JPH0834731A - Granisetron-containing percutaneous preparation - Google Patents

Abstract

PURPOSE:To prepare a percutaneous formulation which can attain a sufficient percutaneous adsorption of granisetron and manifests excellent durability fo its effective concentration in blood. CONSTITUTION:This percutaneous formulation comprises granisetron or its pharmaceutically permissible salt and a percutaneous absorbfacient therefor. The absorbfacient is selected from monohydric or polyhydric 1-20C alcohols, 2-20C fatty acids, esters of 2-20C fatty acids with 1-20C mono- or pulyhydfic alcohols, urea compounds, pyrrolidone derivatives, cyclic monoterpene, 1- dodecylazacycloheptan-2-on, cyclodextrin and thioglycolic acid, particularly polyhydric alcohol single or combination of >= two polyhydric alcohols, or menthol only or a combination thereof with a polyhydric alcohol. This formulation preferably contains granisetron and the percutaneous absorbfaciens in amounts of 0.1-2.0wt.% and 0.1-50wt.%, particularly 0.2-10wt.% and 0.5-30wt/%, respectively.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel transdermal preparation containing granisetron or a pharmaceutically acceptable salt thereof as an active ingredient.

[0002]

2. Description of the Related Art Granisetron [Chemical name: 1-methyl-N- (e
ndo-9-methyl-9-azabicyclo [3.3.1] non-3-yl) -1H-indaz
ole-3-carboxamide] is a selective antagonist of the 5-HT ₃ receptor. This is a useful pharmaceutical compound that exerts an excellent effect of suppressing nausea / vomiting induced by administration of antineoplastic agents by blocking the 5-HT ₃ receptor present in the afferent abdominal vagus nerve terminal. Although the injection of its hydrochloride salt is widely used at present, the transdermal preparation of granisetron is not yet known so far.

[0003]

Granisetron is applied for the purpose of suppressing nausea and vomiting which are often observed when an anti-neoplastic agent is administered to cancer patients. For this reason, granisetron is often applied to physically handicapped patients, and thus oral administration by the patients themselves is difficult and a caregiver is burdened. In addition, administration by injection causes patient distress, and qualitative of life (Q
It becomes an obstacle to OL). Granisetron, for that purpose,
It is necessary to administer continuously for a long period of time, but since oral administration and injections cause such problems continuously, it is possible to administer them easily without causing pain to the patient. The development of a dosage form in which the effective blood concentration lasts for a long period of time with a single administration is desired, and a transdermal preparation has been considered as such a dosage form.

Transdermal preparations generally have the following advantages. That is, a) administration and discontinuation of administration are simple, b) constant blood concentration continues for a long time, c) side effects can be avoided by lowering the maximum blood concentration, d) first pass of liver The effect can be avoided and the bioavailability of the drug can be increased.

Therefore, the present invention provides a percutaneous absorption preparation of granisetron, particularly a percutaneous absorption preparation having high release of granisetron from a base and skin permeation, whereby an effective blood concentration can be maintained for a long period of time. The purpose is to provide.

[0006]

Means for Solving the Problems As a result of various studies to solve the above problems, the present inventors have found that the use of a transdermal absorption enhancer as shown below results in sufficient transdermal absorption of granisetron. The present invention has been completed by the finding that a transdermal preparation that has been achieved and exhibits excellent durability of effective blood concentration can be obtained.

That is, the present invention relates to a percutaneous absorption type pharmaceutical preparation containing, as an active ingredient, granisetron or a pharmaceutically acceptable salt thereof and a percutaneous absorption enhancer.

More preferably, the present invention provides granisetron, or a pharmaceutically acceptable salt thereof, as an active ingredient, a monohydric or polyhydric alcohol having 1 to 20 carbon atoms, a fatty acid having 2 to 20 carbon atoms, 2 to 20 carbon atoms
Of fatty acid with fatty acid and monohydric or polyhydric alcohol having 1 to 20 carbon atoms, urea, pyrrolidone derivative, cyclic monoterpene, 1-dodecylazacycloheptane-2-
The present invention relates to a percutaneous absorption-type pharmaceutical preparation containing one or more percutaneous absorption enhancers selected from on, cyclodextrin and calcium thioglycolate.

In the present invention, the dosage form of the transdermal preparation is not particularly limited and includes, for example, ointments, creams, solutions, lotions, liniments, poultices, plasters,
Mention may be made of patches, gels, plasters or tapes.

In the preparation of the present invention, the active ingredient, granisetron, is in a free form, but its pharmaceutically acceptable salt, for example, inorganic salt such as hydrochloride, sulfate, hydrobromide, nitrate, phosphate and the like. Acid addition salts or inorganic base addition salts such as sodium salts and potassium salts, as well as acetate salts, succinate salts,
It may be in the form of organic acid addition salts such as fumarate, malate and oxalate.

In the present invention, the concentration of the active ingredient, granisetron, in the preparation depends on the dosage form and the base component, but is generally 0.01 to 50% by weight, preferably 0.1 to 20% by weight. , Especially 0.2 to 10% by weight.

In the present invention, as the transdermal absorption enhancer, those usually used in percutaneous absorption type preparations can be used, but preferably monohydric or polyhydric alcohols having 1 to 20 carbon atoms, Fatty acids having 2 to 20 carbon atoms, esters of fatty acids having 2 to 20 carbon atoms and monohydric or polyhydric alcohols having 1 to 20 carbon atoms, ureas, pyrrolidone derivatives, cyclic monoterpenes, 1-dodecylaza Examples include cycloheptan-2-one, cyclodextrin, and calcium thioglycolate.

Examples of the monohydric or polyhydric alcohol having 1 to 20 carbon atoms include methyl alcohol, ethyl alcohol, propyl alcohol, isopropyl alcohol, butyl alcohol, heptyl alcohol, octyl alcohol, capryl alcohol, nonyl alcohol and decyl. Alcohol, undecyl alcohol, lauryl alcohol, tridecyl alcohol, myristyl alcohol, pentadecyl alcohol, cetyl alcohol,
Hexadecyl alcohol, heptadecyl alcohol, stearyl alcohol, oleyl alcohol, nonadecyl alcohol, eicosyl alcohol, ethylene glycol, propylene glycol, 1,3-butanediol,
Glycerin is mentioned. Among these, ethyl alcohol, octyl alcohol, nonyl alcohol, lauryl alcohol, myristyl alcohol, oleyl alcohol, propylene glycol, 1,3-butanediol or glycerin are preferable, and lauryl alcohol or propylene glycol is particularly preferable.

Examples of the fatty acid having 2 to 20 carbon atoms include acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, lauric acid, myristic acid, palmitic acid, Mention may be made of stearic acid, benzoic acid, salicylic acid, lactic acid, oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, maleic acid, fumaric acid, malic acid, tartaric acid or phthalic acid. Among these, lactic acid, fumaric acid, maleic acid,
Lauric acid or myristic acid is preferred, especially lactic acid,
Maleic acid or myristic acid is preferred.

Examples of the ester of a fatty acid having 2 to 20 carbon atoms and a monohydric or polyhydric alcohol having 1 to 20 carbon atoms include, for example, myristyl lactate, cetyl lactate, lauryl lactate, isopropyl myristate, isopropyl palmitate. , Butyl stearate or myristyl myristate. Among these, myristyl lactate,
Cetyl lactate, myristyl myristate or isopropyl myristate is preferred, and isopropyl myristate or cetyl lactate is particularly preferred.

Examples of ureas include urea and thiourea, of which urea is preferred. Examples of the pyrrolidone derivative include 2-pyrrolidone and 1-methyl-2-
Pyrrolidone, 5-methyl-2-pyrrolidone, 1,5-dimethylpyrrolidone or 1-ethylpyrrolidone may be mentioned, of which 1-methyl-2-pyrrolidone is preferred.

Cyclic monoterpenes include menthol or limonene. Among these, menthol is preferable because it has a preferable action such as analgesic action, local anesthetic action and antipruritic action in addition to the transdermal absorption promoting action of granisetron. Menthol may be obtained from natural peppermint or other minno oil, or it may be synthetic.

The above-mentioned percutaneous absorption enhancers may be used alone or in combination, but polyhydric alcohols may be used alone or in combination.
It is preferable to use a combination of two or more kinds, or menthol alone, or a combination of a polyhydric alcohol and menthol. Particularly in the case of a dosage form containing water, it is preferable to use polyhydric alcohols singly or in combination of two or more, or menthol alone or in combination with polyhydric alcohol and menthol.

In the present invention, the concentration of the percutaneous absorption enhancer in the preparation depends on the dosage form and the base, but is generally about 0.01-99.99% by weight, preferably 0.1-5.
0% by weight, especially about 0.5 to 30% by weight.

The formulation of the present invention may further contain a base, an auxiliary agent and / or an additive, if necessary.
As the base, depending on the dosage form of the transdermal preparation of the present invention,
The base usually used in this technical field is used. For example, when the percutaneous absorption preparation of the present invention is used as an ointment or cream, an oily base or an emulsion base can be used as the base.

As the oily base, for example, hydrocarbons, higher alcohols, glycols, higher fatty acids, higher fatty acid esters, vegetable oils or animal oils can be used. Examples of the hydrocarbon include hydrocarbons having 12 to 32 carbon atoms, specifically, liquid paraffin, branched paraffin, solid paraffin, white petrolatum, etc., which are mixtures of various hydrocarbons. , Liquid paraffin or white petrolatum is preferred.

Examples of higher alcohols include lauryl alcohol, tridecyl alcohol, myristyl alcohol, pentadecyl alcohol, cetyl alcohol, hexadecyl alcohol, heptadecyl alcohol, stearyl alcohol, oleyl alcohol, nonadecyl alcohol, eicosyl alcohol, ceryl alcohol. ,
Examples thereof include melysyl alcohol, cetyl alcohol, and stearyl alcohol. Of these, cetyl alcohol and stearyl alcohol are preferable.

As glycols, ethylene glycol, propylene glycol, trimethylene glycol,
Examples thereof include 1,3-butanediol and polyethylene glycol, among which propylene glycol, 1,3-butanediol and polyethylene glycol are preferable. Also, a base containing polyethylene glycol as a main component, for example, a mixture of a low degree of polymerization polyethylene glycol such as Macrogol 400 and a high degree of polymerization polyethylene glycol such as Macrogol 4000 in an appropriate ratio, is an ointment. Can be suitably used as a base.

Examples of the higher fatty acid include 6 carbon atoms.
To 32 saturated or unsaturated fatty acids, such as caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecyl acid, lauric acid, tridecyl acid,
Myristic acid, pentadecyl acid, palmitic acid, heptadecyl acid, stearic acid, oleic acid, nonadecana,
Arachidonic acid, linoleic acid, linolenic acid, behenic acid, lignoceric acid, cerotic acid, heptacosanoic acid, montanic acid, melissic acid, laxeric acid, elaidic acid, brassic acid and the like, among them, myristic acid or oleic acid is preferable. .

The higher fatty acid ester is, for example, (A) an ester of a fatty acid ester having 10 to 32 carbon atoms and an aliphatic monohydric alcohol having 14 to 32 carbon atoms or (B) saturated having 10 to 22 carbon atoms. Alternatively, an ester of unsaturated fatty acid and glycerin or a hydrogenated product thereof may be used.

Examples of the ester (A) include fatty acid esters such as myristyl palmitate, stearyl stearate, myristyl myristate, ceryl lignocerate, lacceryl cerotate and lacceryl laxate, lanolin, beeswax, spermaceti, and the like. Natural waxes derived from plants, such as animal-derived natural waxes, carnauba wax, and candelilla wax are listed.

Examples of the ester (B) include glyceryl monolaurate, glyceryl monomyristate, glyceryl monostearate, glyceryl monooleate,
Glyceryl dilaurate, glyceryl dimyriate,
Examples thereof include glyceryl distearate, glyceryl trilaurate, glyceryl trimysterate, and glyceryl tristearate. Of these, glyceryl monolaurate, glyceryl monomysterate, and glyceryl monooleate are preferable.

Examples of vegetable oils are castor oil, olive oil, soybean oil, sesame oil, gentian oil, safflower oil,
Examples thereof include cottonseed oil or turpentine oil, or vegetable oils and fats hydrogenated therein, and among them, castor oil, olive oil, soybean oil, sesame oil or cottonseed oil is preferable. Examples of animal oils include mink oil, egg yolk oil, squalane and squalene.

Lanolin derivatives can also be used as the oily base. These bases can be used alone or in admixture of two or more. Examples of the emulsion base include an O / W type base, a W / O type base and a suspending base.

As the O / W type base, components such as lanolin, propylene glycol, stearyl alcohol, petrolatum, silicone oil, liquid paraffin and glyceryl monostearate are added in the aqueous phase in the presence or absence of a surfactant. Examples include creams that are emulsified and dispersed. W
As the / O type base, those obtained by emulsifying / dispersing components such as petrolatum, higher aliphatic alcohols and liquid paraffin in the presence of a nonionic surfactant having few hydrophilic groups are added. Can be mentioned. As a suspending base,
An aqueous base which is made into a gel by adding a suspending agent such as starch, glycerin, high-viscosity carboxymethyl cellulose, carboxyvinyl polymer, polyvinyl alcohol, and hydroxypropyl cellulose to water can be mentioned.

When the percutaneous absorption preparation of the present invention is used as a liquid, water or the like can be used as a base. When the percutaneous absorption preparation of the present invention is used as a lotion, it may be any type of suspension type, emulsion type or solution type, and when it is used as a suspension type lotion, As the agent, a mixture of water and a suspending agent such as gums, celluloses and viscosities may be used.

The gums include, for example, sodium alginate, gum arabic, pectin, tragacanth, etc., and the celluloses include, for example, methyl cellulose, hydroxymethyl cellulose or hydroxyethyl starch. Examples of the viscosity agent include bentonite or Veegum HV.

In the case of an emulsified lotion, a base obtained by emulsifying an oily substance such as fatty acid and higher alcohol in water can be used as a base. In the case of a solution type lotion, water, alcohol or the like can be used as a base.

When the percutaneously absorbable preparation of the present invention is used as a liniment, as a base, for example, vegetable oils such as olive oil, soybean oil, sesame oil, gents oil, cottonseed oil, turpentine oil, ethyl alcohol, propyl alcohol, isopropyl alcohol. Alcohols such as or a mixture of alcohols and water are used.

When the percutaneously absorbable preparation of the present invention is used as a poultice, a water-soluble polymer such as polyacrylic acid or a salt thereof, polyvinyl alcohol, polyvinylpyrrolidone, hydroxypropylcellulose or a crosslinked product thereof is used as a base. Is used. Further, these water-soluble polymers are crosslinked with polyvalent metal salts such as alum, aluminum sulfate, aluminum chloride, aluminum hydroxide, magnesium hydroxide or calcium hydroxide, or the water-soluble polymers are irradiated with radiation. Those that have been subjected to such a physical treatment to be crosslinked, and those that have been crosslinked by freeze-thawing are used. The poultice may be placed on a support, and a non-woven fabric is used as the support.

When the present invention is used as a gel, as a base, for example, water-soluble polyacrylic acid or a salt thereof, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose or a salt thereof, polyvinyl alcohol, polyvinylpyrrolidone and the like. The polymer or its cross-linked product is cross-linked with a polyvalent metal salt such as aluminum sulfate, aluminum hydroxide, magnesium hydroxide, calcium hydroxide or aluminum chloride to form a gel, or diisopropanolamine, triethylamine or triethylamine The gel is used by adjusting the pH with ethanolamine, triamylamine or the like.

When the present invention is used as a plaster, a patch, a plaster or a tape, a support, an elastic body, a tackifier, a softening agent, an antiaging agent, a filler, a cross-linking agent, a release treatment agent, etc. The components that make up the pharmaceutical preparation are required, and as these components, commonly used components can be used.
Examples of the support include polyethylene terephthalate, polyethylene, polypropylene, polyvinyl chloride,
A film made of polycarbonate, polyurethane or the like, a non-woven fabric or the like can be used. As the elastic body, natural rubber, SBS, butyl rubber, polyisobutylene, polyvinyl alkyl ether, poly (meth) acrylate, polyurethane, polyamide, ethylene-vinyl acetate copolymer, acrylic acid, acrylic ester-acrylic acid copolymer, Dimethyl polysiloxane, polyisoprene rubber,
Styrene-isoprene-styrene block polymer rubber,
Styrene butadiene rubber, polyisobutylene, butylene rubber, etc. can be used. The tackifier is preferably one that is compatible with the elastic body, and examples thereof include a polyterpene resin, a rosin or its ester, or a phenolic resin. These components are used as necessary, and may be used alone or in combination of two or more.

The percutaneous absorption preparation of the present invention may further contain a preservative, a flavoring agent, an emulsifier, a dispersant, if necessary.
Auxiliary agents or additives such as wetting agents, pH adjusters, stabilizers, preservatives and suspending agents may be contained, and these auxiliary agents or additives are each commonly used in the field of formulation technology. Any of them can be used.

Preservatives include, for example, paraoxybenzoic acid, methylparaben, ethylparaben, propylparaben, chlorobutanol or benzyl alcohol. As an emulsifier, a W / O or O / W type emulsifier is preferably used in a dosage form containing water as a base, for example, in a liquid agent, lotion, poultice or ointment containing water. Examples of the pH adjusting agent include inorganic acids such as hydrochloric acid, sulfuric acid, hydrobromic acid and phosphoric acid, organic acids such as acetic acid, succinic acid, fumaric acid, malic acid, oxalic acid, lactic acid, glutaric acid, salicylic acid and tartaric acid. , Or salts thereof.

The percutaneous absorption preparation of the present invention can be produced by a conventional method. For example, in the case of making an ointment, cream, poultice or gel, according to each dosage form, after kneading, emulsifying, suspending or dissolving the necessary base materials, the base is produced. , Granisetron and the necessary auxiliaries and additives can be prepared by mixing in commonly used mixers such as screw mixers, homogenizers, kneaders or roll mills.

When used as a liniment agent, it can be produced by dissolving granisetron in a base, and further adding and mixing necessary auxiliary agents and additives. The plaster agent, patch agent, plaster agent or tape agent can be produced by a conventional method such as a hot melt method, a solution method or a hot pressing method. For example, in the case of the hot melt method, as an elastic body, a block polymer having fluidity especially at high temperature, for example, styrene-isoprene-styrene, styrene-butadiene-styrene, styrene-ethylene-butylene-styrene or ethylene acetic acid. Vinyl is used,
By mixing such an elastic body and other necessary components,
It can be produced by melting the mixture at high temperature to mix the granisetron homogeneously and coating it on a support. Further, in the case of the solution method, the base is dissolved in an organic solvent such as chloroform, ethyl acetate, hexane, and methyl ethyl ketone, and granisetron and other necessary components are added thereto, and these components are uniformly dissolved or dispersed, It can be manufactured by coating on a support using an applicator. In the case of the hot pressing method, granisetron and other necessary components are kneaded by a roll machine or the like until they are homogeneous, and the resulting mixture is heated to a uniform thickness on a release paper using a calender. It is manufactured by coating so as to form a granisetron-containing layer on a release paper, and laminating and adhering the layer on the surface of a support.

When the solution or lotion is used, it can be produced by adding various base components to water, mixing and stirring, and then adding and mixing granisetron and other necessary components.

[0043]

EXAMPLES The present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

Example 1 Aqueous solution of aminoalkyl methacrylate copolymer in the weight ratios shown in Table 1 (Plastoid E35L, Roehm Phar.
(manufactured by ma), 1-menthol and granisetron hydrochloride were combined and stirred well until homogeneous, to obtain mixed solutions 1 to 3.

Table 1 Mixed solution 1 2 3 Aminoalkylmethacrylate 98.5 98.745 99.945 Aqueous solution of copolymer 1-menthol 1.2 1.20 Granisetron hydrochloride 0.3 0.055 0.055 Next glass A PET film is prepared as a backing layer on a plate, and appropriate amounts of the above mixed solutions 1 to 3 are dropped onto each of them, and the solution is quickly applied using an applicator (10.ML Yawata Seiki Seisakusho) to form a granisetron hydrochloride-containing layer. Was formed on the film. Next, the PET film was removed from the glass plate, dried at 60 ° C. for 30 minutes, and then the silicone-treated PET film was adhered to the dried granisetron hydrochloride-containing layer as a release layer at 43 μg, 7.86 μg and 7.86 μ per cm ^2.
Tape agents 1 to 3 containing g of granisetron hydrochloride were obtained.

Next, male hairless rats (body weight 180
Abdominal excised skin (± 10 g) is sandwiched between horizontal diffusion cells at 37 ° C. in which water is circulated, and distilled water is applied to the receiver (dermis) side.
Add 8 ml, stir with a magnetic stirrer,
The tape preparation 1-30.95 cm ² (containing 40.9 μg, 7.47 μg, and 7.47 μg of granisetron hydrochloride, respectively) was applied to the keratinous side, and a hairless rat skin permeation test of granisetron hydrochloride was conducted. The amount of granisetron in the receiver solution collected over time was measured by high performance liquid chromatography. The results are shown in Fig. 1.

The pharmacokinetic parameters of granisetron hydrochloride are shown in Table 2 (from an interview form of Kytril injection solution). Table 2 Intravenous injection (single) Dose (μg / kg) 40 Maximum blood concentration (C _max ) (ng / ml) 19.5 ± 6.1 AUC (ng hr / ml) 3.1 ± 36.5 Half-life (T _1/2 ) (hr) 3.1 ± 1.2 Distribution volume (Vd) (l) 196 ± 70 Total clearance value (CL) (ml / min) 856 ± 538 In human skin Assuming that the skin permeability of granisetron is the same as that in hairless rat skin, using the data obtained from the hairless rat skin permeation test and the pharmacokinetic parameters of granisetron hydrochloride shown in Table 2, by the convolution method, 43 per cm ²
The tape preparation of the present invention 100 containing 100 μg of granisetron hydrochloride
When cm ² (10 cm × 10 cm) was applied to the skin of a human having a body weight of 60 kg, the plasma granisetron concentration was predicted, and the obtained predicted plasma granisetron concentration curve in human is shown in FIG. 2.

40 μg of granisetron hydrochloride for comparison
/ Kg was intravenously administered to a healthy adult male over 30 minutes, and this was repeated 10 times / 6 days. The plasma granisetron concentration is shown in FIG.

The results shown in FIG. 2 are at a level at which a sufficient drug effect can be expected even when compared with the amount of granisetron in plasma shown in FIG. Further, by changing the skin application area, the dose of granisetron can be easily increased or decreased according to each disease and each patient's condition, which is considerably useful clinically.

Example 2 Chloroform and an adhesive styrene-isoprene-styrene block polymer were added at a polymerization ratio of 3: 1 and stirred well to prepare an adhesive chloroform solution. This solution 20
Granisetron hydrochloride (75 μg) and cetyl lactate (6.2 mg) were added to 0 mg, and the mixture was stirred with a spatula until homogeneous. At this time, chloroform was liable to volatilize, so a quick operation was performed. Prepare a PET film as a backing layer on a glass plate, drop an appropriate amount of a chloroform solution of an adhesive on it, and quickly spread it using an applicator (10.ML Yawata Seiki Seisakusho) to form a layer containing granisetron hydrochloride on the film. Formed. Next, the PET film was removed from the glass plate, dried at 40 ° C. for 30 minutes, and the silicone-treated PET film as a release layer was adhered to the dried granisetron hydrochloride-containing layer to give a tape preparation.

[0051]

As described above, according to the present invention,
Provided is a granisetron-containing percutaneous absorption preparation which is excellent in the release property of granisetron from a base, the absorbability into the skin, and the durability of their effective blood concentration. Furthermore, according to the granisetron-containing transdermal preparation of the present invention, the administration is simple, and the mental and physical pains and anxiety given to the patient at the time of administration are removed, and at the same time, it contributes to the improvement of QOL, A clinically advantageous preparation is obtained.

[Brief description of drawings]

FIG. 1 is a graph showing the cumulative amount of granisetron permeated through hairless rat skin.

FIG. 2 is a graph showing the predicted plasma concentration of granisetron when the tape preparation of the present invention is applied to human skin.

FIG. 3 is a graph showing the concentration of granisetron in plasma when 40 μg / kg of granisetron hydrochloride was repeatedly intravenously administered to a healthy adult male.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI technical display area A61K 47/14 E

Claims (3)

[Claims] 1. A percutaneous absorption-type pharmaceutical preparation comprising, as an active ingredient, granisetron or a pharmaceutically acceptable salt thereof and a percutaneous absorption enhancer. 2. A transdermal absorption enhancer having 1 to 20 carbon atoms.
Monohydric or polyhydric alcohols, fatty acids with 2 to 20 carbon atoms, fatty acids with 2 to 20 carbon atoms and 1 to 1 carbon atoms
One selected from the group consisting of esters with 20 monohydric or polyhydric alcohols, ureas, pyrrolidone derivatives, cyclic monoterpenes, 1-dodecylazacycloheptan-2-one, cyclodextrins, calcium thioglycolate Alternatively, the percutaneously absorbable preparation according to claim 1, which is two or more kinds. 3. The concentration of granisetone in the formulation is 0.0
The percutaneous absorption-type preparation according to claim 1 or 2, wherein the percutaneous absorption enhancer has a concentration of 1 to 50% by weight and a concentration of 0.01 to 99.99% by weight in the preparation.