CN100469367C - Transdermal preparations comprising eperisone, tolperisone or salts thereof - Google Patents

Abstract

The present invention relates to a transdermal preparation comprising skeletal muscle relaxant eperisone, tolperisone or a salt thereof, more specifically, the transdermal preparation is characterized in that, after transmitting eperisone, tolperisone or a salt thereof through In skin procedures, the use of a mixture of acrylic adhesives having hydroxyl groups and non-hydroxyl-containing acrylic adhesives as a matrix in a defined ratio, thereby maximizing the transdermal absorption of eperisone, tolperisone or a salt thereof, Improves the stability of eperisone, toperisone or their salts in the matrix layer and provides superior skin adhesion.

Description

Transdermal preparations comprising eperisone, tolperisone or salts thereof

technical field

The present invention relates to a transdermal preparation comprising a skeletal muscle relaxant, eperisone, tolperisone, or a salt thereof (hereinafter referred to as "eperisone, etc.").

Background technique

Spasticity is a disorder of skeletal muscles due to increased muscle tone, with central nervous system lesions such as ischemic attacks, trauma, and several types of neuronal degeneration. Since different neurotransmitters, neuromodulators, receptors and associated ion channels are involved in the interneuronal control of muscle tone, centrally acting muscle relaxants are commonly used to treat spasticity. Centrally acting muscle relaxants reduce increases in muscle tone and inhibit hyperactive reflexes by antagonizing the activation of receptors associated with agonistic motor functions or by acting on receptors associated with inhibitory functions. The problem with the use of such centrally acting muscle relaxants is central nervous system depression and muscle weakness.

Eperisone, etc. are muscle relaxants that act on the central nervous system with a low incidence of central nervous system depression, and are widely used in the treatment of muscle spasms to relieve muscle stiffness and spinal pain. Eperisone and others inhibit monosynaptic and polysynaptic reflexes by acting on the spinal cord and upper central nervous system, and show muscle relaxation by reducing muscle tension. However, due to the first-pass effect in the absorption process, eperisone et al. exhibit drawbacks, namely very low bioavailability and variable plasma levels. In addition, since the muscle relaxation effect of absorbed eperisone and the like lasts very short, frequent administration is required, and all commercial products are injection or oral preparations, which poses a problem in terms of patient compliance.

In order to solve this problem, many attempts have been made to develop transdermal formulations whereby drugs can enter the body through the surface layer of the skin. US Patent No. 5,252,588 discloses transdermal formulations comprising eperisone and water-swellable cross-linked polyvinylpyrrolidone.

Compared with USP5,252,588, the formulation provided by the present invention exhibits superior skin permeability, and has sufficient viscosity when attached to the skin, so that good adhesion can be achieved throughout the application stage, and produces Less pain and less peeling of the skin, thus more convenient for the patient.

Contents of the invention

An object of the present invention is to provide transdermal preparations which ensure the stability of eperisone and the like in an adhesive, have sufficient skin adhesiveness for application, and simultaneously allow the drug to pass through the skin to the greatest extent.

The present invention relates to a transdermal preparation with an adhesive layer comprising a drug selected from eperisone, tolperisone and salts thereof and an acrylic adhesive with hydroxyl groups and a hydroxyl-free a mixture of acrylic adhesives.

The drug used in the present invention is selected from eperisone, tolperisone and their salts, and as salts, hydrochloride and phosphate are preferred.

Eperisone, tolperisone or their salts can exist in the adhesive in a dissolved or crystal state, preferably, the content of the drug is 5-20% by weight relative to the total weight of the adhesive layer. In general, it is known that the skin permeability of drugs increases proportionally with the drug concentration in the adhesive. Therefore, when the drug concentration in the adhesive is too low, a sufficient amount of the drug cannot be delivered through the skin to achieve a pharmacological effect. However, conversely, when the drug concentration is too high, the skin penetration of the drug does not increase beyond a certain level, and it affects the physical properties of the adhesive layer, negatively affecting the skin adhesion of the formulation.

The acrylic adhesive used in the present invention consists of a mixture of an acrylic adhesive having hydroxyl groups and an acrylic adhesive not containing hydroxyl groups. The weight mixing ratio of the acrylic adhesive with hydroxyl group to the acrylic adhesive without hydroxyl group is preferably 8:2˜5:5. Said adhesive is used in viscous state with added organic solvent, and most of the organic solvent evaporates during the drying process after spreading, leaving only the acrylic adhesive.

An acrylic binder with hydroxyl groups was used to maximize the skin penetration of the drug.

Acrylic adhesives with hydroxyl groups are composed of copolymers of monomers with hydroxyl groups and monomers without hydroxyl groups.

As the monomer having a hydroxyl group, at least one selected from hydroxyethyl (meth)acrylate and hydroxypropyl (meth)acrylate can be used. Preferably, the monomer having a hydroxyl group is preferably used in an amount of 1 to 20% by weight of the total weight of monomers used for polymerization of the acrylic adhesive having a hydroxyl group.

As a hydroxyl group-free monomer, one or more monomers selected from common alkyl (meth)acrylate monomers such as butyl acrylate, methyl acrylate, methyl methacrylate and 2- Ethylhexyl ester, acrylic acid and vinyl acetate.

More specifically, as a hydroxyl group-free monomer, it is preferable to use 2-ethylhexyl acrylate and vinyl acetate together, and the amount of 2-ethylhexyl acrylate used is preferably the total amount of the acrylic adhesive having a hydroxyl group. 49-80% by weight, vinyl acetate is preferably 19-50% by weight of the total weight of the acrylic adhesive having hydroxyl groups.

As a commercial product sold as an acrylic adhesive having a hydroxyl group, Duro-Tak 87-2287, Duro-Tak 87-2510, Duro-Tak 87-2516 and the like (National Starch and Chemical) can be listed.

In addition, as far as the acrylic adhesive without hydroxyl group is concerned, since it does not contain functional groups that react with drugs such as eperisone, the stability of eperisone, etc. Use with acrylic adhesive.

The described hydroxyl-free acrylic adhesive consists of common alkyl (meth)acrylate monomers (such as butyl acrylate, methyl acrylate, methyl methacrylate and 2-ethylhexyl acrylate) and vinyl acetate Copolymer composition of base ester monomers. Preferably, the hydroxyl-free acrylic adhesive consists of 2-ethylhexyl acrylate and vinyl acetate monomers, and 2-ethylhexyl acrylate is preferably 50% of the total weight of the hydroxyl-free acrylic adhesive. - 80% by weight, vinyl acetate is preferably 20-50% by weight of the total weight of the hydroxyl-free acrylic adhesive.

 Multipolymer Solution3067和

 Multipolymer Solution 3083(SOLUTIA)。As commercial products of such hydroxyl-free acrylic adhesives, Duro-Tak 87-4098 (National Starch and Chemical),

Multipolymer Solution3067 and

Multipolymer Solution 3083 (SOLUTIA).

Common acrylic adhesives used in the prior art have carboxyl groups. It comes from the monomeric acrylic used in adhesives. This common acrylic adhesive has only carboxyl groups, or both carboxyl and hydroxyl groups. As such acrylic adhesives, Duro-Tak 87-2074, Duro-Tak 87-2194, Duro-Tak 87-2353, Duro-Tak 87-2677 and Duro-Tak 87-2825 (National Starch and Chemical) can be listed , as an acrylic adhesive having an amide group, Duro-Tak 87-9301 (National Starch and Chemical) can be listed, and also an acrylic adhesive having vinylpyrrolidone such as TSR (Sekisui). This acrylic adhesive was not used in the present invention, but was used as a comparison.

The preparation according to the present invention may contain other solubilizers to increase the content of eperisone etc. in the adhesive layer.

In the present invention, the solubilizing agent is used to make the adhesive layer, in which the main component is an acrylic adhesive, contain eperisone or the like at a certain concentration. As such a solubilizing agent, distilled water, ethanol, isopropanol, diethylene glycol monoethyl ether, polyethylene glycol, glycerin, and dimethyl sulfoxide can be listed, and one or more of them can be used, and Its amount is preferably 1 to 20% by weight of the total weight of the adhesive layer.

Correspondingly, the preparation of the present invention may further contain a skin penetration enhancer to increase the percutaneous absorption rate of eperisone and the like.

As the skin penetration enhancer used in the present invention, higher fatty acids such as oleic acid, higher alcohols such as lauryl alcohol, higher fatty acid esters such as isopropyl myristate, fatty acid esters of glycerin such as glycerol monolaurate , fatty acid ethers of polyethylene glycol such as polyethylene glycol lauryl ether, fatty acid esters of polyethylene glycol such as polyethylene glycol laurate, fatty acid ethers of propylene glycol such as propylene glycol lauryl ether, fatty acid esters of propylene glycol such as Propylene glycol laurate, sorbitan fatty acid esters such as sorbitan monolaurate, polyethylene glycol sorbitan fatty acid esters such as polyethylene glycol sorbitan monolaurate, terpenes such as menthol, menthol Derivatives and limonene, sulfoxides such as dimethylsulfoxide, dodecylsulfoxide, pyrrolidones such as N-methyl-2-pyrrolidone, amides such as lauryldiethanolamide, N-hydroxymethyllactide, sorbitol , urea, squalene, olive oil, mineral oil and their derivatives, one or more of which can be used, and preferably 1-20% by weight of the total weight of the adhesive layer.

As the backing material of the transdermal preparation according to the present invention, backing materials as used in conventional transdermal preparations can be used. For example, materials with good permeability to air and moisture can be used, such as non-woven fabrics, cotton cloths and fabrics, or polyethylene terephthalate, polyurethane, polyethylene, polypropylene, ethylene vinyl acetate Mono- or multi-laminate films of ester and aluminum-treated polyethylene, non-woven or cotton laminated to a water-impermeable plastic film if desired.

The transdermal preparation containing eperisone or the like according to the present invention is characterized as a matrix type or drug-in-adhesive type patch. As far as this patch is concerned, its dosage form is not much different from plasters and cataplasms, so it can be made in the form of plasters or cataplasms.

Detailed ways

Hereinafter, the present invention is explained by Examples and Experimental Examples, but the present invention is not limited by them.

Comparative example 1-1

Element

Topaperone Hydrochloride 20% by weight

Glyceryl monolaurate 5% by weight

Polyethylene glycol (400) 5% by weight

Acrylic adhesive (Duro-Tak 87-2194) 70% by weight (dry weight)

Here, dry weight refers to the weight obtained after evaporation of the organic solvent contained in the adhesive product.

method

1. Add tolperone hydrochloride, glyceryl monolaurate and polyethylene glycol (400) into the acrylic adhesive and dissolve completely by stirring.

2. Spread the mixture onto a release liner to a dry thickness of 25 μm.

3. Dry in an oven at 80°C for 20 minutes.

4. Laminated polyethylene film.

Comparative example 1-2

Element

Topaperone Hydrochloride 20% by weight

Glyceryl monolaurate 5% by weight

Polyethylene glycol (400) 5% by weight

Acrylic adhesive (Duro-Tak 87-9301) 70% by weight (dry weight)

method

1. Add tolperone hydrochloride, glyceryl monolaurate and polyethylene glycol (400) into the acrylic adhesive and dissolve completely by stirring.

2. Spread the mixture onto a release liner to a dry thickness of 25 μm.

3. Dry in an oven at 80°C for 20 minutes.

4. Laminated polyethylene film.

Comparative example 1-3

Element

Topaperone Hydrochloride 20% by weight

Glyceryl monolaurate 5% by weight

Polyethylene glycol (400) 5% by weight

          70重量％(干重)Acrylic adhesive (

70% by weight (dry weight)

Multipolymer Solution 3083)

method

1. Add tolperone hydrochloride, glyceryl monolaurate and polyethylene glycol (400) into the acrylic adhesive and dissolve completely by stirring.

2. Spread the mixture onto a release liner to a dry thickness of 25 μm.

3. Dry in an oven at 80°C for 20 minutes.

4. Laminated polyethylene film.

Comparative example 1-4

Element

Topaperone Hydrochloride 20% by weight

Glyceryl monolaurate 5% by weight

Polyethylene glycol (400) 5% by weight

Acrylic adhesive (Duro-Tak 87-2516) 70% by weight (dry weight)

method

1. Add tolperone hydrochloride, glyceryl monolaurate and polyethylene glycol (400) into the acrylic adhesive and dissolve completely by stirring.

2. Spread the mixture onto a release liner to a dry thickness of 25 μm.

3. Dry in an oven at 80°C for 20 minutes.

4. Laminated polyethylene film.

Comparative example 2-1

Element

Eperisone hydrochloride 5% by weight

Polyoxyethylene(2) lauryl ether 3% by weight

Propylene Glycol 5% by weight

Acrylic adhesive (Duro-Tak 87-2074) 87% by weight (dry weight)

method

1. Add Eperisone Hydrochloride, Polyoxyethylene (2) Lauryl Ether and Propylene Glycol to the acrylic adhesive, and dissolve completely by stirring.

2. Spread the mixture onto a release liner to a dry thickness of 100 μm.

3. Dry in an oven at 80°C for 20 minutes.

4. Laminated polyethylene film.

Comparative example 2-2

Element

Eperisone hydrochloride 5% by weight

Polyoxyethylene(2) lauryl ether 3% by weight

Propylene Glycol 5% by weight

Acrylic adhesive (Duro-Tak 87-2353) 87% by weight (dry weight)

method

1. Add Eperisone Hydrochloride, Polyoxyethylene (2) Lauryl Ether and Propylene Glycol to the acrylic adhesive, and dissolve completely by stirring.

2. Spread the mixture onto a release liner to a dry thickness of 100 μm.

3. Dry in an oven at 80°C for 20 minutes.

4. Laminated polyethylene film.

Comparative example 2-3

Element

Eperisone hydrochloride 5% by weight

Polyoxyethylene(2) lauryl ether 3% by weight

Propylene Glycol 5% by weight

Acrylic adhesive (Duro-Tak 87-4098) 87% by weight (dry weight)

method

1. Add Eperisone Hydrochloride, Polyoxyethylene (2) Lauryl Ether and Propylene Glycol to the acrylic adhesive, and dissolve completely by stirring.

2. Spread the mixture onto a release liner to a dry thickness of 100 μm.

3. Dry in an oven at 80°C for 20 minutes.

4. Laminated polyethylene film.

Comparative example 2-4

Element

Eperisone hydrochloride 5% by weight

Polyoxyethylene(2) lauryl ether 3% by weight

Propylene Glycol 5% by weight

Acrylic adhesive (Duro-Tak 87-2510) 87% by weight (dry weight)

method

1. Add Eperisone Hydrochloride, Polyoxyethylene (2) Lauryl Ether and Propylene Glycol to the acrylic adhesive, and dissolve completely by stirring.

2. Spread the mixture onto a release liner to a dry thickness of 100 μm.

3. Dry in an oven at 80°C for 20 minutes.

4. Laminated polyethylene film.

Comparative example 3

Element

Eperisone hydrochloride 10% by weight

Povidone INF-10 5% by weight

Acrylic Adhesive (TSR) 85% by weight (dry weight)

method

1. Add Eperisone Hydrochloride and Povidone INF-10 into the acrylic adhesive and dissolve completely by stirring.

2. Spread the mixture onto a release liner to a dry thickness of 50 μm.

3. Dry in an oven at 80°C for 20 minutes.

4. Laminated polyester film.

Comparative example 4-1

Element

Eperisone hydrochloride 10% by weight

Propylene Glycol Monolaurate 2.5% by weight

Diethylene glycol monoethyl ether 2.5% by weight

Acrylic adhesive (Duro-Tak 87-4098) 85% by weight (dry weight)

method

1. Add Eperisone Hydrochloride, Propylene Glycol Monolaurate and Diethylene Glycol Monoethyl Ether to the acrylic adhesive, and stir to dissolve completely.

2. Spread the mixture onto a release liner to a dry thickness of 50 μm.

3. Dry in an oven at 80°C for 20 minutes.

4. Laminated polyester film.

Comparative example 4-2

Element

Eperisone hydrochloride 10% by weight

Propylene Glycol Monolaurate 2.5% by weight

Diethylene glycol monoethyl ether 2.5% by weight

Acrylic adhesive (Duro-Tak 87-2287) 85% by weight (dry weight)

method

1. Add Eperisone Hydrochloride, Propylene Glycol Monolaurate and Diethylene Glycol Monoethyl Ether to the acrylic adhesive, and stir to dissolve completely.

2. Spread the mixture onto a release liner to a dry thickness of 50 μm.

3. Dry in an oven at 80°C for 20 minutes.

4. Laminated polyester film.

Comparative example 4-3

Element

Eperisone hydrochloride 10% by weight

Propylene Glycol Monolaurate 2.5% by weight

Diethylene glycol monoethyl ether 2.5% by weight

Acrylic adhesive (Duro-Tak 87-2287) 25.5% by weight (dry weight)

Acrylic adhesive (Duro-Tak 87-4098) 59.5% by weight (dry weight)

method

1. Mix Eperisone Hydrochloride, Propylene Glycol Monolaurate and Diethylene Glycol Monoethyl Ether with the two acrylic binders and dissolve them completely by stirring.

2. Spread the mixture onto a release liner to a dry thickness of 50 μm.

3. Dry in an oven at 80°C for 20 minutes.

4. Laminated polyester film.

Comparative example 4-4

Element

Eperisone hydrochloride 10% by weight

Propylene Glycol Monolaurate 2.5% by weight

Diethylene glycol monoethyl ether 2.5% by weight

Acrylic adhesive (Duro-Tak 87-2287) 34% by weight (dry weight)

Acrylic adhesive (Duro-Tak 87-4098) 51% by weight (dry weight)

method

1. Mix Eperisone Hydrochloride, Propylene Glycol Monolaurate and Diethylene Glycol Monoethyl Ether with the two acrylic binders and dissolve them completely by stirring.

2. Spread the mixture onto a release liner to a dry thickness of 50 μm.

3. Dry in an oven at 80°C for 20 minutes.

4. Laminated polyester film.

Example 1

Element

Eperisone hydrochloride 10% by weight

Propylene Glycol Monolaurate 2.5% by weight

Diethylene glycol monoethyl ether 2.5% by weight

Acrylic adhesive (Duro-Tak 87-2287) 42.5% by weight (dry weight)

Acrylic adhesive (Duro-Tak 87-4098) 42.5% by weight (dry weight)

method

1. Mix Eperisone Hydrochloride, Propylene Glycol Monolaurate and Diethylene Glycol Monoethyl Ether with the two acrylic binders and dissolve them completely by stirring.

2. Spread the mixture onto a release liner to a dry thickness of 50 μm.

3. Dry in an oven at 80°C for 20 minutes.

4. Laminated polyester film.

Example 2

Element

Eperisone hydrochloride 10% by weight

Propylene Glycol Monolaurate 2.5% by weight

Diethylene glycol monoethyl ether 2.5% by weight

Acrylic adhesive (Duro-Tak 87-2287) 51% by weight (dry weight)

Acrylic adhesive (Duro-Tak 87-4098) 34% by weight (dry weight)

method

1. Mix Eperisone Hydrochloride, Propylene Glycol Monolaurate and Diethylene Glycol Monoethyl Ether with the two acrylic binders and dissolve them completely by stirring.

2. Spread the mixture onto a release liner to a dry thickness of 50 μm.

3. Dry in an oven at 80°C for 20 minutes.

4. Laminated polyester film.

Example 3

Element

Eperisone hydrochloride 10% by weight

Propylene Glycol Monolaurate 2.5% by weight

Diethylene glycol monoethyl ether 2.5% by weight

Acrylic adhesive (Duro-Tak 87-2287) 59.5% by weight (dry weight)

Acrylic adhesive (Duro-Tak 87-4098) 25.5% by weight (dry weight)

method

1. Mix Eperisone Hydrochloride, Propylene Glycol Monolaurate and Diethylene Glycol Monoethyl Ether with the two acrylic binders and dissolve them completely by stirring.

2. Spread the mixture onto a release liner to a dry thickness of 50 μm.

3. Dry in an oven at 80°C for 20 minutes.

4. Laminated polyester film.

Example 4

Element

Topaperone Hydrochloride 10% by weight

Propylene Glycol Monolaurate 2.5% by weight

Macrogol 400 2.5% by weight

Acrylic adhesive (Duro-Tak 87-2287) 59.5% by weight (dry weight)

Acrylic adhesive (Duro-Tak 87-4098) 25.5% by weight (dry weight)

method

1. Mix tolperone hydrochloride, propylene glycol monolaurate, and polyethylene glycol 400 with two acrylic adhesives, and dissolve completely by stirring.

2. Spread the mixture onto a release liner to a dry thickness of 50 μm.

3. Dry in an oven at 80°C for 20 minutes.

4. Laminated polyester film.

Experimental Example 1: Skin Permeability Test

The hair on the abdomen of male guinea pigs (350 g) was cut off with hair scissors, completely removed with a razor, and the complete skin at the ideal abdominal position was removed, and stored in a freezer (less than 20° C.) for future experiments.

After thawing, the skin was cut into a size of 2×2 cm ² , and the patch prepared in the comparative example and the embodiment was cut into a size of 1.5×1.5 cm ² , and pasted on the stratum corneum.

The skin was fixed on the Franz-type diffusion cell with the part attached to the patch facing upwards. The lower part of the device was filled with a buffer solution of the required pH, and the diffusion cell was maintained at 37°C. The receiving solution (buffer) was stirred at 600 rpm. After a certain amount of time has elapsed, a certain amount of receiving solution is taken out and filled with an equal amount of fresh buffer solution. The samples were analyzed by HPLC, and the results are shown in Table 1.

Table 1 The amount of eperisone etc. in the transdermal preparations permeated through guinea pig skin

patch number Permeation after 24 hours (μg/cm²) Comparative example 1-1 52.5 Comparative example 1-2 68.3 Comparative example 1-3 33.0 Comparative example 1-4 107.1 Comparative example 2-1 42.9 Comparative example 2-2 76.7 Comparative example 2-3 35.2 Comparative example 2-4 118.1 Comparative example 3 78.5 Comparative example 4-1 50.3 Comparative example 4-2 122.2 Comparative example 4-3 62.9 Comparative example 4-4 80.2 Example 1 83.6 Example 2 92.4 Example 3 102.8 Example 4 98.3

From Table 1 above, it can be determined that the flux of the patches using the acrylic adhesives with hydroxyl groups was higher than that of the patches using other acrylic adhesives.

In addition, among patch preparations containing an acrylic adhesive having a hydroxyl group and an acrylic adhesive not containing a hydroxyl group, a patch using a high concentration of an acrylic adhesive having a hydroxyl group such as Examples 1 to 3 exhibited a higher concentration than the other patches. agent for better flow.

Experimental Example 2: Peeling Experiment

According to the PSTC-1 test method, the peel strength was measured with a textile analyzer (TX2, MHK Trading co.). The prepared patch was cut into a size of 2.5cm×10cm, pasted on a stainless steel substrate, and the peel strength was measured when it desorbed at a constant speed. The results are shown in Table 2.

  Table 2 Peel Strength

patch number Peel strength (g force) Comparative example 1-4 1345 Comparative example 2-4 1587 Comparative example 3 1261 Comparative example 4-2 1337 Example 2 748 Example 3 839

From Table 2 above, it can be determined that, for Comparative Examples 1-4, 2-4, 3, and 4-2, the excessively high peel strength is likely to cause pain to the patient when removed from the skin, and also due to the Increased skin irritation due to injury and physical irritation. On the contrary, Examples 2 and 3 showed appropriate peeling strength, which can reduce the possibility of spontaneous peeling off when the patch is applied, and peel off easily when removing it.

Embodiment 3: Stability experiment

The prepared patch was put into an aluminum package, filled with nitrogen, and stored in an oven at 40° C. and a relative humidity of 75%. After the determined time has elapsed, the package is opened, the drug is taken out, and its residual quantity is determined. The results are shown in Table 3.

Table 3 Residual amount of eperisone etc. in the patch

As can be seen from Table 3 above, eperisone and the like are the most stable in the patches of Comparative Examples 1-3 using a hydroxyl group-free acrylic adhesive. The patches of Comparative Examples 1-4, 2-4 and 4-2 using only the acrylic adhesive having hydroxyl groups had stability problems. However, as a result of mixing the two binders in an appropriate ratio, stability is improved so that no problem occurs in actual storage.

Industrial Applicability

The present invention relates to transdermal preparations containing central nervous system skeletal muscle relaxant eperisone etc. Compared with conventional oral preparations or injections, it can prolong the action time of drugs, thus making it possible to develop once-a-day or once-every-other-day preparations , and exhibit better skin penetration than formulations introduced by prior patents, thereby providing transdermal formulations of smaller size.

Claims (8)

1. the preparation capable of permeating skin that has adhesion layer, described adhesion layer comprise be selected from eperisone, tolperisone with and the medicine of salt and as the acryloid cement that only has hydroxyl and the mixture that does not contain the acryloid cement of functional group of binding agent;

Be 5～20 weight % wherein with respect to the described content of medicines of the gross weight of adhesion layer;

It is described that only to have the acryloid cement of hydroxyl be 8:2～5:5 with the mixing ratio that does not contain the acryloid cement of functional group;

The wherein said acryloid cement that only has hydroxyl is to have the monomer of hydroxyl and the monomeric random copolymer that does not contain functional group;

Described monomer with hydroxyl is to be selected from least a in (methyl) hydroxyethyl acrylate and (methyl) acrylic acid hydroxypropyl ester;

The described monomer that does not contain functional group is at least a monomer that is selected from (methyl) alkyl acrylate monomer and the vinyl-acetic ester; And

The described acryloid cement that does not contain functional group is made up of (methyl) alkyl acrylate monomer and vinyl-acetic ester.

2. according to the preparation capable of permeating skin of claim 1, wherein said salt is hydrochlorate or phosphate.

3. according to the preparation capable of permeating skin of claim 1, wherein said monomer with hydroxyl occupies 1～20 weight % that polymerization generates the monomeric gross weight of the acryloid cement that only has hydroxyl.

4. according to the preparation capable of permeating skin of claim 1, the wherein said monomer that does not contain functional group is 2-ethylhexyl acrylate and vinyl-acetic ester, and the content of this 2-ethylhexyl acrylate is for only having the 49-80 weight % of the acryloid cement gross weight of hydroxyl, and the content of this vinyl-acetic ester is 19-50 weight %.

5. according to the preparation capable of permeating skin of claim 1, the wherein said acryloid cement that does not contain functional group is made up of 2-ethylhexyl acrylate and vinyl-acetic ester, and the content of this 2-ethylhexyl acrylate is the 50-80 weight % that does not contain the acryloid cement gross weight of functional group, and the content of this vinyl-acetic ester is 20-50 weight %.

6. according to the preparation capable of permeating skin of claim 1, it is characterized in that it also contains at least a solubilizing agent that is selected from following group in the 1-20 of adhesion layer gross weight weight % scope: distilled water, ethanol, isopropyl alcohol, TC, Polyethylene Glycol, glycerol and dimethyl sulfoxide.

7. according to the preparation capable of permeating skin of claim 1, it is characterized in that it also contains at least a dermal osmosis accelerator that is selected from following group in the 1-20 of adhesion layer gross weight weight % scope: higher fatty acids, higher alcohol, high-grade aliphatic ester, the fatty acid ester of glycerol, the fatty acid ether of Polyethylene Glycol, the fatty acid ester of Polyethylene Glycol, the fatty acid ether of propylene glycol, the fatty acid ester of propylene glycol, fatty acid esters of sorbitan, the Polyethylene Glycol fatty acid esters of sorbitan, terpene, sulfoxide, ketopyrrolidine, amide, N-hydroxymethyl lactide, sorbitol, urea, Squalene, olive oil, mineral oil and their derivant.

8. preparation capable of permeating skin according to claim 7, wherein said higher fatty acids is an oleic acid, described higher alcohol is a lauryl alcohol, described high-grade aliphatic ester is an isopropyl myristate, the fatty acid ester of described glycerol is the glyceryl monolaurate, the fatty acid ether of described Polyethylene Glycol is polyethylene glycol lauryl ether, the fatty acid ester of described Polyethylene Glycol is a polyethylene glycol laurate, the fatty acid ether of described propylene glycol is the propylene glycol lauryl ether, the fatty acid ester of described propylene glycol is the propylene glycol laurate, described fatty acid esters of sorbitan is an Arlacel-20, described Polyethylene Glycol fatty acid esters of sorbitan is the Polyethylene Glycol Arlacel-20, described terpene is a menthol, menthol derivative and limonene, described sulfoxide is dimethyl sulfoxide and dodecyl sulfoxide, described ketopyrrolidine is the N-N-methyl-2-2-pyrrolidone N-, and described amide is the lauryl diglycollic amide.