JP2017080116A - Medical member - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a medical member that has excellent safety for organisms, has a short hemostatic time, can be easily removed from organisms, is excellent in mechanical strength, flexibility and liquid return inhibition at pressure application, and can cope with various situations.SOLUTION: A medical member has a liquid-absorbing body and a fibroin porous body.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a medical member.

  Silk is one of the bioresource materials that have been used for a long time as an excellent fiber material. In addition to having excellent physical properties as fibers such as touch, gloss, moisture retention, and strength, surgery As can be seen from the fact that it has been used in sutures for medical use, it also has a characteristic of exhibiting excellent biocompatibility. Research on the use of silk focusing on these excellent properties has been underway, and in addition to the development of utilization technology in fiber form, in recent years, research focused on each of fibroin and sericin, which are the main components of silk. Development is also underway.

  Silk is used in a wide variety of forms including not only fibers but also powders, solutions, gels, films, molded bodies, porous bodies, etc., among which silk fibroin porous bodies have excellent biocompatibility of silk fibroin, Utilization of water retention and tactile sensation is expected to expand the application to medical members such as hemostatic materials, wound dressing materials, sustained-release drug carriers, cosmetic members, cell culture supports in tissue engineering and regenerative medical engineering, etc. Yes.

  By the way, hemostasis is one of the most important treatments in the medical field. From the viewpoints of reducing the burden on the patient due to bleeding, improving the prognosis, reducing the burden on the surgeon, etc. Minimizing the volume and ensuring hemostasis is required. Conventionally, absorbent cotton, cotton gauze, and the like have been used as a hemostatic material used in a method of pressing a hemostatic material against a bleeding site, a so-called compression method.

  As materials having a hemostatic effect, gelatin, oxidized cellulose, chitin derivatives and the like are known in addition to collagen made from atelocollagen derived from bovine or pig. Collagen comes into contact with blood to activate platelets, and the activated platelets adhere to collagen to form aggregates, thereby enabling hemostasis (see, for example, Patent Document 1). Gelatin forms a gel in the presence of water such as blood, and exhibits high flexibility to adhere to the shape of the bleeding site and high adhesion to living tissue, allowing for hemostasis by pressing locally. It is known that it can be used as a hemostatic material (see, for example, Patent Document 2). Oxidized cellulose has a strong affinity for hemoglobin in the blood, so that it can be applied to wounded parts in and outside the body for blood coagulation. It is known that hemostatic healing can be achieved by promoting cell expansion (see, for example, Patent Document 3), and chitin derivatives are known to exhibit a hemostatic effect by activating platelets and promoting blood aggregation. (For example, see Patent Document 4).

JP-A-7-316070 JP-A-7-163860 JP 2000-256958 A JP 63-211122 A

However, conventionally used hemostatic materials such as absorbent cotton, gauze, etc. cannot stop hemorrhage immediately, and because of its high adhesion to the wound, it leaves many fibers at the site of use when it is peeled off, It was necessary to remove these fibers.
While the hemostatic material using collagen and gelatin described in Patent Documents 1 and 2 is excellent in biodegradability and absorbability, there is a problem that it is difficult to remove the antigenic telopeptide moiety, Due to the risk of animal-derived infections such as prion contamination, it has been found that it is better to avoid using it in living organisms.

The hemostatic material using oxidized cellulose described in Patent Document 3 has a problem of inducing a foreign body reaction because the material is not a living body-derived material, and also has a problem in handleability because of its water solubility. In addition, since the hemostatic material using the chitin derivative described in Patent Document 4 undergoes swelling gelation by sucking blood, there is a risk of compressing surrounding tissues when used in vivo, There is also a problem that the mechanical strength is lowered when gelled.
Since these hemostatic materials have a high adhering force to a living body, when the haemostatic part is healed or when the hemostatic material is peeled off for reprocessing the haemostatic part, a fragile new tissue is formed due to the adhering force. Injury secondary damage occurred, and it was difficult to remove the hemostatic material without damaging the living body. These problems are not limited to hemostatic materials, but are common to medical members such as wound dressings and drug sustained-release carriers that are used directly on the wound site. Is required. Depending on the place of use, pressure may be applied to the medical member from the outside. When this pressure is applied, the liquid contained in the member oozes out to the surface of the member (also referred to as liquid return), and when the member is used as a hemostatic material and a wound dressing material, the affected area can be kept in a moderately moist state. In addition, when the member is used as a drug sustained-release carrier, there is a problem that the drug is excessively released, which hinders the healing of the affected area. Therefore, the medical member is required to have a liquid return suppressing performance when pressure is applied. Furthermore, since various situations are assumed for the use state of the medical member according to the medical practice, a variety of forms is also required to cope with various situations.

  Therefore, in view of the above problems, the problem of the present invention is excellent in safety to the living body, has a short hemostatic time, has an excellent hemostatic effect, can be easily removed from the living body, has mechanical strength, flexibility, and An object of the present invention is to provide a medical member that is excellent in the performance of suppressing liquid return when pressure is applied and that can cope with various situations.

As a result of intensive studies to achieve the above problems, the present inventor has found that the problems can be solved by the following invention.
1. The medical member which has a liquid absorption and a fibroin porous body.
2. The adhesive film further includes an adhesive film, and the adhesive film covers the liquid absorbent and the fibroin porous body from the liquid absorbent side so that the adhesive film, the liquid absorbent and the fibroin porous body are laminated in this order. 2. The medical member according to 1 above, wherein the surface of the fibroin porous body opposite to the side on which the liquid-absorbing layer is laminated and the surface opposite to the adhesive film is exposed .
3. 3. The medical member according to 1 or 2 above, further comprising a fibroin porous body, wherein the liquid absorption is sandwiched between the fibroin porous bodies.
4). 4. The medical member according to any one of 1 to 3, wherein the fibroin porous body has a thickness of 0.1 to 50 mm.
5. 5. The medical member according to any one of 1 to 4 above, wherein the liquid absorption has a thickness of 0.1 to 50 mm.
6). 6. The medical member according to any one of 1 to 5 above, wherein the fibroin porous material contains fibroin having a protein-equivalent molecular weight of 110,000 to 310,000.
7). 7. The medical member according to any one of 1 to 6 above, wherein the fibroin porous body is a silk fibroin porous body.
8). 8. The medical member according to any one of 1 to 7 above, wherein the fibroin porous material contains 20 to 75% by mass of a hydroxyl group-containing compound having a molecular weight of 1,000 or less.
9. The hydroxyl group-containing compound is at least one selected from glycerin, polyglycerin, polyethylene glycol, triethyl citrate, lactic acid, polyvinyl alcohol, propylene glycol, butylene glycol, alcohol, glycerin fatty acid ester, polyglycerin fatty acid ester, and sorbitan fatty acid ester. 9. The medical member according to 8 above.
10. 10. The medical member according to any one of 1 to 9 above, wherein the liquid absorption is at least one selected from a resin sponge, a rubber sponge, a nonwoven fabric, and a liquid-absorbing polymer material.
11. 11. The medical member according to any one of 1 to 10, which is used for a hemostatic material, a wound dressing material, or a drug sustained release carrier.

  According to the present invention, it is excellent in safety with respect to a living body, has a short hemostatic time, has an excellent hemostatic effect, can be easily removed from a living body, has mechanical strength, flexibility, and performance of suppressing liquid return when pressure is applied. It is possible to obtain a medical member that is excellent in performance and can cope with various situations.

It is a mimetic diagram showing an example of the section and front of the medical member of the present invention. It is a mimetic diagram showing an example of the section and front of the medical member of the present invention. It is a mimetic diagram showing an example of the section and front of the medical member of the present invention. It is a schematic diagram which shows an example of the cross section of the medical member of this invention. It is a schematic diagram which shows an example of the cross section of the medical member of this invention.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the drawings as necessary. However, the present invention is not limited to the following embodiments.
Moreover, the numerical value range shown using "to" in this specification shows the range which includes the numerical value described before and behind "to" as a minimum value and a maximum value, respectively. Furthermore, when referring to the amount of each component in the composition in the present specification, when there are a plurality of substances corresponding to each component in the composition, the plurality of the components present in the composition unless otherwise specified. Means the total amount of substances.

[Medical materials]
The medical member of the present invention is characterized by having a liquid absorption and a fibroin porous body.

(Liquid absorption)
The liquid absorption is not particularly limited as long as it has liquid absorption performance, and for example, a resin sponge, a rubber sponge, a nonwoven fabric, a liquid absorbent polymer material, and the like are preferable. Examples of the resin sponge include urethane sponge, polyolefin sponge, polyvinyl alcohol sponge, silicone sponge and the like, and are available as commercial products. Examples of the rubber sponge include sponges made of natural rubber, diene rubbers such as polybutadiene, and other rubbers such as synthetic rubbers, and are commercially available. Moreover, as a nonwoven fabric, a cotton nonwoven fabric, a rayon nonwoven fabric, a silk nonwoven fabric, an acrylic polymer fiber nonwoven fabric, those composite nonwoven fabrics, etc. are mentioned, It can obtain as a commercial item.
These materials may be appropriately selected according to the desired performance.For example, polyvinyl alcohol sponge is preferable from the viewpoint of hydrophilicity, polyolefin sponge such as polyethylene sponge, polyurethane is preferable from the viewpoint of structure control and strength, A rubber sponge is preferable from the viewpoint of extensibility and toughness, and a silicone sponge is preferable from the viewpoint of water repellency and toughness.

Further, as the liquid-absorbing polymer constituting the liquid-absorbing polymer material, those generally known as water-absorbing resins, for example, polyacrylic acid-based water-absorbing resins such as sodium polyacrylate; starch-acrylonitrile graft copolymer Polymers, starch-acrylic acid graft copolymers, starch-based water-absorbing resins such as starch-acrylamide graft copolymers; polyvinyl alcohol-based water-absorbing resins such as crosslinked polyvinyl alcohol; cellulose derivatives such as sodium carboxymethylcellulose; Can be used.
In addition, liquid absorbents such as polyacrylic acid-based water-absorbent resins and cellulose derivatives are preferred from the viewpoint of facilitating suppression of liquid return upon application of pressure because they gel when absorbing blood, leachate, and the like. For example, in the use of a wound dressing for wet therapy, when the wound is pressed, the absorbed exudate and the like are difficult to return to the wound, and an appropriate moist environment can be provided.

  There is no restriction | limiting in particular in the form of a liquid absorption, What is necessary is just to select suitably according to a desired use, For example, it can be set as forms, such as a film form, a sheet form, a block form, a tubular shape, and a spherical form. Considering the usage as a medical member, for example, when using a resin sponge, it is preferable to use a commercially available product by slicing it into a film, sheet, etc., for example, a water-absorbing polymer material. In the case of using, it is preferable to use a particulate material in a predetermined thickness in addition to a film shape, a sheet shape or the like.

  The size and shape of the liquid-absorbing liquid are not particularly limited and may be appropriately selected according to a desired application. The length and width are approximately 1 to 30 cm, a substantially square shape, a substantially circular shape inscribed in the square shape, a substantially oval shape, A substantially triangular shape is preferred.

  Moreover, there is no restriction | limiting in particular also in the thickness of a liquid absorption, What is necessary is just to select suitably according to a desired use. In consideration of usability as a medical member, strength, handleability, etc. in addition to the function of liquid absorption to ensure liquid absorption capacity, the thickness is preferably 0.1 to 50 mm, more preferably 0.2 to 30 mm Preferably, 0.3 to 15 mm is more preferable, and 0.3 to 5 mm is particularly preferable. Here, the thickness of the porous part in the present invention means an average value when the distance (thickness) in the direction perpendicular to the surface having the maximum area is measured at any ten points in the porous part.

(Fibroin porous material)
The fibroin porous body is not particularly limited as long as the material containing fibroin itself is a porous body having pores. For example, a sponge can be a porous body of the present invention because the material itself constituting the sponge has pores. However, fibers and nonwoven fabrics can be made fine by knitting a thread-like material as a whole. It is a form having pores and is not referred to as a porous body in the present invention.

In the present invention, the fibroin porous material is a fibroin having a protein-equivalent molecular weight of 110,000 to 310,000 in consideration of safety to the living body, hemostatic performance, ease of removal from the living body, mechanical strength, and flexibility. , More preferably 140,000 to 310,000 fibroin, still more preferably 180,000 to 310,000 fibroin. From the same viewpoint, the fibroin porous body is preferably a silk fibroin porous body using silk fibroin.
Here, the protein-converted molecular weight refers to a chromatogram of an evaluation sample obtained using high performance liquid chromatograph (HPLC), glutamate dehydrogenase (molecular weight: 290,000), porcine myocardial lactate dehydrogenase (molecular weight marker) (Molecular weight: 142,000), a calibration curve created using yeast enolase (molecular weight: 67,000), which means the molecular weight converted to the molecular weight of the protein. More specifically, it is described in the examples. It can be measured by the method.

  The content of the fibroin having the above-described molecular weight in terms of protein contained in the porous fibroin is preferably 80% by mass or more, more preferably 90% by mass or more, still more preferably 95% by mass or more, particularly preferably substantially. 100% by mass.

  Further, the silk fibroin porous material is a hydroxyl group-containing compound having a molecular weight of 1,000 or less from the viewpoint of obtaining superior safety to the living body, hemostasis performance, easy removal from the living body, mechanical strength, and flexibility. It is preferable to contain.

The hydroxyl group-containing compound may be any compound having one or more hydroxyl groups per molecule, preferably having 1 to 10 hydroxyl groups per molecule, and more preferably having 1 to 4 hydroxyl groups per molecule. preferable.
Further, the molecular weight of the hydroxyl group-containing compound is 1,000 or less, preferably 800 or less, and more preferably 500 or less. The lower limit of the molecular weight of the hydroxyl group-containing compound is not particularly limited, but is preferably 50 or more, and more preferably 80 or more.

  Specific examples of the hydroxyl group-containing compound 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. These can be used alone or in combination of two or more. Furthermore, when handling property, slice processability, and safety are taken into consideration, glycerin, polyethylene glycol, triethyl citrate, polyglycerin, lactic acid, propylene glycol, and butylene glycol are preferable. Among these, since glycerin has an effect of moisturizing the skin, it is particularly preferable for the medical member application used by being attached to the skin.

20-75 mass% is preferable, as for content of the hydroxyl-containing compound in a fibroin porous body, 25-60 mass% is more preferable, and 25-45 mass% is still more preferable. When the content of the hydroxyl group-containing compound is within the above range, more excellent flexibility, workability, and handling properties can be obtained. More specifically, if it is 20% by mass or more, it is excellent in flexibility, hardly cracked during drying, does not become brittle, is not easily cracked during slicing, and provides excellent handling properties. On the other hand, when it is 75% by mass or less, it has excellent flexibility, small shrinkage before and after lyophilization, good surface tack of the porous material, hardly wraps around the roll during slicing, and has excellent handling properties. It is done.
Moreover, the fibroin porous body can adjust the hardness by changing content within the said range. As the content of the hydroxyl group-containing compound is increased, the porous material becomes more flexible, and can be appropriately adjusted according to the application.

The average pore diameter of the fibroin porous body is preferably 1 to 500 μm, more preferably 5 to 300 μm, and still more preferably 10 to 100 μm. When the average pore diameter is within the above range, more excellent safety to the living body, hemostatic performance, ease of removal from the living body, mechanical strength, and flexibility can be obtained.
Here, the average pore diameter of the fibroin porous body was obtained by taking five scanning electron micrographs of the porous body cross section, and further taking five scanning electron micrographs of the porous body cross section prepared on different days. These 10 scanning electron micrographs are image-processed using image analysis software, and are average values of pore diameters calculated.

The form, size, shape, and thickness of the fibroin porous body are the same as those described for the liquid absorption, and may be appropriately selected in consideration of the relationship with the liquid absorption. Details of this will be described later.
The fibroin porous body may be appropriately processed and used, and the processing method is not particularly limited, and examples thereof include punching using a Thomson blade and slicing processing with a band saw.

The 25% compressive stress of the fibroin porous body is preferably 20 to 25 kPa, and more preferably 20 to 23 kPa. A fibroin porous material having a 25% compressive stress in the above range is excellent in flexibility.
The tear strength of the fibroin porous body is preferably 20 to 50 N / mm, and more preferably 25 to 45 N / mm. A fibroin porous material having a tear strength in the above range is excellent in the balance of mechanical strength, stretchability and flexibility.
Here, the 25% compressive stress and tear strength of the fibroin porous material can be measured by the methods described in Examples.

The tensile strength of the fibroin porous body is preferably 35 to 75 kPa, and more preferably 40 to 70 kPa. A fibroin porous material having a tensile strength in the above range is excellent in mechanical strength, stretchability and flexibility.
The tensile strain of the fibroin porous body is preferably 52 to 67%, more preferably 56 to 65%. A fibroin porous material having a tensile strain in the above range is excellent in stretchability.
Here, the tensile strength and tensile strain mean the stress and strain when the test piece breaks when the test piece is pulled with a universal testing machine or the like, and the value of tensile strain (%) is [[(( Length after deformation−length before deformation) / (length before deformation)] × 100].

The blood coagulation time of the fibroin porous body is preferably 25 minutes or less, more preferably 20 minutes or less, and even more preferably 15 minutes or less, from the viewpoint of enabling rapid hemostasis.
Here, in the present invention, the blood coagulation time means a time measured by the following method, and more specifically, can be measured by the method described in Examples.
Two test tubes charged with 300 mm ³ of fibroin porous material were prepared, and after heating them to 37 ° C., 1.5 mL (200 mm ³ / mL) of blood immediately after blood collection was added. Next, the first test tube is tilted every 30 seconds, and the blood fluidity is visually observed. After blood coagulation is observed in the first test tube, the second test tube is moved every 30 seconds. The blood fluidity was confirmed visually, and the time from the start of blood collection until blood coagulation was observed in the second test tube was defined as the blood coagulation time.

  Further, the adhesion force of the fibroin porous body to the wound where the exudate is generated is preferably 15 g or less, more preferably 12 g or less, more preferably 10 g, from the viewpoint that it can be easily removed from the living body. More preferably, it is as follows. Here, the adhering force is an average adhering strength measured and calculated by the method described in the examples.

(Production of fibroin porous material)
A fibroin porous body can be manufactured using the following fibroin raw materials, for example.

The fibroin raw material used as the raw material for the fibroin porous material can be obtained, for example, by scouring silk raw materials such as silkworms and raw silk containing sericin in addition to fibroin and removing sericin.
There is no restriction | limiting in particular in the silk raw material to be used, A cocoon, a cut cocoon, raw silk, etc. can be used. There are no particular restrictions on the varieties of silkworms, and for example, silk fibroin produced from natural silkworms such as rabbits, wild silkworms, and tengu, transgenic silkworms, and the like can be used. In the present invention, it is preferable to use silk fibroin as a raw material from the viewpoint of obtaining a fibroin porous material that is soft even in a dry state and excellent in appearance after drying and slice processability.

  Usually, the scouring of the silk raw material is performed in a step of heating the silk raw material in an aqueous solution in which an alkaline agent is dissolved. There is no particular limitation on the scouring method, and methods such as hanging kneading, mechanical kneading, bag kneading, and foam kneading can be used.

There is no particular limitation on the alkaline agent used for scouring, and Marcel soap, sodium carbonate, sodium bicarbonate, etc. can be used, but since there is a concern about residual soap, sodium carbonate, sodium bicarbonate is preferably used, and the molecular weight is controlled. Therefore, it is more preferable to use sodium carbonate.
The concentration of the alkaline agent in the aqueous solution is preferably 15% owf to 25% owf. By setting the concentration of the alkaline agent within the above range, sericin can be efficiently removed and a fibroin raw material having a molecular weight suitable for forming a fibroin porous material can be obtained.

  The bath ratio during scouring (ratio of the mass of the aqueous solution in which the alkaline agent is dissolved relative to the mass of the fibroin raw material) is preferably 20 to 100 times. Sericin can be efficiently removed by setting the bath ratio during scouring within the above range.

The heating temperature during scouring is not particularly limited as long as sericin can be sufficiently removed, but in the case of normal pressure, 85 to 100 ° C. is preferable. By setting the temperature within the above range, sericin can be efficiently removed.
The scouring time is not particularly limited as long as sericin can be sufficiently removed, but it is preferably 3 hours to 5 hours. By setting the scouring time within the above range, sericin can be efficiently removed and a fibroin raw material having a molecular weight suitable for forming a fibroin porous material can be obtained.
After scouring, in order to remove alkali and sericin adhering to the fibroin raw material, it is preferable to perform dehydration and drying after hot water washing and water washing.

  The fibroin raw material preferably has a protein-equivalent molecular weight of 160,000 to 410,000, more preferably 200,000 to 360,000, and still more preferably 240,000 to 310,000. By producing a fibroin porous material using a fibroin raw material having a molecular weight in the above range, a fibroin porous material having excellent mechanical strength and flexibility can be obtained.

  Hereinafter, a method for producing a silk fibroin porous material will be described in detail by taking silk fibroin preferable as a fibroin raw material as an example.

  The method for producing the silk fibroin porous material is not limited. For example, after rapidly freezing a silk fibroin aqueous solution, it is immersed in a crystallization solvent and simultaneously melted and crystallized (for example, Japanese Patent Laid-Open No. 8-410997), a method of producing a porous material by maintaining a frozen state for a long time after freezing the silk fibroin aqueous solution (see, for example, JP-A-2006-249115), A method of obtaining a porous material by adding a small amount of a water-soluble liquid organic substance and then freezing and thawing it for a certain time (see, for example, Japanese Patent No. 34122014), and the like.

  As a method for obtaining a silk fibroin aqueous solution used for the production of a silk fibroin porous material, any known method may be used. However, since silk fibroin has low solubility in water, for example, the silk fibroin is dissolved in a solution. Then, a method of removing the drug used for dissolution is preferable. Specifically, for example, a method of dissolving in a neutral salt solution such as an aqueous solution of lithium bromide or an aqueous solution of calcium chloride / ethanol and desalting by dialysis; And a method of dialysis after dissolving in copper ethylenediamine and adding a copper ion dissociator. Among these, the method of dissolving in a neutral salt solution and desalting is preferable because of easy post-treatment and molecular weight adjustment.

  As a neutral salt solution to be used, a lithium bromide aqueous solution and a calcium chloride / ethanol aqueous solution are preferable. In the case of an aqueous lithium bromide solution, the concentration of the neutral salt in the neutral salt solution is preferably 8 to 10 mol / L. In the case of a calcium chloride / ethanol aqueous solution, it is preferable to use a solution in which calcium chloride, ethanol, and water are mixed at a molar ratio of 1: 2: 8. By setting the neutral salt concentration within the above range, silk fibroin can be efficiently dissolved.

  The melting temperature of silk fibroin is not particularly limited as long as it is a temperature at which silk fibroin is dissolved, but in the case of a lithium bromide aqueous solution, 10 to 40 ° C. is preferable. Moreover, in the case of calcium chloride / ethanol aqueous solution, 70-90 degreeC is preferable and 75-85 degreeC is more preferable. By setting the dissolution temperature within the above range, silk fibroin can be efficiently dissolved and a silk fibroin aqueous solution having a molecular weight suitable for forming a silk fibroin porous material can be obtained.

  Although there is no restriction | limiting in particular in the melt | dissolution time of silk fibroin, In the case of lithium bromide aqueous solution, 3 hours-24 hours are preferable and 5 hours-18 hours are more preferable. Moreover, in the case of calcium chloride / ethanol aqueous solution, 10 minutes-60 minutes are preferable and 15 minutes-40 minutes are more preferable. By setting the dissolution time within the above range, silk fibroin can be sufficiently dissolved and a silk fibroin aqueous solution having a molecular weight suitable for forming a silk fibroin porous material can be obtained.

  The concentration of silk fibroin in the silk fibroin aqueous solution is not particularly limited as long as it is a concentration that can be dissolved in the solution, but is preferably 50 g / L to 200 g / L, and more preferably 100 g / L to 150 g / L. By setting the concentration of silk fibroin within the above range, a silk fibroin aqueous solution having a concentration suitable for producing a silk fibroin porous material can be obtained. As a method for adjusting the concentration of silk fibroin in the silk fibroin aqueous solution, a method through concentration by air drying is simple and preferable.

The concentration of silk fibroin can be obtained from the mass reduction by putting the silk fibroin aqueous solution in a container and completely drying, as shown in the following equation.
(Silk fibroin concentration (g / L)) = (mass after drying of silk fibroin aqueous solution (g)) / (volume of silk fibroin aqueous solution before drying (L))

  There is no particular limitation on the desalting method, and desalting can be performed by dialysis using a dialysis membrane, ultrafiltration, or the like. The molecular weight cutoff of the dialysis membrane or ultrafiltration membrane is preferably 5,000 to 40,000, more preferably 5,000 to 10,000. By using a dialysis membrane or ultrafiltration membrane with a molecular weight cut off in the above range, both desalting efficiency and a small loss of silk fibroin can be achieved.

  The protein-equivalent molecular weight of silk fibroin in the silk fibroin aqueous solution is preferably 160,000 to 410,000, more preferably 200,000 to 350,000, and still more preferably 240,000 to 310,000. By producing a silk fibroin porous body using a silk fibroin aqueous solution containing silk fibroin having a molecular weight in the above range, a silk fibroin porous body excellent in mechanical strength and flexibility can be obtained.

  The silk fibroin porous material is preferably produced by adding a specific additive to a silk fibroin aqueous solution, freezing the aqueous solution, and then thawing it. Preferred examples of the additive used here include carboxylic acids, amino acids, water-soluble liquid organic substances, and the like. The carboxylic acids used in the production of the silk fibroin porous material preferably have a pKa of 5.0 or less, more preferably 3.0 to 5.0, and 3.5 to 5.0 Is more preferable.

  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. As the carboxylic acids, aliphatic carboxylic acids are preferable, aliphatic carboxylic acids having 1 to 6 carbon atoms are more preferable, and aliphatic carboxylic acids having 2 to 5 carbon atoms are still more preferable. These aliphatic carboxylic acids may be saturated or unsaturated. Specific examples of such carboxylic acids include monocarboxylic acids such as formic acid, acetic acid, propionic acid, butyric acid, lactic acid, acrylic acid, and 2-butenoic acid; oxalic acid, malonic acid, succinic acid, maleic acid, and the like. Of these, dicarboxylic acids are preferred. These can be used alone or in combination of two or more. In view of safety to the human body, acetic acid, lactic acid and succinic acid are 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, and fatty acids such as monoaminodicarboxylic acids (acidic amino acids) such as aspartic acid and glutamic acid. Preferred examples include aromatic amino acids; aromatic amino acids such as phenylalanine; amino acids having a heterocyclic ring such as hydroxyproline; and acidic amino acids and oxyamino acids such as hydroxyproline, serine, and threonine are preferred from the viewpoint of easy shape adjustment. . From the same viewpoint, monoaminocarboxylic acid is more preferable among acidic amino acids, aspartic acid and glutamic acid are particularly preferable, and hydroxyproline is more preferable among oxyamino acids. These amino acids can be used alone or in combination of two or more.
There are L-type and D-type optical isomers of amino acids, but when L-type and D-type are used, since no difference is seen in the obtained porous material, either amino acid may be used.

  The water-soluble liquid organic substance is a liquid that is liquid at room temperature (20 ° C.) and dissolves or mixes without separation when mixed with water at room temperature (20 ° C.). Examples of 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, and acetonitrile. Etc. are preferred. These can be used alone or in combination of two or more. In consideration of safety to the human body, ethanol, dimethyl sulfoxide, glycerin and acetone are preferable, and ethanol and glycerin are more preferable.

  When the additive is used in the silk fibroin aqueous solution, the content of the additive is preferably 0.1 to 18% by volume, more preferably 0.1 to 5.0% by volume, and 0.5 to 4.0% by volume. Further preferred. By setting the content of the additive within the above range, a silk fibroin porous material having sufficient mechanical strength can be produced.

The silk fibroin porous material can be suitably obtained by, for example, pouring the silk fibroin aqueous solution into a mold or container, freezing it for a certain time, and then thawing it.
The freezing temperature is preferably −10 to −30 ° C., more preferably −15 to −25 ° C. The freezing time is preferably 4 hours or more, and more preferably 6 hours or more so that the silk fibroin aqueous solution to which the additive is added is sufficiently frozen and the frozen state can be maintained for a certain time. In particular, it is preferable that the silk fibroin porous body having excellent mechanical strength is reproducibly formed by freezing by holding at −15 to −25 ° C. for 6 hours to 100 hours.

  Here, the silk fibroin aqueous solution may be frozen at a freezing temperature at a stretch, but it is preferable to pass a supercooled state before freezing in order to obtain a silk fibroin porous body having a uniform structure. For example, a silk fibroin porous material having a uniform structure can be obtained by temporarily holding a silk fibroin aqueous solution to which an additive has been added at −5 ° C. for 2 hours and then freezing it to a freezing temperature.

  The silk fibroin porous material is obtained by freezing the silk fibroin aqueous solution by the above method and then thawing it. There is no restriction | limiting in particular as a melting method, Methods, such as natural melting and storage in a thermostat, are mentioned preferably.

  Additives remain in the silk fibroin porous material thus obtained. The remaining additive may be left as it is or may be removed depending on the application. As a method for removing the additive from the silk fibroin porous material, for example, the simplest method is to immerse and remove the silk fibroin porous material in pure water.

  The silk fibroin porous body has a sponge-like porous structure, and usually the same as the above-mentioned remaining additives unless water is removed by freeze drying or the like in the porous body of the silk fibroin porous body. In addition, water is contained and the structure is soft. When the dried silk fibroin porous material is required, the water-absorbed silk fibroin porous material may be dried. The technique for drying the silk fibroin porous material is not particularly limited, but lyophilization is preferred in the sense of suppressing shrinkage. In the case of freeze-drying, if the drying is finished without completely sublimating the water, the remaining ice melts into water, and the pores are crushed due to the surface tension, so the water is completely sublimated. It is preferable to dry.

The silk fibroin porous material can be made into a shape according to the purpose such as a sheet shape, a block shape, a tubular shape, etc. by appropriately selecting a container into which the silk fibroin aqueous solution is poured.
The container is not limited as long as the silk fibroin solution has a shape and shape that does not flow out, and as the material, a material having high thermal conductivity such as iron, stainless steel, aluminum, gold, silver, copper, or the like is used. From the viewpoint of reducing the process time required for freezing. In addition, the thickness of the mold or 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 is easy to handle and more efficient from the viewpoint of cooling efficiency. Preferably it is 1-3 mm.

  The method of incorporating the hydroxyl group-containing compound into the fibroin porous body is not particularly limited. When producing the fibroin porous body, the method of blending into the fibroin solution or the preparation of the fibroin porous body is immersed in the whole. The method of immersing in the solution containing a hydroxyl-containing compound may be sufficient.

  When the hydroxyl group-containing compound is contained in the fibroin solution, the content of the hydroxyl group-containing compound is not particularly limited, and is preferably 0.5 to 20% by volume, and more preferably 1 to 10% by volume. If the content is within the above range, the hydroxyl group-containing compound is sufficiently introduced into the fibroin porous material, and a fibroin porous material containing a hydroxyl group-containing compound suitable for drying is obtained.

  When the fibroin porous body is immersed in a solution containing a hydroxyl group-containing compound, the immersion time is not particularly limited, but may be any time as long as the concentration of the hydroxyl group-containing compound in the fibroin porous body is uniform. 48 hours are preferable, and 12 to 36 hours are more preferable. When the immersion time is within the above range, the hydroxyl group-containing compound is sufficiently introduced into the fibroin porous body, and there is no variation in concentration in the fibroin porous body, and the hydroxyl group-containing compound is uniformly contained. A homogeneous porous material is obtained.

  In the fibroin porous body thus obtained, the hydroxyl group-containing compound is present in the pores of the fibroin porous body and in the structure of the porous body so as to constitute the porous body itself. A plasticizing effect, a moisturizing effect and a water absorption effect are exhibited. Since it is such a structure, it is thought that the fibroin porous body is soft even in a dry state and has excellent appearance after drying and slice processability.

  In addition, the internal structure and hardness of the fibroin porous body can be adjusted by adjusting the types of fibroin, hydroxyl group-containing compounds, and additives used as raw materials, and the amount of these additives, and have various structures. A fibroin porous material can be obtained.

(Configuration of medical material)
As a medical member of this invention, it has a liquid absorption and a fibroin porous body, For example, what has the structure shown by FIG. 1 is mentioned. A medical member 10 shown in FIG. 1 has a liquid absorbing body 12 and a fibroin porous body 11. The liquid-absorbing liquid 12 and the fibroin porous body 11 may have the same size as shown in the figure (1-a), or may have different sizes as shown in the figure (1-b). FIG. 1 (c) is a schematic view of the medical member 10 shown in FIG.
When the medical member 10 of the present invention is used, it is preferable that the affected part or the like does not touch the fibroin porous body 11 so that the affected part or the like is not touched. When the size is different from that of the fibroin porous body 11, it is preferable that the fibroin porous body 11 is larger as shown in the figure (1-b). In this case, the shape of the liquid absorbent 12 and the fibroin porous body 11 may be the same or different as long as the liquid absorbent and the affected part do not touch each other (FIG. (1-c)).

  When the configuration shown in FIG. 1 is adopted, it may be used as it is, or may be used by being fixed with a dressing film, a bandage, an adhesive tape or the like.

  In addition, the medical member of the present invention further includes an adhesive film, and the adhesive film, the liquid absorbent, and the fibroin porous body are laminated in this order so that the adhesive film, the liquid absorbent and the fibroin porous body are laminated. The surface of the fibroin porous body opposite to the side on which the liquid absorbing layer is laminated and the surface opposite to the adhesive film is exposed. For example, one having the configuration shown in FIG.

  The adhesive film is not particularly limited as long as it is used for fixing a medical member such as a hemostatic material, a wound dressing material, a drug solution sustained release carrier, for example, a so-called vinyl material such as a soft plastic having excellent extensibility. , Non-woven fabrics such as olefin non-woven fabric, urethane non-woven fabric, nylon non-woven fabric, polyester non-woven fabric, vinyl chloride, stretch cotton fabric, sponge sheet, urethane film, olefin film, etc., acrylic adhesive, rubber adhesive, silicone What apply | coated adhesives, such as an adhesive, with a thickness of 10-1000 micrometers normally is used preferably. As the pressure-sensitive adhesive, those having weak skin irritation are preferable.

  The medical member 10 shown in FIG. (2-a) further has an adhesive film 13 on the liquid-absorbing liquid 12 and the fibroin porous body 11 shown in FIGS. (1-b) and (1-c). The pressure-sensitive adhesive film 13, the liquid-absorbing liquid 12, and the fibroin porous body 11 are laminated in this order. The surface of the fibroin porous body 11 opposite to the side on which the liquid absorbing layer 12 is laminated and the side opposite to the side on which the adhesive film 13 is laminated is exposed. The structure is such that the fibroin porous body 11 touches the affected part or the like when using. FIG. (2-b) is a schematic view of the medical member 10 shown in FIG. (2-a) as seen from the fibroin porous body 11 side. The liquid absorbing liquid 12 includes the fibroin porous body 11, the adhesive film 13, and the like. And is not shown because it is hidden in the fibroin porous body 11.

  By using the fibroin porous body 11 shown in the figure (1-b) that is larger than the liquid-absorbing liquid 12, the fibroin porous body 11 and the liquid-absorbing liquid 12 are bonded using an adhesive or the like, or pressure bonded. Even if not, the fibroin porous body 11 and the liquid-absorbing liquid 12 are held by the adhesive film 13. Therefore, in the medical member 10 shown in FIG. 2 in which the laminate shown in FIG. 1 (b) is covered with the adhesive film 13, a foreign substance such as an adhesive is present at the interface between the fibroin porous body 11 and the liquid-absorbing liquid 12. It does not exist or the pores are not crushed by pressure bonding. Therefore, when the medical member 10 shown in FIG. 2 is used as a hemostatic material or wound dressing material that is required to absorb a liquid such as blood generated from an affected area or the like, a liquid such as a drug solution is included in the liquid absorption. Further, when used as a drug solution sustained-release carrier that is gradually released to an affected area through a porous body, it is an example of a preferred embodiment without inhibiting the passage of liquid.

  When the fibroin porous body 11 is larger than the liquid absorbing liquid 12 as shown in FIG. 2, the size of the fibroin porous body 11 depends on the size of the member, but considering the adhesion with the adhesive film 13. The size of the liquid absorbent 12 is preferably such that a margin of 1 to 20 mm is formed on the periphery thereof, and the size of a margin of 1 to 10 mm is more preferable.

  The medical member 10 shown in FIG. 3 has a shape such that a part of the adhesive film 13 covers the peripheral edge of the fibroin porous body 11, and the fibroin porous body 11 and the liquid-absorbing liquid 12 have the same shape. Are the same size. FIG. (3-a) is a schematic diagram of a cross section of the medical member 10, and FIG. (3-b) is a schematic diagram seen from the fibroin porous body 11 side corresponding to this, and the liquid absorbing liquid 12 is a fibroin porous material. Since it is hidden in the mass 11, it is not illustrated.

  In the case of the medical member 10 shown in FIG. (3-a), the fibroin porous body 11 and the liquid absorption 12 are held by the adhesive film 13 that covers the peripheral edge of the fibroin porous body 11, and thus the above diagram. Similarly to the medical member 10 shown in FIG. 2, it is not necessary to bond or press-fit the fibroin porous body 11 and the liquid-absorbing liquid 12. In addition, since the fibroin porous body 11 and the liquid absorbing body 12 can have the same shape and size, the appearance is better than the medical member 10 shown in FIG. Since a part of the periphery of 11 is covered with the adhesive film 13 (see FIG. 3-2), it can be said that the medical member 10 shown in FIG. 2 is superior in this respect.

  When holding the periphery of the fibroin porous body with an adhesive film, the width of the adhesive film is preferably 1 to 20 mm, preferably 1 to 10 mm, depending on the size of the member. More preferred. By making the width of the part held by the adhesive film within the above range, the fibroin porous body and the liquid absorption can be more securely held, and the influence on the exposed area of the fibroin porous body should be reduced. Can do.

  The medical member of the present invention can be configured as shown in FIG. Since the fibroin porous body 11 and the liquid-absorbing liquid 12 are not held by the adhesive film 13, the fibroin porous body 11 and the liquid-absorbing liquid 12 need to be joined by adhesion or pressure bonding. In this case, the adhesion or pressure bonding between the fibroin porous body 11 and the liquid-absorbing liquid 12 is minimized while minimizing the obstruction of the liquid due to the presence of foreign substances such as adhesives at these interfaces or the crushing of the pores. It is important to secure the bonding strength of The medical member 10 shown in FIG. 4 has a good appearance because the shape and size of the fibroin porous body 11 and the liquid absorbent 12 are the same, but at the interface between the fibroin porous body 11 and the liquid absorbent 12. As for the performance of liquid traffic, it is inferior to those without adhesion or pressure bonding.

When adhering the fibroin porous body and the liquid absorbent with an adhesive, it is preferable to suppress the amount of adhesive used as much as possible. For example, after applying the adhesive to only a part of the adhesive surface, it is possible to overlap and adhere Good. As the adhesive, a commercially available resin adhesive can be used. In addition, for example, fibroin can be used like an adhesive by applying an aqueous fibroin solution on the adhesive surface and superimposing and then freezing.
For example, when a resin sponge is used as the liquid absorption, the pressure bonding is performed by heating the surface of the resin sponge to be bonded to the fibroin porous body to a predetermined temperature, and bonding the liquid absorption and the fibroin porous body. A fibroin porous body and a liquid absorbing layer can be laminated and bonded by pressing the periphery.
In the case of a method in which the periphery is pressed at room temperature, it becomes easy to join without heating or the like by giving an appropriate moisture to the periphery of the fibroin porous body in advance. There is no restriction | limiting in particular in the method of giving wetness, For example, the method of giving a water | moisture content with a spray, a brush, etc. is mentioned. The material of the liquid absorbing material in this case is not particularly limited as long as it can be pressed against the fibroin porous body by pressing, and for example, a cotton nonwoven fabric is preferable.

In addition, the medical member of the present invention can also have a configuration as shown in FIG. 5, that is, the medical member 10 of the present invention further includes a fibroin porous body 11b, and the liquid absorbing liquid 12 is a fibroin porous body. A configuration sandwiched between 11a and 11b can also be adopted. In this case, since the peripheral edges of the fibroin porous bodies 11a and 11b are pressure-bonded so as to sandwich the liquid absorbent 12, foreign matter such as an adhesive exists at the interface between the fibroin porous body 11 and the liquid absorbent 12. In addition, since the pores are not crushed by pressure bonding, the flow of liquid is not hindered. On the other hand, since the fibroin porous body 11 is often used, the cost may increase. In addition, although the division | segmentation of the fibroin porous bodies 11a and 11b is not specified in FIG.
The medical member 10 shown in FIG. 5 has a structure in which the fibroin porous bodies 11a and 11b are pressure-bonded. However, the present invention is not limited to the structure in which these porous bodies are pressure-bonded, and the fibroin porous body 11a. And the liquid-absorbing liquid 12 may be bonded or pressure-bonded, and the liquid-absorbing liquid 12 and the fibroin porous body 11b may be bonded or pressure-bonded.

  The medical member shown in FIGS. 1 to 4 is composed of a single fibroin porous body and a liquid absorbing material, but has a plurality of fibroin porous bodies like the medical member shown in FIG. The plurality of fibroin porous bodies may be the same or different. That is, the same fibroin porous body may be the same, different in shape, size and thickness, or different as the porous body, the shape and size. The thickness may be the same or different. Moreover, the liquid absorption may also have a plurality of liquid absorption, and may be the same or different.

  Since the medical member of the present invention can take various configurations, for example, as shown in FIGS. 1 to 5, the hemostatic material can be selected by making the best use of the features of each configuration according to the application. It is possible to cope with various situations required for wound dressings, drug solution sustained release carriers, and the like.

  The medical member of the present invention can be used as it is, or can be used by including a humectant. As the humectant, glycerin, polyvinyl pyrrolidone, polyvinyl alcohol, polyethylene glycol and the like can be used. In the case where the moisturizing agent is included, it is preferable that the moisture content is kept until just before use in a sealed state so as to prevent drying.

  When the medical member of the present invention is used as a drug sustained-release carrier, the drug that can be contained in the member is not particularly limited. For example, proliferation and differentiation of specific cells in an animal body. Promoting endogenous proteins: epidermal growth factor (EGF), insulin-like growth factor (IGF), transforming growth factor (TGF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), platelet derived Fibroblast growth factors (FGF) such as growth factor (PDGF), basic fibroblast growth factor (b-FGF), acidic fibroblast growth factor (a-FGF); hepatocyte growth factor (HGF), etc. Growth factors; antihistamines such as diphenhydrazine hydrochloride, chlorpheniramine, diphenylimidazole; hydrocortisone, prednisolone, Corticosteroids such as lametasone, beclomethasone propionate, flumethasone, betamethasone, beclomethasone propionate, dexitazone, triamcinolone, triamcinolone acetonide, fluocinolone, fluocinolone acetonide, fluocinolone acetonide acetate, clobetasol propionate; acetamino Analgesic and anti-inflammatory agents such as phen, mefenamic acid, flufenamic acid, indomethacin, diclofenac, alclofenac, oxyphenbutazone, phenylbutazone, ibuprofen, flurbibrofen, salicylic acid, methyl salicylate, L-menthol, camphor; penicillin, oxy Tetracycline, fradiomycin sulfate, erythromycin, chloramphenicol, cephalexin, tet Antibiotics cyclin such as Vitamin A, ergocalciferol, cholecalciferol, oct thiamine, vitamins such as riboflavin butyrate; benzocaine, lidocaine, etc. anesthetics such as aminoethyl benzoate preferred. These drugs can be used alone or in combination of two or more.

  In addition to the above-mentioned agents, if necessary, absorption aids such as isopropyl myristate, isopropyl palmitate, N-methylpyrrolidone, N-ethylpyrrolidone, N, N-diethyl-m-triamide, N, N-diethylacetamide, hyaluronic acid, salicylic acid, crotamiton, diethyl sebacate, lauryl alcohol, dimethyl sulfoxide, decimethyl sulfoxide and the like can be blended. By blending these absorption aids, the drug can be absorbed into the barrier membrane by the skin itself, and the function of promoting penetration into blood can be imparted to the drug.

The above-mentioned drug can be added to at least one of the liquid-absorbing material and the fibroin porous body, and can be added to either one or both depending on the amount to be added.
The amount of the above-mentioned drug added is appropriately determined according to the drug to be selected. As a guideline, about 1 μg to 300 mg / 12 cm ² (thickness 2 mm) of drug is absorbed with respect to the drug sustained-release carrier. It is preferable to add so that.
Said chemical | medical agent can be hold | maintained by impregnating or apply | coating at least one of a liquid absorption and a fibroin porous body. Moreover, these chemical | medical agents can be used individually or in combination of multiple types.

  In order to release the drug from the drug sustained-release carrier, it is preferable to keep the silk fibroin porous body in a wet state. When wet therapy is performed at a wound site with exudate, the sustained-released drug can penetrate into the affected area via the exudate. When there is no exudate, it can be used in a wet state with physiological saline or the like.

  EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to these examples.

[Preparation of molecular weight of fibroin raw material]
In order to measure the protein equivalent molecular weight of the fibroin raw material, an aqueous fibroin solution (A) was prepared by the following method.
The fibroin raw material was poured into a 9 mol / L lithium bromide aqueous solution at 20 ° C. so as to have a concentration of 100 g / L, and completely dissolved by stirring for 10 hours. Next, the lysate was centrifuged (rotation speed: 12,000 min ⁻¹ , 5 minutes), and the precipitate was removed by decantation, and then a dialysis tube (trade name: Spectra / Por 1 Dialysis Membrane, MWCO 6,000- 8,000, injected into Spectrum Laboratories, Inc.) for ultrapure water 5L collected from ultrapure water production equipment (PRO-0500 and FPC-0500 (above, model number), manufactured by Organo Corporation) The dialysis for 12 hours was repeated 5 times for desalting. Next, the obtained solution was centrifuged again (rotation speed: 12,000 min ⁻¹ , 30 minutes) to obtain an aqueous fibroin solution (A). The fibroin concentration in the aqueous fibroin solution (A) was measured by the method described above. The obtained fibroin aqueous solution (A) was used as a molecular weight measurement solution of a fibroin raw material.

[Preparation for measurement of protein equivalent molecular weight of aqueous fibroin solution (B)]
The aqueous fibroin solution (B) was prepared by the method described in Example 1 described later, and used as a molecular weight measurement solution.

[Preparation of molecular weight measurement of fibroin contained in fibroin porous material]
In order to measure the molecular weight of fibroin contained in the fibroin porous material, an aqueous fibroin solution (C) was prepared by the following method.
The fibroin porous material was poured into a 9 mol / L lithium bromide aqueous solution at 20 ° C. to a concentration of 100 g / L and completely dissolved by stirring for 10 hours. Next, the lysate was centrifuged (rotation speed: 12,000 min ⁻¹ , 5 minutes), and the precipitate was removed by decantation, and then a dialysis tube (trade name: Spectra / Por 1 Dialysis Membrane, MWCO 6,000- 8,000, injected into Spectrum Laboratories, Inc.) for ultrapure water 5L collected from ultrapure water production equipment (PRO-0500 and FPC-0500 (above, model number), manufactured by Organo Corporation) The dialysis for 12 hours was repeated 5 times for desalting. Next, the obtained solution was centrifuged again (rotation speed: 12,000 min ⁻¹ , 30 minutes) to obtain an aqueous fibroin solution (C). The fibroin concentration in the fibroin aqueous solution (C) was measured by the method described above. The obtained fibroin aqueous solution (C) was used as a molecular weight measurement solution for fibroin contained in the fibroin porous material.

(Preparation of mobile phase)
Put 700 mL of ultrapure water in a glass beaker, and put sodium sulfate (anhydride, Wako Pure Chemical Industries, Ltd., reagent special grade) 14.2 g and urea (Wako Pure Chemical Industries, Ltd., reagent special grade) 120.1 g. The solution thus obtained was immersed in an ultrasonic cleaner with a beaker and subjected to ultrasonic treatment to completely dissolve the solution. To this solution, 20 g of phosphate buffer powder (1.15 mol / L, pH 7.0, manufactured by Wako Pure Chemical Industries, Ltd., for biochemistry) was further added, and ultrasonic treatment was performed again to dissolve. Next, the solution after dissolution was transferred to a measuring flask, made up to 1 L, and stirred to obtain a uniform solution. This solution was used as a mobile phase used for molecular weight measurement.

[Measurement of protein equivalent molecular weight]
When measuring the protein equivalent molecular weight of the fibroin raw material, the fibroin aqueous solution (A) is contained in the fibroin porous material, and when measuring the protein equivalent molecular weight of fibroin contained in the fibroin aqueous solution (B), the fibroin aqueous solution (B) itself is contained in the fibroin porous material. When measuring the protein-equivalent molecular weight of fibroin, each protein-equivalent molecular weight was measured by the following method using an aqueous fibroin solution (C).
Hereinafter, the fibroin aqueous solutions (A) to (C) are referred to as “molecular weight measurement solutions”.
To the molecular weight measurement solution, ultrapure water is added and mixed so that the fibroin concentration becomes 10 g / L, and then the mobile phase is added thereto to dilute it 5 times. The resulting solution is filtered with a 0.45 μm filter (Toyo Roshi). The product was filtered through a trade name, 25HP045AN, manufactured by Co., Ltd., and used as a chromatographic evaluation sample.

  For the measurement, a high-performance liquid chromatograph (HPLC) main body (manufactured by Hitachi High-Technologies Corporation, trade name: Chromamaster (registered trademark)) and an optional UV detector (manufactured by Hitachi High-Technologies Corporation, model number: 5410), In addition to pumps (manufactured by Hitachi High-Technologies Corporation, model number: 5110), autosamplers (manufactured by Hitachi High-Technologies Corporation, model number: 5210), column ovens (manufactured by Hitachi High-Technologies Corporation, model number: 5310), columns (Showa Denko) The HPLC apparatus which combined the product name, SHODEX (trademark) PROTEIN KW-804) by the corporation | Co., Ltd. | KK was used. The measurement conditions were a mobile phase flow rate of 0.5 mL / sec, a column temperature of 30 ° C., and a detection wavelength of UV 220 nm.

  In order to prepare a calibration curve for converting the obtained chromatogram into protein molecular weight, yeast-derived glutamate dehydrogenase (molecular weight: 290,000, Oriental Yeast Co., LTD. Manufactured, trade name: MW-Marker (HPLC)), porcine myocardium-derived lactate dehydrogenase (molecular weight: 142,000, manufactured by Oriental Yeast Co., LTD, trade name: MW-Marker (HPLC)), yeast-derived enolase ( Molecular weight: 67,000, manufactured by Oriental Yeast Co., LTD, trade name: MW-Marker (HPLC)) was used.

  The mobile phase was passed through the HPLC apparatus for 1 hour and waited for the baseline to stabilize. After the baseline was stabilized, 22 μL of an aqueous solution of molecular weight marker dissolved so that each molecular weight marker was 0.05% by mass in the aqueous solution was injected, and a calibration curve was calculated from the peak top of the obtained chromatogram and the molecular weight of the molecular weight marker. Created. The calibration curve is shown in FIG. Subsequently, the protein equivalent molecular weight of fibroin was measured using the calibration curve from the position of the peak top of the chromatogram obtained by injecting 22 μL of the chromatographic evaluation sample.

[Production of porous fibroin]
Example 1
(Alkali refining)
2 L of sodium carbonate aqueous solution was used as a scouring solution, and scouring of sardines was performed under the conditions shown in Table 1. A 3 L glass beaker was used for the scouring container, and heating of scouring was performed while controlling the temperature of a hot stirrer (manufactured by As One Co., Ltd., trade name: CT-5HT) with a K thermocouple, and stirring was appropriately performed with a glass rod. . The obtained scoured slag was thoroughly washed with hot water at 60 ° C. and then washed with pure water. The washed cuttings were naturally dried in a room at 24 ° C. for 2 weeks and completely dried to obtain a fibroin raw material. Next, the reduction rate was calculated according to the following formula. The results are shown in Table 1.
Reduction rate (% by mass) = (mass before scouring−mass after scouring) ÷ mass before scouring × 100
In addition, Table 1 shows the results of preparing the fibroin aqueous solution (A) by the above-described method using the obtained fibroin raw material and measuring the protein equivalent molecular weight of the fibroin raw material.

(Preparation of aqueous fibroin solution (B))
In preparing the fibroin aqueous solution (B), first, the silk fibroin raw material obtained by performing the above alkali scouring is added to 1 L of a 9 mol / L lithium bromide aqueous solution at 20 ° C. so that the concentration becomes 100 g / L. It was completely dissolved by stirring for 10 hours. Next, the lysate was centrifuged (rotation speed: 12,000 min ⁻¹ , 5 minutes), the precipitate was removed by decantation, and then a dialysis tube (trade name: Spectra / Por (registered trademark) 1 Dialysis Membrane, MWCO 6,000-8,000, manufactured by Spectrum Laboratories, Inc.) and ultrapure water sampled from ultrapure water production equipment (PRO-0500 and FPC-0500 (above, model number), manufactured by Organo Corporation) Desalting was performed by repeating dialysis for 12 hours against 5 L of water 5 times. Next, the obtained solution was centrifuged again (rotation speed: 12,000 min ⁻¹ , 30 minutes) to obtain an aqueous fibroin solution (B). The fibroin concentration in the aqueous fibroin solution (B) was measured by the method described above.
Table 1 shows the results of measuring the protein-equivalent molecular weight of fibroin in the fibroin aqueous solution (B) by the above-described method.

(Production of porous fibroin)
Acetic acid and ultrapure water were added to the fibroin aqueous solution (B) so that the fibroin concentration was 30 g / L and the acetic acid concentration was 2.0% (v / v). Next, the obtained solution was poured into a mold made of an aluminum plate (inside size: 400 mm × 300 mm × 10 mm) and cooled to −5 ° C. in advance. And allowed to stand at −5 ° C. for 2 hours. Nybrine (registered trademark) Z1 (trade name, manufactured by MORESCO Co., Ltd.) was used as the refrigerant. Then, it cooled to -20 degreeC with the speed | rate of -3 degreeC / hour, and hold | maintained at the same temperature for 5 hours, and frozen.

  The frozen sample is returned to room temperature by natural thawing, removed from the mold, immersed in ultrapure water, and the acetic acid used is removed by exchanging the ultrapure water twice a day for 3 days. Got the body. Table 1 shows the results of measuring the protein-equivalent molecular weight of fibroin contained in the obtained fibroin porous material by the method described above.

Examples 2-5, 7 and 8
A fibroin porous material was obtained in the same manner as in Example 1 except that the scouring time in Example 1 was changed as shown in Table 1. Table 1 shows the results of measuring the protein-converted molecular weight of fibroin contained in the obtained fibroin raw material, fibroin aqueous solution (B) and fibroin porous material by the method described above.

Example 6
A fibroin porous material was obtained in the same manner as in Example 1 except that the method for preparing the fibroin aqueous solution (B) was changed to the method described below. Table 1 shows the results of measuring the protein-converted molecular weight of fibroin contained in the obtained fibroin raw material, fibroin aqueous solution (B) and fibroin porous material by the method described above.

(Preparation of fibroin aqueous solution (B) -2)
The fibroin aqueous solution (B) has a fibroin concentration of 100 g / L in 1 L of a solution obtained by mixing silk fibroin raw material obtained by alkali scouring with calcium chloride, ethanol and water at 20 ° C. in a molar ratio of 1: 2: 8. The solution was completely dissolved by heating and stirring at 80 ° C. for 40 minutes. Next, the lysate was centrifuged (rotation speed: 12,000 min ⁻¹ , 5 minutes), and the precipitate was removed by decantation, and then a dialysis tube (trade name: Spectra / Por 1 Dialysis Membrane, MWCO 6,000- 8,000, injected into Spectrum Laboratories, Inc.) for ultrapure water 5L collected from ultrapure water production equipment (PRO-0500 and FPC-0500 (above, model number), manufactured by Organo Corporation) The dialysis for 12 hours was repeated 5 times for desalting. Next, the obtained solution was centrifuged again (rotation speed: 12,000 min ⁻¹ , 30 minutes) to obtain an aqueous fibroin solution (B). The fibroin concentration in the aqueous fibroin solution (B) was measured by the method described above.

[Evaluation of mechanical strength]
About the fibroin porous body obtained above, 25% compressive stress, tear strength, tensile strength, and tensile strain were measured under the following conditions. The results are shown in Table 1.

(Measurement of 25% compressive stress)
For the fibroin porous material, a universal testing machine (model number: EZ- (N) S, manufactured by Shimadzu Corporation) was used, the load cell was 50 N, a circular compression plate having a diameter of 8 mm was used as a jig, and the compression speed was 1 mm / Under the conditions of min and 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 formula was 25% compression stress (kPa).
25% compressive stress (kPa) = Load / compression plate area (mm ² ) × 1000 when 25% of the thickness of the material is pressed with the compression plate

(Measurement of tear strength)
About a test piece of fibroin porous material punched into a trouser shape with a size of 100 mm × 15 mm and a cut of 40 mm in length, a universal testing machine (model number: EZ- (N) S, manufactured by Shimadzu Corporation) ), The load cell is 50 N, the gripping tool is a jig for tensile testing, the tearing speed is 200 mm / min, the initial gripping distance is 40 mm, and the median tearing force is measured at a room temperature of 22 ° C. The value calculated by the equation was taken as the tear strength.
Tearing strength = median tearing force (N) / test specimen thickness (mm)

(Measurement of tensile strength and tensile strain)
Using a universal testing machine (model number: EZ- (N) S, manufactured by Shimadzu Corporation) for a test piece of fibroin porous material punched into a size of 50 mm × 5 mm, the load cell is 50 N, and the gripping tool is for tensile test The test piece was pulled under the conditions of a tensile speed of 5 mm / min, a distance between initial grips of 30 mm, and a room temperature of 22 ° C., and the stress and strain when the test piece broke were taken as tensile strength and tensile strain, respectively. .

  As can be seen from Table 1, in Examples 1 to 8, the reduction rate was about 31% by mass, and sericin was almost completely removed.

From Table 1, it was found that in Examples 1 to 7, the 25% compressive stress of the fibroin porous material was lower than that of Example 8 having a high molecular weight and was more excellent in flexibility.
From Table 1, it was found that in Examples 1 to 6 and 8, the tear strength of the fibroin porous material was higher than that of Example 7 having a low molecular weight and was more excellent in mechanical strength.
From Table 1, it was found that in Examples 1 to 6 and 8, the tensile strength of the fibroin porous body was higher than that of Example 7 having a low molecular weight and was more excellent in mechanical strength.
From Table 1, in Examples 1-6, it turned out that the tensile strain of a fibroin porous body is higher compared with Examples 7 and 8 whose molecular weight is higher or lower, and is more excellent in elasticity.

From Table 1, in Examples 1 to 6, the protein equivalent molecular weight of the fibroin raw material and the fibroin aqueous solution was 168,000 to 403,000, but in Example 7, which has a long scouring time, 126,000, the scouring time was short. In Example 8, it was 731,000, and it was found that the molecular weight decreased as the scouring time increased.
From Table 1, in Examples 1 to 6, the protein equivalent molecular weight of the fibroin porous material was 111,000 to 308,000, but in Example 7 having a long scouring time, 92,000, an example having a short scouring time. 8 was 592,000, and it was found that the molecular weight decreased as the scouring time increased.

  From the above results, the protein equivalent molecular weight of the fibroin aqueous solution prepared using the fibroin raw material having a protein equivalent molecular weight of 160,000 to 410,000 is 160,000 to 410,000, and the fibroin aqueous solution is used. The produced fibroin porous material has a protein equivalent molecular weight of 110,000 to 310,000, and the fibroin porous material having such a protein equivalent molecular weight is excellent in mechanical strength, stretchability and flexibility. I found out.

[Measurement of blood coagulation time (evaluation of hemostasis performance)]
Example 9, Comparative Examples 1-4
(1) Test substance First, the fibroin porous material produced in Example 4 was immersed in a 3% by volume glycerin aqueous solution for 48 hours, and then allowed to stand still in a freezer at -25 ° C for 10 hours to completely freeze it. The water of the frozen fibroin porous body was completely sublimated using a freeze dryer to prepare a dried fibroin porous body (porous body A).
As a test substance, this dried fibroin porous body (porous body A), gelatin sponge (manufactured by Astellas Pharma Inc., trade name: Sponzel), chitin sponge (manufactured by Nipro Corporation, trade name: vesquitin F (N)) And an alginate nonwoven fabric (manufactured by Smith & Nephew Co., Ltd., trade name: Algodarm Trionic).

(2) Sample blood Informed consent was performed, and about 40 ml of blood was collected from 3 healthy subjects in the absence of anticoagulant, and the collected blood was designated as blood A, B, and C, respectively. The sample blood was not stored and was used immediately after blood collection.

(3) Measurement of blood coagulation time First, two sets of 300 mm ³ samples were cut out from each of the four types of test substances, and one set of each test substance was placed in two test tubes subjected to siliconization treatment. Two empty test tubes were used as blanks.
After each test tube was heated at 37 ° C. in advance, 1.5 mL (200 mm ³ / mL) of blood A immediately after blood collection was added to each test tube, and a timer was started. The first test tube of each test substance was tilted every 30 seconds, and the blood fluidity was visually observed. Furthermore, after blood coagulation was observed in the first test tube, the second test tube was tilted every 30 seconds, and the blood fluidity was visually confirmed.
The time from the start of blood collection to the time when blood coagulation was observed in the second test tube was defined as the blood coagulation time. The same operation was repeated for blood B and C, and the blood coagulation time was measured. The average value of blood A to C was taken as the blood clotting time of each test substance. The results are shown in Table 2.

  From Table 2, it was found that the porous body A used in the present invention was able to shorten the blood coagulation time as compared with Comparative Example 1 in which no porous body was used, and had a hemostatic effect. Further, it was found that the porous material A used in the present invention has a shorter blood coagulation time than gelatin sponge, has a hemostatic effect equivalent to chitin sponge and alginic acid nonwoven fabric, and is suitable as a hemostatic material. From these results, it was confirmed that the medical member of the present invention can effectively stop hemostasis by arranging the porous body A in a portion in contact with the bleeding site and has an excellent hemostasis effect. .

[Measurement of adherence to living body (evaluation of ease of removal from living body) and evaluation of suitability of wound dressing]
Example 10, Comparative Examples 5-9
(1) Test substance As test substances, dry fibroin porous material (porous material A) produced in Example 9, urethane sponge (manufactured by Smith and Nephew Co., Ltd., trade name: Hydrosite Plus), alginate nonwoven fabric (Smith & Nephew Co., Ltd., trade name: Algoderm Trionic), Non-adhesive gauze (Smith & Nephew Co., Ltd., trade name: Meloline (sterilized)), and hydrocolloid dressing (Three M Japan Co., Ltd., product) Name: Tegaderm hydrocolloid, hereinafter referred to as hydrocolloid).

(2) Test method (measurement of average bond strength)
(Preparation of pressure ulcer model)
Rats (Slc: SD (SPF) 8 weeks old, Nippon SLC Co., Ltd.) were used for the test. Apply an electric hair clipper (Daito Denki Kogyo Co., Ltd., trade name: ELECTRIC CLIPPER MODEL 5500) and an electric shaver (Seiko Syard Co., Ltd., trade name: Cleancut ES-412) over the skin on the right third trochanter in advance. The rats, which had been depilated, were intraperitoneally administered with 50 mg / kg of pentobarbital sodium, further anesthetized by intraperitoneal administration of 20 mg / kg of allobarbital, and fixed in the abdominal position on a wooden fixing plate. Absorbent cotton is put as a cushion between the thigh and the fixing plate, and a 1.02 to 1.03 kg stainless steel rod (diameter 19 mm, diameter 12 mm) is attached to the skin on the right third trochanter. A length of 50 cm) was applied, and pressure loading (902.3 to 911.2 g / cm ² ) was performed for 24 hours. During the pressure loading time, additional anesthesia of sodium pentobarbital and allobarbital was performed. After 24 hours, the pressure load was released and a 5% aqueous glucose solution was orally administered, and 2 days after the release of the pressure load, the necrotic skin was removed surgically under isoflurane anesthesia to obtain a pressure ulcer model.

(Wound site treatment and administration of test substance)
Cover the test substance cut into 2cm square on the pressure ulcer prepared in the rat, cover it with gauze (made by White Cross Co., Ltd.) cut into 3cm square from above, dressing film cut by 4cm square (made by Smith and Nephew Co., Ltd.) , Trade name: Opsite Gentle Roll). Furthermore, the elastic bandage elastic pore No. cut to 5 cm square. Two 50 (made by Nichiban Co., Ltd.) were crossed and pasted, and elastic bandage Elastopore No. 12 (Nichiban Co., Ltd., 1.2 × 60 cm). For the hydrocolloid dressing, the release paper was peeled off and the adhesive surface was applied so that it touched the wound, covered with gauze, and then fixed with an elastic bandage. The test substance was replaced with a new one every two days until the pressure ulcer was completely healed. At the time of exchanging the test substance, the strength of fixation to the wound was measured by the following method. In addition, before applying a new test substance, the wound was wiped with absorbent cotton soaked in physiological saline (manufactured by Otsuka Pharmaceutical Factory). Further, the timing at which the wound was completely epithelialized was determined as healing, and the number of days from the day when each test substance was applied to the day when the wound was completely epithelialized was defined as the number of healing days. Table 3 shows the healing days.

(Measurement of strength of adhesion to wound)
The strength of adhesion of the test substance to the wound was measured with a hanging balance (manufactured by Tenroku Shoji Co., Ltd., high-precision optical digital force gauge). After removing the elastic bandages that were fixed so as not to peel off the test substance when the test substance was exchanged, the test substance was peeled off by pulling the test substance vertically with a hanging balance. The maximum value of the weight at that time was read and recorded, and the average adhesion strength to the wound at the time of replacement of each test substance was calculated according to the following formula. Table 3 shows the calculated average fixing strength.
Average sticking strength (g) = (total sum of weights shown by the hanging scale at the time of each test substance exchange until the pressure ulcer heals (g)) / (number of times each test substance is exchanged)

From Table 3, it was found that the porous body A has a small fixing force to the wound part and can be easily removed from the living body.
When the medical member of the present invention was applied, it was confirmed that the number of days required for healing was shortened compared to the case where gauze was applied to the wound. Moreover, it turned out that it is comparable with the material known as the wound dressing material for the existing wet therapy used in a comparative example. From these results, by disposing this porous body A in the part in contact with the wound part, the medical member of the present invention is not only a hemostatic effect that is a performance as a hemostatic material, but also applied to the wound part, It was confirmed that a healing promoting effect can be expected and it is also suitable as a wound dressing.

Example 11, Comparative Examples 10-12
When the content of glycerin in the dried fibroin porous material (porous material A) produced in Example 9 was evaluated by the following method, it was 41.9% by mass.

(Measurement of glycerin content)
The glycerin content (% by mass) in the dry fibroin porous material is obtained by dividing the mass of glycerin introduced into the dry fibroin porous material by the mass of the dry fibroin porous material after the glycerin is introduced. It was calculated by the following formula.
(Content of glycerin in dry fibroin porous material (mass%)) = ((mass of dry fibroin porous material into which glycerin has been introduced) − (mass of dry fibroin porous material into which glycerin has not been introduced)) / ( Mass of dry fibroin porous material after introduction of glycerin) × 100

(Production of medical materials)
A superabsorbent nonwoven fabric processed by 50 mm × 50 mm × 2 mm (trade name: K0230WHR, a thin nonwoven fabric using Bel Oasis (registered trademark)) processed to 50 mm × 50 mm × 2 mm on the dried fibroin porous body described above. Overlap with a margin of 5 mm at the periphery, and then coat the porous body and the superabsorbent nonwoven fabric with an adhesive film (Smith & Nephew Co., Ltd., trade name: Hydrocytogent roll) from the superabsorbent nonwoven fabric side The medical member was produced by stacking as described above.

  As the medical member obtained in Example 11 and Comparative Example 10, the dried fibroin porous material produced in Example 9 whose apparent volume is the same as the total of the medical member and the nonwoven fabric is referred to as Comparative Example 11. A non-adhesive gauze (Smith and Nephew) having the same apparent volume as Comparative Example 12 was used as Comparative Example 12 with an alginate nonwoven fabric (Smith & Nephew Co., Ltd., trade name: Algoderm Trionic) having the same apparent volume as Comparative Example 10. A water retention test and evaluation of the liquid return rate were performed under the following conditions using a product name: Meroline (sterilized) manufactured by Co., Ltd. as a test substance. The results are shown in Table 4.

(Water retention test)
The test substance was weighed (the mass at this time was defined as the dry mass) and then immersed in ultrapure water for 1 minute. Next, after being held on a wire net for 2 minutes, it was weighed again (the mass at this time is defined as a wet mass), and the water absorption per apparent volume was calculated according to the following formula to evaluate water retention.
Water absorption per apparent volume (g / cm ³ ) = (wet mass (g) −dry mass (g)) / apparent volume of test substance (cm ³ )

(Evaluation of liquid return rate)
The aluminum plate was placed so as to be inclined at 20 ° C. with respect to the ground, and the test substance in the same state as that used for weighing the wet mass in the water retention test was left on the aluminum plate. Next, a 2 kg cylindrical weight having a diameter of 65 mm was placed on the test substance and allowed to stand for 1 minute. After 1 minute, the aluminum plate was shaken to shake off moisture from the test substance, and then the weight was removed and the test substance was weighed (the mass at this time is the mass after pressurization). The liquid return rate was evaluated according to the following formula.
Liquid return rate = 100 − ((mass after pressurization−dry mass) / (wet mass−dry mass))

  From the results of Example 11, it was found that the medical member of the present invention has high water retention. Furthermore, the medical member of Example 11 is used as a wound dressing because there is little liquid return when pressure is applied, and blood and exudate do not return when external pressure is applied during use. In some cases, a moderately moist state can be maintained, and as a hemostatic material, blood hardly oozes out when the wound is filled. On the other hand, in the case of the porous body A alone of Comparative Example 10, the water absorption amount and the liquid return rate do not reach Example 11 combined with the superabsorbent nonwoven fabric, and the fibroin porous body and the liquid absorbent of the present invention are not affected. The excellent effect by the combination with was confirmed. Further, the members of Comparative Examples 11 and 12 also had a water absorption amount and a liquid return rate that did not reach the medical member of the present invention.

  The medical member of the present invention is excellent in safety for a living body, has a short hemostatic time, has an excellent hemostatic effect, can be easily removed from a living body, has mechanical strength, flexibility, and liquid return when pressure is applied. It has excellent suppression performance and can cope with various situations. Therefore, for example, it can be suitably used as a hemostatic material for stopping hemostasis by compressing the affected area, as a wound covering material used for healing of the affected area, and further as a drug sustained release carrier for gradually supplying the drug to the affected area.

10. Medical member 11. Fibroin porous material 12. Absorbing liquid 13. Adhesive film

Claims (11)

  The medical member which has a liquid absorption and a fibroin porous body.   The adhesive film further includes an adhesive film, and the adhesive film covers the liquid absorbent and the fibroin porous body from the liquid absorbent side so that the adhesive film, the liquid absorbent and the fibroin porous body are laminated in this order. 2. The medical use according to claim 1, wherein the surface of the fibroin porous body opposite to the side on which the liquid-absorbing liquid is laminated and the surface opposite to the adhesive film is exposed. Element.   The medical member according to claim 1 or 2, further comprising a fibroin porous body, wherein the liquid absorption is sandwiched between the fibroin porous bodies.   The medical member according to any one of claims 1 to 3, wherein the fibroin porous body has a thickness of 0.1 to 50 mm.   The medical member according to any one of claims 1 to 4, wherein the thickness of the liquid absorption is 0.1 to 50 mm.   The medical member according to any one of claims 1 to 5, wherein the fibroin porous material contains fibroin having a protein-equivalent molecular weight of 110,000 to 310,000.   The medical member according to any one of claims 1 to 6, wherein the fibroin porous body is composed of silk fibroin.   The medical member according to any one of claims 1 to 7, wherein the fibroin porous body contains 20 to 75 mass% of a hydroxyl group-containing compound having a molecular weight of 1,000 or less.   The hydroxyl group-containing compound is at least one selected from glycerin, polyglycerin, polyethylene glycol, triethyl citrate, lactic acid, polyvinyl alcohol, propylene glycol, butylene glycol, alcohol, glycerin fatty acid ester, polyglycerin fatty acid ester, and sorbitan fatty acid ester. The medical member according to claim 8.   The medical member according to any one of claims 1 to 9, wherein the liquid absorbing material is at least one selected from a resin sponge, a rubber sponge, a nonwoven fabric, and a liquid absorbing polymer material.   The medical member according to any one of claims 1 to 10, which is used as a hemostatic material, a wound dressing material, or a drug sustained-release carrier.