JP7035379B2 - External patch with time indicator - Google Patents

Description

The present invention relates to an external patch with a time indicator capable of visually controlling the application time specified in the external patch.

As a means for administering a drug, a method of applying an external patch containing the drug to the skin is generally known. The external patch is widely used for a wide variety of purposes such as those for local action and those for systemic action such as ischemic heart disease therapeutic effect and asthma therapeutic effect.

The external patch has, for example, a structure in which a pressure-sensitive adhesive layer to be attached to the skin is formed on one side surface of a film-shaped or sheet-shaped support layer, and the above-mentioned pressure-sensitive adhesive layer contains a necessary drug. To. The external patch is called a poultice, a plaster, or the like depending on the type of the pressure-sensitive adhesive layer (for example, Patent Document 1).

Japanese Patent Application Laid-Open No. 2003-93434

The external patch is applied to the skin for a certain period of time and then peeled off. Among them, for the purpose of systemic action, the application time for percutaneously absorbing a predetermined amount of the drug and the application to a new external patch The timing of replacement has been decided. For this reason, the user needs to peel off the external patch from the skin and replace it with a new external patch after the application time specified for the external patch has elapsed. However, if the user forgets the elapsed time after applying the external patch and peels it off earlier than the specified application time, the required amount of the drug is not percutaneously absorbed and the medicinal effect cannot be sufficiently obtained. In some cases. In addition, if the user forgets to apply the external patch or remove the external patch and attach a new external patch without removing the already applied external patch, the drug will be applied. There is a problem with safety due to overdose.

The present invention has been made in view of the above problems, and an object of the present invention is to provide an external patch with a time indicator capable of visually controlling the application time specified for the external patch.

In order to achieve the above object, the present invention has an indicator layer, a support layer, a pressure-sensitive adhesive layer containing a drug and a pressure-sensitive adhesive base, and a release layer in this order, and the above-mentioned indicator layer is an external factor. Provided is an external patch with a time indicator, whose color tone changes according to the time history of being affected by the above.

According to the present invention, the user of the external patch can take the external patch out of the bag and put it on the skin by visually detecting the change in the color tone of the indicator layer according to the time history of the action of the external factor. It is possible to confirm the elapsed time from the application, and it is possible to recognize that the external application patch has been applied to the skin beyond the specified application time. As a result, it is possible to prevent forgetting to peel off or replace the external patch, and it is possible to accurately manage the sticking time.

In the present invention, the indicator layer may be an oxygen indicator layer and the external factor may be oxygen. Further, the indicator layer may be a temperature history indicator layer, and the external factor may be a temperature. Further, the indicator layer may be a humidity indicator layer, and the external factor may be humidity.

INDUSTRIAL APPLICABILITY The present invention has an effect that it is possible to provide an indicator capable of accurately controlling the application time specified in the external application patch.

It is a schematic plan view which shows an example of the external patch with a time indicator of this invention. FIG. 5 is a cross-sectional view taken along the line XX of FIG. It is a schematic plan view which shows the other example of the external patch with a time indicator of this invention. It is the schematic sectional drawing which shows the other example of the external patch with a time indicator of this invention.

Hereinafter, the external patch with a time indicator of the present invention will be described. The external patch with a time indicator of the present invention has an indicator layer, a support layer, a pressure-sensitive adhesive layer containing a drug and a pressure-sensitive adhesive base, and a release layer in this order, and the indicator layer is an external factor. The color tone changes according to the time history of the action.

FIG. 1 is a schematic plan view showing an example of an external patch with a time indicator of the present invention, and FIG. 2 is a sectional view taken along line XX of FIG. The external patch 10 with a time indicator of the present invention has an indicator layer 1, a support layer 2, a pressure-sensitive adhesive layer 3 containing a drug and a pressure-sensitive adhesive base, and a release layer 4 in this order. The color tone of the indicator layer 1 changes according to the time history of being affected by an external factor.

According to the present invention, the user of the external patch can take the external patch out of the bag and put it on the skin by visually detecting the change in the color tone of the indicator layer according to the time history of the action of the external factor. It is possible to confirm the elapsed time from the application, and it is possible to recognize that the external application patch has been applied to the skin beyond the specified application time. As a result, it is possible to prevent forgetting to peel off or replace the external patch, and it is possible to accurately manage the sticking time.

Here, in the present invention, "the color tone of the indicator layer changes" means that the color tone before being affected by the external factor is different from the color tone after being affected by the external factor. Specifically, although it depends on the type and composition of the indicator layer, it means changing from colorless to colored, changing from colored to colorless, changing from the first colored to the second colored, and the like. In addition, the mode of these color tone changes may be referred to as a color change mode.

In the external patch with a time indicator of the present invention, the discoloration time from when the indicator layer begins to be affected by the external factor until the color tone changes to a predetermined color can be set as the application time specified for the external patch. The discoloration time of the indicator layer is not particularly limited, but is preferably a time during which the color difference between the color tone before being affected by the external factor and the color tone after being affected by the external factor is 30 or more. This is because it becomes easy to visually detect the change in color tone, and it becomes easy to visually recognize that the application time specified for the external application has passed. The color difference is a difference (ΔE ^* ab) represented by the distance between the chromaticities a ^* and b ^* represented by the L ^* a ^* b ^* color system. Specifically, the color difference (ΔE ^* ab) is recommended by the International Certification Committee (CIE), and in the L ^* a ^* b ^* color system specified in JIS Z8729, ΔE ^* ab = ((ΔL ^* )). ² + (Δa ^* ) ² + (Δb ^* ) ² ) It is a value represented by ^1/2 . The values of L ^* , a ^* , and b ^* can be measured by using, for example, a spectroscopic measuring instrument (manufactured by Gretag Macbeth, trade name: spectrolino), and ΔL ^* , Δa ^* , and Δb ^* are respectively. , L ^* , a ^* , b ^* values of the indicator layer before being affected by the external factor and L ^* , a ^* , b ^* of the indicator layer after the color change time has elapsed due to the action of the external factor. It is the difference with each value.

Further, the discoloration time is appropriately set so as to be a time that makes it easy to visually determine that a predetermined color tone has been reached according to the type of the indicator layer, the type of the drug, and the application time specified for the external patch. can do. The discoloration time can be set within a range of, for example, 4 hours or more and 60 hours or less from the general application time of the external application patch. Specifically, if the drug is a local anesthetic such as lidocaine, the discoloration time can be set within the range of, for example, 4 hours to 6 hours. Further, in the case of a systemic agent, the discoloration time can be set, for example, between 24 hours and 48 hours, and can be set, for example, between 12 hours and 18 hours in consideration of bedtime and the like. It is possible.

Hereinafter, the external patch with a time indicator of the present invention will be described for each configuration.

1. 1. Indicator layer The indicator layer in the present invention is a layer arranged on the surface opposite to the pressure-sensitive adhesive layer of the support layer, and its color tone changes according to the time history under the action of an external factor.

Here, the external factor means a factor that is applied to the indicator layer from the outside and acts on the material contained in the indicator layer to cause a color tone change. The external factor can be appropriately selected depending on the type of the indicator layer, and specific examples thereof include oxygen, temperature, and humidity.

The indicator layer may be at least one selected from the group consisting of an oxygen indicator layer, a temperature history indicator layer, and a humidity indicator layer, depending on the type of the external factor. Hereinafter, the indicator layer corresponding to each external factor will be described.

(1) First Aspect In the first aspect of the indicator layer in the present invention, the indicator layer is an oxygen indicator layer and the external factor is oxygen. In this embodiment, "under the action of an external factor" means that the oxygen indicator layer is "under the action of oxygen", specifically, the oxygen indicator layer absorbs oxygen. It means that the material contained in the oxygen indicator layer is oxidized.

The composition of the oxygen indicator layer may be the same as the composition of a known oxygen indicator as long as it can detect a predetermined amount of oxygen. For example, a composition containing at least a redox dye, a reducing agent, and a binder resin that exhibit different color tones in the reduced state and the oxidized state can be mentioned. In the oxygen indicator layer having the above composition, the redox dye can exhibit different color tones depending on whether it is in the reduced form or the oxidized form. For example, if the redox dye is methylene blue, it can exhibit a reducing color, that is, colorless (leucomethylene blue) by the action of a reducing agent under deoxidation, and can be oxidized to exhibit blue under an oxidizing substance atmosphere.

As the redox dye, known materials can be used, for example, methylene blue, neumethylene blue, neutral red, indigo carmine, acid red, saffron T, phenosafranin, capri blue, nile blue, diphenylamine, xylene cyanol, and the like. Examples thereof include nitrodiphenylamine, ferroin, N-phenylanthral acid and the like. Moreover, leuco dye or the like can also be used.

Further, an antioxidant may be used as the redox dye. This is because it is possible to detect that a predetermined amount of oxygen has been absorbed by utilizing the coloring of the antioxidant. Specific examples of the antioxidant include flavonoid glycosides such as citronin, naringin and rutin, and phenoxyalkanoic acid derivatives.

Examples of the reducing agent include ascorbic acid and its salt, erythorbic acid and its salt, D-arabinose, D-erythrose, D-galactose, D-xylose, D-glucose, D-mannose, D-fractose, D. -Reducing sugars such as lactose, mannose salts, ferrous salts and the like can be mentioned.

Examples of the binder resin include acetal resins such as polyvinyl acetal resin; cellulose resins such as methyl cellulose and ethyl cellulose; butyral resin; acrylic resins; urethane resins; polyester resins having a hydrophilic group introduced therein.

The blending amount of each material in the oxygen indicator layer shall be appropriately set so that the discoloration time until the oxygen indicator changes color to a predetermined color tone becomes equal to the sticking time specified for the external patch. Can be done.

In addition to the above-mentioned materials, the oxygen indicator layer may contain any known material used for an oxygen indicator, such as an alkalizing agent, a surfactant, a filler, and a moisturizer.

The oxygen indicator layer may be formed in the form of a sheet using ink or the like containing the above-mentioned composition, and a tablet containing the above-mentioned composition is enclosed in a packaging material having a gas barrier property to form a sheet. It may be.

(2) Second Aspect A second aspect of the indicator layer in the present invention is a mode in which the indicator layer is a temperature history indicator layer and the external factor is temperature. In this embodiment, the fact that the indicator layer is "affected by an external factor" means that the temperature history indicator layer is "affected by temperature", and specifically, the temperature history indicator layer is cumulative. It means that the temperature reaches a predetermined control temperature or higher for a certain period of time.

Here, the control temperature means the temperature at which the temperature history indicator layer starts the coloring reaction. When the temperature history indicator layer reaches the control temperature or higher, the color change progresses, and when the temperature becomes lower than the control temperature, the color change stops.

The control temperature of the temperature history indicator layer is not particularly limited, and can be appropriately set to a temperature that can be reached when the external patch is attached to the skin. The control temperature may be, for example, 20 ° C. or higher.

Further, in the temperature history indicator layer, the cumulative time obtained by accumulating the time when the temperature reaches a predetermined control temperature or higher can be set as the discoloration time. The cumulative time can be set to be equivalent to the application time specified for the external patch or the predetermined elapsed time after the external patch is applied.

The temperature history indicator layer and its composition are not particularly limited as long as it is possible for a reaction to occur at a predetermined control temperature or higher and the discoloration to proceed to a predetermined color tone, and a known temperature history indicator depending on the discoloration mode. It can be similar to the layer and its composition. The composition of the temperature history indicator layer includes, for example, a composition containing a dye and an organic acid or a metal salt thereof and a conductivity-imparting substance (first composition), and a heat-meltable substance having a melting point corresponding to a controlled temperature and a color. A composition containing the material (second composition), a composition containing the color-developing agent, a color-developing agent that promotes color development of the color-developing agent, and a molten material, and a composition that develops color by contact between the color-developing agent and the color-developing agent (third composition). , Etc. can be mentioned.

Specifically, the composition can be the composition described in JP-A-2004-264830. Further, as the second composition, specifically, the composition described in JP-A-2001-303304, JP-A-2002-294123, etc. can be used. Specifically, the composition can be the composition described in JP-A-2015-72208.

The blending amount of each material in each of the first to third compositions is such that the cumulative time until the temperature history indicator changes to a predetermined color tone is the elapsed time after the external patch is applied, or the external patch. It can be appropriately set so that the blending amount is equal to the specified application time.

The temperature history indicator layer may be a single layer containing any of the above-mentioned compositions, and has a two-layer structure containing a material having any one of the above-mentioned compositions separated into two layers. You may. For example, when the temperature history indicator layer has a third composition, the temperature history indicator layer is formed by laminating a first layer containing a color former and a second layer containing the color developer, and the first layer and the first layer and the second layer containing the developer are laminated. At least one of the second layers can have a two-layer structure containing the molten material. By having the above structure, when the temperature history indicator layer reaches the control temperature or higher, the molten material melts and the color developer in the second layer permeates into the first layer and reacts with the color former. It becomes possible to discolor.

The temperature history indicator layer in the present invention is not limited to the layer having any one of the first to third compositions described above, and other known temperature history indicator layers can be used. For example, the label comp of the temperature-sensitive indicator disclosed in Japanese Patent Application Laid-Open No. 2010-175350, the temperature-time integration indicator disclosed in Japanese Patent Application Laid-Open No. 2012-220308, Japanese Patent Application Laid-Open No. 11-502023 (Patent No. 37635578). ) Can be used as the temperature history indicator layer in the present invention.

(3) Third Aspect A third aspect of the indicator layer in the present invention is a mode in which the indicator layer is a humidity indicator layer and the external factor is humidity. In this embodiment, the fact that the indicator layer is "affected by an external factor" means that the humidity indicator layer is "affected by humidity", and specifically, the humidity indicator layer absorbs a predetermined amount of water. By doing so, the material contained in the humidity indicator layer is deliquescent.

The composition of the humidity indicator layer may be any composition as long as it can detect a predetermined amount of humidity, and may be the same as the composition of a known humidity indicator. For example, a composition containing at least a leuco dye, an acidic compound, and a deliquescent compound can be mentioned. In the above composition, the deliquescent compound is deliquescent by absorbing moisture, and the hue can be changed by reacting with the leuco dye while dissolving the acidic compound. Specific examples of the leuco dye, the acidic compound, and the deliquescent compound include various materials described in JP-A-2007-192614, for example. Further, the composition of the humidity indicator layer can be the composition disclosed in US Patent Application Publication No. 2017/043922.

In addition to the above-mentioned materials, the humidity indicator layer may contain any known material used for the humidity indicator, such as a water-retaining substance such as a water-based resin emulsion or a water-soluble polymer compound.

The blending amount of each material in the humidity indicator layer is appropriately set so that, for example, the time until the humidity indicator layer changes color to a predetermined color tone due to moisture absorption is equal to the sticking time specified for the external patch. Can be set.

The humidity indicator layer may be formed in a sheet shape using an ink or the like containing the above-mentioned composition, and has the above-mentioned composition in which a powder containing the above-mentioned composition is supported on a film and is composited with a non-woven fabric. It may be made into a sheet by enclosing the contained powder or a tablet molded from the above powder in a packaging material.

(4) Others The thickness of the indicator layer can be set so that a change in color tone can be visually detected, and can be appropriately set according to the mode of the indicator layer and its composition. The thickness can be, for example, 2.0 μm or more and 30.0 μm or less.

The color tone of the indicator layer is irreversible. This is because the elapsed time after the external patch is applied to the skin can be accurately measured, and the application time can be controlled more accurately.

The indicator layer may be arranged on the entire surface of one surface of the support layer, or may be partially arranged. Further, the indicator layer may have a pattern shape showing characters, patterns, etc. in a plan view.

At least one indicator layer may be arranged on one surface of the support layer. For example, as illustrated in FIG. 3, two or more indicator layers having different color change times (first to third). Each indicator layer 1A to 1C) may be arranged in parallel. When having one indicator layer, for example, by setting the discoloration time until the color tone changes to a predetermined value to the application time specified for the external patch, the change in the color tone of the indicator layer is specified for the external patch. It is possible to visually detect that the pasting time has passed. Further, when having a plurality of indicator layers, by setting the discoloration time of each indicator layer to a predetermined elapsed time after the external patch is applied, which of the plurality of indicator layers can be used. Depending on whether the color has changed, it is possible to visually detect the elapsed time from the application of the external patch and the elapse of the application time specified in the external patch.

Examples of the discoloration mode (mode in which the color tone changes) of the indicator layer include, but are limited to, a discoloration mode in which the color tone changes from colorless to a color, a discoloration mode in which the first color changes to the second color, and the like. Not done.

The indicator layer adjusts the content of the material contained in the composition, etc., and correlates these parameters with the color change time until the color tone changes to a predetermined color tone, so that the degree of change in the color tone of the indicator layer can be determined. , It is possible to measure the elapsed time since the external patch was applied to the skin.

2. 2. Support layer The support layer in the present invention is arranged between the indicator layer and the pressure-sensitive adhesive layer.

The support layer is not particularly limited as long as it can support the pressure-sensitive adhesive layer and the indicator layer, but it is preferable that the support layer has appropriate flexibility from the viewpoint of enhancing the adhesiveness of the external patch to the skin. .. Further, it is preferable to have impermeableness to the drug in the pressure-sensitive adhesive layer. Examples of such a support layer include a plastic film, a woven fabric, a non-woven fabric, and paper. The material of the plastic film, woven fabric and non-woven fabric can be the same as the material of the support layer in known external patches, for example, polymers such as polyester, polypropylene, polyethylene, polyamide, vinyl acetate and vinyl chloride. Examples thereof include a resin made of a polymer (ethylene-vinyl acetate copolymer, etc.) obtained by copolymerizing the monomers constituting these.

The thickness of the support layer is not particularly limited, but it can usually be about 2 μm or more and 2000 μm or less from the viewpoint of handleability of the patch.

The support layer may be surface-treated such as plasma treatment and corona treatment. Further, the support layer may have a coat layer. Examples of the material of the coat layer include acrylic resin, butyral resin, ethylene-vinyl acetate copolymer, ethylene vinyl alcohol copolymer and the like.

3. 3. Adhesive layer The adhesive layer in the external patch with a time indicator of the present invention is a layer arranged between the release layer and the support layer and containing a drug and an adhesive base. As for the pressure-sensitive adhesive layer, the surface on the release layer side is attached to the user's skin.

The pressure-sensitive adhesive layer is obtained by mixing a drug with a pressure-sensitive adhesive to disperse, solubilize, or emulsify the drug, and depending on the type of the pressure-sensitive adhesive, the external patch of the present invention may be used as a plaster agent ( It can be a tape agent) or a happ agent.

(1) Agent The agent contained in the pressure-sensitive adhesive layer is not particularly limited as long as it exhibits transdermal absorbability, and various agents used in conventionally known external patches can be used. Examples of the above-mentioned drug include the following.
・ Hypnosis / sedative (flurazepam hydrochloride, rilmazafone hydrochloride, phenobarbital, amobarbital, etc.)
・ Antipyretic anti-inflammatory analgesic (butorphanol tartrate, perisoxal citrate, acetaminophen, mephenamic acid, diclofenac sodium, aspirin, alcrophenac, ketoprofen, flurbiprofen, naproxen, pyroxycam, pentazocin, indomethacin, glycol salicylate, aminopyrine, loxoprofen, etc.)
・ Steroidal anti-inflammatory agents (hydrocortisone, prednisolone, dexamethasone, betamethasone, etc.)
・ Excitement / stimulant (methamphetamine hydrochloride, methylphenidate hydrochloride, etc.)
・ Psychoneurotic agents (imiplan hydrochloride, diazepam, celtralin hydrochloride, fluvoxamine maleate, paroxetine hydrochloride, citaloplum hydrobromide, fluoxetine hydrochloride, alprazolam, haloperidol, chromipramine, amitriptyline, decipramine, amoxapine, maplotyline, mianserin Rohepramine, Mianserin, Duroxetine, Benrafexin, Chlorpromazine hydrochloride, Thioridazine, Diazepam, Meprobamate, Ethizolam, Lisperidone, Miltazapine, etc.)
・ Hormonal agents (estradiol, estriol, progesterone, norethisterone acetate, metellonone acetate, testosterone, etc.)
・ Local anesthetic (lidocaine hydrochloride, procaine hydrochloride, tetracaine hydrochloride, dibucaine hydrochloride, propitocaine hydrochloride, etc.)
・ Urinary organ preparations (tamsulosin hydrochloride, propiverine hydrochloride, tolterodine tartrate, fesoterodine, imidafenacin, oxybutynin hydrochloride, terroridine hydrochloride, etc.)
・ Skeletal muscle relaxants (tizanidine hydrochloride, eperisone hydrochloride, prizinol mesylate, suxamethonium hydrochloride, etc.)
・ Reproductive organ agents (ritodrine hydrochloride, meladrin tartrate, etc.)
・ Antiepileptic agents (sodium valproate, clonazepam, carbamazepine, etc.)
・ Autonomic nerve agents (carpronium chloride, neostigmine bromide, bethanechol chloride, etc.)
・ Anti-Parkinson's disease agents (pergolide mesylate, bromocriptine mesylate, trihexyphenidyl hydrochloride, amantadine hydrochloride, ropinirole hydrochloride, talipexol hydrochloride, cabergoline, droxydopa, piperiden, selegiline hydrochloride, etc.)
・ Diuretics (hydroflumethiazide, furosemide, etc.)
・ Respiratory promoter (lobeline hydrochloride, dimorpholamine, naloxone hydrochloride, etc.)
・ Anti-migraine agents (dihydroergotamine mesylate, sumatriptan, ergotamine tartrate, flunaridine hydrochloride, cyproheptazine hydrochloride, etc.)
・ Antihistamines (clemastine fumarate, diphenhydramine tannate, chlorpheniramine maleate, diphenylpyraline hydrochloride, promethazine, etc.)
Bronchodilators (tulobuterol hydrochloride, procaterol hydrochloride, salbutamol sulfate, clenbuterol hydrochloride, phenotelol hydrobromide, terbutaline sulfate, isoprenaline sulfate, formoterol fumarate, etc.)
・ Cardiac stimulants (isoprenaline hydrochloride, dopamine hydrochloride, etc.)
・ Coronary vasodilator (diltiazem hydrochloride, verapamil hydrochloride, isosorbide dinitrate, nitroglycerin, nicorandil, etc.)
・ Peripheral vasodilators (nicamethate citrate, tolazoline hydrochloride, etc.)
・ Smoking cessation aids (nicotine, etc.)
・ Circulatory agents (flunaridine hydrochloride, nicardipine hydrochloride, nitrendine pin, nisoldipine, ferrodipine, amlogipin besilate, nifedipine, nilvadipine, manidipine hydrochloride, benidipine hydrochloride, enalapril maleate, democapril hydrochloride, aracepril, imidapril hydrochloride, lysipril Trandrapril, Perindopril erbumin, athenolol, pindolol, bisoprolol fumarate, meteprolol tartrate, betaxolol hydrochloride, timorol maleate, bopindolol malonate, nipradilol, arotinolol hydrochloride, celiprol hydrochloride, carvegilol, amoslalol hydrochloride, carteolol hydrochloride Bevantrol, terrazocin hydrochloride, bunazocin hydrochloride, prazosin hydrochloride, doxazocin mesylate, balsartane, candesartan cilexetil, rosartan potassium, chronidine hydrochloride, guanfacin hydrochloride, guanabends acetate, etc.)
・ Arrhythmia agents (propranolol hydrochloride, alprenolol hydrochloride, procainamide hydrochloride, mexitylene hydrochloride, nadolol, disopyramide, etc.)
・ Anti-malignant ulcer agents (cyclophosphamide, fluorouracil, degafur, procarbazine hydrochloride, ranimustine, irinotecan hydrochloride, flulysine, etc.)
・ Antihyperlipidemic agents (pravastatin, simvastatin, bezafibrate, probucol, etc.),
・ Hypoglycemic agents (glibenclamide, chlorpropamide, tolbutamide, sodium glymidin, glybsol, buformin hydrochloride, etc.)
・ Stomach Ulcer therapeutic agent (proglumide, cetraxate hydrochloride, spizoflon, cimetidine, glycopyrronium bromide, etc.)
・ Biliary agent (ursodesoxycholic acid, osalmid, etc.)
・ Gastrointestinal motility improving agent (domperidone, cisapride, etc.)
・ Liver disease agents (tiopronin, etc.)
・ Anti-allergic agents (ketotifen fumarate, azelastine hydrochloride, etc.)
・ Antiviral agents (acyclovir, etc.)
・ Antispasmodic agent (betahistine mesylate, diphenidol hydrochloride, etc.)
・ Antibiotics (cephaloridine, cefdinyl, cefpodoxime proxetyl, cefaclor, clarithromycin, erythromycin, methylerythromycin, kanamycin sulfate, cycloserine, tetracycline, benzylpenicillin potassium, propicillin potassium, cloxacin sodium, ampicillin sodium, Bacampicillin hydrochloride, carbenicillin sodium, chloramphenicol, etc.)
・ Agents for addictive poisoning (cyanamide, etc.)
・ Appetite suppressant (mazindol, etc.)
・ Chemotherapeutic agents (Isoniaside, ethionamide, pyrazinamide, etc.)
・ Blood coagulation promoter (ticlopidine hydrochloride, warfarin potassium, etc.)
・ Anti-Alzheimer's agent (physostigmine, donepezil hydrochloride, tacrine, arecoline, xanomeline, rivastigmine, galantamine, etc.)
・ Serotonin receptor antagonist antiemetics (ondansetron hydrochloride, granisetron hydrochloride, ramosetron hydrochloride, azasetron hydrochloride, palonosetron, etc.)
・ Gout remedies (colchicine, probenecid, sulfinpyrazone, etc.)
・ Narcotic analgesics (fentanyl citrate, morphine sulfate, morphine hydrochloride, codeine phosphate, cocaine hydrochloride, pethidine hydrochloride, etc.)
・ Anti-Parkinson's agent (benztropine, levodopa, etc.)
・ Antispasmodic (methylatropine bromide, scopolamine, etc.)

The above-mentioned agent may be a locally acting agent or a systemic acting agent. Above all, the above-mentioned drug is preferably a systemic action drug. This is because it is possible to accurately manage the elapsed time from medium to long time by changing the color tone of the indicator layer. In addition, the above-mentioned agents may be appropriately blended in one kind or two or more kinds.

The content of the drug in the pressure-sensitive adhesive layer is not particularly limited, and can be appropriately set according to the transdermal absorption rate of the drug, the sticking time specified for the external patch, and the like.

(2) Adhesive base The adhesive base contained in the pressure-sensitive adhesive layer preferably has excellent compatibility with the drug and has an adhesive force capable of fixing the external patch to the skin surface for a long time. The pressure-sensitive group may be hydrophilic or hydrophobic. Hydrophobic adhesive bases are used for plasters (tapes). In addition, the hydrophilic adhesive base is used for the poultice.

As the hydrophobic pressure-sensitive adhesive base, a known pressure-sensitive adhesive base used as a plaster agent (tape agent) can be used, and is not particularly limited, but for example, an acrylic pressure-sensitive adhesive or a rubber-based pressure-sensitive adhesive. , Silicone-based adhesives, vinyl ether-based adhesives, urethane-based adhesives, vinyl acetate-based adhesives and the like, and these can be used alone or in combination of two or more. Moreover, these may be emulsified. Among them, an acrylic pressure-sensitive adhesive, a rubber-based pressure-sensitive adhesive, and a silicone-based pressure-sensitive adhesive can be preferably used from the viewpoint of excellent release of the drug.

As the hydrophilic pressure-sensitive adhesive base, a known pressure-sensitive adhesive base used for a poultice can be used, and the present invention is not particularly limited, but for example, polyacrylic acid, sodium polyacrylate, or a polyacrylic acid moiety. In addition to neutralized products, N-vinylacetamide / sodium acrylate copolymer, polyvinyl alcohol, polyvinylpyrrolidone, hydroxymethylcellulose, sodium carboxymethylcellulose, alginic acid, sodium alginate, gelatin, gum arabic, etc., these are aluminum, zinc, magnesium. , Crosslinked with a metal salt such as calcium. Only one kind of these may be used, or two or more kinds thereof may be used.

(3) Additives Various additives can be added to the pressure-sensitive adhesive layer as needed. Examples of the above additives include release promoters, essential oils, transdermal absorption promoters, plasticizers, tackifiers, stabilizers, softeners, fillers, antioxidants, cross-linking agents, preservatives, and ultraviolet rays. Examples include absorbents, soluble / water-swellable polymers, higher alcohols and the like. These can be the same as the additives used in known external patches.

(4) Others The thickness of the pressure-sensitive adhesive layer is not particularly limited, but is preferably a thickness that can contain a desired amount of the drug and can exert a desired pressure-sensitive adhesive force. The thickness can be, for example, 10 μm or more and 300 μm or less.

4. Release layer The release layer in the external patch with a time indicator of the present invention is a layer arranged on the surface opposite to the support layer of the pressure-sensitive adhesive layer, and is peeled off and removed when the external patch with a time indicator is used. It is a layer to be.

As the release layer, a film or the like that can be peeled off from the pressure-sensitive adhesive layer is used. Examples of the release layer include a release film such as a vinyl chloride film, a polyethylene film, a polypropylene film, and a polyester film, a polyethylene terephthalate separator with a chemical ruler, a release paper (release paper), and the like. The release layer may be surface-treated, such as a silicone surface treatment, on the surface in contact with the pressure-sensitive adhesive layer.

5. Color swatch layer The external patch with a time indicator of the present invention may further have a color swatch layer for discriminating the elapsed time from the color of the indicator layer on the surface of the support layer having the indicator layer. By arranging the color sample layer showing the correlation between the elapsed time from the application of the external patch and the color tone of the indicator layer on the surface of the support layer on which the indicator layer is arranged, the color tone and the color sample of the indicator layer are arranged. The elapsed time can be easily specified by comparing with the color of the layer.

In the external patch with a time indicator of the present invention exemplified in FIGS. 1 to 2, the indicator layer 1 and the color sample layer 5 are arranged on the same surface of the support layer 2, and the color sample layer 5 has a color sample layer 5. It has five regions having the same color tone as the color tone of the indicator layer 1 every 6 hours from 0 hour to 24 hours.

The color swatch layer has at least a region of a color tone equivalent to a predetermined color tone after the color change time of the indicator layer has elapsed. Thereby, it is possible to confirm whether or not the indicator layer is in a state after being changed to a predetermined color tone by comparing with the color of the color sample layer. Further, the color sample layer divides the color change time until the indicator layer changes to a predetermined color tone at desired intervals, and forms one or more regions having a color tone equivalent to the color tone of the indicator layer at each divided time. You can also have. Thereby, the elapsed time after the indicator layer is attached can be determined from the color of the color sample layer.

The color swatch layer is a layer that does not cause a change similar to a color tone change in the indicator layer due to the action of an external factor, and contains, for example, an ink composition contained in inks such as water-based inks, oil-based inks, and solvent-free inks. be able to. The ink composition contained in the color swatch layer may contain components contained in known inks such as a coloring material and a resin binder.

The position of the color sample layer in the external patch with a time indicator of the present invention is not particularly limited, but is preferably a position comparable to the color tone of the indicator layer on the surface of the support layer having the indicator layer. The color swatch layer may be arranged in parallel with the indicator layer, or may be arranged so as to surround the outer periphery of the indicator layer.

Further, the color sample layer may be formed on the entire surface of a region other than the arrangement region of the indicator layer on the surface of the support layer having the indicator layer, or may be partially formed. Further, the indicator layer may have a pattern shape showing characters, patterns, etc. in a plan view.

The color swatch layer can be formed, for example, by using an ink obtained by dispersing or dissolving the above-mentioned ink composition in a solvent and following a known printing method such as silk screen printing, gravure printing, offset printing, letterpress printing, flexographic printing and the like. ..

6. Transparent protective layer The external patch with a time indicator of the present invention may further have a transparent protective layer that covers the indicator layer. By having the transparent protective layer that covers the indicator layer, the indicator layer can be protected from the environment exposed on the user's skin, and deterioration and peeling of the indicator layer can be prevented.

The external patch with a time indicator of the present invention exemplified in FIG. 4 has a color sample layer 5 on the surface of the support layer 2 having the indicator layer 1, and is a transparent protective layer so as to cover the indicator layer 1 and the color sample layer 5. 6 is arranged.

The transparent protective layer is made of a transparent material so that the color change of the indicator layer can be visually detected. Examples of the material of the transparent protective layer include transparent resins such as polypropylene, polyethylene, ethylene-vinyl acetate copolymer, butyral resin, and polystyrene resin.

The thickness of the transparent protective layer is not particularly limited and can be appropriately set. The transparent protective layer preferably has a thickness capable of covering at least the indicator layer and having a desired transparency.

The transparent protective layer is at least transparent, but is waterproof, wear-resistant, and reagent-contaminated during manufacturing, depending on the type of indicator layer and the environment in which the indicator layer is exposed while attached on the skin. It is preferable to have prevention and the like.

The transparent protective layer can be arranged so as to cover at least the indicator layer on the surface of the support layer having the indicator layer. When the indicator layer is provided on a part of one surface of the support layer, the transparent protective layer may be arranged so as to cover at least the indicator layer, and the indicator layer and the indicator layer of the support layer are arranged. It may be arranged so as to cover the entire area of the surface. When the color sample layer is provided on the surface of the support layer on which the indicator layer is arranged, the transparent protective layer may be arranged so as to cover the indicator layer and the color sample layer.

The transparent protective layer may be, for example, a heat-laminated film of the transparent resin described above, or may be formed by applying the transparent resin.

7. In addition, the external patch with a time indicator of the present invention may have a packaging bag for enclosing the external patch with a time indicator. The external patch with a time indicator of the present invention is usually stored in a packaging bag until it is applied to the skin and used.

As the packaging bag, one having a gas barrier property for separating the external patch with a time indicator from the outside air and a sealing property for sealing is preferably used. Examples of such a packaging bag include a packaging bag having a gas barrier layer as an outer layer and a heat seal layer as an inner layer. Examples of the gas barrier layer include a metal foil such as aluminum, a gas barrier film having a resin film and a thin film arranged on one surface of the resin film and formed of a metal or an inorganic compound. Further, examples of the heat seal layer include a heat-weldable resin film such as polyethylene and polyolefin.

8. Manufacturing Method The manufacturing method of the external patch with a time indicator of the present invention is not particularly limited, but for example, a coating liquid for forming a pressure-sensitive adhesive layer in which a pressure-sensitive adhesive composition containing a pressure-sensitive adhesive and a drug is mixed with a solvent is used. Preparation step to prepare, time indicator forming step of applying the composition for forming an indicator layer on the support layer and drying to form the indicator layer, the adhesive on the surface of the support layer of the time indicator opposite to the indicator layer. A pressure-sensitive adhesive layer forming step of applying a coating liquid for forming an agent layer and drying to form a pressure-sensitive adhesive layer. It can be formed through an arrangement process.

Further, as the above-mentioned manufacturing method, the above-mentioned preparation step and time indicator forming step, and the above-mentioned coating liquid for forming the pressure-sensitive adhesive layer are applied to one surface of the release layer and dried to form the pressure-sensitive adhesive layer. It can be formed through a layer forming step and a time indicator arranging step of arranging a time indicator on the surface of the pressure-sensitive adhesive layer opposite to the release layer.

In the above manufacturing method, for example, the above-mentioned preparation step and the above-mentioned coating liquid for forming an adhesive layer are applied to one surface of the release layer without performing the time indicator forming step, and the adhesive is dried. The process of forming the pressure-sensitive adhesive layer for forming the layer, the step of arranging the support layer on the surface of the pressure-sensitive adhesive layer opposite to the release layer, and the step of arranging the support layer are opposite to the above-mentioned pressure-sensitive adhesive layer of the support layer. The side surface may have an indicator layer forming step of applying and drying the indicator layer forming composition to form the indicator layer.

The present invention is not limited to the above embodiment. The above embodiment is an example, and any one having substantially the same configuration as the technical idea described in the claims of the present invention and having the same effect and effect is the present invention. It is included in the technical scope of the invention.

1 ... Indicator layer 2 ... Support layer 3 ... Adhesive layer 4 ... Release layer 10 ... External patch with time indicator

Claims (4)

It has an indicator layer, a support layer, a pressure-sensitive adhesive layer containing a drug and a pressure-sensitive adhesive base, and a release layer in this order.
A color swatch layer having a plurality of regions having different color tones is further provided on the surface of the support layer on which the indicator layer is arranged.
The color tone of the indicator layer changes according to the time history of being affected by an external factor such as oxygen, temperature, or humidity .
The color sample is an external patch with a time indicator for determining the elapsed time from the color of the indicator layer . The external patch with a time indicator according to claim 1, wherein the indicator layer is an oxygen indicator layer and the external factor is oxygen. The external patch with a time indicator according to claim 1, wherein the indicator layer is a temperature history indicator layer and the external factor is temperature. The external patch with a time indicator according to claim 1, wherein the indicator layer is a humidity indicator layer and the external factor is humidity.

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