Abstract:
The invention relates to an application system provided with a micro emulsion ( 14 ) containing a medication, said micro emulsion being contained in a medicament reservoir ( 12 ), a first gas connection ( 18 ) to which oxygen can be guided, a nozzle head ( 28 ) comprising recesses ( 29 ) which are arranged on the end of the medicament reservoir ( 12 ) and an atomising nozzle ( 30 ) which is arranged in the nozzle head ( 28 ). Pressure exerted on the microemulsion for atomising as well as the microemulsion emerging therefrom atomises the oxygen into drops by means of a Venturi arrangement in the atomising nozzle ( 30 ).

Description:
RELATED APPLICATIONS 
       [0001]    This application is a continuation of U.S. application Ser. No. 11/665,209, filed Oct. 9, 2007, which is the U.S. National Stage of International Application No. PCT/EP2005/010909, filed on Oct. 11, 2005, published in German, which claims priority under 35 U.S.C. §119 or 365 to German Application No. DE 10 2004 049 574.2, filed Oct. 12, 2004. The entire teachings of the above applications are incorporated herein by reference. 
     
    
     BACKGROUND 
       [0002]    On administering medicinal substances as active substance materials to a patient, a balance is always to be obtained, with the dosage, between desired action and undesired side effects on the body. It is accordingly desirable to bring the medicinal substance as directly as possible to the site of action, in order accordingly to be able to work with minimum total dosages and to place the least possible burden on the body of the patient, and still to achieve the necessary active level at the site of action. This can be achieved by percutaneous administration of medicinal substances. 
         [0003]    The skin, in particular the upper horny layer, represents though a barrier which can be overcome only with difficulty. This applies in particular for water-soluble or sparingly soluble medicinal substances. 
         [0004]    A conventional process for the percutaneous administration of medicinal substances is the application of ointments, creams or gels to the skin. In order to improve the permeation of the active substances, use is made of “penetration promoters”, such as sulfoxides, alcohols, fatty acids, anoids, fusids, and many others. These substances reduce the resistance to penetration of the horny layer and facilitate the permeation of the medicinal substances. 
         [0005]    Dosing possibilities which are only approximate are disadvantages of this process. Because of this, the content of medicinal substances in the preparations has to be kept low as a precaution, resulting in the desired high active level not being reached even in the target tissues. Moreover, despite the use of penetration promoters, the depth of penetration of conventional preparations is only very low. 
         [0006]    Furthermore, different methods are known for overcoming the barrier of the skin (compare  Müller/Hildebrand; Pharmazeutische Technologie: Moderne Arzneiformen [Pharmaceutical Technology: Modern medicinal forms ], ISBN 3-8047-1549-4, chapter 13). 
         [0007]    In particular, transdermal therapeutic systems (TTS) have been developed. TTSs are technical devices which are placed on a specific area of the skin in an adherent fashion and which deliver, by diffusion through the skin, to the body a specific dose of the medicinal substance according to different mechanisms with a specific time-related feed. The objective in this connection is in particular a systemic action with a defined profile of the active level. In order to accelerate the permeation of the medicinal substance into the skin, TTS systems also have ultrasound heads or electrodes, in order to deliver current impulses to the skin and accordingly to promote pore formation in the skin by mechanical or electrical stimuli. 
         [0008]    A disadvantage here is that a targeted local application by means of TTS is not possible. There is the fact that not all medicinal substances can be administered by diffusion. This applies in particular for water-soluble and sparingly soluble medicinal substances. 
         [0009]    Furthermore, medicinal substances are applied to the skin in microemulsions. Because of the low surface tension and large interface in the microemulsion, water-soluble, fat-soluble and sparingly soluble medicinal substances can be dispersed therein. With the help of a microemulsion, success is achieved in introducing the medicinal substances into the horny layer of the skin (stratum corneum) within a short time. 
         [0010]    Even with the help of microemulsions, alone, success is not satisfactorily achieved, though, in temporarily abolishing the barrier function of the skin to the desired extent and in applying all kinds of medicinal substances through the skin. 
         [0011]    It is an object of the invention to remedy the abovementioned disadvantages of the state of the art. 
         [0012]    Specifically, it is an object of the invention to make available preparations (subsequently referred to as medicaments) which satisfactorily penetrate the barrier of the skin. 
         [0013]    Furthermore, it is an object of the invention to make available a system with which it is possible, on any area of the skin, to penetrate the barrier of the skin and to percutaneously apply an active substance or a combination of active substances. 
         [0014]    Furthermore, it is an object of the invention to make available a system with which the medicinal substances to be applied can be accurately dosed. 
         [0015]    It is an additional object of the invention to apply the maximum daily dose locally. 
         [0016]    It has been found, surprisingly, that this and additional unmentioned objects are achieved with the help of a system according to the invention for the percutaneous administration of medicinal substances, exhibiting a microemulsion, into which the medicinal substances are introduced, and a device for the atomization of the microemulsion, preferably in an oxygen-comprising atmosphere (the term “atomization” is to be understood here as the fine dispersing of liquid using a propellant gas). 
         [0017]    Furthermore, these objects are achieved by a microemulsion enriched with oxygen which comprises at least one medicinal substance for percutaneous administration. 
         [0018]    A microemulsion for the percutaneous administration of medicinal substances which exhibit medicinal substances for the improved supply of oxygen to the skin also achieve the object according to the invention. 
         [0019]    The combination of the various mechanisms of the novel process can result in significant synergistic effects in the permeation of active substances into the skin, as is explained subsequently. 
         [0020]    Through the extraordinarily small droplets of the high performance atomizer, the microemulsion charged with active substance is applied to the skin in finely divided form. Because of the low surface tension of the microemulsion, a huge spreading effect arises in this connection. The horny layer of the skin and the microemulsion have similar upper structures, such as lamellae or tubuli, formed from bilipid layers. These upper structures of the horny layer contribute crucially to the resistance to permeation of this layer. The finely dispersed application of the droplets presumably results in “fusion” of the microemulsion with the horny layer according to the principle “similia similibus”. As a result of the fusion, the abovementioned upper structures dissolve and the active substances can diffuse into the skin at a reinforced level. The use of oxygen as propellant gas results in the lipid-comprising droplets of the atomizer being enriched in oxygen. This oxygen is, like the active substances, introduced into the skin layer, which results in an increase in the oxygen partial pressure in the skin. This elevated partial pressure strongly stimulates the microcirculatory flow. Through this, the active substance materials which have diffused in are more strongly entrained convectively inward into the tissue. 
         [0021]    The combined use of microemulsions, fine droplets and oxygen in the process according to the invention also results in an increase in the permeation of active substances in three successive steps: 
         [0022]    1. The microemulsion and accordingly the active substances are very finely divided and spread over the surface of the skin. 
         [0023]    2. The horny layer barrier is overcome and 
         [0024]    3. The microcirculatory transport through the skin is increased, namely first by the high performance atomization, secondly by the microemulsion and thirdly by the oxygen. 
       DETAILED DESCRIPTION OF THE INVENTION 
       [0025]    The skin is the biggest organ in the body and closes off the outside. It has, in its operation, to perform a number of tasks. 
         [0026]    In first place is the protective function against mechanical effects, such as impacts, pressure or rubbing, and against the penetration of bacteria, viruses and fungi through an acidic sheathing. Furthermore, the skin protects against heat, cold, light and harmful substances. 
         [0027]    The skin is also a sense organ: special sensors detect pressure, temperature, pain and itching. 
         [0028]    The skin also intervenes, by regulation of the water and heat budget, in a regulating fashion in the function of the whole body. 
         [0029]    In broad terms, the skin consists of three layers: of the subcutis, of the corium (dermis) and of the epidermis. 
         [0030]    The subcutis consists of fat, large blood vessels, glands and small muscles. It serves, e.g., as “larder” and for the damping of mechanical effects. The dermis, with its collagen and elastomer fibers, brings about hold and elasticity of the skin and accordingly also resistance to tearing. Sensory cells (sensors) for reception of the abovementioned sensations are also located in the dermis. It comprises much hyaluronic acid and chondroitin sulfate, thus glucosaminoglucans, which make possible, as reversible gels, the transport of biological molecules and cytotaxis. 
         [0031]    The epidermis is of particular importance and particular interest in closing off the body from the outside since this layer altogether guarantees the integrity of the skin, the very outermost layer, the horny layer, playing a crucial role. 
         [0032]    This layer consists of a layer, approximately 10 cells thick, of keratinized, i.e. dead, flat cells (horn cells, stratum corneum); it is divided up yet further into an upper loose layer (stratum disjunctum) and into a lower firmer layer, the stratum conjunctum. The horn cells are constantly peeling off toward the outside and are produced by division in the “stratum germinativum”, the germinative layer, located thereunder. 
         [0033]    The particular microstructure of the stratum corneum consists of flat, brick-like keratinized cells (corneocytes). The intracellular matrix is particularly structured. It consists, approximately parallel to the skin surface, of lipoid bilayers: in the stratum corneum, approximately one hundred aqueous and lipid phases alternate. In the formulation sense, the horny layer represents a “water-in-oil emulsion” in the form of a lamellar bilayer. This constantly regenerating layer, with a thickness of only approximately 12 μm, forms, with the help of its complex two-phase upper structures, secure protection for the cells of the stratum germinativum located thereunder: without the horny layer, a “wound bed” is produced. 
         [0034]    The horny layer of the skin is of particular importance for closing off from the outside, especially in its barrier function. This is the case with regard to the density, the oxygen partial pressure (PO 2 ), the pH and the water content. 
         [0035]    The barrier for hydrogen ions, which form an acidic protective sheathing, is particularly important. Equally important is a barrier for oxygen, by putting up great resistance to the diffusion of this. This results in a decrease in the oxygen partial pressure of the air from 150 torr to approximately 50 torr. Accordingly, the vital cells of the skin epithelium of the intact skin are protected from an excessively high oxidatively damaging oxygen partial pressure. 
         [0036]    So advantageous the effective barrier function in the horny layer is for the body, so disadvantageous it proves to be for transdermal transport of medicinal substances. In such cases, the corneal barrier has to be temporarily abolished. 
         [0037]    It has been found, surprisingly, that the barrier function of the skin, by introduction of oxygen into the horny layer and accordingly the increase in the oxygen partial pressure on the tissue side of the stratum corneum, results in an improved transdermal transport of medicinal substances. 
         [0038]    The transmembrane pressure of the oxygen is increased by the increase in the oxygen partial pressure on the tissue side of the stratum corneum, which is presumably a reason for the improved transdermal transport of medicinal substances. 
         [0039]    Because of the above described lamellar structure of alternating water and oil phases in the stratum corneum, microemulsions can be particularly suitably introduced into the stratum corneum (compare Müller/Hildebrand; Pharmazeutische Technologie: Moderne Arzneiformen [Pharmaceutical Technology: Modern medicinal forms], ISBN 3-8047-1549-4, chapter 15). In a preferred embodiment of the invention, these are used as vehicle systems for oxygen or medicinal substances and also base materials for medicaments. 
         [0040]    Such microemulsions are known and are used in cosmetics and the pharmaceutical industry. These are available commercially, for example under the trade name “Nanoemulsion” from Sangui AG. 
         [0041]    Microemulsions within the meaning of the invention are thermodynamically stable systems which exhibit at least water, surfactants and lipid. The term “a surfactant” is understood to mean emulsifiers which can be ionic or nonionic. Examples of surfactants which can be used are known under the trade name Tween, Span and Synperonic PEL 101. 
         [0042]    Lipids which can be used are fatty oils or mineral oils, for example isopropyl myristate and isopropyl palmitate. 
         [0043]    Microemulsions which can be used in the context of this invention can be oil-in-water microemulsions or water-in-oil microemulsions. In this connection, oil droplets in a water matrix or water droplets in an oil matrix are formed. 
         [0044]    Such microemulsions exhibit droplet sizes in the range from 10 nm to 1 μm, preferably from 10 nm to 500 nm, particularly preferably from 10 nm to 300 nm. 
         [0045]    The mean droplet size of a microemulsion which can be used in the context of the invention is not limited. The mean droplet size is preferably less than 300 nm, particularly preferably less than 150 nm. 
         [0046]    Such microemulsions preferably exhibit interfaces of more than 200 m 2  per ml, particularly preferably of more than 400 m 2  per ml and very particularly preferably of more than 600 m 2  per ml. 
         [0047]    Because of the hydrophilic and lipophilic portion of the microemulsions and of the low surface tension and of the large interface, it is possible to disperse, in microemulsions, both water-soluble and fat-soluble and/or sparingly soluble medicinal substances. The choice of the surfactants is in this connection made according to the active substance and the effect desired. Ionic surfactants are generally particularly effective, while nonionic surfactants are particularly kind to the skin. 
         [0048]    Microemulsions according to the invention relate, inter alia, to the medicinal use of liquid medicaments based on microemulsions in the therapy of pain, for the treatment of circulatory disorders and for the healing of wounds in degenerated skin, e.g. in elderly people. 
         [0049]    Medicinal substances based on such microemulsions can, in addition to the parent substances of the microemulsion, exhibit base materials for medicaments and medicinal substances. These base materials and medicinal substances can be of natural and synthetic origin. In the context of this invention, base materials and medicinal substances of natural origin are particularly preferred, without this being limiting. 
         [0050]    Examples of natural base materials and the effect thereof are represented in table 1. Base materials which can be used in the context of this invention are not, however, limited thereto. 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Natural base materials and the effect thereof 
               
             
          
           
               
                   
                 Base materials 
                 Effect 
               
               
                   
                   
               
               
                   
                 
                   Aloe vera 
                 
                 favoring the blood flow 
               
               
                   
                   
                 contributing to moistness 
               
               
                   
                   
                 inhibiting inflammation 
               
               
                   
                   
                 removing wrinkles 
               
               
                   
                   
                 nourishing the skin 
               
               
                   
                   Arnica  oil (fat) 
                 alleviating pain 
               
               
                   
                   
                 inhibiting inflammation 
               
               
                   
                   
                 causing hyperemia 
               
               
                   
                   
                 favoring the blood flow 
               
               
                   
                   
                 healing wounds 
               
               
                   
                 Avocado oil 
                 binding of moisture 
               
               
                   
                   
                 regenerating 
               
               
                   
                   
                 alleviating itching 
               
               
                   
                   
                 healing wounds 
               
               
                   
                   
                 nourishing the skin 
               
               
                   
                 Borage oil 
                 skin regenerating 
               
               
                   
                   
                 alleviating itching 
               
               
                   
                   Centella  oil 
                 regenerating 
               
               
                   
                   
                 regulating connective tissue (scars) 
               
               
                   
                   
                 antiinflammatory 
               
               
                   
                   
                 healing wounds 
               
               
                   
                 Rose of Sharon oil 
                 antiinflammatory 
               
               
                   
                   
                 analgesic 
               
               
                   
                   
                 causing hyperemia 
               
               
                   
                   
                 antispasmodic 
               
               
                   
                 Jojoba oil 
                 inhibiting inflammation 
               
               
                   
                   
                 regenerating 
               
               
                   
                   
                 healing wounds 
               
               
                   
                 Corn oil 
                 antioxidant 
               
               
                   
                 Almond oil 
                 regenerating 
               
               
                   
                   
                 nourishing 
               
               
                   
                 Evening primrose oil 
                 healing wounds 
               
               
                   
                   
                 antibacterial 
               
               
                   
                   
                 alleviating itching 
               
               
                   
                 Neem oil 
                 antibacterial 
               
               
                   
                   
                 antimycotic 
               
               
                   
                 Olive oil 
                 causing hyperemia 
               
               
                   
                   
                 favoring the blood flow 
               
               
                   
                   
                 healing wounds 
               
               
                   
                 Marigold oil 
                 antiinflammatory 
               
               
                   
                   
                 antirheumatic 
               
               
                   
                   
                 favoring the blood flow 
               
               
                   
                 Shea butter 
                 healing wounds 
               
               
                   
                   
                 regenerating 
               
               
                   
                 Grapeseed oil 
                 astringent 
               
               
                   
                 Wheat germ oil 
                 regenerating 
               
               
                   
                   
                 nourishing the skin 
               
               
                   
                 Dog rose oil 
                 contributing to moistness 
               
               
                   
                 Rose hip oil 
                 skin regenerating 
               
               
                   
                   
                 alleviating itching 
               
               
                   
                   
                 nourishing 
               
               
                   
                   
                 healing wounds 
               
               
                   
                   
               
             
          
         
       
     
         [0051]    The medicinal substances which can be used in the context of this invention are not limited. In this connection, natural and synthetic medicinal substances can be used. In the context of this invention, natural medicinal substances obtained from plants are preferred. Essential oils which can be obtained from plant parts are particularly preferred as medicinal substances. Examples of plant species and genera, inclusive of their chemotypes, which comprise essential oils in the most varied plant parts, which can be used as medicinal substances in microemulsions in the context of this invention, and also the therapeutic effect thereof in external application, are represented in table 2; however, these are not limited thereto. 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 Plant species and genera, inclusive of their chemotypes, 
               
               
                 which comprise essential oils in the most varied plant parts, 
               
               
                 and also the therapeutic effect thereof in external application 
               
             
          
           
               
                   
                 Species/Genus/ 
                   
               
               
                 Name 
                 Chemotypes 
                 Properties 
               
               
                   
               
               
                   Angelica  oil 
                 
                   Angelica 
                 
                 skin regenerating 
               
               
                 Valerian oil 
                 
                   Valeriana 
                 
                 diuretic 
               
               
                   
                   
                 skin regenerating 
               
               
                 Basil oil 
                 
                   Ocimum 
                 
                 antibacterial 
               
               
                   
                 Chemotype 
                 antispasmodic 
               
               
                   
                 Methyl chavicol 
                 antiviral 
               
               
                   
                   
                 antiinflammatory 
               
               
                   
                   
                 analgesic 
               
               
                   
                   
                 deblocking 
               
               
                   
                   
                 caring for varicose veins 
               
               
                 Bay oil 
                 
                   Pimenta 
                 
                 antibacterial 
               
               
                 Pimento oil 
                   
                 antimycotic 
               
               
                   
                   
                 antiviral 
               
               
                 Mugwort oil 
                 
                   Artemisia 
                 
                 antiviral 
               
               
                 Benzoin resin 
                 
                   Styrax 
                 
                 antiinflammatory 
               
               
                   
                   
                 antiseptic 
               
               
                   
                   
                 skin regenerating 
               
               
                   
                   
                 cell renewal 
               
               
                 Bergamot oil 
                   Citrus aurantium  var. 
                 antiseptic 
               
               
                   
                 
                   Bergamia 
                 
                 epithelizing 
               
               
                   
                   
                 healing wounds 
               
               
                   
                   
                 skin regenerating 
               
               
                 Winter savory oil 
                 
                   Satureja Montana 
                 
                 analgesic 
               
               
                   
                   
                 antibacterial 
               
               
                   
                   
                 antimycotic 
               
               
                   
                   
                 antiseptic 
               
               
                   
                   
                 immunomodulating 
               
               
                 Birch oil 
                 
                   Betula 
                 
                 antiinflammatory 
               
               
                   
                 98% methyl salicylate 
                 antirheumatic 
               
               
                   
                   
                 antispasmodic 
               
               
                   
                   
                 alleviating pain 
               
               
                   
                   
                 vasodilative 
               
               
                 Cajeput oil 
                 
                   Melaleuca 
                 
                 antibacterial 
               
               
                   
                   
                 antiviral 
               
               
                   
                   
                 caring for varicose veins 
               
               
                   Cassia  oil 
                 
                   Cinnamomum cassia 
                 
                 antibacterial 
               
               
                   
                   
                 anticoagulant 
               
               
                   
                   
                 antimycotic 
               
               
                   
                   
                 antiviral 
               
               
                   
                   
                 causing hyperemia 
               
               
                   Cistus  oil 
                 
                   Cistus 
                 
                 antibacterial 
               
               
                   
                   
                 antihemorrhagic 
               
               
                   
                   
                 antiviral 
               
               
                   Eucalyptus  oil 
                 
                   Eucalyptus 
                 
                 analgesic 
               
               
                   
                   
                 antibacterial 
               
               
                   
                   
                 antimycotic 
               
               
                   
                   
                 antiinflammatory 
               
               
                   
                   
                 antiviral 
               
               
                 Fennel oil 
                 
                   Foeniculum 
                 
                 analgesic 
               
               
                   
                   
                 dehydrating 
               
               
                 Fir needle oil 
                 
                   Abies 
                 
                 antiinflammatory 
               
               
                   
                   
                 causing hyperemia 
               
               
                 Galbanum oil 
                 
                   Ferula 
                 
                 antiinflammatory 
               
               
                   
                   
                 antiseptic 
               
               
                   
                   
                 healing wounds 
               
               
                   Geranium  oil 
                 
                   Pelargonium graveolens 
                 
                 astringent 
               
               
                   
                   
                 antibacterial 
               
               
                   
                   
                 antimycotic 
               
               
                   
                   
                 deblocking 
               
               
                   
                   
                 caring for the skin 
               
               
                   
                   
                 caring for varicose veins 
               
               
                   
                   
                 healing wounds 
               
               
                   Geranium  oil 
                 
                   Geranium macrorrhizum 
                 
                 antiseptic 
               
               
                 “true  geranium ” 
                   
                 epithelizing 
               
               
                 Clove oil 
                 
                   Eugenia caryophyllata 
                 
                 antibacterial 
               
               
                   
                   
                 antimycotic 
               
               
                   
                   
                 antiviral 
               
               
                 Ho wood oil 
                 
                   Cinnamomum 
                 
                 antibacterial 
               
               
                   
                   
                 antimycotic 
               
               
                   
                   
                 antiviral 
               
               
                 Immortelle oil 
                 
                   Helichrysum 
                 
                 analgesic 
               
               
                 Everlasting oil 
                   
                 anticoagulant 
               
               
                   
                   
                 epithelizing 
               
               
                 Ginger oil 
                 
                   Zingiber 
                 
                 analgesic 
               
               
                   
                   
                 causing hyperemia 
               
               
                 Blue camomile oil 
                 
                   Matricaria camomilla 
                 
                 antiinflammatory 
               
               
                   
                   
                 healing wounds 
               
               
                 Roman camomile 
                 
                   Anthemis nobilis 
                 
                 analgesic 
               
               
                 oil 
                   
                 antiinflammatory 
               
               
                 Wild camomile oil 
                 
                   Ormensis mixta 
                 
                 antibacterial 
               
               
                   
                   
                 antimycotic 
               
               
                   
                   
                 healing wounds 
               
               
                 Camphor oil 
                 
                   Cinnamomum 
                 
                 anesthetic 
               
               
                   
                   
                 analgesic 
               
               
                   
                   
                 antibacterial 
               
               
                   
                   
                 antiinfective 
               
               
                   
                   
                 antimycotic 
               
               
                   
                   
                 antirheumatic 
               
               
                   
                   
                 antiviral 
               
               
                   
                   
                 diuretic 
               
               
                   
                   
                 causing hyperemia 
               
               
                   
                   
                 immunomodulating 
               
               
                   
                   
                 rheumatic pain 
               
               
                   
                   
                 spasmolytic 
               
               
                 Pine oil 
                 
                   Pinus 
                 
                 antibacterial 
               
               
                   
                   
                 causing hyperemia 
               
               
                   
                   
                 protecting from edema 
               
               
                 Mountain pine oil 
                 
                   Pinus mugo 
                 
                 antiinflammatory 
               
               
                   
                   
                 immunomodulating 
               
               
                 Lavender oil 
                 
                   Lavendula 
                 
                 analgesic 
               
               
                   
                   
                 antibacterial 
               
               
                   
                   
                 anticoagulant 
               
               
                   
                   
                 antimycotic 
               
               
                   
                   
                 antiinflammatory 
               
               
                   
                   
                 epithelizing 
               
               
                   
                   
                 alleviating itching 
               
               
                 Spanish sage oil 
                 
                   Salvia 
                 
                 analgesic 
               
               
                   
                   
                 antiinfective 
               
               
                   
                   
                 antispasmodic 
               
               
                   
                   
                 tonic 
               
               
                 Lemongrass oil 
                 
                   Cymbopogon 
                 
                 antibacterial 
               
               
                   
                   
                 antiinflammatory 
               
               
                   
                   
                 antiviral 
               
               
                   
                   
                 vasodilative 
               
               
                   
                   
                 immunomodulating 
               
               
                 Laurel oil 
                 
                   Laurus 
                 
                 analgesic 
               
               
                   
                   
                 antibacterial 
               
               
                   
                   
                 anticoagulant 
               
               
                   
                   
                 antispasmodic 
               
               
                   
                   
                 mucolytic 
               
               
                   
                   
                 protecting from edema 
               
               
                 Marjoram oil 
                 
                   Origanum 
                 
                 analgesic 
               
               
                   
                   
                 antibacterial 
               
               
                   
                   
                 antispasmodic 
               
               
                   
                   
                 diuretic 
               
               
                 Manuka oil 
                 
                   Leptospermum 
                 
                 antibacterial 
               
               
                   
                   
                 antimycotic 
               
               
                   
                   
                 antiinflammatory 
               
               
                   
                   
                 antirheumatic 
               
               
                   
                   
                 sedative 
               
               
                   
                   
                 skin regenerating 
               
               
                   
                   
                 alleviating itching 
               
               
                   Melissa  oil 
                 
                   Melissa 
                 
                 analgesic 
               
               
                   
                   
                 antiviral 
               
               
                   
                   
                 inhibiting inflammation 
               
               
                   
                   
                 immunomodulating 
               
               
                   
                   
                 caring for varicose veins 
               
               
                 Myrrh oil 
                 
                   Commiphora 
                 
                 antibacterial 
               
               
                   
                   
                 antiinflammatory 
               
               
                   
                   
                 antiviral 
               
               
                   
                   
                 epithelizing 
               
               
                   
                   
                 skin regenerating 
               
               
                 Niaouli oil 
                 
                   Melaleuca 
                 
                 analgesic 
               
               
                   
                   
                 antiinfective 
               
               
                   
                   
                 antimycotic 
               
               
                   
                   
                 antiviral 
               
               
                   
                   
                 immunomodulating 
               
               
                   
                   
                 caring for varicose veins 
               
               
                 Oregano oil 
                 
                   Origanum 
                 
                 analgesic 
               
               
                   
                   
                 antibacterial 
               
               
                   
                   
                 antimycotic 
               
               
                   
                   
                 antiviral 
               
               
                   
                   
                 causing hyperemia 
               
               
                   
                   
                 immunomodulating 
               
               
                 Patchouli oil 
                 
                   Pogostemon 
                 
                 analgesic 
               
               
                   
                   
                 antiinfective 
               
               
                   
                   
                 antimycotic 
               
               
                   
                   
                 antiinflammatory 
               
               
                   
                   
                 diuretic 
               
               
                   
                   
                 deblocking 
               
               
                   
                   
                 epithelizing 
               
               
                   
                   
                 immunomodulating 
               
               
                 Petitgrain oil 
                 
                   Citrus aurantium 
                 
                 antiinfective 
               
               
                   
                   
                 antiinflammatory 
               
               
                   
                   
                 antispasmodic 
               
               
                 Balsam Peru oil 
                 
                   Myroxylon 
                 
                 antibacterial 
               
               
                   
                   
                 antiinflammatory 
               
               
                   
                   
                 antispasmodic 
               
               
                 Pepper oil (black) 
                 
                   Piper 
                 
                 analgesic 
               
               
                   
                   
                 antibacterial 
               
               
                   
                   
                 antiviral 
               
               
                   
                   
                 diuretic 
               
               
                   
                   
                 causing hyperemia 
               
               
                 Peppermint oil 
                 
                   Mentha 
                 
                 analgesic 
               
               
                   
                   
                 anesthetizing 
               
               
                   
                   
                 antibacterial 
               
               
                   
                   
                 antimycotic 
               
               
                   
                   
                 antiparasitic 
               
               
                   
                   
                 antiviral 
               
               
                   
                   
                 epithelizing 
               
               
                   
                   
                 cooling 
               
               
                   
                   
                 spasmolytic 
               
               
                 Pimento oil 
                 
                   Pimenta 
                 
                 antibacterial 
               
               
                   
                   
                 antimycotic 
               
               
                   
                   
                 antiviral 
               
               
                 Tansy oil 
                 
                   Tanacetum 
                 
                 analgesic 
               
               
                   
                   
                 antiallergic 
               
               
                   
                   
                 alleviating itching 
               
               
                   
                   
                 caring for varicose veins 
               
               
                   Ravensara  oil 
                 
                   Ravensara 
                 
                 antibacterial 
               
               
                   
                   
                 antimycotic 
               
               
                   
                   
                 antiviral 
               
               
                 Rose oil 
                 
                   Rosa damaszena 
                 
                 antiinflammatory 
               
               
                   
                   
                 antiviral 
               
               
                   
                   
                 skin regenerating 
               
               
                 Rosemary oil 
                 
                   Rosmarinus 
                 
                 analgesic 
               
               
                   
                 Chemotype “Moroccan” 
                 diuretic 
               
               
                   
                 Cineol 
                 fungicidal 
               
               
                   
                   
                 causing hyperemia 
               
               
                 Savin oil 
                 
                   Juniperus 
                 
                 analgesic 
               
               
                   
                   
                 causing hyperemia 
               
               
                 Sage oil 
                 
                   Salvia 
                 
                 antibacterial 
               
               
                   
                   
                 antimycotic 
               
               
                   
                   
                 antiviral 
               
               
                 Sandalwood oil 
                 
                   Santalum 
                 
                 deblocking 
               
               
                   
                   
                 epithelizing 
               
               
                 Yarrow oil 
                 
                   Achillea 
                 
                 analgesic 
               
               
                   
                   
                 antiinflammatory 
               
               
                   
                   
                 epithelizing 
               
               
                 Black cumin oil 
                 
                   Nigella 
                 
                 analgesic 
               
               
                   
                   
                 antiallergic 
               
               
                   
                   
                 antiinflammatory 
               
               
                 Spike lavender oil 
                 
                   Lavendula spica 
                 
                 analgesic 
               
               
                   
                   
                 antiinfective 
               
               
                   
                   
                 antiviral 
               
               
                   
                   
                 fungicidal 
               
               
                   Tagetes  oil 
                 
                   Tagetes 
                 
                 antimycotic 
               
               
                 Tea tree oil 
                 
                   Melaleuca 
                 
                 analgesic 
               
               
                   
                   
                 antibacterial 
               
               
                   
                   
                 antimycotic 
               
               
                   
                   
                 antiparasitic 
               
               
                   
                   
                 antiinflammatory 
               
               
                   
                   
                 antiviral 
               
               
                   
                   
                 epithelizing 
               
               
                   
                   
                 immunomodulating 
               
               
                   
                   
                 caring for varicose veins 
               
               
                 Texas cedar oil 
                 
                   Juniperus mexicana 
                 
                 deblocking 
               
               
                   
                   
                 diuretic 
               
               
                   Thuja  oil 
                 
                   Thuja 
                 
                 antiinfective 
               
               
                   
                   
                 antiviral 
               
               
                   
                   
                 diuretic 
               
               
                   
                   
                 epithelizing 
               
               
                   
                   
                 healing wounds 
               
               
                 Thyme oil 
                 
                   Thymus vulgaris 
                 
                 antibacterial 
               
               
                   
                 Chemotype Linalool and 
                 antimycotic 
               
               
                   
                 Geraniol 
                 antiviral 
               
               
                   
                 
                   Thymus 
                 
                 antibacterial 
               
               
                   
                 Chemotype Thujanol 
                 antiviral 
               
               
                   
                   
                 immunomodulating 
               
               
                   
                 
                   Thymus 
                 
                 analgesic 
               
               
                   
                 Chemotype Thymol and 
                 antiinfective 
               
               
                   
                 Carvacrol 
                 immunomodulating 
               
               
                 Vetiver oil 
                 
                   Vetiveria 
                 
                 caring for the skin 
               
               
                   
                   
                 causing hyperemia 
               
               
                 Juniper oil 
                 
                   Juniperus 
                 
                 antibacterial 
               
               
                   
                   
                 antirheumatic 
               
               
                   
                   
                 diuretic 
               
               
                 Frankincense oil 
                 
                   Boswellia 
                 
                 antiinflammatory 
               
               
                   
                   
                 epithelizing 
               
               
                   
                   
                 immunomodulating 
               
               
                 Silver fir oil 
                 
                   Abies 
                 
                 antiseptic 
               
               
                   
                   
                 causing hyperemia 
               
               
                 Wintergreen oil 
                 
                   Gaultheria 
                 
                 antiinflammatory 
               
               
                   
                   
                 antispasmodic 
               
               
                   
                   
                 alleviating pain 
               
               
                   
                   
                 vasodilative 
               
               
                 Hyssop oil 
                 
                   Hyssopus 
                 
                 antibacterial 
               
               
                   
                   
                 antiviral 
               
               
                   
                   Hyssopus  var. 
                 antiinflammatory 
               
               
                   
                 
                   Decumbens 
                 
                 antiviral 
               
               
                 Cinnamon oil 
                 
                   Cinnamomum verum 
                 
                 antibacterial 
               
               
                   
                   
                 antimycotic 
               
               
                   
                   
                 antiparasitic 
               
               
                   
                   
                 antiviral 
               
               
                   
                   
                 causing hyperemia 
               
               
                   
                   
                 immunomodulating 
               
               
                 Lemon oil 
                 
                   Citrus 
                 
                 astringent 
               
               
                   
                   
                 antibacterial 
               
               
                   
                   
                 anticoagulant 
               
               
                   
                   
                 antiviral 
               
               
                   
                   
                 caring for varicose veins 
               
               
                 Cypress oil 
                 
                   Cupressus 
                 
                 astringent 
               
               
                   
                   
                 diuretic 
               
               
                   
                   
                 deblocking 
               
               
                   
                   
                 caring for varicose veins 
               
               
                   
               
             
          
         
       
     
         [0052]    Preferably used medicinal substances and the active properties thereof are listed in table 3. These are subdivided into essential oils, plant extracts and synthetic single substances. The medicinal substances which can be used in the context of this invention are not, though, to be limited thereto. 
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 Active properties of essential oils, plant extracts and 
               
               
                 single substances isolated from these plant extracts 
               
             
          
           
               
                   
                   
                   
                 Chemically/pharmaceutically 
               
               
                   
                   
                   
                 active 
               
               
                 Properties 
                 Essential oils 
                 Plant extracts 
                 substances 
               
               
                   
               
               
                 Astringent 
                   Geranium  oil 
                 Tannins, e.g. 
                   
               
               
                   
                 Lemon oil 
                 
                   Quercus 
                 
               
               
                   
                 Cypress oil 
                 Extract from  Stipites   
               
               
                   
                   
                 
                   Dulcamarae 
                 
               
               
                   
                   
                   Hamamelis  extract 
               
               
                 Acne 
                   
                   
                 Azelain 
               
               
                   
                   
                   
                 Tretinoin 
               
               
                   
                   
                   
                 Isotretinoin 
               
               
                   
                   
                   
                 Adapalene 
               
               
                   
                   
                   
                 Benzoyl peroxide 
               
               
                 Analgesic 
                 Basil oil 
                 Rose of Sharon oil 
                 Carboxylic acids, e.g.: 
               
               
                   
                 Winter savory 
                 
                   Fructus Capsici 
                 
                 Salicylic acid 
               
               
                   
                 oil 
                 (capsaicin) 
                 Diflunisal 
               
               
                   
                 Birch oil 
                 Comfrey extract 
                 Salicylamide 
               
               
                   
                 Fennel oil 
                   Symphytum  extract 
                 Ethenzamide 
               
               
                   
                 Fir needle oil 
                 
                   Harpagophytum 
                 
                 Acetylsalicylic acid 
               
               
                   
                 Ginger oil 
                 
                   Procumbens 
                 
                 Salsalate 
               
               
                   
                 Roman 
                 Willow bark 
                 Acetic acid 
               
               
                   
                 camomile oil 
                 Guaiacwood 
                 derivatives, e.g.: 
               
               
                   
                 Camphor oil 
                   Arnica  extract 
                 Indomethacin/ 
               
               
                   
                 Extra lavender 
                   
                 Acemetacin, 
               
               
                   
                 oil 
                   
                 Proglumetacin 
               
               
                   
                 Spanish sage oil 
                   
                 Diclofenac 
               
               
                   
                 Laurel oil 
                   
                 Tolmetin 
               
               
                   
                 Marjoram oil 
                   
                 Lonazolac 
               
               
                   
                 Melissa oil 
                   
                 Fenbufen 
               
               
                   
                 Niaouli oil 
                   
                 Aceclofenac 
               
               
                   
                 Oregano oil 
                   
                 Etofenamate 
               
               
                   
                 Patchouli oil 
               
               
                   
                 Pepper oil 
               
               
                   
                 Peppermint oil 
               
               
                   
                 Tansy oil 
               
               
                   
                 Rosemary oil 
               
               
                   
                 Savin oil 
               
               
                   
                 Yarrow oil 
               
               
                   
                 Spike lavender 
               
               
                   
                 oil 
               
               
                   
                 Tea tree oil 
               
               
                   
                 Thyme oil 
               
               
                   
                 Wintergreen oil 
               
               
                 Continuation: 
                   
                   
                 Propionic acid 
               
               
                 Analgesic 
                   
                   
                 derivatives, e.g.: 
               
               
                   
                   
                   
                 Ibuprofen 
               
               
                   
                   
                   
                 Ketoprofen 
               
               
                   
                   
                   
                 Flurbiprofen 
               
               
                   
                   
                   
                 Tiaprofenic acid 
               
               
                   
                   
                   
                 Fenoprofen 
               
               
                   
                   
                   
                 Naproxen 
               
               
                   
                   
                   
                 Dexketoprofen 
               
               
                   
                   
                   
                 Dexibuprofen 
               
               
                   
                   
                   
                 Heterocyclic ketoenol 
               
               
                   
                   
                   
                 acids 
               
               
                   
                   
                   
                 Oxicams: 
               
               
                   
                   
                   
                 Piroxicam 
               
               
                   
                   
                   
                 Tenoxicam 
               
               
                   
                   
                   
                 Metoxicam 
               
               
                   
                   
                   
                 Meloxicam 
               
               
                   
                   
                   
                 Lornoxicam 
               
               
                   
                   
                   
                 Anthranilic acid 
               
               
                   
                   
                   
                 derivatives: 
               
               
                   
                   
                   
                 Mefenamic acid 
               
               
                   
                   
                   
                 Flufenamic acid 
               
               
                   
                   
                   
                 Niflumic acid 
               
               
                 Continuation: 
                   
                   
                 Other derivatives: 
               
               
                 Analgesic 
                   
                   
                 Nabumetone 
               
               
                   
                   
                   
                 Azapropazone 
               
               
                   
                   
                   
                 Aceclofenac 
               
               
                   
                   
                   
                 Caffeine 
               
               
                   
                   
                   
                 Pyrazolidiones: 
               
               
                   
                   
                   
                 Azapropazone 
               
               
                   
                   
                   
                 Oxyphenbutazone 
               
               
                   
                   
                   
                 Phenylbutazone/ 
               
               
                   
                   
                   
                 Mofebutazone 
               
               
                   
                   
                   
                 Azapropazone 
               
               
                   
                   
                   
                 Additional substance 
               
               
                   
                   
                   
                 categories: 
               
               
                   
                   
                   
                 Paracetamol 
               
               
                   
                   
                   
                 Niflumic acid 
               
               
                   
                   
                   
                 Bufexamac 
               
               
                 Neuropathies 
                   
                   
                 Pyrazolinones: 
               
               
                 Neuropathic 
                   
                   
                 Propylphenazone 
               
               
                   
                   
                   
                 Metamizole 
               
               
                   
                   
                   
                 Cox-2 inhibitors, e.g. 
               
               
                   
                   
                   
                 Celecoxib 
               
               
                   
                   
                   
                 Rofecoxib 
               
               
                   
                   
                   
                 Valdecoxib 
               
               
                   
                   
                   
                 Etoricoxib 
               
               
                   
                   
                   
                 Parecoxib 
               
               
                   
                   
                   
                 Vitamin B complex 
               
               
                   
                   
                   
                 α-Lipoic acid 
               
               
                   
                   
                   
                 L-Camithin 
               
               
                   
                   
                   
                 Peripheral 
               
               
                   
                   
                   
                 sympathetic blockers: 
               
               
                   
                   
                   
                 Clonidine 
               
               
                   
                   
                   
                 Homeopathic 
               
               
                   
                   
                   
                 preparation 
               
               
                 Anesthetizing 
                 Camphor oil 
                   
                 Ester local anesthetics 
               
               
                   
                 Peppermint oil 
                   
                 Benzocaine 
               
               
                   
                 Thyme oil 
                   
                 Procaine (0) 
               
               
                   
                   
                   
                 Tetracain (0) 
               
               
                   
                   
                   
                 Thymol 
               
               
                 Continuation: 
                   
                   
                 Amide local 
               
               
                 Anesthetizing 
                   
                   
                 anesthetics 
               
               
                   
                   
                   
                 Prilocaine 
               
               
                   
                   
                   
                 Mepivacaine 
               
               
                   
                   
                   
                 Lidocaine 
               
               
                   
                   
                   
                 Etidocaine 
               
               
                   
                   
                   
                 Bupivacaine 
               
               
                   
                   
                   
                 Levobupivacaine 
               
               
                   
                   
                   
                 Ropivacaine 
               
               
                   
                   
                   
                 Articaine 
               
               
                   
                   
                   
                 Fomocaine 
               
               
                 Antiallergic 
                 Black cumin oil 
                   
                 Glucocorticoids 
               
               
                 Antibacterial 
                 Bay oil 
                 Evening primrose oil 
                 Urea 
               
               
                 Antiinfective 
                 Winter savory 
                 Neem oil 
                 Thymol 
               
               
                   
                 oil 
                 Extracts from  Stipites   
                 Chlorhexidine 
               
               
                   
                 Cajeput oil 
                 
                   Dulcamarae 
                 
                 Antibiotics: 
               
               
                   
                   Cassia  oil 
                   
                 Fusidic acid 
               
               
                   
                   Cistus  oil 
                   
                 Mupirocin 
               
               
                   
                   Eucalyptus  oil 
                   
                 Sulfadiazine 
               
               
                   
                   Geranium  oil 
                   
                 Erythromycin 
               
               
                   
                 Clove oil 
                   
                 Clindamycin 
               
               
                   
                 Ho wood oil 
                   
                 Tetracycline 
               
               
                   
                 Camomile oil 
                   
                 Medocycline 
               
               
                   
                 Camphor oil 
               
               
                   
                 Pine oil 
               
               
                   
                 Garlic oil 
               
               
                   
                 Lavender oil 
                   
                 Tyrothricin 
               
               
                   
                 Extra lavender 
                   
                 Gentamycin 
               
               
                   
                 oil 
                   
                 Neomycin 
               
               
                   
                 Spanish sage oil 
                   
                 Bacitracin 
               
               
                   
                 Lemongrass oil 
                   
                 Chloramphenicol 
               
               
                   
                 Marjoram oil 
                   
                 Polymyxin 
               
               
                   
                 Manuka oil 
                   
                 Kanamycin 
               
               
                   
                 Carnation oil 
               
               
                   
                 Niaouli oil 
               
               
                   
                 Oregano oil 
               
               
                   
                 Patchouli oil 
               
               
                   
                 Balsam Peru oil 
               
               
                   
                 Petitgrain oil 
               
               
                   
                 Peppermint oil 
               
               
                   
                 Black pepper oil 
               
               
                   
                 Pimento oil 
               
               
                   
                 Sage oil 
               
               
                   
                 Spike lavender 
               
               
                   
                 oil 
               
               
                   
                 Tea tree oil 
               
               
                   
                 Thuja oil 
               
               
                   
                 Thyme oil 
               
               
                   
                 Juniper oil 
               
               
                   
                 Hyssop oil 
               
               
                   
                 Cinnamon oil 
               
               
                   
                 Lemon oil 
               
               
                 Anti- 
                   Cistus  oil 
                   Hamamelis  extract 
               
               
                 hemorrhagic 
               
               
                 Antihistaminic 
                 Black cumin oil 
                   
                 Glucocorticoids 
               
               
                 Anti- 
                   
                 Sage 
                 Camphoric acid 
               
               
                 hyperhydrotic 
                   
                 Walnut leaves 
                 Methenamine 
               
               
                   
                   
                 Oak bark 
                 Aluminum chlorate 
               
               
                   
                   
                 Tannins, e.g. oak bark 
                 hexahydrate 
               
               
                 Anticoagulant 
                 Immortelle oil 
                   
                 Hirudin 
               
               
                   
                 Everlasting oil 
                   
                 Hirudin derivatives 
               
               
                   
                 Cinnamon oil 
                   
                 Heparins, in particular 
               
               
                   
                 Lavender oil 
                   
                 also low molecular 
               
               
                   
                 Laurel oil 
                   
                 weight 
               
               
                   
                 Lemon oil 
               
               
                 Antimycotic 
                 Bay oil 
                 Neem oil 
                 Azole derivatives: 
               
               
                   
                 Pimento oil 
                 Extracts from  Stipites   
                 Clotrimazole 
               
               
                   
                 Winter savory 
                 
                   Dulcamarae 
                 
                 Bifonazole 
               
               
                   
                 oil 
                   
                 Econazole 
               
               
                   
                   Cassia  oil 
                   
                 Fenticonazole 
               
               
                   
                   Eucalyptus  oil 
                   
                 Isoconazole 
               
               
                   
                   Geranium  oil 
                   
                 Oxiconazole 
               
               
                   
                 Clove oil 
                   
                 Sertaconazole 
               
               
                   
                 Ho wood oil 
                   
                 Tioconazole 
               
               
                   
                 Camphor oil 
                   
                 Miconazole 
               
               
                   
                 Cinnamon oil 
                   
                 Ketoconazole 
               
               
                   
                 Lavender oil 
                   
                 Itraconazole 
               
               
                   
                 Extra lavender 
                   
                 Fluconazole 
               
               
                   
                 oil 
                   
                 Voriconazole 
               
               
                   
                 Manuka oil 
                   
                 Sertaconazole 
               
               
                   
                 Carnation oil 
               
               
                   
                 Niaouli oil 
               
               
                   
                 Oregano oil 
               
               
                   
                 Patchouli oil 
               
               
                   
                 Peppermint oil 
               
               
                 Continuation: 
                 Pimento oil 
                   
                 Squalene epoxidase 
               
               
                 Antimycotic 
                 Rosemary oil 
                   
                 inhibitors, e.g: 
               
               
                   
                 Sage oil 
                   
                 Terbinafin 
               
               
                   
                 Spike lavender 
                   
                 Naftifin 
               
               
                   
                 oil 
                   
                 Morpholines, e.g.: 
               
               
                   
                 Tagetes oil 
                   
                 Amorolfin 
               
               
                   
                 Tea tree oil 
                   
                 Other antimycotically 
               
               
                   
                 Thyme oil 
                   
                 effective substances, 
               
               
                   
                   
                   
                 e.g.: 
               
               
                   
                   
                   
                 Amphotericin B 
               
               
                   
                   
                   
                 Griseofulvin 
               
               
                   
                   
                   
                 Flucytosin 
               
               
                   
                   
                   
                 Ciclopirox 
               
               
                   
                   
                   
                 Nystatin 
               
               
                   
                   
                   
                 Natamycin 
               
               
                   
                   
                   
                 Thiocarbonates 
               
               
                 Combating 
                 Valerian oil 
                 
                   Aesculus 
                 
               
               
                 edema 
                 Basil oil 
                 
                   hippocastanum 
                 
               
               
                 Diuretic 
                 Fennel oil 
                 
                   Ruscus aculeatus 
                 
               
               
                 Deblocking 
                 Geranium oil 
                 
                   Melilotus officinalis 
                 
               
               
                 Dehydrating 
                 Camphor oil 
                 
                   Fagopyrum 
                 
               
               
                 Protecting from 
                 Pine oil 
                 
                   esculentum 
                 
               
               
                 edema 
                 Laurel oil 
                 Red vine leaf extract 
               
               
                   
                 Marjoram oil 
                 
                   Solidago virgaurea 
                 
               
               
                   
                 Patchouli oil 
                 Stinging nettle 
               
               
                   
                 Pepper oil 
               
               
                   
                 Rosemary oil 
               
               
                   
                 Sandalwood oil 
               
               
                   
                 Black cumin oil 
               
               
                   
                 Texas cedar oil 
               
               
                   
                 Thuja oil 
               
               
                   
                 Juniper oil 
               
               
                   
                 Cypress oil 
               
               
                 Antioxidant 
                   
                 Flavonoids 
                 Selenium 
               
               
                   
                   
                 Anthocyans 
                 Manganese 
               
               
                   
                   
                 Proanthoxycyanidines 
                 Copper 
               
               
                   
                   
                 Carotenoids 
                 L-Glutathione 
               
               
                   
                   
                 β-carotene: 
                 L-Cysteine 
               
               
                   
                   
                 Lycopene 
                 Coenzyme Q 10   
               
               
                   
                   
                 Zeaxanthin 
                 α-Lipoic acid 
               
               
                   
                   
                 Vitamin A, C and E 
               
               
                 Antiparasitic 
                 Peppermint oil 
                 Neem oil 
                 Crotamiton 
               
               
                   
                 Cinnamon oil 
                   
                 Permethrin 
               
               
                   
                 Tea tree oil 
                   
                 Benzyl benzoate 
               
               
                   
                   
                   
                 Allethrin 
               
               
                 Anti- 
                 Basil oil 
                 
                   Melilotus officinalis 
                 
                 Steroidal anti- 
               
               
                 inflammatory 
                 Benzoin resin 
                 
                   Ruscus aculeatus 
                 
                 inflammatories, such 
               
               
                   
                 Birch oil 
                 
                   Aesculus 
                 
                 as glucocorticoids 
               
               
                   
                 Camphor oil 
                 
                   hippocastanum 
                 
                 Bufexamac 
               
               
                   
                   Eucalyptus  oil 
                 Rose of Sharon oil 
                 Glycyrrhetinic acid 
               
               
                   
                 Fir needle oil 
                 Marigold 
                 Thymol 
               
               
                   
                 Galbanum oil 
                 
                   Aloe vera 
                 
                 Cavacrol 
               
               
                   
                 Rose of Sharon 
                 Jojoba 
                 Camphor 
               
               
                   
                 oil 
                 Evening primrose oil 
                 Eugenol 
               
               
                   
                 Blue camomile 
                 Borage oil 
                 Cinnamaldehyde 
               
               
                   
                 oil 
                 
                   Cardiospermum 
                 
                 Capsaicin 
               
               
                   
                 Roman 
                 
                   halicacabum 
                 
               
               
                   
                 camomile oil 
                 Tannins, e.g. from 
               
               
                   
                 Mountain pine 
                   Quercus  and 
               
               
                   
                 oil 
                 
                   Synthetica 
                 
               
               
                   
                 Lavender oil 
               
               
                   
                 Extra lavender 
               
               
                   
                 oil 
               
               
                   
                 Lemongrass oil 
               
               
                 Continuation: 
                 Manuka oil 
                 Extracts from  Stipites   
               
               
                 Anti- 
                 Myrrh oil 
                 
                   Dulcamarae 
                 
               
               
                 inflammatory 
                 Carnation oil 
                   Symphytum  extracts 
               
               
                   
                 Patchouli oil 
                   Hamamelis  extract 
               
               
                   
                 Petitgrain oil 
                 Camomile 
               
               
                   
                 Balsam Peru oil 
                   Arnica  oil 
               
               
                   
                 Rosemary oil 
                 Propolis 
               
               
                   
                 Yarrow oil 
               
               
                   
                 Black cumin oil 
               
               
                   
                 Ledum palustre 
               
               
                   
                 oil 
               
               
                   
                 Tea tree oil 
               
               
                   
                 Thyme oil 
               
               
                   
                 Frankincense oil 
               
               
                   
                 Wintergreen oil 
               
               
                   
                 Hyssop oil 
               
               
                   
                 Cinnamon oil 
               
               
                 Antirheumatic 
                 Birch oil 
                 
                   Fructus Capsici 
                 
                 See list analgesically 
               
               
                   
                 Camphor oil 
                 Capsaicin 
                 chemically/ 
               
               
                   
                 Manuka oil 
                 Nicotinic acid 
                 pharmaceutically 
               
               
                   
                 Rosemary oil 
                 Salicylate 
                 effective substances 
               
               
                   
                 Juniper oil 
                 
                   Cortex Salicis 
                 
                 Salicin 
               
               
                   
                 Wintergreen oil 
                 
                   Urtica dioica 
                 
               
               
                   
                 Cinnamon oil 
                 
                   Urtica urens 
                 
               
               
                 Antiseptic 
                 Benzoin resin 
               
               
                   
                 Bergamot oil 
               
               
                   
                 Winter savory 
               
               
                   
                 oil 
               
               
                   
                 Galbanum oil 
               
               
                   
                   Geranium  oil 
               
               
                   
                 Camphor oil 
               
               
                   
                 Silver fir oil 
               
               
                 Antispasmodic 
                 Basil oil 
               
               
                   
                 Birch oil 
               
               
                   
                 Spanish sage oil 
               
               
                   
                 Laurel oil 
               
               
                   
                 Marjoram oil 
               
               
                   
                 Balsam Peru oil 
               
               
                   
                 Petitgrain oil 
               
               
                   
                 Wintergreen oil 
               
               
                 Antiviral 
                 Basil oil 
                 Extractum 
                 Aciclovir/ 
               
               
                   
                 Bay oil 
                 
                   podophyllum 
                 
                 Valciclovir 
               
               
                   
                 Pimento oil 
                 (podophyllin) 
                 Penciclovir/ 
               
               
                   
                 Cajeput oil 
                 Extractum  Melissae   
                 Famciclovir 
               
               
                   
                   Cassia  oil 
                 
                   Fructus Capsici 
                 
                 Idoxuridine/ 
               
               
                   
                   Cistus  oil 
                 Capsaicin 
                 Bivudine 
               
               
                   
                   Eucalyptus  oil 
                   
                 Trifluridine 
               
               
                   
                 Clove oil 
                   
                 Vidarabine 
               
               
                   
                 Ho wood oil 
                   
                 Tromantadine 
               
               
                   
                 Camphor oil 
                   
                 Foscarnet 
               
               
                   
                 Cinnamon oil 
                   
                 Interferon-β 
               
               
                   
                 Lemongrass oil 
                   
                 Podophyllotoxin 
               
               
                   
                 Melissa oil 
               
               
                   
                 Myrrh oil 
               
               
                   
                 Niaouli oil 
               
               
                   
                 Oregano oil 
               
               
                   
                 Pepper oil 
               
               
                   
                 Peppermint oil 
               
               
                   
                 Pimento oil 
               
               
                   
                 Sage oil 
               
               
                   
                 Spike lavender 
               
               
                   
                 oil 
               
               
                   
                 Tea tree oil 
               
               
                   
                 Thuja oil 
               
               
                   
                 Thyme oil 
               
               
                   
                 Hyssop oil 
               
               
                   
                 Lemon oil 
               
               
                 Regenerating 
                   
                 
                   Allium cepa 
                 
                 Heparin 
               
               
                 connective 
                   
                 
                   Centella asiatica 
                 
                 Asiaticoside 
               
               
                 tissue 
               
               
                 Erectile 
                   
                   
                 Alprostadil (PGE 1) 
               
               
                 dysfunction 
                   
                   
                 Sildenafil citrate 
               
               
                   
                   
                   
                 Vardenafil 
               
               
                   
                   
                   
                 Tadalafil 
               
               
                   
                   
                   
                 Favoring the blood 
               
               
                   
                   
                   
                 flow, such as benzyl 
               
               
                   
                   
                   
                 nicotinate 
               
               
                 Epithelizing 
                 Bergamot oil 
               
               
                   
                   Geranium  oil 
               
               
                   
                 Immortelle oil 
               
               
                   
                 Everlasting oil 
               
               
                   
                 Lavender oil 
               
               
                   
                 Extra lavender 
               
               
                   
                 oil 
               
               
                   
                 Myrrh oil 
               
               
                   
                 Patchouli oil 
               
               
                   
                 Peppermint oil 
               
               
                   
                 Sandalwood oil 
               
               
                   
                 Yarrow oil 
               
               
                   
                 Tea tree oil 
               
               
                   
                 Thuja oil 
               
               
                   
                 Frankincense oil 
               
               
                 Binding of 
                   
                 Avocado oil 
                 Urea 
               
               
                 moisture 
                   
                 Dog rose 
                 Glycerol 
               
               
                   
                   
                 
                   Aloe vera 
                 
                 Glycine 
               
               
                 Vasodilative 
                 Lemongrass oil 
                   
                 Nitro preparations 
               
               
                 Hair loss 
                   
                   
                 Finasteride 
               
               
                   
                   
                   
                 Minoxidil 
               
               
                 Nourishing the 
                   Angelica  oil 
                 Dog rose 
                 Amino acids 
               
               
                 skin 
                 Valerian oil 
                 Almond oil 
                 Vitamins 
               
               
                 Caring for the 
                 Benzoin resin 
                 Wheat germ oil 
               
               
                 skin 
                 Bergamot oil 
                 Avocado oil 
               
               
                 Regenerating 
                 Geranium oil 
                 
                   Aloe vera 
                 
               
               
                 the skin 
                 Manuka oil 
                 Borage oil 
               
               
                   
                 Myrrh oil 
                 Jojoba oil 
               
               
                   
                 Vetiver oil 
                 Almond oil 
               
               
                   
                   
                 Shea butter 
               
               
                   
                   
                 Dog rose 
               
               
                 Cardiotonic 
                   
                   Arnica  flowers 
               
               
                   
                   
                 Hawthorn extract 
               
               
                 Causing 
                   Cassia  oil 
                   Arnica  oil 
                 Nicotine salicylate 
               
               
                 hyperemia 
                 Birch oil 
                 Peanut oil 
                 Capsaicin 
               
               
                 Favoring the 
                 Ginger oil 
                 Olive oil 
                 Capsaicinoids 
               
               
                 blood flow 
                 Camphor oil 
                   
                 Caffeine 
               
               
                   
                 Pine oil 
                   
                 Benzyl nicotinate 
               
               
                   
                 Oregano oil 
                   
                 Nonivamide 
               
               
                   
                 Black pepper oil 
                   
                 Nicobexil 
               
               
                   
                 Rosemary oil 
                   
                 Methyl salicylate 
               
               
                   
                 Savin oil 
               
               
                   
                 Vetiver oil 
               
               
                   
                   Eucalyptus  oil 
               
               
                   
                 Turpentine oil 
               
               
                   
                 Camphor 
               
               
                   
                 Silver fir oil 
               
               
                   
                 Cinnamon oil 
               
               
                 Immuno- 
                 Camphor oil 
                 Extracts from  Stipites   
               
               
                 modulating 
                 Cinnamon oil 
                 
                   Dulcamarae 
                 
               
               
                   
                 Lemongrass oil 
                 Viola tricolor 
               
               
                   
                 Melissa oil 
                 Similax species 
               
               
                   
                 Niaouli oil 
                 
                   Phytolacca americana 
                 
               
               
                   
                 Oregano oil 
                 
                   Glycyrrhiza glabra 
                 
               
               
                   
                 Patchouli oil 
                 Mistletoe extract 
               
               
                   
                 Tea tree oil 
                 
                   Bryonia alba 
                 
               
               
                   
                 Thyme oil 
                   Echinacea  extract 
               
               
                   
                 Frankincense oil 
               
               
                 Alleviating 
                 Lavender oil 
                 
                   Melilotus officinalis 
                 
                 Bufexamac 
               
               
                 itching 
                 Manuka oil 
                 
                   Ruscus amleatus 
                 
                 Synthetic tannins 
               
               
                   
                   
                 Fructus Capsici 
                 Glycyrrhetinic acid 
               
               
                   
                   
                 Capsicum (capsaicin) 
               
               
                   
                   
                 Borage oil 
               
               
                   
                   
                 Avocado oil 
               
               
                   
                   
                 Evening primrose oil 
               
               
                   
                   
                 Dog rose oil 
               
               
                   
                   
                 Tannins, e.g. from 
               
               
                   
                   
                 
                   Quercus 
                 
               
               
                   
                   
                   Hamamelis  extract 
               
               
                 Keratolytic 
                   
                 
                   Mahonia aquifolium 
                 
                 Vitamin A acid 
               
               
                 Antipsoriatic 
                   
                   
                 Urea 
               
               
                   
                   
                   
                 Salicylic acid 
               
               
                   
                   
                   
                 Tazarotene 
               
               
                 Cooling 
                 Peppermint oil 
                   
                 Menthol 
               
               
                 Antimitotic 
                   
                   
                 Colchicine 
               
               
                   
                   
                   
                 Colchicine derivatives 
               
               
                 Muscle relaxant 
                   
                   
                 Peripheral, e.g.: 
               
               
                   
                   
                   
                 Stabilizing: 
               
               
                   
                   
                   
                 Tubocurarine 
               
               
                   
                   
                   
                 chloride 
               
               
                   
                   
                   
                 Alcuronium 
               
               
                   
                   
                   
                 chloride 
               
               
                 Continuation: 
                   
                   
                 Preventing 
               
               
                 Muscle relaxant 
                   
                   
                 depolarization: 
               
               
                   
                   
                   
                 Pancuronium 
               
               
                   
                   
                   
                 bromide 
               
               
                   
                   
                   
                 Vecuronium 
               
               
                   
                   
                   
                 bromide 
               
               
                   
                   
                   
                 Atracurium besylate 
               
               
                   
                   
                   
                 Mivacurium 
               
               
                   
                   
                   
                 chloride 
               
               
                   
                   
                   
                 Rocuronium 
               
               
                   
                   
                   
                 bromide 
               
               
                   
                   
                   
                 Cisatracurium 
               
               
                   
                   
                   
                 besylate 
               
               
                   
                   
                   
                 Repolarizing, e.g.: 
               
               
                   
                   
                   
                 Suxamethonium 
               
               
                   
                   
                   
                 chloride 
               
               
                   
                   
                   
                 Reduction of elevated 
               
               
                   
                   
                   
                 skeletal muscle tone: 
               
               
                   
                   
                   
                 Dentrols 
               
               
                   
                   
                   
                 Irreversible inhibition 
               
               
                   
                   
                   
                 of neuromuscular 
               
               
                   
                   
                   
                 transmission: 
               
               
                   
                   
                   
                 
                   Clostridium 
                 
               
               
                   
                   
                   
                 
                   Botulinum 
                 
               
               
                   
                   
                   
                 Botulin and 
               
               
                   
                   
                   
                 derivatives 
               
               
                   
                   
                   
                 Cotylinum (botox) 
               
               
                   
                   
                   
                 Sodium channel 
               
               
                   
                   
                   
                 inhibitors, such as 
               
               
                   
                   
                   
                 tolperisone 
               
               
                   
                   
                   
                 Local anesthetics 
               
               
                   
                   
                   
                 Quinine sulfate 
               
               
                 Caring for 
                 Basil oil 
                   Hamamelis  extracts 
                 Spartine sulfate 
               
               
                 varicose veins 
                 Cajeput oil 
                 
                   Ruscus aculeatus 
                 
                 Digitoxin 
               
               
                   
                 Geranium oil 
                 
                   Melilotus albus 
                 
                 Heparin 
               
               
                   
                 Melissa oil 
                 Red vine leaf 
                 Ergot alkaloids, in 
               
               
                   
                 Niaouli oil 
                 
                   Aesculus 
                 
                 particular 
               
               
                   
                 Tansy oil 
                 
                   hypocastanum 
                 
                 dihydroergotamine 
               
               
                   
                 Tea tree oil 
                 
                   Melilotus officinalis 
                 
                 Diosmin 
               
               
                   
                 Lemon oil 
                   Centella  extract 
                 Flavonoid derivatives 
               
               
                   
                 Cypress oil 
                 
                   Fagopyrum 
                 
               
               
                   
                   
                 
                   esculentum 
                 
               
               
                   
                   
                 
                   Pinus maritima 
                 
               
               
                 Scale-inhibiting 
                 Borage oil 
               
               
                   
                 Evening 
               
               
                   
                 primrose oil 
               
               
                 Sedating 
                   
                 Extractum Valerianae 
               
               
                   
                   
                 Melissa oil 
               
               
                 Spasmolytic 
                 Peppermint oil 
               
               
                   
                 Camphor oil 
               
               
                   
                 Fir needle oil 
               
               
                 Vasodilative 
                 Birch oil 
                 Hawthorn extract 
                 Nitroglycerin 
               
               
                   
                 Wintergreen oil 
                   
                 Benzyl nicotinate 
               
               
                 Healing 
                 Bergamot oil 
                 Dog rose 
               
               
                 wounds 
                 Galbanum oil 
                 Shea butter 
               
               
                 Antitraumatic 
                   Geranium  oil 
                 Olive oil 
               
               
                   
                 Rose of Sharon 
                 Evening primrose oil 
               
               
                   
                 oil 
                   Arnica  oil 
               
               
                   
                 Camomile oil 
                 Avocado oil 
               
               
                   
                 Thuja oil 
                 
                   Aloe vera 
                 
               
               
                   
                   
                 Jojoba oil 
               
               
                   
                   
                 Calendula oil 
               
               
                   
                   
                 Camomile oil 
               
               
                   
                   
                   Hamamelis  extract 
               
               
                   
                   
                 Hypericum oil 
               
               
                   
                   
                 Tannins 
               
               
                   
                   
                   Calendula  extract 
               
               
                   
                   
                   Symphytum  extract 
               
               
                   
                   
                   Hypericum  extract 
               
               
                   
               
             
          
         
       
     
         [0053]    By dissolution or dispersion of the abovementioned base materials, essential oils, plant extracts and/or synthetic single substances in a microemulsion, it is possible, inter alia, to formulate the following medicaments: 
         [0054]    Medicaments for the treatment of external rheumatic pain which exhibit medicinal substances with an analgesic, antiinflammatory, hyperemia-causing and/or spasmolytic effect. 
         [0055]    Medicaments for the treatment of complex peripheral pain syndrome which exhibit medicinal substances with an analgesic, antioxidant, antiinflammatory, spasmolytic, muscle-relaxing, hyperemia-causing and/or local anesthetic effect. 
         [0056]    Medicaments for the treatment of wounds, contusions, strains, sports injuries and edemas which exhibit medicinal substances with a wound-healing, analgesic, thrombolytic, fibrinolytic, epithelizing, anticoagulant, antiinflammatory, antibacterial, antiviral, antimycotic, diuretic, skin-nourishing and/or antitraumatic effect. 
         [0057]    Medicaments for the treatment of chronic wounds which exhibit medicinal substances with an antioxidant, analgesic, antiinflammatory and/or healing effect. 
         [0058]    Medicaments for the treatment of hair loss. 
         [0059]    Medicaments for the treatment of erectile dysfunction. 
         [0060]    Medicaments for the treatment of excess secretion of sweat. 
         [0061]    Medicaments for the treatment of neuralgia which exhibit medicinal substances with an analgesic and/or local anesthetic effect. 
         [0062]    Medicaments for the treatment of diabetic neuropathy which exhibit medicinal substances with an analgesic, hyperemia-causing, alleviating of itching and/or alleviating of burning effect. 
         [0063]    Medicaments for the treatment of varicosis or phlebitis which exhibit medicinal substances with a caring for varicose veins, protecting from edema, alleviating of itching, anticoagulant, fibrinolytic, antispasmodic, diuretic, deblocking, antioxidant and/or hemolytic effect. 
         [0064]    Medicaments for the treatment of hemorrhoids which exhibit medicinal substances with a caring for varicose veins, diuretic and/or epithelizing effect. 
         [0065]    Medicaments for the treatment of acute attacks of gout which exhibit medicinal substances with an antimitotic, antiinflammatory, antioxidant and/or diuretic effect. 
         [0066]    Medicaments for the treatment of mycosis which exhibit medicinal substances with an antimycotic effect. 
         [0067]    Medicaments for the treatment of neurodermatitis and/or eczema which exhibit medicinal substances with an antiinflammatory, alleviating of itching, immunomodulating, skin-regenerating, antioxidant, astringent and/or antiallergic effect. 
         [0068]    Medicaments for the treatment of keratosis which exhibit medicinal substances with a keratolytic effect. 
         [0069]    Medicaments for the treatment of psoriasis which exhibit medicinal substances with a keratolytic, antiinflammatory, alleviating of itching, skin-regenerating and/or antioxidant effect. 
         [0070]    Medicaments for the treatment of acne which exhibit medicinal substances with a keratolytic, antibacterial, antiinflammatory, antioxidant and/or wound-healing effect. 
         [0071]    Medicaments for the treatment of viral infections which exhibit medicinal substances with an antiviral, analgesic, antiinflammatory, keratolytic and/or antioxidant effect. 
         [0072]    Medicaments for the treatment of hematomas which exhibit medicinal substances with a fibrinolytic effect. 
         [0073]    Medicaments for the treatment of rosacea which exhibit medicinal substances with an antiinflammatory and/or antioxidant effect. 
         [0074]    Medicaments for the treatment of scabies which exhibit medicinal substances with an antiparasitic and/or alleviating of itching effect. 
         [0075]    Medicaments for the treatment of degenerated skin which exhibit medicinal substances with an antiinflammatory, antimicrobial, nourishing and/or local anesthetic effect. 
         [0076]    Medicaments for the treatment of angina pectoris or chest pains which exhibit medicinal substances with a hyperemia-causing and/or spasmolytic effect and medicinal substances which interrupt pain stimuli. 
         [0077]    Medicaments for the treatment of pruritus which exhibit medicinal substances with a cooling, local anesthetizing, analgesic, antiinflammatory and/or astringent effect. 
         [0078]    Medicaments for the treatment of scars and keloids which exhibit medicinal substances which regulate connective tissue. 
         [0079]    In a particularly preferred embodiment, several medicaments based on the same microemulsions can be combined to give combination preparations. 
         [0080]    The concentration of the medicinal substances in the microemulsions results from the recommended guidelines of the therapy and the amount of microemulsion which can be handled in practice. 
         [0081]    In concrete terms, the concentration of the medicinal substance in the microemulsion can be between 0 and 100%, concentrations between 10 −8 % and 50% being preferred and concentrations between 10 −6  and 5% being particularly preferred. 
         [0082]    Medicaments according to the invention for percutaneous administration are obtained by enriching, with oxygen, these and other medicaments based on microemulsions. This enriching can take place in the preparation of the medicinal substances. 
         [0083]    The term “microemulsions enriched with oxygen” is understood to mean microemulsions which are enriched with oxygen in a suitable processing stage. Such a processing stage is represented, for example, by the atomization of the microemulsion in an oxygen-comprising atmosphere. In this connection, the oxygen content of this atmosphere is preferably greater than 25 percent by volume, particularly preferably greater than 50 percent by volume and in particular greater than 90 percent by volume. 
         [0084]    Preferably, the microemulsion enriched with oxygen exhibits an oxygen concentration of greater than 10 −3  mol/l, in particular of greater than 5×10 −3  mol/l. 
         [0085]    In order to prevent microemulsions enriched with oxygen in the preparation from re-releasing the oxygen up to the time of application, these microemulsions are preferably packaged in gastight containers. 
         [0086]    In addition, other additives to these medicaments, and to other medicaments based on microemulsions, which improve the oxygen supply of the skin, result in medicaments according to the invention. 
         [0087]    Examples of additives which improve the oxygen supply of the skin are natural oxygen carriers, such as myoglobin and/or hemoglobin, and also fluorocarbons. 
         [0088]    An enriching of the microemulsion with oxygen can also be carried out directly in the administration of the microemulsion with the help of an application system for the percutaneous administration of medicinal substances exhibiting at least one microemulsion comprising medicinal substance and a device for the atomization of the microemulsion. In this connection, enriching with oxygen directly in the administration is preferred. 
         [0089]    In such a system according to the invention, the microemulsion is preferably present in a container which is connected to an atomizing unit, a gas source under pressure being connected to the atomizing unit, and the microemulsion is atomized through the action of the pressurized gas. 
         [0090]    It is likewise possible to at times abolish the barrier function of the stratum corneum by application of a microemulsion according to the invention without medicinal substances which is enriched with oxygen and/or which exhibits an additive which improves the oxygen supply of the skin. This also succeeds by application of a suitable microemulsion without medicinal substances, for example with an application system according to the invention. The medicinal substances to be administered are then applied to the relevant part of the skin in an additional stage. 
         [0091]    On employing the system according to the invention, an oxygen-comprising propellant gas being used, the microemulsions which are applied are enriched with oxygen directly before the entry thereof into the stratum corneum. This results in an increase in the oxygen partial pressure on the tissue side of the stratum corneum and accordingly in stimulation of the cutaneous microcirculation and in improved transdermal transport of the medicinal substances. Likewise, the transdermal transport of medicinal substances can, for example, also be partly caused by an increased transmembrane pressure, here caused by the increase in the oxygen concentration on the tissue side of the stratum corneum. 
         [0092]    The use of this system is particularly suitable with medicaments which exhibit substances sensitive to oxidation and which accordingly can be enriched with oxygen only directly before application. 
         [0093]    It is possible, with an application system according to the invention, to accurately dose the dose of medicinal substance which is to be applied, through which the maximum daily dose can then also be applied. For that, a microemulsion which exhibits the maximum daily dose of one or more medicinal substances is sent into the system for the percutaneous administration of medicinal substances and is administered with this system to a patient. 
         [0094]    An additional effect of the atomizing, which can contribute to improved transdermal transport of medicaments, is the spreading effect. This is based on the fine distribution of the droplets in the atomization. As a result, the microemulsion in the form of small droplets is more effective in falling into depressions, folds and openings in the skin. 
         [0095]    The abovementioned medicaments based on microemulsions form preferred embodiments of a system for the percutaneous administration of medicinal substances in the context of this invention. 
         [0096]    The application system according to the invention for the atomizing of liquid medicaments for the percutaneous administration of medicaments is explained more fully subsequently. 
         [0097]    The implementation of the application system takes place according to the invention with the characteristics given in the patent claims. 
         [0098]    In the application system according to the invention for the atomizing of liquid medicaments for the percutaneous administration of medicaments, a precisely dosed liquid medicament, in particular a microemulsion comprising the medicinal substance, for application to the skin by means of a propellant gas, preferably highly concentrated oxygen, is squeezed under pressure through a microdosing nozzle and is as finely atomized as possible, preferably through use of a suction action established through the Venturi effect. 
         [0099]    A spectrum of droplet sizes can be generated with the microdosing nozzle of the application system, the outlet cross section of the microdosing nozzle being varied by a positionable needle point and accordingly it being possible to change the droplet size. The diameter of the droplets which can be obtained by the atomizing lies in the nanometer range, the mean droplet size measured being less than 1 μm, preferably less than 400 nm, in particular less than 300 nm. The reproducibility of the spectrum of droplet sizes with the application system can be demonstrated by noncontact measuring methods using laser optics. 
         [0100]    From the multitude of the different droplets of an atomization liquid, the individual droplet sizes and the frequency thereof can be determined using laser diffraction spectroscopy. In this connection, the monochromatic light of a laser beam is diffracted more or less strongly by the individual droplets of an atomization liquid, the photomultipliers located on a detector registering different signals and intensities. In line electronics with specific software evaluate these and calculate from this the actual droplet size distribution. 
         [0101]    All liquid medicaments prepared and to be atomized, preferably medicaments based on microemulsions, with particular rheological properties, such as, e.g., viscosity, liquid density, surface tension but in particular below a certain dynamic viscosity, can be sprayed onto the site of the skin to be treated using the application system according to the invention. 
         [0102]    Apart from highly concentrated oxygen, air, nitrogen or a noble gas (helium, argon) can alternatively be used as propellant gas. In this connection, the term “highly concentrated oxygen” is understood to mean a gas which is enriched with at least 90% by volume of oxygen. If propellant gases are used which comprise no oxygen, the microemulsion is already enriched with oxygen and/or comprises additives which improve the oxygen supply of the skin. 
         [0103]    In the atomizing, the medicament prepared is surrounded by propellant gas and mixed with this. In this connection, the propellant gas dissolves in the liquid medicament under pressure, through which a positive property of the liquid active substance stimulating the skin in connection with oxygen can be produced. 
         [0104]    A positive effect of the extremely fine atomizing is the pleasantly cooling action, because of the cold due to evaporation, of the finely atomized medicament in the percutaneous administration of medicaments. 
         [0105]    Because of the reactivity of the highly concentrated oxygen, materials which withstand oxygen are to be used for the individual components of the application system, such as, e.g., glass, special hospital-grade plastics or high-grade steel. 
         [0106]    In the atomizing of the microemulsion, it is advantageous to achieve, depending on the daily dose and body part to be treated, a volumetric flow rate of 1.5 to 5 ml/20 min or 4.5 to 15 ml/h through the outlet cross section of the microdosing nozzle. 
         [0107]    The propellant gas can be withdrawn from a gas container and can be conveyed to the application system via a hose connection. The gas container itself can be a constituent of an oxygen preparation plant (O 2  plant), in which oxygen is obtained from ambient air and is enriched in this. 
         [0108]    Alternatively, in an additional embodiment of application system and gas source, a self-sufficient gas container or a gas connection is also conceivable in a clinic. 
         [0109]    In a preferred embodiment of the invention, the application system is in the form of a self-sufficient system filled with liquid medicament and connected to a propellant gas system. 
         [0110]    The application system according to the invention for the percutaneous administration of medicinal substances, in particular of liquid medicaments based on microemulsions, is more fully explained below with reference to  FIGS. 1 ,  2  and  3 . 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0111]      FIG. 1  shows a diagrammatic representation of an application system, 
           [0112]      FIG. 2  shows an enlarged diagrammatic representation of the region of the application system according to  FIG. 1  in the vicinity of the nozzle and the operating principle thereof, and 
           [0113]      FIG. 3  shows a diagrammatic representation of an additional application system, 
           [0114]      FIG. 4  shows a diagrammatic representation of an additional application system. 
       
    
    
       [0115]      FIG. 1  shows an application system  10  in simplified diagrammatic representation of the individual components. The application system comprises a medicament reservoir  12  which is arranged in a gas reservoir  16  of the application system  10 . The medicament reservoir  12  is tapered at its end in the region  40  of the application system  10  in the vicinity of the nozzle to give a capillary. Depending on the daily dose to be administered, between 1.5 and 5 ml of a medicament  14  are located in the medicament reservoir  12 . The upper end of the medicament reservoir  12  and the gas reservoir  16  of the application system  10  are in the normal position seen to be coaxially formed and are connected to one another via a bypass line  26  or an equalizing pipe  26 . An inlet  18  for filling the medicament reservoir  12  with a medicament  14  and an inlet  20  for filling the gas reservoir  16  with a propellant gas are likewise located at the upper end. The gas reservoir  16  of the application system  10  is connected via a hose connection  22  to a gas container  24 . In the region  40  in the vicinity of the nozzle, the application system  10  has the form of a solid of rotation with a cross section tapering in the direction of the nozzle outlet  50 . The medicinal substance reservoir  12  connects with its tapered end to the atomizing nozzle  30 , which is arranged inside the nozzle head  28 . The nozzle head  28  exhibits, along its axis of rotation, openings  29  via which the gas reservoir  16  is connected flow wise with the surroundings. A needle  32  carried in the upper part of the gas reservoir  16  projects into the atomizing nozzle  30  and narrows the annular cross section thereof. The needle can be vertically positioned by turning a knurled head  34  and the narrowing of the cross section of the atomizing nozzle  30  can thereby be adjusted. 
         [0116]    The manner of operation of the application system  10  represented in  FIG. 1  for the atomizing of a prepared medicament for the percutaneous administration of medicaments is more fully described below. 
         [0117]    Depending on the size of the area of the body part to be treated, the medicament reservoir  12  is filled, via the medicament reservoir inlet  18  of the application system  10 , with a precisely dosed liquid medicament  14 , in particular a liquid medicament based on a microemulsion, preferably from 1.5 to 5 ml. 
         [0118]    For the atomizing of the liquid medicament  14 , the gas reservoir  16  is continuously filled with propellant gas, preferably oxygen, through which an excess pressure builds up in the closed gas reservoir  16 . The propellant gas is withdrawn from the gas container  24  and conveyed to the application system  10  under a predetermined pressure, in the example approximately 2 bar. For this, the gas reservoir  16  is connected via a hose connection  22  to a gas connection  20  of the application system  10 . 
         [0119]    The propellant gas is transported, by the excess pressure in the gas reservoir  16 , up to the outlet  50  of the atomizing nozzle  30  (microdosing nozzle). Since the gas reservoir  16  of the application system  10  in the region  40  in the vicinity of the nozzle has the form of a solid of rotation with a cross section tapering in the direction of the nozzle outlet  40 , the propellant gas is accelerated by the excess pressure in the gas reservoir  16  in the flow direction. The dynamic pressure appearing inside the gas reservoir  16  as a result of the narrowing in the cross section is diverted via a bypass line  26  to bring about the advance of the liquid medicament  14  in the medicament reservoir  12 , the dynamic pressure squeezing the liquid medicament through the atomizing nozzle  30 . A uniform advance is provided by this. 
         [0120]    The end of the medicament reservoir tapering in the region  40  in the vicinity of the nozzle inside the gas reservoir  16  is shaped in such a way that the liquid medicament is prevented from breaking off. 
         [0121]    The openings  29  inside the nozzle head  28  guarantee that the propellant gas accelerated in the direction of the tapering solid of rotation  16  flows around the atomizing nozzle  30  up to the outlet  50  of the nozzle head  28 . 
         [0122]    Having arrived at the outlet  50  of the atomizing nozzle  30 , the liquid medicament is sucked in by the negative pressure appearing in the outlet (Venturi effect) and is at the same time atomized. 
         [0123]    In the atomizing, the prepared medicament  14  is surrounded by the propellant gas and is mixed with this. In this connection, the propellant gas dissolves in the liquid medicament  14 . This results in a strengthened effect of the liquid medicament  14  on the microcirculation, in particular in a liquid medicament based on microemulsions, which can result in percutaneous administration of medicinal substance. The droplet size diameter in the atomizing of the liquid medicament  14  can be varied via the needle  32  inside the atomizing nozzle  30 , by finely positioning the needle  32  by turning the knurled head  38 . If the atomizing nozzle  30  is completely closed by the needle  32 , so that the mass flow of the liquid medicament  14  through the atomizing nozzle  30  is prevented, the atomizing of the medicament comes to a standstill. Then simply propellant gas flows through the outlet  60  of the nozzle head  28 , because of the openings  29  arranged inside the nozzle head  28  along the atomizing nozzle  30 . 
         [0124]    On the other hand, in an additional embodiment not represented, a nozzle with a predetermined internal diameter without an adjusting needle can be used if through this the desired droplet profile is already achieved. 
         [0125]      FIG. 2  shows the operating principle of the atomizing represented diagrammatically in simplified form in  FIG. 1 , the region  40  of the application system  10  in the vicinity of the nozzle being represented for clarification on an enlarged scale. In this connection, the arrows indicate the direction of flow of the gas. 
         [0126]      FIG. 3  shows an additional exemplary embodiment of an application system  70  in cross section. The application system  70  comprises a medicament reservoir  12  which is surrounded by a gas reservoir  16  of the application system  70 . The medicament reservoir  12  is, at its end in the region of the application system  70  in the vicinity of the nozzle, shaped or tapered to give a capillary. Depending on the daily dose to be administered, between 1.5 and 5 ml of a medicament  14  are located in the medicament reservoir  12 . The medicament reservoir  12  and the gas reservoir  16  of the application system  70  are formed coaxially and are connected to one another via a bypass line  26 . A medicament reservoir inlet  18 , for filling with a medicament  14 , and a gas reservoir inlet  20 , for filling the gas reservoir  16  with propellant gas, are located on the upper end of the application system  70 . Both inlets can be closed by caps, not shown. 
         [0127]    The medicament reservoir inlet  18  is shaped in such a way that the liquid medicament  14  can in no case reach the bypass  26  and accordingly run out from the application system  70 . In order to prevent this, the bypass end  27  was shaped in such a way that it projects far into the inlet line of the medicament reservoir  12 . 
         [0128]    The gas reservoir  16  of the application system  70  is connected via a hose connection  22  to a gas container  24 . In the region in the vicinity of the nozzle, the application system  70  has the form of a solid of rotation with a cross section tapering in the direction of the nozzle outlet  50 . The medicinal substance reservoir  12  connects with its tapered end to the atomizing nozzle  30 , which is arranged inside the nozzle head  28 . The nozzle head  28  exhibits, along its axis of rotation, recesses  29  so that the gas reservoir  16  is connected flow wise with the surroundings. A needle  32  carried in the upper part of the application system projects into the atomizing nozzle  30  and narrows the annular cross section thereof. The needle  32  can be positioned vertically by turning the adjustable screw (knurled screw) arranged in the knurled head  34  and through this the narrowing in cross section of the atomizing nozzle  30  can be adjusted. 
         [0129]    The manner of operation of an additional application system  70 , represented in  FIG. 3 , for the atomizing of a prepared medicament for the percutaneous administration of medicaments is described more fully below. 
         [0130]    Depending on the size of the area of the part of the body to be treated, the medicament reservoir  12  is filled, via the medicament reservoir inlet  18  of the application system  70 , with a precisely dosed medicinal substance  14 , in particular in a microemulsion, preferably from 1.5 to 5 ml. 
         [0131]    For the atomizing of the liquid medicament  14 , the gas reservoir  16  is continuously filled with propellant gas, preferably oxygen, through which an excess pressure builds up in the gas reservoir  16 . The propellant gas is withdrawn from a gas container  24  and conveyed to the application system  70  under a predetermined pressure. For this, the gas reservoir  16  is connected via a hose connection  22  to a gas connection  20  of the application system  70 . 
         [0132]    The propellant gas is transported, by the excess pressure in the gas reservoir  16 , up to the outlet  50  of the atomizing nozzle  30  (microdosing nozzle). Since the gas reservoir  16  of the application system  70  in the region  40  in the vicinity of the nozzle has the form of a solid of rotation with a cross section tapering in the direction of the nozzle outlet  40 , the propellant gas is accelerated by the excess pressure in the gas reservoir  16  in the flow direction. The dynamic pressure appearing inside the gas reservoir  16  as a result of the narrowing in the cross section is diverted via a bypass line  26  to bring about the advance of the liquid medicament  14  in the medicament reservoir  12 , the dynamic pressure squeezing the liquid medicament through the atomizing nozzle  30 . A uniform advance is provided by this. 
         [0133]    The end of the medicament reservoir  12  inside the gas reservoir  16 , which end is shaped in the region in the vicinity of the nozzle as an internal capillary, is shaped in such a way that the liquid stream  14  is prevented from breaking off. The recesses  29  inside the nozzle head  28  guarantee that the propellant gas accelerated in the direction of the tapering solid of rotation  16  flows around the atomizing nozzle  30  up to the outlet  50  of the nozzle head  28 . 
         [0134]    Having arrived at the outlet  50  of the atomizing nozzle  30 , the liquid medicament is sucked in by the negative pressure appearing in the outlet (Venturi effect) and is at the same time atomized. 
         [0135]    The droplet size diameter in the atomizing of the liquid medicament  14  can be varied via the needle  32  inside the atomizing nozzle  30 , by finely positioning the needle  32  by turning the knurled screw  36  arranged in the knurled head  38 . If the atomizing nozzle  30  is completely closed by the needle  32 , so that the mass flow of the liquid medicament  14  through the atomizing nozzle  30  is prevented, the atomizing of the medicament comes to a standstill. Then simply propellant gas flows through the outlet  60  of the nozzle head  28 , because of the recesses  29  arranged inside the nozzle head  28  along the atomizing nozzle  30 . 
         [0136]    The conicity of the needle  32  is more strongly developed in comparison with the conicity of the atomizing nozzle  30  for the purposes of a broader atomizing or a broader atomizing angle. 
         [0137]    A broader atomizing angle can furthermore be pursued by the incorporation in the nozzle head  28  of a helix-producing means. 
         [0138]    According to an additional embodiment—shown in FIG.  4 —the medicament reservoir is combined on its upper side directly with the gas source and accordingly has an additional inlet. In this connection, the Venturi formation of the nozzle can be dispensed with if this appears advisable. If, however, Venturi atomizing nozzle is used, a gas supply arrangement corresponding to  FIG. 2  is provided on the outside of the nozzle. A gas reservoir can thus be dispensed with except for the region of the nozzle, if only a gas supply in the region of the nozzle is provided, as is represented in  FIG. 4 . 
         [0139]    Microemulsions and the preparation thereof are described below from examples, which microemulsions can in the context of this invention be enriched with oxygen, for example in the administration in the application system according to the invention. These examples are not to have a limiting effect. 
       Example 1 
     Manufacture of a Water-in-Oil Microemulsion (I) 
       [0140]    5 g of Tween® 80 are mixed with 10 g of Span® 20 and 5 g of ethanol, and 75 g of isopropyl myristate are added. 5 g of water are added dropwise to this mixture with stirring. This gives 100 g of a water-in-oil microemulsion (I). 
       Example 2 
     Manufacture of a Water-in-Oil Microemulsion (II) 
       [0141]    14 g of Span® 20 are mixed with 21 g of Synperonic® PEL 101.60 g of isopropyl palmitate are added thereto. 5 g of water are added dropwise to this mixture with stirring. This gives 100 g of a water-in-oil microemulsion (II). 
       Example 3 
     Manufacture of an Oil-in-Water Microemulsion (III) 
       [0142]    4 g of Tween® 80 are mixed with 12 g of Synperonic® PEL 101.5 g of isopropyl myristate are added thereto. 79 g of a water/polypropylene glycol (1:2) (weight ratio) mixture are added to this mixture with stirring. This gives 100 g of an oil-in-water microemulsion (III). 
       Example 4 
       [0143]    Preparation of a medicament with the medicinal substance procaine, for the local combating of pain, based on an oil-in-water microemulsion: 2 g of procaine chloride are dissolved in 5 ml of water. The solution is added to 93 g of the microemulsion III with stirring. This gives 100 g of the medicament. 
       Example 5 
       [0144]    Preparation of an additional medicament with the medicinal substance procaine, for the local combating of pain, based on a water-in-oil microemulsion: 
         [0000]    2 g of procaine chloride are dissolved in 5 g of 0.01M NaOH. The solution is added dropwise with stirring to 93 g of the microemulsion I. This gives 100 g of the medicament. 
       Example 6 
       [0145]    Preparation of a medicament with the medicinal substance lidocaine, for the local combating of pain, based on a water-in-oil microemulsion: 2 g of lidocaine are dissolved in 98 ml of the microemulsion II. This gives 100 g of the medicament. 
       Example 7 
       [0146]    Preparation of a medicament with the medicinal substance diclofenac, for the local combating of painful inflammation, based on a water-in-oil microemulsion: 
         [0000]    2 g of lidocaine, 2 g of diclofenac and 0.05 g of capsaicin are successively dissolved in 95.95 g of the microemulsion (II). This gives 100 g of the medicament.