WO2017126143A1 - Gel d'acide hyaluronique hydrosoluble et son procédé de production - Google Patents

Gel d'acide hyaluronique hydrosoluble et son procédé de production Download PDF

Info

Publication number
WO2017126143A1
WO2017126143A1 PCT/JP2016/071331 JP2016071331W WO2017126143A1 WO 2017126143 A1 WO2017126143 A1 WO 2017126143A1 JP 2016071331 W JP2016071331 W JP 2016071331W WO 2017126143 A1 WO2017126143 A1 WO 2017126143A1
Authority
WO
WIPO (PCT)
Prior art keywords
hyaluronic acid
water
gel
soluble
soluble hyaluronic
Prior art date
Application number
PCT/JP2016/071331
Other languages
English (en)
Japanese (ja)
Inventor
邦夫 米戸
Original Assignee
株式会社リタファーマ
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 株式会社リタファーマ filed Critical 株式会社リタファーマ
Priority to JP2017562422A priority Critical patent/JP6659052B2/ja
Publication of WO2017126143A1 publication Critical patent/WO2017126143A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/20—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents
    • A23L29/269—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents of microbial origin, e.g. xanthan or dextran
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/20—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents
    • A23L29/275—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents of animal origin, e.g. chitin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • 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
    • A61K8/60—Sugars; Derivatives thereof
    • 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
    • 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

Definitions

  • the present invention relates to a water-soluble hyaluronic acid gel excellent in stability at low temperatures and a method for producing the same.
  • Hyaluronic acid which is excellent in biocompatibility and shows many effective actions including moisturizing action, has attracted attention in the beauty field, medical field, food field and the like.
  • Hyaluronic acid is a linear high-molecular polysaccharide in which ⁇ -DN-acetylglucosamine and ⁇ -D-glucuronic acid are alternately bound, and is distributed in mammalian connective tissue. It is also known to exist in the streptococcal capsule.
  • Commercially available hyaluronic acid is generally prepared by isolation and extraction from a chicken crown, umbilical cord or the like, or a fermentation method using a microorganism such as Streptococcus.
  • gel compositions containing a polymer material have been used in the beauty field, the medical field, the food field, and the like.
  • gel compositions used in the beauty field, the medical field, the food field, and the like are required to be excellent in safety and biocompatibility because they are applied to the human body.
  • hyaluronic acid which is a natural material and excellent in safety and biocompatibility, as a polymer material contained in such a gel composition has been studied.
  • hyaluronic acid is used without using conventionally used gel-forming components such as polyacrylic acid or a salt thereof, xanthan gum, glucomannan, guar gum, locust bean, agar, carrageenan, polyvinyl alcohol and the like. Attempts have been made to develop hyaluronic acid gels that contain gel alone as a gel-forming component.
  • Patent Document 1 discloses a method for preparing a gel composition using crosslinked hyaluronic acid.
  • Patent Document 2 discloses a gel of a photocrosslinkable hyaluronic acid derivative characterized in that 0.0005 to 0.05 photodimerizable crosslinking groups are introduced on average per disaccharide unit constituting hyaluronic acid.
  • Patent Document 3 discloses a method for producing a crosslinked hyaluronic acid gel characterized by stirring and mixing a mixture containing hyaluronic acid 10 W / V% or more, a crosslinking agent, and water under acid or alkaline conditions. It is disclosed.
  • Patent Documents 1 to 3 in many of the hyaluronic acid gels in which hyaluronic acid is used alone as a gel-forming component, chemically modified hyaluronic acid is used. There is a problem that the characteristic as a natural material is lost.
  • Patent Document 4 hyaluronic acid, water having a hyaluronic acid concentration of 5% by mass or more, and a carboxyl group of hyaluronic acid and an equimolar or more acid component are allowed to coexist and the coexistence state is maintained.
  • the hyaluronic acid gel obtained in Patent Document 4 is hardly soluble in water, it is difficult for hyaluronic acid to dissolve in water.
  • the poorly water-soluble hyaluronic acid gel as disclosed in Patent Document 4 is less effective in moisturizing and firming the skin with hyaluronic acid when applied to the skin. Not suitable for use.
  • the hyaluronic acid gel disclosed in Patent Document 4 is obtained by allowing hyaluronic acid, an acid, and water to stand at low temperatures for at least several days, and it takes a long time to produce the hyaluronic acid gel. There is also a problem.
  • Patent Document 5 discloses that a hyaluronic acid gel can be obtained by bringing a hyaluronic acid solution into contact with a water-soluble organic solvent such as methanol, ethanol, isopropanol, and acetone at pH 2.0 to 3.8. Is disclosed.
  • a water-soluble organic solvent such as methanol, ethanol, isopropanol, and acetone at pH 2.0 to 3.8.
  • the method of Patent Document 5 has a problem that it is difficult to use in the beauty field, the medical field, the food field, etc., because these water-soluble organic solvents are contained in a large amount in the hyaluronic acid gel.
  • the hyaluronic acid gel disclosed in Patent Document 5 has a problem that it is difficult to form a sheet by a simple method such as a casting method.
  • Patent Document 6 discloses a hyaluronic acid gel comprising hyaluronic acid, polyvalent carboxylic acid or oxycarboxylic acid, and polyhydric alcohol as constituent components.
  • the hyaluronic acid gel described in Patent Document 6 has an advantage that hyaluronic acid that is not chemically modified can be used, and it is not necessary to use a large amount of an organic solvent.
  • the present invention is substantially free of gel-forming components other than hyaluronic acid, and further contains a sugar (however, excluding liquid polyhydric alcohol that is liquid at 25 ° C.) at room temperature.
  • the main object of the present invention is to provide a water-soluble hyaluronic acid gel having a gel form excellent in stability not only at low temperatures.
  • the present invention also aims to provide a method for producing the water-soluble hyaluronic acid gel, a cosmetic, a medical device composition, a food composition, or a pharmaceutical composition using the water-soluble hyaluronic acid gel. .
  • the present inventor has intensively studied to solve the above problems. As a result, it contains hyaluronic acid, sugar (excluding liquid polyhydric alcohol that is liquid at 25 ° C.), and water, the water content is more than 30% by mass, and gel-forming components other than hyaluronic acid Substantially not contained, and the pH of the aqueous solution measured by the following measurement method is in the range of 1.9 to 6.3, it is difficult to form a saccharide solid even at low temperatures, resulting in stability. It has been found that a water-soluble hyaluronic acid gel having an excellent gel form can be obtained.
  • the present inventor suitably uses such a water-soluble hyaluronic acid gel as a cosmetic, a composition for medical devices, a food composition, a pharmaceutical composition, or the like because it has excellent stability at low temperatures. I found out that I can do it.
  • a water-soluble hyaluronic acid gel is prepared by mixing hyaluronic acid, sugar (except liquid polyhydric alcohol that is liquid at 25 ° C.), water, and, if necessary, an acid other than hyaluronic acid.
  • a step of preparing an aqueous solution for gel formation without substantially mixing a gel-forming component other than hyaluronic acid, and water contained in the aqueous solution for gel formation so that the water content exceeds 30% by mass It has also been found that it can be easily produced by a production method comprising a step of removing.
  • the present invention has been completed by further studies based on these findings.
  • this invention provides the invention of the aspect hung up below.
  • Item 1 Hyaluronic acid, sugar (except liquid polyhydric alcohol that is liquid at 25 ° C.), and water, The water content is over 30% by weight, Substantially free of gel-forming components other than the hyaluronic acid, A water-soluble hyaluronic acid gel in which the pH of an aqueous solution measured by the following measurement method is in the range of 1.9 to 6.3.
  • the water-soluble hyaluronic acid gel according to Item 1 or 2 which contains 100 parts by weight or less of a liquid polyhydric alcohol that is liquid at 25 ° C with respect to 100 parts by weight of the sugar.
  • Item 4. Item 4. The water-soluble hyaluronic acid gel according to any one of Items 1 to 3, wherein the sugar solid is not formed when left at 5 ° C for 48 hours.
  • Item 5. The water-soluble hyaluronic acid gel according to any one of Items 1 to 4, which is in the form of a sheet.
  • Item 7. A food composition using the water-soluble hyaluronic acid gel according to any one of Items 1 to 6.
  • Item 7. A pharmaceutical composition using the water-soluble hyaluronic acid gel according to any one of Items 1 to 6.
  • Item 7. A medical device composition using the water-soluble hyaluronic acid gel according to any one of Items 1 to 6. Item 11.
  • a method for producing a water-soluble hyaluronic acid gel according to any one of Items 1 to 6, For gel formation, mixing hyaluronic acid, sugar (except liquid polyhydric alcohol that is liquid at 25 ° C.), and water, and without substantially mixing gel-forming components other than hyaluronic acid Preparing an aqueous solution; Removing water contained in the aqueous solution for gel formation so that the water content exceeds 30% by mass; A method for producing a water-soluble hyaluronic acid gel comprising: Item 12.
  • a method for producing a water-soluble hyaluronic acid gel according to any one of Items 1 to 6, For gel formation, mixing hyaluronic acid, sugar (except liquid polyhydric alcohol that is liquid at 25 ° C.), and water, and without substantially mixing gel-forming components other than hyaluronic acid Preparing an aqueous solution; Removing water contained in the gel-forming aqueous solution, adding water, and adjusting the water content to be more than 30% by mass; and A method for producing a water-soluble hyaluronic acid gel comprising: Item 13. Item 13.
  • Item 14 A method for producing a water-soluble hyaluronic acid gel according to any one of Items 1 to 6, A gel-forming component other than hyaluronic acid is substantially mixed in an aqueous solution containing the sugar (except liquid polyhydric alcohol that is liquid at 25 ° C.) and water, and having a water content of more than 30% by mass. Without manufacturing, the manufacturing method of water-soluble hyaluronic acid gel provided with the process of adding and dissolving a hyaluronic acid.
  • the present invention contains substantially no gel-forming component other than hyaluronic acid, and further contains sugar (however, excluding liquid polyhydric alcohol that is liquid at 25 ° C.) It is possible to provide a water-soluble hyaluronic acid gel having a gel form excellent in stability even at low temperatures.
  • hyaluronic acid is not chemically modified, and natural materials can be used.
  • the manufacturing method of the said water-soluble hyaluronic acid gel, the cosmetics using the said water-soluble hyaluronic acid gel, the composition for medical devices, the food composition, or the pharmaceutical composition can be provided. .
  • the water-soluble hyaluronic acid gel of the present invention contains hyaluronic acid, sugar (except liquid polyhydric alcohol that is liquid at 25 ° C.), and water, and has a water content of more than 30% by mass. It is characterized in that the pH of the aqueous solution measured by the following measurement method is in the range of 1.9 to 6.3. (Measurement method of pH) Among the components contained in the water-soluble hyaluronic acid gel in an amount containing 1 g of hyaluronic acid, prepare an aqueous solution so that all ionic components except water are dissolved in water to 200 mL, and adjust the pH of the obtained aqueous solution. taking measurement.
  • the water-soluble hyaluronic acid gel of the present invention is substantially free of gel-forming components other than hyaluronic acid due to having such a configuration, and is further a sugar (however, a liquid that is liquid at 25 ° C. Despite the presence of polyhydric alcohol, it has a gel form that is excellent in stability even at low temperatures (for example, even when left at 48C for 48 hours, Sugar solids (eg sugar crystals) are not formed).
  • the water-soluble hyaluronic acid gel of the present invention the method for producing the water-soluble hyaluronic acid gel, cosmetics using the water-soluble hyaluronic acid gel, compositions for medical devices, food compositions, or pharmaceutical compositions (external use, Oral) will be described in detail.
  • the water-soluble hyaluronic acid gel of the present invention contains hyaluronic acid, sugar (however, excluding liquid polyhydric alcohol that is liquid at 25 ° C.), and water.
  • the water-soluble hyaluronic acid gel of the present invention is prepared by preparing an aqueous solution for gel formation containing, for example, hyaluronic acid, sugar, water, and, if necessary, an acid other than hyaluronic acid, and the water content exceeds 30% by mass.
  • it can be produced by adjusting the amount or type of the acid added as necessary so that the pH is in the range of 1.9 to 6.3 by the above measurement method.
  • the water content may be adjusted by, for example, a method of evaporating water from the gel forming aqueous solution.
  • hyaluronic acid is included as a gel-forming component.
  • hyaluronic acid is substantially contained alone as a gel-forming component, and other gel-forming components are not substantially contained.
  • the water-soluble hyaluronic acid gel of the present invention may contain a slight amount of other gel-forming components in addition to hyaluronic acid.
  • gel-forming components are not particularly limited, for example, polyacrylic acid or a salt thereof, xanthan gum, gellan gum, glucomannan, guar gum, locust bean gum, agar, gelatin, pectin, casein, gum arabic, carrageenan, agarose, Known gel forming components such as alginic acid, propylene glycol alginate, carboxymethyl cellulose Na, hydroxypropyl cellulose, polyvinyl alcohol, carboxyvinyl polymer, starch / acrylate graft copolymer, methyl vinyl ether / maleic anhydride copolymer, and the like. .
  • the content of the other gel-forming components is the hyaluronic acid in the composition of the water-soluble hyaluronic acid gel of the present invention.
  • the amount is preferably not more than the amount at which no gel is formed.
  • the content of the other gel-forming component varies depending on the type of the other gelling component, but is 5% by mass or less, preferably 2.5% by mass or less, more preferably in the water-soluble hyaluronic acid gel of the present invention. Is 1% by mass or less, more preferably 0.5% by mass or less, and still more preferably 0.1% by mass or less.
  • hyaluronic acid is used in a concept including hyaluronic acid and a salt thereof. Therefore, “hyaluronic acid and a salt thereof” may be simply referred to as “hyaluronic acid”.
  • the salt of hyaluronic acid is not particularly limited, and examples thereof include sodium hyaluronate, potassium hyaluronate, magnesium hyaluronate, calcium hyaluronate and the like.
  • hyaluronic acid and its salt may be used individually by 1 type, and may be used in combination of 2 or more type.
  • the molecular weight of hyaluronic acid is not particularly limited as long as it can form a gel even when hyaluronic acid alone is used as a gel-forming component, but the gel form contains substantially no gel-forming components other than hyaluronic acid.
  • it is preferably 5.0 ⁇ 10. It is about 4 to 5.0 ⁇ 10 6 daltons, more preferably about 1.0 ⁇ 10 5 to 2.3 ⁇ 10 6 daltons.
  • hyaluronic acid one having a single molecular weight may be used, or plural kinds of molecular weights may be mixed and used.
  • “moderate elasticity” means, for example, a characteristic that when a water-soluble hyaluronic acid gel is pressed with a finger, it repels moderately and does not pull when it is pulled and broken.
  • high mechanical strength means the intensity
  • the form maintaining property refers to the property that, when a water-soluble hyaluronic acid gel is allowed to stand, unlike a high-viscosity solution, the shape when it is left standing is maintained.
  • the origin of hyaluronic acid is not particularly limited, and, for example, those isolated and extracted from chicken crowns, umbilical cords, etc., and those prepared by fermentation using microorganisms such as Streptococcus can be preferably used.
  • a commercially available product can be used as the hyaluronic acid. Since the water-soluble hyaluronic acid gel of the present invention does not need to be chemically modified as hyaluronic acid, it is excellent in biocompatibility and can exhibit the characteristics of natural hyaluronic acid. That is, in the water-soluble hyaluronic acid gel of the present invention, only hyaluronic acid that is not substantially chemically modified may be used as hyaluronic acid.
  • the water-soluble hyaluronic acid gel of the present invention may further contain chemically modified hyaluronic acid as long as the effects of the present invention are not inhibited.
  • chemically modified hyaluronic acid examples include hydroxypropyltrimonium hyaluronate, hydrolyzed alkyl hyaluronate (C12-13) glyceryl, propylene glycol hyaluronate, sodium acetylated hyaluronate, and the like. Chemically modified hyaluronic acid may be used alone or in combination of two or more.
  • the content of hyaluronic acid is not particularly limited as long as it can form a gel, but it is substantially free of gel-forming components other than hyaluronic acid, and is in the form of a gel.
  • the water-soluble hyaluronic acid gel with appropriate elasticity, high mechanical strength, and shape maintaining property while suppressing the formation of solid sugar in the gel at low temperature (for example, about 5 ° C.).
  • the gel When the content of hyaluronic acid in the water-soluble hyaluronic acid gel is less than 0.2% by mass, the gel may not be formed from an aqueous solution for gel formation described below. In addition, when the content of hyaluronic acid in the water-soluble hyaluronic acid gel exceeds 50% by mass, the water-soluble hyaluronic acid gel becomes too hard, and a cosmetic, food, pharmaceutical composition, or medical device composition described later, etc. It may be difficult to use as.
  • Sugar (excluding liquid polyhydric alcohol that is liquid at 25 ° C.) is not particularly limited, and sugars ranging from monosaccharide to disaccharide to decasaccharide can be used.
  • Specific examples of sugar include glucose, fructose, xylitol, sorbitol, trehalose, lactose, maltose, sucrose, raffinose, oligosaccharide (fructo-oligosaccharide, galacto-oligosaccharide, mannan-oligosaccharide, isomaly-oligosaccharide, lactose fructose oligosaccharide, malto-oligosaccharide, soybean Oligosaccharide, xylooligosaccharide, etc.), ⁇ -cyclodextrin, ⁇ -cyclodextrin, ⁇ -cyclodextrin and the like.
  • One type of sugar may be used alone, or two or more types may be
  • the water-soluble hyaluronic acid gel of the present invention preferably contains a sugar having a solubility in 100 g of water at 25 ° C. of 50 g or more.
  • a sugar having a solubility in 100 g of water at 25 ° C. of 50 g or more is formed more effectively, while substantially free of gel-forming components other than hyaluronic acid, and in the form of a gel, further suppressing the formation of sugar solids in the gel at low temperatures.
  • the acid gel can be provided with moderate elasticity, high mechanical strength, and shape maintainability.
  • the water-soluble hyaluronic acid gel of the present invention contains xylitol and / or liquid oligosaccharide (fruc oligosaccharide, lactose fructose oligosaccharide, isomalto oligosaccharide, galac oligosaccharide, xylooligosaccharide, soybean oligosaccharide, etc.) among these sugars. It is preferable.
  • xylitol or liquid oligosaccharide even when the water-soluble hyaluronic acid gel is stored at a low temperature (for example, about 5 ° C.), the formation of sugar solids in the gel is more effectively suppressed. Meanwhile, the water-soluble hyaluronic acid gel can be provided with appropriate elasticity, high mechanical strength, and shape maintenance.
  • the content of the other sugars is 1 part by weight of xylitol and / or liquid oligosaccharides. Is preferably 4 parts by mass or less, more preferably 2.5 parts by mass or less, and still more preferably 1 part by mass or less.
  • the sugar content contained in the water-soluble hyaluronic acid gel is not particularly limited, but from the above viewpoint, it is preferably 0.05 parts by mass or more and 400 parts by mass with respect to 1 part by mass of hyaluronic acid.
  • the sugar content means the total amount of all the sugars.
  • the water content of the water-soluble hyaluronic acid gel of the present invention is more than 30% by mass.
  • the water content is more than 30% by mass, and the pH described later is in the range of 1.9 to 6.3, so that gel-forming components other than hyaluronic acid are substantially contained.
  • it has excellent stability even at low temperatures (for example, about 5 ° C.) despite the fact that it contains sugar (except liquid polyhydric alcohol that is liquid at 25 ° C.). It becomes a water-soluble hyaluronic acid gel having a gel form.
  • a water-soluble hyaluronic acid gel that is substantially free from gel-forming components other than hyaluronic acid, and that suppresses the formation of solid sugar in the gel at low temperatures (eg, about 5 ° C.).
  • the water content of the water-soluble hyaluronic acid gel is preferably 31% by mass to 90% by mass, more preferably 31% by mass to 70% by mass. The mass% or less is mentioned.
  • the water-soluble hyaluronic acid gel of the present invention may further contain a liquid polyhydric alcohol that is liquid at 25 ° C. under 1 atm.
  • a liquid polyhydric alcohol is not particularly limited, but preferably glycerins such as glycerin and diglycerin; propylene glycols such as propylene glycol and dipropylene glycol; 1,3-propanediol, butanediol (1 , 3-butanediol, 1,4-butanediol, etc.), 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol; ethylene such as ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol Glycols, and the like, more preferably glycerin, diglycerin, propylene glycol, 1,3-butanediol, polyethylene glycol 200, polyethylene glycol 400, polyethylene glycol
  • the content of the liquid polyhydric alcohol in the water-soluble hyaluronic acid gel of the present invention is based on 100 parts by mass of sugar. Preferably, it is 100 mass parts or less, More preferably, it is 5 mass parts or more and 50 mass parts or less, More preferably, 10 mass parts or more and 40 mass parts or less are mentioned.
  • the water-soluble hyaluronic acid gel of the present invention is suitably gelled even without containing liquid polyhydric alcohol. That is, the water-soluble hyaluronic acid gel of the present invention does not need to contain substantially liquid polyhydric alcohol.
  • the content of the liquid polyhydric alcohol in the water-soluble hyaluronic acid gel of the present invention may be 1% by mass or less, and further 0.1% by mass or less.
  • the water-soluble hyaluronic acid gel of the present invention can adjust the pH of the aqueous solution measured by the following measuring method to a range of 1.9 to 6.3, for example, by using an acid different from hyaluronic acid. .
  • the pH of the aqueous solution prepared by the measurement method as described above is measured.
  • a water-soluble hyaluronic acid gel contains a large amount of nonionic sugar, etc.
  • blended with a hyaluronic acid gel in water, and measuring the pH of the obtained aqueous solution is used.
  • the acid different from hyaluronic acid is not particularly limited as long as it is acidic when mixed with water, and either an inorganic acid or an organic acid can be used.
  • the inorganic acid include phosphoric acid, hydrochloric acid, sulfuric acid, nitric acid, perchloric acid, and carbonic acid, and preferably phosphoric acid, hydrochloric acid, and sulfuric acid.
  • organic acids include monocarboxylic acids such as formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and lipoic acid; dicarboxylic acids such as succinic acid, phthalic acid, fumaric acid, oxalic acid, malonic acid, and glutaric acid.
  • Acids such as glycolic acid, citric acid, lactic acid, pyruvic acid, malic acid, tartaric acid and salicylic acid; polyhydroxy acids such as glucono- ⁇ -lactone and lactopionic acid; acidic amino acids such as glutamic acid and aspartic acid; (Registered trademark, methyl carboxymethylphenylaminocarboxypropylphosphonate) and the like; ascorbic acid such as ascorbic acid, ethyl ascorbate, ascorbic acid glucoside or derivatives thereof, preferably phosphoric acid, ascorbic acid, citric acid, Glycolic acid, lactic acid, malic acid, tartar
  • acids salicylic acid, ethyl ascorbate, ascorbic acid glucoside, glucono- ⁇ -lactone, and lactopionic acid.
  • An acid may be used individually by 1 type and may be used in combination of 2 or more type.
  • the water-soluble hyaluronic acid gel of the present invention may contain a water-soluble organic solvent (excluding the aforementioned liquid polyhydric alcohol).
  • a water-soluble organic solvent excluding the aforementioned liquid polyhydric alcohol.
  • the content thereof is 10% by mass or less, preferably 5% by mass or less, more preferably 2% by mass or less.
  • the water-soluble organic solvent is not particularly limited, and examples thereof include ethanol, methanol, isopropanol, and acetone.
  • a water-soluble organic solvent may be used individually by 1 type, and may be used in combination of 2 or more types. As described later, the water-soluble hyaluronic acid gel of the present invention is suitably used in the beauty field, the medical field, and the food field.
  • the water-soluble hyaluronic acid gel of the present invention does not substantially contain a water-soluble organic solvent.
  • a water-soluble organic solvent when a water-soluble organic solvent is used, the viscosity of an aqueous solution for gel formation described later tends to increase, and it may be difficult to spread the aqueous solution for gel formation thinly on a substrate or the like. For this reason, when a water-soluble organic solvent is used, it may be difficult to form a water-soluble hyaluronic acid gel into a sheet by a simple method such as a casting method. Also from such a viewpoint, it is preferable that the water-soluble hyaluronic acid gel of the present invention does not substantially contain a water-soluble organic solvent.
  • the elasticity, mechanical strength, shape maintainability, etc. of the water-soluble hyaluronic acid gel of the present invention include the content of each component in the water-soluble hyaluronic acid gel, the molecular weight of the hyaluronic acid, or the pH of the aqueous solution in the aforementioned pH measurement method. It can be adjusted by setting the range to a predetermined range. For example, when the content of hyaluronic acid in the water-soluble hyaluronic acid gel is increased (the ratio is increased), the water-soluble hyaluronic acid gel becomes harder and the elasticity, mechanical strength, and shape maintenance of the water-soluble hyaluronic acid gel are improved. Tend to be higher.
  • the water-soluble hyaluronic acid gel becomes hard, and the elasticity, mechanical strength, and shape maintainability of the water-soluble hyaluronic acid gel tend to increase.
  • the water-soluble hyaluronic acid gel of the present invention is water-soluble.
  • the water solubility of the water-soluble hyaluronic acid gel of the present invention means that a water-soluble hyaluronic acid gel having a thickness of 100 ⁇ m, a length of 4 cm, and a width of 4 cm is placed in 100 mL of a pH 7.4 phosphate buffer at 37 ° C. When it stirs at 120 rpm using a stirrer, it means that it dissolves completely within 4 hours.
  • the shape of the water-soluble hyaluronic acid gel of the present invention is not particularly limited and can be appropriately set according to the application.
  • Examples of the shape of the water-soluble hyaluronic acid gel of the present invention include a sheet shape, a granular shape, and a lump shape.
  • the water-soluble hyaluronic acid gel is in the form of a sheet (water-soluble hyaluronic acid gel sheet), as described later, for example, the water-soluble hyaluronic acid gel of the present invention is applied to the skin, oral cavity, etc. It can be suitably used as a composition or a composition for medical devices. Further, the sheet-like water-soluble hyaluronic acid gel may be used as a food composition such as an oral hygiene improving film or an oral pharmaceutical composition such as an oral sustained release film.
  • the thickness of the water-soluble hyaluronic acid gel sheet is not particularly limited, and may be, for example, about 0.01 to 10 mm, preferably about 0.05 to 5 mm.
  • the water-soluble hyaluronic acid gel when it is in the form of a lump, it can be suitably used as a cosmetic composition for massaging the face and body. It can also be suitably used as a food composition such as a jelly drink or an oral pharmaceutical composition such as a swallowing assistance drink. When the water-soluble hyaluronic acid gel is granular, it can be suitably used as a food composition such as gummy or an oral pharmaceutical composition.
  • the water-soluble hyaluronic acid gel of the present invention contains hyaluronic acid having a moisturizing action and the like, it can be applied to the skin and the like in the beauty field and the medical field. Moreover, since it can also be comprised only with components which can be used for food and medicine, such as hyaluronic acid and sugar, it can be suitably applied to the oral cavity. That is, the water-soluble hyaluronic acid gel of the present invention can be suitably used as a cosmetic, a food composition, a pharmaceutical composition, or a medical device composition.
  • the water-soluble hyaluronic acid gel of the present invention When used as a cosmetic, pharmaceutical composition, or medical device composition, known ingredients (additives) blended in cosmetics, quasi drugs, pharmaceuticals, and medical devices Can be further blended. Examples of such components include whitening ingredients, anti-aging ingredients, oil ingredients, various vitamins and derivatives thereof, various animal and plant extracts, anti-inflammatory agents, antioxidants, pigments, fragrances (aromatic ingredients), preservatives, honey, and the like. Is mentioned. Moreover, when adding a fat-soluble component (additive) to the water-soluble hyaluronic acid gel of the present invention, the fat-soluble component can be added in the form of liposome, emulsion, nanoemulsion or the like. These components may be used alone or in combination of two or more.
  • whitening ingredients include vitamin C or its derivatives, astaxanthin and the like.
  • Specific examples of the anti-aging component include Narusgene (registered trademark, methyl carboxymethylphenylaminocarboxypropylphosphonate), pyrroloquinoline quinone, LR2412 (registered trademark, sodium tetrahydrojasmonate), Green Peel (registered trademark, vegetable essential oil). ) And the like.
  • Specific examples of the oil component include squalane, jojoba oil, olive oil and the like.
  • the water-soluble hyaluronic acid gel of the present invention includes collagen, porphyrin, proteoglycan, acetylglucosamine, hydroxypropylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, lipida (registered trademark, 2-methacryloyloxyethyl phosphorylcholine homopolymer or copolymer), A water-soluble polymer (additive) such as hyaluronic acid having a molecular weight of 10,000 or less or a salt thereof may be blended.
  • One type of water-soluble polymer may be used alone, or two or more types may be used in combination.
  • the water-soluble hyaluronic acid gel of the present invention can be imparted with appropriate elasticity, appropriate mechanical strength, and appropriate shape maintenance, the water-soluble hyaluronic acid gel of the present invention is used as it is as a pack agent. You can also.
  • the water-soluble hyaluronic acid gel of the present invention is used as a pack agent, the water-soluble hyaluronic acid gel of the present invention is preferably in the form of a sheet.
  • the water-soluble hyaluronic acid gel sheet of the present invention is directly applied to the skin and held for a certain period of time, thereby providing the skin with a moisturizing effect by hyaluronic acid.
  • the water-soluble hyaluronic acid gel of the present invention contains known ingredients (additives) blended in the cosmetics, quasi drugs, pharmaceuticals, and medical devices as described above, the water-soluble hyaluronic acid gel sheet of the present invention By adhering directly to the skin, these components can be absorbed transdermally.
  • the water-soluble hyaluronic acid gel of the present invention has water solubility, hyaluronic acid is likely to dissolve into moisture. For this reason, the water-soluble hyaluronic acid gel of the present invention has a high effect of moisturizing and firming the skin with hyaluronic acid when applied to the skin, and is suitable for use in the beauty field. For example, after applying the water-soluble hyaluronic acid gel sheet of the present invention to the skin, the skin is massaged while being gradually dissolved by applying water to the sheet, thereby further enhancing the moisturizing effect of hyaluronic acid dissolved in water. be able to.
  • the water-soluble hyaluronic acid gel of the present invention is excellent in safety and biocompatibility and has high water absorption / water retention, it is suitable for use as a medical device for protecting wound sites and pressure ulcer sites.
  • the water-soluble hyaluronic acid gel of the present invention is excellent in safety and biocompatibility, and has high water absorption / water retention, so that it can be suitably used as a pad for emergency bandages or a covering protective material for pressure ulcers. it can.
  • healing promotion components such as epidermal growth factor, and an antimicrobial component (additive) can also be mix
  • the water-soluble hyaluronic acid gel of the present invention may be used on a support.
  • a water-soluble hyaluronic acid gel sheet By forming a water-soluble hyaluronic acid gel on a support, a water-soluble hyaluronic acid gel sheet can be suitably formed.
  • the support is not particularly limited, and examples thereof include non-woven fabrics, woven fabrics, woven fabrics, paper, polymer films (polyethylene terephthalate, polyolefins such as polyethylene, vinyl chloride, polyurethane films, etc.), and more preferably, From the viewpoint of the adhesive strength between the water-soluble hyaluronic acid gel and the support, a laminate film made of a nonwoven fabric / polymer film, a nonwoven fabric and the like can be mentioned. Further, the water-soluble hyaluronic acid gel on the support may be fixed with an adhesive tape, a hydrogel tape, a supporter, a bandage, a mask, an eye mask or the
  • the water-soluble hyaluronic acid gel of the present invention can be used alone as a product as it is.
  • the product can be a product in which the gel is integrated with an adhesive tape or a support, or a water-soluble hyaluronic acid gel is used as the product, and the adhesive tape, hydrogel tape, supporter, bandage, mask, eye mask.
  • the gel may be fixed and used.
  • the water-soluble hyaluronic acid gel of the present invention can be constituted only by ingredients that can be used for food or medicine, such as hyaluronic acid and sugar, and therefore a food composition containing the water-soluble hyaluronic acid gel, It can also be suitably used as an oral pharmaceutical composition.
  • a known component (additive) to be blended in the food composition can be further blended.
  • such components include sweeteners, fragrances, colorants, acidulants, antioxidants, emulsifiers, preservatives, stabilizers, and the like.
  • blended with an oral pharmaceutical composition can further be mix
  • such components include medicinal ingredients, fragrances, colorants, acidulants, antioxidants, emulsifiers, preservatives, stabilizers, and the like.
  • these components may be used alone or in combination of two or more.
  • the food composition or oral pharmaceutical composition using the water-soluble hyaluronic acid gel of the present invention contains hyaluronic acid, by ingesting the food composition or oral pharmaceutical composition, for example, the skin The effect of increasing the moisture content and enhancing the skin moisturizing effect can be expected. Furthermore, when the food composition or oral pharmaceutical composition contains known components (additives) as described above, the effects of these components can be exhibited. In addition, by using cyclodextrin as a sugar, a bitterness masking effect and sustained release effect due to the action of encapsulating the hydrophobic component of cyclodextrin can be expected.
  • indigestible cyclodextrin as sugar, sugar absorption speed delay action (inhibition of postprandial blood sugar increase), intestinal regulation action, fat absorption speed delay action (postprandial neutral fat increase suppression action) ), Effects of reducing visceral fat, promoting absorption of minerals, and the like can be expected.
  • oligosaccharides as sugars, effects such as the action of adjusting the intestinal environment and the action of increasing the absorption of minerals can be expected.
  • xylitol as a sugar, an effect of inhibiting caries caused by bacteria in the oral cavity of xylitol can be expected.
  • water-soluble hyaluronic acid gel of the present invention is used as a food composition or an oral pharmaceutical composition
  • these forms are not particularly limited.
  • a sheet shape such as an oral hygiene improvement film, a granular shape such as a gummi, and a swallowing It can be a lump like an auxiliary beverage / jelly beverage.
  • the water-soluble hyaluronic acid gel of the present invention can be suitably used as a hydrogel for crystallizing a protein used for X-ray crystallography in a solid phase.
  • the method for producing the water-soluble hyaluronic acid gel of the present invention is not particularly limited.
  • hyaluronic acid, sugar however, excluding liquid polyhydric alcohol that is liquid at 25 ° C.
  • the method of including the process of removing the water contained in the aqueous solution for gel formation is mentioned.
  • hyaluronic acid for example, hyaluronic acid, sugar (however, excluding liquid polyhydric alcohol that is liquid at 25 ° C.), water, and if necessary, acid other than hyaluronic acid is mixed, and gel other than hyaluronic acid is mixed.
  • a method including a step of adjusting is also included.
  • the above-described various components (additives) that are blended as necessary can be mixed.
  • the order of mixing the components is not particularly limited. Moreover, the mixing method of each component is not particularly limited, and may be stirred using, for example, a stirrer.
  • the method for producing the water-soluble hyaluronic acid gel of the present invention it is preferable to set the blending amount of each component so that the pH of the aqueous solution prepared by the above-described pH measurement method has the above-mentioned value.
  • the pH of the aqueous solution prepared by the above-described pH measurement method has the above-mentioned value.
  • the amount of water in the gel-forming aqueous solution is not particularly limited as long as it is an amount capable of forming a water-soluble hyaluronic acid gel having a water content of more than 30% by mass, and is usually 20 for example with respect to 1 part by mass of hyaluronic acid.
  • the amount is about 1000 parts by mass, preferably about 40-400 parts by mass. If the amount of water in the gel forming aqueous solution is too small, the viscosity of the gel forming aqueous solution becomes too high, and it may be difficult to uniformly mix hyaluronic acid, sugar, and water in water. Moreover, when there is too much quantity of water, in order to gelatinize the aqueous solution for gel formation, it will be necessary to remove a lot of water at a next process.
  • the method for removing water from the gel-forming aqueous solution is not particularly limited, and examples thereof include a method of evaporating water from the gel-forming aqueous solution.
  • the evaporation of water is performed by heating and drying the gel-forming aqueous solution with a dryer such as a thermostatic bath, heating and drying the gel-forming aqueous solution by applying hot air to the gel-forming aqueous solution, or heating and drying the gel-forming aqueous solution on a hot plate.
  • a dryer such as a thermostatic bath
  • the gel-forming aqueous solution spread to a uniform thickness on a substrate such as a polyethylene terephthalate film is heated and dried (casting method).
  • a water-soluble hyaluronic acid gel sheet can be easily produced.
  • the temperature for evaporating at least a part of the water from the gel-forming aqueous solution is not particularly limited. About 20 to 110 ° C. in atmospheric pressure. Further, the time for evaporating is not particularly limited, but may be about 0.05 to 48 hours within such a temperature range.
  • a water-soluble hyaluronic acid gel sheet can also be obtained by placing an aqueous gel-forming solution in a container such as a tray or vat so that the gel has a predetermined thickness and drying it in a dryer such as a thermostatic bath (batch method). It can be manufactured easily. That is, by putting a gel-forming aqueous solution in a container and evaporating water, for example, a water-soluble hyaluronic acid gel sheet formed in the container can be used as it is as a final product. Processing steps such as cutting can be omitted.
  • water may be added after preparing a water-soluble hyaluronic acid gel having a low water content.
  • a step of adding water can be performed after removing water contained in the aqueous solution for gel formation.
  • the water content exceeds 30% by performing a step of adding water.
  • the method for producing the water-soluble hyaluronic acid gel of the present invention after removing water contained in the gel-forming aqueous solution, for example, the above-mentioned blended in cosmetics, foods, quasi drugs, pharmaceuticals, medical devices, etc. You may further provide the process of adding various components (additive).
  • the various components additives
  • the amount of the component in the gel can be suitably controlled by adding it together with water after the step of removing water by drying or the like.
  • an appropriate amount of water is required, such as an emulsion or nanoemulsion, the amount of water in the gel can be suitably controlled so as to exceed 30%.
  • the contents of sugar and water in the gel-forming aqueous solution may be set to be the above-mentioned contents when the water-soluble hyaluronic acid gel is used.
  • the method for producing the water-soluble hyaluronic acid gel of the present invention includes sugar (however, excluding liquid polyhydric alcohol that is liquid at 25 ° C.), water, and if necessary, an acid other than hyaluronic acid. And a method comprising a step of adding and dissolving hyaluronic acid in an aqueous solution having a water content of more than 30% by mass without substantially mixing a gel-forming component other than hyaluronic acid.
  • the sugar is a liquid oligosaccharide (fructooligosaccharide, lactose fructose oligosaccharide, isomaltoligosaccharide, galactooligosaccharide, xylooligosaccharide, soybean oligosaccharide, etc.) at room temperature (25 ° C.). It is preferable to use a saccharide that does not form a solid even when water is 50 parts by mass or less with respect to 100 parts by mass of the saccharide. Also in this method, after preparing a water-soluble hyaluronic acid gel, the above-mentioned various components (additives) blended as necessary can be further added.
  • a water-soluble hyaluronic acid gel that is suitably controlled so that the water content exceeds 30% is produced, including the case where an appropriate amount of water is required, such as an emulsion or nanoemulsion. be able to.
  • an appropriate amount of water such as an emulsion or nanoemulsion. be able to.
  • the drying step is not necessary, and thus the amount of the component in the gel can be suitably controlled.
  • this mixed solution is put in a container such as a tray or vat and stored at room temperature for about 24 hours, so that the hyaluronic acid dissolves and the water-soluble hyaluronic acid gel Can be easily manufactured.
  • the water-soluble hyaluronic acid gel of the present invention when the water-soluble hyaluronic acid gel of the present invention is formed into a sheet shape, the above mixed solution is spread on a substrate such as a polyethylene terephthalate film so as to have a uniform thickness, and the room temperature (25 ° C) is about 24 hours.
  • a substrate such as a polyethylene terephthalate film
  • the room temperature (25 ° C) is about 24 hours.
  • the method for producing the water-soluble hyaluronic acid gel of the present invention for example, when the above-mentioned known ingredients (additives) to be blended in cosmetics, foods, quasi drugs, pharmaceuticals, and medical devices are further blended, These components may be added after preparing the water-soluble hyaluronic acid gel.
  • water-soluble hyaluronic acid gel of the present invention is produced as a lump, for example, the above hyaluronic acid, sugar (however, excluding liquid polyhydric alcohol that is liquid at 25 ° C.), and water are mixed.
  • a blocky water-soluble hyaluronic acid gel may be produced by immersing the aqueous hyaluronic acid solution in a solution containing an acid different from hyaluronic acid.
  • Hyaluronic acid (2.3 million): Sodium hyaluronate, trade name “HYALURONSAN HA-LQSH” manufactured by Kewpie Co., Ltd. (Product display: molecular weight 1.6 million to 2.9 million, average molecular weight 2.3 million)
  • Hyaluronic acid 600,000: sodium hyaluronate, Product name "Hyaluronic acid FCH-60” manufactured by Kikkoman Biochemifa Co., Ltd.
  • Hyaluronic acid (Product display: average molecular weight 500,000 to 700,000) Hyaluronic acid (350,000): Hyaluronic acid, product name "Hyaluronic acid HA-" LF-P "(Product display: molecular weight 200,000 to 500,000, average molecular weight 350,000) Hyaluronic acid (100,000): Sodium hyaluronate, trade name “Hyaluronic acid FCH-SU” manufactured by Kikkoman Biochemifa Co., Ltd. (product display: average molecular weight 50,000 to 110,000) Glucose: D (+)-glucose (special grade) manufactured by Wako Pure Chemical Industries, Ltd.
  • Fructose D (-)-fructose (special grade) manufactured by Wako Pure Chemical Industries, Ltd.
  • Xylitol Xylitol (special grade) manufactured by Wako Pure Chemical Industries, Ltd. Sorbitol: D (+)-sorbitol (first grade) manufactured by Wako Pure Chemical Industries, Ltd.
  • Trehalose Trehalose dihydrate (special grade) manufactured by Wako Pure Chemical Industries, Ltd.
  • Maltose D (+)-maltose monohydrate (special grade) manufactured by Wako Pure Chemical Industries, Ltd.
  • Lactose Lactose monohydrate (special grade) manufactured by Wako Pure Chemical Industries, Ltd.
  • Sucrose Sucrose (special grade) manufactured by Wako Pure Chemical Industries, Ltd.
  • ⁇ -cyclodextrin ⁇ -cyclodextrin (special grade) manufactured by Wako Pure Chemical Industries, Ltd.
  • Isomalt-oligosaccharide Trade name “Panolap” manufactured by Hayashibara Co., Ltd.
  • Lactose fructose oligosaccharide Trade name “Lactose Oligo 700” manufactured by Hayashibara Co., Ltd.
  • Maltooligosaccharide Trade name “Tetrap” manufactured by Hayashibara Co., Ltd.
  • Raffinose oligosaccharides Trade name “Raffinose oligosaccharides” from Raw Materials.
  • Non-digestible cyclodextrin Trade name “Indigestible Cyclodextrin” of Raw Materials Co., Ltd.
  • Galactooligosaccharide Product name “Oligomate 55N” manufactured by Yakult Pharmaceutical Co., Ltd.
  • Xylooligosaccharide Product name “Xylooligosaccharide 70L” manufactured by Product Food Saens Co., Ltd.
  • Fructooligosaccharide Trade name “Mayoligo P (liquid)” manufactured by Meiji Food Materia Co., Ltd.
  • Phosphoric acid phosphoric acid (special grade) manufactured by Wako Pure Chemical Industries, Ltd.
  • Sulfuric acid Sulfuric acid (special grade) manufactured by Wako Pure Chemical Industries, Ltd.
  • Vitamin C L (+)-ascorbic acid (special grade) manufactured by Wako Pure Chemical Industries, Ltd.
  • Citric acid Citric acid monohydrate (special grade) manufactured by Wako Pure Chemical Industries, Ltd.
  • Lactic acid DL-lactic acid (special grade) manufactured by Wako Pure Chemical Industries, Ltd.
  • Tartaric acid D (-)-tartaric acid (first grade) manufactured by Wako Pure Chemical Industries, Ltd.
  • Gluconolactone Glucono- ⁇ -lactone manufactured by Wako Pure Chemical Industries, Ltd.
  • Lactopionic acid Lactopionic acid (first grade) manufactured by Wako Pure Chemical Industries, Ltd.
  • Aspartic acid DL-aspartic acid (special grade) manufactured by Wako Pure Chemical Industries, Ltd.
  • Sodium hydroxide Wako Pure Chemical Industries, Ltd. sodium hydroxide (special grade)
  • Examples 1 to 8 Propeller-type rotary stirring with hyaluronic acid (sodium hyaluronate), sugar (xylitol), phosphoric acid, and distilled water so that the composition of the water-soluble hyaluronic acid gel becomes the blending ratio (parts by mass) shown in Table 1
  • the mixture was mixed using an apparatus to prepare a hyaluronic acid aqueous solution.
  • the compounding quantity of distilled water was 200 mass parts with respect to 1 mass part of hyaluronic acid, respectively.
  • this aqueous solution is placed in a plastic petri dish (diameter 9 cm) to a uniform thickness and stored at 70 ° C.
  • the water content is calculated by measuring the weight of the water-soluble hyaluronic acid gel, and each of the water amounts in the gel shown in Table 1 is uniformly distributed on the surface of the water-soluble hyaluronic acid gel. It was applied and stored at room temperature for 24 hours to obtain a water-soluble hyaluronic acid gel sheet having a thickness of about 2 mm.
  • hyaluronic acid sodium hyaluronate
  • phosphoric acid phosphoric acid
  • distilled water for pH measurement
  • Table 1 A 200 mL hyaluronic acid aqueous solution for pH measurement containing 1 g of hyaluronic acid was obtained.
  • the pH of the obtained aqueous hyaluronic acid solution was measured using TwinpH (B-212) manufactured by Horiba, Ltd. The results are shown in Table 1.
  • Example 9 to 19 Propeller-type rotary stirring with hyaluronic acid (sodium hyaluronate), sugar (xylitol), phosphoric acid, and distilled water so that the composition of the water-soluble hyaluronic acid gel has the blending ratio (parts by mass) shown in Table 2
  • the mixture was mixed using an apparatus to prepare a hyaluronic acid aqueous solution.
  • the blending amount of distilled water was 200 parts by mass with respect to 1 part by mass of hyaluronic acid in Examples 9 to 18, and 300 parts by mass with respect to 1 part by mass of hyaluronic acid in Example 19.
  • this aqueous solution is placed in a plastic petri dish (diameter 9 cm) to a uniform thickness and stored at 70 ° C. for 12 to 24 hours, and most of the distilled water is evaporated to form a water-soluble hyaluronic acid gel.
  • a water-soluble hyaluronic acid gel Got.
  • each of the water amounts in the gel shown in Table 2 was uniformly distributed on the surface of this water-soluble hyaluronic acid gel. It was applied and stored at room temperature for 24 hours to obtain a water-soluble hyaluronic acid gel sheet having a thickness of about 2 mm.
  • Examples 20 to 31 and Comparative Examples 1 and 2 Propeller-type rotation of hyaluronic acid (sodium hyaluronate), sugar (sorbitol or xylitol), phosphoric acid, and distilled water so that the composition of the water-soluble hyaluronic acid gel becomes the blending ratio (parts by mass) shown in Table 3
  • a hyaluronic acid aqueous solution was prepared by mixing using a mold stirring device. At this time, the compounding quantity of distilled water was 200 mass parts with respect to 1 mass part of hyaluronic acid, respectively. Next, this aqueous solution is placed in a plastic petri dish (diameter 9 cm) to a uniform thickness and stored at 70 ° C.
  • the water content is calculated by measuring the weight of the water-soluble hyaluronic acid gel, and each of the water amounts in the gel shown in Table 3 is uniformly distributed on the surface of the water-soluble hyaluronic acid gel. It was applied and stored at room temperature for 24 hours to obtain a water-soluble hyaluronic acid gel sheet having a thickness of about 2 mm.
  • Examples 32 to 39 Mix the hyaluronic acid, sugar (xylitol), phosphoric acid, and distilled water using a propeller-type rotary stirrer so that the composition of the water-soluble hyaluronic acid gel has the blending ratio (parts by mass) shown in Table 4.
  • a hyaluronic acid aqueous solution was prepared. At this time, the compounding quantity of distilled water was 200 mass parts with respect to 1 mass part of hyaluronic acid, respectively. Next, this aqueous solution is placed in a plastic petri dish (diameter 9 cm) to a uniform thickness and stored at 70 ° C.
  • Example 40 to 63 In order for the composition of the water-soluble hyaluronic acid gel to have the blending ratio (parts by mass) shown in Table 5, hyaluronic acid (sodium hyaluronate), various sugars, phosphoric acid, and distilled water, a propeller-type rotary stirrer And mixed to prepare an aqueous solution of hyaluronic acid. At this time, the compounding quantity of distilled water was 200 mass parts with respect to 1 mass part of hyaluronic acid, respectively. Next, this aqueous solution is placed in a plastic petri dish (diameter 9 cm) to a uniform thickness and stored at 70 ° C.
  • Examples 64 to 95 In order for the composition of the water-soluble hyaluronic acid gel to have the blending ratio (parts by mass) shown in Table 6, hyaluronic acid (sodium hyaluronate), various sugars, phosphoric acid, and distilled water, And mixed to prepare an aqueous solution of hyaluronic acid. At this time, the compounding quantity of distilled water was 200 mass parts with respect to 1 mass part of hyaluronic acid, respectively. Next, this aqueous solution is placed in a plastic petri dish (diameter 9 cm) to a uniform thickness and stored at 70 ° C.
  • Examples 96 to 103 Mix the hyaluronic acid, sugar (xylitol), various acids, and distilled water using a propeller-type rotary stirrer so that the composition of the water-soluble hyaluronic acid gel has the blending ratio (parts by mass) shown in Table 7.
  • a hyaluronic acid aqueous solution was prepared. At this time, the compounding quantity of distilled water was 200 mass parts with respect to 1 mass part of hyaluronic acid, respectively. Next, this aqueous solution is placed in a plastic petri dish (diameter 9 cm) to a uniform thickness and stored at 70 ° C.
  • the water content is calculated by measuring the weight of the water-soluble hyaluronic acid gel, and each amount of distilled water to be the water content in the gel shown in Table 7 is uniformly applied to the surface of the water-soluble hyaluronic acid gel. It was applied and stored at room temperature for 24 hours to obtain a water-soluble hyaluronic acid gel sheet having a thickness of about 2 mm.
  • Example 65 As a result, in all four volunteers, by treating the water-soluble hyaluronic acid gel sheet obtained in Example 65, a clear skin moist feeling was confirmed as compared with the case of no treatment. Moreover, since the water-soluble hyaluronic acid gel sheet has appropriate elasticity and excellent shape maintenance, it is easy to handle and does not cause problems such as skin irritation.
  • Example 104 to 105 A mixed solution of xylitol, water in the gel (distilled water), and vitamin C was prepared so as to have the blending ratio (parts by mass) shown in Table 8, and placed in a plastic petri dish (diameter 9 cm). Hyaluronic acid was added to this aqueous solution, stirred with a spatula, and stored at room temperature for 48 hours to obtain a water-soluble hyaluronic acid gel sheet having a thickness of about 5 mm. Next, in the same manner as in Examples 1 to 8, the gel sheets obtained in Examples 104 to 105 were visually observed for 48 hours after being stored at 20 ° C. for 48 hours. 1 to 4 were evaluated. The results are shown in Table 8. Next, the properties of the gel sheets after the gel sheets obtained in Examples 104 to 105 were stored for 48 hours at 5 ° C. were evaluated according to the above criteria 1 to 4, respectively. The results are shown in Table 8.
  • the obtained water-soluble hyaluronic acid gel sheet of Example 104 was cut to about 2 cm ⁇ 2 cm and sampled by two volunteers. As a result, both two volunteers chewed while feeling an elastic texture like gummy, and the gel dissolved in the oral cavity over time.
  • the obtained water-soluble hyaluronic acid gel sheet of Example 105 was cut to about 2 cm ⁇ 2 cm and sampled by two volunteers. As a result, both volunteers felt a soft, moderately elastic texture similar to that of an oral nutritional supplement jelly and swallowed the throat as it was.
  • a propeller-type rotating type is prepared by mixing hyaluronic acid (sodium hyaluronate), various liquid oligosaccharides, phosphoric acid, and distilled water so that the composition of the water-soluble hyaluronic acid gel becomes the blending ratio (parts by mass) shown in Table 9.
  • the mixture was mixed using a stirrer to prepare a hyaluronic acid aqueous solution.
  • the compounding quantity of distilled water was 200 mass parts with respect to 1 mass part of hyaluronic acid, respectively.
  • this aqueous solution is placed in a plastic petri dish (diameter 9 cm) to a uniform thickness and stored at 70 ° C.

Abstract

La présente invention concerne un gel d'acide hyaluronique hydrosoluble qui est sous forme de gel très stable, même à basse température, tout en restant sensiblement exempt de tout composant gélifiant autre que l'acide hyaluronique et contenant un saccharide (à l'exclusion d'un polyol liquide étant liquide à 25 °C).<sp /> L'invention concerne un gel d'acide hyaluronique hydrosoluble comprenant de l'acide hyaluronique, un saccharide (à l'exclusion d'un polyol liquide étant liquide à 25 °C) et de l'eau, dans lequel : la teneur en humidité de celui-ci est supérieure à 30 % ; le gel d'acide hyaluronique hydrosoluble est sensiblement exempt de tout composant gélifiant autre que l'acide hyaluronique ; et la valeur de pH d'une solution aqueuse de celui-ci est dans la plage de 1,9 à 6,3, ladite valeur de pH étant mesurée selon le procédé suivant.<sp /> (Procédé de mesure de pH) Dans le gel d'acide hyaluronique hydrosoluble de l'invention en une quantité contenant 1 g d'acide hyaluronique, tous les constituants ioniques à l'exception de l'eau sont dissous dans l'eau et le volume est amené à 200 ml pour préparer ainsi une solution aqueuse. Ensuite, la valeur de pH de la solution aqueuse obtenue est mesurée.
PCT/JP2016/071331 2016-01-21 2016-07-21 Gel d'acide hyaluronique hydrosoluble et son procédé de production WO2017126143A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2017562422A JP6659052B2 (ja) 2016-01-21 2016-07-21 水溶性ヒアルロン酸ゲル及びその製造方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2016-009563 2016-01-21
JP2016009563 2016-01-21

Publications (1)

Publication Number Publication Date
WO2017126143A1 true WO2017126143A1 (fr) 2017-07-27

Family

ID=59362592

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2016/071331 WO2017126143A1 (fr) 2016-01-21 2016-07-21 Gel d'acide hyaluronique hydrosoluble et son procédé de production

Country Status (2)

Country Link
JP (1) JP6659052B2 (fr)
WO (1) WO2017126143A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6950999B1 (ja) * 2020-12-23 2021-10-20 株式会社リタファーマ グミ状可食性組成物及びその製造方法
US11298855B2 (en) 2017-03-07 2022-04-12 Jinwoo Bio Co., Ltd. Method for manufacturing hyaluronate film, and hyaluronate film manufactured thereby

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115068368B (zh) * 2022-06-30 2023-05-23 杭州求是医学科技有限公司 一种导光凝胶及其制备方法

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS61180705A (ja) * 1985-02-06 1986-08-13 Shiseido Co Ltd 皮膚外用組成物
JPH09227385A (ja) * 1996-02-29 1997-09-02 Ofutekusu:Kk 眼手術用補助剤
JP2000229837A (ja) * 1999-02-15 2000-08-22 Denki Kagaku Kogyo Kk 化粧料
JP2008280408A (ja) * 2007-05-09 2008-11-20 Keio Gijuku 球状ヒアルロン酸ゲル粒子の製造方法
WO2015002091A1 (fr) * 2013-07-03 2015-01-08 株式会社リタファーマ Gel d'acide hyaluronique hydrosoluble et procédé pour le produire
WO2015029892A1 (fr) * 2013-08-29 2015-03-05 大日精化工業株式会社 Procédé de fabrication d'un article moulé insoluble dans l'eau et article moulé insoluble dans l'eau

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000237294A (ja) * 1999-02-18 2000-09-05 Denki Kagaku Kogyo Kk ヒアルロン酸ゲルを含有する医用材料
JP2010043022A (ja) * 2008-08-12 2010-02-25 Kao Corp シート状化粧料
JP5305779B2 (ja) * 2008-08-19 2013-10-02 キユーピー株式会社 生野菜サラダの製造方法
RU2015133465A (ru) * 2013-01-11 2017-02-16 Карбилан Терапьютикс, Инк. Стабилизированные композиции, содержащие гиалуроновую кислоту

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS61180705A (ja) * 1985-02-06 1986-08-13 Shiseido Co Ltd 皮膚外用組成物
JPH09227385A (ja) * 1996-02-29 1997-09-02 Ofutekusu:Kk 眼手術用補助剤
JP2000229837A (ja) * 1999-02-15 2000-08-22 Denki Kagaku Kogyo Kk 化粧料
JP2008280408A (ja) * 2007-05-09 2008-11-20 Keio Gijuku 球状ヒアルロン酸ゲル粒子の製造方法
WO2015002091A1 (fr) * 2013-07-03 2015-01-08 株式会社リタファーマ Gel d'acide hyaluronique hydrosoluble et procédé pour le produire
WO2015029892A1 (fr) * 2013-08-29 2015-03-05 大日精化工業株式会社 Procédé de fabrication d'un article moulé insoluble dans l'eau et article moulé insoluble dans l'eau

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11298855B2 (en) 2017-03-07 2022-04-12 Jinwoo Bio Co., Ltd. Method for manufacturing hyaluronate film, and hyaluronate film manufactured thereby
JP6950999B1 (ja) * 2020-12-23 2021-10-20 株式会社リタファーマ グミ状可食性組成物及びその製造方法
WO2022138499A1 (fr) * 2020-12-23 2022-06-30 株式会社リタファーマ Composition comestible gluante et son procédé de production
JP2022099396A (ja) * 2020-12-23 2022-07-05 株式会社リタファーマ グミ状可食性組成物及びその製造方法

Also Published As

Publication number Publication date
JPWO2017126143A1 (ja) 2018-06-28
JP6659052B2 (ja) 2020-03-04

Similar Documents

Publication Publication Date Title
JP6598207B2 (ja) 水溶性ヒアルロン酸ゲル及びその製造方法
JP6519930B2 (ja) 水溶性ヒアルロン酸ゲル及びその製造方法
EP1663326B1 (fr) Mousse gelifiee a base de biopolymere
KR101342192B1 (ko) 콜라겐 산생 증강제와 그 용도
Muzzarelli et al. Chitin and chitosan hydrogels
KR20150070159A (ko) 히알루론산 겔 및 그의 제조 방법
Zhang et al. pH-sensitive alginate hydrogel for synergistic anti-infection
KR101032125B1 (ko) 알기네이트를 함유하는 다공성 성형품의 제조 방법
JP6659052B2 (ja) 水溶性ヒアルロン酸ゲル及びその製造方法
JP4203322B2 (ja) プルラン高含有成形物とその製造方法並びにその用途
CN104958241A (zh) 一种保湿中药面膜产品及其制备方法
JP6836820B1 (ja) 水溶性ヒアルロン酸ゲル及びその製造方法
JP5933178B2 (ja) キトサンカルボキシアルキルアミドのヒドロゲル、その調製方法、並びに、無水生成物、皮膚科組成物および美容用組成物
JP6659051B2 (ja) 水溶性ヒアルロン酸ゲル及びその製造方法
JP6478132B2 (ja) 水溶性ヒアルロン酸ゲル及びその製造方法
JP6512560B2 (ja) 水溶性ヒアルロン酸ゲル及びその製造方法
JP2012254940A (ja) キシログルカン含有組成物、キシログルカン含有貼付用シート及びキシログルカン含有ゲル成形体の製造方法
JP6950999B1 (ja) グミ状可食性組成物及びその製造方法
PL233874B1 (pl) Sposób wytwarzania chusteczek impregnowanych ekstraktem z korzenia jeżówki purpurowej

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16886383

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2017562422

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 16886383

Country of ref document: EP

Kind code of ref document: A1