WO2023176987A1 - Preparation method for biodegradable polymer fibre chip - Google Patents

Preparation method for biodegradable polymer fibre chip Download PDF

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Publication number
WO2023176987A1
WO2023176987A1 PCT/KR2022/003505 KR2022003505W WO2023176987A1 WO 2023176987 A1 WO2023176987 A1 WO 2023176987A1 KR 2022003505 W KR2022003505 W KR 2022003505W WO 2023176987 A1 WO2023176987 A1 WO 2023176987A1
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weight
parts
polymer fiber
biodegradable polymer
acid
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PCT/KR2022/003505
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French (fr)
Korean (ko)
Inventor
이재현
홍성익
김승진
오성훈
한진주
이진희
한명희
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엠엑스바이오 주식회사
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Priority to PCT/KR2022/003505 priority Critical patent/WO2023176987A1/en
Publication of WO2023176987A1 publication Critical patent/WO2023176987A1/en

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    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis

Definitions

  • This application relates to a method of manufacturing a biodegradable polymer fiber chip containing a drug.
  • Tissue adhesion or inflammation usually occurs after dental surgery or during the treatment process.
  • Tissue adhesion refers to the joining of abnormal fibrous connective tissue at the wound site. These tissue adhesions may naturally decompose over time, but in some cases, they may remain in the body and cause aftereffects. Therefore, research is being conducted on fiber sheets as a material that can prevent tissue adhesion and inflammation and effectively treat wounds.
  • casting or molding is used to manufacture drug-containing biodegradable polymer chips and films.
  • the polymer and drug are dissolved together in a solvent and then put into a mold of a certain size and go through a drying process to evaporate the solvent.
  • a film containing a drug is manufactured through a molding process.
  • the prepared mixed solution of polymer and drug must be sufficiently dried to remove moisture and solvent.
  • the solution frame containing the polymer and drug must be fixed for a long time without moving, and depending on the solvent, it may be necessary to heat or maintain a vacuum during the drying process. .
  • Acetic acid is mainly used as a solvent in conventional electrospinning, but problems with residual organic solvents may occur.
  • the residual organic solvent limit for acetic acid is less than 0.5% of the total weight.
  • the amount of acetic acid remaining in the fiber after spinning can be reduced.
  • the polymer solution is sprayed, forming beads rather than fibers. ) can be created.
  • most of the electrospinning solution is not removed during spinning, which causes the fiber to become wet during spinning, resulting in solvent that has not yet been removed remaining in the electrospun fiber, or a re-dissolution phenomenon in which the polymer fibers created in the remaining solvent may melt again. There are possible problems.
  • This institute has developed a method for manufacturing biodegradable polymer fiber chips on an industrial scale by controlling the concentration of biodegradable polymer raw materials and drugs, preparing a raw material solution using organic acids that are harmless to the human body instead of acetic acid, and electrospinning them. We would like to provide
  • One aspect of the present application is to form a mixed solution by mixing (a) a biodegradable polymer raw material, a drug raw material, and an organic acid; (b) electrospinning the mixed solution to produce a polymer fiber sheet in which polymer fibers are entangled in a network form; and (c) compressing and processing the polymer fiber sheet to obtain a biodegradable polymer fiber chip.
  • the desired biodegradable polymer fiber chip can be manufactured by adjusting the drug raw material and its concentration to an optimal ratio.
  • volatile solvents for example, alcohol or formic acid
  • the biodegradable polymer fiber chip of the present application when manufacturing the biodegradable polymer fiber chip of the present application, volatile solvents (for example, alcohol or formic acid) are not used, so it is economically efficient and the biodegradable polymer fiber chip can be manufactured on an industrial scale. You can.
  • mass production and rapid production may be possible due to the high supply amount of the electrospinning solution.
  • the solvent in the polymer solution is removed at the same time as it is spun, and polymer fibers are obtained in the collector, and the fiberized The polymer can be used immediately.
  • electrospun polymer fibers are obtained in the form of fibers with a thickness of nanometers or micrometers, so that the polymer fibers can have a high surface area.
  • the biodegradable polymer fiber chip according to an embodiment of the present application may or may not be subsequently dried, but may not be limited thereto.
  • the drying time is from more than 0 hours to about 12 hours, and is dried in a shorter time than the drying time required for the conventional casting or molding method. and next-day molding work may be possible.
  • the manufacturing efficiency of industrial-scale biodegradable polymer fiber chips can be increased by controlling the speed of the conveyor-type collector, controlling the flow rate of compressed air, and controlling the voltage according to an embodiment of the present application.
  • Figure 1 is a photograph showing a mixed solution of a biodegradable polymer and a drug according to an example of the present application.
  • Figure 2 is a photograph of a polymer fiber sheet according to an example of the present application.
  • 3A to 3C are photographs of a polymer fiber sheet analyzed by a scanning electron microscope at 500 times (a), 1000 times (b), and 2000 times (c), respectively, in an example of the present application.
  • Figure 3d is a photograph showing the diameter of the polymer fiber confirmed by magnifying the polymer fiber sheet 5000 times.
  • Figures 4a and 4b are photographs of a biodegradable polymer fiber chip manufactured from a polymer fiber sheet according to an example of the present application.
  • Figures 5a to 5c are photographs of a polymer fiber sheet analyzed by a scanning electron microscope at 500 times (a), 1000 times (b), and 2000 times (c), respectively, in an example of the present application, and Figure 5d is the above This is a photograph showing the diameter of the polymer fibers confirmed by magnifying the polymer fiber sheet 5000 times.
  • the terms “about,” “substantially,” and the like are used to mean at or close to a numerical value when manufacturing and material tolerances inherent in the stated meaning are presented, and to aid understanding of the present application. It is used to prevent unscrupulous infringers from unfairly exploiting disclosures in which precise or absolute figures are mentioned.
  • step of or “step of” do not mean “step for.”
  • the term "combination(s) thereof" included in the Markushi format expression means a mixture or combination of one or more selected from the group consisting of the components described in the Markushi format expression, It means containing one or more selected from the group consisting of the above components.
  • biodegradable polymer fiber chips may be referred to as “polymer fiber chips” or “biodegradable polymer fiber chips.”
  • One aspect of the present application is to form a mixed solution by mixing (a) a biodegradable polymer raw material, a drug raw material, and an organic acid; (b) electrospinning the mixed solution to produce a polymer fiber sheet in which polymer fibers are entangled in a network form; and (c) compressing and processing the polymer fiber sheet to obtain a biodegradable polymer fiber chip.
  • the organic acid is ascorbic acid, citric acid, tartaric acid, tannic acid, lactic acid, butyric acid, and palmitic acid, but may not be limited thereto.
  • the content of the biodegradable polymer raw material is about 10 parts by weight to about 40 parts by weight, and the content of the drug raw material is about 10 parts by weight to about 70 parts by weight. It could be your wife.
  • the content of the biodegradable polymer raw material is about 10 parts by weight to about 40 parts by weight, about 10 parts by weight to about 30 parts by weight, and about 10 parts by weight to about 20 parts by weight.
  • about 20 parts by weight to about 40 parts by weight, about 20 parts by weight to about 30 parts by weight, or about 30 parts by weight to about 40 parts by weight is about 10 parts by weight to about 40 parts by weight.
  • the content of the drug raw material is about 10 parts by weight to about 70 parts by weight, about 10 parts by weight to about 60 parts by weight, about 10 parts by weight to about 50 parts by weight, about 10 parts by weight to about 40 parts by weight, about 10 parts by weight to about 30 parts by weight, about 10 parts by weight to about 20 parts by weight, about 20 parts by weight to about 70 parts by weight, about 20 parts by weight to about 60 parts by weight, about 20 parts by weight to about 50 parts by weight, about 20 parts by weight to about 40 parts by weight, about 20 parts by weight to about 30 parts by weight, about 30 parts by weight to about 70 parts by weight, about 40 parts by weight to about 70 parts by weight, about 50 parts by weight to about 70 parts by weight, about 60 parts by weight to about 70 parts by weight, about 40 parts by weight to about 70 parts by weight, about 50 parts by weight to about 70 parts by weight, about 60 parts by weight to about 70 parts by weight, about 40 parts by weight to about 70 parts by weight, about 50 parts by weight to about 70 parts by weight, about 60 parts by weight to
  • the content of the organic acid is about 5 parts by weight to about 40 parts by weight, about 5 parts by weight to about 30 parts by weight, and about 5 parts by weight to about 20 parts by weight. parts, about 5 parts by weight to about 10 parts by weight, about 15 parts by weight to about 40 parts by weight, about 15 parts by weight to about 30 parts by weight, about 15 parts by weight to about 20 parts by weight, about 25 parts by weight to about 40 parts by weight. parts, about 25 parts by weight to about 30 parts by weight, or about 35 parts by weight to about 40 parts by weight.
  • a solvent may be additionally included in the mixed solution.
  • the content of the solvent may be greater than 0 parts by weight to about 70 parts by weight based on 100 parts by weight of the mixed solution. In one embodiment of the present application, the solvent is present in an amount of more than 0 parts by weight to about 70 parts by weight, more than 0 parts by weight to about 60 parts by weight, more than 0 parts by weight to about 50 parts by weight, and more than 0 parts by weight to about 40 parts by weight.
  • the drug raw material, organic acid, and/or additive may function as a solvent, but may not be limited thereto.
  • the mixed solution may further include an additive, but may not be limited thereto.
  • the content of the additive may be more than 0 parts by weight to about 20 parts by weight, more than 0 parts by weight to about 10 parts by weight, or about 10 parts by weight to about 20 parts by weight.
  • the additive may be a plasticizer, cross-linking agent, pH adjuster, solubilizer, or viscosity adjuster.
  • the plasticizer can facilitate the molding process by giving fluidity to the biodegradable polymer.
  • the cross-linking agent may control the degree of decomposition by chemically bonding the polymer chains.
  • the pH adjuster may increase or decrease the pH of the solution to keep the drug and polymer stable in the aqueous solution.
  • the solubilizer may be an auxiliary agent that allows polymers and drugs to dissolve in solutions other than solvents.
  • the viscosity regulator may increase or decrease the viscosity of the mixed solution.
  • the processing involves cutting the compressed polymer fiber sheet into chips with a width of about 1 mm to about 20 mm, a length of about 1 mm to about 20 mm, and a thickness of about 0.05 mm to about 5 mm. It may include:
  • the horizontal length of the compressed polymer fiber sheet is about 5 mm to about 20 mm, about 10 mm to about 20 mm, about 15 mm to about 20 mm, about 5 mm to about 15 mm, or from about 3 mm to about 10 mm. In one embodiment of the present application, a preferred horizontal length of the compressed polymer fiber sheet may be about 3 mm to about 10 mm.
  • the longitudinal length of the compressed polymer fiber sheet is about 1 mm to about 20 mm, about 5 mm to about 20 mm, about 10 mm to about 20 mm, about 15 mm to about 20 mm, It may be from about 1 mm to about 15 mm, from about 5 mm to about 15 mm, or from about 3 mm to about 10 mm. In one embodiment of the present application, the preferred vertical length of the compressed polymer fiber sheet may be about 3 mm to about 10 mm.
  • the thickness of the compressed polymer fiber sheet is about 0.05 mm to about 5 mm, about 0.05 mm to about 4 mm, about 0.05 mm to about 3 mm, about 0.05 mm to about 2 mm, about 0.05 mm to about 1 mm, about 0.5 mm to about 5 mm, about 0.5 mm to about 4 mm, about 0.5 mm to about 3 mm, about 0.5 mm to about 2 mm, about 0.5 mm to about 1 mm, about 1 mm to about 5 mm, from about 1 mm to about 4 mm, from about 1 mm to about 3 mm, from about 1 mm to about 2 mm, from about 2 mm to about 5 mm, from about 2 mm to about 4 mm, from about 2 mm to about It can be 3 mm, about 3 mm to about 5 mm, about 3 mm to about 4 mm, or about 4 mm to about 5 mm.
  • the average diameter of the polymer fiber may be from about 0.1 ⁇ m to about 100 ⁇ m, but may not be limited thereto.
  • the average diameter of the polymer fibers is about 0.1 ⁇ m to about 90 ⁇ m, about 0.1 ⁇ m to about 80 ⁇ m, about 0.1 ⁇ m to about 70 ⁇ m, about 0.1 ⁇ m to about 60 ⁇ m, about 0.1 ⁇ m to about 50 ⁇ m, about 0.1 ⁇ m.
  • to about 40 ⁇ m from about 0.1 ⁇ m to about 30 ⁇ m, from about 0.1 ⁇ m to about 20 ⁇ m, from about 0.1 ⁇ m to about 10 ⁇ m, from about 1 ⁇ m to about 100 ⁇ m, from about 1 ⁇ m to about 90 ⁇ m, from about 1 ⁇ m to about 80 ⁇ m, about 1 ⁇ m to about 70 ⁇ m, about 1 ⁇ m to about 60 ⁇ m, about 1 ⁇ m to about 50 ⁇ m, about 1 ⁇ m to about 40 ⁇ m, about 1 ⁇ m to about 30 ⁇ m, about 1 ⁇ m to about 20 ⁇ m , about 1 ⁇ m to about 10 ⁇ m, about 10 ⁇ m to about 100 ⁇ m, about 10 ⁇ m to about 90 ⁇ m, about 10 ⁇ m to about 80 ⁇ m, about 10 ⁇ m to about 70 ⁇ m, about 10 ⁇ m to about 60 ⁇ m, about 10 ⁇ m to about 50 ⁇ m, about 10 ⁇ m to about 40 ⁇
  • the drug may include one or more types selected from anti-inflammatory agents and antibiotics.
  • the drug raw material may be mixed in an amount of about 0.1 parts by weight to about 1,000 parts by weight based on 100 parts by weight of the biodegradable polymer raw material.
  • the drug raw material is about 0.1 part by weight to about 900 parts by weight, about 0.1 part by weight to about 800 parts by weight, about 0.1 part by weight to about 700 parts by weight, and about 0.1 part by weight to about 100 parts by weight of the biodegradable polymer raw material.
  • the antibiotic is chlorohexidine, minocycline, doxycycline, metronidazole, ofloxacin, tetracycline, tinida It may include one or more selected from tinidazole and ketonazole, but is not limited thereto.
  • the anti-inflammatory agent is Ibuprofen, Fenoprofen, Flurbiprofen, Carprofen, Diclofenac, Fenbufen. , Fenclozic Acid, Flufenamic Acid, Indomethacin, Indoprofen, Ketoprofen, Lonazolac, Loxoprofen ( Loxoprofen, Meclofenamic Acid, Mefenamic Acid, Naproxen, Proprionic Acids, Salicylic Acid, Sulindac, Tolmetin ), Meloxicam, Oxicams, Piroxicam, Tenoxicam, Etodolac, and Oxaprozin. It may be, but is not limited to this.
  • the biodegradable polymer raw materials include gelatin, collagen, alginate, chitosan, fibrin, hyaluronic acid, and dextran. ), poly(lactic acid), poly(glycolic acid), poly(lactic-co-glycolic acid), poly(caprolactone) ) and poly(orthoester), but is not limited thereto.
  • the conditions under which the electrospinning is performed may be as follows, but may not be limited thereto:
  • the voltage difference is from about 1 kV to about 100 kV;
  • the radiating distance is from about 1 cm to about 100 cm;
  • the orifice size of the nozzle is about 0.01 mm to about 2 mm;
  • the supply amount of the electrospinning solution is about 1 mL/hr to about 400 mL/hr.
  • the voltage difference of the electrospinning is about 1 kV to about 100 kV, about 1 kV to about 90kV, about 1 kV to about 80kV, about 1 kV to about 70kV, about 1 kV to about 60kV. , about 1 kV to about 50 kV, about 1 kV to about 40 kV, about 1 kV to about 30 kV, about 1 kV to about 20 kV, about 1 kV to about 10 kV, about 10 kV to about 100 kV, about 10 kV to about 90 kV.
  • the electrospinning distance is about 1 cm to about 100 cm, about 1 cm to about 90 cm, about 1 cm to about 80 cm, about 1 cm to about 70 cm, about 1 cm to about 60 cm, about 1 cm to about 50 cm, about 1 cm to about 40 cm, about 1 cm to about 30 cm, about 1 cm to about 20 cm, about 1 cm to about 10 cm, about 10 cm to about 100 cm , about 10 cm to about 90 cm, about 10 cm to about 80 cm, about 10 cm to about 70 cm, about 10 cm to about 60 cm, about 10 cm to about 50 cm, about 10 cm to about 40 cm, about 10 cm to about 30 cm, about 10 cm to about 20 cm, about 20 cm to about 100 cm, about 20 cm to about 90 cm, about 20 cm to about 80 cm, about 20 cm to about 70 cm, about 20 cm to about 60 cm, from about 20 cm to about 50 cm, from about 20 cm to about 40 cm, from about 20 cm to about 30 cm, from about 30 cm to about 100 cm, from about 30 cm to about 90 cm, from about
  • the hole size of the nozzle is about 0.01 mm to about 2 mm, 0.01 mm to about 1 mm, about 0.01 mm to about 0.5 mm, about 0.1 mm to about 2 mm, about 0.1 mm. mm to about 1 mm, about 0.1 mm to about 0.5 mm, or about 1 mm to about 2 mm.
  • the supply amount of the electrospinning solution may be about 1 mL/hr to about 800 mL/hr, or about 1 mL/hr to about 400 mL/hr. In one embodiment of the present application, the supply amount of the electrospinning solution is about 1 mL/hr to about 800 mL/hr, about 1 mL/hr to about 600 mL/hr, about 1 mL/hr to about 400 mL/hr.
  • hr about 200 mL/hr to about 800 mL/hr, about 200 mL/hr to about 600 mL/hr, about 200 mL/hr to about 400 mL/hr, about 200 mL/hr to about 350 mL/hr.
  • the conditions for obtaining the polymer fiber may be as follows, but may not be limited thereto:
  • the compressed air flow rate may be about 100 L/min to about 1,000 L/min. In one embodiment of the present application, the compressed air flow rate is about 100 L/min to about 1,000 L/min, about 100 L/min to about 900 L/min, about 100 L/min to about 800 L/min, about 100 L/min to about 700 L/min, about 100 L/min to about 600 L/min, about 100 L/min to about 500 L/min, about 100 L/min to about 400 L/min, about 100 L /min to about 300 L/min, about 100 L/min to about 200 L/min, about 200 L/min to about 1,000 L/min, about 200 L/min to about 900 L/min, about 200 L/min to about 800 L/min, from about 200 L/min to about 700 L/min, from about 200 L/min to about 600 L/min, from about 200 L/min to about 500 L/min, from about 200 L/min to about 400 L/min, about 200 L/min to about 300 L/min, about 300 L
  • the collector from which the polymer fiber is obtained may have a collector drum rotation speed of about 1 rpm to about 100 rpm, and a moving speed of the conveyor belt may be about 0.01 m/min to about 1 m/min. .
  • the collector drum rotation speed is about 1 rpm to about 100 rpm, about 10 rpm to about 100 rpm, about 10 rpm to about 90 rpm, about 10 rpm to about 80 rpm, about 10 rpm to about 10 rpm.
  • the moving speed of the conveyor belt is about 0.01 m/min to about 1 m/min, about 0.01 m/min to about 0.8 m/min, about 0.01 m/min to about 0.6 m/min. , about 0.01 m/min to about 0.4 m/min, about 0.01 m/min to about 0.2 m/min, about 0.01 m/min to about 0.1 m/min, about 0.05 m/min to about 1 m/min, about 0.05 m/min to about 0.8 m/min, about 0.05 m/min to about 0.6 m/min, about 0.05 m/min to about 0.4 m/min, about 0.05 m/min to about 0.2 m/min, about 0.05 m /min to about 0.1 m/min, about 0.1 m/min to about 1 m/min, about 0.1 m/min to about 0.8 m/min, about 0.1 m/min to about 0.6 m/min.
  • 0.6 m/min about 0.2 m/min to about 0.4 m/min, about 0.4 m/min to about 1 m/min, about 0.4 m/min to about 0.8 m/min, about 0.4 m/min to about 0.6 m /min, from about 0.6 m/min to about 1 m/min, from about 0.6 m/min to about 0.8 m/min, or from about 0.8 m/min to about 1 m/min.
  • Gelatin powder was dissolved in a 20% concentration chlorhexidine gluconate 20% solution. Gelatin powder was used as a biodegradable polymer, and a 20% concentration aqueous solution of chlorhexidine gluconate was used as a solvent and drug to dissolve the biodegradable polymer.
  • a mixed solution of biodegradable polymer and drug was prepared by mixing ascorbic acid powder and glycerol in the solution, and the mixed solution was stirred at a speed of about 200 rpm for 2 hours.
  • composition of the mixed solution is shown in Table 1 below:
  • the mixed solution of the biodegradable polymer and drug was electrospun under the conditions of a voltage difference of 50 kV, a spinning distance of 55 cm, and a nozzle gauge of 23 GA (gauge).
  • the supply amount of the electrospinning solution was adjusted to 200 mL/hr to 400 mL/hr, and a polymer fiber sheet in which fibers were entangled in a network was manufactured through electrospinning (see Figures 2 and 3).
  • the spinning chamber where electrospinning was performed was adjusted to a humidity of 5% to 10% and a temperature of 20°C to 25°C, and the room where the electrospinning machine was operated was controlled to have a humidity of 15% to 35% and a temperature of 20°C to 25°C. .
  • a polymer fiber sheet containing a mixed component of biodegradable polymer and drug was manufactured in each polymer fiber.
  • the polymer fiber sheet was placed in a rectangular mold with one side rounded, and the mold was compressed by applying a pressure of 10 MPa to prepare a circular drug-releasing biodegradable polymer fiber chip.
  • the biodegradable polymer fiber chip was manufactured with a width of 4 mm, a length of 5 mm, and a thickness of 0.4 mm, and the average diameter of the polymer fiber was confirmed to be 2 ⁇ m to 4 ⁇ m (see FIGS. 4 and 5).

Abstract

The present application relates to a preparation method for a biodegradable polymer fibre chip containing a drug.

Description

생분해성 고분자 섬유 칩의 제조방법Manufacturing method of biodegradable polymer fiber chips
본원은, 약물을 함유한 생분해성 고분자 섬유 칩의 제조방법에 관한 것이다.This application relates to a method of manufacturing a biodegradable polymer fiber chip containing a drug.
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. 따라서, 조직유착과 염증을 방지할 수 있고 효과적으로 상처 부위를 치료할 수 있는 물질로서 섬유 시트에 대한 연구가 진행되고 있다. Tissue adhesion or inflammation usually occurs after dental surgery or during the treatment process. Tissue adhesion refers to the joining of abnormal fibrous connective tissue at the wound site. These tissue adhesions may naturally decompose over time, but in some cases, they may remain in the body and cause aftereffects. Therefore, research is being conducted on fiber sheets as a material that can prevent tissue adhesion and inflammation and effectively treat wounds.
치과 응용분야에서는 치주질환 치료 후 치주낭의 염증 발현을 억제하기 위한 많은 시도가 있었으며, 섬유와 약물을 함유한 섬유 칩을 이용하여 탑재된 약물이 지속적으로 방출되도록 하는 종래기술(대한민국 등록특허 제10-1534522호)이 있었다. 그러나, 상기 종래기술은 생분해성 고분자와 약물을 사용하여 섬유를 제조하는 것이나, 이의 제조를 위하여 휘발성 용매(예를 들어, 알코올, 포름산 및 아세트산)가 사용되어야 하고, 이러한 조성에서는 실험실 스케일에서는 섬유 칩이 제조되었으나 산업 스케일로는 목적하는 규격의 섬유 칩이 제조되지 않는 문제점이 있다.In the field of dental applications, many attempts have been made to suppress the development of inflammation in periodontal pockets after treatment of periodontal disease, and a prior art technology (Korean Registered Patent No. 10- 1534522). However, the prior art is to produce fibers using biodegradable polymers and drugs, but volatile solvents (e.g., alcohol, formic acid, and acetic acid) must be used for their production, and in this composition, fiber chips are used in laboratory scale. Although this has been manufactured, there is a problem in that fiber chips of the desired standard cannot be manufactured on an industrial scale.
일반적으로 약물이 함유된 생분해성 고분자 칩 및 필름 제조는 캐스팅 또는 몰딩을 이용한다. 이때, 고분자와 약물을 용매에 함께 녹인 후 일정 크기의 틀에 넣어 용매를 증발시키는 건조 과정을 거친다. 이후, 성형공정을 거쳐 약물이 포함된 필름이 제조되는데, 이때, 제조된 고분자 및 약물의 혼합 용액은 충분히 건조되어 수분 및 용매가 제거되어야 한다. 제조되는 고분자 필름의 형태가 일정한 두께로 유지되도록 하기 위하여, 고분자와 약물이 담긴 용액 틀이 움직임 없이 장시간 고정되어 있어야 하며, 용매에 따라 건조공정 중 가열을 하거나, 진공 상태를 유지해야 하는 경우도 있다. 고분자 필름 내 기포 생성 시 불량품이 제조되기 때문에, 최대한 천천히 용매를 증발시켜 형태를 유지한 상태에서 제거해야 한다. 따라서 12 시간 내지 약 72 시간, 또는 72 시간 이상의 건조 시간이 필요할 수 있다. 이러한 건조시간은 고분자 필름의 생산성을 결정하는데 큰 요인이다.Generally, casting or molding is used to manufacture drug-containing biodegradable polymer chips and films. At this time, the polymer and drug are dissolved together in a solvent and then put into a mold of a certain size and go through a drying process to evaporate the solvent. Afterwards, a film containing a drug is manufactured through a molding process. At this time, the prepared mixed solution of polymer and drug must be sufficiently dried to remove moisture and solvent. In order to maintain the shape of the polymer film being manufactured at a constant thickness, the solution frame containing the polymer and drug must be fixed for a long time without moving, and depending on the solvent, it may be necessary to heat or maintain a vacuum during the drying process. . Since defective products are manufactured when bubbles are created in the polymer film, the solvent must be evaporated as slowly as possible and removed while maintaining its shape. Accordingly, a drying time of 12 hours to about 72 hours, or more than 72 hours may be required. This drying time is a major factor in determining the productivity of polymer films.
종래의 전기방사에 사용되고 있는 용매로써 아세트산이 주로 사용되고 있으나, 잔류 유기용매 문제가 발생할 수 있다. 국내 의약품 잔류유기 용매기준에서, 아세트산의 잔류유기용매 한도는 전체 무게의 0.5% 이하이다. 아세트산을 저농도로 사용하여 전기방사를 하는 경우, 방사 이후 섬유에 잔류하는 아세트산의 양을 감소시킬 수 있으나, 전기방사 시 고분자 용액이 분사(spraying)되는 현상이 일어나 섬유(fiber)가 아닌 비드(bead)가 생성될 수 있다. 또한 전기방사 용액이 방사 중 대부분 제거되지 않아, 방사 중 섬유가 젖는 현상이 발생하여 전기방사 된 섬유에 미처 제거되지 않은 용매가 잔류하거나, 남은 용매에 생성된 고분자 섬유가 다시 녹는 재용해 현상이 발생할 수 있는 문제점이 있다.Acetic acid is mainly used as a solvent in conventional electrospinning, but problems with residual organic solvents may occur. In domestic pharmaceutical residual organic solvent standards, the residual organic solvent limit for acetic acid is less than 0.5% of the total weight. When electrospinning using a low concentration of acetic acid, the amount of acetic acid remaining in the fiber after spinning can be reduced. However, during electrospinning, the polymer solution is sprayed, forming beads rather than fibers. ) can be created. In addition, most of the electrospinning solution is not removed during spinning, which causes the fiber to become wet during spinning, resulting in solvent that has not yet been removed remaining in the electrospun fiber, or a re-dissolution phenomenon in which the polymer fibers created in the remaining solvent may melt again. There are possible problems.
본원은 생분해성 고분자 원료와 약물의 농도를 조절하고, 아세트산을 대신하여 인체에 무해한 유기산을 사용하여 원료 용액을 제조하고 이를 전기방사 함으로써, 산업 스케일로 생분해성 고분자 섬유 칩을 제조할 수 있는 방법을 제공하고자 한다.This institute has developed a method for manufacturing biodegradable polymer fiber chips on an industrial scale by controlling the concentration of biodegradable polymer raw materials and drugs, preparing a raw material solution using organic acids that are harmless to the human body instead of acetic acid, and electrospinning them. We would like to provide
그러나, 본원이 해결하고자 하는 과제는 이상에서 언급한 과제로 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 당업자에게 명확하게 이해될 수 있을 것이다.However, the problem to be solved by the present application is not limited to the problems mentioned above, and other problems not mentioned will be clearly understood by those skilled in the art from the description below.
본원의 일 측면은, (a) 생분해성 고분자 원료, 약물 원료 및 유기산을 혼합하여 혼합용액을 형성하는 것; (b) 상기 혼합용액을 전기방사하여 고분자 섬유가 네트워크 형태로 얽혀 있는 고분자 섬유 시트를 제조하는 것; 및 (c) 상기 고분자 섬유 시트를 압축 및 가공하여 생분해성 고분자 섬유 칩을 수득하는 것을 포함하는, 생분해성 고분자 섬유 칩의 제조방법을 제공한다.One aspect of the present application is to form a mixed solution by mixing (a) a biodegradable polymer raw material, a drug raw material, and an organic acid; (b) electrospinning the mixed solution to produce a polymer fiber sheet in which polymer fibers are entangled in a network form; and (c) compressing and processing the polymer fiber sheet to obtain a biodegradable polymer fiber chip.
본원의 일 구현예에 따른 상기 생분해성 고분자 섬유 칩의 제조방법은, 상기 약물 원료와 그 농도를 최적의 비율로 조절하여, 목적하는 생분해성 고분자 섬유 칩을 제조할 수 있다. In the method for manufacturing the biodegradable polymer fiber chip according to an embodiment of the present application, the desired biodegradable polymer fiber chip can be manufactured by adjusting the drug raw material and its concentration to an optimal ratio.
본원의 일 구현예에 따르면, 본원의 생분해성 고분자 섬유 칩 제조시, 휘발성 용매(예를 들어, 알코올 또는 포름산)를 사용하지 않아, 경제적으로 효율적이며, 생분해성 고분자 섬유 칩을 산업 스케일로 제조할 수 있다.According to one embodiment of the present application, when manufacturing the biodegradable polymer fiber chip of the present application, volatile solvents (for example, alcohol or formic acid) are not used, so it is economically efficient and the biodegradable polymer fiber chip can be manufactured on an industrial scale. You can.
본원의 일 구현예에 따르면, 높은 전기 방사 용액의 공급량으로 인해, 대량 생산 및 빠른 생산이 가능할 수 있다.According to one embodiment of the present application, mass production and rapid production may be possible due to the high supply amount of the electrospinning solution.
본원의 일 구현예에 따르면, 종래에 사용하던 캐스팅 또는 몰딩 방식을 대신하여 전기방사를 수행함으로써, 고분자 용액에 있는 용매가 방사됨과 동시에 제거되며, 콜렉터(collector)에 고분자 섬유가 수득되어, 섬유화된 고분자를 바로 사용할 수 있다.According to one embodiment of the present application, by performing electrospinning instead of the casting or molding method used conventionally, the solvent in the polymer solution is removed at the same time as it is spun, and polymer fibers are obtained in the collector, and the fiberized The polymer can be used immediately.
본원의 일 구현예에 따르면, 전기방사된 고분자 섬유는 나노미터 또는 마이크로미터의 두께의 섬유 형태로 수득되어, 상기 고분자 섬유는 높은 표면적을 가질 수 있다.According to one embodiment of the present application, electrospun polymer fibers are obtained in the form of fibers with a thickness of nanometers or micrometers, so that the polymer fibers can have a high surface area.
본원의 일 구현예에 따른 생분해성 고분자 섬유 칩은 후속적으로 건조되거나, 또는 건조되지 않을 수 있으나, 이에 제한되지 않을 수 있다. 본원의 일 구현예에 따른 생분해성 고분자 섬유 칩이 후속적으로 건조되는 경우, 건조 시간은 0 시간 초과 내지 약 12 시간으로서, 종래의 캐스팅 또는 몰딩 방식에 소요되는 건조 시간보다 단축된 시간에 건조될 수 있으며, 익일 성형작업이 가능할 수 있다.The biodegradable polymer fiber chip according to an embodiment of the present application may or may not be subsequently dried, but may not be limited thereto. When the biodegradable polymer fiber chip according to one embodiment of the present application is subsequently dried, the drying time is from more than 0 hours to about 12 hours, and is dried in a shorter time than the drying time required for the conventional casting or molding method. and next-day molding work may be possible.
본원의 일 구현예에 따른 컨베이어형의 수집기의 속도 조절, 압축 공기의 유량 조절 및 전압 조절을 통해, 산업 스케일의 생분해성 고분자 섬유 칩의 제조 효율을 상승시킬 수 있다.The manufacturing efficiency of industrial-scale biodegradable polymer fiber chips can be increased by controlling the speed of the conveyor-type collector, controlling the flow rate of compressed air, and controlling the voltage according to an embodiment of the present application.
도 1은, 본원의 일 실시예에 있어서, 생분해성 고분자와 약물의 혼합용액을 나타낸 사진이다.Figure 1 is a photograph showing a mixed solution of a biodegradable polymer and a drug according to an example of the present application.
도 2는, 본원의 일 실시예에 있어서, 고분자 섬유 시트의 사진이다. Figure 2 is a photograph of a polymer fiber sheet according to an example of the present application.
도 3a 내지 3c는, 본원의 일 실시예에 있어서, 고분자 섬유 시트를 주사전자현미경(scanning electron microscope)으로 각각 500 배(a), 1000 배(b), 및 2000 배(c)로 분석한 사진이며, 도 3d는 상기 고분자 섬유 시트를 5000 배 확대하여 확인되는 고분자 섬유의 지름을 나타낸 사진이다. 3A to 3C are photographs of a polymer fiber sheet analyzed by a scanning electron microscope at 500 times (a), 1000 times (b), and 2000 times (c), respectively, in an example of the present application. , and Figure 3d is a photograph showing the diameter of the polymer fiber confirmed by magnifying the polymer fiber sheet 5000 times.
도 4a 및 4b는 본원의 일 실시예에 있어서, 고분자 섬유 시트로 제작한, 생분해성 고분자 섬유 칩의 사진이다. Figures 4a and 4b are photographs of a biodegradable polymer fiber chip manufactured from a polymer fiber sheet according to an example of the present application.
도 5a 내지 5c는 본원의 일 실시예에 있어서, 고분자 섬유 시트를 주사전자현미경으로 각각 500 배(a), 1000 배(b), 및 2000 배(c)로 분석한 사진이며, 도 5d는 상기 고분자 섬유 시트를 5000 배 확대하여 확인되는 고분자 섬유의 지름을 나타낸 사진이다.Figures 5a to 5c are photographs of a polymer fiber sheet analyzed by a scanning electron microscope at 500 times (a), 1000 times (b), and 2000 times (c), respectively, in an example of the present application, and Figure 5d is the above This is a photograph showing the diameter of the polymer fibers confirmed by magnifying the polymer fiber sheet 5000 times.
이하, 첨부한 도면을 참조하여 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있도록 본원의 구현예 및 실시예를 상세히 설명한다. 그러나 본원은 여러 가지 상이한 형태로 구현될 수 있으며 여기에서 설명하는 구현예 및 실시예에 한정되지 않는다. 그리고 도면에서 본 발명을 명확하게 설명하기 위해서 설명과 관계없는 부분은 생략하였으며, 명세서 전체를 통하여 유사한 부분에 대해서는 유사한 도면 부호를 붙였다. Hereinafter, with reference to the attached drawings, implementation examples and embodiments of the present invention will be described in detail so that those skilled in the art can easily implement the present invention. However, the present application may be implemented in various different forms and is not limited to the implementation examples and examples described herein. In order to clearly explain the present invention in the drawings, parts that are not related to the description are omitted, and similar parts are given similar reference numerals throughout the specification.
본원 명세서 전체에서, 어떤 부분이 다른 부분과 "연결"되어 있다고 할 때, 이는 "직접적으로 연결"되어 있는 경우뿐 아니라, 그 중간에 다른 소자를 사이에 두고 "전기적으로 연결"되어 있는 경우도 포함한다. Throughout this specification, when a part is said to be “connected” to another part, this includes not only the case where it is “directly connected,” but also the case where it is “electrically connected” with another element in between. do.
본원 명세서 전체에서, 어떤 부재가 다른 부재 "상에" 위치하고 있다고 할 때, 이는 어떤 부재가 다른 부재에 접해 있는 경우뿐 아니라 두 부재 사이에 또 다른 부재가 존재하는 경우도 포함한다.Throughout this specification, when a member is said to be located “on” another member, this includes not only the case where the member is in contact with the other member, but also the case where another member exists between the two members.
본원 명세서 전체에서, 어떤 부분이 어떤 구성요소를 "포함"한다고 할 때, 이는 특별히 반대되는 기재가 없는 한 다른 구성요소를 제외하는 것이 아니라 다른 구성 요소를 더 포함할 수 있는 것을 의미한다.Throughout the specification of the present application, when a part “includes” a certain element, this means that it may further include other elements rather than excluding other elements, unless specifically stated to the contrary.
본 명세서에서 사용되는 정도의 용어 "약", "실질적으로" 등은 언급된 의미에 고유한 제조 및 물질 허용오차가 제시될 때 그 수치에서 또는 그 수치에 근접한 의미로 사용되고, 본원의 이해를 돕기 위해 정확하거나 절대적인 수치가 언급된 개시 내용을 비양심적인 침해자가 부당하게 이용하는 것을 방지하기 위해 사용된다.As used herein, the terms “about,” “substantially,” and the like are used to mean at or close to a numerical value when manufacturing and material tolerances inherent in the stated meaning are presented, and to aid understanding of the present application. It is used to prevent unscrupulous infringers from unfairly exploiting disclosures in which precise or absolute figures are mentioned.
본원 명세서 전체에서 사용되는 정도의 용어 "~ 하는 단계" 또는 "~의 단계"는 "~를 위한 단계"를 의미하지 않는다.As used throughout the specification, the terms “step of” or “step of” do not mean “step for.”
본원 명세서 전체에서, 마쿠시 형식의 표현에 포함된 "이들의 조합(들)"의 용어는 마쿠시 형식의 표현에 기재된 구성 요소들로 이루어진 군에서 선택되는 하나 이상의 혼합 또는 조합을 의미하는 것으로서, 상기 구성 요소들로 이루어진 군에서 선택되는 하나 이상을 포함하는 것을 의미한다.Throughout this specification, the term "combination(s) thereof" included in the Markushi format expression means a mixture or combination of one or more selected from the group consisting of the components described in the Markushi format expression, It means containing one or more selected from the group consisting of the above components.
본원 명세서 전체에서, "A 및/또는 B"의 기재는, "A 또는 B, 또는 A 및 B"를 의미한다.Throughout this specification, description of “A and/or B” means “A or B, or A and B.”
본원 명세서 전체에서, "생분해성 고분자 섬유 칩"은 "고분자 섬유 칩" 또는 "생분해성 고분자 섬유 칩"으로서 지칭될 수 있다.Throughout this specification, “biodegradable polymer fiber chips” may be referred to as “polymer fiber chips” or “biodegradable polymer fiber chips.”
이하, 첨부된 도면을 참조하여 본원의 구현예 및 실시예를 상세히 설명한다. 그러나, 본원이 이러한 구현예 및 실시예와 도면에 제한되는 것은 아니다.Hereinafter, implementation examples and examples of the present application will be described in detail with reference to the attached drawings. However, the present application is not limited to these embodiments, examples, and drawings.
본원의 일 측면은, (a) 생분해성 고분자 원료, 약물 원료 및 유기산을 혼합하여 혼합용액을 형성하는 것; (b) 상기 혼합용액을 전기방사하여 고분자 섬유가 네트워크 형태로 얽혀 있는 고분자 섬유 시트를 제조하는 것; 및 (c) 상기 고분자 섬유 시트를 압축 및 가공하여 생분해성 고분자 섬유 칩을 수득하는 것을 포함하는, 생분해성 고분자 섬유 칩의 제조방법을 제공한다. One aspect of the present application is to form a mixed solution by mixing (a) a biodegradable polymer raw material, a drug raw material, and an organic acid; (b) electrospinning the mixed solution to produce a polymer fiber sheet in which polymer fibers are entangled in a network form; and (c) compressing and processing the polymer fiber sheet to obtain a biodegradable polymer fiber chip.
본원의 일 구현예에 있어서, 상기 유기산은 아스코르브산(ascorbic acid), 시트르산(citric acid), 타타르산(tartaric acid), 탄닌산(tannic acid), 젖산(lactic acid), 뷰티릭산(butyric acid), 및 팔미트산(palmitic acid)에서 선택되는 하나 이상인 것일 수 있으나, 이에 제한되지 않을 수 있다.In one embodiment of the present application, the organic acid is ascorbic acid, citric acid, tartaric acid, tannic acid, lactic acid, butyric acid, and palmitic acid, but may not be limited thereto.
본원의 일 구현예에 있어서, 상기 혼합용액 100 중량부에 대하여, 상기 생분해성 고분자 원료의 함량은 약 10 중량부 내지 약 40 중량부이고, 상기 약물 원료의 함량은 약 10 중량부 내지 약 70 중량부인 것일 수 있다. In one embodiment of the present application, with respect to 100 parts by weight of the mixed solution, the content of the biodegradable polymer raw material is about 10 parts by weight to about 40 parts by weight, and the content of the drug raw material is about 10 parts by weight to about 70 parts by weight. It could be your wife.
예를 들어, 상기 혼합용액 100 중량부에 대하여, 상기 생분해성 고분자 원료의 함량은 약 10 중량부 내지 약 40 중량부, 약 10 중량부 내지 약 30 중량부, 약 10 중량부 내지 약 20 중량부, 약 20 중량부 내지 약 40 중량부, 약 20 중량부 내지 약 30 중량부, 또는 약 30 중량부 내지 약 40 중량부일 수 있다.For example, with respect to 100 parts by weight of the mixed solution, the content of the biodegradable polymer raw material is about 10 parts by weight to about 40 parts by weight, about 10 parts by weight to about 30 parts by weight, and about 10 parts by weight to about 20 parts by weight. , about 20 parts by weight to about 40 parts by weight, about 20 parts by weight to about 30 parts by weight, or about 30 parts by weight to about 40 parts by weight.
예를 들어, 상기 혼합용액 100 중량부에 대하여, 상기 약물 원료의 함량은 약 10 중량부 내지 약 70 중량부, 약 10 중량부 내지 약 60 중량부, 약 10 중량부 내지 약 50 중량부, 약 10 중량부 내지 약 40 중량부, 약 10 중량부 내지 약 30 중량부, 약 10 중량부 내지 약 20 중량부, 약 20 중량부 내지 약 70 중량부, 약 20 중량부 내지 약 60 중량부, 약 20 중량부 내지 약 50 중량부, 약 20 중량부 내지 약 40 중량부, 약 20 중량부 내지 약 30 중량부, 약 30 중량부 내지 약 70 중량부, 약 40 중량부 내지 약 70 중량부, 약 50 중량부 내지 약 70 중량부, 약 60 중량부 내지 약 70 중량부, 약 40 중량부 내지 약 70 중량부, 약 50 중량부 내지 약 70 중량부, 약 60 중량부 내지 약 70 중량부, 약 50 중량부 내지 약 70 중량부, 또는 약 60 중량부 내지 약 70 중량부일 수 있다.For example, with respect to 100 parts by weight of the mixed solution, the content of the drug raw material is about 10 parts by weight to about 70 parts by weight, about 10 parts by weight to about 60 parts by weight, about 10 parts by weight to about 50 parts by weight, about 10 parts by weight to about 40 parts by weight, about 10 parts by weight to about 30 parts by weight, about 10 parts by weight to about 20 parts by weight, about 20 parts by weight to about 70 parts by weight, about 20 parts by weight to about 60 parts by weight, about 20 parts by weight to about 50 parts by weight, about 20 parts by weight to about 40 parts by weight, about 20 parts by weight to about 30 parts by weight, about 30 parts by weight to about 70 parts by weight, about 40 parts by weight to about 70 parts by weight, about 50 parts by weight to about 70 parts by weight, about 60 parts by weight to about 70 parts by weight, about 40 parts by weight to about 70 parts by weight, about 50 parts by weight to about 70 parts by weight, about 60 parts by weight to about 70 parts by weight, about It may be from 50 parts by weight to about 70 parts by weight, or from about 60 parts by weight to about 70 parts by weight.
본원의 일 구현예에 있어서, 상기 혼합용액 100 중량부에 대하여, 상기 유기산의 함량은 약 5 중량부 내지 약 40 중량부, 약 5 중량부 내지 약 30 중량부, 약 5 중량부 내지 약 20 중량부, 약 5 중량부 내지 약 10 중량부, 약 15 중량부 내지 약 40 중량부, 약 15 중량부 내지 약 30 중량부, 약 15 중량부 내지 약 20 중량부, 약 25 중량부 내지 약 40 중량부, 약 25 중량부 내지 약 30 중량부, 또는 약 35 중량부 내지 약 40 중량부일 수 있다. In one embodiment of the present application, with respect to 100 parts by weight of the mixed solution, the content of the organic acid is about 5 parts by weight to about 40 parts by weight, about 5 parts by weight to about 30 parts by weight, and about 5 parts by weight to about 20 parts by weight. parts, about 5 parts by weight to about 10 parts by weight, about 15 parts by weight to about 40 parts by weight, about 15 parts by weight to about 30 parts by weight, about 15 parts by weight to about 20 parts by weight, about 25 parts by weight to about 40 parts by weight. parts, about 25 parts by weight to about 30 parts by weight, or about 35 parts by weight to about 40 parts by weight.
본원의 일 구현예에 있어서, 상기 혼합용액에 용매가 추가 포함될 수 있다.In one embodiment of the present application, a solvent may be additionally included in the mixed solution.
본원의 일 구현예에 있어서, 상기 혼합 용액에서 용매가 추가 포함되는 경우, 상기 혼합용액 100 중량부에 대하여, 상기 용매의 함량은 0 중량부 초과 내지 약 70 중량부일 수 있다. 본원의 일 구현예에 있어서, 상기 용매는 0 중량부 초과 내지 약 70 중량부, 0 중량부 초과 내지 약 60 중량부, 0 중량부 초과 내지 약 50 중량부, 0 중량부 초과 내지 약 40 중량부, 0 중량부 초과 내지 약 30 중량부, 0 중량부 초과 내지 약 20 중량부, 0 중량부 초과 내지 약 10 중량부, 약 10 중량부 내지 약 70 중량부, 약 10 중량부 내지 약 60 중량부, 약 10 중량부 내지 약 50 중량부, 약 10 중량부 내지 약 40 중량부, 약 10 중량부 내지 약 30 중량부, 약 10 중량부 내지 약 20 중량부, 약 20 중량부 내지 약 70 중량부, 약 20 중량부 내지 약 60 중량부, 약 20 중량부 내지 약 50 중량부, 약 20 중량부 내지 약 40 중량부, 약 20 중량부 내지 약 30 중량부, 약 30 중량부 내지 약 70 중량부, 약 30 중량부 내지 약 60 중량부, 약 30 중량부 내지 약 50 중량부, 약 30 중량부 내지 약 40 중량부, 약 40 중량부 내지 약 70 중량부, 약 40 중량부 내지 약 60 중량부, 약 40 중량부 내지 약 50 중량부, 약 50 중량부 내지 약 70 중량부, 약 50 중량부 내지 약 60 중량부, 또는 약 60 중량부 내지 약 70 중량부일 수 있다.In one embodiment of the present application, when a solvent is additionally included in the mixed solution, the content of the solvent may be greater than 0 parts by weight to about 70 parts by weight based on 100 parts by weight of the mixed solution. In one embodiment of the present application, the solvent is present in an amount of more than 0 parts by weight to about 70 parts by weight, more than 0 parts by weight to about 60 parts by weight, more than 0 parts by weight to about 50 parts by weight, and more than 0 parts by weight to about 40 parts by weight. , greater than 0 parts by weight to about 30 parts by weight, greater than 0 parts by weight to about 20 parts by weight, greater than 0 parts by weight to about 10 parts by weight, about 10 parts by weight to about 70 parts by weight, about 10 parts by weight to about 60 parts by weight. , about 10 parts by weight to about 50 parts by weight, about 10 parts by weight to about 40 parts by weight, about 10 parts by weight to about 30 parts by weight, about 10 parts by weight to about 20 parts by weight, about 20 parts by weight to about 70 parts by weight. , about 20 parts by weight to about 60 parts by weight, about 20 parts by weight to about 50 parts by weight, about 20 parts by weight to about 40 parts by weight, about 20 parts by weight to about 30 parts by weight, about 30 parts by weight to about 70 parts by weight. , about 30 parts by weight to about 60 parts by weight, about 30 parts by weight to about 50 parts by weight, about 30 parts by weight to about 40 parts by weight, about 40 parts by weight to about 70 parts by weight, about 40 parts by weight to about 60 parts by weight. , about 40 parts by weight to about 50 parts by weight, about 50 parts by weight to about 70 parts by weight, about 50 parts by weight to about 60 parts by weight, or about 60 parts by weight to about 70 parts by weight.
본원의 일 구현예에 있어서, 상기 혼합용액에서 용매를 추가로 포함하지 않는 경우에는, 약물 원료, 유기산, 및/또는 첨가제가 용매로써 기능하는 것일 수 있으나, 이에 제한되지 않을 수 있다. In one embodiment of the present application, when the mixed solution does not additionally contain a solvent, the drug raw material, organic acid, and/or additive may function as a solvent, but may not be limited thereto.
본원의 일 구현예에 있어서, 상기 (a)에서, 상기 혼합 용액은 첨가제를 추가 포함하는 것일 수 있으나, 이에 제한되지 않을 수 있다. 여기서, 상기 첨가제가 추가 포함되는 경우, 상기 첨가제의 함량은 0 중량부 초과 내지 약 20 중량부, 0 중량부 초과 내지 약 10 중량부, 또는 약 10 중량부 내지 약 20 중량부일 수 있다.In one embodiment of the present application, in (a), the mixed solution may further include an additive, but may not be limited thereto. Here, when the additive is additionally included, the content of the additive may be more than 0 parts by weight to about 20 parts by weight, more than 0 parts by weight to about 10 parts by weight, or about 10 parts by weight to about 20 parts by weight.
본원의 일 구현예에 있어서, 상기 첨가제는 가소제, 가교제, pH 조절제, 가용화제 또는 점도 조절제일 수 있다. 상기 가소제는 생분해성 고분자에 유동성을 주어 성형 공정을 용이하게 할 수 있다. 상기 가교제는 고분자 사슬을 화학적으로 결합시켜 분해도를 조절하는 것일 수 있다. 상기 pH 조절제는 용액의 pH를 증가 또는 감소시켜, 약물 및 고분자를 수용액상에서 안정하게 유지시키는 것일 수 있다. 상기 가용화제는 고분자 및 약물이 용매 외의 용액에 녹을 수 있도록 하는 보조제일 수 있다. 상기 점도 조절제는 혼합 용액의 점도를 증가 또는 감소시키는 것일 수 있다.In one embodiment of the present application, the additive may be a plasticizer, cross-linking agent, pH adjuster, solubilizer, or viscosity adjuster. The plasticizer can facilitate the molding process by giving fluidity to the biodegradable polymer. The cross-linking agent may control the degree of decomposition by chemically bonding the polymer chains. The pH adjuster may increase or decrease the pH of the solution to keep the drug and polymer stable in the aqueous solution. The solubilizer may be an auxiliary agent that allows polymers and drugs to dissolve in solutions other than solvents. The viscosity regulator may increase or decrease the viscosity of the mixed solution.
본원의 일 구현예에 있어서, 상기 가공은, 압축된 고분자 섬유 시트를 가로 약 1 ㎜ 내지 약 20 ㎜, 세로 약 1 mm 내지 약 20 ㎜ 및 두께 약 0.05 mm 내지 약 5 ㎜의 칩 형태로 절단하는 것을 포함하는 것일 수 있다. In one embodiment of the present application, the processing involves cutting the compressed polymer fiber sheet into chips with a width of about 1 mm to about 20 mm, a length of about 1 mm to about 20 mm, and a thickness of about 0.05 mm to about 5 mm. It may include:
본원의 일 구현예에 있어서, 상기 압축된 고분자 섬유 시트의 가로 길이는 약 5 ㎜ 내지 약 20 ㎜, 약 10 ㎜ 내지 약 20 ㎜, 약 15 ㎜ 내지 약 20 ㎜, 약 5 ㎜ 내지 약 15 ㎜, 또는 약 3 ㎜ 내지 약 10 ㎜일 수 있다. 본원의 일 구현예에 있어서, 상기 압축된 고분자 섬유 시트의 바람직한 가로 길이는 약 3 ㎜ 내지 약 10 ㎜일 수 있다.In one embodiment of the present application, the horizontal length of the compressed polymer fiber sheet is about 5 mm to about 20 mm, about 10 mm to about 20 mm, about 15 mm to about 20 mm, about 5 mm to about 15 mm, or from about 3 mm to about 10 mm. In one embodiment of the present application, a preferred horizontal length of the compressed polymer fiber sheet may be about 3 mm to about 10 mm.
본원의 일 구현예에 있어서, 상기 압축된 고분자 섬유 시트의 세로 길이는 약 1 ㎜ 내지 약 20 ㎜, 약 5 ㎜ 내지 약 20 ㎜, 약 10 ㎜ 내지 약 20 ㎜, 약 15 ㎜ 내지 약 20 ㎜, 약 1 ㎜ 내지 약 15 ㎜, 약 5 ㎜ 내지 약 15 ㎜, 또는 약 3 ㎜ 내지 약 10 ㎜일 수 있다. 본원의 일 구현예에 있어서, 상기 압축된 고분자 섬유 시트의 바람직한 세로 길이의 길이는 약 3 ㎜ 내지 약 10 ㎜일 수 있다.In one embodiment of the present application, the longitudinal length of the compressed polymer fiber sheet is about 1 mm to about 20 mm, about 5 mm to about 20 mm, about 10 mm to about 20 mm, about 15 mm to about 20 mm, It may be from about 1 mm to about 15 mm, from about 5 mm to about 15 mm, or from about 3 mm to about 10 mm. In one embodiment of the present application, the preferred vertical length of the compressed polymer fiber sheet may be about 3 mm to about 10 mm.
본원의 일 구현예에 있어서, 상기 압축된 고분자 섬유 시트의 두께는 약 0.05 mm 내지 약 5 ㎜, 약 0.05 mm 내지 약 4 ㎜, 약 0.05 mm 내지 약 3 ㎜, 약 0.05 mm 내지 약 2 ㎜, 약 0.05 mm 내지 약 1 ㎜, 약 0.5 mm 내지 약 5 ㎜, 약 0.5 mm 내지 약 4 ㎜, 약 0.5 mm 내지 약 3 ㎜, 약 0.5 mm 내지 약 2 ㎜, 약 0.5 mm 내지 약 1 ㎜, 약 1 mm 내지 약 5 ㎜, 약 1 mm 내지 약 4 ㎜, 약 1 mm 내지 약 3 ㎜, 약 1 mm 내지 약 2 ㎜, 약 2 mm 내지 약 5 ㎜, 약 2 mm 내지 약 4 ㎜, 약 2 mm 내지 약 3 ㎜, 약 3 mm 내지 약 5 ㎜, 약 3 mm 내지 약 4 ㎜, 또는 약 4 mm 내지 약 5 ㎜일 수 있다. 본원의 일 구현예에 있어서, 상기 압축된 고분자 섬유 시트의 바람직한 두께는 약 0.05 ㎜ 내지 약 3 mm일 수 있다.In one embodiment of the present application, the thickness of the compressed polymer fiber sheet is about 0.05 mm to about 5 mm, about 0.05 mm to about 4 mm, about 0.05 mm to about 3 mm, about 0.05 mm to about 2 mm, about 0.05 mm to about 1 mm, about 0.5 mm to about 5 mm, about 0.5 mm to about 4 mm, about 0.5 mm to about 3 mm, about 0.5 mm to about 2 mm, about 0.5 mm to about 1 mm, about 1 mm to about 5 mm, from about 1 mm to about 4 mm, from about 1 mm to about 3 mm, from about 1 mm to about 2 mm, from about 2 mm to about 5 mm, from about 2 mm to about 4 mm, from about 2 mm to about It can be 3 mm, about 3 mm to about 5 mm, about 3 mm to about 4 mm, or about 4 mm to about 5 mm. In one embodiment of the present application, a preferred thickness of the compressed polymer fiber sheet may be about 0.05 mm to about 3 mm.
본원의 일 구현예에 있어서, 상기 고분자 섬유의 평균 직경은 약 0.1 μm 내지 약 100 μm 일 수 있으나, 이에 제한되지 않을 수 있다. 상기 고분자 섬유의 평균 직경은 약 0.1 μm 내지 약 90 μm, 약 0.1 μm 내지 약 80 μm, 약 0.1 μm 내지 약 70 μm, 약 0.1 μm 내지 약 60 μm, 약 0.1 μm 내지 약 50 μm, 약 0.1 μm 내지 약 40 μm, 약 0.1 μm 내지 약 30 μm, 약 0.1 μm 내지 약 20 μm, 약 0.1 μm 내지 약 10 μm, 약 1 μm 내지 약 100 μm, 약 1 μm 내지 약 90 μm, 약 1 μm 내지 약 80 μm, 약 1 μm 내지 약 70 μm, 약 1 μm 내지 약 60 μm, 약 1 μm 내지 약 50 μm, 약 1 μm 내지 약 40 μm, 약 1 μm 내지 약 30 μm, 약 1 μm 내지 약 20 μm, 약 1 μm 내지 약 10 μm, 약 10 μm 내지 약 100 μm, 약 10 μm 내지 약 90 μm, 약 10 μm 내지 약 80 μm, 약 10 μm 내지 약 70 μm, 약 10 μm 내지 약 60 μm, 약 10 μm 내지 약 50 μm, 약 10 μm 내지 약 40 μm, 약 10 μm 내지 약 30 μm, 약 10 μm 내지 약 20 μm, 약 20 μm 내지 약 100 μm, 약 20 μm 내지 약 90 μm, 약 20 μm 내지 약 80 μm, 약 20 μm 내지 약 70 μm, 약 20 μm 내지 약 60 μm, 약 20 μm 내지 약 50 μm, 약 20 μm 내지 약 40 μm, 약 20 μm 내지 약 30 μm, 약 30 μm 내지 약 100 μm, 약 30 μm 내지 약 90 μm, 약 30 μm 내지 약 80 μm, 약 30 μm 내지 약 70 μm, 약 30 μm 내지 약 60 μm, 약 30 μm 내지 약 50 μm, 약 30 μm 내지 약 40 μm, 약 40 μm 내지 약 100 μm, 약 40 μm 내지 약 90 μm, 약 40 μm 내지 약 80 μm, 약 40 μm 내지 약 70 μm, 약 40 μm 내지 약 60 μm, 약 40 μm 내지 약 50 μm, 약 50 μm 내지 약 100 μm, 약 50 μm 내지 약 90 μm, 약 50 μm 내지 약 80 μm, 약 50 μm 내지 약 70 μm, 약 50 μm 내지 약 60 μm, 약 60 μm 내지 약 100 μm, 약 60 μm 내지 약 90 μm, 약 60 μm 내지 약 80 μm, 약 60 μm 내지 약 70 μm, 약 70 μm 내지 약 100 μm, 약 70 μm 내지 약 90 μm, 약 70 μm 내지 약 80 μm, 약 80 μm 내지 약 100 μm, 약 80 μm 내지 약 90 μm, 또는 약 90 μm 내지 약 100 μm일 수 있다. 본원의 일 구현예에 있어서, 상기 고분자 섬유의 바람직한 평균 직경은 약 0.1 μm 내지 약 10 μm일 수 있다.In one embodiment of the present application, the average diameter of the polymer fiber may be from about 0.1 μm to about 100 μm, but may not be limited thereto. The average diameter of the polymer fibers is about 0.1 μm to about 90 μm, about 0.1 μm to about 80 μm, about 0.1 μm to about 70 μm, about 0.1 μm to about 60 μm, about 0.1 μm to about 50 μm, about 0.1 μm. to about 40 μm, from about 0.1 μm to about 30 μm, from about 0.1 μm to about 20 μm, from about 0.1 μm to about 10 μm, from about 1 μm to about 100 μm, from about 1 μm to about 90 μm, from about 1 μm to about 80 μm, about 1 μm to about 70 μm, about 1 μm to about 60 μm, about 1 μm to about 50 μm, about 1 μm to about 40 μm, about 1 μm to about 30 μm, about 1 μm to about 20 μm , about 1 μm to about 10 μm, about 10 μm to about 100 μm, about 10 μm to about 90 μm, about 10 μm to about 80 μm, about 10 μm to about 70 μm, about 10 μm to about 60 μm, about 10 μm to about 50 μm, about 10 μm to about 40 μm, about 10 μm to about 30 μm, about 10 μm to about 20 μm, about 20 μm to about 100 μm, about 20 μm to about 90 μm, about 20 μm to about 80 μm, about 20 μm to about 70 μm, about 20 μm to about 60 μm, about 20 μm to about 50 μm, about 20 μm to about 40 μm, about 20 μm to about 30 μm, about 30 μm to about 100 μm, about 30 μm to about 90 μm, about 30 μm to about 80 μm, about 30 μm to about 70 μm, about 30 μm to about 60 μm, about 30 μm to about 50 μm, about 30 μm to about 40 μm , about 40 μm to about 100 μm, about 40 μm to about 90 μm, about 40 μm to about 80 μm, about 40 μm to about 70 μm, about 40 μm to about 60 μm, about 40 μm to about 50 μm, about 50 μm to about 100 μm, about 50 μm to about 90 μm, about 50 μm to about 80 μm, about 50 μm to about 70 μm, about 50 μm to about 60 μm, about 60 μm to about 100 μm, about 60 μm to about 90 μm, from about 60 μm to about 80 μm, from about 60 μm to about 70 μm, from about 70 μm to about 100 μm, from about 70 μm to about 90 μm, from about 70 μm to about 80 μm, from about 80 μm to about It may be 100 μm, about 80 μm to about 90 μm, or about 90 μm to about 100 μm. In one embodiment of the present application, a preferred average diameter of the polymer fiber may be about 0.1 μm to about 10 μm.
본원의 일 구현예에 있어서, 상기 약물은 항염증제(anti-inflammatory agent) 및 항생제(antibiotics) 중에서 선택되는 1종 이상을 포함하는 것일 수 있다.In one embodiment of the present application, the drug may include one or more types selected from anti-inflammatory agents and antibiotics.
본원의 일 구현예에 있어서, 상기 약물 원료는 상기 생분해성 고분자 원료 100 중량부에 대하여 약 0.1 중량부 내지 약 1,000 중량부로 혼합되는 것일 수 있다. 상기 약물 원료는 상기 생분해성 고분자 원료 100 중량부에 대하여 약 0.1 중량부 내지 약 900 중량부, 약 0.1 중량부 내지 약 800 중량부, 약 0.1 중량부 내지 약 700 중량부, 약 0.1 중량부 내지 약 600 중량부, 약 0.1 중량부 내지 약 500 중량부, 약 0.1 중량부 내지 약 400 중량부, 약 0.1 중량부 내지 약 300 중량부, 약 0.1 중량부 내지 약 200 중량부, 약 0.1 중량부 내지 약 100 중량부, 약 1 중량부 내지 약 1,000 중량부, 약 1 중량부 내지 약 900 중량부, 약 1 중량부 내지 약 800 중량부, 약 1 중량부 내지 약 700 중량부, 약 1 중량부 내지 약 600 중량부, 약 1 중량부 내지 약 500 중량부, 약 1 중량부 내지 약 400 중량부, 약 1 중량부 내지 약 300 중량부, 약 1 중량부 내지 약 200 중량부, 약 1 중량부 내지 약 100 중량부, 약 100 중량부 내지 약 1,000 중량부, 약 100 중량부 내지 약 900 중량부, 약 100 중량부 내지 약 800 중량부, 약 100 중량부 내지 약 700 중량부, 약 100 중량부 내지 약 600 중량부, 약 100 중량부 내지 약 500 중량부, 약 100 중량부 내지 약 400 중량부, 약 100 중량부 내지 약 300 중량부, 약 100 중량부 내지 약 200 중량부, 약 200 중량부 내지 약 1,000 중량부, 약 200 중량부 내지 약 900 중량부, 약 200 중량부 내지 약 800 중량부, 약 200 중량부 내지 약 700 중량부, 약 200 중량부 내지 약 600 중량부, 약 200 중량부 내지 약 500 중량부, 약 200 중량부 내지 약 400 중량부, 약 200 중량부 내지 약 300 중량부, 약 300 중량부 내지 약 1,000 중량부, 약 300 중량부 내지 약 900 중량부, 약 300 중량부 내지 약 800 중량부, 약 300 중량부 내지 약 700 중량부, 약 300 중량부 내지 약 600 중량부, 약 300 중량부 내지 약 500 중량부, 약 300 중량부 내지 약 400 중량부, 약 400 중량부 내지 약 1,000 중량부, 약 400 중량부 내지 약 900 중량부, 약 400 중량부 내지 약 800 중량부, 약 400 중량부 내지 약 700 중량부, 약 400 중량부 내지 약 600 중량부, 약 400 중량부 내지 약 500 중량부, 약 500 중량부 내지 약 1,000 중량부, 약 500 중량부 내지 약 900 중량부, 약 500 중량부 내지 약 800 중량부, 약 500 중량부 내지 약 700 중량부, 약 500 중량부 내지 약 600 중량부, 약 600 중량부 내지 약 1,000 중량부, 약 600 중량부 내지 약 900 중량부, 약 600 중량부 내지 약 800 중량부, 약 600 중량부 내지 약 700 중량부, 약 700 중량부 내지 약 1,000 중량부, 약 700 중량부 내지 약 900 중량부, 약 700 중량부 내지 약 800 중량부, 약 800 중량부 내지 약 1,000 중량부, 약 800 중량부 내지 약 900 중량부 또는 약 900 중량부 내지 약 1,000 중량부로 혼합되는 것 일 수 있다.In one embodiment of the present application, the drug raw material may be mixed in an amount of about 0.1 parts by weight to about 1,000 parts by weight based on 100 parts by weight of the biodegradable polymer raw material. The drug raw material is about 0.1 part by weight to about 900 parts by weight, about 0.1 part by weight to about 800 parts by weight, about 0.1 part by weight to about 700 parts by weight, and about 0.1 part by weight to about 100 parts by weight of the biodegradable polymer raw material. 600 parts by weight, about 0.1 part by weight to about 500 parts by weight, about 0.1 part by weight to about 400 parts by weight, about 0.1 part by weight to about 300 parts by weight, about 0.1 part by weight to about 200 parts by weight, about 0.1 part by weight to about 100 parts by weight, about 1 part by weight to about 1,000 parts by weight, about 1 part by weight to about 900 parts by weight, about 1 part by weight to about 800 parts by weight, about 1 part by weight to about 700 parts by weight, about 1 part by weight to about 600 parts by weight, about 1 part by weight to about 500 parts by weight, about 1 part by weight to about 400 parts by weight, about 1 part by weight to about 300 parts by weight, about 1 part by weight to about 200 parts by weight, about 1 part by weight to about 100 parts by weight, about 100 parts by weight to about 1,000 parts by weight, about 100 parts by weight to about 900 parts by weight, about 100 parts by weight to about 800 parts by weight, about 100 parts by weight to about 700 parts by weight, about 100 parts by weight to about 600 parts by weight, about 100 parts by weight to about 500 parts by weight, about 100 parts by weight to about 400 parts by weight, about 100 parts by weight to about 300 parts by weight, about 100 parts by weight to about 200 parts by weight, about 200 parts by weight to about 1,000 parts by weight, about 200 parts by weight to about 900 parts by weight, about 200 parts by weight to about 800 parts by weight, about 200 parts by weight to about 700 parts by weight, about 200 parts by weight to about 600 parts by weight, about 200 parts by weight to about 500 parts by weight, about 200 parts by weight to about 400 parts by weight, about 200 parts by weight to about 300 parts by weight, about 300 parts by weight to about 1,000 parts by weight, about 300 parts by weight to about 900 parts by weight, about 300 parts by weight to about 800 parts by weight, about 300 parts by weight to about 700 parts by weight, about 300 parts by weight to about 600 parts by weight, about 300 parts by weight to about 500 parts by weight, about 300 parts by weight to about 400 parts by weight, about 400 parts by weight to about 1,000 parts by weight, about 400 parts by weight to about 900 parts by weight, about 400 parts by weight to about 800 parts by weight, about 400 parts by weight to about 700 parts by weight, about 400 parts by weight to about 600 parts by weight, about 400 parts by weight to about 500 parts by weight, about 500 parts by weight to about 1,000 parts by weight, about 500 parts by weight to about 900 parts by weight, about 500 parts by weight to about 800 parts by weight, about 500 parts by weight to about 700 parts by weight, about 500 parts by weight to about 600 parts by weight, about 600 parts by weight to about 1,000 parts by weight, about 600 parts by weight to about 900 parts by weight, about 600 parts by weight to about 800 parts by weight, about 600 parts by weight to about 700 parts by weight, about 700 parts by weight to about 1,000 parts by weight, about 700 parts by weight to about 900 parts by weight, about 700 parts by weight to about 800 parts by weight, about 800 parts by weight to about 1,000 parts by weight, about 800 parts by weight to about 900 parts by weight, or about 900 parts by weight to about It may be mixed at 1,000 parts by weight.
본원의 일 구현예에 있어서, 상기 항생제는 클로로헥시딘(chlorohexidine), 미노사이클린(minocycline), 독시싸이클린(doxycycline), 메트로니다졸(metronidazole), 오플록사신(ofloxacin), 테트라사이클린(tetracycline), 티니다졸(tinidazole) 및 케토나졸(Ketonazole) 중에서 선택되는 1종 이상을 포함하는 것일 수 있으나, 이에 제한되는 것은 아니다.In one embodiment of the present application, the antibiotic is chlorohexidine, minocycline, doxycycline, metronidazole, ofloxacin, tetracycline, tinida It may include one or more selected from tinidazole and ketonazole, but is not limited thereto.
본원의 일 구현예에 있어서, 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 선택되는 1종 이상을 포함하는 것일 수 있으나, 이에 제한되는 것은 아니다.In one embodiment of the present application, the anti-inflammatory agent is Ibuprofen, Fenoprofen, Flurbiprofen, Carprofen, Diclofenac, Fenbufen. , Fenclozic Acid, Flufenamic Acid, Indomethacin, Indoprofen, Ketoprofen, Lonazolac, Loxoprofen ( Loxoprofen, Meclofenamic Acid, Mefenamic Acid, Naproxen, Proprionic Acids, Salicylic Acid, Sulindac, Tolmetin ), Meloxicam, Oxicams, Piroxicam, Tenoxicam, Etodolac, and Oxaprozin. It may be, but is not limited to this.
본원의 일 구현예에 있어서, 상기 생분해성 고분자 원료는 젤라틴(gelatin), 콜라겐(collagen), 알지네이트(alginate), 키토산(chitosan), 피브린(fibrin), 히알루론산(hyaluronic acid), 덱스트란(dextran), 폴리락트산(poly(lactic acid)), 폴리글리콜산(poly(glycolic acid)), 폴리락트산-코-글리콜산(poly(lactic-co-glycolic acid)), 폴리카프로락톤(poly(caprolactone)) 및 폴리오르토에스테르(poly(orthoester)) 중에서 선택되는 1종 이상을 포함하는 것일 수 있으나, 이에 제한되는 것은 아니다.In one embodiment of the present application, the biodegradable polymer raw materials include gelatin, collagen, alginate, chitosan, fibrin, hyaluronic acid, and dextran. ), poly(lactic acid), poly(glycolic acid), poly(lactic-co-glycolic acid), poly(caprolactone) ) and poly(orthoester), but is not limited thereto.
본원의 일 구현예에 있어서, 상기 전기방사가 수행되는 조건은 하기와 같을 수 있으나, 이에 제한되지 않을 수 있다:In one embodiment of the present application, the conditions under which the electrospinning is performed may be as follows, but may not be limited thereto:
전압 차는 약 1 kV 내지 약 100 kV이며; 방사 거리는 약 1 cm 내지 약 100 ㎝이며; 노즐의 구멍 크기는 약 0.01 mm 내지 약 2 ㎜이고; 및 전기방사 용액의 공급량은 약 1 mL/hr 내지 약 400 mL/hr임.The voltage difference is from about 1 kV to about 100 kV; The radiating distance is from about 1 cm to about 100 cm; The orifice size of the nozzle is about 0.01 mm to about 2 mm; And the supply amount of the electrospinning solution is about 1 mL/hr to about 400 mL/hr.
본원의 일 구현예에 있어서, 상기 전기 방사의 전압 차는, 약 1 kV 내지 약100 kV, 약 1 kV 내지 약 90kV, 약 1 kV 내지 약 80kV, 약 1 kV 내지 약 70kV, 약 1 kV 내지 약 60kV, 약 1 kV 내지 약 50kV, 약 1 kV 내지 약 40kV, 약 1 kV 내지 약 30kV, 약 1 kV 내지 약 20kV, 약 1 kV 내지 약 10kV, 약 10 kV 내지 약 100 kV, 약 10 kV 내지 약 90kV, 약 10 kV 내지 약 80kV, 약 10 kV 내지 약 70kV, 약 10 kV 내지 약 60kV, 약 10 kV 내지 약 50 kV, 약 10 kV 내지 약 40kV, 약 10 kV 내지 약 30kV, 약 10 kV 내지 약 20 kV, 약 20 kV 내지 약 100 kV, 약 20 kV 내지 약 90kV, 약 20 kV 내지 약 80 kV, 약 20 kV 내지 약 70 kV, 약 20 kV 내지 약 60 kV, 약 20 kV 내지 약 50 kV, 약 20 kV 내지 약 40 kV, 약 20 kV 내지 약 30 kV, 약 30 kV 내지 약 100 kV, 약 30 kV 내지 약 90 kV, 약 30 kV 내지 약 80kV, 약 30 kV 내지 약 70 kV, 약 30 kV 내지 약 60 kV, 약 30 kV 내지 약 50kV, 약 30 kV 내지 약 40 kV, 약 40 kV 내지 약 100 kV, 약 40 kV 내지 약 90kV, 약 40 kV 내지 약 80 kV, 약 40 kV 내지 약 70kV, 약 40 kV 내지 약 60 kV, 약 40 kV 내지 약 50 kV, 약 50 kV 내지 약 100 kV, 약 50 kV 내지 약 90 kV, 약 50 kV 내지 약 80 kV, 약 50 kV 내지 약 70 kV, 약 50 kV 내지 약 60 kV, 약 60 kV 내지 약 100 kV, 약 60 kV 내지 약 90 kV, 약 60 kV 내지 약 80 kV, 약 60 kV 내지 약 70 kV, 약 70 kV 내지 약 100 kV, 약 70 kV 내지 약 90 kV, 약 70 kV 내지 약 80 kV, 약 80 kV 내지 약 100 kV, 약 80 kV 내지 약 90 kV, 또는 약 90 kV 내지 약 100 kV일 수 있다. In one embodiment of the present application, the voltage difference of the electrospinning is about 1 kV to about 100 kV, about 1 kV to about 90kV, about 1 kV to about 80kV, about 1 kV to about 70kV, about 1 kV to about 60kV. , about 1 kV to about 50 kV, about 1 kV to about 40 kV, about 1 kV to about 30 kV, about 1 kV to about 20 kV, about 1 kV to about 10 kV, about 10 kV to about 100 kV, about 10 kV to about 90 kV. , about 10 kV to about 80 kV, about 10 kV to about 70 kV, about 10 kV to about 60 kV, about 10 kV to about 50 kV, about 10 kV to about 40 kV, about 10 kV to about 30 kV, about 10 kV to about 20 kV, from about 20 kV to about 100 kV, from about 20 kV to about 90 kV, from about 20 kV to about 80 kV, from about 20 kV to about 70 kV, from about 20 kV to about 60 kV, from about 20 kV to about 50 kV, about 20 kV to about 40 kV, about 20 kV to about 30 kV, about 30 kV to about 100 kV, about 30 kV to about 90 kV, about 30 kV to about 80 kV, about 30 kV to about 70 kV, about 30 kV to About 60 kV, about 30 kV to about 50 kV, about 30 kV to about 40 kV, about 40 kV to about 100 kV, about 40 kV to about 90 kV, about 40 kV to about 80 kV, about 40 kV to about 70 kV, about 40 kV to about 60 kV, about 40 kV to about 50 kV, about 50 kV to about 100 kV, about 50 kV to about 90 kV, about 50 kV to about 80 kV, about 50 kV to about 70 kV, about 50 kV to about 60 kV, from about 60 kV to about 100 kV, from about 60 kV to about 90 kV, from about 60 kV to about 80 kV, from about 60 kV to about 70 kV, from about 70 kV to about 100 kV, from about 70 kV to about It may be 90 kV, about 70 kV to about 80 kV, about 80 kV to about 100 kV, about 80 kV to about 90 kV, or about 90 kV to about 100 kV.
본원의 일 구현예에 있어서, 상기 전기 방사 거리는, 약 1 cm 내지 약 100 ㎝, 약 1 cm 내지 약 90 ㎝, 약 1 cm 내지 약 80 ㎝, 약 1 cm 내지 약 70 ㎝, 약 1 cm 내지 약 60 ㎝, 약 1 cm 내지 약 50 ㎝, 약 1 cm 내지 약 40 ㎝, 약 1 cm 내지 약 30 ㎝, 약 1 cm 내지 약 20 ㎝, 약 1 cm 내지 약 10 ㎝, 약 10 cm 내지 약 100 ㎝, 약 10 cm 내지 약 90 ㎝, 약 10 cm 내지 약 80 ㎝, 약 10 cm 내지 약 70 ㎝, 약 10 cm 내지 약 60 ㎝, 약 10 cm 내지 약 50 ㎝, 약 10 cm 내지 약 40 ㎝, 약 10 cm 내지 약 30 ㎝, 약 10 cm 내지 약 20 ㎝, 약 20 cm 내지 약 100 ㎝, 약 20 cm 내지 약 90 ㎝, 약 20 cm 내지 약 80 ㎝, 약 20 cm 내지 약 70 ㎝, 약 20 cm 내지 약 60 ㎝, 약 20 cm 내지 약 50 ㎝, 약 20 cm 내지 약 40 ㎝, 약 20 cm 내지 약 30 ㎝, 약 30 cm 내지 약 100 ㎝, 약 30 cm 내지 약 90 ㎝, 약 30 cm 내지 약 80 ㎝, 약 30 cm 내지 약 70 ㎝, 약 30 cm 내지 약 60 ㎝, 약 30 cm 내지 약 50 ㎝, 약 30 cm 내지 약 40 ㎝, 약 40 cm 내지 약 100 ㎝, 약 40 cm 내지 약 90 ㎝, 약 40 cm 내지 약 80 ㎝, 약 40 cm 내지 약 70 ㎝, 약 40 cm 내지 약 60 ㎝, 약 40 cm 내지 약 50 ㎝, 약 50 cm 내지 약 100 ㎝, 약 50 cm 내지 약 90 ㎝, 약 50 cm 내지 약 80 ㎝, 약 50 cm 내지 약 70 ㎝, 약 50 cm 내지 약 60 ㎝, 약 60 cm 내지 약 100 ㎝, 약 60 cm 내지 약 90 ㎝, 약 60 cm 내지 약 80 ㎝, 약 60 cm 내지 약 70 ㎝, 약 70 cm 내지 약 100 ㎝, 약 70 cm 내지 약 90 ㎝, 약 70 cm 내지 약 80 ㎝, 약 80 cm 내지 약 100 ㎝, 약 80 cm 내지 약 90 ㎝, 또는 약 90 cm 내지 약 100 ㎝일 수 있다. In one embodiment of the present application, the electrospinning distance is about 1 cm to about 100 cm, about 1 cm to about 90 cm, about 1 cm to about 80 cm, about 1 cm to about 70 cm, about 1 cm to about 60 cm, about 1 cm to about 50 cm, about 1 cm to about 40 cm, about 1 cm to about 30 cm, about 1 cm to about 20 cm, about 1 cm to about 10 cm, about 10 cm to about 100 cm , about 10 cm to about 90 cm, about 10 cm to about 80 cm, about 10 cm to about 70 cm, about 10 cm to about 60 cm, about 10 cm to about 50 cm, about 10 cm to about 40 cm, about 10 cm to about 30 cm, about 10 cm to about 20 cm, about 20 cm to about 100 cm, about 20 cm to about 90 cm, about 20 cm to about 80 cm, about 20 cm to about 70 cm, about 20 cm to about 60 cm, from about 20 cm to about 50 cm, from about 20 cm to about 40 cm, from about 20 cm to about 30 cm, from about 30 cm to about 100 cm, from about 30 cm to about 90 cm, from about 30 cm to about 80 cm, about 30 cm to about 70 cm, about 30 cm to about 60 cm, about 30 cm to about 50 cm, about 30 cm to about 40 cm, about 40 cm to about 100 cm, about 40 cm to about 90 cm , about 40 cm to about 80 cm, about 40 cm to about 70 cm, about 40 cm to about 60 cm, about 40 cm to about 50 cm, about 50 cm to about 100 cm, about 50 cm to about 90 cm, about 50 cm to about 80 cm, about 50 cm to about 70 cm, about 50 cm to about 60 cm, about 60 cm to about 100 cm, about 60 cm to about 90 cm, about 60 cm to about 80 cm, about 60 cm to about 70 cm, from about 70 cm to about 100 cm, from about 70 cm to about 90 cm, from about 70 cm to about 80 cm, from about 80 cm to about 100 cm, from about 80 cm to about 90 cm, or from about 90 cm to It may be about 100 cm.
본원의 일 구현예에 있어서, 상기 노즐의 구멍 크기는, 약 0.01 mm 내지 약 2 ㎜, 0.01 mm 내지 약 1 mm, 약 0.01 mm 내지 약 0.5 ㎜, 약 0.1 mm 내지 약 2 ㎜, 약 0. 1 mm 내지 약 1 ㎜, 약 0.1 mm 내지 약 0.5 ㎜, 또는 약 1 mm 내지 약 2 ㎜일 수 있다. In one embodiment of the present application, the hole size of the nozzle is about 0.01 mm to about 2 mm, 0.01 mm to about 1 mm, about 0.01 mm to about 0.5 mm, about 0.1 mm to about 2 mm, about 0.1 mm. mm to about 1 mm, about 0.1 mm to about 0.5 mm, or about 1 mm to about 2 mm.
본원의 일 구현예에 있어서, 상기 전기 방사 용액의 공급량은, 약 1 mL/hr 내지 약 800 mL/hr, 또는 약 1 mL/hr 내지 약 400 mL/hr일 수 있다. 본원의 일 구현예에 있어서, 상기 전기 방사 용액의 공급량은, 약 1 mL/hr 내지 약 800 mL/hr, 약 1 mL/hr 내지 약 600 mL/hr, 약 1 mL/hr 내지 약 400 mL/hr, 약 200 mL/hr 내지 약 800 mL/hr, 약 200 mL/hr 내지 약 600 mL/hr, 약 200 mL/hr 내지 약 400 mL/hr, 약 200 mL/hr 내지 약 350 mL/hr약 200 mL/hr 내지 약 300 mL/hr, 약 200 mL/hr 내지 약 250 mL/hr, 약 250 mL/hr 내지 약 400 mL/hr, 약 250 mL/hr 내지 약 350 mL/hr, 약 250 mL/hr 내지 약 300 mL/hr, 약 300 mL/hr 내지 약 400 mL/hr, 약 300 mL/hr 내지 약 350 mL/hr, 또는 약 350 mL/hr 내지 약 400 mL/hrmL일 수 있다. In one embodiment of the present application, the supply amount of the electrospinning solution may be about 1 mL/hr to about 800 mL/hr, or about 1 mL/hr to about 400 mL/hr. In one embodiment of the present application, the supply amount of the electrospinning solution is about 1 mL/hr to about 800 mL/hr, about 1 mL/hr to about 600 mL/hr, about 1 mL/hr to about 400 mL/hr. hr, about 200 mL/hr to about 800 mL/hr, about 200 mL/hr to about 600 mL/hr, about 200 mL/hr to about 400 mL/hr, about 200 mL/hr to about 350 mL/hr. 200 mL/hr to about 300 mL/hr, about 200 mL/hr to about 250 mL/hr, about 250 mL/hr to about 400 mL/hr, about 250 mL/hr to about 350 mL/hr, about 250 mL /hr to about 300 mL/hr, about 300 mL/hr to about 400 mL/hr, about 300 mL/hr to about 350 mL/hr, or about 350 mL/hr to about 400 mL/hrmL.
본원의 일 구현예에 있어서, 상기 고분자 섬유의 수득 조건은 하기와 같을 수 있으나, 이에 제한되지 않을 수 있다:In one embodiment of the present application, the conditions for obtaining the polymer fiber may be as follows, but may not be limited thereto:
본원의 일 구현예에 있어서, 압축 공기 유량은 약 100 L/min 내지 약 1,000 L/min일 수 있다. 본원의 일 구현예에 있어서, 상기 압축 공기 유량은 약 100 L/min 내지 약 1,000 L/min, 약 100 L/min 내지 약 900 L/min, 약 100 L/min 내지 약 800 L/min, 약 100 L/min 내지 약 700 L/min, 약 100 L/min 내지 약 600 L/min, 약 100 L/min 내지 약 500 L/min, 약 100 L/min 내지 약 400 L/min, 약 100 L/min 내지 약 300 L/min, 약 100 L/min 내지 약 200 L/min, 약 200 L/min 내지 약 1,000 L/min, 약 200 L/min 내지 약 900 L/min, 약 200 L/min 내지 약 800 L/min, 약 200 L/min 내지 약 700 L/min, 약 200 L/min 내지 약 600 L/min, 약 200 L/min 내지 약 500 L/min, 약 200 L/min 내지 약 400 L/min, 약 200 L/min 내지 약 300 L/min, 약 300 L/min 내지 약 1,000 L/min, 약 300 L/min 내지 약 900 L/min, 약 300 L/min 내지 약 800 L/min, 약 300 L/min 내지 약 700 L/min, 약 300 L/min 내지 약 600 L/min, 약 300 L/min 내지 약 500 L/min, 약 300 L/min 내지 약 400 L/min, 약 400 L/min 내지 약 1,000 L/min, 약 400 L/min 내지 약 900 L/min, 약 400 L/min 내지 약 800 L/min, 약 400 L/min 내지 약 700 L/min, 약 400 L/min 내지 약 600 L/min, 약 400 L/min 내지 약 500 L/min, 약 500 L/min 내지 약 1,000 L/min, 약 500 L/min 내지 약 900 L/min, 약 500 L/min 내지 약 800 L/min, 약 500 L/min 내지 약 700 L/min, 약 500 L/min 내지 약 600 L/min, 약 600 L/min 내지 약 1,000 L/min, 약 600 L/min 내지 약 900 L/min, 약 600 L/min 내지 약 800 L/min, 약 600 L/min 내지 약 700 L/min, 약 700 L/min 내지 약 1,000 L/min, 약 700 L/min 내지 약 900 L/min, 약 700 L/min 내지 약 800 L/min, 약 800 L/min 내지 약 1,000 L/min, 약 800 L/min 내지 약 900 L/min, 또는 약 900 L/min 내지 약 1,000 L/min일 수 있다.In one embodiment of the present application, the compressed air flow rate may be about 100 L/min to about 1,000 L/min. In one embodiment of the present application, the compressed air flow rate is about 100 L/min to about 1,000 L/min, about 100 L/min to about 900 L/min, about 100 L/min to about 800 L/min, about 100 L/min to about 700 L/min, about 100 L/min to about 600 L/min, about 100 L/min to about 500 L/min, about 100 L/min to about 400 L/min, about 100 L /min to about 300 L/min, about 100 L/min to about 200 L/min, about 200 L/min to about 1,000 L/min, about 200 L/min to about 900 L/min, about 200 L/min to about 800 L/min, from about 200 L/min to about 700 L/min, from about 200 L/min to about 600 L/min, from about 200 L/min to about 500 L/min, from about 200 L/min to about 400 L/min, about 200 L/min to about 300 L/min, about 300 L/min to about 1,000 L/min, about 300 L/min to about 900 L/min, about 300 L/min to about 800 L /min, about 300 L/min to about 700 L/min, about 300 L/min to about 600 L/min, about 300 L/min to about 500 L/min, about 300 L/min to about 400 L/min , about 400 L/min to about 1,000 L/min, about 400 L/min to about 900 L/min, about 400 L/min to about 800 L/min, about 400 L/min to about 700 L/min, about 400 L/min to about 600 L/min, about 400 L/min to about 500 L/min, about 500 L/min to about 1,000 L/min, about 500 L/min to about 900 L/min, about 500 L /min to about 800 L/min, about 500 L/min to about 700 L/min, about 500 L/min to about 600 L/min, about 600 L/min to about 1,000 L/min, about 600 L/min to about 900 L/min, about 600 L/min to about 800 L/min, about 600 L/min to about 700 L/min, about 700 L/min to about 1,000 L/min, about 700 L/min to about 900 L/min, about 700 L/min to about 800 L/min, about 800 L/min to about 1,000 L/min, about 800 L/min to about 900 L/min, or about 900 L/min to about 1,000 L/min. It can be L/min.
본원의 일 구현예에 있어서, 상기 고분자 섬유가 수득되는 콜렉터는 콜렉터 드럼 회전 속도가 약 1 rpm 내지 약 100 rpm이며, 컨베이어 벨트의 이동 속도는 약 0.01 m/min 내지 약 1 m/min일 수 있다. In one embodiment of the present application, the collector from which the polymer fiber is obtained may have a collector drum rotation speed of about 1 rpm to about 100 rpm, and a moving speed of the conveyor belt may be about 0.01 m/min to about 1 m/min. .
본원의 일 구현예에 있어서, 상기 콜렉터 드럼 회전 속도는 약 1 rpm 내지 약 100 rpm, 약 10 rpm 내지 약 100 rpm, 약 10 rpm 내지 약 90 rpm, 약 10 rpm 내지 약 80 rpm, 약 10 rpm 내지 약 70 rpm, 약 10 rpm 내지 약 60 rpm, 약 10 rpm 내지 약 50 rpm, 약 10 rpm 내지 약 40 rpm, 약 10 rpm 내지 약 30 rpm, 약 10 rpm 내지 약 20 rpm, 약 20 rpm 내지 약 100 rpm, 약 20 rpm 내지 약 90 rpm, 약 20 rpm 내지 약 80 rpm, 약 20 rpm 내지 약 70 rpm, 약 20 rpm 내지 약 60 rpm, 약 20 rpm 내지 약 50 rpm, 약 20 rpm 내지 약 40 rpm, 약 20 rpm 내지 약 30 rpm, 약 30 rpm 내지 약 100 rpm, 약 30 rpm 내지 약 90 rpm, 약 30 rpm 내지 약 80 rpm, 약 30 rpm 내지 약 70 rpm, 약 30 rpm 내지 약 60 rpm, 약 30 rpm 내지 약 50 rpm, 약 30 rpm 내지 약 40 rpm, 약 40 rpm 내지 약 100 rpm, 약 40 rpm 내지 약 90 rpm, 약 40 rpm 내지 약 80 rpm, 약 40 rpm 내지 약 70 rpm, 약 40 rpm 내지 약 60 rpm, 약 40 rpm 내지 약 50 rpm, 약 50 rpm내지 약 100 rpm, 약 50 rpm 내지 약 90 rpm, 약 50 rpm 내지 약 80 rpm, 약 50 rpm 내지 약 70 rpm, 약 50 rpm 내지 약 60 rpm, 약 60 rpm 내지 약 100 rpm, 약 60 rpm 내지 약 90 rpm, 약 60 rpm 내지 약 80 rpm, 약 60 rpm 내지 약 70 rpm, 약 70 rpm 내지 약 100 rpm, 약 70 rpm 내지 약 90 rpm, 약 70 rpm 내지 약 80 rpm, 약 80 rpm 내지 약 100 rpm, 약 80 rpm 내지 약 90 rpm, 또는 약 90 rpm 내지 약 100 rpm일 수 있다.In one embodiment of the present application, the collector drum rotation speed is about 1 rpm to about 100 rpm, about 10 rpm to about 100 rpm, about 10 rpm to about 90 rpm, about 10 rpm to about 80 rpm, about 10 rpm to about 10 rpm. About 70 rpm, about 10 rpm to about 60 rpm, about 10 rpm to about 50 rpm, about 10 rpm to about 40 rpm, about 10 rpm to about 30 rpm, about 10 rpm to about 20 rpm, about 20 rpm to about 100 rpm rpm, from about 20 rpm to about 90 rpm, from about 20 rpm to about 80 rpm, from about 20 rpm to about 70 rpm, from about 20 rpm to about 60 rpm, from about 20 rpm to about 50 rpm, from about 20 rpm to about 40 rpm, About 20 rpm to about 30 rpm, about 30 rpm to about 100 rpm, about 30 rpm to about 90 rpm, about 30 rpm to about 80 rpm, about 30 rpm to about 70 rpm, about 30 rpm to about 60 rpm, about 30 rpm to about 50 rpm, about 30 rpm to about 40 rpm, about 40 rpm to about 100 rpm, about 40 rpm to about 90 rpm, about 40 rpm to about 80 rpm, about 40 rpm to about 70 rpm, about 40 rpm to About 60 rpm, about 40 rpm to about 50 rpm, about 50 rpm to about 100 rpm, about 50 rpm to about 90 rpm, about 50 rpm to about 80 rpm, about 50 rpm to about 70 rpm, about 50 rpm to about 60 rpm rpm, from about 60 rpm to about 100 rpm, from about 60 rpm to about 90 rpm, from about 60 rpm to about 80 rpm, from about 60 rpm to about 70 rpm, from about 70 rpm to about 100 rpm, from about 70 rpm to about 90 rpm, It may be about 70 rpm to about 80 rpm, about 80 rpm to about 100 rpm, about 80 rpm to about 90 rpm, or about 90 rpm to about 100 rpm.
본원의 일 구현예에 있어서, 상기 컨베이어 벨트의 이동 속도는 약 0.01 m/min 내지 약 1 m/min, 약 0.01 m/min 내지 약 0.8 m/min, 약 0.01 m/min 내지 약 0.6 m/min, 약 0.01 m/min 내지 약 0.4 m/min, 약 0.01 m/min 내지 약 0.2 m/min, 약 0.01 m/min 내지 약 0.1 m/min, 약 0.05 m/min 내지 약 1 m/min, 약 0.05 m/min 내지 약 0.8 m/min, 약 0.05 m/min 내지 약 0.6 m/min, 약 0.05 m/min 내지 약 0.4 m/min, 약 0.05 m/min 내지 약 0.2 m/min, 약 0.05 m/min 내지 약 0.1 m/min, 약 0.1 m/min 내지 약 1 m/min, 약 0.1 m/min 내지 약 0.8 m/min, 약 0.1 m/min 내지 약 0.6 m/min, 약 0.1 m/min 내지 약 0.4 m/min, 약 0.1 m/min 내지 약 0.2 m/min, 약 0.2 m/min 내지 약 1 m/min, 약 0.2 m/min 내지 약 0.8 m/min, 약 0.2 m/min 내지 약 0.6 m/min, 약 0.2 m/min 내지 약 0.4 m/min, 약 0.4 m/min 내지 약 1 m/min, 약 0.4 m/min 내지 약 0.8 m/min, 약 0.4 m/min 내지 약 0.6 m/min, 약 0.6 m/min 내지 약 1 m/min, 약 0.6 m/min 내지 약 0.8 m/min, 또는 약 0.8 m/min 내지 약 1 m/min일 수 있다.In one embodiment of the present application, the moving speed of the conveyor belt is about 0.01 m/min to about 1 m/min, about 0.01 m/min to about 0.8 m/min, about 0.01 m/min to about 0.6 m/min. , about 0.01 m/min to about 0.4 m/min, about 0.01 m/min to about 0.2 m/min, about 0.01 m/min to about 0.1 m/min, about 0.05 m/min to about 1 m/min, about 0.05 m/min to about 0.8 m/min, about 0.05 m/min to about 0.6 m/min, about 0.05 m/min to about 0.4 m/min, about 0.05 m/min to about 0.2 m/min, about 0.05 m /min to about 0.1 m/min, about 0.1 m/min to about 1 m/min, about 0.1 m/min to about 0.8 m/min, about 0.1 m/min to about 0.6 m/min, about 0.1 m/min to about 0.4 m/min, from about 0.1 m/min to about 0.2 m/min, from about 0.2 m/min to about 1 m/min, from about 0.2 m/min to about 0.8 m/min, from about 0.2 m/min to about 0.2 m/min. 0.6 m/min, about 0.2 m/min to about 0.4 m/min, about 0.4 m/min to about 1 m/min, about 0.4 m/min to about 0.8 m/min, about 0.4 m/min to about 0.6 m /min, from about 0.6 m/min to about 1 m/min, from about 0.6 m/min to about 0.8 m/min, or from about 0.8 m/min to about 1 m/min.
이하, 실시예를 참조하여 본원을 좀더 자세히 설명하지만, 본원은 이에 제한되는 것은 아니다.Hereinafter, the present application will be described in more detail with reference to examples, but the present application is not limited thereto.
[실시예][Example]
생분해성 나노섬유 칩의 제조Manufacturing of biodegradable nanofiber chips
1. 혼합용액 제조1. Preparation of mixed solution
20% 농도의 글루콘산클로헥시딘 수용액(chlorhexidine gluconate 20% solution)에 젤라틴(gelatin) 분말을 용해시켰다. 젤라틴 분말은 생분해성 고분자로써 사용되었으며, 20% 농도의 글루콘산클로르헥시딘 수용액은 생분해성 고분자를 녹이기 위한 용매 및 약물로써 사용되었다. 상기 용액에 아스코르브산 분말(ascorbic acid) 및 글리세롤을 혼합하여 생분해성 고분자와 약물의 혼합용액(도 1 참조)을 제조하였으며, 상기 혼합 용액을 200 rpm 정도의 속도로 2 시간 동안 교반하였다. Gelatin powder was dissolved in a 20% concentration chlorhexidine gluconate 20% solution. Gelatin powder was used as a biodegradable polymer, and a 20% concentration aqueous solution of chlorhexidine gluconate was used as a solvent and drug to dissolve the biodegradable polymer. A mixed solution of biodegradable polymer and drug (see Figure 1) was prepared by mixing ascorbic acid powder and glycerol in the solution, and the mixed solution was stirred at a speed of about 200 rpm for 2 hours.
상기 혼합용액의 조성은 하기 표 1과 같다:The composition of the mixed solution is shown in Table 1 below:
재료ingredient 사용목적purpose of use 혼합용액에 대한 무게비율(wt.%)Weight ratio to mixed solution (wt.%)
20% 농도의 글루콘산클로로헥시딘 수용액 (chlorhexidine gluconate 20% solution)Chlorhexidine gluconate 20% solution 용매, 약물solvent, drug 6363
젤라틴(gelatin)gelatin 생분해성 고분자biodegradable polymer 1515
아스코르브산 분말(ascorbic acid)Ascorbic acid powder 유기산, 가용화제, 및 pH 조절제Organic acids, solubilizers, and pH adjusters 1717
글리세롤(glycerol)glycerol 첨가제(가소제)Additives (plasticizers) 55
2. 전기방사를 통해 고분자 섬유 시트 제조2. Manufacturing polymer fiber sheets through electrospinning
상기 생분해성 고분자 및 약물의 혼합용액을 전압 차 50 kV, 방사 거리 55 ㎝, 및 노즐 게이지(nozzle gauge) 23 GA(gauge)의 조건으로 전기방사(electrospinning)하였다. 상기 전기 방사 용액의 공급량은 200 mL/hr 내지 400 mL/hr 로 조절하였으며, 전기방사를 통해 섬유가 네트워크 형태로 얽혀 있는 고분자 섬유 시트를 제조하였다 (도 2 및 3 참조). 전기방사가 진행되는 방사 챔버는, 습도 5% 내지 10%, 및 온도 20℃ 내지 25℃로 조절하였으며, 전기방사기를 운용하는 실은 습도 15% 내지 35%, 및 온도 20℃ 내지 25℃로 조절하였다. 상기 과정을 거쳐, 고분자 섬유 각각에 생분해성 고분자 및 약물의 혼합성분을 포함하는 고분자 섬유 시트를 제조하였다.The mixed solution of the biodegradable polymer and drug was electrospun under the conditions of a voltage difference of 50 kV, a spinning distance of 55 cm, and a nozzle gauge of 23 GA (gauge). The supply amount of the electrospinning solution was adjusted to 200 mL/hr to 400 mL/hr, and a polymer fiber sheet in which fibers were entangled in a network was manufactured through electrospinning (see Figures 2 and 3). The spinning chamber where electrospinning was performed was adjusted to a humidity of 5% to 10% and a temperature of 20°C to 25°C, and the room where the electrospinning machine was operated was controlled to have a humidity of 15% to 35% and a temperature of 20°C to 25°C. . Through the above process, a polymer fiber sheet containing a mixed component of biodegradable polymer and drug was manufactured in each polymer fiber.
3. 고분자 섬유 시트를 이용하여 고분자 섬유 칩 제조3. Manufacturing polymer fiber chips using polymer fiber sheets
일면이 둥근 직사각형 형태의 몰드에 상기 고분자 섬유 시트 0.007 g 내지 0.008 g을 넣고, 10 MPa의 압력을 가해 몰드를 압축하여 원형의 약물 방출 생분해성 고분자 섬유 칩을 제조하였다. 구체적으로, 상기 생분해성 고분자 섬유 칩은 가로 4 mm, 세로 5 mm 및 두께 0.4 mm로 제작되었으며, 상기 고분자 섬유의 직경은 평균 2 μm 내지 4 μm로 확인되었다 (도 4 및 도 5 참조).0.007 g to 0.008 g of the polymer fiber sheet was placed in a rectangular mold with one side rounded, and the mold was compressed by applying a pressure of 10 MPa to prepare a circular drug-releasing biodegradable polymer fiber chip. Specifically, the biodegradable polymer fiber chip was manufactured with a width of 4 mm, a length of 5 mm, and a thickness of 0.4 mm, and the average diameter of the polymer fiber was confirmed to be 2 μm to 4 μm (see FIGS. 4 and 5).
전술한 본원의 설명은 예시를 위한 것이며, 본원이 속하는 기술분야의 통상의 지식을 가진 자는 본원의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다. 예를 들어, 단일형으로 설명되어 있는 각 구성 요소는 분산되어 실시될 수도 있으며, 마찬가지로 분산된 것으로 설명되어 있는 구성 요소들도 결합된 형태로 실시될 수도 있다.The description of the present application described above is for illustrative purposes, and those skilled in the art will understand that the present application can be easily modified into other specific forms without changing its technical idea or essential features. Therefore, the embodiments described above should be understood in all respects as illustrative and not restrictive. For example, each component described as single may be implemented in a distributed manner, and similarly, components described as distributed may also be implemented in a combined form.
본원의 범위는 상기 상세한 설명보다는 후술하는 특허청구범위에 의하여 나타내어지며, 특허청구범위의 의미 및 범위, 그리고 그 균등 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본원의 범위에 포함되는 것으로 해석되어야 한다.The scope of the present application is indicated by the claims described below rather than the detailed description above, and all changes or modified forms derived from the meaning and scope of the claims and their equivalent concepts should be construed as being included in the scope of the present application. .

Claims (16)

  1. (a) 생분해성 고분자 원료, 약물 원료 및 유기산을 혼합하여 혼합용액을 형성하는 것;(a) mixing biodegradable polymer raw materials, drug raw materials, and organic acids to form a mixed solution;
    (b) 상기 혼합용액을 전기방사하여 고분자 섬유가 네트워크 형태로 얽혀 있는 고분자 섬유 시트를 제조하는 것; 및(b) electrospinning the mixed solution to produce a polymer fiber sheet in which polymer fibers are entangled in a network form; and
    (c) 상기 고분자 섬유 시트를 압축 및 가공하여 생분해성 고분자 섬유 칩을 수득하는 것(c) Compressing and processing the polymer fiber sheet to obtain biodegradable polymer fiber chips.
    을 포함하는, 생분해성 고분자 섬유 칩의 제조방법.Method for producing a biodegradable polymer fiber chip, comprising:
  2. 제 1 항에 있어서,According to claim 1,
    상기 유기산은 아스코르브산(ascorbic acid), 시트르산(citric acid), 타타르산(tartaric acid), 탄닌산(tannic acid), 젖산(lactic acid), 뷰티릭산(butyric acid), 및 팔미트산(pamitic acid)에서 선택되는 하나 이상인 것인, 생분해성 고분자 섬유 칩의 제조방법.The organic acids include ascorbic acid, citric acid, tartaric acid, tannic acid, lactic acid, butyric acid, and palmitic acid. A method for producing a biodegradable polymer fiber chip, which is at least one selected from.
  3. 제 1 항에 있어서,According to claim 1,
    상기 혼합용액 100 중량부에 대하여,For 100 parts by weight of the mixed solution,
    상기 생분해성 고분자 원료의 함량은 10 중량부 내지 40 중량부이며,The content of the biodegradable polymer raw material is 10 parts by weight to 40 parts by weight,
    상기 약물 원료의 함량은 10 중량부 내지 70 중량부인 것인, The content of the drug raw material is 10 parts by weight to 70 parts by weight,
    생분해성 고분자 섬유 칩의 제조방법.Method for manufacturing biodegradable polymer fiber chips.
  4. 제 1 항에 있어서, According to claim 1,
    상기 혼합용액 100 중량부에 대하여,For 100 parts by weight of the mixed solution,
    상기 유기산의 함량은 5 중량부 내지 40 중량부인 것인, 생분해성 고분자 섬유 칩의 제조방법.A method for producing a biodegradable polymer fiber chip, wherein the content of the organic acid is 5 parts by weight to 40 parts by weight.
  5. 제 1 항에 있어서, According to claim 1,
    상기 혼합용액은 용매를 추가 포함하는 것인, 생분해성 고분자 섬유 칩의 제조방법.A method for producing a biodegradable polymer fiber chip, wherein the mixed solution further includes a solvent.
  6. 제 1 항에 있어서, According to claim 1,
    (a)에서, 상기 혼합 용액은 첨가제를 추가 포함하는 것인, 생분해성 고분자 섬유 칩의 제조방법.In (a), the mixed solution further includes additives.
  7. 제 6 항에 있어서, According to claim 6,
    상기 혼합용액 100 중량부에 대하여,For 100 parts by weight of the mixed solution,
    상기 첨가제의 함량은 0 중량부 초과 내지 20 중량부 이하인 것인, 생분해성 고분자 섬유 칩의 제조방법.A method for producing a biodegradable polymer fiber chip, wherein the content of the additive is greater than 0 parts by weight and less than or equal to 20 parts by weight.
  8. 제 1 항에 있어서,According to claim 1,
    상기 가공은, 압축된 고분자 섬유 시트를 가로 1 ㎜ 내지 20 ㎜, 세로 1 mm 내지 20 ㎜ 및 두께 0.05 mm 내지 5 ㎜의 칩 형태로 절단하는 것을 포함하는 것인, 생분해성 고분자 섬유 칩의 제조방법.The processing includes cutting the compressed polymer fiber sheet into chips with a width of 1 mm to 20 mm, a length of 1 mm to 20 mm, and a thickness of 0.05 mm to 5 mm. A method of producing a biodegradable polymer fiber chip. .
  9. 제 1 항에 있어서,According to claim 1,
    상기 고분자 섬유의 평균 직경은 0.1 μm 내지 100 μm 인 것인, 생분해성 고분자 섬유 칩의 제조방법.A method of producing a biodegradable polymer fiber chip, wherein the average diameter of the polymer fiber is 0.1 μm to 100 μm.
  10. 제 1 항에 있어서, According to claim 1,
    상기 약물은 항염증제(anti-inflammatory agent) 및 항생제(antibiotics) 중에서 선택되는 1종 이상을 포함하는 것인, 생분해성 고분자 섬유 칩의 제조방법.A method of manufacturing a biodegradable polymer fiber chip, wherein the drug includes at least one selected from anti-inflammatory agents and antibiotics.
  11. 제 1 항에 있어서,According to claim 1,
    상기 약물 원료는 상기 생분해성 고분자 원료 100 중량부에 대하여 0.1 중량부 내지 1000 중량부로 혼합되는 것인, 생분해성 고분자 섬유 칩의 제조방법.The drug raw material is mixed in an amount of 0.1 to 1000 parts by weight based on 100 parts by weight of the biodegradable polymer raw material.
  12. 제 10 항에 있어서,According to claim 10,
    상기 항생제는 클로로헥시딘(chlorohexidine), 미노사이클린(minocycline), 독시싸이클린(doxycycline), 메트로니다졸(metronidazole), 오플록사신(ofloxacin), 테트라사이클린(tetracycline), 티니다졸(tinidazole) 및 케토나졸(Ketonazole) 중에서 선택되는 1종 이상을 포함하는 것인, 생분해성 고분자 섬유 칩의 제조방법.The antibiotics include chlorohexidine, minocycline, doxycycline, metronidazole, ofloxacin, tetracycline, tinidazole and ketonazole ( A method for producing a biodegradable polymer fiber chip comprising at least one selected from Ketonazole).
  13. 제 10 항에 있어서,According to claim 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 선택되는 1종 이상을 포함하는 것인, 생분해성 고분자 섬유 칩의 제조방법.The anti-inflammatory agents include Ibuprofen, Fenoprofen, Flurbiprofen, Carprofen, Diclofenac, Fenbufen, and Fenclozic Acid. ), Flufenamic Acid, Indomethacin, Indoprofen, Ketoprofen, Lonazolac, Loxoprofen, Meclofenamic Acid ( Meclofenamic Acid, Mefenamic Acid, Naproxen, Proprionic Acids, Salicylic Acid, Sulindac, Tolmetin, Meloxicam , a biodegradable polymer fiber chip comprising one or more selected from Oxicams, Piroxicam, Tenoxicam, Etodolac, and Oxaprozin. Manufacturing method.
  14. 제 1 항에 있어서,According to claim 1,
    상기 생분해성 고분자 원료는 젤라틴(gelatin), 콜라겐(collagen), 알지네이트(alginate), 키토산(chitosan), 피브린(fibrin), 히알루론산(hyaluronic acid), 덱스트란(dextran), 폴리락트산(poly(lactic acid)), 폴리글리콜산(poly(glycolic acid)), 폴리락트산-코-글리콜산(poly(lactic-co-glycolic acid)), 폴리카프로락톤(poly(caprolactone)) 및 폴리오르토에스테르(poly(orthoester)) 중에서 선택되는 1종 이상을 포함하는 것인, 생분해성 고분자 섬유 칩의 제조방법.The biodegradable polymer raw materials include gelatin, collagen, alginate, chitosan, fibrin, hyaluronic acid, dextran, and poly(lactic). acid), poly(glycolic acid), polylactic-co-glycolic acid (poly(lactic-co-glycolic acid)), poly(caprolactone), and polyorthoester (poly( A method for producing a biodegradable polymer fiber chip comprising at least one selected from orthoester)).
  15. 제 1 항에 있어서,According to claim 1,
    상기 전기방사가 수행되는 조건은 하기와 같은 것인, 생분해성 고분자 섬유 칩의 제조방법:A method for producing a biodegradable polymer fiber chip under which the electrospinning conditions are as follows:
    전압 차는 1 kV 내지 100 kV이며;The voltage difference is 1 kV to 100 kV;
    방사 거리는 1 cm 내지 100 ㎝이며;The radiation distance is 1 cm to 100 cm;
    노즐의 구멍 크기는 0.01 mm 내지 2.0 ㎜이고; 및The hole size of the nozzle is 0.01 mm to 2.0 mm; and
    전기방사 용액의 공급량은 1 mL/hr 내지 800 mL/hr임.The supply amount of electrospinning solution is 1 mL/hr to 800 mL/hr.
  16. 제 1 항에 있어서,According to claim 1,
    상기 고분자 섬유의 수득 조건은 하기와 같은 것인, 생분해성 고분자 섬유 칩의 제조방법:A method for producing a biodegradable polymer fiber chip, wherein the conditions for obtaining the polymer fiber are as follows:
    압축 공기 유량은 100 L/min 내지 1,000 L/min이며;Compressed air flow rate is 100 L/min to 1,000 L/min;
    콜렉터 드럼(collector drum)의 속도는 1 rpm 내지 100 rpm이며; 및 The speed of the collector drum is 1 rpm to 100 rpm; and
    컨베이어 벨트의 이동 속도는 0.01 m/min 내지 1 m/min임.The moving speed of the conveyor belt is 0.01 m/min to 1 m/min.
PCT/KR2022/003505 2022-03-14 2022-03-14 Preparation method for biodegradable polymer fibre chip WO2023176987A1 (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120240369A1 (en) * 2009-06-15 2012-09-27 Empresa Brasilerira De Pesquisa Agropecuaria - Embrapa Method and apparatus to produce micro and/or nanofiber webs from polymers, uses thereof and coating method
KR20140115486A (en) * 2013-03-20 2014-10-01 강릉원주대학교산학협력단 Drug loaded nanofiber chip for dental use and manufacturing method of the same
KR20150007808A (en) * 2013-07-12 2015-01-21 인하대학교 산학협력단 Complex scaffold comprising nanofiber with nanoparticle to drug-delivery for artificial skin and filler, and method for preparing the same
KR101534522B1 (en) * 2014-09-12 2015-07-07 주식회사 웰나노스 Manufacturing method of drug releasing biodegradable fiber chip for dental use
KR20220108738A (en) * 2021-01-27 2022-08-03 엠엑스바이오 주식회사 Method of manufacturing biodegradable polymer fiber chips

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120240369A1 (en) * 2009-06-15 2012-09-27 Empresa Brasilerira De Pesquisa Agropecuaria - Embrapa Method and apparatus to produce micro and/or nanofiber webs from polymers, uses thereof and coating method
KR20140115486A (en) * 2013-03-20 2014-10-01 강릉원주대학교산학협력단 Drug loaded nanofiber chip for dental use and manufacturing method of the same
KR20150007808A (en) * 2013-07-12 2015-01-21 인하대학교 산학협력단 Complex scaffold comprising nanofiber with nanoparticle to drug-delivery for artificial skin and filler, and method for preparing the same
KR101534522B1 (en) * 2014-09-12 2015-07-07 주식회사 웰나노스 Manufacturing method of drug releasing biodegradable fiber chip for dental use
KR20220108738A (en) * 2021-01-27 2022-08-03 엠엑스바이오 주식회사 Method of manufacturing biodegradable polymer fiber chips

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