a liquid medium and cultured at 20 to 30 ° C. for 10 to 40 days.

  Such media are well known to those of skill in the art. Specifically, the following composition is used, but the composition of the medium used in the present invention is not limited to the following composition.

(Composition of potato dextrose agar)
Potato broth: 1000ml
Glucose: 20g
Powder agar: 15g
(Composition of potato sucrose agar medium)
Potato broth: 1000ml
Sucrose: 20g
Powder agar: 15g
(Composition of peptone dextrose agar)
Polypeptone: 5g
Glucose: 20g
Yeast extract: 2g
Magnesium sulfate heptahydrate: 0.5g
Potassium dihydrogen phosphate: 1g
Powder agar: 20g
Pure water: 1000m1
(Composition of potato dextrose medium)
Potato broth: 1000ml
Glucose: 20g
(Composition of potato sucrose medium)
Potato broth: 1000ml
Sucrose: 20g
(Composition of peptone dextrose medium)
Polypeptone: 5g
Glucose: 20g
Yeast extract: 2g
Magnesium sulfate heptahydrate: 0.5g
Potassium dihydrogen phosphate: 1g
Pure water: 1000ml
When the fruit body is cultured in a medium having the above composition, the mycelium is derived from the fruit body, and then subcultured every 3 to 6 months to preserve the mycelium.

  The culture solution of the cultured mycelium can be used in the present invention as it is or after being concentrated or diluted as necessary. Filtration methods are well known, and for example, filter paper can be used. Further, a membrane filter having a pore size of 10 to 0.45 μm (for example, 10 μm, 5 μm, 1 μm, 0.45 μm) can also be used. As the concentration method, for example, a vacuum concentration method in which an extract prepared using an organic solvent is volatilized by being left under reduced pressure can be used. As a concentration method, a method using ultrafiltration can also be used.

  The solvent used for the extraction of mushroom fruit bodies or cultured mycelium used in the present invention is not particularly limited. For example, one or more organic solvents such as methanol, ethanol, hexane, benzene, acetone, ethyl acetate, chloroform, dichlorochloroform, diethyl ether, 1,3-butylene glycol, glycerin, propylene glycol, and water are used. Can be mixed and used. A preferred solvent is an organic solvent such as ethanol, 1,3-butylene glycol, glycerin, or propylene glycol, or water. Conditions such as extraction time, extraction temperature, and extraction method are not particularly limited. In consideration of solvent persistence, economic efficiency, and work efficiency, the cultured mycelium separated from the fruit body or the culture solution is left as it is or dried, and then pulverized as it is or 1 to 10% of the wet weight of the fruit body or the cultured mycelium. Use double the amount of ethanol or 1,3-butylene glycol, glycerin, propylene glycol and extract for 1-10 days at room temperature, or use 1-10 times the wet weight of fruit body or cultured mycelium It is preferable to use an extract obtained by filtration after extraction at 80 to 100 ° C. for 1 to 10 hours. The extract can be used in the present invention as it is or after being concentrated or diluted as necessary.

  The mushroom composition of the present invention can be used for foods in addition to the external preparation for skin. The shape of the external preparation for skin and food is not particularly limited. For example, it can be used in the form of liquid, gel, cream, granule, solid and the like. When using the mushroom composition of the present invention as an external preparation for skin, lotion, cream, gel, ointment, milky lotion, cosmetic liquid, pack, face wash, cleansing agent, hair care agent, soap, bath preparation, shampoo, rinse, lip It can be incorporated into cosmetics such as sticks, lipsticks and foundations, quasi-drugs, and pharmaceuticals.

(Prescription)
The amount of mushroom fruit body extract or cultured mycelium culture solution or cultured mycelium extract used is 0.00001 to as a concentrate obtained by distilling off the solvent or water with respect to the external skin solvent or the whole food. It is appropriate to add 100% by weight, preferably 0.002 to 20% by weight. When the extract is used without concentrating, generally less than 0.002% by weight cannot provide a sufficient effect. Moreover, generally even if it mixes exceeding 20 weight%, there is no increase in an effect and it is uneconomical. The type of mushroom to be used, the fruit body extract, the cultured mycelium extract or the culture solution is appropriately selected from one or more according to the expected effect.

  The topical skin preparation blended with the present invention is a base material for cosmetics such as oils and fats, waxes, hydrocarbons, silicones, fatty acids, alcohols, esters, surfactants, thickeners and powders. In addition, active ingredients of quasi-drugs and pharmaceuticals, pH adjusters, preservatives, pigments, fragrances, antioxidants, natural product-derived extracts, and the like can be blended as necessary.

  The extracts of the present invention can also be formulated in combination with a pharmaceutically acceptable carrier type (eg, a sterile carrier). The extracts of the invention are formulated and dosed in a manner that complies with medical practice standards (GMP), taking into account individual individuals, methods of administration, dosing schedules, and other factors known to those of skill in the art. Therefore, the target “effective amount” in the present specification is determined by taking such consideration into consideration.

  The therapeutic agent can be oral, rectal, parenteral, intracisternally, intravaginally, intraperitoneally, topically (such as by powder, ointment, gel, instillation, or transdermal patch), oral or oral or It can be administered as a nasal spray. “Pharmaceutically acceptable carrier” refers to a non-toxic solid, semi-solid or liquid filler, diluent, encapsulant or any type of formulation adjuvant. The term “parenteral” as used herein refers to modes of administration including intravenous and intramuscular, intraperitoneal, intrasternal, subcutaneous and intraarticular injections and infusions.

  The therapeutic agents of the present invention are also suitably administered by a sustained release system. Suitable examples of sustained release therapeutic agents are oral, rectal, parenteral, intracisternally, intravaginally, intraperitoneally, topically (powder, ointment, gel, infusion, or transdermal patch) Etc.), or as an oral or nasal spray. “Pharmaceutically acceptable carrier” refers to a non-toxic solid, semi-solid or liquid filler, diluent, encapsulant or any type of formulation adjuvant. The term “parenteral” as used herein refers to modes of administration including intravenous and intramuscular, intraperitoneal, intrasternal, subcutaneous and intraarticular injections and infusions. Suitable examples of sustained release therapeutic agents include suitable polymer materials (eg, semipermeable polymer matrices in the form of molded articles (eg, films or microcapsules)), suitable hydrophobic materials (eg, in acceptable quality oils). Or an ion exchange resin, and poorly soluble derivatives (eg, poorly soluble salts).

  Sustained release matrices include polylactide (US Pat. No. 3,773,919, EP 58,481), a copolymer of L-glutamic acid and γ-ethyl-L-glutamate (Sidman et al., Biopolymers 22: 547-556 (1983)). ), Poly (2-hydroxyethyl methacrylate) (Langer et al., J. Biomed. Mater. Res. 15: 167-277 (1981), and Langer, Chem. Tech. 12: 98-105 (1982)), ethylene vinyl Acetate (Langer et al., Ibid.) Or poly-D-(-)-3-hydroxybutyric acid (EP133,988).

  Sustained release therapeutic agents also include the therapeutic agents of the present invention entrapped in liposomes (generally, Langer, Science 249: 1527-1533 (1990); Treat et al., Liposomes in the Disease of Infectious Disease and Cancer, Loop, -See Berstein and Fiddler (eds.), Liss, New York, pages 317-327 and 353-365 (1989)). Liposomes containing therapeutic agents can be prepared by methods known per se: DE 3,218,121; Epstein et al., Proc. Natl. Acad. Sci. USA 82: 3688-3692 (1985); Hwang et al., Proc. Natl. Acad. Sci. USA 77: 4030-4034 (1980); EP52,322; EP36,676; EP88,046; EP143,949; EP142,641; Japanese Patent Application No. 83-118008; US Pat. No. 4,485,045 And 4,544,545 and EP 102,324. Usually, liposomes are small (about 200-800 cm) unilamellar type, where the lipid content is greater than about 30 mol% cholesterol, and the selected proportion is adjusted for optimal therapeutic agents.

  Other controlled release systems are discussed in the review by Langer (Science 249: 1527-1533 (1990)).

  For parenteral administration, in one embodiment, in general, the therapeutic agent is toxic to the recipient in the desired degree of purity, in a pharmaceutically acceptable carrier, i.e. the dosage and concentration used. It is formulated by mixing in a unit dosage injectable form (solution, suspension or emulsion) with one that is not and compatible with the other ingredients of the formulation. For example, the formulation preferably does not include oxidation and other compounds known to be harmful to therapeutic agents.

  Generally, formulations are prepared by contacting the therapeutic agent uniformly and intimately with liquid carriers or finely divided solid carriers or both. Next, if necessary, the product is shaped into the desired formulation. Preferably, the carrier is a parenteral carrier, more preferably a solution that is isotonic with the blood of the recipient. Examples of such carrier vehicles include water, saline, Ringer's solution, and dextrose solution. Nonaqueous vehicles such as fixed oils and ethyl oleate are also useful herein, as are liposomes.

  The carrier suitably contains minor amounts of additives such as substances that enhance isotonicity and chemical stability. Such substances are not toxic to the recipient at the dosages and concentrations used, such as phosphate, citrate, succinate, acetic acid and other organic acids or their salts. Buffering agents; antioxidants such as ascorbic acid; low molecular weight (less than about 10 residues) polypeptides (eg, polyarginine or tripeptides); proteins such as serum albumin, gelatin or immunoglobulins; polyvinylpyrrolidone Hydrophilic polymers such as: amino acids such as glycine, glutamic acid, aspartic acid or arginine; monosaccharides, disaccharides and other carbohydrates including cellulose or derivatives thereof, glucose, mannose or dextrin; chelating agents such as EDTA Sugar sugars such as mannitol or sorbitol Lumpur; counterions such as sodium; and / or polysorbate include nonionic surfactants such as poloxamers or PEG.

  The therapeutic agent is typically formulated in such a vehicle at a pH of about 3-8 at a concentration of about 0.1 mg / ml to 100 mg / ml, preferably 1-10 mg / ml. It is understood that by using the specific excipients, carriers or stabilizers described above, salts are formed.

  Any drug to be used for therapeutic administration may be in a state free of organisms / viruses other than viruses as an active ingredient, that is, in a sterile state. Aseptic conditions are easily achieved by filtration through sterile filtration membranes (eg, 0.2 micron membranes). Generally, the therapeutic agent is placed in a container having a sterile access port, such as an intravenous solution bag or vial with a stopper that can be punctured with a hypodermic needle.

  The therapeutic agents are typically stored in unit dose or multi-dose containers, such as sealed ampoules or vials, as an aqueous solution or lyophilized formulation for reconstitution. As an example of a lyophilized formulation, a 10 ml vial is filled with 5 ml of a sterile filtered 1% (w / v) aqueous therapeutic agent and the resulting mixture is lyophilized. The lyophilized therapeutic agent is reconstituted with bacteriostatic water for injection to prepare an infusion solution.

  The present invention also provides a pharmaceutical pack or kit comprising one or more containers filled with one or more components of the therapeutic agent of the present invention. A notice of the form prescribed by a government agency that regulates the manufacture, use or sale of a medicinal product or biological product may be attached to such a container, and this notice may be attached to the government regarding the manufacture, use or sale for human administration. Represents institutional approval. In addition, the therapeutic agent may be used in combination with other therapeutic compounds.

  The therapeutic agents of the present invention can be administered alone or in combination with other therapeutic agents. Therapeutic agents that can be administered in combination with the therapeutic agents of the invention include chemotherapeutic agents, antibiotics, steroidal and non-steroidal anti-inflammatory agents, conventional immunotherapeutic agents, other cytokines and / or growth factors. However, it is not limited to these. The combinations can be administered, for example, either simultaneously as a mixture; simultaneously or concurrently but separately; or over time. This includes the presentation that the combined agents are administered together as a therapeutic mixture, and also the procedure where the combined agents are administered separately but simultaneously, eg, through separate intravenous lines to the same individual . Administration in combination further includes separate administration of one of the compounds or agents given first, followed by the second.

  In certain embodiments, the therapeutic agents of the invention are administered in combination with antiretroviral agents, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and / or protease inhibitors.

  In a further embodiment, the therapeutic agent of the invention is administered in combination with an antibiotic. Antibiotics that can be used include aminoglycoside antibiotics, polyene antibiotics, penicillin antibiotics, cephem antibiotics, peptide antibiotics, macrolide antibiotics, tetracycline antibiotics. It is not limited.

  In further embodiments, the therapeutic agents of the invention are administered alone or in combination with an anti-inflammatory agent. Anti-inflammatory agents that can be administered with the therapeutic agents of the present invention include glucocorticoids and non-steroidal anti-inflammatory agents, aminoarylcarboxylic acid derivatives, arylacetic acid derivatives, arylbutyric acid derivatives, arylcarboxylic acids, arylpropionic acid derivatives, pyrazoles, pyrazolones , Salicylic acid derivatives, thiazinecarboxamide, e-acetamidocaproic acid, S-adenosylmethionine, 3-amino-4-hydroxybutyric acid, amixetrine, bendazac, benzidoamine, bucolome, difenpyramide, ditazole, emolphazone, Guaiazulene, nabumetone, nimesulide, orgothein, oxaceptol, paraniline, perizoxal, pifoxime, prochiazone, proxazole, and tenidap That, but is not limited to these.

  In further embodiments, the therapeutic agents of the invention are administered in combination with other therapeutic or prophylactic regimes (eg, radiation therapy).

  Hereinafter, the present invention will be described in detail with reference to examples and the like, but the present invention is not limited thereto.

(Example 1: Preparation of extract from mushroom fruiting body)
Wild swordfish of the wild xylem family that grows naturally in Japan. The fruiting bodies of Genji, Karakasatake of Agaricaceae, Mujinachake of Cypridinaceae, and Yamokogetake of Tobacco spp. Two days later, the ethanol extract and the residue were filtered off using filter paper. The obtained ethanol extract was concentrated under reduced pressure to completely remove the solvent, thereby obtaining an ethanol extract concentrate of fruiting bodies.

(Example 2: Preparation of culture solution from liquid culture of mycelium derived from fruit body)
Wild Dust mushrooms that grow naturally in Japan, Azalea mushrooms, Azalea mushrooms, Agaric mushrooms, Agaric mushrooms, Agaricus mushrooms, Ooiroitake, Hirafusube, Arakawaratake, Azalea, Amanita mushrooms Internal tissue was aseptically cut out from the fruiting bodies of Amanita spp. This tissue was transferred to a potato dextrose agar medium, a potato sucrose agar medium, or a peptone dextrose agar medium, and cultured at 25 ° C. for 20 days. The mycelium grown after 20 days was subcultured on a new agar medium. This operation was repeated twice, and the obtained mycelium was transplanted to a potato dextrose liquid medium, a potato sucrose liquid medium, or a peptone dextrose liquid medium, and cultured in a static field for 40 days. After 40 days, the culture broth and mycelium were filtered off using filter paper. The obtained culture broth was concentrated under reduced pressure to completely remove water, thereby obtaining a culture broth culture broth concentrate.

(Example 3: Preparation of an extract from a liquid culture of mycelium derived from fruit bodies)
Wild Dust mushrooms that grow naturally in Japan, Azalea mushrooms, Azalea mushrooms, Agaric mushrooms, Agaric mushrooms, Agaricus mushrooms, Ooiroitake, Hirafusube, Arakawaratake, Azalea, Amanita mushrooms Internal tissue was aseptically cut out from the fruiting bodies of Amanita spp. This tissue was transferred to a potato dextrose agar medium, a potato sucrose agar medium, or a peptone dextrose agar medium, and cultured at 25 ° C. for 20 days. The mycelium grown after 20 days was subcultured on an agar medium. This operation was repeated twice, and the obtained mycelium was transplanted to a potato dextrose liquid medium, a potato sucrose liquid medium, or a peptone dextrose liquid medium, and cultured in a static field for 40 days. After 40 days, the culture broth and mycelium were filtered off using filter paper. The obtained mycelium was immersed in ethanol of 5 times the raw weight at room temperature for 2 days. Two days later, the ethanol extract of the mycelium and the residue were filtered off using filter paper. The obtained ethanol extract was concentrated under reduced pressure to completely remove the solvent, thereby obtaining an ethanol extract concentrate of the cultured mycelium.

Example 4: Preparation of cosmetic cream formulation containing mushroom extract
A cosmetic cream was formulated using the following ingredients and recipe:
(A) stearic acid 8.0 (wt%),
(B) stearyl alcohol 4.0 (wt%),
(C) butyl stearate 6.0 (wt%),
(D) glyceryl monostearate 2.0 (% by weight),
(E) propylene glycol 5.0 (% by weight),
(F) Potassium hydroxide 0.4 (wt%),
-(G) antiseptic (paraoxybenzoic acid ester) 0.1-0.5 (wt%),
-(H) perfume 0.001-0.1 (wt%),
(I) antioxidant (dibutylhydroxytoluene) 0.05 to 0.15 (% by weight),
・ (J) Ethanol 5.0 (wt%)
(K) Horotake mushroom concentrate of Example 3 0.15 (% by weight),
(L) Concentrate of Example 3 of Arakawakawatake 0.1 (wt%)
(M) Purified water was added as the remaining part.
(Manufacturing method)
1. A part of the above (A) to (D), (E) to (I), and (M) was separately heated and mixed, mixed at 80 ° C., stirred with a homomixer, and then cooled to 50 ° C. .
2. (J) was added to a part of (M), and (K) and (L) were dissolved.
3. The above solutions 1 and 2 were mixed and cooled to 30 ° C.

(Example 5: Preparation of emulsion formulation containing mushroom extract)
The emulsion was formulated using the following ingredients and recipe:
(A) stearic acid 2.0 (wt%),
(B) Cetyl alcohol 1.5 (% by weight),
-(C) Vaseline 4.0 (wt%),
(D) Squalane 5.0 (% by weight),
(E) Glycerol tri-2-ethylhexanoate 2.0 (wt%),
(F) sorbitan monooleate 2.0 (wt%),
(G) Glycerol 9.0 (% by weight),
(H) potassium hydroxide 0.1 (% by weight),
(I) Preservative (paraoxybenzoic acid ester) 0.1 to 0.5 (% by weight),
・ (J) Fragrance 0.001-0.1 (% by weight)
(K) antioxidant (dibutylhydroxytoluene) 0.05 to 0.15 (% by weight),
-(L) Ethanol 5.0 (wt%)
(M) Concentrate of Example 3 of Arakawakawatake 0.1 (wt%),
(N) Concentrate 0.1 (wt%) of Example 3
-(O) Purified water was added as said remainder.
(Manufacturing method)
1. A part of (A) to (F), (G) to (K), and (O) was separately heated and mixed, mixed at 80 ° C, stirred with a homomixer, and then cooled to 50 ° C.
2. (L) was added to a part of (O) to dissolve (M) and (N).
3. The above solutions 1 and 2 were mixed and cooled to 30 ° C.

(Example 6: Preparation of lotion containing mushroom extract)
Lotion was formulated using the following ingredients and recipe:
(A) POE (20) oleyl alcohol ether 0.5 (% by weight)
(B) glycerin 10 (% by weight),
(C) methylcellulose 0.2 (% by weight),
-(D) Preservative (paraoxybenzoic acid ester) 0.1-0.5 (wt%),
-(E) perfume 0.001-0.1 (wt%),
(F) Antioxidant (dibutylhydroxytoluene) 0.05 to 0.15 (% by weight),
・ (G) Ethanol 5.0 (% by weight)
(H) Murasakixiji Example 1 concentrate 0.3 (% by weight),
-(I) Purified water was added as said remainder.
(Manufacturing method)
The above (A) to (I) were uniformly dissolved.

(Example 7: Preparation of pack containing mushroom extract)
The pack was formulated using the following ingredients and recipe:
(A) Glycerin 12 (% by weight),
(B) Montmorillonite 10.0 (wt%),
(C) Titanium oxide 8.0 (wt%),
(D) Kaolin 10.0 (wt%),
(E) Preservative (paraoxybenzoic acid ester) 0.1 to 0.5 (% by weight),
-(F) Fragrance 0.001-0.1 (wt%),
(G) antioxidant (dibutylhydroxytoluene) 0.05 to 0.15 (% by weight),
・ (H) Ethanol 5.0 (% by weight)
(I) Horotake mushroom concentrate of Example 2 0.5 (% by weight),
-(J) Ooshiroitotake concentrate of Example 3 0.5 (wt%),
-(K) Purified water was added as said remainder.
(Manufacturing method)
The above (A) to (K) were uniformly dissolved.

(Example 8: Tyrosinase inhibition test)
In order to investigate the whitening effect of the mushroom-derived composition of the present invention, the tyrosinase activity inhibition rate was examined for the concentrates of Example 1, Example 2 and Example 3. A tyrosinase inhibition test was performed using the following test method at a sample concentration of 1 mg / ml for each concentrate.

(Test method)
1. In the phosphate buffer (pH 6.8), tyrosinase 40 U / ml, L-tyrosine 1 mM, and the concentrates of Examples 1, 2 and 3 dissolved in dimethyl sulfoxide, 2.5 mg / ml were dissolved.
2. Incubate at 37 ° C for 60 minutes.
The absorbance value at 3.475 nm was substituted into the following equation to calculate the tyrosinase activity inhibition rate.
Tyrosinase activity inhibition rate = 100 × {(A−B) − (C−D)} / (A−B)
In this formula, A: the absorbance value after 60 minutes of the control reaction,
B: Absorbance value before reaction of control instead of sample,
C: Absorbance value after 60 minutes of reaction of the sample,
D: Absorbance value before the reaction of the sample.

  Tables 1, 2 and 3 show the concentrates of Examples 1, 2, and 3 showing inhibition of tyrosinase activity.

表１および３に示すキノコの子実体、培養液、培養物抽出物はいずれもコントロールよりも高いチロシナーゼ阻害活性を示した。

Mushroom fruit bodies, culture solutions, and culture extracts shown in Tables 1 and 3 all showed higher tyrosinase inhibitory activity than the control.

  As shown in Table 1, when the fruiting body extract of Example 1 was used, kofukisarnokoshitake and mucinella were the ninyotake of Example 1 in which tyrosinase inhibitory activity was conventionally found in the fruiting body extract, and It showed higher tyrosinase inhibitory activity than the fruit body extract of Shogenji. Murasakiximeji, Mukitake, Oyster mushroom, Karakasatake, and Yatakekotake showed higher tyrosinase inhibitory activity than the fruiting body extract of Ningyotake.

  As shown in Table 2, when the culture solution from the liquid culture of Example 2 was used, the oyster mushroom and the maggot were traditionally found to have tyrosinase inhibitory activity in the fruit body extract. , And higher tyrosinase inhibitory activity than the fruit body extract of Shougenji. In addition, the culture solution of Mukitake, Horotake, Oyster mushroom, and Mushroom, showed higher tyrosinase inhibitory activity than the fruiting body extract of Ningyotake.

  As shown in Table 3, when the extract from the liquid culture of the mycelium of Example 3 was used, the tyrosinase inhibitory activity of the fruit body extract was conventionally increased in the fruit body extract of Mukitake, Aragekawaratake, Tsuriganetake, Magojakushi, Kawarihatsu and Ningyotake. It showed higher tyrosinase inhibitory activity than the fruit extract of Ningyotake of Example 1 and the fruit extract of Shogenji. In addition, the extract of Ooshiroitake, Oyster mushroom, and Yatakekotake showed higher tyrosinase inhibitory activity than the fruiting body extract of Ningyotake.

(Example 9: Free radical scavenging action inhibition test)
1,1-diphenyl-2-picrylhydrazyl (hereinafter abbreviated as DPPH) radical scavenging rate measurement test was conducted as follows.

  In order to investigate the free radical scavenging action, the DPPH radical scavenging rate was examined for the concentrates of Example 1, Example 2, and Example 3. For each concentrate, DPPH radical scavenging test was conducted at each sample concentration of 200 μg / ml, 100 μg / ml, and 20 μg / ml. Method (1) DPPH was dissolved in ethanol and adjusted to 0.1 mmol. (2) A sample dissolved in 50% ethanol aqueous solution was dissolved in Tris-HCl buffer (pH 7.4). (3) The solutions of (1) and (2) were mixed 1: 1 and reacted for 20 minutes at 25 ° C. in the dark. (4) The DPPH radical elimination rate was calculated by substituting the absorbance at 517 nm into the following equation.

  DPPH radical scavenging rate = 100 × (AB) / (CD) A: Absorbance value after reaction of sample, B: Absorbance when sample is added and ethanol is added instead of DPPH, C: Control Absorbance after reaction, D: Absorbance when ethanol was added instead of DPPH as a control.

  Tables 4, 5 and 6 show the concentrates of Examples 1, 2, and 3 showing DPPH radical scavenging rates.

表４〜６に示すように、実施例１、実施例２、実施例３の濃縮物はいずれもコントロールよりも高いＤＰＰＨラジカル消去率を示した。

As shown in Tables 4-6, the concentrates of Example 1, Example 2, and Example 3 all exhibited a higher DPPH radical scavenging rate than the control.

  As shown in Table 4, in the fruit body extract of Example 1, Murasakishimeji, Mukitake, Horotake, Tsuriganetake, Kofukisarokoshitake, Sphagnum, oyster mushroom, Karakasatake, Mudinatake, Mushroom and bamboo shoots have antioxidant activity in the fruit body extract. The DPPH radical scavenging rate was higher than that of the extract of Ningyotake and Syougenji of Example 1 which is known to have. The concentrate derived from Kawarihatsu showed higher DPPH radical scavenging rate than the fruiting body extract of Ningyotake.

  As shown in Table 5, when the culture solution from the liquid culture of Example 2 was used, purple mullet, larva, mushroom, garlic, bamboo larvae, hirafusube, aragara kawatake, edible mushrooms, oyster mushrooms, oyster mushrooms, and mushrooms In addition, the DPPH radical scavenging rate was higher than that of the extract of Ningyotake and Syougenji of Example 1, which is known to have an antioxidant action in the fruiting body extract. In addition, the culture solution of Ooshiroirotake, Kofukisarokoshitake, Ningyotake, and Karakasatake showed higher DPPH radical scavenging rate than the fruiting body extract of Ningyotake.

  As shown in Table 6, when the extract from the liquid culture of the mycelium of Example 3 was used, the oyster mushroom, Murasakishimeji, Mukitake, Horotake, Hirafusube, Aragekawaratake, Tsuriganetake, Magella, Ningyotake, Oyster mushroom, and Mushroom Showed a higher DPPH radical scavenging rate than the extract of Ningyotake and Shogenji of Example 1 which is known to have an antioxidant effect in fruiting body extracts. Dust mushrooms, narcissus mushrooms, kofukisarokoshitake mushrooms, mushrooms, and mushroom mushrooms showed higher DPPH radical scavenging rates than the fruiting body extracts of Ningyotake mushrooms.

(Example 10: Inflammation suppression test)
About the concentrate of Example 1, Example 2, and Example 3, the inflammation suppression test was implemented using the mouse ear. The inflammation suppression test was performed by making each concentrate 2 mg in one ear of a mouse. Method (1) 2 mg of a sample was applied as a methanol solution to one ear of a mouse (CD1 system). (2) After 30 minutes, 0.5 μg of 12-ortho-tetradecanoylphorbol-13-acetate (hereinafter abbreviated as TPA) was applied as an acetone solution to both ears of the mouse as a flame retardant. (3) After 7 hours, a disc having a diameter of 6 to 7 mm was punched from both ears of the mouse, and the weight was substituted into the following equation to calculate the inflammation inhibition rate.

Inflammation inhibition rate = 100 × (A−B) / (A−C) A: Weight of ear coated with TPA solution only, B: Weight of ear coated with TPA solution and sample, C: Weight of original ear ( (It was calculated that the weight increased 2.41 times by applying 0.5 μg of TPA solution.)
This inflammation inhibitory effect is indicative of cell proliferative inflammation suppression. Therefore, the inflammation suppression effect confirmed in the present Example is different from the inflammation suppression due to immunosuppression caused by suppression of IgE production.

  Table 7, Table 8, and Table 9 show the concentrates of Examples 1, 2, and 3 that showed inflammation suppressing action.

表７に示されるように、実施例１の濃縮物はムラサキシメジ、ホウロクタケ、ツリガネタ、マゴジャクシ、カワリハツ、ニンギョウタケ、ヒラタケ、ショウゲンジ、カラカサタケ、ムジナタケ、ヤケコゲタケの濃縮物がコントロールよりも高い炎症抑制率を示した。表８に示されるように、実施例２の濃縮物はツキヨタケ、ムキタケ、ホウロクタケ、オオオシロイタケ、ヒラフスベ、アラゲカワラタケ、ツリガネタケ、マゴジャクシ、カワリハツ、ニンギョウタケ、ショウゲンジ、カラカサタケ、ムジナタケ、ヤケコゲタケの濃縮物がコントロールよりも高い炎症抑制率を示した。表９に示されるように、実施例３の濃縮物はいずれもコントロールよりも高い炎症抑制率を示した。

As shown in Table 7, the concentrate of Example 1 has a higher inflammation inhibition rate than the control when the concentrate of Murasakishimeji, Borotake mushroom, garlic, maggot, Kawarihatsu, Ningyotake, oyster mushroom, chrysanthemum, mushroom, bamboo shoot, and mushroom. Indicated. As shown in Table 8, the concentrates of Example 2 are Tsukiyotake, Mukitake, Horotake, Ooshiroitake, Hirafube, Aragekawaratake, Mushroom, Mushroom, Kawarihatsu, Ningyotake, Shogenji, Karakasatake, Mushroom Taketake It showed a higher inflammation suppression rate than the control. As shown in Table 9, all the concentrates of Example 3 showed a higher inflammation suppression rate than the control.

(Example 11: Water retention measurement test)
About the concentrate of Example 1, Example 2, and Example 3, in order to investigate a moisturizing effect, the skin moisture retention measurement test was implemented. Method (1) 40 μl of a 1 mg / ml 50% ethanol aqueous solution was applied to a human forearm 2 cm × 2 cm. (2) The water retention after 5 minutes, 10 minutes, and 15 minutes at room temperature was measured with a water retention meter (SKIN DIGNOSTIC SD27, manufactured by Integral). (3) The water retention rate of the sample was compared with a control to which only 50% ethanol was applied, and the relative values are shown in the table.

  Table 10, Table 11, and Table 12 show the concentrates of Examples 1, 2, and 3 that showed inflammation-inhibiting action.

表１０〜１２に示すように、実施例１、実施例２、実施例３の濃縮物は肌に塗布することで、いずれもコントロールよりも高い保水率を示した。

As shown in Tables 10-12, the concentrates of Example 1, Example 2, and Example 3 all showed a higher water retention rate than the control when applied to the skin.

(Example 12: Monitoring test)
A monitoring test was performed on the cream of Example 4. Method (1) 16 male and female monitors (11 females, 5 males) aged 20 to 50 years old were asked to use it on the face twice a day for two months. (2) Two months later, the questionnaire results were tabulated according to the following evaluation criteria, and compared with the extract of the prescription example 1 and the control cream with no culture solution added.

  [Evaluation criteria for whitening effect] A Effective for improving pigmentation such as spots and blackening after sunburn. B Slightly effective in improving pigmentation such as spots and darkening after sunburn. C Not effective in improving pigmentation such as spots and darkening after sunburn.

  [Evaluation criteria for free radical scavenging action] A Effective for improving skin aging such as wrinkles and tarmi. B Slightly effective in improving skin aging such as wrinkles and tarmi. C Invalid for improving skin aging such as wrinkles and tarmi.

  [Evaluation criteria for anti-inflammatory action] A Effective for improving rough skin and inflammation. B Slightly effective in improving rough skin and inflammation. C Invalid for improving rough skin and inflammation.

  [Evaluation criteria for moisturizing action] A Effective for improving moisture. B Slightly effective in improving moisture. C Invalid for moisture improvement.

  Table 13 shows the results of the prescription example 1 and the control monitoring test.

モニタリングテストより、処方例１のクリームはコントロールのクリームと比較して美白作用、フリーラジカル消去作用、抗炎症抑制作用、保湿作用について良好な結果が得られた。

From the monitoring test, the cream of Formulation Example 1 gave better results for the whitening action, free radical scavenging action, anti-inflammatory suppressing action, and moisturizing action than the control cream.

  As mentioned above, although this invention has been illustrated using preferable embodiment of this invention, this invention should not be limited and limited to this embodiment. It is understood that the scope of the present invention should be construed only by the claims. It is understood that those skilled in the art can implement an equivalent range from the description of specific preferred embodiments of the present invention based on the description of the present invention and common general technical knowledge. Patents, patent applications, and documents cited herein should be incorporated by reference in their entirety, as if the contents themselves were specifically described herein. Understood.

Using the mushroom fruiting body, culture solution, and cultured mycelium of the present invention, it is possible to easily prepare a skin external preparation, a whitening agent, a free radical scavenger, an anti-inflammatory agent, and a moisturizing agent.

Claims (5)

Cultured mycelium of C. edulis (Fomes fomentarius (L .: Fr.) Kickx) and Ganoderma neo-japonicum Imaz., And Panellus serotin. ), Coriulus hirsutus (Wul .: Fr.) Quel., Fomes formentarius (L .: Fr.) Kickx, Ganodermaceae, Ganodermae. Rusula cyanoxantha (Schaeff.) Fr.), and the ninnin A whitening agent comprising one or more selected from the group consisting of extracts of cultured mycelium of Gyotake (Albatrellas confluens (A. et S .: Fr.) KOtl. Et Pouz.) .   The whitening agent according to claim 1, which is a powder, a solid or a liquid. A method for preparing a whitening agent, which is described below, 1) As a candidate for obtaining a culture solution of cultured mycelium, Fomes fomentarius (L .: Fr.) Kickx and Ganoderma neo -Japonicum Imaz.), As well as candidates for obtaining extracts of cultured mycelium, Panellus serotinus (Pers .: Kuhn.), Alage kawaratake (Wulf .: Fl.) Qur. ), Fomes formentarius (L .: Fr.) Kickx, Ganoderma neo-japonicum Imaz. (Russula cyanoxantha (Schaeff.) Fr.), and a mushroom selected from the group consisting of Ningyotakenaceae (Albatellalus confluens (A. et S .: Fr.) KOtl. Et Pouz.), Or a species selected from the group consisting of A step of selecting two or more types of mushrooms, and 2) a step of obtaining a culture solution of cultured mycelia or an extract of cultured mycelium from the selected mushrooms,
Including the method.   The extraction is performed using a solvent selected from the group consisting of methanol, ethanol, hexane, benzene, acetone, ethyl acetate, chloroform, dichlorochloroform, diethyl ether, 1,3-butylene glycol, glycerin, propylene glycol, and water. The method of claim 3, wherein the method is performed. Cultured mycelium of C. edulis (Fomes fomentarius (L .: Fr.) Kickx) and Ganoderma neo-japonicum Imaz., And Panellus serotin. ), Coriulus hirsutus (Wul .: Fr.) Quel., Fomes formentarius (L .: Fr.) Kickx, Ganodermaceae, Ganodermae. Rusula cyanoxantha (Schaeff.) Fr.), and the ninnin A tyrosinase comprising one or more selected from the group consisting of extracts of cultured mycelium of Gyotake (Albatrellas confluens (A. et S .: Fr.) KOtl. Et Pouz.) A composition for inhibiting activity.