WO2023106475A1 - Feuille de nanofibres pour la régénération et le renforcement de tissu mou et son procédé de fabrication - Google Patents

Feuille de nanofibres pour la régénération et le renforcement de tissu mou et son procédé de fabrication Download PDF

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WO2023106475A1
WO2023106475A1 PCT/KR2021/018796 KR2021018796W WO2023106475A1 WO 2023106475 A1 WO2023106475 A1 WO 2023106475A1 KR 2021018796 W KR2021018796 W KR 2021018796W WO 2023106475 A1 WO2023106475 A1 WO 2023106475A1
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soft tissue
reinforcement
glycolic
lactic acid
nanofiber sheet
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English (en)
Korean (ko)
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김은진
김병남
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주식회사 테라시온 바이오메디칼
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Publication of WO2023106475A1 publication Critical patent/WO2023106475A1/fr

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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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L27/26—Mixtures of macromolecular compounds
    • 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
    • A61L27/38—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
    • A61L27/3839—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 characterised by the site of application in the body
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00—Formation of filaments, threads, or the like
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01D—MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00—Formation of filaments, threads, or the like
    • D01D5/0007—Electro-spinning
    • D01D5/0015—Electro-spinning characterised by the initial state of the material
    • D01D5/003—Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion
    • 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
    • A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/34—Materials or treatment for tissue regeneration for soft tissue reconstruction
    • D—TEXTILES; PAPER
    • D10—INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
    • D10B—INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES
    • D10B2509/00—Medical; Hygiene

Definitions

  • the present invention relates to a nanofiber sheet for soft tissue regeneration and reinforcement and a method for manufacturing the same, and more specifically, the nanofiber sheet for soft tissue regeneration and reinforcement is poly(glycolic-co-lactic acid) (Poly(glycolic-co-latic acid) acid), PGLA) and polyvinylpyrrolidone (Polyvinylpyrrolidone, PVP), including the poly (glycolic-co-lactic acid) (Poly (glycolic-co-latic acid), PGLA) It is characterized in that the molar ratio of glycolic acid block: lactic acid block is 30: 70 to 40: 60.
  • Tissue Engineering is a field of regenerative medicine ranging from cells to artificial organs.
  • a scaffold that serves as a support for cells to attach and grow.
  • a scaffold is a three-dimensional type, and refers to a space where all cells in the body with a three-dimensional structure are attached to differentiate and proliferate.
  • the scaffold plays an important role in the growth of cells seeded in the porous structure and cells migrating from the tissue periphery.
  • scaffolds must provide a suitable environment for cell attachment, differentiation, growth, and cell migration.
  • these scaffolds should serve as a frame for cells to adhere to and form tissues with a sufficiently three-dimensional structure, and are the most basic element in creating artificial living tissues, so they have biocompatibility, biodegradability, toxicity, mechanical and structural properties. All characteristics must be considered.
  • active research has been conducted to develop scaffolds for tissue regeneration using natural materials, synthetic polymers, bioceramics, and polymer-ceramic composite materials as scaffolds for porous tissue engineering.
  • nanostructures such as nanofibers and nanoparticles are one of the effective structures for soft tissue cell support, and there are many reports that they positively affect cell proliferation, generation, and differentiation due to their structural advantages.
  • the present inventors focused on the above technology, prepared a nanofiber sheet for soft tissue regeneration and reinforcement as a support for tissue regeneration, and completed the present invention.
  • an electrospinning system can be largely divided into a fiber raw material solution supply part, a high voltage supply part, and a collector part where nanofibers are formed.
  • Other radiation environments humidity, temperature
  • the solution supply unit consists of a syringe pump and a syringe (or nozzle) that accurately discharge the solution at a constant speed, and the characteristics of the fiber can be controlled according to the design of the shape, diameter, and material of the syringe needle.
  • the high voltage supply unit controls voltage and current with an insulation cable composed of a (+) pole that charges the polymer solution part with a high dielectric constant and a (-) pole that collects the charged solution in the form of nanofiber filaments.
  • the collector part where nanofibers are collected can adjust the arrangement of nanofiber strands according to the design of its shape, movement, speed, etc., and materials of various shapes according to the purpose can be manufactured.
  • the material type used for electrospinning is generally in a well-dissolved solution state, and the properties of the polymer solution used in electrospinning have a great effect on fiber formation.
  • solution properties include the concentration of the polymer solution, viscosity, surface tension, Conductivity, dielectric properties, volatility, etc.
  • concentration of the polymer solution is closely related to the viscosity, and since the viscosity is a measure of the degree of entanglement and fluidity of the polymer chain, it is an important factor affecting the shape, diameter, and speed of the fiber produced during electrospinning.
  • Electrospinning is a technology in which fibers of several nm to several ⁇ m are produced by applying electrostatic force to a polymer solution or melt and spinning by a large potential difference between a charged polymer and a grounded collector plate.
  • the facility and equipment are inexpensive, simple, and , It is a spinning technology that enables spinning with a high spinning speed and small amount, obtains a sheet form through spinning, and is easy to add additives.
  • Technologies using nanofibers, especially nanofibers obtained by electrospinning a polymer solution, as physical barriers to prevent tissue adhesion have been proposed.
  • PLGA which is commonly used as a material for tissue engineering, as a basic material to manufacture biodegradable nanofibers containing antibiotics and use them as tissue adhesion prevention films.
  • this technology has a problem that severe shrinkage occurs in aqueous solution when PLGA, the main material, is made of a hydrophobic polymer as a nanofiber sheet (Hongliang Jiang, Benjamin Chu, "Preparation and characterization of ibuprofen-loaded poly(lactide-co-glycolide) )/poly(ethylene glycol)-g-chitosan electrospun membranes", J. Biomater. Sci. Polymer Edn, Vol. 15. No. 3, 279-296 2004).
  • GUNZE's NEOVEIL as a representative soft tissue reinforcement and repair sheet currently on the market.
  • the NEOVEIL is not a nanofiber unit product, but a fiber fabric nonwoven fabric sheet using micro unit thermal compression.
  • the NEOVEIL is rapidly biodegraded after 3 weeks in vivo, so that the desired effect in regenerating and strengthening soft tissue cannot be obtained if it takes more than 3 weeks to regenerate and strengthen soft tissue.
  • poly (glycolic-co-lactic acid) Poly (glycolic-co-latic acid), PGLA) and polyvinylpyrrolidone (Polyvinylpyrrolidone, PVP)
  • the poly(glycolic-co-lactic acid) Poly(glycolic-co-lactic acid), PGLA) has a glycolic acid block: lactic acid block molar ratio of 30:70 to
  • a nanofiber sheet for soft tissue regeneration and reinforcement of 40: 60 was developed, and it was found that the nanofiber sheet for soft tissue regeneration and reinforcement still maintains its physical properties in vivo for a period of 3 weeks or more and is absorbed into the body within 15 weeks. invention was completed.
  • the present invention has been made to solve the above problems of the prior art, and its purpose is to provide a nanofiber sheet for soft tissue regeneration and reinforcement.
  • the object is to provide a method for manufacturing the nanofiber sheet for regeneration and reinforcement of the soft tissue.
  • biodegradable polymers including Poly(glycolic-co-lactic acid) (PGLA) and polyvinylpyrrolidone (PVP), wherein the poly(glycolic-co-latic acid)
  • PGLA Poly(glycolic-co-lactic acid)
  • PVP polyvinylpyrrolidone
  • the poly(glycolic-co-latic acid) Provided is a nanofibrous sheet for soft tissue regeneration and reinforcement in which the molar ratio of poly(glycolic-co-latic acid) (PGLA) glycolic acid block: lactic acid block is 30:70 to 40:60.
  • PVP polyvinylpyrrolidone
  • PGLA poly (glycolic-co-lactic acid)
  • the average diameter of the fiber cross section may be 500 to 990 nm.
  • Biodegradable polymers including Poly(glycolic-co-lactic acid) (PGLA) and Polyvinylpyrrolidone (PVP), dichloromethane (DCM) and dimethylform obtaining a polymer solution by dissolving in a solvent containing amide (DMF) to obtain a polymer solution; obtaining nanofibers by electrospinning the polymer solution to obtain nanofibers; And a heat treatment step of heat-treating the nanofibers; provides a method for manufacturing a nanofiber sheet for soft tissue regeneration and reinforcement comprising a.
  • PGLA Poly(glycolic-co-lactic acid)
  • PVP Polyvinylpyrrolidone
  • DCM dichloromethane
  • DMF solvent containing amide
  • DMF solvent containing amide
  • nanofibers by electrospinning the polymer solution to obtain nanofibers
  • a heat treatment step of heat-treating the nanofibers provides a method for manufacturing a nanofiber sheet for soft tissue regeneration and reinforcement comprising a.
  • the molar ratio of the glycolic acid block to the lactic acid block of the poly(glycolic-co-lactic acid) (PGLA) may be from 30:70 to 40:60.
  • PVP polyvinylpyrrolidone
  • PGLA poly (glycolic-co-lactic acid)
  • the solvent may include 30 to 50 parts by weight of the dimethylformamide (DMF) based on 50 to 70 parts by weight of dichloromethane (DCM).
  • DMF dimethylformamide
  • DCM dichloromethane
  • the polymer solution may include 8 to 15 parts by weight of the biodegradable polymer based on 90 parts by weight of the solvent.
  • Electrospinning conditions of the nanofiber obtaining step may be a voltage of 15 to 30 kV, a spinning distance of 10 to 20 cm, and a discharge rate of 0.5 to 2 ml/h.
  • the heat treatment step may be heat treatment at 50 to 100 ° C. for 10 to 35 minutes.
  • the average diameter of the cross section of the nanofibers may be 500 to 990 nm.
  • the nanofiber sheet for soft tissue regeneration and reinforcement according to the present invention as described above can regenerate and strengthen soft tissue by maintaining its physical properties even for a period of 3 weeks or more in vivo, and can be absorbed into the body within 15 weeks and harmless to the human body. there is.
  • the nanofiber sheet for soft tissue regeneration and reinforcement may reduce shrinkage in an aqueous solution.
  • Figure 1 is a nanofiber sheet for soft tissue regeneration and reinforcement prepared according to Example (1) of the present invention and a SEM photograph showing it magnified 1000 times.
  • Figure 2 is a SEM photograph showing a nanofiber sheet for soft tissue regeneration and reinforcement prepared according to Example (1) of the present invention at 5000 times magnification.
  • Figure 3 is a SEM photograph showing a nanofiber sheet for soft tissue regeneration and reinforcement prepared by Comparative Example (1) of the present invention at 5000 times magnification.
  • Figure 4 is a graph showing the change in tensile strength of the nanofiber sheet for soft tissue regeneration and reinforcement prepared by Example (1) of the present invention.
  • 5 is a graph showing the change in tensile strength of NEOVEIL mutual sheets.
  • Figure 6 is a SEM picture showing a 5000-fold magnification of the nanofiber sheet for soft tissue regeneration and reinforcement prepared by Comparative Example (4) of the present invention after 3 days of cell proliferation.
  • Figure 7 is a SEM photograph showing a 5000-fold magnification of the nanofiber sheet for soft tissue regeneration and reinforcement prepared by Example (2) of the present invention after 3 days of cell proliferation.
  • Figure 8 is a SEM photograph showing a 5000-fold magnification of the nanofiber sheet for soft tissue regeneration and reinforcement prepared by Example (3) of the present invention after 3 days of cell proliferation.
  • Figure 9 is a SEM photograph showing a 5000-fold magnification of the nanofiber sheet for soft tissue regeneration and reinforcement prepared by Example (1) of the present invention after 3 days of cell proliferation.
  • Figure 10 is a SEM picture showing a 5000-fold magnification of the nanofiber sheet for soft tissue regeneration and reinforcement prepared by Example (4) of the present invention after 3 days of cell proliferation.
  • FIG. 11 is a SEM photograph showing a nanofiber sheet for soft tissue regeneration and reinforcement prepared according to Comparative Example (5) of the present invention at 2500 times magnification.
  • the first aspect of the present application is,
  • biodegradable polymers including Poly(glycolic-co-lactic acid) (PGLA) and polyvinylpyrrolidone (PVP), wherein the poly(glycolic-co-latic acid)
  • PGLA Poly(glycolic-co-lactic acid)
  • PVP polyvinylpyrrolidone
  • the poly(glycolic-co-latic acid) Provided is a nanofibrous sheet for soft tissue regeneration and reinforcement in which the molar ratio of poly(glycolic-co-latic acid) (PGLA) glycolic acid block: lactic acid block is 30:70 to 40:60.
  • nanofiber sheet for soft tissue regeneration and reinforcement according to the first aspect of the present disclosure will be described in detail.
  • the nanofiber sheet for soft tissue regeneration and reinforcement is poly (glycolic-co-lactic acid) (Poly (glycolic-co-latic acid), PGLA) and polyvinylpyrrolidone (Polyvinylpyrrolidone, By including a biodegradable polymer including PVP), shrinkage in an aqueous solution is reduced compared to the case where only Poly (glycolic-co-lactic acid) (PGLA) is used as a biodegradable polymer. , It can regenerate and strengthen soft tissue by still maintaining its physical properties even in the body for a period of 3 weeks or more, and it can be absorbed by the body within 15 weeks and harmless to the body.
  • the molar ratio of the glycolic acid block: lactic acid block of the poly (glycolic-co-lactic acid) (Poly (glycolic-co-lactic acid), PGLA) is 30: 70 to 40: 60
  • Poly (glycolic-co -Latic acid) (Poly(glycolic-co-latic acid), PGLA) can make the average diameter of the nanofiber cross section 500-990 nm.
  • the glycolic acid block of the poly (glycolic-co-lactic acid) (PGLA) the glycolic acid block molar ratio of the lactic acid block is less than 30 and the molar ratio of the lactic acid block is greater than 70
  • the biodegradable polymer is not partially dissolved in the solvent, it is difficult to apply the electrospinning of the present invention, or even if the nanofiber is formed, the thickness of the nanofiber may become irregular because complete fiberization is not achieved, and the thickness variation Large parts can be formed.
  • the glycolic acid block of the poly (glycolic-co-lactic acid) (PGLA) the glycolic acid block molar ratio of the lactic acid block is greater than 40 and the molar ratio of the lactic acid block is less than 60
  • PGLA poly (glycolic-co-lactic acid)
  • the average diameter of the cross section of the fiber may be 500 ⁇ 990 nm. Preferably it may be 550 ⁇ 850nm, more preferably it may be 550 ⁇ 800nm.
  • the nanofiber cross-sectional average diameter is smaller than 500 nm, the nanofiber surface area may be large, but it is difficult to form a support layer necessary for cell growth.
  • the average cross-sectional average diameter of the nanofibers is greater than 990 nm, the space between fibers becomes large, which may inhibit cell growth.
  • the second aspect of the present application is,
  • Biodegradable polymers including Poly(glycolic-co-lactic acid) (PGLA) and Polyvinylpyrrolidone (PVP), dichloromethane (DCM) and dimethylform obtaining a polymer solution by dissolving in a solvent containing amide (DMF) to obtain a polymer solution; obtaining nanofibers by electrospinning the polymer solution to obtain nanofibers; And a heat treatment step of heat-treating the nanofibers; provides a method for manufacturing a nanofiber sheet for soft tissue regeneration and reinforcement comprising a.
  • PGLA Poly(glycolic-co-lactic acid)
  • PVP Polyvinylpyrrolidone
  • DCM dichloromethane
  • DMF solvent containing amide
  • DMF solvent containing amide
  • nanofibers by electrospinning the polymer solution to obtain nanofibers
  • a heat treatment step of heat-treating the nanofibers provides a method for manufacturing a nanofiber sheet for soft tissue regeneration and reinforcement comprising a.
  • biodegradable polymers including poly (glycolic-co-latic acid) (Poly (glycolic-co-latic acid), PGLA) and polyvinylpyrrolidone (PVP) It may include; a polymer solution obtaining step of obtaining a polymer solution by dissolving in a solvent containing dichloromethane (DCM) and dimethylformamide (DMF).
  • DCM dichloromethane
  • DMF dimethylformamide
  • the molar ratio of the glycolic acid block: the lactic acid block of the poly (glycolic-co-lactic acid) (PGLA) is 30: 70 to 40: 60 may be
  • the poly(glycolic-co-lactic acid) (Poly (glycolic-co-latic acid), PGLA) relative to 60 to 90 parts by weight of the polyvinylpyrrolidone (Polyvinylpyrrolidone, PVP) may include 10 to 40 parts by weight.
  • the polyvinylpyrrolidone (PVP) is less than 10 parts by weight, when the nanofiber sheet is applied to the soft tissue, secondary fixation using sutures or tissue adhesives may be essential. Therefore, if the PVP is less than 10 parts by weight, it may be separated from the soft tissue without a process of fixing it to the soft tissue.
  • the polyvinylpyrrolidone (PVP) is greater than 40 parts by weight, soft tissue may not be regenerated.
  • the solvent may include 30 to 50 parts by weight of the dimethylformamide (DMF) based on 50 to 70 parts by weight of dichloromethane (DCM).
  • DCM dichloromethane
  • the amount of dimethylformamide (DMF) is less than 30 parts by weight, dissolution of the biodegradable polymer to the extent that electrospinning may not occur may not occur.
  • the amount of dimethylformamide (DMF) is greater than 50 parts by weight, significant dissolution of the biodegradable polymer may not occur.
  • the polymer solution may include 8 to 15 parts by weight of the biodegradable polymer based on 90 parts by weight of the solvent.
  • the nanofiber cross-sectional diameter may be less than 500 nm, and the nanofiber sheet may be damaged even with a small impact.
  • the nanofiber cross-sectional diameter may be less than 990 nm, and when the nanofiber sheet is applied to soft tissue, soft tissue may not be effectively regenerated.
  • the electrospinning conditions of the nanofiber obtaining step may be a voltage of 15 to 30 kV, a spinning distance of 10 to 20 cm, and a discharge rate of 0.5 to 2 ml/h. If the voltage, radiation distance and ejection speed ranges of the above conditions are out of range, the average diameter of the cross section of the nanofibers may be smaller than 500 nm or larger than 990 nm.
  • the heat treatment step may be a heat treatment for 10 to 35 minutes at 50 to 100 °C.
  • the reason for the heat treatment is to shrink the nanofiber sheet by heat treatment, so that the nanofiber sheet can exist in the living body for 3 weeks or more and 15 weeks or less, since contraction of the nanofiber sheet may occur in the living body. If the temperature and heat treatment time of the heat treatment step are out of the range, the strength of the nanofibers is lowered, and the nanofiber sheet may not exist for 3 weeks or more and 15 weeks or less in the living body.
  • the average diameter of the cross section of the nanofibers may be 500 to 990 nm.
  • PGLA poly(glycolic-co-lactic acid)
  • G glycolic acid block
  • L lactic acid block
  • G:L molar ratio
  • PVP Polyvinylpyrrolidone
  • DCM dichloromethane
  • DMF dimethylformamide
  • Nanofibers were prepared by pre-spinning the polymer solution under conditions of a voltage of 20 kV, a spinning distance of 15 cm, and a discharge rate of 1 ml/h.
  • the nanofibers were subjected to heat treatment using an oven at a heat treatment temperature of 75 to 85 degrees and a heat treatment time of 30 minutes.
  • the average diameter of the nanofiber cross section of the nanofiber sheet of the present invention is 500 ⁇ 990nm.
  • Example (1) It is the same as Example (1) except that PVP in Example (1) was changed to Poly(ethylene oxide) (hereinafter referred to as PEO) and the electrospinning voltage was changed to 18 kV. .
  • PEO Poly(ethylene oxide)
  • the diameter of the nanofiber is larger than 990nm.
  • Example (1) It is the same as Example (1) except that 100 parts by weight of PGLA and 0 parts by weight of PVP were changed in the step of obtaining the polymer solution in Example (1).
  • Example (1) It is the same as Example (1) except that 90 parts by weight of PGLA and 10 parts by weight of PVP were changed in the step of obtaining the polymer solution in Example (1).
  • Example (1) It is the same as Example (1) except that 80 parts by weight of PGLA and 20 parts by weight of PVP were changed in the step of obtaining the polymer solution in Example (1).
  • Example (1) It is the same as Example (1) except that 60 parts by weight of PGLA and 40 parts by weight of PVP were changed in the step of obtaining the polymer solution in Example (1).
  • Example (1) the weight mixing ratio of dichloromethane (hereinafter referred to as DCM) and dimethylformamide (hereinafter referred to as DMF) of the solvent was changed from 60: 40 to 20: 10 by weight mixing ratio of dimethylacetamide and acetone. It is the same as Example (1) except for one point.
  • DCM dichloromethane
  • DMF dimethylformamide
  • biodegradation test samples were prepared for each of the nanofiber sheet prepared according to Example (1) of the present invention and the NEOVEIL sheet of GUNZE. Samples were prepared by weighing 0.3 g, and the samples to be tested after 7, 14, 21, and 28 days were labeled as Day 7, 14, 21, and 28. A total of 12 were produced, 3 for each level.
  • the sheet was soaked in PBS at 36.5° C. in a water bath and left to stand. After that, according to each leveling number, it was taken out every 7, 14, 21, and 28 days, dried, and put in a vacuum oven for a certain period of time. The sheets were then weighed to determine how much they had decreased from the beginning.
  • NEOVEIL's sheet is rapidly decomposed after 3 weeks, and after 4 weeks, 52.89% is decomposed, which is about 10 times greater than the nanofiber sheet prepared by Example (1) of the present invention. abnormal decomposition can be confirmed.
  • the size of the nanofiber sheet prepared by Example (1) of the present invention and the sheet specimen of GUNZE's NEOVEIL mutually was made to be 0.5 cm x 10 cm. Specimens were labeled as Day 7, 14, 21, and 28 for samples to be tested after 7, 14, 21, and 28 days. A total of 25 were produced, 5 for each level. After that, the sheet was left to stand by immersing it in 36.5 ° C. PBS in a water bath. After that, it was taken out and dried every 7, 14, 21, and 28 days according to each leveling number. And the tensile strength of the sheet was measured using UTM with a load cell of 100 N and an extension speed of 5 mm/min.
  • the NEOVEIL mutual sheet has lower tensile strength than the nanofiber sheet prepared in Example (1) of the present invention from the beginning of the test. Also, referring to FIGS. 4 and 5, it can be seen that the tensile strength of the NEOVEIL mutual sheet decreases more rapidly than the tensile strength of the nanofiber sheet prepared according to Example (1) of the present invention.
  • Cell culture was performed on a total of 5 samples of PLGA (65:35) + PVP (0%, 10%, 20%, 30%, 40%).
  • the sheet was perforated into a 12-well plate size, and both sides of the sheet were UV sterilized for 30 minutes each. Then, the sheet was placed in a 12-well plate and PBS was added just enough to wet the sheet. After immediately suctioning the PBS, a glass ring was inserted and the cells and medium were seeded at a ratio of 50,000 cells/2mL. After 1, 3, 5, and 7 days, cells were fixed in PBS containing 2.5% glutaraldehyde for 30 minutes at room temperature.
  • the cells were washed 3 times with PBS and then washed 3 times with sterile water. Dehydration was performed at room temperature using 2 mL each of 50, 70, and 90% EtOH once each. It was dried for 24 hours in a clean bench.
  • the nanofiber sheet contains 0 to 30 parts by weight of PVP, cell proliferation is achieved smoothly, and in the case of 40 parts by weight, cell proliferation is insufficient.
  • the sheet was cut into 2 x 2 cm in size, annealed at a temperature range of 70 ° C to 120 ° C for 30, 60, and 90 minutes, and then immersed in PBS at 37 ° C for 7 days. Then, the shrinkage rate of the sheet was calculated.
  • the nanofiber sheet for soft tissue regeneration and reinforcement according to the present invention as described above can regenerate and strengthen soft tissue by maintaining its physical properties even for a period of 3 weeks or more in vivo, and can be absorbed into the body within 15 weeks and harmless to the human body. there is.
  • the nanofiber sheet for soft tissue regeneration and reinforcement may reduce shrinkage in an aqueous solution.

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Abstract

La présente invention concerne une feuille de nanofibres pour la régénération et le renforcement d'un tissu mou et son procédé de fabrication. Plus spécifiquement, la feuille de nanofibres pour la régénération ou le renforcement d'un tissu mou comprend un polymère biodégradable portant de poly(acide glycolique-co-lactique) (PGLA) et la polyvinylpyrrolidone (PVP), le poly(acide glycolique-co-lactique) (PGLA) contenant un rapport molaire de bloc d'acide glycolique: bloc d'acide lactique allant de 30: 70 à 40: 60.
PCT/KR2021/018796 2021-12-10 2021-12-10 Feuille de nanofibres pour la régénération et le renforcement de tissu mou et son procédé de fabrication WO2023106475A1 (fr)

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Citations (4)

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Publication number Priority date Publication date Assignee Title
US20110076250A1 (en) * 2001-10-10 2011-03-31 Belenkaya Bronislava G Biodegradable Absorbents and Methods of Preparation
JP2013081783A (ja) * 2011-10-11 2013-05-09 Bond University Ltd カスタマイズされた組成物およびその使用
KR101578535B1 (ko) * 2014-07-31 2015-12-18 금오공과대학교 산학협력단 친수성 천연고분자를 함유하는 나노섬유상 다층구조의 유착방지막 및 그 제조방법
US20210128792A1 (en) * 2016-12-28 2021-05-06 Auckland Uniservices Ltd Electrospun matrix and method

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Publication number Priority date Publication date Assignee Title
US20110076250A1 (en) * 2001-10-10 2011-03-31 Belenkaya Bronislava G Biodegradable Absorbents and Methods of Preparation
JP2013081783A (ja) * 2011-10-11 2013-05-09 Bond University Ltd カスタマイズされた組成物およびその使用
KR101578535B1 (ko) * 2014-07-31 2015-12-18 금오공과대학교 산학협력단 친수성 천연고분자를 함유하는 나노섬유상 다층구조의 유착방지막 및 그 제조방법
US20210128792A1 (en) * 2016-12-28 2021-05-06 Auckland Uniservices Ltd Electrospun matrix and method

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Title
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