WO2017065570A1 - Microstructure utilisant un matériau polymère de type gel, et son procédé de fabrication - Google Patents

Microstructure utilisant un matériau polymère de type gel, et son procédé de fabrication Download PDF

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Publication number
WO2017065570A1
WO2017065570A1 PCT/KR2016/011581 KR2016011581W WO2017065570A1 WO 2017065570 A1 WO2017065570 A1 WO 2017065570A1 KR 2016011581 W KR2016011581 W KR 2016011581W WO 2017065570 A1 WO2017065570 A1 WO 2017065570A1
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gel
microstructure
polymer material
region
base region
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PCT/KR2016/011581
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English (en)
Korean (ko)
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정형일
장민규
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주식회사 주빅
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Priority claimed from KR1020160133482A external-priority patent/KR20170044049A/ko
Publication of WO2017065570A1 publication Critical patent/WO2017065570A1/fr

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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

Definitions

  • Subcutaneous drug injection methods are one of the methods commonly used in the treatment of various diseases and drug delivery.
  • Subcutaneous drug injection has advantages such as lower drug denaturation and degradation rate, higher efficiency of drug delivery in the body, and lower side effects through quantitative drug delivery compared to oral drug delivery methods absorbed through the digestive system.
  • hypodermic needles of various diameters are widely used as a subcutaneous drug injection method.
  • hypodermic needles are used in most drug delivery methods.
  • skin damage and pain are inevitable, and side effects such as allergic reaction due to metal material and injection phobia due to pain occur.
  • side effects such as allergic reaction due to metal material and injection phobia due to pain occur.
  • the same site injection due to the wound that occurs when using a conventional subcutaneous injection is impossible, there is a problem such as decreased patient convenience, drug injection efficiency.
  • Microneedles capable of subcutaneous drug injection in a micro size have been developed.
  • Microneedle is a micro-sized structure that can solve problems such as pain, trauma, and patient convenience of conventional hypodermic needles.
  • Biodegradable microneedle is a technology that enables painless drug delivery with minimal invasiveness. It is a field of research.
  • Existing biodegradable microneedles have been manufactured using mold molding method, tensile molding method, and tensile blow molding method. In the case of the molding method, the process of filling the viscous solution into the micro-sized mold is indispensable.
  • the limit of the length of the biodegradable microneedle that can be manufactured and the loss rate in the manufacturing process are high.
  • the microneedle structure is formed by stretching by using the viscosity of the viscous solution, and then, the biodegradable microneedle is formed through a drying process.
  • a high molecular weight polymer material is used, it is impossible to prepare a viscous solution.
  • a low molecular weight polymer material it is difficult to form a structure of the biodegradable microneedles and the strength is weakened.
  • the present invention comprises the steps of (a) forming a gelled base region comprising a polymeric material on a support; And (b) to provide a method of manufacturing a microstructure comprising the step of forming an outer region on the gel-based base region.
  • the present invention comprises the steps of (a) forming a gelled base region comprising a polymeric material on a support; And (b) forming an outer region on the gelled base region.
  • the weight average molecular weight of the polymer material in (a) may be 50kDa to 2,500kDa.
  • the viscosity of the gel-based region may be 5 Pa ⁇ s to 400 Pa ⁇ s at 25 ° C.
  • the gel strength of the gel-based base region may be 0.03N to 5N.
  • the gel base region may be divided into multiple base regions.
  • the drug may be further loaded into the gel-based base region in step (a) or the outer region in step (b).
  • the gel base region may be formed by discharging, attaching, punching, or molding.
  • a precoat layer may be formed on the support in advance.
  • the method may further include modifying the gel base region.
  • the formation of the outer region is performed by coating a coating region including a second polymer material on the gel-based base, and the second polymer material has a weight average molecular weight or a viscosity lower than that of the polymer material. It may be characterized by.
  • the formation of the outer region may be performed by attaching a second microstructure on the gel-based region.
  • the coating area may be divided into multiple coating areas.
  • the coating can be carried out by ejection, immersion or spraying.
  • the coating area may be molded or a separate microstructure may be attached onto the coating area.
  • the molding may be performed by one or more methods selected from the group consisting of molding, drawing, blowing, suction, centrifugal force application and magnetic field application.
  • a microstructure manufactured according to the above method is provided.
  • the base layer comprising a polymer material; And an outer layer including a second polymer material formed on the base layer, wherein the second polymer material has a weight average molecular weight or a viscosity lower than that of the polymer material.
  • the weight average molecular weight of the polymer material may be 50kDa to 2,500kDa.
  • the viscosity of the polymer material may be 5 Pa.s to 400 Pa.s at 25 ° C.
  • the method of manufacturing a microstructure using the gel polymer material according to the present invention even when a high weight average molecular weight polymer material is used, not only the structure of the microstructure can be easily formed, but also the strength of the microstructure can be improved. In addition, when applied to the human body, it is possible to administer a high dose of a polymer substance or drug in the human body.
  • FIG. 1 is a view showing a method of manufacturing a microstructure using a gel polymer material according to various embodiments of the present invention.
  • FIG. 2 is a view showing a support of various materials and various forms.
  • 3 is a diagram showing gel-based base regions formed in various diameters, various heights, and various shapes.
  • FIG. 4 is a diagram showing the formation of a gelled base region by various methods.
  • 5 is a view showing a precoat layer of various materials.
  • FIG. 7 is a diagram illustrating coating regions formed in various shapes.
  • FIG. 9 is an electron micrograph showing a gel-based base region and a microstructure prepared according to Examples 1 to 3.
  • FIG. 10 is an electron micrograph showing the gelled base region and microstructures prepared according to Example 4.
  • FIG. 11 is an electron micrograph showing the gelled base region and microstructures prepared according to Example 5.
  • Example 12 is an electron micrograph showing a microstructure prepared according to Example 6.
  • the present inventors have found that by forming a gel-based base region containing a high weight average molecular weight polymer material, it is possible to successfully manufacture a microstructure having improved strength, and completed the present invention.
  • gel polymer material refers to a high weight average molecular weight polymer material for forming a gel-based base region, and the polymer material may be formed by crosslinking two or more of the same or different low molecular weight materials, and the polymer material. The same or different two or more high molecular materials may form a crosslink.
  • gel refers to a colloidal dispersion system in which the dispersed phase is a solid and the dispersion medium is a liquid, and maintains its form without flowing like a sol. That is, gel is a concept that is distinguished from a liquid (viscous solution) or a solid.
  • any configuration is formed on the "top (or bottom)" of the substrate not only means that any configuration is formed in contact with the top (or bottom) of the substrate, but also the above and the top (or bottom) of the substrate It does not limit to not including another structure between arbitrary structures formed).
  • the present invention comprises the steps of (a) forming a gelled base region comprising a polymeric material on a support; And (b) forming an outer region on the gelled base region.
  • FIG. 1 is a view showing a method of manufacturing a microstructure using a gel polymer material according to various embodiments of the present invention.
  • the gel base region 20 includes the second polymer material.
  • Step (c)
  • the method for producing a microstructure according to the present invention includes the step of forming a gel-based base region including a polymer material on a support [step (a)].
  • the support is used for supporting a gel-based base region containing a polymer material.
  • FIG. 2 is a view showing a support of various materials and various forms.
  • the support 10 may be formed of various materials such as a metal and a polymer material, and may have various shapes such as a substrate and a pillar. In this case, when the support is a substrate, it may have various surface shapes.
  • the present invention is characterized by using a gel-based base region containing a polymer material in order to overcome the limitation of the weight average molecular weight of the polymer material that can be included in the conventional viscous solution.
  • a gel-based base region containing a polymer material formed directly on the support without forming a separate viscous solution on the support, after forming a separate viscous solution on the support first, It may also include the case of using a gel base region comprising a polymer material formed thereon.
  • the weight average molecular weight of the polymer material is preferably 50 kDa to 2,500 kDa, and more preferably 1000 kDa to 2,500 kDa, but is not limited thereto.
  • the weight average molecular weight of the polymer material is less than the above range, there is a problem that gel formation is difficult, and when the weight average molecular weight of the polymer material exceeds the above range, there is a problem that molding is difficult after gel formation.
  • the concentration of the polymer material may be influenced by the weight average molecular weight, preferably 5% (w / v) to 95% (w / v), but is not limited thereto.
  • the concentration of the polymer material is less than 5% (w / v)
  • the concentration of the polymer material exceeds 95% (w / v)
  • the problem of deformation after gel formation is difficult There is this.
  • the polymer material may effectively form a gel-based base region by simultaneously maintaining a weight average molecular weight of 50 kDa to 2,500 kDa and a concentration of 5% (w / v) to 95% (w / v).
  • the polymer material may be a biocompatible or biodegradable material.
  • biocompatible material means a material that is substantially nontoxic to the human body, chemically inert, and not immunogenic, and “biodegradable material” in the present specification may be degraded by body fluids or microorganisms in a living body. Mean material.
  • hyaluronic acid polyester, polyhydroxyalkanoate (PHAs), poly ( ⁇ -hydroxyacid), poly ( ⁇ -hydroxyacid), poly (3- Hydrosulfitrate-co-valorate; PHBV), poly (3-hydroxypropionate; PHP), poly (3-hydroxyhexanoate; PHH), poly (4-hydroxyacid), poly (4-hydroxybutyrate), poly (4-hydroxyvalorate), poly (4-hydroxyhexanoate), poly (esteramide), polycaprolactone, polylactide, polyglycolide, poly (lac Tide-co-glycolide; PLGA), polydioxanone, polyorthoester, polyetherester, polyanhydride, poly (glycolic acid-co-trimethylene carbonate), polyphosphoester, polyphosphoester urethane , Poly (amino acid), polycyanoacrylate, Li (trimethylene carbonate), poly (iminocarbonate), poly (
  • Drugs may be further loaded inside the gelled base region.
  • the drug includes a chemical drug, a protein drug, a peptide drug, a nucleic acid molecule for gene therapy, and a nanoparticle.
  • Drugs that can be used in the present invention include, for example, anti-inflammatory drugs, analgesics, anti-arthritis agents, antispasmodics, antidepressants, antipsychotics, neurostabilizers, anti-anxiety agents, antagonists, antiparkin disease drugs, cholinergic agonists, anticancer agents, Antiangiogenic, immunosuppressive, antiviral, antibiotic, appetite suppressant, analgesic, anticholinergic, antihistamine, antimigraine, hormonal, coronary, cerebrovascular or peripheral vasodilator, contraceptive, antithrombotic, diuretic, anti Hypertension agents, cardiovascular diseases treatment agents, cosmetic ingredients (eg, wrinkle improvement agents, skin aging inhibitors and skin lightening agents) and the like, but are not limited thereto.
  • the viscosity of the gel-based region may be 5 Pa ⁇ s to 400 Pa ⁇ s at 25 ° C. and preferably 100 Pa ⁇ s to 400 Pa ⁇ s, but is not limited thereto. At this time, if the viscosity of the gel-based region is less than the above range, there is a problem that it is difficult to form a gel-shaped base region of a uniform form, and if the viscosity of the gel-based region exceeds the above range, the gel-based region is produced in a uniform length There is a difficult problem.
  • Gel strength of the gel-based base region is preferably 0.03N to 5N, but is not limited thereto. At this time, when the gel strength of the gel-based region (gel strength) is less than 0.03N, there is a problem that the gel-based base is broken during insertion, when the gel strength of the gel-based base region exceeds 5N, according to the increase in the diameter There is a problem of pain during insertion.
  • the gel base region may be divided into multiple base regions, which may be classified according to the polymer material (type, weight average molecular weight, concentration, etc.) included in the gel base region and the loaded drug (type, concentration, etc.). will be.
  • 3 is a diagram showing gel-based base regions formed in various diameters, various heights, and various shapes.
  • the diameter, height and shape of the gel-based base region can be variously adjusted according to the polymer material (type, weight average molecular weight, concentration, etc.), the formation method, and the like. Accordingly, the strength of the final prepared microstructure, the degree of administration of the polymeric material or drug (dose rate, dosage, depth of administration, etc.) can be variously controlled.
  • the gel-based base region may be a single base region, but the gel-based base region may be different depending on the polymer material (type, weight average molecular weight, concentration, etc.) and the loaded drug (type, concentration, etc.). By performing the formation repeatedly, it may be divided into multiple base regions.
  • Formation of the gel base region may be carried out by a method known in the art, it is preferably carried out by ejection, adhesion, punching or molding, but is not limited thereto.
  • FIG. 4 is a diagram showing the formation of a gelled base region by various methods.
  • the formation of the gel base region may be performed by discharging, attaching or punching. Along with this, curing can occur.
  • a precoat layer may be formed on the support in advance.
  • the precoating layer may be formed in advance before forming the gelled base region on the support, wherein the precoating layer not only serves to facilitate the separation of the gelled base region from the support. In addition, it can impart the ability to penetrate the skin due to the improved strength, and can also impart the drug loading function.
  • the precoating layer may be formed by a method known in the art, but is preferably formed by discharge, immersion and spraying, but is not limited thereto. Along with this, curing can occur.
  • 5 is a view showing a precoat layer of various materials.
  • the precoating layer may include the same polymer material as the polymer material included in the gel-based base region (see above), or may include a polymer material different from the polymer material included in the gel-based base region. You can also do it (pictured below).
  • the thickness of the precoat layer may be adjusted in various ways depending on the polymer material (type, weight average molecular weight, concentration, etc.), formation method, and the like included in the precoat layer.
  • the method may further include modifying the gelled base region.
  • the modification of the gelled base region can be carried out through cutting or drying. At this time, the concentration of the polymer material in the gel-based region may be further increased through drying.
  • the gel-based region can modify the shape of the gel-based region through cutting, and as shown in FIG. 6 (b), full drying, partial drying (internal drying, top) Drying) may be modified, and as shown in FIG. 6 (c), the gel base region may be modified by cutting after drying and drying after cutting.
  • the method for producing a microstructure according to the present invention includes the step of forming an outer region on the gel-based base region (step (b)).
  • the formation of the outer region may be carried out by coating a coating region comprising a second polymeric material on the gelled base region, or may be carried out through the attachment of a second microstructure on the gelled base region.
  • the coating region is formed on the gel-based region, it is viscous to facilitate molding May be present in solution. That is, the weight average molecular weight of the second polymer material included in the coating region may be lower than the weight average molecular weight of the polymer material included in the gel-based base region.
  • the viscosity of the outer region may be 0.15 Pa ⁇ s to 400 Pa ⁇ s at 25 ° C., preferably 0.15 Pa ⁇ s to 40 Pa ⁇ s, but is not limited thereto.
  • the second polymer material may be a biocompatible or biodegradable material, and specific types of the biocompatible or biodegradable material are as mentioned above.
  • the second polymer material may be the same as or different from the aforementioned polymer material.
  • the coating area may be further loaded with a drug, the specific type of the drug is also as mentioned above.
  • the coating area may be formed such that the gel-based area is coated entirely, or the gel-based area may be formed to be partially coated.
  • the coating area may be divided into multiple coating areas, which may be classified according to the material (type, weight average molecular weight, concentration, etc.) and the loaded drug (type, concentration, etc.) included in the coating area. .
  • FIG. 7 is a diagram illustrating coating regions formed in various shapes.
  • the shape of the coating area can be variously adjusted according to the material (type, weight average molecular weight, concentration, etc.), the formation method, Accordingly, the strength, penetration, etc. of the final microstructure can be adjusted in various ways.
  • the coating area may be a single coating area, but the formation of the coating area is repeated by varying the material (type, weight average molecular weight, concentration, etc.) and the loaded drug (type, concentration, etc.). May be divided into multiple coating areas.
  • the coating area may be molded or a separate microstructure may be attached onto the coating area.
  • the molding may be performed by one or more methods selected from the group consisting of molding, drawing, blowing, suction, centrifugal force application, and magnetic field application by applying an outward force to the coating area or the viscous droplet. Along with this, curing can occur.
  • the molding of the coating area in (c-1) may have various arrangements of the coating layer 30 ′ depending on the molding method. According to various shapes and arrangements of the coating layer 30 ′, strength, penetrating force, and the like of the final microstructure may be adjusted.
  • the present invention also provides a microstructure manufactured according to the above method.
  • the strength is improved.
  • the present invention is a base layer comprising a polymer material; And an outer layer including a second polymer material formed on the base layer, wherein the second polymer material has a weight average molecular weight or a viscosity lower than that of the polymer material.
  • the weight average molecular weight of the polymer material may be 50kDa to 2,500kDa.
  • the viscosity of the polymer material may be 5 Pa.s to 400 Pa.s at 25 ° C.
  • the base layer is formed from a gel-based base region
  • the outer layer is formed from an outer region, and the gel-based base region, the outer region, and a manufacturing method thereof are as described above.
  • microstructure according to the present invention can be used as microblades, microblades, microknifes, microfibers, microspikes, microprobes, microbarbs, microarrays or microelectrodes.
  • Hyaluronic acid (1250 kDa) 25 (w / v)% gel was applied on an aluminum pillar having a diameter of 190 ⁇ m using a nozzle having a diameter of 190 ⁇ m (MUSASHI engineering, SN-27G-LF) at 100 ⁇ m / s for 4 seconds and Discharge and cure for 6.6 seconds to form a gelled base region which was then cut using a blade.
  • MUSASHI engineering, SN-27G-LF MUSASHI engineering, SN-27G-LF
  • the discharged gel-based region was measured under a condition of 25 ° C. and 30 mm Parallel Plate 1.0 mm Gap using a viscosity meter (Rheosys) before curing.
  • the viscosity was 203 Pa.s, and it was confirmed that the gel base region was successfully prepared.
  • FIG. 9 (a) is an electron micrograph showing a gel-based region formed according to Example 1, in which the diameter of the gel-based region in FIG. 9 (a) is about 62.02 ⁇ m and the height is about 394.12 ⁇ m and about 659.52 ⁇ m, respectively. It was confirmed that the gel base region was successfully prepared.
  • a hyaluronic acid (30 kDa) 40 (w / v)% solution was dispensed on a gel-based base region using a dispenser (MUSASHI engineering, ML-5000xII) at a pressure of 0.2 MPa for 0.22 seconds to form a coating region. Thereafter, the aluminum substrate on which the precoating layer was previously formed was brought into contact with the top of the coating area, and then vertically drawn for 3.3 seconds at a rate of 100 ⁇ m / s. Thereafter, after curing for 1 minute, the aluminum substrate on which the pre-coating layer was previously formed was vertically raised at a rate of 100 ⁇ m / s to finally manufacture the microstructure.
  • a dispenser MUSASHI engineering, ML-5000xII
  • the formed gel-based region was measured at a speed of 3.6 mm / min using a strength meter (Zwick / Roell, Z0.5). As a result, it was confirmed that the gel-based base region was successfully produced with an average strength of 1.3 N.
  • Hyaluronic acid (1250kDa) 25 (w / v)% gel was applied on aluminum pillars with a diameter of 190 ⁇ m using nozzles with internal diameters of 330 ⁇ m and 580 ⁇ m (MUSASHI engineering, SN-23G-LF and SN-20G-LF). Discharged and cured at 100 ⁇ m / s for 6 seconds and 6.5 seconds to form a gel base region, which was then cut using a blade. Thereafter, the microstructures were finally manufactured in the same manner as in Example 1.
  • the discharged gel-based region was measured under a condition of 25 ° C. and 30 mm Parallel Plate 1.0 mm Gap using a viscosity meter (Rheosys) before curing.
  • the viscosity was 203 Pa.s, and it was confirmed that the gel base region was successfully prepared.
  • FIG. 9 (b) is an electron micrograph showing the gel base region formed according to Example 2, in which the diameters of the gel base region in FIG. 9 (b) are about 341.37 ⁇ m and about 575.54 ⁇ m, respectively, and the heights are about 512.49 ⁇ m and At about 444.44 ⁇ m, it was confirmed that the gelled base region was successfully prepared.
  • the formed gel-based region was measured at a speed of 3.6 mm / min using a strength meter (Zwick / Roell, Z0.5). As a result, it was confirmed that the gel-based base region was successfully prepared with an average intensity of 2.2 N.
  • Carbosymethylcellulose (Sigma-Aldrich, Inc.) precoating layer 30 ⁇ m pre-formed on an aluminum substrate, and then hyaluronic acid (1250kDa) 25 (w / v)% gel was applied. Subsequently, the applied hyaluronic acid gel was vertically lowered at a nozzle having a diameter of 190 ⁇ m (MUSASHI engineering, SN-27G-LF) at a speed of 100 ⁇ m / s, and the applied hyaluronic acid gel was mounted inside the nozzle.
  • hyaluronic acid (1250kDa) 25 (w / v)% gel was applied.
  • the applied hyaluronic acid gel was vertically lowered at a nozzle having a diameter of 190 ⁇ m (MUSASHI engineering, SN-27G-LF) at a speed of 100 ⁇ m / s, and the applied hyaluronic acid gel was mounted inside the nozzle.
  • the nozzle on which the hyaluronic acid gel is mounted is placed at a height of 500 ⁇ m on an aluminum substrate on which a precoating layer is formed, and then discharged at a pressure of 0.5 MPa using a dispenser (MUSASHI engineering, ML-5000 ⁇ II) to obtain a gel-based base region. Formed. Thereafter, the microstructures were finally manufactured in the same manner as in Example 1.
  • the discharged gel-based region was measured under a condition of 25 ° C. and 30 mm Parallel Plate 1.0 mm Gap using a viscosity meter (Rheosys) before curing.
  • the viscosity was 203 Pa.s, and it was confirmed that the gel base region was successfully prepared.
  • the formed gel-based region was measured at a speed of 3.6 mm / min using a strength meter (Zwick / Roell, Z0.5). As a result, it was confirmed that the gel-based base region was successfully prepared with an average strength of 1.8 N.
  • FIG. 9 (c) is an electron micrograph showing the gel-based region formed according to Example 3, in which the diameters of the gel-based region in FIG. 9 (c) are about 218.64 ⁇ m and about 196.11 ⁇ m, respectively, and the heights are about 368.34 ⁇ m and At about 446.52 ⁇ m, it was confirmed that the gelled base region was successfully prepared.
  • Figure 9 (d) is an electron micrograph showing the final microstructure prepared according to Example 3, it was confirmed that the microstructure was successfully produced.
  • carboxymethyl cellulose precoat layer was attached to a height of 1.0 mm, dried for 5 minutes, and separated to prepare a gel-based base region.
  • a 55 (w / v)% solution of hyaluronic acid (39 kDa) on the gel-based area was dispensed for 0.22 seconds at a pressure of 0.2 MPa using a dispenser (MUSASHI engineering, ML-5000 II) to form a coating area.
  • a dispenser MUSASHI engineering, ML-5000 II
  • the gel-based base region in which the coating region was formed was mounted in a centrifuge (Hanil, Combi 514-R), and the aluminum substrate on which the pre-coating layer was previously formed was placed at 1.0 mm intervals from the gel-based base region in which the coating region was formed. After rotating for 60 seconds at a speed of 2000rpm, after curing for 1 minute, the microstructure was finally produced.
  • the formed gel-based region was measured at a speed of 3.6 mm / min using a strength meter (Zwick / Roell, Z0.5). As a result, it was confirmed that the gel-based base region was successfully prepared with an average strength of 1.5 N.
  • FIG. 10 (a) is an electron micrograph showing a gel-based region formed according to Example 4, in which the diameters of the gel-based regions in FIG. 10 (a) are each about 557.69 ⁇ m and the heights are about 365.38 ⁇ m, respectively. It was confirmed that this was successfully manufactured.
  • Figure 10 (b) and 10 (c) is an electron micrograph showing the final microstructure prepared according to Example 4, it was confirmed that the microstructure was successfully manufactured.
  • carboxymethyl cellulose precoat layer was attached to a height of 1.0 mm, dried for 5 minutes, and separated to prepare a gel-based base region.
  • the formed gel-based region was measured at a speed of 3.6 mm / min using a strength meter (Zwick / Roell, Z0.5). As a result, it was confirmed that the gel-based base region was successfully prepared with an average strength of 1.5 N.
  • FIG. 11 (a) is an electron micrograph showing a gel-based region formed according to Example 5, wherein the diameter of the gel-based region in FIG. 11 (a) is about 324.74 ⁇ m and the height is about 247.77 ⁇ m, respectively. It was confirmed that this was successfully manufactured.
  • Figure 11 (b) is an electron micrograph showing the final microstructure prepared according to Example 5, it was confirmed that the microstructure was successfully produced.
  • Gel-like base regions were prepared in the same manner as in Example 5. At this time, the discharged gel-based region was measured using a viscosity meter (Rheosys) before curing under conditions of 25 ° C. and 30 mm Parallel Plate 1.0 mm Gap. As a result, the viscosity was 193 Pa? S, and it was confirmed that the gel-based base region was successfully prepared.
  • a viscosity meter Heosys
  • a 55% w / v) solution of hyaluronic acid (39 kDa) was dispensed on the gel-based area using a dispenser (MUSASHI engineering, ML-5000 II) at a pressure of 0.2 MPa for 0.40 seconds to form a coating area.
  • a dispenser MUSASHI engineering, ML-5000 II
  • the gel-based base region in which the coating region was formed was mounted in a centrifuge (Hanil, Combi 514-R), and the aluminum substrate on which the pre-coating layer was previously formed was placed at 1.0 mm intervals from the gel-based base region in which the coating region was formed. After rotating for 60 seconds at a speed of 2000rpm, after curing for 1 minute, the microstructure was finally produced.
  • the formed gel-based region was measured at a speed of 3.6 mm / min using a strength meter (Zwick / Roell, Z0.5). As a result, it was confirmed that the gel-based base region was successfully prepared with an average strength of 1.5 N.
  • 12 (a) and 12 (b) are electron micrographs showing the microstructures finally prepared according to Example 6, wherein the gel-based base diameters were about 485 ⁇ m and about 610 ⁇ m, respectively, and the heights were about 466 ⁇ m and It was about 317 ⁇ m, and the heights of the microstructures were 461 ⁇ m and 495 ⁇ m, respectively.

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Abstract

La présente invention concerne une microstructure et son procédé de fabrication, le procédé comprenant les étapes consistant à : (a) former une région de base de type gel comprenant un matériau polymère sur un support; et (b) former une région extérieure sur la région de base de type gel.
PCT/KR2016/011581 2015-10-14 2016-10-14 Microstructure utilisant un matériau polymère de type gel, et son procédé de fabrication WO2017065570A1 (fr)

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KR10-2015-0143257 2015-10-14
KR20150143257 2015-10-14
KR1020160133482A KR20170044049A (ko) 2015-10-14 2016-10-14 겔형 고분자 물질을 이용한 마이크로구조체 및 이의 제조방법
KR10-2016-0133482 2016-10-14

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WO2017065570A1 true WO2017065570A1 (fr) 2017-04-20

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180056053A1 (en) * 2016-08-26 2018-03-01 Juvic Inc. Protruding microstructure for transdermal delivery

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6334856B1 (en) * 1998-06-10 2002-01-01 Georgia Tech Research Corporation Microneedle devices and methods of manufacture and use thereof
KR20040105811A (ko) * 2002-03-26 2004-12-16 자이단호진 오사카 산교 신코 기코 의료용 시스템 및 그 제조 방법
KR101136738B1 (ko) * 2008-10-02 2012-04-19 주식회사 라파스 송풍에 의한 솔리드 마이크로구조체의 제조방법 및 이로부터 제조된 솔리드 마이크로구조체
US20140005606A1 (en) * 2012-06-29 2014-01-02 Mei-Chin Chen Embeddable micro-needle patch for transdermal drug delivery and method of manufacturing the same
KR20140101903A (ko) * 2013-02-12 2014-08-21 안동대학교 산학협력단 마이크로니들 디바이스의 제조방법
KR20150135748A (ko) * 2014-05-22 2015-12-03 연세대학교 산학협력단 Ccdp 방법에 의한 마이크로구조체의 제조

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6334856B1 (en) * 1998-06-10 2002-01-01 Georgia Tech Research Corporation Microneedle devices and methods of manufacture and use thereof
KR20040105811A (ko) * 2002-03-26 2004-12-16 자이단호진 오사카 산교 신코 기코 의료용 시스템 및 그 제조 방법
KR101136738B1 (ko) * 2008-10-02 2012-04-19 주식회사 라파스 송풍에 의한 솔리드 마이크로구조체의 제조방법 및 이로부터 제조된 솔리드 마이크로구조체
US20140005606A1 (en) * 2012-06-29 2014-01-02 Mei-Chin Chen Embeddable micro-needle patch for transdermal drug delivery and method of manufacturing the same
KR20140101903A (ko) * 2013-02-12 2014-08-21 안동대학교 산학협력단 마이크로니들 디바이스의 제조방법
KR20150135748A (ko) * 2014-05-22 2015-12-03 연세대학교 산학협력단 Ccdp 방법에 의한 마이크로구조체의 제조

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180056053A1 (en) * 2016-08-26 2018-03-01 Juvic Inc. Protruding microstructure for transdermal delivery

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