JPH02255611A - Tape plaster for treating disease - Google Patents

Abstract

PURPOSE:To obtain the subject tape plaster, containing a basic drug of a free base structure on a tacky agent layer laminated onto a flexible support and capable of remarkably improving stability and releasability of the drug without deteriorating cohesive force of the tacky agent and causing irritancy to the skin. CONSTITUTION:A tape pharmaceutical, obtained by including a basic drug of a free base structure in a tacky agent, preferably a nonfunctional tacky agent and laminating the resultant drug-containing tacky agent onto a flexible support and useful for treating diseases. An acrylic polymer obtained by polymerizing an alkyl (meth)acrylate and/or alkoxy-modified monomer thereof, rubber- based tacky agent, etc., are cited as the nonfunctional tacky agent. If the acrylic copolymer having hydroxyl and carboxyl groups in the molecule is used as the tacky agent, the drug is temporarily captured in the tacky agent and sustainedly and quantitatively released for a long period. If the drug in a larger number of mol than that of the above-mentioned functional groups is blended, the uncaptured drug is instantaneously released and then sustainedly released to sustainedly exhibit drug effects.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a tape preparation for treating diseases, which is intended for transdermally administering a basic drug having a free base structure into a living body.

<Prior art> In recent years, drug formulations for treating or preventing diseases by administering drugs into living bodies have been developed to prevent drug metabolism due to the first-pass effect of the liver and various side effects, and to maintain drug administration over a long period of time. Transdermal formulations that can be administered to patients are attracting attention. In particular, tape preparations containing drugs in adhesives are being actively developed because they are easy to administer and the dosage can be strictly controlled.

Tape formulations like 2 are used by attaching an adhesive layer containing a drug to the skin surface, so it is necessary to prevent a decrease in the drug content in the adhesive (drug stability) and to prevent drug release from the adhesive. Various properties are required, such as release properties, adhesion to the skin, appropriate cohesiveness to eliminate adhesive residue on the skin, and non-irritation to the skin. In other words, when developing a tape formulation, it is extremely important to consider the chemical and physical properties of the adhesive used, the chemical properties of the drug contained in the adhesive, and the interaction of these combinations. The reality is that there are almost no tape preparations that satisfy all of the above-mentioned required properties.

Furthermore, drugs are usually provided in the form of a free structure or a salt structure, but drugs in the free structure are said to have the drawbacks of poor drug stability and high skin irritation. Moreover, since it has a lower melting point than drugs with a salt structure, when it is included in an adhesive, it exhibits a plasticizing effect and reduces cohesive force.

<Problems to be Solved by the Invention> The present invention contains a drug in a free structure in an adhesive with good stability, and there is no reduction in the cohesive force of the adhesive due to the plasticizing effect of the drug, and there is no skin irritation. The purpose of this invention is to provide a tape formulation with excellent release properties.

<Means for Solving the Problems> As a result of intensive research to achieve the above object, the present inventors found that when using basic drugs among free structure drugs,
It has been discovered that a tape formulation that relatively satisfies the above-mentioned required properties has been completed, and the present invention has been completed.

That is, the tape preparation for disease treatment of the present invention is formed by laminating a drug-containing adhesive layer containing a basic drug with a free base structure in the adhesive on a flexible support.

In particular, by using a non-functional adhesive as the adhesive, the stability and release properties of the drug are significantly improved, and the use of a specific acrylic copolymer having a hydroxyl group and/or carboxyl group in the molecule as an adhesive. By using a drug consisting of the following, it is possible to quantitatively and sustainably release a drug over a long period of time.

The adhesive used in the present invention has the function of tightly fixing the tape preparation to the skin surface and releasing the basic drug containing the free base structure onto the skin surface. As such an adhesive, it is preferable to use a non-functional adhesive so that it can stably hold the drug I& without decomposing it.

Specific examples of non-functional adhesives include rubber adhesives such as silicone rubber, polyisoprene rubber, polyisobutylene rubber, polybutadiene rubber, and styrene-butadiene (or isoprene)-styrene copolymer rubber; (
Examples include acrylic polymers obtained by polymerizing meth)acrylic acid alkyl esters and/or alkoxy-modified monomers thereof, and other polyester resins can also be used. In addition, to further improve the tackiness of these adhesives, tackifiers such as rosin, modified rosin, petroleum resin, polyterpene resin, polystyrene resin, polybutene resin, liquid polyisobutylene, and liquid paraffin are added to these adhesives. A plasticizer may also be incorporated within the scope of the purpose of the present invention.

The acrylic polymer obtained by polymerizing the above (meth)acrylic acid alkyl ester and/or its alkoxy-modified monomer has 4 to 12 carbon atoms from the viewpoint of skin adhesion.
The main monomer is one or more types of (meth)acrylic acid alkyl esters having an alkyl group (including a cyclic alkyl group such as a cyclohexyl group).
A copolymer containing at least % by weight is preferred.

In addition, the alkoxy-modified monomer of (meth)acrylic acid alkyl ester is one in which the alkyl group of (meth)acrylic acid alkyl ester is modified with an alkoxy group such as a methoxy group or an ethoxy group. Examples include methoxyethyl acrylate, ethoxyethyl (meth)acrylic ester, etc. When copolymerized with the above alkyl acrylate in an amount not exceeding 50% by weight, skin adhesion and drug solubility improve. This is preferable because it becomes an adhesive that has well-balanced properties such as drug stability.

In addition to the above monomers, such acrylic polymers include
Styrene or (meth) to improve adhesive cohesiveness
Copolymerizing nonfunctional monomers such as acrylic acid phenyl ester, (meth)acrylic acid alkyl ester having an alkyl group having 4 or less carbon atoms, such as methyl ester, ethyl ester, and propyl ester of (meth)acrylic acid. You can also do that.

On the other hand, in order to minimize the reactivity with drugs, it is preferable that the adhesive does not have any functional groups as described above.
After repeated studies, the present inventors surprisingly found that an adhesive made of an acrylic copolymer having a hydroxyl group and/or carboxyl group as a functional group in the molecule stabilizes basic drugs with a free base structure. It has been found that the present invention exhibits quantitative sustained release properties over a long period of time, so-called m4g1o-order release properties, without impairing properties.

Such an acrylic copolymer uses the above-mentioned (meth)acrylic acid alkyl ester as the main monomer, and (meth)acrylic acid such as (meth)acrylic acid hydroxyethyl ester and (meth)acrylic acid hydroxypropyl ester. Copolymerizing one or more types of monomers having hydroxyl and/or carboxyl groups in the molecule, such as acid hydroxyalkyl esters, (meth)acrylic acid, (iso)crotonic acid, fumaric acid, maleic acid, and itaconic acid. can be obtained by When copolymerizing, the monomer having the above-mentioned hydroxyl group and/or carboxyl group in the molecule is blended in an amount of 0.5 to 20% by weight, preferably 2 to 10% by weight. If it is less than 0.5% by weight, sustained release properties, especially pseudo zero-order release properties, may be insufficient, and if it exceeds 20% by weight, the cohesive force of the adhesive becomes too high, resulting in poor skin adhesion. may decrease.

In addition, for the acrylic copolymer having a hydroxyl group and/or carboxyl group in the molecule, as a third component monomer,
Non-functional monomers such as styrene, (meth)acrylic acid phenyl ester, (meth)acrylic acid alkyl ester having an alkyl group having 4 or less carbon atoms, such as methyl ester, ethyl ester, propyl ester of (meth)acrylic acid It is also possible to copolymerize bodies.

When the above-mentioned acrylic copolymer having a hydroxyl group and/or carboxyl group in the molecule is used as an adhesive, a basic drug having a free base structure is temporarily captured in the adhesive as described below. Therefore, by compounding the drug in an amount larger than the number of moles of the functional group in the adhesive, the uncaptured drug is initially released and exhibits a rapid effect, and then the captured drug gradually becomes quantitatively pseudo-zero-order. As it is released, it can exert its pharmacological effect continuously over a long period of time. In addition, if the amount of drug is less than the mole of the functional group in the adhesive, it will not have immediate effect, but since the captured drug will be released continuously by pseudo zero-order release, the effective blood concentration will increase. It is an effective tape formulation for drugs with low range.

In addition, if a tape preparation using an acrylic copolymer having carboxyl groups in the molecule as an adhesive causes skin irritation when applied to the skin, it should be noted that alkali metals such as potassium and sodium, calcium, etc. The carboxyl groups in the adhesive can also be inactivated by adding a basic substance such as an alkaline earth metal hydroxide, or a compound having a quaternary amine such as ammonia or ethanolamine. In this case, the amount of the basic substance blended is preferably equal to or less than the number of moles of carboxyl groups in the adhesive.

By changing the amount of basic substances mixed, it is possible to increase the initial release amount of the drug and give it rapid effect.
Drug release properties can be changed freely. Also,
Adding a basic substance increases the adhesive's cohesiveness and improves its hydrophilicity, which prevents adhesive from remaining on the skin.
It also improves the absorption of sweat from the skin surface, which is effective in improving skin adhesion and reducing skin irritation.

As described above, the adhesive used in the present invention has excellent properties in tape preparations for disease treatment containing basic drugs having a free base structure, but if further improvement in cohesive force is desired, Crosslinking treatment may be performed by copolymerization of crosslinkable monomers, blending of various crosslinking agents, irradiation with various types of radiation, etc.

The drug used in the present invention is stably retained in the above-mentioned adhesive, is released onto the skin surface, and is absorbed transdermally into the body, and as a result is effective in treating and preventing various diseases. .

Such drugs are not particularly limited as long as they are basic drugs with a free base structure, and include hydrochloride, sulfate, phosphate, tartrate, maleate, mesylate, fumarate, lactate, Basic drugs having an acid salt structure such as acetate and hydrobromide may be used after being made free by known means.

Specific examples of basic drugs having such a free base structure are classified from the viewpoint of pharmacological action and are shown below.

■Hypnotic/sedative drugs: flurazebam, etc.

■Antipyretic, analgesic and anti-inflammatory drugs: tinoridine, benzydamine, perisoxal, lephetamine, dramadol, diltiazem, buprenorphine, butorphanol, etc.

■Stimulants/stimulants: methamphetamine, etc.

■ Sedatives: meclizine, dffi-isoprenaline, diphenidol, betahistine, etc.

■Psychiatric and neurological racks: Chlorbromazine, triflupromacin, lepomepromazine, perazine, prochlorperazine, trifloperazine, thioproperazine, thioridazine, fluphenazine, belphenazine, spiclomazine and other phenothiazine drugs, flupenthixol Such as phenothiazines! ! (GJ skeletal system prefecture east fluoropipamide, butyrophenone drugs such as moperon, diphenylmethane drugs such as hydroxyzine, carpipramine such as carbyramine, clocabramine, imibramine, desipramine, tributyrin, clocabramine, amitributyline, nortributyline, dosulepine, fritrasen,
MA such as tricyclic antidepressants such as lofepramine, tetracyclic antidepressants such as mianserin and maprotiline, and safrazine.
O inhibitors, benzodiazepines such as chlordiazepoxide, and others such as methylphenidate and vilaradrol.

■ Skeletal muscle relaxants such as niblicinol, eperisone, and tolperisone.

■Analgesics such as niatropine, scopolamine, dicyclomine, diethylaminoethyl diphenylhydroxypropionate, bipetanate, piperidlate, oxyphencyclimine, methixene, papaverine, etc.

■Anti-parkinson drugs: biveridene, trihexyphenidine, amantadine, pyroheptine, prophenamine, mazaticol, etc.

■Antihistamines such as nidiphenhydramine, carbinoxamine, chlorpheniramine, alimemazine, isothipendil, triprolidine, clemizole, sibrohebutadine, homochlorcifrizine, diphenylbilarin, ibroheptine, dimetintin, talemastine, etc.

[Phase] Inotropes: isopreterenol, dopamine, dobramin, metaraminol, etilephrine, norphenephrine, etc.

■Arrhythmic drugs: procainamide, lidocaine, quinidine, propranolol, alprenolol, pfetrol, bupranolol, oxprenolol, indenolol, carteolol, befunolol, acebutolol, bucumolol, timolol, alotinol, shisoviramide, mexiletine, verapamil, abrizin Such.

■Hypertensive drugs: ecalazine, hydralazine, dimethylaminoethyl reserpine, dihydroergotoxin, guanfacine, clonidine, bunazosin, bucumolol, prazosin, propranolol, labeclol, guanabenz, enalapril, guanethidine, betanisin,
such as penbutrol.

■ Vasoconstrictors: phenylephrine, methoxamine, dihydroergotamine, etc.

■ Coronary vasodilation measures: ethaphenone, oxyphethrin, dirazep, diltiazem, trimetaresin, verapamil,
carbochromene, prenylamine, etc.

■ Peripheral vasodilators: isoxsuprine, nimethate, nicotinic alcohol, bametane, traprine, etc.

■Other cardiovascular drugs: nicardibine, pyrithioxine,
flunarizine, meclofenoxate, moxisilito,
ifenbrozil, promincamine, pensifulamine,
such as cinepazide and tiapride.

■ Breathing stimulation mN Niloberine, levalorphan, dimefrine, doxapram, napxone, etc.

■Antitussive expectorant: Codine, dihydrocodeine, dextromethorphan, carbetabenchun, penproperine,
Tipepidine, isoaminyl, zinemorphan, oxelazine, ebrazinone, clobutinol, croconazole, hominoben, noscapine, L-methylcysteine, bromhexine, amproxol, epinephrine, ephedrine, methylephedrine, isopreterenol,
Orciprenaline, terbutaline, salbutanol, trime-supraquinol, chlorbrenaline, methoxyphenamine, hexoprenaline, vilbrol, procaterol, tubuterol, vilbutyrol, phenotyrol,
formotyol, clenbuterol, mabuterol,
Ketotifuene, azelaslan, etc.

[Phase] Hormones: Clomifuene, etc.

@ External drugs for purulent diseases: Mafenide, etc.

■Analgesic, antipruritic, astringent, anti-inflammatory drugs: isothipendil, etc.

■Drugs for parasitic skin diseases: miconazole, econazole,
such as iconazole, sconazole, oxiconazole, and croconazole.

■Vitamin: dicethiamine, cycothiamine, pyridoxine, etc.

[Phase] Hemostatic drug: Adrenochrome guanylhydrazone.

■Blood clotting inhibitor: Ticlopidine.

[Phase] Antidote and addictive drug: deferoxamine, etc.

CI! Urinary medicines: metformin, buformin, etc.

[Phase] Anti-cancer drug: Nitrogen Mustard N-
oxide, improsulfan, nimustine, ancitabine, vinblastine, vincristine, vindesine,
daunorubicin, doxorubicin, tamoxifen, procarbazine, etc.

[Phase] Narcotics: Ethylmorphine, morphine, codeine, dihydrocodeine, cocaine, pedizine, fentanyl.

In the present invention, a drug-containing adhesive layer is prepared by incorporating one or more of the above drugs into an adhesive. The compounding amount of the drug may be any pharmacologically effective amount; however, when using an acrylic copolymer having the above-mentioned hydroxyl group and/or carboxyl group in the molecule as an adhesive, the above-mentioned free base may be added to these functional groups. Since there is a risk that a basic drug having a structure may be trapped, it is preferable to mix the amount in an amount larger than the number of moles of functional groups in the adhesive. The amount to be blended is from equimolar to 20 times the number of moles of the functional group in the adhesive, preferably 1.
The amount should be 1 to 10 times the molar amount. By blending in this manner, the initial release properties of the drug are improved, and the contained drug is continuously released over a long period of time.

In addition, the tape formulation for disease treatment of the present invention contains polyethylene glycol,
Auxiliary substances such as lanolin, olive oil, silicone oil, urea, dimethyl sulfoxide, dimethyl formamide, diisopropyl adipate, isopropyl myristate, and terpene resin are added within a range that does not impede the stability or release properties of the drug, for example, 1 to 1 in the drug-containing adhesive layer. It can also be blended in an amount of 30% by weight, preferably 5 to 15% by weight.

<Effects of the Invention> As described above, the tape preparation for disease treatment of the present invention has good transdermal absorbability because it uses a basic drug with a free base structure as the drug. In particular, by using a non-functional adhesive as the adhesive containing the drug, the stability of the drug is further improved.

On the other hand, if an adhesive made of an acrylic copolymer having hydroxyl or carboxyl groups in the molecule is used as an adhesive,
In addition to the above-mentioned properties, sustained drug release properties are improved. In this case, by making the amount of drug compounded equal to or higher than the number of moles of functional groups in the adhesive, the initial release of the drug is good, and the drug is released continuously over a long period of time, and various release patterns can be designed. It becomes possible to do so.

<Examples> Examples of the present invention will be shown below and explained in more detail. In addition, hereinafter, parts and % in the text indicate parts by weight and % by weight.

Example 1 60 parts of isooctyl acrylate and 40 parts of methyl methacrylate were subjected to a polymerization reaction in ethyl acetate using azobisisobutyronitrile as a polymerization initiator to obtain an adhesive solution.

Scopolamine was blended into the resulting adhesive solution (scopolamine content 1O%/based on solid content), and 9 parts of this was applied to one side of a 1 m thick polyethylene terephthalate film so that the thickness after drying was 40 μm, and dried. A tape preparation for disease treatment of the present invention was obtained.

Example 2 40 parts of butyl acrylate, 20 parts of 2-ethylhexyl acrylate, 40 parts of ethyl methacrylate, 0.1 part of diethylene glycol diacrylate
1 part was polymerized in the same manner as in Example 1 to obtain an adhesive solution.

Timolol is blended into the obtained adhesive solution (timolol content 10%/opposition portion), and this is applied to one side of a 50 μm thick polybutene film so that the thickness after drying is 60 IIm, and dried to obtain the inventive adhesive solution. A tape preparation for disease treatment was obtained.

Example 3 30 parts of polyisobutylene (viscosity average molecular weight: 120,000), 30 parts of polyisobutylene (viscosity average molecular weight: 60,000), and 40 parts of liquid paraffin were uniformly mixed to obtain an adhesive solution.

Propranolol was blended into the obtained adhesive solution (containing propranolol 130%/based on solid content), and this was
It was coated on one side of thick polyethylene terephthalate to a thickness of 40 μm after drying and dried to obtain a tape preparation for disease treatment of the present invention.

Example 4 The same operation as in Example 1 was performed except that 40 parts of N-vinyl-2-pyrrolidone was used instead of 40 parts of methacrylic acid methyl ester in Example 1, and a scopolamine-containing tape for treating skin diseases was prepared. A formulation was obtained.

Example 5 The same operation as in Example 2 was carried out, except that 40 parts of butyl acrylate, 50 parts of 2-ethylhexyl acrylate, and 10 parts of acrylic acid were used as monomers.
A tape preparation containing timolol for disease treatment was obtained. In addition,
The molar ratio between the amount of carboxyl groups and the amount of timolol in the adhesive was 12.49/3.16.

The following characteristic evaluation tests were conducted using the tape formulations obtained in Examples 1 to 5 above.

(Drug stability over time) Each tape preparation piece cut into 5×4 cd was stored at 40° C., and the amount of remaining drug relative to the content before storage was measured. Quantification was performed by high performance liquid chromatography, and the results are shown in Table 1.

(In vitro release test) A piece of rat abdominal skin with hair removed was set in a diffusion cell of a flow system, and the tape preparation (25 m++φ) obtained in Examples 1 and 4 was attached on top of it, and the flow rate was 0. .5aff
Distilled water was passed through the diffusion cell at i/sin, and the drug release concentration was measured at regular intervals (average value of 3 samples). The results are shown in FIG.

(Amount transferred to rabbit skin) Tape formulations obtained in Example 2.3 and Example 5 (
30 φ) was applied to a rabbit (Japanese white native breed) whose back hair had been removed, and the amount of drug remaining in the tape was quantified using high-performance liquid chromatography at regular intervals to measure the amount transferred to the skin ( (average value of 3 samples), and the results are shown in FIG.

Table 1 Example 6 An adhesive solution was obtained in the same manner as in Example 1 except that 96 parts of acrylic acid isononyl ester and 4 parts of acrylic acid were used as monomers.

Timolol was blended into the resulting adhesive solution (timolol content 20%/opposition portion), and this was applied to one side of a 12 μm thick polyethylene terephthalate film with a dry thickness of 4 μm.
The tape preparation for disease treatment of the present invention was obtained by coating and drying so as to give 0 parts m.

The molar ratio between the amount of carboxyl groups and the amount of timolol in the adhesive was 4.44/6.32.

Example 7 Timolol 4t 10%/? A tape preparation was obtained in the same manner as in Example 6, except that the solid content was changed to .

The molar ratio between the amount of carboxyl groups and the amount of timolol in the adhesive was 5.00/3.16.

Example 8 An adhesive solution was obtained in the same manner as in Example 6, except that 95 parts of acrylic acid 2-ethylhexyl ester and 5 parts of methacrylic acid were used as monomers.

Propranolol was blended into the obtained adhesive solution (containing propranolol 130%/based on solid content), and this was
One side of the thick polyethylene film has a dry thickness of 60 mm.
The tape preparation for disease treatment of the present invention was obtained by coating and drying so as to give a part M. The molar ratio between the amount of carboxyl groups and the amount of propranolol in the adhesive is 4.07/11.5.
It was 7.

Example 9 A propranolol-containing tape preparation was obtained by carrying out the same operation as in Example 8, except that 65 parts of acrylic M2-ethylhexyl ester and 35 parts of vinyl acetate were used as monomers.

Example 10 An adhesive solution was obtained in the same manner as in Example 8, except that 80 parts of 2-ethylhexyl acrylate, 15 parts of methyl methacrylate, and 5 parts of 2-hydroxyethyl acrylate were used as monomers. Ta.

Salbutamol was blended into the resulting adhesive solution (salbutamol content 15%/based on solid content), and this was applied to one side of a 50 μm thick ethylene/vinyl acetate copolymer film so that the thickness after drying was 40 μm. The tape preparation for disease treatment of the present invention was obtained by drying. The molar ratio between the amount of hydroxyl groups and the amount of salbutamol in the adhesive is 3.66/6.2.
It was 7.

Example 11 A salbutamol-containing tape preparation was obtained in the same manner as in Example 10, except that 85 parts of 2-ethylhexyl acrylate and 15 parts of methyl methacrylate were used as monomers.

Example 12 95 parts of acrylic acid isooctyl ester, 3 parts of acrylic acid
An adhesive solution was obtained in the same manner as in Example 8, except that 1 part and 2 parts of acrylic acid 2-hydroxyethyl ester were used as the monomer.

Timolol was blended into the obtained adhesive solution (timolol content 20%/opposition portion), and this was applied to one side of a 9 μm thick polyethylene terephthalate film to a thickness of 40 μm after drying.
The tape preparation for disease treatment of the present invention was obtained by applying the tape to a thickness of μm and drying. The molar ratio between the total amount of carboxyl groups and hydroxyl groups in the adhesive and the amount of timolol is 4.
It was 71/6°32.

Example 13 A timolol-containing tape preparation was obtained in the same manner as in Example 6, except that sodium hydroxide was added to the adhesive solution of Example 6 to inactivate 90% of the carboxyl groups in the adhesive. .

Comparative Example A tape preparation was obtained in the same manner as in Example 6 except that timolol maleate was used as the drug.

Using the tape formulations obtained in Examples 6 to 13 and Comparative Example above, the stability of the drug over time, skin adhesion, skin irritation, and amount transferred to rabbit skin were measured. The stability of the drug over time and the amount transferred into the rabbit skin were determined according to the methods described above, and other properties were determined using the following methods. The results are shown in Table 2 and Figures 3-5.

(Skin adhesion) A piece of tape preparation cut to 3 cm diameter was applied to the inner side of a human upper arm, and the adhesion state after 24 hours was visually judged according to the following criteria (average of 6 people).

O: 90% or more of the pasted area is adhered.

Δ: 50 to 90% of the pasted area is adhered.

×: Less than 50% of the pasted area is adhered.

(Skin Irritation) A tape preparation piece cut to 3C11φ was applied to the human chest for 24 hours, and 6 hours after it was removed, the condition of the skin surface was visually judged according to the following criteria. Note that the score is the average value of six people.

0 points 0.5 points 1, 0 points 2, 0 points 3.0 points 4.0 points No reaction Slight erythema Obvious erythema Erythema and papules or edema Erythema and edema and papules or small varicella Major varicella Table 2 *) Adhesive extrusion (slightly negative cohesion) As is clear from the above tables and drawings, when a basic drug with a free base structure is made into a tape formulation, it has relatively excellent release properties, stability, skin adhesion, and skin It also has good irritation properties. Further, when an adhesive having a hydroxyl group or a carboxyl group as a functional group is used, sustained release properties are exhibited. Furthermore, by making the amount of drug larger than the number of moles of functional groups in the adhesive, both initial release properties and sustained release properties can be achieved.

[Brief explanation of drawings]

Fig. 1 is a graph showing the results of in vitro drug release tests from the tape formulations obtained in Examples 1 and 4, and Figs. Fig. 2 is a graph showing the amount of drug transferred to rabbit skin.

Claims (7)

[Claims] (1) A tape preparation for disease treatment comprising a drug-containing adhesive layer containing a basic drug with a free base structure in the adhesive and laminated on a flexible support. (2) The tape preparation for disease treatment according to claim (1), wherein the adhesive is a non-functional adhesive. (3) The tape preparation for disease treatment according to claim (2), wherein the non-functional adhesive is an acrylic polymer obtained by polymerizing a (meth)acrylic acid alkyl ester and/or an alkoxy-modified monomer thereof. (4) Claim (2) wherein the non-functional adhesive is a rubber adhesive.
) A tape preparation for treating the disease described. (5) The tape preparation for disease treatment according to claim (1), wherein the adhesive comprises an acrylic copolymer having a hydroxyl group and/or a carboxyl group in the molecule as a functional group. (6) The tape preparation for disease treatment according to claim (5), wherein the adhesive contains more basic drug than the number of moles of functional groups in the adhesive. (7) The disease treatment according to claim (5), wherein the adhesive is made of an acrylic copolymer having a carboxyl group as a functional group in the molecule, and contains a basic substance in an amount equal to or less than the number of moles of the functional group. tape formulation.