JP4237819B1 - Transdermal preparation - Google Patents

Abstract

[Problem] To provide a percutaneous absorption preparation that can be percutaneously absorbed easily and continuously even with a water-soluble oligomer solution or polymer solution with a simple structure.
[MEANS FOR SOLVING PROBLEMS] A drug indwelling part having a drug holding part for holding a drug therein, an adhesive layer for supporting the drug indwelling part, and a drug having a thickness within a range of 1 to 100 μm A percutaneous absorption-type preparation comprising a support made of an impermeable base material, wherein the drug indwelling part is provided with a pressurizing means for pressurizing the drug holding part, The permeable substrate is broken by needles as an external mechanical stimulus, thereby releasing the drug at a constant rate.
[Selection] Figure 1

Description

  The present invention relates to a transdermally absorbable preparation, and in particular, a transdermally absorbable preparation that can be easily and continuously percutaneously absorbed even if it is an oligomer or polymer drug that is generally not suitable for transdermal absorption. About.

Injection is a typical method for administering a drug when rapid action is desired. Furthermore, in recent years, a needle-free injection method using a jet injector in which a drug (medical solution) is fed into the body using water pressure has been developed and clinically applied to subcutaneous injection of insulin and the like.
However, when an injection or a jet injector is used, since the drug is temporarily sent into the body, there has been a problem that frequent administration is required to maintain the drug effect.

In addition, as a continuous drug administration method, a percutaneous absorption type preparation comprising a drug (drug solution) reservoir and an adhesive layer, a drug reservoir, and a release control film for controlling the drug release amount, Various percutaneous absorption preparations comprising an adhesive layer have been proposed.
As an example of drug administration using a jet injector, Patent Document 1 (Japanese Patent Laid-Open No. 7-255845) discloses a jet injector 102 for making a hole in the stratum corneum of skin by water pressure, as shown in FIG. A reservoir 112 for containing the drug 106 and a drug permeable adhesive layer 110 for closing the opening by the jet injector 102, and the ceiling of the reservoir 112 has an opening by the jet injector 102. Discloses a percutaneous absorption device 100 provided with a rubber 104 for closing a part and a method for promoting percutaneous absorption of a drug using the same.
In the case of such a percutaneous absorption device 100, an opening is formed in the skin surface (not shown) via the reservoir 112 and the adhesive layer 110 by the jet injector 102, and the concentration difference between the reservoir 112 and the drug in the blood vessel is determined. This is a system in which the drug is percutaneously absorbed through this opening.

Patent Document 2 (Japanese Patent Publication No. 11-509123) discloses a percutaneous absorption system for drug release, as shown in FIG. 13, which is a reservoir for containing an active substance 208 as a drug. 210, a transdermal absorption system including a plurality of micro pins 206 or micro blades for administering an active substance and having an opening 204 provided at the tip of the micro pins 206 or micro blades is disclosed. .
In the case of such a percutaneous absorption system, a large number of micro pins 206 or micro blades provided on the bottom surface of the reservoir 210 are pushed into the stratum corneum of the skin, and the diffusion due to the concentration difference between the reservoir 210 and the drug in the blood vessel is basically used. In this method, the active substance 208 as a drug is percutaneously absorbed through an opening 204 provided at the tip of many micro pins.
JP-A-7-255845 (Claims) Japanese National Patent Publication No. 11-509123 (Claims)

  However, according to the percutaneous absorption device 100 disclosed in Patent Document 1 (Japanese Patent Application Laid-Open No. 7-255845) and the percutaneous absorption promotion method for a drug using the device, a drug is formed, although a hole is made in the skin surface. Since the diffusion due to the difference in concentration is basically utilized, the amount of permeation of the drug may be insufficient, and particularly when the drug is an oligomer or polymer, it is difficult to permeate it quickly.

Further, according to the transdermal absorption device 200 disclosed in Patent Document 2 (Japanese Patent Publication No. 11-509123), since the movement of the drug 208 is only a concentration difference, the drug 208 is a low molecular compound having polarity. If it was an oligomer or polymer, it was difficult to absorb it transdermally.
Further, when a large number of micro pins 206 or micro blades are pushed into the skin, the opening 204 at the distal end is blocked, making it difficult to release the drug 208 at a constant rate.
In addition, since it is necessary to provide a large number of micro pins 206 or micro blades, not only is the manufacturing difficult, but the length of the micro pins 206 and the like is limited, and the drug cannot be released into the stratum corneum. It was.
Furthermore, according to the preferred example of the percutaneous absorption device 200 disclosed in Patent Document 2 (Japanese Patent Publication No. 11-509123), a pump or a piezoelectric film may be introduced into the system of the percutaneous absorption device 200. It has been proposed, but this time, a new problem has been seen in that the transdermal absorption device becomes large-scale and portability and economy are impaired.

Therefore, the inventors of the present invention, as a result of intensive studies to solve the above-mentioned problems, pressurize the drug holding part and break the substrate by mechanical stimulation such as an injection needle, The present invention has been completed by discovering that it is excellent in sticking property and can be percutaneously absorbed into a wide variety of drugs continuously and rapidly.
That is, an object of the present invention is to provide a percutaneous absorption type preparation having a simple structure and capable of being percutaneously absorbed easily and continuously even with an oligomer or polymer drug. To do.

According to the present invention, a drug indwelling part having a drug holding part for holding a drug therein, an adhesive layer for supporting the drug indwelling part, and a thickness within a range of 1 to 100 μm. A percutaneous absorption-type preparation comprising a support part made of a certain drug-impermeable base material, and a part or all of the drug indwelling part as a pressurizing means for pressurizing the drug holding part in the drug indwelling part Is composed of an elastic member for pressurizing the drug held in the drug holding portion, and the drug-impermeable base material in the support portion can be broken by a needle-like material as a mechanical stimulus, A transdermal absorption-type preparation characterized in that the drug indwelling part is in a pressurized state is provided, and the above-mentioned problems can be solved.
That is, according to such a percutaneously absorbable preparation, the drug indwelling portion includes a pressurizing means for pressurizing the drug holding portion holding the drug, and the drug-impermeable base material in the support portion is provided. Because it breaks easily due to external mechanical stimulation, even drugs that are not generally suitable for transdermal absorption can be absorbed rapidly and continuously through a drug-impermeable substrate. it can.
In addition, since the support portion has not only an adhesive layer but also a drug-impermeable base material, not only manufacturing is easy, but even when pressurized, liquid leakage may occur, It is possible to effectively prevent the drug indwelling portion from being deformed excessively.
Further, by configuring the above-described pressurizing means from an elastic member as a part or all of the drug indwelling part, the drug holding part in which the drug is easily held in the drug indwelling part can be provided even with a simple structure. Can be pressurized. In addition, with such a structure, it is possible to easily maintain a certain shape even when the drug holding part is pressurized to a relatively high pressure.
Moreover, even if it is a case where a drug holding part is pressurized by making the thickness of the drug-impermeable base material in the support part mentioned above into the value within the range of 1-100 micrometers, it can deform | transform excessively. On the other hand, if it is such a base material, it can be easily broken by a mechanical stimulus such as an injection needle. Further, with this configuration, since the drug indwelling part, the adhesive layer, and the like can be provided on both sides of the base material by using such a base material, the manufacture of a transdermal absorption preparation becomes extremely easy.
Furthermore, by making the above-described drug-impermeable substrate breakable with a needle-like material as a mechanical stimulus, the support unit can be used without using a special device such as a jet injector. The drug-impermeable substrate can be easily broken. In addition, since the tip of the injection needle is thin, by limiting the thickness of the injection needle, etc., the size of the mechanical stimulus from the outside can be easily controlled, and an opening is provided. Even in this case, liquid leakage can be effectively prevented.

Further, another aspect of the present invention provides a drug indwelling part having a drug holding part for holding a drug therein, an adhesive layer for supporting the drug indwelling part, and a thickness in the range of 1 to 100 μm. A transdermal absorption-type preparation comprising a drug-impermeable substrate having a value within the range, and as a pressurizing means for pressurizing the drug holding part in the drug indwelling part, The inside is filled with bubbles, the drug-impermeable base material in the support part can be broken by a needle-like material as a mechanical stimulus, and the drug indwelling part is in a pressurized state. It is a transdermal absorption preparation.
That is, as a pressurizing means for pressurizing the drug holding part in the drug indwelling part, the drug is easily held in the drug indwelling part even if it has a simple structure by filling the inside of the drug holding part with bubbles. The applied drug holding part can be pressurized. In addition, with such a structure, it is possible to easily maintain a certain shape even when the drug holding part is pressurized to a relatively high pressure.

In constituting the transdermal absorption preparation of the present invention, the elastic member is preferably a foam.
If comprised in this way, even if it is a case where a drug is easily inject | poured in a drug holding | maintenance part and it pressurizes, a fixed shape can be maintained easily. In addition, if the elastic member is a foam, it is possible to apply an appropriate pressure to the drug holding portion and to release the drug at a constant rate during use. Furthermore, if the elastic member is a foam, the side walls and the like can be easily manufactured by punching, for example.

In constructing the transdermally absorbable preparation of the present invention, a liquid leakage preventing layer having a thickness of 5 to 2,000 μm is provided on the inner surface and / or outer surface of the drug indwelling portion, or one of the surfaces. Is preferred.
With this configuration, it is possible to effectively prevent liquid leakage from the opening provided by the mechanical stimulation during the mechanical stimulation by the injection needle or the like or after the mechanical stimulation is applied. it can.

In constituting the transdermal preparation of the present invention, the drug is preferably an oligomer or a polymer.
If comprised in this way, the percutaneous absorption type | mold formulation containing the drug which was not able to be used substantially conventionally can be provided.

  DESCRIPTION OF EMBODIMENTS Embodiments relating to a transdermal preparation of the present invention and a method for transdermal absorption of a drug using them will be specifically described with reference to the drawings as appropriate.

[First embodiment]
In the first embodiment, as illustrated in FIG. 1 or FIG. 2, a drug indwelling unit 20 including a drug holding unit 21 for holding a drug therein and an adhesive for supporting the drug indwelling unit 20 A support portion comprising an agent layer (first adhesive layer) 12 and a drug-impermeable base material (first drug-impermeable base material) 11 having a thickness in the range of 1 to 100 μm. 13 is a percutaneous absorption type preparation 10 including the elastic member 14 as a pressurizing means for pressurizing the drug holding part 21 holding the drug 19 in the drug indwelling part 20. Alternatively, the percutaneous absorption is characterized by being filled with bubbles 32 and allowing the drug-impermeable base material 11 in the support portion 13 to be broken by a needle-like material as a mechanical stimulus from the outside. Type formulation drug 10.
Hereafter, it demonstrates concretely for every structural requirement of a transdermal formulation.

1. Drug Indwelling Part (1) Form The drug indwelling part can hold the drug in the drug holding part for a certain period of time in a pressurized state, and gradually remove the drug when at least the drug-impermeable substrate breaks. It is preferable to be in a form that can be released into Moreover, it is preferable that it is an easy form also about manufacture of a drug indwelling part. Therefore, the outer shape of the drug indwelling portion is preferably rectangular as shown in FIGS. 1 to 3 or cylindrical as shown in FIGS. 4 to 6. In FIGS. 4 and 6, a perspective cross section divided into two parts is shown so that the internal state of the cylindrical drug indwelling portion can be well understood.
Moreover, as shown in FIG. 1, when the side wall of the drug indwelling part 20 is comprised from the elastic member 14, and the external shape of the drug indwelling part 20 is made into a cylindrical shape or a rectangle, the thickness of this side wall is usually 1-10 mm. It is preferable to set the side wall height to a value within the range of 1 to 50 mm.
The drug is usually used in the state of a drug solution mixed with or dispersed in a solvent such as water or ethanol. In that case, the drug concentration may be selected as appropriate, but usually it is preferably a value within the range of 0.01 to 90% by weight, and preferably within the range of 0.1 to 50% by weight relative to the total amount. More preferably, it is a value.

(2) Drug In addition, the type of drug held in the drug holding part is not particularly limited. For example, nitroglycerin (angina drug), isosorbate nitrate (angina drug), clonidine (hypertension) Medicine), tulobuterol (bronchial asthma medicine), everizone (muscle pain medicine), salicylic acid (muscle pain medicine), estradiol (hormonal medicine), phennital (cancer pain relieving medicine), scoboramine (vehicle antistatic medicine), lidocaine (anesthetic) Medicine), nicotine (smoking cessation aid) and the like alone or in combination of two or more.
In addition, regarding the type of drug, it may be an oligomer or polymer generally not suitable for transdermal absorption. That is, even if the drug is an oligomer or polymer having a molecular weight in the range of 500 to 100,000, particularly a water-soluble oligomer or polymer, it can penetrate the skin. Examples of such drugs include insulin (a therapeutic agent for diabetes), calcitonin (a therapeutic agent for osteoporosis), and vasopressin (a diuretic).
Further, a predetermined amount of an absorption promoter, for example, alcohols, glycols, vegetable oils, etc. may be added to the drug held in the drug holding part.

(3) Pressurizing condition The pressurizing condition of the drug holding unit is preferably determined in consideration of the type, viscosity, concentration, etc. of the drug held in the drug holding unit. For example, the initial pressure of the drug holding unit is 1 It is preferable to set the value within the range of 0.05 × 10 ^{5 to} 2 × 10 ⁵ Pa.
The reason for this is that when the initial pressure of the drug holding part becomes a value of less than 1.05 × 10 ⁵ Pa, the permeation rate in the case where the drug is an oligomer or a polymer may be remarkably reduced. This is because if the initial pressure of the drug holding part exceeds 2 × 10 ⁵ Pa, the drug permeation rate may be significantly increased or the drug holding part may be damaged.
Therefore, the initial pressure of the drug holding part is more preferably set to a value within the range of 1.1 × 10 ^{5 to} 1.8 × 10 ⁵ Pa, and preferably 1.2 × 10 ^{5 to} 1.7 × 10 ⁵ Pa. More preferably, the value is within the range.

(4) Osmotic pressure Moreover, it is preferable that the osmotic pressure of the drug in the drug holding part is higher than the osmotic pressure of the body fluid. The reason for this is not only the release of the drug by pressurization but also the osmotic pressure of such a drug, so that even oligomers and polymers generally not suitable for transdermal absorption can be more easily and continuously transdermally. This is because it can be absorbed.
Specifically, it is preferable to set the osmotic pressure of the drug within a range of 300 to 500 mOsm.

(5) Division type As shown in Drawing 7 (a), drug indwelling part 20 is divided and percutaneous absorption type provided with drug holding part 21 which consists of a plurality of cells, for example, 2-10 cells. It can also be set as the formulation 70.
FIG. 7B is a perspective view of the side wall formed of the elastic member 14 having two spaces so that the configurations of the drug indwelling unit 20 and the drug holding unit 21 can be easily understood.

2. As shown in FIG. 1, the support part (1) is composed of an adhesive layer 12 for supporting a drug indwelling part 20 including a drug holding part 21 in which a drug 19 is held, and a drug impervious. It is the structure which consists of the base material 11 of. The structure is not particularly limited as long as the drug-impermeable base material 11 can be broken at least by an external mechanical stimulus. It is preferable that the indwelling unit 20 can be affixed, and even if the drug holding unit 21 is in a pressurized state, the drug does not leak and the drug indwelling unit 20 can be held in a predetermined shape. .
Accordingly, the support portion 13 has a rectangular shape as shown in FIGS. 1 to 3 or a shape corresponding to the drug indwelling portion 20 that is cylindrical as shown in FIGS. 4 to 6. Is preferred.
On the other hand, if the thickness of the support portion 13 is excessively thick, it may be difficult to handle for attaching to the skin or the like, and may be easily peeled off. Therefore, the cross-sectional shape of the support portion is preferably a thin film as shown in FIG.

(2) Drug-impermeable substrate (2) -1 type The type of the drug-impermeable substrate in the support is not particularly limited, but a plastic film, for example, a polyester film or a polyamide film. Polyolefin film, polystyrene film, polyvinyl chloride film, fluororesin film, polycarbonate film, polysulfone film, polyimide film, silicone resin film and the like are preferable.
The reason for this is that such a type of base material has appropriate mechanical strength and durability, so that even when the drug holding part is pressurized, the drug oozes out from the base material, This is because the material rarely deforms excessively. Moreover, if it is such a kind of base material, since the breaking strength is also appropriate, it can be easily broken by a mechanical stimulus such as an injection needle. Furthermore, with such a base material, a drug indwelling part, an adhesive layer, and the like can be laminated on both surfaces thereof, so that it is very easy to manufacture a transdermal absorption preparation.
In addition, the drug impermeability of the base material means that there is no significant drug leakage under the pressurizing conditions described later.

(2) -2 Thickness Further, the thickness of the drug-impermeable base material in the support portion is set to a value within the range of 1 to 100 μm.
This is because, when the thickness of the drug-impermeable substrate is less than 1 μm, it may be difficult to support the drug indwelling part or to laminate the adhesive layer. . On the other hand, if the thickness of the base material exceeds 100 μm, it is difficult to follow and adhere to an uneven surface such as skin, or it is difficult to break easily due to mechanical stimulation such as an injection needle. This is because there is a case of becoming.
Accordingly, the thickness of the drug-impermeable base material in the support portion is more preferably set to a value within the range of 10 to 100 μm, and further preferably set to a value within the range of 15 to 50 μm.

(2) -3 Fracture part Moreover, for example, a slit 90 as shown in FIG. 8A, a score line 91 as shown in FIG. It is preferable that at least one fracture portion such as an emboss 92 as shown in (c), a perforation 93 as shown in FIG. 8 (d), or a thin portion 94 as shown in FIG. 8 (e) is provided. .
The reason for this is that by providing such a rupture portion, even a base material that is inherently difficult to break by mechanical stimulation from the outside such as an injection needle can be easily broken, This is because breakage in the substrate other than the place can be effectively prevented.
It should be noted that the slit 90 as shown in FIG. 8 (a), the score line 91 as shown in FIG. 8 (b), and FIG. When the emboss 92 as shown in FIG. 8C and the perforation 93 as shown in FIG. 8D are provided, it is preferable that these broken portions are provided in the vicinity of the center of the substrate. Moreover, it is preferable that such a fracture | rupture part does not penetrate in the thickness direction of a drug-impermeable base material until it gives mechanical irritation.

(2) -4 Transparency etc. Moreover, it is preferable that the drug-impermeable base material in a support part has transparency or translucency. If comprised in this way, since conditions, such as skin, can be visually observed through this base material, a predetermined place can be correctly fractured | ruptured by mechanical stimulation from the outside, such as an injection needle.
Note that the base material itself in the support part does not necessarily have transparency or translucency, and an opening (window part) or a pore is provided in a part of the base material in the support part, such as skin as a base. Anything can be recognized.

(2) -5 Arrangement In addition, the drug-impermeable substrate can be provided at least on the support, but as shown in FIGS. 1 (a) and 1 (b), the drug-impermeable substrate. 11 is preferably used not only for the support part 13 but also for the ceiling part of the drug indwelling part 20.
In this case, it is necessary to break the substrate over at least two places. However, even when pressurized, the deformation is further reduced, and drug leakage before use can be sufficiently prevented. Moreover, the function as a base material in the case of forming a liquid-leakage prevention layer can be exhibited by using a drug-impermeable base material for a ceiling part. Therefore, the liquid leakage prevention layer can be easily provided with a uniform thickness.
Further, as shown in FIGS. 2A and 2B, it is also preferable to extend the base material 11 of the support part to be a part or all of the side wall of the drug indwelling part. If comprised in this way, even if it is a case where it pressurizes, a deformation | transformation of a drug indwelling part will decrease, and the liquid leakage of the drug before use can fully be prevented.
Further, as shown in FIG. 3A, the drug-impermeable base material 11 is used not only for the support part 13 but also for the side wall and the ceiling part of the drug indwelling part 20, and the drug-impermeable base material. It is also preferable to have a generally one-piece structure consisting of 11. And as shown to Fig.3 (a), while laminating | stacking an elastic member on a part of side wall which consists of a drug-impermeable base material, while being able to pressurize a drug efficiently, before using it, Drug leakage can be prevented sufficiently.
As shown in FIG. 3A, when the entire drug indwelling portion 20 is made of a drug-impermeable base material, cap-like objects corresponding to the side wall and the ceiling portion of the drug indwelling portion 20 are prepared in advance. In addition, it is also preferable to have a structure in which an elastic member is filled in and affixed to a film made of a drug-impermeable substrate. If comprised in this way, even if it is a case where a drug holding | maintenance part is pressurized efficiently, while a drug leak can fully be prevented, manufacture also becomes very easy.

(3) Adhesive layer (3) -1 type The type of the adhesive that constitutes the adhesive layer in the support is not particularly limited. For example, an acrylic adhesive, a silicone adhesive, and a rubber adhesive Agents and the like.
In addition, in order to reliably support the drug indwelling part provided with the drug holding part in a pressurized state, the glass transition temperature of these pressure-sensitive adhesives obtained by DSC measurement is set to a value within the range of −40 to −10 ° C. Is preferred.
In addition, in order to securely support the drug indwelling part provided with the drug holding part and prevent the deviation from occurring when the transdermal absorbent is affixed, it may have a predetermined creep resistance. Preferably, for example, when an acrylic pressure-sensitive adhesive is used, partial crosslinking is preferably performed using a urea compound or an isocyanate compound. Moreover, when a silicone type adhesive is used, it is preferable to perform partial crosslinking using a platinum catalyst. Furthermore, when a rubber-based adhesive is used, in order to obtain a predetermined creep resistance, a thermoplastic elastomer having excellent creep resistance such as SBS resin or SIS resin is used as a rubber component, Alternatively, it is preferable to use the rubber component mixed with a self-crosslinkable component.

(3) -2 Arrangement and Thickness Regarding the arrangement of the adhesive layer 12 in the support portion 13, as shown in FIGS. 1 (a) and 1 (b), the adhesive layer 12 is placed on the entire surface of the drug-impermeable layer 11. It may be provided or may be provided in part. Even when it is provided on the entire surface, it is preferable that it is easily broken by a mechanical stimulus such as an injection needle.
Moreover, it is preferable to make the thickness of the adhesive bond layer in a support part into the value within the range of 5-1,000 micrometers.
This is because, when the thickness of the adhesive layer is less than 5 μm, it may be difficult to support the drug indwelling portion or to laminate the adhesive layer uniformly. On the other hand, when the thickness of the adhesive layer exceeds 1,000 μm, it is difficult to follow and adhere to the uneven surface of the skin or the like, or it can be easily broken by a mechanical stimulus such as an injection needle. This is because it may be difficult. Moreover, it is because it may become difficult to permeate | transmit a drug when the thickness of an adhesive bond layer exceeds 1,000 micrometers.
Therefore, the thickness of the adhesive layer is more preferably set to a value within the range of 10 to 100 μm, and further preferably set to a value within the range of 15 to 50 μm.

(3) -3 Transparency etc. Moreover, it is preferable that the adhesive bond layer in a support part has transparency or translucency. This is because, when configured in this way, the situation and position of the skin or the like, which is the adherend to which it is attached, can be visually observed through the adhesive layer and the drug-impermeable substrate. That is, it can be accurately and easily broken after recognizing the adhesive layer in the support portion together with the base material by an external mechanical stimulus such as an injection needle.
As with the drug-impermeable substrate, the adhesive layer itself does not necessarily have transparency or translucency. For example, the adhesive layer is laminated in an island shape or a line shape. Any layer may be used as long as it has a non-applied part or an opening and can recognize the skin as a base.

3. Pressurizing means The pressurizing means provided in the drug indwelling portion is an aspect in which the drug can be percutaneously absorbed easily and continuously through the drug-impermeable base material, and any of the following It is the structure.

(1) Pressurization with air bubbles As shown in FIG. 2 (a), the inside of the drug holding part is filled with gas (compressed air or the like) and made to exist as air bubbles, whereby the drug holding part in which the drug 19 is held. 21 is pressurized. In addition, as shown in FIG. 2B, the gas is injected into the drug holding part 21 holding the drug 19 through the liquid leakage preventing layer using an injection needle or the like and is present as bubbles. Can do.
Further, as shown in FIG. 9 (a), an inflatable portion 81 such as a balloon whose volume is expanded in the drug indwelling portion 20 is provided, and as shown in FIG. 9 (b), a gas is injected therein, By enlarging the expansion site 81, the drug holding part holding the drug 19 can be indirectly pressurized.
This is because, when configured in this way, the gas and the drug are completely separated, so that it is possible to effectively prevent a part of the bubbles from being dissolved in the drug. Also, with this configuration, when the drug is released and the internal pressure decreases, the gas can be injected again to return to the initial pressure.
In addition, when such an expansion | swelling site | part 81 is provided, as a substance inject | poured into an expansion | swelling site | part, not only gas but a liquid may be sufficient.

(2) Pressurization by elastic member As shown in FIG. 1, by configuring a member constituting part or all of the drug indwelling portion 20 from an elastic member, the drug 19 can be utilized by utilizing the return deformation force of the elastic member. Is used to pressurize the drug holding part 21 in which is held. That is, as the drug indwelling part 20, a drug holding part 21 that is a space for holding the drug 19 is provided, and a side wall or the like having a circular or rectangular planar shape is formed and used as a pressurizing unit. it can.
As such an elastic member, a rubber plate made of silicone rubber, natural rubber, chloroprene rubber, isoprene rubber, EVA, SBS, SIS, SBES or NBR rubber can be suitably used. By using such a rubber plate, the drug can be appropriately expanded and contracted by pressurization to release the drug at a constant rate.

Moreover, it is more preferable to use an elastic member made of a foam such as a polyethylene foam or a styrene foam as the elastic member. This is because, by using such a foam, it is possible to easily maintain a certain shape even when the drug is easily injected into the drug holding portion and pressurized. In addition, by using such a foam, an appropriate pressure can be applied as a whole, and the drug can be accurately released at a constant rate during use. Furthermore, if the elastic member is thus a foam, at least the side wall can be easily manufactured by punching or the like.
In order to effectively use the return deformation force of the elastic member, when the volume of the drug holding portion is 100% by volume, for example, the amount of the drug (drug solution) to be filled is within the range of 110 to 300% by volume. It is preferable to use a value.

4). Breaking means In the percutaneous absorption type preparation, as shown in FIG. 1 (b) and FIG. 3 (b), mechanical stimulation for breaking the drug-impermeable substrate 11 in the support portion 13, that is, the breaking means 26 Is capable of gradually releasing the drug without causing drug leakage after puncturing a part of the skin through the drug-impermeable substrate 11 of the support part 13 and then removing the breaking means 26. Any needle-shaped material may be used. Therefore, for example, it is preferable to use at least one of an injection needle (syringe), a pin, a thumbtack, a sewing needle, a staple needle, a wire, a knife, and the like. It is also possible to use needle-free injection such as a jet injector.
Moreover, when using an injection needle (syringe), a SUS 25G injection needle (outer diameter 0.45 mm) and a SUS needle (thickness 0.26 mm, length 1.55 mm) are mentioned as preferable examples. It is done.
It has been found that the release rate of the drug varies significantly depending on the physical size of the mechanical stimulus, for example, the thickness of the injection needle. Therefore, it is preferable to determine the physical magnitude of the mechanical stimulus by calculating from the optimal drug release rate.

5. Liquid Leakage Prevention Layer Further, in constituting the first transdermal absorption-type preparation, it is preferable that a liquid leakage prevention layer is provided on the inner surface and / or outer surface of the drug indwelling portion. That is, as illustrated in FIG. 1, in the percutaneous absorption preparation 10 including the drug indwelling portion 20 and the support portion 13 made of the adhesive layer 12 and the drug-impermeable base material 11, It is preferable to provide the liquid leakage prevention layer 18 above.
The reason for this is that by providing such a liquid leakage prevention layer, a chemical leakage (liquid) occurs during mechanical stimulation given by an injection needle or the like, and thereafter through an opening provided by mechanical stimulation. This is because the occurrence of leakage) can be effectively prevented.

The thickness of the liquid leakage preventing layer is preferably set to a value in the range of 5 to 2,000 μm. This is because if the thickness of the liquid leakage prevention layer is less than 5 μm, the liquid leakage prevention effect may be significantly reduced or it may be difficult to form a uniform thickness. On the other hand, if the thickness of the liquid leakage preventing layer exceeds 2,000 μm, the thickness of the percutaneous absorption preparation may be excessively increased or it may take a long time to form.
Accordingly, the thickness of the liquid leakage preventing layer is more preferably set to a value within the range of 50 to 1,000 μm, and further preferably set to a value within the range of 100 to 500 μm.

Further, the type of the resin constituting the liquid leakage preventing layer is not particularly limited, but it is preferably composed of, for example, silicone rubber, natural rubber, chloroprene rubber, isoprene rubber, or NBR rubber. .
Although not shown, it is also preferable to provide a release film or the like on the outside of the liquid leakage prevention layer and protect the liquid leakage prevention layer with the release film or the like before use.

6). Manufacturing Method With reference to FIGS. 4 to 6, two examples of the manufacturing method of the transdermal absorption preparation according to the first embodiment will be described. However, it is needless to say that the manufacturing method described is not limited and can be appropriately modified.

(1) Manufacturing method 1
In the production method 1 shown in FIG. 4, the constituent members of the percutaneous absorption-type preparation are prepared in advance, and they are combined so that, for example, the percutaneous absorption-type preparation 50 including the cylindrical elastic member 14 is efficiently produced. And it is a method of manufacturing in a short time. The transdermal preparation 50 has an adhesive layer 15 (first adhesive layer and second adhesive layer from below) on the upper and lower surfaces of the drug indwelling portion 20, and these adhesives In this example, two drug-impermeable substrates 11 (a first drug-impermeable substrate and a second drug-impermeable substrate from below) are provided via a layer 15.

(1) -1 Preparation of A Member First, an A member including a liquid leakage prevention layer 18 made of silicone rubber or the like is prepared on the second drug-impermeable base material 11. Although the drug-impermeable base material 11 is provided below the liquid leakage prevention layer 18, the liquid leakage prevention layer 18 is uniformly and easily formed on the drug indwelling portion 20 by being configured in this way. Because it can. Although not shown, it is also preferable to provide a release film on the outside of the release liquid leakage prevention layer 18 in order to protect the liquid leakage prevention layer 18. In addition, since A cylindrical percutaneous absorption type | mold preparation is manufactured, it is preferable to cut | disconnect A member previously circularly.

(1) -2 Preparation of B Member A B member made of a cylindrical elastic member 14 and first and second adhesive layers 15 formed on the upper and lower surfaces thereof is prepared.
In this case, as shown in FIG. 4, it is preferable to provide a release film 17 on the outer side of the adhesive layer 15 on the upper surface and the lower surface so that the B member can be easily handled.

(1) -3 Preparation of C Member Further, a C member that is a support portion 13 including a drug-impermeable base material 11 and an adhesive layer 12 is prepared. In addition, also in C member, as shown in FIG. 4, it is preferable that the peeling film 24 is provided in the outer side of the adhesive bond layer 12 so that handling may be easy.

(1) -4 Lamination and pressure treatment of A to C members Next, after peeling off the release film 17 provided on the upper surface of the B member, the upper surface of the cylindrical elastic member 14 as shown by the arrow in FIG. In addition, the second drug-impermeable base material 11 provided with the liquid leakage preventing layer 18 is laminated by the second adhesive layer 15.
Similarly, after peeling off the release film 17 provided on the lower surface of the B member, as shown by an arrow in FIG. 4, on the lower surface of the cylindrical elastic member 14 in the B member, A first drug-impermeable substrate 11 is laminated with a first adhesive layer 15.
Finally, although not shown in the figure, as an example of the pressurizing process, the drug 19 is injected into the drug holding unit 21 by the syringe through the liquid leakage prevention layer 18 to an internal volume or more to generate an internal pressure in the drug holding unit 21. A percutaneously absorbable preparation 50 is obtained.
By carrying out in this way, even if it is a case where the kind of adhesive, thickness, etc. change, it can manufacture easily and a desired percutaneous absorption type preparation can be manufactured efficiently.

(2) Manufacturing method 2
The production method 2 shown in FIGS. 5 and 6 is a method for efficiently producing the percutaneous absorption type preparation 60 sequentially from the lower support part, for example, a percutaneous absorption type preparation comprising a cylindrical elastic member. Is an efficient and large-scale manufacturing method. In addition, also in this manufacturing method 2, the adhesive layer 15 (the first adhesive layer and the second adhesive layer from below) is provided on the upper and lower surfaces of the drug holding portion 21, and these adhesive layers 15 are attached to the upper and lower surfaces. Thus, a percutaneously absorbable preparation 60 having two drug-impermeable base materials 11 (a first drug-impermeable base material and a second drug-impermeable base material from below) is manufactured. Consider an example.

(2) -1 Creation of Support Section First, as shown in FIG. 5A, an adhesive layer 12 with a release film 24 is prepared. The adhesive layer 12 can be formed using a normal coating method, printing method, or the like.
Next, as shown in FIG. 5B, a first drug-impermeable base material 11 is laminated on the formed adhesive layer 12 to create a support portion. In this case, it is preferable to laminate the first drug-impermeable substrate 11 using the adhesive layer 12.

(2) -2 Creation of drug indwelling part Next, as shown in FIG. 5 (c), on the surface of the drug-impermeable base material 11, an elastic member 14 that will constitute the side wall of the drug indwelling part in the future, The first adhesive layer 15 is laminated on one side. The elastic member 14 is preferably laminated by, for example, a laminating method.
Next, a portion corresponding to the space serving as the drug holding portion 21 in the elastic member 14 of the percutaneous absorption-type preparation is cut out with a cutter or the like to form a drug indwelling portion.

(2) -3 Creation of Liquid Leakage Prevention Layer Next, as shown in FIG. 5D, after the second adhesive layer 15 is formed on the surface of the elastic member 14, the liquid leakage prevention layer 18 is entirely formed. Laminate to.

(2) -4 Creation of Transdermal Absorption Formulation Next, as shown in FIGS. 6E and 6F, for example, a cutter 16 is used to cut out a portion corresponding to the outer shape of the transdermal absorption preparation. In this case, it is preferable to pull out using a shearing force of a cutter or the like, but it is also preferable to use a laser or jet of water or the like.
Finally, as shown in FIG. 6 (g), as a pressurization process, the drug is injected into the drug holding part 21 by the injection needle (syringe) 26 through the liquid leakage prevention layer 18 as an example to the internal volume or more. The percutaneous absorption-type preparation 60 in which an internal pressure is generated in the drug holding part 21 is used.
By implementing in this way, manufacture of the percutaneous absorption type preparation 60 can be automated, and the percutaneous absorption type preparation 60 having a desired size can be efficiently manufactured by a flow operation.

[Second Embodiment]
In the second embodiment, a drug indwelling part having a drug holding part for holding a drug therein, an adhesive layer for supporting the drug indwelling part, and a thickness in the range of 1 to 100 μm A transdermal absorption method of a drug using a transdermal absorption-type preparation comprising a drug-impermeable base material, and comprising the following steps: Absorption method.
(1) A process of attaching a percutaneously absorbable preparation (hereinafter sometimes referred to as an attaching process).
(2) A step of breaking at least the drug-impermeable substrate in the support portion with a needle-like material as a mechanical stimulus from the outside (hereinafter sometimes referred to as a breaking step).
(3) A step of gradually releasing the drug while being pressurized with an elastic member or bubbles as a pressurizing means provided in the drug indwelling portion

1. Attachment process This is the process of applying a percutaneous absorption preparation to the place where the drug is to be absorbed transdermally. It is also preferable to peel off the peeling member attached to the adhesive layer and apply it using a jig such as tweezers as well as bare hands. It is also preferable to apply the transdermal absorption preparation automatically or semi-automatically using a dedicated application jig.
Note that the configuration and the like of the transdermal preparation to be applied can be the same as that described in the first embodiment, and thus the description thereof is omitted here.

2. Breaking step This is a step of breaking at least the drug-impermeable base material of the support portion by an external mechanical stimulus. That is, in the process of applying a mechanical stimulus from the outside using an injection needle (syringe) or the like, breaking the drug-impermeable base material of the support part, and further perforating the skin to facilitate drug release. is there.
When applying mechanical stimulation, it is preferable that a liquid leakage preventing layer 18 is provided around the drug indwelling portion 20 as shown in FIG. This is because, even after the drug-impermeable base material 11 of the support part 13 is broken through the drug indwelling part 20 and then the breaking means is removed, not only liquid leakage does not occur, but the internal pressure is reduced. This is because excessive reduction is reduced.

3. Drug Release Step This is a step of gradually releasing the drug using the internal pressure of the transdermal preparation. The released drug is administered through the skin.
Here, the preferable permeation rate of the drug per unit area depends on the kind of the drug and the like, but it is usually preferable to set the value within the range of 0.1 to 1,000 μg / cm ² / hr. This is because when the permeation rate per unit area is less than 0.1 μg / cm ² / hr, the time until the drug reaches a predetermined concentration may be excessively long. On the other hand, when the permeation rate per unit area exceeds 1,000 μg / cm ² / hr, the drug permeation rate may vary greatly.

  Hereinafter, although the percutaneous absorption type preparation of the present invention will be described in detail based on Examples, it goes without saying that the present invention is not limited by the description of these Examples.

[Example 1]
1. Preparation of percutaneous absorption type preparation An acrylic pressure-sensitive adhesive was applied on a 38 μm-thick release film SP-PET3801 (manufactured by Lintec Corporation) so that the thickness after drying was 25 μm, and then 3 ° C. at 100 ° C. It was dried for a minute to provide an adhesive layer, and a first drug-impermeable base material (polyethylene terephthalate film having a thickness of 17 μm) was laminated to form a support portion.
Next, a silicone pressure-sensitive adhesive is applied to both sides of a polyethylene foam “Pef” (manufactured by Toray Industries, Inc.), which is an elastic member as a pressurizing means, and dried at 100 ° C. for 3 minutes. An agent layer (a first adhesive layer and a second adhesive layer) was provided. This polyethylene foam with an adhesive layer was laminated on the first drug-impermeable substrate in the support portion via the first adhesive layer. The silicone adhesive used was prepared by adding 2 parts by weight of DX-3004 (Shin-Etsu Chemical Co., Ltd.) as a catalyst to 100 parts by weight of X-40-3068 (Shin-Etsu Chemical Co., Ltd.). It is.
Subsequently, the space used as the medicine holding part of a polyethylene foam was cut out using the cutter, and it was set as the drug indwelling part. The thickness of the side wall was 5 mm and the height was 1.5 mm.
Subsequently, a mixture of a silicone resin (“SILASTIC MDX4-4210 Elastomer Base” manufactured by Dow Corning) and a crosslinking agent (“Curing Agent” manufactured by Dow Corning) on the release film SP-PET3801 (manufactured by Lintec Corporation) ( A weight ratio of 10: 1) was applied and heated at 100 ° C. for 7 minutes. The liquid leakage prevention layer made of a silicone film having a thickness of 250 μm was laminated on the polyethylene foam of the drug indwelling portion via the second adhesive layer.
Thus, from below, the release film 24, the acrylic pressure-sensitive adhesive layer 12, the first drug-impermeable substrate (17-μm-thick PET film) 11, and the polyethylene foam are illustrated in FIG. A casing of the transdermal absorption preparation 10 including the drug holding part 21 made of the body 14 and the liquid leakage prevention layer 18 made of a silicone film was prepared.

  In addition, the acrylic pressure-sensitive adhesive layer has a solution-polymerized acrylic pressure-sensitive adhesive solution containing hexamethylene diethylene urea as a cross-linking agent in an amount of 0.2 wt. It was prepared by adding a part. Also, this acrylic pressure-sensitive adhesive solution is a separable flask containing 100 parts by weight of a monomer mixed solution consisting of 65 parts by weight of n-butyl acrylate, 32 parts by weight of 2-ethylhexyl acrylate, and 3 parts by weight of acrylic acid. After adding 50 parts by weight of ethyl acetate to the part, 0.25 parts by weight of azobisisobutyronitrile as a radical initiator was added, and further 80 parts by weight of ethyl acetate was added. It was prepared under the polymerization conditions of 65 ° C. and 12 hours.

Next, a FITC dextran aqueous solution (weight average molecular weight: 4000) having a concentration of 0.5% by weight is injected into the drug holding part in the drug indwelling part via a liquid leakage prevention layer, and 165% of the internal volume (100%). The amount corresponding to 1 was injected, and the FITC dextran aqueous solution was filled so that the internal pressure was applied from the polyethylene foam.
At that time, although the inner wall of the polyethylene foam constituting the side wall of the drug indwelling portion expanded in volume toward the outside, the polyethylene foam up to the outer wall absorbed the volume expansion, and the expansion of the outer wall itself was particularly observed. Was not. Subsequently, the syringe was removed through the liquid leakage preventing layer to obtain a percutaneous absorption preparation for evaluation of Example 1.

2. In vitro evaluation of percutaneously absorbable preparation A vertical diffusion cell was constructed, and the skin of a hairless rat (WBN / ILA-Ht, body weight about 200 g) was cut out and attached, and on the stratum corneum side of the skin of the hairless rat, A percutaneous absorption preparation from which the release film shown in FIG. 1 was removed was affixed.
Next, with purified water at 32 ° C. inserted into the receptor of the vertical diffusion cell, the skin of the hairless rat was pierced and penetrated with the injection needle (26G) through the liquid leakage preventing layer of the transdermal absorption type preparation. Next, after removing this injection needle from the liquid leakage prevention layer, the change in the cumulative amount of FITC dextran concentration permeating from the percutaneous absorption preparation to the purified water in the receptor through the skin of the hairless rat was measured. .
The FITC dextran concentration in the purified water was quantified using a fluorescence spectrophotometer RF-5300PC (manufactured by Shimadzu Corporation). The obtained results are shown in Table 1 and FIG.
From these results, it was confirmed that the measured FITC dextran concentration and time changed substantially linearly, and FITC dextran having a weight average molecular weight of 4000 was permeating at a constant rate. Moreover, even after the injection needle was removed from the liquid leakage prevention layer, the dextran aqueous solution did not leak.

[Example 2 and Example 3]
A percutaneous absorption type preparation was prepared in the same manner as in Example 1 except that the weight average molecular weight of FITC dextran in Example 1 was changed from 4,000 to 20,000 in Example 2 and 40,000 in Example 3. did.
Next, as in Example 1, changes in the FITC dextran concentration permeating through the skin of hairless rats were measured using a vertical diffusion cell. The obtained results are shown in Table 1 and FIG.
As a result, it seems that both of Example 2 and Example 3 are due to an increase in the weight average molecular weight. However, although the measured concentrations themselves are decreasing, the FITC dextran concentration and the time are almost linear. Had changed. Therefore, it was confirmed that even if FITC dextran having a weight average molecular weight of 20,000 or FITC dextran having a weight average molecular weight of 40,000, it permeates at a constant rate.

[Example 4]
1. Preparation of transdermal absorption preparation In Example 4, in the percutaneous absorption preparation in Example 1, the filling amount of FITC dextran into the drug indwelling portion was set to 100% with respect to the internal volume (100%), Bubbles were injected using a syringe. At that time, the volume of the polyethylene foam constituting the side wall of the drug indwelling portion was expanded by about 10%, and compressed air was injected so that the internal pressure was applied to the FITC dextran aqueous solution. Subsequently, the syringe was removed, and a transdermal absorption preparation for evaluation of Example 4 was obtained.

2. Evaluation of Percutaneous Absorption Formulation In the same manner as in Example 1, the change in FITC dextran concentration permeating the stratum corneum of hairless rats was measured using a vertical diffusion cell. The obtained results are shown in Table 1 and FIG.
As a result, in Example 4, the FITC dextran concentration and time changed substantially linearly. Therefore, even when pressurized using bubbles, it was confirmed that FITC dextran having a weight average molecular weight of 4,000 permeates at a constant rate.

[Example 5]
1. Preparation of transdermal absorption preparation A percutaneous absorption preparation was prepared in the same manner as in Example 1, except that the FITC dextran aqueous solution in Example 1 was changed to an insulin (molecular weight: about 6000) aqueous solution having a concentration of 10 U / mL.

2. Evaluation of percutaneously absorbable preparation by in vivo skin permeation experiment Percutaneous absorbable preparation with a peelable film removed from the abdomen of hairless rats (WBN / ILA-Ht, body weight: about 200 g) under urethane anesthesia The skin of the abdomen of the hairless rat was pierced with an injection needle (26G) through the liquid leakage prevention layer of the mold preparation. Next, after removing this injection needle from the liquid leakage prevention layer, the insulin concentration in the plasma of the hairless rat was measured with the enzyme assay method over time using an insulin concentration measurement kit “Insulin Dynapack” (manufactured by Dynapot Co., Ltd.). Measured. The insulin concentration in plasma of hairless rats was 105 μU / mL after 1 hour, 182 μU / mL after 3 hours, and 182 μU / mL after 5 hours. From this result, it was confirmed that even insulin, which is a water-soluble polymer drug, can be administered through the skin. Even in this case, the aqueous insulin solution did not leak after the injection needle was removed from the liquid leakage prevention layer.

[Comparative Examples 1 and 2]
In Comparative Example 1, instead of the drug indwelling portion made of polyethylene foam in Example 1, a drug indwelling portion consisting entirely of PET film was prepared, and the internal volume (100%) was set so that no internal pressure was generated in the drug. In contrast, a percutaneous absorption type preparation was prepared and evaluated in the same manner as in Example 1 except that it was filled to 90%.
In Comparative Example 2, a percutaneous absorption type preparation was prepared and evaluated in the same manner as in Comparative Example 1 except that mechanical stimulation by the injection needle was not further applied in Comparative Example 1.
The obtained results are shown in FIGS. As is understood from the results, it is considered that the pressure is not pressurized in Comparative Example 1, but when compared with Example 1, the permeation amount is reduced to about several percent, and Comparative Example 2 does not permeate at all. Was confirmed.

  As is clear from the above description, according to the percutaneous absorption type preparation of the present invention, the drug holding part in the drug indwelling part is pressurized, and the base material is broken by external mechanical stimulation. In addition, it is possible to easily and continuously percutaneously absorb oligomers and high molecular weight drugs that are excellent in sticking property and generally not suitable for transdermal absorption.

  Further, according to the transdermally absorbable preparation of the present invention, more effective drug administration is possible by using it together with drug administration by a normal syringe. In other words, by administering a drug using a syringe, the immediate effect of the drug can be obtained, and the continuous transdermal preparation enables continuous drug administration and keeps the drug concentration in the blood more constant. Became possible.

(A) It is a figure provided in order to demonstrate the structure of the percutaneous absorption type formulation using an elastic member. (B) It is a figure provided in order to demonstrate the usage method of the percutaneous absorption type formulation using an elastic member. (A) It is a figure provided in order to demonstrate the structure of the percutaneous absorption type formulation using air bubbles. (B) It is a figure provided in order to demonstrate the filling method of the bubble in a transdermal formulation. (A) It is a figure provided in order to demonstrate the structure of the percutaneous absorption type formulation from which base-material arrangement | positioning differs. (B) It is a figure provided in order to demonstrate the usage method of the percutaneous absorption type formulation from which base-material arrangement | positioning differs. It is a figure provided in order to demonstrate the manufacturing method of a percutaneous absorption type formulation. It is a figure provided in order to demonstrate the manufacturing method of a percutaneous absorption type formulation. It is a figure provided in order to demonstrate the manufacturing method of a percutaneous absorption type formulation. It is a figure provided in order to demonstrate the structure of the percutaneous absorption type formulation which has two or more drug indwelling parts. It is a figure provided in order to demonstrate the structure of a base material. It is a figure provided in order to demonstrate the structure of the percutaneous absorption type preparation which has an expansion part. It is a figure which shows the relationship between the discharge | release amount of a percutaneous absorption type pharmaceutical drug using an elastic member, and time. It is a figure which shows the relationship between the discharge | release amount of a percutaneous absorption type pharmaceutical drug using air bubbles, and time. It is a figure provided in order to demonstrate the structure of the percutaneous absorption type formulation using the conventional jet injector. It is a figure provided in order to demonstrate the structure of the percutaneous absorption type formulation which has the conventional micro pin.

Explanation of symbols

10, 30, 50, 60, 70: Percutaneous absorption preparation 11: Drug-impermeable substrate 12: Adhesive layer 13: Support part 14: Elastic member 15: Adhesive layer 18: Liquid leakage prevention layer 19: Drug 20: Drug indwelling part 21: Drug holding part 24: Release film 26: Mechanical stimulation (injection needle)
32: Bubble

Claims (5)

A drug indwelling part having a drug holding part for holding the drug inside, an adhesive layer for supporting the drug indwelling part, and a drug impermeability having a thickness within a range of 1 to 100 μm A percutaneous absorption-type preparation comprising a support portion comprising a base material,
As a pressurizing means for pressurizing the drug holding part in the drug indwelling part, a part or all of the drug indwelling part is composed of an elastic member for pressurizing the drug held in the drug holding part ,
The drug-impermeable base material in the support part can be broken by needles as a mechanical stimulus,
The percutaneous absorption preparation, wherein the drug indwelling part is in a pressurized state. A drug indwelling part having a drug holding part for holding the drug inside, an adhesive layer for supporting the drug indwelling part, and a drug impermeability having a thickness within a range of 1 to 100 μm A percutaneous absorption-type preparation comprising a support portion comprising a base material,
As a pressurizing means for pressurizing the drug holding part in the drug indwelling part, the inside of the drug holding part is filled with bubbles,
The drug-impermeable base material in the support part can be broken by needles as a mechanical stimulus,
The percutaneous absorption preparation, wherein the drug indwelling part is in a pressurized state.   The transdermal absorption preparation according to claim 1, wherein the elastic member is a foam.   4. The liquid leakage prevention layer having a thickness of 5 to 2,000 μm is provided on the inner surface and / or outer surface of the drug indwelling portion, or one of the surfaces. A transdermally absorbable preparation according to 1.   The percutaneously absorbable preparation according to any one of claims 1 to 4, wherein the drug is an oligomer or a polymer.

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