the embodiments of the present invention will be described in detail below . the water - dispersible nanoparticle of the present invention is characterized in that it comprises a blood circulation promoter and a biodegradable polymer . specific examples of a blood circulation promoter that can be used in the present invention are described below , but they are not particularly limited thereto as long as blood circulation promoting effects can be exhibited . the term “ blood circulation promotion ” refers to effects of increasing the blood flow resulting from effects of , for example , blood vessel dilation induced by relaxation , enhancement and stimulation of capillary vessels , and temperature increase . preferably , the blood circulation promoter used in the present invention is an ionic substance or fat - soluble substance . in addition , examples of the blood circulation promoter that can be used in the present invention include synthetic substances , plant extracts , vitamins , and sugars . examples of synthetic substances include minoxidil which is known to have effects of anti - hypertensive agents ; finasteride which is known to have effects of anti - prostatic hypertrophy agents ; and carpronium chloride which is known to have effects as a drug for alopecia areatas . examples of plant extracts include swertia japonica extracts obtained from rhizomes and stolons of plants belonging to the family gentianaceae , carrot extracts obtained from rhizomes and stolons of plants belonging to the family araliaceae , sophora angustifolia extracts obtained from rhizomes and stolons of plants belonging to the family leguminosae , peppermint extracts obtained from peppermint leaves and the like , cepharanthine , which is an alkaloid of a plant belonging to the family menispermaceae , cayenne pepper tinctures obtained from cayenne pepper , ginger tinctures obtained from ginger , and garlic extracts extracted from garlic . preferably , vitamins are vitamin b , vitamin e , and derivatives thereof . examples of vitamin e and derivatives thereof include tocopherol , tocopherol acetate , and nicotinic acid tocopherol , which are preferably naturally occurring α - tocopherols . in addition , examples of vitamin b and derivatives thereof include nicotinic acid , nicotinic acid amide , and nicotinic acid benzyl , which are widely existing hydrophilic and hydrophobic substances . preferably , sugars are mucopolysaccharides . specific examples thereof include heparin , which has a blood - coagulation - inhibiting action . preferably , the blood circulation promoter used in the present invention is a tocophenol derivative , a nicotinic acid derivative , cephalanthin , finasteride , minoxidil , or a swertia japonica extract . according to the present invention , a component used as the above blood circulation promoter can be selected from the group consisting of cosmetic components , quasi - drug components , functional - food components , and pharmaceutical product components . the blood circulation promoter used in the present invention may be used alone or in combinations of two or more . according to the present invention , a blood circulation promoter may be added during , before or after the formation of nanoparticle of the biodegradable polymer . the nanoparticle of the present invention preferably contains the blood circulation promoter in an amount of 0 . 1 % to 100 % by weight with respect to the weight of the biodegradable polymer , and more preferably contains the blood circulation promoter in an amount of 0 . 1 % to 50 % by weight with respect to the weight of the biodegradable polymer . the average particle size of the nanoparticle of the present invention is generally 1 to 1000 nm , preferably 10 to 1000 nm , more preferably 10 to 500 nm , and particularly preferably 15 to 400 nm . the biodegradable polymer used in the present invention may be a protein or a biodegradable synthetic polymer . the type of the biodegradable polymer is not particularly limited . however , a protein having a lysine residue and a glutamine residue is preferable . in addition , such protein having a molecular weight of approximately 10 , 000 to 1 , 000 , 000 is preferably used . the origin of the protein is not particularly limited . however , a human - derived protein , is preferably used . specific examples of a protein that can be used include at least one selected from the group consisting of collagen , gelatin , acid - treated gelatin , albumin , ovalbumin , casein , sodium casein , transferrin , globulin , fibroin , fibrin , laminin , fibronectin , and vitronectin . however , the compound used in the present invention is not limited to the aforementioned compounds . in addition , the origin of the protein is not particularly limited . thus , bovine , swine , and fish , as well as recombinant protein of any thereof , can be used . examples of recombinant gelatin that can be used include , but are not limited to , gelatins described in ep1014176 a2 and u . s . pat . no . 6 , 992 , 172 . among them , casein , acid - treated gelatin , collagen , or albumin is preferable . further , casein or acid - treated gelatin is most preferable . when casein is used in the present invention , the origin of the casein is not particularly limited . casein may be milk - derived or bean - derived . any of α - casein , β - casein , γ - casein , and κ - casein , as well as a mixture thereof , can be used . caseins may be used alone or in combinations of two or more . proteins used in the present invention may be used alone or in combinations of two or more . examples of the biodegradable synthetic polymer include polylactic acid , and poly ( lactic - co - glycolic acid ) ( plga ). according to the present invention , a protein can be subjected to crosslinking treatment during and / or after nanoparticle formation . for the crosslinking treatment , an enzyme can be used . any enzyme may be used without particular limitation as long as it has been known to have an action of causing protein crosslinking . among such enzymes , transglutaminase is preferable . transglutaminase may be derived from a mammal or a microorganism . a recombinant transglutaminase can be used . specific examples thereof include the activa series by ajinomoto co ., inc ., commercially available mammalian - derived transglutaminase serving as a reagent , such as guinea pig liver - derived transglutaminase , goat - derived transglutaminase , rabbit - derived transglutaminase , or human - derived recombinant transglutaminase produced by , for example , oriental yeast co ., ltd ., upstate usa inc ., and biodesign international . the amount of an enzyme used for the crosslinking treatment in the present invention can be adequately determined depending upon protein type . in general , an enzyme can be added in a weight that is 0 . 1 % to 100 % and preferably approximately 1 % to 50 % of the protein weight . the duration for an enzymatic crosslinking reaction can be adequately determined depending upon protein type and nanoparticle size . however , in general , the reaction can be carried out for 1 to 72 hours , and preferably 2 to 24 hours . the temperature for an enzymatic crosslinking reaction can be adequately determined depending upon protein type and nanoparticle size . in general , the reaction can be carried out at 0 ° c . to 80 ° c . and preferably at 25 ° c . to 60 ° c . enzymes used in the present invention may be used alone or in combinations of two or more . nanoparticles of the present invention can be prepared in accordance with patent document : jp patent publication ( kokai ) no . 6 - 79168 a ( 1994 ); or c . coester , journal microcapsulation , 2000 , vol . 17 , pp . 187 - 193 , provided that an enzyme is preferably used instead of glutaraldehyde for a crosslinking method . in addition , according to the present invention , the enzymatic crosslinking treatment is preferably carried out in an organic solvent . the organic solvent used herein is preferably an aqueous organic solvent such as ethanol , isopropanol , acetone , or thf . it is also possible to add at least one component selected from the group consisting of lipids ( e . g ., phospholipid ), anionic polysaccharides , cationic polysaccharides , anionic proteins , cationic proteins , and cyclodextrin to the water - dispersible nanoparticle of the present invention . the amounts of lipid ( e . g . phospholipid ), anionic polysaccharide , cationic polysaccharide , anionic protein , cationic protein , and cyclodextrin to be added are not particularly limited . however , they can be added usually in a weight that is 0 . 1 % to 100 % of the protein weight . in the case of the drug delivery agent of the present invention , it is possible to adjust the release rate by changing the ratio of the above components to the protein . specific examples of phospholipids that can be used in the present invention include , but are not limited to , the following compounds : phosphatidylcholine ( lecithin ), phosphatidylethanolamine , phosphatidylserine , phosphatidylinositol , phosphatidylglycerol , diphosphatidylglycerol , and sphingomyelin . anionic polysaccharides that can be used in the present invention are polysaccharides having an acidic polar group such as a carboxyl group , a sulfate group , or a phosphate group . specific examples thereof include , but are not limited to , the following compounds : chondroitin sulfate , dextran sulfate , carboxymethyl cellulose , carboxymethyl dextran , alginic acid , pectin , carrageenan , fucoidan , agaropectin , porphyran , karaya gum , gellan gum , xanthan gum , and hyaluronic acids . cationic polysaccharides that can be used in the present invention are polysaccharides having a basic polar group such as an amino group . examples thereof include , but are not limited to , the following compounds : polysaccharides such as chitin or chitosan , which comprise , as a monosaccharide unit , glucosamine or galactosamine . anionic proteins that can be used in the present invention are proteins and lipoproteins having a more basic isoelectric point than the physiological ph . specific examples thereof include , but are not limited to , the following compounds : polyglutamic acid , polyaspartic acid , lysozyme , cytochrome c , ribonuclease , trypsinogen , chymotrypsinogen , and α - chymotrypsin . cationic proteins that can be used in the present invention are proteins and lipoproteins having a more acidic isoelectric point than the physiological ph . specific examples thereof include , but are not limited to , the following compounds : polylysine , polyarginine , histone , protamine , and ovalbumin . according to the present invention , it is possible to use casein nanoparticles prepared by the following steps ( a ) to ( c ): ( a ) mixing casein with a basic aqueous medium at a ph of from 8 to less than 11 ; ( b ) adding at least one blood circulation promoter to the solution obtained in step ( a ); and ( c ) injecting the solution obtained in step ( b ) into an acidic aqueous medium at a ph of 3 . 5 to 7 . 5 . further , according to the present invention , it is possible to use casein nanoparticles prepared by the following steps ( a ) to ( c ): ( a ) mixing casein with a basic aqueous medium at a ph of from 8 to less than 11 ; ( b ) adding at least one blood circulation promoter to the solution obtained in step ( a ); and ( c ) lowering the ph of the solution obtained in step ( b ) to a ph value that is ph 1 or more away from the isoelectric point , while stirring the solution . according to the present invention , it is possible to prepare casein nanoparticles of desired sizes . also , with the use of interaction between a hydrophobic blood circulation promoter and a casein hydrophobic domain , it is possible for casein nanoparticles to contain the blood circulation promoter . in addition , it was found that such particles remain stable in an aqueous solution . further , it was found that a particle mixture of casein and ionic polysaccharide or another ionic protein contains an ionic blood circulation promoter . the method for preparing casein nanoparticles of the present invention involves a method wherein casein is mixed with a basic aqueous medium solution and the solution is injected into another acidic aqueous medium , and a method wherein casein is mixed with a basic aqueous medium solution and the ph of the solution is lowered during stirring , for example . the method wherein casein is mixed with a basic aqueous medium solution and the solution is injected into another acidic aqueous medium is preferably carried out using a syringe for convenience . however , there is no particular limitation as long as the injection rate , solubility , temperature , and stirring conditions are satisfied . injection can be carried out usually at an injection rate of 1 ml / min to 100 ml / min . the temperature of the basic aqueous medium can be adequately determined . in general , the temperature is 0 ° c . to 80 ° c . and preferably 25 ° c . to 70 ° c . the temperature of an acidic aqueous medium can be adequately determined . in general , the temperature can be 0 ° c . to 80 ° c . and preferably 25 ° c . to 60 ° c . the stirring rate can be adequately determined . however , in general , the stirring rate can be 100 rpm to 3000 rpm and preferably 200 rpm to 2000 rpm . in the method wherein casein is mixed with a basic aqueous medium solution and the ph of the medium is lowered during stirring , it is preferable to add acid dropwise for convenience . however , there is no particular limitation as long as solubility , temperature , and stirring conditions are satisfied . the temperature of a basic aqueous medium can be adequately determined . however , in general , the temperature can be 0 ° c . to 80 ° c . and preferably 25 ° c . to 70 ° c . the stirring rate can be adequately determined . however , in general , the stirring rate can be 100 rpm to 3000 rpm and preferably 200 rpm to 2000 rpm . the aqueous medium that can be used for the present invention is an aqueous solution or a buffer comprising an organic acid or base or an inorganic acid or base . specific examples thereof include , but are not limited to , aqueous solutions comprising : organic acids such as citric acid , ascorbic acid , gluconic acid , carboxylic acid , tartaric acid , succinic acid , acetic acid , phthalic acid , trifluoroacetic acid , morpholinoethanesulfonic acid , and 2 -[ 4 -( 2 - hydroxyethyl )- 1 - piperazinyl ] ethanesulfonic acid ; organic bases such as tris ( hydroxymethyl ), aminomethane , and ammonia ; inorganic acids such as hydrochloric acid , perchloric acid , and carbonic acid ; and inorganic bases such as sodium phosphate , potassium phosphate , calcium hydroxide , sodium hydroxide , potassium hydroxide , and magnesium hydroxide . the concentration of an aqueous medium used in the present invention is preferably approximately 10 mm to 1 m , and more preferably approximately 20 mm to 200 mm . the ph of a basic aqueous medium used in the present invention is preferably 8 or more and less than 11 , and more preferably 10 to 11 . when the ph is excessively high , there is concern regarding hydrolysis or risks in handling . thus , the ph is preferably in the above range . according to the present invention , the temperature at which casein is mixed with a basic aqueous medium at ph of 8 or more and less than 11 is preferably 0 ° c . to 90 ° c ., more preferably 10 ° c . to 80 ° c ., and further preferably 20 ° c . to 70 ° c . the ph of an acidic aqueous medium used in the present invention is preferably 3 . 5 to 7 . 5 and more preferably 5 to 6 . if the ph is beyond the aforementioned range , there is a tendency where the particle size becomes large . the nanoparticle of the present invention comprises a blood circulation promoter . when the blood circulation promoter is an active component , the nanoparticle of the present invention which comprises such an active component can be administered to the affected part for use . specifically , the nanoparticle of the present invention is useful as a drug delivery agent . preferably , the nanoparticle of the present invention is administered via transdermal or transmucosal absorption , or injection into blood vessel , body cavity or lympho tissue . more preferably , the nanoparticle of the present invention is administered via transdermal or transmucosal absorption . in the present invention , the usage of the drug delivery agent is not particularly limited . for example , the drug delivery agent is used as transdermally absorbable agent , a topical therapeutic agent , an oral therapeutic agent , an intradermal parenteral injection , a subcutaneous parenteral injection , an intramuscular parenteral injection , an intravenous parenteral injection , a cosmetic , a quasi - drug , a functional food , or a supplement . in the present invention , the drug delivery agent may comprise an additive . the type of such additive is not particularly limited . examples of such additive include a moisturizer , a softener , an antiinflammatory agent , a percutaneous absorption promoter , soothing agents , preservatives , antioxidants , coloring agents , thickeners , aroma chemicals , and ph adjusters . specific examples of the moisturizer that can be used in the present invention include , but are not limited to , agar , diglycerin , distearyldimonium hectorite , butylene glycol , polyethylene glycol , propylene glycol , hexylene glycol , coix seed extract , vaserine , urea , hyaluronic acid , ceramide , lipidure , isoflavone , amino acid , collagen , mucopolysaccharide , fucoidan , lactoferrin , sorbitol , chitin , chitosan , malic acid , glucuronic acid , placenta extract , seaweed extract , moutan cortex extract , hydrangeae dulcis folium extract , hypericum extract , coleus extract , euonymus japonica , safflower extract , rosa rugosa flower extract , polyporus sclerotium extract , hawthorn extract , rosemary extract , duku extract , chamomile extract , lamium album extract , litchi chinensis extract , achillea millefolium extract , aloe extract , marronnier extract , thujopsis dolabrata extract , fucus extract , osmoin extract , oat extract , tuberosa polysaccharide , cordyceps sinensis extract , barley extract , orange extract , rehmannia root extract , zanthoxylum fruit extract , and coix seed extract . specific examples of the softener that can be used in the present invention include , but are not limited to , glycerin , mineral oil , and emollient ingredients ( e . g . isopropyl isostearate , polyglyceryl isostearate , isotridecyl isononanoate , octyl isononanoate , oleic acid , glyceryl oleate , cacao butter , cholesterol , mixed fatty acid triglyceride , dioctyl succinate , sucrose acetate stearate , cyclopentanesiloxane , sucrose distearate , octyl palmitate , octyl hydroxystearate , arachidyl behenate , sucrose polybehenate , polymethylsilsesquioxane , myristyl alcohol , cetyl myristate , myristyl myristate , and hexyl laurate ). examples of an antiinflammatory agent used in the present invention may include a compound which is selected from azulene , guaiazulene , diphenhydramine hydrochloride , hydrocortisone acetate , prednisolone , glycyrrhizinic acid , glycyrrhetinic acid , mefenamic acid , phenylbutazone , indometacin , ibuprofen and ketoprofen , and its derivative and its salt ; and a plant extract which is selected from scutellariae radix extract , artemisia capillaris thunb . extract , platycodon grandiflorum extract , armeniacae semen extract , common gardenia extract , sasa veitchii extract , gentiana lutea extract , comfrey extract , white birch extract , malva extract , persicae semen extract , peach blade extract , and loquat blade extract ; proteins ; polysaccharides ; and animal extracts , but are not limited thereto . specific examples of the percutaneous absorption promoter that can be used in the present invention include , but are not limited to , ethanol , isopropyl myristate , citric acid , squalane , oleic acid , menthol , n - methyl - 2 - pyrrolidone , diethyl adipate , diisopropyl adipate , diethyl sebacate , diisopropyl sebacate , isopropyl palmitate , isopropyl oleate , octyldodecyl oleate , isostearyl alcohol , 2 - octyldodecanol , urea , vegetable oil , and animal oil . specific examples of soothing agents that can be used in the present invention include , but are not limited to , the following compounds : benzyl alcohol , procaine hydrochloride , xylocaine hydrochloride , and chlorobutanol . specific examples of preservatives that can be used in the present invention include , but are not limited to , the following compounds : benzoic acid , sodium benzoate , paraben , ethylparaben , methylparaben , propylparaben , butylparaben , potassium sorbate , sodium sorbate , sorbic acid , sodium dehydroacetate , hydrogen peroxide , formic acid , ethyl formate , sodium hypochlorite , propionic acid , sodium propionate , calcium propionate , pectin degradation products , polylysine , phenol , isopropylmethyl phenol , orthophenylphenol , phenoxyethanol , resorcin , thymol , thiram , and tea tree oil . specific examples of antioxidants that can be used in the present invention include , but are not limited to , the following compounds : vitamin a , retinoic acid , retinol , retinol acetate , retinol palmitate , retinyl acetate , retinyl palmitate , tocopheryl retinoate , vitamin c and derivatives thereof , kinetin , β - carotene , astaxanthin , lutein , lycopene , tretinoin , vitamin e , α - lipoic acid , coenzyme q10 , polyphenol , sod , and phytic acid . specific examples of coloring agents that can be used in the present invention include , but are not limited to , the following compounds : krill pigment , orange dye , cacao dye , kaoline , carmines , ultramarine blue , cochineal dye , chrome oxide , iron oxide , titanium dioxide , tar dye , and chlorophyll . specific examples of thickeners that can be used in the present invention include , but are not limited to , the following compounds : quince seed , carrageenan , gum arabic , karaya gum , xanthan gum , gellan gum , tamarind gum , locust bean gum , gum traganth , pectin , starch , cyclodextrin , methylcellulose , ethylcellulose , carboxymethylcellulose , sodium alginate , polyvinyl alcohol , polyvinyl pyrrolidone , carboxyvinyl polymer , and sodium polyacrylate . specific examples of aroma chemicals that can be used in the present invention include , but are not limited to , the following compounds : musk , acacia oil , anise oil , ylang ylang oil , cinnamon oil , jasmine oil , sweet orange oil , spearmint oil , geranium oil , thyme oil , neroli oil , mentha oil , hinoki ( japanese cypress ) oil , fennel oil , peppermint oil , bergamot oil , lime oil , lavender oil , lemon oil , lemongrass oil , rose oil , rosewood oil , anisaldehyde , geraniol , citral , civetone , muscone , limonene , and vanillin . specific examples of ph adjusters that can be used in the present invention include , but are not limited to , the following compounds : sodium citrate , sodium acetate , sodium hydroxide , potassium hydroxide , phosphoric acid , and succinic acid . the dose of the nanoparticle of the present invention can be adequately determined depending upon type and amount of active ingredient and upon user weight and condition , for example . the dose for single administration is generally approximately 10 μg to 100 mg / kg , and preferably 20 μg to 50 mg / kg . in case of via transdermal or transmucosal administration , the nanoparticle can be administered in an amount of approximately 1 μg to 50 mg / cm , and preferably 2 . 5 μg to 10 mg / cm . the present invention is hereafter described in greater detail with reference to the following examples , although the technical scope of the present invention is not limited thereto . milk - derived casein na ( 10 mg ; wako pure chemical industries , ltd .) was mixed with 50 mm phosphate buffer ( ph 9 )( 1 ml ). tocopherol acetate ( 0 . 75 mg ; wako pure chemical industries , ltd .) was dissolved in ethanol ( 0 . 1 ml ). the tocopherol acetate solution was added dropwise to the casein solution during stirring . the resulting liquid mixture ( 1 ml ) was injected into 200 mm phosphate buffer water ( ph 5 ) ( 10 ml ) with the use of a microsyringe at an external temperature of 40 ° c . during stirring at 800 rpm . thus , a water dispersion of casein nanoparticles containing tocopherol acetate was obtained . the particle size of the obtained casein particles was measured with a “ zetasizer nano ” ( sysmex ), and the volume average particle size was determined . it was found to be 18 . 0 nm . nanoparticles were prepared as in example 1 , except that tocopherol acetate ( 3 . 75 mg ; wako pure chemical industries , ltd .) was dissolved in ethanol ( 0 . 1 ml ). the particle size of the obtained particles was measured with a “ zetasizer nano ” ( sysmex ), and the volume average particle size was determined . it was found to be 19 . 2 nm . nanoparticles were prepared as in example 1 , except that tocopherol nicotinate ( 0 . 5 mg ; wako pure chemical industries , ltd .) was dissolved in ethanol ( 0 . 1 ml ). the particle size of the obtained particles was measured with a “ zetasizer nano ” ( sysmex ), and the volume average particle size was determined . it was found to be 19 . 2 nm . nanoparticles were prepared as in example 1 , except that tocopherol nicotinate ( 2 . 5 mg ; wako pure chemical industries , ltd .) was dissolved in ethanol ( 0 . 1 ml ). the particle size of the obtained particles was measured with a “ zetasizer nano ” ( sysmex ), and the volume average particle size was determined . it was found to be 20 . 5 nm . nanoparticles were prepared as in example 1 , except that tocopherol ( 0 . 75 mg ; wako pure chemical industries , ltd .) was dissolved in ethanol ( 0 . 1 ml ). the particle size of the obtained particles was measured with a “ zetasizer nano ” ( sysmex ), and the volume average particle size was determined . it was found to be 18 . 8 nm . nanoparticles were prepared as in example 1 , except that tocopherol ( 3 . 75 mg ; wako pure chemical industries , ltd .) was dissolved in ethanol ( 0 . 1 ml ). the particle size of the obtained particles was measured with a “ zetasizer nano ” ( sysmex ), and the volume average particle size was determined . it was found to be 20 . 3 nm . nanoparticles were prepared as in example 1 , except that nicotinic - acid amide ( 0 . 85 mg ; wako pure chemical industries , ltd .) was dissolved in ethanol ( 0 . 2 ml ). the particle size of the obtained particles was measured with a “ zetasizer nano ” ( sysmex ), and the volume average particle size was determined . it was found to be 20 . 0 nm . nanoparticles were prepared as in example 1 , except that benzyl nicotinate ( 1 . 1 mg ; wako pure chemical industries , ltd .) was dissolved in ethanol ( 0 . 1 ml ). the particle size of the obtained particles was measured with a “ zetasizer nano ” ( sysmex ), and the volume average particle size was determined . it was found to be 17 . 5 nm . nanoparticles were prepared as in example 1 , except that cephalanthin ( 0 . 85 mg ; wako pure chemical industries , ltd .) was dissolved in ethanol ( 0 . 3 ml ). the average particle size of the obtained particles was measured with a light scattering photometer ( microtrack , nikkiso , co ., ltd . ), and was found to be 22 nm . nanoparticles were prepared as in example 1 , except that finasteride ( 0 . 85 mg ; lkt laboratories inc .) was dissolved in ethanol ( 0 . 3 ml ). the average particle size of the obtained particles was measured with a light scattering photometer ( microtrack , nikkiso , co ., ltd . ), and was found to be 29 nm . nanoparticles were prepared as in example 1 , except that minoxidil ( 1 mg ; lkt laboratories inc .) was dissolved in ethanol ( 0 . 02 ml ). the average particle size of the obtained particles was measured with a light scattering photometer ( microtrack , nikkiso , co ., ltd . ), and was found to be 23 . 4 nm . nanoparticles were prepared as in example 1 , except that swertia japonica extract ( 1 . 05 ml ; maruzen pharmaceuticals co ., ltd . ; swertia japonica extract liquid ) was added dropwise . the particle size of the obtained particles was measured with a “ zetasizer nano ” ( sysmex ), and the volume average particle size was determined . it was found to be 26 . 3 nm . nanoparticles were prepared as in example 1 , except that benzyl nicotinate ( 1 . 1 mg ; wako pure chemical industries , ltd .) was dissolved in ethanol ( 0 . 1 ml ) and chili pepper tincture ( 0 . 01 ml ; maruzen pharmaceuticals co ., ltd .) was added dropwise . the particle size of the obtained particles was measured with a “ zetasizer nano ” ( sysmex ), and the volume average particle size was determined . it was found to be 27 . 3 nm . nanoparticles were prepared as in example 1 , except that collagen ( nitta gelatin inc . ), gelatin , acid - treated gelatin , or albumin was used in place of casein . as a result , similar nanoparticles were obtained . water dispersions of casein nanoparticles for examples 8 and 13 and water dispersions obtained by removing casein from those used in examples 8 and 13 for comparative examples ( referred to as comparative example 8a and comparative example 13a , respectively ) were prepared and allowed to stand at 4 ° c . for 16 hour . precipitation was exclusively observed in the water dispersions for comparative examples 8a and 13a , while on the other hand , no precipitation was observed in the water dispersions for examples 8 and 13 . the results indicate that the nanoparticles of the present invention are excellent in terms of stability . dorsal hair of c3h mice at the trichogenous or dormant phase were cut with a hair clipper . on the next day , the mice were shaved with a shaver . the water dispersions of protein nanoparticles containing a blood circulation promoter which were prepared in examples 8 and 9 were separately applied to all shaved areas once daily . the degree of ability to cause phase transition to the growth phase in mouse dorsal hair follicles was examined . as a result , hair growth effects were promoted and activity of causing hair cycle transition from the dormant phase to the growth phase was observed , as compared with the cases of ethanol solutions containing a blood circulation promoter alone ( at the same concentrations ) used in examples 8 and 9 . therefore , it has been revealed that the water dispersions of the present invention cause no excessive skin degreasing or skin irritation caused by an ethanol solution , and exhibit hair growth effects derived from blood circulation promoting effects to a greater extent than the case of using ethanol solution .
it is an object of the present invention to provide a nanoparticle which comprises a blood circulation promoter and a biodegradable polymer , which is safe and excellent in terms of dispersion stability and has high transparency and good absorbability due to its small particle size . the present invention provides a water - dispersible nanoparticle which comprises a blood circulation promoter and a biodegradable polymer .