STAMPER FOR MICRONEEDLE SHEET, PRODUCTION METHOD THEREOF, AND MICRONEEDLE PRODUCTION METHOD USING STAMPER
Microneedle sheets are produced by injecting a needle raw material into a stamper formed with a concavity in a base material. However, because the stamper concavity is very small, there is the problem that air cannot escape due to air and surface tension of the material, thereby preventing a needle from being formed in part. The present invention provides a stamper for producing a microneedle sheet. The stamper comprises a sheet-like base material including a conical concavity formed from a first surface of the sheet-like base material toward a second surface thereof; and a through-hole formed from a bottom of the concavity toward the second surface. Air can escape via this through-hole, allowing a microneedle sheet which is filled with a needle raw material as far as the bottom of the concavity to be obtained.
Latest BIOSERENTACH CO., LTD. Patents:
- Mucoadhesive oral preparation
- VACCINE ADJUVANT AND MICRONEEDLE PREPARATION
- Microneedle-array manufacturing apparatus, microneedle-array manufacturing method, and product having the microneedle array
- MUCOADHESIVE ORAL PREPARATION
- MICRONEEDLE PATCH, METHOD FOR MANUFACTURING SAME, AND APPARATUS FOR MANUFACTURING MICRONEEDLE ARRAY
The present invention relates to a microneedle sheet for injecting a drug into the epidermis of a skin. More specifically, the present invention relates to a stamper, which is a mold, for producing a microneedle, and a method for producing a microneedle sheet using this stamper.
BACKGROUND ARTA microneedle sheet is a sheet in which very small needles having a length of about 1 μm to 500 μm, and a high aspect ratio of the cross-sectional diameter at the base to the length of cross-sectional diameter:length=1:1.5 to 1:3, are arranged at a predetermined density onto a sheet substrate. The microneedle sheet is used for injecting a drug by placing it against mainly a skin portion of a human body, and inserting the microneedles (hereinafter, sometimes referred to simply as “needle”) into the epidermis portion in the skin.
Since the microneedles have a length of about several hundred μm, they cause almost no pain or itchiness. Furthermore, the microneedle portion is formed from a self-dissolving substance so that when the sheet is removed from the skin there is no harm to the body even if the microneedles remain in the skin.
A common method for producing a microneedle sheet will now be described with reference to
Next, the original plate 90 is pressed against a stamper base material 81 to produce a stamper 80 (a mold for a microneedle sheet). Then, a resin polymer solution or a drug 85 is injected into the stamper 80. The resin polymer solution or drug 85 is dried, then stuck onto a fixing substrate 88 to be transferred thereonto and peeled off from the stamper 80, whereby a microneedle sheet 77 can be obtained (see Patent Document 1).
In the method for producing this stamper 80, rather than pressing the original plate 90 against the base material 81, the dissolved resin may be injected into the original plate 90, dried, and then peeled off (see Patent Document 2).
LIST OF PRIOR ART DOCUMENTS Patent Documents [Patent Document 1] Japanese Patent Application Laid-Open No. 2008-245955 [Patent Document 2] Japanese Patent Application Laid-Open No. 2008-006178 [Patent Document 3] Japanese Patent Application Laid-Open No. 2009-083125 SUMMARY OF THE INVENTION Problems to be Solved by the InventionIn either case, the microneedle sheet is produced by injecting a raw material of the needle into a produced stamper. However, since the concavities in the stamper have extremely small dimensions, the raw material of the microneedles is not easily filled into the stamper concavities due to air and surface tension of the material.
More specifically, in
This problem is also described in Patent Documents 2 and 3. Patent Document 2 describes carrying out the filling of the raw material into the stamper under a reduced pressure. Patent Document 3 describes filling a raw material into a stamper concavity while applying a pressure from the raw material side. However, when providing many microneedles, there is the problem that the raw material is not filled in some of the concavities, which means that not all of the planned microneedles can be planted.
Means for Solving the ProblemsThe present invention was created in consideration of the above-described problems. Specifically, the present invention provides a stamper for producing a microneedle sheet formed on a fixing substrate, the stamper comprising a sheet-like base material including:
-
- a conical concavity formed from a first surface of the sheet-like base material toward a second surface thereof; and
- a through-hole formed from a bottom of the concavity toward the second surface. Furthermore, the present invention provides a method for producing the stamper according to the present invention, and a method for producing a microneedle sheet using the inventive stamper.
In the present invention, a through-hole which penetrates as far as an opposite face of a stamper is provided on the bottom of a concavity of the stamper. Therefore, air can easily escape even if air has accumulated in the concavity of the stamper. Consequently, the present invention can obtain a microneedle sheet on which all of the planned microneedles are formed by enabling a raw material to be filled into all of the concavities of the stamper.
Next, examples of the method for producing the stamper according to the present invention will be described. However, the present invention is not limited to these production methods, so long as the gist of the present invention is not departed from.
With reference to
The protrusions 12 stand on the body 11 with a height 13 of from about 1 μm to 500 μm. The reason for the height setting is as follows. Although the epidermis into which the drug or the like is injected using the microneedle sheet is formed from the stratum corneum, stratum granulosum, stratum spinosum, and stratum basale, the thickness of the stratum corneum is different depending on the area of the body. Thus, the height of the protrusions can change depending on the area of the body into which transdermal administration is to be carried out and the drug.
The protrusions 12 have a needle shape with a comparatively high aspect ratio of the cross-sectional diameter at the base to the length of cross-sectional diameter:length=1:1.5 to 1:3. This is because the aspect ratio may change depending on the area to be used. The cross-sectional shape is not especially limited. Examples of shapes which may be preferably used include circular, elliptical, rectangular including square, and the like. Furthermore, a groove may be formed on the surface of the protrusions. This is because a microneedle which reflects the shape of such a groove can be smoothly inserted into the skin.
Next, with reference to
Although the organic compound mainly used for the base material 2 undergoes partial plastic deformation when the conical protrusions 12 are compressed from the surface, an elastic deformed portion also remains. Accordingly, if the protrusions 12 are stripped off, the concavities 3 can become smaller than the shape which has been pushed wider by the protrusions 12 of the original plate. Therefore, it is preferred for the protrusions 12 of the original plate to be produced with a size which is larger than the concavities of the stamper that are to be produced.
Next, with reference to
From this perspective, as illustrated in
Even when the protrusions 12 of the original plate 10 are pre-heated, the through-holes may be formed after the concavities have been formed to midway through the thickness of the base material 2. Alternatively, the concavities and the through-holes may be simultaneously formed by making the protrusions 12 of the original plate 10 penetrate as far as the back face of the base material 2.
As illustrated in
The microneedle sheet is produced using the thus-produced stamper. With reference to
As illustrated in
Furthermore, the stamper 1 may be arranged on a flat mount 18 formed by a porous solid, and the needle raw material 20 can be coated while applying a negative pressure 16 from the back face of the flat mount 18 (see
After the needle raw material 20 is coated on the stamper 1, the needle raw material 20 is dried and peeled from the stamper, thereby completing a microneedle sheet 30 (see
Thus, in the stamper according to the present invention, a through-hole which penetrates as far as an opposite face of the stamper is machined into the bottom of a concavity forming a needle. Therefore, even if air is in the concavity, the air can easily escape, which allows a microneedle sheet which has a high degree of completeness, namely, which has no incomplete needles, to be obtained.
Embodiment 2First, a drug 21 is coated on the stamper (see
The drug solution 21 is dried, and then stays in the inner faces and the bottom portions of the concavities 3 (see
Then, after scraping off the excess drug solution with a squeegee, the needle raw material is immediately coated, and pressure or a negative pressure from the back face may be applied. In this case, the coating is wet-on-wet coating. Therefore, similar to Embodiment 1, air escapes from the through-holes just by coating, so that a microneedle sheet can be obtained which includes the drug in the tips.
Finally, the fixing substrate 88 is stuck to the back face of the dried needle raw material, and peeled from the stamper 1. Here, the obtained microneedle sheet 32 is a microneedle sheet in which the drug 21 is provided in the tips of the needles.
In the present embodiment, the microneedle sheet was formed from two layers, a layer including the drug and a layer forming the needle. However, the structure can have three or more layers.
INDUSTRIAL APPLICABILITYThe present invention can not only be used for a microneedle sheet which injects a drug into the epidermis, but can also be widely used as a method for generating very small protrusions on a substrate.
DESCRIPTION OF REFERENCE NUMERALS1 stamper
2 base material
3 concavity
4 through-hole
5 thickness of base material
10 original plate
11 body of original plate
12 protrusion
13 height of protrusion
15 pressure
16 negative pressure
18 flat mount made of porous solid
20 needle raw material
21 drug
30, 32 microneedle sheet
31 needle
70 micro drill
72 air
77 microneedle sheet
80 conventional stamper
81 conventional stamper base material
85 needle raw material
88 fixing substrate
90 original plate
91 body
92 protrusion
93 length of protrusion
Claims
1. A stamper for producing a microneedle sheet formed on a fixing substrate, the stamper comprising a sheet-like base material including:
- a conical concavity formed from a first surface of the sheet-like base material toward a second surface thereof; and
- a through-hole formed from a bottom of the concavity toward the second surface.
2. A method for producing a stamper for a microneedle sheet formed on a fixing substrate, the method comprising the steps of:
- forming a conical concavity from a first surface of a sheet-like base material toward a second surface of the base material; and
- forming a through-hole from a bottom of the concavity toward the second surface.
3. The method for producing a stamper according to claim 2, wherein
- the step of forming a concavity is a step of pressing an original plate having a conical convexity against the first surface of the sheet-like base material and bringing it into contact with the first surface, and wherein
- the step of forming a through-hole is a step of perforating the second surface of the base material with a tip of the convexity of the original plate pressed against and brought into contact with the base material.
4. The method for producing a stamper according to claim 3, wherein the step of pressing the original plate against the first surface and bringing it into contact with the first surface is a step of preparing the base material made of a resin, heating the original plate and pressing the heated original plate against the base material and bringing it into contact with the base material.
5. A method for producing a microneedle sheet formed on a fixing substrate, the method comprising the steps of:
- forming a conical concavity from a first surface of a sheet-like base material toward a second surface of the base material;
- forming a through-hole from a bottom of the concavity toward the second surface to obtain a sheet-like stamper;
- injecting a needle raw material from the first surface of the stamper; and
- sticking a fixing substrate on the first surface.
6. The method for producing a microneedle sheet according to claim 5, wherein
- the step of injecting a needle raw material includes a step of first injecting a first needle raw material and then a step of injecting at least a second needle raw material.
7. The method for producing a microneedle sheet according to claim 5, wherein
- the step of injecting the needle raw material is a step of injecting while applying a pressure to the stamper from the first surface side.
8. The method for producing a microneedle sheet according to claim 5, wherein
- the step of injecting the needle raw material is a step of injecting while sucking the stamper from the second surface side.
9. The method for producing a microneedle sheet according to claim 6, wherein
- the step of injecting the needle raw material is a step of injecting while applying a pressure to the stamper from the first surface side.
10. The method for producing a microneedle sheet according to claim 6, wherein
- the step of injecting the needle raw material is a step of injecting while sucking the stamper from the second surface side.
Type: Application
Filed: Jan 15, 2010
Publication Date: Aug 11, 2011
Applicant: BIOSERENTACH CO., LTD. (Kyoto)
Inventors: Masashi Motoi (Shiga), Kenshin Honda (Shiga), Toyoharu Terada (Shiga), Tatsuya Okada (Shiga), Yoshitomo Satouchi (Shiga), Kanji Takada (Kyoto)
Application Number: 12/674,716
International Classification: B21G 3/18 (20060101); B21G 1/00 (20060101); B21D 31/00 (20060101);