Put on a tape preparation for percutaneous introduction, containing fentanyl

 

(57) Abstract:

Describes how to put on a tape preparation for percutaneous introduction, containing a salt of fentanyl - ventanilla pressure-sensitive adhesive and sodium acetate. This drug has a small annoying ability in relation to the skin and excellent percutaneous permeability and has a high stability even over time. 6 C.p. f-crystals, 3 tables.

The scope of the invention

The invention relates to printed on the tape preparation for percutaneous introduction, containing fentanyl (chemical name: 1-phenethyl-4-N-propionylanilinopiperidine) or its salt, which is highly excellent in the property of the transdermal permeability and which has a low irritant property in relation to the skin. Put on a tape preparation for percutaneous introduction, containing fentanyl, according to the present invention, as really it is expected, will be used as an anesthetic and analgetika prolongirovannogo steps.

Background of the invention

Fentanyl, in particular ventanilla known as a drug with a strong analgesic effect. However, there is no suitable arcinomatous pain, because the half-life of the drug is short, and therefore its impact is not long, although he is used to introduce a constant speed using a dropper before and after the operation.

In the U.S. market appeared painted on the plaster preparation with prolonged action, containing ventanilla base (trade name: DURAGESIC). However, it has the disadvantage that it is highly irritating to the area of its imposition (the value of PII, showing the primary index of skin irritation from rabbits painted on the plaster of the drug, is of 2.2, which is a very high value compared with the value of this index for the preparation of the present invention, which is from 0.3 to 0.8 (see table 3)).

Furthermore, although attempts have been made to prepare ventanilla as applied to a tape preparation for percutaneous introduction, they have been applied clinically, because the solubility of ventanilla in non-aqueous base is low, and therefore the property of the transdermal permeability of the drug, in which fentanyl is contained in the nonaqueous basis, is very low.

Therefore, the aim of the present invention is RAS tape preparation for percutaneous introduction contains fentanyl which has the property of weak irritation of the skin, which is extremely excellent in the property of the transdermal permeability of fentanyl and which is stable during storage.

The authors of the present invention have conducted serious studies to achieve the above objectives, and as a result, they have found that printed on the tape preparation for percutaneous introduction, which is an extremely excellent property transdermal permeability and which has the property of weak skin irritation, can be obtained by adding sodium acetate to a pressure-sensitive adhesive base containing fentanyl or its salt, and thus made the present invention.

Description of the invention

Thus, the present invention relates to printed on the tape preparation for percutaneous introduction, which contains fentanyl, comprising fentanyl or its salt, a pressure-sensitive adhesive and sodium acetate.

The present invention also relates to printed on the tape preparation for percutaneous introduction, containing fentanyl, which comprises from 0.05 to 20% (wt. /wt.) Ventria.

The present invention also relates to printed on the tape preparation for percutaneous introduction, containing fentanyl, where salt fentanyl is ventanilla.

The present invention also relates to printed on the tape preparation for percutaneous introduction, containing fentanyl, where the mass ratio of ventanilla and sodium acetate in the product is(1 - 5):(0,5 - 2,5).

The present invention also relates to printed on the tape preparation for percutaneous introduction, containing fentanyl, where the mass ratio of ventanilla and sodium acetate in the product is(3 - 5):(1,5 - 2,5).

The present invention also relates to printed on the tape preparation for percutaneous introduction, containing fentanyl, where the mass ratio of ventanilla and sodium acetate in the product is 2:1.

The present invention also relates to printed on the tape preparation for percutaneous introduction, containing fentanyl, which additionally contains oil and/or substance to improve the adhesiveness.

The present invention also relates to printed on the tape preparation for percutaneous introduction, contains fentanyl which d is seeking to put on the tape preparation for percutaneous introduction containing fentanyl, where a pressure-sensitive adhesive includes two components of polyisobutylene and styrene-isoprene-styrene block copolymer.

Best mode for carrying out the present invention

Put on a tape preparation for percutaneous introduction, containing fentanyl, according to the present invention will be explained in detail next.

Pharmacologically active component deposited on the tape preparation for percutaneous introduction, containing fentanyl, the present invention represents himself fentanyl or its salt. Salt of fentanyl is not specifically limited and can be used as its inorganic salt and organic salt. As typical salts of fentanyl can be given citrate, hydrochloride, fumarate and the like. Among them, particularly preferred is ventanilla. Fentanyl or its salt can be used by themselves, and can be used a mixture of at least two of them.

Fentanyl or its salt is preferably contained in the amount inside the range from 0.05 to 20% (wt./wt.) in relation to the total amount of the adhesive layer on the tape preparation for percutaneous entered is to be obtained a sufficient number of penetrated through the skin of matter as applied to a tape preparation for percutaneous introduction and if the number exceeds 20% (wt./wt.), this has a negative effect on the physical properties of the drug, and therefore it is not preferred.

Pressure-sensitive adhesive of the present invention contained in the adhesive layer applied on the tape preparation for percutaneous introduction, containing fentanyl, is not limited, but preferred examples can be given polyisobutylene (PIB), styrene-isoprene-styrene block copolymer (SIS) (for example, Califlex D-1111, Califlex TR-1107, produced by Shell Chemical; JSR5000, JSR5002, SR5100 produced by Japan Synthetic Rubber Co., Ltd.; Quintack 3421, produced by Nippon Zeon Co., Ltd.), isoprene rubber, styrene-butadiene-styrene copolymer (SBS) (for example, Califlex TR-1107, produced by Shell Chemical), acrylic polymer (for example, a copolymer containing at least two components selected from the group comprising 2-ethyl hexyl acrylate, vinyl acetate, acrylate, methacrylate, methoxyethylamine and acrylic acid, such as D-300 (manufactured by Nippon Carbide Industries Co. , Inc.)). These polymers can be used individually or may be used a mixture of at least two of them. Among them, two component, including BIP and SIS, are used preferably. In this case, the th to the pressure of the adhesive is preferably contained in an amount ranging from 0.1 to 98% (wt./wt.), more preferably from 0.1 to 70% (wt./wt.), most preferably from 0.1 to 50% (wt./wt.) in relation to the total amount of the adhesive layer applied to the tape preparation for percutaneous introduction of the present invention. If the number of pressure-sensitive adhesive is less than 0.1% (wt./wt.), the physical properties of the drug will be bad, so this is not preferred. In excess of 98% (wt./wt.), can not be obtained a satisfactory properties adhesion to human skin, and therefore it is not preferred.

The properties of the transdermal permeability of fentanyl or its salts is greatly improved by the introduction of sodium acetate in the adhesive layer applied on the tape preparation of the present invention for percutaneous introduction, containing fentanyl. Sodium acetate is preferably contained in an amount of from 0.01 to 15% (wt./wt.), more preferably from 0.01 to 10% (wt./wt.), most preferably from 0.01 to 5% (wt./wt.) in relation to the total amount of the adhesive layer. If the amount of sodium acetate is less than 0.01% (wt. /Mac. ), there can be obtained a significant effect of improving the transdermal permeability. If the number m

If the salt of fentanyl is ventanilla, the maximum effects on the physical properties and the properties of the transdermal permeability can be obtained when the mass ratio of ventanilla and sodium acetate in the product is(1 - 5): (0,5 - 2,5), preferably(3 - 5): (1,5 - 2,5), more preferably 2:1. If the amount of sodium acetate in the product is less than a specified relationship property transdermal permeability of the drug sharply reduced, and if the amount of sodium acetate in the product exceeds the specified ratio, the drug is mixed, and physical properties such as the property of adhesion will be poor, and therefore it is not preferred.

In addition, the layer of the adhesive preparation of the present invention may be added a substance to increase the stickiness in order to give the drug adhesive properties, since the adhesive properties of the pressure-sensitive adhesive are weak. As preferred examples for improving adhesiveness may be provided polyterpene resin, resin-based oil, rosin, rosin esters, soluble in oil phenolic resins and the like. The quality is learon P-105, Foral 105, Arcon P-100, KE-311, KE-100, Super Ester S-100, Tamanol 521, YS Resin 75, KR-610, and the like.

Substances to improve the adhesiveness is preferably contained in the range from 0, 1 to 70% (wt./wt.), more preferably from 5 to 50% (wt./wt.) and most preferably from 10 to 35% (wt./wt.) in relation to the total number of layer of the adhesive preparation of the present invention.

In addition, as a softening agent in the adhesive layer to improve the processing properties and to control the adhesive applied to the tape preparation of the present invention for percutaneous injection can be present in the oil. As such oils, for example, are the preferred liquid paraffin, squalane, olive oil, oil of Tsubaki, peach oil and peanut oil, and liquid paraffin is preferable.

The oil is preferably contained in the amount inside the range from 1 to 70% (wt./wt.), more preferably from 10 to 60% (wt./wt.) and most preferably from 20 to 50% (wt./wt.) in relation to the total number of layer of the adhesive preparation of the present invention.

In addition, the layer of the adhesive preparation of the present invention depending on the need the deposits can be used any substances, have the effect of increasing uptake in the skin. For example, as examples can be mentioned fatty acid having from 6 to 20 carbon atoms in the chain, aliphatic alcohols, simple or complex esters of fatty acids, aromatic organic acids, aromatic alcohols, simple or complex esters of aromatic organic acids. In addition, as examples can be mentioned esters of lactic acid, esters of acetic acid, monoterpenoid compounds, sesquiterpene compounds, Azone or its derivatives, glycerol esters of fatty acids, sorbitane fatty esters, Polysorbate, polietilenglikolya esters of fatty acids, hardened by polyoxyethylene castor oil, sucrose esters of fatty acids and the like. As specific examples of absorption enhancers are preferred Caprylic acid, capric acid, Caproic acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, lauric alcohol, ministerului alcohol, alerby alcohol, cetyl alcohol, meilleur, isopropylmyristate, myristoleic is CNA acid, methylcinnamic, cresol, catallactic, ethyl acetate, propyl, geraniol, thymol, eugenol, terpineol, 1-menthol, borneol, d-limonene, isoeugenol, isoborneol, nerol, dl-camphor, glycerylmonostearate, glycerylmonostearate, sorbitanoleat, saharozameniteley, Polysorbate 20, polietilenglikolmonostearat, polietilenglikolmonostearat HCO-60 (utverjdenie castor oil), 1-[2-(decillia)ethyl]azacyclopenta-2-he (hereinafter referred to in abbreviated form as "pyramidion"), and most preferred are lauric alcohol, ministerului alcohol, etilenglikolevye and Protodeacon.

These amps transdermal absorption is preferably contained in the amount inside the range from 0.01 to 20% (wt./wt.), more preferably the amount entered in the range from 0.1 to 10% (wt./wt.), most preferably in the amount inside the range from 0.5 to 5% (wt./wt.) in relation to the total amount of the adhesive layer of the tape of the present invention. If the number of amplifier transdermal absorption exceeds 20% (wt./wt.), apparent skin irritation, such as erythema and edema, and if the amount is less than 0.01% (wt./wt.), cannot be achieved the effect of receiving stress the hinnon on the tape preparation of the present invention depending on the need to adsorb water components, such as secreted by the skin sweat may contain a hydrophilic polymer. As the hydrophilic polymer, for example, may be preferred light silicic anhydride, cellulose derivatives (carboxymethylcellulose (CMC), sodium carboxymethylcellulose (N), methylcellulose (MC), hypromellose (HPMC), gidroksipropilzelluloza (GOC), hydroxyethylcellulose (SCE)), derivatives of starch (Pullulan), polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), vinyl acetate (VA), carboxyvinyl polymer (KVP), ethylvinylacetate (EVA), Eudragit, gelatin, polyacrylic acid, sodium polyacrylate, a copolymer of polyisobutylene and maleic anhydride, alginic acid, sodium alginate, carrageenan, Arabian gum, tragakant, gum karaya and polivinilatsetat and most preferred are light silicic anhydride, derivatives of cellulose (N, GPMC, MPC, MC) and Eudragit.

The hydrophilic polymer is preferably contained in the amount inside the range from 0.1 to 20% (wt./wt.), more preferably from 0.5 to 10% (wt./wt.) in relation to the total amount of the adhesive layer on the tape preparation for percutaneous introduction of the present invention.

In addition, aservant, antioxidant and other components.

As an agent for cross-linking are preferred heat shrinkable resin, such as the amino resin, phenolic resin, epoxy resin, alkyd resin, unsaturated polyester, isocyanate compound, block isocyanate compound, an organic agent for cross-linking, inorganic agent for cross-linking, such as metal or compound of the metal. As preservatives are preferred ethyl p-oxybenzoic, propyl p-oxybenzoic, butyl p-oxybenzoic and the like. As antioxidants are preferred tocopherol and its ether derivatives, ascorbic acid, an ester of stearic acid, nordihydroguaiaretic acid, dibutylaminoethanol (OSH), butylhydroxyanisole (BHA) and the like.

An adhesive layer deposited on the tape preparation of the present invention preferably contains a non-aqueous base, and objectives of the present invention can be effectively achieved by transformation bases in non-aqueous.

An adhesive layer comprising the above components may be obtained by any conventional methods. For example, to the be obtained by adding other components, other than polymers, solution polymers in an organic solvent, and then mixing and applying the mixture on the film substrate and drying. When the polymers in the drug composition can be applied using the method of using a hot melt, the drug of the present invention can be obtained by dissolving the polymer component at a high temperature, then add the other components, mixing and applying to the film substrate.

Printed on the tape preparation of the present invention may contain any layers, provided that he has the adhesive layer having the above components, and other layers and components of the layers are not limited. For example, put on a tape preparation for percutaneous introduction may include along with the adhesive layer of the substrate carrying the adhesive layer, a removable lining layer provided on the adhesive layer, and the like.

The substrate layer may contain, for example, the fabric material of non-woven fibers, polyurethane, polyvinyl acetate, grades, polyethylene, polyethylene terephthalate, polybutylene terephthalate, paper, aluminum foil and the like, and a composite material of them.

what edstam from disturbing pain for patients who can't take oral anesthetic analgesic as fentanyl or its salt is absorbed continuously through the skin using applied on the tape preparation of the present invention. In addition, applied to the tape preparation of the present invention may be non-invasive and therefore can reduce the disturbance to patients compared with the method of continuous intradermal injection, which is an invasive method. In addition, the dose can be easily controlled, for example, by cutting the drug depending on the conditions, ages, body weights, sex differences, and other factors of the patients.

Examples

The present invention will be explained in more detail using the following examples. However, the present invention is not limited to the examples, and the present invention extends to all such modifications and variations which will be obvious to a person skilled in this field without deviating from the scope of the present invention. In the examples, all components are given in % (wt./wt.), if not marked otherwise.

Example 1

Sodium acetate and 2.5

The acrylic polymer (D-300) AND 88.5

Colorvision - 1,0

unicitral was added to the ethanol and stirred for dissolution at room temperature. Then a solution of acrylic polymer in ethyl acetate and colorvision was added to the mixture and stirred. Then the mixture was applied to a film of polyethylene terephthalate (PET) (30 μm), and thermally cross linked at 90oC for 15 minutes, and thus, the adhesive layer 50 μm. Using an adhesive layer deposited on the tape preparation for percutaneous introduction of the present invention were obtained using the usual method.

Example 2

Sodium acetate and 1.5

Pyramidion - 3,0

Liquid paraffin - 38,0

Agent for improving adhesiveness based polyterpenes resin is 29.5

Polyisobutylene - 7,5

Styrene-isoprene-styrene block copolymer is 16.5

Antioxidant (wave geotechnologies) - 0,5

Silicate of aluminum and 0.5

Ventanilla - 3,0

The total number of - 100

After all components except sodium acetate, Protodeacon and ventanilla was dissolved and stirred at 180oWith the remaining components were added and dispersively to have a homogeneous mixture. Then the mixture was applied to a film of PET (30 μm) to obtain an adhesive layer 100 μm. Using an adhesive layer deposited on the tape preparation for percutaneous introduction truly the image

Liquid paraffin - 39,5

Agent for improving adhesiveness based polyterpenes resin - 21,7

Polyisobutylene - 6,8

Styrene-isoprene-styrene block-copolymer - 20,4

Antioxidant (wave geotechnologies) - 0,5

Aluminum silicate - 0,6

Ventanilla - 5,0

The total number of - 100

After all components except sodium acetate, Protodeacon and ventanilla was dissolved and stirred at 180oWith the remaining components were added and dispersively to have a homogeneous mixture. Then the mixture was applied to a film of PET (30 μm) to obtain an adhesive layer 100 μm. Using an adhesive layer deposited on the tape preparation for percutaneous introduction of the present invention are obtained by the usual method.

Example 4

Sodium acetate and 2.5

Liquid paraffin is 12.5

Agent for improving adhesiveness based soluble in oil phenolic resin - 39,5

Polyisobutylene - 7,5

Styrene-isoprene-styrene block copolymer is 30.5

Antioxidant (wave geotechnologies) - 0,5

Lauric alcohol - 2,0

Ventanilla - 5,0

The total number of - 100

After all components except lauric alcohol, sodium acetate and ventanilla was dissolved and p is camping. Then the mixture was applied to a film of PET (30 μm) to obtain an adhesive layer 100 μm. Using an adhesive layer deposited on the tape preparation for percutaneous introduction of the present invention was then obtained using a conventional method.

Example 5

Sodium acetate and 1.5

Crotamiton - 3,0

Liquid paraffin is 38.5

Agent for improving adhesiveness based polyterpenes resin is 29.5

Polyisobutylene - 7,5

Styrene-isoprene-styrene block copolymer is 16.5

Antioxidant (wave geotechnologies) - 0,5

Ventanilla - 5,0

The total number of - 100

After stirring for dissolution of sodium acetate, crotamiton, ventanilla and liquid paraffin at 80oThe mixture was mixed with cyclohexanebis solution, in which pre-dissolved styrene-isoprene-styrene block copolymer, polyisobutylene, a substance that increases the stickiness based on polyterpenes resin. Then the mixture was applied to a film of PET (30 μm) and dried at 85oC for 30 minutes to obtain an adhesive layer 50 μm. Using an adhesive layer deposited on the tape preparation for percutaneous introduction of the present invention were obtained using the usual method.

Example 6

Sodium acetate and 2.5

Styrene-isoprene-styrene block-copolymer - 24,0

Antioxidant (wave geotechnologies) - 0,5

Silicate of aluminum and 0.5

Fentanyl - 5,0

The total number of - 100

After all components except sodium acetate and fentanyl was dissolved and stirred at 180oWith the remaining components were added and dispersively to have a homogeneous mixture. Then the mixture was applied to a film of PET (30 μm) to obtain an adhesive layer 100 μm. Using an adhesive layer deposited on the tape preparation for percutaneous introduction of the present invention were obtained using the usual method.

Example 7

Sodium acetate and 0.5

Pyramidion - 3,0

Liquid paraffin - 29,0

Agent for improving adhesiveness based polyterpenes resin was 42.1

Polyisobutylene - 7,0

Styrene-isoprene-styrene block-copolymer - 16,4

Antioxidant (wave geotechnologies) - 0,5

Silicate of aluminum and 0.5

Ventanilla - 1,0

The total number of - 100

Using the above components (ventanilla: sodium acetate = 2: 1), applied to a tape preparation for percutaneous introduction of the present invention were obtained using the method described in example 2.

Example 8

Sodium acetate and 1.5

the Ola - 41,5

Polyisobutylene - 6,9

Styrene-isoprene-styrene block copolymer and 16.2

Antioxidant (wave geotechnologies) - 0,5

Silicate of aluminum and 0.5

Ventanilla - 1,0

The total number of - 100

Using the above components (ventanilla: sodium acetate = 2: 3), applied to a tape preparation for percutaneous introduction of the present invention were obtained using the method described in example 2.

Example 9

Sodium acetate and 2.5

Pyramidion - 3,0

Liquid paraffin - 28,7

Agent for improving adhesiveness based polyterpenes resin - 41,0

Polyisobutylene - 6,8

Styrene-isoprene-styrene block copolymer is 16.0

Antioxidant (wave geotechnologies) - 0,5

Silicate of aluminum and 0.5

Ventanilla - 1,0

The total number of - 100

Using the above components (ventanilla: sodium acetate = 2: 5), applied to a tape preparation for percutaneous introduction of the present invention were obtained using the method described in example 2.

Example 10

Sodium acetate and 0.5

Pyramidion - 3,0

Liquid paraffin - 28,7

Agent for improving adhesiveness based polyterpenes resin - 41,0

Polyisobutylene - 6,8

Styrene-isoprene-styrene block copolymer 0

Using the above components (ventanilla: sodium acetate = 6: 1), applied to a tape preparation for percutaneous introduction of the present invention were obtained using the method described in example 2.

Example 11

Sodium acetate and 1.5

Pyramidion - 3,0

Liquid paraffin is 28.5

Agent for improving adhesiveness based polyterpenes resin - 40,5

Polyisobutylene - 6,8

Styrene-isoprene-styrene block copolymer is 15.7

Antioxidant (wave geotechnologies) - 0,5

Silicate of aluminum and 0.5

Ventanilla - 3,0

The total number of - 100

Using the above components (ventanilla: sodium acetate = 2: 1), applied to a tape preparation for percutaneous introduction of the present invention were obtained using the method described in example 2.

Example 12

Sodium acetate and 2.5

Pyramidion - 3,0

Liquid paraffin - 28,2

Agent for improving adhesiveness based polyterpenes resin - 40,0

Polyisobutylene - 6,7

Styrene-isoprene-styrene block copolymer is 15.6

Antioxidant (wave geotechnologies) - 0,5

Silicate of aluminum and 0.5

Ventanilla - 3,0

The total number of - 100

Using the above components (ventanilla: sodium acetate = 6: 5A, described in example 2.

Example 13

Sodium acetate and 0.5

Pyramidion - 3,0

Liquid paraffin - 28,2

Agent for improving adhesiveness based polyterpenes resin - 40,0

Polyisobutylene - 6,7

Styrene-isoprene-styrene block copolymer is 15.6

Antioxidant (wave geotechnologies) - 0,5

Silicate of aluminum and 0.5

Ventanilla - 5,0

The total number of - 100

Using the above components (ventanilla: sodium acetate = 10: 1), applied to a tape preparation for percutaneous introduction of the present invention were obtained using the method described in example 2.

Example 14

Sodium acetate and 1.5

Pyramidion - 3,0

Liquid paraffin - 28,2

Agent for improving adhesiveness based polyterpenes resin - 39,5

Polyisobutylene is 6.5

Styrene-isoprene-styrene block copolymer and 15.3

Antioxidant (wave geotechnologies) - 0,5

Silicate of aluminum and 0.5

Ventanilla - 5,0

The total number of - 100

Using the above components (ventanilla: sodium acetate = 10: 3), applied to a tape preparation for percutaneous introduction of the present invention were obtained using the method described in example 2.

Example 15

Sodium acetate and 2.5

P the crystals - 38,9

Polyisobutylene is 6.5

Styrene-isoprene-styrene block copolymer and 15.1

Antioxidant (wave geotechnologies) - 0,5

Silicate of aluminum and 0.5

Ventanilla - 5,0

The total number of - 100

Using the above components (ventanilla: sodium acetate = 2: 1), applied to a tape preparation for percutaneous introduction of the present invention were obtained using the method described in example 2.

Comparative examples 1-5

Comparative examples 1-5, each correspond to examples 1-5, respectively. In each comparative example is marked on the tape preparation for percutaneous introduction were obtained using the method described in the corresponding example, with the condition that the sodium acetate used in examples 1-5, were not introduced into the composition in comparative examples.

Research example 1

(Investigation of transdermal permeability in vitro)

For each of the preparations for percutaneous introduction, obtained in examples 1-5, 7-15, and in comparative examples 1-5 were evaluated through studies on transdermal permeability in vitro, using the skin of hairless mice.

After selection of the area of skin in the back hairless mice (aged 6 to 9 weeks) erculiani around the outer periphery of the receptor layer, that the dermal side of the receptor layer. Each is marked on the tape preparations for percutaneous introduction, obtained in examples 1-5, 7-15 and comparative examples 1 to 5 was applied to the side of the stratum corneum and the preparation of the samples was made every hour for 24 hours at a speed of 5 ml/h, feeding saline solution for the receptor layer. Then every hour carefully measured flow rate and the determined concentration of the medicine using the method of high performance liquid chromatography. The permeation rate for each hour was calculated in accordance with the following formula, and the determined speed of penetration in a stationary state. The results are presented in table 1.

Speed transdermal penetration (µg/cm2/h) = [Concentration of drug (ág/ml)flow Rate (ml/h)/surface Area of drug application (cm2)]

As is clear from table 1, applied to the tape preparations for percutaneous introduction, obtained in examples 1-5, 7-15, have a higher rate of transdermal penetration compared to printed on the tape preparations for percutaneous introduction obtained in comparative examples 1-5.

which ratio ventanilla and sodium acetate in drugs is (3 - 5):(1.5 to 2.5), have very high speed transdermal penetration.

Among them, proved to be printed on the tape preparations for percutaneous introduction of examples 1-5, 11 and 15, in which the relationship of ventanilla and sodium acetate in the preparations are 2:1, have an exceptionally high rate of transdermal penetration.

Research example 2

(Primary research irritants skin rabbit)

With respect to each of the marked on the tape preparations for percutaneous introduction, obtained in examples 1-5 were evaluated through primary research stimulus, in vivo, using the skin of the rabbit.

Each is marked on the tape preparations for percutaneous introduction, obtained in examples 1 to 5 were applied to the skin of the rabbit. Decisions were taken in accordance with the criterion of stimulation of the skin, are presented in table 2, as well as with respect to erythema and Eden after 24 and 48 hours after application. The sum of the two scores was accounted for as a point of irritation every time. In addition, the average scores of irritation at each time point was considered as the value of PII. In addition, control groups using an adhesive tape according to P results presented in table 3, it is clear that printed on the tape preparations for percutaneous introduction of examples 1-5, have a very low irritating effect on the skin compared to a traditional product (DURAGESIC) and have the same irritating effect on the skin like an adhesive tape Pharmocopoeia Japonica, which has a low irritating properties.

Industrial application

The present invention fentanyl or its salt can be prepared in the form of a drug for percutaneous introduction, which is laborataries and superior in its properties transdermal permeability, which cannot be achieved by previously known means.

Thus, fentanyl or its salt can be delivered into the body, and pharmacological actions of fentanyl or its salt can be effectively and continuously used by the application printed on the tape preparation of the present invention for percutaneous administration of the drug containing fentanyl.

Thus, the printing on the tape preparation of the present invention for percutaneous introduction, containing fentanyl, is a very useful tool against disturbing pain to the patient the drug for percutaneous introduction containing ventanilla in the amount of from 0.05 to 20 wt. % pressure-sensitive adhesive in an amount of from 0.1 to 98 wt. %, sodium acetate in an amount of from 0.01 to 15 wt. %.

2. Put on a tape preparation for percutaneous introduction, containing ventanilla, p. 1, where the mass ratio of ventanilla and sodium acetate in the product is (1 to 5): (0.5 to 2.5).

3. Put on a tape preparation for percutaneous introduction, containing ventanilla, p. 2, where the mass ratio of ventanilla and sodium acetate in the product is (3 to 5): (1.5-2.5).

4. Put on a tape preparation for percutaneous introduction, containing ventanilla, p. 2, where the mass ratio of ventanilla and sodium acetate in the product is 2: 1.

5. Put on a tape preparation for percutaneous introduction, containing ventanilla, according to any one of paragraphs. 1-4, which additionally contains a substance that increases the stickiness.

6. Put on a tape preparation for percutaneous introduction, containing ventanilla, according to any one of paragraphs. 1-5, which includes an additional amplifier transdermal absorption.

7. Put on a tape preparation for percutaneous introduction, with which the polyisobutylene and styrene-isoprene-styrene block copolymer.

 

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The invention relates to pharmaceutical industry
The invention relates to pharmaceutical industry and medical technology and can be used in the manufacture of adhesive tapes
The invention relates to pharmaceutical industry and relates to medical devices, in particular adhesive tapes used, for example, as a medical adhesive tape

The invention relates to devices for percutaneous application of medicinal substances, more specifically to a composition for percutaneous drug substances, which uses a mixture of polymers to influence the solubility of the drug substance and the speed of its receipt of the product, namely the composition of immiscible polymers among themselves, including soluble polyvinylpyrrolidone (PVP), which can be increased up to the desired maximum concentration of drug substance in the mixture, thus allowing to significantly reduce the size of devices required to achieve therapeutic levels while maintaining the desired properties on drug release and adhesion

The invention relates to decomposing intended for packaging and disposable sanitary products paintings

The invention relates to pharmaceutical industry and can be used in medical institutions and in the home as a remedy to stop bleeding during surgical interventions, as well as in industrial and domestic injuries
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