METHOD FOR MANUFACTURING TRANSDERMAL-ABSORPTION SHEET

• US 20150238413A1
• Filed: 05/12/2015
• Published: 08/27/2015
• Est. Priority Date: 11/13/2012
• Status: Active Grant

• Current Assignee: Fujifilm Corporation (Fujifilm Holdings Corporation)
• Original Assignee: Fujifilm Corporation (Fujifilm Holdings Corporation)
• Inventors: MOCHIZUKI, Aya, CHE, Yanlong, OGAWA, Shotaro, KASAHARA, Seiji
• Granted Patent: US 10,045,936 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• 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
• CPC Class Codes: B29C 39/24 Feeding the material into the mould
• CPC Class Codes: B29L 2031/7544 Injection needles, syringes
• CPC Class Codes: B29L 2031/756 Microarticles, nanoarticles
• CPC Class Codes: F04C 2270/0421 Controlled or regulated

Abstract

A method is provided which enables a drug to be concentrated at needle-like protruding portions and which further allows transdermal-absorption sheets to be manufactured at high production efficiency. The method repeats a step of feeding a drug-containing solution from a liquid feeding apparatus to a mold and filling needle-like recessed portions with the drug-containing solution through a nozzle aligned over the needle-like recessed portions in a state where the nozzle and a front surface of the mold are brought into contact with each other, and a step of moving the liquid feeding apparatus relative to the mold in a state where the nozzle and the front surface of the mold are brought into contact with each other. Thus, the two-dimensionally arranged needle-like recessed portions are filled with the drug-containing solution.

Claims

1. A method for manufacturing a transdermal-absorption sheet with needle-like protruding portions including a drug-containing layer and a non-drug-containing layer, the method comprising:

a step of preparing a mold with two-dimensionally arranged needle-like recessed portions and a liquid feeding apparatus comprising a nozzle with a lip surface and a slit-shaped opening formed on the lip surface;

a step of filling the two-dimensionally arranged needle-like recessed portions with a drug-containing solution by repeating a filling step of feeding the drug-containing solution from the liquid feeding apparatus to the mold and filling one or more of the needle-like recessed portions constituting one line with the drug-containing solution through the nozzle aligned over the needle-like recessed portions in a state where the nozzle and a front surface of the mold are brought in contact with each other, and a moving step of moving the liquid feeding apparatus relative to the mold in a direction perpendicular to a longitudinal direction of the opening in a state where the nozzle and the front surface of the mold are brought in contact with each other;

a step of forming a polymer sheet provided with needle-like protruding portions on a surface of the polymer sheet, the needle-like protruding portions each comprising a drug-containing layer composed of the drug-containing solution and a non-drug-containing layer composed of a non-drug-containing solution and having an inverted shape of the needle-like recessed portions; and

a step of peeling the polymer sheet off from the mold.

2. The method for manufacturing the transdermal-absorption sheet according to claim 1, wherein, in the filling step, the two-dimensionally arranged needle-like recessed portions are filled with the drug-containing solution so that filling is performed on one line or a plurality of lines at a time.

3. The method for manufacturing the transdermal-absorption sheet according to claim 1, wherein the filling step comprises pressurizing an inside of the nozzle.

4. The method for manufacturing the transdermal-absorption sheet according to claim 3, wherein, in the filling step, a pressing force with which the nozzle and the mold are brought into contact with each other is equal to or stronger than a pressurizing force inside the nozzle.

5. The method for manufacturing the transdermal-absorption sheet according to claim 1, wherein the filling step comprises sucking a back surface of the mold with a reduced pressure.

6. The method for manufacturing the transdermal-absorption sheet according to claim 1, wherein the pressing force with which the nozzle and the mold are brought into contact with each other in the filling step is stronger than a pressing force with which the nozzle and the mold are brought into contact with each other in the moving step.

7. The method for manufacturing the transdermal-absorption sheet according to claim 1, wherein, in the moving step, feeding of the drug-containing solution from the liquid feeding apparatus to the mold is stopped while the nozzle is positioned over an area other than the needle-like recessed portions in the mold.

8. The method for manufacturing the transdermal-absorption sheet according to claim 1, wherein, in the moving step, feeding of the drug-containing solution from the liquid feeding apparatus to the mold is started before the nozzle is positioned over the needle-like recessed portions, and the feeding of the drug-containing solution to the mold is stopped before the nozzle is positioned over the area other than the needle-like recessed portions in the mold.

9. The method for manufacturing the transdermal-absorption sheet according to claim 1, wherein at least one of the nozzle and the front surface of the mold is made of an elastically deformable raw material.

10. The method for manufacturing the transdermal-absorption sheet according to claim 1, wherein the mold comprises an air vent hole at a tip of each of the needle-like recessed portions.

11. The method for manufacturing the transdermal-absorption sheet according to claim 1, wherein the step of forming the polymer sheet comprises a step of feeding the non-drug-containing solution to the mold with the needle-like recessed portions filled with the drug-containing solution, and then drying and solidifying the drug-containing solution and the non-drug-containing solution to form the drug-containing layer and the non-drug-containing layer.

12. The method for manufacturing the transdermal-absorption sheet according to claim 1, wherein the step of forming the polymer sheet comprises a step of drying and solidifying the drug-containing solution filled in the needle-like recessed portions in the mold to form the drug-containing layer, feeding the non-drug-containing solution to the mold in which the drug-containing layer is formed in the needle-like recessed portions, and then drying and solidifying the non-drug-containing solution to form the non-drug-containing layer.

13. The method for manufacturing the transdermal-absorption sheet according to claim 1, wherein the step of forming the polymer sheet comprises a step of applying the non-drug-containing solution onto a surface of another support, attaching the another support onto which the non-drug-containing solution is applied to the mold with the needle-like recessed portions filled with the drug-containing solution, and drying and solidifying the drug-containing solution and the non-drug-containing solution to form the drug-containing layer and the non-drug-containing layer.

14. The method for manufacturing the transdermal-absorption sheet according to claim 11, wherein the step of forming the polymer sheet comprises performing at least one of pressurization from the front surface of the mold and reduced pressure suction from the back surface of the mold, when drying and solidifying the drug-containing solution contained in the needle-like recessed portions in the mold.

15. The method for manufacturing the transdermal-absorption sheet according to claim 11, wherein the step of forming the polymer sheet comprises performing at least one of pressurization of the non-drug-containing solution from a front surface of the mold and reduced pressure suction of the non-drug-containing solution from a back surface of the mold.

16. The method for manufacturing the transdermal-absorption sheet according to claim 1, wherein a drug is peptide, protein, nucleic acid, polysaccharide, a vaccine, a medical compound belonging to a water-soluble low-molecular-weight compound, or a cosmetic component.

17. The method for manufacturing the transdermal-absorption sheet according to claim 1, wherein the needle-like protruding portions comprise the drug-containing layer and the non-drug-containing layer, the drug-containing layer further contains hydroxyethyl starch, and the non-drug-containing layer contains hydroxyethyl starch and hyaluronic acid.

18. The method for manufacturing the transdermal-absorption sheet according to claim 1, wherein the needle-like protruding portions comprise the drug-containing layer and the non-drug-containing layer, the drug-containing layer further contains chondroitin sulfate, and the non-drug-containing layer contains hydroxyethyl starch.