JP2006312725A - Hydroxyalkylated hyaluronic acid - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a humectant having a hydroxyalkylated hyaluronic acid as an active constituent and excellent moisture retention effect. <P>SOLUTION: The humectant includes a hydroxyalkylated hyaluronic acid represented by general formula (I) (where R<SP>1</SP>-R<SP>6</SP>is independently a hydrogen atom or an ether bonded hydroxyalkyl group but all of them are not hydrogen atoms, R<SP>7</SP>is a hydrogen atom or an alkali metal atom and n is an integer of 1-10,000). In the hydroxyalkylated hyaluronic acid, the number of hydroxyalkyl groups is preferably 1-10; the hydroxyalkyl group is preferably one or two or greater members selected from the group consisting of 2-hydroxypropyl group, 2-hydroxybutyl group and 2,3-dihydroxypropyl group. The hydroxyalkylated hyaluronic acid has excellent moisture retention effect and hence can be preferably formulated in an external preparation for the skin. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a hydroxyalkylated hyaluronic acid, a composition for external skin containing hydroxyalkylated hyaluronic acid, and a humectant containing hydroxyalkylated hyaluronic acid as an active ingredient.

  Conventionally, various moisturizers are blended in cosmetics and pharmaceuticals for the purpose of further reducing irritation, improving usability, preserving, and the like in order to give a moist feel to skin and hair. Commonly used moisturizers include glycerin, 1,3-butylene glycol, propylene glycol, etc., and these are used alone or in combination, but moisturizing properties, effects on product stability, solubility In terms of feeling of use such as stickiness, it is not always satisfactory, and their use is naturally limited.

On the other hand, hyaluronic acid having a structure in which β-D-N-acetylglucosamine and β-D-glucuronic acid are alternately bonded is a high-molecular substance derived from a living body, and has high water retention, viscosity increase, viscoelasticity, Since it has specific physical properties such as spinnability and high biocompatibility, it is widely used as a moisturizer in the cosmetics field, pharmaceutical field, food field and the like.
For example, Patent Documents 1 and 2 describe an external preparation for skin containing tocopherol and hyaluronic acid in order to enhance moisture retention.
JP 2005-60233 A Japanese Patent Laid-Open No. 2005-60234

However, although hyaluronic acid has a relatively excellent moisturizing ability, it is not yet sufficient, and there is a problem that even if it is formulated in a small amount, a strong sticky feeling is produced on the skin. Moreover, the improvement of the familiarity to the skin at the time of application | coating was also desired.
This invention is made | formed in view of the subject of the said prior art, The objective is to provide the novel substance which has the outstanding moisturizing effect and is excellent also in a usability | use_condition and usability.

（式中、Ｒ^１〜Ｒ^６は、それぞれ独立して水素原子又はエーテル結合されたヒドロキシアルキル基であるが、全部が水素原子ではない。Ｒ^７は水素原子又はアルカリ金属原子であり、ｎは1〜10000の整数である。） In view of the above circumstances, as a result of intensive studies by the present inventors, it was found that by introducing a hydroxyalkyl group into some and all of the hydroxyl groups of hyaluronic acid, a substance having a significantly high moisturizing effect can be obtained. The invention has been completed.
That is, the subject of the present invention is a hydroxyalkylated hyaluronic acid represented by the general formula (I).
(Chemical formula 1)

(Wherein R ^{1 to} R ⁶ are each independently a hydrogen atom or an ether-bonded hydroxyalkyl group, but not all are hydrogen atoms. R ⁷ is a hydrogen atom or an alkali metal atom, and n is (It is an integer from 1 to 10000.)

In the hydroxyalkylated hyaluronic acid, the number of hydroxyalkyl groups is preferably 1 to 10 per repeating structural unit of hyaluronic acid.
The hydroxyalkyl group is preferably one or more selected from a 2-hydroxypropyl group, a 2-hydroxybutyl group, and a 2,3-dihydroxypropyl group.
The external composition for skin of the present invention comprises the hydroxyalkylated hyaluronic acid.
The humectant of the present invention is characterized in that the hydroxyalkylated hyaluronic acid is an active ingredient.

  In the present invention, a remarkably excellent moisturizing effect can be obtained by using a hydroxyalkylated hyaluronic acid in which a hydroxyalkyl group is introduced into some and all of the hydroxyl groups of hyaluronic acid. In addition, the hydroxyalkylated hyaluronic acid of the present invention is also excellent in use feeling.

（式中、Ｒ^１〜Ｒ^６は、それぞれ独立して水素原子又はエーテル結合されたヒドロキシアルキル基であるが、全部が水素原子ではない。Ｒ^７は水素原子又はアルカリ金属原子であり、ｎは1〜10000の整数である。） Hereinafter, embodiments of the present invention will be described in detail.
The hydroxyalkylated hyaluronic acid of the present invention is obtained by introducing a hydroxyalkyl group into part and all of the hydroxyl groups of hyaluronic acid, and is represented by the following general formula (I).
(Chemical formula 2)

(Wherein R ^{1 to} R ⁶ are each independently a hydrogen atom or an ether-bonded hydroxyalkyl group, but not all are hydrogen atoms. R ⁷ is a hydrogen atom or an alkali metal atom, and n is (It is an integer from 1 to 10000.)

Here, the hydroxyalkyl group means one in which one or more hydrogen atoms of a linear, branched or cyclic alkyl group are substituted with a hydroxyl group. As the hydroxyalkyl group, preferably one or two or more hydrogen atoms of a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group and an isobutyl group are substituted with a hydroxyl group, Preferred are 2-hydroxypropyl group, 2-hydroxybutyl group, 2,3-dihydroxypropyl group and the like.
Moreover, as an alkali metal atom, a sodium atom, a potassium atom, a lithium atom, etc. are mentioned, Preferably it is a sodium atom.

The bonding position of the hydroxyalkyl group is arbitrary, and the number of bonds is not limited, but the number of hydroxyalkyl groups per repeating structural unit of hyaluronic acid (per N-acetyl group) is preferably 1 to 10. It is especially preferable that it is ~ 7. In addition, the hydroxyalkylated hyaluronic acid of the present invention may include those in which one or more hydroxyalkyl groups are further ether-bonded to the hydroxyl group of the hydroxyalkyl group introduced into hyaluronic acid. Therefore, the hydroxyalkyl group in R ^{1 to} R ⁶ may have an oxygen atom in the alkyl chain. The number of hydroxyalkyl groups includes such a hydroxyalkyl group substituted with a hydroxyalkyl group. For example, one hydroxyalkyl group substituted with one hydroxyalkyl group has two hydroxyalkyl groups.
In the present invention, the hydroxyalkylated hyaluronic acid may be a plurality of mixtures.

  In the present invention, the hydroxyalkylated hyaluronic acid includes a pharmaceutically acceptable salt form thereof. Specifically, inorganic hydrochloric acid such as hydrochloric acid, sulfuric acid, phosphoric acid and hydrobromic acid; organic acid salts such as acetic acid, lactic acid, maleic acid, fumaric acid, tartaric acid, citric acid, methanesulfonic acid and p-toluenesulfonic acid A sodium salt, potassium salt, ammonium salt, magnesium salt, calcium salt and the like.

The hydroxyalkylated hyaluronic acid represented by the general formula (I) according to the present invention is a novel substance, but is synthesized by a condensation reaction between hyaluronic acid and a polyhydric alcohol, or a condensation reaction between hyaluronic acid and an epoxy compound. be able to. The manufacturing method is not limited to these.
Moreover, its derivative can also be used instead of hyaluronic acid. Specific examples include acetylated hyaluronic acid, hyaluronic acid methyl ester, and the like, and further a protective group or the like introduced into the carboxyl group or hydroxyl group of hyaluronic acid.

The external composition for skin of the present invention comprises a hydroxyalkylated hyaluronic acid represented by the above general formula (I).
In the external composition for skin of the present invention, the amount of the hydroxyalkylated hyaluronic acid represented by the general formula (I) is not particularly limited, but is generally 0.001 to 20% by mass, preferably It is 0.01-10 mass%, Most preferably, it is 0.1-7 mass%. If the amount is less than 0.001% by mass, the desired effect may not be obtained. If the amount exceeds 20% by mass, an increase in effect commensurate with the increase in the compounding amount cannot be substantially expected, and there is a problem in formulation formulation. I have come.

In addition to the above essential components, other moisturizing components can be blended in the composition for external use of the present invention.
Other moisturizing ingredients include, for example, polyethylene glycol, propylene glycol, glycerin, 1,3-butylene glycol, xylitol, sorbitol, maltitol, chondroitin sulfate, hyaluronic acid, mucoitin sulfate, caronic acid, atelocollagen, cholesteryl-12-hydroxy Examples include stearate, sodium lactate, bile salt, dl-pyrrolidone carboxylate, short-chain soluble collagen, diglycerin (EO) PO adduct, Izayobara extract, yarrow extract, merirot extract, alkylene oxide derivatives, etc. It is done.

  Further, in the composition for external use of the present invention, other components usually used in the composition for external use of skin such as cosmetics and pharmaceuticals, for example, powder components, liquid fats and oils, solid fats and oils, as long as the effects of the present invention are not impaired. Waxes, hydrocarbons, higher fatty acids, higher alcohols, esters, silicones, anionic surfactants, cationic surfactants, amphoteric surfactants, nonionic surfactants, water-soluble polymers, thickeners, coating agents, UV absorbers Agent, sequestering agent, lower alcohol, polyhydric alcohol, sugar, amino acid, organic amine, polymer emulsion, pH adjuster, skin nutrient, vitamin, antioxidant, antioxidant aid, fragrance, water, etc. are required Depending on the case, it can be blended appropriately.

  Examples of the powder component include inorganic powders (for example, talc, kaolin, mica, sericite, muscovite, phlogopite, synthetic mica, saucite, biotite, permiculite, magnesium carbonate, calcium carbonate, silicic acid. Aluminum, barium silicate, calcium silicate, magnesium silicate, strontium silicate, metal tungstate, magnesium, silica, zeolite, barium sulfate, calcined calcium sulfate (baked gypsum), calcium phosphate, fluorine apatite, hydroxyapatite, ceramic powder , Metal soap (eg, zinc myristate, calcium palmitate, aluminum stearate), boron nitride, etc .; organic powder (eg, polyamide resin powder (nylon powder), polyethylene powder, polymethyl methacrylate powder, polystyrene Powder, copolymer resin powder of styrene and acrylic acid, benzoguanamine resin powder, polytetrafluoroethylene powder, cellulose powder, etc.); inorganic white pigment (eg, titanium dioxide, zinc oxide, etc.); inorganic red pigment (eg, Iron oxide (Bengara), iron titanate, etc .; Inorganic brown pigments (eg, γ-iron oxide, etc.); Inorganic yellow pigments (eg, yellow iron oxide, loess, etc.); Inorganic black pigments (eg, black oxide) Iron, low-order titanium oxide, etc.); inorganic purple pigments (eg, mango violet, cobalt violet, etc.); inorganic green pigments (eg, chromium oxide, chromium hydroxide, cobalt titanate, etc.); inorganic blue pigments (eg, Pearl pigments (eg titanium oxide coated mica, titanium oxide coated bismuth oxychloride, titanium oxide coated talc, colored oxidation) Tan-coated mica, bismuth oxychloride, fish scale foil, etc.); metal powder pigments (eg, aluminum powder, copper powder, etc.); organic pigments such as zirconium, barium or aluminum lake (eg, red 201, red 202, red 204) No., red 205, red 220, red 226, red 228, red 405, orange 203, orange 204, yellow 205, yellow 401, and blue 404, organic pigments such as red 3 , Red 104, Red 106, Red 227, Red 230, Red 401, Red 505, Orange 205, Yellow 4, Yellow 5, Yellow 202, Yellow 203, Green 3 and Blue No. 1 etc.); natural pigments (for example, chlorophyll, β-carotene, etc.) and the like.

  Examples of liquid oils include avocado oil, camellia oil, turtle oil, macadamia nut oil, corn oil, mink oil, olive oil, rapeseed oil, egg yolk oil, sesame oil, persic oil, wheat germ oil, southern castor oil, castor oil, linseed oil , Safflower oil, cottonseed oil, eno oil, soybean oil, peanut oil, tea seed oil, kaya oil, rice bran oil, cinnagiri oil, Japanese kiri oil, jojoba oil, germ oil, triglycerin and the like.

  Examples of the solid fat include cacao butter, palm oil, horse fat, hydrogenated palm oil, palm oil, beef tallow, sheep fat, hydrogenated beef tallow, palm kernel oil, pork fat, beef bone fat, owl kernel oil, hydrogenated oil, cattle Leg fats, moles, hydrogenated castor oil and the like.

  Examples of waxes include beeswax, candelilla wax, cotton wax, carnauba wax, bayberry wax, ibota wax, whale wax, montan wax, nuka wax, lanolin, kapok wax, lanolin acetate, liquid lanolin, sugar cane wax, lanolin fatty acid isopropyl, hexyl laurate, and reduced lanolin. , Jojoballow, hard lanolin, shellac wax, POE lanolin alcohol ether, POE lanolin alcohol acetate, POE cholesterol ether, lanolin fatty acid polyethylene glycol, POE hydrogenated lanolin alcohol ether, and the like.

Examples of the hydrocarbon oil include liquid paraffin, ozokerite, squalane, pristane, paraffin, ceresin, squalene, petrolatum, microcrystalline wax, and the like.
Examples of higher fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, undecylenic acid, toluic acid, isostearic acid, linoleic acid, linolenic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid ( DHA) and the like.

  Examples of higher alcohols include linear alcohols (eg, lauryl alcohol, cetyl alcohol, stearyl alcohol, behenyl alcohol, myristyl alcohol, oleyl alcohol, cetostearyl alcohol); branched chain alcohols (eg, monostearyl glycerin ether (batyl alcohol) ), 2-decyltetradecinol, lanolin alcohol, cholesterol, phytosterol, hexyl decanol, isostearyl alcohol, octyldodecanol and the like.

  Synthetic ester oils include isopropyl myristate, cetyl octanoate, octyldodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, hexyl decyl dimethyloctanoate, cetyl lactate, myristyl lactate Lanolin acetate, isocetyl stearate, isocetyl isostearate, cholesteryl 12-hydroxystearate, ethylene glycol di-2-ethylhexanoate, dipentaerythritol fatty acid ester, monoisostearate N-alkyl glycol, neopentyl glycol dicaprate, apple Acid diisostearyl, di-2-heptylundecanoic acid glycerin, tri-2-ethylhexanoic acid trimethylolpropane, triisostearic acid trimethylo Propane, tetra-2-ethylhexanoate pentaerythritol, glycerol tri-2-ethylhexanoate, glycerol trioctanoate, glycerol triisopalmitate, trimethylolpropane triisostearate, cetyl 2-ethylhexanoate, 2-ethylhexyl palmi Tate, glyceryl trimyristate, glyceride tri-2-heptylundecanoate, castor oil fatty acid methyl ester, oleyl oleate, acetoglyceride, 2-heptylundecyl palmitate, diisobutyl adipate, N-lauroyl-L-glutamic acid-2 -Octyldodecyl ester, di-2-heptylundecyl adipate, ethyl laurate, di-2-ethylhexyl sebacate, 2-hexyldecyl myristate, 2-hexyldecyl palmitate, 2-hexyldecyl adipate Le, diisopropyl sebacate, 2-ethylhexyl succinate, and triethyl citrate.

  Examples of the silicone oil include linear polysiloxanes (for example, dimethylpolysiloxane, methylphenylpolysiloxane, diphenylpolysiloxane, etc.); cyclic polysiloxanes (for example, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexyl). And silicone resins that form a three-dimensional network structure, various modified polysiloxanes (amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxane, fluorine-modified polysiloxane, etc.) It is done.

  Anionic surfactants include, for example, fatty acid soaps (eg, sodium laurate, sodium palmitate, etc.); higher alkyl sulfates (eg, sodium lauryl sulfate, potassium lauryl sulfate, etc.); alkyl ether sulfates (eg, POE-lauryl sulfate triethanolamine, POE-sodium lauryl sulfate, etc.); N-acyl sarcosine acids (eg, sodium lauroyl sarcosine, etc.); higher fatty acid amide sulfonates (eg, sodium N-myristoyl-N-methyl taurate, palm Oil fatty acid methyl tauride sodium, lauryl methyl tauride sodium, etc .; phosphate ester salt (POE-oleyl ether sodium phosphate, POE-stearyl ether phosphate, etc.); sulfosuccinate (eg, di-2-ethylhexyl sulfo) Sodium succinate, monolauroyl monoethanolamide sodium polyoxyethylene sulfosuccinate, sodium lauryl polypropylene glycol sulfosuccinate, etc.); alkyl benzene sulfonates (eg, sodium linear dodecyl benzene sulfonate, triethanol amine linear dodecyl benzene sulfonate, linear dodecyl) Higher fatty acid ester sulfates (eg, hydrogenated coconut oil fatty acid sodium glycerol sulfate); N-acyl glutamate (eg, monosodium N-lauroyl glutamate, disodium N-stearoyl glutamate, N-myristoyl) -L-glutamic acid monosodium, etc.); sulfated oil (eg funnel oil); POE-alkyl ether carboxylic acid; POE-alkyl allyl ether Α-olefin sulfonates; higher fatty acid ester sulfonates; secondary alcohol sulfates; higher fatty acid alkylolamide sulfates; lauroyl monoethanolamide sodium succinate; N-palmitoyl aspartate ditriethanolamine ; Sodium caseinate and the like.

  Examples of the cationic surfactant include alkyltrimethylammonium salts (eg, stearyltrimethylammonium chloride, lauryltrimethylammonium chloride, etc.); alkylpyridinium salts (eg, cetylpyridinium chloride, etc.); distearyldimethylammonium dialkyldimethylammonium chloride; Poly (N, N'-dimethyl-3,5-methylenepiperidinium chloride); alkyl quaternary ammonium salt; alkyldimethylbenzylammonium salt; alkylisoquinolinium salt; dialkyl morpholinium salt; POE-alkylamine; Examples include alkylamine salts; polyamine fatty acid derivatives; amyl alcohol fatty acid derivatives; benzalkonium chloride; benzethonium chloride and the like.

  Examples of amphoteric surfactants include imidazoline-based amphoteric surfactants (eg, 2-undecyl-N, N, N- (hydroxyethylcarboxymethyl) -2-imidazoline sodium, 2-cocoyl-2-imidazolinium hydroxide). Side-1-carboxyethyloxy disodium salt, etc.); betaine surfactants (for example, 2-heptadecyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, lauryldimethylaminoacetic acid betaine, alkylbetaine, amide betaine) , Sulfobetaine, etc.).

  Examples of the lipophilic nonionic surfactant include sorbitan fatty acid esters (for example, sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, Sorbitan trioleate, diglycerol sorbitan penta-2-ethylhexylate, diglycerol sorbitan tetra-2-ethylhexylate); glycerin polyglycerin fatty acids (eg mono cottonseed oil fatty acid glycerin, monoerucic acid glycerin, sesquioleate glycerin, monostearin) Glycerin acid, α, α'-oleic acid pyroglutamate glycerin, monostearic acid glycerin malic acid, etc.); propylene glycol fatty acid esters (eg monostearies) Propylene glycolate, etc.); hardened castor oil derivative; glycerin alkyl ether, etc.

  Examples of hydrophilic nonionic surfactants include POE-sorbitan fatty acid esters (for example, POE-sorbitan monooleate, POE-sorbitan monostearate, POE-sorbitan monooleate, POE-sorbitan tetraoleate). POE sorbite fatty acid esters (eg, POE-sorbite monolaurate, POE-sorbite monooleate, POE-sorbite pentaoleate, POE-sorbite monostearate, etc.); POE-glycerin fatty acid esters (eg, POE- POE-monooleate such as glycerin monostearate, POE-glycerin monoisostearate, POE-glycerin triisostearate); POE-fatty acid esters (for example, POE-distearate, POE-monodiolate, ethylene glycol distearate, etc.) POE-alkyl ethers (eg POE- Lauryl ether, POE-oleyl ether, POE-stearyl ether, POE-behenyl ether, POE-2-octyldodecyl ether, POE-cholestanol ether, etc.); Pluronic type (eg, Pluronic etc.); POE / POP-alkyl ether (Eg POE / POP-cetyl ether, POE / POP-2-decyltetradecyl ether, POE / POP-monobutyl ether, POE / POP-hydrogenated lanolin, POE / POP-glycerin ether, etc.); Tetra POE / Tetra POP-ethylenediamine condensates (eg Tetronic); POE-castor oil hardened castor oil derivatives (eg POE-castor oil, POE-hardened castor oil, POE-hardened castor oil monoisostearate, POE-hardened castor Oil triisostearate, POE-hardened castor oil monopyroglutamic acid monoisostearic acid diester, POE-hardened castor oil maleic acid, etc.) POE-beeswax lanolin derivatives (eg POE-sorbite beeswax); alkanolamides (eg coconut oil fatty acid diethanolamide, lauric acid monoethanolamide, fatty acid isopropanolamide, etc.); POE-propylene glycol fatty acid ester; POE-alkylamine POE-fatty acid amide; sucrose fatty acid ester; alkyl ethoxydimethylamine oxide; trioleyl phosphate and the like.

  Examples of natural water-soluble polymers include plant-based polymers (for example, gum arabic, gum tragacanth, galactan, guar gum, carob gum, caraya gum, carrageenan, pectin, agar, quince seed (malmello), alge colloid (guckweed extract), starch (Rice, corn, potato, wheat), glycyrrhizic acid); microbial polymers (eg, xanthan gum, dextran, succinoglucan, bullulan, etc.); animal polymers (eg, collagen, casein, albumin, gelatin, etc.), etc. Is mentioned.

  Semi-synthetic water-soluble polymers include, for example, starch polymers (eg, carboxymethyl starch, methylhydroxypropyl starch, etc.); cellulose polymers (methylcellulose, ethylcellulose, methylhydroxypropylcellulose, hydroxyethylcellulose, sodium cellulose sulfate) Hydroxypropylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, crystalline cellulose, cellulose powder and the like); alginic acid polymers (for example, sodium alginate, propylene glycol alginate, etc.) and the like.

  Synthetic water-soluble polymers include, for example, vinyl polymers (eg, polyvinyl alcohol, polyvinyl methyl ether, polyvinyl pyrrolidone, carboxyvinyl polymer); polyoxyethylene polymers (eg, polyethylene glycol 20,000, 40,000, 60,000). Polyoxyethylene polyoxypropylene copolymer, etc.); acrylic polymers (for example, sodium polyacrylate, polyethyl acrylate, polyacrylamide, etc.); polyethyleneimine; cationic polymers, and the like.

  Examples of thickeners include gum arabic, carrageenan, caraya gum, gum tragacanth, carob gum, quince seed (malmello), casein, dextrin, gelatin, sodium pectate, sodium alginate, methylcellulose, ethylcellulose, CMC, hydroxyethylcellulose, hydroxypropyl Cellulose, PVA, PVM, PVP, sodium polyacrylate, carboxyvinyl polymer, locust bean gum, guar gum, tamarind gum, cellulose dialkyldimethylammonium sulfate, xanthan gum, magnesium aluminum silicate, bentonite, hectorite, silicate A1Mg (vee gum), Examples thereof include laponite and silicic anhydride.

  Examples of UV absorbers include benzoic acid UV absorbers (eg, paraaminobenzoic acid (hereinafter abbreviated as PABA), PABA monoglycerin ester, N, N-dipropoxy PABA ethyl ester, N, N-diethoxy PABA ethyl ester. N, N-dimethyl PABA ethyl ester, N, N-dimethyl PABA butyl ester, N, N-dimethyl PABA ethyl ester, etc.); anthranilic acid-based UV absorbers (for example, homomenthyl-N-acetyl anthranilate, etc.); Salicylic acid ultraviolet absorbers (for example, amyl salicylate, menthyl salicylate, homomenthyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate, p-isopropanol phenyl salicylate, etc.); cinnamic acid ultraviolet absorbers (for example, octylmethoxycinnamate, ethyl) -4-Isopropylcinname , Methyl-2,5-diisopropylcinnamate, ethyl-2,4-diisopropylcinnamate, methyl-2,4-diisopropylcinnamate, propyl-p-methoxycinnamate, isopropyl-p-methoxycinnamate, isoamyl-p -Methoxycinnamate, octyl-p-methoxycinnamate (2-ethylhexyl-p-methoxycinnamate), 2-ethoxyethyl-p-methoxycinnamate, cyclohexyl-p-methoxycinnamate, ethyl-α-cyano-β -Phenyl cinnamate, 2-ethylhexyl-α-cyano-β-phenyl cinnamate, glyceryl mono-2-ethylhexanoyl-diparamethoxy cinnamate, etc.); benzophenone UV absorbers (for example, 2,4-dihydroxybenzophenone) 2,2'-dihydroxy-4-methoxybenzophenone, 2,2'-dihydroxy-4,4'-dimethoxybenzo Phenone, 2,2 ', 4,4'-tetrahydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2-hydroxy-4-methoxybenzophenone-5- Sulfonate, 4-phenylbenzophenone, 2-ethylhexyl-4′-phenyl-benzophenone-2-carboxylate, 2-hydroxy-4-n-octoxybenzophenone, 4-hydroxy-3-carboxybenzophenone, etc.); 3- (4'-methylbenzylidene) -d, l-camphor, 3-benzylidene-d, l-camphor; 2-phenyl-5-methylbenzoxazole; 2,2'-hydroxy-5-methylphenylbenzotriazole; 2 -(2'-hydroxy-5'-t-octylphenyl) benzotriazole; 2- (2'-hydroxy-5'-methylphenylbenzotriazole; dibenzalazine; dianisoylmethane; 4-methoxy-4'-t-butyl Dibenzoylmethane; 5- (3,3-dimethyl-2-norbornylidene) -3-pentan-2-one, dimorpholino pyridazinone like.

  Examples of the sequestering agent include 1-hydroxyethane-1,1-diphosphonic acid, 1-hydroxyethane-1,1-diphosphonic acid tetrasodium salt, disodium edetate, trisodium edetate, tetrasodium edetate Sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, phosphoric acid, citric acid, ascorbic acid, succinic acid, edetic acid, trisodium ethylenediaminehydroxyethyl triacetate and the like.

  Examples of the lower alcohol include ethanol, propanol, isopropanol, isobutyl alcohol, t-butyl alcohol and the like.

  Examples of the polyhydric alcohol include divalent alcohols (for example, ethylene glycol, propylene glycol, trimethylene glycol, 1,2-butylene glycol, 1,3-butylene glycol, tetramethylene glycol, 2,3-butylene glycol, Pentamethylene glycol, 2-butene-1,4-diol, hexylene glycol, octylene glycol, etc.); trivalent alcohol (eg, glycerin, trimethylolpropane, etc.); tetravalent alcohol (eg, 1,2,6) Pentaerythritol such as hexanetriol); pentahydric alcohol (eg, xylitol, etc.); hexavalent alcohol (eg, sorbitol, mannitol, etc.); polyhydric alcohol polymer (eg, diethylene glycol, dipropylene glycol, triethylene glycol, polypropylene Glycol, tetraethylene glycol, diglycerin, polyethylene glycol, triglycerin, tetraglycerin, polyglycerin, etc.); divalent alcohol alkyl ethers (for example, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, ethylene) Glycol monophenyl ether, ethylene glycol monohexyl ether, ethylene glycol mono 2-methylhexyl ether, ethylene glycol isoamyl ether, ethylene glycol benzyl ether, ethylene glycol isopropyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol dibutyl ether, etc.) ; Dihydric alcohol alkyl ester Tellurium (for example, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, diethylene glycol butyl ether, diethylene glycol methyl ethyl ether, triethylene glycol monomethyl ether, triethylene glycol monoethyl ether, propylene glycol monomethyl ether , Propylene glycol monoethyl ether, propylene glycol monobutyl ether, propylene glycol isopropyl ether, dipropylene glycol methyl ether, dipropylene glycol ethyl ether, dipropylene glycol butyl ether, etc.); divalent alcohol Ether esters (eg, ethylene glycol monomethyl ether acetate, ethylene glycol monoethyl ether acetate, ethylene glycol monobutyl ether acetate, ethylene glycol monophenyl ether acetate, ethylene glycol diazinate, ethylene glycol disuccinate, diethylene glycol monoethyl ether acetate, diethylene glycol) Monobutyl ether acetate, propylene glycol monomethyl ether acetate, propylene glycol monoethyl ether acetate, propylene glycol monopropyl ether acetate, propylene glycol monophenyl ether acetate, etc .; glycerin monoalkyl ether (for example, xyl alcohol, ceralkyl alcohol) Sugar alcohol (eg, sorbitol, maltitol, maltotriose, mannitol, sucrose, erythritol, glucose, fructose, amylolytic sugar, maltose, xylitolose, amylolytic sugar reducing alcohol, etc.); Solid; tetrahydrofurfuryl alcohol; POE-tetrahydrofurfuryl alcohol; POP-butyl ether; POP / POE-butyl ether; tripolyoxypropylene glycerin ether; POP-glycerin ether; POP-glycerin ether phosphate; POP / POE-pentaneerythritol Examples include ether and polyglycerin.

  Monosaccharides include, for example, tricarbon sugars (eg, D-glyceryl aldehyde, dihydroxyacetone, etc.); tetracarbon sugars (eg, D-erythrose, D-erythrulose, D-treose, erythritol, etc.); pentose sugars (eg, , L-arabinose, D-xylose, L-lyxose, D-arabinose, D-ribose, D-ribulose, D-xylulose, L-xylulose, etc .; hexose (eg, D-glucose, D-talose, D) -Bucicose, D-galactose, D-fructose, L-galactose, L-mannose, D-tagatose, etc.); pentose sugar (eg, aldheptose, heproose, etc.); octose sugar (eg, octulose, etc.); For example, 2-deoxy-D-ribose, 6-deoxy-L-galactose, 6-deoxy-L-mannose, etc .; amino sugar (eg, D-glucosamine, D-galactosamine, shea Acid, Aminouron acid, muramic acid); uronic acid (e.g., D- glucuronic acid, D- mannuronic acid, L- guluronic acid, D- galacturonic acid, L- iduronic acid) and the like.

Examples of the oligosaccharides include sucrose, gnocyanose, umbelliferose, lactose, planteose, isoliquinoses, α, α-trehalose, raffinose, lycnose, umbilicin, stachyose verbus courses and the like.
Examples of the polysaccharide include cellulose, quince seed, chondroitin sulfate, starch, galactan, dermatan sulfate, glycogen, gum arabic, heparan sulfate, hyaluronic acid, tragacanth gum, keratan sulfate, chondroitin, xanthan gum, mucoitin sulfate, guar gum, dextran, kerato sulfate. , Locust bean gum, succinoglucan, caronic acid and the like.

  Examples of amino acids include neutral amino acids (eg, threonine, cysteine, etc.); basic amino acids (eg, hydroxylysine, etc.) and the like. Examples of amino acid derivatives include acyl sarcosine sodium (lauroyl sarcosine sodium), acyl glutamate, acyl β-alanine sodium, glutathione, and pyrrolidone carboxylic acid.

Examples of the organic amine include monoethanolamine, diethanolamine, triethanolamine, morpholine, triisopropanolamine, 2-amino-2-methyl-1,3-propanediol, and 2-amino-2-methyl-1-propanol. Is mentioned.
Examples of the polymer emulsion include an acrylic resin emulsion, a polyethyl acrylate emulsion, an acrylic resin liquid, a polyacryl alkyl ester emulsion, a polyvinyl acetate resin emulsion, and a natural rubber latex.

Examples of the pH adjuster include buffers such as lactic acid-sodium lactate, citric acid-sodium citrate, and succinic acid-sodium succinate.
Examples of vitamins include vitamins A, B1, B2, B6, C, E and derivatives thereof, pantothenic acid and derivatives thereof, biotin and the like.
Examples of the antioxidant include tocopherols, dibutylhydroxytoluene, butylhydroxyanisole, gallic acid esters and the like.

  Examples of the antioxidant assistant include phosphoric acid, citric acid, ascorbic acid, maleic acid, malonic acid, succinic acid, fumaric acid, kephalin, hexametaphosphate, phytic acid, and ethylenediaminetetraacetic acid.

  Other components that can be blended include, for example, preservatives (ethyl paraben, butyl paraben, etc.); anti-inflammatory agents (eg, glycyrrhizic acid derivatives, glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokitiol, zinc oxide, allantoin, etc.); whitening agents (for example, , Placenta extract, saxifrage extract, arbutin, etc.); various extracts (eg, Dokudami extract, duckweed extract, merirot extract, nettle extract, licorice extract, peonies extract, scorpion extract, loofah extract, kina extract, yukinoshita extract, clara Extract, potato extract, fennel extract, primrose extract, rose extract, sage extract, lemon extract, sicon extract, aloe extract, ginger root extract, eucalyptus extract, cedar extract, sage extract, thyme extract, Extract, seaweed extract, cucumber extract, clove extract, raspberry extract, melissa extract, carrot extract, maroni extract, peach extract, peach leaf extract, mulberry extract, cornflower extract, hamamelis extract, placenta extract, thymus extract, silk extract, etc.), activation Agents (for example, royal jelly, photosensitizer, cholesterol derivatives, etc.); blood circulation promoters (for example, nonyl acid wallenylamide, nicotinic acid benzyl ester, nicotinic acid β-butoxyethyl ester, capsaicin, gingerone, cantharis tincture, ectamol, tannic acid, α-borneol, tocopherol nicotinate, inositol hexanicotinate, cyclandrate, cinnarizine, trazoline, acetylcholine, verapamil, cephalanthin, γ-oryzano Le etc.); anti-seborrhoeic agents (e.g., sulfur, thianthol and the like); anti-inflammatory agents (e.g., tranexamic acid, thiotaurine, and a hypotaurine and the like) and the like.

The dosage form of the external composition for skin of the present invention can be arbitrarily selected, such as a solution system, a solubilization system, an emulsification system, a powder dispersion system, a water-oil two-layer system, a water-oil-powder three-layer system, etc. Can take a wide range of dosage forms. In addition, the product form of the composition for external use of the skin of the present invention is also arbitrary, such as facial cleansers, lotions, emulsions, creams, packs, and other facial cosmetics, foundations, lipsticks, eye shadows, makeup cosmetics and body cosmetics, It can be used for hair cosmetics, oral cosmetics, aromatic cosmetics, cleaning agents, ointments and the like.
The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto. Unless otherwise specified, the blending amount is expressed in mass% with respect to the system in which the component is blended.

[Synthesis Example 1 of Hydroxypropyl Hyaluronic Acid]
Hyaluronic acid (1.0 g) having a molecular weight of about 900,000 was added to a mixed liquid of propylene oxide (2.1 mL) and water (2.25 mL) and stirred. A 2 mol / L aqueous sodium hydroxide solution (0.2 mL) was added to the mixture, and the mixture was stirred at room temperature for 30 minutes, and then allowed to stand for 3 days. Water was added to the resulting reaction solution and sufficiently dialyzed, and then water was removed from the hydroxypropyl hyaluronic acid aqueous solution remaining in the dialysis tube to obtain hydroxypropyl hyaluronic acid.
(Analysis by 1H-NMR)
When JEOL EX-400 was used and measured with a D ₂ O solvent at 30 ° C., signals were observed at δ 1.03-1.09 ppm, 1.95 ppm, 3.36-3.95 ppm, and 4.47 ppm. The results are shown in FIG.
Also, the CH ₃ signal derived from the N- acetyl groups, from each of the integral value of CH ₃ signal derived from the 2-hydroxypropyl group, the number of the introduction of hydroxypropyl groups and about 4 per N- acetyl groups calculated.
(Molecular weight measurement)
When the molecular weight was measured by HPLC-GPC, the molecular weight of the resulting hydroxypropyl hyaluronic acid was about 380,000.

[Synthesis example of hydroxybutyl hyaluronic acid]
Hyaluronic acid (0.5 g) having a molecular weight of about 900,000 was added to a mixture of 1,2-epoxybutane (1.05 mL) and water (1.125 mL) and stirred. A 2 mol / L aqueous sodium hydroxide solution (0.125 mL) was added to the mixture, and the mixture was stirred at room temperature for 30 minutes, and then allowed to stand for 5 days. Acetone was added to the resulting reaction solution, and the resulting precipitate was washed several times with acetone. The obtained precipitate was dissolved in water and sufficiently dialyzed, and then water was removed from the aqueous hydroxybutyl hyaluronic acid solution remaining in the dialysis tube to obtain hydroxybutyl hyaluronic acid.
(Analysis by 1H-NMR)
Using JEOL EX-400 and measuring with a D ₂ O solvent at 30 ° C., δ 0.85 ppm, 1.20-1.50 ppm, 1.95 ppm, 3.20-3.90 ppm, 4.30-4. A signal was observed at 60 ppm. The results are shown in FIG.
Further, N- acetyl groups and CH ₃ from the signal, 2 from each of the integral value of CH ₃ signal derived from the hydroxybutyl group, the number of the introduction of hydroxy butyl about per N- acetyl groups 3.2 It was calculated as pieces.
(Molecular weight measurement)
When the molecular weight was measured by HPLC-GPC, the molecular weight of the obtained hydroxybutyl hyaluronic acid was about 380,000.

[Synthesis example of hyaluronic acid glyceride]
Hyaluronic acid (0.5 g) having a molecular weight of about 900,000 was added to a mixture of glycidol (1.32 mL) and water (1.125 mL) and stirred. A 2 mol / L aqueous sodium hydroxide solution (0.125 mL) was added to the mixture, and the mixture was stirred at room temperature for 30 minutes and then allowed to stand for 4 days. Ethanol was added to the resulting reaction solution, and the resulting precipitate was dissolved in water and sufficiently dialyzed. Then, water was removed from the aqueous hyaluronic acid glyceride solution remaining in the dialysis tube to obtain hyaluronic acid glyceride.
(Analysis by 1H-NMR)
When JEOL EX-400 was used and measured with a D ₂ O solvent at 30 ° C., signals were observed at δ 1.95 ppm, 3.20-4.10 ppm, and 4.35-4.60 ppm. The results are shown in FIG.
Moreover, from the integrated values of the signal derived from CH _{3 of the} N-acetyl group and the signal derived from —CH ₂ — of the glyceryl group (2,3-dihydroxypropyl group), the number of introduced glyceryl groups is N-acetyl group. It was calculated to be about 6 pieces per piece.
(Molecular weight measurement)
When the molecular weight was measured by HPLC-GPC, the obtained hyaluronic acid glyceride had a molecular weight of about 390,000.

[Synthesis Example 2 of Hydroxypropyl Hyaluronic Acid]
To a mixed solution of propylene oxide (10.5 mL) and water (11.25 mL), hyaluronic acid (5.0 g) having a molecular weight of about 100,000 was added and stirred. A 2 mol / L aqueous sodium hydroxide solution (1.25 mL) was added to the mixture, and the mixture was stirred at room temperature for 3 days. After adding water to the obtained reaction liquid and sufficiently dialyzing it, the aqueous hydroxypropyl hyaluronic acid solution remaining in the dialysis tube was lyophilized to remove the water to obtain about 2.3 g of hydroxypropyl hyaluronic acid.
When JEOL EX-400 was used and measured with a D ₂ O solvent at 30 ° C., a signal was observed at substantially the same position as that of the hydroxypropyl hyaluronic acid of Example 1.
Also, the CH ₃ signal derived from the N- acetyl groups, from each of the integral value of CH ₃ signal derived from the 2-hydroxypropyl group, the number of the introduction of hydroxypropyl groups is about 2 per N- acetyl groups calculated.
Moreover, when the molecular weight was measured by HPLC-GPC, the molecular weight of the obtained hydroxypropyl hyaluronic acid was about 86,000.

Moisturizing effect First , the moisturizing effect test method and evaluation criteria used in the present invention will be described.
As a “test solution”, a 5% aqueous solution of the dry residue of each sample was used.
(1) Moisture evaporation rate After dropping 10 μL of the test solution (5% aqueous solution of the dry residue of each sample) onto a 2.0 × 2.0 cm filter paper, the weight loss is measured for 10 minutes every minute, The weight (μg / min) decreasing per minute was determined and evaluated based on the following criteria.
◎: Less than 0.50 ○: 0.50 or more and less than 0.55 Δ: 0.55 or more and less than 0.60 ×: 0.60 or more

(2) Transdermal moisture evaporation (TEWL)
After washing the upper arm of the panel of 20 men and women, apply 0.1 mL / cm ^{2 of} the test solution, and measure the TEWL values before and immediately after application with a moisture evaporation measuring device (Meeco). The rate of change was calculated based on the above, the average value was calculated, and evaluated based on the following criteria. It can be evaluated that the higher the TEWL change rate, the higher the moisturizing effect.
TEWL change rate (%) = (TEWL value before application−TEWL value after application) / (TEWL value before application) × 100
◎: 20 or more ○: 10 or more Δ: 3 or more and less than 10 ×: less than 3

(3) Skin conductance After washing the upper arm of 20 male and female panels, apply 0.1 mL / cm ^{2 of} the test solution, measure skin conductance before and immediately after application, and change rate based on the following formula: The average value was calculated and evaluated based on the following criteria. It can be evaluated that the larger the skin conductance change rate, the more the stratum corneum moisture increases and the higher the moisturizing effect.
Skin conductance change rate (%) = (conductance value after application−conductance value before application) / (conductance value before application) × 100
◎: 20 or more ○: 10 or more Δ: 3 or more and less than 10 ×: less than 3

(Table 1) (Evaluation 1) (Evaluation 2) (Evaluation 3)
Glycerin ○ ○ ○
1,3-butylene glycol × × ×
Propylene glycol △ △ △
Hyaluronic acid ○ ○ ○
Hydroxyalkylated hyaluronic acid of general formula (I)
(Synthesized in Example 1) ◎ ◎ ◎
As shown in Table 1, it was recognized that hydroxypropyl hyaluronic acid, which is a hydroxyalkylated hyaluronic acid represented by the general formula (I), has an excellent moisturizing effect as compared with conventional moisturizing components.

Surface tension reduction ability (test method)
A solution obtained by dissolving hydroxyalkylated hyaluronic acid or hyaluronic acid at a predetermined concentration in pure water is used as a test solution, and a measurement temperature is 25 ° C. using a dynamic contact angle tensiometer (DCAT21, DataPhysics Instruments GmbH, Filderstadt, Germany). The surface tension was measured.
4 and 5, hyaluronic acid (molecular weight 900,000) as a raw material of Example 1 and hydroxypropyl hyaluronic acid of Example 1 (molecular weight about 360,000, substitution degree about 4) are 1 × 10 ⁻⁷ to 1 The result of having measured the surface tension in the density | concentration range of * 10 < ^-1 > g / dL is shown.

The surface tension of the hyaluronic acid aqueous solution was almost the same as the surface tension of water (71.79 mN / m) (FIG. 4), whereas the hydroxypropyl hyaluronic acid aqueous solution had a surface concentration of 1 × 10 ⁻² g / dL or more. A decrease in tension was observed, and the concentration decreased to 54.54 mN / m at a concentration of 1 × 10 ⁻¹ g / dL (FIG. 5). As a result, since the hydroxyalkyl group has a hydrophobic portion (alkyl chain) and a hydrophilic portion (hydroxy group), hyaluronic acid has amphipathic properties due to the introduction of the hydroxyalkyl group, and exhibited surface tension reducing ability. Inferred. Different from hyaluronic acid, hydroxyalkylated hyaluronic acid can be considered to be a bio-related polymer having amphiphilic properties.

Table 2 below shows the hydroxypropyl hyaluronic acid of Example 1 (molecular weight of about 360,000, degree of substitution of about 4) and hydroxypropyl hyaluronic acid of Example 4 (molecular weight of about 86,000, degree of substitution of about 2). It is the result of having compared surface tension about aqueous solution.
The hyaluronic acid (about 100,000), which is the raw material of Example 4, did not show the ability to reduce the surface tension, but the hydroxypropyl hyaluronic acid of Example 4 was 1 × 10 ⁻² as in Example 1. The surface tension reducing ability was exhibited at a concentration of g / dL or higher, and the concentration decreased to 59.7 mN / m at 1 × 10 ⁻² g / dL or higher. The hydroxypropyl hyaluronic acid of Example 4 had a slightly lower surface tension reducing ability than the hydroxypropyl hyaluronic acid of Example 1, which was presumed to be due to the low degree of substitution in Example 4.

(Table 2)
――――――――――――――――――――――――――
Concentration Surface tension (mN / m)
(G / dL) Example 1 Example 4
――――――――――――――――――――――――――
1 × 10 ⁻¹ 53.5 59.7
1 × 10 ⁻² 70.8 71.3
1 × 10 ⁻³ 71.7 71.9
1 × 10 ⁻⁴ 71.7 71.7
1 × 10 ⁻⁵ 71.8 71.9
――――――――――――――――――――――――――

Table 3 below shows the familiarity with the skin when a hydroxyalkylated hyaluronic acid aqueous solution with a concentration of 1 × 10 ⁻¹ g / dL is applied, compared with an aqueous solution (control) of the same concentration of hyaluronic acid (molecular weight about 100,000). It is the result of evaluation. The evaluation criteria are as follows.
○: Compared to control.
Δ: Almost equivalent to control.
X: worse than control.

(Table 3)
――――――――――――――――――――――――――――――
Hydroxyalkylation Familiarity evaluation Hyaluronic acid ――――――――――――――――――――――――――――――
Example 1 ○
Example 2 ○
Example 3 ○
Example 4 ○
――――――――――――――――――――――――――――――
From Table 3, it is understood that the hydroxyalkylated hyaluronic acid of the present invention has a better familiarity with the skin than hyaluronic acid. This is presumed to be due to the surface tension reducing ability and amphiphilicity of hydroxyalkylated hyaluronic acid.

Solubility in ethanol The solubility of hydroxyalkylated hyaluronic acid and hyaluronic acid in ethanol was compared. The results are shown in Table 4.
(Table 4)
――――――――――――――――――――――――――――――
Hydroxyalkylation 0.1% by weight Solution solubility Hyaluronic acid (Solvent: 70% ethanol)
――――――――――――――――――――――――――――――
Example 1 Dissolution Example 2 Dissolution Example 3 Dissolution Example 4 Dissolution ――――――――――――――――――――――――――――――
Hyaluronic acid (molecular weight about 400,000) Precipitation ――――――――――――――――――――――――――――――

When hyaluronic acid was added to 70% ethanol at a concentration of 0.1% by mass, it did not dissolve and precipitate was formed. On the other hand, any hydroxyalkylated hyaluronic acid was completely dissolved without precipitation at the same concentration.
Therefore, it is understood that hydroxyalkylated hyaluronic acid has higher solubility in ethanol than hyaluronic acid and has a wide range of applications in preparations.
Although the preferable example is described to the composition for external use of the skin of this invention below, it is not limited to this. The following external compositions for skin were all excellent in moisturizing effect and familiar.

It is the figure which showed the NMR data of hydroxypropyl hyaluronic acid. It is the figure which showed the NMR data of hydroxybutyl hyaluronic acid. It is the figure which showed the NMR data of the hyaluronic acid glyceride. It is a figure which shows the relationship between the density | concentration of hyaluronic acid aqueous solution, and the surface tension of this aqueous solution. It is a figure which shows the relationship between the density | concentration of hydroxypropyl hyaluronic acid aqueous solution, and the surface tension of this aqueous solution.

Claims (5)

Hydroxyalkylated hyaluronic acid represented by the general formula (I).
(Chemical formula 1)

(Wherein R ^{1 to} R ⁶ are each independently a hydrogen atom or an ether-bonded hydroxyalkyl group, but not all are hydrogen atoms. R ⁷ is a hydrogen atom or an alkali metal atom, and n is (It is an integer from 1 to 10000.)   2. The hydroxyalkylated hyaluronic acid according to claim 1, wherein the number of hydroxyalkyl groups is 1 to 10 per repeating structural unit of hyaluronic acid.   The hydroxy group according to claim 1 or 2, wherein the hydroxyalkyl group is one or more selected from a 2-hydroxypropyl group, a 2-hydroxybutyl group, and a 2,3-dihydroxypropyl group. Alkylated hyaluronic acid.   An external composition for skin comprising the hydroxyalkylated hyaluronic acid according to any one of claims 1 to 3.   A humectant comprising the hydroxyalkylated hyaluronic acid according to any one of claims 1 to 3 as an active ingredient.

Images