Pharmaceutical composition for topical application

Abstract

A topical pharmaceutical composition which has a hydrophilic outer phase, at least one pharmaceutical active ingredient and at least one carrier substance. The carrier substance has at least two lamellar double membrane layers arranged one over another in the manner of a sandwich, wherein between adjacent double membrane layers, aligned parallel to each other, a layer of an inner phase is arranged. The active ingredient is distributed in the double membrane layer and in the layer of the inner phase such that the layer of the inner phase contains the active ingredient in a concentration range between 2% by weight and 98% by weight and the double membrane layer contains the active ingredient in a concentration between 98% by weight and 2% by weight, and the outer phase has no or almost no active ingredient.

1 . A pharmaceutical composition, to be applied topically, which has a hydrophilic outer phase, at least one pharmaceutical active ingredient and at least one carrier substance for the active ingredient, wherein the carrier substance forms such structures, which comprises at least two lamellar double membrane layers, arranged one over another in the manner of a sandwich, wherein between adjacent double membrane layers, aligned parallel to each other, a layer of an inner phase is respectively arranged, characterized in that the active ingredient is distributed in the double membrane layer and in the layer of the inner phase such that the layer of the inner phase contains the active ingredient in a concentration range between 2% by weight and 98% by weight and the double membrane layer contains the active ingredient in a concentration between 98% by weight and 2% by weight, respectively in relation to the total concentration of active ingredient, that the outer phase has no or almost no active ingredient, and that the carrier is selected from the group consisting of monoglycerides, diglycerides, triglycerides, preferably distilled middle-chain monoglycerides, sphingolipids, phosphatidylcholine, phospholipids, fatty alcohols, fatty acids and derivatives of the previously mentioned compounds. 
     
     
         2 . Composition according to  claim 1 , characterized in that the inner phase contains the active ingredient in a concentration range between 15% by weight and 85% by weight, preferably in a concentration range between 25% by weight and 75% by weight, and the double membrane layer contains the active ingredient in a concentration range between 85% by weight and 15% by weight, preferably in a concentration range between 75% by weight and 25% by weight, respectively in relation to the total concentration of active ingredient. 
     
     
         3 . Composition according to  claim 1 , characterized in that the concentration of the active ingredient in the inner phase and in the double membrane layer is different. 
     
     
         4 . Composition according to  claim 1 , characterized in that the outer phase has the active ingredient in a concentration of up to a maximum of 5% by weight in relation to the total concentration of active ingredient. 
     
     
         5 . Composition according to  claim 4 , characterized in that the outer phase has the active ingredient in a concentration between 0% by weight and 2% by weight in relation to the total concentration of active ingredient. 
     
     
         6 . Composition according to  claim 1 , characterized in that the composition contains a hydrophobic active ingredient and that the active ingredient is arranged predominantly, preferably of at least 70% by weight in relation to the total concentration of active ingredient, inside the double membrane layer. 
     
     
         7 . Composition according to  claim 6 , characterized in that inside the double membrane layer the hydrophobic active ingredient is embedded in a concentration between 80% by weight and 90% by weight in relation to the total concentration of active ingredient. 
     
     
         8 . Composition according to  claim 1 , characterized in that the composition contains a hydrophilic active ingredient and that the active ingredient is arranged predominantly, preferably of at least 70% by weight in relation to the total concentration of active ingredient, inside the inner phase. 
     
     
         9 . Composition according to  claim 8 , characterized in that inside the inner phase the hydrophilic active ingredient is embedded in a concentration between 80% by weight and 90% by weight in relation to the total concentration of active ingredient. 
     
     
         10 . Composition according to  claim 1 , characterized in that the active ingredient is anchored within the composition by means of a lipophilic compound on or in the double membrane layer. 
     
     
         11 . Composition according to  claim 10 , characterized in that the lipophilic compound is embedded in the double membrane layer and the active ingredient which is anchored herewith is arranged within the inner phase. 
     
     
         12 . Composition according to  claim 11 , characterized in that the lipophilic compound fixes the active ingredient by intermolecular interactions, in particular by hydrogen bonding or by Van der Waals forces. 
     
     
         13 . Composition according to  claim 1 , characterized in that the inner phase and the outer phase are identical. 
     
     
         14 . Composition according to  claim 1 , characterized in that the inner phase and/or the outer phase are liquids. 
     
     
         15 . Composition according to  claim 14 , characterized in that the inner phase and the outer phase are respectively a liquid, in particular water. 
     
     
         16 . Composition according to  claim 1 , characterized in that the composition contains as pharmaceutical active ingredient at least one locally or systemically acting active ingredient. 
     
     
         17 . Composition according to  claim 16 , characterized in that the active ingredient is a pharmaceutical active ingredient and is selected from the group consisting of analgesics, antirheumatics, antiallergics, antibiotics, antimycotics, antiphlogistics, balneotherapeutics, corticoid active ingredients, antiseptics, circulation-enhancing active ingredients, sedatives, anaesthetics, spasmolytics and wound treatment agents, respectively alone or in a mixture. 
     
     
         18 - 21 . (canceled) 
     
     
         22 . Composition according to  claim 1 , characterized in that the composition contains an anti-inflammatory active ingredient, which is selected from the group which comprises ursolic acid, soya sterol, 18-beta-glycyrrhetic acid, gamma oryzanol, ferulic acid, avenanthramides and derivatives of the previously mentioned active ingredients. 
     
     
         23 . Composition according to  claim 1 , characterized in that the composition has the active ingredient in a concentration between 0.01% by weight and 35% by weight, preferably between 0.1% by weight and 15% by weight in relation to the composition ready for use. 
     
     
         24 . (canceled) 
     
     
         25 . Composition according to  claim 1 , characterized in that the composition contains as carrier substance a hydrogenated phospholipid, in particular a hydrogenated phosphatidylcholine. 
     
     
         26 . Composition according to  claim 25 , characterized in that the hydrogenated phospholipid has at least 60% by weight hydrogenated phosphatidylcholine. 
     
     
         27 . Composition according to  claim 1 , characterized in that the composition has the carrier substance in a concentration between 0.5% by weight and 30% by weight, preferably in a concentration between 0.7% by weight and 10% by weight, in relation to the composition ready for use. 
     
     
         28 . Composition according to  claim 25 , characterized in that the hydrogenated phospholipid has a phase transition temperature over 30° C. and under 70° C. 
     
     
         29 . Composition according to  claim 1 , characterized in that the composition has the outer phase and the inner phase in a total concentration between 5% and 90% in relation to the weight of the composition ready for use. 
     
     
         30 . Composition according to  claim 1 , characterized in that the composition further contains at least one alcohol, in particular a polyvalent alcohol. 
     
     
         31 . Composition according to  claim 30 , characterized in that the composition has as alcohol phenylethyl alcohol, pentylene glycol, caprylyl glycol, decylene glycol and/or glycerine. 
     
     
         32 . Composition according to  claim 1 , characterized in that the composition has a N-acyl ethanolamine in a concentration between 0.01% by weight and 10% by weight, preferably between 0.1% by weight and 3% by weight, in relation to the composition ready for use. 
     
     
         33 . Composition according to  claim 32 , characterized in that the acyl radical of the N-acyl ethanolamine is a C1-C24-acyl radical. 
     
     
         34 . Composition according to  claim 32 , characterized in that the N-acyl ethanolamine is selected from the group which comprises N-acetyl ethanolamine, N-oleoyl ethanolamine, N-linolenoyl ethanolamine, N-cocoyl ethanolamine and N-palmitoyl ethanolamine. 
     
     
         35 . Composition according to  claim 1 , characterized in that the composition furthermore has at least one preservative, an antioxidant, a thickener and/or a gelling agent. 
     
     
         36 . Composition according to  claim 35 , characterized in that the composition has as thickener or respectively as gelling agent a natural colloid or a natural hydrocolloid and/or a synthetic colloid or a synthetic hydrocolloid. 
     
     
         37 . (canceled) 
     
     
         38 . Composition according to  claim 1 , characterized in that the composition is formulated as a composition which is able to be applied topically and has a viscosity at 20° C. between 2.000 mPas and 40.000 mPas, preferably between 12.000 mPas and 25,000 mPas. 
     
     
         39 . Composition according to  claim 1 , characterized in that the composition has a pH-value between 4.0 and 7.6. 
     
     
         40 . Composition according to  claim 1 , characterized in that the composition has the double membrane layer in a concentration between 10% and 95%, preferably between 30% and 95%, in relation to the weight of the carrier substance contained in the composition. 
     
     
         41 . Composition according to  claim 1 , characterized in that the composition contains a structure which comprises between 2 and 15 lamellar double membrane layers arranged one over the other in the manner of a sandwich. 
     
     
         42 . Composition according to  claim 1 , characterized in that each individual double membrane has a thickness between 4 nm and 20 nm, preferably between 4 nm and 8 nm. 
     
     
         43 . Composition according to  claim 1 , characterized in that the layer of the inner phase, arranged between adjacent double membrane layers, has a thickness between 2 nm and 10 nm.