WO2017115906A1 - Puce de fibre dentaire biodégradable à libération de médicament, et son procédé de fabrication - Google Patents

Puce de fibre dentaire biodégradable à libération de médicament, et son procédé de fabrication 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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English (en)
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/fr

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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

La présente invention concerne : une puce de fibre dentaire biodégradable à libération de médicament dans laquelle des fibres biodégradables présentant un diamètre moyen de 0,01 à 100 µm, sont entrelacées en forme de réseau et comprimées de manière à former une puce de fibre ayant une largeur de 0,5 à 50 mm, une hauteur de 0,5 à 50 mm et une épaisseur de 0,05 à 5 mm, et des pores sont répartis entre les fibres biodégradables entrelacées en forme de réseau. La fibre biodégradable comprend, en tant que constituants, un polymère naturel biodégradable, un médicament et un agent de réticulation. L'invention décrit également un procédé de fabrication associé. Selon la présente invention, les fibres biodégradables forment une structure de réseau (filet), de manière à être facilement insérées dans ou fixées au site d'une plaie, et même si le mélange avec un liquide organique se produit, l'écoulement ne se produit pas à la position de fixation, de façon à être applicable efficacement uniquement à un site de cicatrisation De plus, la fibre biodégradable contient elle-même un médicament comme constituant, ce qui permet au médicament contenu d'être libéré en continu pendant une période prédéterminée, peut être utilisée pour la désinfection, antibiotiques et similaires, présente une excellente biostabilité, n'a pas d'effet secondaire, même après l'insertion dans un corps animal ou humain, et permet à un médicament d'être élué pendant longtemps.
PCT/KR2016/000385 2015-12-31 2016-01-14 Puce de fibre dentaire biodégradable à libération de médicament, et son procédé de fabrication WO2017115906A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20000073589A (ko) * 1999-05-12 2000-12-05 오석송 치주질환치료용 생체분해성 유도조직재생막 및 그 제조방법
JP2002541085A (ja) * 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 歯内治療用繊維およびその使用方法
KR20100045158A (ko) * 2008-10-23 2010-05-03 주식회사 원바이오젠 유착방지막 용도의 생분해성 나노섬유시트 및 그 제조방법
KR20140115486A (ko) * 2013-03-20 2014-10-01 강릉원주대학교산학협력단 약물이 탑재된 치과용 나노섬유 칩의 제조방법
KR101534522B1 (ko) * 2014-09-12 2015-07-07 주식회사 웰나노스 치과용 약물 방출 생분해성 섬유 칩의 제조방법

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002541085A (ja) * 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 歯内治療用繊維およびその使用方法
KR20000073589A (ko) * 1999-05-12 2000-12-05 오석송 치주질환치료용 생체분해성 유도조직재생막 및 그 제조방법
KR20100045158A (ko) * 2008-10-23 2010-05-03 주식회사 원바이오젠 유착방지막 용도의 생분해성 나노섬유시트 및 그 제조방법
KR20140115486A (ko) * 2013-03-20 2014-10-01 강릉원주대학교산학협력단 약물이 탑재된 치과용 나노섬유 칩의 제조방법
KR101534522B1 (ko) * 2014-09-12 2015-07-07 주식회사 웰나노스 치과용 약물 방출 생분해성 섬유 칩의 제조방법

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