DE102006001162A1 - Patch cover for atopic dermatitis - Google Patents

Abstract

Plaster covering diseased skin (eczema, itching, scaly, dry, weeping areas) as a result of atopic dermatitis.

Description

The atopic dermatitis (atopic dermatitis, atopic eczema) is one chronic, non-contagious skin disease that occurs in batches. It is characterized by rough, scaly and whitish skin as well as eczematic, often weeping and ignited skin lesions, V. A. in the field of body flexion (Elbow, squat, palms, etc.) and is accompanied of strong, agonizing Itching. These symptoms can be attributed to altered skin properties or disorders of the immune system. there is especially the dehydration of the skin due to a greatly increased transepidermal Moisture loss caused by an altered lipid composition, too mention. The inflammations are due to released histamine from the mast cells, due a fault the immune reaction to allergens. Accompanied is one Sick leave always from a strong itching, the patient tried to relieve by scratching. However, this further promotes histamine release and with it the inflammation. This can even lead to open, bleeding wounds, which in turn increases the risk of infection. Further changes the skin properties, e.g. the absence of natural moisturizing factors as well as the diminished activity of welding and sebaceous glands make the skin rough and flaky. The extent of skin involvement can range from discrete, circumscribed areas to areal Disease of the entire skin organ vary. This disease occurs especially among children and adolescents and represents one of the most common Teething problems (incidence 3-4%; Jung, Dermatology, 1991) at all dar. The skin lesions usually begin in the head area (scalp, cheeks) and spread then over the neck continues on arms and legs. Triggers for the relapses may provocation factors such as. the climate, the season, infections, allergen exposure, food resources and emotional factors. Atopic diseases (e.g., asthma bronchial and allergic rhinoconjunctivitis) are characterized by a strong willingness to normally harmless environmental influences (e.g. Food, washing and care products, animal hair, wool, dust mites, Pollen, etc ...) allergic to react.

The exact cause for this disease is not clear. it is supposed that a hereditary predisposition plays a major role. Another Thesis makes the changed, "more sterile" living conditions, i.e. the less contact with environmental influences, which challenge the immune system and "train," responsible.

Atopic dermatitis is a multifunctional disease, therefore, the treatment of this skin disease takes place in several steps. In the first, acute phase, initially trying the itching by cooling associations or antipruritic substances such as polidocanol (in Baleum Hermal ^® plus, oil bath), or antihistamines (Sorentol ^®, Fenestil ^® cream) to relieve. Then it tries to stem the inflammation. For this purpose, for example, prescription cortisone preparations (eg Ebenol ^® cream, Fenistil ^® Hydrocort ointment) are used. But even prescription preparations, such as calcineurin inhibitors pimecrolimus (Elidel Cream ^®, for example, in or Douglan cream ^®) or tacrolimus (Protopic ointment example in ^®) are used. Furthermore, the stabilization of the skin condition by proper washing and regular care is an important measure. In addition to nourishing oil baths (eg Balmandol ^® , Linola ^® Fett N oil bath, Balneum Hermal ^® F), creams, ointments or lotions are also used (eg Linola ^® Gamma cream, Menalind ^® derm cream / lotion, Eucerin ^® Omega cream / lotion / fatty ointment ) that contain gamma-linolenic acid as an important building block of the epidermal lipid layer. Some creams should also protect the affected areas of skin from further irritation by forming a film and on a moist wound and skin environment for better healing create (eg Atopiclair ^®).

It has now surprisingly been found that the application of a self-adhesive plaster preparation (hereinafter referred to as plaster, cf. 1 ) consisting of a cover layer ( 1 ), a matrix ( 3 ) and a protective film ( 2 ) can be used very effectively against the symptoms of atopic dermatitis, such as itching, eczema or rhagades.

MVTR:

Water Vapor Transmission Rate in g/m²/24h

Δm:

Masse an permeierten Wasser in g

S:

Fläche des Testobjektes in cm²

T:

Testzeit in h

In addition, the plaster also provides an active, mechanical protection against external stimuli such as scratching, contact with clothing or environmental influences of daily life (eg pollen, detergents, dirt). The plaster with a size of preferably 30-70 cm ² and a matrix weight of preferably 40-80 g / m ² , is applied to the diseased skin areas. Due to the significantly altered properties of atopic skin (dry, rough, high moisture loss) and the location of the diseased areas (usually in body bends), the structure of the patch must be designed so that it adheres sufficiently for about 10-12h under these conditions. A decisive factor for the adhesion under increased mechanical stress is the flexibility of the cover layer which must be elastic in at least one direction (longitudinally or laterally), but better in both directions. The second important factor for sufficient adhesion in this specific application is the moisture accumulation below the patch due to the high water evaporation. If too much moisture accumulates, the plaster dissolves early, if too little water is retained, the regeneration process is slowed down. It It has now been shown that the cover layer must have semi-occlusive properties in addition to its elastic properties. That is, the system must be sufficiently occlusive for a good healing, but also sufficiently permeable to ensure the necessary adhesion. The indicator for semi-occlusive properties is the Moisture Vapor Transmission Rate (MVTR), which describes the amount of water in g which, under standardized conditions, can permeate through 1 m ^{2 of} the test material within 24 h (cf. Formula 1): Formula 1: Moisture Vapor Transmission Rate Calculation:

MVTR:

Water vapor transmission rate in g / m ² / 24h

Dm:

Mass of permeated water in g

S:

Area of the test object in cm ²

T:

Test time in h

It has been found that covering layers of natural materials (eg silk, cotton) or of synthetic plastics are suitable for this specific application, such as, for example:
Polyurethane (PU), eg UcecoatAB, Fa. Cytec
Polypropylene (PP), eg CoTran 9729, Fa. 3M
Ethyl vinyl acetate (EVA), eg CoTran 9702, Fa. 3M
Polyethylene terephthalate (PET), eg Fa. KO Braun

The cover layer may be present in the form of a film, a fabric or a nonwoven. Typical MVTR values for some cover layers are in 2 shown. Furthermore, it has been found that elastic cover layers with MVTR between 4000 and 15000 g / m ² / 24h are good materials for this application. However, the MVTR of the cover layer is only one part of the assessment basis for the properties of this plaster system. Another important aspect is the MVTR of the patch (covering layer and matrix). If this value is 3000 to 8500 g / m ² / 24h are obtained good results with respect to adhesion and efficacy.

Of course it is Also, the pressure-sensitive adhesive polymer responsible for the adhesion of the patch. It is important that the pressure-sensitive adhesive polymer as possible causes little irritation and gentle on the diseased skin can be deducted. It was found that especially acrylate glue (e.g., DT 2852) well meet this requirement. But also polyisobutylene, Silicone, isoprene, styrenic, melt pressure-sensitive adhesive and any mixtures can be used. The matrix of the patch contains itching-alleviating substances. It has a combination of menthol in a concentration of preferably 4-10% and polidocanol in a concentration of preferably 3-7% as proved particularly effective. In wearing tests it was found that The itching in atopic skin was significantly reduced.

Further it has been shown that the addition of substances for refatting, Care or moisturizing (e.g., fatty acids, tincture hypericum, vitamins, urea) has a positive impact on the regeneration of the skin noticeably softer and smoother. This will also the healing process significantly accelerated. The matrix may also contain adjuvants Plasticizers or tackifiers, such as octyldodecyl stearates (e.g., ceraphyl) or rosin resins (e.g., Staybelite).

One special aspect is the ease of handling this application form. Patients, especially the largest target group children and adolescents, are able to quickly and easily diseased the patch Apply skin areas. Due to the plaster concept - protection / therapy / care - provides after a short time and with little effort a noticeable Relief.

wear tests

One first wearing test was performed on 6 healthy persons. aim It was the wearing properties of the patch according to Comparative Example 1 to determine. This formulation contains menthol and polidocanol as therapeutically active substances. As a self-adhesive adhesive layer the acrylate polymer DT 87-2852 from National Starch was used. The cover layer used was Cotran 9720 from 3M. The 6 test persons In each case a patch and an instruction / questionnaire were handed out. The Plasters should be over Night on the fat-free, clean and dry palm, alternatively Knee, elbow or wrist inside be glued. The evaluation showed that the adhesion of the patch can be improved, the wearing characteristics but predominantly inconspicuous and were pleasant. A test person bothered to wear the patch in another, itching and reddening of the skin occurred. For all test persons the patch could be removed easily and without glue residue on the skin. The conclusion was that more flexible and thinner cover layers better results adhesion could deliver.

Based on these results, another wearing test was carried out. The decisive factor was that this test was performed on a person suffering from atopic dermatitis. Inventive Example 1 was used as the test article det. This formulation contains menthol and polidocanol as therapeutically active substances, National Starch's acrylate polymer DT 87-2852 as a self-adhesive layer, Ceraphil 230 as a plasticizer, and the Staybelite Ester 10 thermoplastic resin as a tackifier. The cover layer used was the bi-elastic polyurethane film Platilon U73 from Epurex Film. The subject wore the patch during the day on atopic skin in the area of the wrist inside. The plaster completely dissolved after 15 minutes due to the formation of moisture under the covering layer. In order to be able to assess further properties of the atopic skin, the plaster was fixed with Leukoplast. After 7 hours, the patch was removed. There was a significant improvement in the skin, which was softer and smoother, which was attributed to the occlusive patch (albeit fixed with Leukoplast). Next, the initially deep rhagades receded and their redness disappeared almost completely. Overall, the effect was judged to be very pleasant.

One further wearing test with Example 2 according to the invention with menthol and polidocanol as therapeutically active substances and the acrylate polymer DT 87-2852 from National Starch as a self-adhesive adhesive layer. As a cover layer was the bi-elastic PET fabric from the company K. O. Braun used. Adhesion of the Pflasters was over 7 h very good. The formed moisture under the fabric solved that Plaster does not stop. The subject cleaned up the wearing properties as inconspicuous and pleasant. The plaster could easily and without glue residue on removed from the skin. The affected skin became softer and smoother. The rhagades receded and their redness decreased from.

One Another wearing test on atopic skin was with the examples of the invention 3 to 5 performed. The patches contained menthol and polidocanol as therapeutic effective substances, as well as the acrylate polymer DT 87-2852 as self-adhesive Adhesive layer. The covering layer used was UcecoatAB from the company Cytec, Cotran 9700 and Cotran 9702 (both from 3M). The plaster with Cotran 9700 and UcecoatAB both stuck well over 10 hours. The wearing properties of both test items were considered unremarkable and pleasantly rated. The skin became much better. The patch with Cotran 9702 fell off after a few hours at night and became not rated further.

Examples

Inventive example 1:

In order to produce 3500 cm ^{2 of} a patch laminate according to the invention on a laboratory scale, 0.67 g of menthol and 1.35 g of thesitol and 0.34 g of Ceraphil 230 in 1.80 g of ethanol abs. added and stirred until a clear, homogeneous solution is obtained. 43.03 g of Durotak 87-2852 are added to this solution and the mixture is stirred for 30 minutes until a homogeneous mass has formed (adhesive mass). Subsequently, 4.38 g of Staybelite Ester 10 are dissolved in 3.40 g of n-heptane and then added to the adhesive mass. This finished mass is stirred for 30 minutes until it is homogeneous and free of bubbles. The finished mass is spread using a doctor blade in a gap thickness of 250 microns on a siliconized polyester film, so that after the immediate cooling, a matrix weight of 61.5 g / m ^{2 is} obtained. After laminating with Platilon U73 25μ plasters with a size of 40 cm ^{2 are} punched out of the laminate and packed in four-edge sealing bags.

Inventive example 2:

To prepare 3500 cm ^{2 of} a patch laminate according to the invention on a laboratory scale, 1.14 g of menthol and 2.28 g of thesitol in 1.80 g of ethanol abs. added and stirred until a clear, homogeneous solution is obtained. 72.73 g of Durotak 87-2852 are added to this solution and the mixture is stirred for 30 minutes until the mass is homogeneous. Subsequently, 3.40 g of n-heptane are weighed out and stirred for a further 30 min. The mass is again homogeneous and free of bubbles. This mass is spread by means of a doctor blade in a gap thickness of 330 microns on a siliconized polyester film, so that after the immediate cooling, a matrix weight of 81 g / m ^{2 is} obtained. After lamination with PET fabric, Fa. KOBraun, patches with a size of 40 cm ^{2 are} punched out of the laminate and packed in four-edge sealed bags.

Inventive example 3:

To produce 1500 cm ^{2 of} a patch laminate according to the invention on a laboratory scale, 0.49 g of menthol and 0.98 g of thesitol in 0.80 g of ethanol abs. added and stirred until a clear, homogeneous solution is obtained. 31.76 g of Durotak 87-2852 are added to this solution and the mixture is stirred for 30 minutes until the mixture is homogeneous. Subsequently, 1.40 g of n-heptane are weighed out and stirred for a further 30 min. The mass is again homogeneous and free of bubbles. This mass is spread by means of a doctor blade in a gap thickness of 330 microns on a siliconized polyester film, so that after the immediate cooling, a matrix weight of 81 g / m ^{2 is} obtained. After lamination with UcecoatAB, patches of 40 cm ² size are punched out of the laminate and packed in four-edge sealed bags.

Inventive example 4:

To produce 2500 cm ^{2 of} a patch laminate according to the invention on a laboratory scale, 0.81 g of menthol and 1.63 g of thesitol in 1.30 g of ethanol abs. added and stirred until a clear, homogeneous solution is obtained. 52.93 g of Durotak 87-2852 are added to this solution and the mixture is stirred for 30 minutes until a homogeneous mass has formed.

Subsequently, 2.40 g of n-heptane are weighed out and stirred for a further 30 min. The mass is homogeneous and free of bubbles. This mass is spread by means of a doctor blade in a gap thickness of 330 microns on a siliconized polyester film, so that after the immediate cooling, a matrix weight of 81 g / m ^{2 is} obtained. After being laminated with Cotran 9700, patches with a size of 40 cm ^{2 are} punched out of the laminate and packed in four-edge sealing bags.

Inventive example 5:

To produce 2500 cm ^{2 of} a patch laminate according to the invention on a laboratory scale, 0.81 g of menthol and 1.63 g of thesitol in 1.30 g of ethanol abs. added and stirred until a clear, homogeneous solution is obtained. To this solution are added 52.93 g of Durotak 87-2852 and stirred for 30 minutes until the mass is homogeneous. Subsequently, 2.40 g of n-heptane are weighed out and stirred for a further 30 min. The mass is homogeneous and free of bubbles. This mass is spread by means of a doctor blade in a gap thickness of 330 microns on a siliconized polyester film, so that after the immediate cooling, a matrix weight of 81 g / m ^{2 is} obtained. After lamination with Cotran 9702, patches with a size of 40 cm ^{2 are} punched out of the laminate and packed in four-edge sealing bags.

Comparative Example 1

To produce 2000 cm ^{2 of} a patch laminate on a laboratory scale, 0.50 g of menthol, 1.00 g of thesitol and 0.25 g of Ceraphil 230 in 1.40 g of ethanol abs. added and stirred until a clear, homogeneous solution is obtained. 31.97 g of Durotak 87-2852 are added to this solution and stirred for 1 hour until the mass is homogeneous and free from bubbles. This mass is spread by means of a doctor blade in a gap thickness of 300 microns on a siliconized polyester film, so that after the immediate cooling, a matrix weight of 64.5 g / m ^{2 is} obtained. After being laminated with Cotran 9720, patches with a size of 40 cm ^{2 are} punched out of the laminate and packed in four-edge sealing bags.

Claims (23)

Self-adhesive plaster preparation, consisting of a cover layer, a matrix and a protective film, wherein The preparation is such that the symptoms of atopic Dermatitis such as itching, eczema or rhagades can be alleviated and the preparation forms a machanic protection against external stimuli and environmental influences. Paving preparation according to claim 1, characterized that the effective structure provides a self-adhesive matrix, the Inseparably connected to the cover layer and on diseased skin how eczema, rhagades, scaly skin areas can be applied. Patch preparation according to one of the preceding claims, characterized in that the cover layer is a film, a fabric or a fleece consisting of synthetic plastics such as polyurethane, Polypropylene, ethyl vinyl acetate or polyethylene terephthalate or from natural Materials like silk or cotton is. Patch preparation according to one of the preceding claims, characterized characterized in that the film used as cover layer, fabric or Nonwoven longitudinally elastic, sideways-elastic or is bi-elastic. Paving preparation according to one of the preceding claims, characterized in that the film, fabric or nonwoven used as the cover layer is semi-occlusive and their MVTR (Moisture Vapor Transmission Rate) between 50 g / m ² / 24h and 15000 g / m2 / 24h preferred between 1000 g / m ^2/24 and 10000 g / m ^2/24 h and in particular between 4000 g / m ² / 24h and 8500 g / m ² / 24h is located. Patch preparation according to one of the preceding claims, characterized in that the plaster preparation (cover layer and Matrix) is semi-occlusive and its MVTR (Moisure Vapor Transmission Rate) between 1000 g / m2 / 24h and 12000 g / m2 / 24h preferably between 3000 g / m2 / 24h and 8500 g / m2 / 24h. Patch preparation according to one of the preceding claims, characterized in that the self-adhesive matrix consists of a pressure-sensitive adhesive polymer or copolymer from the group of polyacrylates, polyisobutylenes, the polyisoprenes, the polystyrenes, the silicone adhesive, the melt pressure-sensitive adhesive as well any mixture of two or more of said polymers is. Patch preparation according to one of the preceding claims, characterized characterized in that the self-adhesive matrix polidocanol in one Concentration of 1-20%, preferably 3-7% and menthol at a concentration of 2-20%, preferably 4-10%. Patch preparation according to one of the preceding claims, characterized characterized in that the self-adhesive matrix is used for the treatment of contains atopic dermatitis, those from the group of - corticoids (e.g., hydrocortisone, prednisone, dexamethasone) - antihistamines (eg bromopheniramine, bamipin) Immunosuppressants (e.g. Calcineurin inhibitors Taerolimus, Pimecrolimus) - antibiotics (e.g., erythromycin, clindamycin, tetracycline) - anti-inflammatory (e.g., ibuprofen, mometasone furoate, betamethasone valerate) - homeopathic remedies (e.g., Cardiospermum mother tincture, Dulcamara extract) - Vegetable Extracts (for example St. John's wort extract) Tannins (e.g., tannin) are selected. Paving preparation according to one of the preceding Claims, characterized in that the self-adhesive matrix auxiliaries for refatting and Care of the skin contains. A plaster preparation according to claim 10, in that that for refatting and care used excipients from the group of - fatty alcohols, fatty acids and fats, fatty acid ethanolamides (Moisturizing agent) - sugar alcohols and esters of glycerol, - natural moisturizing factors, e.g. Amino acids, urea, NMP, PVP, carbohydrates - Vegetable and animal extracts and oils, e.g. Lanolin, almond oil, Tincture hypericum, collagen - Vitamins and minerals - silicones are selected. Paving preparation according to one of the preceding Claims, characterized in that the self-adhesive matrix auxiliaries contains as plasticizer. A plaster preparation according to claim 12, in that the adjuvants used as plasticizers from the group of - aromatic or aliphatic dicarboxylic acids, or Salts or esters thereof - multivalent Alcohols, or derivatives thereof, or their polymers - Olefinalkohole from 5 carbon atoms or their derivatives - ethanolamines - polyester, or fatty acid esters, or hydroxycarboxylic acid ester Epoxides - vegetable or animal extracts or oils or resins selected are. Paving preparation according to one of the preceding Claims, characterized in that the self-adhesive matrix auxiliaries contains as a tackifier. Paving preparation according to claim 14, in that that the auxiliaries used as tackifiers belong to the group of - Resin acids or their esters (rosin resins) or their hydrogenated forms - Aliphatic and aromatic hydrocarbon resins or any mixtures from that - Terpene resins - Liquid resins are selected. Paving preparation according to one of the preceding Claims, characterized in that the with the self-adhesive matrix inseparable cover layer forms a mechanical scratch protection. Paving preparation according to one of the preceding Claims, characterized in that the inseparable self-adhesive matrix bonded to the cover layer and their ingredients, especially menthol and polidocanol, a Represents therapy for the itching. Paving preparation according to one of the preceding Claims, characterized in that the inseparable self-adhesive matrix bonded to the cover layer and / or their ingredients a therapy against skin dehydration represents. Paving preparation according to one of the preceding Claims, characterized in that the inseparable self-adhesive matrix bonded to the cover layer and their ingredients moisturizing and / or caring. Paving preparation according to one of the preceding claims, characterized in that the self-adhesive matrix inseparably bonded to the covering layer has a weight per unit area of 20 to 200 g / m ² , preferably 40 to 100 g / m ² and in particular 80 g / m ² . Paving preparation according to one of the preceding claims, characterized in that the plaster has a size of 5 to 500 cm ² , preferably from 20 to 150 cm ² and in particular 30 to 70 cm ² . Paving preparation according to one of the preceding Claims, characterized in that the Plasters can be applied easily and safely by atopic people. This especially for the largest audience, the children and adolescents. Paving preparation according to one of the preceding Claims, characterized in that the Plaster over a period of 1-24 h, preferably 4-15 h and especially 6-10 h be worn.