MICRONEEDLE, APPARATUS FOR MANUFACTURING MICRONEEDLE, AND METHOD OF MANUFACTURING MICRONEEDLE USING APPARATUS

• US 20200129745A1
• Filed: 10/31/2018
• Published: 04/30/2020
• Est. Priority Date: 10/31/2018
• Status: Active Grant

• Current Assignee: Gachon University of Industry-Academic Cooperation Foundation
• Original Assignee: Gachon University of Industry-Academic Cooperation Foundation
• Inventors: PARK, Jung Hwan, JEONG, Hye Rin, PARK, Jee Hyun
• Granted Patent: US 10,980,993 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/0046 Solid microneedles
• CPC Class Codes: A61M 2037/0053 Methods for producing microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles

Abstract

Disclosed are a microneedle, an apparatus for manufacturing a microneedle including a support part containing a medicinal solution for coating a microneedle, a controller for controlling the temperature of the medicinal solution contained in the support part, and a dryer for drying the medicinal solution coated on the microneedle, and a method of manufacturing the microneedle using the apparatus. According to the configuration, the temperature of the medicinal solution can be adjusted such that a viscosity suitable for coating with the medicinal solution is maintained, whereby the quality of a microneedle coated with the medicinal solution can be improved, and denaturation of active ingredients in the medicinal solution can be prevented, which causes stability increase.

Claims

1. An apparatus for manufacturing a microneedle coated with a medicinal solution, the apparatus comprising:

a support part containing a medicinal solution for coating a microneedle; and

a controller configured to control the temperature of the medicinal solution contained in the support part,

wherein the controller lowers the temperature of the medicinal solution and maintains the temperature at a predetermined temperature.

2. The apparatus according to claim 1, wherein the support part is a container with an open top, and

the controller is provided at a bottom of the support part and serves to lower the temperature of the support part to a low temperature.

3. The apparatus according to claim 1, wherein the controller comprises:

a temperature holding member installed at a bottom of the support part and configured to maintain the temperature of the medicinal solution; and

a cooling member provided at a bottom of the support part and configured to cool the support part,

wherein the temperature holding member is provided between the cooling member and the support part.

4. The apparatus according to claim 3, wherein the temperature holding member comprises a Peltier effect device, and the cooling member comprises a cooling fan cooled by a refrigerant.

5. The apparatus according to claim 1, further comprising a chamber, wherein the support part and the controller are installed in the chamber and an internal temperature of the chamber is adjustable.

6. The apparatus according to claim 5, wherein an inside of the chamber is cooled and is maintained at a predetermined temperature, and a process of immersing the microneedle in the support part to coat a surface of the microneedle with a medicinal solution is performed inside the chamber cooled to low temperature.

7. The apparatus according to claim 1, further comprising a dryer configured to dry the microneedle coated with the medicinal solution, wherein the dryer serves to adjust temperature.

8. The apparatus according to claim 7, wherein the dryer is cooled and is maintained at a predetermined temperature.

9. An apparatus for manufacturing a microneedle coated with a medicinal solution, wherein the apparatus comprises:

a support part containing a medicinal solution for coating a microneedle;

a controller configured to control the temperature of the medicinal solution contained in the support part;

a chamber in which the support part and the controller are installed and an internal temperature of which is adjustable; and

a dryer configured to dry the microneedle,

wherein the temperature of at least one of the medicinal solution, an internal space of the chamber, in which the microneedle is coated with the medicinal solution, and a space, in which the microneedle is dried, is lowered and is maintained at a predetermined temperature.

10. A method of manufacturing a microneedle, the method comprising:

adjusting the temperature of a medicinal solution; and

coating a surface of the microneedle with the medicinal solution by supporting the microneedle with the medicinal solution,

wherein, in the adjusting, the medicinal solution is cooled and is maintained at a predetermined temperature.

11. The method according to claim 10, wherein, in the adjusting, the medicinal solution immersed in a support part is cooled using a cooling member, and then the temperature of the medicinal solution is maintained at a predetermined temperature using a temperature holding member comprising a Peltier effect device.

12. The method according to claim 10, wherein the coating is performed inside a chamber that is cooled to and maintained at a predetermined temperature.

13. The method according to claim 10, further comprising drying the microneedle coated with the medicinal solution after the coating,

wherein the drying is performed inside a dryer that is cooled to and maintained at a predetermined temperature.

14. The method according to claim 10, wherein the medicinal solution is prepared by mixing a solvent with a biocompatible substance.

15. The method according to claim 14, wherein the biocompatible substance comprises one or more selected from the group consisting of hyaluronic acid, alginic acid, pectin, carrageenan, chondroitin(sulfate), dextran(sulfate), chitosan, polylysine, collagen, gelatin, carboxymethyl chitin, fibrin, agarose, pullulan polylactide, polyglycolide (PGA), a polylactide-glycolide copolymer (PLGA), hyaluronic acid, alginic acid, carrageenan, chondroitin(sulfate), dextran(sulfate), chitosan, polylysine, collagen, gelatin, carboxymethyl chitin, fibrin, agarose, pullulan polyanhydride, polyorthoester, polyetherester, polycaprolactone, polyesteramide, poly(butyric acid), poly(valeric acid), polyurethane, polyacrylate, an ethylene-vinyl acetate polymer, acryl-substituted cellulose acetate, non-degradable polyurethane, polystyrene, polyvinyl chloride, polyvinyl fluoride, poly(vinylimidazole), chlorosulfonate polyolefin, polyethylene oxide, polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polymethacrylate, hydroxypropyl methylcellulose (HPMC), ethyl cellulose (EC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose, cyclodextrin, and a copolymer of monomers and cellulose forming such a polymer.

16. The method according to claim 14, wherein the medicinal solution is mixed with an additive for improving mechanical strength, wherein the additive is formed of one or more selected from the group consisting of trehalose, glucose, maltose, lactose, lactulose, fructose, turanose, melitose, melezitose, dextran, sorbitol, xylitol, palatinit, mannitol, poly((lactide), poly(glycolide), poly((lactide-co-glycolide), polyanhydride, polyorthoester, polyetherester, polycaprolactone, polyesteramide, poly(butyric acid), poly(valeric acid), polyurethane, polyacrylate, an ethylene-vinyl acetate polymer, acryl-substituted cellulose acetate, non-degradable polyurethane, polystyrene, polyvinyl chloride, polyvinyl fluoride, poly(vinylimidazole), chlorosulphonate polyolefin, polyethylene oxide, polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polymethacrylate, hydroxypropyl methylcellulose (HPMC), ethyl cellulose (EC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose, and cyclodextrin and a copolymer of monomers forming such a polymer.

17. The method according to claim 14, wherein the medicinal solution is mixed with an active ingredient, wherein the active ingredient comprises at least any one of a synthetic medicine, a protein/peptide medicine, a hormone, a hormone analogue, an enzyme, an enzyme inhibitor, a signal transduction protein or a portion thereof, an antibody or a portion thereof, a single-chain antibody, a binding protein or a binding domain thereof, an antigen, an adherent protein, a structural protein, a regulatory protein, a toxin protein, a cytokine, a transcription regulator, a blood coagulation factor, and a vaccine.

18. The method according to claim 17, wherein the protein/peptide medicine comprises at least any one of vaccines, allergic antigens, insulin, insulin-like growth factor 1 (IGF-1), growth hormone, erythropoietin, granulocyte-colony stimulating factors (G-CSFs), granulocyte/macrophage-colony stimulating factors (GM-CSFs), interferon alpha, interferon beta, interferon gamma, interleukin-1 alpha and beta, interleukin-3, interleukin-4, interleukin-6, interleukin-2, epidermal growth factors (EGFs), calcitonin, adrenocorticotropic hormone (ACTH), tumor necrosis factor (TNF), atobisban, buserelin, cetrorelix, deslorelin, desmopressin, dynorphin A (1-13), elcatonin, eleidosin, eptifibatide, growth hormone releasing hormone-II (GHRH-II), gonadorelin, goserelin, histrelin, leuprorelin, lypressin, octreotide, oxytocin, pitressin, secretin, sincalide, terlipressin, thymopentin, thymosine, triptorelin, bivalirudin, carbetocin, cyclosporine, exedine, lanreotide), luteinizing hormone-releasing hormone (LHRH), nafarelin, parathyroid hormone, pramlintide, enfuvirtide (T-20), thymalfasin, and ziconotide.

19. The method according to claim 14, wherein a solvent is added to the medicinal solution, wherein the solvent comprises at least one of inorganic or organic solvents comprising distilled water (DI water), methanol, ethanol, chloroform dibutyl phthalate, dimethyl phthalate, ethyl lactate, glycerin, isopropyl alcohol, lactic acid, and propylene glycol.

20. A microneedle manufactured by the method according to claim 10.