Tendon reconstruction sheet material

Abstract

Provided is a tendon reconstruction sheet material comprising: a support body; and a porous body that is expandable by water absorption. A useful tendon reconstruction sheet material is thereby provided.

Description

Tendon reconstruction sheet material

[0001] The present invention relates to a tendon reconstruction sheet material and the like.

[0002] When rod-shaped or tubular tissues such as tendons, ligaments, blood vessels, bile ducts, and pancreatic ducts are injured, the injured tissues are treated by natural healing or surgical reattachment.

[0003] Furthermore, in the treatment of damaged tissue, devices have been proposed that enhance the healing ability of damaged tissue (for example, Patent Document 1: U.S. Pat. No. 10,265,156; Patent Document 2: U.S. Pat. No. 9,017,404; Non-Patent Document 1: J. Surg. Res., 2010 Apr.; 159(2), pp. 765-771).

[0004] Furthermore, sheet-like protective materials such as VersaWrap (trade name), TenoGlide (trade name), and TenoMend (trade name) are used to promote the healing of damaged tissue.

[0005] Furthermore, materials containing a porous body and a support are used as materials for guiding nerve regeneration (for example, Patent Document 3: International Publication No. 2017 / 159700).

[0006] U.S. Patent No. 10,265,156 U.S. Patent No. 9,017,404 International Publication No. 2017 / 159700

[0007] J. Surg. Res. , 2010 Apr. ;159(2), p765-771

[0008] Conventional devices for enhancing the healing ability of damaged tissue, even in sheet form, have problems such as difficulty in adhering to the tissue and being prone to tearing when fixed with a fixative. Therefore, there is a need for the development of a device, particularly a tendon reconstruction sheet material, that is flexible, can be adhered to the tissue, and is strong enough to be fixed with a fixative.

[0009] The problem to be solved by the present invention is to provide a tendon reconstruction sheet material that is flexible, can be adhered to tissue, and has the strength to be able to be fixed with a fixing material.

[0010] After extensive research, the inventors discovered that a tendon reconstruction sheet material comprising a porous body that can swell upon absorbing water and a support is useful as a tendon reconstruction sheet material, and thus completed the present invention.

[0011] That is, the present invention provides a tendon reconstruction sheet material. The present invention also provides a tendon reconstruction method and a tendon treatment method, which comprise applying a tendon reconstruction sheet to the tendon of a subject requiring tendon reconstruction. Furthermore, the present invention provides a method for producing a tendon reconstruction sheet material, which comprises pressing a material comprising a porous body that can swell upon absorption of water and a support. Specifically, the present invention is as follows.

[0012] (1-1) A tendon reconstruction sheet material comprising a porous body that can swell upon absorption of water and a support. (1-2) The tendon reconstruction sheet material according to (1-1), wherein the porous body that can swell upon absorption of water comprises a plant-derived bioabsorbable polysaccharide and / or a bioabsorbable polysaccharide having a carboxy group. (1-3) The tendon reconstruction sheet material according to (1-1) or (1-2), wherein the porous body that can swell upon absorption of water comprises a crosslinked alginic acid. (1-4) The tendon reconstruction sheet material according to any one of (1-1) to (1-3), wherein the support comprises at least one selected from the group consisting of one or more polymers having monomers selected from glycolic acid, lactic acid, caprolactone, amino acids, dioxanone, gluconate, ethylene oxide, hydroxybutyric acid, phosphate esters, and alphahydroxy acids, one or more copolymers obtained by polymerizing two or more of these monomers, and oxidized cellulose. (1-5) The tendon reconstruction sheet material according to any one of (1-1) to (1-4), wherein the porous body capable of swelling by water absorption contains a crosslinked body crosslinked with a compound represented by the following general formula (I): １ HN-(CH ２ ) ｎ -NHR ２ (I) [wherein, R １ and R ２ are each independently a hydrogen atom or a group of the formula: -COCH(NH ２ )-(CH ２ ) ４ -NH ２and n is an integer of 2 to 18.] (1-6) The tendon reconstruction sheet material according to any one of (1-1) to (1-5), wherein the porous material capable of swelling upon water absorption includes a crosslinked product crosslinked with at least one selected from the group consisting of a diN-hydroxysuccinimide salt of diaminoethane, a diN-hydroxysuccinimide salt of diaminohexane, a tetraN-hydroxysuccinimide salt of N,N'-di(lysyl)-diaminoethane, and a triN-hydroxysuccinimide salt of N-(lysyl)-diaminohexane. (1-7) The tendon reconstruction sheet material according to any one of (1-1) to (1-6), wherein the porous material capable of swelling upon water absorption has a xerogel form. (1-8) The tendon reconstruction sheet material according to any one of (1-1) to (1-7), wherein the porous material capable of swelling upon water absorption and the support are mixed in one layer. (1-9) The tendon reconstruction sheet material according to any one of (1-1) to (1-8), having a thickness in a dry state of 0.1 mm to 5 mm. (1-10) The tendon reconstruction sheet material according to any one of (1-1) to (1-9), having a thickness after swelling of 1.1 to 30 times the thickness before swelling. (1-11) The tendon reconstruction sheet material according to any one of (1-1) to (1-10), having a porosity before swelling of 70% to 99%. (1-12) The tendon reconstruction sheet material according to any one of (1-1) to (1-11), having a cumulative pore volume before swelling of 1.5 mL / g to 35 mL / g. (1-13) The tendon reconstruction sheet material according to any one of (1-1) to (1-11), having a thickness of 0.1 mm to 5 mm in a dry state. (1-14) The tendon reconstruction sheet material according to any one of (1-1) to (1-14), having a thickness of 0.1 mm to 5 mm in a dry state. (1-15) The tendon reconstruction sheet material according to any one of (1-1) to (1-15), having a thickness of 0.1 mm to 5 mm in a dry state. (1-16) The tendon reconstruction sheet material according to any one of (1-1) to (1-16), having a thickness of 0.1 mm to 5 mm in a dry state. (1-17) The tendon reconstruction sheet material according to any one of (1-1) to (1-17), having a thickness of 0.1 mm to 5 mm in a dry state. (1-18) The tendon reconstruction sheet material according to any one of (1-1) to (1-18), having a thickness of 0.1 mm to 5 mm in a dry state. (1-19) The tendon reconstruction sheet material according to any one of (1-1) to (1-9), having a thickness after swelling of ２ The amount of support contained per unit area is 0.05 mg / cm ２ ~30 mg / cm ２ (1-14) The tendon reconstruction sheet material according to any one of (1-1) to (1-12), ２ The content of alginic acids contained in the product is 0.2 mg / cm, calculated as the content of sodium alginate. ２ ~12 mg / cm ２(1-15-1) The tendon reconstruction sheet material according to any one of (1-1) to (1-14), which is pressed. (1-15-2) The tendon reconstruction sheet material according to (1-15-1), which has a porosity of 70% to 96% before swelling. (1-15-3) The tendon reconstruction sheet material according to (1-15-1) or (1-15-2), which has a cumulative pore volume of 1.5 mL / g to 20 mL / g before swelling. (1-16-1) The tendon reconstruction sheet material according to any one of (1-1) to (1-15-3), which is used by being wrapped around a tendon requiring tendon reconstruction. (1-16-2) The tendon reconstruction sheet material according to any one of (1-1) to (1-15-3), which is used by being wrapped around a tendon requiring tendon reconstruction, covering the damaged area and encircling the tendon. (1-16-3) The tendon reconstruction sheet material according to any one of (1-1) to (1-15-3), which is used by wrapping the tendon in need of tendon reconstruction around the tendon, covering the ruptured site. (1-17) The tendon reconstruction sheet material according to any one of (1-1) to (1-16-3), which is used by being fixed with a fixing material. (1-18) The tendon reconstruction sheet material according to any one of (1-1) to (1-17), which is in the form of a flat plate. (1-19) The tendon reconstruction sheet material according to any one of (1-1) to (1-18), which is used by adhering closely to the tendon due to swelling of the porous body. (1-20) The tendon reconstruction sheet material according to any one of (1-1) to (1-19), which is used in combination with a humoral factor or cells.

[0013] (2-1) A method for tendon reconstruction, comprising applying the tendon reconstruction sheet material according to any one of (1-1) to (1-17) to a tendon of a subject requiring tendon reconstruction. (2-2) A method for tendon treatment, comprising applying the tendon reconstruction sheet material according to any one of (1-1) to (1-17) to a tendon of a subject requiring tendon reconstruction. (2-3) The method according to (2-1) or (2-2), wherein applying the tendon reconstruction sheet material is carried out by wrapping the tendon reconstruction sheet material around the tendon requiring tendon reconstruction. (2-4) The method according to (2-1) or (2-2), wherein applying the tendon reconstruction sheet material is carried out by wrapping the tendon reconstruction sheet material around the tendon requiring tendon reconstruction, covering the damaged area. (2-5) The method according to (2-1) or (2-2), wherein applying the tendon reconstruction sheet material is carried out by wrapping the tendon reconstruction sheet material around the tendon requiring tendon reconstruction, covering the ruptured area. (2-6) The method according to any one of (2-1) to (2-5), wherein the tendon reconstruction sheet material is flat. (2-7) The method according to any one of (2-1) to (2-6), wherein the tendon reconstruction sheet material is used in close contact with the tendon by swelling of the porous body. (2-8) The method according to any one of (2-1) to (2-7), wherein the tendon reconstruction sheet material is used in combination with a humoral factor or cells.

[0014] (3-1) A method for producing a tendon reconstruction sheet material, comprising a step of pressing a material comprising a porous body that can swell upon absorption of water and a support. (3-2) A method for producing a tendon reconstruction sheet material according to (3-1), wherein the porous body that can swell upon absorption of water comprises a plant-derived bioabsorbable polysaccharide and / or a bioabsorbable polysaccharide having a carboxy group. (3-3) A method for producing a tendon reconstruction sheet material according to (3-1) or (3-2), wherein the porous body that can swell upon absorption of water comprises a crosslinked alginic acid. (3-4) A method for producing a tendon reconstruction sheet material according to any one of (3-1) to (3-3), wherein the support comprises at least one selected from the group consisting of one or more polymers having monomers selected from glycolic acid, lactic acid, caprolactone, amino acids, dioxanone, gluconate, ethylene oxide, hydroxybutyric acid, phosphate esters, and alphahydroxy acids, one or more copolymers obtained by polymerizing two or more of these monomers, and oxidized cellulose. (3-5) A method for producing a sheet material for tendon reconstruction according to any one of (3-1) to (3-4), in which the porous body capable of swelling by water absorption is crosslinked with a compound represented by the following general formula (I): １ HN-(CH ２ ) ｎ -NHR ２ (I) [wherein, R １ and R ２ are each independently a hydrogen atom or a group of the formula: -COCH(NH ２ )-(CH ２ ) ４ -NH ２and n is an integer of 2 to 18.] (3-6) A method for producing a tendon reconstruction sheet material according to any one of (3-1) to (3-5), wherein the porous material capable of swelling upon water absorption includes a crosslinked product crosslinked with at least one selected from the group consisting of a diN-hydroxysuccinimide salt of diaminoethane, a diN-hydroxysuccinimide salt of diaminohexane, a tetraN-hydroxysuccinimide salt of N,N'-di(lysyl)-diaminoethane, and a triN-hydroxysuccinimide salt of N-(lysyl)-diaminohexane. (3-7) A method for producing a tendon reconstruction sheet material according to any one of (3-1) to (3-6), wherein the porous material capable of swelling upon water absorption has a xerogel form. (3-8) A method for producing a tendon reconstruction sheet material according to any one of (3-1) to (3-7), wherein the porous material capable of swelling upon water absorption and the support are mixed in a single layer. (3-9) The method for producing a tendon reconstruction sheet material according to any one of (3-1) to (3-8), wherein the thickness of the tendon reconstruction sheet material in a dry state is 0.1 mm to 5 mm. (3-10) The method for producing a tendon reconstruction sheet material according to any one of (3-1) to (3-9), wherein the thickness of the tendon reconstruction sheet material after swelling is 1.1 to 30 times the thickness before swelling. (3-11) The method for producing a tendon reconstruction sheet material according to any one of (3-1) to (3-10), wherein the porosity of the tendon reconstruction sheet material before swelling is 70% to 96%. (3-12) The method for producing a tendon reconstruction sheet material according to any one of (3-1) to (3-11), wherein the cumulative pore volume of the tendon reconstruction sheet material before swelling is 1.5 mL / g to 20 mL / g. (3-13) A method for producing a tendon reconstruction sheet material according to any one of (3-1) to (3-11), wherein the cumulative pore volume of the tendon reconstruction sheet material before swelling is 1.5 mL / g to 20 mL / g. ２ The amount of support contained per unit area is 0.05 mg / cm ２ ~30 mg / cm ２ (3-14) The method for producing a tendon reconstruction sheet material according to any one of (3-1) to (3-12), ２ The content of alginic acids contained in the product is 0.2 mg / cm, calculated as the content of sodium alginate. ２ ~12 mg / cm ２(3-15-1) The method for producing a tendon reconstruction sheet material according to any one of (3-1) to (3-14), wherein the tendon reconstruction sheet material is used by being wrapped around a tendon that requires tendon reconstruction. (3-15-2) The method for producing a tendon reconstruction sheet material according to any one of (3-1) to (3-14), wherein the tendon reconstruction sheet material is used by being wrapped around a tendon that requires tendon reconstruction, covering the damaged area. (3-15-3) The method for producing a tendon reconstruction sheet material according to any one of (3-1) to (3-14), wherein the tendon reconstruction sheet material is used by being wrapped around a tendon that requires tendon reconstruction, covering the ruptured area. (3-16) The method for producing a tendon reconstruction sheet material according to any one of (3-1) to (3-15-3), wherein the tendon reconstruction sheet material is used by being fixed with a fixing material. (3-17) The manufacturing method according to any one of (3-1) to (3-16), wherein the tendon reconstruction sheet material is flat. (3-18) The manufacturing method according to any one of (3-1) to (3-17), wherein the tendon reconstruction sheet material is used in close contact with the tendon by swelling of the porous body. (3-19) The manufacturing method according to any one of (3-1) to (3-18), wherein the tendon reconstruction sheet material is used in combination with a humoral factor or cells.

[0015] (4-1) A combination of a porous body that can swell upon absorption of water and a support, for use in treating tendons in a subject requiring tendon reconstruction. (4-2) The combination according to (4-1), in which the porous body that can swell upon absorption of water contains a plant-derived bioabsorbable polysaccharide and / or a bioabsorbable polysaccharide having a carboxy group. (4-3) The combination according to (4-1) or (4-2), in which the porous body that can swell upon absorption of water contains a crosslinked alginate. (4-4) The combination according to any one of (4-1) to (4-3), in which the support contains at least one selected from the group consisting of one or more polymers having monomers of glycolic acid, lactic acid, caprolactone, amino acids, dioxanone, gluconate, ethylene oxide, hydroxybutyric acid, phosphate esters, or alphahydroxy acids, one or more copolymers obtained by polymerizing two or more of these monomers, and oxidized cellulose. (4-5) The combination according to any one of (4-1) to (4-4), wherein the porous body that can swell by absorbing water includes a crosslinked body crosslinked with a compound represented by the following general formula (I): １ HN-(CH ２ ) ｎ -NHR ２ (I) [wherein, R １ and R ２ are each independently a hydrogen atom or a group of the formula: -COCH(NH ２ )-(CH ２ ) ４ -NH ２and n represents an integer of 2 to 18.] (4-6) The combination according to any one of (4-1) to (4-5), wherein the porous material capable of swelling upon absorption of water includes a crosslinked material crosslinked with at least one selected from the group consisting of a diN-hydroxysuccinimide salt of diaminoethane, a diN-hydroxysuccinimide salt of diaminohexane, a tetraN-hydroxysuccinimide salt of N,N'-di(lysyl)-diaminoethane, and a triN-hydroxysuccinimide salt of N-(lysyl)-diaminohexane. (4-7) The combination according to any one of (4-1) to (4-6), wherein the porous material capable of swelling upon absorption of water has a xerogel form. (4-8) The combination according to any one of (4-1) to (4-7), wherein the porous material capable of swelling upon absorption of water and the support are mixed in one layer. (4-9) The combination according to any one of (4-1) to (4-8), wherein the thickness of the tendon reconstruction sheet material comprising the combination in a dry state is 0.1 mm to 5 mm. (4-10) The combination according to any one of (4-1) to (4-9), wherein the thickness of the tendon reconstruction sheet material comprising the combination after swelling is 1.1 to 30 times the thickness before swelling. (4-11) The combination according to any one of (4-1) to (4-10), wherein the porosity of the tendon reconstruction sheet material comprising the combination is 70% to 99%. (4-12) The combination according to any one of (4-1) to (4-11), wherein the cumulative pore volume before swelling of the tendon reconstruction sheet material comprising the combination is 1.5 mL / g to 35 mL / g. (4-13) The combination according to any one of (4-1) to (4-11), wherein the cumulative pore volume of the tendon reconstruction sheet material comprising the combination before swelling is 1.5 mL / g to 35 mL / g. ２ The amount of support contained per unit area is 0.05 mg / cm ２ ~30 mg / cm ２ (4-14) A tendon reconstruction sheet material 1 cm long containing the above combination. ２ The content of alginic acids contained in the product is 0.2 mg / cm, calculated as the content of sodium alginate. ２ ~12 mg / cm ２(4-15-1) The combination according to any one of (4-1) to (4-14), wherein a tendon reconstruction sheet material comprising the combination is pressed. (4-15-2) The combination according to (4-15-1), wherein a porosity of a tendon reconstruction sheet material comprising the combination before swelling is 70% to 96%. (4-15-3) The combination according to (4-15-1) or (4-15-2), wherein a cumulative pore volume of a tendon reconstruction sheet material comprising the combination before swelling is 1.5 mL / g to 20 mL / g. (4-16-1) The combination according to any one of (4-1) to (4-15-3), wherein a tendon reconstruction sheet material comprising the combination is used by being wrapped around a tendon requiring tendon reconstruction. (4-16-2) The combination according to any one of (4-1) to (4-15-3), wherein a tendon reconstruction sheet material including the above-mentioned combination is used by wrapping the tendon in need of tendon reconstruction, covering the damaged area, all around the tendon. (4-16-3) The combination according to any one of (4-1) to (4-15-3), wherein a tendon reconstruction sheet material including the above-mentioned combination is used by wrapping the tendon in need of tendon reconstruction, covering the ruptured area, all around the tendon. (4-17) The combination according to any one of (4-1) to (4-16-3), wherein a tendon reconstruction sheet material including the above-mentioned combination is used by being fixed with a fixing material. (4-18) The combination according to any one of (4-1) to (4-17), wherein a tendon reconstruction sheet material including the above-mentioned combination is flat. (4-19) The combination according to any one of (4-1) to (4-18), wherein a porous body swells to adhere the tendon to the tendon. (4-20) A combination according to any one of (4-1) to (4-19), wherein the tendon reconstruction sheet material containing the combination is used in combination with a humoral factor or cells.

[0016] The present invention provides a tendon reconstruction sheet material comprising a porous body that can swell by absorbing water and a support.

[0017] 1A and 1B are diagrams showing how to set up a sample when observing the swelling state and how to set up a sample when performing a bending test.

[0018] According to the present invention, there is provided a flexible tendon reconstruction sheet material comprising a porous body that can swell by absorbing water and a support. Hereinafter, the tendon reconstruction sheet material may be referred to as a "sheet material."

[0019] "Flexibility" means that the sheet material can bend easily, i.e., is flexible enough to not break even when bent. The tendon reconstruction sheet material of the present invention is flexible enough to be easily bent with the fingers and wrapped around a tendon.

[0020] "Wrapping" refers to covering the surface of a rod-shaped or tubular tissue (e.g., a tendon). When the tendon reconstruction sheet of the present invention is wrapped around a tendon, the wrapping area may be either completely around the tendon or only part of the tendon, and an appropriate area can be selected. The tendon reconstruction sheet material of the present invention is preferably used in a manner where it is wrapped around the tendon completely while covering the damaged area.

[0021] "Tendon reconstruction" means encouraging the healing of damaged tendons.

[0022] A "tendon reconstruction sheet material" is a device used to protect a damaged tendon and promote healing during the treatment of a damaged tendon.

[0023] "Injury" refers to a state of being damaged, and includes a state of being torn (for example, a state of being partially torn, a state of being completely torn).

[0024] "Before swelling" refers to the time before the tendon reconstruction sheet material of the present invention or the porous body contained in the tendon reconstruction sheet material of the present invention swells due to water absorption, that is, the time when it is in a dry state.

[0025] "After swelling" refers to the point 20 minutes after the tendon reconstruction sheet material of the present invention or the porous body contained in the tendon reconstruction sheet material of the present invention has absorbed the entire amount of water determined in advance.

[0026] "Fixing material" refers to known materials such as threads, clips, staples, or adhesives that are used to fix the tendon reconstruction sheet material of the present invention between each other, or between the tendon reconstruction sheet of the present invention and the tissue to which it is applied.

[0027] In this specification, a numerical range indicated using "to" indicates a range that includes the numerical values ​​before and after "to" as the minimum and maximum values, respectively.

[0028] 1. Porous body The tendon reconstruction sheet material of the present invention contains a porous body. The porous body contained in the tendon reconstruction sheet material of the present invention has the property of swelling upon water absorption, and may hereinafter be referred to as a "porous body that can swell upon water absorption."

[0029] The porous body used in the present invention may be, for example, a crosslinked body having a crosslinked structure in at least a part of its structure. The crosslinked body used in the present invention can be obtained by crosslinking raw materials or by using raw materials that naturally have a crosslinked structure.

[0030] The raw materials for the porous body used in the present invention include bio-derived polymers (natural polymers), synthetic polymers, derivatives thereof, and combinations thereof, which are absorbed by the living body and do not have harmful effects on the living body.

[0031] Examples of biopolymers include bioabsorbable polysaccharides derived from plants, bioabsorbable polysaccharides derived from animals, bioabsorbable polysaccharides derived from microorganisms, proteins, and bioabsorbable polysaccharides having a carboxy group in the molecule.

[0032] Examples of plant-derived bioabsorbable polysaccharides include polysaccharides such as alginic acid, carboxymethyl starch, hyaluronic acid, and carboxymethyl cellulose, as well as esters or salts thereof.

[0033] Examples of animal-derived bioabsorbable polysaccharides include polysaccharides such as hyaluronic acid, chitin, and chitosan, as well as esters or salts thereof.

[0034] Examples of bioabsorbable polysaccharides derived from microorganisms include dextran, its esters, and salts thereof.

[0035] Examples of proteins include collagen, gelatin, elastin, and fibrin.

[0036] Examples of bioabsorbable polysaccharides having a carboxy group in the molecule include polysaccharides such as alginic acid, carboxymethyl starch, hyaluronic acid, and carboxymethyl cellulose, as well as esters or salts thereof.

[0037] Examples of synthetic polymers include poly(ethylene glycol), poly(vinyl alcohol), derivatives thereof, and combinations thereof.

[0038] Preferably, the raw material for the porous body used in the present invention is a biopolymer, and preferably, the biopolymer is a plant-derived bioabsorbable polysaccharide or a bioabsorbable polysaccharide having a carboxy group in the molecule.

[0039] The plant-derived bioabsorbable polysaccharides and bioabsorbable polysaccharides having a carboxy group in the molecule used in the present invention are preferably those that are degraded and absorbed in the body and have no cell adhesive properties, and particularly preferably at least one selected from alginic acid, its esters, and its salts. "At least one selected from alginic acid, its esters, and its salts" may be referred to as "alginic acids."

[0040] The alginic acids used in the present invention are polysaccharides extracted from brown algae such as Lessonia, Macrocystis, Laminaria, Ascophyllum, Durvillea, Sculpin, Eisenia bicolor, and Laminaria kelp, and are linear polymers of two uronic acids, D-mannuronic acid (M) and L-guluronic acid (G). More specifically, they are block copolymers formed by the arbitrary combination of a homopolymer fraction of D-mannuronic acid (MM fraction), a homopolymer fraction of L-guluronic acid (GG fraction), and a randomly arranged fraction of D-mannuronic acid and L-guluronic acid (M / G fraction).

[0041] The composition ratio (M / G ratio) of D-mannuronic acid to L-guluronic acid in alginic acids varies depending on the type of organism from which they are derived, and is also affected by the location and season of the organism. The gel properties of alginic acids are affected by the M / G ratio. The M / G ratio of the alginic acids used in the present invention is preferably 0.5 to 2.0, more preferably 0.6 to 1.8, and even more preferably 0.7 to 1.5.

[0042] Of the alginic acids used in the present invention, the alginate ester is preferably propylene glycol alginate.

[0043] Among the alginic acids used in the present invention, examples of alginate salts include monovalent salts of alginic acid and divalent salts of alginic acid, with monovalent salts being preferred.

[0044] Preferred examples of the monovalent salt of alginic acid include sodium alginate, potassium alginate, and ammonium alginate, more preferably sodium alginate or potassium alginate, and particularly preferably sodium alginate.

[0045] It is known that the molecular weight of alginic acids may vary depending on the measurement method. For example, the weight-average molecular weight of the alginic acids used in the present invention, as measured by gel permeation chromatography (GPC) or gel filtration chromatography (collectively referred to as size exclusion chromatography), is preferably 200,000 to 3,000,000, more preferably 500,000 to 2,500,000, and even more preferably 1,000,000 to 2,000,000.

[0046] When gel permeation chromatography is used, the column may be, for example, GMPW-XL x 2 + G2500PW-XL (7.8 mm ID x 300 mm), the eluent may be, for example, a 200 mM aqueous sodium nitrate solution, and the molecular weight standard may be, for example, pullulan.

[0047] The absolute weight average molecular weight (absolute molecular weight) of the alginic acids used in the present invention, measured by GPC-MALS, is preferably 50,000 to 600,000, more preferably 80,000 to 500,000, and even more preferably 150,000 to 400,000.

[0048] When GPC-MALS is used, the detectors that can be used include, for example, an RI detector and a light scattering detector (MALS).

[0049] The molecular weight of alginic acids becomes smaller than that when they are first extracted from brown algae due to heat drying, purification, etc. Alginic acids with different molecular weights can be produced by selecting the brown algae used as raw material, drying conditions, and purification method. Furthermore, it is possible to obtain alginic acids with the desired molecular weight by mixing them with alginic acids from different lots with different molecular weights.

[0050] The plant-derived bioabsorbable polysaccharide or bioabsorbable polysaccharide having a carboxy group in the molecule used in the present invention is preferably low in endotoxin, and more preferably has been treated to reduce endotoxin content. Low endotoxin means that the endotoxin level is so low that it does not substantially induce inflammation or fever.

[0051] The endotoxin reduction treatment can be carried out by known methods described in, for example, JP-A-9-324001, JP-A-8-269102, JP-T-2002-530440, WO 93 / 13136, U.S. Pat. No. 5,589,591, etc., or methods similar thereto.

[0052] The endotoxin level of the bioabsorbable polysaccharide used in the present invention, as measured by Limulus Alkaline Lysate (LAL), is preferably 500 endotoxin units (EU) / g or less, more preferably 100 EU / g or less, particularly preferably 50 EU / g or less, and particularly preferably 30 EU / g or less. Low-endotoxin treated sodium alginate is available from, for example, Sea Matrix (registered trademark) (Mochida Pharmaceutical Co., Ltd.), PRONOVA ＴＭ It is available commercially as UP LVG (FMC BioPolymer).

[0053] In the present invention, the method for crosslinking the raw material of the porous body may be, for example, a physical crosslinking method or a chemical crosslinking method. Examples of the physical crosslinking method include photocrosslinking by ultraviolet irradiation, thermal crosslinking by heat, or ionic crosslinking by salt, while examples of the chemical crosslinking method include a crosslinking method using a gaseous or liquid crosslinking agent. The chemical crosslinking method is preferred as the crosslinking method used in the present invention.

[0054] Examples of crosslinking agents for the chemical crosslinking method used in the present invention include aldehydes such as glutaraldehyde and formaldehyde, glycidyl ethers such as ethylene propylene diglycidyl ether, glycerol polyglycidyl ether and 1,4-butanediol glycidyl ether (BDDE), isocyanates such as hexamethylene diisocyanate and α-tolidine isocyanate, diamines such as diaminoethane and diaminopentane, carbodiimides such as dichloroethane, calcium gluconate, and genipin.

[0055] Preferred examples of the crosslinking agent used in the present invention include aldehydes such as glutaraldehyde and formaldehyde, and diamines such as diaminoethane and diaminopentane.

[0056] When the raw material for the porous body used in the present invention is a bioabsorbable polysaccharide having a carboxy group in the molecule, the crosslinking agent is preferably at least one selected from amine compounds and salts thereof, which are included in the compounds represented by the following general formula (I). Here, the compound represented by the following general formula (I) may be referred to as the amine compound (I). R １ HN-(CH ２ ) ｎ -NHR ２ (I) [wherein, R １ and R ２ are each independently a hydrogen atom or a group of the formula: -COCH(NH ２ )-(CH ２ ) ４ -NH ２ and n is an integer of 2 to 18.

[0057] Examples of the amine compound (I) used in the present invention include diaminoalkanes and / or salts thereof, such as diaminoethane, diaminopropane, diaminobutane, diaminopentane, diaminohexane, diaminoheptane, diaminooctane, diaminononane, diaminodecane, diaminododecane, and diaminooctadecane; and mono- or di(lysyl)diaminoalkanes and / or salts thereof, such as N-(lysyl)-diaminoethane, N,N'-di(lysyl)-diaminoethane, N-(lysyl)-diaminohexane, and N,N'-di(lysyl)-diaminohexane. One or more of these diamines and salts thereof can be used.

[0058] The amine compound (I) and / or salt thereof used in the present invention is preferably a compound of the above general formula (I) in which n is 2 to 8 and / or a salt thereof.

[0059] As a component that forms a salt of the amine compound (I) used in the present invention, N-hydroxysuccinimide is preferred.

[0060] As the crosslinking agent comprising the amine compound (I) and / or a salt thereof used in the present invention, diN-hydroxysuccinimide salt of diaminoethane, diN-hydroxysuccinimide salt of diaminohexane, tetraN-hydroxysuccinimide salt of N,N'-di(lysyl)-diaminoethane, tert-N-hydroxysuccinimide salt of N-(lysyl)-diaminohexane, etc. are particularly preferred from the viewpoints of safety and biocompatibility, with diN-hydroxysuccinimide salt of diaminoethane being particularly preferred.

[0061] When the raw material for the porous body used in the present invention is an alginic acid, the crosslinking agent is preferably the above-mentioned amine compound (I) and / or a salt thereof, and particularly preferably, diN-hydroxysuccinimide salt of diaminoethane.

[0062] When the raw material of the porous body used in the present invention is gelatin, thermal crosslinking or chemical crosslinking using glutaraldehyde as a crosslinking agent can be used.

[0063] When the raw material of the porous material used in the present invention is hyaluronic acid, chemical crosslinking using 1,4-butanediol glycidyl ether (BDDE) as a crosslinking agent can be used.

[0064] When the raw material of the porous body used in the present invention is collagen, chemical crosslinking using genipin as a crosslinking agent can be used.

[0065] When a chemical crosslinking method is used in the present invention, a condensing agent may be used together with the crosslinking agent. Examples of the condensing agent used in the present invention include 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC·HCl) or other salts, 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate (CMC), and 1,3-bis(2,2-dimethyl-1,3-dioxolan-4-ylmethyl)carbodiimide (BDDC), and preferably EDC·HCl.

[0066] The porous body used in the present invention can be produced by gelling these raw materials using a crosslinking agent or condensing agent as needed, and then freeze-drying or drying. Freeze-drying or drying can be performed using techniques known to those skilled in the art, and may include a primary drying step, a secondary drying step, or the like.

[0067] In some embodiments, the porous body used in the present invention has the form of a xerogel, which is a gel that has lost the solvent in its three-dimensional network structure, leaving only the network.

[0068] The porous body used in the present invention has the property of swelling when it absorbs water, and its thickness in a dry state is, for example, 0.1 mm to 5 mm, preferably 0.2 mm to 1 mm, and more preferably 0.3 mm to 0.5 mm.

[0069] The porous body used in the present invention may be either pressed or unpressed.

[0070] In the present invention, "pressing" can be performed by applying pressure to the freeze-dried or dried porous body using a press such as a roller press or a plate press.

[0071] The ratio of the thickness of the porous body after pressing to the thickness before pressing (thickness after pressing / thickness before pressing) is, for example, 1 / 100 to 1 / 2, preferably 1 / 50 to 1 / 5, more preferably 1 / 30 to 1 / 8, and even more preferably 1 / 20 to 1 / 10.

[0072] The pressing conditions were the same as those for the tendon reconstruction sheet material described below.

[0073] The thickness of the porous body used in the present invention increases when it swells due to water absorption. The ratio of the thickness after swelling to the thickness before swelling (thickness after swelling / thickness before swelling) of the porous body used in the present invention is preferably 1.1 to 30 times, more preferably 1.2 to 25 times, and even more preferably 1.5 to 20 times.

[0074] The cross-sectional area of ​​the porous body used in the present invention increases when it swells due to water absorption. The ratio of the cross-sectional area after swelling to the cross-sectional area before swelling (cross-sectional area after swelling / cross-sectional area before swelling) of the porous body used in the present invention is preferably 1.2 to 35 times, more preferably 1.3 to 30 times, and even more preferably 2 to 25 times.

[0075] The porous body used in the present invention swells, allowing the tendon reconstruction sheet material of the present invention to adhere closely to the tendon. By adhering the sheet material to the damaged tendon, the intrusion of fibroblasts and other cells that hinder healing can be prevented, promoting healing of the damaged area and preventing contracture after tissue repair.

[0076] The thickness and cross-sectional area of ​​the porous body before and after swelling can be determined as follows. First, a dry porous body is cut to 35 mm x 20 mm, the long sides are wrapped around a bent round pipe (outer diameter 4.1 mm), the porous body is fixed by clips, and the round pipe is removed. Then, a rod-shaped or tubular tissue model (outer diameter 3.0 mm) is inserted so as not to come into contact with the dry porous body. First, the thickness or cross-sectional area of ​​the porous body before swelling is measured. Next, 1000 μL of water is slowly dripped onto the entire porous body surrounding the rod-shaped or tubular tissue model to swell the porous body, and the thickness or cross-sectional area of ​​the porous body after swelling is measured. Measurements are performed at room temperature (20°C to 25°C) and at a humidity of 50% to 70%. If the size of the porous body is smaller than 35 mm x 20 mm and the above test cannot be performed, the porous body may be placed on a petri dish and water dripped onto the entire porous body to swell it. The amount of water to be dropped in this case is adjusted in proportion to the size of the porous body, with 1000 μL of water being the standard for the size of the porous body (35 mm × 20 mm). In either case, the thickness or cross-sectional area is measured 20 minutes after the entire amount of water has been dropped.

[0077] The porosity of the porous body used in the present invention before swelling is preferably 70 to 99%, more preferably 75 to 99%, and even more preferably 85 to 99%.

[0078] In the present invention, "porosity" refers to the ratio of the volume of voids to the volume of a solid. The porosity in the present invention can be determined, for example, by mercury porosimetry, as described in the method for measuring the porosity of a tendon reconstruction sheet material below.

[0079] The porosity of the pressed porous body before swelling is preferably 70 to 96%, more preferably 75 to 95%, and even more preferably 85 to 90%. The porosity of the unpressed porous body before swelling is preferably 96 to 99%, more preferably 97 to 99%, and even more preferably 98 to 99%.

[0080] In addition, the cumulative pore volume of the porous material used in the present invention before swelling is preferably 1.5 to 35 mL / g, more preferably 2 to 33 mL / g, and even more preferably 2.5 to 31 mL / g.

[0081] In the present invention, the "cumulative pore volume" refers to the ratio of the volume of voids to the mass of a solid. The cumulative pore volume in the present invention can be determined, for example, by mercury intrusion porosimetry, as described in the method for measuring the cumulative pore volume of the tendon reconstruction sheet material below.

[0082] The cumulative pore volume of the pressed porous body is preferably 1.5 to 20 mL / g, more preferably 2 to 10 mL / g, and even more preferably 2.5 to 8 mL / g. The cumulative pore volume of the unpressed porous body is preferably 25 to 35 mL / g, more preferably 26 to 33 mL / g, and even more preferably 27 to 31 mL / g.

[0083] The method for adjusting the porosity and cumulative pore volume of the porous body used in the present invention before and after pressing is the same as the method for adjusting the porosity and cumulative pore volume of the tendon reconstruction sheet material before and after pressing, as described below.

[0084] The porous material used in the present invention is not limited, but is preferably, for example, one containing a "crosslinked alginic acid."

[0085] The "crosslinked alginic acid" used in the present invention can be obtained, for example, by mixing alginic acids, a crosslinking agent, and a condensing agent to obtain a gel, which is then freeze-dried or dried. Alternatively, it can be obtained by obtaining a gel through ionic bond crosslinking or hydrophobic bond crosslinking, and then freeze-drying or drying.

[0086] In some embodiments, the porous body used in the present invention has a thickness of 1 cm ２ The content of alginic acids per unit area is preferably 0.2 mg / cm in terms of the content of sodium alginate. ２ ~12 mg / cm ２ , more preferably 0.5 mg / cm ２ ~7 mg / cm ２ , more preferably 1 mg / cm ２ ~6 mg / cm ２ , particularly preferably 1 mg / cm ２ ~5 mg / cm ２ is.

[0087] The porous material used in the present invention may be a commercially available product molded into a sheet. Examples of commercially available porous materials include Skin Collage Sheet (a freeze-dried form of collagen, manufactured by Ishii Clinic). These commercially available porous materials may also be used after being pressed, for example.

[0088] 2. Support The tendon reconstruction sheet material of the present invention includes a support in addition to the porous body. In some embodiments, the support can provide the tendon reconstruction sheet material with strength that allows it to be fixed with a fixative, and preferably the support can provide the tendon reconstruction sheet material with strength that allows it to be fixed with a fixative even after the tendon reconstruction sheet material has absorbed moisture such as blood in the trocar or in the surgical field. In some embodiments, the support can prevent deformation of the material due to freeze-drying or drying, and can improve the production efficiency of the tendon reconstruction sheet material.

[0089] The raw materials for the support used in the present invention include biocompatible polymers that do not have harmful effects on the living body.

[0090] The biocompatible polymer may be a homopolymer or a copolymer.

[0091] Examples of homopolymers include polymers containing glycolic acid, lactic acid, caprolactone, amino acids, dioxanone, gluconate, ethylene oxide, hydroxybutyric acid, phosphate esters, or alphahydroxy acids as monomers, or oxidized cellulose, and preferably polyglycolic acid (PGA) or polylactic acid (PLA), more preferably polyglycolic acid (PGA).

[0092] Examples of copolymers include polymers obtained by polymerizing two or more of the above-mentioned monomers, preferably a copolymer of glycolic acid and lactic acid (also called polyglactin or PLGA) or a copolymer of ethylene oxide and lactic acid, and more preferably a copolymer of glycolic acid and lactic acid (PLGA).

[0093] The support used in the present invention has a form with numerous voids, and is not particularly limited, but preferably has the form of a nonwoven fabric or a woven fabric.

[0094] Examples of nonwoven fabrics include nonwoven fabrics produced from the biocompatible polymers by a dry method, a wet method, a spunbonding method, a meltblown method, or an airlaid method, and fabrics produced by turning woven fabrics produced from the biocompatible polymers into nonwoven fabrics by a chemical bonding method (permeation method, spray method), a thermal bonding method, a needle punching method, a hydroentanglement method, or the like.

[0095] Examples of woven fabrics include fabrics woven with threads made from the biocompatible polymers.

[0096] The support used in the present invention may be a commercially available support molded into a sheet, such as polylactic acid nonwoven fabric (Tokano Co., Ltd.), PGA sheet (M type) (Nikke Medical Co., Ltd.), or BIOFELT (trade name, Biomedical Structures).

[0097] 3. Tendon Reconstruction Sheet Material The tendon reconstruction sheet material of the present invention comprises a porous body and a support. In the tendon reconstruction sheet material of the present invention, the porous body and the support may be mixed in a single layer or may be laminated together, and preferably are mixed in a single layer.

[0098] The tendon reconstruction sheet material of the present invention can be produced, for example, as follows. A tendon reconstruction sheet material in which a porous body and a support are mixed in one layer can be produced by first placing a support on a tray before adding a solution of raw materials for the porous body, then pouring in the solution of raw materials for the porous body, gelling, and then freeze-drying. Alternatively, it can be produced by placing a support on a tray before adding a solution of raw materials for the porous body, then pouring in the solution of raw materials for the porous body that has been whipped with a high-speed stirrer, etc., after gelling, and then drying. Freeze-drying or drying can be performed using common technical knowledge known to those skilled in the art, and primary and secondary drying steps, etc., may be included.

[0099] A tendon reconstruction sheet material having a layer of porous body and a layer of support laminated thereto can be produced by pouring a solution of the raw materials of the porous body into a tray without a support, gelling it, and then freeze-drying or drying it to produce a produced porous body or a commercially available porous body, and then layering the produced or commercially available support on top of the produced porous body or a commercially available support. In some embodiments, the tendon reconstruction sheet material obtained in this manner contains the porous body in the form of a xerogel.

[0100] The following describes an example of a method for producing a tendon reconstruction sheet material that includes a porous body containing a crosslinked alginate and a support. This method can also be applied to cases where other porous bodies are used.

[0101] A tendon reconstruction sheet material comprising a porous body containing a crosslinked alginate and a support can be obtained, for example, by placing the support on a tray, pouring in an alginate solution, a crosslinking agent, and a condensing agent, carrying out a crosslinking reaction, and freeze-drying the resulting gel. Alternatively, the sheet material can be obtained by placing the support on a tray, pouring in an alginate solution, a crosslinking agent, and a condensing agent, whisking the mixture, carrying out a crosslinking reaction, and drying the resulting gel. Other crosslinking methods, such as ionic bond crosslinking or hydrophobic bond crosslinking, may also be used for the crosslinking reaction, or these may be used in combination. The tendon reconstruction sheet material obtained in this manner has a structure in which the porous body containing the crosslinked alginate and the support are mixed in a single layer.

[0102] The solvent used for the alginic acid solution is not particularly limited as long as it is a solvent that is applicable to living organisms, but is preferably an aqueous solvent, such as purified water, distilled water, ion-exchanged water, Milli-Q water, physiological saline, phosphate-buffered physiological saline, DMSO, etc. The solvent is preferably sterilized, and preferably has been treated to reduce endotoxins.

[0103] The concentration of alginic acids in the crosslinking reaction is preferably 0.1% by weight to 5% by weight, more preferably 0.5% by weight to 3% by weight, from the viewpoint of maintaining the mechanical strength of the gel and an appropriate water content.

[0104] The molar ratio of the crosslinking agent used in the crosslinking reaction is not particularly limited, but is preferably 1 mol % to 50 mol %, more preferably 5 mol % to 40 mol %, based on the total number of carboxy groups possessed by the alginic acid.

[0105] The molar ratio of the condensing agent used in the crosslinking reaction is not particularly limited, but is preferably 50 mol % to 300 mol %, more preferably 100 mol % to 200 mol %.

[0106] The temperature for the crosslinking reaction is, for example, preferably 4°C to 37°C, and more preferably 20°C to 30°C from the viewpoint of reaction efficiency.

[0107] The time for the crosslinking reaction is, for example, preferably 6 to 96 hours, more preferably 24 to 85 hours, and even more preferably 36 to 80 hours, from the viewpoint of reaction efficiency.

[0108] The crosslinking rate can be controlled, for example, by the molar ratio of the crosslinking agent used and the time of the crosslinking reaction. Since the crosslinking reaction progresses over time, a high crosslinking rate can be achieved by extending the reaction time. A low crosslinking rate results in a soft gel with a high water content, while a high crosslinking rate results in a strong gel with a low water content. The crosslinking rate can be appropriately selected depending on the application of the alginate crosslinked product.

[0109] Furthermore, a tendon reconstruction sheet material comprising a porous body containing a crosslinked alginate and a support can be obtained, for example, by freeze-drying or drying an alginate gel obtained in a tray without a support, and then layering it on a support. The tendon reconstruction sheet material obtained in this manner has a structure in which a porous body containing a crosslinked alginate and a support are layered.

[0110] The tendon reconstruction sheet material thus obtained contains crosslinked alginate in the form of a xerogel.

[0111] In the case of a tendon reconstruction sheet material comprising a porous body containing a crosslinked alginic acid and a support, ２ The content of alginic acids per unit area is preferably 0.2 mg / cm in terms of the content of sodium alginate. ２ ~12 mg / cm ２ , more preferably 0.5 mg / cm ２~7 mg / cm ２ , more preferably 1 mg / cm ２ ~6 mg / cm ２ , particularly preferably 1 mg / cm ２ ~5 mg / cm ２ is.

[0112] The tendon reconstruction sheet material of the present invention can be purified by removing unreacted raw materials such as condensing agents with a cleaning solution before freeze-drying or drying the gel obtained from the porous raw materials. The cleaning solution is not particularly limited, but examples that can be used include water and ECF (Extra Cellular Fluid). ECF is purified water containing CaCl ２ (2.5 mM) and NaCl (143 mM). The washing solution may be used after passing it through a sterilizing filter, if necessary. After washing the tendon reconstruction sheet material with ECF, it is preferable to wash it with water to remove any remaining calcium.

[0113] Tendon reconstruction sheet material of the present invention 1 cm ２ The amount of support contained per unit area is, for example, 0.05 mg / cm ２ ~30 mg / cm ２ , preferably 0.1 mg / cm ２ ~10 mg / cm ２ , more preferably 0.5 mg / cm ２ ~7 mg / cm ２ , more preferably 1 mg / cm ２ ~5 mg / cm ２ is.

[0114] The thickness of the tendon reconstruction sheet material of the present invention in a dry state is, for example, 0.1 mm to 5 mm, preferably 0.2 mm to 1 mm, and more preferably 0.3 mm to 0.5 mm.

[0115] The tendon reconstruction sheet material of the present invention may be pressed or unpressed. Pressed sheets are preferable because, compared to unpressed sheets, the porous nature of the sheet, which swells upon water absorption, is more pronounced, making it easier to adhere the sheet material to the tissue for tendon reconstruction. In addition, the sheet material swells more slowly upon water absorption, maintaining a dry state that makes it easier to handle, making it easier to handle during surgery.

[0116] In the case of a tendon reconstruction sheet material in which a porous body and a support are mixed in one layer, pressing can be performed after freeze-drying or drying. In the case of a tendon reconstruction sheet material in which a layer of a porous body and a layer of a support are laminated, the porous body alone can be pressed before or after the porous body and the support are layered. Pressing improves the flexibility of the tendon reconstruction sheet material, thereby preventing breakage when the tendon reconstruction sheet material is bent in a dry state.

[0117] Pressing can be performed by applying pressure to the freeze-dried or dried tendon reconstruction sheet material using a press such as a roller press or a flat press.

[0118] The ratio of the thickness after pressing to the thickness before pressing of a tendon reconstruction sheet material in which a porous body and a support are mixed in one layer (thickness after pressing / thickness before pressing) is, for example, 1 / 100 to 1 / 2, preferably 1 / 50 to 1 / 5, more preferably 1 / 30 to 1 / 8, and even more preferably 1 / 20 to 1 / 10.

[0119] When the press is a roller press, the gap between the rollers and the rotation speed of the rollers may be appropriately adjusted to obtain a tendon reconstruction sheet material of the desired thickness, for example.

[0120] When the press is a plate press, the pressing pressure, pressing time, and holding time can be appropriately adjusted to obtain a tendon reconstruction sheet material of the desired thickness. The pressing pressure is, for example, 5 kN to 50 kN, preferably 10 kN to 40 kN, and more preferably 15 kN to 30 kN. The pressing time is, for example, 3 to 30 seconds, preferably 4 to 20 seconds, and more preferably 5 to 10 seconds. The holding time is, for example, 5 to 60 seconds, preferably 10 to 50 seconds, and more preferably 20 to 40 seconds.

[0121] The tendon reconstruction sheet material of the present invention can be cut to any size and shape using scissors or other tools to suit the area of ​​tissue to which it is to be applied. The thickness does not have to be uniform, and it may have a gradient structure, with one side being thick and the other being thin.

[0122] Furthermore, when the tendon reconstruction sheet material of the present invention is placed on a tendon, the porous body swells with the body fluids around the tendon, and therefore the tendon reconstruction sheet material of the present invention does not need to be immersed in physiological saline or the like to swell before being placed on the tendon.

[0123] The thickness of the tendon reconstruction sheet material of the present invention increases when the porous body contained in the sheet material swells due to water absorption. The ratio of the thickness of the tendon reconstruction sheet material of the present invention after swelling to the thickness before swelling (thickness after swelling / thickness before swelling) is preferably 1.1 to 30 times, more preferably 1.2 to 15 times, and even more preferably 1.5 to 8 times.

[0124] The cross-sectional area of ​​the tendon reconstruction sheet material of the present invention increases when the porous body contained in the sheet material swells due to water absorption. The ratio of the cross-sectional area of ​​the tendon reconstruction sheet material of the present invention after swelling to the cross-sectional area before swelling (cross-sectional area after swelling / cross-sectional area before swelling) is preferably 1.2 to 35 times, more preferably 1.3 to 30 times, and even more preferably 2 to 25 times.

[0125] The tendon reconstruction sheet material of the present invention can adhere to the tendon by swelling. By adhering the sheet material to the damaged tendon, the intrusion of fibroblasts and other cells that hinder healing is prevented, and healing of the damaged area is promoted.

[0126] The thickness and cross-sectional area of ​​the tendon reconstruction sheet material before and after swelling can be determined as follows. First, a dry tendon reconstruction sheet material is cut to 35 mm x 20 mm, and the long sides are wrapped around a bent round pipe (outer diameter 4.1 mm). The tendon reconstruction sheet material is then clamped and secured with clips (see Figure 1). The round pipe is then removed, and a rod-shaped or tubular tissue model (outer diameter 3.0 mm) is inserted into the resulting space. The thickness or cross-sectional area of ​​the tendon reconstruction sheet material before swelling is measured. Next, 1000 μL of water is slowly dripped onto the entire tendon reconstruction sheet material surrounding the rod-shaped or tubular tissue model, causing the tendon reconstruction sheet material to swell. The thickness or cross-sectional area of ​​the swollen tendon reconstruction sheet material is then measured. Measurements are performed at room temperature of 20°C to 25°C and humidity of 50% to 70%. If the size of the tendon reconstruction sheet material is smaller than 35 mm x 20 mm and the above test cannot be performed, the tendon reconstruction sheet material may be placed on a petri dish and water dripped onto the entire tendon reconstruction sheet material to swell it. The amount of water dripped is adjusted in proportion to the size of the tendon reconstruction sheet material, with 1000 μL of water per tendon reconstruction sheet material (35 mm x 20 mm) being the standard. In either case, the thickness or cross-sectional area is measured 20 minutes after the entire amount of water has been dripped. Specifically, the thickness and cross-sectional area of ​​the tendon reconstruction sheet material before and after swelling can be measured using the method described in Example 4. Measurements can also be made using other tools, such as calipers.

[0127] In the tendon reconstruction sheet material of the present invention, the porosity before swelling is preferably 70 to 99%, more preferably 75 to 99%, and even more preferably 85 to 99%.

[0128] The porosity of the pressed tendon reconstruction sheet material before swelling is preferably 70-96%, more preferably 75-95%, and even more preferably 85-90%. The porosity of the unpressed tendon reconstruction sheet material before swelling is preferably 96-99%, more preferably 97-99%, and even more preferably 98-99%.

[0129] In addition, in the tendon reconstruction sheet material of the present invention, the cumulative pore volume before swelling is preferably 1.5 to 35 mL / g, more preferably 2 to 33 mL / g, and even more preferably 2.5 to 31 mL / g.

[0130] The cumulative pore volume of the pressed tendon reconstruction sheet material is preferably 1.5 to 20 mL / g, more preferably 2 to 10 mL / g, and even more preferably 2.5 to 8 mL / g. The cumulative pore volume of the unpressed tendon reconstruction sheet material is preferably 25 to 35 mL / g, more preferably 26 to 33 mL / g, and even more preferably 27 to 31 mL / g.

[0131] The porosity and cumulative pore volume can be determined by mercury intrusion porosimetry using, for example, an AutoPore IV 9520 (manufactured by Micromeritics Instrument Corporation) as a measuring device. The measurement conditions include, for example, the following conditions.

[0132] Pore ​​diameter: Approximately 0.0036 to 200 μm The pore diameter is calculated using the Washburn formula (PD = -4σ cos θ). P: pressure, D: pore diameter, σ: surface tension of mercury, θ: contact angle between mercury and sample. Surface tension of mercury: 480 dynes / cm. Contact angle between mercury and sample: 140 degrees.

[0133] Specifically, the porosity and cumulative pore volume of the tendon reconstruction sheet material can be determined by the method described in Example 6.

[0134] The tendon reconstruction sheet material of the present invention can be used in a dry state and is flexible, making it easy to perform operations such as rolling the sheet material.

[0135] The maximum test force (N) of the tendon reconstruction sheet material of the present invention is preferably 0.1 to 2.5 (N), more preferably 0.15 to 2.0 (N), and even more preferably 0.2 to 1.0 (N).

[0136] The maximum test force can be determined, for example, using a small tabletop testing machine EZ-graph (manufactured by Shimadzu Corporation) as a measuring device. Specifically, it can be determined by the method described in Example 5.

[0137] Furthermore, the tendon reconstruction sheet material of the present invention can be wrapped around a rod-shaped or tubular tissue having a diameter of 1 mm to 10 mm without cracking or tearing, whether in a dry or swollen state.

[0138] The tendon reconstruction sheet material of the present invention has sufficient strength to be fixed with a fixing material. Furthermore, the tendon reconstruction sheet material of the present invention has sufficient strength to be fixed with a fixing material even after absorbing moisture such as blood from the surgical field.

[0139] The duration of these strengths of the tendon reconstruction sheet material can be adjusted by appropriately adjusting the material of the porous body and / or support, the combination of the porous body and support, the shape of the tendon reconstruction sheet material, the cumulative pore volume, the porosity, the fiber diameter of the support, etc.

[0140] The tendon reconstruction sheet material of the present invention may be sterilized by, for example, gamma ray sterilization, electron beam sterilization, ethylene oxide gas sterilization, ethanol sterilization, etc., and preferably electron beam sterilization.

[0141] The tendon reconstruction sheet material of the present invention can be defined by any combination of two or more of the above-mentioned elements. Examples of the elements include the raw material of the porous body, whether or not the porous body is crosslinked, the type of crosslinking agent used for the porous body, whether or not the porous body or tendon reconstruction sheet material is pressed, the thickness ratio of the porous body or tendon reconstruction sheet material before and after pressing (thickness after pressing / thickness before pressing), the raw material of the support, the form of the porous body or support, whether the porous body layer and the support layer are mixed in one layer or laminated, the thickness of the porous body or tendon reconstruction sheet material in a dry state, the thickness ratio of the porous body or tendon reconstruction sheet material before and after swelling (thickness after swelling / thickness before swelling), the ratio of the cross-sectional area of ​​the porous body or tendon reconstruction sheet material before and after swelling (cross-sectional area after swelling / cross-sectional area before swelling), the maximum test force in a bending test of the tendon reconstruction sheet material, the porosity of the porous body or tendon reconstruction sheet material before swelling, the cumulative pore volume of the porous body or tendon reconstruction sheet material before swelling, and the thickness per 1 cm of the tendon reconstruction sheet material. ２ The amount of support or porous body raw material contained per unit area is referred to as the amount of support or porous body raw material contained per unit area.

[0142] As an example of a combination of each element, the tendon reconstruction sheet material of the present invention is a tendon reconstruction sheet material in which the raw material for the porous body is a bioabsorbable polysaccharide derived from a plant, the tendon reconstruction sheet material is pressed, the thickness of the tendon reconstruction sheet material in a dry state is 0.1 mm to 5 mm, and the raw material for the support is at least one selected from the group consisting of one or more polymers whose monomers are glycolic acid, lactic acid, caprolactone, amino acids, dioxanone, gluconate, ethylene oxide, hydroxybutyric acid, phosphate esters, or alphahydroxy acids, one or more copolymers obtained by polymerizing two or more of these monomers, and oxidized cellulose. Another example of a combination of elements is a tendon reconstruction sheet material of the present invention, in which the raw material for the porous body is a bioabsorbable polysaccharide derived from a plant, the tendon reconstruction sheet material is pressed, the thickness of the tendon reconstruction sheet material in a dry state is 0.1 mm to 5 mm, and the thickness of the tendon reconstruction sheet material after swelling is 1.1 to 30 times that before swelling, and the raw material for the support is at least one selected from the group consisting of one or more polymers whose monomers are glycolic acid, lactic acid, caprolactone, amino acids, dioxanone, gluconate, ethylene oxide, hydroxybutyric acid, phosphate esters, or alphahydroxy acids, one or more copolymers obtained by polymerizing two or more of these monomers, and oxidized cellulose.

[0143] As another example of a combination of each element, the tendon reconstruction sheet material used in the present invention has a porous body made from a plant-derived bioabsorbable polysaccharide, a dry thickness of the tendon reconstruction sheet material of 0.1 mm to 5 mm, and a support material made from at least one selected from the group consisting of one or more polymers whose monomers are glycolic acid, lactic acid, caprolactone, amino acids, dioxanone, gluconate, ethylene oxide, hydroxybutyric acid, phosphate esters, or alphahydroxy acids, one or more copolymers obtained by polymerizing two or more of these monomers, and oxidized cellulose. Another example of a combination of elements is the tendon reconstruction sheet material used in the present invention, in which the raw material for the porous body is a bioabsorbable polysaccharide derived from a plant, the thickness of the tendon reconstruction sheet material in a dry state is 0.1 mm to 5 mm, the raw material for the support is at least one selected from the group consisting of one or more polymers whose monomers are glycolic acid, lactic acid, caprolactone, amino acids, dioxanone, gluconate, ethylene oxide, hydroxybutyric acid, phosphate esters, or alphahydroxy acids, one or more copolymers obtained by polymerizing two or more of these monomers, and oxidized cellulose, and the maximum test force in a bending test is 0.1 to 2.5 N. Another example of a combination of elements is the tendon reconstruction sheet material used in the present invention, in which the raw material for the porous body is a bioabsorbable polysaccharide derived from a plant, the thickness of the tendon reconstruction sheet material in a dry state is 0.1 mm to 5 mm, and the thickness of the tendon reconstruction sheet material after swelling is 1.1 to 30 times that before swelling, the raw material for the support is at least one selected from the group consisting of one or more polymers whose monomers are glycolic acid, lactic acid, caprolactone, amino acids, dioxanone, gluconate, ethylene oxide, hydroxybutyric acid, phosphate esters, or alphahydroxy acids, one or more copolymers obtained by polymerizing two or more of these monomers, and oxidized cellulose, and the maximum test force in a bending test is 0.1 to 2.5 N.

[0144] Another example of a combination of elements is a tendon reconstruction sheet material used in the present invention, in which the raw material for the porous body is a bioabsorbable polysaccharide having carboxy groups in the molecule, the porous body is cross-linked, the cross-linking agent used for the cross-linked body is a diamine, the tendon reconstruction sheet material is pressed, and the thickness of the tendon reconstruction sheet material in a dry state is 0.1 mm to 5 mm.

[0145] Another example of a combination of elements is a tendon reconstruction sheet material used in the present invention, in which the raw material for the porous body is a bioabsorbable polysaccharide having a carboxy group in the molecule, and the raw material for the support is at least one selected from the group consisting of one or more polymers whose monomers are glycolic acid, lactic acid, caprolactone, amino acids, dioxanone, gluconate, ethylene oxide, hydroxybutyric acid, phosphate ester, or alphahydroxy acid, one or more copolymers obtained by polymerizing two or more of these monomers, and oxidized cellulose, and the tendon reconstruction sheet material is pressed, and the cumulative pore volume of the tendon reconstruction sheet material before swelling is 1.5 to 20 mL / g.

[0146] 4. Method of Use The tendon reconstruction sheet material of the present invention is used in a tendon reconstruction method, which includes applying it to the tendon of a subject requiring tendon reconstruction. The tendon reconstruction sheet material of the present invention is highly safe because it is absorbed and decomposed by the body after the six months required for tendon reconstruction, and is eventually metabolized and excreted.

[0147] Here, "applying" refers to placing the tendon reconstruction sheet material on a tendon requiring tendon reconstruction. Preferably, the tendon reconstruction sheet material is placed in contact with the tendon requiring tendon reconstruction. More preferably, the tendon reconstruction sheet material is wrapped around the tendon requiring tendon reconstruction. Particularly preferably, the tendon reconstruction sheet material is wrapped around the tendon requiring tendon reconstruction and fixed with a fixation material.

[0148] The method of using the tendon reconstruction sheet material involves exposing the target tendon, cutting it to an appropriate size depending on the length and width of the tendon requiring tendon reconstruction, and applying it to the tendon. The "subject" refers to a human or a non-human organism, such as a bird or non-human mammal (e.g., cow, monkey, cat, mouse, rat, guinea pig, hamster, pig, dog, rabbit, sheep, or horse).

[0149] The tendon reconstruction sheet material of the present invention may be applied in a dry state or in a state swollen with physiological saline or the like, but is preferably applied in a dry state.

[0150] After application of the tendon reconstruction sheet material of the present invention to a tendon requiring tendon reconstruction, the tendon reconstruction sheet material may be fixed to the damaged area of ​​the tissue (e.g., the stump of the tendon) with a fixing material, if necessary. Fixing materials include, for example, thread, clips, staples, and adhesives.

[0151] The tendon reconstruction sheet material of the present invention may be used in combination with humoral factors or cells. The method for combining them is not particularly limited, but examples include a method in which the tendon reconstruction sheet material contains these humoral factors or cells.

[0152] The humoral factors are not particularly limited as long as they are useful for tissue regeneration, and examples thereof include bFGF, NGF, hepatocyte growth factor, immunosuppressive factors, anti-inflammatory factors, etc. The cells are not particularly limited as long as they are useful for tissue regeneration, and examples thereof include autologous or allogeneic cultured mesenchymal stem cells, bone marrow mesenchymal stem cells, neural stem cells, bone marrow-derived mononuclear cells, adipose-derived stem cells, in vivo pluripotent stem cells, ES cells, neural progenitor cells, iPS cells, etc.

[0153] Next, the present invention will be explained in more detail with reference to examples, but the present invention is not limited to these examples.

[0154] Example 1 Preparation of Ethylenediamine-Crosslinked Alginate Crosslinked Material Containing Polyglycolic Acid (PGA) (1) Preparation of Sodium Alginate Aqueous Solution Sodium alginate having an endotoxin content of less than 50 EU / g (SM30, Sea Matrix (registered trademark), sold by Mochida Pharmaceutical Co., Ltd., M / G ratio 0.4 to 1.8) was dissolved in Milli-Q water to obtain a 1 w / vol% aqueous sodium alginate solution.

[0155] (2) Preparation of crosslinking agent: A solution of 23 g of N-hydroxysuccinimide dissolved in 1,000 mL of methanol was mixed with a solution of 6.7 mL of diaminoethane dissolved in 100 mL of methanol. The resulting crystals were collected by filtration on a glass filter and dried to obtain approximately 27 mg of di-N-hydroxysuccinimide salt of diaminoethane (EDA·2HOSu) to be used as a crosslinking agent.

[0156] (3) Preparation of crosslinked alginate: 100 mL of sodium alginate aqueous solution, 220 mg of a crosslinking agent (EDA·2HOSu), and 1.6 g of a condensing agent (1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride) (EDC·HCl) were mixed. The resulting solution was applied to a sheet-shaped nonwoven fabric of polyglycolic acid (PGA) (100 mg / cc, 3.0 mg / cm). ２ The alginate crosslinked material was placed on a tray covered with non-woven PGA Biofelt (Biomedical Structures (USA)) with a sodium alginate content of 2.0 mg / cm. ２ The mixture was allowed to stand at room temperature for 3 days to obtain a gel.

[0157] The gel was washed with a washing solution to remove unreacted crosslinker, condensation agent, and reaction by-products. The washing solution was ECF (Extra Cellular Fluid: purified water containing 2.5 mM CaCl2 and 143 mM NaCl, passed through a 0.22 μm filter (e.g., Millipak 20, Millipore) and an endotoxin removal filter (Prepscale UF Cartridge PLGC CDUF 001 LG, Millipore). The gel was then washed with distilled water to remove excess salts.

[0158] After washing, the gel was freeze-dried to obtain a crosslinked alginate. The thickness was about 4 mm and about 5 mm. ２ The content of alginic acids per unit weight is 2.0 mg / cm2, calculated as the content of sodium alginate. ２ In addition, the sheet material 1 cm ２ The amount of support (i.e., PGA) contained per unit area is 3.0 mg / cm ２ It was.

[0159] The resulting crosslinked alginate was sterilized by electron beam.

[0160] Example 2 Preparation of Sheet Material (1) ALG+PGA The crosslinked alginate prepared in Example 1 was pressed to prepare a sheet material. Before pressing, the thickness when dry was approximately 4 mm and approximately 5 mm. For sheets with a thickness of approximately 5 mm, the sheets were pressed using a small benchtop roller press SA-601 (manufactured by Tester Sangyo Co., Ltd.). After pressing, the thicknesses of the sheet material ALG+PGA when dry were approximately 0.1, 0.2, 0.3, 0.4, 0.5, and 1 mm, respectively. The thickness was changed by adjusting the gap between the rolls and the roller rotation speed.

[0161] (2) A CLG+PLA skin collage sheet (product name: Skin Collage Sheet, freeze-dried collagen, manufactured by Ishii Clinic, Lot No. 210740, 81500) was pressed with a precision pressurizing device (CYPM-20, manufactured by Shinto Kogyo Co., Ltd.), and then layered with a polylactic acid nonwoven fabric (manufactured by Tokano Co., Ltd.). The thickness of the polylactic acid nonwoven fabric was 0.3 mm, and the thickness of the skin collage sheet before pressing was 1 mm. After layering, the thickness of the sheet material when dry was approximately 0.4 and 0.5 mm. The thickness was changed by adjusting the pressing time and holding time.

[0162] (3) CLG + PGA This was produced by stacking a Skin Collage sheet and a PGA sheet (M type, manufactured by Nikke Medical Co., Ltd., Lot No. 220322) and pressing them together using a CYPM-20 press (manufactured by Shinto Kogyo Co., Ltd.). Before pressing, the thickness of the Skin Collage sheet was 1 mm, and the thickness of the PGA was 0.2 mm. After pressing, the thickness of the sheet material when dry was 0.4 mm. The thickness was changed by adjusting the pressing time and holding time.

[0163] Example 3: Preparation of rod-shaped or tubular tissue model. A stainless steel (SUS) rod (manufactured by Hikari Mall Co., Ltd., outer diameter 2.0 mm) was cut to a length of approximately 80 mm. A polytetrafluoroethylene (PTFE) tube (manufactured by MonotaRO Co., Ltd., inner diameter 2.0 mm, outer diameter 3.0 mm) was cut to a length of 40 mm. A UV-curable adhesive (Henkel AG & Co. KGaA) was applied to the center 40 mm of the SUS rod and inserted into the cut PTFE tube. The adhesive was cured using a penlight to fix the SUS rod and PTFE tube together. The rod obtained in this manner was used as a "rod-shaped or tubular tissue model" for subsequent experiments.

[0164] Example 4: Observation of swollen state The sheet material prepared in Example 2 was cut to 35 mm x 20 mm, and the long side was bent and wrapped around a SUS round pipe (manufactured by Hikari Mall Co., Ltd., outer diameter 4.1 mm) as shown in Figure 1. A clip was inserted from the side to clamp and secure the sheet material. The SUS round pipe was removed, taking care not to displace the clip. The rod-shaped or tubular tissue model prepared in Example 3 was inserted into the space left after the SUS round pipe was removed. The sheet material together with the clip was clamped in a mini-vice, and the inserted rod-shaped or tubular tissue model was fixed. The rod-shaped or tubular tissue model was placed so that it was perpendicular to the camera of a digital microscope (VHX-7000, manufactured by Keyence Corporation).

[0165] First, the position of the rod-shaped or tubular tissue model was adjusted so that the sheet material did not come into contact with the model in a dry state. Photographs were taken, and the thickness and cross-sectional area of ​​the sheet material before swelling were measured.

[0166] The sheet material was left to stand for 20 minutes in a state where the entire sheet material was saturated with 1000 μL of water. After swelling, a photograph of the sheet material was taken, and the thickness and cross-sectional area of ​​the swollen sheet material were measured.

[0167] The thickness and cross-sectional area of ​​the sheet material were measured using software that came standard with the digital microscope.

[0168] The measurement results of the thickness and cross-sectional area are shown in Table 1.

[0169]

[0170] The swelling and adhesion were visually confirmed and the results are shown in Table 2.

[0171]

[0172] From the above results, it was confirmed that the tendon reconstruction sheet material comprising a porous body and a support has sufficient flexibility to be wrapped around rod-shaped or tubular tissue, swells upon absorbing water, and adheres closely to the rod-shaped or tubular tissue model.

[0173] The ratio of the cross-sectional area after swelling to the cross-sectional area before swelling of the tendon reconstruction sheet material containing alginic acid cross-linked body as the porous body and PGA as the support (cross-sectional area after swelling / cross-sectional area before swelling) was approximately 2.2 times, and the ratio of the thickness after swelling to the thickness before swelling (thickness after swelling / thickness before swelling) was approximately 2.2 to 3.4 times.

[0174] The ratio of the cross-sectional area after swelling to the cross-sectional area before swelling of the tendon reconstruction sheet material containing collagen as a porous body and PLA as a support (cross-sectional area after swelling / cross-sectional area before swelling) was approximately 2.2 times, and the ratio of the thickness after swelling to the thickness before swelling (thickness after swelling / thickness before swelling) was approximately 1.9 to 2.1 times.

[0175] Example 5 Bending Test A bending test was performed using the ALG+PGA sheet material (thickness: 0.1 mm, 0.2 mm, 0.5 mm, 4 mm) prepared in Example 2 as a sample. Each sheet material was cut into a 50 mm square. As shown in Figure 2, the cut sheet material was sandwiched between auxiliary plates at the top and bottom, and the auxiliary plates were further fixed with clip-type grips so that the sheet material did not bend and the distance between the auxiliary plates was 30 mm. Next, a load was applied to the sheet material in the compression direction via the clip-type grips, and the maximum test force (N) observed during the deformation of the sheet material was measured. Measurements were performed using a small desktop testing machine, EZ-graph (manufactured by Shimadzu Corporation), with a load cell capacity of 10 N (lower detection limit 0.04 N), a test speed of 5 mm / min, and 23°C.

[0176] The results are shown in the table below.

[0177]

[0178] Tendon reconstruction sheet materials (thicknesses of 0.1 mm to 4 mm) containing cross-linked alginate as a porous material and PGA as a support were confirmed to bend flexibly without cracking in bending tests. It was confirmed that thickness correlated with maximum test force (N), with a tendency for the maximum test force to increase as the thickness increased.

[0179] Example 6 Cumulative Pore Volume and Porosity The sheet materials ALG+PGA (thickness: 0.3 mm, 1 mm, 5 mm) produced in Example 2 were used as samples to determine the cumulative pore volume and porosity.

[0180] The samples were vacuum dried at room temperature for 24 hours. The measurement device used was an AutoPore IV 9520 (manufactured by Micromeritics Instrument Corporation). The cumulative pore volume and porosity of each sheet material were determined by mercury intrusion porosimetry.

[0181] The measurement conditions are as follows: Pore diameter: Approximately 0.0036 to 200 μm The pore diameter was calculated using the Washburn formula (PD = -4σ cos θ). P: pressure, D: pore diameter, σ: surface tension of mercury, θ: contact angle between mercury and sample. Surface tension of mercury: 480 dynes / cm. Contact angle between mercury and sample: 140 degrees.

[0182] The results are shown in the table below.

[0183]

[0184] Example 7: Winding test A cylindrical metal rod with a length of 10 cm and a diameter of 1 mm or 5 mm was prepared as a rod-shaped or tubular tissue model. Each sheet material was cut to 27.5 mm x 10 mm, and the dried sheet material was wound around the rod-shaped or tubular tissue model. A preferred embodiment of the sheet material can be wound around the rod-shaped or tubular tissue model without cracking or breaking.

[0185] Example 8: In vivo tendon adhesion prevention effect in rabbits The sheet material used was the ALG+PGA sheet material (thickness: 0.3 mm) prepared in Example 2, cut into 10 mm x 35 mm. The animal used was a female rabbit (New Zealand white) weighing approximately 3.0 kg.

[0186] For both legs, the calcaneal tendon bundles were exposed and the tendons were injured by making an approximately 7 mm incision with a scalpel, with the scalpel blade inserted in a medial-lateral direction and parallel to the longitudinal axis of the tendon.

[0187] Treatment group: The sheet material was dry wrapped around the injured calcaneal tendon of the right leg, then secured with sutures and then sutured to the tendon using an appropriate size suture. The tendon sheath, subcutaneous tissue and skin were then closed with appropriate absorbable sutures.

[0188] Sham group: The same surgery as the treatment group was performed, except that no sheet material was placed on the injured calcaneal tendon of the left leg.

[0189] Three weeks after surgery, all animals were weighed, sedated with 5 mg of acepromazine maleate, and then euthanized by intravenous injection of sodium pentobarbital-based euthanasia solution.

[0190] For evaluation of the calcaneal tendon site, a surgical incision was made to expose the calcaneal tendon site. Each injury site and surrounding tissue / muscle were macroscopically examined for alterations in normal structure and the presence of adhesions, and the severity and extent of peritendinous adhesions were scored using the following semiquantitative grading scale:

[0191] Grades: Grade 1: No adhesions Grade 2: Thin membranes (separated by blunt dissection) Grade 3: Mild (slightly separated by sharp dissection)

[0192] The results are shown in the table below.

[0193]

[0194] From these results, it was found that the treatment group was more effective in preventing adhesions than the sham group in all individuals, and the tendon reconstruction sheet material containing alginate crosslinked material and PGA as a support was effective in promoting healthy healing (P<0.01). Significant differences were tested using a t-test.

[0195] In particular, adhesion between the tendon sheath and tendon was reduced in the treatment group, and free gliding (the tendon can move freely within the tendon sheath due to the absence of adhesion) was improved compared to the sham group.

[0196] Furthermore, three weeks after implantation, the sheet material had decomposed to the point where it was barely visible to the naked eye. The sheet material had no effect on tendon regeneration, and no abnormalities were observed.

[0197] Furthermore, the above tests confirmed that the tendon reconstruction sheet material of the present invention is flexible enough to be wrapped around a tendon, has strength sufficient to withstand the operations required in surgery, such as fixation with a fixation material, and has the property of swelling by absorbing moisture in the surgical field and adhering closely to the tendon, leading to healthy healing.

Claims

1. A tendon reconstruction sheet material comprising a porous body that can swell by absorbing water and a support.

2. A tendon reconstruction sheet material as described in claim 1, wherein the porous body that can swell by absorbing water contains bioabsorbable polysaccharides derived from plants and / or bioabsorbable polysaccharides having carboxy groups.

3. A tendon reconstruction sheet material according to claim 1 or 2, wherein the porous body capable of swelling by water absorption contains a cross-linked alginic acid.

4. A tendon reconstruction sheet material according to any one of claims 1 to 3, wherein the support comprises at least one selected from the group consisting of one or more polymers having glycolic acid, lactic acid, caprolactone, amino acids, dioxanone, gluconate, ethylene oxide, hydroxybutyric acid, phosphate esters, or alphahydroxy acids as monomers, one or more copolymers obtained by polymerizing two or more of these monomers, and oxidized cellulose.

5. A tendon reconstruction sheet material according to any one of claims 1 to 4, wherein the support comprises at least one selected from the group consisting of polyglycolic acid (PGA), polylactic acid (PLA) and polyglactin (PLGA).

6. A tendon reconstruction sheet material according to any one of claims 1 to 5, having a thickness in a dry state of 0.1 mm to 5 mm.

7. A tendon reconstruction sheet material according to any one of claims 1 to 6, wherein the thickness after swelling is 1.1 to 30 times the thickness before swelling.

8. A tendon reconstruction sheet material according to any one of claims 1 to 7, having a porosity of 70% to 99% before swelling.

9. A pressed tendon reconstruction sheet material according to any one of claims 1 to 8.

10. The tendon reconstruction sheet material according to any one of claims 1 to 9, which is used by being wrapped around a tendon requiring tendon reconstruction.

11. The tendon reconstruction sheet material according to any one of claims 1 to 10, which is used by being fixed with a fixing material.

12. A method for tendon reconstruction, comprising applying a tendon reconstruction sheet material comprising a porous body that can swell by absorbing water and a support to a tendon of a subject requiring tendon reconstruction.

13. A method for treating tendons, comprising applying a tendon reconstruction sheet material comprising a porous body that can swell by absorbing water and a support to the tendon of a subject requiring tendon reconstruction.

14. The method according to claim 12 or 13, wherein applying the tendon reconstruction sheet material is carried out by wrapping the tendon reconstruction sheet material around the tendon requiring tendon reconstruction.

15. The method according to claim 14, wherein applying the tendon reconstruction sheet material is carried out by fixing the tendon reconstruction sheet material with a fixation material.

16. A method for producing a tendon reconstruction sheet material, comprising a step of pressing a material comprising a porous body that can swell by absorbing water and a support.

17. A combination of a porous body that can swell by absorbing water and a support for use in treating the tendon of a subject requiring tendon reconstruction.

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