JP5473996B2 - Device for transdermal drug delivery packaging - Google Patents

Description

  The present invention relates to a percutaneous absorption preparation having a support and a plurality of fine needles formed on the support for holding a target substance, and more particularly to an administration device for the percutaneous absorption preparation.

  As a preparation technique for transdermally administering a drug with high efficiency, a microneedle has been studied. The fine needle is a fine needle that does not feel pain even if it is stabbed into the skin.

  These fine needles have a hollow structure similar to that of an injection needle, and are of a type for injecting a chemical solution or a fine needle made of a biodegradable polymer such as polylactic acid. Furthermore, dissolution type fine needles based on water-soluble polymer substances have also been developed. That is, the target substance can be administered into the skin by holding the target substance in the base of the water-soluble polymer substance and inserting it into the skin, and then the base is dissolved by moisture in the skin.

  For example, Patent Document 1 describes that a fine needle is formed using a polymer substance that is soluble in the body and spinnable as a base. In Patent Document 2, in order to improve the bioavailability of the target substance contained in the fine needle, the fine needle is divided into a body insertion portion and a pressing portion, and the purpose is only for the body insertion portion. It describes the retention of substances.

  Patent Documents 1 and 2 also describe a sheet-like percutaneous absorption preparation in which a plurality of the fine needles are formed on a support such as a patch sheet.

  An administration device for administering a percutaneous absorption preparation to the skin has also been developed. For example, in Patent Document 3, a piston having a percutaneous absorption preparation attached to the tip thereof in FIGS. A transdermally absorbable preparation administration device having a casing for carrying out and a coil compression spring for driving a piston is described. However, this transdermally absorbable preparation administration device (1) is complicated and expensive, (2) the fine needle is not protected from moisture, (3) is difficult to use stably with one hand, (4) There is a problem that a sealing function for maintaining a sterilized state at the time of manufacture is lacking.

  In particular, in the case of a percutaneous absorption preparation having a fine needle prepared using a water-soluble and leaky polymer substance such as chondroitin sulfate, dextran, and hyaluronic acid as a base, if it is left in an air atmosphere, There is a possibility that the tip portion of the fine needle will soften by sucking.

  In addition, when administering a transdermal preparation to the skin of the abdomen, the administration device can be operated using both hands, but when administering the transdermal absorption preparation to the skin of the arm, it can be applied to the skin with one hand. Skin-absorbing preparations Some patients have difficulty administering a percutaneous absorption preparation vertically.

International Publication No. 2006/080508 International Publication No. 2009/066763 JP 2005-533625 A

  The present invention solves the above-mentioned conventional problems, and the object of the present invention is to prevent moisture from deteriorating the performance of the fine needle under sealing conditions until it is used after the preparation for transdermal absorption. Another object of the present invention is to provide a transdermally absorbable preparation-packaging administration device that can be kept hygienic, prevents breakage in the transportation process, and can be easily pressed vertically against the skin with one hand during administration.

The present invention provides a support rod having a flat tip surface perpendicular to the length direction, a transdermal preparation having a rear surface bonded to the tip surface, and the support rod sliding in the length direction. A percutaneously absorbable preparation administration device having a guide tube containing a support rod and having a flange perpendicular to the length direction at the distal end portion;
A packaging container that is self-supporting and flexible, covers the entirety of the transdermal absorption preparation administration device, and seals the transdermal absorption preparation administration device;
Disclosed is a transdermally absorbable preparation package administration device.

  In one certain form, the said packaging container is a PTP packaging container.

  In one certain form, the said packaging container can open the part corresponding to the front surface of a percutaneous absorption preparation, and the front surface of the flange of a guide cylinder.

  In one certain form, the said support rod is an injection rod, the said guide cylinder penetrates the injection needle mounting wall of an injection cylinder, and this flange is a wing | blade for holding | maintenance of an injection cylinder.

  In one certain form, it further has a means for driving the support rod accommodated in the guide pipe | tube toward the skin which is the administration object for the front end surface of this support rod.

  In one certain form, it has further the stopper which fixes a support bar with respect to a guide cylinder so that the position of the front end surface of a support bar may be maintained behind the front surface of the flange of a guide cylinder.

  In one certain form, the side wall of a guide cylinder has the vent hole which connects the inside and outside of a guide cylinder in the vicinity of the front-end | tip of a guide cylinder.

  In one certain form, the said support rod has a vent hole which connects the space in a guide cylinder which exists ahead from the front end surface of this support rod, and the space which exists behind the front end surface of a support rod.

  In one certain form, the said support bar has a hole which penetrates this support bar from the rear-end part of a bar | burr to the front-end | tip part of a bar | burr in the length direction, and reaches the rear surface of a percutaneous absorption preparation.

  Using the transdermally absorbable preparation packaging and administration device of the present invention, after producing the percutaneously absorbable preparation, it is moisture-proof so as not to impair the performance of the fine needle under sealed conditions until it is used, and is kept hygienic. It is possible to prevent damage during the transportation process and to easily press the skin vertically with one hand during administration.

It is sectional drawing of the transdermally absorbable preparation packaging administration device which is one Embodiment of this invention. It is sectional drawing of the percutaneous absorption preparation packaging administration device which is other embodiment of this invention. It is sectional drawing of the percutaneous absorption preparation packaging administration device which is other embodiment of this invention. It is sectional drawing of the percutaneous absorption preparation packaging administration device which is other embodiment of this invention. It is sectional drawing of the percutaneous absorption preparation packaging administration device which is other embodiment of this invention. It is sectional drawing of the percutaneous absorption preparation packaging administration device which is other embodiment of this invention. It is sectional drawing of the percutaneous absorption preparation packaging administration device which is other embodiment of this invention. It is sectional drawing of the percutaneous absorption preparation packaging administration device which is other embodiment of this invention.

  Referring to FIG. 1, the package administration device of the present invention is composed of three parts. The first part is a support bar 11 that holds the transdermally absorbable preparation 12 on the tip surface. The support bar 11 has a flat front end surface that is perpendicular to the length direction. The transdermally absorbable preparation 12 has a support and a plurality of fine needles holding a target substance. The fine needle is formed on the front surface of the support, and the rear surface of the support is bonded to the front end surface of the support bar 11.

  The fine needle is preferably prepared using a water-soluble, more preferably water-soluble and leaky polymer substance as a base. This is because the problem of the present invention in which the base material absorbs moisture in the atmosphere and prevents the tip portion of the fine needle from being softened is effectively achieved.

  Adhesion of the back surface of the support of the transdermally absorbable preparation to the tip surface of the support bar may be performed using an adhesive member such as an adhesive, a pressure sensitive adhesive, and a double-sided tape. However, it is necessary to adjust the adhesive force appropriately so that the percutaneous absorption preparation can be separated from the support rod after the percutaneous absorption preparation collides with the skin.

  The second part is a guide tube 13 for pressing the support bar 11 holding the transdermal absorption preparation vertically against the skin with one hand. The guide tube 13 accommodates the support bar so that the support bar slides in the length direction.

  It is preferable that the support rod 11 has a circular cross-sectional shape cut by a plane perpendicular to the length direction, and the diameter is substantially constant from the front end portion to the rear end portion. This is because it has a distal end surface enough to attach the transdermal absorption preparation, and it is easy to slide in the length direction inside the guide tube while keeping the distal end surface perpendicular to the longitudinal direction.

  However, it has a distal end surface that is perpendicular to the length direction and is capable of attaching a percutaneous absorption preparation, and slides inside the guide tube in the length direction while maintaining the distal end surface perpendicular to the length direction. As long as it can move, the cross-sectional shape and diameter of the support bar 11 may change in the middle. For example, the support bar 11 may have a form in which a disk having a front end surface is supported by a support made of a plate formed by a cross or radial combination, or a form having a front end face supported by a thinner bar-like support.

  The guide tube 13 has a flange 14 perpendicular to the length direction at the tip. The flange 14 comes into contact with the skin to be administered when the transdermal absorption preparation is administered. Thereby, the length direction of the guide tube is set perpendicular to the skin. An adhesive 17 may be provided on the surface of the flange 14 in order to ensure contact with the skin.

  The third part is a packaging container 20 for storing a percutaneously absorbable preparation administration device having a support rod for holding a percutaneously absorbable preparation and a guide tube under sealed conditions. The packaging container 20 covers the whole device for transdermal absorption preparation administration and seals it. The packaging container 20 is self-supporting and can maintain a space between the tips of the fine needles. In addition, the packaging container 20 is flexible, and the guide tube is placed from the outside of the packaging container in a state where the transdermal absorption preparation administration device is accommodated in the packaging container without taking the transdermal absorption preparation administration device out of the packaging container. Can be held and fixed by hand, and the support bar can be pushed.

  The packaging container 20 is provided with a seal portion 26 around the edge, and the moisture-proof film 21 is detachably bonded. As a result, the portions corresponding to the front surface of the transdermally absorbable preparation of the packaging container and the front surface of the flange of the guide tube can be opened. In order to ensure contact with the skin, an adhesive 17 may be provided around the edge of the packaging container, for example, around the seal portion. Also, adhere to the bottom of the packaging container so that the fine needle is securely stored in the guide tube until administration, that is, the position of the tip of the fine needle is maintained behind the front surface of the flange of the guide tube. An agent 17 may be provided to adhere the rear surface of the support bar.

  Part 3 uses pharmaceutical packaging, such as PTP packaging that can maintain hygiene without damaging the performance of the percutaneous absorption preparation and prevent breakage in the transportation process until it is used after manufacture. It is preferable.

  The transdermally absorbable preparation administration device used in the present invention can be produced by improving the components of a commercially available syringe, for example, a disposable syringe. For example, an injection rod can be used as the support rod 11. As the guide tube 14, the tip of the syringe barrel can be cut to penetrate the injection needle mounting wall and the front and back can be reversed. In that case, the holding wing of the syringe barrel functions as the flange 14.

  With reference to FIG. 2, the support rod 11 may be provided with a hole that penetrates from the rear end portion of the rod in the length direction to the front end portion of the rod and reaches the rear surface of the transdermally absorbable preparation. After the percutaneous absorption preparation is collided with the skin, when the percutaneous absorption preparation packaging administration device is removed from the skin, the percutaneous absorption preparation is pressed against the skin through a stick through this hole. Can be left on.

  With reference to FIGS. 3 and 4, a vent hole that communicates the inside and outside of the guide tube 13 may be provided on the side wall of the guide tube 13 in the vicinity of the tip of the guide tube 13. By doing so, when the support bar is pushed toward the skin, the air in the guide cylinder existing ahead of the front end surface of the support bar is released outside the guide cylinder. That is, the air existing between the tip surface of the support bar and the skin is not compressed, and the collision pressure against the skin of the transdermal absorption preparation is not weakened.

  For the same purpose, the support rod may be provided with a vent hole that communicates the space in the guide tube that exists in front of the tip surface of the support rod and the space that exists in the rear of the tip surface of the support rod.

  1-4 can be used as follows, for example.

  First, the guide tube 13 is grasped from the outside of the packaging container 20 with one hand, the end of the moisture-proof film 26 is grasped with the other hand, and peeled off from the seal portion 26. Thereby, the part corresponding to the front surface of the percutaneous absorption preparation of a packaging container and the front surface of the flange of a guide cylinder opens. While holding the opened transdermal preparation packaging administration device with one hand from the outside of the packaging container, the opening is applied to the administration target portion of the skin. As a result, the edge of the packaging container 20 and the surface of the flange 14 of the guide cylinder are fixed to the skin by an adhesive 17, for example.

  The rear end of the support bar is pushed down from the outside of the packaging container to drive the support bar toward the skin. The support rod may be driven manually or using an elastic member such as a spring or rubber. Thereby, the front surface of the transdermally absorbable preparation collides with the skin, and the fine needle is inserted into the skin. Next, a thin stick is inserted into the hole of the support bar shown in FIG. 2 or 4 from the rear end of the support bar to press the percutaneously absorbable preparation against the skin. Then, the percutaneous absorption preparation package administration device is removed from the skin while performing the operation. As a result, the transdermally absorbable preparation is separated from the transdermally absorbable preparation package administration device and left on the skin. Thereafter, a tape, for example, a medical adhesive tape is applied from the rear surface of the transdermal absorption preparation, and the transdermal absorption preparation is fixed on the skin.

  Referring to FIG. 5, the transdermally absorbable preparation administration device used in the present invention is injected in order to prevent the percutaneously absorbable preparation from absorbing moisture before it is taken out from the packaging container 20 and administered to the patient's skin. While sealing with the moisture-proof film 15 at the exit of the cylinder, a packing 22 may be provided in the upper gap between the injection rod and the injection cylinder. The moisture-proof film 15 is removed by grasping the catching hand 16 for peeling immediately before administration. Further, the packing 22 is automatically removed by an operation of pushing down the injection rod.

  The transdermally absorbable preparation packaging and administration device of the present invention is such that the fine needle is securely stored in the guide tube until administration, that is, the position of the tip of the fine needle is maintained behind the front surface of the flange of the guide tube. Thus, a stopper 18 for fixing the support rod to the guide tube may be provided on the side wall of the guide tube. Thus, the fine needle can be securely stored in the guide tube until administration, and a space can be maintained between the tip of the fine needle.

  In this case, as a means for driving the support bar 11 toward the skin, a hook 23 is provided on the side wall of the guide tube, the middle part of the rubber 19 extends to the rear end part 25 of the support bar, and both ends are fixed to the hook 23. You may keep it.

  Referring to FIG. 6, the stopper 18 has a rod shape having a predetermined length, and may be configured to support between the rear end surface of the guide tube and the rear end portion of the support rod. Further, the driving means of the support rod 11 may be a spring 24 in which both ends are fixed to the rear end portion of the guide tube and the rear end portion 25 of the support rod in an extended state.

  The operation of applying the tip of the guide tube of the transdermally absorbable preparation administration device from which the moisture-proof film 15 has been removed to the skin and the operation of releasing the stopper can be performed with one hand. For this reason, in a transdermal preparation preparation device having a combination of a stopper for fixing the support rod to the guide tube and a means for driving the support rod toward the skin, basically, it can be adjusted with a fixed force with one hand. The percutaneously absorbable preparation can be vertically impacted against and pressed against the skin.

  With reference to FIGS. 7 and 8, a vent hole that communicates the inside and the outside of the guide tube 13 may be provided on the side wall of the guide tube 13 in the vicinity of the tip of the guide tube 13. By doing so, when the support bar is pushed toward the skin, the air in the guide cylinder existing ahead of the front end surface of the support bar is released outside the guide cylinder. That is, the air existing between the tip surface of the support bar and the skin is not compressed, and the collision pressure against the skin of the transdermal absorption preparation is not weakened.

  Specific embodiments will be described below with reference to examples. Of course, the present invention is not limited to the following examples.

Example 1
The rubber attached to the tip of the injection rod of a 10 ml disposable syringe (Terumo syringe ss-10ESz manufactured by Terumo Corporation) was removed. The tip of the syringe barrel was excised from the 0 milliliter display line. In order to attach the rubber band to the syringe barrel, an attachment ring was fitted on the outside and fixed with an adhesive, or a cut was made in the syringe barrel instead of the attachment ring. The injection rod was inserted from the cut surface of the syringe barrel. The syringe rod and syringe were connected with a rubber band.

  30 mg of sodium sodium (homemade), 0.2 mg of Evans blue (Nacalai Tesque) and 30 mg on a silicon substrate with an inverted conical pore with a depth of about 500 microns per square centimeter and an opening diameter of about 300 microns A viscous concentrated solution prepared by adding 80 μl of purified water to sodium chondroitin sulfate C (Wako Pure Chemical Industries, Ltd.) was applied.

  It was covered with Saran Wrap (Kureha Chemical), rotated with a tabletop centrifuge (Kubota 4000) at 3000 rpm for 5 minutes with the silicon resin substrate, and filled under load using centrifugal force. After removing the Saran wrap and removing the residue on the silicon resin substrate, add 30 μl of purified water to 30 mg of chondroitin sulfate C sodium salt and 0.5 mg of Hibiswaco 103 (Wako Pure Chemical Industries, Ltd.) on the silicon substrate. It was applied to the holes.

  It was covered with Saran Wrap (Kureha Chemical), and the silicon resin substrate was rotated for 5 minutes with a desktop centrifuge and filled under load using centrifugal force. An adhesive prepared by adding 36 ml of purified water to 1.6 g of Hibiswako 103 (Wako Pure Chemical Industries, Ltd.) was applied to a cellulose acetate tablet base having a diameter of 15 mm, and then covered on a silicon base. The tablet was dried at 30 ° C. for 2 hours while being pressed against the silicone substrate, and then the tablet was peeled off from the silicone substrate to obtain a transdermal absorption preparation having a diameter of 15 mm.

  After the back surface of the transdermal absorption preparation was affixed to the flat part of the tip of the injection rod, the tip of the injection rod was pulled up to the 7-ml display line of the syringe barrel, and a stopper was inserted and fixed in the hole opened in the syringe barrel. Sealing was carried out using a circular polyethylene film having a diameter of 20 mm, which was provided with a part for removal on the holding wing of the syringe barrel. An adhesive made of an acrylate copolymer was applied to the outer part of the retaining wing not covered with a seal film, and covered with a film having a width of 20 mm and a length of 30 mm. The above injection rod and syringe were put in a PTP package and sealed (FIG. 5).

  The prepared PTP package was opened and the administration device was taken out. The syringe was peeled off with a handle for removing the sealing film from the syringe. Further, the film covering the adhesive surface was peeled off, and the syringe barrel was fixed perpendicularly to the skin by sticking the retaining wing of the syringe barrel to the skin of the left arm.

  When the stopper holding the injection rod was removed from the syringe barrel, a fine needle of the transdermal absorption preparation attached to the tip of the injection rod pierced the skin. After pressing for about 1 minute in that state, the administration device was removed. When the skin was observed, blue dots derived from Evans Blue were transferred, and the microneedle was successfully administered to the skin. The pressure applied by the injection rod was measured with a digital force gauge (FGN-2, Nidec Symposium) and found to be 4.75N.

Example 2
The rubber attached to the tip of the injection rod of a 10 ml disposable syringe (Terumo syringe ss-10ESz manufactured by Terumo Corporation) was removed. The syringe was excised from the tip of the syringe to the 5 milliliter mark. The injection rod was inserted from the cut surface of the syringe barrel. The injection rod and syringe were connected with a metal spring.

  After the same transdermal absorption preparation as prepared in Example 1 was applied to the flat part of the tip of the injection rod, the tip of the injection rod was pulled up to the 8 ml display line of the syringe barrel, and the syringe barrel edge and injection A stopper was fitted between the stick's thumb and the part pressed by the thumb. Sealing was carried out using a circular polyethylene film having a diameter of 20 mm, which was provided with a part for removal on the holding wing of the syringe barrel. An adhesive made of an acrylate copolymer was applied to the outer part of the holding wing not covered with the sealing film, and covered with a film having a width of 20 mm and a length of 30 mm. The above injection rod and syringe were put in a PTP package and sealed (FIG. 6).

  Male rats weighing 357 grams were anesthetized with pentobarbital and fixed supine on the operating table. The abdominal body hair was removed, and a cut of about 4 cm in length was made with a scalpel in the left and right abdomen. A plate 3 cm wide, 15 cm long and 0.5 cm thick was inserted into the abdominal cavity so as to penetrate the abdomen of the rat. The prepared PTP package was opened and the administration device was taken out. The syringe was peeled off with a handle for removing the sealing film from the syringe. The film covering the adhesive was peeled off, and the syringe barrel was fixed perpendicularly to the skin by attaching the wing for holding the syringe barrel to the abdominal skin of the rat.

  When the stopper that fixes the injection rod and syringe is removed, the fine needle of the transdermal absorption preparation attached to the tip of the injection rod pierces the skin, the blue dots derived from Evans Blue are transferred, and the microneedle is successfully applied to the skin. I was able to administer it. The pressure applied by the injection rod was measured with a digital force gauge (FGN-2, Nidec Symposium) and found to be 5.23N.

Example 3
The rubber attached to the tip of the injection rod of a 10 ml disposable syringe (Terumo syringe ss-10ESz manufactured by Terumo Corporation) was removed and the opposite side was cut to a length of 20 mm. From the tip of the syringe barrel up to the 11 ml display line was excised. The injection rod was inserted from the cut surface of the syringe barrel. The same percutaneously absorbable preparation having a diameter of 15 mm as that prepared in Example 1 was attached to the flat portion at the tip of the injection rod.

  In the same manner as in Example 1, an adhesive made of an acrylate copolymer was applied to the holding blade of the syringe barrel. Adhesive was also applied to the upper end of the injection rod, the injection rod and the syringe barrel were placed in PTP packaging, and the upper end of the injection rod was adhered to the inner surface of the PTP packaging material. PTP packaging was completed by heat sealing with an aluminum sheet. The percutaneously absorbable preparation was stored in an upward state (FIG. 1).

  The prepared PTP package was opened by pulling the non-adhesive piece on the aluminum foil side. The adhesive was applied to the skin of the left arm using the adhesive applied to the wing for holding the syringe barrel in the PTP package. When the fine needle of the percutaneous absorption preparation was pierced into the skin by hitting the upper part of the PTP package with the palm of the right hand, it was successfully administered to the skin. The pressure applied to the injection rod with the right hand was measured with a digital force gauge FGN-5 and found to be 15.3N.

11 ... support rod,
12 ... Transdermal absorption preparation,
13 ... guide tube,
14 ... Flange,
15 ... moisture-proof film,
16 ... Patcher for peeling,
17 ... adhesive,
18 ... stopper,
19 ... rubber,
20: Packaging container,
21 ... moisture-proof film,
22 ... Packing,
23 ... Hook,
24 ... Spring,
25 ... the rear end of the support rod,
26: Seal part.

Claims (8)

A support bar having a flat tip surface perpendicular to the length direction, a percutaneous absorption preparation having a rear surface bonded to the tip surface, and the support rod stored so that the support rod slides in the length direction A transdermal preparation administration device having a guide tube having a flange perpendicular to the length direction at the tip, and
A packaging container that is self-supporting and flexible, covers the entirety of the transdermal absorption preparation administration device, and seals the transdermal absorption preparation administration device;
A transdermally absorbable preparation packaging administration device comprising :
The transdermally absorbable preparation has a support and a plurality of fine needles holding a target substance,
The fine needle is prepared using a water-soluble polymer substance as a base,
The packaging container is a PTP packaging container;
The PTP packaging container can open a portion corresponding to the front surface of the transdermally absorbable preparation and the front surface of the flange of the guide tube,
A moisture-proof film is peelably bonded to the opening of the PTP packaging container.
Device for transdermal drug delivery packaging. The percutaneous absorption preparation package administration device according to claim 1 , further comprising means for driving the support bar accommodated in the guide tube toward the skin to be administered with the tip surface of the support bar. The percutaneous absorption preparation packaging according to claim 1 or 2 , further comprising a stopper for fixing the support rod to the guide tube so that the position of the tip surface of the support rod is maintained behind the front surface of the flange of the guide tube. Administration device. The percutaneous absorption preparation packaging and administration device according to any one of claims 1 to 3 , wherein the side wall of the guide tube has a vent hole communicating with the inside and outside of the guide tube in the vicinity of the tip of the guide tube. The support rod is any one of claim 1 to 4 having a vent hole communicating with the space existing behind the front end surface of the space and the support rod guide tube present in front of the front end surface of the support rod A transdermally absorbable preparation packaging administration device according to 1. The support rod penetrates through the support rod in the longitudinal direction from the rear end of the rod to the tip of the rod, in any one of claims 1 to 5 having a hole that reaches the rear surface of the percutaneously absorbable preparation The transdermally absorbable preparation packaging administration device described. The said support rod is an injection rod, the said guide cylinder penetrates the injection needle mounting wall of an injection cylinder, and this flange is a wing | blade for holding | maintenance of an injection cylinder. The transdermally absorbable preparation packaging administration device described. Grasping the guide tube from the outside of the packaging container and opening the portions corresponding to the front surface of the percutaneous absorption preparation of the packaging container and the front surface of the flange of the guide tube;
  While holding the transdermal absorption preparation packaging administration device from the outside of the packaging container, apply the opening of the packaging container to the administration target portion of the skin; and
  8. The method according to claim 1, wherein the support bar is driven toward the skin so that the front surface of the percutaneous absorption preparation collides with the skin and a fine needle is inserted into the skin. The transdermally absorbable preparation package administration device according to one item.

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