WO2014038885A1 - Feuille de sous-muqueuse d'intestin grêle biocompatible ayant un temps de dégradation in vivo réglable et son procédé de préparation - Google Patents

Feuille de sous-muqueuse d'intestin grêle biocompatible ayant un temps de dégradation in vivo réglable et son procédé de préparation Download PDF

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WO2014038885A1
WO2014038885A1 PCT/KR2013/008067 KR2013008067W WO2014038885A1 WO 2014038885 A1 WO2014038885 A1 WO 2014038885A1 KR 2013008067 W KR2013008067 W KR 2013008067W WO 2014038885 A1 WO2014038885 A1 WO 2014038885A1
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small intestinal
intestinal submucosa
sheet
biocompatible
crosslinking agent
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PCT/KR2013/008067
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Korean (ko)
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김다연
진링메이
박지훈
김문석
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아주대학교산학협력단
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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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
    • A61L27/3687—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/02—Adhesive bandages or dressings
    • 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
    • A61L15/40—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing ingredients of undetermined constitution or reaction products thereof, e.g. plant or animal extracts
    • A—HUMAN NECESSITIES
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    • 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
    • A61L15/44—Medicaments
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    • 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
    • A61L15/64—Use of materials characterised by their function or physical properties specially adapted to be resorbable inside the body
    • 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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/0005—Ingredients of undetermined constitution or reaction products thereof
    • 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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0015—Medicaments; Biocides
    • A—HUMAN NECESSITIES
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    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0042—Materials resorbable by the body
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3629—Intestinal tissue, e.g. small intestinal submucosa
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
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    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
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    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C—CHEMISTRY; METALLURGY
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    • C12N2533/00—Supports or coatings for cell culture, characterised by material
    • C12N2533/30—Synthetic polymers
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    • C12N2533/00—Supports or coatings for cell culture, characterised by material
    • C12N2533/30—Synthetic polymers
    • C12N2533/40—Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers

Definitions

  • the present invention relates to a biocompatible small intestinal submucosa sheet capable of controlling the degradation period in vivo, and a method of manufacturing the same.
  • Natural materials are derived from natural materials, animals and the human body and have very good biocompatibility.
  • a representative example is an extracellular matrix (ECM), which is a biomaterial extracted from a complex human body and an animal, and has characteristics that can control the function of cells.
  • ECM extracellular matrix
  • the support made of natural material is evaluated as an ideal tissue engineering support material because it can provide excellent bio-functionality and biodegradability as well as less inflammatory response after implantation into a living body.
  • the small intestinal submucosa of pigs is a cell-free tissue and almost no immune response. More than 90% of the components are composed of type I and type II collagen in the skin. Consisting of small amounts of type V and VI collagen.
  • the small intestinal submucosa of pigs is glycoaminoglycan and fibronectin, chondroitin sulfate, heparin, heparin sulfate, hyaluronic acid and basic fibroblast growth factor-2 (FGF-) as extracellular matrix (ECM).
  • NGF nerve growth factor
  • TGF- ⁇ transforming growth factor- ⁇
  • EGF epidermal growth factor
  • vascular endothelial growth factor vascular
  • cytokines such as endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1), so that the cell functions in terms of cell adhesion, growth, migration and differentiation. By helping, it can be applied to many fields besides tissue regeneration.
  • Tissue engineering is a field that requires mutual cooperation between disciplines applied to the regeneration of biological substitutes for the purpose of restoring or preserving lost organ function using the principles of bioscience and engineering. Artificial organs can be developed and applied as a tissue engineering support for regenerating damaged tissue.
  • small intestinal submucosa The study of the small intestinal submucosa was initiated by Badylak at "Purdue University" in the United States, and is being actively researched by many leading pharmaceutical companies such as "COOK". As a result of this study, small intestinal submucosa is currently commercialized as a vein or artery, and a graft of the dermis, epithelium, bone, and graft regeneration of the bile duct and tightening the bladder of the incontinence patient. Therefore, many studies are expected as a small intestinal submucosa as a biocompatible material that can be variously applied as various bio substitutes.
  • the present inventors formed a crosslink by reacting with a crosslinking agent in the small intestinal submucosa, which hardly caused an immune reaction while studying biocompatible materials, and thus the mechanical properties were improved in proportion to the presence or absence of crosslinking and the crosslinking reaction time. This delay was confirmed and the present invention was completed.
  • the present invention is to provide a biocompatible small intestinal submucosa sheet capable of controlling the in vivo degradation period in which crosslinking is formed by reacting the small intestinal submucosa of animals other than humans with a crosslinking agent.
  • the present invention is to provide a method for producing a biocompatible small intestinal submucosa sheet capable of controlling the degradation period in vivo.
  • the present invention provides a biocompatible small intestinal submucosa sheet capable of controlling in vivo degradation period in which crosslinking is formed by reacting small intestinal submucosa of animals other than humans with a crosslinking agent.
  • the present invention also provides a method for producing a biocompatible small intestinal submucosa sheet capable of controlling the degradation period in vivo.
  • the biocompatible small intestinal submucosa sheet according to the present invention can delay the degradation period in vivo by forming a crosslink with a crosslinking agent, and can control the degradation period according to the type of crosslinking agent and the degree of crosslinking formation according to the crosslinking time. It can be used very usefully as a support for tissue engineering, drug carrier, wound dressing or hemostatic agent.
  • FIG. 1 is a view showing the chemical structure of the crosslinking agent that can be used as a crosslinking agent of the small intestinal submucosal tissue sheet of the present invention.
  • Figure 2 is a diagram showing the chemical structure of the crosslinking agent prepared by reacting with EDC-NHS after introducing a carboxyl group at the PEG terminal according to Example 2-1 of the present invention and its NMR spectrum.
  • Figure 3 is a diagram showing the chemical structure of the crosslinking agent prepared by introducing a carboxyl group in the terminal and / or side chain of the PCLA polymer according to Example 2-2 of the present invention and reacted with DCC and its NMR spectrum thereof.
  • Figure 4 is a diagram schematically showing the degradation behavior of the biocompatible small intestinal submucosa sheet through crosslinking of the present invention.
  • Example 5 is a view illustrating the degradation behavior of the biocompatible small intestinal submucosa sheet prepared in Example 1 of the present invention.
  • Figure 6 is a diagram showing the change in weight with time of the biocompatible small intestinal submucosa sheet prepared in Example 1 of each cross-linking agent.
  • Figure 7 is a diagram showing the decomposition behavior of the biocompatible small intestinal submucosa sheet prepared in Example 2 according to the crosslinking reaction time.
  • Example 8 is a view showing the weight change with time of the biocompatible small intestinal submucosa sheet prepared in Example 2 according to the type of crosslinking agent.
  • the present invention provides a biocompatible small intestinal submucosa sheet capable of controlling in vivo degradation period in which crosslinking is formed by reacting small intestinal submucosa of animals other than humans with a crosslinking agent.
  • the present invention also provides a method for producing a biocompatible small intestinal submucosa sheet capable of controlling the degradation period in vivo.
  • the present invention also provides a support for tissue engineering, drug carrier, wound dressing, and hemostatic agent including the small intestinal submucosa sheet.
  • the small intestinal submucosa sheet according to the present invention is characterized by separating small intestinal submucosa of animals other than humans, preferably mammals except humans, and reacting it with a crosslinking agent to form crosslinks.
  • the crosslinking agent that can be used in the present invention may be at least one selected from the group consisting of aldehyde compounds, water-soluble carbodiimide compounds, organic solvent soluble carbodiimide compounds, epoxy compounds and diisocyanates, more preferably water-soluble carbodiimide 1-ethyl-3- (3-dimethylaminopropylcarbodiimide), 1-ethyl-3- (2-morpholinyl-4-ethyl) carbodiimide as the compound, and dicyclohexyl as the organic solvent soluble carbodiimide compound
  • aldehyde-based compounds include, but are not limited to, compounds shown in FIG. 1 such as formaldehyde, glutaraldehyde, dextrin aldehyde, and the like.
  • the crosslinking agent that can be used in the present invention may be a biocompatible polymer having a carboxyl group at the terminal or side chain
  • the biocompatible polymer is polyethylene glycol (PEG, poly ethylene glycol), polycaprolactone (PCL, polycaprolactone), glycolide (GA, glycolide), lactide (LA, lactide), or one or more selected from the group consisting of copolymers (co-polymers), but is not limited thereto.
  • the biocompatible polymer having a carboxyl group at the terminal or side chain may be a crosslinking agent represented by the following Formula 1 or Formula 2.
  • n is an integer representing a repeating unit of polyethylene glycol, preferably an integer of 1 to 20.
  • n is an integer representing a repeating unit of polyethylene glycol, preferably an integer of 1 to 20
  • m represents an integer constituting the polyester and is an integer of 1 to 10.
  • the animal includes, but is not limited to, pigs, cows, rabbits, mice, and the like.
  • Small intestinal submucosa sheet according to the present invention can be used for various purposes as a sheet that can control the decomposition period by forming crosslinks using various crosslinking agents.
  • the small intestinal submucosa is rich in ECM (extracellular matrix) and cytokines to help the cell's functional aspects such as cell adhesion, growth, migration, differentiation, and wound healing in addition to the tissue engineering support.
  • ECM extracellular matrix
  • cytokines to help the cell's functional aspects such as cell adhesion, growth, migration, differentiation, and wound healing in addition to the tissue engineering support.
  • Including a drug in a dressing, a tissue sheet, or a drug carrier, a wound dressing, or a hemostatic agent may be applied to many fields.
  • Adipose tissue was removed using a pig's ileum within 4 hours after death. After washing the inside and outside of the plant cleanly with water, the plant was cut to a length of about 10 cm and placed in saline. A physical force was applied to the washed factory to remove the dense layer on the outer layer, and then reversed to remove the mucosal muscle layer, thereby separating only the small intestinal submucosa layer. It was washed again with brine and then stored in a -80 ° C low temperature cooler. One side of the small intestinal submucosa stored at ⁇ 80 ° C. was cut and unfolded, and then lyophilized to prepare a sheet-like small intestinal mucosa.
  • FIG. 1 A crosslinking agent capable of causing a crosslinking reaction to the small intestinal submucosa sheet is shown in FIG. 1.
  • EDC Aminopropyl carbodiimide
  • CDI carbonyldiimidazole
  • DCC dicyclohexylcarbodiimide
  • formalin formailn
  • toluene was used as a solvent, 1.3 times glutaric anhydride (Glutaric anhydride) was added to the hydroxyl group (OH) of polyethylene glycol, and the mixture was stirred for 24 hours under acetic acid as a catalyst.
  • Polyethylene glycol, 1-ethyl-3- (3-dimethylaminopropylcarbodiimide) (EDC) and N-hydroxysuccinimide (NHS) having a carboxyl group were dissolved in distilled water in a molar ratio of 1: 2: 2. After stirring for 2 hours, a crosslinking agent having biocompatibility and biodegradability represented by Chemical Formula 1 was prepared.
  • n is an integer representing a repeating unit of polyethylene glycol, preferably an integer of 1 to 20.
  • PCLA polyethylene glycol / poly (caprolactone-co-lactide)
  • toluene is used as a solvent, and 1.3 times glutaric anhydride is added to the hydroxyl group (OH) of polyethylene glycol / poly (caprolactone-co-lactide), and acetic acid is used as a catalyst. Stir for hours.
  • Polyethylene glycol / poly (caprolactone-co-lactide) (PCLA) and dicyclohexylcarbodiimide (DCC) having a carboxyl group were dissolved in distilled water in a molar ratio of 1: 1, followed by stirring for 2 hours.
  • a crosslinking agent having biocompatibility and biodegradation represented by 2 was prepared.
  • n is an integer representing a repeating unit of polyethylene glycol, preferably an integer of 1 to 20
  • m represents an integer constituting the polyester and is an integer of 1 to 10.
  • Example 1-1 To 20 ml of a phosphate buffer solution in which the biocompatible crosslinker prepared in Example 2-1 was dissolved at 50 mM concentration, the small intestinal submucosa sheet prepared in Example 1-1 was added and stirred at room temperature for 24 hours. Crosslinking reaction was performed.
  • N is an integer which represents the repeating unit of polyethylene glycol, Preferably it is an integer of 1-20.
  • n is an integer which shows the repeating unit of polyethyleneglycol, Preferably it is an integer of 1-20, m shows the segment which comprises polyester, and is an integer of 1-10.
  • the small intestinal submucosa prepared in Example 1 was cut into 2 ⁇ 2 cm 2 and placed in a 20 ml vial, followed by 5 ml of phosphate buffer solution added with collagenase (60 ⁇ g / ml), for 60 hours. Decomposition behavior was carried out at 37 °C, 1000 rpm environment for a while to determine the degree of decomposition.
  • FIG. 4 A schematic diagram of the degradation behavior experiment of the biocompatible small intestinal submucosa sheet of the present invention is shown in FIG. 4, and the results of the degradation behavior observation are shown in FIG. 5.
  • the cross-linked small intestinal submucosa sheet is not decomposed than the general small intestinal submucosa sheet was not cross-linked, it was confirmed that the shape is maintained excellently.
  • Crosslinking was performed for 24 hours (1 day) or 72 hours (3 days) using the biocompatible crosslinking agent prepared in Example 2, and then lyophilized to prepare a crosslinked small intestinal submucosa sheet.
  • Subcutaneous intestinal mucosa in sheet form was cut into 2 ⁇ 2 cm 2 and placed in a 20 ml vial. Then, 5 ml of phosphate buffer solution containing collagenase (60 ⁇ g / ml) was added. Decomposition behavior was carried out at to confirm the degree of decomposition morphologically.
  • the small intestinal submucosa sheet crosslinked with a biocompatible crosslinking agent was not degraded compared to the general small intestinal submucosa sheet without crosslinking, and the shape was maintained excellently.
  • the shape retention of the small intestinal submucosa sheet was superior to the case where the crosslinking was carried out for 24 hours compared to the case where the crosslinking was performed for 24 hours. Therefore, it can be seen that the longer the crosslinking reaction time, the better the physical properties of the small intestinal submucosa sheet.
  • the initial weight of the small intestinal submucosa sheet was not significantly different depending on the type of crosslinking agent. However, as shown in 2-1, the sheet was very well preserved.

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  • Urology & Nephrology (AREA)

Abstract

La présente invention concerne une feuille de sous-muqueuse d'intestin grêle biocompatible ayant un temps de dégradation in vivo réglable, dans laquelle la sous-muqueuse d'intestin grêle d'un animal réagit avec un agent de réticulation pour former une liaison réticulée. La présente invention concerne également un procédé de préparation de la feuille de sous-muqueuse d'intestin grêle biocompatible. La feuille de sous-muqueuse d'intestin grêle biocompatible selon la présente invention peut retarder le temps de dégradation in vivo par la liaison réticulée de l'agent de réticulation, et peut régler le temps de dégradation en fonction du degré de la formation de la liaison réticulée sur la base du type d'agent de réticulation et du temps de réticulation. Par conséquent, la feuille de sous-muqueuse d'intestin grêle biocompatible selon la présente invention peut être utilisée significativement de manière utile en tant qu'échafaudage pour l'ingénierie tissulaire, vecteur de médicament, pansement pour plaie ou agent antihémorragique.
PCT/KR2013/008067 2012-09-06 2013-09-06 Feuille de sous-muqueuse d'intestin grêle biocompatible ayant un temps de dégradation in vivo réglable et son procédé de préparation WO2014038885A1 (fr)

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KR1020120098560A KR101409312B1 (ko) 2012-09-06 2012-09-06 생체 내 분해기간 조절이 가능한 생체적합성 소장점막하조직 시트, 및 이의 제조방법
KR10-2012-0098560 2012-09-06

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KR101997966B1 (ko) * 2016-06-30 2019-07-09 아주대학교산학협력단 생분해기간 조절이 가능한 생체적합성 연골유래조직 시트
KR102358610B1 (ko) * 2018-06-22 2022-02-04 아주대학교산학협력단 소장점막하조직을 이용한 피부 재생 또는 창상 치유용 이중층 나노 섬유 시트 및 이의 제조방법

Citations (3)

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US20020103542A1 (en) * 2000-09-18 2002-08-01 Bilbo Patrick R. Methods for treating a patient using a bioengineered flat sheet graft prostheses
KR100482651B1 (ko) * 2002-06-19 2005-04-13 한국화학연구원 조직공학용 천연／합성 하이브리드 담체 및 이의 제조방법
JP2009519791A (ja) * 2005-12-20 2009-05-21 サミット（ジーデー） バイオテク シーオー．， エルテーデー． 生体創傷被覆材および作製方法

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KR101288088B1 (ko) * 2011-09-09 2013-07-22 아주대학교산학협력단 생체내 분해기간이 조절 가능한 생체적합성 소장점막하조직 하이드로젤의 제조방법

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020103542A1 (en) * 2000-09-18 2002-08-01 Bilbo Patrick R. Methods for treating a patient using a bioengineered flat sheet graft prostheses
KR100482651B1 (ko) * 2002-06-19 2005-04-13 한국화학연구원 조직공학용 천연／합성 하이브리드 담체 및 이의 제조방법
JP2009519791A (ja) * 2005-12-20 2009-05-21 サミット（ジーデー） バイオテク シーオー．， エルテーデー． 生体創傷被覆材および作製方法

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