Resin composition, medical material, and method for producing resin composition

Abstract

Provided is a resin composition that contains a first polymer compound and a second polymer compound. The first polymer compound has, in the main chain, a first repeat unit in which a plurality of amino acid residues are bonded by peptide bonds. The second polymer compound has, at a terminal of a side chain, a peptide chain or polypeptide chain in which a plurality of amino acid residues are bonded by peptide bonds. The plurality of amino acid residues constituting the first repeat unit of the first polymer compound contains amino acid residues deriving from at least two amino acids selected from the group consisting of glycine, alanine, serine, tyrosine, and valine. The plurality of amino acid residues constituting the peptide chain or polypeptide chain of the second polymer compound contains amino acid residues deriving from at least two of the amino acids that constitute the first repeat unit.

Description

Resin composition, medical material, and method for producing resin composition

[0001] The present invention relates to a resin composition, a medical material, and a method for producing the resin composition.

[0002] Patent Document 1 discloses a porous body having a porous portion and a coating portion containing silk fibroin and alcohol. Patent Document 2 discloses a regenerated silk fibroin fiber containing a polyurethane resin composition that combines strength and flexibility. Patent Document 3 discloses a silk fibroin biocompatible polyurethane membrane matrix. Non-Patent Documents 1 to 6 disclose composite materials obtained by mixing polyurethane and silk fibroin. (Prior Art Documents) (Patent Documents) (Patent Document 1) JP 2017-052829 A (Patent Document 2) JP 2018-193624 A (Patent Document 3) JP 2019-511339 A (Non-Patent Documents) (Non-Patent Document 1) Yasuhiro Fukuda et al. , "Relationship between structure and physical strength of silk fibroin nanofiber sheet dependent on "insolution treatment", Journal of Applied Polymer Science, 2017, Vol. 134, No. 32, 45560 (Non-patent Document 2) Chikako T Nakazawa, et al. , "Solid-state NMR studies for the development of non-woven biomaterials based on silk fibroin and Polyurethane", Polymer Journal, 2017, 49, p. 583-586 (Non-patent Document 3) Derya Aytemiz et al. , "Compatibility Evaluation of Non-Woven Sheet Composite of Silk Fibroin and Polyurethane in the Wet "State", Polymers, 2018, Vol. 10, No.8,874 (Non-patent Document 4) Kazumi Shimada et al. , "The effect of a silk Fibroin / Polyurethane blend patch on rat Vessels", Organogenesis, 2017, Vol. 13, No. 4, 115-124 (Non-Patent Document 5) Chantawong P et al. , "Effect of silk fibroin concentration on vascular remodeling in rat model", Journal of Materials Science: Materials in Medicine, 2017, 28, 191 (Non-Patent Document 6) Shimada, R. et al. , "Development of a new surgical sheet containing both silk fibroin and thermoplastic polyurethane for cardiovascular Surgery", Surgery Today, 2017, 48, 486-494. General disclosure

[0003] In a first aspect of the present invention, a resin composition is provided. The resin composition includes, for example, a first polymer compound and a second polymer compound. In the resin composition, the first compound has, for example, a first repeating unit in the main chain, in which a plurality of amino acid residues are peptide-bonded. In the resin composition, the second polymer compound has, for example, a peptide chain or polypeptide chain in which a plurality of amino acid residues are peptide-bonded at the end of a side chain. In the resin composition, the plurality of amino acid residues constituting the first repeating unit of the first polymer compound include, for example, amino acid residues derived from at least two amino acids selected from the group consisting of glycine, alanine, serine, tyrosine, and valine. In the resin composition, the plurality of amino acid residues constituting the peptide chain or polypeptide chain of the second polymer compound include, for example, amino acid residues derived from at least two amino acids constituting the first repeating unit.

[0004] In any of the above resin compositions, the plurality of amino acid residues constituting the first repeating unit of the first polymer compound may include amino acid residues derived from at least two amino acids selected from the group consisting of glycine, alanine, and serine. In any of the above resin compositions, the first polymer compound may have 1 to 30 first repeating units.

[0005] In any of the above resin compositions, the polypeptide chain may have a second repeating unit formed by peptide bonds of multiple amino acid residues. In any of the above resin compositions, the multiple amino acid residues constituting the second repeating unit may include amino acid residues derived from at least two types of amino acids constituting the first repeating unit. In any of the above resin compositions, the polypeptide chain may have 1 to 50 second repeating units.

[0006] In any of the above resin compositions, the side chain of the second polymer compound may include a peptide chain or a polypeptide chain. The side chain of the second polymer compound may include a peptide chain or a polypeptide chain and a linker connecting the main chain of the second polymer compound. In any of the above resin compositions, the second polymer compound may include a first side chain having a peptide chain or a polypeptide chain at its terminal. The second polymer compound may include a second side chain having a functional peptide, an ester group, or a substituted or unsubstituted amide group at its terminal.

[0007] In any of the above resin compositions, the first polymer compound may be fibroin or a derivative thereof. In any of the above resin compositions, the second polymer compound is selected from the group consisting of polyurethane, poly-D-lactic acid (PDLA), poly-L-lactic acid (PLLA), poly-DL-lactic acid (PDLLA), poly(ε-caprolactone) (PCL), polyglactin, polyethylene carbonate, polyglycolic acid (PGA), collagen, gelatin, chitosan, casein, keratin, sericin, polymethyl methacrylate (PMMA), polyamide, cellulose, polyhydroxyalkanoate (PHA), polybutylene succinate (PBS), glucose, polyvinyl alcohol (PVA), polyester, polyhydroxybutyric acid (PHB), polymalic acid (PMA), poly(p-dioxanone) (PDS, PDO), polypropylene glycol (PPG), poly(lactic-co-glycolic acid copolymer) (PLGA), polybutylene succinate (PBS), hydroxyapatite, poly The polymer may include at least one polymer compound selected from the group consisting of butylene adipate-co-terephthalate (PBAT), polyethylene adipate terephthalate (PEAT), tetrapolyethylene glycol (PTE), sodium polyacrylate (SAP), poly(sodium 4-styrenesulfonate) (PSS), polydiallyldimethylammonium chloride (PDDA), poly(2-methoxyethyl acrylate) (PMEA), polyacrylic acid (PAA), polyethyl acrylate (PEA), polybutyl acrylate (PBA), polyacrylamide (PAM), polymethacrylic acid, polymaleic anhydride, and polytrimethylene carbonate (PTMC), as well as derivatives thereof, and which has a peptide chain or polypeptide chain formed by peptide bonds between a plurality of amino acid residues at the end of its side chain.

[0008] In any of the above resin compositions, the mass ratio of the first polymer compound to the second polymer compound may be 1:99 to 99:1. Any of the above resin compositions may have the following shape: (i) fiber, (ii) nonwoven fabric, (iii) sheet or film, (iv) tube or roll, or (v) block, sponge, pad, or columnar.

[0009] In a second aspect of the present invention, a medical material is provided. The medical material includes, for example, any of the resin compositions according to the first aspect. The medical material may be an artificial blood vessel, a cardiac repair patch, an artificial valve, a drug-releasing material, an adhesion barrier, an artificial bone, an artificial cartilage, or a wound dressing.

[0010] A third aspect of the present invention provides a method for producing a resin composition. The method includes, for example, preparing a first polymer compound having a first repeating unit in its main chain, the first repeating unit being composed of multiple amino acid residues linked by peptide bonds. The method also includes, for example, preparing a second polymer compound having a peptide or polypeptide chain at the end of its side chain, the peptide or polypeptide chain being composed of multiple amino acid residues linked by peptide bonds. The method also includes, for example, mixing the first polymer compound with the second polymer compound to produce a resin composition containing the first polymer compound and the second polymer compound. In the method, the multiple amino acid residues constituting the repeating unit of the first polymer compound include, for example, amino acid residues derived from at least two amino acids selected from the group consisting of glycine, alanine, serine, tyrosine, and valine. In the method, the multiple amino acid residues constituting the peptide or polypeptide chain of the second polymer compound include, for example, at least two amino acid residues constituting the first repeating unit.

[0011] In the above method, the step of preparing a second polymer compound may include a step of preparing a third polymer compound, which is a polymer compound different from the first polymer compound and the second polymer compound and has at least one of a carboxy group and an amino group introduced into its main chain. In the above method, the step of preparing the second polymer compound may include a step of preparing a peptide or polypeptide containing at least two types of amino acid residues constituting the first repeating unit. In the above method, the step of preparing the second polymer compound may include a step of reacting at least one of a carboxy group and an amino group of the third polymer compound with the peptide or polypeptide to produce the second polymer compound. In the above method, the ratio of the number of moles of either the carboxy group or the amino group of the third polymer compound to the number of moles of either the functional group modified by the peptide or polypeptide may be 0.1 or more and 1 or less.

[0012] The above summary of the invention does not list all of the necessary features of the present invention, and subcombinations of these features may also constitute inventions.

[0013] 1 shows an SEM image of the appearance of Example 1. 2 shows an SEM image of the appearance of Comparative Example 1. 3 shows an SEM image of the appearance of Comparative Example 2. 4 shows the test results of the infiltration tensile test of the Examples and Comparative Examples. 5 shows the test results of the Young's modulus of the Examples and Comparative Examples. 6 shows the test results of the maximum stress of the Examples and Comparative Examples. 7 shows the test results of the yield stress of the Examples and Comparative Examples. 8 shows the test results of the elongation at break of the Examples and Comparative Examples. 9 shows the test results of the yield elongation of the Examples and Comparative Examples.

[0014] The present invention will be described below through embodiments of the invention, but the following embodiments do not limit the scope of the invention. Furthermore, not all of the combinations of features described in the embodiments are necessarily essential to the solution of the invention. In the drawings, the same reference numerals are used to designate the same or similar parts, and redundant explanations may be omitted.

[0015] I. Overview of Resin Composition

[0016] According to this embodiment, a resin composition is provided that includes: (A) a polymer compound (sometimes referred to as a first polymer compound) having, in its main chain, a repeating unit (sometimes referred to as a first repeating unit) in which a plurality of amino acid residues are peptide-bonded; and (B) a polymer compound (sometimes referred to as a second polymer compound) having, at the end of its side chain, a peptide chain or polypeptide chain in which a plurality of amino acid residues are peptide-bonded. The resin composition can be obtained, for example, by mixing the first polymer compound and the second polymer compound.

[0017] In this embodiment, the monomer or combination of monomers constituting the first polymer compound is different from the monomer or combination of monomers constituting the second polymer compound, i.e., the first polymer compound and the second polymer compound are different in type.

[0018] In recent years, polymer blends have been developed by mixing different polymers to develop materials with new properties and / or functions distinct from those of the individual polymers that make up the polymer blend. However, because different polymers are generally thermodynamically incompatible with each other, the adhesion at the interface between the different polymers that make up the polymer blend is reduced. This reduction in adhesion at the interface between different polymers can affect the mechanical properties and / or degradation behavior of the polymer blend. Examples of degradation behavior include material degradation over long-term use and peeling between different polymers.

[0019] The inventors came up with the idea of ​​providing a structure at the end of the side chain of one polymer that interacts relatively strongly with the repeating units of the other polymer. This local interaction at the interface between different polymers improves the mutual solubility (sometimes referred to as compatibility) between the different polymers. As a result, the adhesion at the interface between the different polymers improves, improving the mechanical properties of the polymer blend. Examples of mechanical properties include maximum stress, yield stress, elongation at break, elongation at yield, and Young's modulus.

[0020] The inventors have come up with the idea of ​​applying the above-mentioned concept to polymer blends of fibroin and other types of polymers. Fibroin has excellent biocompatibility. Therefore, fibroin-containing materials are suitable for use as medical materials or scaffold materials for cell culture. In particular, fibroin-containing materials with improved mechanical properties are particularly suitable for use as medical materials that require mechanical properties tailored to the application in addition to cell affinity, low inflammation, and / or blood compatibility.

[0021] (A. First Polymer Compound) In this embodiment, the first polymer compound has a repeating unit (as described above, sometimes referred to as a first repeating unit) in which a plurality of amino acid residues are bonded in the main chain. By reacting the plurality of amino acids, a repeating unit in which a plurality of amino acid residues derived from each of the plurality of amino acids are bonded via peptide bonds is obtained.

[0022] The amino acid may be an α-amino acid in which the amino group and the carboxy group are bonded to the same carbon atom. At least some of the amino acids constituting the first repeating unit may be α-amino acids. All of the amino acids constituting the first repeating unit may be α-amino acids. Each of the plurality of amino acids may be, independently of one another, an α-amino acid selected from the group consisting of glycine (Gly or G), alanine (Ala or A), valine (Val or V), leucine (Leu or L), isoleucine (Ile or I), serine (Ser or S), threonine (Thr or T), aspartic acid (Asp or D), glutamic acid (Glu or E), lysine (Lys or K), arginine (Arg or R), phenylalanine (Phe or F), tyrosine (Tyr or Y), tryptophan (Trp or W), histidine (His or H), proline (Pro or P), cysteine ​​(Cys or C), methionine (Met or M), asparagine (Asn or N), and glutamine (Gln or Q).

[0023] The first polymer compound may be a polypeptide or protein formed by peptide-bonding a plurality of amino acid residues, or a derivative thereof. By reacting a plurality of amino acids, a polypeptide or protein is obtained in which a plurality of amino acid residues derived from each of the plurality of amino acids are peptide-bonded. The N-terminal amino acid and the C-terminal amino acid constituting the polypeptide or protein may be included in the above amino acid residues.

[0024] The first polymer compound may be fibroin or a derivative thereof. When the first polymer compound is fibroin or a derivative thereof, the plurality of amino acid residues constituting the first repeating unit include, for example, amino acid residues derived from at least two kinds of amino acids selected from the group consisting of glycine, alanine, serine, tyrosine, and valine.

[0025] Fibroin contains crystalline and semi-crystalline regions. The proportion of crystalline regions in fibroin is approximately 53 mol %, and the proportion of semi-crystalline regions in fibroin is approximately 27 mol %. The repeating amino acid sequence in the crystalline region of fibroin is (GAGAS) ｎ where n is an integer between 1 and 20. The repeating amino acid sequence of the semi-crystalline region of fibroin is ((GX) ｓ GY) ｔ Here, X is A or V. Furthermore, s is, for example, an integer of 1 to 10, and t is, for example, an integer of 1 to 20.

[0026] In one embodiment, the plurality of amino acid residues constituting the first repeat unit described above comprises amino acid residues derived from at least two amino acids selected from the group consisting of glycine, alanine, and serine, and the amino acid sequence of the first repeat unit may be identical to the repetitive amino acid sequence or a portion thereof of the crystalline region of fibroin.

[0027] As described below, the first polymer compound containing fibroin is not limited to fibroin derived from natural silk, and therefore the first polymer compound may contain a repetitive amino acid sequence different from the repetitive amino acid sequence contained in fibroin derived from natural silk.

[0028] The amino acid sequence of the first repeating unit may be GA, AG, or AS. The amino acid sequence of the first repeating unit may be GAG, AGA, GGA, GAS, or any sequence containing these. The amino acid sequence of the first repeating unit may be GAGA, AGAS, or any sequence containing these. In these cases, the first polymer compound has, for example, 1 to 30 first repeating units. The first polymer compound may have 1 to 20 first repeating units. The first polymer compound may have 2 to 6 first repeating units.

[0029] In another embodiment, the plurality of amino acid residues constituting the first repeat unit described above comprises amino acid residues derived from at least two amino acids selected from the group consisting of glycine, alanine, tyrosine and valine. The amino acid sequence of the first repeat unit may be identical to the repetitive amino acid sequence or a portion thereof of a semicrystalline region of fibroin.

[0030] As described above, the first polymeric compound containing fibroin is not limited to fibroin derived from natural silk, and therefore the first polymeric compound may contain a repetitive amino acid sequence different from the repetitive amino acid sequence contained in fibroin derived from natural silk.

[0031] The amino acid sequence of the first repeating unit may be GY, GA or AG, GV or VG, or any sequence containing these. The amino acid sequence of the first repeating unit may be GGY, AGY, VGY, or any sequence containing these. In these cases, the first polymer compound has, for example, 1 to 30 first repeating units. The first polymer compound may have 1 to 20 first repeating units. The first polymer compound may have 2 to 6 first repeating units.

[0032] More specifically, the amino acid sequence of the first repeating unit may be GG or GA. In this case, the first polymer compound may have, for example, 1 to 20 first repeating units, or the first polymer compound may have 2 to 6 first repeating units.

[0033] (Method of Producing Fibroin) In one embodiment, the fibroin may be silk fibroin derived from natural silk produced by silkworms or spiders. Preferably, the fibroin is silk fibroin derived from silk produced by silkworms (sometimes referred to as silkworm silk). In another embodiment, the fibroin may be derived from a silk protein produced by genetic engineering. Examples of genetically engineered silk proteins include silk proteins produced by bacteria, yeast, animal or plant cells, transgenic plants, transgenic animals, etc. that have been genetically modified to produce silk proteins. Genetically engineered silk proteins include, for example, silk protein repeat sequences of fibroin.

[0034] In silkworm silk, fibroin is coated with sericin. Fibroin derived from natural silkworm silk can be obtained by removing sericin from silkworm silk. In one embodiment, the composition may contain 10 to 35% by mass of sericin as an impurity relative to the mass of fibroin. In another embodiment, the content of sericin in the composition is preferably less than 20% (mass ratio) relative to the mass of fibroin, more preferably less than 10% (mass ratio), and even more preferably less than 5% (mass ratio).

[0035] (Fibroin Derivatives) Examples of fibroin derivatives include compounds in which fibroin is partially modified with any functional group. As described above, the fibroin may be derived from natural silk or may be derived from a genetically engineered silk protein.

[0036] (B. Second Polymer Compound) In this embodiment, the second polymer compound has a peptide chain or polypeptide chain formed by peptide bonds between multiple amino acid residues at the end of a side chain. By reacting multiple amino acids, a peptide chain or polypeptide chain is obtained in which multiple amino acid residues derived from each of the multiple amino acids are bonded. The N-terminal amino acid and C-terminal amino acid constituting the peptide chain or polypeptide chain may be included in the above amino acid residues.

[0037] (Main Chain) In this embodiment, the monomers constituting the main chain of the second polymer compound are not particularly limited. The main chain of the second polymer compound may be constituted by a plurality of types of monomers.

[0038] (Side Chain) As described above, in this embodiment, a peptide chain or polypeptide chain formed by peptide bonds of multiple amino acid residues is arranged at the end of the side chain of the second polymer compound. The multiple amino acid residues constituting the peptide chain or polypeptide chain may include amino acid residues derived from at least two types of amino acids constituting the first repeating unit described above.

[0039] This allows for local interactions between the peptide or polypeptide chain and the first repeating unit when the first polymer compound and the second polymer compound are mixed to form a resin composition, improving the compatibility between the first polymer compound and the second polymer compound. As a result, a resin composition having excellent mechanical properties can be obtained. As described above, examples of mechanical properties include maximum stress, yield stress, elongation at break, elongation at yield, and Young's modulus.

[0040] As described above, in this embodiment, the plurality of amino acid residues constituting the peptide or polypeptide chain may, for example, include amino acid residues derived from at least two types of amino acids constituting the first repeat unit. The amino acid sequence of the peptide or polypeptide chain may be identical to a portion of the amino acid sequence of the first repeat unit. The amino acid sequence of the peptide or polypeptide chain may be identical to the amino acid sequence of the first repeat unit.

[0041] The polypeptide chain has, for example, a repeating unit (sometimes referred to as a second repeating unit) formed by peptide bonds of multiple amino acid residues. By reacting multiple amino acids, a second repeating unit is obtained in which multiple amino acid residues derived from each of the multiple amino acids are peptide-bonded.

[0042] The plurality of amino acid residues constituting the second repeat unit may include at least two types of amino acid residues constituting the first repeat unit. The plurality of amino acid residues constituting the second repeat unit may include at least three or more types of amino acid residues constituting the first repeat unit. The amino acid sequence of the second repeat unit may be identical to a portion of the amino acid sequence of the first repeat unit. The amino acid sequence of the second repeat unit may be identical to the amino acid sequence of the first repeat unit. The amino acid sequence of the second repeat unit may be determined, for example, so that the degree of hydrophobic interaction between the second repeat unit and at least a portion of the first repeat unit is greater than a predetermined level.

[0043] The polypeptide chain may have, for example, 1 to 50 second repeat units. The polypeptide chain may have 1 to 40 second repeat units, or 1 to 30 second repeat units. The polypeptide chain may have, for example, 2 to 50 second repeat units, or 2 to 40 second repeat units, or 2 to 30 second repeat units.

[0044] As described above, fibroin or a derivative thereof has repeating amino acid sequences of (GAGAS)n and ((GX)sGY)t. Here, n is, for example, an integer from 1 to 20, s is, for example, an integer from 1 to 10, and t is, for example, an integer from 1 to 20. Furthermore, X is A or V. Therefore, when the first polymer compound is fibroin or a derivative thereof, any of the amino acid sequences exemplified as the amino acid sequence of the first repeating unit can be used as the amino acid sequence of the peptide chain or polypeptide chain. When the first polymer compound is fibroin or a derivative thereof, the amino acid sequence of the peptide chain or polypeptide chain may be (GA)u, (GAGAS)n, or ((GX)sGY)t, or any amino acid sequence containing these. Here, u is, for example, an integer from 1 to 10.

[0045] (Side Chain Structure) In one embodiment, the second polymer compound may be the above-mentioned peptide chain or polypeptide chain. For example, a carboxy group of a polymer compound (sometimes referred to as a third polymer compound) having at least one carboxy group and / or amino group introduced into the main chain reacts with the amino group at the N-terminus of the above-mentioned peptide chain or polypeptide chain to obtain a second polymer compound having a peptide chain or polypeptide chain arranged on its side chain. Similarly, a carboxy group of the above-mentioned third polymer compound reacts with the carboxy group at the C-terminus of the above-mentioned peptide chain or polypeptide chain to obtain a second polymer compound having a peptide chain or polypeptide chain arranged on its side chain.

[0046] In another embodiment, the side chain of the second polymer compound comprises (i) the peptide chain or polypeptide chain described above, and (ii) a linker. The linker connects the main chain of the second polymer compound to the peptide chain or polypeptide chain. In one embodiment, the linker is bonded to the amino group at the N-terminus of the peptide chain or polypeptide chain. In another embodiment, the linker is bonded to the carboxy group at the C-terminus of the peptide chain or polypeptide chain.

[0047] Examples of linkers include glycols such as ethylene glycol, polyethylene glycol, and derivatives thereof. Other examples of linkers include polyglycolic acid, polycaprolactone, and polylactic acid. The number of carbon atoms in the linker may be 2 to 4,000, 2 to 2,000, or 2 to 1,000.

[0048] In yet another embodiment, the second polymeric compound comprises a first side chain having a peptide or polypeptide chain at its terminal end and a second side chain having a functional peptide, an ester group, or a substituted or unsubstituted amide group at its terminal end, the first side chain and the second side chain being bonded, for example, to different carbon atoms on the main chain of the second polymeric compound.

[0049] Examples of functional peptides include REDV, IKVAV, YIGSR, RGD, SVVYGLR, etc. These peptides improve the adhesive ability, proliferation ability, migration ability and / or angiogenic ability of fibroblasts, endothelial cells, smooth muscle cells, etc.

[0050] The ester group and amide group are introduced, for example, to cap the unmodified carboxy group introduced into the third polymer compound. The ester group is formed, for example, by bonding the carboxy group with an alcohol such as ethylene glycol or polyethylene glycol. The amide group is formed, for example, by bonding the carboxy group with an amino acid.

[0051] (Specific Examples of Second Polymer Compound) Examples of the second polymer compound include polyurethane, poly-D-lactic acid (PDLA), poly-L-lactic acid (PLLA), poly-DL-lactic acid (PDLLA), poly(ε-caprolactone) (PCL), polyglactin, polyethylene carbonate, polyglycolic acid (PGA), collagen, gelatin, chitosan, casein, keratin, sericin, polymethyl methacrylate (PMMA), polyamide, cellulose, polyhydroxyalkanoate (PHA), polybutylene succinate (PBS), glucose, polyvinyl alcohol (PVA), polyester, polyhydroxybutyric acid (PHB), polymalic acid (PMA), poly(p-dioxanone) (PDS, PDO), polypropylene glycol (PPG), poly(lactic-co-glycolic acid) (PLGA), polybutylene succinate (PBS), hydroxyapatite, and polybutylene. The resin composition includes at least one polymer compound selected from the group consisting of adipate-co-terephthalate (PBAT), polyethylene adipate terephthalate (PEAT), tetrapolyethylene glycol (PTE), sodium polyacrylate (SAP), poly(sodium 4-styrenesulfonate) (PSS), polydiallyldimethylammonium chloride (PDDA), poly(2-methoxyethyl acrylate) (PMEA), polyacrylic acid (PAA), polyethyl acrylate (PEA), polybutyl acrylate (PBA), polyacrylamide (PAM), polymethacrylic acid, polymaleic anhydride, and polytrimethylene carbonate (PTMC), as well as derivatives thereof, the polymer compound having a peptide chain or polypeptide chain formed by peptide bonds between multiple amino acid residues at the end of its side chain. This results in a resin composition with excellent biocompatibility and mechanical properties. The resin composition with excellent biocompatibility and mechanical properties is suitable for use as a medical material or a scaffold material for cell culture.

[0052] The second polymeric compound is, for example, at least one polymeric compound selected from the group consisting of polyurethane, polyurea, natural rubber, polycarbonate, and derivatives thereof, and includes a polymeric compound having a peptide chain or polypeptide chain formed by peptide bonds between multiple amino acid residues at the end of a side chain. The polyurethane, polyurea, and / or polycarbonate may be a homopolymer or a copolymer. An example of the polycarbonate is polyethylene carbonate. This results in a resin composition with particularly excellent biocompatibility and mechanical properties. The resin composition with excellent biocompatibility and mechanical properties is suitable for use as a medical material or a scaffold material for cell culture.

[0053] (An example of another embodiment) In this embodiment, the resin composition has been described in detail using an example in which the resin composition contains two types of polymer compounds. However, the resin composition is not limited to this embodiment. In other embodiments, the resin composition may contain three or more types of polymer compounds. For example, the resin composition contains one or more types of first polymer compounds and two or more types of second polymer compounds. For example, the resin composition contains two or more types of first polymer compounds and one or more types of second polymer compounds.

[0054] (II. Composition of Resin Composition) In this embodiment, the mass ratio of the first polymer compound to the second polymer compound is, for example, 1:99 to 99:1. The mass ratio of the first polymer compound to the second polymer compound may be 20:80 to 80:20, or may be 30:70 to 70:30. The mass ratio of the first polymer compound to the second polymer compound may be 40:60 to 60:40, or may be 45:55 to 55:45.

[0055] The greater the ratio of the mass of the first polymer compound to the mass of the second polymer compound, the closer the physical properties of the resin composition become to the physical properties of the first polymer compound. For example, when the first polymer compound is SF and the second compound is polyurethane (sometimes referred to as PU), the greater the ratio of the mass of the first polymer compound to the mass of the second polymer compound, the lower the maximum stress, the lower the yield stress, the higher the Young's modulus, the lower the elongation at break, and the lower the elongation at yield of the resin composition.

[0056] Similarly, the smaller the ratio of the mass of the first polymeric compound to the mass of the second polymeric compound, the closer the physical properties of the resin composition become to the physical properties of the second polymeric compound. For example, if the first polymeric compound is SF and the second compound is polyurethane (sometimes referred to as PU), the smaller the ratio of the mass of the first polymeric compound to the mass of the second polymeric compound, the higher the maximum stress, yield stress, Young's modulus, break elongation, and yield elongation of the resin composition become. As a result, the elastic range of the resin composition expands. By expanding the elastic range of the resin composition, the physical properties of the resin composition can be appropriately adjusted according to needs.

[0057] (III. Physical Properties of Resin Composition) (Young's Modulus) In this embodiment, the resin composition has a Young's modulus of, for example, 2 MPa or more and 20 MPa or less. The resin composition may have a Young's modulus of 2 MPa or more and 15 MPa or less. The Young's modulus of the resin composition is calculated in accordance with, for example, ISO 527-1 or JIS K 7161.

[0058] Specifically, first, a test specimen to be measured is prepared. The shape and size of the test specimen are, for example, a JIS dumbbell No. 7. The thickness of the test specimen in a dry state is measured. The thickness of the test specimen may be the thickness at a single location on the test specimen, or may be the average value of the thicknesses at multiple locations. Next, a tensile load of 5 mm / min is applied to the test specimen in the air at 20°C, and the test specimen is pulled in the direction of its long side, while measuring the tensile stress (sometimes referred to as normal stress) and elongation (sometimes referred to as strain, elongation, etc.).

[0059] The tensile stress [MPa] was calculated by multiplying the tensile load [N] by the cross-sectional area [mm ２ ]. The above cross-sectional area is the area of ​​a surface obtained by cutting the sample piece in a plane approximately perpendicular to the tensile direction. The elongation [%] is calculated using the following formula 1: [Formula 1] Elongation [%] = 100 × (L - Lo) / Lo In formula 1, Lo is the length of the sample before the start of the test, and L is the length of the sample during the test.

[0060] Young's modulus is calculated as the ratio of tensile stress to elongation within the tensile proportional limit (sometimes called the elastic region). In this embodiment, Young's modulus is calculated from the slope of the tangent to the SS curve (sometimes called a stress-strain diagram). The slope of the tangent is calculated, for example, from data on stress for strains of 1% to 6%.

[0061] It is anticipated that it may be difficult to calculate Young's modulus based on the above procedure due to sample characteristics or other factors. For example, in JIS K 7161, test specimens (sometimes referred to as samples) are conditioned according to the specifications of the material being tested. Unless otherwise specified, conditioning is recommended for 16 hours or more at a temperature of 21-25°C and a humidity of 40-60%. However, depending on the material, the physical properties may differ significantly between the wet and dry states. Examples of such materials include (i) biopolymers such as collagen, fibrin, alginic acid, hyaluronic acid, fibroin (e.g., silk fibroin), and sericin (e.g., silk sericin), and (ii) polyvinyl alcohol, polyglycolic acid, and polyglactin. In such cases, Young's modulus can be derived, for example, based on the underwater tensile test (sometimes referred to as an immersion tensile test) described below or a test similar to the underwater tensile test.

[0062] (Procedure for calculating Young's modulus based on underwater tensile test) First, a resin composition is immersed in ultrapure water at 37°C for 24 hours or more. Next, a test piece in a hydrated state to be measured is cut out from near the center of the resin composition. The shape and size of the sample piece are, for example, a JIS dumbbell No. 7. This allows the test piece in a hydrated state to be obtained.

[0063] Next, the thickness of the test piece in a hydrated state is measured. The thickness of the test piece may be the thickness at a single point on the test piece, or may be the average value of the thicknesses at multiple points on the test piece.

[0064] Next, an underwater tensile test is performed using an EZ Graph manufactured by Shimadzu Corporation. The underwater tensile test is performed in water at 37°C with a gripping distance of 12 mm and a tensile speed of 5 mm / min. The number of measurement trials is set to, for example, six or more. The stress [Pa] and strain [%] are calculated based on the test force [N], displacement [mm], film thickness [mm], and sample length [mm] obtained from the underwater tensile test. A stress-strain curve is created by plotting the measurement results with stress on the vertical axis and strain on the horizontal axis. Young's modulus is calculated based on the stress for strains of 1 to 6%.

[0065] (Maximum Stress) In this embodiment, the resin composition has a maximum stress of, for example, 1 MPa or more and 20 MPa or less. The resin composition may have a maximum stress of 1 MPa or more and 15 MPa or less, or may have a maximum stress of 1 MPa or more and 10 MPa or less. The maximum stress of the resin composition can be adjusted by (i) the type of the first polymer compound and / or the second polymer compound, (ii) the content of peptide chains or polypeptide chains in the second polymer compound or the modification rate described below, (iii) the mass ratio of the first polymer compound to the second polymer compound, etc.

[0066] The maximum stress of the resin composition is derived, for example, in accordance with ISO 527-1 and JIS K 7161. The maximum stress of the resin composition is defined, for example, as the maximum value of the tensile stress explained in relation to the method for deriving Young's modulus. Specifically, the maximum value of the measured tensile stress from the time when the above test is started to the time when the test piece breaks or the maximum stroke of the test is reached is derived as the maximum stress of the resin composition.

[0067] (Elongation at break) In this embodiment, the resin composition has, for example, an elongation at break of 10% or more and 200% or less. The resin composition may have an elongation at break of 10% or more and 150% or less. The elongation at break of the resin composition can be adjusted by (i) the type of the first polymer compound and / or the second polymer compound, (ii) the content of peptide chains or polypeptide chains in the second polymer compound or the modification rate described below, (iii) the mass ratio of the first polymer compound to the second polymer compound, etc.

[0068] The breaking elongation of the resin composition is calculated, for example, in accordance with ISO 527-1 and JIS K 7161. The breaking elongation of the resin composition is defined, for example, as the maximum value of the elongation explained in relation to the method for deriving Young's modulus. Specifically, the maximum value of the measured elongation from the time when the above test is started to the time when the test piece breaks or when the maximum stroke of the test is reached is calculated as the breaking elongation of the resin composition.

[0069] (Yield elongation) In this embodiment, the resin composition has a yield elongation of, for example, 5% or more and 100% or less. The resin composition may have a yield elongation of 5% or more and 60% or less. The yield elongation of the resin composition can be adjusted by (i) the type of the first polymer compound and / or the second polymer compound, (ii) the content of peptide chains or polypeptide chains in the second polymer compound or the modification rate described below, (iii) the mass ratio of the first polymer compound to the second polymer compound, etc.

[0070] The yield elongation of a resin composition is derived, for example, in accordance with ISO 527-1 and JIS K 7161. The yield elongation of a resin composition is defined, for example, as the elongation at the yield point. The yield point is defined, for example, as the intersection of a tangent to the Young's modulus as the slope and a tangent at the point where the slope immediately before break becomes parallel. Specifically, in the stress-strain curve described in relation to the method for deriving the Young's modulus, the position of the intersection between the tangent to the elastic deformation region of the curve and the tangent to the plastic deformation region of the curve is calculated. The yield point is derived in this way. The elongation at the yield point is also derived as the yield elongation.

[0071] (Yield Stress) In this embodiment, the resin composition has a yield stress of, for example, 0.5 MPa or more and 10 MPa or less. The resin composition may have a yield stress of 0.5 MPa or more and 8 MPa or less. The yield stress of the resin composition can be adjusted by (i) the type of the first polymer compound and / or the second polymer compound, (ii) the content of peptide chains or polypeptide chains in the second polymer compound or the modification rate described below, (iii) the mass ratio of the first polymer compound to the second polymer compound, etc.

[0072] The yield stress of a resin composition is derived, for example, in accordance with ISO 527-1 and JIS K 7161. The yield stress of a resin composition is defined, for example, as the stress at the yield point described above. Specifically, in the stress-strain curve described in relation to the method for deriving Young's modulus, the position of the intersection between the tangent to the elastic deformation region of the curve and the tangent to the plastic deformation region of the curve is calculated. This derives the yield point. Furthermore, the stress at the yield point is derived as the yield stress.

[0073] (IV. Shape and Use of Resin Composition) In the present embodiment, the shape of the resin composition is not particularly limited. The resin composition has, for example, (i) a fiber shape, (ii) a nonwoven fabric shape, (iii) a sheet shape or a film shape, (iv) a tube shape or a roll shape, or (iv) a block shape, a sponge shape, a pad shape, or a column shape.

[0074] In this embodiment, the resin composition is used for, for example, medical materials, scaffolding materials for cell culture, functional apparel materials, and general industrial silk products. Examples of medical materials include artificial blood vessels, cardiac repair patches, artificial valves, sustained-release drug materials, adhesion inhibitors, artificial bones, artificial cartilage, and wound dressings.

[0075] In particular, devices intended for the regeneration of blood vessels, the heart, and their surrounding tissues require cell affinity, low inflammation, and hemocompatibility, as well as mechanical properties suited to the environment of the implantation site. For example, according to an embodiment in which the first polymer compound is fibroin or a derivative thereof, a resin composition can be obtained that (i) has excellent biocompatibility and (ii) is excellent in Young's modulus, breaking elongation, maximum stress, yield stress, and / or yield elongation. Since the resin composition according to the above embodiment is inhibited from plastic deformation, the resin composition is particularly suitable for use in, for example, cardiovascular tissue engineering devices that function in dynamic environments. Examples of cardiovascular tissue engineering devices include artificial blood vessels, cardiac repair patches, and artificial valves.

[0076] (V. Method for Producing Resin Composition) In this embodiment, the resin composition is produced by mixing a first polymer compound and a second polymer compound that have been prepared in advance. In this embodiment, the procedure for preparing the first polymer compound is not particularly limited. The first polymer compound can be produced by a known method for producing the target compound.

[0077] In this embodiment, the procedure for preparing the second polymer compound is not particularly limited, but the second polymer compound is produced, for example, according to the following procedure. First, the above-described third polymer compound is prepared. As described above, the third polymer compound is a polymer compound different from the first polymer compound and the second polymer compound, and is a polymer compound having at least one of a carboxy group and an amino group introduced into the main chain.

[0078] The procedure for introducing at least one of a carboxyl group and an amino group into the main chain of a polymer compound can be, for example, a procedure for subjecting a polymer compound having a carbonate group to any known surface treatment, such as plasma irradiation treatment, chlorination treatment, or plasma irradiation treatment.

[0079] Next, a peptide or polypeptide containing at least two types of amino acid residues constituting the first repeating unit is prepared. The peptide or polypeptide can be produced by a known method for producing the target compound. Next, at least one of the carboxyl group and the amino group of the third polymer compound is reacted with the peptide or polypeptide. This results in a second polymer compound.

[0080] The ratio of the number of moles of functional groups modified with peptides or polypeptides to the number of moles of either the carboxyl group or the amino group of the third polymer compound (sometimes referred to as the modification rate) is, for example, 0.1 to 1 (or 10% to 100%). The modification rate may be expressed as a percentage. The modification rate may be 0.1 to 0.5 (i.e., 10% to 50%).

[0081] (Measurement of Modification Rate) The modification rate is determined, for example, by a BCA protein assay. The BCA protein assay is performed, for example, according to the following procedure. First, a dilution series of a standard solution is prepared. Bovine serum albumin (BCA) is used as the standard solution. Five dilution series are prepared: 0 μg / mL, 100 μg / mL, 200 μg / mL, 400 μg / mL, and 800 μg / mL.

[0082] Next, BCA Reagent A (main component: sodium bicinchoninate):BCA Reagent B (main component: copper sulfate pentahydrate) were mixed at a volume ratio of 100:1 to prepare the Working Solution. Next, each of the five series of standard solutions was mixed with the Working Solution to prepare five series of mixed solutions. Each mixed solution was obtained by mixing 50 μL of the standard solution with 1 mL of the Working Solution. Each mixed solution was then placed in a water bath at 37°C for 30 minutes.

[0083] Next, a ratio beam spectrophotometer (U-5100, manufactured by Hitachi, Ltd.) is used to measure the absorbance of light at 562 nm for each of the five dilution series described above. The measurement mode of the ratio beam spectrophotometer is set to quantitative calculation. The number of standard tests, n, is set to n=4. Using the above measurement results, a calibration curve showing the relationship between BSA concentration [μg / mL] and absorbance of light at 562 nm is created.

[0084] Next, a sample for measurement is prepared. First, a solution of the second polymer compound to be measured (sometimes referred to as a sample solution) is prepared. Next, 50 μL of the sample solution is mixed with 1 mL of Working Solution, and the mixture is then placed in a water bath at 37° C. for 30 minutes.

[0085] Next, the absorbance at 562 nm is measured using a ratio beam spectrophotometer (U-5100, manufactured by Hitachi, Ltd.). The measurement mode of the ratio beam spectrophotometer is set to quantitative calculation. The number of standard tests n is set to n = 4. The above measurement results are substituted into the above-mentioned calibration curve to derive the concentration [μg / mL] of the peptide or polypeptide in the sample solution. Next, the number of moles MA [mol] of the peptide or polypeptide in the sample solution is calculated using the concentration of the peptide or polypeptide in the sample solution, the volume of the sample solution, the dilution ratio of the sample solution, the molecular weight of the peptide or polypeptide, etc.

[0086] On the other hand, the number of moles MB of carboxyl or amino groups exposed on the main chain of the polymer compound (the third polymer compound described above) before the second polymer compound is modified with a peptide or polypeptide is provided, for example, by the manufacturer or seller of the third polymer compound. The modification rate is calculated by dividing the MA by the MB and multiplying the result by 100.

[0087] (Fiber-like or nonwoven fabric-like resin composition) According to one embodiment, first, a solution (sometimes referred to as a spinning dope) of a mixture of a first polymer compound and a second polymer compound is prepared. The solvent of the spinning dope may be an aqueous solvent or an organic solvent. Next, fibers or nonwoven fabric are produced using a spinning device. For example, threads of the resin composition are produced by ejecting the spinning dope from the nozzle of the spinning device. The threads are accumulated to produce a nonwoven fabric of the resin composition. In the above procedure, any known method for producing fibers or nonwoven fabrics, such as electrospinning, solution blowing, or melt blowing, may be used.

[0088] (Film-, Tube-, or Block-Shaped Resin Composition) According to another embodiment, first, a first polymer compound and a second polymer compound are dissolved in an appropriate solvent to prepare a mixed solution of the first polymer compound and the second polymer compound. Next, the mixed solution is poured into an appropriate container or mold. Thereafter, the solvent in the mixed solution is evaporated. The solvent evaporation may be performed at room temperature, at an ultra-low temperature (i.e., freeze-drying), or at a high temperature. The solvent evaporation may be performed at normal pressure or at a low pressure. This produces a resin composition having the shape of (i) a sheet or film, (ii) a tube or roll, or (iii) a block, sponge, pad, or column.

[0089] The present invention will be described in more detail below with reference to examples and reference examples. It should be noted that the present invention is not limited to the following examples as long as it does not deviate from the gist of the present invention.

[0090] (Example 1) First, 250 g of raw silk reeled from domesticated silkworm cocoons was immersed in a 95°C aqueous solution of 0.02 M sodium carbonate (special grade, manufactured by Wako Pure Chemical Industries, Ltd.) and stirred for 30 minutes to be degummed. Next, the degummed raw silk was washed three times with purified water at 40°C. This almost completely removed the sericin remaining in the raw silk after degumming. Thereafter, the fibers from which the sericin had been removed were further washed with purified water and then dried. This yielded silk fibroin (sometimes abbreviated as SF) fibers.

[0091] Next, the SF was added to a 9 M aqueous solution of lithium bromide (manufactured by Wako Pure Chemical Industries, Ltd.) and dissolved under shaking conditions of 37°C and 100 rpm. This resulted in an SF solution. Lithium bromide was then removed from the SF solution by dialysis. For the dialysis, a dialysis cell tube boiled for 20 minutes was used. The dialysis was carried out at 4°C, with water changes three times a day. The dialysis was terminated when the electrical conductivity of the purified water reached 2 μS / cm or less 10 hours or more after the water change.

[0092] Next, impurities were removed from the dialysis-treated SF aqueous solution by centrifugation. The centrifugation was carried out for 30 minutes at 4°C and 8500 rpm. The impurity removal process by centrifugation was carried out twice in total. After that, a small amount of the SF aqueous solution from which the impurities had been removed was dropped into several petri dishes, and the concentration was measured by measuring the weight after drying.

[0093] Next, the SF concentration in the SF aqueous solution from which the impurities had been removed was adjusted to 1% (w / v) using pure water. The SF aqueous solution with the adjusted concentration was transferred to an eggplant flask, pre-frozen with liquid nitrogen, and then freeze-dried. This yielded an SF sponge.

[0094] Synthesis Example 2: 200 mg of water-dispersible polyurethane (sometimes abbreviated as WPU) having carboxy groups in the molecular chain was mixed with 1 mg of pure water. This resulted in a 20% (w / v) WPU aqueous dispersion. The adjusted concentration of the WPU aqueous dispersion was transferred to an eggplant flask, pre-frozen with liquid nitrogen, and then freeze-dried. This resulted in a WPU sponge.

[0095] WPU was added to a silicon mold and pre-frozen at -20°C for 3 days, after which the pre-frozen WPU was placed in a sample bottle, pre-frozen again using liquid nitrogen, and freeze-dried to obtain a WPU sponge.

[0096] Synthesis Example 3: 200 mg of water-dispersible polyurethane (sometimes abbreviated as WPU) having a carboxy group in the molecular chain was mixed with 1 mg of pure water to obtain a 20% (w / v) WPU aqueous dispersion.

[0097] Next, some of the carboxy groups of WPU were converted to peptide (H ２ The peptide having the amino group sequence GAGAGA is sometimes referred to as a model peptide.

[0098] Specifically, 7.668 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) hydrochloride, 21.714 mg of N-hydroxysuccinimide (NHS) sodium salt, and 18 mL of MES buffer were mixed to prepare an EDC / NHS solution. A 2-morpholinoethanesulfonic acid (MES) aqueous solution and a sodium hydroxide aqueous solution were used to prepare an MES buffer, and the pH of the EDC / NHS solution was adjusted to 5.4 by adding the buffer while stirring for 30 minutes. The EDC / NHS solution was prepared at room temperature (23°C).

[0099] Next, 32 mg of GA peptide was added to the EDC / NHS solution, and 12 mL of sodium hydroxide was added to adjust the pH to 7.4. This was stirred at room temperature for 24 hours to obtain a polymer in which some of the carboxy groups of the water-dispersible polyurethane had been modified with the model peptide (sometimes abbreviated as WPU-G), and a solution containing unreacted model peptide (sometimes referred to as a reaction solution).

[0100] Next, unreacted model peptide was removed from the reaction solution by dialysis using a dialysis membrane (manufactured by Japan Medical Science Co., Ltd.) with a molecular weight cutoff of 3500. The dialysis was carried out at 4°C, with water exchanged three times a day, and was terminated after three days.

[0101] Next, the WPU-G aqueous solution was transferred to a recovery flask, pre-frozen with liquid nitrogen, and then freeze-dried to obtain a WPU-G sponge.

[0102] Example 1 175 mg of the SF sponge obtained in Synthesis Example 1 and 175 mg of the WPU-G sponge obtained in Synthesis Example 3 were added to 5000 μL of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) (Sigma), and the mixture was stirred at room temperature and 300 rpm for 15 hours. This resulted in an SF / WPU-G HFIP solution. The SF:WPU-G (mass ratio) was 1:1. The SF concentration in the HFIP solution was 3.5% (w / v). The WPU-G concentration in the HFIP solution was 3.5% (w / v).

[0103] Next, a nonwoven sheet of SF / WPU-G was produced using an HFIP solution of SF / WPU-G as a spinning solution and an electrospinning device (Fluidnatek LE-50, manufactured by Bioinicia). The applied voltage of the electrospinning device was set to 28 kV. The discharge rate of the spinning solution was set to 1.3 mL / h. The discharge distance was set to 15 cm.

[0104] Next, the silk fibroin in the nonwoven fabric was insolubilized. Specifically, the produced nonwoven fabric sheet was placed together with the collection plate of an electrospinning device at 100% relative humidity and 37°C for 2 hours. Next, the insolubilized nonwoven fabric sheet was immersed in water together with the collection plate, and the nonwoven fabric sheet was peeled off from the collection plate. This resulted in an SF / WPU-G nonwoven fabric sheet. An SEM image of the produced nonwoven fabric sheet is shown in Figure 1.

[0105] Comparative Example 1: 250 mg of the SF sponge obtained in Synthesis Example 1 was added to 5000 μL of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) (Sigma), and the mixture was stirred at room temperature and 300 rpm for 15 hours. This resulted in a HFIP solution of SF. The SF concentration in the HFIP solution was 5% (w / v).

[0106] Thereafter, a SF nonwoven fabric sheet was produced using the same procedure as in Example 1. The applied voltage of the electrospinning device was set to 25 kV. The discharge rate of the spinning dope was set to 1.3 mL / h. The discharge distance was set to 15 cm. An SEM image of the produced SF nonwoven fabric sheet is shown in Figure 2.

[0107] Comparative Example 2: 175 mg of the SF sponge obtained in Synthesis Example 1 and 175 mg of the WPU sponge obtained in Synthesis Example 2 were added to 5000 μL of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) (Sigma), and the mixture was stirred at room temperature and 300 rpm for 15 hours. This resulted in a HFIP solution of SF / WPU. The SF:WPU (mass ratio) was 1:1. The SF concentration in the HFIP solution was 3.5% (w / v). The WPU concentration in the HFIP solution was 3.5% (w / v).

[0108] Thereafter, a nonwoven fabric sheet of SF / WPU was produced using the same procedure as in Example 1. The applied voltage of the electrospinning device was set to 28 kV. The discharge rate of the spinning dope was set to 1.3 mL / h. The discharge distance was set to 15 cm. An SEM image of the produced nonwoven fabric sheet of SF / WPU is shown in Figure 3.

[0109] (Evaluation) (Evaluation of Mechanical Properties) The above-described underwater tensile test was carried out on the nonwoven fabrics obtained in Example 1, Comparative Example 1, and Comparative Example 2. The results of the underwater tensile test for Example 1, Comparative Example 1, and Comparative Example 2 are shown in Figure 4. Figure 4 shows the SS curves obtained by the underwater tensile test for Example 1, Comparative Example 1, and Comparative Example 2.

[0110] Based on the results of the underwater tensile test, the Young's modulus of the examples and comparative examples was calculated. The Young's modulus of the nonwoven fabric sheet of Example 1 was 10.2 [MPa]. The Young's modulus of the nonwoven fabric sheets of Comparative Examples 1 and 2 was 13.3 [MPa] and 6.97 [MPa], respectively. The measurement results of the Young's modulus of the nonwoven fabric sheets of Example 1, Comparative Example 1, and Comparative Example 2 are shown in Figure 5.

[0111] According to the procedure described above, the maximum stress was calculated for each of the nonwoven fabrics obtained in Example 1, Comparative Example 1, and Comparative Example 2. The maximum stress of the nonwoven fabric sheet of Example 1 was 7.95 [MPa]. The maximum stress of the nonwoven fabric sheets of Comparative Examples 1 and 2 was 3.58 [MPa] and 3.05 [MPa], respectively. The measurement results of the maximum stress of the nonwoven fabric sheets of Example 1, Comparative Example 1, and Comparative Example 2 are shown in Figure 6.

[0112] According to the above-described procedure, the yield stress was calculated for each of the nonwoven fabrics obtained in Example 1, Comparative Example 1, and Comparative Example 2. The yield stress of the nonwoven fabric sheet of Example 1 was 4.41 [MPa]. The yield stress of the nonwoven fabric sheets of Comparative Examples 1 and 2 was 2.05 [MPa] and 2.4 [MPa], respectively. The measurement results of the yield stress of the nonwoven fabric sheets of Example 1, Comparative Example 1, and Comparative Example 2 are shown in Figure 7.

[0113] According to the above-described procedure, the breaking elongation was calculated for each of the nonwoven fabrics obtained in Example 1, Comparative Example 1, and Comparative Example 2. The breaking elongation of the nonwoven fabric sheet of Example 1 was 117%. The breaking elongation of the nonwoven fabric sheets of Comparative Examples 1 and 2 was 81.2% and 60.5%, respectively. The measurement results of the breaking elongation of the nonwoven fabric sheets of Example 1, Comparative Example 1, and Comparative Example 2 are shown in Figure 8.

[0114] According to the above-described procedure, the yield elongation was calculated for each of the nonwoven fabrics obtained in Example 1, Comparative Example 1, and Comparative Example 2. The yield elongation of the nonwoven fabric sheet of Example 1 was 43.4%. The yield elongations of the nonwoven fabric sheets of Comparative Examples 1 and 2 were 15.4% and 34.5%, respectively. The measurement results of the yield elongation of the nonwoven fabric sheets of Example 1, Comparative Example 1, and Comparative Example 2 are shown in Figure 9.

[0115] 5 to 9, different alphabets in each graph indicate significant differences. As shown in Figures 5 to 9, the nonwoven fabric sheet of Example 1 exhibited significantly improved mechanical properties compared to the nonwoven fabric sheets of Comparative Examples 1 and 2.

[0116] (Evaluation of Chemical Properties) (Modification Ratio) According to the procedure described above, the modification ratio was calculated for the nonwoven fabric obtained in Example 1. The modification ratio of WPU-G in Synthesis Example 3 was 19.7%. In other words, 19.7% of the COOH groups of the WPU used to prepare WPU-G were modified with the model peptide.

[0117] (Compatibility) Dynamic mechanical analysis (DMA) was performed on the nonwoven fabrics obtained in each of Example 1 and Comparative Example 2 to measure the glass transition temperature Tg [°C] of the WPU contained in each nonwoven fabric, and the glass transition temperature Tg [°C] and crystalline relaxation temperature Tm [°C] of the SF.

[0118] A DVA205 manufactured by IT Measurement & Control Co., Ltd. was used for the dynamic viscoelasticity measurements. The temperature range was set to 100 to 300°C. The heating rate was set to 2°C / min. The frequency was set to 1 Hz. The gripping distance was 25 mm. The number of tests was set to 3 or more. Using the DVA205, the storage modulus, loss modulus, and loss tangent (tan δ) of each sample were measured. The Tg and Tm were calculated from the peak top temperature of the loss tangent.

[0119] In SF / WPU-G of Example 1, the Tg of WPU was −53.6±3.22° C., the Tg of SF was 203±1.32° C., and the Tm of SF was 284±1.29° C.

[0120] In the SF / WPU of Comparative Example 2, the Tg of the WPU was −56.9±3.53° C., the Tg of the SF was 204±1.00° C., and the Tm of the SF was 272±0.19° C.

[0121] The above measurement results show that the difference in Tg between WPU and SF in SF / WPU-G of Example 1 is smaller than the difference in Tg between WPU and SF in SF / WPU of Comparative Example 2. The smaller the difference in Tg between different polymers, the better the compatibility of the different polymers. Therefore, it can be seen that the compatibility of SF and PU was improved by modifying part of the side chain of WPU with the model peptide.

[0122] Furthermore, according to the above measurement results, the Tm of SF in SF / WPU-G of Example 1 is 10°C or more higher than the Tm of SF in SF / WPU of Comparative Example 2. In other words, it can be seen that the thermal stability of the resin composition was improved due to the interaction between the crystalline region of SF and the model peptide of PU.

[0123] Although the present invention has been described above using embodiments, the technical scope of the present invention is not limited to the scope described in the above embodiments. It will be apparent to those skilled in the art that various modifications and improvements can be made to the above embodiments. Furthermore, to the extent that they are not technically inconsistent, the details described for a particular embodiment can be applied to other embodiments. It is apparent from the claims that such modifications and improvements can also be included within the technical scope of the present invention.

[0124] It should be noted that the order of execution of each process, such as operations, procedures, steps, and stages, in the materials and manufacturing methods thereof shown in the claims, specification, and drawings is not specifically stated as "before," "prior to," etc., and that the process may be carried out in any order unless the product of a previous process is used in a later process. Even if the operations in the claims, specification, and drawings are described using "first," "next," etc. for convenience, this does not mean that they must be carried out in this order.

Claims

1. A first polymer compound having a first repeating unit in its main chain, in which multiple amino acid residues are linked by peptide bonds, A second polymer compound having a peptide chain or polypeptide chain at the end of a side chain, in which multiple amino acid residues are linked by peptide bonds, A resin composition containing, The plurality of amino acid residues constituting the first repeating unit of the first polymer compound include amino acid residues derived from at least two amino acids selected from the group consisting of glycine, alanine, serine, tyrosine, and valine. The first polymer compound is fibroin or a derivative thereof. The peptide chain or polypeptide chain of the second polymer compound has a second repeating unit formed by peptide bonds between a plurality of amino acid residues, and the amino acid sequence of the second repeating unit is the same as or a part of the amino acid sequence of the first repeating unit. The amino acid sequence of the first repeating unit of the first polymer compound is: GA, AG, GAG, AGA, or GAGA, or any amino acid sequence containing these, Resin composition.

2. The first polymer compound has one to thirty of the first repeating units, The resin composition according to claim 1.

3. The amino acid sequence of the peptide chain or polypeptide chain of the second polymer compound is (GA)u, (GAGAGS)n, or ((GX)sGY)t, or any amino acid sequence including these amino acid sequences, where u and s each represent an integer from 1 to 10, n and t each represent an integer from 1 to 20, and X represents A. The resin composition according to claim 1.

4. The polypeptide chain has one to fifty of the second repeating units. The resin composition according to claim 1.

5. The side chain of the second polymer compound is The peptide chain or the polypeptide chain, A linker connecting the peptide chain or the polypeptide chain and the main chain of the second polymer compound, including, The resin composition according to claim 1.

6. The second polymer compound is A first side chain having the peptide chain or polypeptide chain at its terminal, A second side chain having a functional peptide, ester group, or substituted or unsubstituted amide group at its terminus, including, The resin composition according to claim 1.

7. The mass ratio of the first polymer compound to the second polymer compound is 1:99 to 99:

1. The resin composition according to claim 1.

8. The second polymer compound is polyurethane, poly-D lactic acid (PDLA), poly-L lactic acid (PLLA), poly-DL lactic acid (PDLLA), poly(ε-caprolactone) (PCL), polyglucin, polyethylene carbonate, polyglycolic acid (PGA), collagen, gelatin, chitosan, casein, keratin, sericin, polymethyl methacrylate (PMMA), polyamide, cellulose, polyhydroxyalkanoate (PHA), polybutylene succinate (PBS), glucose, polyvinyl alcohol (PVA), polyester, polyhydroxybutyric acid (PHB), polymalic acid (PMA), poly(p-dioxanone) (PDS, PDO), polypropylene glycol (PPG), poly(glycolic acid lactate copolymer) (PLGA), polybutylene succinate (PBS), hydroxyapatite, polybutylene A polymer compound selected from the group consisting of dipate-co-terephthalate (PBAT), polyethylene adipate-terephthalate (PEAT), tetrapolyethylene glycol (PTE), sodium polyacrylate (SAP), sodium poly-4-styrene sulfonate (PSS), polydiallyldimethylammonium chloride (PDDA), poly(2-methoxyethyl acrylate) (PMEA), polyacrylic acid (PAA), polyethyl acrylate (PEA), polybutyl acrylate (PBA), polyacrylamide (PAM), polymethacrylic acid, polymaleic anhydride, and polytrimethylene carbonate (PTMC), and derivatives thereof, comprising a polymer compound having a peptide chain or polypeptide chain at the end of its side chain, wherein a plurality of amino acid residues are linked by peptide bonds. The resin composition according to claim 1.

9. The resin composition has the following shapes: (i) fibrous, (ii) nonwoven fabric, (iii) sheet or film, (iv) tube or roll, or (v) block, sponge, pad or columnar. The resin composition according to claim 1.

10. A resin composition comprising any one of claims 1 to 9, Medical materials.

11. Artificial blood vessels, cardiac repair patches, artificial valves, drug release materials, adhesion prevention materials, artificial bones, artificial cartilage, or wound dressings. The medical material according to claim 10.

12. The process involves preparing a first polymer compound having a first repeating unit in which multiple amino acid residues are linked by peptide bonds in the main chain, The steps include: preparing a second polymer compound having a peptide chain or polypeptide chain at the end of a side chain, in which multiple amino acid residues are linked by peptide bonds; A step of mixing the first polymer compound and the second polymer compound to produce a resin composition containing the first polymer compound and the second polymer compound, It has, The plurality of amino acid residues constituting the repeating unit of the first polymer compound include amino acid residues derived from at least two amino acids selected from the group consisting of glycine, alanine, serine, tyrosine, and valine. The first polymer compound is fibroin or a derivative thereof. The peptide chain or polypeptide chain of the second polymer compound has a second repeating unit formed by peptide bonds between a plurality of amino acid residues, and the amino acid sequence of the second repeating unit is the same as or a part of the amino acid sequence of the first repeating unit. The amino acid sequence of the first repeating unit of the first polymer compound is: GA, AG, GAG, AGA, or GAGA, or any amino acid sequence containing these, A method for producing a resin composition.

13. The step of preparing the second polymer compound is: A step of preparing a third polymer compound, which is a polymer compound different from the first polymer compound and the second polymer compound, and in which at least one of a carboxyl group and an amino group is introduced into the main chain; A step of preparing a peptide or polypeptide having the second repeating unit, The steps include: reacting at least one of the carboxyl group and the amino group of the third polymer compound with the peptide or polypeptide to produce the second polymer compound; including, The method according to claim 12.

14. The ratio of the number of moles of the carboxyl group and the amino group of the third polymer compound to the number of moles of the functional group modified by the peptide or polypeptide is 0.1 or more and 1 or less. The method according to claim 13.