WO2017115906A1 - Drug releasing dental biodegradable fiber chip, and manufacturing method therefor - Google Patents

Drug releasing dental biodegradable fiber chip, and manufacturing method therefor Download PDF

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Publication number
WO2017115906A1
WO2017115906A1 PCT/KR2016/000385 KR2016000385W WO2017115906A1 WO 2017115906 A1 WO2017115906 A1 WO 2017115906A1 KR 2016000385 W KR2016000385 W KR 2016000385W WO 2017115906 A1 WO2017115906 A1 WO 2017115906A1
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biodegradable
acid
drug
fiber
natural polymer
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PCT/KR2016/000385
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French (fr)
Korean (ko)
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최원열
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주식회사 웰나노스
강릉원주대학교산학협력단
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Publication of WO2017115906A1 publication Critical patent/WO2017115906A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B5/00—Layered products characterised by the non- homogeneity or physical structure, i.e. comprising a fibrous, filamentary, particulate or foam layer; Layered products characterised by having a layer differing constitutionally or physically in different parts
    • B32B5/02—Layered products characterised by the non- homogeneity or physical structure, i.e. comprising a fibrous, filamentary, particulate or foam layer; Layered products characterised by having a layer differing constitutionally or physically in different parts characterised by structural features of a fibrous or filamentary layer

Definitions

  • the present invention relates to a drug-release biodegradable fiber chip and a method for manufacturing the same, and more particularly, since the biodegradable fibers form a network (network) structure, not only can be easily inserted or attached to the wound site, but also mixed with body fluids. Since the flow does not occur at the attached position, it can effectively work only at the treatment site, and since the biodegradable fiber itself contains the drug as a component, the release of the drug contained can be continuously performed for a certain period of time.
  • the present invention relates to a dental drug-releasing biodegradable fiber chip which can be used as a biodeterminant, has no side effects even after being inserted into an animal or a human body, and enables long-term drug dissolution, and a method of manufacturing the same.
  • U.S. Publication 2003/0026770 discloses periodontal regeneration composition and method of using same.
  • the periodontal regeneration composition is injected with a needle and used to treat periodontality.
  • the needle injection method cannot be performed by a person in need of treatment, and requires a high level of expertise for the injection of the composition using the needle, and the injected composition is easily mixed with body fluids. There is a problem that can occur in the flow can not effectively act only on the treatment site.
  • Tissue adhesion or inflammation occurs mainly after oral surgery.
  • Tissue adhesion refers to the binding of abnormal fibrous connective tissue at the wound site. These tissue adhesions are naturally degraded over time, but in some cases they can remain in vivo and cause sequelae.
  • the present invention provides a simpler manufacturing process, easier mass production, better reproducibility, and improved biodegradability for the method for manufacturing a dental drug-release biodegradable fiber chip as disclosed in Korean Patent Publication No. 10-1534522. It was developed by researching ways to improve the electrical or mechanical properties of fiber chips.
  • the problem to be solved by the present invention is that the biodegradable fibers form a network (network) structure, not only can be easily inserted or attached to the wound site, but also mixed with body fluids, so that the flow does not occur at the attached position, so that only the treated area is effectively treated.
  • the biodegradable fiber itself contains the drug as a component, so that the drug can be released continuously for a certain period of time, and can be used for disinfection and antibiotics.
  • the present invention provides a dental drug-release biodegradable fiber chip capable of prolonged drug dissolution without causing side effects even after insertion into the body of a human body.
  • the problem to be solved by the present invention is to provide a method for manufacturing a dental drug-release biodegradable fiber chip with a simple manufacturing process, mass production, and excellent reproducibility.
  • biodegradable fibers having an average diameter of 0.01 to 100 ⁇ m are entangled in a network form to form a fiber chip having a width of 0.5 to 50 mm, a length of 0.5 to 50 mm, and a thickness of 0.05 to 5 mm, and entangled in a network form.
  • Pores are distributed between the biodegradable fibers, wherein the biodegradable fibers comprise a biodegradable natural polymer, a drug and a cross-linking agent as constituents, and the biodegradable natural polymer comprises gelatin, It comprises at least one substance selected from collagen, alginate, chitosan, fibrin, fibrin, hyaluronic acid and dextran, wherein the drug is anti-inflammatory It provides a dental drug-release biodegradable fiber chip comprising at least one substance selected from an agent) and antibiotics (antibiotics).
  • the biodegradable fiber may further include one or more biodegradable synthetic polymers selected from polyaniline, polycarbonate, polyethyleneglycol, and polyvinyl alcohol as components. It is preferable that the natural polymer and the biodegradable synthetic polymer have a weight ratio of 1: 0.001 to 1.
  • the biodegradable fiber is composed of polylactic acid (polylactic acid), polyglycolic acid (polyglycolic acid), polylactic acid co-glycolic acid (poly (lactic-co-glycolic acid)), polycaprolactone (polycaprolactone) and poly It may further comprise at least one biodegradable synthetic polymer selected from orthoesters (polyorthoester), the biodegradable natural polymer and the biodegradable synthetic polymer is preferably made of a weight ratio of 1: 0.001 to 1.
  • the cross-linking agent constituting the biodegradable fiber is 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1-ethyl-3- (3-dimethylamino propyl) carbodiimide hydrochloride, hyaluronic acid, pectin, oxidized sucrose, glyceraldehyde, glutaraldehyde, formaldehyde, carbodiimide, crab Nipine (genipin), sugars (sugars), transglutaminase (transglutaminase) and may include one or more materials selected from epoxy compounds (epoxy compounds), the biodegradable natural polymer and the crosslinking agent 1: 0.0001 ⁇ It is desirable to achieve a weight ratio of 0.5.
  • the biodegradable natural polymer and the drug preferably form a weight ratio of 1: 0.001 to 10.
  • the anti-inflammatory agent is ibuprofen (Ibuprofen), Fenoprofen (Fenoprofen), Flurbiprofen (Flurbiprofen), Carprofen (Carprofen), Diclofenac, Difenfenac, Fenbufen, Fenclozic acid (Fenclozic Acid ), Flufenamic Acid, Indomethacin, Indoprofen, Ketoprofen, Lonazolac, Loxoprofen, Meclofenamic Acid ( Meclofenamic Acid, Mefenamic Acid, Naproxen, Proprionic Acids, Salicilic Acid, Sulindac, Tolmetin, Meloxycam And one or more substances selected from Oxycams, Piroxicam, Tenoxicam, Etodolac, and Oxaprozin.
  • Ibuprofen ibuprofen
  • Fenoprofen Flurbiprofen
  • Carprofen Carprofen
  • the antibiotics include chlorohexidine, minocycline, doxycycline, metronidazole, meofidazole, ofloxacin, tetratracycline, tinidazole, and ketonazole Ketonazole).
  • the present invention comprises the steps of (a) adding a biodegradable natural polymer, drug and a cross-linking agent to the solvent to form a mixed solution of the biodegradable natural polymer, drug and cross-linking agent and (b) electrospinning the mixed solution to prepare a fiber sheet in which biodegradable fibers having an average diameter of 0.01 to 100 ⁇ m are entangled in a network form, and (c) punching while compressing the fiber sheet.
  • a fiber chip having a width of 0.5 to 50 mm, a length of 0.5 to 50 mm, and a thickness of 0.05 to 5 mm, wherein the biodegradable natural polymer is gelatin, collagen, alginate.
  • Type 1 It provides a method for producing a dental drug release biodegradable fiber chips comprising the material on.
  • the step (c) is a step of rolling the fiber sheet to form a roll and punching the rolled fiber sheet while compressing the fiber having a width of 0.5 to 50 mm, a length of 0.5 to 50 mm, and a thickness of 0.05 to 5 mm.
  • Forming a chip may include.
  • step (a) one or more biodegradable synthetic polymers selected from polyaniline, polycarbonate, polyethyleneglycol, and polyvinyl alcohol may be further added, and the biodegradable natural It is preferable to add the biodegradable synthetic polymer so that the polymer and the biodegradable synthetic polymer have a weight ratio of 1: 0.001 to 1.
  • polylactic acid polylactic acid
  • polyglycolic acid polyglycolic acid
  • polylactic acid-co-glycolic acid poly (lactic-co-glycolic acid)
  • polycaprolactone polycaprolactone
  • polyorthoester At least one biodegradable synthetic polymer selected from (polyorthoester) may be further added, and the biodegradable synthetic polymer may be added such that the biodegradable natural polymer and the biodegradable synthetic polymer have a weight ratio of 1: 0.001 to 1.
  • the cross-linking agent is 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1-ethyl-3- (3-dimethylamino propyl) carbodiimide hydrochloride), hyaluronic acid , Pectin, oxidized sucrose, glyceraldehyde, glutaraldehyde, formaldehyde, carbodiimide, genipin, sugars It may include one or more materials selected from transglutaminase and epoxy compounds, wherein in step (a) the biodegradable natural polymer and the crosslinking agent is a weight ratio of 1: 0.0001 to 0.5 It is preferable to add to make.
  • the solvent is acetic acid, ethyl acetate, sodium alginate, 1,1,1,3,3,3 nucleofluoro-2-propanol (1,1,1,3, 3,3 hexafluoro-2-propanol), 2,2,2-trifluoroethanol, isopropanol, and formic acid.
  • step (a) the biodegradable natural polymer and the drug are preferably added in a weight ratio of 1: 0.001 to 10.
  • the anti-inflammatory agent is ibuprofen (Ibuprofen), Fenoprofen (Fenoprofen), Flurbiprofen (Flurbiprofen), Carprofen (Carprofen), Diclofenac, Difenfenac, Fenbufen, Fenclozic acid (Fenclozic Acid ), Flufenamic Acid, Indomethacin, Indoprofen, Ketoprofen, Lonazolac, Loxoprofen, Meclofenamic Acid ( Meclofenamic Acid, Mefenamic Acid, Naproxen, Proprionic Acids, Salicilic Acid, Sulindac, Tolmetin, Meloxycam And one or more substances selected from Oxycams, Piroxicam, Tenoxicam, Etodolac, and Oxaprozin.
  • Ibuprofen ibuprofen
  • Fenoprofen Flurbiprofen
  • Carprofen Carprofen
  • the antibiotics include chlorohexidine, minocycline, doxycycline, metronidazole, meofidazole, ofloxacin, tetratracycline, tinidazole, and ketonazole Ketonazole).
  • Dental drug release biodegradable fiber chip of the present invention is capable of sustained drug release, can be used for disinfection, antibiotics and the like.
  • biodegradable fibers form a network (network) structure, not only can be easily inserted or attached to the wound site, but also, the release of the contained drug can be continuously performed for a period of time.
  • Dental drug-release biodegradable fiber chips are excellent in biostability and do not cause side effects even after insertion into animals or human bodies, and allow long-term drug dissolution.
  • Dental drug release biodegradable fiber chip manufacturing method of the present invention has the advantages of a simple manufacturing process, mass production, and excellent reproducibility.
  • FIG. 1 to 3 are field emission scanning electron microscope (FE-SEM) photographs of the fiber sheets prepared according to Experimental Example 1.
  • FIG. 1 to 3 are field emission scanning electron microscope (FE-SEM) photographs of the fiber sheets prepared according to Experimental Example 1.
  • FIG. 4 is a field emission scanning electron microscope (FE-SEM) photograph of the fiber sheet prepared according to Experimental Example 2.
  • FIG. 4 is a field emission scanning electron microscope (FE-SEM) photograph of the fiber sheet prepared according to Experimental Example 2.
  • FIG. 5 is a field emission scanning electron microscope (FE-SEM) photograph of the fiber sheet prepared according to Experimental Example 3.
  • FIG. 5 is a field emission scanning electron microscope (FE-SEM) photograph of the fiber sheet prepared according to Experimental Example 3.
  • FIG. 6 to 8 are field emission scanning electron microscope (FE-SEM) photographs of the fiber sheets prepared according to Experimental Example 4.
  • FIG. 6 to 8 are field emission scanning electron microscope (FE-SEM) photographs of the fiber sheets prepared according to Experimental Example 4.
  • FIG. 9 to 11 are field emission scanning electron microscope (FE-SEM) images of the surface of the drug-release biodegradable fiber chip prepared according to Experimental Example 5.
  • FIG. 9 to 11 are field emission scanning electron microscope (FE-SEM) images of the surface of the drug-release biodegradable fiber chip prepared according to Experimental Example 5.
  • the biodegradable fibers having an average diameter of 0.01 to 100 ⁇ m are entangled in a network form and compressed to be 0.5-50mm wide, 0.5-50mm long and 0.05 thick Forming a fiber chip having a thickness of ⁇ 5 mm, pores are distributed between the biodegradable fibers intertwined in a network form, wherein the biodegradable fibers are composed of a biodegradable natural polymer, a drug and a cross-linking agent as a component.
  • the biodegradable natural polymer includes gelatin, collagen, alginate, chitosan, fibrin, hyaluronic acid, and dextran.
  • the drug includes at least one substance selected from anti-inflammatory agent (anti-inflammatory agent) and antibiotic (antibiotics).
  • the method for preparing a dental drug-release biodegradable fiber chip comprises the steps of: (a) adding a biodegradable natural polymer, drug and a cross-linking agent to the solvent, Forming a mixed solution of a cross-linking agent, and (b) electrospinning the mixed solution to prepare a fiber sheet in which biodegradable fibers having an average diameter of 0.01 to 100 ⁇ m are entangled in a network form.
  • biodegradable natural polymer Includes at least one substance selected from gelatin, collagen, alginate, chitosan, fibrin, hyaluronic acid and dextran, and the drug Silver It includes one or more substances selected from anti-inflammatory agents and antibiotics (antibiotics).
  • the drug is used to mean a substance that is used for therapeutic purposes for humans or animals.
  • Biodegradability is used to mean a property that can be decomposed by a liquid such as water or body fluids, microorganisms such as bacteria, enzymes of other organisms.
  • the biodegradable fibers forming the chip form a network (network), not only can be easily inserted or attached to the wound site, but also mixed with body fluids, so that the flow does not occur at the attached position, so that the biodegradable fibers can effectively work only at the treatment site.
  • the biodegradable fiber itself contains the drug as a component, so that the drug can be released continuously for a certain period of time, and can be used for disinfection and antibiotics.
  • a dental drug-release biodegradable fiber chip capable of prolonged drug dissolution after insertion into the body and a method of manufacturing the same.
  • the biodegradable fibers having an average diameter of 0.01 to 100 ⁇ m are entangled in a network form and compressed to be 0.5-50mm wide, 0.5-50mm long and 0.05 thick Forming a fiber chip having a thickness of ⁇ 5 mm, pores are distributed between the biodegradable fibers intertwined in a network form, wherein the biodegradable fibers are composed of a biodegradable natural polymer, a drug and a cross-linking agent as a component.
  • the biodegradable natural polymer includes gelatin, collagen, alginate, chitosan, fibrin, hyaluronic acid, and dextran.
  • the drug includes at least one substance selected from anti-inflammatory agent (anti-inflammatory agent) and antibiotic (antibiotics).
  • the biodegradable fiber may further include one or more biodegradable synthetic polymers selected from polyaniline, polycarbonate, polyethyleneglycol, and polyvinyl alcohol as components. It is preferable that the natural polymer and the biodegradable synthetic polymer have a weight ratio of 1: 0.001 to 1.
  • the biodegradable synthetic polymer can increase the electrical properties (eg, electrical conductivity) of the biodegradable fibers, and can improve the mechanical properties (eg, tensile strength).
  • the biodegradable fiber is composed of polylactic acid (polylactic acid), polyglycolic acid (polyglycolic acid), polylactic acid co-glycolic acid (poly (lactic-co-glycolic acid)), polycaprolactone (polycaprolactone) and poly It may further comprise at least one biodegradable synthetic polymer selected from orthoesters (polyorthoester), the biodegradable natural polymer and the biodegradable synthetic polymer is preferably made of a weight ratio of 1: 0.001 to 1.
  • the cross-linking agent constituting the biodegradable fiber is 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1-ethyl-3- (3-dimethylamino propyl) carbodiimide hydrochloride, hyaluronic acid, pectin, oxidized sucrose, glyceraldehyde, glutaraldehyde, formaldehyde, carbodiimide, crab Nipine (genipin), sugars (sugars), transglutaminase (transglutaminase) and may include one or more materials selected from epoxy compounds (epoxy compounds), the biodegradable natural polymer and the crosslinking agent 1: 0.0001 ⁇ It is desirable to achieve a weight ratio of 0.5.
  • the biodegradable natural polymer and the drug preferably form a weight ratio of 1: 0.001 to 10.
  • the anti-inflammatory agent is ibuprofen (Ibuprofen), Fenoprofen (Fenoprofen), Flurbiprofen (Flurbiprofen), Carprofen (Carprofen), Diclofenac, Difenfenac, Fenbufen, Fenclozic acid (Fenclozic Acid ), Flufenamic Acid, Indomethacin, Indoprofen, Ketoprofen, Lonazolac, Loxoprofen, Meclofenamic Acid ( Meclofenamic Acid, Mefenamic Acid, Naproxen, Proprionic Acids, Salicilic Acid, Sulindac, Tolmetin, Meloxycam And one or more substances selected from Oxycams, Piroxicam, Tenoxicam, Etodolac, and Oxaprozin.
  • Ibuprofen ibuprofen
  • Fenoprofen Flurbiprofen
  • Carprofen Carprofen
  • the antibiotics include chlorohexidine, minocycline, doxycycline, metronidazole, meofidazole, ofloxacin, tetratracycline, tinidazole, and ketonazole Ketonazole).
  • the method for preparing a dental drug-release biodegradable fiber chip comprises the steps of: (a) adding a biodegradable natural polymer, drug and a cross-linking agent to the solvent, Forming a mixed solution of a cross-linking agent, and (b) electrospinning the mixed solution to prepare a fiber sheet in which biodegradable fibers having an average diameter of 0.01 to 100 ⁇ m are entangled in a network form.
  • biodegradable natural polymer Includes at least one substance selected from gelatin, collagen, alginate, chitosan, fibrin, hyaluronic acid and dextran, and the drug Silver It includes one or more substances selected from anti-inflammatory agents and antibiotics (antibiotics).
  • the step (c) is a step of rolling the fiber sheet to form a roll and punching the rolled fiber sheet while compressing the fiber having a width of 0.5 to 50 mm, a length of 0.5 to 50 mm, and a thickness of 0.05 to 5 mm.
  • Forming a chip may include.
  • step (a) one or more biodegradable synthetic polymers selected from polyaniline, polycarbonate, polyethyleneglycol, and polyvinyl alcohol may be further added, and the biodegradable natural It is preferable to add the biodegradable synthetic polymer so that the polymer and the biodegradable synthetic polymer have a weight ratio of 1: 0.001 to 1.
  • polylactic acid polylactic acid
  • polyglycolic acid polyglycolic acid
  • polylactic acid-co-glycolic acid poly (lactic-co-glycolic acid)
  • polycaprolactone polycaprolactone
  • polyorthoester At least one biodegradable synthetic polymer selected from (polyorthoester) may be further added, and the biodegradable synthetic polymer may be added such that the biodegradable natural polymer and the biodegradable synthetic polymer have a weight ratio of 1: 0.001 to 1.
  • the cross-linking agent is 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1-ethyl-3- (3-dimethylamino propyl) carbodiimide hydrochloride), hyaluronic acid , Pectin, oxidized sucrose, glyceraldehyde, glutaraldehyde, formaldehyde, carbodiimide, genipin, sugars It may include one or more materials selected from transglutaminase and epoxy compounds, wherein in step (a) the biodegradable natural polymer and the crosslinking agent is a weight ratio of 1: 0.0001 to 0.5 It is preferable to add to make.
  • the solvent is acetic acid, ethyl acetate, sodium alginate, 1,1,1,3,3,3 nucleofluoro-2-propanol (1,1,1,3, 3,3 hexafluoro-2-propanol), 2,2,2-trifluoroethanol, isopropanol, and formic acid.
  • step (a) the biodegradable natural polymer and the drug are preferably added in a weight ratio of 1: 0.001 to 10.
  • the anti-inflammatory agent is ibuprofen (Ibuprofen), Fenoprofen (Fenoprofen), Flurbiprofen (Flurbiprofen), Carprofen (Carprofen), Diclofenac, Difenfenac, Fenbufen, Fenclozic acid (Fenclozic Acid ), Flufenamic Acid, Indomethacin, Indoprofen, Ketoprofen, Lonazolac, Loxoprofen, Meclofenamic Acid ( Meclofenamic Acid, Mefenamic Acid, Naproxen, Proprionic Acids, Salicilic Acid, Sulindac, Tolmetin, Meloxycam And one or more substances selected from Oxycams, Piroxicam, Tenoxicam, Etodolac, and Oxaprozin.
  • Ibuprofen ibuprofen
  • Fenoprofen Flurbiprofen
  • Carprofen Carprofen
  • the antibiotics include chlorohexidine, minocycline, doxycycline, metronidazole, meofidazole, ofloxacin, tetratracycline, tinidazole, and ketonazole Ketonazole).
  • a biodegradable natural polymer, drug and a cross-linking agent are added to the solvent to form a mixed solution of the biodegradable natural polymer, drug and a cross-linking agent.
  • biodegradable synthetic polymers selected from polyaniline, polycarbonate, polyethyleneglycol, and polyvinyl alcohol may be further added to the solvent.
  • the biodegradable synthetic polymer may increase the electrical properties (eg, electrical conductivity) of the biodegradable fiber, and improve the mechanical properties (eg, tensile strength)
  • the biodegradable natural polymer and the biodegradable synthesis It is preferable to add the biodegradable synthetic polymer so that the polymer has a weight ratio of 1: 0.001 to 1.
  • the solvent is polylactic acid (polylactic acid), polyglycolic acid (polyglycolic acid), polylactic acid co-glycolic acid (poly (lactic-co-glycolic acid)), polycaprolactone (polycaprolactone) and polyorthoester (polyorthoester)
  • biodegradable synthetic polymer selected from among the above may be further added. It is preferable to add the biodegradable synthetic polymer so that the biodegradable natural polymer and the biodegradable synthetic polymer have a weight ratio of 1: 0.001 to 1.
  • the solvent is acetic acid, ethyl acetate, sodium alginate, 1,1,1,3,3,3 nucleofluoro-2-propanol (1,1,1,3, 3,3 hexafluoro-2-propanol), 2,2,2-trifluoroethanol, isopropanol, formic acid or mixtures thereof and the like.
  • deionized water may be further mixed to adjust the viscosity, stabilize the solvent, and to suppress a sudden phase change of the electrospun material in the collector.
  • the biodegradable natural polymer comprises at least one material selected from gelatin, collagen, alginate, alginate, chitosan, fibrin, hyaluronic acid, and dextran. It may include.
  • collagen in biodegradable natural polymers is used as a hemostatic agent by increasing the concentration of platelets, clumping platelets and activating platelets, and is a protein found in many mammals.
  • the fiber sheet is made of a biodegradable natural polymer, drug and a crosslinking agent as a constituent, and punched into the desired chip shape while compressing to produce a fiber chip, and then implanted into a living body for dental purposes. After this time, the biodegradable natural polymer is naturally absorbed into the living body, which does not need to be removed after transplantation.
  • the drug includes one or more substances selected from anti-inflammatory agents and antibiotics.
  • the anti-inflammatory agent is ibuprofen (Ibuprofen), Fenoprofen (Fenoprofen), Flurbiprofen (Flurbiprofen), Carprofen (Carprofen), Diclofenac, Difenfenac, Fenbufen, Fenclozic acid (Fenclozic Acid ), Flufenamic Acid, Indomethacin, Indoprofen, Ketoprofen, Lonazolac, Loxoprofen, Meclofenamic Acid ( Meclofenamic Acid, Mefenamic Acid, Naproxen, Proprionic Acids, Salicilic Acid, Sulindac, Tolmetin, Meloxycam And one or more substances selected from Oxycams, Piroxicam, Tenoxicam, Etodolac, and Oxaprozin.
  • Ibuprofen ibuprofen
  • Fenoprofen Flurbiprofen
  • Carprofen Carprofen
  • the antibiotics include chlorohexidine, minocycline, doxycycline, metronidazole, meofidazole, ofloxacin, tetratracycline, tinidazole, and ketonazole Ketonazole).
  • the biodegradable natural polymer and the drug are preferably mixed in a weight ratio of 1: 0.001 to 10 (biodegradable natural polymer: drug).
  • the biodegradable natural polymer is preferably added 3 to 300g per 100ml solvent.
  • the cross-linking agent is 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1-ethyl-3- (3-dimethylamino propyl) carbodiimide hydrochloride), hyaluronic acid , Pectin, oxidized sucrose, glyceraldehyde, glutaraldehyde, formaldehyde, carbodiimide, genipin, sugars It may include one or more substances selected from transglutaminase and epoxy compounds.
  • the crosslinking agent cures the biodegradable natural polymer, helps the biodegradable natural polymer and the drug to be mixed with each other to form biodegradable fibers, and helps the biodegradable fibers to form a fiber sheet while forming a network (network) structure.
  • the biodegradable natural polymer and the crosslinking agent are preferably added in a weight ratio of 1: 0.0001 to 0.5 (biodegradable natural polymer: crosslinking agent).
  • the sugars include D-Fructose and D-glucose.
  • biodegradable fibers are formed by using an electrospinning method.
  • Electrospinning is a method in which a biodegradable fiber is formed by spinning a mixed solution of a biodegradable natural polymer, drug and a crosslinking agent through a fine nozzle, and a fiber sheet in which the biodegradable fibers are entangled in a network form is produced.
  • Electrospinning of the biodegradable natural polymer, drug and crosslinking agent was carried out under the conditions of voltage difference 1-100kV, spinning flow rate 0.001-10ml / hr, spinning distance 0.5-50cm, and hole size 0.01-2.0mm.
  • a fiber sheet is produced in which biodegradable fibers are intertwined in the form of a network.
  • the electrospinning method it is possible to control the diameter of the biodegradable fiber including the biodegradable natural polymer, the drug and the crosslinking agent as constituents, and thus to adjust the amount of the drug released after fabrication of the fiber chip in an appropriate amount.
  • biodegradable natural polymer If biodegradable natural polymer is used, it is naturally absorbed into the living body over time, so there is no need for follow-up after treatment such as dental treatment, and since the fiber sheet contains the drug as a component, disinfection, bacteria removal, Effects such as microbial killing can be obtained.
  • the biodegradable fiber produced by the electrospinning method is preferably such that the average diameter has a size of 0.01 to 100 ⁇ m.
  • Electrospinning uses relatively simple equipment.
  • a nozzle is disposed between a first electrode and a second electrode having a first electrode in a mixed solution of a biodegradable natural polymer, a drug and a crosslinking agent, and the other second electrode in a collector, and having opposite polarities to each other.
  • drug and crosslinking agent is emitted and the mixed solution of the biodegradable natural polymer, drug and crosslinking agent is collected in the collector and the solvent is evaporated.
  • the diameter of the biodegradable fiber produced by electrospinning may be controlled by adjusting the pore size of the nozzle for spinning the mixed solution of the biodegradable natural polymer, the drug and the crosslinking agent.
  • a fiber chip having a size suitable for use in dentistry such as 0.5 to 50 mm long, 0.5 to 50 mm long and 0.05 to 5 mm thick, by punching into a desired shape while compressing the fiber sheet produced by electrospinning. It can be formed as.
  • the fiber sheet may be loaded into a puncher to form a fiber chip of a desired shape while compression and cutting are performed together.
  • the fibrous sheet is loaded into a puncher and compressed to allow cutting.
  • Forming a fiber chip by punching the fiber sheet into a desired shape while compressing the fiber sheet may be achieved by laminating a plurality of fiber sheets and by punching while compressing the plurality of stacked fiber sheets by 0.5-50 mm in width and 0.5-50 in length.
  • Forming a fiber chip having a mm and a thickness of 0.05-5 mm For example, a plurality of fibrous sheets are laminated and charged into a puncher to cut while compressing the stacked plurality of fibrous sheets.
  • the step of punching the fiber sheet into a desired shape while compressing the fiber sheet to form a fiber chip may be rolled up to form a roll and rolled the fiber sheet and punched while compressing the rolled fiber sheet to a width of 0.5 to 50 mm.
  • the method may include forming a fiber chip having a length of 0.5 to 50 mm and a thickness of 0.05 to 5 mm. The fiber sheet is rolled up to form a roll and loaded into a puncher to cut the fiber sheet while compressing the rolled fiber sheet.
  • the pressure to be pressed is set in consideration of the thickness of the fiber chip and the like, and preferably about 0.1 to 100 MPa.
  • the fiber sheet was cut into a fiber chip having a size suitable for use in dental work, such as a chip having a width of 0.5-50 mm, a length of 0.5-50 mm, and a thickness of 0.05-5 mm
  • the compression process and the cutting process have to be performed separately, which is not good in terms of process simplification and productivity.
  • the dental drug-release biodegradable fiber chip thus manufactured is compressed into a network in which biodegradable fibers having an average diameter of 0.01 to 100 ⁇ m are entangled in a network form, having a width of 0.5 to 50 mm, a length of 0.5 to 50 mm, and a thickness of 0.05 to 5 mm. Pores are distributed between the biodegradable fibers that make up the fiber chip and are entangled in a network form, and the biodegradable fiber comprises a biodegradable natural polymer, a drug and a cross-linking agent as components.
  • the biodegradable fiber may further include one or more biodegradable synthetic polymers selected from polyaniline, polycarbonate, polyethyleneglycol, and polyvinyl alcohol as components.
  • the biodegradable fiber is composed of polylactic acid (polylactic acid), polyglycolic acid (polyglycolic acid), polylactic acid co-glycolic acid (poly (lactic-co-glycolic acid)), polycaprolactone (polycaprolactone) and poly It may further comprise at least one biodegradable synthetic polymer selected from orthoesters (polyorthoester), the biodegradable natural polymer and the biodegradable synthetic polymer is preferably made of a weight ratio of 1: 0.001 to 1.
  • the drug is eluted from the dental drug-release biodegradable fiber chip, and the eluted drug contains one or more substances selected from anti-inflammatory agents and antibiotics.
  • the dental drug-release biodegradable fiber chip of the present invention is composed of the components constituting the biodegradable fiber drug is capable of continuous drug release, can be used for disinfection, antibiotics and the like.
  • the biodegradable fibers form a network structure, the biodegradable fibers can be easily inserted or attached to the wound site, and the release of the contained drug can be continued for a certain period of time.
  • Dental drug-release biodegradable fiber chips are excellent in biostability and do not cause side effects even after insertion into animals or human bodies, and allow long-term drug dissolution.
  • the biodegradable fiber diameter, drug content and the like of the dental drug-release biodegradable fiber chip By adjusting the biodegradable fiber diameter, drug content and the like of the dental drug-release biodegradable fiber chip, it is possible to deliver the optimal drug dissolution amount to the body of the animal or human body in real time. By determining the content of the drug and the elution (elution) can be delivered to the optimal drug, there is an advantage that can control the drug dissolution amount according to the time.
  • chlorhexidine digluconate 6 ml of chlorhexidine digluconate (CHD), 6 ml of acetic acid as a solvent, and 2 ml of deionized water (DI water) were mixed.
  • the chlorhexidine digluconate (CHD) is a type of chlorhexidine antibiotic.
  • Glutaraldehyde was added to the solution in which gelatin was dissolved to form a mixed solution of biodegradable natural polymer, drug, and a crosslinking agent.
  • the glutaraldehyde was diluted by mixing 1 ml of glutaraldehyde with 9 ml of deionized water, and 0.05 ml was added to the solution in which the gelatin was dissolved. The mixing was performed by stirring for 20 minutes at a speed of about 30 rpm.
  • the biodegradable fibers were subjected to electrospinning under the conditions of a voltage difference of 20 kV, a spinning flow rate of 0.2 to 1.0 ml / hr, a spinning distance of 15 cm, and a nozzle gauge of 23 gage (GA).
  • a voltage difference of 20 kV a voltage difference of 20 kV
  • a spinning flow rate of 0.2 to 1.0 ml / hr a spinning distance of 15 cm
  • a nozzle gauge of 23 gage (GA) To prepare a fiber sheet intertwined in the form of a network.
  • the humidity during electrospinning was about 40% and the temperature was about 22 ° C.
  • the fiber sheet thus prepared consists of a mixture of biodegradable natural polymers, drugs and crosslinkers.
  • FIG. 1 to 3 are field emission scanning electron microscope (FE-SEM) photographs of the fiber sheets prepared according to Experimental Example 1.
  • FIG. 1 to 3 are field emission scanning electron microscope (FE-SEM) photographs of the fiber sheets prepared according to Experimental Example 1.
  • the fiber sheet prepared according to Experimental Example 1 was confirmed that the fine fibers having a diameter of about 669 ⁇ 995 nm is entangled in the form of a network.
  • a mixed solution of a biodegradable natural polymer, a drug and a crosslinking agent was formed in the same manner as in Experimental Example 1, and the mixed solution was subjected to a voltage difference of 20 kV, a spinning flow rate of 0.2 to 1.0 ml / hr, a spinning distance of 15 cm, and a nozzle gauge 25 Electrospinning was performed under the condition of gage (GA) to prepare a fiber sheet in which biodegradable fibers were entangled in a network form. The humidity during electrospinning was about 40% and the temperature was about 22 ° C.
  • FIG. 4 is a field emission scanning electron microscope (FE-SEM) photograph of the fiber sheet prepared according to Experimental Example 2.
  • FIG. 4 is a field emission scanning electron microscope (FE-SEM) photograph of the fiber sheet prepared according to Experimental Example 2.
  • the fiber sheet manufactured according to Experimental Example 2 had fine fibers having a diameter of about 671 nm to 1.37 ⁇ m being entangled in a network form.
  • a mixed solution of a biodegradable natural polymer, drug and a crosslinking agent was formed in the same manner as in Experimental Example 1, and the mixed solution was subjected to a voltage difference of 20 kV, a spinning flow rate of 0.2 to 1.0 ml / hr, a spinning distance of 15 cm, and a nozzle gauge 27 Electrospinning was performed under the condition of gage (GA) to prepare a fiber sheet in which biodegradable fibers were entangled in a network form. The humidity during electrospinning was about 40% and the temperature was about 22 ° C.
  • FIG. 5 is a field emission scanning electron microscope (FE-SEM) photograph of the fiber sheet prepared according to Experimental Example 3.
  • FIG. 5 is a field emission scanning electron microscope (FE-SEM) photograph of the fiber sheet prepared according to Experimental Example 3.
  • the fiber sheet manufactured according to Experimental Example 3 was confirmed that fine fibers having a diameter of about 766 to 996 nm are entangled in a network form.
  • a mixed solution of a biodegradable natural polymer, a drug and a crosslinking agent was formed in the same manner as in Experimental Example 1, and the mixed solution was subjected to a voltage difference of 20 kV, a spinning flow rate of 0.2 to 1.0 ml / hr, a spinning distance of 15 cm, and a nozzle gauge 32 Electrospinning was performed under the condition of gage (GA) to prepare a fiber sheet in which biodegradable fibers were entangled in a network form. The humidity during electrospinning was about 40% and the temperature was about 22 ° C.
  • FIG. 6 to 8 are field emission scanning electron microscope (FE-SEM) photographs of the fiber sheets prepared according to Experimental Example 4.
  • FIG. 6 to 8 are field emission scanning electron microscope (FE-SEM) photographs of the fiber sheets prepared according to Experimental Example 4.
  • the fiber sheets prepared according to Experimental Example 4 had fine fibers having a diameter of about 118.1 to 208.8 nm being entangled in a network form.
  • FIG. 9 to 11 are field emission scanning electron microscope (FE-SEM) images of the surface of the drug-release biodegradable fiber chip prepared according to Experimental Example 5.
  • FIG. 9 to 11 are field emission scanning electron microscope (FE-SEM) images of the surface of the drug-release biodegradable fiber chip prepared according to Experimental Example 5.
  • the dental drug release biodegradable fiber chip of the present invention is capable of sustained drug release, and can be used in the dentistry for disinfection, antibiotic use, and the like.

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Abstract

The present invention relates to: a drug releasing dental biodegradable fiber chip in which biodegradable fibers, which have an average diameter of 0.01-100 μm, are entwined in a network shape and compressed so as to form a fiber chip having a width of 0.5-50 mm, a height of 0.5-50 mm and a thickness of 0.05-5 mm, and pores are distributed between the biodegradable fibers entwined in the network shape, wherein the biodegradable fiber comprises, as constituent components, a biodegradable natural polymer, a drug and a cross-linking agent; and a manufacturing method therefor. According to the present invention, the biodegradable fibers form a network (net) structure so as to be easily insertable into or attachable to a wound site, and even if mixing with a body fluid occurs, flowing does not occur at the attached position, so as to be effectively applicable only at a healing site. In addition, the biodegradable fiber itself contains a drug as a constituent component, thereby enabling the contained drug to be continuously released for a predetermined period, can be used for disinfection, antibiotics and the like, has excellent biostability, has no side effects even after insertion into an animal or human body, and enables a drug to be eluted for a long time.

Description

치과용 약물 방출 생분해성 섬유 칩 및 그 제조방법Dental drug-release biodegradable fiber chips and manufacturing method thereof
본 발명은 약물 방출 생분해성 섬유 칩 및 그 제조방법에 관한 것으로, 더욱 상세하게는 생분해성 섬유가 네트워크(망) 구조를 이루므로 상처 부위에 쉽게 삽입 또는 부착할 수 있을 뿐만 아니라, 체액과 섞이더라도 부착된 위치에서 유동이 발생하지 않으므로 치료 부위에만 효과적으로 작용할 수 있으며, 생분해성 섬유 자체가 약물을 구성성분으로 포함하고 있어 함유된 약물의 방출이 일정기간 동안 지속적으로 이루어질 수 있고, 소독용, 항생제용 등으로 사용할 수 있으며, 생체안정성이 뛰어나고, 동물이나 인체의 신체에 삽입 후에도 부작용이 발생하지 않고, 장기간의 약물 용출이 가능한 치과용 약물 방출 생분해성 섬유 칩 및 그 제조방법에 관한 것이다.The present invention relates to a drug-release biodegradable fiber chip and a method for manufacturing the same, and more particularly, since the biodegradable fibers form a network (network) structure, not only can be easily inserted or attached to the wound site, but also mixed with body fluids. Since the flow does not occur at the attached position, it can effectively work only at the treatment site, and since the biodegradable fiber itself contains the drug as a component, the release of the drug contained can be continuously performed for a certain period of time. The present invention relates to a dental drug-releasing biodegradable fiber chip which can be used as a biodeterminant, has no side effects even after being inserted into an animal or a human body, and enables long-term drug dissolution, and a method of manufacturing the same.
미국 공개공보 2003/0026770은 치주 재생 조성물 및 이를 이용하는 방법(Periodontal regeneration composition and method of using same)을 제시하고 있다. 미국 공개공보 2003/0026770에서는 치주 재생 조성물을 바늘로 주입하여 치주 치료에 사용하고 있다. 그러나, 바늘로 주입하는 방법은 치료를 필요로 하는 사람이 스스로는 할 수 없을 뿐만 아니라 바늘을 이용한 조성물의 주입을 위해서는 고도의 전문적 능력이 요구되며, 주입된 조성물은 체액과 쉽게 섞이게 되므로 주입된 위치에서 유동이 발생할 수 있어 치료 부위에만 효과적으로 작용할 수 없다는 문제점이 있다. U.S. Publication 2003/0026770 discloses periodontal regeneration composition and method of using same. In U.S. Publication 2003/0026770, the periodontal regeneration composition is injected with a needle and used to treat periodontality. However, the needle injection method cannot be performed by a person in need of treatment, and requires a high level of expertise for the injection of the composition using the needle, and the injected composition is easily mixed with body fluids. There is a problem that can occur in the flow can not effectively act only on the treatment site.
치과 수술 후 또는 치료 과정에서 조직유착이나 염증이 주로 발생한다. 조직유착은 상처 부위에서 비정상적인 섬유성 연결조직이 결합되는 것을 말한다. 이러한 조직유착은 시간이 흐름에 따라 자연적으로 분해되기도 하지만 일부의 경우에는 생체 내에 잔류함으로써 후유증을 유발하기도 한다. Tissue adhesion or inflammation occurs mainly after oral surgery. Tissue adhesion refers to the binding of abnormal fibrous connective tissue at the wound site. These tissue adhesions are naturally degraded over time, but in some cases they can remain in vivo and cause sequelae.
이러한 문제점들을 고려하여 본 발명의 발명자들은 약물을 지속적으로 적당량으로 방출할 수 있어 조직유착과 염증 등을 방지할 수 있으면서 상처 부위에만 효과적으로 치료 작용할 수 있는 물질로서 섬유 칩을 연구하였으며, 특허출원이 이루어져 특허등록(대한민국 등록특허공보 제10-1534522호)도 되었다. In consideration of these problems, the inventors of the present invention have studied fiber chips as substances capable of effectively releasing a drug in a continuous amount and effectively treating only wounds while preventing tissue adhesion and inflammation. Patent registration (Korean Registered Patent Publication No. 10-1534522) was also made.
본 발명은 대한민국 등록특허공보 제10-1534522호에 제시된 치과용 약물 방출 생분해성 섬유 칩의 제조방법에 대하여 제조 공정을 더욱 간단하게 하고 대량 생산이 더욱 용이하도록 하며 재현성이 더욱 우수하도록 개선하고 생분해성 섬유 칩의 전기적 또는 기계적 특성 등을 향상시킬 수 있는 방안을 연구하여 개발한 것이다. The present invention provides a simpler manufacturing process, easier mass production, better reproducibility, and improved biodegradability for the method for manufacturing a dental drug-release biodegradable fiber chip as disclosed in Korean Patent Publication No. 10-1534522. It was developed by researching ways to improve the electrical or mechanical properties of fiber chips.
[선행기술문헌][Preceding technical literature]
[특허문헌][Patent Documents]
미국 공개공보 2003/0026770United States Publication 2003/0026770
대한민국 등록특허공보 제10-1534522호Republic of Korea Patent Publication No. 10-1534522
본 발명이 해결하고자 하는 과제는 생분해성 섬유가 네트워크(망) 구조를 이루므로 상처 부위에 쉽게 삽입 또는 부착할 수 있을 뿐만 아니라, 체액과 섞이더라도 부착된 위치에서 유동이 발생하지 않으므로 치료 부위에만 효과적으로 작용할 수 있으며, 생분해성 섬유 자체가 약물을 구성성분으로 포함하고 있어 함유된 약물의 방출이 일정기간 동안 지속적으로 이루어질 수 있고, 소독용, 항생제용 등으로 사용할 수 있으며, 생체안정성이 뛰어나고, 동물이나 인체의 신체에 삽입 후에도 부작용이 발생하지 않고, 장기간의 약물 용출이 가능한 치과용 약물 방출 생분해성 섬유 칩을 제공함에 있다. The problem to be solved by the present invention is that the biodegradable fibers form a network (network) structure, not only can be easily inserted or attached to the wound site, but also mixed with body fluids, so that the flow does not occur at the attached position, so that only the treated area is effectively treated. The biodegradable fiber itself contains the drug as a component, so that the drug can be released continuously for a certain period of time, and can be used for disinfection and antibiotics. The present invention provides a dental drug-release biodegradable fiber chip capable of prolonged drug dissolution without causing side effects even after insertion into the body of a human body.
또한, 본 발명이 해결하고자 하는 과제는 제조 공정이 간단하고, 대량 생산이 가능하며, 재현성이 우수한 치과용 약물 방출 생분해성 섬유 칩의 제조방법을 제공함에 있다.In addition, the problem to be solved by the present invention is to provide a method for manufacturing a dental drug-release biodegradable fiber chip with a simple manufacturing process, mass production, and excellent reproducibility.
본 발명은, 평균 직경이 0.01∼100㎛인 생분해성 섬유들이 네트워크 형태로 얽혀서 압축되어 가로 0.5∼50㎜, 세로 0.5∼50㎜ 및 두께 0.05∼5㎜를 갖는 섬유 칩을 이루고, 네트워크 형태로 얽혀있는 상기 생분해성 섬유들 사이에 기공들이 분포하며, 상기 생분해성 섬유는 생분해성 천연 고분자, 약물 및 가교제(cross-linking agent)를 구성 성분으로 포함하고, 상기 생분해성 천연 고분자는 젤라틴(gelatin), 콜라겐(collagen), 알지네이트(alginate), 키토산(chitosan), 피브린(fibrin), 히알루론산(hyaluronic acid) 및 덱스트란(dextran) 중에서 선택된 1종 이상의 물질을 포함하며, 상기 약물은 항염증제(anti-inflammatory agent) 및 항생제(antibiotics) 중에서 선택된 1종 이상의 물질을 포함하는 것을 특징으로 하는 치과용 약물 방출 생분해성 섬유 칩을 제공한다. According to the present invention, biodegradable fibers having an average diameter of 0.01 to 100 µm are entangled in a network form to form a fiber chip having a width of 0.5 to 50 mm, a length of 0.5 to 50 mm, and a thickness of 0.05 to 5 mm, and entangled in a network form. Pores are distributed between the biodegradable fibers, wherein the biodegradable fibers comprise a biodegradable natural polymer, a drug and a cross-linking agent as constituents, and the biodegradable natural polymer comprises gelatin, It comprises at least one substance selected from collagen, alginate, chitosan, fibrin, fibrin, hyaluronic acid and dextran, wherein the drug is anti-inflammatory It provides a dental drug-release biodegradable fiber chip comprising at least one substance selected from an agent) and antibiotics (antibiotics).
상기 생분해성 섬유는 구성 성분으로 폴리아닐린(polyaniline), 폴리카보네이트(polycarbonate), 폴리에틸렌글리콜(polyethyleneglycol) 및 폴리비닐알콜(polyvinyl alcohol) 중에서 선택된 1종 이상의 생분해성 합성 고분자를 더 포함할 수 있으며, 상기 생분해성 천연 고분자와 상기 생분해성 합성 고분자는 1:0.001∼1의 중량비를 이루는 것이 바람직하다.The biodegradable fiber may further include one or more biodegradable synthetic polymers selected from polyaniline, polycarbonate, polyethyleneglycol, and polyvinyl alcohol as components. It is preferable that the natural polymer and the biodegradable synthetic polymer have a weight ratio of 1: 0.001 to 1.
상기 생분해성 섬유는 구성 성분으로 폴리락트산(polylactic acid), 폴리글리콜산(polyglycolic acid), 폴리락트산-코-글리콜산(poly(lactic-co-glycolic acid)), 폴리카프로락톤(polycaprolactone) 및 폴리오르토에스테르(polyorthoester) 중에서 선택된 1종 이상의 생분해성 합성 고분자를 더 포함할 수 있으며, 상기 생분해성 천연 고분자와 상기 생분해성 합성 고분자는 1:0.001∼1의 중량비를 이루는 것이 바람직하다.The biodegradable fiber is composed of polylactic acid (polylactic acid), polyglycolic acid (polyglycolic acid), polylactic acid co-glycolic acid (poly (lactic-co-glycolic acid)), polycaprolactone (polycaprolactone) and poly It may further comprise at least one biodegradable synthetic polymer selected from orthoesters (polyorthoester), the biodegradable natural polymer and the biodegradable synthetic polymer is preferably made of a weight ratio of 1: 0.001 to 1.
상기 생분해성 섬유의 구성 성분을 이루는 상기 가교제(cross-linking agent)는 1-에틸-3-(3-디메틸아미노프로필)카보디이미드 하이드로클로라이드(1-ethyl-3-(3-dimethylamino propyl) carbodiimide hydrochloride), 히알루론산(hyaluronic acid), 펙틴(pectin), 산화자당(oxidized sucrose), 글리세르알데히드(glyceraldehyde), 글루타르알데히드(glutaraldehyde), 포름알데히드(formaldehyde), 카보디이미드(carbodiimide), 게니핀(genipin), 설탕류(sugars), 트랜스글루타미나아제(transglutaminase) 및 에폭시화합물(epoxy compounds) 중에서 선택된 1종 이상의 물질을 포함할 수 있으며, 상기 생분해성 천연 고분자와 상기 가교제는 1:0.0001∼0.5의 중량비를 이루는 것이 바람직하다.The cross-linking agent constituting the biodegradable fiber is 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1-ethyl-3- (3-dimethylamino propyl) carbodiimide hydrochloride, hyaluronic acid, pectin, oxidized sucrose, glyceraldehyde, glutaraldehyde, formaldehyde, carbodiimide, crab Nipine (genipin), sugars (sugars), transglutaminase (transglutaminase) and may include one or more materials selected from epoxy compounds (epoxy compounds), the biodegradable natural polymer and the crosslinking agent 1: 0.0001∼ It is desirable to achieve a weight ratio of 0.5.
상기 생분해성 천연 고분자와 약물은 1:0.001∼10의 중량비를 이루는 것이 바람직하다.The biodegradable natural polymer and the drug preferably form a weight ratio of 1: 0.001 to 10.
상기 항염증제는 이부프로펜(Ibuprofen), 페노프로펜(Fenoprofen), 플루르비프로펜(Flurbiprofen), 카르프로펜(Carprofen), 디클로페낙(Diclofenac), 펜부펜(Fenbufen), 펜클로즈산((Fenclozic Acid), 플루페남산(Flufenamic Acid), 인도메타신(Indomethacin), 인도프로펜(Indoprofen), 케토프로펜(Ketoprofen), 로나졸락(Lonazolac), 록소프로펜(Loxoprofen), 메클로페남산(Meclofenamic Acid), 메페남산(Mefenamic Acid), 나프록신(Naproxen), 프로프리온산(Proprionic Acids), 살리실산(Salicilic Acid), 설린닥(Sulindac), 톨메틴(Tolmetin), 멜록시캄(Meloxicam), 옥시캄(Oxicams), 피록시캄(Piroxicam), 테녹시캠(Tenoxicam), 에토돌락(Etodolac) 및 옥사프로진(Oxaprozin) 중에서 선택된 1종 이상의 물질을 포함할 수 있다.The anti-inflammatory agent is ibuprofen (Ibuprofen), Fenoprofen (Fenoprofen), Flurbiprofen (Flurbiprofen), Carprofen (Carprofen), Diclofenac, Difenfenac, Fenbufen, Fenclozic acid (Fenclozic Acid ), Flufenamic Acid, Indomethacin, Indoprofen, Ketoprofen, Lonazolac, Loxoprofen, Meclofenamic Acid ( Meclofenamic Acid, Mefenamic Acid, Naproxen, Proprionic Acids, Salicilic Acid, Sulindac, Tolmetin, Meloxycam And one or more substances selected from Oxycams, Piroxicam, Tenoxicam, Etodolac, and Oxaprozin.
상기 항생제는 클로로헥시딘(chlorohexidine), 미노사이클린(minocycline), 독시싸이클린(doxycycline), 메트로니다졸(metronidazole), 오플록사신(ofloxacin), 테트라사이클린(tetracycline), 티니다졸(tinidazole) 및 케토나졸(Ketonazole) 중에서 선택된 1종 이상의 물질을 포함할 수 있다.The antibiotics include chlorohexidine, minocycline, doxycycline, metronidazole, meofidazole, ofloxacin, tetratracycline, tinidazole, and ketonazole Ketonazole).
또한, 본 발명은, (a) 용제에 생분해성 천연 고분자, 약물 및 가교제(cross-linking agent)를 첨가하여 생분해성 천연 고분자, 약물 및 가교제(cross-linking agent)의 혼합용액을 형성하는 단계와, (b) 상기 혼합용액을 전기방사를 실시하여 평균 직경이 0.01∼100㎛인 생분해성 섬유들이 네트워크 형태로 얽혀있는 섬유 시트를 제조하는 단계 및 (c) 상기 섬유 시트를 압축하면서 펀칭(punching)하여 가로 0.5∼50㎜, 세로 0.5∼50㎜ 및 두께 0.05∼5㎜를 갖는 섬유 칩을 형성하는 단계를 포함하며, 상기 생분해성 천연 고분자는 젤라틴(gelatin), 콜라겐(collagen), 알지네이트(alginate), 키토산(chitosan), 피브린(fibrin), 히알루론산(hyaluronic acid) 및 덱스트란(dextran) 중에서 선택된 1종 이상의 물질을 포함하고, 상기 약물은 항염증제(anti-inflammatory agent) 및 항생제(antibiotics) 중에서 선택된 1종 이상의 물질을 포함하는 것을 특징으로 하는 치과용 약물 방출 생분해성 섬유 칩의 제조방법을 제공한다.In addition, the present invention comprises the steps of (a) adding a biodegradable natural polymer, drug and a cross-linking agent to the solvent to form a mixed solution of the biodegradable natural polymer, drug and cross-linking agent and (b) electrospinning the mixed solution to prepare a fiber sheet in which biodegradable fibers having an average diameter of 0.01 to 100 µm are entangled in a network form, and (c) punching while compressing the fiber sheet. Forming a fiber chip having a width of 0.5 to 50 mm, a length of 0.5 to 50 mm, and a thickness of 0.05 to 5 mm, wherein the biodegradable natural polymer is gelatin, collagen, alginate. And at least one substance selected from chitosan, fibrin, hyaluronic acid and dextran, and the drug is selected from an anti-inflammatory agent and an antibiotics. Type 1 It provides a method for producing a dental drug release biodegradable fiber chips comprising the material on.
상기 (c) 단계는, 복수의 섬유 시트를 적층하는 단계 및 적층된 복수의 섬유 시트를 압축하면서 펀칭하여 가로 0.5∼50㎜, 세로 0.5∼50㎜ 및 두께 0.05∼5㎜를 갖는 섬유 칩을 형성하는 단계를 포함할 수 있다.In the step (c), the step of laminating a plurality of fiber sheets and punching the stacked plurality of fiber sheets to form a fiber chip having a width of 0.5 to 50 mm, a length of 0.5 to 50 mm and a thickness of 0.05 to 5 mm It may include the step.
상기 (c) 단계는, 상기 섬유 시트를 말아 감아서 두루마리 형태로 만드는 단계 및 두루마리 형태의 섬유 시트를 압축하면서 펀칭하여 가로 0.5∼50㎜, 세로 0.5∼50㎜ 및 두께 0.05∼5㎜를 갖는 섬유 칩을 형성하는 단계를 포함할 수 있다.The step (c) is a step of rolling the fiber sheet to form a roll and punching the rolled fiber sheet while compressing the fiber having a width of 0.5 to 50 mm, a length of 0.5 to 50 mm, and a thickness of 0.05 to 5 mm. Forming a chip may include.
상기 (a) 단계에서 폴리아닐린(polyaniline), 폴리카보네이트(polycarbonate), 폴리에틸렌글리콜(polyethyleneglycol) 및 폴리비닐알콜(polyvinyl alcohol) 중에서 선택된 1종 이상의 생분해성 합성 고분자를 더 첨가할 수 있고, 상기 생분해성 천연 고분자와 상기 생분해성 합성 고분자가 1:0.001∼1의 중량비를 이루게 상기 생분해성 합성 고분자를 첨가하는 것이 바람직하다.In step (a), one or more biodegradable synthetic polymers selected from polyaniline, polycarbonate, polyethyleneglycol, and polyvinyl alcohol may be further added, and the biodegradable natural It is preferable to add the biodegradable synthetic polymer so that the polymer and the biodegradable synthetic polymer have a weight ratio of 1: 0.001 to 1.
상기 (a) 단계에서 폴리락트산(polylactic acid), 폴리글리콜산(polyglycolic acid), 폴리락트산-코-글리콜산(poly(lactic-co-glycolic acid)), 폴리카프로락톤(polycaprolactone) 및 폴리오르토에스테르(polyorthoester) 중에서 선택된 1종 이상의 생분해성 합성 고분자를 더 첨가할 수 있고, 상기 생분해성 천연 고분자와 상기 생분해성 합성 고분자가 1:0.001∼1의 중량비를 이루게 상기 생분해성 합성 고분자를 첨가하는 것이 바람직하다.In the step (a) polylactic acid (polylactic acid), polyglycolic acid (polyglycolic acid), polylactic acid-co-glycolic acid (poly (lactic-co-glycolic acid)), polycaprolactone (polycaprolactone) and polyorthoester At least one biodegradable synthetic polymer selected from (polyorthoester) may be further added, and the biodegradable synthetic polymer may be added such that the biodegradable natural polymer and the biodegradable synthetic polymer have a weight ratio of 1: 0.001 to 1. Do.
상기 가교제(cross-linking agent)는 1-에틸-3-(3-디메틸아미노프로필)카보디이미드 하이드로클로라이드(1-ethyl-3-(3-dimethylamino propyl) carbodiimide hydrochloride), 히알루론산(hyaluronic acid), 펙틴(pectin), 산화자당(oxidized sucrose), 글리세르알데히드(glyceraldehyde), 글루타르알데히드(glutaraldehyde), 포름알데히드(formaldehyde), 카보디이미드(carbodiimide), 게니핀(genipin), 설탕류(sugars), 트랜스글루타미나아제(transglutaminase) 및 에폭시화합물(epoxy compounds) 중에서 선택된 1종 이상의 물질을 포함할 수 있으며, 상기 (a) 단계에서 상기 생분해성 천연 고분자와 상기 가교제는 1:0.0001∼0.5의 중량비를 이루게 첨가되는 것이 바람직하다.The cross-linking agent is 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1-ethyl-3- (3-dimethylamino propyl) carbodiimide hydrochloride), hyaluronic acid , Pectin, oxidized sucrose, glyceraldehyde, glutaraldehyde, formaldehyde, carbodiimide, genipin, sugars It may include one or more materials selected from transglutaminase and epoxy compounds, wherein in step (a) the biodegradable natural polymer and the crosslinking agent is a weight ratio of 1: 0.0001 to 0.5 It is preferable to add to make.
상기 용제는 아세트산(acetic acid), 에틸아세테이트(ethyl acetate), 알긴산나트륨(sodium alginate), 1,1,1,3,3,3 핵사플루오로-2-프로판올(1,1,1,3,3,3 hexafluoro-2-propanol), 2,2,2-트리플루오로에탄올(2,2,2-trifluoroethanol), 이소프로판올 및 포름산 중에서 선택된 1종 이상의 물질을 포함할 수 있다.The solvent is acetic acid, ethyl acetate, sodium alginate, 1,1,1,3,3,3 nucleofluoro-2-propanol (1,1,1,3, 3,3 hexafluoro-2-propanol), 2,2,2-trifluoroethanol, isopropanol, and formic acid.
상기 (a) 단계에서 상기 생분해성 천연 고분자와 약물은 1:0.001∼10의 중량비를 이루게 첨가되는 것이 바람직하다.In step (a), the biodegradable natural polymer and the drug are preferably added in a weight ratio of 1: 0.001 to 10.
상기 항염증제는 이부프로펜(Ibuprofen), 페노프로펜(Fenoprofen), 플루르비프로펜(Flurbiprofen), 카르프로펜(Carprofen), 디클로페낙(Diclofenac), 펜부펜(Fenbufen), 펜클로즈산((Fenclozic Acid), 플루페남산(Flufenamic Acid), 인도메타신(Indomethacin), 인도프로펜(Indoprofen), 케토프로펜(Ketoprofen), 로나졸락(Lonazolac), 록소프로펜(Loxoprofen), 메클로페남산(Meclofenamic Acid), 메페남산(Mefenamic Acid), 나프록신(Naproxen), 프로프리온산(Proprionic Acids), 살리실산(Salicilic Acid), 설린닥(Sulindac), 톨메틴(Tolmetin), 멜록시캄(Meloxicam), 옥시캄(Oxicams), 피록시캄(Piroxicam), 테녹시캠(Tenoxicam), 에토돌락(Etodolac) 및 옥사프로진(Oxaprozin) 중에서 선택된 1종 이상의 물질을 포함할 수 있다.The anti-inflammatory agent is ibuprofen (Ibuprofen), Fenoprofen (Fenoprofen), Flurbiprofen (Flurbiprofen), Carprofen (Carprofen), Diclofenac, Difenfenac, Fenbufen, Fenclozic acid (Fenclozic Acid ), Flufenamic Acid, Indomethacin, Indoprofen, Ketoprofen, Lonazolac, Loxoprofen, Meclofenamic Acid ( Meclofenamic Acid, Mefenamic Acid, Naproxen, Proprionic Acids, Salicilic Acid, Sulindac, Tolmetin, Meloxycam And one or more substances selected from Oxycams, Piroxicam, Tenoxicam, Etodolac, and Oxaprozin.
상기 항생제는 클로로헥시딘(chlorohexidine), 미노사이클린(minocycline), 독시싸이클린(doxycycline), 메트로니다졸(metronidazole), 오플록사신(ofloxacin), 테트라사이클린(tetracycline), 티니다졸(tinidazole) 및 케토나졸(Ketonazole) 중에서 선택된 1종 이상의 물질을 포함할 수 있다.The antibiotics include chlorohexidine, minocycline, doxycycline, metronidazole, meofidazole, ofloxacin, tetratracycline, tinidazole, and ketonazole Ketonazole).
본 발명의 치과용 약물 방출 생분해성 섬유 칩은 지속적인 약물 방출이 가능하고, 소독용, 항생제용 등으로 사용할 수 있다. Dental drug release biodegradable fiber chip of the present invention is capable of sustained drug release, can be used for disinfection, antibiotics and the like.
생분해성 섬유가 네트워크(망) 구조를 이루므로 상처 부위에 쉽게 삽입 또는 부착할 수 있을 뿐만 아니라, 함유된 약물의 방출이 일정기간 동안 지속적으로 이루어질 수 있는 장점이 있다.Since the biodegradable fibers form a network (network) structure, not only can be easily inserted or attached to the wound site, but also, the release of the contained drug can be continuously performed for a period of time.
치과용 약물 방출 생분해성 섬유 칩이 생체에 삽입되는 경우, 섬유 칩을 제거하거나 하는 등의 후속조치가 필요없는 장점이 있고, 약물의 지속적 방출에 의해 소독, 세균 제거, 미생물 사멸 등과 같은 효과를 얻을 수 있는 장점이 있다.When a drug release biodegradable fiber chip is inserted into a living body, there is an advantage that no further action such as removing the fiber chip is required, and effects such as disinfection, bacteria removal, and microbial death are obtained by continuous release of the drug. There are advantages to it.
치과용 약물 방출 생분해성 섬유 칩은 생체안정성이 뛰어나며, 동물이나 인체의 신체에 삽입 후에도 부작용이 발생하지 않고, 장기간의 약물 용출이 가능하다. Dental drug-release biodegradable fiber chips are excellent in biostability and do not cause side effects even after insertion into animals or human bodies, and allow long-term drug dissolution.
치과용 약물 방출 생분해성 섬유 칩의 섬유 직경, 약물 함량 등을 조절하여 최적의 약물 용출량을 실시간으로 동물 또는 인체의 신체에 전달하는 것이 가능하다. 약물의 함량과 용출(elution)을 파악하여 최적의 약물을 전달할 수 있고, 이를 이용하여 시간에 따라 약물 용출량 제어가 가능한 장점이 있다.It is possible to control the fiber diameter, drug content and the like of the dental drug release biodegradable fiber chip to deliver the optimal drug dissolution amount to the body of the animal or human body in real time. By determining the content of the drug and the elution (elution) can be delivered to the optimal drug, there is an advantage that can control the drug dissolution amount according to the time.
치료할 부위에 쉽게 삽입 또는 부착할 수 있고, 치과 치료를 필요로 하는 사람이 혼자서도 사용할 수 있으며, 치과 치료를 위해 부착된 치과용 약물 방출 생분해성 섬유 칩은 체액과 섞이더라도 부착된 위치에서 유동이 발생하지 않으므로 치료 부위에만 효과적으로 작용할 수 있는 장점이 있다. Easily inserted or attached to the site to be treated, can be used alone by someone in need of dental treatment, and dental drug-release biodegradable fiber chips attached for dental treatment generate flow in the attached position even when mixed with body fluids. It does not have the advantage that it can work effectively only in the treatment area.
본 발명의 치과용 약물 방출 생분해성 섬유 칩 제조방법은 제조 공정이 간단하고, 대량 생산이 가능하며, 재현성이 우수한 장점이 있다.Dental drug release biodegradable fiber chip manufacturing method of the present invention has the advantages of a simple manufacturing process, mass production, and excellent reproducibility.
도 1 내지 도 3은 실험예 1에 따라 제조된 섬유 시트의 전계방출 주사전자현미경(field emission scanning electron microscope; FE-SEM) 사진이다. 1 to 3 are field emission scanning electron microscope (FE-SEM) photographs of the fiber sheets prepared according to Experimental Example 1. FIG.
도 4는 실험예 2에 따라 제조된 섬유 시트의 전계방출 주사전자현미경(FE-SEM) 사진이다. 4 is a field emission scanning electron microscope (FE-SEM) photograph of the fiber sheet prepared according to Experimental Example 2. FIG.
도 5는 실험예 3에 따라 제조된 섬유 시트의 전계방출 주사전자현미경(FE-SEM) 사진이다. 5 is a field emission scanning electron microscope (FE-SEM) photograph of the fiber sheet prepared according to Experimental Example 3. FIG.
도 6 내지 도 8은 실험예 4에 따라 제조된 섬유 시트의 전계방출 주사전자현미경(FE-SEM) 사진이다. 6 to 8 are field emission scanning electron microscope (FE-SEM) photographs of the fiber sheets prepared according to Experimental Example 4. FIG.
도 9 내지 도 11은 실험예 5에 따라 제조된 약물 방출 생분해성 섬유 칩의 표면을 관찰한 전계방출 주사전자현미경(FE-SEM) 사진이다. 9 to 11 are field emission scanning electron microscope (FE-SEM) images of the surface of the drug-release biodegradable fiber chip prepared according to Experimental Example 5. FIG.
본 발명의 바람직한 실시예에 따른 치과용 약물 방출 생분해성 섬유 칩은, 평균 직경이 0.01∼100㎛인 생분해성 섬유들이 네트워크 형태로 얽혀서 압축되어 가로 0.5∼50㎜, 세로 0.5∼50㎜ 및 두께 0.05∼5㎜를 갖는 섬유 칩을 이루고, 네트워크 형태로 얽혀있는 상기 생분해성 섬유들 사이에 기공들이 분포하며, 상기 생분해성 섬유는 생분해성 천연 고분자, 약물 및 가교제(cross-linking agent)를 구성 성분으로 포함하고, 상기 생분해성 천연 고분자는 젤라틴(gelatin), 콜라겐(collagen), 알지네이트(alginate), 키토산(chitosan), 피브린(fibrin), 히알루론산(hyaluronic acid) 및 덱스트란(dextran) 중에서 선택된 1종 이상의 물질을 포함하며, 상기 약물은 항염증제(anti-inflammatory agent) 및 항생제(antibiotics) 중에서 선택된 1종 이상의 물질을 포함한다. Dental drug-release biodegradable fiber chip according to a preferred embodiment of the present invention, the biodegradable fibers having an average diameter of 0.01 to 100㎛ are entangled in a network form and compressed to be 0.5-50mm wide, 0.5-50mm long and 0.05 thick Forming a fiber chip having a thickness of ˜5 mm, pores are distributed between the biodegradable fibers intertwined in a network form, wherein the biodegradable fibers are composed of a biodegradable natural polymer, a drug and a cross-linking agent as a component. The biodegradable natural polymer includes gelatin, collagen, alginate, chitosan, fibrin, hyaluronic acid, and dextran. Including the above substances, the drug includes at least one substance selected from anti-inflammatory agent (anti-inflammatory agent) and antibiotic (antibiotics).
본 발명의 바람직한 실시예에 따른 치과용 약물 방출 생분해성 섬유 칩의 제조방법은, (a) 용제에 생분해성 천연 고분자, 약물 및 가교제(cross-linking agent)를 첨가하여 생분해성 천연 고분자, 약물 및 가교제(cross-linking agent)의 혼합용액을 형성하는 단계와, (b) 상기 혼합용액을 전기방사를 실시하여 평균 직경이 0.01∼100㎛인 생분해성 섬유들이 네트워크 형태로 얽혀있는 섬유 시트를 제조하는 단계 및 (c) 상기 섬유 시트를 압축하면서 펀칭(punching)하여 가로 0.5∼50㎜, 세로 0.5∼50㎜ 및 두께 0.05∼5㎜를 갖는 섬유 칩을 형성하는 단계를 포함하며, 상기 생분해성 천연 고분자는 젤라틴(gelatin), 콜라겐(collagen), 알지네이트(alginate), 키토산(chitosan), 피브린(fibrin), 히알루론산(hyaluronic acid) 및 덱스트란(dextran) 중에서 선택된 1종 이상의 물질을 포함하고, 상기 약물은 항염증제(anti-inflammatory agent) 및 항생제(antibiotics) 중에서 선택된 1종 이상의 물질을 포함한다.The method for preparing a dental drug-release biodegradable fiber chip according to a preferred embodiment of the present invention comprises the steps of: (a) adding a biodegradable natural polymer, drug and a cross-linking agent to the solvent, Forming a mixed solution of a cross-linking agent, and (b) electrospinning the mixed solution to prepare a fiber sheet in which biodegradable fibers having an average diameter of 0.01 to 100 μm are entangled in a network form. And (c) punching the fiber sheet while compacting to form a fiber chip having a width of 0.5 to 50 mm, a length of 0.5 to 50 mm and a thickness of 0.05 to 5 mm, wherein the biodegradable natural polymer Includes at least one substance selected from gelatin, collagen, alginate, chitosan, fibrin, hyaluronic acid and dextran, and the drug Silver It includes one or more substances selected from anti-inflammatory agents and antibiotics (antibiotics).
이하, 첨부된 도면을 참조하여 본 발명에 따른 바람직한 실시예를 상세하게 설명한다. 그러나, 이하의 실시예는 이 기술분야에서 통상적인 지식을 가진 자에게 본 발명이 충분히 이해되도록 제공되는 것으로서 여러 가지 다른 형태로 변형될 수 있으며, 본 발명의 범위가 다음에 기술되는 실시예에 한정되는 것은 아니다. Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings. However, the following embodiments are provided to those skilled in the art to fully understand the present invention, and may be modified in various forms, and the scope of the present invention is limited to the embodiments described below. It doesn't happen.
이하에서, 약물이라 함은 사람 또는 동물에 대하여 치료 목적으로 이용되는 물질을 의미하는 것으로 사용한다. Hereinafter, the drug is used to mean a substance that is used for therapeutic purposes for humans or animals.
생분해성이라 함은 물이나 체액과 같은 액체, 세균 등의 미생물, 다른 생물의 효소 등에 의해서 분해될 수 있는 성질을 의미하는 것으로 사용한다. Biodegradability is used to mean a property that can be decomposed by a liquid such as water or body fluids, microorganisms such as bacteria, enzymes of other organisms.
본 발명은 칩을 이루는 생분해성 섬유가 네트워크(망) 구조를 이루므로 상처 부위에 쉽게 삽입 또는 부착할 수 있을 뿐만 아니라, 체액과 섞이더라도 부착된 위치에서 유동이 발생하지 않으므로 치료 부위에만 효과적으로 작용할 수 있으며, 생분해성 섬유 자체가 약물을 구성성분으로 포함하고 있어 함유된 약물의 방출이 일정기간 동안 지속적으로 이루어질 수 있고, 소독용, 항생제용 등으로 사용할 수 있으며, 생체안정성이 뛰어나고, 동물이나 인체의 신체에 삽입 후에도 부작용이 발생하지 않고, 장기간의 약물 용출이 가능한 치과용 약물 방출 생분해성 섬유 칩 및 그 제조방법을 제시한다. In the present invention, since the biodegradable fibers forming the chip form a network (network), not only can be easily inserted or attached to the wound site, but also mixed with body fluids, so that the flow does not occur at the attached position, so that the biodegradable fibers can effectively work only at the treatment site. The biodegradable fiber itself contains the drug as a component, so that the drug can be released continuously for a certain period of time, and can be used for disinfection and antibiotics. Disclosed is a dental drug-release biodegradable fiber chip capable of prolonged drug dissolution after insertion into the body and a method of manufacturing the same.
본 발명의 바람직한 실시예에 따른 치과용 약물 방출 생분해성 섬유 칩은, 평균 직경이 0.01∼100㎛인 생분해성 섬유들이 네트워크 형태로 얽혀서 압축되어 가로 0.5∼50㎜, 세로 0.5∼50㎜ 및 두께 0.05∼5㎜를 갖는 섬유 칩을 이루고, 네트워크 형태로 얽혀있는 상기 생분해성 섬유들 사이에 기공들이 분포하며, 상기 생분해성 섬유는 생분해성 천연 고분자, 약물 및 가교제(cross-linking agent)를 구성 성분으로 포함하고, 상기 생분해성 천연 고분자는 젤라틴(gelatin), 콜라겐(collagen), 알지네이트(alginate), 키토산(chitosan), 피브린(fibrin), 히알루론산(hyaluronic acid) 및 덱스트란(dextran) 중에서 선택된 1종 이상의 물질을 포함하며, 상기 약물은 항염증제(anti-inflammatory agent) 및 항생제(antibiotics) 중에서 선택된 1종 이상의 물질을 포함한다. Dental drug-release biodegradable fiber chip according to a preferred embodiment of the present invention, the biodegradable fibers having an average diameter of 0.01 to 100㎛ are entangled in a network form and compressed to be 0.5-50mm wide, 0.5-50mm long and 0.05 thick Forming a fiber chip having a thickness of ˜5 mm, pores are distributed between the biodegradable fibers intertwined in a network form, wherein the biodegradable fibers are composed of a biodegradable natural polymer, a drug and a cross-linking agent as a component. The biodegradable natural polymer includes gelatin, collagen, alginate, chitosan, fibrin, hyaluronic acid, and dextran. Including the above substances, the drug includes at least one substance selected from anti-inflammatory agent (anti-inflammatory agent) and antibiotic (antibiotics).
상기 생분해성 섬유는 구성 성분으로 폴리아닐린(polyaniline), 폴리카보네이트(polycarbonate), 폴리에틸렌글리콜(polyethyleneglycol) 및 폴리비닐알콜(polyvinyl alcohol) 중에서 선택된 1종 이상의 생분해성 합성 고분자를 더 포함할 수 있으며, 상기 생분해성 천연 고분자와 상기 생분해성 합성 고분자는 1:0.001∼1의 중량비를 이루는 것이 바람직하다. 상기 생분해성 합성 고분자는 생분해성 섬유의 전기적 특성(예컨대 전기전도도)을 증가시킬 수 있고, 기계적 특성(예컨대, 인장강도(tensile strength)을 향상시킬 수 있다. The biodegradable fiber may further include one or more biodegradable synthetic polymers selected from polyaniline, polycarbonate, polyethyleneglycol, and polyvinyl alcohol as components. It is preferable that the natural polymer and the biodegradable synthetic polymer have a weight ratio of 1: 0.001 to 1. The biodegradable synthetic polymer can increase the electrical properties (eg, electrical conductivity) of the biodegradable fibers, and can improve the mechanical properties (eg, tensile strength).
상기 생분해성 섬유는 구성 성분으로 폴리락트산(polylactic acid), 폴리글리콜산(polyglycolic acid), 폴리락트산-코-글리콜산(poly(lactic-co-glycolic acid)), 폴리카프로락톤(polycaprolactone) 및 폴리오르토에스테르(polyorthoester) 중에서 선택된 1종 이상의 생분해성 합성 고분자를 더 포함할 수 있으며, 상기 생분해성 천연 고분자와 상기 생분해성 합성 고분자는 1:0.001∼1의 중량비를 이루는 것이 바람직하다.The biodegradable fiber is composed of polylactic acid (polylactic acid), polyglycolic acid (polyglycolic acid), polylactic acid co-glycolic acid (poly (lactic-co-glycolic acid)), polycaprolactone (polycaprolactone) and poly It may further comprise at least one biodegradable synthetic polymer selected from orthoesters (polyorthoester), the biodegradable natural polymer and the biodegradable synthetic polymer is preferably made of a weight ratio of 1: 0.001 to 1.
상기 생분해성 섬유의 구성 성분을 이루는 상기 가교제(cross-linking agent)는 1-에틸-3-(3-디메틸아미노프로필)카보디이미드 하이드로클로라이드(1-ethyl-3-(3-dimethylamino propyl) carbodiimide hydrochloride), 히알루론산(hyaluronic acid), 펙틴(pectin), 산화자당(oxidized sucrose), 글리세르알데히드(glyceraldehyde), 글루타르알데히드(glutaraldehyde), 포름알데히드(formaldehyde), 카보디이미드(carbodiimide), 게니핀(genipin), 설탕류(sugars), 트랜스글루타미나아제(transglutaminase) 및 에폭시화합물(epoxy compounds) 중에서 선택된 1종 이상의 물질을 포함할 수 있으며, 상기 생분해성 천연 고분자와 상기 가교제는 1:0.0001∼0.5의 중량비를 이루는 것이 바람직하다.The cross-linking agent constituting the biodegradable fiber is 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1-ethyl-3- (3-dimethylamino propyl) carbodiimide hydrochloride, hyaluronic acid, pectin, oxidized sucrose, glyceraldehyde, glutaraldehyde, formaldehyde, carbodiimide, crab Nipine (genipin), sugars (sugars), transglutaminase (transglutaminase) and may include one or more materials selected from epoxy compounds (epoxy compounds), the biodegradable natural polymer and the crosslinking agent 1: 0.0001∼ It is desirable to achieve a weight ratio of 0.5.
상기 생분해성 천연 고분자와 약물은 1:0.001∼10의 중량비를 이루는 것이 바람직하다.The biodegradable natural polymer and the drug preferably form a weight ratio of 1: 0.001 to 10.
상기 항염증제는 이부프로펜(Ibuprofen), 페노프로펜(Fenoprofen), 플루르비프로펜(Flurbiprofen), 카르프로펜(Carprofen), 디클로페낙(Diclofenac), 펜부펜(Fenbufen), 펜클로즈산((Fenclozic Acid), 플루페남산(Flufenamic Acid), 인도메타신(Indomethacin), 인도프로펜(Indoprofen), 케토프로펜(Ketoprofen), 로나졸락(Lonazolac), 록소프로펜(Loxoprofen), 메클로페남산(Meclofenamic Acid), 메페남산(Mefenamic Acid), 나프록신(Naproxen), 프로프리온산(Proprionic Acids), 살리실산(Salicilic Acid), 설린닥(Sulindac), 톨메틴(Tolmetin), 멜록시캄(Meloxicam), 옥시캄(Oxicams), 피록시캄(Piroxicam), 테녹시캠(Tenoxicam), 에토돌락(Etodolac) 및 옥사프로진(Oxaprozin) 중에서 선택된 1종 이상의 물질을 포함할 수 있다.The anti-inflammatory agent is ibuprofen (Ibuprofen), Fenoprofen (Fenoprofen), Flurbiprofen (Flurbiprofen), Carprofen (Carprofen), Diclofenac, Difenfenac, Fenbufen, Fenclozic acid (Fenclozic Acid ), Flufenamic Acid, Indomethacin, Indoprofen, Ketoprofen, Lonazolac, Loxoprofen, Meclofenamic Acid ( Meclofenamic Acid, Mefenamic Acid, Naproxen, Proprionic Acids, Salicilic Acid, Sulindac, Tolmetin, Meloxycam And one or more substances selected from Oxycams, Piroxicam, Tenoxicam, Etodolac, and Oxaprozin.
상기 항생제는 클로로헥시딘(chlorohexidine), 미노사이클린(minocycline), 독시싸이클린(doxycycline), 메트로니다졸(metronidazole), 오플록사신(ofloxacin), 테트라사이클린(tetracycline), 티니다졸(tinidazole) 및 케토나졸(Ketonazole) 중에서 선택된 1종 이상의 물질을 포함할 수 있다.The antibiotics include chlorohexidine, minocycline, doxycycline, metronidazole, meofidazole, ofloxacin, tetratracycline, tinidazole, and ketonazole Ketonazole).
본 발명의 바람직한 실시예에 따른 치과용 약물 방출 생분해성 섬유 칩의 제조방법은, (a) 용제에 생분해성 천연 고분자, 약물 및 가교제(cross-linking agent)를 첨가하여 생분해성 천연 고분자, 약물 및 가교제(cross-linking agent)의 혼합용액을 형성하는 단계와, (b) 상기 혼합용액을 전기방사를 실시하여 평균 직경이 0.01∼100㎛인 생분해성 섬유들이 네트워크 형태로 얽혀있는 섬유 시트를 제조하는 단계 및 (c) 상기 섬유 시트를 압축하면서 펀칭(punching)하여 가로 0.5∼50㎜, 세로 0.5∼50㎜ 및 두께 0.05∼5㎜를 갖는 섬유 칩을 형성하는 단계를 포함하며, 상기 생분해성 천연 고분자는 젤라틴(gelatin), 콜라겐(collagen), 알지네이트(alginate), 키토산(chitosan), 피브린(fibrin), 히알루론산(hyaluronic acid) 및 덱스트란(dextran) 중에서 선택된 1종 이상의 물질을 포함하고, 상기 약물은 항염증제(anti-inflammatory agent) 및 항생제(antibiotics) 중에서 선택된 1종 이상의 물질을 포함한다.The method for preparing a dental drug-release biodegradable fiber chip according to a preferred embodiment of the present invention comprises the steps of: (a) adding a biodegradable natural polymer, drug and a cross-linking agent to the solvent, Forming a mixed solution of a cross-linking agent, and (b) electrospinning the mixed solution to prepare a fiber sheet in which biodegradable fibers having an average diameter of 0.01 to 100 μm are entangled in a network form. And (c) punching the fiber sheet while compacting to form a fiber chip having a width of 0.5 to 50 mm, a length of 0.5 to 50 mm and a thickness of 0.05 to 5 mm, wherein the biodegradable natural polymer Includes at least one substance selected from gelatin, collagen, alginate, chitosan, fibrin, hyaluronic acid and dextran, and the drug Silver It includes one or more substances selected from anti-inflammatory agents and antibiotics (antibiotics).
상기 (c) 단계는, 복수의 섬유 시트를 적층하는 단계 및 적층된 복수의 섬유 시트를 압축하면서 펀칭하여 가로 0.5∼50㎜, 세로 0.5∼50㎜ 및 두께 0.05∼5㎜를 갖는 섬유 칩을 형성하는 단계를 포함할 수 있다.In the step (c), the step of laminating a plurality of fiber sheets and punching the stacked plurality of fiber sheets to form a fiber chip having a width of 0.5 to 50 mm, a length of 0.5 to 50 mm and a thickness of 0.05 to 5 mm It may include the step.
상기 (c) 단계는, 상기 섬유 시트를 말아 감아서 두루마리 형태로 만드는 단계 및 두루마리 형태의 섬유 시트를 압축하면서 펀칭하여 가로 0.5∼50㎜, 세로 0.5∼50㎜ 및 두께 0.05∼5㎜를 갖는 섬유 칩을 형성하는 단계를 포함할 수 있다.The step (c) is a step of rolling the fiber sheet to form a roll and punching the rolled fiber sheet while compressing the fiber having a width of 0.5 to 50 mm, a length of 0.5 to 50 mm, and a thickness of 0.05 to 5 mm. Forming a chip may include.
상기 (a) 단계에서 폴리아닐린(polyaniline), 폴리카보네이트(polycarbonate), 폴리에틸렌글리콜(polyethyleneglycol) 및 폴리비닐알콜(polyvinyl alcohol) 중에서 선택된 1종 이상의 생분해성 합성 고분자를 더 첨가할 수 있고, 상기 생분해성 천연 고분자와 상기 생분해성 합성 고분자가 1:0.001∼1의 중량비를 이루게 상기 생분해성 합성 고분자를 첨가하는 것이 바람직하다.In step (a), one or more biodegradable synthetic polymers selected from polyaniline, polycarbonate, polyethyleneglycol, and polyvinyl alcohol may be further added, and the biodegradable natural It is preferable to add the biodegradable synthetic polymer so that the polymer and the biodegradable synthetic polymer have a weight ratio of 1: 0.001 to 1.
상기 (a) 단계에서 폴리락트산(polylactic acid), 폴리글리콜산(polyglycolic acid), 폴리락트산-코-글리콜산(poly(lactic-co-glycolic acid)), 폴리카프로락톤(polycaprolactone) 및 폴리오르토에스테르(polyorthoester) 중에서 선택된 1종 이상의 생분해성 합성 고분자를 더 첨가할 수 있고, 상기 생분해성 천연 고분자와 상기 생분해성 합성 고분자가 1:0.001∼1의 중량비를 이루게 상기 생분해성 합성 고분자를 첨가하는 것이 바람직하다.In the step (a) polylactic acid (polylactic acid), polyglycolic acid (polyglycolic acid), polylactic acid-co-glycolic acid (poly (lactic-co-glycolic acid)), polycaprolactone (polycaprolactone) and polyorthoester At least one biodegradable synthetic polymer selected from (polyorthoester) may be further added, and the biodegradable synthetic polymer may be added such that the biodegradable natural polymer and the biodegradable synthetic polymer have a weight ratio of 1: 0.001 to 1. Do.
상기 가교제(cross-linking agent)는 1-에틸-3-(3-디메틸아미노프로필)카보디이미드 하이드로클로라이드(1-ethyl-3-(3-dimethylamino propyl) carbodiimide hydrochloride), 히알루론산(hyaluronic acid), 펙틴(pectin), 산화자당(oxidized sucrose), 글리세르알데히드(glyceraldehyde), 글루타르알데히드(glutaraldehyde), 포름알데히드(formaldehyde), 카보디이미드(carbodiimide), 게니핀(genipin), 설탕류(sugars), 트랜스글루타미나아제(transglutaminase) 및 에폭시화합물(epoxy compounds) 중에서 선택된 1종 이상의 물질을 포함할 수 있으며, 상기 (a) 단계에서 상기 생분해성 천연 고분자와 상기 가교제는 1:0.0001∼0.5의 중량비를 이루게 첨가되는 것이 바람직하다.The cross-linking agent is 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1-ethyl-3- (3-dimethylamino propyl) carbodiimide hydrochloride), hyaluronic acid , Pectin, oxidized sucrose, glyceraldehyde, glutaraldehyde, formaldehyde, carbodiimide, genipin, sugars It may include one or more materials selected from transglutaminase and epoxy compounds, wherein in step (a) the biodegradable natural polymer and the crosslinking agent is a weight ratio of 1: 0.0001 to 0.5 It is preferable to add to make.
상기 용제는 아세트산(acetic acid), 에틸아세테이트(ethyl acetate), 알긴산나트륨(sodium alginate), 1,1,1,3,3,3 핵사플루오로-2-프로판올(1,1,1,3,3,3 hexafluoro-2-propanol), 2,2,2-트리플루오로에탄올(2,2,2-trifluoroethanol), 이소프로판올 및 포름산 중에서 선택된 1종 이상의 물질을 포함할 수 있다.The solvent is acetic acid, ethyl acetate, sodium alginate, 1,1,1,3,3,3 nucleofluoro-2-propanol (1,1,1,3, 3,3 hexafluoro-2-propanol), 2,2,2-trifluoroethanol, isopropanol, and formic acid.
상기 (a) 단계에서 상기 생분해성 천연 고분자와 약물은 1:0.001∼10의 중량비를 이루게 첨가되는 것이 바람직하다.In step (a), the biodegradable natural polymer and the drug are preferably added in a weight ratio of 1: 0.001 to 10.
상기 항염증제는 이부프로펜(Ibuprofen), 페노프로펜(Fenoprofen), 플루르비프로펜(Flurbiprofen), 카르프로펜(Carprofen), 디클로페낙(Diclofenac), 펜부펜(Fenbufen), 펜클로즈산((Fenclozic Acid), 플루페남산(Flufenamic Acid), 인도메타신(Indomethacin), 인도프로펜(Indoprofen), 케토프로펜(Ketoprofen), 로나졸락(Lonazolac), 록소프로펜(Loxoprofen), 메클로페남산(Meclofenamic Acid), 메페남산(Mefenamic Acid), 나프록신(Naproxen), 프로프리온산(Proprionic Acids), 살리실산(Salicilic Acid), 설린닥(Sulindac), 톨메틴(Tolmetin), 멜록시캄(Meloxicam), 옥시캄(Oxicams), 피록시캄(Piroxicam), 테녹시캠(Tenoxicam), 에토돌락(Etodolac) 및 옥사프로진(Oxaprozin) 중에서 선택된 1종 이상의 물질을 포함할 수 있다.The anti-inflammatory agent is ibuprofen (Ibuprofen), Fenoprofen (Fenoprofen), Flurbiprofen (Flurbiprofen), Carprofen (Carprofen), Diclofenac, Difenfenac, Fenbufen, Fenclozic acid (Fenclozic Acid ), Flufenamic Acid, Indomethacin, Indoprofen, Ketoprofen, Lonazolac, Loxoprofen, Meclofenamic Acid ( Meclofenamic Acid, Mefenamic Acid, Naproxen, Proprionic Acids, Salicilic Acid, Sulindac, Tolmetin, Meloxycam And one or more substances selected from Oxycams, Piroxicam, Tenoxicam, Etodolac, and Oxaprozin.
상기 항생제는 클로로헥시딘(chlorohexidine), 미노사이클린(minocycline), 독시싸이클린(doxycycline), 메트로니다졸(metronidazole), 오플록사신(ofloxacin), 테트라사이클린(tetracycline), 티니다졸(tinidazole) 및 케토나졸(Ketonazole) 중에서 선택된 1종 이상의 물질을 포함할 수 있다.The antibiotics include chlorohexidine, minocycline, doxycycline, metronidazole, meofidazole, ofloxacin, tetratracycline, tinidazole, and ketonazole Ketonazole).
이하에서, 본 발명의 바람직한 실시예에 따른 치과용 약물 방출 생분해성 섬유 칩의 제조방법을 더욱 구체적으로 설명한다. Hereinafter, a method for manufacturing a dental drug-release biodegradable fiber chip according to a preferred embodiment of the present invention will be described in more detail.
용제에 생분해성 천연 고분자, 약물 및 가교제(cross-linking agent)를 첨가하여 생분해성 천연 고분자, 약물 및 가교제(cross-linking agent)의 혼합용액을 형성한다.A biodegradable natural polymer, drug and a cross-linking agent are added to the solvent to form a mixed solution of the biodegradable natural polymer, drug and a cross-linking agent.
상기 용제에 폴리아닐린(polyaniline), 폴리카보네이트(polycarbonate), 폴리에틸렌글리콜(polyethyleneglycol) 및 폴리비닐알콜(polyvinyl alcohol) 중에서 선택된 1종 이상의 생분해성 합성 고분자를 더 첨가할 수 있다. 상기 생분해성 합성 고분자는 생분해성 섬유의 전기적 특성(예컨대 전기전도도)을 증가시킬 수 있고, 기계적 특성(예컨대, 인장강도(tensile strength)을 향상시킬 수 있다. 상기 생분해성 천연 고분자와 상기 생분해성 합성 고분자가 1:0.001∼1의 중량비를 이루게 상기 생분해성 합성 고분자를 첨가하는 것이 바람직하다.One or more biodegradable synthetic polymers selected from polyaniline, polycarbonate, polyethyleneglycol, and polyvinyl alcohol may be further added to the solvent. The biodegradable synthetic polymer may increase the electrical properties (eg, electrical conductivity) of the biodegradable fiber, and improve the mechanical properties (eg, tensile strength) The biodegradable natural polymer and the biodegradable synthesis It is preferable to add the biodegradable synthetic polymer so that the polymer has a weight ratio of 1: 0.001 to 1.
상기 용제에 폴리락트산(polylactic acid), 폴리글리콜산(polyglycolic acid), 폴리락트산-코-글리콜산(poly(lactic-co-glycolic acid)), 폴리카프로락톤(polycaprolactone) 및 폴리오르토에스테르(polyorthoester) 중에서 선택된 1종 이상의 생분해성 합성 고분자를 더 첨가할 수도 있다. 상기 생분해성 천연 고분자와 상기 생분해성 합성 고분자가 1:0.001∼1의 중량비를 이루게 상기 생분해성 합성 고분자를 첨가하는 것이 바람직하다.The solvent is polylactic acid (polylactic acid), polyglycolic acid (polyglycolic acid), polylactic acid co-glycolic acid (poly (lactic-co-glycolic acid)), polycaprolactone (polycaprolactone) and polyorthoester (polyorthoester) At least one biodegradable synthetic polymer selected from among the above may be further added. It is preferable to add the biodegradable synthetic polymer so that the biodegradable natural polymer and the biodegradable synthetic polymer have a weight ratio of 1: 0.001 to 1.
상기 용제는 아세트산(acetic acid), 에틸아세테이트(ethyl acetate), 알긴산나트륨(sodium alginate), 1,1,1,3,3,3 핵사플루오로-2-프로판올(1,1,1,3,3,3 hexafluoro-2-propanol), 2,2,2-트리플루오로에탄올(2,2,2-trifluoroethanol), 이소프로판올, 포름산 또는 이들의 혼합물 등일 수 있다. 상기 용제에는 점도를 조절하고 용제의 안정화를 도모하며 전기 방사된 물질이 컬렉터에서 급격하게 상변화되는 것을 억제하기 위하여 탈이온수(deionized water)가 더 혼합될 수 있다. The solvent is acetic acid, ethyl acetate, sodium alginate, 1,1,1,3,3,3 nucleofluoro-2-propanol (1,1,1,3, 3,3 hexafluoro-2-propanol), 2,2,2-trifluoroethanol, isopropanol, formic acid or mixtures thereof and the like. In the solvent, deionized water may be further mixed to adjust the viscosity, stabilize the solvent, and to suppress a sudden phase change of the electrospun material in the collector.
상기 생분해성 천연 고분자는 젤라틴(gelatin), 콜라겐(collagen), 알지네이트(alginate), 키토산(chitosan), 피브린(fibrin), 히알루론산(hyaluronic acid) 및 덱스트란(dextran) 중에서 선택된 1종 이상의 물질을 포함할 수 있다. 예컨대, 생분해성 천연 고분자 중 콜라겐은 혈소판의 농도를 증가시키고, 혈소판을 뭉치게 하고 혈소판을 활성화시켜 지혈제로도 사용되며, 포유동물에 많이 있는 단백질이다. 생분해성 천연 고분자, 약물 및 가교제를 구성성분으로 포함하는 섬유 시트로 제작하고, 압축하면서 원하는 칩 형태로 펀칭(punching)하여 섬유 칩을 제작한 후, 치과용으로 생체에 이식 등을 하게 되면, 시간이 지나게 되면 생분해성 천연 고분자는 자연적으로 생체에 흡수되게 되므로 이식 후에 별도로 제거할 필요가 없는 장점이 있다. The biodegradable natural polymer comprises at least one material selected from gelatin, collagen, alginate, alginate, chitosan, fibrin, hyaluronic acid, and dextran. It may include. For example, collagen in biodegradable natural polymers is used as a hemostatic agent by increasing the concentration of platelets, clumping platelets and activating platelets, and is a protein found in many mammals. When the fiber sheet is made of a biodegradable natural polymer, drug and a crosslinking agent as a constituent, and punched into the desired chip shape while compressing to produce a fiber chip, and then implanted into a living body for dental purposes. After this time, the biodegradable natural polymer is naturally absorbed into the living body, which does not need to be removed after transplantation.
상기 약물은 항염증제(anti-inflammatory agent) 및 항생제(antibiotics) 중에서 선택된 1종 이상의 물질을 포함한다. The drug includes one or more substances selected from anti-inflammatory agents and antibiotics.
상기 항염증제는 이부프로펜(Ibuprofen), 페노프로펜(Fenoprofen), 플루르비프로펜(Flurbiprofen), 카르프로펜(Carprofen), 디클로페낙(Diclofenac), 펜부펜(Fenbufen), 펜클로즈산((Fenclozic Acid), 플루페남산(Flufenamic Acid), 인도메타신(Indomethacin), 인도프로펜(Indoprofen), 케토프로펜(Ketoprofen), 로나졸락(Lonazolac), 록소프로펜(Loxoprofen), 메클로페남산(Meclofenamic Acid), 메페남산(Mefenamic Acid), 나프록신(Naproxen), 프로프리온산(Proprionic Acids), 살리실산(Salicilic Acid), 설린닥(Sulindac), 톨메틴(Tolmetin), 멜록시캄(Meloxicam), 옥시캄(Oxicams), 피록시캄(Piroxicam), 테녹시캠(Tenoxicam), 에토돌락(Etodolac) 및 옥사프로진(Oxaprozin) 중에서 선택된 1종 이상의 물질을 포함할 수 있다.The anti-inflammatory agent is ibuprofen (Ibuprofen), Fenoprofen (Fenoprofen), Flurbiprofen (Flurbiprofen), Carprofen (Carprofen), Diclofenac, Difenfenac, Fenbufen, Fenclozic acid (Fenclozic Acid ), Flufenamic Acid, Indomethacin, Indoprofen, Ketoprofen, Lonazolac, Loxoprofen, Meclofenamic Acid ( Meclofenamic Acid, Mefenamic Acid, Naproxen, Proprionic Acids, Salicilic Acid, Sulindac, Tolmetin, Meloxycam And one or more substances selected from Oxycams, Piroxicam, Tenoxicam, Etodolac, and Oxaprozin.
상기 항생제는 클로로헥시딘(chlorohexidine), 미노사이클린(minocycline), 독시싸이클린(doxycycline), 메트로니다졸(metronidazole), 오플록사신(ofloxacin), 테트라사이클린(tetracycline), 티니다졸(tinidazole) 및 케토나졸(Ketonazole) 중에서 선택된 1종 이상의 물질을 포함할 수 있다.The antibiotics include chlorohexidine, minocycline, doxycycline, metronidazole, meofidazole, ofloxacin, tetratracycline, tinidazole, and ketonazole Ketonazole).
상기 생분해성 천연 고분자와 약물은 1:0.001∼10(생분해성 천연 고분자:약물)의 중량비로 혼합하는 것이 바람직하다. 상기 생분해성 천연 고분자는 용제 100㎖당 3∼300g을 첨가하는 것이 바람직하다. The biodegradable natural polymer and the drug are preferably mixed in a weight ratio of 1: 0.001 to 10 (biodegradable natural polymer: drug). The biodegradable natural polymer is preferably added 3 to 300g per 100ml solvent.
상기 가교제(cross-linking agent)는 1-에틸-3-(3-디메틸아미노프로필)카보디이미드 하이드로클로라이드(1-ethyl-3-(3-dimethylamino propyl) carbodiimide hydrochloride), 히알루론산(hyaluronic acid), 펙틴(pectin), 산화자당(oxidized sucrose), 글리세르알데히드(glyceraldehyde), 글루타르알데히드(glutaraldehyde), 포름알데히드(formaldehyde), 카보디이미드(carbodiimide), 게니핀(genipin), 설탕류(sugars), 트랜스글루타미나아제(transglutaminase) 및 에폭시화합물(epoxy compounds) 중에서 선택된 1종 이상의 물질을 포함할 수 있다. 상기 가교제는 생분해성 천연 고분자를 경화시키고, 생분해성 천연 고분자와 약물이 서로 혼화되어 생분해성 섬유를 형성하는데 도움을 주며, 생분해성 섬유가 네트워크(망) 구조를 이루면서 섬유 시트를 형성하게 하는데 도움을 준다. 상기 생분해성 천연 고분자와 상기 가교제는 1:0.0001∼0.5(생분해성 천연 고분자:가교제)의 중량비를 이루게 첨가되는 것이 바람직하다. 상기 설탕류는 D-프럭토스(D-Fructose), D-글루코스(D-glucose) 등을 그 예로 들 수 있다. The cross-linking agent is 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1-ethyl-3- (3-dimethylamino propyl) carbodiimide hydrochloride), hyaluronic acid , Pectin, oxidized sucrose, glyceraldehyde, glutaraldehyde, formaldehyde, carbodiimide, genipin, sugars It may include one or more substances selected from transglutaminase and epoxy compounds. The crosslinking agent cures the biodegradable natural polymer, helps the biodegradable natural polymer and the drug to be mixed with each other to form biodegradable fibers, and helps the biodegradable fibers to form a fiber sheet while forming a network (network) structure. give. The biodegradable natural polymer and the crosslinking agent are preferably added in a weight ratio of 1: 0.0001 to 0.5 (biodegradable natural polymer: crosslinking agent). Examples of the sugars include D-Fructose and D-glucose.
상기 혼합용액을 전기방사를 실시하여 생분해성 섬유가 네트워크 형태로 얽혀있는 섬유 시트를 제조한다. Electrospinning the mixed solution to produce a fiber sheet in which the biodegradable fibers are entangled in a network form.
본 발명에서는 전기방사법을 이용하여 생분해성 섬유를 형성한다. 전기방사법은 미세한 노즐을 통해 생분해성 천연 고분자, 약물 및 가교제의 혼합용액이 방사되면서 생분해성 섬유가 형성되고, 상기 생분해성 섬유가 네트워크(network) 형태로 얽혀있는 섬유 시트를 생산할 수 있는 방법이다. In the present invention, biodegradable fibers are formed by using an electrospinning method. Electrospinning is a method in which a biodegradable fiber is formed by spinning a mixed solution of a biodegradable natural polymer, drug and a crosslinking agent through a fine nozzle, and a fiber sheet in which the biodegradable fibers are entangled in a network form is produced.
생분해성 천연 고분자, 약물 및 가교제의 혼합용액을 전압차 1∼100kV, 방사 유속 0.001∼10㎖/hr, 방사 거리 0.5∼50㎝, 노즐의 구멍 크기 0.01∼2.0㎜의 조건으로 전기방사를 실시하여 생분해성 섬유가 네트워크 형태로 얽혀있는 섬유 시트를 제조한다. Electrospinning of the biodegradable natural polymer, drug and crosslinking agent was carried out under the conditions of voltage difference 1-100kV, spinning flow rate 0.001-10ml / hr, spinning distance 0.5-50cm, and hole size 0.01-2.0mm. A fiber sheet is produced in which biodegradable fibers are intertwined in the form of a network.
전기방사법을 사용함으로써 생분해성 천연 고분자, 약물 및 가교제를 구성 성분으로 포함하는 생분해성 섬유의 직경을 조절할 수 있고, 이에 따라 섬유 칩 제작 후 방출되는 약물의 양을 적당량으로 조절가능하다.By using the electrospinning method, it is possible to control the diameter of the biodegradable fiber including the biodegradable natural polymer, the drug and the crosslinking agent as constituents, and thus to adjust the amount of the drug released after fabrication of the fiber chip in an appropriate amount.
생분해성 천연 고분자를 사용할 경우, 시간이 지나게 되면 자연적으로 생체에 흡수되게 되므로 치과 치료 등의 처치 후 후속조치가 필요없는 장점이 있으며, 섬유 시트는 약물을 구성성분으로 포함하고 있으므로 소독, 세균 제거, 미생물 사멸 등과 같은 효과를 얻을 수 있다.If biodegradable natural polymer is used, it is naturally absorbed into the living body over time, so there is no need for follow-up after treatment such as dental treatment, and since the fiber sheet contains the drug as a component, disinfection, bacteria removal, Effects such as microbial killing can be obtained.
전기방사법에 의해 제조되는 생분해성 섬유는 평균 직경이 0.01∼100㎛ 크기를 갖게 하는 것이 바람직하다. The biodegradable fiber produced by the electrospinning method is preferably such that the average diameter has a size of 0.01 to 100㎛.
전기방사법은 비교적 간단한 장비를 사용한다. 전기방사 장치는, 제1 전극이 생분해성 천연 고분자, 약물 및 가교제의 혼합용액 내에 위치하고, 다른 제2 전극은 컬렉터(collector)에 위치하며, 서로 반대 극성을 가지는 제1 및 제2 전극 사이에서 노즐을 통해 생분해성 천연 고분자, 약물 및 가교제의 혼합용액이 방사되고 방사된 생분해성 천연 고분자, 약물 및 가교제의 혼합용액은 컬렉터에 수집되면서 용제가 증발되게 된다. Electrospinning uses relatively simple equipment. In the electrospinning apparatus, a nozzle is disposed between a first electrode and a second electrode having a first electrode in a mixed solution of a biodegradable natural polymer, a drug and a crosslinking agent, and the other second electrode in a collector, and having opposite polarities to each other. Through the mixed solution of the biodegradable natural polymer, drug and crosslinking agent is emitted and the mixed solution of the biodegradable natural polymer, drug and crosslinking agent is collected in the collector and the solvent is evaporated.
제1 전극과 제2 전극에 인가되는 전압의 차이, 생분해성 천연 고분자의 특성, 생분해성 천연 고분자의 분자량, 생분해성 천연 고분자의 농도, 생분해성 천연 고분자, 약물 및 가교제의 혼합용액 점도, 방사 유속, 생분해성 천연 고분자, 약물 및 가교제의 혼합용액을 방사하는 노즐의 구멍 크기 등을 조절하여 전기방사에 의해 생성되는 생분해성 섬유의 직경 등을 조절할 수 있다. The difference in voltage applied to the first electrode and the second electrode, the characteristics of the biodegradable natural polymer, the molecular weight of the biodegradable natural polymer, the concentration of the biodegradable natural polymer, the viscosity of the mixed solution of the biodegradable natural polymer, the drug and the crosslinking agent, the spinning flow rate The diameter of the biodegradable fiber produced by electrospinning may be controlled by adjusting the pore size of the nozzle for spinning the mixed solution of the biodegradable natural polymer, the drug and the crosslinking agent.
전기방사에 의해 제조된 섬유 시트를 압축하면서 원하는 형태로 펀칭(punching)하여 치과용으로의 사용에 적합한 크기, 예컨대 가로 0.5∼50㎜, 세로 0.5∼50㎜ 및 두께 0.05∼5㎜를 갖는 섬유 칩으로 형성할 수 있다. 섬유 시트를 펀처(puncher)에 장입하여 압축과 절단이 함께 이루어지게 하면서 원하는 형태의 섬유 칩을 형성할 수 있다. 예컨대, 섬유 시트를 펀처(puncher)에 장입하여 압축하면서 절단이 이루어지게 한다. 섬유 시트를 압축하면서 원하는 형태로 펀칭(punching)하여 섬유 칩으로 형성하는 단계는 복수의 섬유 시트를 적층하는 단계 및 적층된 복수의 섬유 시트를 압축하면서 펀칭하여 가로 0.5∼50㎜, 세로 0.5∼50㎜ 및 두께 0.05∼5㎜를 갖는 섬유 칩을 형성하는 단계를 포함할 수 있다. 예컨대, 복수의 섬유 시트를 적층하고 펀처(puncher)에 장입하여 적층된 복수의 섬유 시트를 압축하면서 절단이 이루어지게 한다. 또한, 섬유 시트를 압축하면서 원하는 형태로 펀칭(punching)하여 섬유 칩으로 형성하는 단계는 상기 섬유 시트를 말아 감아서 두루마리 형태로 만드는 단계 및 두루마리 형태의 섬유 시트를 압축하면서 펀칭하여 가로 0.5∼50㎜, 세로 0.5∼50㎜ 및 두께 0.05∼5㎜를 갖는 섬유 칩을 형성하는 단계를 포함할 수 있다. 상기 섬유 시트를 말아 감아서 두루마리 형태로 만들고 펀처(puncher)에 장입하여 두루마리 형태의 섬유 시트를 압축하면서 절단이 이루어지게 한다. 이때, 가압되는 압력은 섬유 칩의 두께 등을 고려하여 설정하며, 바람직하게는 0.1∼100MPa 정도이다. 전기방사에 의해 제조된 섬유 시트를 압축한 후, 치과용으로의 사용에 적합한 크기, 예컨대 가로 0.5∼50㎜, 세로 0.5∼50㎜ 및 두께 0.05∼5㎜를 갖는 칩 형태로 절단하여 섬유 칩으로 형성할 수도 있는데, 이러한 경우에는 압축 공정과 절단 공정을 각각 수행해야 하므로 공정 단순화와 생산성 측면 등에서 좋지 않다. A fiber chip having a size suitable for use in dentistry, such as 0.5 to 50 mm long, 0.5 to 50 mm long and 0.05 to 5 mm thick, by punching into a desired shape while compressing the fiber sheet produced by electrospinning. It can be formed as. The fiber sheet may be loaded into a puncher to form a fiber chip of a desired shape while compression and cutting are performed together. For example, the fibrous sheet is loaded into a puncher and compressed to allow cutting. Forming a fiber chip by punching the fiber sheet into a desired shape while compressing the fiber sheet may be achieved by laminating a plurality of fiber sheets and by punching while compressing the plurality of stacked fiber sheets by 0.5-50 mm in width and 0.5-50 in length. Forming a fiber chip having a mm and a thickness of 0.05-5 mm. For example, a plurality of fibrous sheets are laminated and charged into a puncher to cut while compressing the stacked plurality of fibrous sheets. In addition, the step of punching the fiber sheet into a desired shape while compressing the fiber sheet to form a fiber chip may be rolled up to form a roll and rolled the fiber sheet and punched while compressing the rolled fiber sheet to a width of 0.5 to 50 mm. The method may include forming a fiber chip having a length of 0.5 to 50 mm and a thickness of 0.05 to 5 mm. The fiber sheet is rolled up to form a roll and loaded into a puncher to cut the fiber sheet while compressing the rolled fiber sheet. At this time, the pressure to be pressed is set in consideration of the thickness of the fiber chip and the like, and preferably about 0.1 to 100 MPa. After compressing the fiber sheet produced by electrospinning, the fiber sheet was cut into a fiber chip having a size suitable for use in dental work, such as a chip having a width of 0.5-50 mm, a length of 0.5-50 mm, and a thickness of 0.05-5 mm In this case, the compression process and the cutting process have to be performed separately, which is not good in terms of process simplification and productivity.
이렇게 제조된 치과용 약물 방출 생분해성 섬유 칩은, 평균 직경이 0.01∼100㎛인 생분해성 섬유들이 네트워크 형태로 얽혀서 압축되어 가로 0.5∼50㎜, 세로 0.5∼50㎜ 및 두께 0.05∼5㎜를 갖는 섬유 칩을 이루고, 네트워크 형태로 얽혀있는 상기 생분해성 섬유들 사이에 기공들이 분포하며, 상기 생분해성 섬유는 생분해성 천연 고분자, 약물 및 가교제(cross-linking agent)를 구성 성분으로 포함한다. 상기 생분해성 섬유는 구성 성분으로 폴리아닐린(polyaniline), 폴리카보네이트(polycarbonate), 폴리에틸렌글리콜(polyethyleneglycol) 및 폴리비닐알콜(polyvinyl alcohol) 중에서 선택된 1종 이상의 생분해성 합성 고분자를 더 포함할 수 있으며, 상기 생분해성 천연 고분자와 상기 생분해성 합성 고분자는 1:0.001∼1의 중량비를 이루는 것이 바람직하다. 상기 생분해성 섬유는 구성 성분으로 폴리락트산(polylactic acid), 폴리글리콜산(polyglycolic acid), 폴리락트산-코-글리콜산(poly(lactic-co-glycolic acid)), 폴리카프로락톤(polycaprolactone) 및 폴리오르토에스테르(polyorthoester) 중에서 선택된 1종 이상의 생분해성 합성 고분자를 더 포함할 수 있으며, 상기 생분해성 천연 고분자와 상기 생분해성 합성 고분자는 1:0.001∼1의 중량비를 이루는 것이 바람직하다.The dental drug-release biodegradable fiber chip thus manufactured is compressed into a network in which biodegradable fibers having an average diameter of 0.01 to 100 μm are entangled in a network form, having a width of 0.5 to 50 mm, a length of 0.5 to 50 mm, and a thickness of 0.05 to 5 mm. Pores are distributed between the biodegradable fibers that make up the fiber chip and are entangled in a network form, and the biodegradable fiber comprises a biodegradable natural polymer, a drug and a cross-linking agent as components. The biodegradable fiber may further include one or more biodegradable synthetic polymers selected from polyaniline, polycarbonate, polyethyleneglycol, and polyvinyl alcohol as components. It is preferable that the natural polymer and the biodegradable synthetic polymer have a weight ratio of 1: 0.001 to 1. The biodegradable fiber is composed of polylactic acid (polylactic acid), polyglycolic acid (polyglycolic acid), polylactic acid co-glycolic acid (poly (lactic-co-glycolic acid)), polycaprolactone (polycaprolactone) and poly It may further comprise at least one biodegradable synthetic polymer selected from orthoesters (polyorthoester), the biodegradable natural polymer and the biodegradable synthetic polymer is preferably made of a weight ratio of 1: 0.001 to 1.
치과용 약물 방출 생분해성 섬유 칩이 생체에 삽입되는 경우, 시간이 지나게 되면 생분해성 천연 고분자는 자연적으로 생체에 흡수되게 되므로 섬유 칩을 제거하거나 하는 등의 후속조치가 필요없는 장점이 있다.When a dental drug-release biodegradable fiber chip is inserted into a living body, the biodegradable natural polymer is naturally absorbed into the living body over time, and thus there is no need for follow-up measures such as removing the fiber chip.
시간이 경과하면서 치과용 약물 방출 생분해성 섬유 칩으로부터 약물이 용출되게 되며, 용출되는 약물은 항염증제(anti-inflammatory agent) 및 항생제(antibiotics) 중에서 선택된 1종 이상의 물질을 포함하고 있다. Over time, the drug is eluted from the dental drug-release biodegradable fiber chip, and the eluted drug contains one or more substances selected from anti-inflammatory agents and antibiotics.
본 발명의 치과용 약물 방출 생분해성 섬유 칩은 약물이 생분해성 섬유를 구성하는 성분을 이루어져 지속적인 약물 방출이 가능하고, 소독용, 항생제용 등으로 사용할 수 있다. The dental drug-release biodegradable fiber chip of the present invention is composed of the components constituting the biodegradable fiber drug is capable of continuous drug release, can be used for disinfection, antibiotics and the like.
생분해성 섬유가 네트워크(망) 구조를 이루므로 상처 부위에 쉽게 삽입 또는 부착할 수 있을 뿐만 아니라, 함유된 약물의 방출이 일정기간 동안 지속적으로 이루어질 수 있는 장점이 있다.Since the biodegradable fibers form a network structure, the biodegradable fibers can be easily inserted or attached to the wound site, and the release of the contained drug can be continued for a certain period of time.
치과용 약물 방출 생분해성 섬유 칩은 생체안정성이 뛰어나며, 동물이나 인체의 신체에 삽입 후에도 부작용이 발생하지 않고, 장기간의 약물 용출이 가능하다. Dental drug-release biodegradable fiber chips are excellent in biostability and do not cause side effects even after insertion into animals or human bodies, and allow long-term drug dissolution.
치과용 약물 방출 생분해성 섬유 칩의 생분해성 섬유 직경, 약물 함량 등을 조절하여 최적의 약물 용출량을 실시간으로 동물 또는 인체의 신체에 전달하는 것이 가능하다. 약물의 함량과 용출(elution)을 파악하여 최적의 약물을 전달할 수 있고, 이를 이용하여 시간에 따라 약물 용출량 제어가 가능한 장점이 있다.By adjusting the biodegradable fiber diameter, drug content and the like of the dental drug-release biodegradable fiber chip, it is possible to deliver the optimal drug dissolution amount to the body of the animal or human body in real time. By determining the content of the drug and the elution (elution) can be delivered to the optimal drug, there is an advantage that can control the drug dissolution amount according to the time.
이하에서, 본 발명에 따른 실험예들을 구체적으로 제시하며, 다음에 제시하는 실험예들에 의하여 본 발명이 제한되는 것은 아니다. Hereinafter, experimental examples according to the present invention are specifically presented, and the present invention is not limited by the following experimental examples.
<실험예 1>Experimental Example 1
클로헥시딘 디글루코네이트(chlorhexidine digluconate; CHD) 6㎖와, 용제인 아세트산(acetic acid) 6㎖, 그리고 탈이온수(deionized water; DI water) 2㎖를 혼합하였다. 상기 클로헥시딘 디글루코네이트(chlorhexidine digluconate; CHD)은 항생제인 클로로헥시딘(chlorhexidine)의 일종이다. 6 ml of chlorhexidine digluconate (CHD), 6 ml of acetic acid as a solvent, and 2 ml of deionized water (DI water) were mixed. The chlorhexidine digluconate (CHD) is a type of chlorhexidine antibiotic.
상기 클로헥시딘 디글루코네이트(CHD), 상기 아세트산 및 상기 탈이온수의 혼합액에 젤라틴(gelatin) 2g을 혼합하였다. 상기 혼합은 30rpm 정도의 속도로 1시간 동안 교반하여 수행하였다. 상기 젤라틴은 우피(bovine skin)에서 분리한 제품을 사용하였다. 젤라틴이 상기 혼합액에 완전히 용해되는 것을 육안으로 확인할 수 있었다. 2 g of gelatin was mixed with the mixed solution of chlorhexidine digluconate (CHD), the acetic acid and the deionized water. The mixing was performed by stirring for 1 hour at a rate of about 30 rpm. The gelatin was used as a product separated from the bovine skin. It was confirmed visually that the gelatin was completely dissolved in the mixed solution.
상기 젤라틴이 용해된 용액에 글루타르알데히드(glutaraldehyde)를 첨가하여 생분해성 천연 고분자, 약물 및 가교제의 혼합용액을 형성하였다. 상기 글루타르알데히드는 탈이온수 9㎖에 글루타르알데히드 1㎖를 혼합하여 희석시킨 후, 0.05㎖를 취하여 상기 젤라틴이 용해된 용액에 첨가하였다. 상기 혼합은 30rpm 정도의 속도로 20분 동안 교반하여 수행하였다. Glutaraldehyde was added to the solution in which gelatin was dissolved to form a mixed solution of biodegradable natural polymer, drug, and a crosslinking agent. The glutaraldehyde was diluted by mixing 1 ml of glutaraldehyde with 9 ml of deionized water, and 0.05 ml was added to the solution in which the gelatin was dissolved. The mixing was performed by stirring for 20 minutes at a speed of about 30 rpm.
이와 같이 제조된 혼합용액을 전압차 20kV, 방사 유속 0.2∼1.0㎖/hr, 방사 거리 15㎝, 노즐 게이지(nozzle gauge) 23 gage(GA)의 조건으로 전기방사(electrospinning)를 실시하여 생분해성 섬유가 네트워크 형태로 얽혀있는 섬유 시트를 제조하였다. 전기 방사 시의 습도는 40% 정도 였으며, 온도는 22℃ 정도 였다. 이렇게 제조된 섬유 시트는 생분해성 천연 고분자, 약물 및 가교제의 혼합성분으로 이루어진다. The biodegradable fibers were subjected to electrospinning under the conditions of a voltage difference of 20 kV, a spinning flow rate of 0.2 to 1.0 ml / hr, a spinning distance of 15 cm, and a nozzle gauge of 23 gage (GA). To prepare a fiber sheet intertwined in the form of a network. The humidity during electrospinning was about 40% and the temperature was about 22 ° C. The fiber sheet thus prepared consists of a mixture of biodegradable natural polymers, drugs and crosslinkers.
도 1 내지 도 3은 실험예 1에 따라 제조된 섬유 시트의 전계방출 주사전자현미경(field emission scanning electron microscope; FE-SEM) 사진이다. 1 to 3 are field emission scanning electron microscope (FE-SEM) photographs of the fiber sheets prepared according to Experimental Example 1. FIG.
도 1 내지 도 3을 참조하면, 실험예 1에 따라 제조된 섬유 시트는 직경이 669∼995 nm 정도인 미세 섬유가 네트워크 형태로 얽혀져 있는 것을 확인할 수 있었다. 1 to 3, the fiber sheet prepared according to Experimental Example 1 was confirmed that the fine fibers having a diameter of about 669 ~ 995 nm is entangled in the form of a network.
<실험예 2>Experimental Example 2
실험예 1과 동일하게 생분해성 천연 고분자, 약물 및 가교제의 혼합용액을 형성하였으며, 상기 혼합용액을 전압차 20kV, 방사 유속 0.2∼1.0㎖/hr, 방사 거리 15㎝, 노즐 게이지(nozzle gauge) 25 gage(GA)의 조건으로 전기방사(electrospinning)를 실시하여 생분해성 섬유가 네트워크 형태로 얽혀있는 섬유 시트를 제조하였다. 전기 방사 시의 습도는 40% 정도 였으며, 온도는 22℃ 정도 였다.A mixed solution of a biodegradable natural polymer, a drug and a crosslinking agent was formed in the same manner as in Experimental Example 1, and the mixed solution was subjected to a voltage difference of 20 kV, a spinning flow rate of 0.2 to 1.0 ml / hr, a spinning distance of 15 cm, and a nozzle gauge 25 Electrospinning was performed under the condition of gage (GA) to prepare a fiber sheet in which biodegradable fibers were entangled in a network form. The humidity during electrospinning was about 40% and the temperature was about 22 ° C.
도 4는 실험예 2에 따라 제조된 섬유 시트의 전계방출 주사전자현미경(FE-SEM) 사진이다. 4 is a field emission scanning electron microscope (FE-SEM) photograph of the fiber sheet prepared according to Experimental Example 2. FIG.
도 4를 참조하면, 실험예 2에 따라 제조된 섬유 시트는 직경이 671nm∼1.37㎛ 정도인 미세 섬유가 네트워크 형태로 얽혀져 있는 것을 확인할 수 있었다. Referring to FIG. 4, it was confirmed that the fiber sheet manufactured according to Experimental Example 2 had fine fibers having a diameter of about 671 nm to 1.37 μm being entangled in a network form.
<실험예 3>Experimental Example 3
실험예 1과 동일하게 생분해성 천연 고분자, 약물 및 가교제의 혼합용액을 형성하였으며, 상기 혼합용액을 전압차 20kV, 방사 유속 0.2∼1.0㎖/hr, 방사 거리 15㎝, 노즐 게이지(nozzle gauge) 27 gage(GA)의 조건으로 전기방사(electrospinning)를 실시하여 생분해성 섬유가 네트워크 형태로 얽혀있는 섬유 시트를 제조하였다. 전기 방사 시의 습도는 40% 정도 였으며, 온도는 22℃ 정도 였다.A mixed solution of a biodegradable natural polymer, drug and a crosslinking agent was formed in the same manner as in Experimental Example 1, and the mixed solution was subjected to a voltage difference of 20 kV, a spinning flow rate of 0.2 to 1.0 ml / hr, a spinning distance of 15 cm, and a nozzle gauge 27 Electrospinning was performed under the condition of gage (GA) to prepare a fiber sheet in which biodegradable fibers were entangled in a network form. The humidity during electrospinning was about 40% and the temperature was about 22 ° C.
도 5는 실험예 3에 따라 제조된 섬유 시트의 전계방출 주사전자현미경(FE-SEM) 사진이다. 5 is a field emission scanning electron microscope (FE-SEM) photograph of the fiber sheet prepared according to Experimental Example 3. FIG.
도 5를 참조하면, 실험예 3에 따라 제조된 섬유 시트는 직경이 766∼996nm 정도인 미세 섬유가 네트워크 형태로 얽혀져 있는 것을 확인할 수 있었다. Referring to FIG. 5, the fiber sheet manufactured according to Experimental Example 3 was confirmed that fine fibers having a diameter of about 766 to 996 nm are entangled in a network form.
<실험예 4>Experimental Example 4
실험예 1과 동일하게 생분해성 천연 고분자, 약물 및 가교제의 혼합용액을 형성하였으며, 상기 혼합용액을 전압차 20kV, 방사 유속 0.2∼1.0㎖/hr, 방사 거리 15㎝, 노즐 게이지(nozzle gauge) 32 gage(GA)의 조건으로 전기방사(electrospinning)를 실시하여 생분해성 섬유가 네트워크 형태로 얽혀있는 섬유 시트를 제조하였다. 전기 방사 시의 습도는 40% 정도 였으며, 온도는 22℃ 정도 였다.A mixed solution of a biodegradable natural polymer, a drug and a crosslinking agent was formed in the same manner as in Experimental Example 1, and the mixed solution was subjected to a voltage difference of 20 kV, a spinning flow rate of 0.2 to 1.0 ml / hr, a spinning distance of 15 cm, and a nozzle gauge 32 Electrospinning was performed under the condition of gage (GA) to prepare a fiber sheet in which biodegradable fibers were entangled in a network form. The humidity during electrospinning was about 40% and the temperature was about 22 ° C.
도 6 내지 도 8은 실험예 4에 따라 제조된 섬유 시트의 전계방출 주사전자현미경(FE-SEM) 사진이다. 6 to 8 are field emission scanning electron microscope (FE-SEM) photographs of the fiber sheets prepared according to Experimental Example 4. FIG.
도 6 내지 도 8을 참조하면, 실험예 4에 따라 제조된 섬유 시트는 직경이 118.1∼208.8nm 정도인 미세 섬유가 네트워크 형태로 얽혀져 있는 것을 확인할 수 있었다. 6 to 8, it was confirmed that the fiber sheets prepared according to Experimental Example 4 had fine fibers having a diameter of about 118.1 to 208.8 nm being entangled in a network form.
<실험예 5>Experimental Example 5
실험예 1에 따라 제조된 섬유시트 0.012∼0.014g을 펀처(puncher)에 장입하고, 10MPa의 압력을 가면서 펀칭(punching)하여 원형의 칩(chip) 형태(지름 0.5mm, 두께 0.4mm)로 제작하여 약물 방출 생분해성 섬유 칩을 형성하였다. 0.012 to 0.014 g of the fiber sheet prepared according to Experimental Example 1 was charged into a puncher, and punched under a pressure of 10 MPa to produce a circular chip shape (0.5 mm in diameter and 0.4 mm in thickness). Thereby forming drug release biodegradable fiber chips.
도 9 내지 도 11은 실험예 5에 따라 제조된 약물 방출 생분해성 섬유 칩의 표면을 관찰한 전계방출 주사전자현미경(FE-SEM) 사진이다. 9 to 11 are field emission scanning electron microscope (FE-SEM) images of the surface of the drug-release biodegradable fiber chip prepared according to Experimental Example 5. FIG.
도 9 내지 도 11을 참조하면, 표면에서는 수 ㎛의 섬유 직경이 관찰되었으며, 다공성의 구조를 갖고 있었다. 9 to 11, a fiber diameter of several micrometers was observed on the surface, and it had a porous structure.
이상, 본 발명의 바람직한 실시예를 들어 상세하게 설명하였으나, 본 발명은 상기 실시예에 한정되는 것은 아니며, 본 발명의 기술적 사상의 범위 내에서 당 분야에서 통상의 지식을 가진 자에 의하여 여러 가지 변형이 가능하다.As mentioned above, although the preferred embodiment of this invention was described in detail, this invention is not limited to the said embodiment, A various deformation | transformation by a person of ordinary skill in the art within the scope of the technical idea of this invention is carried out. This is possible.
본 발명의 치과용 약물 방출 생분해성 섬유 칩은 지속적인 약물 방출이 가능하고, 치과에서 소독용, 항생제용 등으로 사용할 수 있으므로 산업상 이용가능성이 있다. The dental drug release biodegradable fiber chip of the present invention is capable of sustained drug release, and can be used in the dentistry for disinfection, antibiotic use, and the like.

Claims (13)

  1. 평균 직경이 0.01∼100㎛인 생분해성 섬유들이 네트워크 형태로 얽혀서 압축되어 가로 0.5∼50㎜, 세로 0.5∼50㎜ 및 두께 0.05∼5㎜를 갖는 섬유 칩을 이루고, Biodegradable fibers having an average diameter of 0.01 to 100 μm are entangled into a network to form a fiber chip having a width of 0.5 to 50 mm, a length of 0.5 to 50 mm and a thickness of 0.05 to 5 mm,
    네트워크 형태로 얽혀있는 상기 생분해성 섬유들 사이에 기공들이 분포하며,Pores are distributed between the biodegradable fibers entangled in a network form,
    상기 생분해성 섬유는 생분해성 천연 고분자, 약물 및 가교제(cross-linking agent)를 구성 성분으로 포함하고, The biodegradable fiber comprises a biodegradable natural polymer, drugs and cross-linking agents (components) as a component,
    상기 생분해성 천연 고분자는 젤라틴(gelatin), 콜라겐(collagen), 알지네이트(alginate), 키토산(chitosan), 피브린(fibrin), 히알루론산(hyaluronic acid) 및 덱스트란(dextran) 중에서 선택된 1종 이상의 물질을 포함하며,The biodegradable natural polymer comprises at least one material selected from gelatin, collagen, alginate, alginate, chitosan, fibrin, hyaluronic acid, and dextran. Include,
    상기 약물은 항염증제(anti-inflammatory agent) 및 항생제(antibiotics) 중에서 선택된 1종 이상의 물질을 포함하는 것을 특징으로 하는 치과용 약물 방출 생분해성 섬유 칩.The drug drug-release biodegradable fiber chip, characterized in that it comprises at least one substance selected from anti-inflammatory agents (anti-inflammatory agents) and antibiotics (antibiotics).
  2. 제1항에 있어서, 상기 생분해성 섬유는 구성 성분으로 폴리아닐린(polyaniline), 폴리카보네이트(polycarbonate), 폴리에틸렌글리콜(polyethyleneglycol) 및 폴리비닐알콜(polyvinyl alcohol) 중에서 선택된 1종 이상의 생분해성 합성 고분자를 더 포함하며,According to claim 1, wherein the biodegradable fiber further comprises at least one biodegradable synthetic polymer selected from polyaniline (polyaniline), polycarbonate, polyethylene glycol (polyethyleneglycol) and polyvinyl alcohol as a component ,
    상기 생분해성 천연 고분자와 상기 생분해성 합성 고분자는 1:0.001∼1의 중량비를 이루는 것을 특징으로 하는 치과용 약물 방출 생분해성 섬유 칩.The biodegradable natural polymer and the biodegradable synthetic polymer comprises a weight ratio of 1: 0.001 to 1 dental drug release biodegradable fiber chip.
  3. 제1항에 있어서, 상기 생분해성 섬유는 구성 성분으로 폴리락트산(polylactic acid), 폴리글리콜산(polyglycolic acid), 폴리락트산-코-글리콜산(poly(lactic-co-glycolic acid)), 폴리카프로락톤(polycaprolactone) 및 폴리오르토에스테르(polyorthoester) 중에서 선택된 1종 이상의 생분해성 합성 고분자를 더 포함하며,According to claim 1, wherein the biodegradable fibers are made of polylactic acid (polylactic acid), polyglycolic acid (polyglycolic acid), polylactic acid-co-glycolic acid (poly (lactic-co-glycolic acid)), polycapro It further comprises at least one biodegradable synthetic polymer selected from lactone (polycaprolactone) and polyorthoester,
    상기 생분해성 천연 고분자와 상기 생분해성 합성 고분자는 1:0.001∼1의 중량비를 이루는 것을 특징으로 하는 치과용 약물 방출 생분해성 섬유 칩.The biodegradable natural polymer and the biodegradable synthetic polymer comprises a weight ratio of 1: 0.001 to 1 dental drug release biodegradable fiber chip.
  4. 제1항에 있어서, 상기 생분해성 섬유의 구성 성분을 이루는 상기 가교제(cross-linking agent)는 1-에틸-3-(3-디메틸아미노프로필)카보디이미드 하이드로클로라이드(1-ethyl-3-(3-dimethylamino propyl) carbodiimide hydrochloride), 히알루론산(hyaluronic acid), 펙틴(pectin), 산화자당(oxidized sucrose), 글리세르알데히드(glyceraldehyde), 글루타르알데히드(glutaraldehyde), 포름알데히드(formaldehyde), 카보디이미드(carbodiimide), 게니핀(genipin), 설탕류(sugars), 트랜스글루타미나아제(transglutaminase) 및 에폭시화합물(epoxy compounds) 중에서 선택된 1종 이상의 물질을 포함하며,The method of claim 1, wherein the cross-linking agent constituting the biodegradable fiber comprises 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1-ethyl-3- ( 3-dimethylamino propyl) carbodiimide hydrochloride, hyaluronic acid, pectin, oxidized sucrose, glyceraldehyde, glutaraldehyde, formaldehyde, carbodi It contains one or more substances selected from carbodiimide, genipin, sugars, transglutaminase and epoxy compounds,
    상기 생분해성 천연 고분자와 상기 가교제는 1:0.0001∼0.5의 중량비를 이루는 것을 특징으로 하는 치과용 약물 방출 생분해성 섬유 칩.The biodegradable natural polymer and the crosslinking agent is a drug release biodegradable fiber chip, characterized in that the weight ratio of 1: 0.0001 to 0.5.
  5. 제1항에 있어서, 상기 생분해성 천연 고분자와 약물은 1:0.001∼10의 중량비를 이루며,The method of claim 1, wherein the biodegradable natural polymer and the drug comprises a weight ratio of 1: 0.001 to 10,
    상기 항염증제는 이부프로펜(Ibuprofen), 페노프로펜(Fenoprofen), 플루르비프로펜(Flurbiprofen), 카르프로펜(Carprofen), 디클로페낙(Diclofenac), 펜부펜(Fenbufen), 펜클로즈산((Fenclozic Acid), 플루페남산(Flufenamic Acid), 인도메타신(Indomethacin), 인도프로펜(Indoprofen), 케토프로펜(Ketoprofen), 로나졸락(Lonazolac), 록소프로펜(Loxoprofen), 메클로페남산(Meclofenamic Acid), 메페남산(Mefenamic Acid), 나프록신(Naproxen), 프로프리온산(Proprionic Acids), 살리실산(Salicilic Acid), 설린닥(Sulindac), 톨메틴(Tolmetin), 멜록시캄(Meloxicam), 옥시캄(Oxicams), 피록시캄(Piroxicam), 테녹시캠(Tenoxicam), 에토돌락(Etodolac) 및 옥사프로진(Oxaprozin) 중에서 선택된 1종 이상의 물질을 포함하고,The anti-inflammatory agent is ibuprofen (Ibuprofen), Fenoprofen (Fenoprofen), Flurbiprofen (Flurbiprofen), Carprofen (Carprofen), Diclofenac, Fenbufen (Fenbufen), Fenclozic acid (Fenclozic Acid ), Flufenamic Acid, Indomethacin, Indoprofen, Ketoprofen, Lonazolac, Loxoprofen, Meclofenamic Acid ( Meclofenamic Acid, Mefenamic Acid, Naproxen, Proprionic Acids, Salicilic Acid, Sulindac, Tolmetin, Meloxycam At least one substance selected from Oxycams, Piroxicam, Tenoxicam, Etodolac and Oxaprozin,
    상기 항생제는 클로로헥시딘(chlorohexidine), 미노사이클린(minocycline), 독시싸이클린(doxycycline), 메트로니다졸(metronidazole), 오플록사신(ofloxacin), 테트라사이클린(tetracycline), 티니다졸(tinidazole) 및 케토나졸(Ketonazole) 중에서 선택된 1종 이상의 물질을 포함하는 것을 특징으로 하는 치과용 약물 방출 생분해성 섬유 칩.The antibiotics include chlorohexidine, minocycline, doxycycline, metronidazole, meofidazole, ofloxacin, tetratracycline, tinidazole, and ketonazole Dental drug release biodegradable fiber chip comprising at least one material selected from Ketonazole.
  6. (a) 용제에 생분해성 천연 고분자, 약물 및 가교제(cross-linking agent)를 첨가하여 생분해성 천연 고분자, 약물 및 가교제(cross-linking agent)의 혼합용액을 형성하는 단계;(a) adding a biodegradable natural polymer, a drug and a cross-linking agent to the solvent to form a mixed solution of the biodegradable natural polymer, the drug and a cross-linking agent;
    (b) 상기 혼합용액을 전기방사를 실시하여 평균 직경이 0.01∼100㎛인 생분해성 섬유들이 네트워크 형태로 얽혀있는 섬유 시트를 제조하는 단계; 및(b) electrospinning the mixed solution to prepare a fiber sheet in which biodegradable fibers having an average diameter of 0.01 to 100 µm are entangled in a network form; And
    (c) 상기 섬유 시트를 압축하면서 펀칭(punching)하여 가로 0.5∼50㎜, 세로 0.5∼50㎜ 및 두께 0.05∼5㎜를 갖는 섬유 칩을 형성하는 단계를 포함하며,(c) punching the fiber sheet while compressing to form a fiber chip having a width of 0.5 to 50 mm, a length of 0.5 to 50 mm, and a thickness of 0.05 to 5 mm,
    상기 생분해성 천연 고분자는 젤라틴(gelatin), 콜라겐(collagen), 알지네이트(alginate), 키토산(chitosan), 피브린(fibrin), 히알루론산(hyaluronic acid) 및 덱스트란(dextran) 중에서 선택된 1종 이상의 물질을 포함하고,The biodegradable natural polymer comprises at least one material selected from gelatin, collagen, alginate, alginate, chitosan, fibrin, hyaluronic acid, and dextran. Including,
    상기 약물은 항염증제(anti-inflammatory agent) 및 항생제(antibiotics) 중에서 선택된 1종 이상의 물질을 포함하는 것을 특징으로 하는 치과용 약물 방출 생분해성 섬유 칩의 제조방법.The drug is a method for producing a dental drug-release biodegradable fiber chip, characterized in that it comprises at least one substance selected from anti-inflammatory agents (anti-inflammatory agents) and antibiotics (antibiotics).
  7. 제6항에 있어서, 상기 (c) 단계는, The method of claim 6, wherein step (c) comprises:
    복수의 섬유 시트를 적층하는 단계; 및Laminating a plurality of fiber sheets; And
    적층된 복수의 섬유 시트를 압축하면서 펀칭하여 가로 0.5∼50㎜, 세로 0.5∼50㎜ 및 두께 0.05∼5㎜를 갖는 섬유 칩을 형성하는 단계를 포함하는 것을 특징으로 하는 치과용 약물 방출 생분해성 섬유 칩의 제조방법.Punching the laminated plurality of fiber sheets while compressing to form a fiber chip having a width of 0.5 to 50 mm, a length of 0.5 to 50 mm and a thickness of 0.05 to 5 mm. Chip manufacturing method.
  8. 제6항에 있어서, 상기 (c) 단계는,The method of claim 6, wherein step (c) comprises:
    상기 섬유 시트를 말아 감아서 두루마리 형태로 만드는 단계; 및Rolling up the fiber sheet to form a roll; And
    두루마리 형태의 섬유 시트를 압축하면서 펀칭하여 가로 0.5∼50㎜, 세로 0.5∼50㎜ 및 두께 0.05∼5㎜를 갖는 섬유 칩을 형성하는 단계를 포함하는 것을 특징으로 하는 치과용 약물 방출 생분해성 섬유 칩의 제조방법.And punching the rolled fiber sheet in compression to form a fiber chip having a width of 0.5 to 50 mm, a length of 0.5 to 50 mm, and a thickness of 0.05 to 5 mm. Manufacturing method.
  9. 제6항에 있어서, 상기 (a) 단계에서 폴리아닐린(polyaniline), 폴리카보네이트(polycarbonate), 폴리에틸렌글리콜(polyethyleneglycol) 및 폴리비닐알콜(polyvinyl alcohol) 중에서 선택된 1종 이상의 생분해성 합성 고분자를 더 첨가하고,The method of claim 6, wherein the step (a) further comprises at least one biodegradable synthetic polymer selected from polyaniline (polyaniline), polycarbonate, polyethylene glycol (polyethyleneglycol) and polyvinyl alcohol (polyvinyl alcohol),
    상기 생분해성 천연 고분자와 상기 생분해성 합성 고분자가 1:0.001∼1의 중량비를 이루게 상기 생분해성 합성 고분자를 첨가하는 것을 특징으로 하는 치과용 약물 방출 생분해성 섬유 칩의 제조방법.The biodegradable natural polymer and the biodegradable synthetic polymer is added to the biodegradable synthetic polymer to form a weight ratio of 1: 0.001 to 1, characterized in that the method for producing a dental drug-release biodegradable fiber chip.
  10. 제6항에 있어서, 상기 (a) 단계에서 폴리락트산(polylactic acid), 폴리글리콜산(polyglycolic acid), 폴리락트산-코-글리콜산(poly(lactic-co-glycolic acid)), 폴리카프로락톤(polycaprolactone) 및 폴리오르토에스테르(polyorthoester) 중에서 선택된 1종 이상의 생분해성 합성 고분자를 더 첨가하고,According to claim 6, wherein in the step (a) polylactic acid (polylactic acid), polyglycolic acid (polyglycolic acid), polylactic acid-co-glycolic acid (poly (lactic-co-glycolic acid)), polycaprolactone ( adding at least one biodegradable synthetic polymer selected from polycaprolactone) and polyorthoester,
    상기 생분해성 천연 고분자와 상기 생분해성 합성 고분자가 1:0.001∼1의 중량비를 이루게 상기 생분해성 합성 고분자를 첨가하는 것을 특징으로 하는 치과용 약물 방출 생분해성 섬유 칩의 제조방법.The biodegradable natural polymer and the biodegradable synthetic polymer is added to the biodegradable synthetic polymer to form a weight ratio of 1: 0.001 to 1, characterized in that the method for producing a dental drug-release biodegradable fiber chip.
  11. 제6항에 있어서, 상기 가교제(cross-linking agent)는 1-에틸-3-(3-디메틸아미노프로필)카보디이미드 하이드로클로라이드(1-ethyl-3-(3-dimethylamino propyl) carbodiimide hydrochloride), 히알루론산(hyaluronic acid), 펙틴(pectin), 산화자당(oxidized sucrose), 글리세르알데히드(glyceraldehyde), 글루타르알데히드(glutaraldehyde), 포름알데히드(formaldehyde), 카보디이미드(carbodiimide), 게니핀(genipin), 설탕류(sugars), 트랜스글루타미나아제(transglutaminase) 및 에폭시화합물(epoxy compounds) 중에서 선택된 1종 이상의 물질을 포함하며,The method of claim 6, wherein the cross-linking agent is 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1-ethyl-3- (3-dimethylamino propyl) carbodiimide hydrochloride), Hyaluronic acid, pectin, pectin, oxidized sucrose, glyceraldehyde, glutaraldehyde, formaldehyde, carbodiimide, genipin ), Sugars, transglutaminase and one or more substances selected from epoxy compounds,
    상기 (a) 단계에서 상기 생분해성 천연 고분자와 상기 가교제는 1:0.0001∼0.5의 중량비를 이루게 첨가되는 것을 특징으로 하는 치과용 약물 방출 생분해성 섬유 칩의 제조방법.In step (a), the biodegradable natural polymer and the cross-linking agent is a method for producing a dental drug-release biodegradable fiber chip, characterized in that added in a weight ratio of 1: 0.0001 to 0.5.
  12. 제6항에 있어서, 상기 용제는 아세트산(acetic acid), 에틸아세테이트(ethyl acetate), 알긴산나트륨(sodium alginate), 1,1,1,3,3,3 핵사플루오로-2-프로판올(1,1,1,3,3,3 hexafluoro-2-propanol), 2,2,2-트리플루오로에탄올(2,2,2-trifluoroethanol), 이소프로판올 및 포름산 중에서 선택된 1종 이상의 물질을 포함하는 것을 특징으로 하는 치과용 약물 방출 생분해성 섬유 칩의 제조방법.The method of claim 6, wherein the solvent is acetic acid (ethyl acetate), sodium alginate (sodium alginate), 1,1,1,3,3,3 nuxafluoro-2-propanol (1, 1,1,3,3,3 hexafluoro-2-propanol), 2,2,2-trifluoroethanol, isopropanol and formic acid A method for producing a dental drug-release biodegradable fiber chip.
  13. 제6항에 있어서, 상기 (a) 단계에서 상기 생분해성 천연 고분자와 약물은 1:0.001∼10의 중량비를 이루게 첨가되며,According to claim 6, wherein the biodegradable natural polymer and the drug in the step (a) is added in a weight ratio of 1: 0.001 to 10,
    상기 항염증제는 이부프로펜(Ibuprofen), 페노프로펜(Fenoprofen), 플루르비프로펜(Flurbiprofen), 카르프로펜(Carprofen), 디클로페낙(Diclofenac), 펜부펜(Fenbufen), 펜클로즈산((Fenclozic Acid), 플루페남산(Flufenamic Acid), 인도메타신(Indomethacin), 인도프로펜(Indoprofen), 케토프로펜(Ketoprofen), 로나졸락(Lonazolac), 록소프로펜(Loxoprofen), 메클로페남산(Meclofenamic Acid), 메페남산(Mefenamic Acid), 나프록신(Naproxen), 프로프리온산(Proprionic Acids), 살리실산(Salicilic Acid), 설린닥(Sulindac), 톨메틴(Tolmetin), 멜록시캄(Meloxicam), 옥시캄(Oxicams), 피록시캄(Piroxicam), 테녹시캠(Tenoxicam), 에토돌락(Etodolac) 및 옥사프로진(Oxaprozin) 중에서 선택된 1종 이상의 물질을 포함하고,The anti-inflammatory agent is ibuprofen (Ibuprofen), Fenoprofen (Fenoprofen), Flurbiprofen (Flurbiprofen), Carprofen (Carprofen), Diclofenac, Difenfenac, Fenbufen, Fenclozic acid (Fenclozic Acid ), Flufenamic Acid, Indomethacin, Indoprofen, Ketoprofen, Lonazolac, Loxoprofen, Meclofenamic Acid ( Meclofenamic Acid, Mefenamic Acid, Naproxen, Proprionic Acids, Salicilic Acid, Sulindac, Tolmetin, Meloxycam At least one substance selected from Oxycams, Piroxicam, Tenoxicam, Etodolac and Oxaprozin,
    상기 항생제는 클로로헥시딘(chlorohexidine), 미노사이클린(minocycline), 독시싸이클린(doxycycline), 메트로니다졸(metronidazole), 오플록사신(ofloxacin), 테트라사이클린(tetracycline), 티니다졸(tinidazole) 및 케토나졸(Ketonazole) 중에서 선택된 1종 이상의 물질을 포함하는 것을 특징으로 하는 치과용 약물 방출 생분해성 섬유 칩의 제조방법.The antibiotics include chlorohexidine, minocycline, doxycycline, metronidazole, meofidazole, ofloxacin, tetratracycline, tinidazole, and ketonazole Ketonazole) a method for producing a dental drug-release biodegradable fiber chip comprising at least one substance selected from.
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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20000073589A (en) * 1999-05-12 2000-12-05 오석송 Biodegradable guided tissue regeneration in teriodontal dental therapy and methods of producing the same
JP2002541085A (en) * 1999-04-02 2002-12-03 フォーシス デンタル インファーマリー フォー チルドレン Endodontic fibers and methods of using same
KR20100045158A (en) * 2008-10-23 2010-05-03 주식회사 원바이오젠 Biodegradable nanofiber sheet for anti-adhesion membrane and process for preparing the same
KR20140115486A (en) * 2013-03-20 2014-10-01 강릉원주대학교산학협력단 Drug loaded nanofiber chip for dental use and manufacturing method of the same
KR101534522B1 (en) * 2014-09-12 2015-07-07 주식회사 웰나노스 Manufacturing method of drug releasing biodegradable fiber chip for dental use

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002541085A (en) * 1999-04-02 2002-12-03 フォーシス デンタル インファーマリー フォー チルドレン Endodontic fibers and methods of using same
KR20000073589A (en) * 1999-05-12 2000-12-05 오석송 Biodegradable guided tissue regeneration in teriodontal dental therapy and methods of producing the same
KR20100045158A (en) * 2008-10-23 2010-05-03 주식회사 원바이오젠 Biodegradable nanofiber sheet for anti-adhesion membrane and process for preparing the same
KR20140115486A (en) * 2013-03-20 2014-10-01 강릉원주대학교산학협력단 Drug loaded nanofiber chip for dental use and manufacturing method of the same
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