WO2017085964A1 - Gel d'acide hyaluronique hydrosoluble et son procédé de production - Google Patents

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

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Publication number
WO2017085964A1
WO2017085964A1 PCT/JP2016/071330 JP2016071330W WO2017085964A1 WO 2017085964 A1 WO2017085964 A1 WO 2017085964A1 JP 2016071330 W JP2016071330 W JP 2016071330W WO 2017085964 A1 WO2017085964 A1 WO 2017085964A1
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Prior art keywords
hyaluronic acid
water
gel
acid gel
soluble
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PCT/JP2016/071330
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English (en)
Japanese (ja)
Inventor
邦夫 米戸
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株式会社リタファーマ
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Priority to JP2017551547A priority Critical patent/JP6659051B2/ja
Publication of WO2017085964A1 publication Critical patent/WO2017085964A1/fr

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    • 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 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 main object of the present invention is to provide a water-soluble hyaluronic acid gel having a gel form although it does not substantially contain gel-forming components other than hyaluronic acid. Furthermore, 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. .
  • hyaluronic acid sugar (however, excluding liquid polyhydric alcohol which is liquid at 25 ° C.) and water, the water content is 15 parts by mass or less with respect to 1 part by mass of hyaluronic acid. Therefore, hyaluronic acid is a gel-forming component in spite of substantially no gel-forming component other than hyaluronic acid (ie, hyaluronic acid is substantially contained alone as a gel-forming component). It was found that a water-soluble hyaluronic acid gel was formed.
  • such a water-soluble hyaluronic acid gel hardly forms a solid in the gel and can be suitably used as a cosmetic, a composition for medical devices, a food composition, a pharmaceutical composition, or the like.
  • a water-soluble hyaluronic acid gel is prepared by mixing hyaluronic acid, sugar (except liquid polyhydric alcohol that is liquid at 25 ° C.), and water, and a gel-forming component other than hyaluronic acid. It has also been found that it can be easily produced by a production method comprising a step of preparing an aqueous solution for gel formation without substantially mixing and a step of evaporating water contained in the aqueous solution for gel formation. 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 15 parts by mass or less with respect to 1 part by mass of the hyaluronic acid, A water-soluble hyaluronic acid gel substantially free of gel-forming components other than the hyaluronic acid.
  • Item 2. Item 2. The water-soluble hyaluronic acid gel according to Item 1, wherein the water content is 50 parts by mass or less with respect to 100 parts by mass of the sugar.
  • Item 3. Item 3.
  • Item 4. The water-soluble hyaluronic acid gel according to any one of Items 1 to 3, comprising 100 parts by mass or less of liquid polyhydric alcohol that is liquid at 25 ° C with respect to 100 parts by mass of the sugar.
  • Item 8. A pharmaceutical composition using the water-soluble hyaluronic acid gel according to any one of Items 1 to 7.
  • Item 8. A medical device composition using the water-soluble hyaluronic acid gel according to any one of Items 1 to 7. Item 12.
  • Item 15 A method for producing a water-soluble hyaluronic acid gel according to any one of Items 1 to 7, A gel-forming component other than hyaluronic acid is substantially mixed with an aqueous solution containing 50 parts by mass or less of water with respect to 100 parts by mass of the sugar (excluding liquid polyhydric alcohol that is liquid at 25 ° C.). Without manufacturing, the manufacturing method of water-soluble hyaluronic acid gel provided with the process of adding and dissolving a hyaluronic acid. Item 16. Item 16. The method for producing a water-soluble hyaluronic acid gel according to Item 15, further comprising a step of adding an additive after preparing the water-soluble hyaluronic acid gel.
  • a water-soluble hyaluronic acid gel having a gel form although it contains substantially no gel-forming component other than hyaluronic acid.
  • 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 (however, excluding liquid polyhydric alcohol which is liquid at 25 ° C.) and water, and the water content is 1 part by mass of hyaluronic acid. On the other hand, it is 15 parts by mass or less, and is characterized by substantially not including a gel-forming component other than hyaluronic acid.
  • 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, for example, by preparing a gel-forming aqueous solution containing hyaluronic acid, sugar, and water, and the water content in the water-soluble hyaluronic acid gel is 1 mass of the hyaluronic acid. It can manufacture by setting it as 15 mass parts or less with respect to a part.
  • 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 practically contained alone as a gel-forming component and is substantially free of other gel-forming components.
  • 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 viewpoint of providing the water-soluble hyaluronic acid gel with appropriate elasticity, high mechanical strength, and shape maintenance while suppressing the formation of solid sugars in the gel for example, about 0.4 to 50% by mass, Preferably about 0.6 to 30% by mass, more preferably about 0.9 to 10% by mass.
  • the gel When the content of hyaluronic acid in the water-soluble hyaluronic acid gel is less than 0.4% by mass, the gel may not be formed from the 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.
  • the gel is formed substantially without any gel-forming components other than hyaluronic acid, and the water-soluble hyaluronic acid gel is moderately formed while suppressing the formation of solid sugar in the gel.
  • 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 water-soluble hyaluronic acid gel is water-soluble while suppressing the formation of sugar solids in the gel even when stored at low temperature (for example, about 5 ° C).
  • Hyaluronic acid gel can be provided with moderate 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 content of sugar contained in the water-soluble hyaluronic acid gel is not particularly limited, but from the above viewpoint, it is preferably 1 part by mass or more and 200 parts by mass or less with respect to 1 part by mass of hyaluronic acid. More preferably, they are 1 mass part or more and 150 mass parts or less, More preferably, 5 mass parts or more and 100 mass parts or less are mentioned.
  • the sugar content means the total amount of all the sugars.
  • the content of water contained in the water-soluble hyaluronic acid gel of the present invention is 15 parts by mass or less with respect to 1 part by mass of hyaluronic acid. From the above viewpoint, the content of water contained in the water-soluble hyaluronic acid gel of the present invention is preferably 0.5 parts by mass or more and 15 parts by mass or less, more preferably 1 with respect to 1 part by mass of hyaluronic acid. The mass is 12 parts by mass or more.
  • content of the water contained in the water-soluble hyaluronic acid gel of this invention becomes like this.
  • it is 50 mass parts or less with respect to 100 mass parts of sugars, More preferably, it is 5 mass parts or more and 50 masses Part or less, more preferably 10 parts by weight or more and 40 parts by weight or less.
  • 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 may further contain an acid and / or a base different from hyaluronic acid.
  • the acid and base different from hyaluronic acid are not particularly limited as long as they are mixed with water and show acidity or alkalinity, and may be used alone or in combination of two or more. May be used.
  • the content of the acid and / or base is not particularly limited, but in the water-soluble hyaluronic acid gel of the present invention, the pH measured by the measurement method described below is preferably in the range of 2.0 to 12.0, more The range of 2.4 to 11.5 is preferable.
  • 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.
  • the water-soluble hyaluronic acid gel when it 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, and a granular shape such as a gummi can do.
  • 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.), and water are mixed, and And a method comprising preparing a gel-forming aqueous solution without substantially mixing gel-forming components other than hyaluronic acid and removing water contained in the gel-forming aqueous solution.
  • 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 amount of water in the aqueous solution for gel formation is such that the amount of water contained in the water-soluble hyaluronic acid gel can form a gel of 15 parts by mass or less with respect to 1 part by mass of hyaluronic acid by the water removal step. If there are, there is no particular limitation, and usually, for example, about 20 to 1000 parts by mass, preferably about 40 to 400 parts by mass, per 1 part by mass of hyaluronic acid. 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 was suitably controlled by performing a step of adding water after forming a water-soluble hyaluronic acid gel having a low water content by removing most of the water contained in the gel-forming aqueous solution.
  • a water-soluble hyaluronic acid gel can be produced.
  • a step of adding the above various components (additives) may be further provided.
  • the various components (additives) can be easily added.
  • 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. Further, even when an appropriate amount of water is required, such as an emulsion or nanoemulsion, the amount of water in the gel can be suitably controlled.
  • 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 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 is 50 mass parts or less with respect to 100 mass parts of saccharide
  • sugar however, except liquid polyhydric alcohol which is a liquid at 25 degreeC.
  • a method comprising a step of adding and dissolving hyaluronic acid in an aqueous solution without substantially mixing gel-forming components other than hyaluronic acid can be mentioned.
  • 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.
  • 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.
  • 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.
  • Glycerin Glycerin (special grade) manufactured by Wako Pure Chemical Industries, Ltd.
  • Diglycerin Diglycerin manufactured by Wako Pure Chemical Industries, Ltd.
  • Butanediol 1,3-butanediol (special grade) manufactured by Wako Pure Chemical Industries, Ltd.
  • Phosphoric acid phosphoric acid (special grade) manufactured by Wako Pure Chemical Industries, Ltd.
  • Sodium hydroxide Wako Pure Chemical Industries, Ltd. sodium hydroxide (special grade)
  • Examples 1 to 13 and Comparative Example 1 Using a propeller-type rotary stirrer, hyaluronic acid (sodium hyaluronate), sugar (xylitol), and distilled water are used so that the composition of the water-soluble hyaluronic acid gel is as shown in Table 1 (part by mass).
  • hyaluronic acid aqueous solution 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.
  • Example 14 to 19 Propeller-type rotary agitation of hyaluronic acid (sodium hyaluronate, hyaluronic acid), sugar (xylitol), 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 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.
  • Hyaluronic acid sodium hyaluronate
  • sugar xylitol
  • aqueous solutions of sodium hydroxide (1N in Examples 20 to 23) so that the composition of the water-soluble hyaluronic acid gel is as shown in Table 3 (parts by mass).
  • NaOH sodium hyaluronate
  • sugar xylitol
  • aqueous solutions of sodium hydroxide 1N in Examples 20 to 23
  • the composition of the water-soluble hyaluronic acid gel is as shown in Table 3 (parts by mass).
  • NaOH sodium hyaluronate
  • sugar xylitol
  • aqueous solutions of sodium hydroxide 1N in Examples 20 to 23
  • 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.
  • 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.
  • hyaluronic acid sodium hyaluronate
  • sodium hydroxide aqueous solution (1N NaOH) in Examples 20 to 23, and 10% in Examples 24 to 26 so that the mixing ratio (parts by mass) shown in Table 3 was obtained.
  • Phosphoric acid and distilled water were mixed using a propeller-type rotary stirrer to obtain 200 mL of a hyaluronic acid aqueous solution for pH measurement containing 1 g of hyaluronic acid.
  • 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 3.
  • Examples 27 to 44 Mix the hyaluronic acid (sodium hyaluronate), various sugars, 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 45 to 62 Mix the hyaluronic acid (sodium hyaluronate), various sugars, and distilled water using a propeller-type rotary stirrer so that the composition of the water-soluble hyaluronic acid gel is as shown in Table 5 (part by mass).
  • a hyaluronic acid aqueous solution was prepared.
  • 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.
  • Examples 63 to 80 Mix the hyaluronic acid (sodium hyaluronate), various sugars, 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 6.
  • 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.
  • Hyaluronic acid, various sugars, and distilled water are mixed 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.
  • 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. for 12 to 24 hours, and most of the distilled water is evaporated to form a water-soluble hyaluronic acid gel.
  • a plastic petri dish diameter 9 cm
  • 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.
  • this aqueous solution is placed in a plastic petri dish (diameter 9 cm) so as to have a uniform thickness and stored at 50 ° C. for 12 to 24 hours to evaporate most of the distilled water to a thickness of about 2 mm.
  • a water-soluble hyaluronic acid gel sheet was obtained.
  • the weight of the water-soluble hyaluronic acid gel was measured, and it was confirmed that it matched the total weight of the blended sodium hyaluronate, xylitol, and liquid polyhydric alcohol.
  • Example 6 ⁇ Storage test at low temperature>
  • the gel sheets obtained in Example 6, Example 27, Example 39, Example 41, and Example 43 were each stored at 5 ° C. for 12 hours, and the gel was observed.
  • the water-soluble hyaluronic acid gels of Example 6, Example 39, Example 41, and Example 43 were colorless and transparent gels, and no saccharide solids were observed in the gels.
  • the water-soluble hyaluronic acid gel of Example 27 was a hard sheet on which sugar crystals were precipitated.
  • Example 6 Example 9, Example 39, Example 40, Example 41, Example 42, Example 43, and Example 44 except that the thickness of the hyaluronic acid gel sheet was about 100 ⁇ m.
  • the obtained hyaluronic acid gel sheet (4 cm ⁇ 4 cm) was placed in 100 mL of a pH 7.4 phosphate buffer, and stirred at 37 ° C. with a stir bar at 120 rpm for 4 hours. As a result, all the hyaluronic acid gel sheets were completely dissolved, and it was confirmed that the hyaluronic acid gel sheets were water-soluble.
  • Example 55 ⁇ Moisturizing effect evaluation by sticking test of water-soluble hyaluronic acid gel sheet>
  • the water-soluble hyaluronic acid gel sheet (2 cm ⁇ 2 cm) of Example 55 was attached to the right forearm of four volunteers for 1 hour. Thereafter, about 10 mL of purified water was added little by little on the gel and dissolved while massaged for about 3 minutes, then washed with purified water and allowed to dry naturally. The moisture retention state of the skin of the left forearm portion of the same volunteer who was treated with this water-soluble hyaluronic acid gel sheet and the untreated left forearm portion was observed.
  • Example 100 to 114 Hyaluronic acid, liquid oligosaccharide, and distilled water were mixed using a propeller-type rotary stirrer so that the composition of the water-soluble hyaluronic acid gel would be the blending ratio (parts by mass) shown in Table 10.
  • An aqueous acid 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. for 12 to 24 hours, and most of the distilled water is evaporated to form a water-soluble hyaluronic acid gel.
  • a plastic petri dish diameter 9 cm
  • 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 10 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.

Abstract

La présente invention concerne un gel d'acide hyaluronique hydrosoluble qui est sous la forme d'un gel malgré le fait qu'il ne contient sensiblement pas de composant gélifiant autre que l'acide hyaluronique. Le gel d'acide hyaluronique hydrosoluble comprend de l'acide hyaluronique, un saccharide (à l'exclusion d'un polyol liquide existant sous la forme d'un liquide à 25 °C) et de l'eau, la teneur en eau étant de pas plus de 15 parties en poids par partie en poids d'acide hyaluronique, et il ne contient sensiblement aucun composant gélifiant autre que l'acide hyaluronique.<sp />
PCT/JP2016/071330 2015-11-17 2016-07-21 Gel d'acide hyaluronique hydrosoluble et son procédé de production WO2017085964A1 (fr)

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JPH09227385A (ja) * 1996-02-29 1997-09-02 Ofutekusu:Kk 眼手術用補助剤
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JP6836820B1 (ja) * 2019-06-26 2021-03-03 株式会社リタファーマ 水溶性ヒアルロン酸ゲル及びその製造方法

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