Exudate absorbing material and method for producing exudate absorbing material

Abstract

The purpose of the present invention is to provide an exudate absorbing material excellent in exudate absorption performance and biocompatibility. The exudate absorbing material according to the present invention is an exudate absorbing material (α) containing: (A) a protein; and (B) an organic acid (salt) having a hydroxy group. The protein (A) has a polypeptide chain (Y) and / or a polypeptide chain (Y'). The total number of the polypeptide chain (Y) and the polypeptide chain (Y') in the protein (A) is 1-100. The polypeptide chain (Y) is a polypeptide chain including 2-200 contiguous repeats of an amino acid sequence (X), the amino acid sequence (X) being at least one of: VPGVG sequence (1), which is the amino acid sequence represented by SEQ ID NO: 1; GVGVP sequence (4), which is the amino acid sequence represented by SEQ ID NO: 4; GPP sequence; GAP sequence; and GAHGPAGPK sequence (3), which is the amino acid sequence represented by SEQ ID NO: 3. The polypeptide chain (Y') is a polypeptide chain in which 5% or less of amino acids in the polypeptide chain (Y) are substituted with lysine and / or arginine, wherein the total number of lysine and arginine is 1-100.

Description

Exudate absorbent material and method for manufacturing the same

[0001] The present invention relates to an exudate-absorbing material and a method for making the same.

[0002] Known examples of exudate absorbents include starch-acrylic acid graft materials (see, for example, Patent Document 1).

[0003] Japanese Patent Application Publication No. 06-200

[0004] The technology of Patent Document 1 uses a pressure-sensitive adhesive that is temporarily attached, but its biocompatibility is insufficient. Furthermore, its exudate absorption is also insufficient. The object of the present invention is to provide an exudate-absorbing material that is excellent in exudate absorption and biocompatibility.

[0005] The present inventors have conducted extensive research to solve the above problems and have arrived at the present invention.That is, the present invention provides an exudate-absorbing material (α) containing a protein (A) and an organic acid (salt) (B) having a hydroxyl group, wherein the protein (A) has a polypeptide chain (Y) and / or a polypeptide chain (Y′), the total number of the polypeptide chains (Y) and the polypeptide chains (Y′) in the protein (A) is 1 to 100, and the polypeptide chain (Y) is selected from the group consisting of a VPGVG sequence (1) which is the amino acid sequence shown in SEQ ID NO: 1, a GVGVP sequence (4) which is the amino acid sequence shown in SEQ ID NO: 4, a GPP sequence, a GAP sequence, and a GAP sequence shown in SEQ ID NO: 3. an exudate-absorbing material in which at least one amino acid sequence (X) of the GAHGPAGPK sequence (3) shown in the formula (I) is a polypeptide chain consisting of 2 to 200 consecutive amino acids, and the polypeptide chain (Y') is a polypeptide chain in which 5% or less of the amino acids in the polypeptide chain (Y) are substituted with lysine and / or arginine, and the total number of the lysines and arginines is 1 to 100; a method for producing an exudate-absorbing material (α) containing a protein (A) and an organic acid (salt) (B) having a hydroxyl group, the method comprising: and an organic acid (salt) (B) which is soluble in water to obtain an aqueous solution having a concentration of the protein (A) of 12.5 to 150 g / L; and a freeze-drying step of freeze-drying the aqueous solution in a container to form an exudate-absorbing material (α), wherein the protein (A) has a polypeptide chain (Y) and / or a polypeptide chain (Y'), the total number of the polypeptide chains (Y) and (Y') in the protein (A) is 1 to 100, and the polypeptide chain (Y) is an amino acid sequence represented by SEQ ID NO: 1. A method for producing an exudate-absorbing material (α), wherein at least one amino acid sequence (X) selected from the group consisting of a PGVG sequence (1), a GVGVP sequence (4) which is an amino acid sequence shown in SEQ ID NO: 4, a GPP sequence, a GAP sequence, and a GAHGPAGPK sequence (3) which is an amino acid sequence shown in SEQ ID NO: 3, is a polypeptide chain of 2 to 200 consecutive amino acids, and wherein the polypeptide chain (Y') is a polypeptide chain in which 5% or less of the amino acids in the polypeptide chain (Y) are substituted with lysine and / or arginine, and the total number of the lysines and arginines is 1 to 100.

[0006] The exudate-absorbing material (α) of the present invention has the following advantages: (1) excellent exudate absorption, (2) excellent biocompatibility.

[0007] <Protein (A)> The protein (A) of the present invention has a polypeptide chain (Y) and / or a polypeptide chain (Y'), the total number of the polypeptide chains (Y) and the polypeptide chains (Y') in the protein (A) is 1 to 100, the polypeptide chain (Y) is a polypeptide chain consisting of 2 to 200 consecutive amino acids of at least one amino acid sequence (X) selected from the VPGVG sequence (1) shown in SEQ ID NO: 1, the GVGVP sequence (4) shown in SEQ ID NO: 4, the GPP sequence, the GAP sequence, and the GAHGPAGPK sequence (3) shown in SEQ ID NO: 3, and the polypeptide chain (Y') is a polypeptide chain in which 5% or less of the amino acids in the polypeptide chain (Y) are substituted with lysine and / or arginine, and the total number of the lysines and arginines is 1 to 100.

[0008] The amino acid sequence (X) constituting the polypeptide chain (Y) may be of one type or of two or more types.

[0009] As the amino acid sequence (X), the VPGVG sequence (1) and the GVGVP sequence (4) are preferred from the viewpoints of exudate absorbency and biocompatibility.

[0010] Specific examples of the polypeptide chain (Y) include (VPGVG) ｂ Sequence, (GVGVP) ｃ Sequence and (GAHGPAGPK) ｄ In addition, b to d each represent the number of consecutive amino acid sequences (X) and are integers of 2 to 200. When one molecule of protein (A) contains a plurality of polypeptide chains (Y), the polypeptide chains (Y) may be the same or different, and may be (VPGVG). ｂ Sequence, (GVGVP) ｃ Sequence and (GAHGPAGPK) ｄThe protein (A) may have one or more types selected from the group consisting of sequences. Furthermore, when the protein (A) has multiple polypeptide chains (Y), the number of consecutive amino acid sequences (X) may be the same for each polypeptide chain (Y) or different for each polypeptide chain (Y). That is, the protein (A) may have multiple polypeptide chains (Y) in which the numbers b to d of consecutive amino acid sequences (X) are the same, or multiple polypeptide chains (Y) in which b to d are different. From the viewpoint of exudate absorbency and biocompatibility, the polypeptide chain (Y) may be (VPGVG) ｂ Sequence and (GVGVP) ｃ The sequence is preferred.

[0011] The polypeptide chain (Y) is a polypeptide chain having 2 to 200 consecutive amino acid sequences (X) (2 to 200 of the above b to d), and from the viewpoint of exudate absorbency and biocompatibility, the number of consecutive amino acid sequences (X) is preferably 2 to 100 (2 to 100 of the above b to d), more preferably 2 to 50 (2 to 50 of the above b to d), and particularly preferably 2 to 40 (2 to 40 of the above b to d).

[0012] The polypeptide chain (Y') is a polypeptide chain in which 5% or less of the amino acids in the polypeptide chain (Y) are substituted with lysine and / or arginine, and the total number of substituted lysines and arginines is 1 to 100.

[0013] Whether or not a protein (A) is a polypeptide chain (Y') is determined by whether or not the polypeptide chain (Y) is obtained when all lysines (K) and arginines (R) in the sequence of the protein (A) are replaced with other amino acids [glycine (G), alanine (A), valine (V), proline (P), or histidine (H)].

[0014] In the polypeptide chain (Y'), the proportion of substituted lysine and / or arginine is preferably 0.06% to 5%, more preferably 0.5 to 5%, and particularly preferably 1 to 5%, from the viewpoints of exudate absorbency and biocompatibility.

[0015] The polypeptide chain (Y') may contain an amino acid sequence (X') in which 60% or less of the amino acids in the amino acid sequence (X) are substituted with lysine and / or arginine. Furthermore, the types of the amino acid sequence (X) and / or the amino acid sequence (X') constituting the polypeptide chain (Y') may each be one type or two or more types.

[0016] Specific examples of the amino acid sequence (X') include the GKGVP sequence (7) shown in SEQ ID NO: 7, the GKGKP sequence (8) shown in SEQ ID NO: 8, the GKGRP sequence (9) shown in SEQ ID NO: 9, and the GRGRP sequence (10) shown in SEQ ID NO: 10. From the viewpoints of exudate absorbency and biocompatibility, the amino acid sequence (X') is preferably at least one sequence selected from the group consisting of the GKGVP sequence (7), the GKGKP sequence (8), and the GRGRP sequence (10), and more preferably the GKGVP sequence (7) and the GKGKP sequence (8). The total number of polypeptide chains (Y) and polypeptide chains (Y') in one molecule of protein (A) is 1 to 100. The total number is preferably 1 to 80, and more preferably 1 to 60.

[0017] It is preferable from the viewpoint of exudate absorbency and biocompatibility that the total number of polypeptide chains (Y) and polypeptide chains (Y') in one molecule of protein (A) is within the above range.

[0018] In addition, when protein (A) contains polypeptide chains (Y) having different types and / or different numbers of consecutive amino acid sequences (X), each is counted as one, and the number of polypeptide chains (Y) is the total number of the polypeptide chains (Y). The same applies to polypeptide chains (Y'). Protein (A) of the present invention preferably satisfies the following relational formula (1): 0.50≦[total number of amino acids constituting amino acid sequence (X) contained in protein (A) and amino acid sequences (X') contained in protein (A)] / [total number of amino acids constituting protein (A)]≦0.80 (1)

[0019] The ratio of the number of amino acids can be determined using a protein sequencer. Specifically, it can be determined by the following measurement method. <Measurement Method> Protein (A) is decomposed to approximately 30 residues or less using two or more cleavage methods that can cleave at specific amino acid residues. After that, the protein is separated by high-performance liquid chromatography (HPLC) and the amino acid sequence is read using a protein sequencer. The obtained amino acid sequence is subjected to peptide mapping to determine the entire sequence of protein (A). Then, "(the total number of amino acids constituting amino acid sequence (X) contained in protein (A) and amino acid sequence (X') contained in protein (A)) / (the total number of amino acids constituting protein (A))" is calculated.

[0020] From the viewpoints of exudate absorbency and biocompatibility, the protein (A) preferably has a polypeptide chain (S) in which 2 to 50 consecutive GAGAGS sequences (2), which is the amino acid sequence shown in SEQ ID NO: 2, are linked together. From the viewpoints of exudate absorbency and biocompatibility, the number of consecutive GAGAGS sequences (2) in the polypeptide chain (S) is preferably 2 to 40, more preferably 2 to 30, and particularly preferably 2 to 10.

[0021] In protein (A), the ratio of the number of amino acids in all GAGAGS sequences (2) to the total number of amino acids in protein (A) [{number of GAGAGS sequences (2) in protein (A) × 6} / {total number of amino acids in protein (A)} × 100] is preferably 5 to 50%, more preferably 10 to 47.5%, and particularly preferably 20 to 45%, from the viewpoints of exudate absorbency and biocompatibility. The ratio of the number of amino acids in all GAGAGS sequences (2) to the total number of amino acids in protein (A) can be determined using a protein sequencer. Specifically, it is determined by the following measurement method.

[0022] <Proportion of the number of amino acids in all GAGAGS sequences (2) to the total number of amino acids in protein (A)> Protein (A) is decomposed to approximately 30 residues or less using two or more cleavage methods that can cleave at specific amino acid residues. After separation by high performance liquid chromatography (HPLC), the amino acid sequence is read using a protein sequencer. The obtained amino acid sequence is subjected to peptide mapping to determine the entire sequence of protein (A). The ratio of the number of amino acids in all GAGAGS sequences (2) to the total number of amino acids in protein (A) is then calculated using the following measurement formula: Percentage (%) of the number of amino acids in all GAGAGS sequences (2) to the total number of amino acids in protein (A) = [{number of GAGAGS sequences (2) × 6} / {total number of amino acids in protein (A)}] × 100

[0023] When the protein (A) has a total of two or more polypeptide chains of at least one type selected from the group consisting of polypeptide chain (Y), polypeptide chain (Y'), and polypeptide chain (S), an intervening amino acid sequence (Z) may be present between these chains. The intervening amino acid sequence (Z) is a peptide sequence in which one or more amino acids are linked, and is not a GAGAGS sequence (2), an amino acid sequence (X), or an amino acid sequence (X'). From the viewpoints of exudate absorbency and biocompatibility, the number of amino acids constituting the intervening amino acid sequence (Z) is preferably 1 to 30, more preferably 1 to 15, and particularly preferably 1 to 10. Specific examples of the intervening amino acid sequence (Z) include the VAAGY sequence (11) shown in SEQ ID NO: 11, the GAAGY sequence (12) shown in SEQ ID NO: 12, and an LGP sequence. The ratio of the number of amino acids in all intervening amino acid sequences (Z) to the total number of amino acids in protein (A) [Σ{(number of amino acids in intervening amino acid sequences (Z)) × (number of intervening amino acid sequences (Z))} / {total number of amino acids in protein (A)} × 100] is preferably 0 to 25%, more preferably 0 to 22.5%, and particularly preferably 0.01 to 15%, from the viewpoints of exudate absorbency and biocompatibility.

[0024] From the viewpoint of in vivo degradability, the protein (A) may have a terminal amino acid sequence (T) at its terminal in addition to the GAGAGS sequence (2), the amino acid sequence (X), the amino acid sequence (X'), and the intervening amino acid sequence (Z). The terminal amino acid sequence (T) may be located at one or both terminals of the protein (A). The terminal amino acid sequence (T) does not include the purification tag described below. The terminal structure of the protein (A) is preferably a structure in which the terminal amino acid sequence (T) is bound to the polypeptide chain (Y). The terminal amino acid sequence (T) is a peptide sequence in which one or more amino acids are bound, and is not the GAGAGS sequence (2), the amino acid sequence (X), or the amino acid sequence (X'). From the viewpoint of in vivo degradability, the number of amino acids constituting the terminal amino acid sequence (T) is preferably 1 to 100, more preferably 1 to 50, and particularly preferably 1 to 40. Specific examples of the terminal amino acid sequence (T) include the amino acid sequence MDPVVLQRRDWENPGVTQLNRLAAHPPFASDPM (13), which is the amino acid sequence shown in SEQ ID NO: 13.

[0025] The ratio of the number of amino acids in the terminal amino acid sequence (T) to the total number of amino acids in the protein (A) is preferably 0 to 25%, more preferably 0 to 22.5%, and particularly preferably 0.01 to 15%, from the viewpoint of in vivo degradability.

[0026] As described below, protein (A) may be produced using bacteria by bioengineering techniques. In such cases, to facilitate the purification or detection of the expressed protein (A), the protein (A) may have, in addition to the terminal amino acid sequence (T), a protein or peptide having a special amino acid sequence at the N- or C-terminus (hereinafter referred to as a "purification tag"). Affinity purification tags are used as purification tags. Examples of such purification tags include a 6xHis tag consisting of polyhistidine, a V5 tag, an Xpress tag, an AU1 tag, a T7 tag, a VSV-G tag, a DDDDK tag, an S tag, CruzTag09™, CruzTag22™, CruzTag41™, a Glu-Glu tag, a Ha.11 tag, and a KT3 tag. Below are examples of combinations of each purification tag (i) with a ligand (ii) that recognizes and binds to that tag. (i-1) glutathione-S-transferase (GTS) (ii-1) glutathione (i-2) maltose-binding protein (MBP) (ii-2) amylose (i-3) HQ tag (ii-3) nickel (i-4) Myc tag (ii-4) anti-Myc antibody (i-5) HA tag (ii-5) anti-HA antibody (i-6) FLAG tag (ii-6) anti-FLAG antibody (i-7) 6xHis tag (ii-7) nickel or cobalt Examples of a method for introducing the purification tag sequence include a method in which a nucleic acid encoding the purification tag is inserted into the 5' or 3' end of a nucleic acid encoding the protein (A) in an expression vector, and a method in which a commercially available vector for introducing a purification tag is used.

[0027] In protein (A), the ratio of the total number of amino acids in all intervening amino acid sequences (Z) constituting protein (A), the total number of amino acids in all terminal amino acid sequences (T) constituting protein (A), and the total number of amino acids in the purification tag is preferably 0 to 25%, more preferably 0 to 22.5%, and particularly preferably 0.01 to 15%, based on the total number of amino acids in protein (A), from the viewpoint of in vivo degradability.

[0028] When the protein (A) contains a polypeptide chain (Y) and / or a polypeptide chain (Y') and a polypeptide chain (S), it is preferable that the polypeptide chain (Y) or the polypeptide chain (Y') and the polypeptide chain (S) are chemically bonded alternately from the viewpoint of exudate absorbency and biocompatibility.

[0029] The ratio of the number of GAGAGS sequences (2) to the total number of amino acid sequences (X) and (X') (GAGAGS sequences (2):total of amino acid sequences (X) and (X')) is preferably 1:1.5 to 1:20, more preferably 1:1.5 to 1:6, and particularly preferably 1:2 to 1:5, from the viewpoint of exudate absorbency and biocompatibility. Some preferred examples of proteins (A) are shown below.

[0030] (A1): A protein in which the amino acid sequence (X) is the GVGVP sequence (4). (A11): A protein having a polypeptide chain (Y'1) in which one amino acid in a polypeptide chain (Y1) consisting of 2 to 200 consecutive GVGVP sequences (4) is substituted with lysine (K). (A11-1): A protein having a polypeptide chain (Y'1) and a polypeptide chain (S1) consisting of 2 to 200 consecutive GAGAGS sequences (2). (A11-2): An amino acid sequence (GVGVP) consisting of 8 consecutive GVGVP sequences (4) as shown in SEQ ID NO: 14. ８ The amino acid sequence shown in SEQ ID NO: 6 in which one amino acid in the polypeptide chain (Y11) of sequence (14) is replaced with lysine (K) (GVGVP). ４ GKGVP (GVGVP) ３ A protein having a polypeptide chain (S1) of sequence (6) (Y'11) and 2 to 200 consecutive GAGAGS sequences (2): an amino acid sequence shown in SEQ ID NO: 5 with 4 consecutive GAGAGS sequences (2) (GAGAGS) ４ The polypeptide chain (S1-1) of sequence (5) and the polypeptide chain (GVGVP) shown in SEQ ID NO: 6 ４ GKGVP (GVGVP) ３ Proteins having the sequence (6) include the following proteins: (i) (GAGAGS) ４ 12 sequences (5) and (GVGVP)４ GKGVP (GVGVP) ３ The amino acid sequence (GAGAGS) shown in SEQ ID NO: 15 is added to the 13 sequences (6) which are chemically bonded alternately. ２ A protein (SELP8K) having the amino acid sequence of SEQ ID NO: 16 and a molecular mass of approximately 80 kDa, to which the sequence (15) is chemically bound. (ii) (GAGAGS) ４ Sequences (5) and (GVGVP) ４ GKGVP (GVGVP) ３ A protein (SELP8K4) having an amino acid sequence (27) represented by SEQ ID NO: 27, which has four units of each of the sequences (6), which are chemically bonded alternately, and has a molecular mass of approximately 30 kDa. (A11-2-2): A protein having an amino acid sequence represented by SEQ ID NO: 15, which has two consecutive GAGAGS sequences (2) (GAGAGS). ２ Polypeptide chain (S1-2) having sequence (15) and (GVGVP) ４ GKGVP (GVGVP) ３ (i) a protein having the sequence (6) (GAGAGS) ２ Sequences (15) and (GVGVP) ４ GKGVP (GVGVP) ３ A protein (SELP0K) having 17 amino acids of sequence (6) each, which are chemically bonded alternately, and having a molecular mass of approximately 82 kDa, the amino acid sequence of sequence (17) shown in SEQ ID NO: 17.

[0031] (A11-3): The GVGVP sequence (4) is the amino acid sequence shown in SEQ ID NO: 18 in which one amino acid in the 12 consecutive polypeptide chains is substituted with lysine (K) (GVGVP). ６ GKGVP (GVGVP) ５ A protein (A11-3-1) having a polypeptide chain (S1) of 2 to 200 consecutive GAGAGS sequences (2) (Y'12) and an amino acid sequence represented by SEQ ID NO: 19, which has 4 consecutive GAGAGS sequences (2) (GAGAGS). ４ Sequence (19) and (GVGVP) ６ GKGVP (GVGVP)5 sequence (18) and a protein (i) (GAGAGS)４ 12 sequences (19) and (GVGVP) ６ GKGVP (GVGVP) ５ The compound has 13 sequences (18) which are chemically bonded alternately to each other, and (GAGAGS) ２ A protein (SELP8K12) having the amino acid sequence (20) shown in SEQ ID NO: 20 and a molecular mass of approximately 105 kDa, to which the sequence (15) is chemically bound.

[0032] (A2): A protein in which the amino acid sequence (X) is the VPGVG sequence (1). (A21): A protein having a polypeptide chain (Y2) in which 2 to 200 consecutive VPGVG sequences (1) are present and a GAGAGS sequence (2). (i) The GAGAGS sequence (2) is the amino acid sequence shown in SEQ ID NO: 24 (VPGVG). ４ The amino acid sequence shown in sequence (24) and sequence number 25 (VPGVG) ８ Each has 40 copies of the sequence (25), which are (VPGVG) ４ Sequence (24), GAGAGS sequence (2), (VPGVG) ８ A protein (ELP1.1) having a molecular mass of approximately 200 kDa and an amino acid sequence represented by SEQ ID NO: 26, which has a structure formed by chemically bonding 40 blocks of the sequence (25) in order.

[0033] (A3): A protein having a polypeptide chain (Y1) of 2 to 200 consecutive GVGVP sequences (4) and a polypeptide chain (S1) of 2 to 200 consecutive GAGAGS sequences (2). Specifically, the following proteins are included: (i) (GAGAGS) is the amino acid sequence shown in SEQ ID NO: 21. ８ The amino acid sequence shown in sequence (21) and sequence number 22 (GVGVP) ４０ A protein (SELP6.1) having five amino acids of sequence (22), each of which is chemically bonded alternately, and having a molecular mass of approximately 110 kDa, the amino acid sequence of sequence (23) shown in SEQ ID NO: 23.

[0034] Among these, the protein of sequence (16) (SELP8K), the protein of sequence (17) (SELP0K), the protein of sequence (20) (SELP8K12), the protein of sequence (23) (SELP6.1), the protein of sequence (26) (ELP1.1), or the protein of sequence (27) (SELP8K4) is preferred. Furthermore, protein (A) may be a protein having an amino acid sequence that is 70% or more homologous to the amino acid sequence of the protein of sequence (16) (SELP8K), the protein of sequence (17) (SELP0K), the protein of sequence (20) (SELP8K12), the protein of sequence (23) (SELP6.1), the protein of sequence (26) (ELP1.1), or the protein of sequence (27) (SELP8K4). Furthermore, this homology is preferably 80% or more, and more preferably 90% or more.

[0035] The molecular mass of protein (A) as determined by SDS-PAGE (SDS polyacrylamide gel electrophoresis) is preferably 15 to 200 kDa, more preferably 30 to 150 kDa, and particularly preferably 70 to 120 kDa, from the viewpoint of in vivo degradability.

[0036] In the present invention, protein (A) can be obtained by extraction from natural products, organic synthesis (enzymatic methods, solid-phase synthesis, liquid-phase synthesis, etc.), genetic recombination, etc. Regarding organic synthesis, methods such as those described in "Lectures on Biochemical Experiments 1, Chemistry of Proteins IV (July 1, 1981, edited by the Japanese Biochemical Society, published by Tokyo Kagaku Dojin Co., Ltd.)" and "Continued Lectures on Biochemical Experiments 2, Chemistry of Proteins (Part 2) (May 20, 1987, edited by the Japanese Biochemical Society, published by Tokyo Kagaku Dojin Co., Ltd.)" can be applied. Regarding genetic recombination, methods such as those described in Japanese Patent No. 3338441 can be applied. Although protein (A) can be obtained by extraction from natural products, organic synthesis, and genetic recombination, genetic recombination is preferred from the viewpoints of easily modifying the amino acid sequence and enabling inexpensive mass production.

[0037] <Organic Acid (Salt) (B) Having a Hydroxy Group> In the present invention, the organic acid (salt) (B) having a hydroxyl group refers to an organic acid having a hydroxyl group and / or an organic acid salt having a hydroxyl group. Examples of the organic acid (salt) (B) having a hydroxyl group include ascorbic acid (salt) and citric acid (salt). Examples of the salt include sodium salt and potassium salt. Of these, from the viewpoints of exudate absorbency and biocompatibility, preferred are ascorbic acid, citric acid, and sodium ascorbate, and more preferred is ascorbic acid. The organic acid (salt) (B) having a hydroxyl group may be used alone or in combination of two or more.

[0038] <Exudate-absorbing material (α)> The exudate-absorbing material (α) of the present invention contains a protein (A) and a hydroxyl-containing organic acid (salt) (B). The weight ratio of the hydroxyl-containing organic acid (salt) (B) to the protein (A) [weight of the hydroxyl-containing organic acid (salt) (B) / weight of the protein (A)] is preferably 0.01 to 0.25, and more preferably 0.02 to 0.1, from the viewpoints of exudate absorbency and biocompatibility.

[0039] The exudate absorbent material (α) is preferably in the form of a sponge. In this case, the density is preferably 50 to 600 mg / cm from the viewpoints of handling and exudate absorption. ３ and more preferably 75 to 450 mg / cm ３ , particularly preferably 100 to 350 mg / cm ３ is.

[0040] The exudate-absorbing material (α) can be produced, for example, by the following method: (1) A purified protein (A) and a hydroxyl-containing organic acid (salt) (B) are dissolved in deionized water to obtain an aqueous solution, (2) the aqueous solution is placed in a container, freeze-dried, and molded to obtain the exudate-absorbing material (α).

[0041] The density of the exudate-absorbing material (α) can be appropriately adjusted by adjusting the concentration of the aqueous solution containing the protein (A) and the hydroxyl-containing organic acid (salt) (B) in the freeze-drying step of the molding method, for example, by adjusting the density within the preferred range described below.

[0042] In the freeze-drying step, the aqueous solution is preferably poured into a mold (such as a metal mold) corresponding to the desired shape and freeze-dried. This allows the production of a shape-reliable exudate-absorbing material (α). The shape of the exudate-absorbing material (α) is not particularly limited, but may be a sheet, a rectangular parallelepiped, a cylinder, or the like.

[0043] The weight proportion of the protein (A) contained in the aqueous solution is preferably 12.5 to 150 g / L, more preferably 25 to 100 g / L, and particularly preferably 25 to 50 g / L, based on the volume of the aqueous solution.

[0044] Furthermore, the freeze-drying preferably comprises primary drying and secondary drying. The temperature during primary drying is preferably −35 to −5° C. from the viewpoint of moldability. The degree of vacuum during primary drying is preferably 0 to 20 Pa from the viewpoint of moldability. The time during primary drying is preferably 1 to 200 hours from the viewpoint of moldability. The temperature during secondary drying is preferably 5 to 35° C., more preferably 5 to 30° C. from the viewpoint of moldability. The degree of vacuum during secondary drying is preferably 0 to 20 Pa from the viewpoint of moldability. The time during secondary drying is preferably 1 to 200 hours from the viewpoint of moldability. Drying in two stages, primary drying and secondary drying, improves exudate absorbency and moldability.

[0045] The exudate-absorbing material (α) of the present invention can be used as a dressing material for covering external wounds. For example, it may be used for primary healing and secondary healing, and is more preferably used for secondary healing. More specifically, it can be used for pressure ulcers, ischemic ulcers, diabetic ulcers, open wounds, postoperative dehiscence wounds, infected wounds, burns, etc. It is particularly suitable for wounds that produce a lot of exudate (e.g., ischemic ulcers).

[0046] When using the exudate absorbent material (α) of the present invention, for example, the wound surface may be cleansed and then the exudate absorbent material (α) may be applied to the wound surface. Furthermore, it is preferable to apply the exudate absorbent material (α) to the wound by a procedure of applying a cover dressing, fixing, and protecting the wound. Such a method also corresponds to the method of the present invention for treating at least one wound selected from the group consisting of pressure ulcers, ischemic ulcers, diabetic ulcers, open wounds, postoperative dehiscence wounds, infected wounds, and burns. Furthermore, the use of the exudate absorbent material (α) on at least one wound selected from the group consisting of pressure ulcers, ischemic ulcers, diabetic ulcers, open wounds, postoperative dehiscence wounds, infected wounds, and burns also corresponds to the use of the exudate absorbent material of the present invention.

[0047] This specification describes the following:

[0048] The present invention (1) provides an exudate-absorbing material (α) containing a protein (A) and an organic acid (salt) (B) having a hydroxyl group, wherein the protein (A) has a polypeptide chain (Y) and / or a polypeptide chain (Y'), the total number of the polypeptide chains (Y) and the polypeptide chains (Y') in the protein (A) is 1 to 100, the polypeptide chain (Y) is a polypeptide chain consisting of 2 to 200 consecutive amino acids (X) of at least one of the amino acid sequences (X) selected from the VPGVG sequence (1) shown in SEQ ID NO: 1, the GVGVP sequence (4) shown in SEQ ID NO: 4, the GPP sequence, the GAP sequence, and the GAHGPAGPK sequence (3) shown in SEQ ID NO: 3, and the polypeptide chain (Y') is a polypeptide chain in which 5% or less of the amino acids in the polypeptide chain (Y) are substituted with lysine and / or arginine, and the total number of the lysine and arginine residues is 1 to 100.

[0049] The present invention (2) is an exudate-absorbing material according to the present invention (1), wherein the organic acid (salt) (B) having a hydroxyl group is at least one selected from the group consisting of ascorbic acid (salt) and citric acid (salt).

[0050] The present invention (3) is the exudate-absorbing material according to the present invention (1) or (2), wherein the weight ratio of the organic acid (salt) (B) having a hydroxyl group to the protein (A) [weight of the organic acid (salt) (B) having a hydroxyl group / weight of the protein (A)] is 0.01 to 0.25.

[0051] The present invention (4) is the exudate absorbing material according to any one of the present inventions (1) to (3), wherein the exudate absorbing material has a fixed shape.

[0052] The present invention (5) is characterized in that the density of the exudate absorbent material is 50 to 600 mg / cm ３ The exudate-absorbing material according to any one of the present inventions (1) to (4),

[0053] The present invention (6) is the exudate-absorbing material according to any one of the present inventions (1) to (5), wherein the protein (A) has a molecular mass of 15 to 200 kDa as determined by SDS-PAGE (SDS polyacrylamide gel electrophoresis).

[0054] The present invention (7) is an exudate-absorbing material according to any one of the present inventions (1) to (6), wherein the protein (A) has the amino acid sequence shown in SEQ ID NO: 16, the amino acid sequence shown in SEQ ID NO: 17, the amino acid sequence shown in SEQ ID NO: 20, the amino acid sequence shown in SEQ ID NO: 23, the amino acid sequence shown in SEQ ID NO: 26, the amino acid sequence shown in SEQ ID NO: 27, or an amino acid sequence having a homology of 70% or more with any of these amino acid sequences.

[0055] The present invention (8) is a method for producing an exudate-absorbing material (α) containing a protein (A) and an organic acid (salt) (B) having a hydroxyl group, the method comprising the steps of: dissolving the protein (A) and the organic acid (salt) (B) having a hydroxyl group in water to obtain an aqueous solution having a protein (A) concentration of 12.5 to 150 g / L; and freeze-drying the aqueous solution in a container to form the exudate-absorbing material (α), wherein the protein (A) has a polypeptide chain (Y) and / or a polypeptide chain (Y'), and the total number of the polypeptide chains (Y) and the polypeptide chains (Y') in the protein (A) is 1 to 100. wherein the polypeptide chain (Y) is a polypeptide chain having 2 to 200 consecutive amino acids of at least one amino acid sequence (X) selected from the amino acid sequence VPGVG (1) shown in SEQ ID NO: 1, the amino acid sequence GVGVP (4) shown in SEQ ID NO: 4, the amino acid sequence GPP, the amino acid sequence GAP, and the amino acid sequence GAHGPAGPK (3) shown in SEQ ID NO: 3, and the polypeptide chain (Y') is a polypeptide chain in which 5% or less of the amino acids in the polypeptide chain (Y) are substituted with lysine and / or arginine, and the total number of the lysines and arginines is 1 to 100.

[0056] The present invention (9) is a method for producing the exudate-absorbing material (α) according to the present invention (8), wherein in the freeze-drying step, primary drying is carried out under conditions of a temperature of −35 to −5° C., a degree of vacuum of 0 to 20 Pa, and a time of 1 to 200 hours, and then secondary drying is carried out under conditions of a temperature of 5 to 35° C., a degree of vacuum of 0 to 20 Pa, and a time of 1 to 200 hours.

[0057] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0058] <Production Example 1> [Preparation of SELP8K] Preparation of a SELP8K-producing strain Plasmid pPTS0345 encoding SELP8K was prepared according to the method described in the Examples of Japanese Patent No. 4088341. The prepared plasmid was transformed into Escherichia coli to obtain a SELP8K-producing strain. Hereinafter, this SELP8K-producing strain was used to produce (GAGAGS), a type of polypeptide (A). ４ 12 sequences (6) and (GVGVP) ４ GKGVP (GVGVP) ３ This shows a method for producing SELP8K (polypeptide (A1)), a polypeptide of sequence (16) with a molecular mass of approximately 80 kDa, which has 13 units of sequence (7) chemically bonded alternately.

[0059] Culturing of the SELP8K-producing strain: An overnight culture of the SELP8K-producing strain grown at 30°C was used to inoculate 50 ml of LB medium in a 250 ml flask. Kanamycin was added to the LB medium to a final concentration of 50 μg / ml to form a culture medium, and the culture medium was incubated at 30°C with stirring (200 rpm). When the turbidity of the culture medium reached OD600 = 0.8 (using a UV1700 spectrophotometer, manufactured by Shimadzu Corporation), 40 ml of the culture medium was transferred to another flask preheated to 42°C and cultured at 42°C for approximately 2 hours. The culture medium was then cooled on ice, the turbidity OD600 of the culture medium was measured, and the E. coli cells were collected by centrifugation.

[0060] Purification of SELP8K Protein was purified from the harvested E. coli biomass by the following steps: Step 1: cell lysis, Step 2: removal of insoluble debris by centrifugation, Step 3: ammonium sulfate precipitation, Step 4: ultrafiltration, Step 5: cation exchange chromatography, Step 6: ultrafiltration, and Step 7: lyophilization. In this manner, purified SELP8K (polypeptide (A1)) with a molecular mass of approximately 85 kDa was obtained.

[0061] Step 1: Cell Lysis 200 g of deionized water was added to 100 g of collected E. coli, and the cells were lysed using a high-pressure homogenizer (55 MPa) to obtain a cell lysate containing lysed cells. The pH of the cell lysate was then adjusted to 4.0 with glacial acetic acid.

[0062] Step 2: Removal of insoluble debris by centrifugation The cell lysate was further centrifuged (6300 rpm, 4°C, 30 minutes) to recover the supernatant.

[0063] Step 3: Ammonium sulfate precipitation A saturated ammonium sulfate solution was added to the supernatant recovered in step 2 so that the ammonium sulfate concentration was 25% by weight. After that, the mixture was left to stand for 8 to 12 hours, and the precipitate was recovered by centrifugation. The recovered precipitate was dissolved in deionized water. Next, a saturated ammonium sulfate solution was added to the dissolved solution so that the ammonium sulfate concentration was 25% by weight. After that, the mixture was left to stand for 8 to 12 hours, and the precipitate was recovered by centrifugation. The recovered precipitate was dissolved in deionized water to obtain a solution.

[0064] Step 4: Ultrafiltration The solution obtained in step 3 was subjected to an ultrafiltration device (hollow fiber, manufactured by GE Healthcare) with a molecular mass cutoff of 30,000. Ultrafiltration was performed using 20 times the amount of deionized water with respect to the solution obtained in step 3, to obtain a polypeptide solution after ultrafiltration.

[0065] Step 5: Cation Exchange Chromatography The ultrafiltered polypeptide solution was added to 10 mM sodium acetate buffer to adjust the polypeptide concentration to 20 g / L, and then subjected to an AKTA Prime (Amersham) equipped with a cation exchange column HiPrepSP XL16 / 10 (GE Healthcare). 500 mM sodium acetate buffer was used as the eluent, and the eluted fraction was collected.

[0066] Step 6: Ultrafiltration The eluted fraction obtained in step 5 was treated in the same manner as in "4: Ultrafiltration" above to obtain a polypeptide solution after ultrafiltration.

[0067] Step 7: Freeze-Drying The polypeptide solution obtained in step 6 was diluted with deionized water to a polypeptide concentration of 3 g / L, and placed in a stainless steel tray so that the water level was 10 mm or less. The solution was then placed in a freeze-dryer (manufactured by Nippon Techno Service Co., Ltd.) and frozen at -30°C for 24 hours. After freezing, the solution was subjected to primary drying at a vacuum of 5 Pa or less and -30°C for 110 hours, and secondary drying at a vacuum of 5 Pa or less and 30°C for 48 hours to obtain SELP8K (protein (A-1)). Protein (A) was identified using the Western blotting method described below. Regarding protein (A-1), the ratio of [the total number of amino acids constituting amino acid sequence (X) contained in protein (A) and the amino acid constituting amino acid sequence (X') contained in protein (A)] / [the total number of amino acids constituting protein (A)]] was 0.54. The ratio of the number of GAGAGS sequences (2) to the total number of amino acid sequences (X) and (X') in one molecule of protein (A-1) (GAGAGS sequences (2):total of amino acid sequences (X) and (X')) is 1:2.

[0068] Identification of SELP8K (A-1) Analysis was performed by Western blotting using rabbit anti-SELP8K antibody and rabbit anti-6xHis antibody (Roland) against the 6xHis tag in the C-terminal sequence. The Western blotting procedure was as follows. A band showing antibody reactivity with each antibody was observed at the apparent molecular mass of 80 kDa. Table 1 shows the measured amino acid composition ratios of protein (A) obtained by amino acid composition analysis using an amino acid analysis system (Prominence, Shimadzu Corporation) and the theoretical amino acid composition ratios of SELP8K predicted from the synthetic gene sequence. From these, protein (A) is a polypeptide chain (Y) consisting of eight consecutive GVGVP sequences (4), in which one of the valines (V) in the chain is replaced with a lysine (K) (GVGVP)4GKGVP(GVGVP)3 sequence (6), and a polypeptide chain (Y'11) consisting of 13 consecutive GVGVP sequences (4), in which one of the valines (V) in the chain is replaced with a lysine (K) (GAGAGS). ４The polypeptide chain (S1-1) of sequence (5) is chemically bonded alternately to the polypeptide chain (S1-1) of sequence (5), and the amino acid sequence (GAGAGS) of sequence number 15 is added to the polypeptide chain (S1-1). ２ It was confirmed that the protein (SELP8K) had the sequence (16) formed by chemically bonding the sequence (15).

[0069]

[0070] Western Blotting: 20 μL of Western blot sample was mixed with 10 μL of 3xSDS buffer (containing 150 mM Tris HCl (pH 6.8), 300 mM dithiothreitol, 6% by weight sodium dodecyl sulfate (SDS), 0.3% by weight bromophenol blue, and 30% by weight glycerol) and heated at 95°C for 5 minutes to prepare a sample for electrophoresis. SDS-PAGE was performed using 15 μL of this sample for electrophoresis. After electrophoresis, the gel was transferred to a polyvinylidene fluoride membrane (hereinafter referred to as "membrane"), which was then immersed in blocking buffer (containing 20 mM Tris (pH 7.6), 137 mM NaCl, 0.1% by weight Tween 20, and 5% by weight skim milk) and shaken at room temperature for 1 hour to block the membrane. After blocking, the membrane was washed for 2 minutes with TBS-T [containing 20 mM Tris (pH 7.6), 137 mM NaCl, and 0.1% by weight Tween 20]. Next, the membrane was immersed in a primary antibody solution (primary antibodies: anti-SELP8K antibody and anti-His-tag antibody (manufactured by Rockland) diluted 1:500 with TBS-T) and left overnight at 4°C to allow the antibody reaction to occur. After the reaction, the membrane was washed four times with TBS-T for 5 minutes each, and then immersed in a solution of a secondary antibody capable of binding to the primary antibody and conjugated with horseradish peroxidase as a labeling enzyme (secondary antibody: ECL anti-rabbit IgG HRP-linked F(ab')2 fragment (GE Healthcare) diluted 1:2000 with TBS-T), and allowed to stand at room temperature for 30 minutes to carry out an antibody reaction. After the reaction, the membrane was washed four times with TBS-T for 5 minutes each, and then an enzyme reaction was carried out using an ECL-Advance Western Blotting Detection Kit (GE Healthcare). The bands were exposed to light using a Luminometer ForECL (GE Healthcare), and observed with a chemiluminescence fluorescence imaging device.

[0071] Example 1: 12.5 mg of "SELP8K" (protein (A)) and 1.0 mg of ascorbic acid (B-1) were diluted with deionized water to obtain 1 mL of a solution [protein (A) concentration: 12.5 mg / mL, weight ratio (B) / (A) = 0.008]. 0.5 mL of this solution was placed in a cylindrical mold with a diameter of 9.85 mm and a depth of 17.5 mm. The solution was then placed in a freeze dryer (manufactured by Nippon Techno Service Co., Ltd.) and frozen at -40°C for 16 hours. After freezing, the solution was subjected to primary drying at a vacuum of 8 Pa or less and -20°C for 90 hours, followed by secondary drying at a vacuum of 8 Pa or less and 20°C for 24 hours, yielding a cylindrical sponge-like exudate absorbent material (α-1). The resulting exudate absorbent material was evaluated as described below.

[0072] Examples 2 to 14 and Comparative Examples 1 to 3 Exudate absorbent materials (α-2) to (α-14) according to Examples 2 to 14 and exudate absorbent materials (rα-1) to (rα-2) according to Comparative Examples 1 and 2 were obtained in the same manner as in Example 1, except that the protein (A), the weight of (A), (B), and the weight ratio (B) / (A) in Example 1 were changed according to Table 2. Note that a commercially available starch-acrylic acid graft was used for Comparative Example 3.

[0073] Example 15 (GAGAGS) was prepared in the same manner as in Production Example 1, except that "plasmid pPT0364 encoding SELP0K" was used instead of "plasmid pPT0345 encoding SELP8K." ２ Sequences (15) and (GVGVP) ４ GKGVP (GVGVP) ３ A protein (SELP0K) having a molecular mass of approximately 82 kDa and an amino acid sequence (17) represented by SEQ ID NO: 17, which has 17 units of each of the sequences (6) chemically bonded alternately, was obtained. Next, an exudate-absorbing material (α-15) according to Example 15 was obtained in the same manner as in Example 1, except that the weights of proteins (A), (A), (B), and the weight ratio (B) / (A) in Example 1 were determined according to Table 2.

[0074] Example 16 (GAGAGS) was prepared in the same manner as in Production Example 1, except that "plasmid pPT0345-4 encoding SELP8K4" was used instead of "plasmid pPT0345 encoding SELP8K" in Production Example 1. ４ Sequences (5) and (GVGVP) ４ GKGVP (GVGVP) ３ A protein (SELP8K4) having sequence (27), which has four copies of sequence (6) each, chemically bonded alternately, and has a molecular mass of approximately 30 kDa, was obtained. The exudate-absorbing material (α-16) of Example 16 was then obtained in the same manner as in Example 1, except that the weights of proteins (A), (A), (B), and the weight ratio (B) / (A) in Example 1 were determined according to Table 2.

[0075] Example 17 (GAGAGS) was prepared in the same manner as in Production Example 1, except that "plasmid pPT0345-12 encoding SELP8K12" was used instead of "plasmid pPT0345 encoding SELP8K" in Production Example 1. ４ 12 sequences (19) and (GVGVP) ６ GKGVP (GVGVP) ５ The compound has 13 sequences (18) which are chemically bonded alternately to each other, and (GAGAGS) ２ A protein (SELP8K12) having a molecular mass of approximately 105 kDa and an amino acid sequence (20) chemically bonded to sequence (15) was obtained. The exudate-absorbing material (α-17) of Example 17 was obtained in the same manner as in Example 1, except that the weights of proteins (A), (A), (B), and the weight ratio (B) / (A) were determined in accordance with Table 2.

[0076] Example 18: The procedure of Production Example 1 was repeated except that "plasmid pPT0102-1 encoding ELP1.1" was used instead of "plasmid pPT0345 encoding SELP8K." GAGAGS sequence (2), the amino acid sequence shown in SEQ ID NO: 24 (VPGVG), was prepared. ４ The amino acid sequence shown in sequence (24) and sequence number 25 (VPGVG)８ Each has 40 copies of the sequence (25), which are (VPGVG) ４ Sequence (24), GAGAGS sequence (2), (VPGVG) ８ A protein (ELP1.1) having a molecular mass of approximately 200 kDa and an amino acid sequence (26) represented by SEQ ID NO: 26, was obtained, which has a structure formed by chemically bonding 40 blocks bonded in the order of sequence (25). Next, an exudate-absorbing material (α-18) according to Example 18 was obtained in the same manner as in Example 1, except that the weights of proteins (A), (A), (B), and the weight ratio (B) / (A) in Example 1 were determined according to Table 2.

[0077] Example 19 A plasmid encoding SELP6.1 (GAGAGS) having the amino acid sequence shown in SEQ ID NO: 21 was prepared in the same manner as in Preparation Example 1, except that the plasmid encoding SELP8K (pPT0345) was replaced with the plasmid encoding SELP6.1 (pPT0270-1). ８ The amino acid sequence shown in sequence (21) and sequence number 22 (GVGVP) ４０ A protein (SELP6.1) having a molecular mass of approximately 110 kDa and an amino acid sequence (23) represented by SEQ ID NO: 23, was obtained, which has five units of each of the sequences (22), which are chemically bonded alternately. Next, an exudate-absorbing material (α-19) according to Example 9 was obtained in the same manner as in Example 1, except that the weights of proteins (A), (A), (B), and the weight ratio (B) / (A) in Example 1 were determined according to Table 2.

[0078] (1) Density (unit: mg / cm ３ The diameter and height of each sponge-like exudate absorbent material were measured using a dial gauge, and the volume was measured. The weight was also measured using a balance, and the density (mg / cm) was calculated from the volume and weight. ３ ) was calculated.

[0079] (2) Absorption rate of exudate (unit: seconds) This test was carried out in accordance with JIS L1907. 10 μL of saline was dropped using a micropipette from 10 mm above the exudate absorbent material. The time from when the water droplet reached the test piece until the water droplet was completely absorbed by the test piece was calculated by analyzing the video. The average of five measurements is shown.

[0080] (3) Biocompatibility Each exudate absorbent material was directly applied to the skin of a mouse and the mouse was kept for one week. After that, the exudate absorbent material was peeled off, and the mouse's skin was observed and evaluated according to the following <Evaluation criteria>. <Evaluation criteria> ◯: No inflammation at all ○: Almost no inflammation ×: Inflammation

[0081]

[0082] The results in Table 2 show that the exudate absorbent material (α) of the present invention is superior to the comparative material in terms of exudate absorption and also in terms of biocompatibility.

[0083] The exudate-absorbing material (α) of the present invention has excellent exudate absorption properties and also has excellent biocompatibility, and therefore can be used in a variety of applications, including daily pharmaceutical applications and medical applications.

Claims

1. An exudate-absorbing material (α) containing a protein (A) and an organic acid (salt) (B) having a hydroxyl group, wherein the protein (A) has a polypeptide chain (Y) and / or a polypeptide chain (Y'), the total number of the polypeptide chains (Y) and the polypeptide chains (Y') in the protein (A) is 1 to 100, the polypeptide chain (Y) is a polypeptide chain consisting of 2 to 200 consecutive amino acids (X) of at least one of the amino acid sequences (X) selected from the VPGVG sequence (1) shown in SEQ ID NO: 1, the GVGVP sequence (4) shown in SEQ ID NO: 4, the GPP sequence, the GAP sequence, and the GAHGPAGPK sequence (3) shown in SEQ ID NO: 3, and the polypeptide chain (Y') is a polypeptide chain in which 5% or less of the amino acids in the polypeptide chain (Y) are substituted with lysine and / or arginine, and the total number of the lysine and arginine residues is 1 to 100.

2. The exudate absorbing material according to claim 1, wherein the organic acid (salt) (B) having a hydroxyl group is at least one selected from the group consisting of ascorbic acid (salt) and citric acid (salt).

3. The exudate absorbent material according to claim 1, wherein the weight ratio of the organic acid (salt) (B) having a hydroxyl group to the protein (A) [weight of the organic acid (salt) (B) having a hydroxyl group / weight of the protein (A)] is 0.01 to 0.

25.

4. The exudate absorbent material according to claim 1, wherein said exudate absorbent material is shapable.

5. The density of the exudate absorbent material is 50 to 600 mg / cm ３ 2. The exudate-absorbing material according to claim 1, wherein 6. The exudate absorbent material according to claim 1, wherein the molecular mass of said protein (A) determined by SDS-PAGE (SDS polyacrylamide gel electrophoresis) method is 15 to 200 kDa.

7. The exudate absorbing material described in claim 1, wherein the protein (A) has an amino acid sequence shown in SEQ ID NO: 16, an amino acid sequence shown in SEQ ID NO: 17, an amino acid sequence shown in SEQ ID NO: 20, an amino acid sequence shown in SEQ ID NO: 23, an amino acid sequence shown in SEQ ID NO: 26, an amino acid sequence shown in SEQ ID NO: 27, or an amino acid sequence having a homology of 70% or more with these amino acid sequences.

8. A method for producing an exudate-absorbing material (α) containing a protein (A) and an organic acid (salt) (B) having a hydroxyl group, comprising: a step of preparing an aqueous solution in which the protein (A) and the organic acid (salt) (B) having a hydroxyl group are dissolved in water to obtain an aqueous solution having a protein (A) concentration of 12.5 to 150 g / L; and a step of freeze-drying the aqueous solution in a container to form an exudate-absorbing material (α), wherein the protein (A) has a polypeptide chain (Y) and / or a polypeptide chain (Y'), and the total number of the polypeptide chains (Y) and the polypeptide chains (Y') in the protein (A) is 1 to 100, A method for producing an exudate-absorbing material (α), wherein the polypeptide chain (Y) is a polypeptide chain consisting of 2 to 200 consecutive amino acids (X) of at least one of the amino acid sequences (X) selected from the group consisting of the VPGVG sequence (1) shown in SEQ ID NO: 1, the GVGVP sequence (4) shown in SEQ ID NO: 4, the GPP sequence, the GAP sequence, and the GAHGPAGPK sequence (3) shown in SEQ ID NO: 3, and the polypeptide chain (Y') is a polypeptide chain in which 5% or less of the amino acids in the polypeptide chain (Y) are substituted with lysine and / or arginine, and the total number of the lysines and arginines is 1 to 100.

9. A method for producing an exudate absorbent material (α) according to claim 8, wherein the freeze-drying step involves primary drying at a temperature of -35 to -5°C, a degree of vacuum of 0 to 20 Pa, and a time of 1 to 200 hours, followed by secondary drying at a temperature of 5 to 35°C, a degree of vacuum of 0 to 20 Pa, and a time of 1 to 200 hours.

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