Device in the form of a patch for topical application protivougrevoe composition and method of its manufacture
(57) Abstract:The invention provides a device in the form of a patch for topical application protivougrevoe, comprising a synthetic pressure-sensitive adhesive material used as a carrier or associated with the carrier, and the specified media evenly distributed protivougrevoe composition comprising an effective amount of at least two active ingredients from at least two different groups of active ingredients from the group including keratolytic agents, agents against irritation, antiseptic agents, antimicrobial agents, hormones, antagonists hormones, hormone antagonists and other agents suitable for the treatment of acne. The patch provides maximum efficiency with minimized adverse effects due to the limited penetration of the composition into the systemic circulation. 2 C. and 24 C.p. f-crystals, 6 tab., 4 Il. Device for delivery of a drug in the form of strips and the manufacturing method are intended for the local treatment of acne and acne diseases.Acne affect 90% of adolescents, and also men and women on the third and the fourth ten years of the Il J. New Approaches to Acne Treatment, ed. Martin Dunitz, London, 1989.Common acne is a chronic disorder of the hair follicles (organ system), characterized by comedones (black blackheads), papules, pustules, cysts, nodules, and often scars that appear on the most visible areas of the skin, especially on the face, chest, back and sometimes on the neck and upper arms.System of hair follicles is mainly under the control of endogenous hormones (mainly androgens), which are present in unusually high concentrations in the blood during adolescence and puberty, which leads to the excessive production of sebum. The condition may be aggravated by simultaneous increase of keratinization of the corneal layer of the skin (stratum corneum). With the proliferation of the corneal cells can form impenetrable tube or black eel, along with increased production of sebum is an ideal environment for the proliferation of resident strains of the skin, such as gram-positive anaerobic bacteria, Propionibacterium acnes.Ultimately, sealed bags break and give the opportunity to release their contents, which causes local swelling and inflammation. From what.Acne is a multistage disease, which in the most severe cases leads to hospitalization of the patient and a strong discomfort with the remaining long scars on the skin. Requires such improved method for the treatment of acne, which would effectively protected from disease development to the most severe forms and which could be used by the majority of the victims without any side effects.Currently, there are many available techniques for the treatment of acne, but each method has an unpleasant restrictions that it would be desirable to overcome. For the most part, acne treatment is performed compositions for topical application in the form of creams, gels, emulsions or lotions that contain the selected agents. These agents include hormones or agonists or antagonists hormones (EP A1 0563813 and US 5439923), antimicrobial agents (US 4446145, GB 2088717, GB 2090135, GB 1054124, US 5409917), salicylic acid (US 4514385, US 4355028, EP A1 0052705, FR-A 2581542 and FR-A 2607498). The problems associated with local treatment of acne with creams, gels, emulsions and lotions that include a lack of accuracy of the application and the associated lack of precise control of the dose at the target site. Applying creams, gels, emulsions and lotions leads erga normal healthy skin exposure protivopravnych compositions. For example, salicylic acid is an irritant towards normal skin with prolonged exposure and especially in high concentrations.Oral administration protivopravnych agents used currently for severe cases of acne. They are described in the overview Sykes N. I. and Webster G. F. Acne, A Review of Optimum Treatment, Drugs 48, 59-70 (1994). Described numerous side effects, which occur when oral administration protivopravnych agents. For example, isotretinoin, which is a derivative of vitamin a, is associated with the risk of teratogenicity and can be dangerous for women of childbearing age. Oral administration of antibiotics suitable for the treatment of acne, can cause side effects, including abdominal cramps, black tongue, cough, diarrhea, fatigue, irritation of the mouth and other unwanted symptoms.Salicylic acid was used for the treatment of acne in the form of adhesive hydrophilic gel dressings (US 5258421)and in combination with Pantothenic acid or a derivative of Pantothenic acid in the cleansing swabs (PCT WO 93/21899).Furthermore, in U.S. patent 5409917 described plaster containing cephalosporin for the treatment of acne, and uses a method of making nicotine is timization protivougrevoe content and placement of the patch on the numerous open areas of the skin, such as the face, the patch was not accepted as a method of delivering protivougrevoe composition.Thus, there remains a need for methods and devices for treating patients with acne that would have minimal side effects would be of maximum effectiveness and could be simple and easy to use.The present invention is directed to satisfaction of the requirements for the treatment of acne and acne diseases such a way as to minimize side effects and maximize the effectiveness of the treatment. The present invention is directed to the local device for drug delivery, having the form of a patch with a size and thickness suitable for prolonged delivery protivopravnych agents to the selected area, characterized as acne. The patch contains at least two suitable for the treatment of acne agent, in the form of a mixture of components.More precisely, the invention provides a device in the form of a patch for topical application protivougrevoe, comprising a synthetic pressure-sensitive adhesive material used as a carrier or associated with the carrier, and is then the specified protivougrevoe composition includes an effective amount of at least two active ingredients from at least two different groups of active components, and that these at least two different groups selected from the group including keratolytic agents, agents against irritation, antiseptic agents, antimicrobial agents, hormones, antagonists hormones, hormone antagonists and other agents suitable for the treatment of acne.In another embodiment of the patch for the treatment of acne and acne skin diseases includes topically-acceptable carrier for topical application, such as acrylic fiber, paper, silicones, cellulose and so on; humidifiers; antioxidants; stabilizers, where the patch is capable of delivering an effective amount of protivopravnych agents to the skin with acne, subject to treatment (i.e. black blackheads, pustules, papules).Fig. 1 is a side view of three-layer patch for delivery of agents for the treatment of acne disease.Fig. 2A is a side view four-patch for delivery of agents for the treatment of acne disease.Fig.2b is a top view of the same patch as in Fig.2A.Fig.Onstreet flow of salicylic acid through the stratum corneum person for the two patches in accordance with the invention and gel.Fig. 4b is an enlargement of Fig.4A for the two patches in accordance with the invention.The term "topically acceptable carrier", as used in this description, refers to substances that have essentially no toxicity towards human tissues.The term "local application", as used in this description, refers to the direct application of the epidermis.The term "stable", as used in this description, is defined as having a shelf life in excess of few weeks.The term "effective amount", as used here, refers to the amount sufficient to provide protivougrevoe effect.The present invention provides a method and device for the treatment of patients suffering from acne, where the device is optimized to minimize side effects and maximize efficiency and is simple and easy to use. Local treatment of acne and acne diseases disclosed here uses plaster to achieve local protivougrevoe effect that occurs due to suppression of proliferation of corneal cells and microbes involved in the pathogenesis of acne, and reduce Swee agents into the stratum corneum (the outer layer of the epidermis, open to the external environment) and that they subsequently penetrated into the cuticle (skin) where prevue disease, at the same time having a very limited penetration into the systematic circulation. This is demonstrated by studies of stream penetration through the skin (example 12 below), which shows that the amount of salicylic acid, which passes through the stratum corneum, is very small in comparison with the same quantity of gel composition containing 2% salicylic acid.In order to ensure that the patch is simple and easy to use, have been identified suitable size and thickness of the individual patch. The patch proposed by the present invention may be manufactured in various sizes, depending on the treated surface (i.e. black blackheads, papules, pustules). The size of the patch is considered small if it is in the range from 0.5 to 2 cm2and big is the patch to 40 cm2. Usually the size of the patch is from 0.5 to 1.3 cm2and preferably 0.8 cm2.The patch of the invention is stable and is able to safely and effectively deliver protivougrevoe composition. For example, stored plaster the tion, which can happen during storage, but before the expiry of the specified retention period, are assumed to be harmless.An example of a patch that is appropriate for the treatment of acne, is shown in Fig.1. In this embodiment, the patch may include a layer of the support film 1, a separate synthetic pressure-sensitive adhesive layer 2 and releasing the lining 3, and protivougrevoe the drug contained in the synthetic pressure-sensitive adhesive layer.In another embodiment, more than one matrix may be placed between releasing the lining and the support layer (see Fig.2A and 2b). In accordance with Fig. 2A and 2b and example 4 describes the plaster containing layer support film 1, a synthetic pressure-sensitive adhesive layer 4, a paper matrix 5 and releasing the lining 3. The patch can have a paper matrix with a diameter of 5/8 inch (approximately 1,6 cm) and/or peripheral adhesive layer with a diameter of 7/8 inch (about 2.2 cm).Layer supporting film 1 may be made of plastic or fabric, woven or non-woven material can be porous or impermeable. Porous materials are sometimes used in connection with the fact that some skin resideat be made of any suitable material, such as paper, cellophane, plastic film, such as polyethylene, polyester, polyurethane, polyvinyl chloride and polyamide; fabric or metal foil which is impermeable and does not react with protivougrevoe composition, dispersed in the adhesive polymer matrix. The supporting film may be a composite or transparent, or opaque, or flesh-colored, or alteromonas, or their combination, with a thickness in the range from 1 to 5 mils (from about 25 to 130 microns), typically from 2 to 3.5 mils (about 50 to 90 microns) and preferably 3 mils (about 76 microns) and can be made of SethgapTM9720 (3M), Saranex(Dow Chemicals), Multilam polyester film flesh-colored 1009 (SM) or any other material of which it is known that he has the required properties.The patch has an adhesive polymer matrix 2, which is immediately adjacent to the support layer and made of a synthetic adhesive materials such as acrylic fiber, rubber, silicone, cellulose, paper or other suitable material that can have properties that are pressure sensitive and adhere to the skin directly or through a peripheral adhesive material. Sticky polim is OK. Sticky polymer matrix may consist of more than one layer, but preferably consists of a single layer. The thickness of the adhesive polymer matrix is in the range of 0.5 to 30 mils (about 13-760 μm), usually 0.5-6 mils (13-152 μm), preferably from 0.5 to 2.5 mils (approximately 13-64 μm) and more preferably of 2.5 mils (approximately 64 μm). In the sticky polymer matrix contains a mixture protivopravnych agents, including any component of keratolytics, agents against irritation, antiseptics, antimicrobial agents, hormones, agonists hormones, hormone antagonists and other agents suitable for the treatment of acne, preferably together with solubilization.Sticky polymer matrix can be made of inert materials that are biologically - and topically-acceptable and compatible with distributed active substance.Preferably, topically-acceptable polymers with adhesive properties can be polymers with acrylic base, such as a series of GELVAsold by Monsanto, and a series of DURO-TAKsold by National Starch; polymers with elastomeric base, such as a series of DURO-TAKsold by National Starch; polymers with silicone which can also be made from paper materials, preferably Whatman filter paper that sticks to the skin through a peripheral adhesive layer. The thickness of this adhesive polymer matrix usually is 7 mils (about 178 microns).Releasing the lining 3 is placed near the surface of the adhesive polymer matrix on the surface opposite to the support layer. Releasing the lining can be made from materials impervious to all substances dissolved in the given matrix, which can be easily removed or released before use. Releasing the lining can be made from materials such as polyvinyl chloride, polyester, grades, polystyrene, polyethylene, paper, etc. covered or not sticky material, but, preferably, with easy release silicone composition.Preferably, releasing the lining is made from natural high-strength polystyrene film grade code: 10106 or 15462) sold REXAM Release, or silikonizirovannoj polyester film sold by REXAM Release. The thickness of the releasing lining may be in the range from 3 to 10 mils (about 76 to 250 μm) or, preferably, soo 2 cm2and a thickness in the range from 7 to 24 mils (about 178 to about 610 μm).In a variant embodiment of the invention has been selected combination protivopravnych agents for the treatment of acne. These agents include keratolytic agent such as salicylic acid, in combination with the agent against irritation, antiseptic, antimicrobial agent and/or other struggling with acne compounds, such as urea, allantoin, connection hydroxyquinoline solution for delivery via a patch directly on the area to be processed. The presence of the agent against counteracts irritation local irritation associated with the application of keratolytic on the skin. Antiseptic limits the growth of organisms that cause acne. Moreover, the antimicrobial agent can increase the total protivougrevoe properties of composition at medium and severe stages of the disease. The use of a solubilizer ensures that the active agents in the patch are in a form suitable for diffusion from the patch to the skin.Antimicrobial agents commonly used for local application can be penicillins, cephalosporins, other beta-lactam compounds, aminoglycosides, tetracyclines, erythromycin the local application on the skin with acne, are erythromycin, tetracycline, clindamycin, cephalosporins.Antiseptics commonly used for local application on the skin with acne, are triclosan (Irgasan DP 300), phenoxyisopropyl, resorcinol, chlorhexidine, povidone and iodine.Keratolytic agents commonly used for local application on the skin with acne breakouts are salicylic acid, benzoyl peroxide, sulfur, retinoic acid, and any of a number of fruit acids and alpha hydroxy acids.Agents against irritation, commonly used for local application on the skin with acne are-bisabolol (-bisabolol), farnesol, chamomile extract and glycerrhetinic acid.Soljubilizatory used in protivopravnych the compositions of the present invention include any component of glycerin, propylene glycol, polyalcohol, sorbitol and derivatives of sorbitol, preferably, servicemanual.Compositions of the present invention may also include other topically-acceptable agents, such as solvents, antioxidants, moisturizers, etc.In accordance with the preferred embodiment, the invention provides a device which includes, in relation to the total weight of occhialino from 0.1 to 2.0 wt.% and more preferably 0.6 wt.%;
- one or more agents against irritation, each in an amount of from 0.01 to 5.0 wt.%, preferably from 0.01 to 3.0 wt.% and more preferably 1.0 wt.%;
one or more antiseptic agents, each in an amount of from 0.05 to 2.0 wt. %, preferably from 0.1 to 1.0 wt.% and more preferably 0.3 wt.%;
one or more of solubilization, each in an amount of from 0.1 to 5 wt.%, preferably from 1 to 3.0 wt.% and more preferably 2 wt.%.Further, the invention is illustrated using examples. The examples should not be construed as limiting the scope of the claims of the invention, which is defined by the attached claims. Examples are using salicylic acid as a keratolytic agent in an amount of from 0.1 to 2 wt.% together with the agent against irritation, such as bisabolol, in the amount of from 0.01 to 3 wt.%, antiseptic agent, such as triclosan (Irgasan DP 300) in an amount of from 0.1 to 1 wt.% and solubilizer, such as servicemanual in the amount of from 0.1 to 5 wt.%, all of which are distributed in the various sticky polymer matrices. Controlled delivery is achieved within at least 4 hours, preferably for at least 24 hours or more predpoll for drug delivery in the form of a patch.The adhesive composition of the polymer matrix used in the manufacture of the patch for the topical treatment of acne and acne skin diseases, contains salicylic acid as a keratolytic agent, as shown in table 1.A method of manufacturing a tape having the above composition, the following: salicylic acid (0.6 g), Irgasan DP 300 (0.3 g), -bisabolol (1.0 g), servicemanual (2.0 g) are added to 293,88 g of the solution multipolymer resin Gelva737 (total solids of about 32.7%) and the mixture was stirred at ambient temperature until, until you dissolve all the ingredients. The mixture defend for several minutes to remove all air bubbles.From the sticky mixture forms a system patch is as follows.With a suitable device for applying (square steel Multi tool Clearance Applicator sold by BYK Gardner) with slit for casting in size from 5 to 10 mils (about 130-250 μm) put a layer of adhesive mixture on silikonizirovannaya polyester film and dried in a drying oven at 76-78oC for 15-18 minutes. Then layer on a sticky film breathable polyurethane film (Bertek Med (REXAM Release). The final thickness of the dried polymer matrix is, thus, from 3 to 5 mils (approximately 76-130 μm).Multilayer laminated material is then cut to obtain a bandage round shape with a nominal size of 1 cm2(the actual size of 0.8 cm2) and a thickness of from 7 to 18 mils (approximately 178-457 μm).Example 2
The manufacturer of the adhesive polymer matrix.The procedure of example 1 is repeated to obtain the adhesive polymer matrix. As the sticky material in this example, use the polymer acrylic-based GELVA788. Thus obtained the patch finally has a round shape, size 1 cm2and a thickness of from 8 to 24 mils (approximately 203-610 μm).Example 3
Manufacturer of adhesive polymer matrix containing a mixture of sticky materials.The composition of the adhesive polymer matrix, described in this example, these quantities are presented in table 2.Homogeneous mixture is produced by mixing 18,95 g of acrylic solution Duro-Tak87-2287 (total solids content of approximately 50.7 per cent) and 238,92 g of acrylic solution Duro-Tak87-2353 (the total content of sabola (1.0 g), Irgasan DP 300 (0.3 g), servicemanual (2.0 g) and the mixture was stirred at ambient temperature until, until you dissolve all the ingredients. The mixture is then aged for several minutes to remove all air bubbles.From the sticky mixture to form a system patch is as follows.With a suitable device for applying an opening for casting size 5 mil (approximately 130 μm) put a layer of adhesive mixture on silikonizirovannaya polyester film. The coating is left to dry in a drying oven at 80oC for 17 minutes and then laminated with an impermeable plastic film.The process ends with the cutting of the multilayer laminate adhesive round shape, size 1 cm2and a thickness of 7.5 to 20 mils (approximately 190-500 μm), which is finally placed in the pocket of the elastic layered film consisting of paper, low density polyethylene, aluminum and Surlyn.
Production of devices for drug delivery in the form of a patch containing a flat adhesive layer and the polymer matrix, which may or may not have adhesive properties.In this prophetic example is distributed in the polymeric matrix, in which the polymer may possess or not to possess adhesive properties.The method of manufacture of this patch are as follows: to 10 g of ethanol AR add salicylic acid (0.1 g), -bisabolol (0.1 g), Irgasan DP 300 (0.03 g) and servicemanual (0.2 g) and the mixture is stirred until then, until you dissolve all the ingredients.Pieces of Whatman filter paper impregnated with 3 ml of the indicated solution of ethanol and leave to drain when the ambient temperature. Soaked pieces of paper is then dried in a drying oven at 40oC for 5 minutes and finally cut into pieces of desired size and shape (i.e. circular shape with a diameter of 5/8 inch or area of 5 cm2).Silikonizirovannaya polyester film cover flat adhesive material, acrylic-based, such as Duro-Tak87-2287 or Duro-Tak87-2353. A two-layer system is dried in a drying oven at 78-80oC for 15 minutes and then layer a polyethylene film, such as SethgapTM9720. The entire system is cut into pieces of the desired size and shape (i.e. circular shape with a diameter of 7/8 inches or size 7 cm2).Polyester film is removed and posisteme put on a polystyrene film, which can be rough on the back side (see Fig.2A and 2b).Example 5
Production of devices for drug delivery in the form of strips as in example 4, containing an additional adhesive layer.The procedure of example 4 is repeated to make a patch, which opened layered material is applied to the polystyrene film coated completely or partially flat sticky material.Example 6
Stability is made of plaster.The patch proposed by the present invention remains stable for two years. Methods such as composite analysis for salicylic acid and physical tests (such as the 90odynamic test to overcome the force of adhesion of the matrix patch to a steel plate, as in "Test Methods for Pressure Sensitive Adhesive Tape, which developed The Technical Committee of the Pressure Sensitive Tape Council, 11th ed), used to determine its stability during this time.Moreover, the stability of the proposed patch has been checked under the conditions of the external environment. The result, expressed as a percentage of the amount of salicylic acid and triclosan, found in the plaster over time, shown in Fig.3.Example 8
Study of primary skin irritation
Study of primary skin irritation in accordance with the Requirements per FDA 21 CFR 58, carried out using patches containing salicylic acid, as disclosed in the preferred embodiments the embodiment, in order to determine the potential irritation or corrosive effect, which occurs when exposed to the skin of rabbit analyte.The skin of six healthy new Zealand rabbits was cut so close to the skin as possible, in the experimental area for twenty-four hours before applying the analyte.The analyzed material was applied on intact and abraded skin, and each study plot covered square gauze patch size of 1 inch, attached non-irritating tape. The skin was exposed to the effect of the analyte within 24 hours and conducted inspections of animals on the symptoms of erythema (redness), swelling and any damage or other toxic effects cereali very faint redness on some specimens debonded skin on some of the investigated areas, but no swelling. In addition, no other toxic effects were observed during the study.The index of primary irritation assessment was of 0.54, which indicates that the test substance is not considered a primary irritant to the skin, as defined in 16 CFR 1500.3 (C) (4).Example 9
Test contact delayed hypersensitivity - modified allergic reaction Buhler.Test contact hypersensitivity of the delayed type, in accordance with the requirements of the FBA per 9 CFR 2.31, was performed using patches containing salicylic acid, as disclosed in the preferred embodiments the embodiment, in order to determine the ability of the analyte to induce systematic allergic response.The experimental method consists of two stages:
1. Preliminary stage.One group of 20 Guinea pigs were exposed to the effect of the patch with a test substance and one group of 10 Guinea pigs were exposed to the effect of dinitrochlorobenzene (DNCB), a known sensitizer. The day before dosing the animals completely sheared hair so close to the skin as possible, using the electric is OK each of the 20 Guinea pigs and attached with non-irritating tape. The patches were left attached for 6 hours and then removed. The study sites were checked for redness after 24 and 48 hours after application. This procedure was repeated at the same site once a week for the next two weeks, so there were three 6-hour exposure. After the last application of plaster animals were left without treatment for about two weeks.To the positive control group of 10 Guinea pigs used the solution of 0.75% DNCB in 50% ethanol and tested them as described above.In table.3-6 shows the individual indicators for the patch with a test substance and positive control.Redness was not observed for the analyte during the three preliminary stages.During this test, the animals show from absent to syncope and syncope drain redness.2. The control stage (symptoms).After two weeks of rest for the test group and the positive control were subjected to provocative test for naturgeschichte impact areas. The test substance was applied to the test group, and DNCB - polozola application. The results are presented in the following tables.During the control phase was not observed redness in the group of the analyte or analyte on naturgeschichte its effects plots in any moment.During this test, the animals show from absent to syncope and syncope drain redness.Example 10.Test patch on a second defeat for the determination of contact sensitization and photosensitization.The purpose of this study was to determine the people-volunteers and skin contact sensitization and photosensitization from patches containing salicylic acid, as described in the preferred embodiments the embodiment of the present invention, in order to claim to be "hypoallergenic" products.Forty (40) healthy volunteers of both sexes 20-55 years were involved in the study.1. Preliminary stage.In this part of the applied test patch on a second defeat in combination with maximization analysis. On the intact skin of the upper back forty volunteers inflicted 1% solution of lauryl sodium. Then put the 48 hours and the site was inspected 30 minutes after removal of the patch. Then on the same patch was applied the new patch. New patches were applied three times per week and 48 hours after their removal was assessed. Re-apply patches using this method continued for three weeks (a total of ten applications).Additional patch tests were performed in order to determine the contact photosensitization patch. During the preliminary stage and in parallel with repeated tests of the patch area to test patches were irradiated in five cases, using solar stimulator or UVA (5 j) after removing repeated five patches (consistently). Phototoxic potential of the test patch were analyzed after 1, 6 and 24 hours after a single treatment.2. The control stage (symptoms).After a three-week period was followed by a rest period of fifteen. At the end of the rest period, the patch was tested as follows.A solution of sodium lauryl inflicted on his back first, followed by the patch with the test substance. In the control study, the patches were removed after 48 hours after application and were assessed after 24, 48 and 72 hours after application. During ccali UVA (5 j). Reading was made after 72 and 96 hours after application.Assessment for both stages was carried out by one and the same researcher in the same conditions. The calculation was based on the standard ICDRG scale. The results were negative for both stages and, thus, the monitoring patch may be regarded as "hypoallergenic" and "dermatologically examined".Example 11
The test is repeated irritation in humans.The aim of this study was to provide a quick and easy determination of the possible irritation caused by the studied patch. Due to the low sensitivity of the human skin against irritants compared to animals, research on humans is usually done by re-deposition of the studied patch.The study involved 20 volunteers, men or women (15-50 years), have not had any problems with the skin of the upper back.A patch with a test substance is initially applied on the upper back volunteer for 24 hours, attaching it non-irritating Scanpor tape, and then removed. One hour after removal of the skin area gently wiped with flannelette analyte lasted for 20 days (total 10 coating with a period of rest during the weekend).As a result, not discovered any symptoms of redness, swelling or exudate induced by the studied patch, and thus, the product can be considered as "non-irritating".Example 12
Permeability protivopravnych patches.In order to determine the local effect protivopravnych patches in accordance with the invention, determine percutaneous absorption (flux) of salicylic acid from the sticky matrix of the invention in vitro, using the human cadaver skin, in accordance with the methodology described in: Franz T. Percutaneous absorption on the relevance of the in vitro data, J. Invest. Derm. 64, 190-195, 1975.To study flow used in vitro stratum corneum of the skin of the human body. Using fresh, immediately after death, the skin samples were separated stratum corneum from the skin using the techniques described Kligman A. M. et al. Preparation of the isolated sheets of the human stratum corneum, Arch. Derm. 88, 702, 1963.A comparative study to determine the flow through the skin (expressed as the total amount of salicylic acid penetrated through the unit area to a point in time) between protivougrevoe the patch of the invention (patch 1), the same patch, but with a sticky matrix of double thickness (patch 2) and the control Glitt demonstrates a very limited penetration for protivopravnych patches both thicknesses of the adhesive matrix, compared with the penetration for the control gel composition, thereby ensuring that the local effect of the proposed protivougrevoe patch. 1. Device in the form of adhesive tape for local application protivougrevoe, comprising a synthetic pressure-sensitive adhesive material used as a carrier or associated with the carrier, and the specified media evenly distributed protivougrevoe composition, characterized in that the specified protivougrevoe composition includes an effective amount of at least one keratolytic agent and at least one agent against irritation.2. The device under item 1, characterized in that the specified protivougrevoe composition further includes an effective amount of one or more active ingredients selected from the group including antiseptic agents and antimicrobial agents.3. The device under item 1 or 2, characterized in that the specified protivougrevoe composition also includes one or more of solubilization.4. Device according to any one of paragraphs. 1-3, characterized in that it additionally comprises one or more acceptable nose is h to the total mass of the carrier and composition, one or more keratolytic agents, each in an amount of from 0.1 to 10.0 wt. %, preferably from 0.1 to 2.0 wt. % and more preferably 0.6. %; one or more agents against irritation, each in an amount of from 0.01 to 5.0 wt. %, preferably from 0.01 to 3.0 wt. % and more preferably 1.0 mass. %; one or more antiseptic agents, each in an amount of from 0.05 to 2.0 wt. %, preferably from 0.1 to 1.0 wt. % and more preferably 0.3 wt. % and one or more solubilization, each in an amount of from 0.1 to 5 wt. %, preferably from 1 to 3.0 wt. % and more preferably 2 wt. %.6. Device according to any one of paragraphs. 1-5, in which a synthetic adhesive material provided with a layer supporting film on one side and releasing lining attached on the opposite side and the opposite side is in contact with the skin surface when applied.7. The device under item 6, in which the support film is impenetrable.8. The device under item 6, in which the support film is breathable.9. Device according to any one of paragraphs. 1-8, in which the synthetic media is a few with the second polymer matrix.11. The device under item 10, in which the adhesive polymer matrix is formed from one or more adhesive polymers.12. The device under item 11, in which the adhesive tape includes a supporting film, releasing the lining and at least one layer of adhesive polymer matrix located between the support film and releasing lining, and protivougrevoe the composition is uniformly distributed, at least one of the layers with the adhesive polymer matrix.13. Device according to any one of paragraphs. 10-12, in which the adhesive polymer matrix is made of one or more polymers selected from the group consisting of polymers with acrylic base polymer with an elastomeric base polymer with a silicone-based, locally acceptable and adhesive properties.14. Device according to any one of paragraphs. 1-13, in which the keratolytic agent is selected from the group consisting of salicylic acid, benzoyl peroxide, sulfur, retinoic acid, and any of a number of fruit acids and alpha hydroxy acids.15. Device according to any one of paragraphs. 1-14, in which the agent against irritation selected from the group consisting of a-bisabolol, farnesol, glycerrhetinic acid and the extract consisting of triclosan, phenoxyisopropyl, resorcinol, chlorhexidine, povidone and iodine.17. Device according to any one of paragraphs. 3-16, in which the solubilizer is selected from the group consisting of glycerol, propylene glycol, polyalcohol, sorbitol and derivatives of sorbitol, preferably of sorbitanoleat.18. Device according to any one of paragraphs. 1-17, which further includes an antimicrobial agent, preferably selected from the group consisting of erythromycin, tetracycline, cephalosporin and clindamycin.19. Device according to any one of paragraphs. 1-18, providing a prolonged delivery of the composition for at least 4 hours, preferably at least 24 hours, more preferably 8 o'clock20. Device according to any one of paragraphs. 1-19, which has a size in the range from 0.5 to 2 cm2and a thickness in the range from 7 to 24 mils (about 178 to about 610 μm).21. Device according to any one of paragraphs. 1-20, in which the keratolytic agent is salicylic acid.22. Device according to any one of paragraphs. 1-21, in which an effective amount of salicylic acid is 0.6. %.23. Device according to any one of paragraphs. 1-22, in which the antiseptic agent is triclosan.Prisposoblenie according to any one of paragraphs. 1-24, in which the solubilizer is servicemanual.26. Method for the production of devices for delivery of a medicinal product according to any one of paragraphs. 1-25, comprising: (a) mixing a separate adhesive material or a mixture of sticky materials with protivougrevoe composition, effective amounts keratolytic agent and agent (agents) against irritation thus, to obtain a mixture, and (b) laminating the mixture on one side of the release liner and the second side of the support film.
FIELD: pharmaceutical industry.
SUBSTANCE: invention is characterized by that system contains underlayer, therapeutical substance storage layer, and agent attaching the system on the person's skin and allowing access of nicotine to skin. System is transparent (opacity factor below 48.6%).
EFFECT: facilitated transcutaneous transport of nicotine.
8 cl, 1 tbl