Tissue protective material

Abstract

Provided herein is a flexible sheet-like tissue protective material comprising: a porous body that can be swollen due to water absorption; and a support that contains a biocompatible polymer. Consequently, a useful tissue protective material and the like are provided.

Description

tissue protection material

[0001] The present invention relates to a flexible sheet-like tissue protection material and the like.

[0002] Rod-shaped or tubular tissues include nerves, tendons, ligaments, blood vessels, bile ducts, pancreatic ducts, and other tissues. When these rod-shaped or tubular tissues are ruptured, the two ends of the ruptured tissue are reattached either by natural healing or surgically. Specifically, surgical reattachment is performed by suturing the two ends together. This suturing is performed using an appropriate method, and there are various methods depending on the tissue. Rod-shaped or tubular tissues that have been reattached by natural healing or surgically are relatively weak until they are completely healed, and when a force exceeding their repair strength is applied to the reattached tissue, the tissue may rupture again.

[0003] In order to reinforce and repair torn or reattached rod-shaped or tubular tissue, it has been proposed to place implants, devices, etc. on the inside or outside of the torn tissue at both ends of the tissue tear to reinforce the repair of the tissue at the torn portion until the tissue is completely healed (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 materials such as VersaWrap (trade name), TenoGlide (trade name), and TenoMend (trade name) have been commercially available.

[0005] Here, Patent Document 3 (International Publication No. 2017 / 159700) describes the use of a crosslinked product obtained by covalently crosslinking a bioabsorbable polysaccharide having a carboxyl group in the molecule with a specific crosslinking reagent, and a material containing a bioabsorbable polymer, as a material for inducing nerve regeneration.

[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] An object of the present invention is to provide a useful tissue protection material and the like.

[0009] As a result of extensive research, the present inventors have found that a flexible sheet-like tissue protection material comprising a porous body that can swell upon absorption of water and a support containing a biocompatible polymer is useful as a tissue protection material, and have completed the present invention. That is, the present invention provides the following tissue protection materials, etc.

[0010] [1] A flexible sheet-like tissue protection material comprising a porous body capable of swelling upon water absorption and a support containing a biocompatible polymer. [2] The tissue protection material according to [1] above, which is used by being wrapped around a rod-shaped or tubular tissue requiring tissue protection. [3] The tissue protection material according to [2] above, which is used by being wrapped around a rod-shaped or tubular tissue requiring tissue protection and then fixed with a fixing material. [4] The tissue protection material according to any one of [1] to [3] above, which comprises a pressed porous body as the porous body capable of swelling upon water absorption. [5] The tissue protection material according to any one of [1] to [4] above, which has a thickness of 0.1 mm to 5 mm in a dry state. [6] The tissue protection material according to [5] above, which has a thickness after swelling of the porous body capable of swelling upon water absorption that is 1.1 to 30 times the thickness of the tissue protection material before swelling. [7] The tissue protection material according to [5] above, wherein the cross-sectional area of ​​the tissue protection material after swelling of the water-swellable porous body is 1.2 to 35 times the cross-sectional area of ​​the tissue protection material before swelling. [8] The tissue protection material according to [6] or [7] above, wherein the gripping force of the water-swellable porous body after swelling is greater than the gripping force of the tissue protection material before swelling. [9] The tissue protection material according to any one of [1] to [8] above, wherein the biocompatible polymer is selected from the group consisting of polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone, and copolymers thereof, poly(amino acids), polydioxanone, polygluconate, polylactic acid-polyethylene oxide copolymer, oxidized cellulose, poly(hydroxybutyric acid), polyanhydrides, polyphosphate esters, poly(alphahydroxy acids), related copolymer materials, and mixtures thereof.

[10] The tissue protection material according to any one of the above [1] to [9], wherein the tissue protection material is for protecting the rod-shaped or tubular tissue, and the rod-shaped or tubular tissue is selected from the group consisting of nerves, tendons, ligaments, blood vessels, bile ducts, and pancreatic ducts. [10-1] The tissue protection material according to any one of the above [1] to

[10] , wherein the tissue protection material is flat.[10-2] The tissue protective material according to any one of the above [1] to [10-1], wherein the tissue protective material is used in close contact with rod-shaped or tubular tissue by swelling of the porous body. [10-3] The tissue protective material according to any one of the above [1] to [10-2], wherein the tissue protective material is used in combination with a humoral factor or cells.

[0011]

[11] A tissue protection method comprising applying a flexible sheet-like tissue protection material comprising a porous body capable of swelling upon water absorption and a support comprising a biocompatible polymer to a rod-shaped or tubular tissue of a subject requiring tissue protection.

[12] The method according to

[11] above, wherein applying the tissue protection material is carried out by wrapping the tissue protection material around the rod-shaped or tubular tissue requiring tissue protection.

[13] The method according to

[12] above, wherein applying the tissue protection material is carried out by wrapping the tissue protection material around the rod-shaped or tubular tissue requiring tissue protection and then fixing it with a fixing material.

[14] The method according to any one of

[11] to

[13] above, wherein the tissue protection material comprises a pressed porous body as the porous body capable of swelling upon water absorption.

[15] The method according to any one of

[11] to

[14] above, wherein the tissue protection material has a thickness in a dry state of 0.1 mm to 5 mm.

[16] The method according to

[15] above, wherein the thickness of the tissue protection material after swelling of the water-swellable porous body is 1.1 to 30 times the thickness of the tissue protection material before swelling.

[17] The method according to

[15] above, wherein the cross-sectional area of ​​the tissue protection material after swelling of the water-swellable porous body is 1.2 to 35 times the cross-sectional area of ​​the tissue protection material before swelling.

[18] The method according to

[16] or

[17] above, wherein the gripping force of the tissue protection material after swelling of the water-swellable porous body is greater than the gripping force of the tissue protection material before swelling.

[19] The method according to any one of

[11] to

[18] above, wherein the biocompatible polymer is selected from the group consisting of polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone, and copolymers thereof, poly(amino acids), polydioxanone, polygluconates, polylactic acid-polyethylene oxide copolymers, oxidized cellulose, poly(hydroxybutyric acid), polyanhydrides, polyphosphate esters, poly(alphahydroxy acids), related copolymer materials, and mixtures thereof.

[20] The method according to any one of

[11] to

[19] above, wherein the tissue protection material is for protecting the rod-shaped or tubular tissue, and the rod-shaped or tubular tissue is selected from the group consisting of nerves, tendons, ligaments, blood vessels, bile ducts, and pancreatic ducts. [20-1] The method according to any one of

[11] to

[20] above, wherein the tissue protection material is flat.[20-2] The method according to any one of

[11] to [20-1] above, wherein the tissue protective material is used in close contact with rod-shaped or tubular tissue by swelling the porous body. [20-3] The method according to any one of

[11] to [20-2] above, wherein the tissue protective material is used in combination with a humoral factor or cells.

[0012]

[21] A method for producing a flexible sheet-shaped tissue protection material comprising a porous body that can swell by absorbing water and a support containing a biocompatible polymer, the method comprising pressing a material comprising the porous body and the support containing the biocompatible polymer.

[22] The method according to

[21] above, wherein the biocompatible polymer is selected from the group consisting of polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone and copolymers thereof, poly(amino acids), polydioxanone, polygluconates, polylactic acid-polyethylene oxide copolymers, oxidized cellulose, poly(hydroxybutyric acid), polyanhydrides, polyphosphate esters, poly(alphahydroxy acids), related copolymer materials, and mixtures thereof.

[23] The method according to

[21] or

[22] above, wherein the tissue protection material is for protecting rod-shaped or tubular tissue, and the rod-shaped or tubular tissue is selected from the group consisting of nerves, tendons, ligaments, blood vessels, bile ducts, and pancreatic ducts.

[0013]

[31] A therapeutic method involving tissue protection, comprising applying a flexible sheet-shaped tissue protection material comprising a porous body capable of swelling upon water absorption and a support comprising a biocompatible polymer to the tissue of a subject in need of treatment.

[32] The method according to

[31] above, wherein applying the tissue protection material is carried out by wrapping the tissue protection material around a rod-shaped or tubular tissue in need of tissue protection.

[33] The method according to

[32] above, wherein applying the tissue protection material is carried out by wrapping the tissue protection material around a rod-shaped or tubular tissue in need of tissue protection, and then fixing the tissue protection material with a fixing material.

[34] The method according to any one of

[31] to

[33] above, wherein the tissue protection material comprises a pressed porous body as the porous body capable of swelling upon water absorption.

[35] The method according to any one of

[31] to

[34] above, wherein the tissue protection material has a thickness in a dry state of 0.1 mm to 5 mm.

[36] The method according to

[35] above, wherein the thickness of the tissue protection material after swelling of the water-swellable porous body is 1.1 to 30 times the thickness of the tissue protection material before swelling.

[37] The method according to

[35] above, wherein the cross-sectional area of ​​the tissue protection material after swelling of the water-swellable porous body is 1.2 to 35 times the cross-sectional area of ​​the tissue protection material before swelling.

[38] The method according to

[36] or

[37] above, wherein the gripping force of the tissue protection material after swelling of the water-swellable porous body is greater than the gripping force of the tissue protection material before swelling.

[39] The method according to any one of

[31] to

[38] above, wherein the biocompatible polymer is selected from the group consisting of polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone, and copolymers thereof, poly(amino acids), polydioxanone, polygluconates, polylactic acid-polyethylene oxide copolymers, oxidized cellulose, poly(hydroxybutyric acid), polyanhydrides, polyphosphate esters, poly(alphahydroxy acids), related copolymer materials, and mixtures thereof.

[40] The method according to any one of

[31] to

[39] above, wherein the tissue protection material is for protecting the rod-shaped or tubular tissue, and the rod-shaped or tubular tissue is selected from the group consisting of nerves, tendons, ligaments, blood vessels, bile ducts, and pancreatic ducts. [40-1] The method according to any one of

[31] to

[40] above, wherein the tissue protection material is flat.[40-2] The method according to any one of

[31] to [40-1] above, wherein the tissue protective material is used in close contact with rod-shaped or tubular tissue by swelling the porous body. [40-3] The method according to any one of

[31] to [40-2] above, wherein the tissue protective material is used in combination with a humoral factor or cells.

[0014]

[41] A combination of a porous body that can swell upon water absorption and a support containing a biocompatible polymer, for use in treatments including tissue protection.

[42] The combination according to

[41] above, wherein a flexible sheet-like tissue protection material comprising the combination is used by being wrapped around a rod-shaped or tubular tissue requiring tissue protection.

[43] The combination according to

[42] above, wherein a flexible sheet-like tissue protection material comprising the combination is used by being wrapped around a rod-shaped or tubular tissue requiring tissue protection, and then fixed with a fixing material.

[44] The combination according to any one of

[41] to

[43] above, wherein the flexible sheet-like tissue protection material comprising the combination comprises a pressed porous body as the porous body that can swell upon water absorption.

[45] The combination according to any one of

[41] to

[44] above, wherein the thickness of the flexible sheet-like tissue protection material comprising the combination in a dry state is 0.1 mm to 5 mm.

[46] The combination according to

[45] above, wherein the thickness of the tissue protection material after swelling of the water-swellable porous body is 1.1 to 30 times the thickness of the tissue protection material before swelling.

[47] The combination according to

[45] above, wherein the cross-sectional area of ​​the tissue protection material after swelling of the water-swellable porous body is 1.2 to 35 times the cross-sectional area of ​​the tissue protection material before swelling.

[48] The combination according to

[46] or

[47] above, wherein the gripping force of the tissue protection material after swelling of the water-swellable porous body is greater than the gripping force of the tissue protection material before swelling.

[49] The combination according to any one of

[41] to

[48] above, wherein the biocompatible polymer is selected from the group consisting of polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone, and copolymers thereof, poly(amino acids), polydioxanone, polygluconates, polylactic acid-polyethylene oxide copolymers, oxidized cellulose, poly(hydroxybutyric acid), polyanhydrides, polyphosphate esters, poly(alphahydroxy acids), related copolymer materials, and mixtures thereof.

[50] The combination according to any one of

[41] to

[49] above, wherein the flexible sheet-shaped tissue protection material comprising the combination is for protecting the rod-shaped or tubular tissue, and the rod-shaped or tubular tissue is selected from the group consisting of nerves, tendons, ligaments, blood vessels, bile ducts, and pancreatic ducts.[50-1] The combination according to any one of

[41] to

[50] above, wherein the flexible sheet-like tissue protection material comprising the combination is flat. [50-2] The combination according to any one of

[41] to [50-1] above, wherein the flexible sheet-like tissue protection material comprising the combination is used in close contact with rod-shaped or tubular tissue by swelling of the porous body. [50-3] The combination according to any one of

[41] to [50-2] above, wherein the flexible sheet-like tissue protection material comprising the combination is used in combination with a humoral factor or cells.

[0015] The present invention provides useful tissue protection materials and the like. Some embodiments of the tissue protection material have one or more of the following characteristics: -Strength enough to be sutured and not easily torn or ripped; -Flexible and able to be wrapped around rod-shaped or tubular tissue; -Excellent operability in both dry and wet states; -Can be re-attached to target tissue; -High adhesion to tissue.

[0016] FIG. 1 is a diagram showing an evaluation system for a grip test. FIG. 2 is a diagram showing a method for producing sheet materials: (A) CLG, (B) CLG+PLA, (C) CLG+PGA. FIG. 3 is a diagram showing an evaluation system for observing the swelling state. (A) and (B) Winding and fixing of sheet materials around a pipe, (C) Relationship between a tubular tissue model and sheet material. FIG. 4 is a diagram showing the cross-sectional state of the sheet material before swelling. FIG. 5 is a diagram showing the cross-sectional state of the sheet material after swelling.

[0017] Here, a flexible sheet-like tissue protection material is provided, which includes a porous body that can swell by absorbing water and a support containing a biocompatible polymer. Hereinafter, the flexible sheet-like tissue protection material may be referred to as a "sheet material."

[0018] The term "flexible" means that the sheet-shaped tissue protection material is flexible and bends easily, i.e., the sheet-shaped tissue protection material is flexible and does not break when bent. Preferably, the sheet-shaped tissue protection material is flexible enough to be wrapped around a rod-shaped or tubular tissue.

[0019] "Wrapping" or "being wrapped" refers to covering the surface of a rod-shaped or tubular tissue. When the tissue protection material of the present invention is wrapped around a rod-shaped or tubular tissue, the area may be such that it completely surrounds the rod-shaped or tubular tissue, or may be limited to a portion of the rod-shaped or tubular tissue, and an appropriate area can be selected as appropriate. The tissue protection material of the present invention is preferably used in a manner that it is wrapped around the rod-shaped or tubular tissue completely while covering the damaged area.

[0020] "Tissue protection" specifically means protecting damaged, ruptured, or reattached rod-shaped or tubular tissue by covering it. The tissue to which the tissue protection material is applied is preferably rod-shaped or tubular tissue. Examples of rod-shaped or tubular tissue include tissues such as nerves, tendons, ligaments, blood vessels, bile ducts, and pancreatic ducts. In some preferred embodiments, the rod-shaped or tubular tissue is a nerve. In other embodiments, the rod-shaped or tubular tissue is a tendon.

[0021] "Before swelling" refers to the time before the tissue protective material of the present invention or the porous body contained in the tissue protective material of the present invention swells due to water absorption, i.e., the time when the tissue protective material is in a dry state. Note that "before swelling" may also be expressed as "Dry," "when dry," or "in a dry state."

[0022] "After swelling" refers to the point in time 20 minutes after the completion of dripping a predetermined amount of water onto the tissue protection material of the present invention or the porous body contained in the tissue protection material of the present invention. Note that "after swelling" may also be expressed as "wet" or "at the time of swelling."

[0023] 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.

[0024] 1. Porous body capable of swelling upon water absorption The tissue protection material of the present invention includes a porous body capable of swelling upon water absorption. "Capable of swelling upon water absorption" means that the porous body, which is a sponge-like material, swells when it absorbs water, such as moisture in a living body. Preferably, the porous body swells after the tissue protection material is placed on the tissue, and there is no need to immerse it in water beforehand to cause it to swell.

[0025] The raw materials for the porous body used in the present invention include biopolymers (natural polymers), synthetic polymers, their derivatives, or combinations thereof, which are absorbed by the body and do not have harmful effects on the body. Examples of biopolymers include biocompatible polysaccharides derived from plants, animals, and microorganisms, as well as proteins. Examples of biocompatible polysaccharides derived from plants include polysaccharides such as carboxymethyl starch, hyaluronic acid, and carboxymethyl cellulose, as well as their esters and salts. Examples of biocompatible polysaccharides derived from animals include polysaccharides such as hyaluronic acid, chitin, and chitosan, as well as their esters and salts. Examples of biocompatible polysaccharides derived from microorganisms include dextran, its esters, and salts. Examples of proteins include collagen, gelatin, elastin, and fibrin. Examples of synthetic polymers include poly(ethylene glycol) and poly(vinyl alcohol). Derivatives or combinations of these are also preferred. A preferred embodiment of the raw material for the porous body used in the present invention is a biopolymer. Another preferred embodiment of the raw material for the porous body used in the present invention is a biocompatible polysaccharide derived from a plant.

[0026] Another preferred embodiment of the raw material for the porous body used in the present invention is a biocompatible polysaccharide having a carboxy group in the molecule. Examples of biocompatible polysaccharides having a carboxy group in the molecule include polysaccharides such as carboxymethyl starch, hyaluronic acid, and carboxymethyl cellulose, as well as their esters and salts. It is preferable that the biocompatible polysaccharide be decomposed and absorbed in the body.

[0027] The porous body used in the present invention may have crosslinks at least in part, and preferably has crosslinks.

[0028] Examples of crosslinking methods include physical crosslinking methods such as photocrosslinking by ultraviolet irradiation, thermal crosslinking, and ionic crosslinking by salts, and chemical crosslinking methods using a gaseous or solution-like crosslinking agent. In the present invention, it is preferable to use a chemical crosslinking method.

[0029] The crosslinking agent for the porous body used in the present invention can be any conventionally known crosslinking agent, and examples of such crosslinking agents 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.

[0030] Preferred examples of the crosslinking agent for the porous body used in the present invention include aldehydes such as glutaraldehyde and formaldehyde, and diamines such as diaminoethane and diaminopentane.

[0031] For example, when the raw material for the porous body used in the present invention is gelatin, physical crosslinking by heat or chemical crosslinking using glutaraldehyde as a crosslinking agent can be used. Another example is when the raw material for the porous body used in the present invention is hyaluronic acid, chemical crosslinking using 1,4-butanediol glycidyl ether (BDDE) as a crosslinking agent can be used. Another example is when the raw material for the porous body used in the present invention is collagen, chemical crosslinking using genipin as a crosslinking agent can be used.

[0032] In some embodiments, the porous body is in the form of a xerogel. A xerogel is a gel in a dried state. A gel contains a solvent such as water in a three-dimensional network structure, but a xerogel is a structure that has lost the solvent and is left with only a network. Here, a xerogel is sometimes called a "sponge."

[0033] The porous body capable of swelling upon water absorption used in the present invention is preferably a pressed porous body, an unpressed porous body, etc., and more preferably a pressed or unpressed porous body obtained by freeze-drying a solution of a polymer raw material, a pressed or unpressed porous body obtained by drying a solution of a polymer raw material after phase separation (solid-liquid, liquid-liquid), etc. The porous body capable of swelling upon water absorption used in the present invention is more preferably a pressed porous body, and more preferably a pressed porous body obtained by freeze-drying a solution of a polymer raw material, a pressed porous body obtained by drying a solution of a polymer raw material after phase separation (solid-liquid, liquid-liquid), etc.

[0034] The ratio of the thickness of the porous body that can swell by absorbing water 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. In some embodiments, the thickness of the porous body in a dry state after pressing 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.

[0035] "The porous body that can swell upon water absorption swells" means that the porous body that can swell upon water absorption in a dry state swells upon water absorption, and the thickness of the tissue protection material after swelling becomes, for example, 1.1 times or more, preferably 1.1 to 30 times, more preferably 1.2 to 25 times, and even more preferably 1.5 to 20 times the thickness of the tissue protection material before swelling. Alternatively, "the porous body that can swell upon water absorption swells" means that the porous body that can swell upon water absorption in a dry state swells upon water absorption, and the cross-sectional area of ​​the tissue protection material after swelling becomes, for example, 1.2 times or more, preferably 1.2 to 35 times, more preferably 1.3 to 30 times, and even more preferably 2 to 25 times the cross-sectional area of ​​the tissue protection material before swelling.

[0036] The porous body used in the present invention is preferably one that can adhere the tissue protective material of the present invention to rod-shaped or tubular tissue by swelling. By adhering the tissue protective material to damaged rod-shaped or tubular tissue, it is possible to prevent the intrusion of fibroblasts and other cells that hinder healing, promote healing of the damaged area, and prevent contracture after tissue repair.

[0037] The thickness and area of ​​the tissue protection material before and after swelling can be determined, for example, as follows. First, a dry tissue protection 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 tissue protection material is then clamped and fixed with clips (see Figure 3(A)). The round pipe is removed, and a rod-shaped or tubular tissue model (outer diameter 3.0 mm) is then inserted without contacting the dry tissue protection material. The thickness or cross-sectional area of ​​the tissue protection material before swelling is measured. Next, 1000 μL of water is dripped onto the entire tissue protection material surrounding the tissue model. 20 minutes after the dripping is complete, the thickness or cross-sectional area of ​​the swollen tissue protection material is measured. The measurement is performed in an environment at room temperature of 20°C to 25°C and humidity of 50% to 70%. Note that if the size of the tissue protection material is smaller than 35 mm x 20 mm and the above test cannot be performed, the tissue protection material may be placed on a petri dish and water may be dripped onto the entire tissue protection material. In this case, the amount of water to be dropped is adjusted in proportion to the size of the tissue protection material used in the test, with 1000 μL of water being the standard for the size of the tissue protection material (35 mm × 20 mm). Specifically, the thickness and area of ​​the tissue protection material before and after swelling can be measured by the method described in Example 3.

[0038] In a porous body that can swell by absorbing water, the porosity before swelling is not particularly limited as long as the porous body can swell by absorbing water, but one embodiment of the porosity before swelling is preferably 70 to 99%, more preferably 75 to 99%, and even more preferably 85 to 99%.

[0039] 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%.

[0040] In a porous body that can swell by absorbing water, the cumulative pore volume before swelling is not particularly limited as long as the porous body can swell by absorbing water, but one embodiment of the cumulative pore volume before swelling 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. One embodiment of the cumulative pore volume of an 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.

[0041] The porosity and cumulative pore volume of the porous body used in the present invention 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.

[0042] 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.

[0043] The porosity and cumulative pore volume of a porous body that can swell upon absorption of water can be appropriately adjusted by adjusting the type, molecular weight, content, etc. of the raw materials of the porous body. Furthermore, for porous bodies obtained by freeze-drying, the porosity and cumulative pore volume of the porous body can be appropriately adjusted by setting the freeze-drying conditions, such as temperature, time, speed, etc. Furthermore, the porosity and cumulative pore volume of the porous body obtained in this manner can be appropriately adjusted by pressing the porous body under various conditions.

[0044] The porous body used in the present invention can be produced by making these raw materials into a solution and freeze-drying it. Alternatively, the porous body can be produced by making the raw materials into a solution, whipping the solution with a stirrer, and then drying it. Freeze-drying or drying can be carried out using common technical knowledge known to those skilled in the art. The conditions for freeze-drying or drying can be adjusted as appropriate, and a primary drying step, a secondary drying step, etc. may be included.

[0045] The porous body may be a commercially available product molded into a sheet. Examples of commercially available porous bodies include Skin Collage Sheet (a freeze-dried collagen product, manufactured by Ishii Clinic) and Collagen Sponge for 35 mm Dishes (a freeze-dried collagen product, manufactured by Koken Co., Ltd.). These commercially available porous bodies can be pressed to obtain a swellable porous body.

[0046] A preferred combination of porous bodies used in the present invention is a porous body whose raw material is a plant-derived biocompatible polysaccharide, which is pressed, whose thickness swells by 1.1 to 30 times upon water absorption, and whose dry thickness after pressing is 0.1 mm to 5 mm.

[0047] 2. Support The tissue protection material used in the present invention includes a support containing a biocompatible polymer in addition to a porous body that can swell upon water absorption. In some embodiments, the support can provide the tissue protection material with strength that allows it to be sutured, and preferably, the support can provide the tissue protection material with strength that allows it to be sutured even after absorbing water such as blood in a trocar or at the surgical site during surgery. In some embodiments, the support can also improve manufacturing efficiency by preventing material deformation due to freeze-drying. In some embodiments, the support can increase the strength of the tissue protection material, making it less likely to break even in moving parts such as the knee. In some embodiments, the tissue protection material does not require any retaining material other than the support to maintain its sheet shape.

[0048] The support may be one that does not have a harmful effect on the living body. Preferably, the support has a form with numerous pores.

[0049] Biocompatible polymers contained in the support used in the present invention include, but are not limited to, biocompatible polymers selected from the group consisting of polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone, and copolymers thereof, poly(amino acids), polydioxanone, polygluconates, polylactic acid-polyethylene oxide copolymers, oxidized cellulose, poly(hydroxybutyric acid), polyanhydrides, polyphosphate esters, poly(alphahydroxy acids), related copolymer materials, and mixtures thereof. Copolymers of polyglycolic acid and polylactic acid (also referred to herein as "PLGA") are known, for example, as polyglactin. These polymers are used as suture materials and have excellent biocompatibility. It is preferable that the biocompatible polymers contained in the support used in the present invention are bioabsorbable.

[0050] In some embodiments, the biocompatible polymer is preferably one selected from the group consisting of polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone, copolymers thereof, and mixtures thereof, more preferably polyglycolic acid (PGA) or polylactic acid (PLA), and particularly preferably polyglycolic acid (PGA).

[0051] The support containing a biocompatible polymer is not particularly limited, but is preferably used in a form containing fibers such as nonwoven fabric or woven fabric.

[0052] Examples of woven fabrics include fabrics made using yarns containing fibers made from the biocompatible polymers.

[0053] Specific examples of the nonwoven fabric include nonwoven fabrics produced by a dry method, a wet method, a spunbond method, a meltblown method, an airlaid method, etc. Alternatively, the nonwoven fabric may be a woven fabric that has been made into a nonwoven fabric by a chemical bond method (permeation method, spray method), a thermal bond method, a needle punch method, a hydroentanglement method, etc.

[0054] The support may be a commercially available sheet-shaped support. Examples of commercially available supports include polylactic acid nonwoven fabric (Tokano Co., Ltd.), PGA sheet (M type) (manufactured by Nikke Medical Co., Ltd.), and BIOFELT (trade name, manufactured by Biomedical Structures).

[0055] A preferred combination of supports used in the present invention includes a support made of a biocompatible polymer that contains polyglycolic acid as a raw material and a support that is a nonwoven fabric and contains a biocompatible polymer.

[0056] 3. Tissue Protection Material The tissue protection material comprises a porous body that can swell upon absorption of water and a support. The arrangement of the porous body that can swell upon absorption of water and the support in the tissue protection material is not particularly limited. A layer of the support and a layer of the porous body that can swell upon absorption of water may be laminated, a layer of the porous body that can swell upon absorption of water may be sandwiched between two layers of the support, or both may be mixed in one layer.

[0057] The tissue protection material can be manufactured, for example, as follows. When manufacturing a porous body from a solution of raw materials for the porous body, a support is placed in the mold before pouring the solution of raw materials for the porous body into the mold, and the raw material solution for the porous body is poured onto the support and freeze-dried to form a porous body on the support, thereby producing a material comprising a support and a porous body. Alternatively, a support is placed in the mold before pouring the solution of raw materials for the porous body into the mold, and the raw material solution for the porous body is thoroughly whipped using a high-speed stirrer or the like before pouring it into the mold, and then dried to form a porous body on the support, thereby producing a material comprising a support and a porous body. Freeze-drying or drying can be carried out using technical common sense known to those skilled in the art. The conditions for freeze-drying or drying can be adjusted as appropriate, and a primary drying process, a secondary drying process, etc. may be included.

[0058] Alternatively, a manufactured or commercially available porous body can be overlaid or attached to a support to produce a material in which a layer of support and a layer of porous body are laminated.

[0059] Here, as the porous body that can swell by absorbing water, various porous bodies described above in "1. Porous body that can swell by absorbing water" can be used, and as the support, various supports described above in "2. Support" can be used.

[0060] In some embodiments, the tissue protection material includes a pressed porous body as the porous body that can swell by absorbing water. The porous body alone may be pressed before being attached to the support, or the material including the porous body and the support may be pressed.

[0061] The pressing can be carried out using a press such as a roller press or a plate press.

[0062] The ratio of the thickness of the tissue protection material before and after 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. In some embodiments, the thickness of the tissue protection material in a dry state after pressing 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.

[0063] The conditions for setting the press, such as the pressing pressure, thickness of the sheet after pressing, and pressing time, are not particularly limited as long as the press can be used safely.

[0064] For example, in the case of a roller press, the gap between the rollers and the roller speed can be adjusted to obtain a pressed tissue protection material of a desired thickness.

[0065] For example, in the case of a flat plate press, the tissue protection material before pressing is set, and a pressure of 15 to 25 kN is applied for 5 to 10 seconds, and then the pressure is maintained at 15 to 25 kN for 10 to 40 seconds, thereby obtaining a pressed tissue protection material of the desired thickness.

[0066] "The tissue protective material swells" means that the tissue protective material in a dry state swells by absorbing water, and the thickness of the swollen tissue protective material is, for example, 1.1 times or more, preferably 1.1 to 30 times, more preferably 1.2 to 25 times, and even more preferably 1.5 to 20 times the thickness of the tissue protective material before swelling. Alternatively, "the tissue protective material swells" means that the tissue protective material in a dry state swells by absorbing water, and the cross-sectional area of ​​the swollen tissue protective material is, for example, 1.2 times or more, preferably 1.2 to 35 times, more preferably 1.3 to 30 times, and even more preferably 2 to 25 times the cross-sectional area of ​​the tissue protective material before swelling.

[0067] In some embodiments, the size of the tissue protection material is not particularly limited and can be selected appropriately taking into account the range of tissue to be applied. The size of the sheet of the tissue protection material is not particularly limited, as it can be cut into any size and shape using scissors or other tools to fit the range of tissue to be applied. For example, when the shape of the sheet is expressed as length x width x height (thickness), the length and width are not particularly limited, and the height (thickness) is preferably 0.1 mm to 5 mm, more preferably 0.2 mm to 4 mm, and even more preferably 0.3 mm to 3 mm. More preferably, in addition to such height (thickness), the length and width are each 1 mm to 300 mm x 1 mm to 300 mm, particularly preferably 3 mm to 200 mm x 3 mm to 200 mm, and even more preferably 5 mm to 150 mm x 5 mm to 150 mm. The thickness does not have to be uniform, and the sheet may have a gradient structure, with one side thick and the other thin.

[0068] In a preferred embodiment, the tissue protection material is preferably sterilized. Examples of sterilization include, but are not limited to, gamma ray sterilization, electron beam sterilization, ethylene oxide gas sterilization, and ethanol sterilization. In some preferred embodiments, the tissue protection material is irradiated with electron beams or gamma rays, thereby achieving a sterilization effect. The tissue protection material is preferably irradiated with electron beams and / or gamma rays at an absorbed dose of 1 kGy to 100 kGy, more preferably 3 kGy to 60 kGy, even more preferably 5 kGy to 40 kGy, and particularly preferably 5 kGy to 30 kGy.

[0069] When the tissue protection material is subjected to the tear test described below, the maximum test force is preferably 0.10 (N) to 10.0 (N), and more preferably 0.10 (N) to 5.0 (N). The tissue protection material as described above is a sheet material that does not crack, tear, or rip when suturing with suture thread or when fixed with a medical clip, medical stapler, or the like, whether in a dry or swollen state.

[0070] The tear test is performed as follows: The material to be tested is cut to a size of 2 cm length x 2 cm width (thickness does not matter). The length and width cut surfaces intersect perpendicularly. Since this test examines the tear strength of the material itself, the thickness of the material to be tested is used as is, but a thickness of 0.1 mm to 5 mm is typically desirable. The material is held with a double clip at a position 5 mm away from one of the cut surfaces (holding portion A). The area of ​​the material extending 10 mm from the cut surface (B) opposite holding portion A is immersed in saline for 15 minutes. A needle-tipped suture is passed through the center of the material 5 mm away from the cut surface (B), and both ends of the suture are fixed to the instrument. Holding portion A is pulled parallel to the square surface of the material at a speed of 10 mm / min until the material tears, and the pulling load is measured as the test force (N). The maximum test force (N) is the point at which the test force is at its maximum. It is desirable to measure the tensile load using a small physical property testing machine (EZ-graph, manufactured by Shimadzu Corporation), but if such a machine is not available, a similar load measuring machine may be used.

[0071] The size of the double clip used for gripping portion A is preferably 15 to 19 mm wide. The suture used for the test is preferably "Vicryl (registered trademark)" with a thread thickness of 4-0, but if this is unavailable, a suture made of polyglactin 910 (glycolic acid / lactic acid polyester: 90 / 10) with a thread thickness of 4-0 may be used. The needle used is preferably a round SH-1 needle, but if this is unavailable, a needle compatible with similar sutures may be used.

[0072] Preferably, when determining the maximum test force of a material, the material is cut, the test force is measured with n=3 to 10, and the average of the maximum test forces is determined as the maximum test force of the material.

[0073] When the tissue protection material of a preferred embodiment is subjected to the wrapping test described below, it can be wrapped around a rod-shaped or tubular tissue model without cracking or tearing, both when dry and when swollen.

[0074] The wrapping test is performed as follows: A cylindrical metal rod 10 cm long and 1 mm, 5 mm, or 10 mm in diameter is prepared and used as a rod-shaped or tubular tissue model. Each tissue protection material is cut to 27.5 mm x 10 mm, and the tissue protection material in its dry state or after swelling is wrapped around the rod-shaped or tubular tissue model and secured with clips or sutured with sutures. Specifically, the test is performed according to the method of Example 5.

[0075] The tissue protection material of the present invention can be subjected to the bending test described below. The bending test is carried out as follows. Each tissue protection material is cut into a 50 mm square. The cut tissue protection material is sandwiched between auxiliary plates from above and below, and the auxiliary plates are further fixed with a clip-type jig so that the tissue protection material does not bend and the distance between the auxiliary plates is 30 mm. Next, a load is applied to the tissue protection material in the compression direction via the clip-type jig, and the maximum test force (N) observed during the process of deformation of the tissue protection material is measured. The measurement is carried out 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.

[0076] A bending test shows that the tissue protection material of a preferred embodiment has appropriate flexibility. The preferred range of maximum test force (bending strength) of the tissue protection material of the present invention according to this test 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.

[0077] In the tissue protection material used in the present invention, the porosity before swelling is not particularly limited as long as the tissue protection material can swell by absorbing water, but one embodiment of the porosity before swelling is preferably 70 to 99%, more preferably 75 to 99%, and even more preferably 85 to 99%.

[0078] In one embodiment, the porosity of the pressed tissue protection material before swelling is preferably 70 to 96%, more preferably 75 to 95%, and even more preferably 85 to 90%. In one embodiment, the porosity of the unpressed tissue protection material before swelling is preferably 96 to 99%, more preferably 97 to 99%, and even more preferably 98 to 99%.

[0079] In the tissue protection material used in the present invention, the cumulative pore volume before swelling is not particularly limited as long as the tissue protection material can swell by absorbing water, but one embodiment of the cumulative pore volume before swelling 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. One embodiment of the cumulative pore volume of the unpressed tissue protection material is preferably 25 to 35 mL / g, more preferably 26 to 33 mL / g, and even more preferably 27 to 31 mL / g.

[0080] The cumulative pore volume and porosity of the tissue protective material of the present invention can be measured by the methods described below.

[0081] The cumulative pore volume and porosity of the porous body of each sheet material that can swell by absorbing water are determined by mercury intrusion using an AutoPore IV 9520 (manufactured by Micromeritics Instrument Corporation) as a measuring device.

[0082] The measurement conditions are, for example, 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.

[0083] The tissue protection material used in the present invention can be fixed with a fixing material. A preferred embodiment of the tissue protection material can be fixed with a microclip. Another preferred embodiment of the tissue protection material allows a needle for suturing to be easily passed through. Another preferred embodiment of the tissue protection material increases its gripping force on rod-shaped or tubular tissue upon swelling, and can be fixed to rod-shaped or tubular tissue with as few sutures as two stitches.

[0084] A preferred embodiment of the tissue protection material has the strength to allow suturing even after absorbing water such as blood in a trocar or at the surgical site during surgery. The duration for which the tissue protection material maintains the strength to allow suturing can be adjusted by appropriately adjusting the material of the porous body and / or support that can swell upon absorption of water, the combination of the porous body that can swell upon absorption of water and the support, the shape of the tissue protection material, the porosity of the porous body that can swell upon absorption of water, the fiber diameter of the support, etc.

[0085] A preferred embodiment of the tissue protection material is one that can be easily reattached to tissue even when wet.

[0086] The tissue protective material used in the present invention can be defined by any combination of two or more of the following factors: the raw material of the porous body, whether or not the porous body is crosslinked, the type of crosslinker used for the porous body, whether or not the porous body or tissue protective material is pressed, the thickness ratio of the porous body or tissue protective material before and after pressing, the raw material of the biocompatible polymer contained in the support, the morphology of the biocompatible polymer contained in the support, the thickness of the porous body or tissue protective material in a dry state, the thickness or cross-sectional area ratio of the porous body or tissue protective material before and after swelling, the grip strength of the tissue protective material, the maximum test force in a bending test of the tissue protective material, the maximum test force in a tear test of the tissue protective material, the porosity of the porous body or tissue protective material, and the cumulative pore volume of the porous body or tissue protective material. As an example of a combination of the above elements, the tissue protection material used in the present invention is a tissue protection material in which the raw material for the porous body is a biocompatible polysaccharide derived from a plant, the tissue protection material is pressed, the thickness of the tissue protection material after swelling is 1.1 to 30 times that before swelling, the dry thickness of the tissue protection material after pressing is 0.1 mm to 5 mm, and the raw material for the biocompatible polymer contained in the support is one selected from the group consisting of polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone, copolymers thereof, and mixtures thereof.

[0087] Another example of a combination of the above elements is a tissue protective material used in the present invention, in which the raw material for the porous body is a plant-derived biocompatible polysaccharide, the thickness of the tissue protective material after swelling is 1.1 to 30 times that before swelling, and the dry thickness of the tissue protective material after pressing is 0.1 mm to 5 mm, the raw material for the biocompatible polymer contained in the support is one selected from the group consisting of polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone, copolymers thereof, and mixtures thereof, and the maximum test force in a bending test of the tissue protective material is 0.1 to 2.5 N. Another example of a combination of the above elements is a tissue protective material used in the present invention, in which the raw material for the porous body is a biocompatible polysaccharide having a carboxy group in the molecule, the porous body is crosslinked, the crosslinking agent used for the crosslinked body is a diamine, the tissue protective material is pressed, and the dry thickness of the tissue protective material after pressing is 0.1 mm to 5 mm. As another example of a combination of the above elements, the tissue protection material used in the present invention is a tissue protection material in which the raw material for the porous body is a biocompatible polysaccharide having a carboxy group in the molecule, the raw material for the biocompatible polymer contained in the support is one selected from the group consisting of polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone, copolymers thereof, and mixtures thereof, the tissue protection material is pressed, and the cumulative pore volume of the tissue protection material is 1.5 to 20 mL / g.

[0088] 4. Method of Use In some embodiments, the tissue protective material is used in a tissue protection method, which includes applying the material to the tissue of a subject in need of tissue protection. In other embodiments, the tissue protective material is used in a treatment method, including tissue protection, which includes applying the material to the tissue of a subject in need of treatment. The tissue protective material of a preferred embodiment is highly safe because it is absorbed and decomposed after several months required for tissue protection, and is eventually metabolized and excreted.

[0089] The tissue to which the tissue protection material is applied is preferably a rod-shaped or tubular tissue. Examples of rod-shaped or tubular tissue include nerves, tendons, ligaments, blood vessels, bile ducts, and pancreatic ducts. In some preferred embodiments, the rod-shaped or tubular tissue is a nerve. In other preferred embodiments, the rod-shaped or tubular tissue is a tendon.

[0090] Here, "applying" refers to placing the tissue protection material on tissue requiring protection. Preferably, the tissue protection material is placed so that it comes into contact with the tissue requiring protection. More preferably, the tissue protection material is used by being wrapped around a rod-shaped or tubular tissue requiring tissue protection. Particularly preferably, the tissue protection material is used by being wrapped around a rod-shaped or tubular tissue requiring tissue protection, and then fixed with a fixing material. Note that fixing materials referred to here include, but are not limited to, medical sutures, medical clips, medical stapler needles, medical adhesives, etc.

[0091] The tissue protection material is used by exposing the tissue area to be protected on a subject, forming a tissue protection material of an appropriate size according to the length and width of the tissue to be protected, and applying it to the damaged area of ​​the tissue to be protected. 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, and horse).

[0092] When the porous material that can swell by absorbing water is in a xerogel state, it may be applied as is in a dry state, or may be applied in a gel state after being soaked in physiological saline, purified water, or the like. That is, the tissue protection material may be in a gel form. Preferably, the tissue protection material is applied as is in a dry state.

[0093] After applying the tissue protection material to the damaged area of ​​the tissue to be protected, it is not necessary to suture the tissue protection material to the damaged area of ​​the tissue, but if necessary, the tissue protection material may be sutured to the damaged area of ​​the tissue (e.g., the stump of a rod-shaped or tubular tissue).

[0094] In some embodiments, the tissue protective material may be used in combination with humoral factors such as factors useful for tissue regeneration or growth, physiologically active substances, or cells. The method of combination use is not particularly limited, and for example, these factors or cells may be incorporated into the tissue protective material. The humoral factors are not particularly limited as long as they can be used as supplementary factors for regenerating tissue, and examples include bFGF, NGF, hepatocyte growth factor, immunosuppressants, and anti-inflammatory agents. Examples of cells include, but are not limited to, 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, and CD133+ cells.

[0095] Further provided herein is a use of a porous body that can swell by absorbing water and a support comprising a biocompatible polymer for producing the aforementioned tissue protection material, wherein the tissue protection material is applied to tissue requiring tissue protection, preferably rod-shaped or tubular tissue. Specific uses are as described above.

[0096] Further provided herein is a support comprising a porous body that can swell by absorbing water and a biocompatible polymer, for use in protecting tissue in need of protection, preferably rod-shaped or tubular tissue. Also provided herein is a combination of a porous body that can swell by absorbing water and a support comprising a biocompatible polymer, for use in treatment including tissue protection. Specific uses are as described above.

[0097] Next, the present invention will be explained in more detail with reference to examples, but the present invention is not limited to these examples.

[0098] Example 1: Preparation of a 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, and the SUS rod and PTFE tube were fixed together. Markings were made with an oil-based pen 10 mm from both ends of the PTFE tube. (See also the evaluation system for the grip test in Figure 1.)

[0099] Example 2 Preparation of tissue protection material The following tissue protection material was prepared.

[0100]

[0101] A commercially available collagen sheet (product name: Skin Collage Sheet, freeze-dried collagen, manufactured by Ishii Clinic, Lot No. 210740, 81500) was pressed using a precision processing device (CYPM-20, manufactured by Shinto Kogyo Co., Ltd.) and used as a porous sheet material of the present invention (Figure 2(A)). The collagen sheet had a thickness of approximately 1 mm before pressing and approximately 0.2 mm after pressing. The CLG (collagen) + PLA (polylactic acid) sheet material was prepared by stacking the pressed CLG on PLA (Figure 2(B)). Furthermore, a commercially available polylactic acid nonwoven fabric (manufactured by Tokano Co., Ltd.) was used without pressing. The thickness of the CLG + PLA sheet material prepared in this manner was approximately 0.5 mm.

[0102] The CLG+PGA (polyglycolic acid) sheet material was prepared by stacking a commercially available collagen sheet (same as above) and a PGA sheet (M type, manufactured by Nikke Medical Co., Ltd., Lot No. 220322) and then pressing them using the precision processing device (FIG. 2(C)). The thickness of the CLG+PGA sheet material prepared in this manner was approximately 0.4 mm.

[0103] Example 3: Observation of swollen state The CLG+PLA sheet material prepared in Example 2 was cut to 35 mm x 20 mm, and the long sides were bent and wrapped around a SUS round pipe (manufactured by Hikari Mall Co., Ltd., outer diameter 4.1 mm). At this time, the CLG+PLA sheet material was wrapped so that the CLG was on the inside. A push-in clip (PC-8S, manufactured by Tokin Corporation) was inserted from the side to clamp and secure the sheet material (Figs. 3(A) and (B)). The SUS round pipe was removed, taking care not to displace the clip. The tubular tissue model prepared in Example 1 was then inserted (Fig. 3(C)).

[0104] Next, the sheet material and the tubular tissue model were fixed using clips in a mini-vice (ST-80, manufactured by Taiyo Electric Industrial Co., Ltd.) and placed perpendicular to the camera of a digital microscope (VHX-7000, manufactured by Keyence Corporation). The position of the tubular tissue model was adjusted so that the sheet material and the tubular tissue model did not come into contact in a dry state, and a photograph was taken. The entire sheet material was soaked in 1000 μL of water and allowed to stand for 20 minutes. A photograph was taken of the sheet material after it had swelled. The thickness and cross-sectional area were measured using the software installed in the digital microscope. The results are shown in Figures 4, 5, and Table 2.

[0105] Figure 4 shows an image of a cross section of the sheet material CLG+PLA before swelling. Figure 5 shows an image of a cross section of the sheet material CLG+PLA after swelling. Table 2 shows the values ​​of the sheet material before and after swelling, as well as the swelling ratio.

[0106]

[0107] The swelling degree was calculated from the thickness of the sheet material CLG + PLA as follows: That is, the sheet thickness was measured at multiple arbitrary points on the cross section of the sheet material before and after swelling using a microscope, and the swelling ratio was calculated by averaging the ratios before and after swelling. Also, the swelling degree was calculated from the cross-sectional area as follows: That is, the cross-sectional area of ​​the sheet material before and after swelling was measured using a digital microscope, and the swelling ratio was calculated from the ratio before and after swelling.

[0108] Observation of the swelling state confirmed that the sheet material swelled with water and fitted to the tissue (swelling ratio in cross-sectional thickness, i.e., the ratio of the thickness after swelling to the thickness before swelling (thickness after swelling / thickness before swelling) was 2.0 times, and swelling ratio in cross-sectional area, i.e., 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) was 2.2 times).

[0109] The same test was also performed on the sheet material CLG+PGA prepared in Example 2. Observation of the swelling state confirmed that the sheet material swelled with water and fitted to the tissue. The thickness of the sheet material before and after swelling, as well as the swelling ratio, are shown in Table 3 below.

[0110]

[0111] Example 4: Grip Test A grip test was performed using the CLG+PLA sheet material prepared in Example 2. The evaluation system for the grip test is shown in Figure 1. Each sheet material was cut to 20 mm x 35 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). At this time, the CLG+PLA sheet material was wrapped with the CLG facing inward. A push-in 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. Then, the rod-shaped or tubular tissue model prepared as described above was inserted. At this time, a considerable clearance (≧1 mm) was left between the sheet material and the rod-shaped or tubular tissue model.

[0112] A balance dish was tied to the ends of two pieces of kite thread (1 mm diameter) of the same length in a balance-like manner, and the opposite ends were fixed to both ends of an SUS round pipe into which a rod-shaped or tubular tissue model had been inserted. Pulleys with clamps were attached to both sides of the workbench, and a vice was placed at the center of the pulley to fix it so that it would not move. Two pieces of kite thread were passed through each pulley, and the balance dish was hung on both ends of the workbench. A clip was clamped in the vice to fix the sheet material so that it would not move. The position of the pulley was adjusted so that the kite thread would not bend.

[0113] The position of the model was adjusted left and right so that the marking positions on the model and both ends of the fixed sheet material were aligned. For "Dry (before swelling)," the sheet material was used as is. For "Wet (after swelling)," 1000 μL of water was added to the sheet material, which was then left to soak for 20 minutes. Then, a fixed amount of water (100-1000 μL) was dropped into one of the balance dishes of the test system using a micropipette. The amount of water dropped (ml) when the model was completely removed was recorded, and the results are shown in Table 4 below.

[0114]

[0115] In the wet state, the amount of dripping when the model was completely removed was 10.7 mL, which is an increase compared to 3.6 mL in the dry state. In other words, it can be seen that the gripping force of the sheet material increases in the swollen state.

[0116] Example 5: Winding Test: A cylindrical metal rod 10 cm long and 1 mm, 5 mm, or 10 mm in diameter was prepared and used as a rod-shaped or tubular tissue model. The CLG+PLA and CLG+PGA sheets prepared in Example 2 were each cut to 27.5 mm x 10 mm, and the dry or swollen sheet was wrapped around the rod-shaped or tubular tissue model and secured with clips or sutured. The preferred sheet material, both dry and swollen, can be wrapped around the rod-shaped or tubular tissue model without cracking or breaking.

Claims

1. A flexible sheet-shaped tissue protection material comprising a porous body that can swell when it absorbs water, and a support containing a biocompatible polymer.

2. The tissue protection material according to claim 1, which is used by being wrapped around a rod-shaped or tubular tissue requiring tissue protection.

3. The tissue protection material according to claim 2, which is used by wrapping the tissue protection material around a rod-shaped or tubular tissue that requires tissue protection, and then fixing the tissue protection material with a fixing material.

4. The tissue protection material according to any one of claims 1 to 3, wherein the tissue protection material comprises a pressed porous body as a porous body that can swell by absorbing water.

5. The tissue protection material according to any one of claims 1 to 4, wherein the tissue protection material has a thickness in a dry state of 0.1 mm to 5 mm.

6. The tissue protection material according to claim 5, wherein the thickness of the tissue protection material after swelling of the porous body that can swell by absorbing water is 1.1 to 30 times the thickness of the tissue protection material before swelling.

7. The tissue protection material according to claim 5, wherein the cross-sectional area of ​​the tissue protection material after swelling of the porous body that can swell by absorbing water is 1.2 to 35 times the cross-sectional area of ​​the tissue protection material before swelling.

8. The tissue protection material according to claim 6 or 7, wherein the gripping force of the tissue protection material after swelling of the porous body that can swell by absorbing water is greater than the gripping force of the tissue protection material before swelling.

9. The tissue protection material of any one of claims 1 to 8, wherein the biocompatible polymer is selected from the group consisting of polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone and copolymers thereof, poly(amino acids), polydioxanone, polygluconates, polylactic acid-polyethylene oxide copolymers, oxidized cellulose, poly(hydroxybutyric acid), polyanhydrides, polyphosphate esters, poly(alphahydroxy acids), related copolymer materials, and mixtures thereof.

10. The tissue protection material according to any one of claims 1 to 9, wherein the tissue protection material is for protecting the rod-shaped or tubular tissue, and the rod-shaped or tubular tissue is selected from the group consisting of nerves, tendons, ligaments, blood vessels, bile ducts, and pancreatic ducts.

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