Method for manufacturing transdermal-absorption sheet

Patent metadata

Field	Value
Publication number	US-10045936-B2
Application number	US-201514709644-A
Country	US
Kind code	B2
Filing date	May 12, 2015
Priority date	Nov 13, 2012
Publication date	Aug 14, 2018
Grant date	Aug 14, 2018

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.

First claim

What is claimed is:

1. A method for manufacturing a transdermal-absorption polymer sheet with needle-like protruding portions including a drug-containing layer and a non-drug-containing layer, the method comprising:
a step of providing a mold with needle-like recessed portions that are arranged in a two-dimensional array 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 of the two-dimensional array 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 having an inverted shape of the needle-like recessed portions on the 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
a step of peeling the polymer sheet off from the mold,
wherein the step of forming the polymer sheet includes:
solidifying the drug-containing solution so as to form the drug-containing layer of the needle-like protruding portions,
providing a non-drug-containing solution to the mold after the solidification step, and
solidifying the non-drug-containing solution so as to form the non-drug-containing layer of the needle-like protruding portions,

wherein the non-drug-containing solution is a polymer solution, and
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 a first line of the needle-like recessed portions in the direction of the relative movement between the nozzle and the mold, and the feeding of the drug-containing solution to the mold is stopped before the nozzle is positioned over a last line of the needle-like recessed portions in the direction of the relative movement between the nozzle and the mold.

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

4. The method for manufacturing the transdermal-absorption polymer 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 polymer 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 polymer sheet according to claim 4 , 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 polymer 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 polymer 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.

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

10. The method for manufacturing the transdermal-absorption polymer 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.

11. The method for manufacturing the transdermal-absorption polymer 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.

12. The method for manufacturing the transdermal-absorption polymer 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.

13. The method for manufacturing the transdermal-absorption polymer sheet according to claim 10 , 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.

14. The method for manufacturing the transdermal-absorption polymer sheet according to claim 10 , 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.

15. The method for manufacturing the transdermal-absorption polymer 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.

16. The method for manufacturing the transdermal-absorption polymer 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

Assignees

• Fujifilm Corp

Inventors

• Mochizuki Aya
• Kasahara Seiji
• Che Yanlong
• Ogawa Shotaro

Classifications

• F04C2270/0421

  Controlled or regulated · CPC title

• B29L2031/756

  Microarticles, nanoarticles · CPC title

• A61K9/0021 Primary

  Intradermal administration, e.g. through microneedle arrays or needleless injectors · CPC title

• A61M37/0015

  by using microneedles · CPC title

• A61M2037/0053

  Methods for producing microneedles · CPC title