WO2019103404A1 - Micro-aiguille et son procédé de fabrication - Google Patents
Micro-aiguille et son procédé de fabrication Download PDFInfo
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- WO2019103404A1 WO2019103404A1 PCT/KR2018/014067 KR2018014067W WO2019103404A1 WO 2019103404 A1 WO2019103404 A1 WO 2019103404A1 KR 2018014067 W KR2018014067 W KR 2018014067W WO 2019103404 A1 WO2019103404 A1 WO 2019103404A1
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- linear
- fibers
- microneedle
- fiber
- microneedle matrix
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0023—Drug applicators using microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0046—Solid microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0053—Methods for producing microneedles
Definitions
- the present invention relates to a micro needle and a method of manufacturing the same.
- microneedles have been extensively fabricated using materials that can have reasonable mechanical strength such as silicon, metal, and glass. However, when injected into the human body due to the characteristics of the material of the microneedles, if a force exceeding a certain level is applied, the broken microneedles may remain in the skin or may enter the tissues and cause side effects such as inflammation reaction or disease.
- a microneedle matrix including a base and a plurality of sub-microneedles formed on at least one side of the base; And at least one linear fiber secured to the base of the microneedle matrix and containing at least one or more effective materials.
- the at least one linear fibers may be entirely embedded entirely within the base of the microneedle matrix.
- the at least one linear fibers protrude above the surface of the base portion of the microneedle matrix, and the protruding portion of the at least one linear fiber is bonded to the material constituting the base of the microneedle matrix . ≪ / RTI >
- one side of the at least one linear fiber is embedded in the base of the microneedle matrix, and the other side of the one side is exposed to the outside of the base.
- the exposed other side of the at least one linear fiber may be in contact with a reservoir of the effective materials to serve as a core to deliver the active materials of the storage source to the microneedle matrix.
- the at least one linear fiber may comprise a strand formed by longitudinally twisting a plurality of linear fibers.
- the strands may be formed by one or more linear fibers twisted in the longitudinal direction.
- the at least one linear fiber can accommodate the effective materials in a dispersed form.
- the at least one linear fiber may comprise cilia.
- the at least one linear fiber may comprise a surface void.
- the at least one linear fiber may encapsulate the active materials in a lump form therein.
- the at least one linear fibers may extend from one end of the microneedle to the other end opposite to the one end.
- the at least one linear fiber may have a mesh structure.
- the at least one linear fiber may comprise at least one of natural fiber, regenerated fiber, semi-synthetic fiber or synthetic fiber.
- the at least one linear fiber may have fat-soluble properties.
- the microneedle matrix and the at least one linear fiber may comprise a biodegradable material.
- the biodegradable material may be selected from the group consisting of nucleic acids, carbohydrates, proteins (e.g. collagen, silk fibroin, albumin, amino acid, gelatin) and polymers based on the proteins, polysaccharides and derivatives of the polysaccharides And examples thereof include cellulose, agarose, chitosan, hparin, alginate, hyarulonic acid, dextran, chondroitin sulfate, dextran sulfate dextran sulfate, acacia gum, tragacanthin, pectin, alginic acid, agar, carrageenan, galactomannans, Xanthan, Natural polymers such as beta-cyclodextrin, amylose (water soluble starch), fibrin, pullulan, heparin, alginate, inulin, starch and
- the average thickness of the at least one linear fiber may be greater than the average thickness of the base of the microneedle matrix.
- the average thickness of the at least one linear fiber may range from 0.01 denier to 10 denier.
- the active substances are selected from natural polymers, insulin, vaccines and hormone drugs, Paclitaxel, Carmustine, dacarbazine, Etoposide, Fluorouracil, Camptothecin, Meclofenamic acid, Sulindac, Piroxicam, Meloxicam, Tenoxicam, Diclofenac, Aceclofenac (see, for example, Aceclofenac, Rebamipide, Enalapril maleate, Captopril, Ramipril, Fosinopril, Benazepril, Quinapril, Such as temocapril, Cilazapril, Lisinopril, Cetirizine, Diphenhydramine, Fexofenadine, Pseudoephedrine, Methylephedrine, , Dextromethorphan (Dextro methoxycinnamate, methorphan, guaifenesin, noscapine, trimethquinol, Doxy
- the content of the active materials may range from 0.01 wt% to 100 wt% of the total weight of the microneedles.
- a microneedle matrix including a base and a plurality of sub-microneedles formed on at least one side of the base; And microneedles dispersed in the microneedle matrix and comprising linear fibers receiving at least one effective material.
- a micro needle layer is provided. And linear fibers contained in the microneedle layer and containing at least one or more effective materials.
- a micro needle layer is provided. And a microneedle patch coupled to the microneedle layer and including linear fibers receiving at least one or more effective materials.
- the linear fibers may have a fabric structure to support the microneedle layer.
- a micro needle layer is provided. And a microneedle mask coupled to the microneedle layer and including linear fibers receiving at least one effective material.
- the linear fibers may have a fabric structure to support the microneedle layer.
- a method of preparing a micro needle matrix comprising: preparing a precursor of a microneedle matrix; Preparing a mold comprising an array of cavities with a relief shape to form a plurality of microneedles; Filling the cavity with a precursor of the microneedle matrix to overflow; Disposing linear fibers that contain effective materials in a precursor of the filled microneedle matrix; And drying the precursor of the microneedle matrix in the mold to form microneedles having a plurality of microneedles formed on at least one side of the base of the microneedle matrix and including linear fibers to receive the effective materials; And separating the micro needle from the template.
- a method of preparing a needle matrix comprising: preparing a precursor of a needle matrix; Preparing a mold comprising an array of cavities with a relief shape to form a plurality of microneedles; Disposing linear fibers to receive effective materials in the mold; Filling the precursor of the microneedle matrix so that the linear fibers containing the effective materials are sufficiently embedded by the precursor of the microneedle matrix; Drying a precursor of the microneedle matrix in the mold to form microneedles having a plurality of microneedles formed on at least one surface of the base of the microneedle matrix and including linear fibers to receive the effective materials; And separating the micro needle from the template.
- the method may further comprise forming the effective materials on the inside or the surface of the at least one linear fiber.
- the step of forming the effective materials on the inside or the surface of the at least one linear fiber may include the steps of dipping the at least one linear fiber in a mixed solution in which the effective material is dispersed, .
- the step of forming the effective materials on the inside or on the surface of the at least one linear fiber comprises the steps of: preparing a mixed solution phase-separated with the effective materials and the effective materials; Injecting the mixed solution into an injection machine to inject linear fibers; And solidifying the injected linear fibers.
- the step of solidifying the injected linear fibers may comprise irradiating the injected linear fibers with light.
- the step of solidifying the injected linear fiber may include the step of solidifying the injected linear fiber in water at a temperature of -20 ° C to 0 ° C.
- the loading amount of the effective materials can be loaded on the microneedle matrix Can be freely adjusted irrespective of the solubility of the at least one linear fibers and also the microneedles can be provided which can precisely control the loading amount of the effective substances in the entire microneedles by controlling the amount of effective substances to be mounted on the at least one linear fibers .
- a method of manufacturing a microneedle capable of easily manufacturing a microneedle having the above-described advantages can be provided.
- FIG. 1A-1C illustrate microneedles according to various embodiments of the present invention.
- FIGS 2A-2E illustrate the structure of linear fibers that accommodate at least one active material in accordance with various embodiments of the present invention.
- Figures 3A-3B illustrate the arrangement of a plurality of linear fibers in a micro needle according to various embodiments of the present invention, respectively.
- FIG. 4 is a flowchart illustrating a method of manufacturing a micro needle according to an embodiment of the present invention.
- FIG. 5 is a flowchart showing a method of manufacturing a micro needle according to another embodiment of the present invention.
- 6A to 6C are optical microscope images showing microneedles according to various embodiments of the present invention, respectively.
- first, second, etc. are used herein to describe various elements, components, regions, layers and / or portions, these members, components, regions, layers and / It is obvious that no. These terms are only used to distinguish one member, component, region, layer or section from another region, layer or section. Thus, a first member, component, region, layer or section described below may refer to a second member, component, region, layer or section without departing from the teachings of the present invention.
- FIG. 1A-1C illustrate microneedles (NP1, NP2, NP3) according to various embodiments of the present invention.
- the microneedles NP1, NP2 and NP3 are fixed to the base portion BL of the microneedle matrix MX and the microneedle matrix MX and include at least one effective material ES And may include at least one linear fiber (ST) that receives the linear fibers (ST).
- the microneedle matrix MX may include a base portion BL and a plurality of sub-microneedles N formed on at least one side of the base portion BL.
- the microneedle matrix may contain biodegradable materials to minimize adverse side effects on the skin and to effectively deliver effective materials (ES).
- the biodegradable material can be swollen or absorbed into living tissues within a few seconds to a few hours when it is applied to the skin.
- the biodegradable material may include a biodegradable polymer, and the biodegradable polymer may include a natural polymer and a synthetic polymer or a combination thereof.
- the biodegradable polymer is a substance that can be decomposed or transformed into a low molecular weight compound by metabolism of organisms such as bacteria, algae, fungi, etc.
- the biodegradable polymer may be prepared from a plant, a microorganism or an animal raw material which can be used as chemical energy such as biomass.
- the natural polymer may be a nucleic acid, a carbohydrate, a protein (e.g., collagen, silk fibroin, albumin, amino acid, gelatin), a polymer based on the protein and a polysaccharide and a derivative of the polysaccharide
- the active ingredient may be selected from the group consisting of cellulose, agarose, chitosan, hparin, alginate, hyarulonic acid, dextran, chondroitin sulfate, dextran sulfate, but are not limited to, lactose, sulfate, acacia gum, tragacanthin, pectin, alginic acid, agar, carrageenan, galactomannans, Xanthan, Beta-cyclodextrin, amylose (water soluble starch), fibrin, pullulan, heparin, alginate, inulin, starch, glycogen or combinations thereof.
- the chitosan, the dextran, the tragacanthin, the hyaluronic acid, the pectin, the alginic acid, the agar, the galactomannan, the xanthan gum, the beta-cyclodextrin, The rose may have water solubility.
- the natural polymer of the present invention is not limited thereto, and any polymer having biodegradability and no harmfulness may be applied.
- the synthetic polymer is selected from the group consisting of polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), polystyrene (PS) and polyaniline (PAN), polyamino acid, polyanhydride, polyorthos ester, polylysine, (NIPAAm-co-AAc), poly (N-isopropylacrylamide-co-ethylmethacrylate), poly (N-isopropylacrylamide) (NIPAAm-co-EMA), polyvinyl acetate / polyvinyl alcohol (PVAc / PVA), poly (N-vinylpyrrolidone) (PVP), poly (methyl methacrylate-co-hydroxyethyl methacrylate ), Poly (PEG-copeptide), alginate-g- (polyethylene oxide-polypropylene oxide-polyethylene oxide) (alginate-g- (PEOPPO-PEO)), poly (polylactic acid-co-glycolic acid)
- the synthetic polymers of the present invention are not limited thereto.
- the synthetic polymer may be selected from the group consisting of polyglycolic acid (PGA), polylactic acid (PLA), polylactic acid-glycolic acid copolymer (PLGA), polylactic acid (PLLA), poly-epsilon-caprolactone (PCL), polyethylene glycol (PEG), polyethylene oxide (PEO), polycaprolactone (PCL) (PHBV), poly [(3-hydroxybutyrate) -co- (3-hydroxyvalerate) (PHBV), polydioxanone (PDO), poly [ ), Poly (ester urethane) (PEUU), poly [(L-lactide) -co- (D-lactide)], poly [ethylene-co- (vinyl alcohol)] (PVOH), polyacrylic acid
- the polyglycolic acid (PGA), polylactic acid (PLLA), and polylactic acid-glycolic acid copolymer (PLGA) may be used in combination with the
- a plurality of sub-microneedles N formed on at least one side of the base BL may include a tip that can fit into the skin and a support for supporting the tip.
- the structure and shape of the submicro-needles (N) may have a shape that widens from the tip to the support when viewed from the tip to the support.
- the present invention is not limited to this, and any shape can be used as long as the micro needles can be inserted into the skin.
- the submicro needles N are formed of the same biodegradable material as the base BL of the microneedle matrix MX and can be integrated with the base BL.
- the average width of the base of the submicro beads N may be in the range of 10 [mu] m to 550 [mu] m.
- the average height of the submicro-needles N may be in the range of 100 mu m to 1000 mu m.
- the micro needle NP1 may have a form in which at least one linear fiber ST is completely completely embedded in the base portion BL of the microneedle matrix MX.
- the microneedles NP2 are arranged such that a portion of at least one linear fiber ST protrudes above the surface of the base BL of the microneedle matrix MX,
- the protruding portion of one or more linear fibers ST may have a shape covered with a material constituting the base portion BL of the microneedle matrix MX.
- the protruding surface portion of the at least one linear fiber ST can be protected from external contamination by being covered by the material constituting the base BL of the microneedle matrix MX.
- the extent to which the protruding surface portion of the at least one linear fiber ST is covered by the material constituting the base BL of the microneedle matrix MX is determined by the ratio Can be determined by at least one of the amount of the precursor of the microneedle matrix (MX), the thickness of the linear fibers (ST) and the drying time of the precursor of the microneedle matrix (MX) in the manufacturing method.
- the selection of the micro needles NP1 and NP2 shown in Figs. 1A and 1B is carried out in such a manner that the application area of the micro needles NP1 and NP2, the size including the thickness of the microneedle matrix MX, (ES) to be contained in the microneedles (NP1, NP2) or the volume ratio of at least one linear fiber (ST) to the volume, the strength of the microneedle matrix (MX) And the present invention is not limited thereto.
- the micro needle NP1 of FIG. 1A is superior in adhesion to the micro needle NP2 of FIG. 1B, and in the case of FIG. 1A, the fibers containing the effective materials ES are inserted into the micro needle base So that the drug delivery efficiency can be increased.
- the microneedles NP3 are formed such that one side SL1 of at least one linear fiber ST is embedded in the base BL of the microneedle matrix MX,
- the other side portion SL2 of the linear fibers ST opposite to the one side portion SL1 may have a shape exposed to the outside of the base portion.
- the exposed other side portion SL2 of the at least one linear fibers ST is brought into contact with a reservoir (not shown) of the effective materials ES to remove the effective materials ES of the storage source It can serve as a wick for delivering it to the microneedle matrix (MX).
- the reservoir may be a nonwoven fabric, paper, paper, fabric, cotton, sponge or gauze that contains a solution containing the active substances (ES), and may be formed by extruding the nonwoven, paper, paper, fabric, cotton, sponge,
- the effective materials ES are arranged on the microneedles NP3 due to the mediation by the at least one linear fibers ST by arranging the effective materials ES on the other side SL2 of the at least one linear fibers ST exposed to the non- To the sub-microneedles (N)
- the active materials (ES) can be applied by applying or coating the other materials (ES) on the other side (SL2) of the at least one linear fibers (ST)
- the active materials (ES) can be transferred to the sub-microneedles (N) via at least one linear fiber (ST).
- the one side portion SL1 of the linear fibers ST is embedded in the base portion BL of the microneedle matrix MX and the other side portion SL2 on the opposite side of the one side portion SL1 of the linear fibers ST is embedded in the base portion BL of the microneedle matrix MX.
- the degree of exposure to the outside is determined by the amount of the precursor of the microneedle matrix MX, the thickness of the linear fibers ST and the thickness of the microneedle matrix MX in the manufacturing method of the microneedles NP1, NP2, And the drying time of the precursor.
- the micro needle NP3 having the shape as shown in FIG. 1C is manufactured by the method of manufacturing the micro needles NP1, NP2 and NP3 described later and the other side SL2 of at least one linear fiber ST is exposed (ES) to the active material (ES) by introducing the active materials (ES) through the exposed exposed side of the at least one linear fibers (ST) after the micro needles (NP1, NP2, NP3) And can be mounted on the linear fibers ST.
- at least one linear fiber ST is fixed to the base BL through the drying process of the microneedle matrix MX without receiving the effective materials ES during the production of the microneedles NP3. .
- the effective material (ES) when the effective material (ES) is mounted after the drying process of the microneedle matrix (MX), the heat required in the drying or heat treatment step during the manufacturing process of the microneedles (NP1, NP2, NP3)
- the effective materials ES can be stably contained in the linear fibers ST by mounting the effective materials ES which can be deteriorated by the staple fibers in the subsequent step.
- At least one linear fiber ST which is fixed to the base BL of the microneedle matrix MX and accommodates an effective material, may be a natural fiber, a synthetic fiber, Fibers may be combined, and the present invention is not limited to these materials as long as it is suitable for accommodating an effective substance.
- the at least one linear fibers ST may optionally be water-soluble or may be lipophilic.
- the water-soluble fiber is referred to as a water-soluble fiber and the oil-soluble fiber is referred to as an oil-soluble fiber.
- the water-soluble fibers may be provided by natural fibers or regenerated fibers, and the oil-soluble fibers may be provided by semi-synthetic fibers or synthetic fibers, but the present invention is not limited thereto.
- the natural fiber refers to fibers obtained from animals, microorganisms or plants.
- the natural fibers are eco-friendly and harmless to the human body, and are excellent in absorbency.
- the natural fibers may include cellulose-based fibers and protein-based fibers, or a combination thereof, but the present invention is not limited thereto.
- fibers such as guar gum / guar gum hydrolyzate, glucomannan (konjac, konjac mannan), cardiolipin, indigestible maltodextrin, soybean fiber, throat, wheat germ, barley fiber, gum arabic, inulin / chicory extract, polydextrose , Or hanji fiber or paper fiber.
- the cellulosic fiber may be at least one of cotton, linen, and linen.
- the protein-based fiber may be at least one of wool and silk fibers.
- the micro needles (NP1, NP2, NP3) to which the linear fibers (ST) as the natural fibers are applied have the advantages of minimizing the skin irritation and having excellent adhesion to the skin and having a small side effect.
- the regenerated fiber is originally a polymer, but is not made in the form of fiber at all, or even if it is in a fiber form, it is not formed in a form suitable for weaving, and it is said to be once melted and regenerated in a form easy to use as fiber.
- the regenerated fibers are excellent in absorbability and can withstand high temperatures.
- the regenerated fibers include, for example, cellulose-based and protein-based fibers.
- Representative cellulose-based fibers include rayon fibers.
- the rayon fiber may be at least one of copper ammonia rayon, viscose rayon, strong rayon, polynic rayon, and lyocell.
- micro needles (NP1, NP2, NP3) to which the regenerated fiber linear fibers (ST) are applied are characterized in that they are resistant to heat. Therefore, during the manufacturing process of the micro needles (NP1, NP2, NP3) It may be useful to mount effective materials (ES) which can be degraded by the required heat or other environmental factors.
- the linear fibers ST which are water-soluble fibers are brought into contact with the skin by the water exposed in the air, and moisture contained in the microneedle matrix MX itself, or micro- It can be dissolved by the biomaterial transferred from the needle to the base of the micro needle. Accordingly, if the linear fibers ST contain the effective materials ES therein, the linear fibers ST can be stained with the microneedle matrix MX The active substances ES contained in the linear fibers ST and trapped therein can be delivered to the skin by the water contained in the linear fibers ST itself or dissolved by the water transferred through the micro needles. At this time, the effective materials (ES) accommodated and trapped in the linear fibers ST can be transferred to the skin due to the dissolving property of the water-soluble fibers, so that they can exhibit their pharmaceutical, pharmaceutical or cosmetic effects.
- linear fibers ST are water-soluble, they may be useful when mounting water-soluble effective materials (ES), but the present invention is not limited thereto.
- ES water-soluble effective materials
- the natural fibers or the regenerated fibers are water-soluble, lipophilic active materials (ES) can be mounted by the structural characteristics of the linear fibers of Figs. 2B to 2E described later.
- the natural fiber or the regenerated fiber is fat-soluble, water-soluble effective substances (ES) can be stably mounted in the same manner.
- the semisynthetic fiber refers to a fiber made by applying a chemical change to a regenerated fiber in which a natural polymer material is made into a fiber form by physical or chemical means.
- the semisynthetic fiber may be at least one of an acetate fiber and a triacetate fiber, but the present invention is not limited thereto.
- the synthetic fiber refers to a fiber formed by polymerizing a low molecular weight material to a high molecular weight material by a chemical method.
- the synthetic fibers are light and vaginal, weak to heat, not excellent in absorbency, and may generate static electricity.
- the synthetic fibers may be selected from the group consisting of polyamide fibers such as nylon fibers, polyester fibers such as polyester fibers, polyurethane fibers, polyethylene fibers, polyvinyl chloride fibers, polyvinylidene fibers, polytetrafluoroethylene fibers, Polyvinyl alcohol-based fibers, polyacrylonitrile-based fibers, polypropylene-based fibers, and Korean paper fibers or paper fibers, but the present invention is not limited thereto.
- At least one or more linear fibers ST may be biodegradable fibers (hereinafter referred to as biodegradable fibers).
- the biodegradable fibers may be composed of a biodegradable polymer disclosed as a material constituting a microneedle matrix.
- the biodegradable fibers include polylactic acid (PLA) fibers, polyhydroxyalkanoate (PHA) fibers, poly-3-hydroxybutyrate (PLA) fibers prepared by condensation of lactic acid produced by fermenting corn starch (PHB), chitosan fiber, chitosan-coated alginic acid fiber, bacterial cellulose fiber, gelatin fiber (PHB), polyhydroxybutyric acid
- PHA polylactic acid
- PHA polyhydroxyalkanoate
- PLA poly-3-hydroxybutyrate
- PHA polyhydroxybutyrate
- the present invention is not limited thereto and may be applied to any fiber that is harmless to the human body and composed of a substance decomposable in nature.
- the average thickness of the linear fibers ST may be greater than the average thickness of the base portion BL of the microneedle matrix MX.
- the average thickness of the at least one linear fiber can be in the range of 0.01 denier to 10 denier. If the thickness of the at least one linear fiber is less than 0.01 denier, the thickness of the at least one linear fiber tends to be small so that it tears easily during manufacturing and distribution, or the effective material contained therein is not sufficiently transferred to the skin If the thickness of at least one linear fiber (ST) exceeds 10 denier, there is a problem that the fibers are made thick and stiff and have poor adhesion to the skin.
- linear fibers may be woven rather than singly and used in the form of nonwoven fabric, woven fabric, or woven fabric, or in the form of paper and paper, and may be used cosmetically as a mask pack or mask patch, It can be used in the form of bands.
- the at least one effective substance (ES) contained in at least one linear fiber (ST) may be a substance having a medical, pharmaceutical or cosmetic efficacy.
- Such medicinal or pharmaceutical efficacy substances may be selected from natural polymers, insulin, vaccine and hormone drugs, Paclitaxel, Carmustine, dacarbazine, Etoposide, Fluorouracil, Camptothecin, Meclofenamic acid, Sulindac, Piroxicam, Meloxicam, Tenoxicam, Diclofenac, Aceclofenac (see, for example, Aceclofenac, Rebamipide, Enalapril maleate, Captopril, Ramipril, Fosinopril, Benazepril, Quinapril, Such as temocapril, Cilazapril, Lisinopril, Cetirizine, Diphenhydramine, Fexofenadine, Pseudoephedrine, Methylephedrine, , Dextromethorphan (D
- the substance having the above-mentioned cosmetic efficacy may be at least one selected from the group consisting of ethyl ascorbyl ether, oil soluble licorice extract, mulberry extract, ascorbyl glucoside, magnesium ascorbyl phosphate, niacinamide, alpha-bisabolol, ascorbyl tetraisopalmitate, Alpha-lipoic acid, benzene-1,4-diol, hydroxyacids and arbutin, which are known to those skilled in the art .
- the natural polymer may be at least one of a polysaccharide such as starch and cellulose, a protein such as a polypeptide, and a nucleic acid such as a polynucleotide, but the present invention is not limited thereto.
- the peptide is a hormone that transmits or commands a signal to facilitate the functions of organs in vivo such as the respiratory organs and digestive organs, and can be expected to amplify several thousands or more in a very small amount.
- the peptide can have the same shape as the protein existing in the body, and thus can be applied to our skin.
- the peptides can be used in the fields of medicine and cosmetics.
- the protein refers to a plurality of linked chains of various kinds of amino acids.
- the protein is an important nutrient in the formation of major human constituents such as nails, hairs, skin, bones and muscles. Since the protein is a major component of an antibody against an antigen such as an external pathogen, it is an immune-related substance. If the protein is deficient, the immune component can not be properly supplied to the lung or stomach mucosa, and the disease may be caused.
- the insulin is secreted from the beta cells of the insulin, and the glucose in the blood is introduced into the cells and stored in the form of glycogen.
- the insulin can promote the conversion of fatty acids into fatty acids and oxidation of glucose in adipose tissue and promote absorption of amino acids to synthesize proteins in muscles.
- the insulin can be used as a therapeutic agent for diabetes, an agent for treating obesity and a therapeutic agent for liver disease.
- the vaccine may be administered to the human body by weakening or completely killing the exogenously introduced antigen, that is, the pathogen, so as to form an antibody capable of resisting the antigen, so that the immune response is promptly displayed when the same antigen is introduced into the human body later. can do.
- the vaccine may be used for the prevention of infectious diseases such as chronic infections or subacute infections in urology, dermatology and gynecology.
- the synthetic organic compound may include alpha-lipoic acid, benzene-1,4-diol, hydroxyacids, and arbutin.
- the alpha-lipoic acid is a kind of fatty acid, a compound important for energy generation, and a substance that plays an important role in the sulfation network required for life support.
- the alpha-lipoic acid may comprise alpha-lipoic acid, artificially synthesized alpha-lipoic acid and commercially available alpha-lipoic acid separated from a sample containing alpha-lipoic acid.
- the alpha-lipoic acid can promote the production of glutathione, vitamin C and vitamin E. Therefore, the above-mentioned alpha-lipoic acid can be used as an agent for preventing and treating vascular diseases due to intracellular energy enhancer, inhibition of adipocyte differentiation and inhibition of increase in vascular lipid flow.
- the hydroquinone can inhibit the activity of tyrosinase involved in the formation of the melanin pigment, which is a cause of stain. Accordingly, the hydroquinone can be used for skin whitening in the field of cosmetics.
- the arbutin refers to the addition of glucose to the hydroquinone.
- the arbutin may include arbutin isolated from a sample containing arbutin, artificially synthesized arbutin, and commercially available arbutin.
- arbutin is a hydroquinone glycoside having a structure in which beta-D-glucose is bonded to hydroquinone, and arbutin is currently used in some whitening cosmetics.
- the hydroxy acid refers to a compound having a hyroxyl group and a carboxy group in the same molecule.
- the hydroxy acids may include alpha-hydroxyacids (AHA), beta-hydroxyacids (BHA), polyhydroxy acids, and bionic acids .
- alpha-hydroxy acid and beta-hydroxy acid can exert excellent peeling effect, improve moisturizing effect and whitening effect, and can be used as a peeling agent in the field of cosmetics.
- the kind and function of the above-mentioned effective substances (ES) are only illustrative and the present invention is not limited thereto.
- the active substances (ES) may comprise an effective substance having a fat-soluble property (hereinafter referred to as a fat-soluble active substance).
- the fat soluble active substance may be selected from the group consisting of insulin, a vaccine and a hormone drug, Paclitaxel, Carmustine, dacarbazine, Etoposide, Fluorouracil, Camptothecin
- the compounds of the present invention may be selected from the group consisting of Meclofenamic acid, Sulindac, Piroxicam, Meloxicam, Tenoxicam, Diclofenac, Aceclofenac, Rebamipide, Enalapril maleate, Captopril, Ramipril, Fosinopril, Benazepril, Quinapril, Temocapril, Cilazapril, Lisinopril, Cetirizine, Diphenhydramine, Fexofenadine, Pseudoephedrine, Methylephedrine, Dextromethorphan
- the active substances (ES) may include an effective substance having water solubility (hereinafter referred to as a water soluble active substance).
- the water soluble active material may comprise a natural polymer.
- the water-soluble active substance differs in physical or chemical properties from the stratum corneum having liposoluble properties, it is difficult to permeate the stratum corneum, so that it contains at least one linear fiber (ST) accommodating effective substances (ES)
- ST linear fiber
- ES effective substances
- the at least one effective substance (ES) accommodated by the at least one linear fibers (ST) can accommodate the same kind of effective materials and can accommodate different kinds of effective materials.
- one effective material accommodated by at least one linear fiber (ST) may be lipophilic and the other active material may be water soluble.
- one active material that is accommodated by at least one linear fiber (ST) may be a material that may have medical efficacy, and the other active material may be a material that may have cosmetic efficacy.
- the content of the at least one effective substance (ES) contained in at least one linear fiber (ST) may be in the range of 0.01 wt% to 100 wt% of the total weight of the micro needle (NP1, NP2, NP3).
- the above 100 wt% is a value higher than 20 wt% that the conventional active substance can be contained in the micro needle.
- the effective drug when the effective drug is contained between the pores of the fiber and the drug release rate is not in the fiber, it dissolves within 10 minutes to 2 hours depending on the dissolution rate of the water-soluble polymer, but when the fiber is used,
- the drug release rate can be increased by 2 to 10 times, and the drug release rate can be freely adjusted according to the pores of the fibers, the absorbency of the fibers, the content of the fibers, and can be increased up to 48 hours.
- the biodegradable material constituting the microneedle matrix MX is generally made of a water-soluble substance
- Soluble active substances (ES) are uniformly accommodated throughout the microneedle matrix (MX) because they are not well mixed due to different physical or chemical properties between the active substances Can be.
- linear fibers (ST) are applied to a material or structure having excellent affinity with effective materials (ES), depending on the physical or chemical properties of the effective materials (ES)
- ES effective materials
- MX microneedle matrix
- ES active materials
- the active substances ES are applied directly to the microneedle matrix MX by the linear fibers ST rather than directly to the microneedle matrix MX so that the entire microneedles NP1, It is possible to precisely control the loading amount of the effective materials (ES). For example, by comparing the weight of the fibers before the effective materials ES are received and the weight of the fibers after the effective materials ES are received, the loading amount of the effective materials ES in the entire micro needles NP1, NP2, Precise control is possible.
- Figures 2A-2E illustrate the structure of linear fibers (ST), each containing at least one active material (ES) according to various embodiments of the present invention.
- the linear fibers ST fixed to the base BL of the microneedle matrix MX may be a single linear fiber, and may have a linear structure in the form of an elongated shape.
- the linear fibers (ST) can accommodate at least one effective substance (ES).
- the linear fibers ST can accommodate effective materials (ES) dispersed in the form of fine lumps on the surface of the linear fibers ST as shown in Fig. 2A.
- the linear fibers ST may accommodate the active materials (ES) in a form in which the active materials (ES) are wholly or partially coated on the surface.
- the linear fibers ST accommodate the effective materials (ES)
- they can be supplemented by the following embodiments in addition to the above-mentioned embodiments.
- the linear fibers ST may be a strand (STD) formed by twisting a plurality of linear fibers ST1, ST2, and ST3.
- the strand STD may be a bundle of a plurality of linear fibers formed by longitudinally twisting one or a plurality of linear fibers ST1, ST2, ST3 as shown in Fig. 2B.
- the present invention is not limited to this, and it is possible to have a structure in which a plurality of linear fibers can be gathered to form a bundle of fibers, regardless of the number or type of linear fibers.
- the strand STD may have a gap or a fine space SP between one linear fiber ST1 and one linear fiber ST1 and another adjacent linear fiber ST2.
- the microspaces SP can allow the active materials ES to be absorbed into the interior of the strand (STD) as well as to the surface of the strand (STD), for example, by capillary action.
- the size or the ratio of the fine space (SP) can be appropriately selected according to the content of the effective materials (ES) among the total weight of the micro needles (NP1, NP2, NP3).
- the strand STD is a space in which the effective materials ES can be accommodated in the micro needles NP1, NP2 and NP3 by providing a fine space SP between the plurality of linear fibers ST1, ST2 and ST3. (SP). Accordingly, there is an advantage that the kinds of effective materials (ES) that can be mounted on the micro needles (NP1, NP2, NP3) can be diversified and the content of the effective materials (ES) can be improved.
- FIG. 2B illustrates that the active material (ES) is mounted only in a space between adjacent linear fibers constituting the strand (STD), and the present invention is not limited thereto.
- the strand (STD) may contain at least one effective substance (ES) in a dispersed form on the surface of the linear fibers or the entire surface of the strand (STD) constituting the strand (STD) ES) may be coated in a layer structure.
- the linear fibers ST may have cilia 10S.
- the cilia 10S can be formed by injection or spinning processes to form linear fibers ST, or by applying friction to the fiber surface arbitrarily.
- the cilia 10S can hold the active substances ES or hold the active substances ES by Van der Waal's force.
- the cilia 10S also contains active materials (ES) between the surface of the linear fibers ES, the surface of the linear fibers ES and the cilia 10S and also between the cilia 10S_1 and the cilia 10S_2. So that the linear fibers ST can increase the surface area between the linear fibers ST and the active materials ES by increasing the surface area at which the linear fibers ST can accommodate the effective materials ES, The active substances can be stably accommodated in the linear fibers (ST) irrespective of whether the active substances are lipid soluble or water soluble.
- the linear fibers ST may have a surface void (10V).
- the surface voids (10V) may have the form of hemispherical, pinhole, U, V, or combinations thereof as non-limiting examples.
- a hemispherical surface void (10V) is disclosed.
- Surface voids (10V) are structures that can trap effective materials (ES).
- the surface voids (10 V) allow the linear fibers (ST) to have the effective materials (ES) and the linear fibers (ST), even when the active materials (ES) have low wettability to the linear fibers (ST) So that it can stably exist on the surface of the substrate.
- the surface void (10 V) can increase the surface area where the active materials (ES) can be accommodated or induce a capillary phenomenon so that a large amount of effective materials (ES) can be accommodated on the surface of the linear fibers can do.
- the linear fibers ST may receive effective materials (ES) therein.
- the active materials (ES) may have different physical or chemical properties than the linear fibers (ST).
- the material constituting the linear fibers ST may be water-soluble and the active materials ES may be a lipophilic material.
- the substances constituting the linear fibers ST may be lipophilic and the active substances ES may be water-soluble.
- the linear fibers ST may be subjected to phase separation as shown in Fig. 2E because of the physical or chemical properties of the materials constituting the linear fibers ST and the active materials ES having different physical or chemical properties from each other, ,
- the active substances (ES) can be accommodated in the form of particles in the form of active substances (ES).
- the linear fibers ST may be linear fibers
- the water soluble substance constituting the water soluble substance ST is dissolved by the moisture exposed in the air by the contact with the skin or by the water contained in the microneedle matrix MX itself to be loaded on the linear fibers ST
- the pharmaceutical, pharmaceutical or cosmetic efficacy of the active substances (ES) can be exerted.
- the microneedles NP1, NP2, and NP3 employing the linear fibers ST as shown in FIG. 2E have different physical or chemical properties from the microneedle matrix MX and are mixed well with the microneedle matrix MX It is possible to mount an effective material (ES) which is difficult to be mounted on the microneedle matrix MX.
- a linear fiber having a surface void (10V) as shown in Fig. 3C may be formed in the form of a strand as shown in Fig. 2B to accommodate a stable and large amount of effective materials ES.
- Figures 3A and 3B illustrate the arrangement of a plurality of linear fibers in a micro needle according to various embodiments of the present invention, respectively.
- At least one or more linear fibers ST fixed to the base BL of the microneedle matrix MX are arranged at one end DD1 of the microneedles NP1, NP2, NP3, And extend across the other end DD2.
- the plurality of linear fibers ST having the elongated shape may be arranged in a line as shown in Fig. 3A.
- At least one or more linear fibers ST fixed to the base BL of the microneedle matrix MX may have a mesh structure.
- the mesh structure may be a structure in which at least one or more linear fibers ST1 and ST2 are crossed with each other.
- the linear fibers ST having the mesh structure can accommodate the effective materials ES not only at the surface thereof but also at the point where at least one or more linear fibers ST1 and ST2 intersect with each other. Therefore, the linear fibers ST having the mesh structure can have an advantage that a large amount of the active materials (ES) can be mounted.
- the mesh structure may have an eye such as a through hole or a pore.
- the eye such as the through hole or the pore of the mesh structure may be a square, a pentagon, a hexagon, or an indeterminate form (see Figs. 6B and 6F, respectively), but the present invention is not limited thereto.
- the eyes of the mesh structure can function to vent water by helping to discharge moisture or alcohol.
- the linear fibers ST may include irregularly-shaped nonwoven structures other than a regular-shaped structure such as a mesh structure.
- the staple fibers may be arranged to form an irregular or random structure.
- the arrangement of the plurality of linear fibers ST disclosed with reference to FIGS. 3A and 3B can be suitably selected according to the application site since it can improve the flexibility and strength of the microneedle matrix MX.
- the linear fibers ST are arranged in a one- Where microneedles can be applied, and where it is advantageous to apply them in such a manner that they attach to areas of large step variation, such as eyes or faces, such as mask packs or mask patches, linear fibers ST are arranged in a mesh structure, Can be applied.
- a microneedle matrix including a base and a plurality of sub-microneedles formed on at least one side of the base; And microneedles dispersed in the microneedle matrix and comprising linear fibers receiving at least one effective material.
- a micro needle layer is provided. And linear fibers contained in the microneedle layer and containing at least one or more effective materials.
- a micro needle layer is provided. And a microneedle patch coupled to the microneedle layer and including linear fibers receiving at least one or more effective materials.
- the linear fibers may have a fabric structure to support the microneedle layer.
- a micro needle layer is provided. And a microneedle mask coupled to the microneedle layer and including linear fibers receiving at least one effective material.
- the linear fibers may have a fabric structure to support the microneedle layer.
- FIG. 4 is a flowchart illustrating a method of manufacturing a micro needle according to an embodiment of the present invention.
- a precursor of the microneedle matrix MX is prepared (S100).
- the precursor of the microneedle matrix (MX) may be a mixed solution in which a biodegradable substance, an effective substance and a solvent are mixed.
- the biodegradable material contained in the precursor of the micro needle matrix (MX) may be the same as the biodegradable material described above, but the present invention is not limited thereto.
- the solvent contained in the precursor of the microneedle matrix (MX) may include water, alcohol and other organic solvents.
- the alcohol examples include alcohols such as ethanol, isopropanol, acetone, ethyl acetate, acetone nitrile, and methylene chloride.
- the organic solvent may include an anhydrous or a lower alcohol having 1 to 4 carbon atoms, chloroform, 1,3-butylene glycol, hexane, diethyl ether, and butyl acetate.
- a mold including an array of recessed cavities for forming a plurality of submicron needles N is prepared (S110).
- the mold may include an edge frame that acts as a protective film to prevent the precursor of the microneedle matrix MX from flowing out of the mold when the precursor of the microneedle matrix MX is filled.
- the mold may be formed of a metal, ceramic, glass, thermoplastic or thermosetting resin material, but the present invention is not limited thereto.
- the mold may have a coating separation layer formed on the mold inner wall so that the micro needles NP1, NP2, NP3 are formed and then separated smoothly from the mold.
- the mold may be filled with a precursor of the microneedle matrix MX to such an extent that the negative-shaped cavity overflows (S120).
- the precursor of the microneedle matrix MX may be filled in powder, molten or gel form in the cavity of the mold.
- a microneedle matrix MX is applied to the mold so that at least one or more linear fibers ST can be sufficiently immersed in the precursor of the filled microneedle mattress MX, It is possible to charge a large amount of the precursor of The present invention is not limited thereto, and the amount of the precursor of the microneedle matrix (MX) can be adjusted depending on the application.
- the linear fibers ST may be a microneedle matrix MX may be further performed by heating and melting before being placed in the mold filled with the precursor of the precursor (e.g., MX).
- At least one or more linear fibers ST containing at least one effective substance (ES) may be disposed in the precursor of the microneedle matrix (MX) filled in the mold (S130).
- pre-fabricated linear fibers ST are prepared, The linear fibers ST are immersed in the dispersion solution containing the active materials ES so that the dispersion solution containing the active materials ES is dispersed in the linear fibers ST itself or between adjacent linear fibers ST By adsorbing to adjacent portions, at least one or more linear fibers (ST) can be produced that contain effective materials (ES).
- the effective materials (ES) in the matrix constituting the linear fibers ST as described with reference to Figure 2E, it is possible to use, for example, a cellulosic, nylon or polyester (ES) and solvent are mixed and solidified after the precursor constituting the linear fibers (ST) for producing the fibers is mixed with the mixed solution containing the effective materials (ES) and the solvent to solidify the at least one linear fiber (ST) can be manufactured.
- the precursor constituting the linear fiber may have the same or different physical or chemical properties as the active materials (ES).
- the solvent may include water, an alcohol, or an organic solvent capable of dissolving or dispersing the precursor, but the present invention is not limited thereto.
- the mixed solution may further include a matrix of the linear fibers ST and a surfactant for stably dissolving or dispersing the effective materials in the mixed solution.
- a surfactant for stably dissolving or dispersing the effective materials in the mixed solution.
- the solidification after immersing the mixed solution can be accomplished by conventional drying methods such as hot air drying, low temperature drying, vacuum drying, and ultraviolet drying.
- conventional drying methods such as hot air drying, low temperature drying, vacuum drying, and ultraviolet drying.
- the present invention is not limited thereto.
- the precursor may further comprise a solidifying agent suitable for the photoinitiator, and the manufacturing techniques used in conventional fiber manufacturing processes may be applied thereto.
- a precursor of the microneedle matrix MX is added on the linear fibers ST after at least one linear fiber ST has been placed in the mold filled with the precursor of the microneedle matrix MX. As shown in FIG. Further, in one embodiment, depending on the physical or chemical properties of the linear fibers ST, a constant pressure is applied so that the linear fibers ST can be sufficiently immersed in the precursor of the microneedle matrix MX filled in the mold .
- the precursor of the microneedle matrix MX filled in the mold is dried to have a plurality of sub-microneedles N formed on at least one surface of the base BL of the microneedle matrix MX, (NP1, NP2, NP3) containing at least one or more linear fibers (ST) that accommodate the above-mentioned effective materials (ES) may be formed (S140).
- the precursor of the microneedle matrix MX is cooled and / or depressurized, depending on the chemical or physical properties of the active materials ES accommodated by the linear fibers ST and the linear fibers ST. , Frozen or heated and dried at a temperature within the range of 50 to 100 ° C.
- the present invention is not limited thereto, and it is possible that the precursor of the microneedle matrix MX can be solidified.
- the micro needle When solidification of the micro needle matrix (MX) is completed, the micro needle can be separated from the template (S150).
- FIG. 5 is a flowchart showing a method of manufacturing a micro needle according to another embodiment of the present invention.
- a step S200 of preparing a precursor of a microneedle matrix MX a step of preparing a template including an array of recessed cavities for forming a plurality of sub- microneedles N (S230), placing the linear fibers (ST) in the mold (S230), aligning the linear fibers (ST) containing the effective materials (ES)
- the precursor of the microneedle matrix MX is dried in the mold so that a plurality of sub-grooves are formed on at least one surface of the base layer BL of the microneedle matrix MX, (S250) of forming microneedles (NP1, NP2, NP3) having microneedles (N) and containing linear fibers (ST) accommodating effective materials (ES) , NP3) as the template
- the microneedle may be fabricated (NP1, NP2, NP3) to the step (S260) of separating.
- step S200 of FIG. 5 corresponds to step S100 of FIG. 4
- step S210 of FIG. 5 corresponds to step S110 of FIG. 4
- step S220 of FIG. 5 corresponds to step S130 of FIG.
- the step S120 and the step S240 of FIG. 5 are the same as or similar to the step S140 of FIG. 4 and the step S250 of FIG. 5 are the same as or similar to the step S150 of FIG. 4. Therefore, the description of the steps S100 to S150 of FIG. can do.
- the method of manufacturing the microneedles shown in Fig. 5 is characterized in that the precursor of the microneedle matrix MX filled in the mold is first filled and then the linear fibers ST are placed in a very light
- the linear fibers ST may be difficult to be sufficiently immersed in the precursor of the microneedle matrix MX filled in the mold, so that the linear fibers ST are first placed on the mold S230,
- the linear fibers ST absorb the precursor of the microneedle matrix MX and can be sufficiently immersed in the precursor of the microneedle matrix MX with an increased weight Lt; / RTI >
- 6A to 6C are SEM (Scanning Electron Microscope) images of a micro needle according to various embodiments of the present invention, respectively.
- 6A is an SEM image showing the sides of the micro needles NP1, NP2 and NP3
- FIG. 6B is an image showing regular bottom faces of the micro needles NP1, NP2 and NP3, NP2, and NP3).
- NP1, NP2, NP3 Micro needle
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Abstract
La présente invention concerne une micro-aiguille et son procédé de fabrication. La micro-aiguille selon un mode de réalisation de la présente invention comprend : une matrice de micro-aiguille comprenant une partie base et une pluralité de sous-micro-aiguilles formées sur au moins une surface de la partie base; et au moins une fibre linéaire fixée à la partie base de la matrice de micro-aiguille et contenant au moins un principe actif.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2017-0158805 | 2017-11-24 | ||
| KR1020170158805A KR102369530B1 (ko) | 2017-11-24 | 2017-11-24 | 마이크로 니들 및 이의 제조 방법 |
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| Publication Number | Publication Date |
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| WO2019103404A1 true WO2019103404A1 (fr) | 2019-05-31 |
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| Application Number | Title | Priority Date | Filing Date |
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| PCT/KR2018/014067 Ceased WO2019103404A1 (fr) | 2017-11-24 | 2018-11-19 | Micro-aiguille et son procédé de fabrication |
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| KR (1) | KR102369530B1 (fr) |
| WO (1) | WO2019103404A1 (fr) |
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| CN110935097A (zh) * | 2019-12-03 | 2020-03-31 | 广州新济薇娜生物科技有限公司 | 改善皮肤增生性瘢痕的微针贴片及其制备方法 |
| US11517729B2 (en) | 2018-08-20 | 2022-12-06 | University Of Washington | Integrated fiber microneedle device for drug and vaccine delivery |
| CN115803078A (zh) * | 2020-06-30 | 2023-03-14 | 株式会社Lg生活健康 | 含有微纤维网络结构体的微针 |
| US12186515B2 (en) | 2020-04-28 | 2025-01-07 | Ticona Llc | Microneedle assembly |
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| KR102625911B1 (ko) * | 2020-01-30 | 2024-01-18 | 건국대학교 산학협력단 | 지성 피부 개선을 위한 폴리프로필렌을 포함하는 마이크로니들 |
| CN111588689B (zh) * | 2020-06-20 | 2023-08-11 | 温州医科大学 | 一种角膜微创可溶性微针贴片及其制备方法与应用 |
| KR102611702B1 (ko) * | 2021-05-12 | 2023-12-11 | 주식회사 페로카 | 마이크로니들 패치의 제조 방법 |
| CN113198102B (zh) * | 2021-05-17 | 2023-04-07 | 上海天引生物科技有限公司 | 调控力学作用的微针贴 |
| KR102836377B1 (ko) * | 2021-12-20 | 2025-07-21 | (주)그로젠바이오 | 마이크로니들 패치 제조 방법 |
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| US11517729B2 (en) | 2018-08-20 | 2022-12-06 | University Of Washington | Integrated fiber microneedle device for drug and vaccine delivery |
| CN110935097A (zh) * | 2019-12-03 | 2020-03-31 | 广州新济薇娜生物科技有限公司 | 改善皮肤增生性瘢痕的微针贴片及其制备方法 |
| CN110935097B (zh) * | 2019-12-03 | 2021-10-29 | 广州新济薇娜生物科技有限公司 | 改善皮肤增生性瘢痕的微针贴片及其制备方法 |
| US12186515B2 (en) | 2020-04-28 | 2025-01-07 | Ticona Llc | Microneedle assembly |
| CN115803078A (zh) * | 2020-06-30 | 2023-03-14 | 株式会社Lg生活健康 | 含有微纤维网络结构体的微针 |
| CN115803078B (zh) * | 2020-06-30 | 2025-11-21 | 株式会社Lg生活健康 | 含有微纤维网络结构体的微针 |
Also Published As
| Publication number | Publication date |
|---|---|
| KR102369530B1 (ko) | 2022-03-03 |
| KR20190060516A (ko) | 2019-06-03 |
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