Microneedle patch case

Abstract

Providing a patch case that is easily attached to a microneedle applicator, easily separable from the microneedle patch upon insertion and disposable for use. The main feature of the patch case according to the present invention is characterized in that it is made of a thermoplastic polymer and is capable of holding a microneedle patch comprising a support film which can be heat-sealed with the thermoplastic polymer. Preferably, the thermoplastic polymer of the body and the fusible material of the support film are both polyolefins or both are the same thermoplastic polymer. In addition, if the patch case is attached to the front of the applicator, sanitary situation can be maintained even with continuous use of the applicator, since the applicator does not contact the skin of the recipient.

Claims

1. A patch case comprising a thermoplastic polymer material, holding a microneedle patch comprising a support film which is heat-sealable to the thermoplastic polymer material, wherein a fusion surface of the microneedle patch is attached to the underside of an edge of the patch case by thermal fusion, and a break strength of a thermally fused portion is 0.01 to 20 N per unit, the unit being the area of a circle having a diameter of 1 cm, the break strength being quantified by compressing the fusion surface from above using a cylindrical rod having a diameter equal to a diameter of the fusion surface.

2. The patch case of claim 1, wherein the thermoplastic polymer material and a micro-sealable material of the support film are both polyolefins.

3. The patch case holding the microneedle patch as claimed in claim 1, wherein the thermoplastic polymer material and a heat-sealable material of the support film are the same thermoplastic polymers.

4. The patch case holding the microneedle patch according to claim 1, wherein a thermal fusion pattern is three or more points of multiple-point fusion, dashed-line fusion, solid-line fusion, or full-feature fusion.

5. The patch case holding the microneedle patch as claimed in claim 1, further comprising a clasp or a screw for attaching the patch case to a front face of an applicator.

6. A method of using the patch case as claimed in claim 1, comprising holding the microneedle patch in the patch case, heat fusing the support film of an adhesive tape to the thermoplastic polymer material, said support film being made of a thermoplastic polymer holding thereon a material capable of being heat-fused with the thermoplastic polymer material, and attaching the patch case to a front surface of an applicator.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 is a perspective view of an embodiment of a patch case of Example 1.

(2) FIG. 2 is a plan view and a cross-sectional view of another embodiment of the patch case of Example 1.

(3) FIG. 3 is an explanatory view of attachment of a microneedle patch to a patch case by thermal fusion.

(4) FIG. 4 is a perspective view of a patch case of Example 2.

(5) FIG. 5 is a photograph of the patch case of Example 2 attached to an applicator.

(6) FIG. 6 is an example of an device for three-point thermal fusion bonding of a patch case and a support film.

(7) FIG. 7 shows various heat fusion patterns of the patch case and the support film. Upper left: 3-point fusion (2 points in one location), middle left: 6-point fusion (oval), lower left: wavy solid line fusion, middle upper: 3-point fusion (perfect circle), middle: solid line partial fusion, middle: full point fusion, upper right: dash line fusion, middle right: solid line fusion, lower right: full point fusion.

(8) FIG. 8 is a stress-strain curve of a welded support film.

DETAILED DESCRIPTION OF THE INVENTION

(9) Embodiments of the present invention will be described below based on examples.

(10) However, the present invention is not limited to the content of the examples.

Example 1

(11) In this example, the patch case of the present invention was used with applicator of Patent Document 9.

(12) When used with other applicators, modifications in shape and dimensions are of course necessary.

(13) Such modifications may be made within the scope of the present invention.

(14) In the applicator of Patent Document 9, a patch case to which a microneedle patch is mounted is inserted from a side surface of the applicator.

(15) The patch case of the present embodiment was fabricated by injection molding using polypropylene (Novatec MA3H, Nippon Polypropylene Industries, Ltd.) as the material of the two embodiments.

(16) One perspective view thereof is shown in FIG. 1, and another plan view and a center cross-sectional view thereof are shown in FIG. 2.

(17) Both are of approximately the same size, with a circular hole of the same size in the central (the inner diameter of which is shown as A in FIG. 1) and a slightly smaller inner diameter edge at the bottom of the hole (shown as B in FIG. 1).

(18) One difference between the two is that the edges of FIG. 1 are all connected, while the edges of FIG. 2 are flared.

(19) The diameter (A) of the central hole was 29 mm in both cases, and the width (B) of the edge was 3 mm in both cases.

(20) In the patch case of FIG. 1, the microneedle patch was thermally fused under the edge, while in the patch case of FIG. 2, the microneedle patch was adhered over the edge using an adhesive applied to the adhesive tape of the microneedle patch.

(21) That is. the two prototype patch cases differ in the installation method and the bonding method, and the effects of these differences were compared in this example.

(22) Reflecting this difference, in FIG. 1, a comparison was made between a case in which the support film was fused to the patch case and then the microneedle array was adhered and a case in which the microneedle array was adhered and held to the adhesive surface and the adhesive surface of the support film was adhered to the upper surface of the patch case.

(23) In FIG. 2, the microneedle array was bonded to the support film and then to the patch case.

(24) Incidentally, it is also possible to attach from below by a fusion bonding method using the one shown in FIG. 2.

(25) The material of the microneedle array used was hyaluronic acid, and about 260 needles with a height of 0.8 mm were standing on a circular substrate with a diameter of 10 mm.

(26) The support film had a circular diameter of 28 mm, and the material was a polypropylene/PET laminate film (Panac Co., Ltd.), and an acrylic adhesive (HiPAS, manufactured by Cosmed Pharmaceutical Co., Ltd.) was applied to a thickness of 50 μm on the PET, which is the front surface (lower side as viewed from the patch case).

(27) When the patch case of FIG. 1 was used, the microneedle patch was placed under the edge of the central hole in the patch case, the polypropylene side of the support film was placed under the edge, and spot welding was performed at six directions equiangularly and equidistantly spaced from below the edge to secure the support film to the patch case.

(28) This is performed by an device as shown in FIG. 6 for thermally fusing the patch case and the support film.

(29) The upper metal portion is heated to press the pointed three points against the adhesive surface of the support film to fuse the support film and the patch case.

(30) This figure is a schematic view of three-point fusion.

(31) A more detailed description will be given with reference to FIG. 3.

(32) FIG. 3 shows across-sectional view of the body 2 of the patch case and its edges 5 and the support films 3, 4 of the microneedle array 1 attached to the edges.

(33) The support film in this case is a laminate of an adhesive tape 4 and a thermoplastic film 3.

(34) The microneedle patch is placed on the edge 5 of a patch case made of thermoplastics.

(35) The six pointed metal fusing heads 6 are heated above the melting point of the thermoplastic resin and pressed from above the adhesive tape 4 to fuse the support film and the patch case.

(36) As a metal fusing head, a 6 mm iron round rod whose tip end was sharpened to a tip angle of about 15 degrees and whose tip end was processed into a spherical surface having a radius of about 0.5 mm was used.

(37) Each fusing head is heated uniformly.

(38) Light fusing is desirable to the range that the support film does not separate from the case during storage.

(39) Although the microneedle array is adhered to the support film before fusing in the drawing, the microneedle array may be adhered and held at the central of the support film after the support film and the patch case are thermally fused.

(40) In this example, the temperature of the tip of the fusing head was about 190° C.

(41) A stopper was provided so that the heated tip of the fusing head was stopped when it was pushed about 0.5 mm deep from the surface of the support film, and the stopper was set so as not to be pushed further.

(42) The fuser head was held in contact for about 0.5 seconds after striking the stopper, and the fuser head was immediately released.

(43) When the support film was fused first, the microneedle array was adhesively held in the center portion of the support film after the fusing operation.

(44) In addition, the whole was packaged in aluminum bags to ensure safety during storage and transportation.

(45) In order to optimize the fusing state, it is desirable to adjust three conditions: the temperature of the fusing metal rod, the pushing amount of the fusing metal rod, and the holding time of the fusing metal rod at the pushing position.

(46) It is also effective to lower the adhesiveness of the welding metal rod to the pressure-sensitive adhesive by applying a fluorine resin or the like.

(47) It is necessary to satisfy the condition that the fusing is ensured, the support film is not detached from the patch case during storage, and all the fused portions are reliably detached uniformly during use.

(48) At the application, the fusion between the support film and the patch case was peeled off by impact (the impact direction is indicated by the arrow 7 in FIGS. 2 and 3) from the back surface direction of the microneedle patch, and the microneedle allay was administered to the skin of the subject.

(49) The prepared patch case/microneedle patch was attached to an applicator of Patent Document 9 and administered to the skin.

(50) One time after dose, the microneedle allays were collected and observations were made under a microscope to determine whether all microneedles were inserted vertically into the skin and evenly dissolved.

(51) The performance of two prototype patch cases was compared.

(52) The results are given in Table 1.

(53) Ten administrations were made to determine the number of microneedles which were nearly straight and dissolved to the root (appropriate case) and the number microneedles which were bent and not sufficiently dissolved (inappropriate case).

(54) TABLE-US-00001 TABLE 1 Evaluation result of ten administrations Bonding method of Appropriate Inappropriate Patch case microneedle patch case case case In FIG. 1 Thermally fused to the under 10 0 surface of the edge Adhered to the upper surface 2 8 of the edge In FIG. 2 Thermally fused to the under 10 0 surface of the edge Adhered to the upper surface 7 3 of the edge

(55) The following conclusions can be drawn from the results in Table 1.

(56) (1) The removing of microneedle patch from the patch case can be much smoother by the heat fusion method than by the adhesive method.

(57) (2) The microneedle patch can be smoothly removed by mounting it below the edge of the patch case.

Example 2

(58) Mounting the patch case/microneedle patch on the front most surface of the applicator has the advantage that the applicator does not contact the skin during dose.

(59) In order to mount the patch case on the foremost surface of the applicator, a prototype patch case 10 as shown in FIG. 4 was manufactured.

(60) The patch case 10 includes two clasps 11 for mounting to an applicator.

(61) FIG. 5 shows a patch case 10 to which a microneedle patch is attached by thermal fusion, and is fitted and attached to an applicator 12 by using a clasp.

(62) The patch case may be disposable, and the microneedle patch may be shipped with the patch case preloaded.

(63) Since the patch case is attached to the front of the applicator, when the microneedle patch is administered to the subject, the patch case contacts the skin of the subject, but the applicator does not contact the skin of the subject.

(64) When successively dose microneedle patches to multiple recipients, the same applicator can be used successively without risk of cutaneous infection by replacing the disposable patch case to which the microneedle patches are attached.

Example 3-6, Comparative Example 1-2

(65) Patch cases with support films having different break strengths were produced by varying the heat-fusing conditions.

(66) A polyethylene (50 μm thick)/PET (20 mm thick) laminated film (Panac Corporation) was used as the support film.

(67) The support film was a PET film having was circular with a diameter of 28 mm, and an acrylic adhesive (HiPAS, manufactured by Cosmedy Pharmaceutical Co., Ltd.) was applied to a thickness of 50 μm on the PET film having a diameter of 28 mm and a front surface (downward side as viewed from the patch case).

(68) The patch case was injection molded in the shape of FIG. 4 and the material was high density polyethylene (Novatech HD, Nippon Polyethylene Co., Ltd.).

(69) The edge of the patch case, 5 in FIG. 3, had an area sufficient to heat bond the support film, and the inner diameter of the patch case was 2.3 cm.

(70) The support film and the patch case were fused together in the same manner as in Example 1.

(71) The temperature of the tip of the fusing head was about 190° C.

(72) The heated fuser head tip was pressed and fused about 0.2 mm to 0.5 mm from the surface of the support film.

(73) The fuser head was held in contact for 0.3 to 1 second and immediately released.

(74) The degree of fusing was varied by varying the depth of indentation and the contact time.

(75) The break strength of 5 samples of the fused product produced under the same conditions was measured, and the maximum value and the minimum value thereof were defined as “the fracture strength under the present condition”.

(76) The break strength of the thermal fusion was quantified by compressing the fusion surface from above of a patch case with a support film having a structure shown in FIG. 3 using a 1 cm diameter cylindrical rod using a tensile tester.

(77) The study was carried out at 40-60% relative humidity at room temperature.

(78) As the tensile study, a small tabletop tester EZ Test EZSX manufactured by Shimadzu Seisakusho Co., Ltd. was used.

(79) The compression speed was 10 mm/min.

(80) Details of the dosing study were as follows.

(81) The applicator as shown in FIG. 5 was fitted with a patch case with a microneedle patch having a microneedle array centrally adhered thereto.

(82) The microneedle patch was set on the applicator and applied into the abdominal of shaved male Wistar rats and microneedle arrays were immediately collected.

(83) The skin at the administration site was wetted with an aqueous solution of 1% Gentian Violet 8 (Wako Pure Chemical Industries, Ltd.), and the skin condition after wiping with gauze was observed to evaluate the administration result.

(84) The material of the microneedle array used was polyglycolic acid (Kureha Corporation), and about 800 needles with a height of 0.6 mm were erected on a circular substrate with a diameter of 10 mm.

(85) All samples were stored and tested for transport stability prior to dosing.

(86) In this test, peeling of the fused portion was observed 10 times by repeating natural dropping of the integrated microneedle array/support film/case from a height of 1 m to the floor. The results are shown in Table 2.

(87) TABLE-US-00002 TABLE 2 Fusing condition (the depth of The fracture Example, indentation/ strength under The Comparative the contact time) the present administration Example Heat-fusing pattern (mm/second)) condition (N) Transport stability test result Example 3 6-point fusion 0.3/0.3 0.5~1.0 No problem Appropriate (perfect circle) Example 3 6-point fusion 0.3/0.3 Same as above No problem Appropriate (perfect circle) Example 4 6-point fusion 0.5/0.5 3.0~5.0 No problem Appropriate (perfect circle) Example 4 6-point fusion 0.5/0.5 Same as above No problem Appropriate (perfect circle) Example 5 dash line fusion 0.5/0.5  7.0~10.0 No problem Appropriate Example 5 dash line fusion 0.5/0.5 Same as above No problem Appropriate Example 6 dash line fusion 0.5/1.0 10.0~20.0 No problem Appropriate Example 6 dash line fusion 0.5/1.0 Same as above No problem Appropriate Example 7 full point fusion 0.2/1.0 0.01~0.06 No problem Appropriate Example 7 full point fusion 0.2/1.0 Same as above No problem Appropriate Comparative solid line fusion 0.5/1.0 30~40 No problem Inappropriate Example 1 Comparative solid line fusion 0.5/1.0 Same as above No problem Inappropriate Example 1 Comparative 3-point fusion 0.3/0.2 0.005~0.009 Partial peeling of — Example 2 (perfect circle) the fused portion Comparative 3-point fusion 0.3/0.2 Same as above Partial peeling of — Example 2 (perfect circle) the fused portion Appropriate: It was observed that due to depth of blue color of the skin stained all the microneedles were inserted. Inappropriate: It was observed that due to depth of blue color of the stained skin a part of microneedles cannot be inserted. Further, a part of the substrate sheet remained without peeled.

DESCRIPTION OF THE SYMBOLS

(88) 1 Microneedle array 2 Patch case 3 Support film of microneedle patch 4 Adhesive-tape of microneedle patch 5 Edge of the patch case 6 Fuser heads of metal 7 Impact direction of the applicator 10 Patch Case for Applicator Front Mounting 11 Clamp 12 Applicator