Adhesion preventive material

Abstract

To provide an antiadhesive material having good handleability and improved long-term antiadhesive properties.SOLUTION: The present invention relates to an adhesion-preventing material comprising a fiber sheet and an oil agent attached to the fiber sheet, wherein the oil agent comprises liquid paraffin and a surfactant. In the present invention, the adhesion-preventing material preferably has a peak derived from an oil agent in the vicinity of a wave number of 2860cm-1 in analysis by Fourier-transform ultraviolet spectroscopy-total reflection measurement method. In the present invention, the surfactant preferably has intermediate water in which an exothermic peak based on low-temperature crystallization of water is observed at 0 °C or lower in a temperature rising process in differential scanning calorimetry (DSC) in a wet state.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an anti-adhesion material that can be suitably used to prevent adhesion of tissues where adhesions may occur. [Background technology]

[0002] Adhesion formation is a condition in which tissues that should be separate become connected, and it is said that adhesions occur in approximately 90% of patients who undergo surgery. Specifically, when an organ surface is damaged during surgery, an inflammatory reaction is triggered, resulting in the deposition of fibrin. The inflammatory reaction triggered by the absorption of fibrin leads to the formation of fibrous adhesions, which then promote angiogenesis and fibroblast proliferation, further organizing the adhesions and leading to the formation of strong adhesions. Adhesion formation can lead to complications such as organ dysfunction, and adhesion removal procedures during reoperations can increase the risk of bleeding and organ damage. Therefore, various adhesion barriers have been proposed to prevent adhesion formation. For example, Patent Document 1 proposes an adhesion barrier comprising a sponge-like laminate applicable to living organisms, which comprises first and second sponge-like layers of a low-endotoxin monovalent metal salt of alginic acid, at least a portion of which is crosslinked with a curing agent, wherein the weight-average molecular weight of the monovalent metal salt of alginic acid in the first layer is higher than that of the monovalent metal salt of alginic acid in the second layer.Patent Document 2 proposes an adhesion barrier comprising decellularized tissue and a biocompatible polymer. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] International Publication No. 2019 / 138583 [Patent Document 2] International Publication No. 2016 / 143746 Summary of the Invention [Problem to be solved by the invention]

[0004] In Patent Document 1, the adhesion prevention effect of an anti-adhesion material is evaluated one week after organ damage, and in Patent Document 2, the adhesion prevention effect of an anti-adhesion material is evaluated one week, four weeks, and one month after organ damage. However, for example, in cases such as pediatric heart disease, surgery may be required every 3 to 12 months, and there is a need for anti-adhesion materials to reduce adhesions 3 to 12 months after cardiac surgery, improve surgical procedures such as adhesion removal, prevent organ damage, shorten the time required for reoperation, and reduce the burden on patients. Therefore, there is a need for further improvements in the handleability and long-term adhesion prevention properties of adhesion anti-adhesion materials.

[0005] In order to solve the above-mentioned problems of the conventional art, the present invention provides an anti-adhesion material that is easy to handle and has improved long-term adhesion prevention properties. [Means for solving the problem]

[0006] The present invention relates to an anti-adhesion material comprising a fiber sheet and an oily agent adhered to the fiber sheet, the oily agent comprising liquid paraffin and a surfactant. [Effects of the Invention]

[0007] The present invention can provide an adhesion barrier that is easy to handle and has improved long-term adhesion prevention properties. Particularly preferably, by applying the adhesion barrier of the present invention to the surface of cardiovascular tissue before each surgery, severe adhesion between the pericardium and the heart or myocardium can be effectively prevented. [Brief explanation of the drawings]

[0008] [Figure 1] 1 is an IR spectrum showing the analysis results of the nonwoven fabric (anti-adhesion material) of Example 1 by the FTIR-ATR method. [Figure 2] 1 is an IR spectrum showing the analysis results of the nonwoven fabric of Comparative Example 1 by the FTIR-ATR method. [Figure 3] 1 is an IR spectrum showing the analysis results of the oil solution used in Example 1 by the FTIR-ATR method. [Figure 4] 1 is a differential scanning calorimetry (DSC) curve showing the results of DSC measurement of the nonwoven fabric of Comparative Example 1 and the surfactant used in Example 1. DETAILED DESCRIPTION OF THE INVENTION

[0009] The inventors of the present invention conducted extensive research to solve the above-mentioned problems. As a result, they found that using an adhesion barrier in which an oil agent containing liquid paraffin and a surfactant is attached to a fiber sheet improves the handleability of the adhesion barrier and improves long-term adhesion prevention. Specifically, it is believed that the use of a fiber sheet as the substrate improves the handleability of the adhesion barrier, and the combined use of liquid paraffin and a surfactant as the oil agent improves the long-term adhesion prevention. In particular, it has been confirmed that the adhesion barrier effectively inhibits severe adhesions over a long period of time (e.g., after 3 months) after application to the surface of a cardiac wound and enables the pericardium to be separated from the heart or myocardium without bleeding, making it suitable for use in cases requiring surgery every 3 months, such as pediatric heart disease.

[0010] In this specification, when a numerical range is indicated with "to", the numerical range includes both end values ​​(upper and lower limits). For example, a numerical range of "A to B" includes both end values ​​A and B, and is the same range as "A or more and B or less". Any number within that range and any range included within that range are specifically disclosed. In addition, when multiple numerical ranges are described in this specification, they are intended to include numerical ranges that combine the upper and lower limits of different numerical ranges as appropriate.

[0011] The adhesion barrier includes a fiber sheet. The fibers constituting the fiber sheet preferably contain a biocompatible polymer as a main component. In one or more embodiments of the present invention, the term "main component" refers to a component that accounts for 80% by mass or more of the total. In one or more embodiments of the present invention, the term "biocompatible" refers to biodegradability, meaning that the material is broken down, metabolized, and eliminated in the body, or remaining in the body without decomposing and having no adverse effects on biological functions. Examples of biodegradable polymers include, but are not limited to, polylactic acid (PLA), polyglycolic acid (PGA), ε-polycaprolactone (PCL), alginate, collagen, and gelatin. Examples of biocompatible polymers that can be placed in the body include, but are not limited to, PGA, alginate, collagen, cellulose, carboxymethylcellulose, and gelatin.

[0012] The fibers constituting the fiber sheet preferably contain 85% by mass or more of the biocompatible polymer, more preferably 90% by mass or more, and even more preferably 95% by mass or more, and may be substantially 100% by mass. In addition to the biocompatible polymer, the fibers constituting the fiber sheet may optionally contain 20% by mass or less, 15% by mass or less, 10% by mass or less, or 5% by mass or less of other components. The other components may be crosslinkers, plasticizers, other additives, etc.

[0013] From the viewpoints of strength and biocompatibility, the fibers constituting the fiber sheet preferably contain polyglycolic acid as a primary component, preferably containing 80% by mass or more of polyglycolic acid, more preferably 85% by mass or more, even more preferably 90% by mass or more, and even more preferably 95% by mass or more, and may even consist essentially of 100% by mass. Fibers containing polyglycolic acid as a primary component may optionally contain, in addition to polyglycolic acid, 20% by mass or less, 15% by mass or less, 10% by mass or less, or 5% by mass or less of other components. The other components may be the biocompatible polymers described above other than polyglycolic acid, or may be crosslinkers, plasticizers, other additives, and the like.

[0014] The fibers constituting the fiber sheet may be either long fibers or short fibers. Long fibers can be obtained by spinning the biocompatible polymer described above into fibers by any appropriate spinning method such as melt spinning, dry spinning, or wet spinning. Short fibers can be obtained by cutting long fibers to a predetermined length, for example, 100 mm or less, or 25 to 78 mm.

[0015] The single fiber fineness of the fibers constituting the fiber sheet is not particularly limited, but from the viewpoint of biodegradability and fiber strength, it is preferably 1 to 50 dtex, more preferably 2 to 10 dtex, and even more preferably 3 to 7 dtex.

[0016] The shape of the fiber sheet is not particularly limited, and examples include woven fabrics, knitted fabrics, nonwoven fabrics, and composites thereof. The woven fabric may be a staple fiber woven fabric obtained by spinning staple fibers containing the biocompatible polymer as a main component into yarns using a conventional method and then weaving them using a conventional method, or a filament woven fabric obtained by weaving filaments containing the biocompatible polymer as a main component into yarns using a conventional method. The knitted fabric may be a staple fiber knitted fabric obtained by spinning staple fibers containing the biocompatible polymer as a main component into yarns using a conventional method and then knitting them using a conventional method, or a filament knitted fabric obtained by knitting filaments containing the biocompatible polymer as a main component into yarns using a conventional method.

[0017] The nonwoven fabric may be obtained by forming short fibers containing the biocompatible polymer as a main component into a sheet-like web using a carding machine or the like, and then entangling or bonding (adhering) the fibers in the resulting web by needle punching or heat molding to fix the shape.

[0018] The nonwoven fabric may also be a spunbond nonwoven fabric obtained by collecting fibers primarily composed of the biocompatible polymer directly on the surface of a net or roller without winding immediately after spinning. The nonwoven fabric may also be a meltblown nonwoven fabric obtained by melting the biocompatible polymer, then discharging the resulting molten or solution of the biocompatible polymer from a nozzle while blowing it with compressed air or the like and collecting it on the surface of a net or roller. Alternatively, the nonwoven fabric may be a flash-spun nonwoven fabric obtained by dissolving the biocompatible polymer in a solvent, then discharging the resulting solution of the biocompatible polymer from a nozzle while blowing it with compressed air or the like and collecting it on the surface of a net or roller. In particular, a nonwoven fabric obtained by knitting long fibers (filaments) on a knitting machine and then needle-punching the fibers to entangle them is preferred, as it has a shape that is less likely to shed fiber fragments inside the body during and after surgery.

[0019] The adhesion preventing material contains an oil agent attached to the fiber sheet. In the adhesion preventing material, the oil agent composed of liquid paraffin and a surfactant is attached in an amount of preferably 0.1 to 20% by mass, more preferably 0.2 to 15% by mass, and even more preferably 0.3 to 10% by mass, relative to the mass of the fiber sheet. When the amount of oil agent attached is 0.1% by mass or more, the occurrence of severe adhesions can be effectively prevented over a long period of time (e.g., 3 months after application) after application of the adhesion preventing material to the surface of tissue where adhesions may occur, such as a wound. When the amount of oil agent attached is 20% by mass or less, the sheet is prevented from slipping off when grasped with tweezers or from slipping off the application site during surgery, ensuring good handleability.

[0020] The blending amounts of liquid paraffin and surfactant in the oil agent are not particularly limited. For example, from the viewpoint of easily exerting a synergistic effect of the liquid paraffin and surfactant, when the total of the liquid paraffin and surfactant is taken as 100% by mass, the oil agent preferably contains 30 to 90% by mass of liquid paraffin and 10 to 70% by mass of surfactant, and more preferably contains 50 to 70% by mass of liquid paraffin and 30 to 50% by mass of surfactant.

[0021] The liquid paraffin is a mixture of hydrocarbons obtained from crude petroleum through processes such as distillation and refining, and is not particularly limited as long as it is liquid at room temperature (5 to 40°C) and atmospheric pressure (101,325 Pa). The number of carbon atoms in the hydrocarbon is not particularly limited, and may be, for example, 15 or more, 20 or more, or 20 to 45. There is no particular limitation on the presence or absence of double bonds in the hydrocarbon, but those containing a large amount of saturated hydrocarbons are preferably used. Furthermore, the hydrocarbon structure may include any of linear, branched, and cyclic structures, and liquid paraffins of any specific gravity can be used. In particular, liquid paraffins and light liquid paraffins listed in the Japanese Pharmacopoeia are preferred, with light liquid paraffins being more preferred. It may also contain an appropriate type of tocopherol as a stabilizer. The liquid paraffins may be used alone or in combination of two or more types.

[0022] From the viewpoint of improving the dispersibility of liquid paraffin, the surfactant is preferably a nonionic surfactant, and more preferably a polyoxyethylene alkyl ether. The average degree of polymerization of the ethylene oxide group in the polyoxyethylene alkyl ether may be 5 to 50. Specific examples of polyoxyethylene alkyl ethers include polyoxyethylene lauryl ether, polyoxyethylene myristyl ether, polyoxyethylene octyldodecyl ether, polyoxyethylene cetyl ether, polyoxyethylene oleyl ether, and polyoxyethylene stearyl ether. One type of surfactant may be used alone, or two or more types may be used in combination.

[0023] From the viewpoint of enhancing the synergistic effect with liquid paraffin and further improving adhesion prevention properties over a long period of time (e.g., after 3 months) after application of the adhesion barrier to the surface of tissues, such as wounds, where adhesions may occur, the surfactant preferably contains intermediate water (hereinafter also referred to simply as intermediate water) in which an exothermic peak due to low-temperature crystallization of water is observed at 0°C or below during the temperature rise process in differential scanning calorimetry (DSC) when wetted. A nonionic surfactant that contains intermediate water when wetted is more preferred, and a polyoxyethylene alkyl ether that contains intermediate water when wetted is even more preferred. As used herein, "when wetted" refers to a state in which moisture is present on the surface of an organ in a living body; for example, the surfactant can be wetted as described in the Examples. The polyoxyethylene alkyl ether preferably contains polyoxyethylene oleyl ether, as it is more likely to contain intermediate water when wetted.

[0024] In this specification, the amount of oil applied to a fiber sheet can be measured by the method described in 8.27 Solvent Extraction in JIS L 1013 Chemical Fiber Filament Yarn Testing Methods (2018). If the amount of oil applied to a fiber sheet during the manufacturing process can be confirmed, this may be used as the amount of oil applied to the fiber sheet of the resulting product.

[0025] The method for applying the oil (liquid paraffin and surfactant) to the fiber sheet is not particularly limited as long as it can adhere the oil to the fiber sheet. For example, when applying the oil to the fiber sheet, an oil composition containing an oil and water can be used. Specifically, for example, an oil composition containing an oil and water can be applied to fibers as a spinning oil in the spinning process, and then dried to produce a fiber sheet using the fibers to which the oil has been applied. Alternatively, in the weaving or knitting process, an oil composition containing an oil and water can be applied to spun yarn before or after the yarn path, and then dried to adhere the oil to the fiber sheet. Alternatively, an oil composition containing an oil and water can be applied to woven fabrics, knitted fabrics, and nonwoven fabrics as a post-treatment, and then dried to adhere the oil to the fiber sheet. The method for applying the oil composition containing an oil and water to fibers, spun yarns, woven fabrics, knitted fabrics, and nonwoven fabrics is not particularly limited, and may be any of dipping, coating, spraying, etc. The drying method after application of the oil agent composition is not particularly limited, and can be, for example, air drying or drying in a dryer. In the oil agent composition, liquid paraffin is emulsified and dispersed in water by a surfactant. This allows the liquid paraffin and surfactant to be uniformly applied to the fiber sheet. From the viewpoint of uniformly applying the liquid paraffin and surfactant to the fiber sheet and easily exerting the synergistic effect of the liquid paraffin and the surfactant, the oil agent composition preferably contains 5 to 10 mass% liquid paraffin, 2 to 10 mass% surfactant, and 80 to 93 mass% water, and more preferably contains 6 to 9 mass% liquid paraffin, 3 to 8 mass% surfactant, and 83 to 91 mass% water.

[0026] A method for applying an oil to a polyglycolic acid long fiber nonwoven fabric, which is a preferred example of a fiber sheet, will be described below.

[0027] The polyglycolic acid long fiber nonwoven fabric preferably contains 90% by mass or more, more preferably 95% by mass or more, of polyglycolic acid. The polyglycolic acid long fiber nonwoven fabric may consist essentially of 100% by mass of polyglycolic acid. The polyglycolic acid long fiber nonwoven fabric may contain, in addition to polyglycolic acid, 10% by mass or less, or 5% by mass or less of other components as needed. The other components may be the above-mentioned biocompatible polymers other than polyglycolic acid, or may be crosslinkers, plasticizers, other additives, etc.

[0028] The polyglycolic acid long fiber nonwoven fabric is not particularly limited, but from the viewpoint of increasing tensile strength, it is preferably a long fiber needle-punched nonwoven fabric obtained by needle-punching a knitted or woven fabric made of polyglycolic acid long fibers, and more preferably a long fiber needle-punched nonwoven fabric obtained by needle-punching a knitted fabric (also called a knitted fabric) made of polyglycolic acid long fibers. The knitted fabric may be flat knitted or circular knitted.

[0029] Specifically, the oil can be applied to the polyglycolic acid long fiber nonwoven fabric as follows. (1) An oil composition, specifically an oil composition containing 5 to 10% by mass of liquid paraffin, 2 to 10% by mass of a surfactant, and 80 to 97% by mass of water, is sprayed onto the polyglycolic acid long fibers using a sprayer, and then air-dried to adhere the oil to the polyglycolic acid long fibers. (2) The polyglycolic acid filaments to which the oil agent has been applied are woven and knitted to produce a knitted fabric. (3) A polyglycolic acid long fiber needle-punched nonwoven fabric is produced by needle-punching a knitted or woven fabric. If necessary, multiple knitted or woven fabrics may be stacked together to obtain a predetermined thickness, and then needle-punched.

[0030] The anti-adhesion material has excellent long-term adhesion prevention properties (for example, adhesion prevention properties after 3 months) when applied to tissues where adhesions may occur, such as wounds, and is therefore required to have a wavelength of 2860 cm in an analysis by FTIR (Fourier transform ultraviolet spectroscopy)-ATR (attenuated total reflectance) method.-1 It is preferable that the peak derived from the oil agent is present in the vicinity of the peak.

[0031] The bending resistance of the adhesion barrier is not particularly limited, but from the viewpoint of improving handleability when applied to tissues where adhesions may occur, such as wounds, the bending resistance measured by the 41.5° cantilever method is preferably 20 to 80 mm, and more preferably 25 to 70 mm.

[0032] The basis weight of the adhesion preventing material is not particularly limited, but from the viewpoint of improving the handling property and adhesion prevention property when applied to tissues where adhesion may occur, such as wounds, it is preferred to use a weight of 10 to 200 g / m 2 It is preferable that the density is 20 to 180 g / m 2 More preferably, it is 30 to 160 g / m 2 More preferably, it is 40 to 140 g / m 2 It is particularly preferred that:

[0033] The thickness of the anti-adhesion material is not particularly limited, but from the viewpoint of improving handling properties and anti-adhesion properties when applied to tissues where adhesions may occur, such as wounds, the thickness is preferably 0.1 to 2.0 mm, more preferably 0.2 to 1.8 mm, even more preferably 0.3 to 1.6 mm, and particularly preferably 0.4 to 1.4 mm.

[0034] The tensile strength of the adhesion barrier is not particularly limited, but from the viewpoint of improving handleability and adhesion prevention when applied to tissue where adhesions may occur, such as wounds, it is preferably 2 to 50 N, more preferably 5 to 40 N, and even more preferably 10 to 20 N. Furthermore, when the adhesion barrier has a tensile strength of 10 N or more, it also provides good suturing properties after application to the surface of tissue where adhesions may occur, such as wounds.

[0035] The breaking elongation of the adhesion barrier is not particularly limited, but from the viewpoint of improving handling properties and adhesion prevention when applied to tissues where adhesions may occur, such as wounds, it is preferably 100 to 1000%, more preferably 200 to 700%, and even more preferably 300 to 500%.

[0036] The adhesion barrier has high long-term adhesion prevention properties when applied to tissues where adhesions may occur, and preferably has an adhesion score of 2 or less both 3 months and 6 months after application to a cardiac wound. In this specification, the adhesion score is determined based on the degree of necessary pericardium removal and the degree of crushing and bleeding of the cardiac surface and / or myocardium, and an adhesion score of 2 or less indicates no bleeding upon removal. The adhesion score can be specifically evaluated and determined as described in the Examples.

[0037] The adhesion barrier can inhibit adhesions and prevent severe adhesions by applying it to targets requiring adhesion prevention, such as tissues where adhesions may occur. Because the fibers constituting the fiber sheet are primarily composed of biocompatible polymers, the adhesion barrier is highly safe. The adhesion barrier inhibits severe adhesions both 3 and 6 months after application to tissues where adhesions may occur, such as wounds, demonstrating excellent long-term adhesion prevention properties.

[0038] Examples of tissues in which adhesions may occur include tissues that have sustained damage to the surface of an organ during surgery, tissues that have become inflamed or are at risk of becoming inflamed due to the surface drying during surgery, etc. Specific examples of tissues in which adhesions may occur include the pericardium, heart, epicardium, pleura, abdominal wall, peritoneum, bladder, amniotic membrane, uterus, dura mater, diaphragm, small intestine, large intestine, stomach, anus, pancreas, spleen, liver, kidney, lung, skin, esophagus, ligaments, and tendons, with preferred examples being the pericardium and abdominal wall.

[0039] The anti-adhesion material is preferably prepared in an appropriate size depending on the area, shape, irregularities, etc. of the surface of the tissue where adhesions may occur, and is applied to the surface of the tissue where adhesions may occur. After applying the anti-adhesion material to the surface of the tissue where adhesions may occur, the anti-adhesion material and the surface of the tissue where adhesions may occur may be sutured together, if necessary. Since the anti-adhesion material contains a fiber sheet, the suture strength is high.

[0040] The anti-adhesion material may be used in humans or in organisms other than humans. The organisms other than humans may be, for example, birds or non-human mammals. Examples of non-human mammals include cows, monkeys, cats, mice, rats, guinea pigs, hamsters, ferrets, pigs, dogs, rabbits, sheep, goats, and horses.

[0041] Before, simultaneously with, or after applying the adhesion barrier to tissues where adhesions may occur, concomitant medications such as antibiotics such as streptomycin, penicillin, tobramycin, amikacin, gentamicin, neomycin, and amphotericin B, aspirin, nonsteroidal antipyretic analgesics (NSAIDs), and anti-inflammatory drugs such as acetaminophen may be administered. These medications may be mixed into the adhesion barrier. Because the adhesion barrier contains a fiber sheet, it is easy for the medication to be impregnated into the adhesion barrier.

[0042] By impregnating the adhesion barrier with a drug solution and administering it, it is possible to simultaneously prevent adhesion and achieve local sustained release of the drug in the abdominal cavity, thoracic cavity, cardiac cavity, subarachnoid cavity, serous cavity (peritoneal cavity, pleural cavity, pericardial cavity), joint cavity, etc. Furthermore, by carrying the drug in layers with different dissolution rates, it is possible to release the drug at both a fast and a slow sustained release rate. [Example]

[0043] The present invention will be described in more detail below using examples, but the present invention is not limited to the following examples.

[0044] The measurement and evaluation methods used in the examples and comparative examples will be explained below.

[0045] (Metsuke) Measured according to JIS L 1913:2018 6.2 Weight per unit area (ISO method).

[0046] (Thickness) Measured using JIS L 1913:2018 6.1 Thickness (ISO method) Method B.

[0047] (bending resistance) The bending resistance of the nonwoven fabric was measured by the 41.5° cantilever method (ISO method) of JIS L 1913:2010 6.7.

[0048] (tensile strength) Measured according to JIS L 1913:2018 6.3 Tensile strength and elongation (ISO method).

[0049] (breaking elongation) Measured according to JIS L 1913:2018 6.3 Tensile strength and elongation (ISO method).

[0050] (Differential scanning calorimetry) Using a DSC7000X differential scanning calorimeter (Hitachi High-Tech Science Corporation), the temperature was lowered from 30°C to -100°C at a rate of 5°C per minute, held for 5 minutes, and then increased from -100°C to 50°C at a rate of 5°C per minute, held for 1 minute. For surfactants, the target surfactant was added with twice the amount of pure water and allowed to soak for one week. The sample was then placed in a 45°C thermostatic chamber for 12 hours to moisten the sample. After this, 3-5 mg of the moist surfactant was placed in an aluminum pan and sealed with an autosealer. For fiber sheets, the sheet was cut with scissors to a length (approximately 3 mm) long enough to fit in the pan. 3-5 mg of the cut fibers were placed in the pan, covered with a breathable nonwoven fabric, and air-dried for 12 hours at room temperature (25°C). After drying, the aluminum pan was sealed with an autosealer and used for measurement.

[0051] (Fourier transform ultraviolet spectroscopy - total reflectance measurement method) Using a Fourier transform ultraviolet spectrophotometer FT / IR-4200 (manufactured by JASCO Corporation), the ATR method was used at a wave number of 4000 cm -1 From 500cm -1 The infrared transmittance was measured in the range of .

[0052] Example 1 An oil agent composition consisting of 8% by mass of liquid paraffin, 2% by mass of polyoxyethylene oleyl ether 1 (average degree of polymerization of ethylene oxide groups: 16), 2% by mass of polyoxyethylene oleyl ether 2 (average degree of polymerization of ethylene oxide groups: 20), and 88% by mass of water was sprayed onto polyglycolic acid long fibers (multifilament yarn, filament count: 10, single fiber fineness: 5.5 dtex, total fineness: 55 dtex), and then air-dried in a room at room temperature of 25°C, to adhere 0.5% by mass of an oil agent consisting of liquid paraffin, polyoxyethylene oleyl ether 1, and polyoxyethylene oleyl ether 2 (mass ratio: liquid paraffin: polyoxyethylene oleyl ether 1: polyoxyethylene oleyl ether 2 = 8:2:2) to the polyglycolic acid long fibers. Thereafter, a fabric (basis weight: 20 g / m) was knitted using a circular knitting machine using the polyglycolic acid long fibers to which the oil agent had been applied. 2 The resulting knitted fabric was laid flat, and four pieces were stacked on top of each other to avoid wrinkles, and then needle punched to a thickness of 0.61 mm and a basis weight of 81 g / m. 2 A needle-punched nonwoven fabric of this size was obtained.

[0053] (Comparative Example 1) A needle-punched nonwoven fabric obtained in the same manner as in Example 1 was subjected to ultrasonic cleaning in ethanol to remove the oils (liquid paraffin and polyoxyethylene oleyl ether), and then dried to obtain a nonwoven fabric.

[0054] (Comparative Example 2) A tissue substitute artificial fiber fabric (weight 32 g / m) made from commercially available PGA was used. 2 A sheet with a thickness of 0.15 mm, manufactured by Gunze Medical Japan Ltd., product name "Neoveil (registered trademark)" sheet, 015 type) was used.

[0055] (Comparative Example 3) Seprafilm (Kaken Pharmaceutical Co., Ltd., a biodegradable film consisting of sodium hyaluronate:carboxymethylcellulose = 2:1 (mass ratio)), a commercially available absorbable adhesion barrier, was used.

[0056] The bending resistance, tensile strength, and breaking elongation of the nonwoven fabrics of Example 1 and Comparative Example 1, the tissue substitute artificial fiber fabric of Comparative Example 2, and the Seprafilm of Comparative Example 3 were measured as described above, and the results are shown in Table 1 below.

[0057] [Table 1]

[0058] The nonwoven fabric (adhesion prevention material) of Example 1 is easier to apply to the surface of tissue where adhesions may occur, such as wounds, and has good handleability, compared to Seprafilm of Comparative Example 3. Furthermore, the nonwoven fabric (adhesion prevention material) of Example 1 has a bending resistance within the range of 20 to 80 mm, making it more excellent in handleability. The nonwoven fabric (adhesion prevention material) of Example 1 has a tensile strength of 10 N or more, and also has good suturing properties after application to the surface of tissue where adhesions may occur, such as wounds.

[0059] The nonwoven fabrics of Example 1 and Comparative Example 1, and the oil used in Example 1 were subjected to FTIR analysis as described above, and the results are shown in FIGS. As can be seen from FIGS. 1 to 3, the nonwoven fabric of Example 1 has a wave number of 2860 cm -1 The nonwoven fabric of Comparative Example 1 has a peak at a wavenumber of 2860 cm (surrounded by a dashed line) derived from the oil agent. -1 There is no peak in the vicinity.

[0060] The nonwoven fabrics of Example 1 and Comparative Example 1, the tissue substitute artificial fiber fabric of Comparative Example 2, and Seprafilm of Comparative Example 3 were used as samples to evaluate the adhesion prevention properties of these samples in an in vivo test. The results are shown in Table 3 below.

[0061] (In vivo test) After anesthetizing a dog (beagle), the pericardium surrounding the heart was incised, the surface of the heart was scraped with a file-like sponge, a sample was placed on the wounded surface of the heart, and blood was applied to the sample. The pericardium was then sutured, and the sample was fixed with sutures in several places to prevent movement. In Reference Example 1, the incision in the pericardium was sutured without placing a sample. After a 3-month or 6-month implantation period, the degree of adhesion between the pericardium and the scraped area on the heart surface was evaluated using an adhesion score to confirm adhesion prevention. For both the 3-month and 6-month implantation periods, the nonwoven fabrics of Example 1 and Comparative Example 1 were used in two dogs, the tissue substitute artificial fiber fabric of Comparative Example 2 and Seprafilm of Comparative Example 3 were used in one dog, and Reference Example 1 was used in two dogs. The criteria for adhesion scores are shown in Table 2 below.

[0062] [Table 2]

[0063] [Table 3]

[0064] The adhesion score after 3 months of implantation when the nonwoven fabric of Example 1 to which an oil solution composed of liquid paraffin and polyoxyethylene oleyl ether was applied was 2, while the adhesion score after 3 months of implantation when the nonwoven fabric of Comparative Example 1 from which liquid paraffin and polyoxyethylene oleyl ether had been removed and the artificial tissue substitute fabric of Comparative Example 2 were used was 3. This indicates that the nonwoven fabric of Example 1 had high adhesion prevention properties and had adhesion prevention properties equivalent to those of Seprafilm of Comparative Example 3. There is a significant difference between adhesion scores of 2 and 3 in terms of the presence or absence of bleeding. If bleeding occurs during removal, as in adhesion score 3, hemostasis or a blood transfusion is required, lengthening the surgery. Furthermore, while Seprafilm of Comparative Example 3 had good adhesion prevention properties, it took time to place it on the injured cardiac surface during the implantation procedure and had poor handleability. In contrast, the nonwoven fabric of Example 1 was easy to place on the injured cardiac surface during the implantation procedure and had good handleability. The nonwoven fabric coated with the oil agent consisting of liquid paraffin and polyoxyethylene oleyl ether of the present invention can be suitably used as an adhesion barrier in surgery for cardiac diseases that require reoperation, such as pediatric cardiac diseases that require surgery every three months.

[0065] The nonwoven fabrics of Example 1 and Comparative Example 1 were used to carry out the in vitro test described below to confirm their effect on the proliferation of human skin fibroblasts. The results are shown in Table 4 below.

[0066] (In vitro test) (Test Example 1) A polystyrene tissue culture plate (TCPS, 24 wells, Corning) was coated with 0.5% PMPC (2-methacryloyloxyethyl phosphorylcholine polymer) and left to dry overnight at room temperature. The nonwoven fabric of Example 1 was placed on the bottom of the PMPC-coated TCPS and used as a culture vessel. DMEM (Dulbecco's Modified Eagle Medium) / F12 containing 10% FBS (fetal bovine serum) was used as the culture medium. Normal human dermal fibroblast (NHDF) cells (passage number: 5) were seeded at a density of 1.0 × 10 cells per area of ​​the bottom of the culture vessel. 4 cell / cm 2After culturing for 1 hour, 24 hours, 3 days, or 7 days, the number of cells was measured using Cell Counting Kit-8.

[0067] (Test Example 2) The number of NHDF cells was measured after culturing for 1 hour, 24 hours, 3 days, or 7 days in the same manner as in Test Example 1, except that the nonwoven fabric of Comparative Example 1 was placed on the bottom surface of the PMPC-coated TCPS and used as the culture vessel.

[0068] (Control Test Example 1) The number of NHDF cells was measured after culturing for 1 hour, 24 hours, 3 days, or 7 days in the same manner as in Test Example 1, except that TCPS was used as the culture vessel.

[0069] [Table 4]

[0070] In Test Example 1, which used the nonwoven fabric of Example 1 to which the oil solution composed of liquid paraffin and polyoxyethylene oleyl ether was applied, the number of attached cells was reduced in cultures of 24 hours or more, particularly for 7 days, compared to Test Example 1, which used the nonwoven fabric of Comparative Example 1 from which the liquid paraffin and polyoxyethylene oleyl ether had been removed, confirming that the nonwoven fabric to which the oil solution composed of liquid paraffin and polyoxyethylene oleyl ether was applied inhibits the proliferation of NHDF cells.It is presumed that in tissues where adhesions may occur, such as wounds after cardiac surgery, the nonwoven fabric to which the oil solution composed of liquid paraffin and polyoxyethylene oleyl ether is applied inhibits the proliferation of fibroblasts, thereby exerting an adhesion prevention effect and providing excellent adhesion prevention properties over the long term (for example, after 3 months).

[0071] The nonwoven fabric of Comparative Example 1 and the polyoxyethylene oleyl ether used in Example 1 were analyzed by differential scanning calorimetry as described above, and the results are shown in Figure 4. In Figure 4, a is the DSC curve of the nonwoven fabric of Comparative Example 1, b is the DSC curve of polyoxyethylene oleyl ether 1 used in Example 1, and c is the DSC curve of polyoxyethylene oleyl ether 2 used in Example 1. As can be seen from Figure 4, polyoxyethylene oleyl ether 1 and polyoxyethylene oleyl ether 2 used in Example 1 contain intermediate water in a wet state, which exhibits an exothermic peak due to low-temperature crystallization of water at 0°C or below during the temperature rise process in differential scanning calorimetry (DSC). The nonwoven fabric of Comparative Example 1 exhibits only an endothermic peak of water (contained in the nonwoven fabric) at 0°C. While this is speculation, it is speculated that in tissues where adhesions may occur, such as wounds, the hydrophobic liquid paraffin attached to the nonwoven fabric of this Example prevents fibroblast adhesion, and the polyoxyethylene oleyl ether, which contains intermediate water when wet, inhibits fibrin deposition (antithrombotic effect) through a synergistic effect, thereby inhibiting severe adhesions and improving adhesion prevention over long periods, for example, after 3 months and / or 6 months.

[0072] The present invention is not particularly limited, but it is desirable to include, for example, the following embodiments. [1] A fiber sheet and an oil agent attached to the fiber sheet, The oil agent is an adhesion preventing material containing liquid paraffin and a surfactant. [2] The anti-adhesion material according to [1], wherein the oil is attached in an amount of 0.1 to 20% by mass relative to the mass of the fiber sheet. [3] The adhesion preventing material according to [1] or [2], wherein the surfactant is a polyoxyethylene alkyl ether. [4] The adhesion preventing material according to [3], wherein the polyoxyethylene alkyl ether includes polyoxyethylene oleyl ether. [5] The adhesion preventing material according to any one of [1] to [4], wherein the surfactant has intermediate water in which, when wetted, an exothermic peak due to low-temperature crystallization of water is observed at 0°C or below during the temperature rise process in differential scanning calorimetry (DSC). [6] The adhesion barrier according to any one of [1] to [5], wherein the fiber sheet is a nonwoven fabric. [7] An anti-adhesion material according to any one of [1] to [6], wherein the fibers constituting the fiber sheet are primarily composed of one or more biocompatible polymers selected from the group consisting of polyglycolic acid, polylactic acid, alginate, cellulose, and carboxymethylcellulose. [8] The anti-adhesion material according to any one of [1] to [7], which has a bending resistance of 20 to 80 mm as measured by the 41.5° cantilever method. [9] Basis weight: 10 to 200 g / m 2 The anti-adhesion material according to any one of [1] to [8], wherein

[10] The anti-adhesion material according to any one of [1] to [9], which has a thickness of 0.1 to 2.0 mm.

[11] Fourier transform ultraviolet spectroscopy-attenuated total reflection analysis showed a wave number of 2860 cm -1 The anti-adhesion material according to any one of [1] to

[10] , which has a peak derived from an oil agent in the vicinity of

Claims

1. A fiber sheet and an oil agent attached to the fiber sheet, The oil agent is an adhesion preventing material containing liquid paraffin and a surfactant.

2. The adhesion preventing material according to claim 1, wherein the oil is attached in an amount of 0.1 to 20% by mass relative to the mass of the fiber sheet.

3. The adhesion preventing material according to claim 1 , wherein the surfactant is a polyoxyethylene alkyl ether.

4. The adhesion preventing material according to claim 3 , wherein the polyoxyethylene alkyl ether comprises polyoxyethylene oleyl ether.

5. The adhesion preventing material according to claim 1, wherein the surfactant has intermediate water in which, when wetted, an exothermic peak due to low-temperature crystallization of water is observed at 0°C or below during the temperature rise process in differential scanning calorimetry (DSC).

6. The adhesion preventing material according to claim 1 , wherein the fiber sheet is a nonwoven fabric.

7. The adhesion preventing material according to claim 1, wherein the fibers constituting the fiber sheet are primarily composed of one or more biocompatible polymers selected from the group consisting of polyglycolic acid, polylactic acid, alginate, cellulose, and carboxymethylcellulose.

8. The adhesion preventing material according to claim 1, which has a bending resistance of 20 to 80 mm as measured by the 41.5° cantilever method.

9. Weight per unit area: 10 to 200 g / m 2 The anti-adhesion material according to claim 1,

10. The adhesion preventing material according to claim 1, which has a thickness of 0.1 to 2.0 mm.

11. In the analysis by Fourier transform ultraviolet spectroscopy-attenuated total reflection measurement method, the wave number was 2860 cm -1 The adhesion preventing material according to any one of claims 1 to 10, which has a peak derived from an oil agent in the vicinity of

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