JP2009233808A - Hollow needle sheet and manufacturing method for the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a manufacturing method for a hollow needle sheet forming hollow needles simply and highly accurately, and also to provide the hollow needle sheet manufactured by the manufacturing method. <P>SOLUTION: After a polymer solution 20 containing a polymer is injected into a mold 10 which has needle-like recessed portions 12, the polymer solution 20 is desiccated. At this point, the polymer solution 20 is desiccated and contracted while maintaining a state in which the polymer solution 20 is closely attached to a recessed wall surface 14 of the mold 10. This enables a polymer sheet 22 formed with hollow needle-like protruded portions 24. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a hollow needle sheet having a hollow needle having a high aspect ratio structure and a method for producing the same.

  In recent years, functional films having a high aspect ratio structure formed on the surface have been applied in various fields. For example, in the medical technology field, a percutaneous absorption system that efficiently administers a drug to a patient via the patient's skin surface or skin stratum corneum by using a functional membrane having a high aspect ratio structure attracts attention. ing.

  Solid structures and hollow structures with various external shapes such as a needle shape, a tip knife shape, and an arrowhead shape have been proposed as a high aspect ratio structure for a transdermal absorption system. Among these, a hollow needle structure having a hollow needle shape is useful in that the percutaneous absorption efficiency can be improved by encapsulating the drug in the hollow part.

  For example, Patent Document 1 discloses a technique in which a hollow needle having a through-hole communicating with a hollow portion formed at the tip is immersed in a solution containing a drug, and the drug is filled into the hollow part through the through-hole by a capillary phenomenon. Is disclosed.

Patent Document 2 discloses a technique for forming a hollow needle having a capillary cavity by injection molding a saccharide material using a needle-shaped concave mold.
JP-T-2004-504120 JP 2003-238347 A

  However, Patent Document 1 does not disclose a specific method for forming a hollow needle having a hollow inside.

  Moreover, when forming a hollow needle by injection molding like patent document 2, after inject | pouring molten resin into a mold, the gas assist method which inject | pours inert gas and forms hollow is used. However, since the shape of the hollow needle is a high aspect ratio structure having a sharp tip, it is difficult to form a hollow needle having a high hollow ratio with high accuracy by the gas assist method.

  This invention is made | formed in view of such a situation, and relates to the manufacturing method of the hollow needle sheet which can form a hollow needle easily and with high precision, and the hollow needle sheet manufactured by the said manufacturing method.

  In the invention according to claim 1, the application step of applying a polymer solution to the mold having a needle-like concave portion, and the polymer sheet having a hollow convex portion that is a reverse shape of the needle-like concave portion are formed. A drying shrinkage step for drying and shrinking the polymer solution while maintaining a state in which the polymer solution is in close contact with the needle-shaped recess, and a peeling step for peeling the polymer sheet formed in the drying shrinkage step from the mold. It is related with the manufacturing method of the hollow needle sheet characterized by including.

  According to the manufacturing method concerning Claim 1, the hollow convex part along a needle-shaped recessed part can be formed easily and with high precision using the film thickness reduction | decrease of the polymer solution in a drying shrinkage | contraction process.

  Here, the state in which the polymer solution is in close contact with the needle-shaped recess means a state in which the polymer solution is not peeled from the needle-shaped recess, that is, a state in which no gap is generated between the polymer solution and the needle-shaped recess. Or the state according to this.

  The invention described in claim 2 relates to the method of manufacturing a hollow needle sheet according to claim 1, wherein the mold contains a silicone resin.

  According to the manufacturing method according to claim 2, the polymer sheet can be peeled from the mold without damaging in the peeling step by utilizing the characteristics of the silicone resin having good peelability.

  Invention of Claim 3 is related with the manufacturing method of the hollow needle sheet of Claim 1 or 2 with which the film thickness of the said polymer sheet is adjusted based on the shape of the said needle-shaped recessed part. .

  According to the manufacturing method which concerns on Claim 3, the hollow needle of various shapes can be formed by adjusting the film thickness of a polymer sheet according to the shape of a needle-shaped recessed part.

  The invention described in claim 4 relates to the method for producing a hollow needle sheet according to any one of claims 1 to 3, wherein the polymer solution contains a drug.

  According to the manufacturing method which concerns on Claim 4, the hollow needle sheet which contains a chemical | medical agent and can be utilized as a percutaneous absorption system can be produced. If the hollow needle sheet is used to administer the patient, the hollow convex portion has a hollow structure, so that the time required for dissolving the hollow convex portion in the patient body, that is, the medication time can be shortened.

  The invention described in claim 5 further includes a drug injection step of injecting a drug into the hollow portion of the hollow convex portion of the polymer sheet. The present invention relates to a method for manufacturing a hollow needle sheet.

  According to the manufacturing method which concerns on Claim 5, the chemical | medical agent is included and the hollow needle sheet | seat which can be utilized as a percutaneous absorption system can be produced.

  The invention described in claim 6 is characterized in that the hollow ratio of the hollow convex portion of the polymer sheet is 50% or more and 95% or less. The present invention relates to a method for producing the described hollow needle sheet.

  Invention of Claim 7 is related with the manufacturing method of the hollow needle sheet as described in any one of Claims 1-6 by which the back surface of the said hollow convex part of the said polymer sheet is open | released.

  The invention described in claim 8 relates to the method for producing a hollow needle sheet according to any one of claims 1 to 7, wherein the polymer solution contains a polymer of a biodegradable material.

  The invention described in claim 9 relates to the method for producing a hollow needle sheet according to any one of claims 1 to 8, wherein the polymer solution contains a polymer of a biocompatible material.

  Invention of Claim 10 is related with the hollow needle sheet manufactured by the manufacturing method of the hollow needle sheet as described in any one of Claims 1-9.

  According to the present invention, the polymer solution is dried and shrunk while maintaining the state in which the polymer solution is in close contact with the needle-shaped recess of the mold, thereby making it easy to utilize the film thickness reduction of the polymer solution due to drying shrinkage. And a hollow needle can be formed with high precision.

  Embodiments of the present invention will be described below with reference to the accompanying drawings. First, a method for manufacturing a hollow needle sheet according to an embodiment of the present invention will be described, and then a structure of the hollow needle sheet manufactured by the method will be described.

  Drawing 1 (a)-(d) is a figure showing a situation until a hollow needle sheet concerning one embodiment of the present invention is manufactured.

  First, as shown to Fig.1 (a), the mold 10 which has the needle-shaped recessed part 12 is prepared. The needle-like recess 12 is a recessed area compared to the flat surface 16 of the mold 10, and is defined by the recess wall surface 14.

  The material of the mold 10 is not particularly limited, but from the viewpoint of preventing damage during peeling of the hollow needle sheet, the gas permeability is low from the viewpoint of using a resin having good peelability or facilitating formation of the hollow needle. Metal can be used. For example, silicone rubber can be used as a resin having good releasability, and nickel or copper can be used as a metal having low gas permeability.

  Next, as shown in FIG. 1B, a polymer solution 20 is applied to the mold 10.

  Examples of the method for applying the polymer solution 20 include bar coating, spin coating, spray coating, and dropping using a dispenser. Especially, since the aspect which dripped the polymer solution 20 using a dispenser can control the dripping amount with high precision irrespective of the viscosity of the polymer solution 20, it is preferable.

  The polymer solution 20 is a solution in which a polymer is dispersed in a solvent such as water, alcohol, or methyl ethyl ketone (MEK). The polymer solution 20 may contain various additives in addition to the solvent and the polymer. For example, a drug to be administered to a patient may be added to the polymer solution 20.

  The polymer of the polymer solution 20 is preferably a material (biodegradable material) that is easily degraded in the living body and a material having biocompatibility (biocompatible material). For example, sugars such as glucose, maltose, and pullulan, and biodegradable polymers such as gelatin, polylactic acid, and lactic acid / glycolic acid copolymer can be used. Among them, pullulan and gelatin are materials that can be cast at a low temperature. Therefore, when a drug is added to the polymer solution 20, it is preferable in terms of preventing thermal deterioration of the drug during molding of the polymer sheet.

  The polymer concentration of the polymer solution 20 is preferably 5 to 50% by weight from the viewpoint of forming a hollow needle having a sufficiently high hollow ratio. The viscosity of the polymer solution 20 is preferably 5 Pa · sec or less, and more preferably 2 Pa · sec or less, from the viewpoint of facilitating filling of the polymer solution 20 into the recess 12.

  The application amount (film thickness) of the polymer solution 20 is preferably adjusted as appropriate in consideration of the polymer concentration of the polymer solution 20 so that a hollow needle sheet having a desired film thickness can be obtained.

  Next, as shown in FIG. 1C, the polymer solution 20 is dried and shrunk while maintaining the state in which the polymer solution 20 is in close contact with the concave wall surface 14 of the mold 10. Examples of a method for drying and shrinking the polymer solution 20 include a method of volatilizing the solvent of the polymer solution 20 by heating, blowing, or reducing pressure.

  Here, the state in which the polymer solution 20 is in close contact with the recess wall surface 14 is a state in which the polymer solution 20 is not peeled from the recess wall surface 14, that is, a gap is generated between the polymer solution 20 and the recess wall surface 14. The state which is not, or the state equivalent to this. In order to prevent the generation of a gap between the polymer solution 20 and the concave wall surface 14, it is preferable to use a mold 10 made of a material having low gas permeability. This is because it is possible to suppress the gas from passing through the mold 10 and entering between the polymer solution 20 and the concave wall surface 14 to form a void.

  In the process of drying shrinkage of the polymer solution 20, the film thickness of the polymer solution 20 is reduced at a constant shrinkage rate corresponding to the polymer concentration, so that the polymer sheet 22 that has been dried and shrunk has a shape along the surface of the mold 10. . That is, a hollow needle-like convex portion 24 having a hollow portion 26 is formed in the needle-like concave portion 12 of the mold 10 along the concave wall surface 14.

  In order to form the hollow part 26 in the hollow needle-like convex part 24, the film thickness t of the polymer sheet 22 is appropriately set according to the shape (for example, diameter (width) or depth) of the needle-like concave part 12 of the mold 10. It is preferable to set the value. For example, in the case of the needle-like recess 12 having a diameter (width) of 400 μm and a depth of 2000 μm, the film thickness t of the polymer sheet 22 is preferably 200 μm or less, and more preferably 150 μm or less. The film thickness t of the polymer sheet 22 means the thickness of the polymer sheet 22 on the flat surface 16 of the surface of the mold 10 (the film thickness of the base portion 28 shown in FIG. 2). In this way, by adjusting the film thickness of the polymer sheet 22 according to the diameter (width) and depth of the needle-like concave portion 12, the hollow needle-like convex portion 24 can be formed with high accuracy.

  And the polymer sheet 22 which has a hollow needle-like convex part 24 as shown in FIG.1 (d) is obtained by peeling from the mold 10. FIG.

  As an aspect of peeling of the polymer sheet 22, for example, a method in which a sheet having an adhesive layer on one side is attached to the back surface of the polymer sheet 22 and the whole sheet is peeled off, or a method in which a suction cup is adsorbed on the back side of the polymer sheet Etc.

  Next, the structure of the polymer sheet 22 manufactured by the above process will be described.

  FIG. 2 is a cross-sectional view showing a structural example of a polymer sheet manufactured by the method according to the present embodiment.

  As shown in FIG. 2, the polymer sheet 22 has hollow needle-like convex portions 24 in which hollow portions 26 are formed. Although only one hollow needle-like convex portion 24 is shown in FIG. 2, a plurality of hollow needle-like convex portions 24 may be arranged two-dimensionally or three-dimensionally (shown in FIG. 1 (d)).

  The shape of the hollow needle-like convex portion 24 is preferably a high aspect ratio structure having a height of 10 to 2000 μm and an aspect ratio of 1 or more. For example, a columnar shape such as a cylinder or a prism, a cone or a pyramid The shape may be a cone shape, a combination of a column shape and a cone shape (referred to as “conical column shape”, also referred to as “pencil shape”), or a shape similar to these. As the pyramid shape, for example, a triangular pyramid shape combining a triangular prism and a triangular pyramid, a polygonal pyramid shape represented by a quadrangular pyramid shape combining a quadrangular column and a quadrangular pyramid, and a conical column shape combining a cylinder and a cone Etc. FIG. 2 illustrates a cone-shaped hollow needle-like convex portion 24 having a cone-shaped tip portion and a column-shaped root portion.

  Here, the height of the hollow needle-like convex portion 24 means the protrusion length H from the surface of the base portion 28, and the aspect ratio A of the hollow needle-like convex portion 24 is the height of the hollow needle-like convex portion 24 ( Using projection length) H and width (diameter) D, it is defined by A = H / D.

The tip thickness H ₁ of the hollow needle-like convex portion 24 is one of important factors that determine the needle strength of the hollow needle-like convex portion 24, and depends on the polymer concentration of the polymer solution 20 and the film thickness of the polymer sheet 22. It is adjustable. The length H ₂ of the tip (cone) of the hollow needle-like convex portion 24 is also one of the important factors that determine the needle strength of the hollow needle-like convex portion 24, and the shape of the needle-like concave portion 12. It is possible to adjust by appropriately changing.

  The back surface of the hollow needle-like convex portion 24 is not sealed but is opened. The hollow portion 26 of the hollow needle-like convex portion 24 is defined by a needle inner surface 32 having a shape recessed so as to follow the shape of the needle outer surface 30.

  Moreover, it is preferable that the hollow rate of the hollow part 26 is 50 to 95% from a viewpoint of ensuring sufficient hollow volume, maintaining the intensity | strength of the hollow needle-like convex part 24. FIG. Here, the hollow ratio of the hollow needle-shaped convex portion 24 means a hollow ratio calculated by ignoring the base portion 28 and paying attention only to the hollow needle-shaped convex portion 24.

  As described above, by providing the hollow portion 26 in the hollow needle-like convex portion 24, the time required for dissolution of the hollow needle-like convex portion 24 in the patient's body, that is, the medication time can be shortened. Efficient drug administration is possible.

  Further, the hollow portion 26 can be filled with a medicine. FIG. 3 is a cross-sectional view showing a structural example of a polymer sheet in which a hollow portion is filled with a medicine.

  An adhesive sheet 34 is provided on the back surface of the polymer sheet 22 shown in FIG. 3 for the purpose of preventing leakage of the medicine filled in the hollow part 26 of the hollow needle-like convex part 24. The medicine filled in the hollow part 26 is absorbed into the patient after the hollow needle-like convex part 24 is biodegraded. The chemical | medical agent with which the hollow part 26 is filled may be a dry powder form, and may be a liquid form.

  The filling of the drug into the hollow part 26 can be performed regardless of whether or not the drug is added to the polymer solution 20, and the addition of the drug to the polymer solution 20 and the filling of the drug into the hollow part 26 may be used in combination. Is possible. In the case where the addition of the drug to the polymer solution 20 and the filling of the drug into the hollow portion 26 are used in combination, the types of the drug added to the polymer solution 20 and the drug filled into the hollow portion 26 can be freely combined. Good.

  In particular, by adding the primary drug to be administered first to the polymer solution 20 and filling the hollow part 26 with the secondary drug to be administered later, two drugs having different efficacy are put in the patient at a time interval. Can be administered. In this case, the administration interval (time difference) between the primary drug and the secondary drug can be adjusted by the film thickness of the hollow needle-like convex portion 24.

  Next, a method for producing the mold 10 used for producing the polymer sheet 22 will be described. Examples of a method for producing the mold 10 include a method of drilling the needle-like recess 12 in a metal plate by machining using a drill, a method of molding the original plate with a resin, and a method of forming an inverted shape of the original plate by electroforming. It is done.

  FIG. 4 is a view showing a mold manufacturing method by resin molding. After the resin solution is cast on the original plate 40 and solidified, it is peeled off from the original plate 40 to produce the mold 10. The original plate 40 used for the production of the mold 10 may be produced by machining a metal material, or produced by finely processing an inorganic material such as quartz, glass or silicon by electron beam lithography and etching. Also good. If the original 40 is produced using a highly durable material, it is possible to repeat the production of the mold 10 by repeatedly using one original 40.

  The mold 10 produced by the above method may be used alone, or a plurality of molds 10 may be used side by side. FIG. 5 is a view showing a large area mold including a plurality of molds.

  A large area mold 100 shown in FIG. 5 has a configuration in which a plurality of molds 10 are fixed to a substrate 44 through an adhesive layer 42. If the polymer sheet 22 is manufactured using the large area mold 100, the production efficiency is greatly improved.

  As described above, according to the present embodiment, the hollow hollow needle-shaped convex portion 24 is obtained by drying and shrinking the polymer dissolved solution 20 while maintaining the state in which the polymer dissolved solution 20 is in close contact with the concave wall surface 14 of the mold 10. The polymer sheet 22 having can be easily produced.

  Further, by selecting a silicone resin having excellent peelability as the material of the mold 10, the polymer sheet 22 can be peeled from the mold 10 without damaging the polymer sheet 22.

  Furthermore, the hollow needle-like convex part 24 is formed with high accuracy by adjusting the film thickness t of the polymer sheet 22 based on the shape of the needle-like concave part 12 (for example, the width and depth of the needle-like concave part). Can do.

  As described above, an example of the present invention has been described in detail. However, the present invention is not limited to this example, and various improvements and modifications may be made without departing from the scope of the present invention.

  For example, in the above-described embodiment, the example in which the polymer solution 20 is dried and contracted after the polymer solution 20 is applied to the mold 10 has been described. However, the polymer solution 20 is dissolved before the polymer solution 20 is dried and contracted. You may accelerate | stimulate filling to the needle-shaped recessed part 12 of the liquid 20. FIG. As a method of accelerating the filling of the polymer solution 20 into the needle-shaped recess 12, a method of pressurizing the polymer solution 20 after casting the polymer solution 20 into the mold 10, or a method of pressing the polymer solution 20 under reduced pressure in the mold 10. The method of returning to atmospheric pressure after casting is mentioned.

  FIG. 6 is a view showing a pressure filling device that promotes filling of the polymer solution into the needle-like concave portion.

  A pressure filling device 50 shown in FIG. 6 includes a pressure vessel 52 having an inlet 58 and a discharge port 60, a pedestal 54 provided inside the pressure vessel 52, and a compressor 56 that feeds pressurized fluid into the pressure vessel 52. including. Below, operation | movement of the pressurization filling apparatus 50 is demonstrated.

  In a state where the mold 10 into which the polymer solution 20 has been cast is placed on the pedestal 54, the pressurized fluid is fed into the pressure resistant container 52 through the inlet 58 by the compressor 56. The pressurization by the compressor 56 is performed, for example, under the condition that the pressure is in the range of 0.01 to 5 MPa and the pressurization time is 5 sec to 5000 sec. The casting of the polymer solution 20 may be performed in the pressure vessel 52.

  As the pressurized fluid, gas or liquid can be used. Examples of the gas that can be used as the pressurized fluid include air. From the viewpoint of preventing dissolution of the pressurized fluid in the polymer solution 20, a gas having a low dissolution rate in the polymer solution 20 should be selected. Is preferred. For example, when the solvent of the polymer solution 20 is water, nitrogen gas is preferably used as the pressurized fluid.

  From the viewpoint of preventing an increase in viscosity due to volatilization of the polymer solution 20, a liquid of the same type as the solvent of the polymer solution 20 is stored in the pressure vessel 52 in advance, and the inside of the pressure vessel 52 is saturated with the vapor of the liquid. It is preferable to be in a state.

  In this way, by promoting the filling of the polymer solution 20 into the needle-shaped recess 12, a state in which the polymer solution 20 is in close contact with the wall surface 14 of the recess can be positively created. Is easy to form.

  In the above-described embodiment, the example of producing the hollow needle sheet having the hollow needle-like convex portion 24 has been described. However, the present invention is not limited to this, and various high aspect ratio hollow structures such as hollow micropillars. The present invention can also be applied to the production of a sheet on which is formed.

  By the method according to the above-described embodiment, a hollow needle sheet was produced as shown below, and the hollow state of the hollow needle was evaluated.

[Example 1]
<Mold production>
First, in a region of 10 mm × 10 mm in a central portion of a smooth copper plate of 40 mm × 40 mm, the tip is a cone having a bottom diameter of 400 μm and a height of 1000 μm by cutting using a diamond tool, and the root is 400 μm in diameter and high Conical columnar (pencil-shaped) concave portions that are 1000 μm thick cylinders were formed at a pitch of 460 μm to prepare an original plate. Using this original plate, a transfer product of silicone rubber (manufactured by Shin-Etsu Chemical Co., Ltd., RTV rubber for Shin-Etsu silicone mold making) was produced, and a mold having a thickness of 5 mm and a size of 40 mm × 40 mm was obtained. In the central portion of the mold 10 mm × 10 mm, a conical columnar concave portion was formed in which a tip portion was a cone having a bottom diameter of 400 μm and a height of 1000 μm, and a root portion was a cylinder having a diameter of 400 μm and a height of 1000 μm.

<Preparation of polymer solution>
Gelatin (Nitta Gelatin KK, Nitta Gelatin 732) was dissolved in water to prepare an aqueous solution having a gelatin concentration of 20% by weight. This gelatin aqueous solution was stirred at 40 ° C. and kept at 40 ° C. The viscosity of the gelatin aqueous solution at 40 ° C. was about 300 mPa · sec.

<Polymer solution casting>
An opening of 30 mm × 30 mm was provided in the central portion of a silicone sheet having a size of 40 mm × 40 mm and a thickness of 3 mm (manufactured by Shin-Etsu Finetech Co., Ltd., Shinetsu Silicon Sheet BA grade). The silicone sheet was laminated and bonded to the mold in a state where the conical columnar hole pattern portion of the mold was positioned so as to be exposed from the opening of the silicone sheet. Then, 0.5 ml of polymer solution was dripped at the mold (silicone sheet opening) to which the silicone sheet was adhered using a dispenser.

<Pressure filling device>
An acrylic bottom plate having a thickness of 1 mm was welded to an acrylic pipe having an inner diameter of 150 mm, a length of 150 mm, and a thickness of 10 mm, and an acrylic flange having an O-ring groove engraved in the upper opening was attached. Then, the lid | cover which can be fixed with a volt | bolt was attached to the flange, and the pressure-resistant container was produced.

  The lid was provided with two through-holes (inlet and outlet), the inlet was connected to a compressor, and a valve was provided at the outlet. A pressure gauge was placed between the inlet and the compressor.

  An acrylic stage having a diameter of 100 mm supported by a leg having a height of 50 mm was installed inside the pressure vessel. Furthermore, the entire pressure vessel was covered with a heating jacket.

<Pressure filling of polymer solution>
In order to prevent volatilization of water which is a solvent of the polymer solution, hot water was stored up to a height of 40 mm at the bottom of the pressure vessel. The mold in which the polymer solution was cast was placed on the stage in the pressure vessel, an O-ring was sandwiched between the flange and the lid, and the pressure vessel was sealed with a bolt. After heating the inside of a pressure vessel to 40 degreeC with the heating jacket, compressed air was inject | poured in the pressure vessel from the compressor. Thereby, the pressure in the pressure vessel was held at 0.5 MPa for 5 minutes.

<Drying process>
The mold was taken out from the pressure vessel, put into an oven, and dried at 50 ° C. for 12 hours. By the drying treatment, the polymer solution was solidified to obtain a polymer sheet.

<Peeling process>
After the silicone sheet laminated and adhered to the mold was removed, an adhesive tape was attached to the back surface of the polymer sheet, and the entire adhesive tape was peeled off from the mold.

<Molded product>
The polymer sheet peeled from the mold had conical columnar needles formed on the surface, and the thickness of the base portion was 100 ± 20 μm. When the conical columnar needle of the polymer sheet was measured to calculate the hollowness of the conical columnar needle, the hollowness was 80%.

[Example 2]
According to the method of Example 1, 0.5 ml of a polymer solution having a gelatin concentration of 5% by weight was dropped with a dispenser. The finally obtained polymer sheet had a base film thickness of 30 ± 10 μm and a hollowness of 95%.

[Example 3]
In the method of Example 1, 3 ml of a polymer solution having a gelatin concentration of 5% by weight was dropped with a dispenser. The finally obtained polymer sheet had a base film thickness of 150 ± 20 μm and a hollowness of 95%.

[Comparative Example 1]
Using a mold having a conical columnar recess having a width of 200 μm, 0.5 ml of a polymer solution having a gelatin concentration of 20% by weight was dropped by a dispenser in the same manner as in Example 1. The polymer sheet finally obtained had a base film thickness of 100 ± 20 μm. The conical columnar needle of the polymer sheet had a solid structure with no hollow part.

[Comparative Example 2]
In the method of Example 1, 3 ml of a polymer solution having a gelatin concentration of 20% by weight was dropped with a dispenser. The finally obtained polymer sheet had a base film thickness of 650 ± 20 μm. The conical columnar needle of the polymer sheet had a solid structure with no hollow part.

[Comparison study of Examples and Comparative Examples]
The measurement results of the film thickness and the hollowness of the polymer sheets in Examples 1 to 3 and Comparative Examples 1 and 2 are shown in the following table.

  From this table, it can be seen that the film thickness of the polymer sheet varies depending on the gelatin concentration and the amount of the polymer solution dropped. When the film thickness of the polymer sheet was 100 ± 20 μm (Example 1), 30 ± 10 μm (Example 2), and 150 ± 20 μm (Example 3), a hollow needle could be formed. On the other hand, when the width of the conical columnar recess was 200 μm (Comparative Example 1) or when the film thickness of the polymer sheet was 650 ± 20 μm (Comparative Example 2), a hollow needle could not be formed (the hollow ratio was 0%).

[Hollow needle formation conditions]
When the needle is hollow, the needle is formed along the concave wall surface 14 of the mold 10, so that the needle width is substantially the same as the width of the needle-shaped concave portion 12, while the polymer is dissolved when the needle is solid. Since the liquid 20 is peeled off from the recess wall surface 14, the needle width is smaller than the width of the needle-like recess 12. By utilizing this property, it is possible to judge whether the needle is solid or hollow by comparing the width of the conical columnar recess of the mold with the width of the needle.

  Experiments on the hollow needle formation conditions were performed by changing the film thickness of the polymer sheet and the polymer concentration.

  According to the method of Example 1, four types of polymer solutions having gelatin concentrations of 5% by weight, 10% by weight, 15% by weight and 20% by weight, respectively, were prepared and poured into molds with various dropping amounts. . As in Example 1, a mold having a conical columnar concave pattern in which a tip portion is a cone having a bottom diameter of 400 μm and a height of 1000 μm, and a root portion is a cylinder having a diameter of 400 μm and a height of 1000 μm was used. .

  The film thickness (basic film thickness) of the produced polymer sheet and the width of the needle-like convex portion (needle width) of the polymer sheet were measured. Furthermore, when the hollow needle was formed in the polymer sheet, the tip thickness of the hollow needle was also measured.

  FIG. 7 is a graph showing the relationship between the film thickness (base film thickness) of the polymer sheet and the width of the needle-like convex portion (needle width).

  As can be seen from FIG. 7, when the basal film thickness is smaller than a predetermined value (about 170 μm), the needle width is substantially the same as the width of the conical columnar recess (400 μm), so that a hollow needle is formed. I understand. On the other hand, when the base film thickness is larger than the predetermined value (about 170 μm), it can be seen that a solid needle is formed because the needle width is smaller than the width of the conical columnar recess. When the base film thickness was around 170 μm, hollow needles and solid needles were mixed.

  Thus, when the film thickness t of the polymer sheet was 200 μm or less, a hollow needle was formed.

  FIG. 8 is a graph showing the relationship between the film thickness (base film thickness) of the polymer sheet and the tip thickness of the hollow needle.

  As can be seen from FIG. 8, when the polymer concentration was 10% by weight or more, the tip thickness of the hollow needle tended to decrease as the base film thickness decreased. On the other hand, when the polymer concentration was 5% by weight, no clear correlation was found between the base film thickness and the tip thickness of the hollow needle.

  Thus, the tip thickness of the hollow needle could be adjusted by the film thickness and polymer concentration of the polymer sheet.

It is a figure which shows a mode until the acicular array sheet which concerns on one Embodiment of this invention is manufactured. It is sectional drawing which shows the structural example of the polymer sheet manufactured by the method which concerns on this embodiment. It is sectional drawing which shows the structural example of the polymer sheet which filled the hollow part with the chemical | medical agent. It is a figure which shows the mold preparation method by resin mold taking. It is a figure which shows the large area mold containing a some mold. It is a figure which shows the pressurization filling apparatus which pressurizes and fills a polymer solution to a needle-shaped recessed part. It is a graph which shows the relationship between a base film thickness and a needle width. It is a graph which shows the relationship between a base film thickness and the tip thickness of a hollow needle.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 10 ... Mold, 12 ... Needle-shaped recessed part, 14 ... Recessed wall surface, 16 ... Flat surface, 20 ... Polymer solution, 22 ... Polymer sheet, 24 ... Hollow needle-shaped convex part, 26 ... Hollow part, 28 ... Base part, 30 ... needle outer surface, 32 ... needle inner surface, 34 ... adhesive sheet, 40 ... original, 42 ... adhesive layer, 44 ... substrate, 100 ... large area mold

Claims (10)

An application step of applying a polymer solution to a mold having a needle-like recess;
Dry shrinkage for drying and shrinking the polymer solution while maintaining the state in which the polymer solution is in close contact with the needle-like recess so as to form a polymer sheet having a hollow convex portion that is an inverted shape of the needle-like recess. Process,
A method for producing a hollow needle sheet, comprising: a peeling step of peeling the polymer sheet formed in the drying shrinkage step from the mold.   The method for manufacturing a hollow needle sheet according to claim 1, wherein the mold includes a silicone resin.   The method for producing a hollow needle sheet according to claim 1 or 2, wherein the film thickness of the polymer sheet is adjusted based on the shape of the needle-like recess.   The said polymer solution contains a chemical | medical agent, The manufacturing method of the hollow needle sheet as described in any one of Claims 1-3 characterized by the above-mentioned.   The method for producing a hollow needle sheet according to any one of claims 1 to 4, further comprising a drug injection step of injecting a drug into a hollow portion of the hollow convex portion of the polymer sheet.   The hollow needle sheet manufacturing method according to any one of claims 1 to 5, wherein a hollow ratio of the hollow convex portion of the polymer sheet is 50% or more and 95% or less.   The method for producing a hollow needle sheet according to any one of claims 1 to 6, wherein a back surface of the hollow convex portion of the polymer sheet is open.   The said polymer solution contains the polymer of biodegradable material, The manufacturing method of the hollow needle sheet as described in any one of Claims 1-7 characterized by the above-mentioned.   The said polymer solution contains the polymer of biocompatible material, The manufacturing method of the hollow needle sheet as described in any one of Claims 1-8 characterized by the above-mentioned.   The hollow needle sheet manufactured by the manufacturing method of the hollow needle sheet as described in any one of Claims 1-9.

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