Delivery system for percutaneous absorption drug preparation and method for manufacturing same

Provided is a novel delivery system for a percutaneous absorption drug preparation. The delivery system for a percutaneous absorption drug preparation is provided with: a solvent-impermeable first sheet; a solvent-impermeable second sheet that is bonded to the top surface of the first sheet and comprises a non-sealed area and a sealed area surrounding the non-sealed area, said non-sealed area and sealed area being formed between the first sheet and the second sheet, and a cutting part circularly extending along the outer peripheral edge of the non-sealed area; a percutaneous absorption drug preparation-holding member that is disposed between the first sheet and the second sheet in the non-sealed area and fixed to the second sheet inside the cutting part; and a pressure-sensitive adhesive third sheet that is removably bonded to the top surface of the second sheet.

TECHNICAL FIELD

The present invention relates to a delivery system for a percutaneous absorption drug preparation and a method for manufacturing the same.

BACKGROUND ART

Conventionally, there has been known a delivery system for a percutaneous absorption drug preparation, which retains, with an aid of an adhesive sheet, a percutaneous absorption drug preparation carrying member carrying a material having a medicinal ingredient for a percutaneous absorption drug preparation on the skin.

For example, Patent Document 1 discloses a wound dressing. The wound dressing includes a backing material, a pressure-sensitive adhesive layer coating a portion of the backing material, an absorbent web affixed to the backing material by an adhesive means and providing voids to an exudate from a wound, and the pressure-sensitive adhesive layer contains an antibacterial agent restraining microorganisms from entering the web from the external environment.

Patent Document 2 discloses an iontophoresis delivery system for a drug. This system includes a backing (closure) having a recess, a drug-absorbent substance stored in the recess, a web bonded in a peelable manner to the backing to cover the recess, and a reservoir attached to an inner surface of the web such that a drug aliquot absorbed in the drug-absorbent substance is absorbed in a patient contact surface.

Patent Document 3 discloses a wound covering material covering and protecting a wound surface of the body. This wound covering material comprises an adhesive supporting material made up of a film or a nonwoven fabric etc., an adhesive layer disposed on one surface of the adhesive supporting material, and a hydrous gel layer, and the hydrous gel layer is affixed to the adhesive layer.

Other delivery systems for percutaneous absorption drug preparations having similar configurations are also proposed in Patent Documents 4 to 6.

PRIOR ART DOCUMENTS

Patent Documents

SUMMARY OF THE INVENTION

Problem to be Solved by the Invention

It is an object of the present invention to provide a novel delivery system for a percutaneous absorption drug preparation and a method for manufacturing the same, the system being different in configuration from the above-described delivery systems for percutaneous absorption drug preparations.

Means for Solving Problem

A delivery system for a percutaneous absorption drug preparation according to an embodiment of the present invention comprises

(b) a solvent-impermeable second sheet affixed to an upper surface of the first sheet, forming a non-sealing region and a sealing region surrounding the non-seal region with the first sheet, and having a cutting part formed to annularly extend along an outer circumferential edge of the non-sealing region;

(c) a percutaneous absorption drug preparation carrying member disposed between the first sheet and the second sheet in the non-sealing region and fixed to the second sheet inside the cutting part; and

(d) a third sheet affixed in a peelable manner to an upper surface of the second sheet.

A delivery system for a percutaneous absorption drug preparation according to an embodiment of the present invention comprises

(a) a backing sheet having a base material layer and an adhesive layer disposed on a lower surface of the base material layer;

(b) a solvent-impermeable base sheet affixed in a peelable manner to a lower surface of the adhesive layer and having an annular cutting part, an inner region located inside the annular cutting part, and an outer region located outside the annular cutting part;

(c) a percutaneous absorption drug preparation carrying member fixed to the base sheet in the inner region of the base sheet; and

(d) a solvent-impermeable cover sheet disposed on a lower surface of the base sheet to cover at least the inner region, fixed to the base sheet in the outer region of the base sheet, and continuously sealing the circumference of the inner region,

(e) the device allowing the outer region of the base sheet to be peeled off along with the cover sheet fixed to the outer region while leaving the inner region of the base sheet on the backing sheet along with the percutaneous absorption drug preparation carrying member.

A method for manufacturing a delivery system for a percutaneous absorption drug preparation according to an embodiment of the present invention comprises

a step 1 of supplying a solvent-impermeable base sheet including an outer region and an inner region surrounded by the outer region;

a step 2 of forming an annular cutting part in the base sheet along an outer circumferential edge of the inner region;

a step 3 of disposing a percutaneous absorption drug preparation carrying member in the inner region on a lower surface of the base sheet;

a step 4 of fixing the percutaneous absorption drug preparation carrying member to the base sheet;

a step 5 of allowing the percutaneous absorption drug preparation carrying member to carry a drug preparation;

a step 6 of disposing a solvent-impermeable cover sheet on the lower surface of the base sheet to cover the percutaneous absorption drug preparation carrying member carrying the drug preparation;

a step 7 of fixing the cover sheet to the base sheet and sealing the circumference of the inner region in the outer region; and

a step 8 of affixing a backing sheet in a peelable manner to an upper surface of the base sheet.

Effect of the Invention

According to the delivery system for a percutaneous absorption drug preparation of the present invention and the delivery system for a percutaneous absorption drug preparation manufactured by the method for manufacturing of the present invention, the cover sheet (first sheet) is peeled off when used. At this time, the base sheet (second sheet) is broken at the cutting part, and the outer region of the base sheet is peeled off along with the cover sheet while the inner region of the base sheet (second sheet) is left on the backing sheet along with the percutaneous absorption drug preparation carrying member. Therefore, the percutaneous absorption drug preparation carrying member does not peel off regardless of which direction the delivery system for a percutaneous absorption drug preparation is oriented in when unsealed.

By using the delivery system for a percutaneous absorption drug preparation of the present invention, a liquid drug preparation can be sealed and distributed without leakage or volatilization and diffusion, and can be affixed for administration after simply peeling off the member covering the drug as is the case with typical patches without the need of cumbersome operations when used.

By using the delivery system for a percutaneous absorption drug preparation of the present invention, a constant amount of the liquid drug preparation can be used for transdermally administering the liquid drug preparation to a constant skin area. Contrarily, if a liquid drug preparation were administered as a lotion to the skin, a dose may be unstable, and it may be difficult to keep a dosage constant because the liquid drug applied to the skin can adheres to clothes etc. However, by using the delivery system for a percutaneous absorption drug preparation of the present invention, the troubles as described above can be overcome. As compared to ointment formulations and tapes, liquid drug preparations have good releasability and favorable transdermal absorbability and, therefore, by using the delivery system for a percutaneous absorption drug preparation of the present invention, preparation of patches of liquid drug preparations can be facilitated. As described above, the delivery system for a percutaneous absorption drug preparation of the present invention serves as a new system for liquid drug preparations to enable the expansion of the field in which liquid drug preparations can be utilized and the development of new applications of the liquid drug preparations.

MODES FOR CARRYING OUT THE INVENTION

An embodiment and a method for manufacturing of a delivery system for a percutaneous absorption drug preparation (hereinafter simply referred to as a “system”) according to the present invention will now be described with reference to the accompanying drawings.

1-1. Overall Structure

Referring toFIGS. 1 and 2, the system is generally denoted by reference numeral10and is constituted by laminating a plurality of sheets or films. In an embodiment, the system10has a main part made up of three sheets or films, i.e. a lower-layer cover sheet (first sheet)11, an intermediate-layer base sheet (second sheet)12, and an upper-layer backing sheet (third sheet). As shown inFIG. 1, the system10has a quadrangular planar shape; however, the shape is not limited thereto and may be circular, elliptical, or other polygonal shapes.

The lower-layer cover sheet11and the intermediate-layer base sheet12are preferably formed of a plastic sheet or film or a laminated film made of a solvent-impermeable material and are not particularly limited as long as the sheets are those used with normal heat sealing. Specific examples of the material include polyolefins such as polyethylene and polypropylene, polyesters such as polyethylene terephthalate, polybutylene terephthalate, and polyethylene naphthalate, polyvinyl chloride, polyvinylidene chloride, Polyamide such as nylon-6 and nylon-66, polyimide, ethylene vinyl alcohol, etc., as well as copolymers of these polymers. Preferably, a material used for a sheet or a film made of a plastic-sheet or plastic-film material is a composite material having an aluminum foil disposed between top and bottom plastic layers or a composite material having an aluminum-deposited plastic layer disposed between top and bottom plastic layers.

The base sheet12is partitioned into a central inner region15and an outer region16surrounding the inner region15. At an annular boundary between the inner region15and the outer region16, a cutting part17is formed. The cutting part17may be a continuous cut or intermittent perforations. The cutting part17may be a so-called full cut reaching from an upper surface to a lower surface of the base sheet12or may be a so-called half cut leaving an uncut portion near the upper surface or the lower surface of the base sheet12. In the case of the full cut, the cutting part is preferably so-called perforations partially leaving an uncut portion. To facilitate avoidance of evaporation and scattering of a solvent of the percutaneous absorption drug preparation contained inside, the cutting part is preferably a so-called half cut. In the shown embodiment, the cutting part17is a half cut extending from the upper surface to near the lower surface.

The cover sheet11and the base sheet12are bonded and sealed by heat sealing18to continuously surround the inner region15in the outer region16such that a non-sealing space (non-sealing region)19A is formed in the inner region15with a seal region19B formed on the outside thereof. As shown in the figures, the non-sealing space19A preferably extends beyond the cut part17and reaches the outer region16.

In the non-sealing space19A, a percutaneous absorption drug preparation carrying member20is stored. The percutaneous absorption drug preparation carrying member20is fixed to the base sheet12by a heat bonding part21. As shown in the figures, the percutaneous absorption drug preparation carrying member20needs not to be bonded on the entire surface and may be spot-welded only in a plurality of small regions. The welding temperature for the fixation is a temperature higher than the melting point of the base sheet12and is preferably a temperature lower than the melting point of the percutaneous absorption drug preparation carrying member20.

1-3. Percutaneous Absorption Drug Preparation Carrying Member

The percutaneous absorption drug preparation-carrying member (hereinafter referred to as “carrying member”)20is not particularly limited as long as the member is capable of stably containing or retaining a liquid or pasty percutaneous absorption agent22. For example, cotton fabrics such as absorbent cotton and gauze, nonwoven fabrics, synthetic fiber fabrics such as polyester, polyethylene, and polyvinyl, sponge, and paper are usable. For the sponge, synthetic sponge such as urethane foam or natural sponge is usable. In any case, the carrying member20can optimally be selected in accordance with a type of the percutaneous absorption drug preparation carried by the member.

To facilitate welding to the base sheet12, the carrying member20is desirably made of a material not melting at the melting point of the material of the base sheet12. For example, when polyolefins are used for the base sheet12, the carrying member20is desirably made of a material having the melting point higher than that of the polyolefins used. Preferably, examples can include polyesters having such a melting point.

The percutaneous absorption drug preparation22is a liquid, gel-like, or paste-like material containing a medicinal ingredient. For example, the drug preparation can be a liquid having a medicinal ingredient dissolved or dispersed in an inorganic solvent such as water or in an organic solvent. The organic solvent may be any solvents usable as external preparations without particular limitation. An organic ionic liquid is a solvent having a high dissolving power and is also included in these solvents. Furthermore, a mixture thereof is also included. Examples of the organic solvent include fatty acid esters such as isopropyl palmitate, isopropyl myristate, cetyl lactate, diethyl sebacate, hexyl laurate, cetyl isooctanoate, lauryl lactate, and ethyl oleate, glycols such as ethylene glycol, propylene glycol, 1,3-butylene glycol, polyethylene glycol, polypropylene glycol, and glycerin, and alcohols such as ethanol, propanol, isopropanol, and butanol.

Examples of the organic ionic liquid include a Brønsted type salt composed of a fatty acid and an organic amine compound which is liquid at room temperature. The fatty acid and the organic amine compound are not particularly limited as long as these are usable as a patch. Examples include fatty acids such as levulinic acid, octanoic acid, decanoic acid, oleic acid, stearic acid, and isostearic acid, and lower alkylamines such as diethanolamine, diisopropanolamine, triethanolamine, and triisopropanolamine.

Examples of the amphoteric surfactant include phosphatidylcholine, lauryldimethylaminoacetic acid betaine, 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, etc. For another example, lauroyl diethanol amide can also be used.

The percutaneous absorption drug preparation can be a percutaneous absorption liquid drug having a medicinal ingredient dissolved or dispersed in propylene glycol in the presence of phosphatidylcholine.

The “medicinal ingredient” is not particularly limited as long as the ingredient is usable as a percutaneous absorption drug preparation, and examples thereof include nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin, flurbiprofen, ketoprofen, and diclofenac, local anesthetics such as lidocaine and dibucaine, tramadol, eperisone, ramelteon, donepezil, escitalopram, galantamine, ramelteon, morphine, oxycodone, paroxetine, ropinirole, pergolide, ondansetron, raloxifene, rotigotine, aripiprazole, fentanyl, apomorphine, memantine, amantadine, tulobuterol, tolbutamide, glibenclamide, oxybutynin, neostigmine, nicardipine, dopamine, etc. Furthermore, a combination of these medicinal ingredients can be used. A medicinal ingredient converted to an ionic liquid due to a combination of an acid and a base is also usable. Preferable examples include a combination between the NSAID described above serving as an acid and the local anesthetic serving as a base.

The “solvent” refers to an aqueous solution for dissolving the medicinal ingredient or the organic solvent described above. The organic solvent further refers to those containing the percutaneous absorption promoter described above. Therefore, the organic solvent may be any solvents usable for a patch for percutaneous absorption without particular limitation. An organic ionic liquid is a solvent having a high dissolving power and is also included in these solvents. Furthermore, a mixture thereof is also included. Therefore, the percutaneous absorption drug preparations having the medicinal ingredients dissolved in the organic ionic liquid and the organic solvent are also usable.

The backing sheet13has a base material layer23and an adhesive layer24disposed on the lower surface of the base material layer23. The base material layer23is made up of a nonwoven fabric, a woven fabric, a synthetic resin sheet, or a composite thereof. Examples of these materials of the backing sheet include polyethylene, polypropylene, polycarbonate, polyesters, polyamide, polyvinyl chloride, cotton, urethane, etc., and further include composites thereof.

The adhesive layer24is made up of an adhesive material capable of exerting a required adhesive force for the upper surface of the base sheet12. When the cutting part17of the base sheet12is the full cut, an adhesive is used that can prevent the percutaneous absorption drug preparation stored in the non-sealing space19A between the cover sheet11and the base sheet12from passing and leaking through the interface between the adhesive layer24and the base sheet12to the outside. Specifically, acrylic, synthetic-rubber-based, and natural-rubber-based adhesives etc. can appropriately be selected and used, and preferable examples include acrylic adhesives mainly composed of a copolymer of an acrylic monomer such as 2-ethylhexyl acrylate, butyl acrylate, ethyl acrylate, and methyl methacrylate, and synthetic-rubber-based adhesives such as tackifiers including a styrene-isoprene-styrene copolymer (SIS) and a terpene resin. To improve liquid resistance, trimellitate ester plasticizer or polyester plasticizer can be used together as a plasticizer.

As shown inFIGS. 1 and 2, preferably, a release sheet (fourth sheet)25is disposed between the base sheet12and the backing sheet13along one edge of the system10. As shown inFIG. 2, the release sheet25is made of a band-like sheet or film and may be folded at a fold line26in the longitudinal direction. For example, the sheet may be made up of two seat portions27,28with the fold line26interposed therebetween. As shown in the figures, the width of one of the two seat portions27,28is larger than the width of the other. The release sheet25folded in this way is disposed between the base sheet12and the backing sheet13with a longitudinal end edge portion of a wide sheet portion27made coincident with an edge29of the backing sheet13. Therefore, the release sheet25has the upper surface of the wide sheet portion27affixed to and retained by the adhesive layer24of the backing sheet13. The lower surface of the narrow sheet portion28on the other side is in contact with the base sheet12without being affixed thereto.

Although not particularly limited, the release sheet25can be made up of a sheet of polyethylenes, polypropylenes, polyesters, etc. These sheets can have a sheet surface silicon-processed so as to facilitate peeling from a plaster.

2. Method for Manufacturing

A method for manufacturing a system having the configuration described above will be described with reference toFIG. 3. AlthoughFIG. 2shows the cover sheet11on the lower side and the backing sheet13on the upper side in consideration of the usage state of the system, the positions are inverted fromFIG. 2in a manufacturing process described below, so that the backing sheet and the cover sheet11are positioned on the lower side and the upper side, respectively.

The manufacturing process includes the following steps 1 to 10. Each of the steps will hereinafter be described.

Step 1: Supply of Base Sheet

In a manufacturing process30shown inFIG. 3, the base sheet12is continuously supplied from the left side to the right side ofFIG. 3.

Step 2: Formation of Cutting Part

A cutter31is brought into contact with the lower surface of the base sheet12to form the cutting part17. Although not shown, a support table is disposed on the side opposite to the cutter31across the base sheet12, and the cutting part17is formed in the base sheet12sandwiched by the cutter31and the support table. As described above, the type of the cutter31is selected depending on the type of the cutting part17(a continuous cut, perforations, a full cut, or a half cut).

Step 3: Supply of Carrying Member

A carrying member supplying device32places the carrying member20on the upper surface of the base sheet12.

Step 4: Fixation of Carrying Member

The carrying member20and the base sheet12are welded at a plurality of positions by, for example, an ultrasonic spot welding machine33to form the heat bonding part21.

Step 5: Supply of Drug Preparation

The percutaneous absorption drug preparation22is supplied from a drug preparation supplying device34to the carrying member20.

Step 6: Supply of Cover Sheet

The cover sheet11is supplied and overlaid on the base sheet and the carrying member.

Step 7: Heat Sealing

A heat sealer35is used for the heat sealing18of the base sheet12and the outer region16of the cover sheet11and an outside region thereof. The inner region15having the carrying member20located therein is not heat-sealed.

Step 8: Supply of Backing Sheet

The backing sheet13is supplied and overlaid on the base sheet12.

The base sheet12with the backing sheet13overlaid thereon is pressed from above and below by a laminating device36to cause the backing sheet13to adhere to the base sheet12through the adhesive layer24of the backing sheet13.

A laminated body made up of a plurality of sheets laminated as described above is punched out by a punching cutter37having a blade along the contour of the system10.

Although not particularly mentioned in the above description of the process, the double-folded release sheet25may be attached to the edge of the backing sheet13in advance to supply at Step 8 the backing sheet13having the release sheet25affixed in this way, or a step of supplying the double-folded release sheet25may be provided before Step 8.

In the above description, the step of forming the cutting part17in the base sheet12is provided immediately before the carrying member supply step 3; however, the cutting part formation step may be provided at any time point before the backing sheet supply step.

3. Use

The use of the system10manufactured as above will be described.

As shown inFIGS. 4A, 4B and 4C, when used, the base sheet12and the cover sheet11are held by the adhesion portion thereof contacting with the release sheet25and are peeled off from the backing sheet13. In this regard, as shown inFIG. 4A, the base sheet12has the cutting part17formed between the inner region15and the outer region16thereof. Therefore, the inner region15of the base sheet12remains on the backing sheet13because of the adhesive layer24without being peeled off from the backing sheet13. The carrying member20fixed to the inner region15of the base sheet12also remains on the backing sheet13along with the inner region15.

Subsequently, as shown inFIG. 4B, the system10with the cover sheet11and the outer region16of the base sheet12removed is affixed such that the adhesive layer24is placed on a skin40. Lastly, as shown inFIG. 4C, the release sheet25is peeled off and the whole of the adhesive layer24is affixed to the skin40.

As described above, according to the system10of the embodiment, the drug preparation carrying member20is retained on the backing sheet13after the cover sheet11and the outer region16of the base sheet12are peeled off from the system10, and therefore can directly be affixed to the skin40along with the backing sheet13. Additionally, since it is not necessary to perform an operation such as adjusting the position of the carrying member20with respect to the backing sheet13, the drug preparation does not adhere to the user's finger.

EXPLANATIONS OF LETTERS OR NUMERALS