Patent Application
20200094034
The present application claims priority under 35 U.S.C § 119 to Japanese Patent Application No. 2018-180248 filed on Sep. 26, 2018, which is hereby expressly incorporated by reference, in its entirety, into the present application.
The present invention relates to a method for producing a transdermal absorption sheet and particularly to a technique for supplying a liquid material for a transdermal absorption sheet.
As a method for administering a drug or the like through a living body surface, that is, a skin or mucous membrane, a method in which a chemical is injected by using a transdermal absorption sheet on which microneedles (needle-like protruding portions) having a high aspect ratio and containing a drug are formed, and inserting the needle-like protruding portions into the skin has been used.
As a method for producing a transdermal absorption sheet, a method is known in which a polymer solution or the like is poured into a mold in which needle-like recessed portions that are inverted shapes of needle-like protruding portions are formed, to transfer the shapes. In this case, it is required that the liquid material is supplied, held and dried in a state in which a predetermined pattern shape is applied to the mold (so-called patch shape). On the other hand, considering shape transfer, a material having peelability is often used as a material for constituting the mold, and the mold inevitably has water repellency in many cases. By simply applying or drawing the liquid material to the mold having water repellency, a transdermal absorption sheet cannot be formed since the liquid material shrinks and is repelled. Various proposals are made to address this problem.
For example, JP2016-168325A discloses a method for producing a transdermal absorption sheet by supplying and drying a polymer layer forming liquid using a mold including a step portion around the region in which needle-like recessed portions are formed. In addition, JP2016-106676A discloses a method for producing a needle-like body by supplying a needle-like body forming aqueous solution to an intaglio plate, and drying and peeling off the solution.
However, in a case where a liquid material is supplied into a mold having a step portion, bubbles may be entrained in the step portion. In a case where the bubbles rise in the liquid material and diffuse from the liquid material into the atmosphere, the liquid material is repelled and there arises a problem that a transdermal absorption sheet is not formed.
The present invention is made in consideration of these circumstances, and an object thereof is to provide a method for producing a transdermal absorption sheet capable of supplying a liquid material into a mold having a step portion while suppressing the entrainment of bubbles.
A method for producing a transdermal absorption sheet according to a first aspect of the present invention comprises: a step of preparing a mold having a plurality of needle-like recessed portions, and a step portion which surrounds the plurality of needle-like recessed portions and is higher than a needle-like recessed portion formed surface; and a step of supplying a liquid material for a transdermal absorption sheet from a jetting opening of a filling head to a region surrounded the step portion of the mold, in which the filling head includes a head main body having an inner wall surface defining a supply pipe, and the inner wall surface includes a tapered pipe surface defining a tapered pipe having a diameter gradually increased toward the jetting opening of the head main body.
According to the first aspect, it is possible to suppress the entrainment of bubbles in the liquid material.
In the method for producing a transdermal absorption sheet according to a second aspect of the present invention, a diameter of a tip end of the head main body is smaller than an inner diameter of the step portion. According to the second aspect, even in a case where the filling head and the mold are separated from each other, it is possible to fix the liquid material in the step portion.
In the method for producing a transdermal absorption sheet according to a third aspect of the present invention, in the step of the supplying, a supply end position of the liquid material from the filling head is further separated from the mold than a supply start position of the liquid material from the filling head. According to the third aspect, even in a case where the filling head and the mold are misaligned, it is possible to fix the liquid material in the step portion.
In the method for producing a transdermal absorption sheet according to a fourth aspect of the present invention, while the filling head is moved from the start position to the end position, the liquid material is continuously supplied. According to the fourth aspect, it is possible to continuously supply the liquid material.
In the method for producing a transdermal absorption sheet according to a fifth aspect of the present invention, while the filling head is moved from the start position to the end position, the liquid material is intermittently supplied. According to the fifth aspect, it is possible to intermittently supply the liquid material.
In the method for producing a transdermal absorption sheet according to a sixth aspect of the present invention, the head main body has a tapered surface having a diameter gradually decreased toward a tip end of the head main body. According to the sixth aspect, even in a case where the filling head and the mold are misaligned, it is possible to allow the liquid material to reach the step portion.
The method for producing a transdermal absorption sheet according to a seventh aspect of the present invention further comprises: a step of performing suction from a surface of the mold opposite to the needle-like recessed portion formed surface. According to the seventh aspect, it is possible to fill the needle-like recessed portions with the liquid material.
The method for producing a transdermal absorption sheet according to an eighth aspect of the present invention further comprises: a step of forming a transdermal absorption sheet by drying the liquid material and separating the formed transdermal absorption sheet from the mold after the step of the supplying. According to the eighth aspect, it is possible to form a transdermal absorption sheet.
In the method for producing a transdermal absorption sheet according to a ninth aspect of the present invention, the liquid material is a polymer solution. According to the ninth aspect, it is possible to apply the polymer solution as the liquid material for a transdermal absorption sheet.
The method for producing a transdermal absorption sheet according to a tenth aspect of the present invention further comprises: a step of forming a drug layer including a drug at a tip end of the needle-like recessed portion before the step of the supplying. According to the tenth aspect, it is possible to produce a transdermal absorption sheet having a two-layer structure.
In the method for producing a transdermal absorption sheet according to an eleventh aspect of the present invention, the mold is formed of silicone resin. According to the eleventh aspect, the silicone resin is durable against transfer by repeated pressurizing and has good peelability.
In the method for producing a transdermal absorption sheet according to a twelfth aspect of the present invention, the step portion circumferentially surrounds the plurality of needle-like recessed portions, and the head main body is cylindrical. According to the twelfth aspect, it is possible to stably fix the liquid material in the circumferential step portion. The cylindrical head main body makes it easy to spread the liquid material concentrically.
According to the aspects of the present invention, it is possible to suppress the entrainment of bubbles in the liquid material.
Hereinafter, preferable embodiments of the present invention is described below in accordance with the accompanying drawings. The present invention is described using the following preferable embodiments. However, many techniques may be used to vary the embodiments without departing from the scope of the present invention, and embodiments other than the present embodiments may be used. Thus, all the variations within the scope of the present invention are included in the claims.
In the drawings, components designated by the same reference numeral are similar components with similar functions. In addition, in the present specification, in a case where a numerical range is described using “to”, numerical values for an upper limit and a lower limit illustrated with “to” are also included in the numerical range.
Transdermal Absorption Sheet
An example of a transdermal absorption sheet (microneedle array) will be described.
The sheet-like shape means a flat shape as a whole, which is thinner than the two facing first surface 102A and second surface 102B having a large area, and the first surface 102A and the second surface 102B do not have to be completely flat. In addition, the base 102 shown in
The protruding pattern 110 is constituted of a plurality of needle-like protruding portions 112 constituted to include a drug. The needle-like protruding portions 112 are provided on the first surface 102 A. The needle-like protruding portion 112 includes a needle portion 114 and a frustum portion 116 connecting the needle portion 114 and the base 102.
On the first surface 102A of the transdermal absorption sheet 100, a plurality of the frustum portions 116 are arranged. The frustum portion 116 has two bottoms and has a three-dimensional structure surrounded by a pyramidal surface. A bottom having a wide area (lower bottom) of the two bottoms of the frustum portion 116 is connected to the base 102. A bottom having a narrow area (upper bottom) of the two bottoms of the frustum portion 116 is connected to the needle portion 114. Out of the two bottoms of the frustum portion 116, the area of the bottom in the direction away from the base 102 is small.
The needle portion 114 has a bottom having a wide area and has a shape in which the tip end distant from the bottom has the narrowest area. Since the bottom having a wide area of the needle portion 114 is connected to the upper bottom of the frustum portion 116, the needle portion 114 has a shape tapered in a direction away from frustum portion 116. The needle-like protruding portion 112 constituted of the needle portion 114 and the frustum portion 116 has a tapered shape from the base 102 toward the tip end as a whole. A plurality of the needle-like protruding portions 112 of 4 to 2500 are provided on the base 102. However, the embodiment is not limited to this number.
In
Mold
The recessed pattern 130 is constituted of a plurality of needle-like recessed portions 132 provided on the flat portion 122. The needle-like recessed portion 132 has a shape corresponding to the needle-like protruding portion 112 of the transdermal absorption sheet 100 and is constituted of a tip end recessed portion 134 corresponding to the needle portion 114 and a cup portion 136 corresponding to the frustum portion 116.
The tip end recessed portion 134 has a shape tapered in the depth direction (thickness direction) of the mold 120. The tip end recessed portion 134 can be formed to have a diameter of 150 μm to 500 μm and a height of 150 μm to 2000 μm. In addition, the cup portion 136 has an opening on the side of the first surface 120A of the mold 120 and has a shape that narrows in the depth direction toward the second surface 120B of the mold 120. The cup portion 136 is connected to the tip end recessed portion 134 at the narrowest portion. The cup portion 136 can be formed to have a diameter of 500 μm to 1000 μm and a height of 100 μm to 500 μm.
The shape of the needle-like recessed portion 132 is not limited to this example. Between the tip end recessed portion 134 and the cup portion 136, an intermediate recessed portion having a constant width in the depth direction, such as a column, a square pole, or a polygonal pole, may be provided. In addition, a through-hole passing through the mold 120 and reaching the second surface 120B may be formed at the tip end of the tapered shape. The arrangement, pitch, number, and the like of the needle-like recessed portions 132 are determined according to the arrangement, pitch, number, and the like of the needle-like protruding portions 112 required for the transdermal absorption sheet 100.
The flat portion 122, which is a needle-like recessed portion formed surface, has a flat or substantially flat shape corresponding to the base 102 of the transdermal absorption sheet 100. The step portion 124 circumferentially surrounds the recessed pattern 130 and is higher than the flat portion 122. The term “higher than the flat portion 122” means that the distance from the second surface to the step portion 124 is larger than the distance from the second surface 120B to the flat portion 122 using the second surface 120B as the reference. Since the second surface 120B is flat, the distance to the top portion of the step portion 124 is larger than the distance to the flat portion 122 using the second surface 120B as the reference. A difference between the two distances is a height H. The width W of the step portion 124 in the radial direction of the mold 120 is preferably 1.5 mm or more. In the embodiment, the case where the step portion 124 circumferentially surrounds the recessed pattern 130 is shown, but the shape of the step portion 124 is not particularly limited. For example, the step portion 124 may surround the recessed pattern 130 in a polygonal shape, or the step portion 124 may surround the recessed pattern 130 in a curved form with multiple curvatures. The shape of the step portion 124 is determined in consideration of the amount of liquid material, the physical properties (surface tension, viscosity, and wettability with respect to the mold), and the like. In a case where the step portion 124 is circular, the liquid material is fixed at the same strength all around the step portion 124 and thus the liquid material can be stably fixed. For example, in a case where the step portion 124 is rectangular or the step portion 124 has a curvature higher than the other portions, the fixation between the liquid material and the step portion 124 is weakened. There is a concern that the movement of the contact line described later may occur at the weakly fixed portion.
In the embodiment, since the angle formed by the flat portion 122 and the step portion 124 is 90 degrees, an inner diameter ID of the step portion 124 matches the diameter of the flat portion 122.
The material used for the mold 120 is preferably a material having flexibility and more preferably a material having high gas permeability. The oxygen permeability, which is representative of gas permeability, is preferably more than 1×10−12 (mL/s·m·Pa) and even more preferably more than 1×10−10 (mL/s·m·Pa). By producing the mold 120 using a material with high gas permeability, the liquid material filled in the needle-like recessed portion 132 can be sucked by suction from the second surface 120 B of the mold 120, and the filling into the needle-like recessed portion 132 can be promoted. In addition, the air present in the needle-like recessed portion 132 can be removed from the second surface 120B side. Thus, it is possible to produce the transdermal absorption sheet 100 with few defects.
Specifically, examples of such materials include materials obtained by melting a silicone resin (for example, SYLGARD 184 (registered trademark) manufactured by Dow Corning Toray Co., Ltd. or 1310ST manufactured by Shin-Etsu Chemical Co., Ltd.), an ultraviolet curable resin, a polystyrene resin, a polymethylmethacrylate resin, an epoxy resin, a polyethylene terephthalate resin, a polyoxymethylene resin, a polytetrafluoroethylene resin, a polyethylene resin, a phenolic resin, and a urethane resin, and materials obtained by dissolving any of above resins into a solvent.
Among these, the silicone resin is durable against transfer by repeated pressurizing and has good peelability from the material. The silicone resin can be suitably used as the material for the mold 120.
A method of producing a transdermal absorption sheet according to a first embodiment will be described with reference to the drawings.
The term “constant inner diameter” includes a case where the inner diameter is completely constant and a case where the inner diameter is substantially constant. The inner diameter, the length, and the like of the cylindrical pipe 154A are appropriately determined. Therefore, the term “cylindrical” includes being perfectly cylindrical and being substantially cylindrical. Although the cylindrical filling head 150 is shown in the embodiment, the shape of the filling head 150 is not particularly limited.
As shown in
The supply of the liquid material 170 for a transdermal absorption sheet is started. The liquid material 170 which has passed through the cylindrical pipe 154A is supplied from the jetting opening 156 of the filling head 150 to the region surrounded by the step portion 124 of the mold 120. In a case where the center of the filling head 150 matches with the center of the mold 120, the liquid material 170 is supplied to the center of the mold 120. As shown in
As shown in
As shown in
As shown in
As shown in
The filling head 150 and the mold 120 at the end position where the supply of the liquid material 170 is ended are relatively separated from each other. The liquid material 170 is transferred to the mold 120. In the first embodiment, the start position and the end position are the same.
Regarding a taper angle α of the filling head 150, as shown in
As shown in
In order to fill the needle-like recessed portions 132 constituting the recessed pattern 130 with the liquid material 170, it is preferable to perform suction from the second surface 120B, which is the surface of the mold 120 opposite to the flat portion 122.
As shown in
As shown in
In the embodiment, the case where the liquid material 170 is supplied to the region surrounded by the step portion 124 of the mold 120, the needle-like recessed portions 132 of the receded pattern 130 are filled with the liquid material, and the liquid material is dried to form the transdermal absorption sheet 100 is described, but the embodiment is not limited thereto.
For example, a drug layer can be formed on the tip end side of each of the needle-like recessed portions 132 of the recessed pattern 130 before the liquid material 170 is supplied. After the drug layer is formed, a transdermal absorption sheet 100 having a two-layer structure can be produced by supplying the liquid material 170 not including a drug. The solidified drug layer can suppress diffusion of the drug layer into the liquid material 170.
As the liquid material 170, a polymer solution is preferable. It is preferable to use a water-soluble material as the material of the polymer solution. As the material of a resin polymer of the polymer solution, it is preferable to use a biocompatible resin. As such a resin, it is preferable to use saccharides such as glucose, maltose, pullulan, sodium chondroitin sulfate, sodium hyaluronate, and hydroxyethyl starch, proteins such as gelatin, or a biodegradable polymer such as polylactic acid or a lactic acid-glycolic acid copolymer. In a case where the transdermal absorption sheet 100 is separated from the mold 120, since the transdermal absorption sheet 100 can be released using a base material (not shown), these materials can be suitably used. Although the concentration varies depending on the material, the concentration of the resin polymer in the polymer solution not including a drug is preferably 10% by mass or more and 50% by mass or less. In addition, a solvent used for the polymer solution may be other than hot water as long as the solvent has volatility, and alcohols such as ethanol can be used.
The above-mentioned polymer solution including a predetermined amount of drug can be applied as a liquid material for forming a drug layer. Whether or not a predetermined amount of drug is included is determined by whether or not the drug effect can be exerted in a case where the body surface is punctured. Therefore, including a predetermined amount of drug means including the drug in an amount that exerts a medicinal effect in a case where the body surface is punctured.
The drug is not limited as long as the drug accomplishes the functions of the drug. Particularly, the drug is preferably selected from peptide, protein, nucleic acid, polysaccharide, a vaccine, a medical compound belonging to a water-soluble low-molecular-weight compound, or a cosmetic component.
As the method for preparing the polymer solution, in a case of using a water-soluble polymer (such as gelatin), a water-soluble powder may be dissolved into water, and after the dissolution, a drug may be added to the solution or a water-soluble polymer powder may be poured and dissolved in a liquid containing a drug dissolved therein. In a case where the polymer is difficult to dissolve into water, the polymer may be dissolved by heating. The temperature may be selected, as appropriate, depending on the kind of the polymer material, but the solution is preferably heated to a temperature of about 20° C. or higher and 40° C. or lower as required. The viscosity of the polymer solution is preferably 200 mPa·s or less, and more preferably 50 mPa·s or less for the polymer solution including a drug. The viscosity of the polymer solution is preferably 2000 mPa·s or less and more preferably 500 mPa·s or less for the solution not including a drug. Appropriate adjustment of the viscosity of the polymer solution facilitates injection of the polymer solution into the recessed pattern 130 of the mold 120 (refer to
A method of producing a transdermal absorption sheet according to a second embodiment will be described with reference to
As shown in
The filling head 200 includes a head main body 202 as the filling head 150. The head main body 202 includes a jetting opening 204, and an inner wall surface 208 that defines a supply pipe 206. The supply pipe 206 includes a cylindrical pipe 206A, and a tapered pipe 206B. The inner wall surface 208 has a cylindrical pipe surface 208A that defines the cylindrical pipe 206A and a tapered pipe surface 208B that defines the tapered pipe 206B.
In the second embodiment, as shown in
As shown in
In a case where the supply of the liquid material 170 is ended, the filling head 200 and mold 120 are relatively separated from each other. The liquid material 170 is transferred to the mold 120. As shown in
In a case where the outer diameter of the head main body 202 of the filling head 200 is extremely smaller than the inner diameter of the step portion 124, there is a concern that the liquid material 170 may not reach the step portion 124 simultaneously. Therefore, it is preferable to make the filling head 200 small enough to allow the liquid material 170 supplied from the filling head 200 to sufficiently reach the step portion 124 in consideration of the error of each dimension and the operation error.
Next, a modified example of the second embodiment will be described.
The liquid material 170 is gathered on the side with a large gap between the filling head 200 and the step portion 124. On the side with a small gap between the filling head 200 and the step portion 124, the amount of the liquid material 170 is small and thin. In a case where the supply of the liquid material 170 is ended and the filling head 150 and the mold 120 are relatively separated from each other in this state, there is a concern that the liquid material 170 may not be fixed at the corner portion 124A of the step portion 124.
Therefore, as shown in
In the state shown in
The liquid material 170 can be supplied to the mold 120 continuously while the filling head 200 is moved from the start position to the end position. The supply of the liquid material 170 is not interrupted until the filling head 200 reaches the end position from the start position. In a case of supplying the liquid material 170 continuously, the supply rate from the start position to the end position may or may not be constant. The supply of the liquid material 170 is ended at the end position.
In addition, while the filling head 200 is moved from the start position to the end position, the liquid material 170 can be supplied to the mold 120 intermittently. The interruption of the supply of the liquid material 170 is allowed until the filling head 200 reaches the end position from the start position. For example, the liquid material 170 is supplied from the filling head 200 at the start position by a predetermined amount. The supply of the liquid material 170 is interrupted and the filling head 200 is moved to the end position. The liquid material 170 is supplied from the filling head 200 at the end position by a predetermined amount. The supply of the liquid material 170 is ended at the end position.
In a case where the supply of the liquid material 170 is ended, the filling head 200 and the mold 120 are relatively moved from each other. The liquid material 170 is transferred to the mold. The liquid material 170 is fixed at the corner portion 124A of the step portion 124. In the second embodiment, it is preferable that the shape of the step portion 124 surrounding the recessed pattern 130 and the outer shape of the filling head 200 are similar. The similar shape facilitates the liquid material 170 to reach the step portion 124 simultaneously or nearly simultaneously.
As in the first embodiment, by drying the liquid material 170, the transdermal absorption sheet 100 is formed, and the transdermal absorption sheet 100 is separated from the mold 120.
The modified example can be applied to the case where the filling head 150 of the first embodiment is used.
A method of producing a transdermal absorption sheet according to a third embodiment will be described with reference to
As shown in
As in the first embodiment, by drying the liquid material 170, the transdermal absorption sheet 100 is formed, and the transdermal absorption sheet 100 is separated from the mold 120.
In addition, the modified example (in which the start position and the end position different are different) of the second embodiment can be applied to a case where the filling head 300 of the third embodiment is used.
Hereinafter, the present invention will be more specifically described using examples of the present invention. The materials, used amounts, ratios, treatment contents, treatment procedures, and the like shown in the following examples can be appropriately changed without departing from the gist of the present invention. Therefore, the scope of the present invention should not be interpreted in a limited manner based on the specific examples illustrated below.
Preparation of Mold
A precursor for preparing a mold was prepared. The precursor was prepared by, on the surface of a smooth Ni plate having a side of 40 mm, forming protruding portions having a needle-like structure, two-dimensionally arranged in 10 columns×10 rows, by grinding, and further, forming a cylinder shape having a height of 500 μm, centered on the middle of a two-dimensional array of 10 columns×10 rows, by cutting. The protruding portion having a needle-like structure includes a truncated cone shape and a cone formed in the truncated cone shape. The diameter of the bottom of the truncated cone shape was 500 μm and the height of the truncated cone shape was 150 μm. The height of the cone was 500 μm. The pitch of the two-dimensionally arranged protruding portions having a needle-like structure was 1000 μm.
Three kinds of precursors with different diameters of cylindrical shapes were prepared. The diameter of the cylindrical shape of each precursor is 12 mm, 16 mm, and 20 mm.
On each precursor, a film of silicone rubber (SILASTIC-MDX4-4210, manufactured by Dow Corning Corporation) having a thickness of 0.6 mm was formed, thermally cured, and peeled off. At the center portion of the silicone rubber (the inverted article of the precursor), the protruding portions having a needle-like structure, two-dimensionally arranged in 10 columns×10 rows, were formed. The silicone rubber was cut off to leave a planar surface with a side of 30 mm and the obtained portion was used as a mold. A surface of the mold corresponding to the wider opening of each of the needle-like protruding portions was the first surface of the mold, and the surface of the mold opposite to the first surface was the second surface.
In each mold, step portions each having inner diameters of 12 mm, 16 mm, and 20 mm corresponding to the cylindrical shape of the precursors was formed. The height of the step portion was 500 μm (0.5 mm).
Preparation of Polymer Solution
A polymer solution was prepared as a liquid material. A solution obtained by dissolving chondroitin sulfate (manufactured by Maruha Nichiro Foods Co., Ltd.) in water and adjusting the concentration to 40% was used as a liquid material for producing a transdermal absorption sheet. After preparation, the polymer solution was exposed to a reduced pressure environment of 3 kPa for 4 minutes to perform sufficient degassing.
Hereinafter, all the preparation steps of the transdermal absorption sheet were performed under the environment of a temperature of 5° C. and a relative humidity of 35% RH.
Supply and Drying of Polymer Solution
The polymer solution was sent by a dispenser (manufactured by Musashi Engineering, Inc.) while adjusting the jetting amount of the polymer solution and the clearance between the mold and the filling head. The polymer solution was supplied to the mold. Thereafter, it was confirmed whether or not the shape of the transdermal absorption sheet was maintained after 12 hours had passed. The evaluation was performed based on the following standards. In addition, the operation of the filling head for liquid supply was performed using a bench-top robot manufactured by Musashi Engineering, Inc.
Experiment 1
As filling heads used for supply, three kinds of filling heads having tip end outer circumferential diameters of 13 mm, 17 mm, and 21 mm each of which are 1 mm larger than the inner diameter of the step portion of each mold were prepared. Each filling head has a tapered pipe surface (tapered structure). The opening diameter (taper opening diameter) of the tapered pipe of each filling head was 11 mm, 15 mm, and 19 mm each of which are 1 mm smaller than the inner diameter of the step portion of each mold. The depth of the tapered pipe was 0.5 mm. The diameter of the cylindrical pipe of each filling head was 5 mm. The filling head was formed of fluorocarbon resin.
The distance between the filling head and the flat portion (needle-like recessed portion formed surface) of the mold was set to 0.5 mm, and was used as the start position. The filling head is moved to the start position. The supply of the polymer solution was started from the filling head. The amount of the polymer solution supplied was such an amount that the step portion was filled with the polymer solution and the amount slightly exceeded the height of the step portion. The filling head was not moved until the supply of the polymer solution was ended. The start position and the end position were not changed.
As a comparative example, a filling head having three kinds of outer circumferential diameters not having a tapered pipe surface was prepared. Only the cylindrical pipe was provided in the filling head of the comparative example.
The evaluation was performed 20 times for each combination of the filling head and the mold, and the number of times of entrainment of bubbles immediately after the supply of the polymer solution was counted. Table 1 shows the conditions and the evaluation results.
According to Test Nos. 2, 4, and 6 in Table 1, it can be understood that in a case where the polymer solution is supplied from the filling head having a tapered structure to the mold with a step portion, the number of times of entrainment of bubbles is reduced and the polymer solution can be pinned. On the other hand, according to Test Nos. 1, 3, and 5 in Table 1, in the filing head not having a tapered structure, the number of times of entrainment of bubbles was large.
Experiment 2
In Experiment 1, it was possible to reduce the entrainment of bubbles by the filling head having a tapered structure. On the other hand, in a case where the filling head and the mold are relatively separated from each other after the supply of the polymer solution is ended, the polymer solution fixed at the corner portion of the step portion is drawn to the filling head. The polymer solution may not be fixed to the step portion and the contact line of the air-liquid interface may be moved to the middle of the step portion or to the flat portion of the mold.
In Experiment 2, in order to handle the above case, a mold with a step portion having an inner diameter of 16 mm and two kinds of filling heads having an outer circumferential diameter (outer diameter) of 15 mm and 14 mm were prepared. As in Experiment 1, it was visually confirmed whether or not the number of time of the entrainment of bubbles and movement of the contact line of the air-liquid interface of the polymer solution occurred. The evaluation was performed in the same manner as in Experiment 1 in a state after 20 trials were conducted. Table 2 shows the conditions and the evaluation results.
According to Test No. 7, in the filling head in which the outer circumferential diameter the filling head is larger than the inner diameter of the step portion and a tapered structure is provided, the number of times of entrainment of bubbles is small. On the other hand, in a case where the filling head is separated from the mold, the movement of the contact line of the air-liquid interface was observed. In 7 portions of 15 portions in which the movement was observed, as time had passed, the contact line was moved to the flat portion of the mold and a transdermal absorption sheet could not be formed.
According to Test Nos. 8 and 9, the number of times of entrainment of bubbles was small and the number of times the movement of the contact line was observed was small. Thus, a transdermal absorption sheet could be stably formed.
Experiment 3 In Experiment 2, in a case where the number of trials was increased more than 20 times, even in a case where the outer circumferential diameter (outside diameter) of the filling head was smaller than the inner diameter of the step portion of the mold, the movement of the contact line was observed.
In observation, in a case where the center position of the mold step and the center position of the filling head were largely misaligned, the step portion of the mold was in contact with the tip end of the filling head. The contact causes an insufficient supply of polymer solution. After the end of the supply of the polymer solution, the polymer solution was thin at the contact position.
In Experiment 3, in order to handle the above case, the supply start position of the filling head and the supply end position of the filling head were changed. At the start position, half of the total supply amount from the filling head was supplied to the mold and the supply was interrupted. The filling nozzle was separated (pulled up) from 0.3 mm mold at 5 mm/s. This position was set as the end position and half of the total supply amount from the filling head was supplied to the mold.
In Experiment 2, the gap between the step portion and the filling head was large on the opposite side of the contact position while sandwiching the center position of the step portion therebetween. This gap made it difficult for the polymer solution to reach the step portion and thus the entrainment of bubbles was caused.
In Experiment 3, in order to handle the above case, a tapered surface with a taper angle of 45° was provided on the outer circumferential portion of the tip end of the filling head so as to gradually reduce the diameter toward the tip. The outer diameter of the tip end of the tapered surface of the filling head was smaller than the inner diameter of the step portion, and the outer diameter of the filling head excluding the tapered surface was larger than the inner diameter of the step portion. The attempt was made to make the polymer solution to easily reach the step portion.
In the experiment, from a state in which the center position of the step of the mold matched with the center position of the filling head visually, the setting of the bench-top robot was adjusted, the positions were forced to be misaligned by 0.5 mm, and the polymer solution was supplied 10 times. Table 3 shows the conditions and the evaluation results.
According to Test 10, the entrainment of bubbles and the movement of the contact line were observed. According to Test 11, even in a state in which the step portion was in contact with the filling head, by supplying the polymer solution by pulling up the filling head, the movement of the contact line of the polymer solution could be prevented.
According to Test 12, even in a state in which the filling head and the step portion were separated from each other, the tapered surface provided at the tip end of the filling head caused the polymer solution to flow until the solution reached to the step portion. In a state in which the entrainment of bubbles did not occur, and in a state in which the movement of the contact line did not occur, a transdermal absorption sheet could be formed.
According to Test 13, the entrainment of bubbles did not occur. On the other hand, the movement of the contact line was observed. According to Experiment 3, it can be assumed that the tapered structure and the tapered surface of the filling head reduce the number of times of the entrainment of bubbles and the pulling up of the filling head reduces the movement of the contact line.
Others
The technical scope of the present invention is not limited to the scope described in the above embodiments. The configuration and the like in each embodiment can be appropriately combined in the embodiments without departing from the spirit of the present invention.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2018-180248 | Sep 2018 | JP | national |
