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WO2019071587A1 - Kit de matériau de renforcement de tissu biologique et matériau de renforcement de tissu biologique - Google Patents

Kit de matériau de renforcement de tissu biologique et matériau de renforcement de tissu biologique Download PDF

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Publication number
WO2019071587A1
WO2019071587A1 PCT/CN2017/106126 CN2017106126W WO2019071587A1 WO 2019071587 A1 WO2019071587 A1 WO 2019071587A1 CN 2017106126 W CN2017106126 W CN 2017106126W WO 2019071587 A1 WO2019071587 A1 WO 2019071587A1
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Prior art keywords
cellulose
biological tissue
reinforcing material
hydroxy groups
produced
Prior art date
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Ceased
Application number
PCT/CN2017/106126
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English (en)
Inventor
Chiaki Tanaka
Yoshinari Yui
Shojiro Matsuda
Hideki TAKAMORI
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Gunze Medical Devices (shenzhen) Ltd
Gunze Ltd
Original Assignee
Gunze Medical Devices (shenzhen) Ltd
Gunze Ltd
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Application filed by Gunze Medical Devices (shenzhen) Ltd, Gunze Ltd filed Critical Gunze Medical Devices (shenzhen) Ltd
Priority to PCT/CN2017/106126 priority Critical patent/WO2019071587A1/fr
Priority to JP2019571585A priority patent/JP6868129B2/ja
Priority to CN201780094073.3A priority patent/CN111050812B/zh
Publication of WO2019071587A1 publication Critical patent/WO2019071587A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/28—Polysaccharides or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/425—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • A61L31/10—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/146—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/04—Materials for stopping bleeding
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2420/00—Materials or methods for coatings medical devices
    • A61L2420/02—Methods for coating medical devices

Definitions

  • the present invention relates to a biological tissue-reinforcing material kit and a biological tissue-reinforcing material which are capable of more reliably reinforcing weakened tissues while preventing air leakage or fluid leakage without using fibrin glue, which is a blood product.
  • Pneumothorax occurs mainly due to air leakage into a thoracic cavity from a stump or suture site of the lung after resection, a site of the lung after partial resection to remove lung cancer, or a damaged area of lung tissue due to injury; or air leakage into a thoracic cavity from a tear of cysts (called bullae) which are transformed from some alveoli.
  • Such leakage has been treated by pleurodesis in which lung tissue is allowed to adhere to pleura using drugs or through artificial chemical burns.
  • Pleurodesis can prevent recurrence of pneumothorax to some extent.
  • lung tissue does not tightly adhere to pleura, the recurrence rate increases. If further surgery is necessary, the adhesion between lung tissue and parietal pleura needs to be removed, which unfortunately prolongs a surgical time or causes bleeding during removal of the adhesion. Therefore, new treatment alternative to pleurodesis has been sought.
  • pancreatic juice dissolves granulation tissue that is responsible for wound healing, and prevents the growth of granulation tissue, leading to difficulty in regeneration of pancreatic tissue.
  • leaked pancreatic juice may digest blood vessels to cause postoperative hemorrhage, a life-threatening complication.
  • Non-Patent Literatures 1 to 4 suggest that this method reduces the recurrence rate of pneumothorax more than usual pleurodesis.
  • Non-Patent Literature 5 suggests that such a method is also used to prevent bleeding after liver resection in the field of digestive surgery.
  • Non-Patent Literature 1 J. Pediatric Surg, 42, 1225-1230 (2007)
  • Non-Patent Literature 2 Interact. Cardiovasc. Thorac. Surg, 6, 12-15 (2007)
  • Non-Patent Literature 3 The Journal of the Japanese Association for Chest Surgery, 19 (4) , 628-630 (2005)
  • Non-Patent Literature 4 The Journal of the Japanese Association for Chest Surgery, 22 (2) , 142-145 (2008)
  • Non-Patent Literature 5 The Japanese Journal of Clinical and Experimental Medicine, 84, 148 (2007)
  • the present invention is a biological tissue-reinforcing material kit including: a fiber structure, sponge body, or film made of a bioabsorbable polymer; and a powder made of etherified cellulose that is produced through etherification of hydroxy groups of cellulose or made of esterified cellulose that is produced through esterification of hydroxy groups of cellulose.
  • the present inventors have investigated the cause of air leakage or fluid leakage from a reinforced area of biological tissue having been reinforced using fibrin glue and a fiber structure or the like made of a bioabsorbable polymer in combination, and found that the problem occurs at an adhesion area attached with fibrin glue.
  • Fibrin glue which gels in a short time, is very useful as biological glue.
  • fibrin glue in the form of a gel is relatively hard, cohesive failure or interfacial peeling is likely to occur due to impact.
  • cohesive failure or interfacial peeling may be caused by a very high pressure applied to lung tissue when the patient coughs or sneezes. Since gelled fibrin glue has almost no adhesion, once separated, it cannot adhere again. Air leakage or fluid leakage is considered to occur at such a separation area.
  • weakened tissues can be more reliably reinforced by using a powder made of etherified cellulose that is produced through etherification of hydroxy groups of cellulose (hereinafter, also referred to simply as ′′etherified cellulose′′ ) or made of esterified cellulose that is produced through esterification of hydroxy groups of cellulose (hereinafter, also referred to simply as ′′esterified cellulose′′ ) instead of fibrin glue, and the use of such a powder enables production of a biological tissue-reinforcing material causing no air leakage or fluid leakage. Accordingly, the inventors completed the present invention.
  • Etherified cellulose or esterified cellulose is a compound proven to be very safe, and gels in a short time like fibrin glue to act as glue to attach a fiber structure made of a bioabsorbable polymer to biological tissues. Furthermore, since such a powder has a certain level of adhesion even after it gels, if cohesive failure or interfacial peeling occurs due to high pressure, it can adhere again to prevent air leakage or fluid leakage. In addition, in the application to damaged areas with large surface irregularities, the etherified cellulose or esterified cellulose in the form of powder can enter between the irregularities and gels to be closely attached to the surfaces. Thus, air leakage or fluid leakage can be prevented.
  • the biological tissue-reinforcing material kit of the present invention includes: a fiber structure, sponge body, or film made of a bioabsorbable polymer; and a powder made of etherified cellulose.
  • the fiber structure, sponge body, or film made of a bioabsorbable polymer is designed to exhibit a tissue-reinforcing effect, an air leakage prevention effect, and a fluid leakage prevention effect when it is attached to a damaged or weakened organ.
  • the powder made of etherified cellulose absorbs moisture to become a gel, and acts as glue to attach the film, fiber structure, or sponge body made of a bioabsorbable polymer to biological tissues.
  • the fiber structure, sponge body, or film made of a bioabsorbable polymer and the powder made of etherified cellulose may be combined at the time of use or may be combined in advance as a composite.
  • Non-limiting examples of the bioabsorbable polymer include synthetic absorbable polymers such as ⁇ -hydroxy acid polymers, for example, polyglycolide, polylactide (D, L, DL isomer) , glycolide-lactide (D, L, DL isomer) copolymers, glycolide- ⁇ -caprolactone copolymers, lactide (D, L, DL isomer) - ⁇ -caprolactone copolymers, poly (p-dioxanone) , or glycolide-lactide (D, L, DL isomer) - ⁇ -caprolactone copolymers; and natural absorbable polymers such as collagen, gelatin, chitosan, or chitin.
  • synthetic absorbable polymers such as ⁇ -hydroxy acid polymers, for example, polyglycolide, polylactide (D, L, DL isomer) , glycolide-lactide (D, L, DL isomer) copoly
  • a natural absorbable polymer may be used together therewith.
  • an ⁇ -hydroxy acid polymer which is a homopolymer or copolymer of at least one monomer selected from the group consisting of glycolide, lactide, ⁇ -caprolactone, dioxanone, and trimethylene carbonate is preferably used because of its high strength.
  • An ⁇ -hydroxy acid polymer which is a homopolymer or copolymer of a monomer containing glycolide is more preferably used because the polymer shows appropriate decomposition behavior.
  • the preferable lower limit of the weight average molecular weight of the polyglycolide is 30,000, and the preferable upper limit is 1,000,000.
  • Polyglycolide having a weight average molecular weight of less than 30,000 has insufficient strength and may not impart a sufficient tissue-reinforcing effect.
  • Polyglycolide having a weight average molecular weight of more than 1,000,000 slowly decomposes in the body and therefore may cause a foreign-body reaction.
  • the more preferable lower limit of the weight average molecular weight of the polyglycolide is 50,000, and the more preferable upper limit is 300,000.
  • the fiber structure made of a bioabsorbable polymer may be in any form, including the form of a non-woven fabric, a knitted fabric, a woven fabric, gauze, or yarn, or a combination of these forms.
  • the form of a non-woven fabric is preferred.
  • the weight per unit area of the non-woven fabric is not particularly limited, and the preferable lower limit is 5 g/m 2 , and the preferable upper limit is 300 g/m 2 .
  • a non-woven fabric having a weight per unit area of less than 5 g/m 2 has insufficient strength for a biological tissue-reinforcing material, and may not reinforce weakened tissues.
  • a non-woven fabric having a weight per unit area of more than 300 g/m 2 may be poor in adhesion to tissues.
  • the more preferable lower limit of the weight per unit area of the non-woven fabric is 10 g/m 2 , and the more preferable upper limit is 100 g/m 2 .
  • the non-woven fabric may be produced by any method, and examples of the method include conventionally known methods such as electrospinning deposition, melt blowing, needle punching, spun bonding, flash spinning, hydroentanglement, air laying, thermal bonding, resin bonding, or wet processing.
  • the weight per unit area of the sponge body made of a bioabsorbable polymer is not particularly limited, and the preferable lower limit is 5 g/m 2 , and the preferable upper limit is 1,000 g/m 2 .
  • a sponge body made of a bioabsorbable polymer having a weight per unit area of less than 5 g/m 2 has insufficient strength for a biological tissue-reinforcing material, and may not reinforce weakened tissues.
  • a sponge body made of a bioabsorbable polymer having a weight per unit area of more than 1,000 g/m 2 may be poor in adhesion to tissues.
  • the more preferable lower limit of the weight per unit area of the sponge body made of a bioabsorbable polymer is 30 g/m 2 , and the more preferable upper limit is 500 g/m 2 .
  • the thickness of the fiber structure or sponge body made of a bioabsorbable polymer is not particularly limited, and the preferable lower limit is 5 ⁇ m, and the preferable upper limit is 1 mm.
  • a fiber structure or sponge body made of a bioabsorbable polymer having a thickness of less than 5 ⁇ m has insufficient strength and may not impart a sufficient tissue-reinforcing effect.
  • a fiber structure or sponge body made of a bioabsorbable polymer having a thickness of more than lmm may not closely adhere to tissues to be insufficiently fixed.
  • the more preferable lower limit of the thickness of the fiber structure or sponge body made of a bioabsorbable polymer is 10 ⁇ m, and the more preferable upper limit is 0.5 mm.
  • the thickness of the film made of a bioabsorbable polymer is not particularly limited, and the preferable lower limit is 10 ⁇ m, and the preferable upper limit is 800 ⁇ m.
  • a film made of a bioabsorbable polymer having a thickness of less than 10 ⁇ m has insufficient strength and may not impart a sufficient tissue-reinforcing effect.
  • a film made of a bioabsorbable polymer having a thickness of more than 800 ⁇ m may not closely adhere to tissues to be insufficiently fixed.
  • the more preferable lower limit of the thickness of the film made of a bioabsorbable polymer is 20 ⁇ m, and the more preferable upper limit is 300 ⁇ m.
  • the fiber structure, sponge body, or film made of a bioabsorbable polymer may be subjected to hydrophilization.
  • the fiber structure subjected to hydrophilization rapidly absorbs moisture such as physiological saline upon contact, and is therefore readily handled.
  • Non-limiting examples of the hydrophilization include plasma treatment, glow discharge treatment, corona discharge treatment, ozone treatment, surface graft treatment, and ultraviolet irradiation treatment.
  • plasma treatment is preferred because this treatment markedly increases the water absorption rate without changing the outward appearance of the non-woven fabric.
  • the etherified cellulose is produced through etherification of hydroxy groups of cellulose.
  • hydroxyalkylated cellulose represented by the formula (1) below such as hydroxyethylated cellulose in which hydroxy groups of the cellulose have been replaced with hydroxyethyl groups or hydroxypropylated cellulose in which hydroxy groups of the cellulose have been replaced with hydroxypropyl groups.
  • hydroxyethylated cellulose is preferred because it is proven to be very safe.
  • n represents an integer
  • R represents hydrogen or-R′OH in which R′represents an alkylene group.
  • the molar ratio of a diethylene glycol group to an ethylene glycol group is preferably 0.1 to 1.0, and the molar ratio of a triethylene glycol group to an ethylene glycol group (triethylene glycol group/ethylene glycol group) is preferably 0.1 to 0.5 in the hydroxyethylated cellulose.
  • the etherified cellulose having molar ratios within such ranges imparts excellent initial adhesion when the fiber structure, sponge body, or film made of a bioabsorbable polymer adheres to biological tissue through the powder made of the etherified cellulose, and the high adhesion is maintained after adhesion. Even if cohesive failure or interfacial peeling occurs due to high pressure, the fiber structure, sponge body, or film can adhere again to prevent air leakage or fluid leakage.
  • the numbers of moles of ethylene glycol groups, diethylene glycol groups, and triethylene glycol groups in the hydroxyethylated cellulose can be measured, for example, by NMR or thermal decomposition GC-MS.
  • the preferable lower limit of the average number of molecules (MS) of alkylene oxides bonded to an anhydroglucose unit is 1.0, and the preferable upper limit is 4.0.
  • the etherified cellulose having a MS within such a range can gel in a short time with high gel strength, enabling closer adhesion and fixation to tissues.
  • MS is less than 1.0, gelled hydroxyethylated cellulose tends to be less viscous.
  • the MS is more than 4.0, gelationtends to take a long time.
  • the more preferable lower limit of the MS is 1.3, and the more preferable upper limit is 3.0.
  • the preferable lower limit of the average degree of substitution (DS) of alkylene oxides to hydroxy groups at positions 2, 3, and 6 of an anhydroglucose unit is 0.2, and the preferable upper limit is 2.5.
  • the etherified cellulose having a DS within such a range can gel in a short time with high gel strength, enabling closer adhesion and fixation to tissues.
  • the DS is less than 0.2, gelation may take a long time.
  • the DS is more than 2.5, the strength may decrease.
  • the more preferable lower limit of the DS is 0.3, and the more preferable upper limit is 1.5.
  • the MS and DS can be calculated by determining the NMR spectrum of an aqueous solution of the hydroxyethylated cellulose, and measuring the intensities of signals belonging to carbon atoms of an anhydroglucose ring and carbon atoms of a substituent group in the spectrum (see, for example, JP H6-41926 B) .
  • 0.2 g of a sample, 30 mg of an enzyme (cellulase) , and an internal standard material are dissolved in 3 mL of heavy water.
  • the resulting solution is subjected to ultrasonication for 4 hours, and its NMR spectrum is determined using an NMR measuring device (e.g. JNM-ECX400P available from JEOL) under the conditions of the number of scanning of 700, pulse width of 45°, and observed frequency of 31,500 Hz.
  • an NMR measuring device e.g. JNM-ECX400P available from JEOL
  • the etherified cellulose may be cellulose that is produced through etherification and carboxylation of hydroxy groups of cellulose so that part of unetherified hydroxy groups are carboxylated (hereinafter, also referred to as ′′etherified and carboxylated cellulose′′ ) .
  • ′′etherified and carboxylated cellulose′′ carboxylated
  • the etherified and carboxylated cellulose is produced through etherification and carboxylation of hydroxy groups of cellulose.
  • hydroxyalkylated and carboxylated cellulose such as hydroxyethylated and carboxylated cellulose in which hydroxy groups of the cellulose have been replaced with hydroxyethyl groups and carboxyl groups, or hydroxypropylated and carboxylated cellulose in which hydroxy groups of the cellulose have been replaced with hydroxypropyl groups and carboxyl groups.
  • Particularly preferred is hydroxyethylated and carboxylated cellulose because it is proven to be very safe.
  • hydroxyalkylated and carboxylated cellulose represented by the following formula (2) :
  • n represents an integer
  • R represents hydrogen or -R′OH in which R′represents an alkylene group.
  • the molar ratio of a diethylene glycol group to an ethylene glycol group is preferably 0.1 to 1.5, and the molar ratio of a triethylene glycol group to an ethylene glycol group (triethylene glycol group/ethylene glycol group) is preferably 0.1 to 1.0 in the hydroxyethylated and carboxylated cellulose.
  • the lower limit of the average number of molecules (MS) of alkylene oxide bonded to an anhydroglucose unit is preferably 1.0, and the upper limit is preferably 4.0.
  • the lower limit of the average degree of substitution (DS) of alkylene oxides to hydroxy groups at positions 2, 3, and 6 of an anhydroglucose unit is preferably 0.2, and the upper limit is preferably 2.5.
  • the average number of molecules (MS) , the average degree of substitution (DS) , and the numbers of moles of ethylene glycol groups, diethylene glycol groups, and triethylene glycol groups in the hydroxyethylated and carboxylated cellulose can be measured, for example, by NMR or thermal decomposition GC-MS.
  • the hydroxyethylated cellulose can be produced, for example, by reacting an ethylene oxide with alkali cellulose which is produced by treating cellulose with an aqueous solution of an alkali.
  • alkali cellulose is produced from a fiber structure made of cellulose as a raw material by treating the fiber structure with an aqueous solution of an alkali such as sodium hydroxide. To the resulting alkali cellulose are added a certain amount of an ethylene oxide and a reaction solvent to carry out a reaction.
  • an alkali such as sodium hydroxide.
  • the etherified and carboxylated cellulose can be produced by, for example, carboxylating and then etherifying cellulose.
  • the cellulose may be carboxylated as follows, for example. Through a reaction with 2, 2, 6, 6-tetramethylpiperidine-l-oxyl (TEMPO) as an oxidant and sodium hypochlorite, hydroxy groups of the cellulose are oxidized to aldehyde (TEMPO oxidation step) . Subsequently, the cellulose is reacted with sodium chlorite so that the aldehyde is carboxylated (carboxylation step) .
  • TEMPO 2, 2, 6, 6-tetramethylpiperidine-l-oxyl
  • the resulting carboxylated cellulose is treated with an aqueous solution of an alkali such as sodium hydroxide (alkali treatment step) and is then reacted with an ethylene oxide to be etherified (hydroxyethylated) (hydroxyethylation step) .
  • alkali treatment step an alkali such as sodium hydroxide
  • ethylene oxide an ethylene oxide
  • etherified and carboxylated cellulose can be prepared.
  • carboxyl groups are mainly introduced to position 6 of cellulose, and hydroxyethyl groups are mainly introduced to position 2 or 6.
  • the esterified cellulose is produced through esterification of hydroxy groups of cellulose.
  • phosphorylated cellulose produced through phosphorylation of hydroxy groups of cellulose, nitrocellulose produced through nitration of hydroxy groups of cellulose, cellulose sulfate produced through sulfation of hydroxy groups of cellulose, and cellulose acetate produced through acetylation of hydroxy groups of cellulose.
  • Preferred of these is phosphorylated cellulose because it is proven to be very safe.
  • the shape of the powder made of etherified cellulose or esterified cellulose is not particularly limited.
  • the average particle size of the powder made of etherified cellulose or esterified cellulose is not particularly limited, and the preferable lower limit is 1 ⁇ m, and the preferable upper limit is 100 ⁇ m.
  • a powder made of etherified cellulose or esterified cellulose having an average particle size of less than 1 ⁇ m may be difficult to treat.
  • a powder made of etherified cellulose or esterified cellulose having an average particle size of more than 100 ⁇ m is less likely to absorb water, takes a long time to gel, and may not be readily handled.
  • the more preferable lower limit of the average particle size of the powder made of etherified cellulose or esterified cellulose is 5 ⁇ m, and the more preferable upper limit is 50 ⁇ m.
  • the powder made of etherified cellulose or esterified cellulose having an average particle size within the more preferable range can readily enter between the irregularities, thereby better preventing air leakage or fluid leakage.
  • the powder made of etherified cellulose or esterified cellulose may be used as it is in the form of powder but may be used as a dispersion (or paste) in an amphiphilic medium.
  • the powder in the form of a dispersion can be more readily treated and also can better enter between the irregularities upon application to damaged areas with large surface irregularities. Damaged areas may repel a hydrophilic medium.
  • an amphiphilic medium is used to allow the powder to enter between the irregularities.
  • amphiphilic medium may be used as long as it allows the powder made of etherified cellulose or esterified cellulose to be uniformly dispersed therein without causing gel formation.
  • amphiphilic medium examples include polyethylene glycol, methanol, ethanol, 2-propanol, polypropylene glycol, and glycerol. Preferred of these is polyethylene glycol because of its ability to excellently disperse the powder made of etherified cellulose or esterified cellulose, easy control of the viscosity, and high safety.
  • the biological tissue-reinforcing material of the present invention is used to stop bleeding from a damaged or weakened organ or tissue, or to prevent air leakage or fluid leakage in the field of surgery.
  • the biological tissue-reinforcing material is favorably used to prevent air leakage due to pneumothorax or after resection of lung cancer in the field of chest surgery.
  • the film, fiber structure, or sponge body made of a bioabsorbable polymer and the powder made of etherified cellulose or esterified cellulose may be combined at the time of use.
  • the powder made of etherified cellulose or esterified cellulose is sprinkled thereon so that the powder absorbs moisture to become a gel.
  • the resulting composite can be readily attached to an affected area.
  • a dispersion prepared by dispersing the powder made of etherified cellulose or esterified cellulose in an amphiphilic medium is applied to an affected area, a phosphate buffer or physiological saline is dropped to cause gel formation, and the film, fiber structure, or sponge body made of a bioabsorbable polymer is attached to the gel.
  • the film, fiber structure, or sponge body made of a bioabsorbable polymer may be combined with the powder made of etherified cellulose or esterified cellulose in advance.
  • a phosphate buffer or physiological saline is dropped onto the film, fiber structure, or sponge body made of a bioabsorbable polymer, and the powder made of etherified cellulose or esterified cellulose is sprinkled thereon so that the powder absorbs moisture to become a gel, followed by drying.
  • a biological tissue-reinforcing material in which the film, fiber structure, or sponge body made of a bioabsorbable polymer is partly or entirely coated with the powder made of etherified cellulose that is produced through etherification of hydroxy groups of cellulose or made of esterified cellulose that is produced through esterification of hydroxy groups of cellulose can be produced.
  • a biological tissue-reinforcing material can be readily attached to an affected area, for example, just by applying the material preliminary immersed into a phosphate buffer or physiological saline to the affected area.
  • the biological tissue-reinforcing material absorbs blood or fluid to thereby exhibit adhesion.
  • Fig. 1 is a view schematically illustrating a pressure tester used in the pressure test performed in examples.
  • Fig. 2 is a cross-sectional view of a filter holder 2 on which an urethane sponge 7 and a collagen film 8 are mounted.
  • the present invention can provide a biological tissue-reinforcing material kit and a biological tissue-reinforcing material which are capable of more reliably reinforcing weakened tissues while preventing air leakage or fluid leakage without using fibrin glue, which is a blood product.
  • a powder made of a commercial hydroxyethylated cellulose (available from Wako Pure Chemical Industries, Ltd., average particle size: 20 ⁇ m, molar ratio of a diethylene glycol group to an ethylene glycol group (diethylene glycol group/ethylene glycol group) : 1.06, molar ratio of a triethylene glycol group to an ethylene glycol group (triethylene glycol group/ethylene glycol group) : 4.01) was prepared.
  • a 150- ⁇ m-thick non-woven fabric made of polyglycolide (NEOVEIL Type NV-M015G available from Gunze Limited) was cut to have a length of 5.0 cm and a width of 5.0 cm to prepare a fiber structure made of a bioabsorbable polymer.
  • a pressure test was performed using a pressure tester 1 illustrated in Fig. 1.
  • An about 130- ⁇ m-thick collagen film (available from Nippi. Inc. ) was punched out into a rectangular shape with a length of 5.5 cm and a width of 5.0 cm, and the film was washed with 70%ethanol, and liquid was wiped off (collagen film 8) .
  • An about 2-mm-thick urethane sponge 7 (available from Inoac Corporation, ST15, cell diameter: 50 ⁇ m, porosity: 85%) was punched out to have a diameter of 20 mm using a puncher.
  • the collagen film 8 was placed on the urethane sponge.
  • the urethane sponge 7 represents a damaged area with large surface irregularities.
  • a 3-mm-diameter hole 6 was formed in the center of the collagen film 8 using a puncher.
  • Fig. 2 shows a cross-sectional view of the filter holder 2 on which the urethane sponge 7 and the collagen film 8 were mounted.
  • a 20-mL syringe 3 (Terumo Syringe SS-20ESZ available from Terumo Corporation) and a pressure gauge 5 (digital manometer FUSO-8230 available from Fusorika Co., Ltd. ) were placed at the downstream of the filter holder 2 via a three way cock 4, thereby preparing a pressure tester.
  • the pressure tester 1 illustrated in Fig. 1 can measure pressures up to 200 mmHg.
  • a small amount of a 70%ethanol solution was sprayed to one surface of the non-woven fabric made of polyglycolide using a spray to wet the surface of the non-woven fabric.
  • 0.2 g of the powder made of hydroxyethylated cellulose was uniformly sprayed over the surface of the non-woven fabric made of polyglycolide.
  • the resulting non-woven fabric was dried at 60°C for two hours, thereby providing a biological tissue-reinforcing material in which one surface of the non-woven fabric made of polyglycolide was coated with the powder made of hydroxyethylated cellulose.
  • the biological tissue-reinforcing material was punched into a 11-mm-diameter circular shape to give a test sample for measurement.
  • a 100 ⁇ m-thick film made of polyglycolide was prepared by a heat press molding method. The film was cut to have a length of 5.0 cm and a width of 5.0 cm to prepare a film made of a bioabsorbable polymer.
  • a biological tissue-reinforcing material kit prepared using the film made of a bioabsorbable polymer instead of the fiber structure made of a bioabsorbable polymer was subject to the pressure tests as in Example 1.
  • a biological tissue-reinforcing material kit prepared using the powder or the dispersion was subject to the pressure tests as in Example 1.
  • a powder made of phosphorylated cellulose was prepared as in Example 3.
  • a biological tissue-reinforcing material kit prepared using the powder or the dispersion was subject to the pressure tests as in Example 2.
  • a 11-mm-diameter circular piece was punched out from a 150- ⁇ m-thick non-woven fabric made of polyglycolide (NEOVEIL Type NV-M015G, available from Gunze Limited) .
  • a collagen film prepared as in Example 1 was set on the filter holder of the pressure tester used in Example 1. Then, 20 ⁇ L of a solutionA of fibrin glue (available fromCSL Behring K.K., Beriplast P) was dropped onto the center of the collagen film in such a manner as to avoid the hole in the collagen film, and was spread into a shape with a diameter of approximately ll mm. Next, the non-woven fabric punched into a 11-mm-diameter circle was placed on the spread solution A and impregnated with the solution A. Subsequently, 20 ⁇ L of the solution A was dropped onto the non-woven fabric, and the non-woven fabric was sufficiently impregnated with the solution A. Thereafter, 20 ⁇ L of a solution B was dropped onto the non-woven fabric.
  • a solutionA of fibrin glue available fromCSL Behring K.K., Beriplast P
  • a 150- ⁇ m-thick non-woven fabric made of polyglycolide (NEOVEIL Type NV-M015G available from Gunze Limited) was cut to have a length of 5.0 cm and a width of 5.0 cm to prepare a fiber structure made of a bioabsorbable polymer.
  • a 320- ⁇ m-thick fiber structure made of oxidized cellulose (available from Johnson & Johnson K.K., Surgicel) was cut to have a length of 5.0 cm and a width of 5.0 cm.
  • the fiber structure made of oxidized cellulose, the non-woven fabric made of polyglycolide, and the fiber structure made of oxidized cellulose were stacked in the stated order, and they were integrated by needle punching, thereby providing a biological tissue-reinforcing material.
  • the biological tissue-reinforcing material was subjected to the pressure tests as in Example 1.
  • the present invention can provide a biological tissue-reinforcing material kit and a biological tissue-reinforcing material which are capable of more reliably reinforcing weakened tissues while preventing air leakage or fluid leakage without using fibrin glue, which is a blood product.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Surgery (AREA)
  • Vascular Medicine (AREA)
  • Dispersion Chemistry (AREA)
  • Hematology (AREA)
  • Materials Engineering (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Materials For Medical Uses (AREA)

Abstract

La présente invention concerne un kit de matériau de renforcement de tissu biologique et un matériau de renforcement de tissu biologique qui sont capables de renforcer de manière plus fiable des tissus affaiblis tout en empêchant une fuite d'air ou une fuite de fluide sans utiliser de colle à la fibrine, qui est un produit sanguin. L'invention concerne également un kit de matériau de renforcement de tissu biologique comprenant : une structure fibreuse, un corps d'éponge, ou un film fait d'un polymère bioabsorbable ; et une poudre faite de cellulose éthérifiée qui est produite par éthérification de groupes hydroxy de cellulose ou faite de cellulose estérifiée qui est produite par estérification de groupes hydroxy de cellulose.
PCT/CN2017/106126 2017-10-13 2017-10-13 Kit de matériau de renforcement de tissu biologique et matériau de renforcement de tissu biologique Ceased WO2019071587A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
PCT/CN2017/106126 WO2019071587A1 (fr) 2017-10-13 2017-10-13 Kit de matériau de renforcement de tissu biologique et matériau de renforcement de tissu biologique
JP2019571585A JP6868129B2 (ja) 2017-10-13 2017-10-13 生体組織補強材料キット及び生体組織補強材料
CN201780094073.3A CN111050812B (zh) 2017-10-13 2017-10-13 生物组织增强材料套件和生物组织增强材料

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PCT/CN2017/106126 WO2019071587A1 (fr) 2017-10-13 2017-10-13 Kit de matériau de renforcement de tissu biologique et matériau de renforcement de tissu biologique

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101332309A (zh) * 2006-01-12 2008-12-31 张镁 水溶性多糖类复合医用敷料及制备方法
WO2013082073A1 (fr) * 2011-12-02 2013-06-06 Ethicon, Inc. Dispositif hémostatique biorésorbable comprenant un liant en polyéthylèneglycol
WO2016089201A1 (fr) * 2014-12-04 2016-06-09 Universiti Putra Malaysia Composition de film et procédé associé
WO2016169041A1 (fr) * 2015-04-24 2016-10-27 Gunze Limited Substance de renforcement de tissus biologiques
US20170165394A1 (en) * 2014-02-12 2017-06-15 Aesculap Ag Medical device and method for the production thereof

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19505709A1 (de) * 1995-02-20 1996-08-22 Stockhausen Chem Fab Gmbh Schichtförmig aufgebauter Körper zur Absorption von Flüssigkeiten sowie seine Herstellung und Verwendung
DE19505708A1 (de) * 1995-02-20 1996-08-22 Stockhausen Chem Fab Gmbh Flächenförmige, superabsorbierende Gebilde
US6500777B1 (en) * 1996-06-28 2002-12-31 Ethicon, Inc. Bioresorbable oxidized cellulose composite material for prevention of postsurgical adhesions
GB2314842B (en) * 1996-06-28 2001-01-17 Johnson & Johnson Medical Collagen-oxidized regenerated cellulose complexes
JPH10298435A (ja) * 1997-04-24 1998-11-10 Dainippon Ink & Chem Inc 生分解性成形物、生分解性材料及びそれらの製造方法
GB2354708B (en) * 1999-10-01 2004-06-02 Johnson & Johnson Medical Ltd Compositions for the treatment of wound contracture
WO2002087643A1 (fr) * 2001-04-30 2002-11-07 Beijing Textile Research Institute Matieres styptiques de derives ether de cellulose hydrosolubles
JP2003126235A (ja) * 2001-08-17 2003-05-07 Terumo Corp 医療用貼付材
CN1185263C (zh) * 2001-10-08 2005-01-19 东华大学 医用可吸收氧化再生纤维素止血材料的制备方法
CA2521661A1 (fr) * 2003-04-04 2004-10-14 Tissuemed Limited Formulations pour adhesifs tissulaires
SA111320355B1 (ar) * 2010-04-07 2015-01-08 Baxter Heathcare S A إسفنجة لايقاف النزف
CN102028966B (zh) * 2010-12-29 2013-04-17 苏州方策科技发展有限公司 一种具有高度吸水溶胀性能的壳聚糖止血膜的制作方法
WO2015152204A1 (fr) * 2014-03-31 2015-10-08 東レ株式会社 Feuille multicouche, feuille intégrée l'utilisant, et leur procédé de fabrication

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101332309A (zh) * 2006-01-12 2008-12-31 张镁 水溶性多糖类复合医用敷料及制备方法
WO2013082073A1 (fr) * 2011-12-02 2013-06-06 Ethicon, Inc. Dispositif hémostatique biorésorbable comprenant un liant en polyéthylèneglycol
US20170165394A1 (en) * 2014-02-12 2017-06-15 Aesculap Ag Medical device and method for the production thereof
WO2016089201A1 (fr) * 2014-12-04 2016-06-09 Universiti Putra Malaysia Composition de film et procédé associé
WO2016169041A1 (fr) * 2015-04-24 2016-10-27 Gunze Limited Substance de renforcement de tissus biologiques

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CN111050812A (zh) 2020-04-21
CN111050812B (zh) 2022-02-25

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