WO2007004832A1 - Composition comprising an extract of crinum asiaticum linne having anti-allergic and anti-inflammatory activity - Google Patents

Abstract

The present invention is related to a topical composition and cosmetic composition comprising an extract of Crinum asiaticum Linne as an active ingredient in an amount effective to treat and alleviate allergy and inflammatory diseases. The extract of Crinum asiaticum Linne is very useful in the alleviation or treatment of allergy and inflammatory disease as a form of topical medicament or cosmetic composition.

Description

Description

COMPOSITION COMPRISING AN EXTRACT OF CRINUM ASIATICUM LINNE HAVING ANTI-ALLERGIC AND ANTIINFLAMMATORY ACTIVITY

Technical Field

[1] The present invention is related to a cosmetic and topical composition comprising the extract of Crinum asiaticum Linne having anti-allergic and anti-inflammatory activity

[2]

Background Art

[3] Allergic diseases, a hyper-sensitivity caused by unbalanced immune system is representative biochemical phenomenon showing specific response to outer antigen, such as anaphylaxis, allergic rhinitis, asthma, atopic dermatitis, food allergies and urticaria, which inflicts on from 10 to 40% of the population in many countries and the disease are increasing recently.

[4] Normal human immune system maintains the balance between ThI response controlling cellular immunity and Th2 response controlling humoral immunity, however if the balance is broken, these imbalance due to overproduction of Th2 response results in abnormal response such as excessive increase of blood IgE, histamine release etc in allergic patient. Various factors, i.e., interleukins such as in- terleukin 4, 5, 6 and FM-CSF etc are released when it is exposed to the outer antigen. Those cytokines are reacted with B-lymphocyte in lymphoid gland and the lymphocyte modifies blood plasma cell to release IgE antibody. IgE antibody mediates inflammatory response by serial process, i.e., the antibody is attached to mast cell and eosinophil which causes to release various factors, for example, histamine, serotonin, leucotriene B4, C4, D4, E4, PAF, prostaglandin D, cytokines such as IL-I, IL-3, IL-4, IL-5 and IL-6, GM-CSF, TNF-a, bradykinin etc.

[5] It has been reported that the agent to prevent and to treat allergic disease, shall inhibit excessive Th2 response, effectively induce ThI response, stabilize T immune response, and block the IgE-mediated inflammatory response by directly or indirectly acting on B cell reproducing excessive IgE (J. Allergy. Clin. Immunol, 115(3). pp459-465, 2005; J. Allergy. Clin. Immunol, 113(5). pp983-986, 2004).

[6] Various outer stress, for example, UV or oxidative stress such as oxygen radical, free radical etc, activates inflammatory factors resulting in various disease or skin aging. The inflammation is characterized by the increase of oxygen addition reaction of arachidonic acid metabolized through 5-lypoxygenase pathway reproducing leucotriene and cycloxygenase pathway reproducing prostaglandin, of which enzymes have been a main target to develop anti-inflammatory drugs. Cycloxygenase-2, one of two cycloxygenases plays important roles in inflammatory process and the inhibition of cyclooxygenase-2 is effective strategy to develop anti-inflammatory drugs without irreversible adverse reaction caused by the inhibition of cycloxygenase- 1 ( Prostaglands lekot. Essent, Fatty Acids, 69f5^*>. pp329-337, 2003; Neurosurgery, 56Gt. pp590-604, 2005).

[7] Nitric oxide (NO), a potent inflammatory mediator, is reproduced from L-arginine by the action of NOS enzyme and occurs in many types of cells caused by various stimuli, i.e., stress such as UV, endotoxin, cytokines etc. Those inflammatory stimuli increase the expression of inducible-NOS in the cell, reproduce NO and activate macrophage, which results in inflammatory response (Biochem. Pharmacol. 42, ppl849-1857, 1991).

[8] Interleukin-8 (IL-8) is a chemotaxic factor reproduced in several cells, for example, monocyte, fibroblast, endothelial cell, keratinocyte and the production of IL-8 in endothelial cell is induced by IL-I, TNF (Tumor necrosis Factor) or lipopoly saccharide. It induces histamine release from basophilic cell as well as induces the release of lysosomal enzyme from neutrophil in both normal and atopic subjects. Moreover, it increases the surface expression of Mac-1 (CDllb/CD18) in neutrophil without new protein synthesis, which contributes the attachment of neutrophil to vascular endothelial cell.

[9] Conventionally available agents to treat inflammation and allergy diseases can be classified into four categories, i.e., (1) Steroidal anti-inflammatory agent (2) NSAID (Non-steroidal anti-inflammatory drug) (3) anti-histamine (4) anti-leucotrienes. The former agents among them, i.e., (1) and (2) have various side effects such as vomiting, growth retardation, osteoporosis etc in long-term treatment in spite of their potent immune inhibitory activities and the latter agents among them, i.e., (3) and (4) also have various side effects such as drowsiness, vertigo etc in spite of their temporal alleviating activities.

[10] Accordingly, there has been still needed to develop more effective drugs and cosmetics in treating and alleviating allergy and inflammation diseases without side effect than conventionally used drugs till now.

[11] Crinum asiaticum Linne is distributed at seashore region in Korea, tropical Asian countries, Japan, North America etc and it has been reported that the root extract of Crinum asiaticum Linne comprises alkaloids, amino acids etc (Chung B. S et al, Do- haehyangyakdaesajeon, Youngrimsa, 2ⁿ Ed. pl97-198, 1998).

[12] However, there has been not reported or disclosed on the preventing or alleviating activity of an extract of Crinum asiaticum Linne showing potent anti-allergy and anti- inflammatory effects in any of above cited literatures, and the disclosures of which are incorporated herein by reference

[13] To investigate the anti-allergy and anti-inflammatory effect of an extract of Crinum asiaticum Linne, distributed in Cheju island, the inventors of present invention have intensively carried out various experiments including in vitro experiments such as inhibitory test on iNOS and COX2 gene expression, PGE2, IL-6, IL-8 production and degranulation of mast cell, animal model experiments such as anti-allergy test, carrageenan-induced rat-paw-edema inhibition test, arachinodonic acid induced mouse-ear-edema test together with clinical test such as patch test. As a result of these investigations, the inventors finally completed the present invention by confirming that an extract of Crinum asiaticum Linne, strongly inhibited and alleviated both of allergy and inflammation disease.

[14]

Disclosure of Invention Technical Problem

[15] Accordingly, there have been still needed to discover more effective drug to treat and prevent alleviate allergy and inflammatory diseases without toxicity till now. Technical Solution

[16] Accordingly, it is an object of the present invention to provide a topical composition comprising an extract of Crinum asiaticum Linne as an active ingredient in an amount effective to treat and alleviate allergy and inflammatory diseases.

[17] The term "extract" disclosed herein comprises the extract which can be extracted with at least one solvent selected from water, C -C lower alkyl alcohol such as methanol, ethanol, butanol etc, propylene glycol, glycerin, ethyl acetate, butylenes glycol, ether, or chloroform, preferably, water, methanol, ethanol, more preferably, ethanol.

[18] The term Crinum asiaticum Linne disclosed herein comprises all the species cultivated or distributed in Korea, tropical Asian countries, Japan, North America etc, preferably, Korea, more preferably, Cheju island in Korea.

[19] The term "allergy disease" disclosed herein comprises the disease selected from anaphylaxis, allergic rhinitis, asthma, food allergies and urticaria, preferably, urticaria, and the term "inflammation disease" disclosed herein comprises skin disease selected from dermatitis such as atopic dermatitis, contact dermatitis, cradle cap, diaper rash, windburn etc, pimple, psoriasis, eczema, preferably, dermatitis, psoriasis or eczema.

[20]

[21] An inventive extract may be prepared in accordance with the following preferred embodiment. [22] For the present invention, the above described extract can be prepared by follows;

[23] For example, the dried root or stem of Crinum asiaticum Linne is sliced into small pieces. The pieces is mixed with about 1 to 30-fold, preferably, 3 to 10-fold volume of distilled water, alcohols such as methanol, ethanol and the like, or the mixtures thereof, preferably, ethanol; and is extracted at the temperature ranging from 10°C to 120°C, preferably 15 to 80°C, for the period ranging from about 0.5 hour to 10 days, preferably 3 hour to seven days with 2 to 5 times, by sonication, reflux or conventional extraction, preferably, reflux extraction to obtain herbal extract. The herbal extract is filtered and concentrated at 40 to 80°C under reduced pressure. The extract is concentrated and then dried by freeze drying or vacuum drying to obtain purposed extract.

[24] It is another object of the present invention to provide a process for preparing an extract of Crinum asiaticum Linne as described above.

[25]

[26] In accordance with another aspect of the present invention, there is also provided a method of treating and alleviating allergy and inflammatory diseases in a mammal comprising topically administering to said mammal an effective amount of an extract of Crinum asiaticum Linne.

[27] In accordance with the other aspect of the present invention, there is also provided a use of an extract of Crinum asiaticum Linne for manufacture of topical preparation employed for treating and alleviating allergy and inflammatory diseases in mammals including human as an active ingredient.

[28]

[29] The inventive composition may additionally comprise conventional carrier, adjuvants or diluents in accordance with a using method. It is preferable that said carrier is used as appropriate substance according to the usage and application method, but it is not limited. Appropriate diluents are listed in the written text of Remington's Pharmaceutical Science (Mack Publishing co, Easton PA).

[30]

[31] Hereinafter, the following formulation methods and excipients are merely exemplary and in no way limit the invention.

[32]

[33] The inventive composition according to the present invention can be provided as a topical composition containing pharmaceutically acceptable carriers, adjuvants or diluents, e.g., lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starches, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxy benzoate, propylhydroxy benzoate, talc, magnesium stearate and mineral oil. The formulations may additionally include fillers, anti-agglutinating agents, lubricating agents, wetting agents, flavoring agents, emulsifϊers, preservatives and the like. The compositions of the invention may be formulated so as to provide quick, sustained or delayed release of the active ingredient after their administration to a patient by employing any of the procedures well known in the art.

[34] For topical administration, the inventive extract of the present invention can be formulated in the form of ointments and creams including topical preparation such as cream, ointment, lotion, gel, balm, patch, paste, spray solution, aerosol and the like.

[35]

[36] The inventive composition of the present invention in pharmaceutical dosage forms may be used in the form of their pharmaceutically acceptable salts, and also may be used alone or in appropriate association, as well as in combination with other pharmaceutically active compounds.

[37]

[38] The desirably effective amount of the inventive extract or composition varies depending on the condition and the weight of the subject, severity, drug form, route and period of administration, and may be chosen by those skilled in the art. However, in order to obtain desirable effects, it is generally recommended to topically administer at the amount ranging 0.01-lOg/kg, preferably, 1 to 5g/kg by weight/day of the inventive extract of the present invention. The dose may be administered in a single or multiple doses per day. In terms of composition, the inventive extract should be present between 0.01 to 80% by weight, preferably 0.5 to 50% by weight based on the total weight of the composition.

[39]

[40] The present inventors demonstrated that the anti-allergy and anti-inflammatory effects of inventive composition is potent by accomplishing in vitro experiments such as inhibitory test on iNOS and COX2 gene expression, the production of PGE2, IL-6 and IL-8 and degranulation of mast cell, animal model experiments such as anti-allergy test, carageenan-induced rat-paw-edema inhibition test, arachinodonic acid induced mouse-ear-edema test together with human clinical test such as patch test., therefore it is confirmed that above described extract is very useful in the alleviation or treatment of allergy and inflammatory disease as a form of topical medicament or cosmetic composition.

[41] It is the other object of the present invention to provide a cosmetic composition comprising an extract of Crinum asiaticum Linne as an active ingredient in an amount effective to treat and alleviate allergy and inflammatory diseases.

[42] It is preferable that the present cosmetic composition contains 0.001-40%, more preferably, 0.01- 10% by the weight of the inventive composition based on the total weight of the composition. The other components may be a mixture of the ingredients of a conventional cosmetic composition well known in the art.

[43]

[44] Cosmetic formulations containing above composition may be prepared in any form such as skin lotion, skin softner, skin toner, astringent, lotion, milk lotion, moisture lotion, nutrient lotion, massage cream, nutrient cream, moisture cream, hand cream, foundation, essence, nutrient essence, pack, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, treatment, beauty solution and the like.

[45] Hereinafter, the following formulation methods and excipients are merely exemplary and in no way limit the invention.

[46]

[47] The cosmetic composition of the present invention can comprises additional additives selected from the group consisting of water soluble vitamin, lipid soluble vitamin, peptide polymer, polysaccharide polymer, sphingolipid and sea-weed extract.

[48] Preferable water soluble vitamins are any one which can be mixed with cosmetic, however, various vitamin such as vitamin B 1 , B2 , B 6 , pyridoxine, pyridoxine HCl, vitamin B , pantothenic acid, nicotinic acid, nicotinamide, folic acid, vitamin C, vitamin H etc, the salt thereof such as thiamin HCl salt, ascorbic acid Na salt etc or their derivatives such as ascorbic acid-2-phosphonic acid Na salt, ascorbic acid- 2-phosphonic acid Mg salt are preferable and those can be obtained by conventional method such as microbial conversion method, purification method from the microbial cultivates, enzymatic method or chemical synthetic method.

[49] Preferable lipid soluble vitamins are any one which can be mixed with cosmetic, however, various vitamin such as vitamin A, D , D , E (dl-a-tocopherol, d- a-tocopherol, d-d-tocopherol) and their derivatives such as palmitic acid ascorbate, stearic acid ascorbate, dipalmitic acid ascorbate, acetic acid- dl-a-tocopherol, nicotinic acid dl-a-tocopherol vitamin E, dl-pantothenyl alcohol, D-pantothenyl alcohol, pantothenyl ethylether etc. including the lipid soluble vitamin used in examples of present invention are preferable and those can be obtained by conventional method such as microbial conversion method, purification method from the microbial cultivates, enzymatic method or chemical synthetic method.

[50] Preferable peptide polymers are any one which can be mixed with cosmetic, however, collagen, hydrolysable collagen, gelatin, elastin, hydrolysable gelatin, keratin etc. including the peptide polymer used in examples of present invention are preferable.

[51] Preferable polysaccharide polymers are any one which can be mixed with cosmetic, however, hydroxy ethyl cellulose, xanthin gum, hyaluronic acid Na, chondroitin sulfate or their salt (Na salt etc) and the like are preferable. For example, chondroitin sulfate or the salt thereof etc can be used by being purified from mammal or fishes ordinarily. [52] Preferable sphingolipid are any one which can be mixed with cosmetic, however, ceramide, pit-sphingosin, sphingo-lipopolysaccharide and the like are preferable. Sphingo-lipid can be obtained by being purified from mammal, fish, shellfish, yeast or plant etc in conventional method.

[53] Preferable seaweed extract is any one which can be mixed with cosmetic, however, the extract of brown algae, red algae, green algae and the like or the purified carrageenan, alginic acid, arginic acid Na, K isolated therefrom are preferable. Algae extract can be obtained by being purified from seaweed in conventional method.

[54] The cosmetic composition of the present invention may combine with other ingredients used in conventional cosmetic composition, if necessary, together with above described essential ingredient.

[55] Preferable above described other ingredients may comprise oil ingredient, humectants, emollients, surfactants, organic or inorganic dye, organic powder, ultraviolet ray absorbing agent, preservatives, antiseptics, antioxidants, plant extract, pH controller, alcohol, pigments, perfumes, refrigerants, blood circulator, antihidrotic, distilled water etc.

[56] Preferable oil ingredients may comprise ester oil, hydrocarbon oil, silicone oil, fluoride oil, animal oil, plant oil and so on.

[57] Preferable ester oil described above may comprise glyceryl tri-2-ethyl hexanoic acid, cetyl 2-ethyl hexanoic acid, isopropyl myristic acid, butyl myristic acid, isopropyl palmitic acid, ethyl stearic acid, octyl palmitic acid, isocetyl isostearic acid, butyl stearic acid, ethyl linoleic acid, isopropyl linoleic acid, ethyl oleic acid, isocetyl myristic acid, isostearyl myristic acid, isostearyl palmitic acid, octyldodecyl myristic acid, isocetyl isostearic acid, diethyl sebasic acid, isopropyl adipic acid, isoalkyl neopetanoic acid, glyceryl tri(capryl, capric acid), trimethylopropane tri-2-ethyl hexanoic acid, trimethylopropane triisostearic acid, pentaerythritol tetra-2 ethyl hexanoic acid, cetyl caprylic acid, decyl lauric acid, hexyl lauric acid, decyl myristic acid, myristyl myristic acid, cetyl myristic acid, stearyl stearic acid, decyl oleic acid, cetyl licinoleic acid, isostearyl lauric acid, isotridecyl myristic acid, isocetyl palmitic acid, octyl stearic acid, isocetyl stearic acid, isodecyl oleic acid, octyldodecyl oleic acid, octyldodecyl linoleic acid, isopropyl isostearic acid, cetostearyl 2-ethyl hexanoic acid, stearyl 2-ethyl hexanoic acid, hexyl isostearic acid, ethylene glycol dioctanoic acid, ethylene glycol dioleic acid, propylene glycol dicapric acid, propylene glycol di(capryl, capric acid), propylene glycol dicaprylic acid, neopentylglycol dicapric acid, neopentylglycol dioctanoic acid, glyceryl tricaprylic acid, glyceryl triundecylic acid, glyceryl triisopalmitic acid, glyceryl triisostearic acid, octyldodecyl neopentanoic acid, isostearyl octanoic acid, octyl isononanoic acid, hexyldecyl neodecanoic acid, octyldodecyl neodecanoic acid, isocetyl isostearic acid, isostearyl isostearic acid, octyldecyl isostearic acid, polyglycerin oleanoic acid ester, polyglycerin isostearic acid ester, triisocetyl citric acid, triisoalkyl citric acid, triisooctyl citric acid, lauryl lactic acid, myristyl lactic acid, cetyl lactic acid, octyldecyl lactic acid, triethyl citric acid, acetyltriethyl citric acid, acetyl tributyl citric acid, trioctyl citric acid, diisostearyl maleic acid, di 2-ethylhexyl hydroxy stearic acid, 2-ethyl hexyl succinic acid, diisobutyl adipic acid, diisopropyl sebasinic acid, dioctyl sebacinic acid, cholesteryl stearic acid, cholesteryl isostearic acid, cholesteryl hydroxy stearic acid, cholesteryl hydroxy stearic acid, cholesteryl oleic acid, dihydrocholesteryl oleic acid, pitsteryl isostearic acid, pitsteryl oleic acid, isocetyl 12-stealoyl hydroxy stearic acid, stearyl 12-stealoyl hydroxy stearic acid, isostearyl 12-stealoyl hydroxy stearic acid.

[58] Preferable hydrocarbon oil described above may comprise squalene, liquid paraffin, α-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybuden, micro- crystalline wax, vaselin and the like.

[59] Preferable silicone oil may comprise polymethylsilicone, methylphenylsilicone, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dode- camethylcyclosiloxane, dimethyl siloxane-methyl cetyloxysiloxan copolymer, dimethyl siloxane-methyl stealoxysiloxane copolymer, alkyl modified silicone oil, amino modified silicone oil and the like.

[60] Preferable fluoride oil can comprise perfluoropolyether and the like.

[61] Preferable animal or plant oil can comprise avocado oil, almond oil, olive oil, sesame oil, rice husk oil, safflower oil, soy-bean oil, corn oil, rape oil, amygdalin oil, palm kernel oil, palm oil, pimaja oil, sunflower oil, fruite seed oil, cotton seed oil, coconut palm oil cucui nut oil, wheat embryo bud oil, rice embryo bud oil, sia butter, evening-primrose oil, marker daymia nut oil, medo home oil, egg yolk oil, lanolin, hempseed oil, mink oil, orange nippy oil, hohoba oil, carnawa wax, liquid lanolin, solid pimaja wax and the like.

[62] Preferable humectants can comprise water-soluble low molecular humectants, lipophilic low molecular humectants, water-soluble polymer and lipid soluble polymer.

[63] Specifically, preferable water soluble low molecular humectants can comprise cerin, glutamine, sorbitol, mannitol, pyrrolidone-carboxylic acid Na, glycerin, propylene glycol, 1,3-butylene glycol, ethylene glycol, polyethylene glycol (polymerization index. >2), polypropylene glycol (polymerization index >2), lactic acid, lactate salt and the like.

[64] Preferable lipid soluble low molecular humectants can comprise cholesterol, cholesteryl ester and the like.

[65] Preferable water soluble polymer can comprise carboxy vinyl polymer, poly asparaginic acid salt, tragacanth, xanthin gum, HMC (hydroxy methyl celluose), HEC (hydroxy ethyl celluose), HPC (hydroxy propyl celluose), carboxymethylcellulose, water soluble chitin, chitosan, dextrin and the like.

[66] Preferable lipid soluble polymer can comprise polyvinylpyrrolidone-eicocene copolymer, polyvinylpyrrolidone-hexadecene copolymer, nitrocellulose, dextrin fatty acid ester, silicone polymer and the like.

[67] Preferable emollients can comprise long chain acyl glutamic acid cholesteryl ester, cholesteryl hydroxy stearic acid, 12-hydroxy stearic acid, rogic acid, lanolin fatty acid cholesteryl ester and the like.

[68] Preferable surfactant can comprise nonionic surfactants, anionic surfactants, cationic surfactants, ambivalent surfactants and the like.

[69] Specifically, preferable non-ionic surfactants can comprise self-emulsified monostearic acid glycerin, propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, polyoxyethylene (POE) sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE solid pimaja oil, POE pimaja oil, POE-POP copolymer, POE-POP alkyl ether, polyether modified silicone, lauric acid alkanol amide, alkyl amine oxide, hydrogen addition soybean phospholipid and the like.

[70] Preferable anionic surfactants can comprise fatty acid soap, a-acyl sulfonic acid salt, alkyl sulfonic acid salt, alkyl ally sulfonic acid, alkyl naphthalene sulfonic acid salt, alkyl sulfonic acid salt, POE alkylether sulfate salt, alkyl amide sulfate salt, alkyl phosphate salt, POE alkyl phosphate salt, alkylamide phosphate salt, alkyloylalkyl taurine salt, N-acyl-amino acid salt, POE alkyl ether carboxylic acid salt, alkyl sulfo succinic aid salt, alkyl sulfo-acetic acid salt, acylated hydrolysable collagen peptide salt, perfluoro alkyl phosphate ester and the like.

[71] Preferable cationic surfactant can comprise alkyl trimethyl ammonium chloride, stearyl trimethyl ammonium chloride, stearyl trimethyl ammonium bromide, se- tostearyltrimethyl ammonium chloride, distearyl dimethyl ammonium chloride, stearyl dimethyl benzyl ammonium chloride, vehenyltrimethyl ammonium bromide, ben- zalkonium chloride, diethylamino ethyl amide stearic acid, dimethylaminopropyl amide stearic acid, lanolin derivatives quaternary ammonium and the like.

[72] Preferable ambivalent surfactants can comprise carboxy betaine type, amide betaine type, hydroxy sulfo betaine type, phosphobetaine type, aminocarboxylic acid, imidazoline derivatives type, amide amine type and the like.

[73] Preferable organic and inorganic dyes can comprise silicic acid, anhydrous silicic acid, magnesium silicic acid, talc, ceracyte, mica, caolin, bengala, clay, bentonite, titan film mica, oxy chlorine bismuth, zirconium oxide, magnesium oxide, zinc oxide, titan oxide, aluminium oxide, calcium sulfate, barium sulfate, magnesium sulfate, calcium carbonate, magnesium carbonate, ferrous oxide, chromium oxide, chromium hydroxide, calamine, carbon black and the complex thereof as an inorganic dyes; polyamide, polyester, polypropylene, polystyrene, polyurethane, vinyl resin, urea resin, phenol resin, fluoride resin, silicone resin, acryl resin, melamine resin, epoxy resin, polycarbonated resin, divinyl benzene-styrene copolymer, silk powder, cellulose, CI pigment yellow, CI pigment orange as an organic dyes; and their complex etc.

[74] Preferable organic powder can comprise metal soap such as calcium stearate; alkyl phosphonate metal salt such as sodium zinc cetylic acid, zinc laurylic acid, calcium laurylic acid; acylamino acid polyvalent metal salt such as calcium N- lauroyl-b-alanine, zinc N-lauroyl-b-alanine, calcium N-lauroyl-glycine etc.; amide sulfonic acid polyvalent metal salt such as calcium N-lauroyl-taurine, calcium N- palmitoyl-taurine; N-acyl basic amino acid such as Nε-lauroyl-L-lysine, Nε- palmitoyl-lysine, Na-palmitoyl ornitine, Na-lauroly arginine, hardened lanolin fatty acid acyl arginine and the like; N-acylpolypeptide such as N-lauroylglycyl glycine; a- amino fatty acid such as a-amino caprylic acid, a-amino lauric acid and the like; polyethylene, polypropylene, nylon, polymethylmetacrylate, polystyrene, di- vinylbenzene-styrene copolymer, ethylene tetrafluoride and so on.

[75] Preferable ultraviolet absorbing agents can comprise paraaminobenzoic acid, paraa- monoethyl benzoate, paraamino amyl benzoate, paraamino octyl benzoate, ethyleneglycol salicylate, phenyl salicylate, octyl salicylate, benzyl salicylate, butylphenyl salicylate, homomentyl salicylate, benzyl cinnamic acid, paramethoxy 2-ethoxy ethyl cinnamic acid, paramethoxy octyl cinnamic acid, diparamethoxy mono- 2-ethylhexane glyceryl cinnamic acid, paramethoxy isopropyl cinnamic acid, di- isopropyl-diisopropyl cinnamate ester mixture, urokanic acid, ethyl urokanic acid, hydroxy methoxy benzophenone, hydroxymethoxy benzophenone sulfonic acid and their salt, dihydroxy methoxy benzophenone, dihydroxy methoxy benzophenone disulfonate Na, dihydroxy benzophenone, tetrahydroxybenzophenone, A-tert - butyl-4'-methoxydibenzoylmethane, 2,4,6-trianilino-p -

(carbo-2'-ethylhexyl- 1 '-oxy)- 1 ,3,5-triazine, 2-(2-hydroxy-5-methylphenyl) ben- zotriazole and the like.

[76] Preferable preservatives can comprise hinokitiol, trichloric acid, trichlorohydroxy- diphenylether, chlorohexidine glucuronate, phenoxyethanol, resorcine, isopropyl- methylphenol, azulene, salicylic acid, zinc pilithione, bezalconium HCl, photo- sensitizer 301, mononitroguaiacol Na, undecylenic acid etc.

[77] Preferable antioxidants can comprise butylhydroxyanisole, propyl gallate, el- lisorbate and the like.

[78] Preferable pH controller can comprise citric acid, sodium citrate, malic acid, sodium malate, fumaric acid, sodium fumaric acid, succinic acid, sodium succinic acid, sodium hydroxide, sodium hydrogen phosphate and the like.

[79] Preferable alcohol can comprise cetyl alcohol etc. [80] Furthermore, other ingredient addable to above described component and the amount thereof is not limited within the scope of the purpose and effect of the present invention, however, it is preferable that the amount of the other ingredients ranges from 0.01 to 5%, more preferably, 0.01 to 3% in that of total composition.

[81] The cosmetic composition of the present invention can be modified as a solution, emulsion, cohesive mixture etc.

[82] Above described ingredients such as water-soluble vitamin, lipid soluble vitamin, peptide polymer, polysaccharide polymer, sphingolipid, sea weed extract and addable ingredients which can be added other than above described ingredients if necessary, can be obtained by conventional methods disclosed in the literature (Matsumoto Mithio; Manual for the development of transdermal applied preparation. Seisi Press, 1^st Ed., 1985).

[83] Inventive compounds of the present invention have no toxicity and adverse effect therefore, they can be used with safe.

[84] It will be apparent to those skilled in the art that various modifications and variations can be made in the compositions, use and preparations of the present invention without departing from the spirit or scope of the invention.

[85]

[86]

Advantageous Effects

[87] The present invention providesa topical composition and cosmetic composition comprising an extract of Crinum asiaticum Linne as an active ingredient in an amount effective to treat and alleviate allergy and inflammatory diseases. Best Mode for Carrying Out the Invention

[88] It will be apparent to those skilled in the art that various modifications and variations can be made in the compositions, use and preparations of the present invention without departing from the spirit or scope of the invention.

[89]

[90] The present invention is more specifically explained by the following examples.

However, it should be understood that the present invention is not limited to these examples in any manner.

[91]

Mode for the Invention

[92] The following Reference Example, Examples and Experimental Examples are intended to further illustrate the present invention without limiting its scope.

[93]

[94] Example 1. The preparation of inventive extract according to various extraction solvent

[95] 1-1. inventive extract (1)

[96] 60Og of dried root of Crinum asiaticum Linne cut into small pieces, mixed with 2.5kg of 30% aqueous butylenes glycol and the mixture was subjected to extraction with stirring at room temperature for 7 days. After successive filtration of the extract through 400 mesh filter cloth and then filter paper (pore size, 0.45 μm) to remove the debris, 2.26 kg of inventive extract (1) was obtained. (17.5 g of powder as dried basis, yield 2.92%)

[97] [98] 1-2. inventive extract (2)-(9) [99] Except adopting different solvents disclosed in Table 1 from that of Example 1-1, all the procedure was identical with those of Example 1-1 to obtain various inventive extract of Crinum asiaticum Linne., i.e., inventive extract (2) to inventive extract (9) of the present invention.

[100] [101]

[102] 1-3. inventive extract (10) [103] lkg of dried stem of Crinum asiaticum Linne cut into small pieces, mixed with 3kg of 70% ethanol and the mixture was subjected to extraction with stirring at room temperature for 7 days. After successive filtration of the extract through 400 mesh filter cloth and then filter paper (pore size, 0.45 μm) to remove the debris, 2.81 kg of inventiveextract (10) was obtained. (22.7 g of powder as dried basis, yield 3.78%)

[104] [105] 1-4. inventive extract (11) [106] 60Og of dried root of Crinum asiaticum Linne cut into small pieces and mixed with 2.5kg of 30% aqueous butylenes glycol. The mixture was subjected to reflux extraction with stirring at 80°C for 3 hours and slowly cooled to R.T. After successive filtration of the extract through 400 mesh filter cloth and then filter paper (pore size, 0.45 μm) to remove the debris, 2.38 kg of inventive extract (11) was obtained. (20.7 g of powder as dried basis, yield 3.45%)

[107] [108] 1-5. inventive extract (12)-(19) [109] Except adopting different solvents disclosed in Table 2 from that of Example 1-4, all the procedure was identical with those of Example 1-4 to obtain various inventive extract of Crinum asiaticum Linne., i.e., inventive extract (12) to inventive extract (19) of the present invention.

[HO] Table 2

[111] 1-6. inventive extract (20) [112] 1 kg of dried stem of Crinum asiaticum Linne cut into small pieces and mixed with 3kg of 70% ethanol. The mixture was subjected to reflux extraction with stirring at 80°C for 3 hours and slowly cooled to R.T. After successive filtration of the extract through 400 mesh filter cloth and then filter paper (pore size, 0.45 μm) to remove the debris, 2.81 kg of inventive extract (20) was obtained. (30.7 g of powder as dried basis, yield 5.12%)

[113] [114] 1-7. inventive extract (21) [115] 600 g of dried root of Crinum asiaticum Linne cut into small pieces and mixed with 2.5 kg of 100% ethanol. The mixture was subjected to reflux extraction with stirring at 70°C for 3 hours and slowly cooled to R.T. After filtration of the extract through filter paper (Whatman No. 5) to remove the debris, the filtrate was concentrated by rotary evaporator under reduced pressure and dried with freezing dryer to obtain 22.98 g of dried inventive extract (21) of Crinum asiaticum Linne (yield: 3.83%).

[116] [117] [118] 1-8. inventive extract (22)-(24) [119] Except adopting different solvents disclosed in Table 3 from that of Example 1-7, all the procedure was identical with those of Example 1-7 to obtain various extract of Crinum asiaticum Linne., i.e., inventive extract (22) to inventive extract (24) of the present invention.

[120] Table 3

[121] 1-9. inventive extract (25) [122] 1 kg of dried stem of Crinum asiaticum Linne cut into small pieces and mixed with 3 kg of 70% ethanol. The mixture was subjected to reflux extraction with stirring at 70°C for 3 hours and slowly cooled to R.T. After filtration of the extract through filter paper (Whatman No. 5) to remove the debris, the filtrate was concentrated by rotary evaporator under reduced pressure and dried with freezing dryer to obtain 32.1 g of dried inventive extract (25) of Crinum asiaticum Linne(yield: 3.21%).

[123] [124] 1-10. inventive extract (26) [125] 600 g of dried root of Crinum asiaticum Linne cut into small pieces and mixed with 2.5 kg of 100% ethanol adjusted to pH 3.5. The mixture was subjected to reflux extraction with stirring at 70°C for 3 hours and slowly cooled to R.T. After filtration of the extract through filter paper (Whatman No. 5) to remove the debris, the filtrate was concentrated by rotary evaporator under reduced pressure and dried with freezing dryer to obtain 31.44 g of dried inventive extract (26) of Crinum asiaticum Linne(yield: 5.24%).

[126] [127] 1-11. inventive extract (27)-(29) [128] Except adopting different solvents disclosed in Table 4 from that of Example 1-10, all the procedure was identical with those of Example 1-10 to obtain various extract of Crinum asiaticum Linne., i.e., inventive extract (27) to inventive extract (29) of the present invention.

[129] Table 4

[130] Example 2. Preparation of inventive skin lotion composition [131] [132] The inventive skin lotion composition comprising inventive extract (26) of Crinum asiaticum Linne., (Example 2) and the comparative composition which does not comprise inventive extract (Comparative Example 2) to compare were prepared according to the prescription disclosed in Table 5 and both of them were used as test samples in following tests.

[133] Table 5

[134] Example 3. Preparation of inventive nutrition lotion composition (1) [135] The inventive nutrient lotion composition comprising inventive extract (26) of Crinum asiaticum Linne., (Example 3) and the comparative composition which does not comprise an inventive extract (Comparative Example 3) to compare were prepared according to the prescription disclosed in Table 6 and both of them were used as test samples in following tests. [136] Table 6

[137] Example 4. Preparation of inventive nutrition lotion composition (2) [138] [139] The inventive nutrient lotion composition comprising inventive extract (26) of Crinum asiaticum Linne., (Example 4) and the comparative composition which does not comprise an inventive extract (Comparative Example 4) to compare were prepared according to the prescription disclosed in Table 7 and both of them were used as test samples in following tests.

[140] Table 7

[141] Example 5. Preparation of inventive massage cream composition [142] [143] The inventive massage cream composition comprising inventive extract (26) of Crinum asiaticum Linne., (Example 5) and the comparative composition which does not comprise an inventive extract (Comparative Example 5) to compare were prepared according to the prescription disclosed in Table 8 and both of them were used as test samples in following tests.

[144] Table 8

[145] [146] Example 6. Preparation of inventive essence composition [147] [148] The inventive essence composition comprising inventive extract (26) of Crinum asiaticum Linne., (Example 6) and the comparative composition which does not comprise an inventive extract (Comparative Example 6) to compare were prepared according to the prescription disclosed in Table 9 and both of them were used as test samples in following tests.

[149] Table 9

[150] [151] Experimental Example 1. Cytotoxicity assay [152] [153] In order to determine the cytotoxicity of inventive extract, following experiment was performed according to the procedure disclosed in the literature (J. Immunol. Methods, 65Q-21 pp55-63, 1983).

[154] Human fibroblast cell line (ATCC 2706) was inoculated into 24 well plates added with DMEM culture medium containing 10% fetal blood serum (Dubelcco's modified Eagle Medium, BRL, USA) in the concentration of 1x10 cells/ml. 24 hours after the inoculation, the medium was replaced with serum free medium. Various concentration of test samp ^rle was added thereto and incubated in 5% CO 2 incubator at 37°C for one day. After the incubation, the supernatant was removed and 200 μl of 5% PBS solution was added thereto to wash. MTT solution was added to each well in the amount of 1.0 ml/well and 4 h later, the remaining MTT solution was removed. DMSO was added to each well per 1.0 ml/well and the absorbance of each well was determined at 570 nm. The determined cell viability was calculated according to following math figure 1 and the calculated result was shown in Table 10.

[155] MathFigure 1

Ce l l viabi l ity (80 = [0. D _{1 3701n} of test sample/ 0. D . ^ of control ] X 100

[156] Table 10

[157] As can be seen in Table 10, the inventive extract (26) had not shown cytotoxicity until the concentration reached at 100 μg/ml and showed cell proliferating activity at 100 μg/ml on the contrary. However, the cytotoxicity appeared at the concentration of 200 μg/ml.

[158]

[159] Experimental Example 2. Anti-allergy test.

[160]

[161] In order to determine the anti-allergy activity of inventive extract, following experiment was performed according to the procedure disclosed in the literature ( Planta. Med. 64, pp577-578, 1998).

[162]

[163] RBL-2H3 mast cell was inoculated into 24 well plates added with 15% FBS-MEM

(fetal Bovine Serum-modified Eagle Medium, Gibco Ltd.) in the concentration of 1 x 10 cells/ml and attached therewith. 0.5 μg/ml of IgE was added thereto and the medium was incubated 24 h after the incubation. The medium was removed and washed with 0.5 ml of siragianan buffer solution I (pH 7.2) containing 119 mM NaCl, 5 mM KCl, 0.4mM MgCl , 25mM PIPES, 40 mM NaOH. 160 μl of siragianan buffer solution II (pH 7.2) prepared by adding 5.6 mM glucose, ImM CaCl and 0.1% BSA to siraganian buffer solution I, was further added thereto to react at 37°C for 10 minutes. 20 μl of test sample was added thereto and the mixture was reacted at 37°C for 10 minutes. 20 μl of 1 μg/ml DNP-BSA was added thereto and then reacted at 37°C for 30 minutes. The reacted solution was transferred to e-tube to perform centrifugation and the mixture of 20 μl of supernatant and 20 μl of 1 mM p-ni- trophenyl-N-acetyl-β-D-glucosamide were added to 96 well plates to react at 37°C for 1 h. After treating with 200 μl of stopping agent (0.1M Na CO ), the absorbance was determined at 405 nm and the anti-allergy activity was calculated according to following math figure 2. The calculated result was shown in Table 11.

[164] MathFigure 2

Ant i-al lergy act ivity (X)

= [ (0. D ₁ Jc_1511111 of test sample - 0. D ₁J_0511n, of Blank - 0. D ₁J₀₅J₁₁₁₁ of spontaneous) /

(0 D _JOOM, of control - 0 D _405™ of blank - O . D ^,_m of spontaneous] X 100

[165] * Control: group not treated with test sample; Blank: group treated with test sample and substrate only; Spontaneous: non-treated group not treated with DNP-IgE and test sample. [166] Table 11

[167] As can be seen in Table 11, the inventive extract (26) inhibits more than 50% at 25 μg/ml and completely inhibits the degranulation of mast cell at the concentration of 200 μg/ml.

[168] [169] Experimental Example 3. iNOS activity inhibition test. [170] [171] In order to determine the anti-inflammatory activity of inventive extract, following iNOS inhibition test using Raw264.7 cell was performed according to the procedure disclosed in the literature (Anal. Biochem. Y2&, ppl31-138, 1982).

[172] [173] Raw 264.7 cell, a mouse macrophage, was inoculated into 24 well plates added with 10% FBS-DMEM (fetal Bovine Serum-Dulbecco's Modified Eagle Medium, Gibco Ltd.) without phenol-red in the concentration of 8 X 10 cells/ml and attached therewith. One day after the inoculation, various concentrations of samples were added thereto and the medium was incubated for 18 h. 1 μg/ml of lipopolysaccharide (Sigma Co. Ltd) was added thereto and the medium was incubated. 24 h after the incubation, the supernatant was recovered and added to 96 well plates. Equivalent amount of Griess reagent (Sigma Co. Ltd) was added thereto and the solution was softly stirred for 10 minutes at R.T to determine their absorbance at 570nm. Calibration curve was calculated using sodium nitrate as a standard and the formed amount of nitric oxide in each culture medium treated with test samples was determined. The NO production rate (%) of each test sample was calculated comparing with the NO reproduction rate (%) of the group treated with lipopolysaccharide (100%) and the result was shown in Table 12.

[174] Table 12

[175] As can be seen in Table 12, the inventive extract (26) inhibits iNOS activity in a dose dependent manner and the NO reproduction rate at 200 μg/ml was reduced to that of control group treated with medium alone.

[176] [177] Experimental Example 4. inhibitory effect on iNOS and COX2 gene expression.

[178] [179] In order to determine the anti-inflammatory activity of inventive extract, following inhibition test of iNOS and COX2 gene expression using Raw264.7 cell was performed according to the procedure disclosed in the literature (J. Agri. Food Chem., 52, pp71-78, 2004).

[180] [181] Lipoplysaccharide was treated to Raw 264.7 cell, a mouse macrophage, to induce iNOS and COX2 gene expression and the inhibitory activity of test samples was determined by RT-PCR method.

[182] Raw 264.7 cell was inoculated into 100mm dish added with 10% FBS-DMEM (Fetal Bovine Serum- Dulbecco's Modified Eagle Medium, Gibco Ltd.) in the concentration of 8 X 10⁵ cells/ml and attached therewith. One day after the inoculation, various concentrations of samples were added thereto and the medium was incubated for 18 h. 1 μg/ml of lipopolysaccharide (Sigma Co. Ltd) was added thereto and the medium was incubated. 8 h after the incubation, the medium was removed and then 1 ml of trizol reagent (Invitrogen Co. Ltd) was added thereto and the amount of isolated RNA according to the manual of Invirogen Co. Ltd was determined and subjected to RT-PCR method. RT-PCR was performed by following condition:

[183] a) kit: All-in-one RT-PCR kit (Superbio Co. Ltd ); [184] b) iNOS primer; [185] Sense: 5'-CAGTTCTGCGCCTTTGCTCAT-3 [186] Anti-sense: 5'-GGTGGTGCGGCTGGACTTT-3 [187] (condition: reverse-transcription at 50°C for 30 minutes, inactivation of reverse- transcriptase enzyme at 96°C for 3 minutes, PCR reaction with the cycles of 32 cycles/ minute repeating condition, i.e., at 94°C for 30 sec, 60°C for 30 sec, and 72°C for 1 min);

[188] c) COX2 primer; [189] Sense: 5'-CTGAAGCCCACCCCAAAC-3 [190] Anti-sense: 5'-AACCCAGGTCCTCGCTTATG-3 [191] (condition: reverse-transcription at 50°C for 30 minutes, inactivation of reverse- transcriptase enzyme at 96°C for 3 minutes, PCR reaction with the cycles of 32 cycles/ minute repeating condition, i.e., at 94°C for 30 sec, 55°C for 30 sec, and 72°C for 1 min);

[192] d) Actin primer; [193] Sense: 5'-GAGACCTTCAACACCCCAGCC-3 [194] Anti-sense: 5'-GGCCATCTCTTGCTCGAAGTC-3 [195] (condition: reverse-transcription at 50°C for 30 minutes, inactivation of reverse- transcriptase enzyme at 96°C for 3 minutes, PCR reaction with the cycles of 22 cycles/ minute repeating condition, i.e., at 94°C for 1 min, 62°C for 1 min, and 72°C for 1 min);

[196] Table 13

[197] As can be seen in Table 13, the inventive extract (26) inhibits the gene expression of iNOS and COX2 at 100 μg/ml, which level is similar to that of control group. Accordingly, it has been confirmed that the inventive extract has potent anti-inflammatory activity.

[198] [199] Experimental Example 5. inhibiting effect on the production of PGE2, IL-6 and IL-8.

[200] In order to determine the anti-inflammatory activity of inventive extract, following inhibition test of the production of PGE2, IL-6 and IL-8using fibroblast was performed according to the procedure disclosed in Assay kit provider's manual. (PGE2: Assay Design Co. Ltd; ILs: Endogen Co. Ltd)

[201] [202] Human fibroblast cell line (ATCC 2706) was inoculated into 6 well plates in the concentration of 1 x 10 cells/ml and incubated for 24 hours at 37°C in 5% CO incubator. After the incubation, 500 μ ^r M H 2 O 2 was treated thereto to stimulate the cell for 24 h and various concentration of test samples were added thereto to incubate for 48 h. The medium solution was recovered to subject to ELISA assay. The amount of PGE2 and ILs was determined according to the manual using by Assay kit. The inventive extract (17) prepared in Example 1-5 was used as a test sample and the inhibition activity was calculated according to math figure 3. The result was shown in Table 14.

[203] MathFigure 3

Inhibit ion act ivity (%) = {1-ftest sample-control) / (HΛik-control) } x 100

[204] * Test sample: the amount in the group treated with test sample; control: the amount in t hhee ggrroouupp treated with control; H O : the amount in the group treated with H O . [205] Table 14

[206] As can be seen in Table 14, the inventive extract (17) potently inhibited the reproduction of PGE , IL-6 and IL-8. It has been confirmed that the inventive extract reduced the production of IL-6 by about 90% at 100 μg/ml, and IL-8 to less than the level in control at 25 microgram/ml.

[207] [208] Experimental Example 6. Human patch test. [209] [210] In order to determine the treating or alleviating effect of inventive compositions (2)-(6) comparing with comparative compositions (2)-(6) prepared in Examples 2-6 on the skin irritation, following experiment was performed as follows.

[211] [212] 100 healthy male and female volunteers were divided into two groups and 0.2 g of the compositions and 0.08% sodium lauryl sulfate (SLS) solution were patched at each back skin for 24 h. 4 h after the removal of patch, the skin condition was observed by eye and the irritation index was calculated according to math figure 4. The result was shown in Table 15. [213] MathFigure 4

Irr itat ion Index =

{ (The number of (+ -) x 1) + (The number of (+) x 2) + (The number of (++)

x 3) }/ The number of tested persons [214] Table 15

[215] [216] As can be seen in Table 15, the inventive compositions comprising an inventive extract (26) showed more potent irritation- alleviating activity than comparative compositions which do not contain inventive extract.

[217] [218]

Industrial Applicability [219] As described in the present invention, present invention provides a topical composition and cosmetic composition comprising an extract of Crinum asiaticum Linne as an active ingredient in an amount effective to treat and alleviate allergy and inflammatory diseases. The extract of Crinum asiaticum Linne shows potent inhibitory effect on the production of PGE2, IL-6 and IL-8, mast cell degranulation, carrageenan- induced rat-paw-edema, arachinodonic acid induced mouse-ear and human irritated skin, therefore, it is confirmed that the above described extract is very useful in the alleviation or treatment of allergy and inflammatory disease as a form of topical medicament or cosmetic composition.

[220]

[221]

Sequence Listing

[222]

[223] sequence number 1 is sense primer for iNOS :

5'-CAGTTCTGCGCCTTTGCTCAT-S' [224] sequence number 2 is anti sense primer for iNOS

15'-GGTGGTGCGGCTGGACTTT-S'

[225] sequence number 3 is sense primer for COX 2 : 5'-CTGAAGCCCACCCCAAAC-S'

[226] sequence number 4 is anti sense primer for COX 2 :

5'-AACCCAGGTCCTCGCTTATG-S' [227] sequence number 5 is sense primer for Actin :

5'-GAGACCTTCAACACCCCAGCC-S' [228] sequence number 6 is anti sense primer for Actin :

5'-GGCCATCTCTTGCTCGAAGTC-S'

Claims

Claims

[1] A topical composition comprising an extract of Crinum asiaticum Linne as an active ingredient in an amount effective to treat and alleviate allergy and inflammatory diseases.

[2] The topical composition according to claim 1, wherein said extract is extracted with at least one solvent selected from water, C -C lower alkyl alcohol, propylene glycol, glycerin, ethyl acetate, butylene glycol, ether, or chloroform

[3] The topical composition according to claim 1, wherein said allergy disease is selected from atopic dermatitis, anaphylaxis, allergic rhinitis, asthma, food allergies or urticaria.

[4] The topical composition according to claim 1, wherein said inflammation disease is selected from dermatitis, pimple, psoriasis, or eczema.

[5] A use of an extract of Crinum asiaticum Linne for manufacture of topical preparation employed for treating and alleviating allergy and inflammatory diseases in mammals including human as an active ingredient.

[6] A cosmetic composition comprising an extract of Crinum asiaticum Linne as an active ingredient in an amount effective to treat and alleviate allergy and inflammatory diseases.

[7] The cosmetic composition according to claim 6, wherein said extract is extracted with at least one solvent selected from water, C 1 -C 4 lower alkyl alcohol, propylene glycol, glycerin, ethyl acetate, butylene glycol, ether, or chloroform.

[8] The cosmetic composition according to claim 6, wherein said composition is a form selected from skin lotion, skin softner, skin toner, astringent, lotion, milk lotion, moisture lotion, nutrient lotion, massage cream, nutrient cream, moisture cream, hand cream, foundation, essence, nutrient essence, pack, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, treatment, or beauty solution.

[9] The cosmetic composition according to claim 6, wherein said composition contains 0.01- 10% by the weight of the inventive composition based on the total weight of the composition.