JP7290755B2 - Methods for producing sterile products - Google Patents

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to methods for producing sterile products, and more particularly to methods for producing sterile products that involve both in-house and out-of-household production.

A percutaneous absorption sheet is known in which needle-like projections with a high aspect ratio containing a drug are formed. The transdermal absorption sheet is attached to the surface of a living body such as the skin, so that the medicine on the needle-like projections can be administered into the living body.

A transdermal absorption sheet is produced by filling a solution containing a drug into the needle-shaped recesses of a mold, in which needle-shaped recesses are formed by reversing the needle-shaped protrusions, drying the solvent, and then adding excipients. It can be produced by filling the needle-shaped recesses of the mold with the solution, drying the solvent, and peeling off the mold.

Since the transdermal absorption sheet is a pharmaceutical product, it is required to manufacture the transdermal absorption sheet under an aseptic environment using equipment such as an aseptic room. However, if all the steps of manufacturing a transdermal absorption sheet are carried out in an aseptic environment, it is necessary to widen the facility for the aseptic environment. Therefore, in order to reduce manufacturing costs and equipment costs, it is conceivable to seal the mold filled with the solution in a drying container and dry the solvent of the solution outside the sterile environment. Then, when re-carrying into an aseptic environment after drying, it is necessary to sterilize the surface of the drying container before re-carrying.

For example, in the following Patent Documents 1 and 2, the filling process and the storage process are performed under an aseptic environment, the drying process is performed outside the aseptic environment, and when returning to the aseptic environment, the electrons on the surface of the drying container It is described that an aseptic treatment step such as irradiation is performed.

WO2019/146277 WO2019/171842

In the method for producing the transdermal absorption sheet described in Patent Document 1 and Patent Document 2, the opening of the container body is closed with a microbe-impermeable and gas-permeable porous sheet. sealed inside. Since the porous sheet is adhered to the drying container body by heat sealing, if the porous sheet is peeled off after the drying process, the porous sheet will be distorted, making it impossible to reuse and increasing the manufacturing cost. It was a factor in swelling.

SUMMARY OF THE INVENTION The present invention has been made in view of such circumstances, and an object of the present invention is to provide a method for producing aseptic products in which the drying container can be reused.

In order to achieve the object of the present invention, a method for producing a sterile product according to the present invention includes storing a first polymer solution in a container body under an aseptic environment, and providing a first polymer solution around the opening of the container body. By bonding the first lid on one adhesive surface and covering the opening with the first lid, the first drying container comprising the container body and the first lid is provided with the first polymer solution. a storing step, a first carrying-out step of carrying out the first drying container after the first storing step to outside the sterile environment, a first drying step of drying the first polymer solution after the first carrying-out step, a first A first electron beam irradiation step of irradiating an electron beam from an electron beam source toward the surface of the first drying container after the first drying step, and a sterile environment for the first drying container after the first electron beam irradiation step. A first carrying-in step of carrying in, a first opening step of peeling off the first lid body after the first carrying-in step and opening the first drying container, and storing the second polymer solution in the container main body under an aseptic environment. a second bonding surface provided around the opening of the container body, different from the first bonding surface, to adhere the second lid, and cover the opening with the second lid, whereby the container body and the second lid are bonded together; a second housing step of housing the second polymer solution in the second drying container, a second carrying-out step of carrying the second drying container after the second housing step out of the aseptic environment, and a second After the carry-out step, a second drying step of drying the second polymer solution stored in the second drying container, and an electron beam emitted from an electron beam source toward the surface of the second drying container after the second drying step. A second electron beam irradiation step of irradiating a second electron beam irradiation step, a second carrying-in step of carrying the second drying container after the second electron beam irradiation step into an aseptic environment, peeling off the second lid body after the second carrying-in step, 2 and a second opening step of opening the drying container.

In order to achieve the object of the present invention, the method for producing a sterile product according to the present invention includes a first filling step of filling needle-shaped recesses of a mold having needle-shaped recesses with a first polymer solution under a sterile environment. , the mold after the first filling step is stored in the container body under a sterile environment, the first lid is adhered to the first adhesive surface provided around the opening of the container body, and the opening is attached to the first lid By covering with, the first housing step of housing the mold in the first drying container composed of the container body and the first lid, and the first drying container after the first housing step are carried out of the sterile environment. a first carrying-out step; after the first carrying-out step, a first drying step of drying the first polymer solution in the mold stored in the first drying container to form a first layer; 1 A first electron beam irradiation step of irradiating the surface of the drying container with an electron beam from an electron beam source, and a first carrying-in step of carrying the first drying container after the first electron beam irradiation step into an aseptic environment. a first opening step of peeling off the first lid after the first carrying-in step and opening the first drying container; a first removing step of removing the mold from the first drying container after the first opening step; A second filling step of filling the second polymer solution onto the first layer formed in the needle-shaped concave portion of the mold after the first removing step under an aseptic environment; It is housed in the container body, the container body is provided around the opening of the container body, the second lid is adhered to the second bonding surface different from the first bonding surface, and the opening is covered with the second lid. A second storage step of storing the mold in a second drying container composed of a second lid and a second storage step, a second carrying out step of carrying out the second drying container after the second storage step outside the aseptic environment, a second After the 2 carry-out step, a second drying step of drying the second polymer solution in the mold stored in the second drying container to form a second layer, and a surface of the second drying container after the second drying step. A second electron beam irradiation step of irradiating an electron beam from an electron beam source toward the second electron beam irradiation step, a second carrying-in step of carrying the second drying container after the second electron beam irradiation step into a sterile environment, and after the second carrying-in step It has a second opening step of peeling off the second lid and opening the second drying container, and a second removing step of removing the mold from the second drying container after the second opening step.

In one aspect of the present invention, the container body has a flange around the opening, the second adhesive surface is provided on the opening side of the flange, and the first adhesive surface is provided outside the second adhesive surface. preferably.

One aspect of the present invention includes a cutting step of cutting the container body and the second lid of the second drying container on the second adhesive surface after the second drying step and before the second electron beam irradiation step. It is preferable to have

In one aspect of the present invention, the first lid and the second lid are preferably made of a material impermeable to microorganisms and gas permeable.

In one aspect of the present invention, the bonding between the first lid body and the first bonding surface and the bonding between the second lid body and the second bonding surface are preferably performed by heat sealing.

In one aspect of the present invention, it is preferable that the container body further has at least one adhesive surface that adheres to the lid around the opening.

In one aspect of the present invention, the voltage of the electron beam source is preferably 200 kV or less.

In one aspect of the present invention, the first polymer solution preferably contains a drug.

In one aspect of the present invention, the sterile product is preferably a transdermal absorption sheet.

In one aspect of the present invention, the sterile product is preferably a drug, quasi-drug, or cosmetic.

According to the present invention, the container body of the drying container can be reused, and the manufacturing cost can be reduced.

1 is an overall perspective view of a transdermal absorption sheet. FIG. It is process drawing of the manufacturing method of a mold. It is process drawing of the manufacturing method of a mold. It is process drawing of the manufacturing method of a mold. It is a flow chart of a manufacturing method of a percutaneous absorption sheet. It is a figure explaining the manufacturing method of a percutaneous absorption sheet. It is a figure explaining the manufacturing method of a percutaneous absorption sheet. It is a figure explaining the manufacturing method of a percutaneous absorption sheet. It is a cross-sectional view of the first drying container. It is a figure which shows arrangement|positioning of an electron beam source and a container for 1st drying. It is the schematic which shows the electron beam irradiated by a 1st electron beam irradiation process. It is a figure explaining the adhesion|attachment state of the container for 2nd drying of a 2nd accommodation process. It is a figure explaining a cutting process. It is a figure explaining other embodiment of a peeling process. It is a perspective view of a jig for conveyance. FIG. 16 is a cross-sectional view taken along line 16-16 of FIG. 15; It is the schematic which shows the electron beam irradiated by a 1st electron beam irradiation process. It is the schematic which shows the electron beam irradiated by a 1st electron beam irradiation process. It is a figure for demonstrating the inside of a jig for conveyance. It is a figure for demonstrating the inside of a jig for conveyance. It is a figure for demonstrating the inside of a jig for conveyance. 4 is a flow chart of another method for manufacturing a sterile article of manufacture;

Hereinafter, preferred embodiments of the method for producing a sterile product according to the present invention will be described with reference to the accompanying drawings. In this specification, the term "~" is used to include the numerical values before and after it as lower and upper limits.

[Manufacturing method of transdermal absorption sheet]
As an example of the method for producing a sterile product according to the present invention, a method for producing a transdermal absorption sheet will be described. FIG. 1 is an overall perspective view of a transdermal absorption sheet 1. FIG. As shown in FIG. 1, the transdermal absorption sheet 1 is composed of a sheet portion 2 and a plurality of needle-like protrusions 10 (also called microneedles or microneedles) arranged on the surface of the sheet portion 2. there is

(Preparation of mold)
FIGS. 2 to 4 are diagrams showing steps of manufacturing a mold for manufacturing a transdermal absorption sheet. As shown in FIG. 2, first, an original plate 11 for making a mold is produced.

There are two methods for producing the original plate 11 . One is to apply a photoresist on a silicon substrate, perform exposure and development, and then perform etching such as RIE (Reactive Ion Etching) to form a conical shape on the surface of the original plate 11 . This is a method of fabricating an array of portions 12 (needle-like projections). When performing etching such as RIE, it is possible to form the conical portion 12 by performing etching from an oblique direction while rotating the silicon substrate.

Another method is to form an array of shapes 12 such as quadrangular pyramids on the surface of an original plate 11 by processing a metal substrate such as nickel using a cutting tool such as a diamond bit.

Next, a mold is produced. Specifically, as shown in FIG. 3, a mold 13 is produced from an original plate 11 . The following method is conceivable, in which the shape of the original plate 11 can be accurately transferred to the mold 13 and can be peeled off, and the manufacturing can be performed at low cost.

In the first method, silicone resin obtained by adding a curing agent to polydimethylsiloxane (for example, Sylgard 184 manufactured by Dow Corning) is poured into the original plate 11, cured by heat treatment at 100° C., and then separated from the original plate 11. The method.

A second method is to pour a UV (ultraviolet) curable resin that is cured by irradiating ultraviolet rays onto the original plate 11 , irradiate the original plate 11 with ultraviolet rays in a nitrogen atmosphere, and then peel it off from the original plate 11 .

In the third method, a plastic resin such as polystyrene or polymethyl methacrylate dissolved in an organic solvent is poured into the original plate 11 coated with the release agent, dried to evaporate the organic solvent, and cured. , is a method of peeling from the original plate 11 .

As a result, the mold 13 is manufactured in which the needle-like concave portions 15 that are inverted shapes of the cones or pyramids of the original plate 11 are arranged in a two-dimensional array. FIG. 4 shows the mold 13 produced in this way. It should be noted that the mold 13 can be easily manufactured any number of times in any of the above methods.

As a material used for the mold 13, an elastic material or a metal material can be used. Among them, a material having elasticity is preferable, and a material having high gas permeability is more preferable. Oxygen permeability, which is representative of gas permeability, is preferably greater than 1×10 ⁻¹² mL/(s・m・Pa), and is preferably greater than 1×10 ⁻¹⁰ mL/(s・m・Pa). More preferred. By setting the gas permeability within the above range, the air existing in the needle-like concave portions 15 of the mold 13 can be expelled from the mold 13 side, so that a medical transdermal absorption sheet with few defects can be manufactured.

Specific examples of such materials include silicone resins (eg, Sylgard 184, 1310ST), UV curable resins, and plastic resins (eg, polystyrene, polymethyl methacrylate) melted or dissolved in solvents. be able to. Among these materials, silicone rubber-based materials can be preferably used because they have durability against transfer by repeated pressurization and have good releasability from the material. Metal materials include Ni, Cu, Cr, Mo, W, Ir, Tr, Fe, Co, MgO, Ti, Zr, Hf, V, Nb, Ta, α-aluminum oxide, zirconium oxide, and stainless steel. (Starbucks material), etc., or alloys thereof.

(Polymer solution)
The polymer solution, which is the solution of the polymer resin that is the material of the transdermal absorption sheet 1, will be described. The polymer solution consists of a liquid containing a drug (equivalent to the first polymer solution) and a base liquid (second polymer solution) that mainly serves as a material for the sheet portion 2 of the transdermal absorption sheet and does not contain a drug (second polymer solution). equivalent to liquid).

It is preferable to use a biocompatible resin as the material of the resin polymer used in the polymer solution. Examples of such resins include sugars such as glucose, maltose, pullulan, dextran, sodium chondroitin sulfate, sodium hyaluronate, hydroxypropyl cellulose and hydroxyethyl starch, proteins such as gelatin, polylactic acid, lactic acid-glycolic acid copolymers, and the like. of biodegradable polymers are preferably used. Among these, sodium chondroitin sulfate, hydroxypropylcellulose, or dextran can be preferably used. In addition, since gelatin-based materials have adhesion to many substrates and have strong gel strength as a gelling material, they can be adhered to the substrate in the peeling process described later, and the mold can be removed from the substrate. can be used to release the polymer sheet. Although the concentration varies depending on the material, it is preferable that the solution contains 10 to 50% by mass of the resin polymer. Moreover, the solvent used for the dissolution may be any solvent other than hot water as long as it has volatility, and methyl ethyl ketone, alcohol, or the like can be used. In addition, it is possible to dissolve a drug to be supplied into the body together with the solution of the polymer resin depending on the application.

As a method for preparing the polymer solution, when using a water-soluble polymer (eg, gelatin), the polymer solution can be produced by dissolving the water-soluble powder in water and adding a chemical to the solution. If it is difficult to dissolve in water, it may be dissolved by heating. Although the temperature can be appropriately selected depending on the type of polymer material, it is preferable to heat at a temperature of about 60° C. or less. Moreover, when using a polymer that melts with heat (such as maltose), it can be produced by heating and melting the raw material and the chemical. The heating temperature is preferably a temperature at which the raw material melts, specifically about 150°C.

The viscosity of the polymer resin solution is preferably 2000 Pa·s or less, more preferably 1000 Pa·s or less. By appropriately adjusting the viscosity of the polymer resin solution, the solution can be easily injected into the recesses of the mold. Further, the liquid containing the drug preferably has a viscosity of 100 Pa·s or less, more preferably 10 Pa·s or less.

(drug)
The drug is not limited as long as it has a function as a drug. In particular, it is preferable to select from peptides, proteins, nucleic acids, polysaccharides, vaccines, pharmaceutical compounds belonging to water-soluble low-molecular-weight compounds, and cosmetic ingredients. The water-soluble polymeric substance to be contained in the drug-containing polymer solution is preferably one that does not interact with the drug to be contained. For example, when a protein is used as a drug, when a charged macromolecular substance is mixed, the protein and the macromolecular substance form an aggregate due to electrostatic interaction, resulting in aggregation and precipitation. Therefore, when a charged substance is used as a drug, it is preferable to use a water-soluble polymeric substance having no charge, such as hydroxyethyl starch or dextran.

(Manufacturing of transdermal absorption sheet)
A method of manufacturing a percutaneous absorption sheet using the mold 13 will be described. As used herein, the term "sterile environment" refers to a manufacturing area classified as grade A under the Environmental Monitoring Law for Aseptic Pharmaceutical Manufacturing Areas. At times, the number of particles of 0.5 μm or more is 3520/m ³ or less, and the number of particles of 5.0 μm or more is 20/m ³ or less. Colony forming unit) or less/m ³ , falling bacteria or less 1 CFU/plate, surface adhering microorganisms or less of 1 CFU/24 to 30 cm ² of contact plate, or gloves of 1 CFU or less/5 fingers.

Each embodiment will be described below.

<First Embodiment>
FIG. 5 is a flow chart of a method for manufacturing a transdermal absorption sheet. 6 to 8 are diagrams for explaining the method of manufacturing the percutaneous absorption sheet.

The method for manufacturing a transdermal absorption sheet according to the present embodiment comprises a first filling step (step S12), a first storage step (step S14), a first carry-out step (step S16), and a first drying step (step S18), a first electron beam irradiation step (step S20), a first carrying-in step (step S22), a first opening step (step S24), a first extraction step (step S26), and a second filling step. (Step S28), a second storage step (Step S30), a second carry-out step (Step S32), a second drying step (Step S34), a cutting step (Step S36), and a second electron beam to be irradiated It consists of an irradiation step (step S38), a second loading step (step S40), a second opening step (step S42), a second removal step (step S44), and a peeling step (step S46).

[First filling step: step S12]
The first filling step is a step of filling the needle-shaped concave portion 15 of the mold 13 with the first polymer solution 22 containing a drug under a sterile environment.

As shown in FIG. 6, first, a mold 13 having a needle-like concave portion 15 is prepared inside an aseptic chamber 40 under an aseptic environment. The sterile room 40 can be, for example, an isolator. The mold 13 is previously sterilized (aseptic treatment) to kill germs adhering to the mold 13 . Sterilization may include autoclaving or electron beam irradiation.

The needle-like recesses 15 of the mold 13 are filled with a first polymer solution 22 containing a drug. As a filling method, only the needle-like concave portion 15 may be filled by bringing the tip of the slit nozzle into contact with the mold 13 . Alternatively, the first polymer solution 22 may be applied onto the mold 13 using a nozzle, a dispenser, or the like, and the needle-shaped concave portions 15 may be filled with the first polymer solution 22 by bringing the blade into contact with the mold 13 . .

[First housing step: step S14]
The first housing step is a step of housing the mold 13 in which the needle-like recesses 15 are filled with the first polymer solution 22 in the first drying container 28 under an aseptic environment.

Like the mold 13, the first drying container 28 is previously sterilized. FIG. 9 is a cross-sectional view of the first drying container 28. As shown in FIG. As shown in FIG. 9 , the first drying container 28 is composed of a container body 24 and a first lid 26 . The first drying vessel 28 is formed at least in part from a material that is impermeable to microorganisms and gas. In FIG. 9, the first lid 26 is made of a microbe-impermeable and gas-permeable material. By forming a part of the first drying container 28 with a material that is impermeable to microorganisms and gas-permeable, the first polymer solution 22 can be dried and dried from the outside of the first drying container 28. It is possible to prevent contamination of foreign substances and bacteria. As a result, even if the first drying container 28 is placed outside the sterile environment, the sterile environment can be maintained inside the first drying container 28 . "Microorganism impermeability" is sufficient if it is the level of microorganism impermeability possessed by commercially available sterilization packaging materials (sterilization bags, etc.). Therefore, the level of microbial impermeability may be appropriately selected from commercially available sterile packaging materials according to the purpose. More specifically, materials with LRV≧3.0 are preferred as microbial impermeability. LRV can be calculated by the following formula.

LRV= _log10 (A/B)
A: The number of microorganisms per 1 ml before permeating the material B: The number of microorganisms per 1 ml after permeating the material The higher the LRV, the lower the number of microorganisms that permeate, so the upper limit of the LRV is not particularly limited. , the upper limit is preferably LRV≦9. In order to ensure such impermeability to microorganisms, it is common to use a material with a pore size of 0.2 μm. In addition, the material impermeable to microorganisms can be either a material used against microorganisms in gas or a material used against microorganisms in liquid.

The level of gas permeability can also be appropriately selected depending on the purpose. By having gas permeability, the gas generated by the drying in the first drying container 28 can escape to the outside of the first drying container 28, and the drying can proceed. As the gas permeability, a material having a moisture permeability of 1500 to 1640 g/m ² /24 hours measured under conditions of 23° C. and 85% relative humidity in accordance with TAPI T523 is preferred, and 1615 g/m ² /24 hours. Certain materials are more preferred.

A porous sheet can be used as such a material having microbial impermeability and gas permeability, and specifically, a high-density polyethylene nonwoven fabric sheet can be used. A high-density polyethylene nonwoven fabric sheet is a sheet obtained by randomly laminating polyethylene ultrafine filaments having a fiber diameter of 0.5 to 10 μm and bonding them only by heat and pressure. For example, Tyvek Sheet (registered trademark) (manufactured by DuPont) can be mentioned.

In the first drying container 28 shown in FIG. 9, the first lid 26 is made of a material impermeable to microorganisms and gas. Therefore, the container main body 24 is not particularly limited as long as it is a material through which foreign substances, bacteria, and the like do not permeate. For example, resin or metal can be used.

The container main body 24 and the first lid 26 are connected by using the flange 25 provided around the opening 23 of the container main body 24 as a connecting surface. The flange portion 25 is provided around the opening 23 with a first adhesion surface 25A to which the first lid 26 is adhered and a second adhesion surface 25B to which the second lid 126 is adhered. In FIG. 9, the second adhesive surface 25B is provided on the opening 23 side of the collar portion 25, and the first adhesive surface 25A is provided outside the second adhesive surface 25B.

In the first housing step, as also shown in FIG. 6, the first lid 26 and the container body 24 are adhered to close the opening 23 with the first lid 26, and the first drying container 28 is closed. to seal the space inside the Since the first housing step is performed in the sterile room 40, the inside of the first drying container 28 can be kept in a sterile environment. The container main body 24 and the first lid body 26 can be bonded, for example, by heat sealing, and the first bonding surface 25A is preferably provided with an adhesive that melts with heat.

[First unloading step: step S16]
The first unloading step is a step of unloading the first drying container 28 containing the mold 13 to the outside of the sterile room 40 (outside the sterile environment). Since the mold 13 is stored inside the sealed first drying container 28 in the first storing step, even if the first drying container 28 is carried out of the sterile room 40, the first drying container The first polymer solution 22 inside 28 is not contaminated with bacteria and foreign matter.

[First drying step: step S18]
The first drying step is a step of drying the first polymer solution 22 in the needle-like concave portion 15 of the mold 13 housed in the first drying container 28 outside the sterile environment.

It is preferable that the first drying step be performed in a drying chamber whose temperature and humidity can be adjusted. If the drying speed of the first polymer solution 22 increases, the shrinkage due to drying proceeds rapidly, making it difficult to form the needle-like protrusions 10 (see FIG. 1) along the shape of the needle-like recesses 15. It should be dried.

Although it takes about three hours to dry the first polymer solution 22 , according to the present embodiment, the first drying step is performed outside the sterile room 40 so that the next mold 13 can be used inside the sterile room 40 . can perform the first filling step. Therefore, the next transdermal absorption sheet 1 can be manufactured without waiting for the end of the first drying step, and productivity can be improved.

[First electron beam irradiation step: step S20]
After the drying of the first polymer solution 22 is completed by the first drying step, the first drying container 28 is returned inside the sterile chamber 40 as shown in FIG. In the first electron beam irradiation step, before the first drying container 28 containing the mold 13 is carried into the sterile room 40, an electron beam is emitted from the electron beam source 50 toward the surface of the first drying container 28. is a step of sterilizing the surface of the first drying container 28 by irradiating it with.

FIG. 10 is a diagram showing an example of the arrangement of the electron beam source 50 and the first drying container 28 in the first electron beam irradiation step. Here, the surface of the first drying container 28 is irradiated with electron beams from three electron beam sources 50A, 50B, and 50C arranged in three equiangular directions with respect to the first drying container 28. . The method for supporting the first drying container 28 is not particularly limited as long as the surface of the first drying container 28 can be irradiated with an electron beam. Since electron beams are easily scattered, the irradiation direction of the electron beams does not matter, and the surface of the first drying container 28 can be sterilized with the arrangement shown in FIG. For sterilization, the voltage of the electron beam sources 50A, 50B, and 50C with which the surface of the first drying container 28 is irradiated is preferably 200 kV or less. By setting the voltage to 200 kV or less, the effect of sterilizing the surface of the first drying container 28 can be obtained. If the voltage exceeds 200 kV, the electron beam reaches the inside of the first drying container 28, which is not preferable. As for the electron dose, the surface of the first drying container 28 is preferably irradiated with an electron dose of 15 kGy (kilogray) or more, and in the present embodiment, the surface of the first drying container 28 is irradiated with an electron dose of 15 kGy. be.

FIG. 11 is a schematic diagram showing electron beams irradiated in the first electron beam irradiation step. In FIG. 11, the electron beam source 50A is arranged above the first drying container 28 in order to explain the change in the electron beam dose. As shown in FIG. 11, an electron beam is emitted from the electron beam source 50A, and the first lid body 26 is irradiated with an electron beam dose of 15 kGy. Thereby, the first lid body 26 is sterilized. Further, the electron beam emitted from the electron beam source 50A is shielded by the first lid 26, and the electron beam dose applied to the inside of the needle-like concave portion 15 is 1 kGy or less. That is, the first lid member 26 functions as a shield disposed at a position on a straight line connecting the electron beam source 50A and the needle-like recessed portion 15 . As a result, the dried first polymer solution 22 (intermediate, formulation) inside the needle-shaped concave portion 15 and the drug (raw material) contained in the first polymer solution 22 are adversely affected by the irradiation of the electron beam. can be suppressed.

Further, although not shown in FIG. 11, electron beams are emitted from the electron beam sources 50B and 50C, respectively, and the container body 24 is irradiated with an electron dose of 15 kGy. Thereby, the container body 24 is sterilized. Also, the electron beams emitted from the electron beam sources 50B and 50C are shielded by the container main body 24 . Therefore, the dose of electron beams emitted from the electron beam sources 50B and 50C and applied to the inside of the needle-like concave portion 15 is 1 kGy or less. That is, the container main body 24 functions as a shield disposed on a straight line connecting the electron beam sources 50B and 50C and the needle-like concave portion 15 . As a result, the influence of the electron beam on the first polymer solution 22 inside the needle-shaped concave portion 15 and the drug contained in the first polymer solution 22 can be suppressed.

In this case, a plurality of electron beam sources 50A, 50B, and 50C are used. The electron beam may be irradiated, or the direction of the first drying container 28 is changed with respect to one electron beam source 50 that irradiates the electron beam in one direction, and electrons are emitted from the first drying container 28 in a plurality of directions. A line may be emitted.

[First carrying-in step: step S22]
The first carrying-in step is a step of carrying the first drying container 28 sterilized after the first electron beam irradiation step into an aseptic environment. As shown in FIG. 7, the first drying container 28 is carried into the sterile room 40 . Since the surface of the first drying container 28 has been sterilized by the first electron beam irradiation process, even if the first drying container 28 is returned to the inside of the aseptic chamber 40, the aseptic environment inside the aseptic chamber 40 is maintained. be able to.

[First Unsealing Step: Step S24]
The first opening step is a step of opening the first lid body 26 of the first drying container 28 carried into the aseptic chamber 40 in the first carrying-in step. The mold 13 is housed in the first drying container 28 under an aseptic environment in the first housing step. Therefore, even in the subsequent first unloading process, first drying process, first electron beam irradiation process, and first transporting process, the inside of the first drying container 28 is kept sterile. Further, since the surface of the first drying container 28 is sterilized by the first electron beam irradiation step, even if the first lid body 26 of the first drying container 28 is opened by the first opening step, the surface is sterile. Aseptic conditions within the chamber 40 and the first drying container 28 can be maintained.

[First removal step: step S26]
The first removal step is a step of removing the mold 13 from the container body 24 of the first drying container 28 . Since the surface of the first drying container 28 is sterilized by the first electron beam irradiation process, the sterile environment inside the sterile room 40 can be maintained, and the mold 13 can be removed from the first drying container 28 to the sterile room 40 . The mold 13 can be kept aseptic even if it is taken out immediately.

[Second filling step: step S28]
The second filling step is a step of filling the needle-like concave portions 15 of the mold 13 with the second polymer solution 32 (base liquid). A layer (first layer) 30 containing a drug, which is a layer obtained by drying the first polymer solution 22 , is formed in the needle-like concave portion 15 of the mold 13 . A second polymer solution 32 is filled on the layer 30 containing the drug.

As a method of filling the second polymer solution 32, a method of applying with a dispenser can be applied. In addition to application by a dispenser, application by bar application, spin application, spray application, or the like can be applied.

[Second storage step: step S30]
The second housing step is a step of housing the mold 13 filled with the second polymer solution 32 in the second drying container 128 under an aseptic environment. As in the first housing step, the mold 13 after the second filling step is housed in the container body 24 through the opening 23 , and the opening 23 is closed with the second lid 126 . This makes the inside of the second drying container 128 an aseptic environment.

The second drying container 128 used in the second storage process is composed of the container body 24 used in the first storage process to the first carrying-in process and the second lid 126 . As shown in FIG. 9, the container body 24 has a first adhesive surface 25A and a second adhesive surface 25B on a flange 25 provided around the opening 23. As shown in FIG. In the second housing step, as shown in FIG. 12, it is connected to the second cover body 126 by the second adhesive surface 25B. As a result, the opening 23 is closed, and the inside of the second drying container 128 is brought into an aseptic environment. The region of the flange 25 where the first adhesive surface 25A is provided may be deformed in shape due to the peeling of the first lid body 26 in the first unsealing step. In that case, even if the first adhesive surface 25A is adhered to the second lid 126, it cannot be completely adhered, and adhesion to the second lid 126 that ensures impermeability to microorganisms may be difficult. . By bonding the second bonding surface 25B, it is possible to reliably seal.

By providing the container body 24 with different first adhesive surfaces 25A and second adhesive surfaces 25B for bonding the first lid 26 and the second lid 126, the container body 24 can be used repeatedly, It is possible to reduce the cost of manufacturing the percutaneous absorption sheet.

[Second Unloading Step: Step S32]
The second carrying-out step is, as shown in FIG. 7, a step of carrying out the second drying container 128 containing the mold 13 to the outside of the sterile room 40 (outside the sterile environment). Since the mold 13 is housed inside the sealed second drying container 128 in the second housing step, even if the second drying container 128 is carried out of the sterile room 40, the second drying container The second polymer solution 32 and the like inside 128 are not contaminated with bacteria and foreign substances.

[Second drying step: step S34]
The second drying step is a step of drying the second polymer solution 32 in the needle-like concave portions 15 of the mold 13 housed in the second drying container 128 outside the sterile environment. A 2nd drying process can be performed by the method similar to a 1st drying process. A percutaneous absorption sheet 36 composed of a drug-containing layer 30 and a drug-free layer (second layer) 34 is formed on the mold 13 after the second drying step (see FIG. 8).

It takes 7 to 8 hours to dry the second polymer solution 32, but by performing the second drying process outside the sterile room 40, the first filling process or the second filling process is performed inside the sterile room 40. be able to. Therefore, the next transdermal absorption sheet 1 can be manufactured without waiting for the end of the second drying step, and productivity can be improved.

In this way, the first drying process and the second drying process can be carried out to the outside of the sterile room 40 and performed outside the sterile environment. step) and storage step (first storage step and second storage step), and space for drying step (first drying step and second drying step) is unnecessary. Therefore, in the manufacturing facility, the sterile environment area such as the sterile room 40 can be narrowed, so that the cost of the manufacturing facility can be reduced.

[Cutting step: step S36]
The cutting step is a step of cutting the outer peripheral portion of the collar portion 25 of the second drying container 128 from the second adhesive surface 25B. As shown in FIG. 12, in the second housing step, the container main body 24 and the second lid body 126 are bonded together on the second bonding surface 25B. 25A), a region where the second lid body 126 and the flange portion 25 are not bonded is formed. As shown in FIG. 13, in the cutting step, by cutting the second lid body 126 and the collar portion 25 from above the second adhesive surface 25B, the area outside the second adhesive surface 25B can be cut. As a result, in the next second electron beam irradiation step, the blind spot where the electron beam is not irradiated, that is, the portion outside the second bonding surface 25B where the second cover 126 and the collar portion 25 are not bonded can be cut. can be done. Further, when adhesive residue is generated on the first adhesive surface 25A, which is the surface of the container body 24 to be adhered to the first lid 26, bacteria may adhere to the first adhesive surface 25A by carrying the container body 24 out of the aseptic environment. There is By cutting the flange portion 25 outside the second adhesive surface 25B in the cutting step, it is possible to remove bacteria adhering to the first adhesive surface 25A. The cutting step can be omitted if the entire surface of the second drying container 128 can be irradiated with an electron beam and the entire surface can be sterilized.

[Second electron beam irradiation step: step S38]
Returning to FIG. 8, the second electron beam irradiation step to the peeling step will be described. In the second electron beam irradiation step, before the second drying container 128 containing the mold 13 is carried into the sterile room 40 in the second carrying-in step of the next step, the surface of the second drying container 128 is In this step, the surface of the second drying container 128 is sterilized by irradiating electron beams from the electron beam source 50 toward the surface of the second drying container 128 . The second electron beam irradiation step can be performed by the same method as the first electron beam irradiation step.

Also, in the cutting step, by cutting the outer peripheral portion of the collar portion 25 of the second drying container 128, it is possible to eliminate blind spots where electron beams are not irradiated, and the entire surface can be reliably sterilized by electron beam irradiation. can.

[Second loading step: step S40]
The second carrying-in step is a step of carrying the second drying container 128 sterilized after the second electron beam irradiation step into an aseptic environment. As shown in FIG. 8, the second drying container 128 is carried into the sterile room 40 . Since the surface of the second drying container 128 has been sterilized by the second electron beam irradiation process, even if the second drying container 128 is returned to the inside of the aseptic chamber 40, the aseptic environment inside the aseptic chamber 40 is maintained. be able to.

[Second Unsealing Step: Step S42]
The second opening step is a step of opening the second lid 126 of the second drying container 128 carried into the sterile room 40 in the second carrying-in step. The mold 13 is housed in the second drying container 128 under an aseptic environment in the second housing step. Therefore, even in the subsequent second unloading process, second drying process, second electron beam irradiation process, and second transporting process, the inside of the second drying container 128 is kept sterile. In addition, since the surface of the second drying container 128 is sterilized by the second electron beam irradiation process, even if the second lid 126 of the second drying container 128 is opened by the second opening process, it is sterile. Aseptic conditions within chamber 40 and second drying container 128 can be maintained.

[Second removal step: step S44]
The second removal step is a step of removing the mold 13 from the container body 24 of the second drying container 128 . Since the surface of the second drying container 128 is sterilized by the second electron beam irradiation process, the sterile environment inside the sterile room 40 can be maintained, and the mold 13 can be removed from the second drying container 128 to the sterile room 40 . The mold 13 can be kept aseptic even after being taken out.

[Peeling process: step S46]
The peeling step is a step of peeling the transdermal absorption sheet 36 from the mold 13 . A peeling method is not particularly limited. It is desirable that the drug-containing layer 30 and the drug-free layer (second layer) 34 not bend or break during peeling. By performing the peeling process in the sterile room 40, foreign matter and bacteria can be prevented from adhering to the surface of the transdermal absorption sheet .

As shown in FIG. 8 by a cross-section MA of the mold 13 and the transdermal absorption sheet 36, the mold 13 removed from the second drying container 128 in the second removal step includes the drug-containing layer 30 and the drug-free layer 30. A transdermal absorption sheet 36 composed of a layer 34 is formed. For peeling of the transdermal absorption sheet 36 from the mold 13, as shown in the cross section MB, a substrate 38 is placed on the transdermal absorption sheet 36 with a sucker (not shown) and pulled up vertically while being sucked by air. can do. Peeling in this manner prevents the drug-containing layer 30 and the drug-free layer 34 from bending.

Section MC in FIG. 8 shows the transdermal absorption sheet 36 peeled from the mold 13 . The transdermal absorption sheet 36 is composed of a drug-containing layer 30 and a substantially drug-free layer 34 . The transdermal absorption sheet 36 corresponds to the transdermal absorption sheet 1 shown in FIG. The needle-shaped convex portion 10 is configured by a part of.

In the peeling step, in addition to the method of peeling the substrate by sucking it with air as described above, as shown in FIG. After the sheet-like substrate 38 on which the adhesive layer is formed is adhered, the substrate 38 can be peeled off from the edge by turning over.

As in the present embodiment, when a structure of needle-like projections with a high aspect ratio is separated from the mold 13, a large contact area causes strong stress. Needle-shaped protrusions 10 may be destroyed and remain in needle-shaped recesses 15 without being separated from mold 13, and the produced transdermal absorption sheet may have defects. In the present embodiment, it is preferable that the material forming the mold 13 is made of a material that is easily peeled off. In addition, by using a highly elastic and soft material for the mold 13, the stress applied to the needle-like protrusions 10 during peeling can be alleviated.

As described above, according to the method for manufacturing an aseptic product of the present embodiment, the container body 24 is repeatedly used in the second housing step even after the first lid body 26 is peeled off in the first opening step. can reduce the cost of the drying vessel. therefore. The cost of manufacturing sterile products can be reduced.

Although the method for producing a sterile product according to the present invention has been described above, the present invention is not limited to the above examples, and some improvements or modifications may be made without departing from the gist of the present invention. .

In the above-described embodiment, the container body 24 has two adhesive surfaces, the first adhesive surface 25A and the second adhesive surface 25B, on the collar portion 25. is not limited to Further, one or more bonding surfaces with the lid may be provided inside the second bonding surface 25B (around the opening 23 side). The number of times the container body 24 can be reused can be increased by providing a surface to be adhered to the lid.

In the sterile room 40 after the second extraction process, a packaging process can be performed in addition to the peeling process. By carrying out the packaging process in the sterile room 40, the transdermal absorption sheet can be prevented from being exposed to a non-sterile environment.

<Second embodiment>
In the first embodiment, the mold 13 is handled as it is, but a transfer jig for mounting the mold 13 may be used.

FIG. 15 is a perspective view of the transfer jig 60. FIG. 16 is a cross-sectional view taken along line 16-16 of FIG. 15. FIG. The transportation jig 60 is composed of a pedestal portion 62 and a cap portion 64 . The pedestal portion 62 and the cap portion 64 are each made of resin or metal.

The mold 13 is placed on the pedestal portion 62 . The first filling step (step S12) and the second filling step (step S28) can be performed with the mold 13 placed on the pedestal portion 62 .

The cap portion 64 is attached to the pedestal portion 62 and covers the upper surface of the needle-like concave portion 15 of the mold 13 . After the first filling step (step S12) and before the first storing step (step S14), and after the second filling step (step S28) and after the second storing step (step S30). ). With the cap portion 64 of the transfer jig 60 attached, the mold 13 is placed in the first drying container 28 and the second drying container 28 in the first housing step (step S14) and the second housing step (step S30). It is housed in the container 128 for use.

A plurality of through holes 66 (an example of communication paths) extending in the vertical direction are provided on the top surface of the cap portion 64 . The through-holes 66 serve as passages for water vapor during drying. By appropriately setting the size, number, arrangement, etc. of the through-holes 66 communicating with the cap portion 64, the drying time of the first polymer solution 22 in the first drying step (step S18) and the second drying step ( The drying time of the second polymer solution 32 in step S34) can be adjusted to an appropriate time.

The transfer jig 60 functions as an electron beam shield. Even if an electron dose of 15 kGy is irradiated from the side and bottom surfaces of the transfer jig 60, the electron dose irradiated to the inside of the needle-like concave portion 15 of the mounted mold 13 is 1 kGy or less.

17A and 17B are schematic diagrams showing electron beams irradiated in the first electron beam irradiation step when the transfer jig 60 is used. It should be noted that the second electron beam irradiation step can also be carried out using a transfer jig in the same manner. As shown in FIG. 17, in the first drying container 28, a plurality of molds 13 mounted on a conveying jig 60 are stored.

As shown in FIG. 17, an electron beam is emitted from the electron beam source 50A, and the first lid body 26 is irradiated with an electron beam dose of 15 kGy. This electron beam is shielded by the first lid 26 . Therefore, the dose of the electron beam emitted from the electron beam source 50A and applied to the inside of the needle-like concave portion 15 is 1 kGy or less. Also in the second electron beam irradiation step, the electron beam is similarly shielded by the second lid 126 .

<Third Embodiment>
FIG. 18 is a schematic diagram showing electron beams irradiated in the first electron beam irradiation step of the third embodiment. A plurality of molds 13 mounted on a transfer jig 60 are stored in the first drying container 28 shown in FIG. Also, one porous sheet 29 is provided between the first lid body 26 and the transportation jig 60 . The same configuration can be used in the second electron beam irradiation step.

As shown in FIG. 18, an electron beam is emitted from the electron beam source 50A, and the first lid body 26 is irradiated with an electron beam dose of 15 kGy. Thereby, the first lid body 26 is sterilized. If the electron beam cannot be sufficiently shielded by the first lid 26, the electron beam passing through the first lid 26 will pass through the through hole 66 extending in the vertical direction if there is no shield to shield the electron beam. and irradiates the needle-like concave portion 15 of the mold 13 . In the third embodiment, a porous sheet 29 is arranged as a shield at a position on a straight line connecting the first lid 26 and the needle-shaped concave portion 15 .

Even if the electron beam cannot be sufficiently shielded by the first lid 26 alone, the electron beam irradiated inside the needle-shaped concave portion 15 can be reduced to 1 kGy or less by further disposing the porous sheet 29. can be done. Thereby, the influence of the electron beam on the dried first polymer solution 22 inside the needle-shaped concave portion 15 and the drug contained in the first polymer solution 22 can be suppressed.

The porous sheet 29 may be placed on the mold 13 after the mold 13 is housed in the container body 24 through the opening 23 in the first housing step (step S14) and the second housing step (step S30). . When the transfer jig 60 is used, it may be placed on the transfer jig 60 . As a result, the porous sheet 29 placed on the needle-shaped concave portion 15 shields the electron beam passing through the first lid body 26 arranged on the upper surface of the first drying container 28 in the first electron beam irradiation step. can do.

Here, the porous sheet 29 is arranged as a shield, but any material that can shield the electron beam, such as a resin or metal plate or sheet, may be used. From the viewpoint of properly drying the first polymer solution 22, a porous material that does not hinder the evaporation of water is preferable, and a material with high gas permeability is preferable.

<Fourth Embodiment>
The transfer jig 60 shown in FIGS. 15 and 16 has a plurality of through holes 66 extending in the vertical direction on the top surface of the cap portion 64, so that it acts as a shield against electron beams irradiated from the top surface. It didn't work, but the following modifications are possible.

FIG. 19 is a diagram for explaining the transfer jig 68, and is a cross-sectional view similar to FIG. The through hole 66 is not provided in the cap portion 64 of the transfer jig 68 . For this reason, the cap part 64 functions as a shield against the electron beam irradiated from the upper surface, and even if the electron beam dose of 15 kGy is irradiated from the upper surface, the inside of the needle-shaped concave portion 15 of the mounted mold 13 is irradiated. The electron dose applied is 1 kGy or less. The same applies to the side surfaces and the bottom surface. By adopting a configuration in which the through holes 66 are not provided in this way, the transfer jig 68 can function as a shield.

FIG. 20 is a diagram for explaining the inside of the transfer jig 70, and is a cross-sectional view similar to FIG. The cap portion 64 of the transfer jig 70 is provided with a plurality of through holes 66 extending from the inside of the top surface of the cap portion 64 to the outside of the side surface. Therefore, the electron beam irradiated from the upper surface of the cap portion 64 can be shielded by the cap portion 64 and the electron beam does not directly enter the inside of the cap portion 64 . By arranging the through-holes 66 so as not to be parallel to the straight line connecting the electron beam source 50 and the needle-shaped concave portion 15, the transfer jig 70 can be made to function as a shield.

FIG. 21 is a diagram for explaining the inside of the transfer jig 72, and is a cross-sectional view similar to FIG. The cap portion 64 of the transfer jig 72 is provided with a plurality of through holes 66 extending horizontally from the inner side to the outer side of the cap portion 64 . Therefore, the electron beam irradiated from the upper surface of the cap portion 64 can be shielded by the cap portion 64 and the electron beam does not directly enter the inside of the cap portion 64 . By arranging the through-holes 66 so as not to be parallel to the straight line connecting the electron beam source 50 and the needle-shaped concave portion 15, the transfer jig 72 can function as a shield.

In the above-described embodiment, the mold 13 is used to produce the percutaneous absorption sheet 1 (36) having needle-like protrusions that are the inverted shape of the mold 13, but the present invention is not limited to this. The present invention can be applied when the first polymer solution and the second polymer solution are dried in an aseptic environment to produce an aseptic product. Examples of aseptic products include pharmaceuticals, quasi-drugs, cosmetics, and the like.

FIG. 22 is a flow chart of another method for manufacturing a sterile article of manufacture. As shown in FIG. 22, in the method for manufacturing a sterile product according to the modification, the first polymer solution is stored in the container body under a sterile environment, and the first adhesive surface provided around the opening of the container body is used. A first containing step (step S112), a first carrying-out step (step S114) of carrying out the first drying container after the first housing step to the outside of the sterile environment (step S114), and a first drying of drying the first polymer solution after the first carrying-out step. A step (step S116), a first electron beam irradiation step (step S118) of irradiating an electron beam from an electron beam source toward the surface of the first drying container after the first drying step, and a first electron beam irradiation step. A first carrying-in step (step S120) of carrying the subsequent first drying container into an aseptic environment, and a first opening step (step S120) of peeling off the first lid body after the first carrying-in step and opening the first drying container ( In step S122), the second polymer solution is housed in the container body under an aseptic environment, and the second lid body is adhered to the second adhesive surface provided around the opening of the container body and different from the first adhesive surface. a second housing step (step S124) of housing the second polymer solution in the second drying container composed of the container body and the second lid by covering the opening with the second lid; A second carrying-out step (step S126) of carrying out the second drying container after the process to the outside of the sterile environment, and a second carrying-out step of drying the second polymer solution stored in the second drying container after the second carrying-out step. a second drying step (step S128), a second electron beam irradiation step (step S130) of irradiating an electron beam from an electron beam source toward the surface of the second drying container after the second drying step, and a second electron beam A second carrying-in step (step S132) of carrying the second drying container after the irradiation step into an aseptic environment, and a second opening of peeling off the second lid after the second carrying-in step and opening the second drying container. and a step (step S134). In addition, when the first polymer solution and the second polymer solution are processed in the sterile room 40 after the first opening step and the second opening step, the first extraction step and the second extraction step may be performed. . Further, after the second drying step, a cutting step of cutting on the second adhesive surface may be performed before the second electron beam irradiation step. In the sterile room 40 after the second unsealing process, for example, a packaging process can be performed, and when the packaging process includes a filling process, for example, capping is performed.

Also, depending on the aseptic product to be manufactured, the first drying step and the second drying step can be freeze-drying. In the case of freeze-drying, the first drying container and the second drying container are made of a gas-impermeable material such as resin or metal, and the inside of the first drying container and the second drying container is evacuated. Provide a suction port for The suction port is provided with opening/closing means so as to maintain a sterile environment inside.

Freeze-drying first freezes the first polymer solution and the second polymer solution. Cooling for freezing can be performed outside the sterile room 40 because the interior of the first drying container and the second drying container is a sterile environment. Freeze-drying can be performed by a conventional method. For example, vacuum-drying is performed at a temperature lower than the melting point of the solvent while sucking from the suction port, and further vacuum-drying is performed at room temperature (20 ° C.) to perform freeze-drying. It can be carried out.

1, 36 Transdermal absorption sheet 2 Sheet part 10 Needle-like protrusion 11 Original plate 12 Shape part 13 Mold 15 Needle-like recess 22 First polymer solution 23 Opening 24 Container main body 26 First lid 28 First drying container 29 Porous sheet 30 Drug-containing layer 32 Second polymer solution 34 Drug-free layer 38 Substrate 40 Aseptic chambers 50, 50A, 50B, 50C Electron beam sources 60, 68, 70, 72 Transfer jig 62 Pedestal 64 Cap portion 66 Through hole 126 Second lid 128 Second drying container 130 Cutting means

Claims (11)

The first polymer solution is stored in the container body under a sterile environment, and the first lid body is adhered to the first adhesive surface provided around the opening of the container body, and the opening is attached to the first lid body. a first housing step of housing the first polymer solution in a first drying container composed of the container body and the first lid by covering with;
A first carrying-out step of carrying out the first drying container after the first storing step to the outside of the sterile environment;
a first drying step of drying the first polymer solution after the first carry-out step;
a first electron beam irradiation step of irradiating an electron beam from an electron beam source toward the surface of the first drying container after the first drying step;
a first carrying-in step of carrying the first drying container after the first electron beam irradiation step into an aseptic environment;
A first opening step of peeling off the first lid body after the first carrying-in step and opening the first drying container;
The second polymer solution is stored in the container body under a sterile environment, and a second lid is adhered to a second adhesive surface provided around the opening of the container body and different from the first adhesive surface, a second housing step of housing the second polymer solution in a second drying container composed of the container body and the second lid by covering the opening with the second lid;
A second carrying-out step of carrying out the second drying container after the second storing step to outside the sterile environment;
a second drying step of drying the second polymer solution stored in the second drying container after the second carrying-out step;
a second electron beam irradiation step of irradiating an electron beam from an electron beam source toward the surface of the second drying container after the second drying step;
a second carrying-in step of carrying the second drying container after the second electron beam irradiation step into an aseptic environment;
A second opening step of peeling off the second lid body after the second carrying-in step and opening the second drying container;
A method for producing a sterile product comprising: a first filling step of filling the needle-shaped recesses of a mold having needle-shaped recesses with a first polymer solution under an aseptic environment;
The mold after the first filling step is housed in a container body under an aseptic environment, a first lid body is adhered to the first adhesive surface provided around the opening of the container body, and the opening is a first housing step of housing the mold in a first drying container composed of the container body and the first lid by covering the mold with the first lid;
A first carrying-out step of carrying out the first drying container after the first storing step to the outside of the sterile environment;
a first drying step of drying the first polymer solution in the mold stored in the first drying container after the first carrying-out step to form a first layer;
a first electron beam irradiation step of irradiating an electron beam from an electron beam source toward the surface of the first drying container after the first drying step;
a first carrying-in step of carrying the first drying container after the first electron beam irradiation step into an aseptic environment;
A first opening step of peeling off the first lid body after the first carrying-in step and opening the first drying container;
a first removing step of removing the mold from the first drying container after the first opening step;
a second filling step of filling a second polymer solution onto the first layer formed in the needle-like concave portion of the mold after the first removing step in an aseptic environment;
The mold after the second filling step is housed in the container body under an aseptic environment, and a second lid body is provided around the opening of the container body with a second adhesive surface different from the first adhesive surface. and covering the opening with the second lid to store the mold in a second drying container composed of the container body and the second lid;
A second carrying-out step of carrying out the second drying container after the second storing step to outside the sterile environment;
a second drying step of drying the second polymer solution in the mold stored in the second drying container after the second carrying-out step to form a second layer;
a second electron beam irradiation step of irradiating an electron beam from an electron beam source toward the surface of the second drying container after the second drying step;
a second carrying-in step of carrying the second drying container after the second electron beam irradiation step into an aseptic environment;
A second opening step of peeling off the second lid body after the second carrying-in step and opening the second drying container;
a second removing step of removing the mold from the second drying container after the second opening step;
A method for producing a sterile product comprising: The container body has a collar around the opening,
The second adhesive surface is provided on the opening side of the collar, and the first adhesive surface is provided outside the second adhesive surface.
A method for producing a sterile product according to claim 1 or 2. After the second drying step and before the second electron beam irradiation step, a cutting step of cutting the container body and the second lid of the second drying container on the second adhesive surface,
A method for producing a sterile product according to any one of claims 1-3. wherein the first lid and the second lid are made of a material impermeable to microorganisms and gas permeable;
A method for producing a sterile product according to any one of claims 1-4. The bonding between the first lid and the first bonding surface and the bonding between the second lid and the second bonding surface are performed by heat sealing.
A method for producing a sterile product according to any one of claims 1-5. The container body further has one or more adhesive surfaces around the opening that adhere to the lid,
A method for producing a sterile product according to any one of claims 1-6. The voltage of the electron beam source is 200 kV or less,
A method for producing a sterile product according to any one of claims 1-7. wherein the first polymer solution contains a drug;
A method for producing a sterile product according to any one of claims 1-8. The sterile product is a transdermal absorption sheet,
A method for producing a sterile product according to any one of claims 1-9. The sterile product is a drug, quasi-drug, or cosmetic,
A method for producing a sterile product according to any one of claims 1-10.

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