WO2011102462A1 - 修飾ヒアルロン酸および/またはその塩、ならびにその製造方法およびこれを含む化粧料 - Google Patents
修飾ヒアルロン酸および/またはその塩、ならびにその製造方法およびこれを含む化粧料 Download PDFInfo
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- WO2011102462A1 WO2011102462A1 PCT/JP2011/053504 JP2011053504W WO2011102462A1 WO 2011102462 A1 WO2011102462 A1 WO 2011102462A1 JP 2011053504 W JP2011053504 W JP 2011053504W WO 2011102462 A1 WO2011102462 A1 WO 2011102462A1
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- hyaluronic acid
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/345—Alcohols containing more than one hydroxy group
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
- C08B37/0072—Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
- C08L5/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
Definitions
- the present invention relates to a modified hyaluronic acid and / or a salt thereof, a production method thereof and a cosmetic containing the same.
- Hyaluronic acid is widely distributed in living tissues such as chicken crown, umbilical cord, skin, cartilage, vitreous body, and joint fluid, and is widely used as a component of cosmetics, pharmaceuticals, and foods, for example.
- Patent Document 1 Japanese Patent Application Laid-Open No. 6-25306 describes solvent-insolubilized hyaluronic acid in which a fatty acid residue is bonded to an alcoholic hydroxyl group of hyaluronic acid.
- the solvent-insolubilized hyaluronic acid described in Patent Document 1 has low solubility in water and ethanol, it is not suitable for blending into products containing water or ethanol (for example, cosmetics, pharmaceuticals, foods).
- the present invention provides a modified hyaluronic acid and / or salt thereof, which has a high modifying effect on a living tissue such as skin and is excellent in water solubility, a production method thereof, and a cosmetic containing the same.
- the modified hyaluronic acid and / or salt thereof according to one embodiment of the present invention includes a glycerin skeleton-containing group represented by the following general formula (1).
- R 1 represents a linear or branched alkyl group or alkenyl group.
- modified hyaluronic acid and / or salt thereof refers to hyaluronic acid and / or a salt thereof in which an organic group is introduced at least partially, and is different from hyaluronic acid and / or a salt thereof. It has a structure.
- the “organic group” refers to a group having a carbon atom.
- the “hydrocarbon group-containing group” refers to an organic group having a hydrocarbon group at least partially.
- the “hydrocarbon group” in the “hydrocarbon group-containing group” is a carbonization contained in hyaluronic acid and / or a salt thereof. What is different from a hydrogen group.
- the “glycerin skeleton” refers to a structural unit represented by —O—CH 2 —CHOH—CH 2 —O—.
- the name glycerin skeleton is derived from the fact that this glycerin skeleton constitutes a part of glycerin (HO—CH 2 —CHOH—CH 2 —OH).
- R 1 may be a linear or branched alkyl group or alkenyl group having 6 to 20 carbon atoms.
- the glycerin skeleton-containing group may be bonded to at least one carbon atom constituting the hyaluronic acid skeleton.
- the modified hyaluronic acid and / or salt thereof can be obtained by reacting hyaluronic acid and / or salt thereof with a compound represented by the following general formula (2).
- R 1 represents a linear or branched alkyl group or alkenyl group.
- R 1 may be a linear or branched alkyl group or alkenyl group having 6 to 20 carbon atoms.
- the number of the glycerin skeleton-containing groups contained in one structural unit of hyaluronic acid may be 0.001 to 0.5.
- the kinematic viscosity of a 1% aqueous solution of the modified hyaluronic acid and / or salt thereof may be 50 mm 2 / s or less.
- a method for producing a modified hyaluronic acid and / or salt thereof according to another embodiment of the present invention is a method for producing the modified hyaluronic acid and / or salt thereof, wherein the hyaluronic acid and / or salt thereof is represented by the following general formula ( A step of reacting with the compound represented by 2).
- R 1 represents a linear or branched alkyl group or alkenyl group.
- a cosmetic according to another embodiment of the present invention contains the modified hyaluronic acid and / or a salt thereof.
- the modified hyaluronic acid and / or salt thereof having a hydrocarbon group-containing group has a transmittance X defined by the following formula (i) of 40% or more, and The transmittance Y defined by (ii) is 50% or more.
- X T 2 / T 1 ⁇ 100 (%) (i) (In the formula, T 1 is a light transmittance of a wavelength of 660 nm and an optical path length of 10 mm in water, and T 2 is a wavelength in water containing a modified hyaluronic acid having 1% hydrocarbon group-containing group and / or a salt thereof.
- T 3 is the transmittance of light having a wavelength of 660 nm and an optical path length of 10 mm in a 70 vol% ethanol-containing ethanol-water mixture
- T 4 is a modified hyaluronic acid having a 1% hydrocarbon group-containing group and / or Or the transmittance of light having a wavelength of 660 nm and an optical path length of 10 mm in an ethanol-water mixed solution containing 70 vol% ethanol containing the salt thereof.
- the transmittance X may be 60% or more.
- the transmittance Y may be 70% or more.
- the hydrocarbon group contained in the hydrocarbon group-containing group is a linear or branched alkyl group or alkenyl having 6 to 20 carbon atoms. Can be a group.
- the number of the hydrocarbon group-containing group contained in one structural unit of hyaluronic acid may be 0.001 to 0.2.
- the kinematic viscosity of a 1% aqueous solution can be 50 mm 2 / s or less.
- a cosmetic according to still another embodiment of the present invention contains the modified hyaluronic acid having a hydrocarbon group-containing group and / or a salt thereof.
- the modified hyaluronic acid and / or salt thereof includes the glycerin skeleton-containing group represented by the general formula (1), it is possible to achieve both hydrophilicity and hydrophobicity. It has a modifying effect (for example, a skin barrier function repairing effect) and is excellent in water solubility. Therefore, the above-mentioned modified hyaluronic acid and / or salt thereof can be used for various products (cosmetics, foods, pharmaceuticals) containing, for example, water, and have a high modifying effect (for example, skin) (Barrier function repair effect).
- a modifying effect for example, a skin barrier function repairing effect
- FIG. 1 (a) shows the 1 H-NMR spectrum (observation frequency 400 MHz, internal standard substance: DSS (0 ppm), solvent: heavy water) of the modified hyaluronic acid obtained in Example 1, and FIG.
- FIG. 2 shows a photomicrograph of the sample obtained in Comparative Example 11.
- FIG. 3 shows the measured values of TEWL when the test solution 1 and the test solution 2 are applied.
- FIG. 4 shows the improvement rate (%) when 3 days have elapsed after application when Test Solution 1 and Test Solution 2 are applied.
- % means “mass%” and “part” means “part by mass”.
- Modified hyaluronic acid and / or salt thereof 1.1. Structure 1.1.1. Glycerin skeleton-containing group (hydrocarbon group-containing group)
- the modified hyaluronic acid and / or salt thereof according to the present embodiment includes a glycerin skeleton-containing group represented by the following general formula (1) (hereinafter also simply referred to as “glycerin skeleton-containing group”).
- R 1 represents a linear or branched alkyl group or alkenyl group.
- R 1 in the general formula (1) is bonded to one of oxygen atoms that do not constitute a hydroxyl group contained in the glycerin skeleton-containing group, and the glycerin skeleton-containing group
- the hydroxyl group contained in is a secondary hydroxyl group
- the other oxygen atom that does not constitute the hydroxyl group contained in the glycerin skeleton-containing group is bonded to the carbon atom that constitutes hyaluronic acid and / or a salt thereof.
- examples of the linear or branched alkyl group represented by R 1 include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, tert-butyl group, n-pentyl group, isopentyl group, neopentyl group, tert-pentyl group, 2-methylbutyl group, 1-methylbutyl group, n-hexyl group, isohexyl group, 3-methylpentyl group, 2-methylpentyl group 1-methylpentyl group, n-heptyl group, n-octyl group, isooctyl group, 2-ethylhexyl group, n-nonyl group, n-decyl group, n-undecyl group, n-dodecyl group, n-tridecyl
- examples of the linear or branched alkenyl group represented by R 1 include a vinyl group, an allyl group, a propenyl group, an isopropenyl group, a butenyl group, an isobutenyl group, and a pentenyl group.
- the linear or branched alkyl group or alkenyl group represented by R 1 is more effective in improving the skin barrier function and is more excellent in water solubility.
- the number of carbon atoms is preferably 6-20, more preferably 8-18, and even more preferably 10-16.
- the group represented by R 1 is preferably an alkyl group.
- the skin barrier function repair is performed.
- the number of carbon atoms of the linear or branched alkyl group or alkenyl group represented by R 1 exceeds 20, water solubility may be low.
- Hyaluronic acid refers to a polysaccharide having one or more constituent units composed of disaccharides of glucuronic acid and N-acetylglucosamine.
- the “hyaluronic acid salt” is not particularly limited, but is preferably a food or pharmaceutically acceptable salt, for example, sodium salt, potassium salt, calcium salt, zinc salt, magnesium salt, ammonium salt, Examples include alkyl ammonium salts.
- Hyaluronic acid is basically a disaccharide or more containing at least one disaccharide unit in which the 1-position of ⁇ -D-glucuronic acid and the 3-position of ⁇ -DN-acetyl-glucosamine are bonded, and ⁇ Basically composed of -D-glucuronic acid and ⁇ -DN-acetyl-glucosamine and having a plurality of disaccharide units bonded thereto, and derivatives thereof such as hydrolyzable protecting groups such as acyl groups Those having the above can also be used.
- the sugar may be an unsaturated sugar, and examples of the unsaturated sugar include non-reducing terminal sugars, usually those having unsaturated carbon atoms between positions 4 and 5 of glucuronic acid.
- the modified hyaluronic acid and / or salt thereof according to the present embodiment contains a glycerin skeleton contained in one constituent unit of hyaluronic acid in that it can further enhance the effect of repairing the barrier function of the skin and is superior in water solubility.
- the number of groups is preferably from 0.001 to 0.5, more preferably from 0.005 to 0.2, and even more preferably from 0.01 to 0.15.
- “one constituent unit of hyaluronic acid” means one constituent unit composed of disaccharides of glucuronic acid and N-acetylglucosamine.
- the solubility in ethanol is low and the hydrophobicity is low. Since it is not sufficient, the effect of repairing the barrier function of the skin may not be sufficient.
- the number of glycerin skeleton-containing groups contained in one constituent unit of hyaluronic acid exceeds 0.5, water solubility may be low.
- the number of glycerin skeleton-containing groups contained in one structural unit of hyaluronic acid can be identified by 1 H-NMR spectrum analysis.
- the glycerin skeleton-containing group can be bonded to at least one carbon atom constituting the hyaluronic acid skeleton.
- the “carbon atom constituting the hyaluronic acid skeleton” refers to a carbon atom contained in glucuronic acid and N-acetylglucosamine constituting the hyaluronic acid.
- modified hyaluronic acid and / or by introducing a glycerin skeleton-containing group by reacting compound 1 or compound 2 described later to at least one of the carboxyl group and hydroxyl group contained in the raw material hyaluronic acid and / or salt thereof Or its salt can be obtained.
- the glycerin skeleton-containing group is bonded to the modified hyaluronic acid and / or salt thereof, for example, the modified hyaluronic acid according to the present embodiment and / or a 1 H-NMR spectrum of a salt thereof, in comparison with 1 H-NMR spectrum of hyaluronic acid and / or its salt as the starting material, a methylene group in the glycerin skeleton-containing group of the modified hyaluronic acid (-CH 2 - ) In the peak indicating protons.
- the glycerin skeleton-containing group includes, for example, the 4-position carbon atom (C-4) and the 6-position carbon constituting the modified hyaluronic acid and / or salt thereof.
- Atom (C-6), and carbon atoms at the 2-position (C-2), 3-position carbon atom (C-3), and 5-position carbon of glucuronic acid constituting the modified hyaluronic acid and / or salt thereof It can be bonded to at least one selected from carbonyl groups bonded to the atom (C-5). More specifically, the modified hyaluronic acid and / or salt thereof according to the present embodiment can be a compound represented by the following general formula (3).
- R 2 to R 6 independently represent a hydroxyl group or a glycerin skeleton-containing group represented by the general formula (1) (except when R 2 to R 6 all represent a hydroxyl group).
- N represents a number from 1 to 750.
- the hydrogen atom bonded to the nitrogen atom of N-acetylglucosamine bonded to the carbon atom (C-2) at the 2-position is a glycerin represented by the general formula (1). It may be substituted with a skeleton-containing group.
- n is preferably 1 to 50 from the viewpoint that the effect of repairing the barrier function of the skin can be further enhanced and water solubility is excellent. More preferably, it is ⁇ 25.
- the kinematic viscosity of an aqueous solution of modified hyaluronic acid and / or a salt thereof can be measured using an Ubbelohde viscometer (manufactured by Shibata Kagaku Kikai Kogyo Co., Ltd.). At this time, an Ubbelohde viscometer having a coefficient such that the number of seconds of flow is 200 to 1000 seconds is selected. The measurement is performed in a constant temperature water bath at 30 ° C. so that there is no temperature change.
- the kinematic viscosity (unit: mm 2 / s) can be obtained from the product of the number of seconds of flow of the aqueous solution measured by the Ubbelohde viscometer and the coefficient of the Ubbelohde viscometer.
- the kinematic viscosity of the 1% aqueous solution of the modified hyaluronic acid and / or salt thereof according to the present embodiment is superior to the permeability to the skin of the skin, and the effect of repairing the barrier function of the skin can be further enhanced. It is preferably 50 mm 2 / s or less, more preferably 0.1 to 10 mm 2 / s, and further preferably 0.5 to 3 mm 2 / s.
- the kinematic viscosity of a 1% aqueous solution of the modified hyaluronic acid and / or salt thereof according to this embodiment is 0.1 to 10 mm 2 / s (more preferably 0.5 to 3 mm 2 / s), a glycerin skeleton-containing group
- the skin has excellent permeability to the skin and can further enhance the effect of repairing the barrier function of the skin.
- the average molecular weight of hyaluronic acid and / or a salt thereof is a value measured by the following method.
- Equation (A) The specific viscosity is measured by (Equation (A)), and the reduced viscosity at each concentration is calculated (Equation (B)).
- a graph is drawn with the reduced viscosity on the vertical axis and the concentration (g / 100 mL) of the product converted to dry matter on the horizontal axis, and the intrinsic viscosity is determined from the intersection of the straight line connecting the points and the vertical axis. Substituting the intrinsic viscosity obtained here into Laurent's formula (formula (C)) to calculate the average molecular weight (TC Laurent, M. Ryan, A. Pietruszkiewicz,: BBA, 42, 476-485 (1960)) .
- the modified hyaluronic acid and / or salt thereof has a transmittance X of light (wavelength 660 nm, optical path length 10 mm) in water containing 1% modified hyaluronic acid and / or salt thereof with respect to water. 20% or more, more preferably 40% or more, and still more preferably 80% or more.
- the light transmittance X in water containing the modified hyaluronic acid and / or salt thereof is an index indicating the solubility of the modified hyaluronic acid and / or salt in water.
- the modified hyaluronic acid and / or salt thereof having a light transmittance X of 40% or more in water containing the modified hyaluronic acid and / or salt thereof is excellent in solubility in water and contains water. It is easy to mix into the product to be used.
- the modified hyaluronic acid and / or salt thereof is light (wavelength 660 nm, optical path) in an ethanol-water mixed solution (ethanol content 70% by volume) containing 1% modified hyaluronic acid and / or salt thereof.
- the transmittance Y of 10 mm in length is preferably 20% or more, more preferably 50% or more, and 70% or more with respect to the ethanol-water mixture (ethanol content 70% by volume). Is more preferable.
- the light transmittance Y in the ethanol-water mixed solution containing the modified hyaluronic acid and / or its salt is an index indicating the solubility of the modified hyaluronic acid and / or its salt in ethanol.
- the modified hyaluronic acid and / or salt thereof in which the light transmittance Y in the ethanol-water mixed solution containing the modified hyaluronic acid and / or salt thereof is 50% or more is excellent in solubility in ethanol. It is easy to mix in a product containing ethanol and has high hydrophobicity.
- the modified hyaluronic acid and / or its salt according to this embodiment is, for example, a compound represented by the following general formula (2) (this specification) And also referred to as “Compound 1” in the text.)
- a compound represented by the following general formula (4) also referred to as “compound 2” in the present specification
- the modified hyaluronic acid according to the present embodiment and / or Or a salt may be prepared.
- raw material hyaluronic acid and / or its salt (hereinafter referred to as “raw material hyaluronic acid and / or its salt”) is substituted with an alkylammonium salt and then reacted with compound 1 or compound 2. It is preferable.
- R 1 represents a linear or branched alkyl group or alkenyl group.
- the group represented by R 1 in the general formula (2) include those exemplified as the groups represented by R 1 in the general formula (1).
- R 1 has the same meaning as R 1 in the general formula (2), and X represents a halogen atom.
- Examples of the halogen atom represented by X in the general formula (4) include a chlorine atom, a bromine atom, and an iodine atom.
- Raw material The raw material hyaluronic acid and / or salt thereof used in the production of the modified hyaluronic acid and / or salt thereof according to the present embodiment is extracted from a biological tissue such as an animal (for example, chicken crown, umbilical cord, skin, joint fluid, etc.). May be used, or those obtained by culturing microorganisms, animal cells or plant cells (for example, fermentation using a bacterium of the genus Streptococcus), chemically synthesized or enzymatically synthesized, etc. be able to.
- a biological tissue such as an animal (for example, chicken crown, umbilical cord, skin, joint fluid, etc.). May be used, or those obtained by culturing microorganisms, animal cells or plant cells (for example, fermentation using a bacterium of the genus Streptococcus), chemically synthesized or enzymatically synthesized, etc. be able to.
- the average molecular weight of the raw material hyaluronic acid and / or salt thereof is preferably from 400 to 1,000,000, more preferably from 1,000 to 300,000, more preferably from 2000 to 1,000, in terms of achieving both hydrophilicity and appropriate hydrophobicity. More preferably, it is 50,000.
- the raw material hyaluronic acid and / or salt thereof either the crude extract or the purified product may be used, but the purity of the purified product, specifically hyaluronic acid and / or salt thereof, is 90% (mass ratio). The above are preferred.
- the reaction between hyaluronic acid and / or a salt thereof and compound 1 or compound 2 may be unfavorable.
- Examples of such compound 3 include quaternary alkyl ammonium hydroxides having 2 to 18 carbon atoms, such as tetraethylammonium hydroxide, tetrapropylammonium hydroxide, and tetrabutylammonium hydroxide. That is, the quaternary alkyl ammonium salt of hyaluronic acid is preferably, for example, a quaternary alkyl ammonium salt having 2 to 18 carbon atoms.
- Examples of the quaternary alkyl ammonium salt include tetraethyl ammonium salt, tetrapropyl ammonium salt, tetrabutyl ammonium salt, tetrapentyl ammonium salt, and tetrahexyl ammonium salt.
- reaction of Alkylammonium Salt with Compound 1 or Compound 2 The reaction of quaternary alkyl ammonium salt of hyaluronic acid with Compound 1 or Compound 2 can be carried out in an organic solvent.
- the reaction temperature is usually 0 to 200 ° C.
- the reaction time is usually 0.1 to 48 hours.
- the organic solvent used in the above reaction include dimethylformamide (DMF), dimethyl sulfoxide (DMSO), tetrahydrofuran and the like, and these can be used alone or in combination.
- Compound 1 may be used alone or in combination of two or more. Specific examples of compound 1 include, for example, methyl glycidyl ether, ethyl glycidyl ether, propyl glycidyl ether, butyl glycidyl ether, octyl glycidyl ether, decyl glycidyl ether, dodecyl glycidyl ether, tridecyl glycidyl ether, myristyl glycidyl ether, palmityl glycidyl Examples thereof include alkyl glycidyl ethers such as ether and stearyl glycidyl ether, and alkenyl glycidyl ethers such as allyl glycidyl ether.
- Compound 2 may be used alone or in combination of two or more. Specific examples of compound 2 include, for example, methyl 3-chloro-2-hydroxypropyl ether, ethyl 3-chloro-2-hydroxypropyl ether, propyl 3-chloro-2-hydroxypropyl ether, butyl 3-chloro-2- Hydroxypropyl ether, octyl 3-chloro-2-hydroxypropyl ether, decyl 3-chloro-2-hydroxypropyl ether, dodecyl 3-chloro-2-hydroxypropyl ether, tridecyl 3-chloro-2-hydroxypropyl ether, myristyl 3 -Chloro-2-hydroxypropyl ether, palmityl 3-chloro-2-hydroxypropyl ether, stearyl 3-chloro-2-hydroxypropyl ether, allyl 3-chloro-2-hydroxypropyl ether
- the concentration of sodium salt and / or potassium salt in the reaction solution is preferably 5 to 20%. If the concentration of either the sodium salt or potassium salt is less than 5%, precipitation may not be possible in the next step of obtaining the precipitate. If it exceeds 20%, the sodium salt or potassium salt may be precipitated together with the modified hyaluronic acid and / or its salt in the step of obtaining the next precipitate.
- the method for producing the modified hyaluronic acid and / or salt thereof after adding the sodium salt and / or potassium salt to the reaction solution, alcohol is added to the reaction solution to cause precipitation.
- a step of obtaining a product can be further included.
- the alcohol include methanol and ethanol, and ethanol is preferable.
- the precipitate is modified hyaluronic acid and / or a salt thereof. That is, by adding alcohol to the reaction solution to obtain a precipitate (modified hyaluronic acid and / or salt thereof), it can be separated from the remaining reagent to obtain modified hyaluronic acid and / or salt thereof.
- the precipitate may be washed with a solvent in which the modified hyaluronic acid and / or salt thereof is difficult to dissolve (for example, water-containing alcohol). Thereafter, the precipitate is dried to obtain a purified modified hyaluronic acid and / or a salt thereof.
- a solvent in which the modified hyaluronic acid and / or salt thereof is difficult to dissolve for example, water-containing alcohol.
- the above-described step of obtaining a precipitate may be repeated a plurality of times.
- the kinematic viscosity of the modified hyaluronic acid and / or salt thereof when the kinematic viscosity of the modified hyaluronic acid and / or salt thereof is low (for example, when the kinematic viscosity is 10 mm 2 / s), the above-described case has occurred. In the method, a precipitate may not be obtained even when alcohol is added to the reaction solution. In this case, in the method for producing the modified hyaluronic acid and / or salt thereof according to this embodiment, the pH of the reaction solution is adjusted to 3 or less after the step of adding sodium salt and / or potassium salt to the reaction solution.
- the “suspension” is a mixture in which solid fine particles are dispersed in a liquid.
- the suspension may be in a state where the solid is dispersed in the liquid and the liquid is cloudy, or may be separated into a suspension phase and a supernatant phase.
- the suspension is preferably separated into a suspension phase and a supernatant phase in that the modified hyaluronic acid and / or a salt thereof is likely to precipitate in a later step.
- the water-soluble organic solvent is added at least in an amount necessary for the solution to change into the suspension.
- the water-soluble organic solvent include alcohol solvents such as methanol, ethanol, 1-propanol, and 2-propanol, ketone solvents such as acetone and methyl ethyl ketone, tetrahydrofuran, acetonitrile, and the like. Can be used in combination. Of these, ethanol is preferred.
- the amount of the water-soluble organic solvent added is 1 part or more, preferably 2 to 50 parts, more preferably 5 to 20 parts with respect to 1 part of the solution containing the modified hyaluronic acid and / or salt thereof. In this case, when the addition amount of the water-soluble organic solvent is less than 1 part with respect to 1 part of the solution containing the modified hyaluronic acid and / or a salt thereof, suspension is hardly generated.
- the solution before adding the water-soluble organic solvent is pH 3 or less, preferably pH 0.5 to 2.5, more preferably pH 1 to 2. If the pH of the solution before the addition of the water-soluble organic solvent exceeds 3, suspension is unlikely to occur even if the water-soluble organic solvent is added, and even if the pH of the solution is adjusted to 3.5 to 8 in the subsequent step. Further, the modified hyaluronic acid and / or its salt is difficult to precipitate. In addition, if the pH of the solution before the addition of the water-soluble organic solvent is too low, a large amount of salt is produced when the pH of the solution is adjusted to 3.5 to 8 in the subsequent step, which may not be preferable. .
- the suspension is adjusted to pH 3.5 to 8 to precipitate the modified hyaluronic acid and / or salt thereof.
- the suspension is preferably adjusted to pH 4 to 7 and more preferably adjusted to pH 4 to 6 in that a higher recovery rate can be achieved.
- the modified hyaluronic acid and / or salt thereof according to this embodiment has a high modifying effect (particularly, a skin barrier function repairing effect) on a living tissue such as skin.
- the modified hyaluronic acid and / or salt thereof according to the present embodiment may be applied to or contacted with the surface of a living tissue, and in particular applied to or contacted with the skin of the face, arms, fingers, feet, joints, etc. It is preferable to do so.
- the modified hyaluronic acid and / or salt thereof according to the present embodiment can be used, for example, as a component of cosmetics as described later. That is, the cosmetic according to one embodiment of the present invention contains modified hyaluronic acid and / or a salt thereof.
- the modified hyaluronic acid and / or salt thereof according to this embodiment is excellent in solubility in ethanol. For this reason, when mix
- the modified hyaluronic acid and / or salt thereof according to the present embodiment includes a glycerin skeleton-containing group represented by the general formula (1), so that both hydrophilicity and hydrophobicity can be achieved.
- the skin barrier function repair effect can be demonstrated.
- the mechanism by which the modified hyaluronic acid and / or salt thereof according to the present embodiment exerts a skin barrier function repairing effect is estimated as follows. That is, when the modified hyaluronic acid and / or salt thereof according to the present embodiment is applied to the skin, the hyaluronic acid skeleton site of the modified hyaluronic acid and / or salt thereof according to the present embodiment forms water that constitutes the stratum corneum of the skin.
- the glycerin skeleton-containing group of the modified hyaluronic acid and / or salt thereof according to the present embodiment is arranged in the lipid layer constituting the stratum corneum of the skin.
- the lamellar structure which consists of the water layer and lipid layer which the stratum corneum of skin originally has is repaired, and the barrier function which the lamellar structure originally has is repaired.
- the effect of repairing the skin barrier function can be exhibited.
- hydrophobicity is brought about by R 1 in the glycerin skeleton-containing group (hydrocarbon group-containing group), and the modified hyaluronic acid and / or its It is presumed that hydrophilicity is brought about by a hydroxyl group (including a hydroxyl group in a glycerin skeleton-containing group (hydrocarbon group-containing group)) and / or a carboxyl group contained in the salt.
- the modified hyaluronic acid and / or salt thereof according to the present embodiment When the modified hyaluronic acid and / or salt thereof according to the present embodiment is applied to the skin, for example, the glycerin skeleton-containing group (hydrocarbon group-containing group) of the modified hyaluronic acid and / or salt according to the present embodiment in the stratum corneum of the skin.
- R 1 in the group enters the lipid layer
- the hyaluronic acid skeleton part contained in the modified hyaluronic acid and / or salt thereof according to the present embodiment enters the aqueous layer to repair the lamellar structure of the skin, Water evaporation can be prevented. Thereby, it is guessed that the moisturizing power of skin can be improved.
- modified hyaluronic acid and / or salt thereof according to the present embodiment is excellent in water solubility by including the glycerin skeleton-containing group represented by the general formula (1), for example, in various products containing water. It can be used by adding.
- the modified hyaluronic acid and / or salt thereof according to the present embodiment is excellent in solubility in water and ethanol
- the modified hyaluronic acid and / or salt thereof according to the present embodiment is applied, for example, to a product that is a water-containing liquid. When it mix
- Modified hyaluronic acid and / or salt thereof having a hydrocarbon group-containing group has a hydrocarbon group-containing group and has a transmittance defined by the following formula (i) X can be 40% or more, and the transmittance Y defined by the following formula (ii) can be 50% or more.
- T 1 is a light transmittance of a wavelength of 660 nm and an optical path length of 10 mm in water
- T 2 is a wavelength in water containing a modified hyaluronic acid having 1% hydrocarbon group-containing group and / or a salt thereof. (The transmittance of light at 660 nm and optical path length 10 mm.)
- T 3 is the transmittance of light having a wavelength of 660 nm and an optical path length of 10 mm in a 70 vol% ethanol-containing ethanol-water mixture
- T 4 is a modified hyaluronic acid having a 1% hydrocarbon group-containing group and / or Or the transmittance of light having a wavelength of 660 nm and an optical path length of 10 mm in an ethanol-water mixed solution containing 70 vol% ethanol containing the salt thereof.
- the transmittance X of the modified hyaluronic acid and / or salt thereof having a hydrocarbon group-containing group is 40%, preferably the transmittance X is 60% or more, more preferably the transmittance X Is 80% or more, it is excellent in solubility in water and can be easily blended into a product containing moisture.
- the transmittance Y of the modified hyaluronic acid and / or salt thereof having a hydrocarbon group-containing group is 50%, preferably the transmittance Y is 70% or more, more preferably the transmittance Y Is 80% or more, it is excellent in solubility in ethanol, can be easily blended into a product containing ethanol, and has high hydrophobicity.
- the modified hyaluronic acid and / or salt thereof having a hydrocarbon group-containing group has a transmittance X of 40% or more (preferably 60% or more, more preferably 80% or more), and the transmittance.
- Y is 50% or more (preferably 70% or more, more preferably 80% or more), it is possible to achieve both hydrophilicity and hydrophobicity. , Skin barrier function repairing effect) and excellent in water solubility.
- the hydrocarbon group-containing group is a group having a hydrocarbon group at least in part.
- the hydrocarbon group is a linear or branched alkyl group or alkenyl group.
- Examples of the linear or branched alkyl group include a methyl group, an ethyl group, and an n-propyl group.
- linear or branched alkenyl group examples include a vinyl group, an allyl group, a propenyl group, an isopropenyl group, a butenyl group, an isobutenyl group, a pentenyl group, an isopentenyl group, a hexenyl group, a heptenyl group, and an octenyl group.
- the hydrocarbon group-containing group has a higher effect of repairing the barrier function of the skin and is more excellent in water solubility.
- a group represented by the following general formula (iii) is preferable.
- R 1 represents a hydrocarbon group.
- the hydrocarbon group-containing group is a group represented by the general formula (iii), for example, —O—CH 2 — R 1 in the general formula (iii) is bonded to one of the oxygen atoms that do not constitute a hydroxyl group contained in the CHOH—CH 2 —O— moiety, and the —O—CH 2 —CHOH—CH 2 —O— moiety
- the hydroxyl group contained is a secondary hydroxyl group
- the other oxygen atom not constituting the hydroxyl group contained in the —O—CH 2 —CHOH—CH 2 —O— moiety is a carbon constituting hyaluronic acid and / or a salt thereof.
- hydrocarbon groups contained in the hydrocarbon group-containing group (for example, the hydrocarbon group-containing group is represented by the general formula (iii) in that the effect of repairing the barrier function of the skin is higher and the water solubility is superior.
- the hydrocarbon group represented by R 1 ) is preferably 6-20, more preferably 8-18, and even more preferably 10-16.
- the hydrocarbon group contained in the hydrocarbon group-containing group (for example, when the hydrocarbon group-containing group is a group represented by the general formula (iii), the hydrocarbon group represented by R 1 ) is alkyl. It is preferably a group.
- a hydrocarbon group contained in the hydrocarbon group-containing group (for example, the hydrocarbon group-containing group is represented by the general formula (iii))
- the hydrocarbon contained in the hydrocarbon group-containing group When the number of carbon atoms of a group (for example, a hydrocarbon group-containing group is a group represented by the general formula (iii) or a hydrocarbon group represented by R 1 ) exceeds 20, water solubility may be low. .
- the modified hyaluronic acid and / or salt thereof according to this embodiment includes a hydrocarbon group-containing group (for example, a group represented by the above general formula (iii)), the transmittance X is 40% or more, and When the transmittance Y is 50% or more, both hydrophilicity and hydrophobicity can be achieved, and thus an excellent barrier function repair effect on the skin can be exhibited.
- the modified hyaluronic acid and / or salt thereof according to the present embodiment is excellent in solubility in ethanol, it has higher hydrophobicity than ordinary unmodified hyaluronic acid. It can be suitably used for cosmetics with a large amount.
- the modified hyaluronic acid and / or salt thereof according to the present embodiment includes a hydrocarbon group-containing group (for example, a group represented by the general formula (iii)), and the transmittance X is 40% or more, And, since the transmittance Y is 50% or more, both hydrophilicity and hydrophobicity can be achieved, so that the excellent barrier function repairing effect of the skin can be exhibited and the water solubility is excellent. It is easy to use by adding to various products containing water.
- a hydrocarbon group-containing group for example, a group represented by the general formula (iii)
- the transmittance X is 40% or more
- the transmittance Y is 50% or more, both hydrophilicity and hydrophobicity can be achieved, so that the excellent barrier function repairing effect of the skin can be exhibited and the water solubility is excellent. It is easy to use by adding to various products containing water.
- the cosmetics which concern on one Embodiment of this invention contain the said modified hyaluronic acid and / or its salt.
- the cosmetic according to the present embodiment can contain the modified hyaluronic acid and / or salt thereof as a humectant.
- the cosmetic according to the present embodiment usually contains 0.001 to 5% of the modified hyaluronic acid and / or salt thereof. If the content is less than 0.001%, a satisfactory moisturizing effect and smoothness cannot be obtained, so that the feeling of bulkiness of the skin during use may not be improved. If the content exceeds 5%, the viscosity becomes too high and it may be difficult to extend the whole skin.
- the cosmetic according to the present embodiment is a water-containing liquid
- the cosmetic according to the present embodiment contains the modified hyaluronic acid and / or salt thereof according to the present embodiment, which has excellent solubility in water and ethanol. Excellent transparency.
- the aspect of the cosmetic according to the present embodiment is not particularly limited, and examples thereof include skin cosmetics.
- skin cosmetics By using the above-mentioned modified hyaluronic acid and / or salt thereof in skin cosmetics, it has an appropriate viscosity and has a high effect of repairing the barrier function of the skin, so it moisturizes the skin and improves the feel. In addition, the feeling of bulkiness of the skin can be improved.
- Examples of skin cosmetics according to the present embodiment include facial cleansers, cleansing agents, lotions (for example, whitening lotions), creams (for example, vanishing cream, cold cream), milky lotions, cosmetic liquids, packs (for example)
- skin cosmetics for example, jelly-type peel-off type, paste-type wipe-off type, powder-type wash-out type), cleansing, foundation, lipstick, lip balm, lip gloss, lip liner, blusher, shaving lotion, after sun lotion, deodorant lotion, body lotion (hand care lotion) Body oils, soaps, and bath additives.
- the modified hyaluronic acid and / or salt thereof according to the present embodiment is excellent in solubility in ethanol and has moderate hydrophobicity. Therefore, when the modified hyaluronic acid and / or salt thereof according to this embodiment is blended in a cosmetic containing an oily raw material, it can be mixed well without causing separation or precipitation. Therefore, the cosmetic according to the present embodiment is a cosmetic containing an oily raw material (for example, cream, milky lotion, cosmetic liquid, pack, lipstick, lip balm, lip gloss, lip liner, oil cleansing, foundation, eye shadow, eye liner. ).
- an oily raw material for example, cream, milky lotion, cosmetic liquid, pack, lipstick, lip balm, lip gloss, lip liner, oil cleansing, foundation, eye shadow, eye liner.
- an excellent moisturizing effect can be exhibited by containing the modified hyaluronic acid and / or salt thereof.
- the cosmetic according to the present embodiment by containing the modified hyaluronic acid and / or salt thereof, it is adjusted to an appropriate viscosity, so that it can improve the feeling of bulkiness of the skin during use. it can.
- the skin by containing the modified hyaluronic acid and / or salt thereof, the skin can be moisturized, and for example, the feeling of bulkiness of the skin can be improved. it can.
- the following ingredients may be further blended in the cosmetic according to the present embodiment.
- the component include cationized polysaccharides (eg, cationized hyaluronic acid, cationized hydroxyethyl cellulose, cationized guar gum, cationized starch, cationized locust bean gum, cationized dextran, cationized chitosan, and cationized honey) ), Anionic surfactants (eg, alkylbenzene sulfonates, polyoxyalkylene alkyl ether sulfates, alkyl sulfates, olefin sulfonates, fatty acid salts, dialkylsulfosuccinates, etc.), nonionic surfactants (eg , Polyoxyethylene fatty acid esters, polyoxyethylene hydrogenated castor oil derivatives, etc.), cationic surfactants (eg, alkyltrimethylammonium salts, dialkyldimethyl
- —NHC ( ⁇ O) CH 3 (bonded to N-acetylglucosamine constituting one structural unit of hyaluronic acid, observed in the vicinity of 2.0 ppm in the 1 H-NMR spectrum of the modified hyaluronic acid.
- the integrated value of the peak representing the proton of CH 2- is calculated, and from these integrated values, the following formulas (5) to (9) are used, so that the modified hyaluronic acid is included in one structural unit of hyaluronic acid.
- the number of glycerin skeleton-containing groups or palmitoyl groups was calculated.
- the modified hyaluronic acid has a glycerin skeleton-containing group in which R 1 is an n-dodecyl group or an n-tridecyl group (test numbers 2 to 10 in Table 1)
- R 1 is an n-dodecyl group or an n-tridecyl group
- the carbon atom of the glycerol skeleton-containing group represented by R 1 was calculated as 12.5 which is the average of the number of carbon atoms of the n-dodecyl group and the number of carbon atoms of the n-tridecyl group (dodecyl group).
- 12 carbon atoms of the n-tridecyl group 12 carbon atoms of the n-tridecyl group).
- the peak appearing in the vicinity of 1.3 ppm corresponds to a total of 19 hydrogen atoms from the integrated value of the CH 3 hydrogen atom peak of the N-acetyl group.
- the modified hyaluronic acid has a glycerin skeleton-containing group in which R 1 is an n-butyl group (test number 1 in Table 1)
- R 1 is an n-butyl group having 4 carbon atoms
- the peak appearing in the vicinity of 1.3 ppm is a hydrogen atom 2 from the integrated value with respect to the integrated value of the CH 3 hydrogen atom peak of the N-acetyl group.
- the modified hyaluronic acid has a glycerin skeleton-containing group in which R 1 is a palmityl group (test number 11 in Table 1)
- R 1 is a palmityl group having 16 carbon atoms
- the peak appearing in the vicinity of 1.3 ppm is a total of 26 hydrogen atoms based on the integrated value of the CH 3 hydrogen atom peak of the N-acetyl group.
- the modified hyaluronic acid has a glycerin skeleton-containing group in which R 1 is a stearyl group (test numbers 12 and 13 in Table 1)
- R 1 is a stearyl group having 18 carbon atoms
- the peak appearing near 1.3 ppm is a total of 30 hydrogen atoms based on the integrated value of the CH 3 hydrogen atom peak of the N-acetyl group.
- the modified hyaluronic acid does not have a glycerin skeleton-containing group but has a palmitoyl group (test numbers 14 and 15 in Table 1)
- the peak appearing in the vicinity of 1.3 ppm is based on the integrated value with respect to the integrated value of the CH 3 hydrogen atom peak of the N-acetyl group. This corresponds to a total of 24 hydrogen atoms, and the 24 hydrogen atoms correspond to the palmitoyl group, 12 (methylene group) in parentheses of —C ( ⁇ O) —CH 2 —CH 2 — (CH 2 ) 12 —CH 3. Number of groups) ⁇ 2 hydrogen atoms. Therefore, the number of palmitoyl groups contained in one structural unit of hyaluronic acid is calculated by the following formula (9).
- Example 1 To a 1 L beaker, 5.0 g of hyaluronic acid (molecular weight: 8000, manufactured by QP Corporation) was dissolved in 500 mL of water, and a 40% tetrabutylammonium hydroxide aqueous solution was added with stirring to adjust the pH to 7.2. After pH adjustment, freeze drying was performed to obtain 10.2 g of tetrabutylammonium salt of hyaluronic acid.
- Example 1 a modified hyaluronic acid (test number 6 in Table 1) containing a glycerin skeleton-containing group represented by the general formula (1).
- the kinematic viscosity of the modified hyaluronic acid obtained in Example 1 was 1.2 mm 2 / s.
- FIG. 1A shows a 1 H-NMR spectrum (observation frequency 400 MHz, internal standard substance: DSS (0 ppm), solvent: heavy water) of the modified hyaluronic acid obtained in this example.
- a 1 H-NMR spectrum (observation frequency 400 MHz, internal standard substance: DSS (0 ppm) of hyaluronic acid (manufactured by QP Corporation, average molecular weight 8000) of a raw material (having no glycerin skeleton-containing group), Solvent: heavy water) is shown in FIG.
- the peak present in the vicinity of 1.3 ppm is presumed to be a peak indicating the proton of the methylene group (—CH 2 —) in the glycerin skeleton-containing group of the modified hyaluronic acid. Is done.
- Example 1 in the method for producing the modified hyaluronic acid of Example 1, the same method as in Example 1 was used except that the type of reaction reagent, solvent, reaction temperature, and reaction time were changed as shown in Table 1.
- the modified hyaluronic acids of Test Nos. 1-5 and 7-15 were prepared.
- modified hyaluronic acid in which the number of carbon atoms of R 1 of the glycerin skeleton-containing group is as shown in Table 1 was obtained. It was confirmed from the 1 H-NMR spectrum that a glycerin skeleton-containing group was introduced into the modified hyaluronic acid obtained in Table 1 by the same method as described above.
- the kinematic viscosities of the modified hyaluronic acids of Test Nos. 1 to 15 were all 0.5 to 3 mm 2 / s.
- the modified hyaluronic acid of the present invention (test numbers 1 to 13) has a glycerin skeleton-containing group represented by the above general formula (1), and thus has excellent solubility in water and ethanol.
- the modified hyaluron in which the number of carbon atoms of R 1 in the glycerin skeleton-containing group is 6 to 20 and the number of the glycerin skeleton-containing groups contained in one structural unit of hyaluronic acid is 0.001 to 0.5.
- the acids (test numbers 3-9 and 11-13) were superior in solubility in water and ethanol.
- the modified hyaluronic acid of the comparative examples does not have the glycerin skeleton-containing group represented by the general formula (1), the solubility in water and ethanol is increased. I can understand that it is inferior.
- Example 2 Modification in the production method of the modified hyaluronic acid of Example 1 was performed in the same manner as in Example 1 except that hyaluronic acid (molecular weight 8000, manufactured by Kewpie Corporation) was changed to hyaluronic acid (molecular weight 300,000, manufactured by Kewpie Corporation). Hyaluronic acid was made. Further, it was confirmed from 1 H-NMR spectrum that a glycerin skeleton-containing group was introduced into the modified hyaluronic acid obtained in Example 2 by the same method as described above.
- the number of glycerin skeleton-containing groups contained in one structural unit of hyaluronic acid is 0.03, and the light transmittance X in 1% modified hyaluronic acid-containing water is 100%.
- the light transmittance Y of the 1% modified hyaluronic acid-containing ethanol-water mixture was 100%.
- the kinematic viscosity of the modified hyaluronic acid obtained in Example 2 was 3.5 mm 2 / s.
- Example 3 To a 1 L beaker, 5.0 g of hyaluronic acid (molecular weight 1 million, manufactured by QP Corporation) was dissolved in 500 mL of water, and a 40% tetrabutylammonium hydroxide aqueous solution was added with stirring to adjust the pH to 7.2. After pH adjustment, freeze drying was performed to obtain 10.2 g of tetrabutylammonium salt of hyaluronic acid.
- the precipitate was collected by filtration and washed 3 times with 50 mL of 80% ethanol. The obtained precipitate was vacuum-dried at 60 ° C. to produce modified hyaluronic acid. Further, it was confirmed from the 1 H-NMR spectrum that a glycerin skeleton-containing group was introduced into the modified hyaluronic acid obtained in Example 3 by the same method as described above.
- the number of glycerin skeleton-containing groups contained in one structural unit of hyaluronic acid is 0.02, and the light transmittance X in 1% modified hyaluronic acid-containing water is 100%.
- the light transmittance Y of the 1% modified hyaluronic acid-containing ethanol-water mixture (ethanol content 70% by volume) was 75%.
- the kinematic viscosity of the modified hyaluronic acid obtained in Example 3 was 46 mm 2 / s.
- Example 1 a lotion containing the modified hyaluronic acid obtained in Example 1 was prepared according to the formulation described below.
- Modified hyaluronic acid (Example 1) 0.2% Sodium hyaluronate 0.1% Hydrolyzed hyaluronic acid 0.1% Collagen peptide 0.1% 1,3-butylene glycol 5.0% Glycerol 3.0% Isostearyl alcohol 0.1% Tocopherol acetate 0.1% POE (20) sorbitan monolaurate 0.5% POE (15) lauryl alcohol ether 0.5% Zinc pyrrolidonecarboxylate 0.1% Ethylparaben 0.1% Methylparaben 0.15% Ethanol 5.0% Perfume Appropriate amount Purified water Remaining
- Example 2 an emulsion containing the modified hyaluronic acid obtained in Example 1 was prepared according to the formulation described below.
- Modified hyaluronic acid (Example 1) 0.3% Pentylene glycol 5.0% Glycerol 3.0% Squalane 5.0% Stearic acid 0.5% Stearyl alcohol 2.0% Vaseline 4.0% Sorbitan stearate 1.0% POE (10) monostearate 1.0% Carboxy vinyl polymer 0.5% Polyquaternium-51 0.1% Methylparaben 0.15% Propylparaben 0.1% Potassium hydroxide 0.1% BHT 0.02% EDTA-2 sodium 0.02% Perfume Appropriate amount Purified water Remaining
- Example 3 the cream (emollient cream) which mix
- Modified hyaluronic acid (Example 2) 0.5% Polyethylene glycol 4.0% 1,3-propanediol 6.0% Squalane 11.0% Dimethicone 1.0% Cetanol 6.0% Stearic acid 2.0% Hydrogenated cocoglyceryl 4.0% Tricaprylin 8.0% Glycerol monostearate 3.0% POE (20) cetyl alcohol ether 2.0% Coenzyme Q10 0.03% Ceramide 0.1% Dilauroyl glutamate ricin sodium 0.1% EDTA-2 sodium 0.02% Propylparaben 0.1% Methylparaben 0.15% Perfume Appropriate amount Purified water Remaining
- Example 4 a cosmetic liquid (whitening moisturizing essence) containing the modified hyaluronic acid obtained in Example 2 was prepared according to the formulation described below.
- Modified hyaluronic acid (Example 2) 0.8% Sodium hyaluronate 0.2% Hydrolyzed hyaluronic acid 0.1% 1,3-butylene glycol 5.0% Glycerin 1.5% POE sorbitan monostearate 1.0% Sorbitan monostearate 0.5% Xanthan gum 0.2% Sodium alginate 0.2% Carboxyvinyl polymer 0.2% Potassium hydroxide 0.1% Olive oil 0.2% Tocopherol 0.1% EDTA-2 sodium 0.02% Arginine 0.15% Dipotassium glycyrrhizinate 0.05% Arbutin 0.2% Retinol palmitate 0.2% Cousin extract 0.2% Seaweed extract 0.2% Tranexamic acid 0.1% Elastin 0.1% Collagen 0.1% Magnesium phosphate ascorbate 0.1%
- Example 5 a cosmetic liquid pack (paste peel-off type) containing the modified hyaluronic acid obtained in Example 1 was prepared according to the formulation described below.
- Modified hyaluronic acid (Example 1) 0.5% Polyvinyl acetate emulsion 17.0% Polyvinyl alcohol 11.0% Sorbitol 5.0% Polyethylene glycol 400 5.0% Squalane 2.5% POE sorbitan monostearate 1.0% Titanium oxide 4.0% Talc 8.0% Ethanol 8.0% Methylparaben 0.15% Perfume Appropriate amount Purified water Remaining
- Example 6 the face wash (cleansing foam) which mix
- Modified hyaluronic acid (Example 1) 0.2% Cationized hyaluronic acid 0.1% (Hypo Veil, manufactured by QP Corporation) Glycerin 10.0% Polyethylene glycol 400 15.0% Dipropylene glycol 10.0% Sodium lauroyl glutamate 20.0% POE (2) monostearate 5.0% Palm fatty acid sodium glutamate 8.0% Alkyl betaine 2.0% EDTA-2 sodium 0.02% Propylparaben 0.1% Methylparaben 0.15% Perfume Appropriate amount Purified water Remaining
- Example 7 a sunscreen (milky lotion) containing the modified hyaluronic acid obtained in Example 1 was prepared according to the formulation described below.
- Modified hyaluronic acid (Example 1) 0.2% 1,3-butylene glycol 3.0% Dipropylene glycol 3.0% Cyclomethicone 5.0% Dimethicone 5.0% Cetanol 1.0% Vaseline 1.0% Octyl methoxycinnamate 5.0% Titanium oxide 2.0% Zinc oxide 2.0% Sorbitan stearate 1.0% POE (20) sorbitan monostearate 1.0% Phenoxyethanol 0.8% Methylparaben 0.1% Perfume Appropriate amount Purified water Remaining
- Example 8 a lip balm containing the modified hyaluronic acid obtained in Example 1 was prepared according to the formulation described below.
- Modified hyaluronic acid (Example 1) 0.1% Microcrystalline wax 1.5% Ceresin 12.0% Squalane 10.0% Decamethyltetrasiloxane 10.0% Diisostearyl malate 5.0% Candelilla wax 2.0% Vaseline 8.0% Glyceryl hydroxystearate 2.0% Menthol 0.05% Liquid paraffin 1.0% Tocopherol acetate 0.1% Tocopherol 0.05% Propylparaben 0.1% Perfume Appropriate amount Purified water Remaining
- Example 9 the shampoo which mix
- Modified hyaluronic acid (Example 1) 0.2% Cationized hyaluronic acid 0.1% (Hypo Veil, manufactured by QP Corporation) POE (20) sodium lauryl ether sulfate 11.0% Lauroyl sodium aspartate 10.0% Coconut oil fatty acid amidopropyl betaine 4.0% Coconut oil fatty acid monoethanolamide 2.0% EDTA-2 sodium 0.1% Sodium benzoate 0.2% Phenoxyethanol 0.8% Methylparaben 0.1% Perfume Appropriate amount Purified water Remaining
- Example 10 the hair conditioner which mix
- Modified hyaluronic acid (Example 1) 0.3% Cationized hyaluronic acid 0.2% (Hypo Veil, manufactured by QP Corporation) Stearyl alcohol 4.0% Cetanol 1.5% Hydroxyethyl urea 1.0% Aminopropyl dimethicone 1.5% Dimethicone 0.5% Hydrolyzed silk 1.0% 1,3-butylene glycol 1.0% Glycerol 3.0% Cetyl 2-ethylhexanoate 2.0% Isocetyl myristate 0.4% L-Arginine 0.1% Trehalose 0.1% Sorbitol 0.1% Keratin peptide 0.1% POE (4) stearyl ether 1.0% Stearic acid dimethylaminopropylamide 3.0% Distearyldimethylammonium chloride 0.2% Sodium benzoate 0.3% Phenoxyethanol 0.8%
- Test Example 11 (Skin Barrier Function Repair Confirmation Test) In a 2 mL Eppendorf tube, treatment liquid (ceramide II (manufactured by Takasago Fragrance Co., Ltd.), ceramide III (manufactured by Cosmo Farm), ceramide IV (manufactured by Cosmo Farm), 4 mg each, stearic acid 8 mg (manufactured by Wako Pure Chemical Industries, Ltd.), Cholesterol (manufactured by Kanto Chemical Co., Inc.) 8 mg, cholesterol sulfate (manufactured by Sigma) 2 mg, pure water 140 mg, and modified hyaluronic acid 1 mg of each test number of Example 1) were added and stirred at room temperature using a vortex for 2 minutes.
- a cross image (a part surrounded by a circle) represents a part where a lamella structure is formed.
- a lipid layer and an aqueous layer usually form a lamellar structure, and this lamellar structure exerts a skin barrier function. Therefore, in this test example, it can be said that the more the lamella structure is formed, the higher the repair ability of the skin barrier function.
- Test Example 12 Human skin barrier function repair confirmation test
- the modified hyaluronic acid of the present invention was applied to human skin, and the transdermal water loss (TEWL) was evaluated.
- Sample Sample 1 Modified hyaluronic acid obtained in Example 1 above
- Sample 1 was dissolved in purified water to give a 1% aqueous solution, and test solution 1 was obtained.
- Sample 2 was dissolved in purified water to give a 1% aqueous solution, and test solution 2 was obtained.
- Test Method Two areas with a diameter of 1 cm were placed on the inner side of the subject's forearm and used as test sites.
- TEWL of a test part was measured using a moisture evaporation measuring device (Cutometer MPA580 manufactured by CK-Electronic).
- the epidermal horny layer at the test site was removed by tape stripping until the TEWL value reached 15 to 25 g / m 2 ⁇ h, and skin barrier function destruction treatment was performed.
- Test Solution 1 or Test Solution 2 was applied to the test site.
- the number of coatings was twice a day in the morning and afternoon, and the coating amount was 20 ⁇ L each time.
- test subject washed the test site before measuring TEWL and rested for 20 minutes.
- Measurement was performed at the time of 1 day and 3 days after application of each test solution after the skin barrier function destruction treatment.
- Table 3 and FIG. 3 show the measured values of TEWL when Test Solution 1 and Test Solution 2 are applied.
- FIG. 4 shows the improvement rate (%) at the elapse of 3 days after application when Test Solution 1 and Test Solution 2 in Table 3 were applied, respectively.
- TEWL represents the amount of moisture transferred from the inside of the skin to the outside.
- Skin barrier function destruction treatment destroys the lamellar structure of the stratum corneum of the skin and increases TEWL. Therefore, in this test example, it can be said that the ability to repair the barrier function of the skin increases as TEWL decreases.
- the TEWL after applying the test solution showed a significantly low value when 1 day after application and 3 days after application, compared to TEWL immediately after exfoliation. .
- the modified hyaluronic acid containing the glycerin skeleton-containing group represented by the general formula (1) has a repair function of the skin barrier function.
- Sample A Modified hyaluronic acid obtained in Example 1 above
- Sample B Control
- Hyaluronic acid molecular weight 8000, manufactured by QP Corporation
- the 1% modified hyaluronic acid-containing water prepared using Sample A was visually transparent and no precipitation occurred. From this, it can be understood that the modified hyaluronic acid is almost dissolved in the 1% modified hyaluronic acid-containing water prepared using the sample A.
- the 1% modified hyaluronic acid-containing water prepared using the sample A can be used as a raw material for a lotion containing an oily raw material (a cosmetic material having high hydrophobicity), for example.
- the 1% hyaluronic acid-containing water prepared using the sample B was not visually turbid, but it was confirmed that a white precipitate was formed at the bottom of the container containing the lotion. .
- modified hyaluronic acid containing a glycerin skeleton-containing group represented by the general formula (1) can be suitably blended in cosmetics having high hydrophobicity.
- the present invention includes configurations that are substantially the same as the configurations described in the embodiments (for example, configurations that have the same functions, methods, and results, or configurations that have the same purposes and results).
- the invention includes a configuration in which a non-essential part of the configuration described in the embodiment is replaced.
- the invention includes a configuration that achieves the same effect as the configuration described in the embodiment or a configuration that can achieve the same object.
- the invention includes a configuration in which a known technique is added to the configuration described in the embodiment.
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Abstract
Description
(式中、R1は直鎖状または分岐状のアルキル基またはアルケニル基を表す。)
X=T2/T1×100(%) ・・・(i)
(式中、T1は水における波長660nm、光路長10mmの光の透過率であり、T2は1%の炭化水素基含有基を有する修飾ヒアルロン酸および/またはその塩を含有する水における波長660nm、光路長10mmの光の透過率である。)
Y=T4/T3×100(%) ・・・(ii)
(式中、T3は70容量%エタノール含有エタノール-水混合液における波長660nm、光路長10mmの光の透過率であり、T4は1%の炭化水素基含有基を有する修飾ヒアルロン酸および/またはその塩を含有する70容量%エタノール含有エタノール-水混合液における波長660nm、光路長10mmの光の透過率である。)
1.1.構造
1.1.1.グリセリン骨格含有基(炭化水素基含有基)
本実施形態に係る修飾ヒアルロン酸および/またはその塩は、下記一般式(1)で表されるグリセリン骨格含有基(以下、単に「グリセリン骨格含有基」ともいう。)を含む。
(式中、R1は直鎖状または分岐状のアルキル基またはアルケニル基を表す。)
本発明において、「ヒアルロン酸」とは、グルクロン酸とN-アセチルグルコサミンとの2糖からなる構成単位を1以上有する多糖類をいう。また、「ヒアルロン酸の塩」としては、特に限定されないが、食品または薬学上許容しうる塩であることが好ましく、例えば、ナトリウム塩、カリウム塩、カルシウム塩、亜鉛塩、マグネシウム塩、アンモニウム塩、アルキルアンモニウム塩等が挙げられる。
本発明において、修飾ヒアルロン酸および/またはその塩の水溶液の動粘度は、ウベローデ粘度計(柴田科学器械工業株式会社製)を用いて測定することができる。この際、流下秒数が200~1000秒になるような係数のウベローデ粘度計を選択する。また、測定は30℃の恒温水槽中で行ない、温度変化のないようにする。
本発明において、ヒアルロン酸および/またはその塩の平均分子量は、以下の方法にて測定された値である。
比粘度 = {試料溶液の所要流下秒数)/(0.2mol/L塩化ナトリウム溶液の所要流下秒数)}-1
還元粘度(dL/g)= 比粘度/(本品の換算した乾燥物に対する濃度g/100mL))
極限粘度(dL/g)=3.6×10-4M0.78
M:平均分子量
本実施形態に係る修飾ヒアルロン酸および/またはその塩は、1%の修飾ヒアルロン酸および/またはその塩を含有する水における光(波長660nm、光路長10mm)の透過率Xが、水に対して、20%以上であることが好ましく、40%以上であることがより好ましく、80%以上であることがさらに好ましい。ここで、修飾ヒアルロン酸および/またはその塩を含有する水における上記光の透過率Xは、修飾ヒアルロン酸および/またはその塩の水への溶解性を示す指標である。特に、修飾ヒアルロン酸および/またはその塩を含有する水における上記光の透過率Xが40%以上である修飾ヒアルロン酸および/またはその塩は、水への溶解性に優れており、水分を含有する製品へ配合し易いものである。
本実施形態に係る修飾ヒアルロン酸および/またはその塩は、例えば、ヒアルロン酸および/またはその塩を下記一般式(2)で表される化合物(本明細書において「化合物1」ともいう。)と反応させる工程によって得られる。あるいは、ヒアルロン酸および/またはその塩を下記一般式(4)で表される化合物(本明細書において「化合物2」ともいう。)と反応させることによって、本実施形態に係る修飾ヒアルロン酸および/または塩を調製してもよい。なお、反応性を高めるために、原料のヒアルロン酸および/またはその塩(以下「原料ヒアルロン酸および/またはその塩」という。)をアルキルアンモニウム塩に置換した後に、化合物1または化合物2と反応させることが好ましい。
本実施形態に係る修飾ヒアルロン酸および/またはその塩の製造に使用される原料ヒアルロン酸および/またはその塩は、動物等の生体組織(例えば鶏冠、さい帯、皮膚、関節液など)から抽出されたものでもよく、または、微生物、動物細胞もしくは植物細胞を培養して得られたもの(例えばストレプトコッカス属の細菌等を用いた発酵法)、化学的または酵素的に合成されたものなどを使用することができる。
原料ヒアルロン酸および/またはその塩をヒアルロン酸のアルキルアンモニウム塩に変換する場合、例えば、原料ヒアルロン酸および/またはその塩に化合物(以下「化合物3」ともいう。)を反応させることにより、ヒアルロン酸の第四級アルキルアンモニウム塩を得ることができる。このような化合物3としては、例えば、水酸化テトラエチルアンモニウム、水酸化テトラプロピルアンモニウム、水酸化テトラブチルアンモニウム等の炭素原子数2~18の水酸化第四級アルキルアンモニウムが挙げられる。すなわち、ヒアルロン酸の第四級アルキルアンモニウム塩は例えば、炭素原子数2~18の第四級アルキルアンモニウム塩であることが好ましい。第四級アルキルアンモニウム塩としては、例えば、テトラエチルアンモニウム塩、テトラプロピルアンモニウム塩、テトラブチルアンモニウム塩、テトラペンチルアンモニウム塩、テトラヘキシルアンモニウム塩が挙げられる。
ヒアルロン酸の第四級アルキルアンモニウム塩と化合物1または化合物2との反応は、有機溶媒中で行うことができる。ここで、反応温度は通常0~200℃であり、反応時間は通常0.1~48時間である。上記反応で使用する有機溶媒としては、例えば、ジメチルホルミアミド(DMF)、ジメチルスルホキシド(DMSO)、テトラヒドロフラン等が挙げられ、これらを単独でまたは組み合わせて使用することができる。
本実施形態に係る修飾ヒアルロン酸および/またはその塩の製造方法においては、ヒアルロン酸および/またはその塩を化合物1と反応させる工程の後、ナトリウム塩およびカリウム塩またはいずれか一方を反応液に添加する工程をさらに含むことができる。
本実施形態に係る修飾ヒアルロン酸および/またはその塩は、例えば皮膚等の生体組織に対する高い改質効果(特に、皮膚のバリア機能修復効果)を有している。本実施形態に係る修飾ヒアルロン酸および/またはその塩は、生体組織の表面に塗布または接触して摂取させてもよいし、特に、顔、腕、手指、足、関節などの皮膚に塗布または接触させるのが好ましい。
本実施形態に係る修飾ヒアルロン酸および/またはその塩は上記一般式(1)で表されるグリセリン骨格含有基を含むことにより、親水性および疎水性の両立を図ることができるため、優れた皮膚のバリア機能修復効果を発揮できる。
本実施形態に係る修飾ヒアルロン酸および/またはその塩は、炭化水素基含有基を有し、下記式(i)で規定される透過率Xが40%以上であり、かつ、下記式(ii)で規定される透過率Yが50%以上であることができる。
(式中、T1は水における波長660nm、光路長10mmの光の透過率であり、T2は1%の炭化水素基含有基を有する修飾ヒアルロン酸および/またはその塩を含有する水における波長660nm、光路長10mmの光の透過率である。)
(式中、T3は70容量%エタノール含有エタノール-水混合液における波長660nm、光路長10mmの光の透過率であり、T4は1%の炭化水素基含有基を有する修飾ヒアルロン酸および/またはその塩を含有する70容量%エタノール含有エタノール-水混合液における波長660nm、光路長10mmの光の透過率である。)
(式中、R1は炭化水素基を表す。)
本発明の一実施形態に係る化粧料は、上記修飾ヒアルロン酸および/またはその塩を含有する。例えば、本実施形態に係る化粧料は、上記修飾ヒアルロン酸および/またはその塩を保湿剤として含有することができる。また、本実施形態に係る化粧料は、上記修飾ヒアルロン酸および/またはその塩を通常、0.001~5%含有する。含有量が0.001%未満では、満足な保湿効果や滑らかさが得られないため、使用時の皮膚のかさつき感を改善することができない恐れがある。含有量が5%を超えると、粘度が高くなりすぎ皮膚全体に伸ばしにくくなる恐れがある。さらに、本実施形態に係る化粧料が含水液である場合、水およびエタノールに対する溶解性に優れる本実施形態に係る修飾ヒアルロン酸および/またはその塩を含有するため、本実施形態に係る化粧料は透明性に優れている。
以下、実施例によって本発明をさらに詳細に説明するが、本発明は実施例に限定されない。
3.1.1.平均分子量
本実施例において、(修飾)ヒアルロン酸の平均分子量は、上述の実施形態で説明された方法で測定された。
なお、ここでは、R1で表されるグリセリン骨格含有基の炭素原子を、n-ドデシル基の炭素原子数およびn-トリデシル基の炭素原子数の平均である12.5として算出した(ドデシル基の炭素原子数12、n-トリデシル基の炭素原子数13)。また、この場合、1.3ppm付近に出現するピークが、N-アセチル基のCH3の水素原子のピークの積算値に対する積算値から、水素原子合計19個分に相当し、この19個分の水素原子は、R1=-CH2-CH2-(CH2)9.5-CH3の括弧内の9.5(メチレン基の個数)×2個の水素原子であると推測される。よって、以下の式(5)により、ヒアルロン酸1構成単位に含まれるグリセリン骨格含有基の数を算出する。
なお、R1が炭素原子数4のn-ブチル基の場合、1.3ppm付近に出現するピークは、N-アセチル基のCH3の水素原子のピークの積算値に対する積算値から、水素原子2個分に相当し、この2個分の水素原子は、R1=-CH2-CH2-(CH2)1-CH3の括弧内の1(メチレン基の個数)×2個の水素原子であると推測される。よって、以下の式(6)により、ヒアルロン酸1構成単位に含まれるグリセリン骨格含有基の数を算出する。
なお、R1が炭素原子数16のパルミチル基の場合、1.3ppm付近に出現するピークは、N-アセチル基のCH3の水素原子のピークの積算値に対する積算値から、水素原子合計26個分に相当し、この26個分の水素原子は、R1=-CH2-CH2-(CH2)13-CH3の括弧内の13(メチレン基の個数)×2個の水素原子であると推測される。よって、以下の式(7)により、ヒアルロン酸1構成単位に含まれるグリセリン骨格含有基の数を算出する。
なお、R1が炭素原子数18のステアリル基の場合、1.3ppm付近に出現するピークは、N-アセチル基のCH3の水素原子のピークの積算値に対する積算値から、水素原子合計30個分に相当し、この30個分の水素原子は、R1=-CH2-CH2-(CH2)15-CH3の括弧内の15(メチレン基の個数)×2個の水素原子であると推測される。よって、以下の式(8)により、ヒアルロン酸1構成単位に含まれるグリセリン骨格含有基の数を算出する。
なお、パルミトイル基の場合、1.3ppm付近に出現するピークは、N-アセチル基のCH3の水素原子のピークの積算値に対する積算値から、
水素原子合計24個分に相当し、この24個分の水素原子は、パルミトイル基、-C(=O)-CH2-CH2-(CH2)12-CH3の括弧内の12(メチレン基の個数)×2個の水素原子であると推測される。よって、以下の式(9)により、ヒアルロン酸1構成単位に含まれるパルミトイル基の数を算出する。
各実施例で得られた修飾ヒアルロン酸を水およびエタノール-水混合液(エタノール含量70容量%)それぞれに添加して、1%修飾ヒアルロン酸含有水および1%修飾ヒアルロン酸含有エタノール-水混合液(エタノール含量70容量%)を調製した。次に、分光光度計として(株)島津製作所製「マルチパーパス分光光度UV-2450」を使用し、波長660nm、光路長10mmの光の透過率X,Yをそれぞれ測定した。なお、対照側のセルとして、それぞれの溶媒である水およびエタノール-水混合液(エタノール含量70容量%)を用いて測定した。
上述の実施形態の欄で説明した方法により動粘度を算出した。
1Lビーカーにヒアルロン酸(分子量8000、キユーピー株式会社製)5.0gを水500mLに溶解させ、さらに40%水酸化テトラブチルアンモニウム水溶液を攪拌しながら加えて、pHを7.2に調整した。pH調整後、凍結乾燥させ、ヒアルロン酸のテトラブチルアンモニウム塩を10.2g得た。30mLサンプル瓶に得られたヒアルロン酸のテトラブチルアンモニウム塩1.0g、C12~13アルキルグリシジルエーテル(反応試薬)(四日市合成株式会社製)2.0g、およびジメチルホルミアミド(DMF)10mLを入れ、攪拌しながら80℃水浴上で8時間反応させた。反応終了後、12.5%塩化ナトリウム水溶液を10mL加え、8%塩酸にてpH1.0に調整した。次いで、エタノール50mLを撹拌しながらゆっくり加え、ヒアルロン酸を沈殿させた。次いで、25%水酸化ナトリウムでpHを7.0に調整し、沈殿物をろ過にて回収し、80%エタノール50mLで3回洗浄した。得られた沈殿物を60℃で真空乾燥させて、上記一般式(1)で表されるグリセリン骨格含有基を含む修飾ヒアルロン酸(表1の試験番号6)を0.48g得た。また、実施例1で得られた修飾ヒアルロン酸(表1の試験番号6)の動粘度は1.2mm2/sであった。
実施例1の修飾ヒアルロン酸の製造方法において、ヒアルロン酸(分子量8000、キユーピー株式会社製)をヒアルロン酸(分子量30万、キユーピー株式会社製)に変更した以外は実施例1と同様の方法で修飾ヒアルロン酸を製した。また、上述した方法と同様の方法にて、実施例2で得られた修飾ヒアルロン酸にグリセリン骨格含有基が導入されていることを1H-NMRスペクトルから確認した。
1Lビーカーにヒアルロン酸(分子量100万、キユーピー株式会社製)5.0gを水500mLに溶解させ、さらに40%水酸化テトラブチルアンモニウム水溶液を攪拌しながら加えて、pHを7.2に調整した。pH調整後、凍結乾燥させ、ヒアルロン酸のテトラブチルアンモニウム塩を10.2g得た。30mLサンプル瓶に得られたヒアルロン酸のテトラブチルアンモニウム塩1.0g、C12~13アルキルグリシジルエーテル(反応試薬)(四日市合成株式会社製)2.0g、およびジメチルホルミアミド(DMF)20mLを入れ、攪拌しながら80℃水浴上で8時間反応させた。反応終了後、12.5%塩化ナトリウム水溶液を10mL加え、25%水酸化ナトリウムでpHを7.0に調整し、エタノール50mLを撹拌しながらゆっくり加え、ヒアルロン酸を沈殿させた。沈殿物をろ過にて回収し、80%エタノール50mLで3回洗浄した。得られた沈殿物を60℃で真空乾燥させて、修飾ヒアルロン酸を製した。また、上述した方法と同様の方法にて、実施例3で得られた修飾ヒアルロン酸にグリセリン骨格含有基が導入されていることを1H-NMRスペクトルから確認した。
本試験例では、以下に記す処方にて、実施例1で得られた修飾ヒアルロン酸を配合した化粧水を調製した。
修飾ヒアルロン酸(実施例1) 0.2%
ヒアルロン酸ナトリウム 0.1%
加水分解ヒアルロン酸 0.1%
コラーゲンペプチド 0.1%
1,3-ブチレングリコール 5.0%
グリセリン 3.0%
イソステアリルアルコール 0.1%
酢酸トコフェロール 0.1%
POE(20)ソルビタンモノラウリル酸エステル 0.5%
POE(15)ラウリルアルコールエーテル 0.5%
ピロリドンカルボン酸亜鉛 0.1%
エチルパラベン 0.1%
メチルパラベン 0.15%
エタノール 5.0%
香料 適量
精製水 残量
本試験例では、以下に記す処方にて、実施例1で得られた修飾ヒアルロン酸を配合した乳液を調製した。
修飾ヒアルロン酸(実施例1) 0.3%
ペンチレングリコール 5.0%
グリセリン 3.0%
スクワラン 5.0%
ステアリン酸 0.5%
ステアリルアルコール 2.0%
ワセリン 4.0%
ステアリン酸ソルビタン 1.0%
POE(10)モノステアリン酸エステル 1.0%
カルボキシビニルポリマー 0.5%
ポリクオタニウム-51 0.1%
メチルパラベン 0.15%
プロピルパラベン 0.1%
水酸化カリウム 0.1%
BHT 0.02%
EDTA-2ナトリウム 0.02%
香料 適量
精製水 残量
本試験例では、以下に記す処方にて、実施例2で得られた修飾ヒアルロン酸を配合したクリーム(エモリエントクリーム)を調製した。
修飾ヒアルロン酸(実施例2) 0.5%
ポリエチレングリコール 4.0%
1,3-プロパンジオール 6.0%
スクワラン 11.0%
ジメチコン 1.0%
セタノール 6.0%
ステアリン酸 2.0%
水添ココグリセリル 4.0%
トリカプリリン 8.0%
モノステアリン酸グリセリン 3.0%
POE(20)セチルアルコールエーテル 2.0%
コエンザイムQ10 0.03%
セラミド 0.1%
ジラウロイルグルタミン酸リシンナトリウム 0.1%
EDTA-2ナトリウム 0.02%
プロピルパラベン 0.1%
メチルパラベン 0.15%
香料 適量
精製水 残量
本試験例では、以下に記す処方にて、実施例2で得られた修飾ヒアルロン酸を配合した美容液(美白保湿エッセンス)を調製した。
修飾ヒアルロン酸(実施例2) 0.8%
ヒアルロン酸ナトリウム 0.2%
加水分解ヒアルロン酸 0.1%
1,3-ブチレングリコール 5.0%
グリセリン 1.5%
POEソルビタンモノステアリン酸エステル 1.0%
ソルビタンモノステアリン酸エステル 0.5%
キサンタンガム 0.2%
アルギン酸ナトリウム 0.2%
カルボキシビニルポリマー 0.2%
水酸化カリウム 0.1%
オリーブ油 0.2%
トコフェロール 0.1%
EDTA-2ナトリウム 0.02%
アルギニン 0.15%
グリチルリチン酸ジカリウム 0.05%
アルブチン 0.2%
パルミチン酸レチノール 0.2%
クジンエキス 0.2%
海藻エキス 0.2%
トラネキサム酸 0.1%
エラスチン 0.1%
コラーゲン 0.1%
リン酸アスコルビン酸マグネシウム 0.1%
クエン酸ナトリウム 1.0%
クエン酸 0.1%
プロピルパラベン 0.1%
メチルパラベン 0.15%
香料 適量
精製水 残量
本試験例では、以下に記す処方にて、実施例1で得られた修飾ヒアルロン酸を配合した美容液パック(ペースト状ピールオフタイプ)を調製した。
修飾ヒアルロン酸(実施例1) 0.5%
ポリ酢酸ビニルエマルジョン 17.0%
ポリビニルアルコール 11.0%
ソルビトール 5.0%
ポリエチレングリコール400 5.0%
スクワラン 2.5%
POEソルビタンモノステアリン酸エステル 1.0%
酸化チタン 4.0%
タルク 8.0%
エタノール 8.0%
メチルパラベン 0.15%
香料 適量
精製水 残量
本試験例では、以下に記す処方にて、実施例1で得られた修飾ヒアルロン酸を配合した洗顔料(クレンジングフォーム)を調製した。
修飾ヒアルロン酸(実施例1) 0.2%
カチオン化ヒアルロン酸 0.1%
(キユーピー株式会社製、ヒアロベール)
グリセリン 10.0%
ポリエチレングリコール400 15.0%
ジプロピレングリコール 10.0%
ラウロイルグルタミン酸ナトリウム 20.0%
POE(2)モノステアリン酸エステル 5.0%
パーム脂肪酸グルタミン酸ナトリウム 8.0%
アルキルベタイン 2.0%
EDTA-2ナトリウム 0.02%
プロピルパラベン 0.1%
メチルパラベン 0.15%
香料 適量
精製水 残量
本試験例では、以下に記す処方にて、実施例1で得られた修飾ヒアルロン酸を配合したサンスクリーン(乳液)を調製した。
修飾ヒアルロン酸(実施例1) 0.2%
1,3-ブチレングリコール 3.0%
ジプロピレングリコール 3.0%
シクロメチコン 5.0%
ジメチコン 5.0%
セタノール 1.0%
ワセリン 1.0%
メトキシケイヒ酸オクチル 5.0%
酸化チタン 2.0%
酸化亜鉛 2.0%
ステアリン酸ソルビタン 1.0%
POE(20)ソルビタンモノステアリン酸エステル 1.0%
フェノキシエタノール 0.8%
メチルパラベン 0.1%
香料 適量
精製水 残量
本試験例では、以下に記す処方にて、実施例1で得られた修飾ヒアルロン酸を配合したリップクリームを調製した。
修飾ヒアルロン酸(実施例1) 0.1%
マイクロクリスタリンワックス 1.5%
セレシン 12.0%
スクワラン 10.0%
デカメチルテトラシロキサン 10.0%
リンゴ酸ジイソステアリル 5.0%
キャンデリラロウ 2.0%
ワセリン 8.0%
ヒドロキシステアリン酸グリセリル 2.0%
メントール 0.05%
流動パラフィン 1.0%
酢酸トコフェロール 0.1%
トコフェロール 0.05%
プロピルパラベン 0.1%
香料 適量
精製水 残量
本試験例では、以下に記す処方にて、実施例1で得られた修飾ヒアルロン酸を配合したシャンプーを調製した。
修飾ヒアルロン酸(実施例1) 0.2%
カチオン化ヒアルロン酸 0.1%
(キユーピー株式会社製、ヒアロベール)
POE(20)ラウリルエーテル硫酸ナトリウム 11.0%
ラウロイルアスパラギン酸ナトリウム 10.0%
ヤシ油脂肪酸アミドプロピルベタイン 4.0%
ヤシ油脂肪酸モノエタノールアミド 2.0%
EDTA-2ナトリウム 0.1%
安息香酸ナトリウム 0.2%
フェノキシエタノール 0.8%
メチルパラベン 0.1%
香料 適量
精製水 残量
本試験例では、以下に記す処方にて、実施例1で得られた修飾ヒアルロン酸を配合したヘアコンディショナーを調製した。
修飾ヒアルロン酸(実施例1) 0.3%
カチオン化ヒアルロン酸 0.2%
(キユーピー株式会社製、ヒアロベール)
ステアリルアルコール 4.0%
セタノール 1.5%
ヒドロキシエチルウレア 1.0%
アミノプロピルジメチコン 1.5%
ジメチコン 0.5%
加水分解シルク 1.0%
1,3-ブチレングリコール 1.0%
グリセリン 3.0%
2-エチルヘキサン酸セチル 2.0%
ミリスチン酸イソセチル 0.4%
L-アルギニン 0.1%
トレハロース 0.1%
ソルビトール 0.1%
ケラチンペプチド 0.1%
POE(4)ステアリルエーテル 1.0%
ステアリン酸ジメチルアミノプロピルアミド 3.0%
塩化ジステアリルジメチルアンモニウム 0.2%
安息香酸ナトリウム 0.3%
フェノキシエタノール 0.8%
メチルパラベン 0.1%
香料 適量
精製水 残量
2mLエッペンドルフチューブに、処理液(セラミドII(高砂香料工業社製)、セラミドIII(コスモファーム社製)、セラミドIV(コスモファーム社製)各4mg、ステアリン酸8mg(和光純薬工業社製)、コレステロール(関東化学社製)8mg、コレステロール硫酸(シグマ社製)2mg、純水140mg、実施例1の各試験番号の修飾ヒアルロン酸1mg)を入れ、室温にてボルテックスを用いて2分間撹拌した。次に、80℃恒温槽上で5分間加熱した後、ボルテックスを用いて2分間撹拌し、10℃恒温槽で5分間冷却した後、室温にて超音波処理を5分間行った。この操作を4回繰り返し、以下の手順で顕微鏡観察用サンプルを作製した。
本試験例においては、本願発明の修飾ヒアルロン酸をヒト皮膚に塗布して、経皮水分蒸発量(trans epidermal water loss:TEWL)の評価を行った。
3.16.1-1.被験者
年齢26~34歳の成人(n=9)を対象に試験を行った。
試料1:上記実施例1で得られた修飾ヒアルロン酸
試料2(対照):ヒアルロン酸(分子量8000、キユーピー株式会社製)
試料1を精製水に溶解し1%水溶液としたものを試験液1、試料2を精製水に溶解し1%水溶液としたものを試験液2とした。
被験者の前腕内側部に直径1cmの領域を2ヵ所設置し、これを試験部位とした。
下記の試料A0.1gを、エタノール:水=70:30(容積比)のエタノール-水混合液10mLに添加して、1%修飾ヒアルロン酸含有水を調製した。同様に、試料Aの代わりに、試料Bを用いて1%ヒアルロン酸含有水を調製した。
試料A:上記実施例1で得られた修飾ヒアルロン酸
試料B(対照):ヒアルロン酸(分子量8000、キユーピー株式会社製)
Claims (16)
- 下記一般式(1)で表されるグリセリン骨格含有基を含む、修飾ヒアルロン酸および/またはその塩。
-O-CH2-CHOH-CH2-OR1 ・・・(1)
(式中、R1は直鎖状または分岐状のアルキル基またはアルケニル基を表す。) - 前記一般式(1)において、R1が炭素原子数6~20の直鎖状または分岐状のアルキル基またはアルケニル基である、請求項1に記載の修飾ヒアルロン酸および/またはその塩。
- 前記グリセリン骨格含有基がヒアルロン酸骨格を構成する炭素原子の少なくとも1つに結合している、請求項1または2に記載の修飾ヒアルロン酸および/またはその塩。
- 前記一般式(2)において、R1が炭素原子数6~20の直鎖状または分岐状のアルキル基またはアルケニル基である、請求項4に記載の修飾ヒアルロン酸および/またはその塩。
- ヒアルロン酸1構成単位に含まれる前記グリセリン骨格含有基の数が0.001~0.5である、請求項1~5のいずれか1項に記載の修飾ヒアルロン酸および/またはその塩。
- 1%水溶液の動粘度が50mm2/s以下である、請求項1~6のいずれか1項に記載の修飾ヒアルロン酸および/またはその塩。
- 請求項1~8のいずれか1項に記載の修飾ヒアルロン酸および/またはその塩を含有する、化粧料。
- 下記式(i)で規定される透過率Xが40%以上であり、かつ、下記式(ii)で規定される透過率Yが50%以上である、炭化水素基含有基を有する修飾ヒアルロン酸および/またはその塩。
X=T2/T1×100(%) ・・・(i)
(式中、T1は水における波長660nm、光路長10mmの光の透過率であり、T2は1%の炭化水素基含有基を有する修飾ヒアルロン酸および/またはその塩を含有する水における波長660nm、光路長10mmの光の透過率である。)
Y=T4/T3×100(%) ・・・(ii)
(式中、T3は70容量%エタノール含有エタノール-水混合液における波長660nm、光路長10mmの光の透過率であり、T4は1%の炭化水素基含有基を有する修飾ヒアルロン酸および/またはその塩を含有する70容量%エタノール含有エタノール-水混合液における波長660nm、光路長10mmの光の透過率である。) - 前記透過率Xが60%以上である、請求項10に記載の炭化水素基含有基を有する修飾ヒアルロン酸および/またはその塩。
- 前記透過率Yが70%以上である、請求項10または11に記載の炭化水素基含有基を有する修飾ヒアルロン酸および/またはその塩。
- 前記炭化水素基含有基に含まれる炭化水素基が、炭素原子数6~20の直鎖状または分岐状のアルキル基またはアルケニル基である、請求項10~12のいずれか1項に記載の炭化水素基含有基を有する修飾ヒアルロン酸および/またはその塩。
- ヒアルロン酸1構成単位に含まれる前記炭化水素基含有基の数が0.001~0.2である、請求項10~13のいずれか1項に記載の炭化水素基含有基を有する修飾ヒアルロン酸および/またはその塩。
- 1%水溶液の動粘度が50mm2/s以下である、請求項10~14のいずれか1項に記載の炭化水素基含有基を有する修飾ヒアルロン酸および/またはその塩。
- 請求項10~15のいずれか1項に記載の炭化水素基含有基を有する修飾ヒアルロン酸および/またはその塩を含有する、化粧料。
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EP11744748.2A EP2537867B1 (en) | 2010-02-19 | 2011-02-18 | Modified hyaluronic acid and/or salt thereof, method for producing same and cosmetic comprising same |
CN201180009872.9A CN102770459B (zh) | 2010-02-19 | 2011-02-18 | 修饰透明质酸和/或其盐、及其制造方法以及含有它的化妆品 |
KR1020127024231A KR101726016B1 (ko) | 2010-02-19 | 2011-02-18 | 치환 히알루론산 및/또는 그 염, 그리고 그 제조 방법 및 이것을 함유하는 화장료 |
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JP2016108270A (ja) * | 2014-12-05 | 2016-06-20 | 花王株式会社 | 化粧料 |
JP2019509385A (ja) * | 2016-03-24 | 2019-04-04 | メルツ ファルマ ゲーエムベーハー ウント コンパニー カーゲーアーアー | 修飾ヒアルロン酸、その製造方法、およびそれらの使用 |
WO2017203550A1 (ja) * | 2016-05-26 | 2017-11-30 | 株式会社オフテクス | 加水分解ヒアルロン酸誘導体及びカチオン系殺菌剤を含有するコンタクトレンズ用液剤 |
JPWO2017203550A1 (ja) * | 2016-05-26 | 2018-07-12 | 株式会社オフテクス | 加水分解ヒアルロン酸誘導体及びカチオン系殺菌剤を含有するコンタクトレンズ用液剤 |
CN109562183A (zh) * | 2016-05-26 | 2019-04-02 | 日本欧得士株式会社 | 含有水解透明质酸衍生物以及阳离子系杀菌剂的隐形眼镜用液体制剂 |
US10525159B2 (en) | 2016-05-26 | 2020-01-07 | Ophtecs Corporation | Liquid preparation for contact lenses comprising hydrolyzed hyaluronic acid derivative and cationic bactericide |
CN109562183B (zh) * | 2016-05-26 | 2022-06-28 | 日本欧得士株式会社 | 含有水解透明质酸衍生物以及阳离子系杀菌剂的隐形眼镜用液体制剂 |
JP7229412B1 (ja) | 2022-06-14 | 2023-02-27 | キユーピー株式会社 | 脂質ナノ粒子及びその製造方法 |
WO2023243187A1 (ja) * | 2022-06-14 | 2023-12-21 | キユーピー株式会社 | 脂質ナノ粒子及びその製造方法 |
JP2023182310A (ja) * | 2022-06-14 | 2023-12-26 | キユーピー株式会社 | 脂質ナノ粒子及びその製造方法 |
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KR101726016B1 (ko) | 2017-04-11 |
CN102770459B (zh) | 2016-01-20 |
CN102770459A (zh) | 2012-11-07 |
KR20120140242A (ko) | 2012-12-28 |
EP2537867A1 (en) | 2012-12-26 |
US20120316329A1 (en) | 2012-12-13 |
JP2012021166A (ja) | 2012-02-02 |
US9107842B2 (en) | 2015-08-18 |
EP2537867A4 (en) | 2013-08-21 |
JPWO2011102462A1 (ja) | 2013-06-17 |
EP2537867B1 (en) | 2016-11-02 |
JP4845071B2 (ja) | 2011-12-28 |
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