KR20160050989A - Matrix Type Transdermal patch containing Granisetron and the treating method of vomitting thereby - Google Patents

Abstract

The present invention relates to a matrix-type transdermal absorption patch containing granisetron and a method for treating and preventing vomiting using the same. According to the present invention, the tramsder,a; adsorption patch ensures a simple injection method and exhibits long-term medicinal effects, thereby maximizing drug compliance in a patient and reducing high concentration deviance occurring during absorption and metabolic pathways after oral administration. In addition, the blood concentration of a drug having a short half life can be maintained consistently for a desired amount of time, and the patch is easy to remove when stopping the administration. Manufactured in a small size, the patch of the present invention can increase convenience of the user and minimizes skin irritation due to improved adhesiveness as well.

Description

[0001] The present invention relates to a matrix type transdermal patch comprising granisetron and a method for treating and preventing vomiting using the same,

The present invention relates to a matrix type transdermal patch containing granitolone and a method of treating and preventing vomiting using the same. More specifically, the present invention relates to a matrix type transdermal patch comprising granitolone, The present invention relates to a matrix type transdermal patch comprising granisetron which can minimize the effective blood concentration of a drug for 1 to 7 days, and a method for treating and preventing vomiting using the same.

Many patients receiving chemotherapy receive chemotherapy-induced nausea and vomiting (CINV). Even after the anticancer treatment schedule is over, the quality of life deteriorates due to decreased food, performance scale and deterioration of nutritional status. Sometimes it is a major cause of poor compliance with chemotherapy.

Thus, CINV is an important issue for the patient, and the patient is one of the most painful of the surgical procedures and even takes precedence over pain. Therefore, from the viewpoint of the patient, it is necessary to develop the antiepileptic effective in these fields. As a clinical problem, CINV is difficult to handle and requires a nurse to prevent recurrence of vomiting, which can have a very serious clinical sequelae. Therefore, inhibition of CINV is essential from the perspective of the patient and the clinician.

In addition, inhibition of CINV is financially important. In the United States of America and others, many surgeries are performed in the daytime treatment environment, and it is receiving financial attention whether patients can return home on the day without staying overnight. In other countries, the prevalence of daytime treatment is increasing, with a prospect that it may reach more than 50% within 5 to 10 years.

In western countries and Japan, the number of surgeries performed per year is 65 million, and many anesthetists now use prophylactic antagonists such as low doses of methoclopramide (10 mg) before or during surgery , And many have not used prophylactic antagonists because of the low efficacy of the drugs currently in use, and the annoying side effects such as dysthymia and drowsiness.

Therefore, a safer and more efficient port soil is required for CINV.

Anti-vomiting agents are currently administered via intravenous, oral, or rectal routes. Intravenous administration may be performed only under the supervision of a physician and may cause serious discomfort to the patient, for example, redness or burn at the injection site. Since children do not like needles, these problems can be exacerbated in pediatric care, and there is always a concern for wounds caused by needles. Oral administration often suffers from the disadvantage of having to be administered up to four times a day, as well as patients suffering from severe areas and vomiting and those with cancer of the head and neck, Can not be swallowed properly. Also, due to the pulsatile delivery characteristics of oral administration, side effects may often occur when doses deviating from therapeutic doses are administered. Rectal administration of rectal administration can avoid to some extent the pulsatile delivery properties of oral administration, but this method is not very convenient for drug administration and can not be widely accepted.

Therefore, there is a need to develop a parenteral drug delivery system capable of maintaining a constant plasma concentration of an anti-vomiting agent for a long period of time. For example, the percutaneous administration system, which is one of the controlled release systems, is a system that can maintain the effective blood concentration for a long time by attaching patches once. It is a simple administration method and manifests long-term medicinal effect, Can be maximized and the concentration concentration fluctuation that occurs through absorption and metabolism during oral administration can be reduced and the blood concentration of the drug with a short half-life can be kept constant for a desired period of time, It has an advantage that it can be easily removed when it is necessary to stop the administration.

Korean Patent Registration No. 10-0390870 discloses a method of preparing a patch formulation which is administered at an appropriate skin permeation rate for at least 24 hours using an appropriate skin penetration enhancer to maintain the effective blood concentration.

Japanese Patent Laid-Open No. 8-34731 discloses percutaneous pharmaceutical preparations of Granisetron using formulations such as creams, liniment, lotions, gels, tapes, and patches. These formulations include a carrier and penetration enhancer. The examples described in this publication confirmed the flux using rat skin. However, although the rat skin has permeability about 10 times greater than that of human skin, there is a problem that a patch having a surface area of 100 cm 2 must be used.

As described above, various researches on the antiepileptic drugs are under way, but there is a continuing need for studies on a drug delivery system that is excellent in convenience and excellent in absorbability in the body.

SUMMARY OF THE INVENTION The present invention has been made to overcome the above-mentioned problems, and it is an object of the present invention to provide a method and a device for enhancing convenience through small size, improving the adhesive property to minimize skin irritation, The present invention provides a matrix-type transdermal absorption patch containing granisetron which can be maintained.

To this end, A drug storage layer provided on a lower surface of the support layer, the drug storage layer containing granisetron, a polymer for forming a matrix, a tackifier resin, and a skin penetration enhancer; A release controlling adhesive layer provided on a lower surface of the drug storage layer and adapted to control the amount of drug contained in the drug storage layer and to be in contact with the skin; And a releasable release layer provided on a lower surface of the release-controlled pressure-sensitive adhesive layer.

In a preferred embodiment of the present invention, the support layer is selected from the group consisting of polyethylene, polypropylene, ethylene vinyl acetate copolymer, vinylon, polyester, polyurethane, nylon, polyacrylonitrile, polyethylene terephthalate and polyolefin It may be more than one kind.

In a preferred embodiment of the present invention, the thickness of the support layer may be 5 to 500 탆.

In one preferred embodiment of the present invention, the drug storage layer comprises 5 to 30% by weight of granisetron, 40 to 70% by weight of a polymer for forming a matrix, 10 to 30% by weight of a tackifier resin, 30% by weight.

In one preferred embodiment of the present invention, the polymer for forming the matrix is selected from the group consisting of a styrene-ethylene-isoprene-styrene copolymer, a styrene-butadiene-styrene copolymer, , A styrene-butadiene copolymer, a silicone rubber, and polyisoburylene.

In one preferred embodiment of the present invention, the polymer for forming the matrix may further include a tackifying resin.

In a preferred embodiment of the present invention, the tackifier resin is selected from the group consisting of rosin glycerin ester resin, hydrogenated rosin glycerin ester resin, rosin pentaerythritol ester resin, hydrogenated rosin pentaerythritol ester resin, alpha methyl styrene resin, An alicyclic hydrocarbon resin having 5 to 9 carbon atoms, an aromatic hydrocarbon resin, a hydrogenated dicyclopentadiene resin, a terpene resin, a coumarone indene resin, and a terpene phenol resin. have.

In one preferred embodiment of the present invention, the skin penetration enhancer may be included in an amount of 5 to 25% by weight based on the total weight of the drug storage layer.

In a preferred embodiment of the present invention, the skin penetration enhancer is selected from the group consisting of N-cyclohexyl-2-pyrrolidone, 1-butyl-3-dodecyl-2-pyrrolidone 1-butyl-3-dodecyl-2-pyrrolidone, 1,5-dimethyl-2-pyrrolidone, 2-pyrrolidone, 1-hexyl4-methyloxycarbonyl-2-pyrrolidone, 1-hexyl-2-pyrrolidone ), 1- (2-hydroxyethyl) pyrrolidone, 3-hydroxy-N-methyl-2- pyrrolidone, 1-lauryl-4-methyloxycarbonyl-2-pyrrolidone, Nmethyl-2-pyrrolidone, N-carprylyl-2-pyrrolidone, N-dodecyl-2-pyrrolidone, glycerol lauryl alcohol ), Oleyl alcohol, isopropyl myristole But are not limited to, isopropyl myristate, sorbitan mono-oleate, propylene monolaurate, propylene mono-oleate, oleylmacrogolglyceride, oleic acid oleic acid, lauroylmacrogoglyceride, linoleoylmacrogoglyceride, propylene glycol caprylate / caprate, sorbitan monostearate monooleate Sorbitan monostearate mono-oleate, glycerol monolaurate, propylene glycol monolaurate, propylene glycol monocaprylate, sorbitan monolaurate, Lauryl lactate, caprylic / capric triglyceride, caprylic / capric triglyceride, , Corn oil PEG-8 ester, corn oil PEG-6 ester, or triacetin.

In a preferred embodiment of the present invention, the thickness of the drug storage layer may be 30-120 [mu] m.

In a preferred embodiment of the present invention, the release-controlling and pressure-sensitive adhesive layer may contain an acrylic pressure-sensitive adhesive.

In one preferred embodiment of the present invention, the acrylic pressure-sensitive adhesive is at least one selected from the group consisting of acrylic acid, 2-ethylhexyl acrylate, butyl acrylate, 2-hydroxyethyl acrylate, methyl methacrylate, methyl acrylate, glycidyl methacrylate , Vinyl acetate, N-vinyl-2-pyrrolidone, diacetone acrylamide, t-octylacrylamide and 2- (dimethylaminoethyl) methacrylate.

In a preferred embodiment of the present invention, the thickness of the release-controlling pressure-sensitive adhesive layer may be 10-200 탆.

In a preferred embodiment of the present invention, the release layer is formed of at least one polymer film selected from the group consisting of polyester, polyvinyl chloride, polyvinylidene chloride, polyethylene terephthalate and copolymers thereof, Or may be a release paper coated with a silicone resin or a fluorine resin on one side of a glossy paper or a glossy paper on which a polyolefin is laminated.

In a preferred embodiment of the present invention, the thickness of the release layer may be 15 to 500 mu m.

In a preferred embodiment of the present invention, the surface of the emission-controlling adhesive layer contacting the skin may have a surface area of 10 to 60 cm 2.

In a preferred embodiment of the present invention, the Raney-matrix type transdermal patch containing the set theory can mean skin permeation amount is ² 50 ~ 850 ㎍ / cm during the set theory Raney 1 to 7 in.

Another aspect of the present invention is a method for treating and preventing vomiting characterized in that the matrix type transdermal patch containing the granisetron is contacted with the surface of the skin for 1 to 7 days to infiltrate granisetron transdermally .

According to the present invention, it is possible to maximize the adherence and compliance of a patient by manifesting a long-term drug efficacy by simple administration method, and it is possible to reduce a severe concentration deviation through absorption and metabolism during oral administration, and the blood concentration Can be kept constant for a desired period of time, and can be easily removed when it is necessary to stop the administration, and it can be manufactured in a small size to increase the convenience of the patient and improve the adhesive property to minimize skin irritation.

1 is a cross-sectional view of a matrix type transdermal absorption patch containing granisetron according to the present invention.

The present invention relates to a matrix type transdermal patch comprising granisetron, which can be detached in the form of a patch on the skin, has a small size, increases the convenience of the user, can maintain the blood concentration of the drug for a predetermined period of time And to a method of treating and preventing vomiting using the same.

Accordingly, the present invention provides a semiconductor device comprising: a supporting layer; A drug storage layer provided on a lower surface of the support layer, the drug storage layer containing granisetron, a polymer for forming a matrix, a tackifier resin, and a skin penetration enhancer; A release controlling adhesive layer provided on a lower surface of the drug storage layer and adapted to control the amount of drug contained in the drug storage layer and to be in contact with the skin; And a releasable release layer provided on a lower surface of the release-controlled pressure-sensitive adhesive layer. Hereinafter, the present invention will be described in more detail by constituent elements.

The matrix type transdermal absorption patch containing granitectone according to the present invention comprises a support layer. The support layer may include a drug storage layer containing granisetron, a polymer for forming a matrix, a tackifier resin, and a skin penetration promoter on the lower surface, and may be bent or bent so as to adhere to the skin, And it is preferable that the drug contained in the drug storage layer is a material that does not permeate, and is not particularly limited thereto.

The support layer may be a polymer commonly used in percutaneous absorption preparations, and preferably a polyethylene, a polypropylene, an ethylene vinyl acetate copolymer, a vinylon, a polyester, a polyurethane, a nylon, a polyacrylonitrile, a polyethylene terephthalate And at least one selected from the group consisting of polyolefins.

At this time, the thickness of the support layer is preferably 5 to 500 占 퐉, more preferably 5 to 300 占 퐉. When the support layer has a thickness of less than 5 탆, it is difficult to protect the drug because of its thin thickness. When the support layer is more than 500 탆, it is difficult to bend when adhered to skin.

The matrix type percutaneous absorption patch containing granitectone according to the present invention is provided on one side of the support layer and is provided with a drug storage layer containing granisetron, a polymer for forming a matrix, a tackifier resin and a skin permeation accelerator .

The above granisetron (N-endo-9-methyl-9-azabicyclo [3.3.1] non-3-yl-1-methylindazole-3-carboxamide hydrochloride) or its salt is included as an active ingredient having port- The drug is stored in the drug storage layer in the form of a matrix, is released through the release-controlling adhesive layer and absorbed into the percutaneous layer, thereby controlling vomiting of the patient.

In addition, the drug storage layer may be formed in a matrix form through the polymer for forming the matrix, and may contain granisetron, a tackifying resin, and a skin permeation promoting material. At this time, it is preferable to use rubber as the polymer for forming the matrix. Although the rubber has a low glass transition temperature (Tg) and exhibits thermoplasticity and is excellent in mechanical properties, it can serve as an adhesive base. However, since the adhesive force may be low with rubber alone, a desired adhesive property can be secured by adding a tackifier resin, Layer can be introduced to secure the desired adhesive property. The rubber may be a biocompatible rubber, preferably a styrene-ethylene-isoprene-styrene copolymer, a styrene-butadiene-styrene copolymer, a styrene- Butadiene copolymer, a styrene-butadiene copolymer, a silicone rubber, and polyisoburylene.

  The tackifier resin is used to obtain a desired adhesive force in a proper amount when it is difficult to obtain a desired tack adhesive force with rubber alone. The tackifier resin may be selected from the group consisting of rosin glycerin ester resin, hydrogenated rosin glycerin ester resin, rosin pentaerythritol ester resin, Alicyclic saturated hydrocarbon resin having 5 to 9 carbon atoms, aliphatic hydrocarbon resin having 5 to 9 carbon atoms, aromatic hydrocarbon resin, hydrogenated dicyclopentadiene resin, terpene resin, coumarone indene resin , Terpene phenol resin, and the like.

In addition, the skin permeation enhancer is added to improve the permeation amount of the granisetron absorbed through the skin. Examples of the N-cyclohexyl-2-pyrrolidone, 1-butyl 3-dodecyl-2-pyrrolidone, 1,5-dimethyl-2-pyrrolidone, 1- Ethyl-2-pyrrolidone, 1-hexyl-4-methyloxycarbonyl-2-pyrrolidone, 1-hexyl- 1-hexyl-2-pyrrolidone, 1- (2-hydroxyethyl) pyrrolidone, 3-hydroxy- 2-pyrrolidone, 1-lauryl-4-methyloxycarbonyl-2-pyrrolidone, N-methyl- 2-pyrrolidone, N-carprylyl-2-pyrrolidone, N-dodecyl-2 -pyrrolidone, glycerol lauryl alcohol, alcohol, oleyl alcohol, isopropyl myristrate, sorbitan mono-oleate, propylene monolaurate, propylene mono-oleate, Oleic acid, oleuroacrogolglyceride, oleic acid, lauroylmacrogoglyceride, linoleoylmacrogoglyceride, propylene glycol caprylate / caprylate, and the like. glycol caprylate / caprate, sorbitan monostearate mono-oleate, glycerol monolaurate, propylene glycol monolaurate, propylene glycol monocaprylate, glycol monocaprylate, sorbitan monolaurate, lauryl lactate, It is preferably at least one selected from the group consisting of caprylic / capric triglyceride, corn oil PEG-8 ester, corn oil PEG-6 ester or triacetin.

In a matrix type transdermal patch comprising granisetron according to the present invention, the drug storage layer comprises 5 to 30% by weight of granisetron, 40 to 70% by weight of a polymer for forming a matrix, Preferably 10 to 20% by weight of granisetron, 40 to 60% by weight of a polymer for forming a matrix, 10 to 20% by weight of a tackifier resin, By weight and 5 to 25% by weight of a skin penetration enhancer.

When the granisetron and the salt thereof are contained in an amount of less than 5% by weight based on the total weight of the drug storage layer, granisetron fails to penetrate the skin to an appropriate level. When the content exceeds 30% by weight, There is a problem that crystals are formed due to high concentration or the adhesive strength is lowered.

When the polymer for forming the matrix is contained in an amount of less than 40% by weight based on the total weight of the drug storage layer, the adhesive agent is insufficient and the mechanical properties are poor. When the polymer is contained in an amount exceeding 70% by weight, And there is a problem that the adhesive strength is lowered.

The tackifier resin may be included in an amount of 10 to 30% by weight based on the total weight of the drug-containing adhesive layer. If it is used in an amount less than 10% by weight, the effect of improving the adhesive strength of the preparation due to the combination of the tackifier resin becomes insufficient, and when it is used in excess of 30% by weight, skin irritation is increased when the preparation is peeled.

When the skin penetration enhancer is contained in an amount of less than 5% by weight based on the total weight of the drug storage layer, the desired skin permeation promoting effect can not be sufficiently obtained. When the content is more than 30% by weight, the adhesive property is deteriorated.

At this time, the thickness of the drug storage layer is preferably 30 to 120 탆, more preferably 50 to 90 탆. When the thickness of the drug storage layer is less than 30 탆, the concentration of granisetron, which is a drug contained in the drug storage layer, is excessively high, crystallization occurs in the preparation, and adhesion is too low, When the thickness exceeds 120 탆, the concentration of granisetron, which is a drug contained in the drug storage layer, is too low and proper skin permeation is difficult to be achieved.

The matrix type percutaneous absorption patch containing granisetron according to the present invention may be provided on the lower surface of the drug storage layer to control the amount of drug contained in the drug storage layer, Layer. The release-controlled pressure-sensitive adhesive layer functions to control the amount of drug released while permeating the drug released from the drug storage layer, and can be attached to the skin by including a pressure-sensitive adhesive. In addition, it prevents the skin from dropping out of the preparation due to excessive moisture or sweat release, maintains skin adhesion, enhances the reliability of the preparation, and controls the skin absorption of the drug.

The release-controlled pressure-sensitive adhesive layer preferably contains an acrylic pressure-sensitive adhesive. The acrylic pressure-sensitive adhesive is preferably one or more selected from the group consisting of no functional groups or functional groups of -COOH, -0H or -NH ₂ , and acrylic acid, 2-ethylhexyl acrylate, butyl acrylate, 2- Acrylates such as methyl methacrylate, methyl methacrylate, glycidyl methacrylate, vinyl acetate, N-vinyl-2-pyrrolidone, diacetone acrylamide, t-octylacrylamide, 2- (dimethylaminoethyl) It is preferable that one kind is selected from the group consisting of acrylate and acrylate.

At this time, the thickness of the emission controllable adhesive layer is preferably 10 to 200 mu m, more preferably 10 to 150 mu m. When the thickness of the release-controlling and pressure-sensitive adhesive layer is less than 10 탆, it is difficult to control the initial release dose, and when the thickness is more than 200 탆, the skin can not penetrate to an appropriate level.

It is preferable that the surface of the release-controlled adhesive layer that is in contact with the skin has a surface area of 10 to 60 cm 2. If the surface area is less than 10 cm 2, there is a problem that the drug permeation amount is lowered. If the surface area is more than 60 cm 2, the area is too wide to use as a patch.

The matrix type transdermal absorption patch according to the present invention comprises a granisetron, wherein the releasable peeling layer is provided on a lower surface of the release-controlling adhesive layer and is detachable. The release layer prevents the drug from being released from the release-controlled adhesive layer, and is separated and removed immediately before use to allow the release-controlled adhesive layer to adhere to the skin.

At this time, the peeling layer may be formed of at least one polymer film selected from the group consisting of polyester, polyvinyl chloride, polyvinylidene chloride, polyethylene terephthalate and copolymers thereof, a polyolefin laminated film or a polyolefin- It is preferable that the release paper is coated with a silicone resin or a fluorine resin on one surface of the base paper.

In addition, the thickness of the release layer is preferably 15 to 500 탆, more preferably 50 to 200 탆. When the peeling layer is less than 15 탆, it is difficult to produce. When the peeling layer is more than 500 탆, the peeling easiness is deteriorated.

And the average skin permeation amount for 1 to 7 days of the matrix-type transdermal patches are those Raney set Raney containing a set of theory theory according to the present invention is 50 ~ 850 ㎍ / cm ^2, preferably at average skin for 5 to 7 and the transmission amount is 550 ~ 850 ㎍ / cm ^2, more preferably the average skin permeation amount for 7 days 750 ~ 850 ㎍ / cm ² . According to the present invention it is 1 to 7 that stable Raney set theory is applied to the skin while an average transmission amount may reach 50 ~ 850 ㎍ / cm ^2.

In addition, the present invention relates to a method for producing a granular percutaneous absorption patch comprising the step of contacting a matrix type transdermal patch containing the granisetron to the surface of the skin for 1 to 7 days, preferably 5 to 7 days, more preferably 7 days, The present invention provides a method for treating and preventing vomiting characterized by infiltrating the rats with transdermal route. The matrix type transdermal patch containing the granisetron according to the present invention is brought into contact with the surface of the skin and maintained for 1 to 7 days, preferably 5 to 7 days, more preferably 7 days, Rancizinate can be infiltrated transdermally, which can cure or prevent vomiting.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following examples are provided to illustrate the present invention, but the scope of the present invention is not limited by the following examples.

[ Example ]

Example  One. Granisset Ron  Containing matrix type Of transdermal absorption patch  Produce

, 53 wt% of rubber-based pressure-sensitive adhesive (polyisobutylene polymer, polyisobutylene low molecular weight), 20 wt% of hydrogenated rosin ester resin (SYN-TECH CHEM. & PHARM CO. 100 ml of toluene was added to the mixture so that the total amount of the solids became 35% and completely dissolved. Then, the adhesive solution containing the drug was applied onto the polyester film fixed on the applicator and dried at 100 ° C for 10 minutes at a speed of 1000 rpm Thereby forming a drug storage layer having a thickness of 73.5 탆.

The release-controlled adhesive layer was applied on a PET release film coated with a fluororesin in an amount of 100% by weight of an acrylic adhesive (DT-9301, 43%), and then dried in a wrap coater at 100 DEG C and 1000 rpm for 5 minutes to completely remove the solvent Dried, and made to a thickness of 20 탆. Thereafter, the release film of the drug-bed spreading layer was removed and lapped with the release-controlling adhesive layer to complete the percutaneous absorption preparation according to the present invention.

Example  2 to 7. Granisset Ron  Containing matrix type Of transdermal absorption patch  Produce

A percutaneous absorption patch was prepared in the same manner as in Example 1, except that the composition of the drug storage layer in Example 1 was adjusted to the same contents as in Table 1 below.

Support layer
thickness
(탆) Drug storage layer (%) Release Control Adhesive Layer (%) Emission control adhesive layer
thickness
(탆) Polyester film Granisset Ron Polymers for matrix formation Tackifying resin Skin permeation accelerator Acrylic
adhesive Acrylic
adhesive Granisset Ron Polyiso
Butylene
Polymer Polyiso
Butylene
Low molecule Hydrogenation
Rosin ester Isopropyl myristate DT
-9301 DT
-9301 Example 1 12 23 40 10 15 100 20 Example 2 12 23 40 10 15 100 30 Example 3 12 23 40 10 15 100 40 Example 4 12 18 45 10 15 100 20 Example 5 12 18 45 10 15 100 30 Example 6 12 18 45 10 15 100 40

Comparative Example  One. Harbor Transdermal absorption patch

SANCUSO PATCH (34.3 mg / 52 cm 2) of AVEVA containing an acrylic pressure-sensitive adhesive was used for the drug storage layer.

Comparative Example  2 to 7. Harbor Transdermal absorption patch

A percutaneous absorption patch was prepared in the same manner as in Example 1, except that the composition of the drug storage layer in Example 1 was adjusted to the same contents as in Table 2 below.

Support layer thickness
(탆) Drug storage layer (%) Emission control
Adhesive layer (%) Release Adjustment Adhesive Layer Thickness
(탆) Polyester film Granisset Ron Polymers for matrix formation Tackifying resin Skin permeation accelerator Acrylic
adhesive Acrylic
adhesive Granisset Ron Polyiso
Butylene
Polymer Polyiso
Butylene
Low molecule Hydrogenation
Rosin ester Isopropyl myristate DT
-9301 DT
-9301 Comparative Example 2 25 8 22.2 39.8 20 10 - - Comparative Example 3 25 8 22.2 39.8 15 15 - - Comparative Example 4 25 8 22.2 39.8 10 20 - - Comparative Example 5 25 12 18 40 20 10 - - Comparative Example 6 25 12 23 40 10 15 - - Comparative Example 7 25 12 18 45 10 15 - -

Experimental Example  1. Measurement of drug-mediated skin permeation rate

The diffusion device for drug permeation experiment (Franzcel) was prepared by adding 0.1% by weight of sodium azide to a phosphate buffer solution having a pH of 7.4 in order to prevent skin decay. The experimental diffuser was filled with the receiving phase, the temperature was maintained at 32.0 ° C, and the skin was cut using human cadaver skin according to the donor cell size. Over time, 250 μl of the buffer solution in which the drug was diffused over time was taken to quantify the drug permeated by liquid chromatography. The median skin permeation rate at 7 days after permeation of the drug into the percutaneous absorption patch prepared according to the present invention was compared with Comparative Example. The results are shown in Table 3 below.

Cumulative 2-day permeability
(ug / cm ² ) 7 days cumulative permeability
(ug / cm ² ) Patch size
(cm ² ) Example 1 556.706 ± 0.156 832.313 ± 1.552 35 Example 2 438.771 + 0.017 797.413 ± 0.435 35 Example 3 412.368 ± 1.957 750.686 ± 2.169 35 Example 4 362.541 ± 2.435 843.641 + - 2.562 25 Example 5 366.022 ± 0.834 847.515 ± 2.775 25 Example 6 360.972 ± 1.905 770.313 + 1.648 25 Comparative Example 1 317.213 + 0.958 501.537 + 1.058 52 Comparative Example 2 48.987 + 0.649 246.579 ± 0.672 52 Comparative Example 3 133.874 + 0.885 348.658 ± 1.546 52 Comparative Example 4 161.796 ± 1.702 394.248 ± 2.587 52 Comparative Example 5 327.622 ± 1.883 633.466 + 0.374 35 Comparative Example 6 553.427 + 1.886 834.259 + - 0.691 35 Comparative Example 7 365.411 + 1.957 865.506 ± 0.085 35

Table 3 shows that the skin permeation rate tends to increase with increasing isopropyl myristate (IPM) content of the drug storage layer. In addition, DT-9301 was used as the release- It is possible to control the amount of loading, and it can be seen that skin adhesion is maintained and high skin permeability is exhibited.

Accordingly, the present invention provides a percutaneous absorption preparation which can control the skin permeation amount of a drug and has good skin adhesion.

Claims (16)

Supporting layer;
A drug storage layer provided on a lower surface of the support layer, the drug storage layer containing granisetron, a polymer for forming a matrix, a tackifier resin, and a skin penetration enhancer;
A release controlling adhesive layer provided on a lower surface of the drug storage layer and adapted to control the amount of drug contained in the drug storage layer and to be in contact with the skin; And
A releasable releasable layer provided on a lower surface of the release-controlled adhesive layer;
≪ / RTI > wherein the matrix-type percutaneous absorption patch comprises granisetron.
The method according to claim 1, wherein the support layer comprises at least one member selected from the group consisting of polyethylene, polypropylene, ethylene vinyl acetate copolymer, vinylon, polyester, polyurethane, nylon, polyacrylonitrile, polyethylene terephthalate and polyolefin The matrix-type transdermal absorption patch according to claim 1, wherein the matrix-type transdermal absorption patch comprises granisetron.
The matrix type transdermal absorption patch according to claim 1, wherein the thickness of the support layer is 5 to 500 占 퐉.
The drug storage layer according to claim 1, wherein the drug storage layer comprises 5 to 30% by weight of granisetron, 40 to 70% by weight of a polymer for forming a matrix, 10 to 30% by weight of a tackifier resin and 5 to 30% Wherein the matrix-type percutaneous absorption patch comprises granisetron.
The method according to claim 1, wherein the polymer for forming the matrix is selected from the group consisting of styrene-ethylene-isoprene-styrene copolymer, styrene-butadiene-styrene copolymer, styrene-butadiene- wherein the matrix-type transdermal patch comprises at least one selected from the group consisting of styrene-butadiene copolymers, silicone rubbers, and polyisoburylenes.
The tackifier resin according to claim 1, wherein the tackifier resin is selected from the group consisting of rosin glycerin ester resin, hydrogenated rosin glycerin ester resin, rosin pentaerythritol ester resin, hydrogenated rosin pentaerythritol ester resin, alpha methyl styrene resin, At least one selected from the group consisting of a saturated hydrocarbon resin, an aliphatic hydrocarbon resin having 5 to 9 carbon atoms, an aromatic hydrocarbon resin, a hydrogenated dicyclopentadiene resin, a terpene resin, a coumarone indene resin, and a terpene phenol resin Of the matrix-type percutaneous absorption patch.
The skin permeation enhancer according to claim 1, wherein the skin permeation enhancer is N-cyclohexyl-2-pyrrolidone, 1-butyl- 3-dodecyl-2-pyrrolidone, 1,5-dimethyl-2-pyrrolidone and 1-ethyl- 1-hexyl-2-pyrrolidone, 1-hexyl-2-pyrrolidone, 1- (2-hydroxyethyl) pyrrolidone, 3-hydroxy-N-methyl-2-pyrrolidone, Lauryl-4-methyloxycarbonyl-2-pyrrolidone, N-methyl-2-pyrrolidone, N- N-carprylyl-2-pyrrolidone, N-dodecyl-2-pyrrolidone, glycerol lauryl alcohol, Oleyl alcohol, isopropyl myristate, Propylene glycol monooleate, sorbitan monooleate, propylene monolaurate, propylene mono-oleate, oleylmacrogolglyceride, oleic acid, lauro < RTI ID = 0.0 & Propyleneglycol caprylate / caprate, sorbitan monostearate mono-oleate, linoleyl glyceryl glyceride, caprolactam, caprolactam, caprolactam, Glycerol monolaurate, propylene glycol monolaurate, propylene glycol monocaprylate, sorbitan monolaurate, lauryl lactate, sorbitan monolaurate, sorbitan monolaurate, ), Caprylic / capric triglyceride, corn oil PEG-8 ester , Corn oil PEG-6 ester, or triacetin. The matrix type transdermal patch according to claim 1, wherein the matrix-type percutaneous absorption patch comprises granisetron.
The matrix type transdermal absorption patch according to claim 1, wherein the thickness of the drug storage layer is 30 to 120 탆.
The matrix type transdermal patch according to claim 1, wherein the release-controlling adhesive layer contains acrylic pressure-sensitive adhesive.
The acrylic pressure-sensitive adhesive composition according to claim 9, wherein the acrylic pressure-sensitive adhesive is selected from the group consisting of acrylic acid, 2-ethylhexyl acrylate, butyl acrylate, 2-hydroxyethyl acrylate, methyl methacrylate, methyl acrylate, glycidyl methacrylate, Acrylate, N-vinyl-2-pyrrolidone, diacetone acrylamide, t-octylacrylamide and 2- (dimethylaminoethyl) methacrylate. A matrix-type transdermal absorption patch comprising:
The matrix type transdermal absorption patch according to claim 1, wherein the thickness of the release-controlling adhesive layer is 10 to 200 占 퐉.
The laminate of claim 1, wherein the release layer comprises at least one polymer film selected from the group consisting of polyester, polyvinyl chloride, polyvinylidene chloride, polyethylene terephthalate and copolymers thereof, a polyolefin- Wherein the laminate is a release paper coated with a silicone resin or a fluorine resin on one side of the laminated gloss paper.
The matrix type transdermal absorption patch according to claim 1, wherein the release layer has a thickness of 15 to 500 mu m.
The matrix type transdermal patch according to claim 1, wherein a surface of the release-controlling adhesive layer which is in contact with the skin has a surface area of 10 to 60 cm 2.
The method of claim 1, wherein the Raney set in a matrix-type transdermal absorption patch is characterized in that the average skin permeation amount for 1 to 7 days of Raney set Ron is 50 ~ 850 ㎍ / cm ² containing the above that Raney set theory Rhone A matrix-type transdermal absorption patch comprising:
A method for the treatment and prevention of vomiting characterized in that a matrix type transdermal patch containing the granisetron of any one of claims 1 to 15 is contacted with the surface of the skin for 1 to 7 days to penetrate the granisetron transdermally .

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