WO2015178147A1 - Feuille de fibroïne poreuse, feuille médicale, matériau de recouvrement de plaie, et procédé de production de feuille de fibroïne poreuse - Google Patents

Feuille de fibroïne poreuse, feuille médicale, matériau de recouvrement de plaie, et procédé de production de feuille de fibroïne poreuse Download PDF

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Publication number
WO2015178147A1
WO2015178147A1 PCT/JP2015/062024 JP2015062024W WO2015178147A1 WO 2015178147 A1 WO2015178147 A1 WO 2015178147A1 JP 2015062024 W JP2015062024 W JP 2015062024W WO 2015178147 A1 WO2015178147 A1 WO 2015178147A1
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Prior art keywords
fibroin porous
silk fibroin
sheet
porous sheet
thickness
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PCT/JP2015/062024
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English (en)
Japanese (ja)
Inventor
直祐 角
一稔 小林
松本　直子
努 川上
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日立化成株式会社
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Priority to JP2016521006A priority Critical patent/JP6551403B2/ja
Publication of WO2015178147A1 publication Critical patent/WO2015178147A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • 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
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/44—Medicaments
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
    • C08J9/28—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K5/00—Use of organic ingredients
    • C08K5/04—Oxygen-containing compounds
    • C08K5/05—Alcohols; Metal alcoholates
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L89/00—Compositions of proteins; Compositions of derivatives thereof

Definitions

  • the present invention relates to a fibroin porous sheet, a medical sheet, a wound dressing, and a method for producing a fibroin porous sheet.
  • Porous materials made using biological substances such as proteins and saccharides are used in cosmetics and esthetics for the purpose of moisturizing, etc. for use in esthetic salons or individuals; medical treatments such as wound dressings and drug sustained-release carriers Field: Daily necessities such as disposable diapers and sanitary products; Water purification field that can be used as a support for microorganisms, bacteria, etc .; Cell culture support (scaffolding materials) and tissue regeneration support in tissue engineering, regenerative medical engineering, etc. It can be used in a wide range of industries such as the body.
  • saccharides such as cellulose and chitin, and protein groups such as collagen, keratin, and silk fibroin are known.
  • fibroin particularly silk fibroin, is industrially utilized because it is excellent in stable supply of raw materials and price stability. Furthermore, it has a track record of being used for a long time as a surgical suture, in addition to clothing applications, and has recently been used as an additive for foods and cosmetics. Since silk fibroin has no problem with respect to safety to the human body, use in the field of utilization of porous materials is being studied.
  • Patent Document 1 a method in which a silk fibroin aqueous solution is rapidly frozen and then immersed in a crystallization solvent and melted and crystallized at the same time.
  • Patent Document 2 A method for producing a porous body (see Patent Document 2), adding a small amount of a water-soluble organic solvent to a silk fibroin aqueous solution, and then freezing and melting for a certain time to obtain a silk fibroin porous body Techniques (see Patent Document 3 and Non-Patent Document 1) are known.
  • Patent Document 5 there is a report that a porous material having a homogeneous structure excellent in water absorption can be obtained by using a porous material such as paper on the inner wall of the container using the technique of Patent Document 3 (Patent Document). 4). Furthermore, there is a report of an example of processing a silk fibroin porous body using a slicing apparatus (see Patent Document 5).
  • the porous body produced by the methods described in Patent Documents 1 to 3 has a non-porous film on the surface, there is room for improvement in the water absorption rate.
  • the porous body produced by the technique described in Patent Document 4 is formed on the surface although a part of the non-porous film formed on the surface of the porous body is peeled off by the porous material on the surface of the container.
  • the non-porous film cannot be completely removed, and the porous material on the surface of the container and the silk fibroin porous body are firmly fixed, so that the film is thin (for example, 2.5 mm or less, preferably thick).
  • Patent Document 5 describes an example in which the produced porous body is processed by a slicing apparatus.
  • the processing accuracy is poor in processing in a water-containing state, and the 25% compression hardness is 200 kPa to 800 kPa.
  • processing into a thin sheet for example, a thickness of 2.5 mm or less, preferably 1 mm or less
  • a sufficient water absorption speed and water retention are required even in the case of a thin sheet.
  • the present invention provides a thin fibroin porous sheet that has no non-porous coating over the entire surface of at least one surface of the sheet and is excellent in water absorption rate, water retention and adhesion, and a medical device using the fibroin porous sheet. It is an object of the present invention to provide a wound sheet, a wound dressing material using the fibroin porous sheet, and a method for producing the fibroin porous sheet.
  • the present invention relates to the following [1] to [16].
  • [1] A fibroin porous sheet having a 25% compression hardness of 200 kPa to 800 kPa and a thickness of 0.25 mm to 2.5 mm, in which at least one surface of the sheet does not have a non-porous coating over the entire surface.
  • [2] The fibroin porous sheet according to the above [1], having a thickness of 0.25 mm to 1 mm.
  • Positive thickness variation (%) ⁇ (maximum thickness (mm)) / (average thickness (mm)) ⁇ 100 ⁇ ⁇ 100 (1)
  • Negative thickness variation (%) 100 ⁇ ⁇ (minimum thickness (mm)) / (average thickness (mm) ⁇ 100 ⁇ (2)
  • [7] The fibroin porous sheet according to any one of the above [1] to [6], comprising a hydroxyl group-containing compound.
  • [8] The fibroin porous sheet according to the above [7], wherein the hydroxyl group-containing compound is glycerin.
  • a method for producing a fibroin porous sheet comprising compressing a dry fibroin porous material having a 25% compression hardness of 200 kPa to 800 kPa at a compression rate of 7% to 40% and slicing with a band saw.
  • the porous sheet according to the present invention is a thin sheet having a thickness of 0.25 mm to 2.5 mm, which is difficult to produce despite being flexible with a 25% compression hardness of 200 kPa to 800 kPa. And at least one surface of a sheet does not have a non-porous film over the whole surface. Therefore, although it is thin, it is excellent in water absorption speed and water retention, and is excellent in adhesion. Furthermore, the porous sheet according to the present invention includes those having excellent transparency at the time of water absorption.
  • the fibroin porous sheet according to the present invention has a non-porous coating on at least one surface of the sheet, a 25% compression hardness of 200 kPa to 800 kPa, and a thickness of 0.25 mm to 2.5 mm. It is a fibroin porous sheet. It is preferable that both surfaces of the sheet, that is, both the front surface and the back surface do not have a non-porous film over the entire surface.
  • “there is no non-porous coating over the entire surface” means a state in which pores exist in any section when the surface of interest is divided into 25 cm vertically and horizontally at an arbitrary length of 5 cm ⁇ 5 cm. .
  • the sheet Since at least one surface of the sheet does not have a non-porous film over the entire surface, the water absorption speed and moisture retention are excellent, and since the thickness is as thin as 0.25 to 2.5 mm, the adhesion is excellent. In particular, when the thickness is 1 mm or less, the transparency at the time of water absorption is excellent. In addition, since it becomes difficult to process by giving flexibility by setting the 25% compression hardness to 800 kPa or less, it is usually difficult to make the thickness 2.5 mm or less. I am letting.
  • the fibroin porous body has a non-porous coating on the entire surface thereof, but as described above, the fibroin porous sheet of the present invention does not have a non-porous coating on the entire surface of at least one of the sheets.
  • the method for producing the fibroin porous sheet of the present invention will be described in detail later. For example, it can be obtained by processing a dry fibroin porous material containing a hydroxyl group-containing compound.
  • the thickness of the fibroin porous sheet of the present invention is 0.25 mm to 2.5 mm. If the thickness of the sheet is 0.25 mm or more, the silk fibroin porous sheet has sufficient strength and can be handled and processed. On the other hand, if the sheet thickness is 2.5 mm or less, the adhesiveness is excellent, and if it is 1 mm or less, the transparency at the time of water absorption is also excellent. From the same viewpoint, the thickness of the fibroin porous sheet is preferably 0.25 mm to 2.0 mm, more preferably 0.25 mm to 1 mm, and further preferably 0.4 mm to 0.8 mm.
  • the pore area ratio is preferably 60% to 99%, more preferably 80% to 99%, and still more preferably 85% to 98. %.
  • the pore area ratio is 60% or more, the water absorption rate, water retention and adhesion tend to be sufficient, and when it is 99% or less, sufficient water retention tends to be maintained.
  • the area ratio is measured by subjecting a scanning electron micrograph to image processing using image analysis software ImageJ (manufactured by National Institutes of Health, USA).
  • the pore size (average pore diameter) of the fibroin porous sheet is preferably 1 ⁇ m to 300 ⁇ m, more preferably 5 ⁇ m to 200 ⁇ m, still more preferably 10 ⁇ m to 100 ⁇ m, and particularly preferably 15 ⁇ m to 50 ⁇ m.
  • the porosity is preferably 80% or more, more preferably 90% or more, and further preferably 95% or more.
  • the porosity is a value obtained as follows. First, the obtained porous body is left in pure water for 1 day to completely absorb water, weighed (wet mass), freeze-dried to completely remove water in the porous body, and weighed again. (Dry mass).
  • the area of the fibroin porous sheet of the present invention can be appropriately determined according to the application, and is not particularly limited, but is preferably 15 cm 2 to 1200 cm 2 . Within this range, it is easy to use for each application such as face mask, eye mask, wound dressing and the like. From the above viewpoint, the area of the fibroin porous sheet is more preferably 15 cm 2 to 1000 cm 2 . It should be noted that processing a thin fibroin porous sheet of such a size as 0.25 mm to 2.5 mm while suppressing the variation in thickness is difficult to process the fibroin porous material in a normal manner. This is difficult and has been achieved for the first time by processing by the method described in detail later.
  • the positive thickness variation and the negative thickness variation of the fibroin porous sheet of the present invention are both preferably within 15%, and more preferably within 10%.
  • the thickness variation is determined by the following method. (Thickness variation) As shown in FIG. 5, the thickness of 12 points of the sheet was measured, and the thickness variation was calculated from the maximum value, the minimum value, and the average value according to the following equation.
  • Positive thickness variation (%) ⁇ (maximum thickness (mm)) / (average thickness (mm)) ⁇ 100 ⁇ ⁇ 100 (1)
  • Negative thickness variation (%) 100 ⁇ ⁇ (minimum thickness (mm)) / (average thickness (mm) ⁇ 100 ⁇ (2)
  • These thickness variations are preferably as small as possible, but in particular if they are 15% or less, there is an advantage that the thinned portion during processing is not easily broken. In addition, there is an advantage that adhesion at a thick portion is difficult to be lowered and is not easily peeled off during mounting. From the above viewpoint, the thickness variation is more preferably 10% or less.
  • the lower limit of the thickness variation is preferably as small as described above, but is about 1% in manufacturing.
  • the fibroin porous sheet of the present invention preferably contains a hydroxyl group-containing compound.
  • a hydroxyl group-containing compound By containing the hydroxyl group-containing compound in the manufacturing process of the fibroin porous sheet described in detail later, while suppressing the occurrence of cracks due to freeze-drying, to suppress a crack during processing by giving a certain degree of flexibility, In addition, a sheet having a 25% compression hardness of 200 kPa to 800 kPa can be obtained.
  • the hydroxyl group-containing compound may be one having one or more hydroxyl groups per molecule, preferably one having 1 to 10 hydroxyl groups per molecule, more preferably one having 1 to 4 hydroxyl groups per molecule. Those having 2 to 4 hydroxyl groups per molecule are more preferred.
  • the molecular weight of the hydroxyl group-containing compound is preferably 1000 or less, more preferably 800 or less, more preferably 500 or less, further preferably 200 or less, and particularly preferably 150 or less. preferable.
  • the lower limit of the molecular weight of the hydroxyl group-containing compound is not particularly limited, but is preferably 30 or more, more preferably 50 or more, and further preferably 70 or more.
  • the hydroxyl group-containing compound examples include glycerin, polyglycerin, polyethylene glycol, triethyl citrate, lactic acid, polyvinyl alcohol, propylene glycol, butylene glycol, alcohol, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, and the like.
  • 1 type can be used independently or 2 or more types can be used together.
  • glycerin, polyethylene glycol, triethyl citrate, polyglycerin, lactic acid, propylene glycol, and butylene glycol are preferred from the viewpoints of handling properties, slice processability, and safety.
  • glycerin has an effect of moisturizing the skin, it is more preferable in applications where it is applied to the skin such as skin care materials and wound dressings.
  • the color difference of the fibroin porous sheet of the present invention is not particularly limited, but the color difference is preferably 0.50 to 7.94.
  • the color difference is a value obtained by the measurement method described in the examples. If the color difference is 0.50 or more, it is advantageous in that the sheet can be easily seen, and if the color difference is 7.94 or less, the color change is small when applied to the skin, so that the face, arms or legs It is advantageous in that it can easily relieve a sense of incongruity when it is attached to the like. From the above viewpoint, the color difference of the fibroin porous sheet is more preferably 0.5 to 5.0, and further preferably 0.8 to 5.0.
  • the color difference per unit thickness is not particularly limited, but is preferably 2.1 / mm to 7.8 / mm. If the color difference per unit thickness is 2.1 / mm or more, it is advantageous in that the sheet is easily visible, and if it is 7.8 / mm or less, the color change is small when applied to the skin. It is advantageous in that it is easy to relieve a sense of discomfort when worn on the face, arms or feet. From the above viewpoint, the color difference per unit thickness is more preferably 2.1 / mm to 5.0 / mm, and further preferably 2.5 / mm to 5.0 / mm.
  • the fibroin constituting the fibroin porous sheet of the present invention is preferably silk fibroin from the viewpoint of obtaining excellent water absorption rate, excellent water retention, flexibility, texture and the like.
  • the fibroin porous sheet of the present invention can be obtained by processing a fibroin porous material. Specifically, a dry fibroin porous material having a 25% compression hardness of 200 kPa to 800 kPa is compressed at a compression rate of 7% to 40% and sliced with a band saw.
  • a fibroin porous sheet is demonstrated in detail.
  • the fibroin porous body is not particularly limited as long as it is a porous body composed of fibroin. From the viewpoint of obtaining excellent water absorption speed, excellent water retention, flexibility, texture, etc., it is a silk fibroin porous body. Preferably there is.
  • the fibroin porous material is obtained by, for example, freezing a fibroin aqueous solution in which additives such as carboxylic acids, amino acids, and water-soluble liquid organic substances are added to a fibroin aqueous solution to obtain a frozen material, and then frozen water in the frozen material. A technique obtained by melting is used. According to this technique, a fibroin porous body excellent in shape stability and strength tends to be obtained.
  • fibroin examples include silk fibroin produced from natural silkworms such as rabbits, wild silkworms, and tengu, and transgenic silkworms. In consideration of the simplicity of the production process, silk fibroin obtained from rabbit cocoons is preferred. Hereinafter, silk fibroin will be described as an example, but the present invention is not limited thereto.
  • the silk fibroin used as a raw material for the silk fibroin porous material may be any one as long as it is produced from silkworms such as rabbits, wild silkworms, and tengu, as described above, and the production method thereof is not limited.
  • the silk fibroin porous material is obtained from a silk fibroin solution, but when dissolved in water, silk fibroin has low solubility in water and is difficult to directly dissolve in water.
  • any known method may be used, but a method in which silk fibroin is dissolved in a high concentration lithium bromide aqueous solution, followed by desalting by dialysis and concentration by air drying is simple.
  • the silk fibroin porous material used in the present invention may be produced by any method, but due to reproducibility and high strength of the obtained porous material, a specific additive is added to the silk fibroin aqueous solution to obtain the aqueous solution. It is preferred to produce by freezing and then thawing.
  • the concentration of silk fibroin is preferably 1 to 10% by mass / volume%, more preferably 1.5 to 8% by mass / volume in the silk fibroin solution. More preferably, it is 0.0 to 6 mass / volume%. By setting within this range, it is possible to efficiently produce a silk fibroin porous body that has sufficient strength and is difficult to break during slicing.
  • additives examples include carboxylic acids, amino acids, water-soluble liquid organic substances, and the like. These additives can be used individually by 1 type, or can also use 2 or more types together.
  • the carboxylic acids are not particularly limited as long as they are organic acids having at least one carboxy group in the molecule, and examples thereof include monocarboxylic acids, dicarboxylic acids, and tricarboxylic acids.
  • the pKa is preferably 5.0 or less, more preferably 3.0 to 5.0, and even more preferably 3.5 to 5.0.
  • the carboxylic acids aliphatic carboxylic acids are preferable. For example, saturated or unsaturated monocarboxylic acids, dicarboxylic acids, and tricarboxylic acids having 1 to 6 carbon atoms can be preferably used.
  • aliphatic carboxylic acids can be used individually by 1 type, or can use 2 or more types together.
  • acetic acid, lactic acid, and succinic acid are more preferable, and acetic acid is more preferable.
  • the amino acid is not particularly limited, and examples thereof include monoaminocarboxylic acids such as valine, leucine, isoleucine, glycine, alanine, serine, threonine, and methionine; monoaminodicarboxylic acids (acidic amino acids) such as aspartic acid and glutamic acid. Aliphatic amino acids are mentioned. In addition, aromatic amino acids such as phenylalanine and amino acids having a heterocyclic ring such as hydroxyproline are also included. Among these, acidic amino acids and oxyamino acids such as hydroxyproline, serine and threonine are preferable from the viewpoint of ease of shape adjustment.
  • monoaminodicarboxylic acid is more preferable among acidic amino acids, aspartic acid and glutamic acid are particularly preferable, and hydroxyproline is more preferable among oxyamino acids.
  • amino acids can be used alone or in combination of two or more.
  • Amino acids include L-type and D-type optical isomers, but when L-type and D-type are used, there is no difference in the resulting porous material. Good.
  • the water-soluble liquid organic substance is liquid at room temperature (20 ° C.) and dissolves or mixes without separation when mixed with water at room temperature (20 ° C.).
  • water-soluble liquid organic substances include alcohols such as methanol, ethanol, isopropanol, and butanol; polyhydric alcohols such as glycerin and propylene glycol; dimethyl sulfoxide (DMSO); dimethylformamide (DMF); pyridine; acetone; Etc. are preferred. These can be used individually by 1 type or can use 2 or more types together. Among these, it is preferable to use ethanol, dimethyl sulfoxide, glycerin, and acetone from the viewpoint of safety to the human body.
  • the content of the additive is preferably 0.1 to 18% by volume, more preferably 0.1 to 5.0% by volume, More preferably, it is 4.0 volume%. By setting within this range, it tends to be easy to manufacture a porous body having sufficient strength.
  • the amino acid content is preferably 1 to 500 parts by mass, more preferably 5 to 50 parts by mass, and further preferably 10 to 30 parts by mass with respect to 100 parts by mass of silk fibroin. preferable.
  • the silk fibroin porous material to which the additive is added can be produced by pouring the silk fibroin solution to which the additive has been added into a mold or a container, freezing it in a low-temperature thermostatic bath, and then thawing it. it can.
  • the freezing temperature is not particularly limited as long as the silk fibroin solution containing the additive is frozen, but is preferably ⁇ 30 ° C. to ⁇ 10 ° C., more preferably ⁇ 25 ° C. to ⁇ 15 ° C.
  • the freezing time is preferably 4 hours or more at a predetermined freezing temperature so that it can be sufficiently frozen and kept in a frozen state for a certain time.
  • the silk fibroin solution may be frozen to a freezing temperature all at once, but once it is kept at about ⁇ 5 ° C. for about 2 hours to be in a supercooled state and then lowered to the freezing temperature. Freezing is preferable for obtaining a porous body having high mechanical strength.
  • the structure and strength of the porous body can be controlled to some extent by adjusting the time taken from ⁇ 5 ° C. to the freezing temperature. Thereafter, the silk fibroin porous material is obtained by thawing the frozen silk fibroin solution.
  • the melting method is not particularly limited, and examples include natural melting and a method of holding in a thermostatic bath.
  • the silk fibroin porous material thus obtained contains additives, but if it is necessary to remove the additives depending on the application, the additives are removed from the silk fibroin porous material by an appropriate method.
  • the simplest method is to remove the additive by immersing the silk fibroin porous material in pure water or ultrapure water.
  • the silk fibroin porous body has a sponge-like porous structure. Normally, this silk fibroin porous body contains water unless it is removed by drying, and is a flexible structure in a water-containing state. is there. On the other hand, a dried silk fibroin porous material can be obtained by drying the silk fibroin porous material.
  • freeze-drying is preferable. In the case of freeze-drying, if the drying is completed without completely sublimating the water, the pores are crushed due to the surface tension of the remaining water. Therefore, it is preferable to dry until the water is completely sublimated.
  • the silk fibroin porous material contains the hydroxyl group-containing compound before the lyophilization.
  • the hydroxyl group-containing compound By containing the hydroxyl group-containing compound, cracking due to freeze-drying is suppressed, cracking during processing is suppressed by giving a certain degree of flexibility, and 25% compression hardness is 200 kPa to 800 kPa.
  • a flexible sheet can be obtained.
  • a silk fibroin porous material having a hardness suitable for slicing can be obtained by drying by the above method.
  • the processing accuracy tends to be low because it is too soft during processing, and when the silk fibroin porous body is pressed against the slicing blade, the water inside the silk fibroin porous body is squeezed out. This tends to make it difficult to process.
  • the silk fibroin porous sheet wet with water or a cosmetic liquid it can be easily wetted by being immersed in water or a cosmetic liquid after processing.
  • the method for containing the hydroxyl group-containing compound in the silk fibroin porous body is not particularly limited, and when the silk fibroin porous body is produced, the method of blending it into the silk fibroin solution, You may make it soak in the solution containing the hydroxyl-containing compound of the grade which immerses.
  • the immersion time is not particularly limited, if the immersion time is short, the amount of the hydroxyl group-containing compound introduced into the silk fibroin porous material is small, or the concentration varies depending on the place in the silk fibroin porous material. Problems can occur.
  • the content of the hydroxyl group-containing compound is preferably 20 to 60% by mass, more preferably 25 to 50% by mass, and 25 to 45% by mass. More preferably.
  • concentration of the hydroxyl group-containing compound within the above range, a silk fibroin porous material excellent in flexibility, workability, and handling properties tends to be easily obtained. More specifically, when it is 20% by mass or more, it is excellent in flexibility, is not easily cracked when dried, does not become brittle, is not easily cracked during slicing, and excellent handling properties tend to be obtained.
  • the hardness of the porous material obtained can be adjusted by changing a hydroxyl-containing compound density
  • the silk fibroin porous material can be made into a shape according to the purpose, such as a film shape, a sheet shape, a block shape, a tubular shape, a spherical shape, etc., by appropriately selecting a mold and a container for producing the silk fibroin porous material.
  • a sheet-like material having no irregularities.
  • the shape or container of the silk fibroin solution so long as it does not flow out.
  • the material is iron, stainless steel, aluminum, gold, or the like. It is preferable to use a material having high thermal conductivity such as silver, copper and the like.
  • the thickness of the mold and the wall of the container is preferably 0.5 mm or more from the viewpoint of its function and deformation due to expansion during freezing, etc., and it is easy to handle and has cooling efficiency. From the viewpoint, it is more preferably 1 to 3 mm.
  • type and container used here can provide a mold release layer in the inner wall surface in contact with the silk fibroin solution inside for the purpose of prevention of adhesion
  • a sheet made of a fluororesin such as polytetrafluoroethylene (PTFE), tetrafluoroethylene-hexafluoropropylene copolymer (FEP), tetrafluoroethylene-perfluoroalkyl vinyl ether copolymer (PFA);
  • PTFE polytetrafluoroethylene
  • FEP tetrafluoroethylene-hexafluoropropylene copolymer
  • PFA tetrafluoroethylene-perfluoroalkyl vinyl ether copolymer
  • Preferable examples include a release-treated sheet made of polyethylene terephthalate (PET), polypropylene (PP) or the like; a coating made of a fluororesin such as PTFE, FEP
  • the silk fibroin porous material can be easily taken out from the container.
  • the thickness of the release layer is preferably 1000 ⁇ m or less, more preferably 500 ⁇ m or less, and even more preferably 200 ⁇ m or less, from the point that heat conduction is hardly inhibited.
  • the silk fibroin porous sheet can be obtained by slicing the silk fibroin porous body following the drying step described above.
  • a slicing method used for manufacturing the fibroin porous sheet of the present invention for example, as shown in FIG. 1, a silk fibroin porous material sandwiched between upper and lower rolls is sliced against a band saw, FIG.
  • Fig. 4 there is a method of slicing by fixing the fibroin porous body with a suction chuck or a frictional force and moving the blade in the horizontal direction.
  • the fibroin porous sheet excellent in the transparency at the time of water absorption is obtained by making thickness into 1.0 mm or less. Further, in the slicing process, it is preferable from the viewpoint of water absorption speed and transparency to excise a non-porous film formed on at least one surface, preferably the entire surface, of the silk fibroin porous body.
  • the device for slicing the silk fibroin porous material sandwiched between the upper and lower rolls shown in FIG. 1 to the band saw has a band saw rotating between the upper and lower rolls whose vertical position can be adjusted.
  • the transported silk fibroin porous material is fed between upper and lower rolls, pressed against a rotating band saw, and cut to obtain a fibroin porous sheet.
  • This apparatus can obtain a fibroin porous sheet having an arbitrary thickness by adjusting the positions of the upper and lower rolls.
  • by setting the preferred compression ratio and the height distance between the upper roll and the band saw it is possible to obtain a fibroin porous sheet that is thin, excellent in adhesion and in some cases transparency at the time of water absorption, with high thickness accuracy. it can.
  • the positive thickness variation and the negative thickness variation of the silk fibroin porous sheet are each preferably 15% or less, and more preferably 10% or less.
  • a silk fibroin porous material having a preferable hardness and slicing it by setting a preferable compression ratio and a height distance between the upper roll and the band saw such a silk fibroin porous sheet having a small thickness variation can be obtained. can get.
  • the compression rate and the height distance between the upper roll and the band saw are defined as shown in FIGS. 3 and 4, respectively.
  • the compression ratio is (AB) / A when the thickness of the silk fibroin porous sheet is “A” and the distance between the upper roll and the lower roll is “B”. Multiply by 100. ] (See FIG.
  • the height distance between the upper roll and the band saw is defined as the distance from the intersection of the straight line indicating the shortest distance between the upper roll and the lower roll and the extension line of the tip of the band saw blade to the upper roll (see FIG. 4). ).
  • the hardness of the silk fibroin porous material to be subjected to slicing is such that the 25% compression hardness is 200 kPa to 800 kPa, preferably 250 kPa to 800 kPa, and more preferably 300 kPa to 600 kPa.
  • the 25% compression hardness is 200 kPa or more, the processing accuracy is improved, and slice processing to a thickness of 2.5 mm or less is facilitated.
  • the 25% compression hardness is 800 kPa or less, the porous body can be prevented from cracking during slicing, and sufficient flexibility can be obtained.
  • the 25% compression hardness of the silk fibroin porous sheet obtained by slicing a silk fibroin porous body having a 25% compression hardness in the above range is composed of the same porous body, The value is equivalent to the above.
  • the thickness of the silk fibroin porous material to be sliced is not particularly limited, but is preferably 1 mm to 50 mm, more preferably 2 mm to 40 mm, and further preferably 2.5 mm to 20 mm.
  • a porous body having a thickness in this range it can be processed with high accuracy.
  • limiting in particular in the shape of the silk fibroin porous body provided to a slicing process When it is the objective to obtain a silk fibroin porous sheet, it is preferable that it is a shape which has two flat sides. Specifically, a rectangular parallelepiped, a cube, a cylinder, a triangular prism, etc. are mentioned.
  • the compression rate in slicing is 7 to 40%, preferably 10 to 40%, more preferably 10 to 30%.
  • the compression rate is calculated from the thickness of the silk fibroin porous body before slicing and the set distance between the upper and lower rolls of the slicing machine as shown in the following equation.
  • Compression rate ⁇ (silk fibroin porous body thickness ⁇ distance between upper and lower rolls) / silk fibroin porous body thickness ⁇ ⁇ 100
  • the silk fibroin porous body when the silk fibroin porous body is compressed at a compression rate of less than 7%, the upper and lower rolls cannot be sandwiched between the silk fibroin porous body, and the silk fibroin porous body that hits the band saw flows in the rotation direction of the band saw. Therefore, it cannot be sliced.
  • the compressibility And slicing with the above-mentioned band source slicer with the distance between the upper roll and the band saw adjusted as appropriate has a thin thickness of 0.2 to 2.5 mm and a non-porous coating on at least one surface. It became possible to process into a silk fibroin porous sheet without it. Also, variation in thickness within the sheet is minimized by using a dry silk fibroin porous material with appropriate hardness, and setting the compression rate and the distance between the upper roll and the band saw to appropriate values. can do.
  • the height distance between the upper roll and the band saw is preferably 0.2 mm to 1.0 mm, and more preferably 0.2 mm to 0.9 mm. By setting within this range, a thin sheet can be sliced with low thickness variation.
  • the thickness to be excised is not particularly limited as long as the non-porous film can be removed, but it is 0.1 mm to 2 mm. Is preferably 0.2 mm to 1.5 mm, and more preferably 0.3 mm to 1 mm.
  • a silk fibroin porous body has a non-porous film on the entire surface thereof, but it is not necessary to remove the non-porous film by slicing all of the non-porous film. For example, after slicing two opposite faces of a rectangular parallelepiped and removing the non-porous film, the entire surface of the non-porous film is removed by further punching or manual cutting. A fibroin porous sheet can also be obtained. However, since it is difficult to punch or manually process a wide surface with high processing accuracy, it is preferable to perform the slicing when removing a non-porous film having an area of at least 20 cm 2 or more.
  • a slicing process may be performed after a punching process and vice versa.
  • a method of a punching process For example, the punching by the hand press which uses a Thomson blade, or a hydraulic press is mentioned.
  • the non-porous coating is cut from the entire surface of a single silk fibroin porous material to obtain a single silk fibroin porous sheet.
  • a manufacturing method can be used.
  • 10 mm-thick rectangular parallelepiped silk fibroin porous bodies are sliced 1 mm each, and after removing the non-porous film, the remaining two-sided non-porous film is removed and the 8 mm-thick rectangular parallelepiped is removed.
  • 8 sheets of 1 mm thick silk fibroin porous sheet having no non-porous coating on the two opposite faces are obtained by slicing a 1 mm silk fibroin porous sheet 7 times from the silk fibroin porous body of
  • a method of obtaining eight 1 mm thick silk fibroin porous sheets having no non-porous film on the entire surface by punching with a Thomson blade or the like from the surface from which the non-porous film has been removed may be mentioned.
  • slicing may be performed one by one in order from the top.
  • slice processing may be performed alternately.
  • a silk fibroin porous sheet has a non-porous film on both sides thereof, but a silk fibroin porous sheet characterized by having no non-porous film on both surfaces of the sheet by slicing as described above. Obtainable. Moreover, the silk fibroin porous sheet from which the non-porous film of the whole surface was removed can be obtained by performing a punching process further. Also, a wet porous body is usually too flexible to be processed into a thin sheet, but if it is a dry silk fibroin porous body containing a hydroxyl group-containing compound, the thickness can be increased by slicing. Processing into a thin sheet of 0.25 mm to 2.5 mm becomes possible.
  • such a thin sheet particularly a sheet having a thickness of 1 mm or less
  • a thin sheet can be suitably used for applications in which transparency at the time of water absorption is high and transparency can be utilized.
  • skin care material applications such as face masks and eye masks and medical applications such as wound dressings
  • the sheet does not stand out when worn and there is no sense of incongruity.
  • the fibroin porous sheet of the present invention is thin as described above, it is flexible, easily follows a wound part, and is easy to use on a curved surface having a high curvature such as a fingertip part.
  • the non-porous film which existed on both surfaces of the fibroin porous body is removed by processing, the pores are exposed despite being thin.
  • this invention also provides the medical sheet
  • the present invention also provides a wound dressing using the fibroin porous sheet of the present invention.
  • the medical sheet and wound dressing of the present invention are made using the fibroin porous sheet of the present invention.
  • a fibroin porous sheet as a wound dressing, in addition to alleviating pain by sticking to the wound part, it absorbs exudate that exudes from the wound and holds it on the wound surface and is contained in the exudate It is also desirable to have water retention so that it can be used for wet therapy to heal wounds by actively utilizing the ingredients.
  • the fibroin porous sheet of the present invention is excellent in adhesion, without impairing the merits of texture such as flexibility and touch, and also excellent in water absorption speed and water retention.
  • the medical sheet and wound dressing of the present invention alleviate the pain caused by being applied to the wound part, absorb the exudate exuding from the wound or the like and hold it in the wound part, and the exudate It is excellent in the characteristics that can actively utilize the components contained in it, and the characteristics that can be used in moving parts such as arms and elbows, and can be suitably used in wet therapy.
  • the medical sheet and wound dressing of the present invention can contain a drug by taking advantage of its excellent water absorption rate.
  • a drug By including a drug, the medical sheet and wound dressing of the present invention can be given a function of promoting wound healing.
  • a drug such as a bactericide, antibiotic, or physiologically active substance may be impregnated or applied to the medical sheet or wound dressing of the present invention.
  • These drugs can be used alone or in combination of two or more.
  • the medical sheet and wound dressing of the present invention can be configured such that the fibroin porous sheet of the present invention is fixed with a dressing film, bandage, adhesive tape or the like. Since the fibroin porous sheet is soft even in a dry state, it can be used as it is as a medical sheet and a wound dressing, or it can be used as a medical sheet and a wound dressing containing a moisturizing agent.
  • the humectant include glycerin, polyvinyl pyrrolidone, polyvinyl alcohol, and polyethylene glycol. In the case of a medical sheet or wound dressing containing a moisturizing agent, keep the medical sheet or wound dressing in a sealed state and keep it dry until just before use. Is preferred.
  • the medical sheet and wound dressing of the present invention are preferably composed only of the fibroin porous sheet of the present invention, and the porous layer composed of the fibroin porous sheet of the present invention and a fine layer on one surface. It is also preferable that it consists of a film layer which does not have a hole. As its usage, it is preferable that a porous layer (a surface not having a non-porous film) is in contact with the wound surface and a film layer is formed on the opposite surface opposite to the wound surface. This is because, when such a wound dressing is applied to wet therapy, exudate from the wound surface can be absorbed and retained, and there is an effect of suppressing evaporation and diffusion of the exudate.
  • a drug in the porous layer it is possible to have a function of promoting wound healing.
  • healing can be promoted by impregnating or applying a bactericidal agent, antibiotics, physiologically active substance, or the like to the porous layer.
  • antibiotics antibiotics
  • physiologically active substance or the like
  • these drugs can be used alone or in combination of two or more.
  • the number of pores of the film layer can be controlled, and a film layer having a small amount of pores can be formed as necessary.
  • the film layer since the film layer has very few pores, the surface is smooth. Therefore, by using the film layer as the wound surface side, it is possible to give a function of preventing adhesion and to control the liquid permeability of the film layer to control the drug release rate.
  • the wound dressing material of the present invention is composed of the porous layer and a film layer having no pores on both sides, the rate of absorbing exudate from the wound surface as described above may be reduced. However, it has a function of suppressing evaporation of exudate and a function of preventing adhesion to the wound surface, which is useful. Further, when the wound dressing of the present invention is composed of only a porous layer, it is assumed that exudate from the wound surface passes through the porous layer and exudes to the opposite side. Since the porous material itself has sufficient water retention, the covering material sufficiently exhibits the effects of the present invention and is useful. Evaporation can also be suppressed by using a dressing film with low moisture permeability.
  • Example 1 preparation of silk fibroin solution
  • the silk fibroin aqueous solution was obtained by dissolving scoured sashimi (manufactured by Nagasuna Coffee Co., Ltd.) in a 9M lithium bromide aqueous solution, removing insolubles by centrifugation, and then repeating dialysis against ultrapure water. .
  • the obtained silk fibroin aqueous solution was air-dried in a dialysis tube and concentrated. Acetic acid was added as an additive to this concentrated solution to prepare a silk fibroin solution having a silk fibroin concentration of 3 mass / volume% and an acetic acid concentration of 2 volume%.
  • the silk fibroin porous material produced as described above was immersed in a 10 L 2% by volume glycerin aqueous solution for 96 hours, and then immersed in a freeze dryer “FD-550P” (model number, Tokyo Rika Instrument Co., Ltd.). And dried for 3 days to obtain a dried silk fibroin porous material. Further, the mass of the dried silk fibroin porous material was measured.
  • the concentration of the hydroxyl group-containing compound in the dried silk fibroin porous material is calculated by dividing the amount of the hydroxyl group-containing compound introduced into the dried silk fibroin porous material by the dry mass of the porous material after introduction of the hydroxyl compound, and Calculated. ⁇ (Mass of dried silk fibroin porous material after introduction of hydroxyl compound) ⁇ (Mass of dried silk fibroin porous material without introduction of hydroxyl group compound) ⁇ / (Mass of dried silk fibroin porous material after introduction of hydroxyl compound)
  • the silk fibroin porous material produced as described above is a band source slicer “KMK-09-0005-HT” in which the compression ratio of the upper and lower rolls is set to 15% and the height distance between the upper roll and the band saw is set to 0.65 mm. ”(Made by Kitajima Machine Knife Co., Ltd.) and sliced as shown in FIG. 1, and after removing the non-porous film on one side of the 400 mm ⁇ 300 mm surface of the porous body, 10%, the height distance between the upper roll and the band saw was set to 0.20 mm, and the surface from which the non-porous film was removed was sliced again with a band source slicer to obtain a silk fibroin porous sheet.
  • the thickness, size, processability and 25% compression hardness of the silk fibroin porous sheet were evaluated by the following method.
  • Slicing availability Slicing is performed under the set conditions, and it is possible to obtain a sheet without any problems such as cracking or wrapping. When the sheet is cracked, it is cracked. The case where the fibroin porous material flowed and could not be sliced was defined as a flow.
  • Size measurement When the size of the silk fibroin porous sheet was measured with a ruler, it was 382 mm ⁇ 286 mm, which was equivalent to the size of the silk fibroin porous body before cutting.
  • the thickness of the silk fibroin porous sheet was measured with the thickness gauge “547-321” (Mitutoyo Co., Ltd.) as shown in FIG. The thickness of the porous sheet was used. (25% compression hardness)
  • a universal testing machine “EZ- (N) S” (model number, manufactured by Shimadzu Corporation) was used, the load cell was 50 N, and the compression speed was 1 mm using a circular compression plate with a diameter of 8 mm as a jig. / Min, at a room temperature of 22 ° C., the load when 25% of the thickness of the material was pressed with a compression plate was measured, and the value calculated by the following equation was taken as 25% compression hardness (kPa).
  • 25% compression hardness (kPa) (Load (N) / area of compression plate (mm 2 ) when 25% of material thickness is pressed with compression plate)) ⁇ 1000 (Electron microscope observation) 6 and 7 show the results of observing the structure of the surface from which the non-porous film before slicing and the non-porous film after slicing have been removed using a scanning electron microscope. Using a scanning electron microscope “XL30-FEG” (manufactured by Philips), measurement was performed in a low vacuum Pt deposition mode and an acceleration voltage of 10 kV. 6 and 7 show that the non-porous film has been removed by slicing.
  • Examples 2-14 Silk fibroin concentration of the silk fibroin solution poured into the container, additive type, container size, concentration of glycerin solution to be immersed, slicer setting when making porous sheet (compression rate and height distance between upper roll and band saw) A silk fibroin porous sheet was obtained in the same manner as in Example 1 except for changing to the one shown in Table 1.
  • Corresponding container sizes are as follows (length x width x thickness). * 1: 400mm x 300mm x 10mm * 2: 400mm x 300mm x 5mm * 3: 400mm x 300mm x 20mm * 4: 150mm x 50mm x 10mm
  • Example 15 The silk fibroin solution was prepared in the same manner as in Example 1, the silk fibroin porous material was produced, and the hydroxyl group-containing compound was introduced. The resulting dried silk fibroin porous material into which the hydroxyl compound was introduced was compressed into upper and lower rolls. As shown in FIG. 1, using a band source slicer “KMK-09-0005-HT” (manufactured by Kitajima Machine Knife Co., Ltd.) with a height of 15% and a height distance between the upper roll and the band saw set to 0.4 mm.
  • KMK-09-0005-HT manufactured by Kitajima Machine Knife Co., Ltd.
  • the surface from which the non-porous film has been removed is further sliced under the conditions shown in Table 2 to obtain a silk fibroin porous sheet Got.
  • Example 16 Using the remainder of the silk fibroin porous material used in obtaining the silk fibroin porous sheet in Example 15, further slicing was performed on the surface sliced in Example 15 under the conditions shown in Table 2. And a silk fibroin porous sheet was obtained.
  • Example 17 Using the remaining silk fibroin porous material used in obtaining the silk fibroin porous sheet in Example 16, further slicing was performed on the surface sliced in Example 16 under the conditions shown in Table 2. And a silk fibroin porous sheet was obtained.
  • Corresponding container sizes are as follows (length x width x thickness). * 1: 400mm x 300mm x 10mm From Examples 15 to 23 in Table 2, it was found that a plurality of sheets can be obtained from one block by repeatedly slicing one silk fibroin porous material. Further, it was found that a silk fibroin porous sheet having an arbitrary thickness can be obtained by changing the height distance between the upper roll and the band saw even from a silk fibroin porous body that has been repeatedly sliced.
  • Example 24 Comparative Examples 1-5 Preparation of a silk fibroin porous sheet was attempted in the same manner as in Example 1 except that the concentration of the glycerin solution to be immersed and the setting of the slicer (the compressibility and the height distance between the upper roll and the band saw) were changed. The results are shown in Table 3.
  • Comparative Example 4 It was found that slicing to a thickness thinner than 0.2 mm was more difficult than Comparative Example 1. It was found that slicing could not be performed if the compression rate was not set to an appropriate value as compared with Comparative Examples 2 and 3. In Comparative Example 4, the produced silk fibroin porous material was already cracked after drying, and when it was sliced, it was further broken and a sheet could not be obtained. Thus, a hydroxyl group-containing compound (glycerin) It was found that a good porous sheet could not be obtained by slicing when no was added. From Comparative Example 5, it was found that if a large amount of the hydroxyl group-containing compound (glycerin) was added, the porous body was wound around the roll during slicing and could not be sliced.
  • Example 6 Comparative Example 6 In Example 1, it replaced with the silk fibroin porous sheet, and produced the sheet
  • Example 7 Comparative Example 7 In Example 1, it replaced with the silk fibroin porous sheet and produced the sheet
  • Table 4 shows the results of evaluating the transparency and adhesion of Examples 1 to 6, Example 24, and Comparative Examples 6 and 7 by the following method.
  • Transparency evaluation Silk fibroin porous sheets (Examples 1 to 6 and Example 24) completely absorbed on a Japanese skin standard color plate (Bio Skin Plate (Bio Color), manufactured by Beaulux Co., Ltd.) and Comparative Examples 6 and 7
  • the color difference ⁇ E * ab (D65) was measured in the SCE mode from the porous sheet using a color difference meter “CM-700d” (manufactured by Konica Minolta).
  • the reference color was the Japanese skin standard color plate.
  • the transparency is higher as the color difference compared to the reference color is smaller.
  • the color difference per unit thickness was calculated by the following formula, and 10 or less was defined as being transparent.
  • (Color difference per unit thickness, mm ⁇ 1 ) (Color difference ⁇ E * ab) / (Thickness, mm)
  • the word “aiueo” was used to evaluate the adhesiveness after changing the expression.
  • the evaluation criteria were as follows. 5 points: Excellent contact feeling, close contact with the unevenness, and expression may be changed. 4 points: Excellent contact feeling, close contact with unevenness, and expression may be changed. 3 points: Excellent contact feeling and close contact along the unevenness, but it is said to change the expression. 2 points: Inferior to the feeling of adhesion, and uneven parts are lifted. 1 point: There is no feeling of adhesion and sticking is difficult.
  • the silk fibroin porous sheets of Examples 1 to 6 having a thickness of 0.2 to 1 mm are transparent because of small color difference and color difference per unit thickness.
  • the color differences per unit thickness were all 10 mm ⁇ 1 or less.
  • the silk fibroin porous bodies of Examples 1 to 6 have a lower color difference per unit thickness compared to a cotton nonwoven fabric widely used as a face mask material, and are transparent if they have the same thickness. I understood. Further, it was found that the silk fibroin porous sheets of Examples 1 to 6 and the silk fibroin porous sheet of Example 24 were excellent in adhesion as compared with the nonwoven fabrics of Comparative Examples 6 and 7.
  • Comparative Example 8 A silk fibroin solution was prepared under the same conditions as in Example 1, and after producing a silk fibroin porous body, a porous body in a wet state without introducing a hydroxyl group-containing compound and lyophilization Example 1 Cutting with a band source slicer was attempted under the same conditions as above, but the water was squeezed and the crushed porous material passed between the blade and the lower roll and could not be processed.
  • Comparative Example 9 The porous body in a wet state prepared by the same operation as in Comparative Example 8 was cut with a cutter to try to produce a porous sheet. Although cutting was attempted by applying a blade at an interval of 0.25 mm, the porous body was crushed and deformed by the pressure when pressing the cutter, and the porous body escaped from the blade because it was too soft. It was difficult to process into a sheet.
  • Comparative Example 10 The porous body in a wet state prepared by the same operation as in Comparative Example 8 was cut with a cutter to try to produce a porous sheet. Although cutting was attempted by applying blades at intervals of 1 mm, the porous body was crushed and deformed by the pressure applied when the cutter was pressed, and the porous body escaped from the blades because it was too soft. It was difficult to process.
  • Comparative Example 11 The silk fibroin porous material prepared by preparing a silk fibroin solution, producing a silk fibroin porous material, introducing a hydroxyl group-containing compound, and freeze-drying by the same operation as in Example 1 was cut with a cutter, I tried to make it. Although cutting was attempted by applying a blade at an interval of 0.25 mm, the porous body was crushed and deformed by the pressure when pressing the cutter, and the porous body escaped from the blade because it was too soft. It was difficult to process into a sheet.
  • Comparative Example 12 Preparation of a silk fibroin solution, production of a silk fibroin porous material, introduction of a hydroxyl group-containing compound, and freeze-drying were carried out in the same manner as in Example 1 to cut the produced silk fibroin porous material with a cutter to produce a porous sheet. Tried. As a result of cutting by applying a blade at intervals of 1 mm, it was possible to obtain a silk fibroin porous sheet having a size of about 3 cm ⁇ 4 cm and a thickness of about 1 mm, but a sheet having a size larger than that was obtained. It was difficult because the accuracy of the thickness was poor.
  • Table 5 shows the results of evaluating the thickness variations of Example 1, Example 6, and Comparative Example 12 by the following method.
  • the thickness variation was determined by the method described in the specification text. Further, since the silk fibroin porous sheet obtained in Comparative Example 12 had an irregular upper size and 12 points were difficult to measure, 5 points were measured as shown in FIG.
  • Comparative Example 13 The size of the mold made of the aluminum plate was set to 400 mm ⁇ 300 mm ⁇ 1 mm, and hard filter paper No. A silk fibroin solution was prepared and a silk fibroin porous body was produced in the same manner as in Example 1 except that 4A (manufactured by ADVANTEC) was attached. As a result, the filter paper affixed to the mold made of an aluminum plate and the silk fibroin porous body were firmly fixed and did not peel off, and only fragments were obtained even when forcibly peeling off.
  • Example 25 A dried silk fibroin porous material was obtained in the same manner as in Example 1 except that the size of the mold made of the aluminum plate was 100 mm ⁇ 100 mm ⁇ 6.0 mm and the concentration of the glycerol aqueous solution to be immersed was 3% by volume. The obtained silk fibroin porous body was sliced to obtain a silk fibroin porous sheet having a thickness of 3.0 mm. Using this silk fibroin porous sheet, a water absorption rate test was conducted according to the following method. The results are shown in Table 6.
  • Comparative Example 14 A dried silk fibroin porous material was obtained in the same manner as in Example 1 except that the size of the mold made of the aluminum plate was 100 mm ⁇ 100 mm ⁇ 3.0 mm and the concentration of the glycerin aqueous solution to be immersed was 3% by volume. Using this dried silk fibroin porous material, a water absorption rate test was conducted in the same manner as in Example 25. The results are shown in Table 6.
  • Example 15 The dried silk fibroin porous material was the same as in Example 1 except that the size of the mold made of the aluminum plate was set to an inner diameter of 100 mm ⁇ 100 mm ⁇ 3.0 mm, and the obtained silk fibroin porous material was not immersed in the glycerin aqueous solution. Got the body. Using this dried silk fibroin porous material, a water absorption rate test was conducted in the same manner as in Example 25. The results are shown in Table 6.
  • Example 25 From the results of Example 25 and Comparative Examples 14 and 15, in the wound dressing of the present invention, since the non-porous film present on both surfaces of the fibroin porous body is usually removed by processing, the pores are exposed. It was found that the liquid absorption speed was excellent.
  • Example 26 A silk fibroin porous sheet was prepared in the same manner as in Example 1, and a water retention test was performed according to the following method. As a result, the water retention rate was as large as 1710%, and a large amount of leachate could be absorbed, which proved useful as a wound dressing.
  • the silk fibroin porous sheet of the present invention is used in cosmetics and esthetics for the purpose of moisturizing, etc. for use in esthetic salons or individuals; skin care fields such as face masks and eye masks; wound dressings, drug sustained-release carriers, hemostatic sponges Medical fields such as disposable diapers, sanitary products, daily necessities, water purification and environmental fields that can be used as a support for microorganisms, bacteria, etc .; cell culture supports (scaffolds) in tissue engineering, regenerative medical engineering, etc. It is applicable to various industries such as materials) and tissue regeneration supports.

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Abstract

L'invention concerne : une feuille de fibroïne poreuse qui est mince, présente une excellente vitesse d'absorption d'eau, rétention d'eau et adhésivité, et présente de préférence une transparence supérieure lorsque l'eau a été absorbée; et son procédé de production. Plus précisément, l'invention concerne : une feuille de fibroïne n'ayant pas de film non poreux à travers la totalité d'au moins une surface de la feuille, et présentant une dureté à 25 % de compression de 200 à 800 kPa et une épaisseur de 0,25 à 2,5 mm; une feuille médicale comprenant la feuille poreuse de fibroïne; et un matériau de recouvrement de plaie comprenant la feuille de fibroïne poreuse. L'invention concerne également un procédé de production d'une feuille de fibroïne poreuse par compression d'un corps poreux de fibroïne séchée ayant une dureté à 25 % de compression de 200 à 800 kPa à un taux de compression de 7 à 40 %, puis tranchage du produit obtenu au moyen d'une scie à ruban.
PCT/JP2015/062024 2014-05-21 2015-04-20 Feuille de fibroïne poreuse, feuille médicale, matériau de recouvrement de plaie, et procédé de production de feuille de fibroïne poreuse WO2015178147A1 (fr)

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JP2014161378A (ja) * 2013-02-21 2014-09-08 Hitachi Chemical Co Ltd 美容用フェイスマスク

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JP2009214275A (ja) * 2008-03-12 2009-09-24 Toyo Tire & Rubber Co Ltd 研磨パッド
JP2011231096A (ja) * 2010-04-06 2011-11-17 Hitachi Chem Co Ltd スキンケア用シート
JP2012080915A (ja) * 2010-10-06 2012-04-26 Hitachi Chemical Co Ltd 創傷被覆材
JP2014133832A (ja) * 2013-01-10 2014-07-24 Hitachi Chemical Co Ltd 多孔質材料及び多孔質シート
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