HK1116666B - Anhydrous multiphase gel system - Google Patents

Description

The present invention relates to a topical composition in the form of a water-free multiphase gel system.

The most diverse topical compositions are known to the present state of technology.

Creams are emulsions that contain a dispersed phase and a dispersive agent.The main difference is between water-in-oil and oil-in-water emulsions, depending on the type of emulsifier used.

Many users of creams find their ease of distribution and the fact that creams do not feel sticky and greasy on the skin particularly advantageous.

However, a disadvantage of creams is that they have only a small occlusion, which hydrates the horn layer of the skin and allows it to absorb three to five times its weight in water, making it more permeable.

The use of creams as carriers of active substances is also limited, as the water essential to lotions greatly limits or even excludes the absorption of hydrolysis sensitive substances.

Ointments, on the other hand, are usually semi-solid forms of fat-based dosage, suitable for external application. One type of ointment is anhydrous hydrocarbon ointment (fat ointment), which contains straight or branched hydrocarbons with chain lengths from C16 to C30 and can also contain cyclic alkanes. A typical formulation contains liquid hydrocarbons (mineral oils and liquid paraffins) mixed with hydrocarbons with longer alkyl chains (medium chain lengths of about 35 to 50 carbon atoms, usually n- and iso-paraffins) with high melting points, for example, hard petroleum jelly and wax.

The advantage of these anhydrous compounds is that they have a high occlusion on the skin.

However, the disadvantage is that ointments are usually very sticky and greasy, which causes many users to feel uncomfortable when they are applied and they are not easily distributed on the skin.

Furthermore, the applicability of these anhydrous ointments as a release system for topical active substances is limited because many active substances have a relatively poor solubility in a hydrocarbon ointment, which limits the incorporation of these substances into these topical systems and often does not allow them to be used in an effective concentration.

To a certain extent, the solvent volume available for an active substance in the hydrocarbon ointment can be increased by processing the ointment bases with solvents which are miscible with hydrocarbons, such as isopropylmyristat, but this only increases the solubility of active substances in the phthalates which are soluble in solvents which are miscible with hydrocarbons.

Err1:Expecting ',' delimiter: line 1 column 527 (char 526)

Another important aspect that determines the quality of a topical formula is that it causes a high degree of penetration of the cosmetic, nursing and/ or therapeutic components contained in it into the skin.

It is known that penetration can be increased by the use of penetration enhancers. For example, substances that solvate the polar components of skin lipids, such as water, dimethyl sulfoxide (DMSO) and ethanol, work by increasing the resulting volume of the lipid layers of the skin for both hydrophilic and lipophilic active substances promoting penetration. Substances that interact with the unpolar components of skin lipids can affect the microfluidity of the membranes and thus improve penetration. These include isopropylmyrostat, isopropyl sorbitate and oilseed oil. Alcohol can directly penetrate into the substrate, often increasing the penetration of a substance such as propylene glycol, glycol giddol and lipolymers, which also improve the active substance.

In most cases, there is an acceleration of penetration, which is mainly explained by the following mechanisms: most often, the vehicle interacts with the intercellular lipids in the stratum corneum, which can either lead to lipid fluidization or even release some lipid fractions from the stratum corneum. Interactions with the lipids are possible, depending on the property of the vehicle, with the polar head groups and/or with the lipophilic fatty acids of the lipids.

In addition to the penetration of vehicles, the increased hydration of the stratum corneum under occlusive conditions must also be taken into account and, as described above, the hydrocarbon ointments known to the art exhibit a strong occlusion.

If an active substance has only a low propensity to pass from the topical application to the skin, the composition must be modified to achieve optimal dermal availability.

Err1:Expecting ',' delimiter: line 1 column 504 (char 503)

According to the invention, the problem is solved by providing a composition in the form of an anhydrous multiphase gel system consisting of an outer lipid matrix and a polymer-gelled inner phase, characterised by the fact that the lipid phase contains skin-tolerant lipid, further characterised by boiling the soluble polymers or polymer mixtures by means of a source containing OH groups, further characterised by the fact that the source still contains carbon dioxide diester or mixtures of carbon dioxide diester available by (a) Fusion of the lipid phase to form a liquid lipid phase; (b) Mixing and homogenization of soluble polymers or polymer mixtures to form a polymer phase to be dispersed, including OH-containing source materials and further carbon dioxide esters or mixtures of carbon dioxide esters;

The system of the invention is preferred where the lipid phase contains skin-tolerant lipids.

It is particularly desirable that lipids are selected from petrolatum, paraffin, microcrystalline wax, squalene, cetylstearyloctanoate, ethylleucate, glyceryltricaprylate/caprate, myristylmyristat, propylene glycoldicaprate, cetyl ester, isopropylmyrisate, isopropyl palmitate, mono-, di- and triglycerides, ethoxylated glycerol, polyethylene glycol esters, sorb esters, hard fatty acids, hard fatty acids (NovatabatTM), dibutyl dibasic, ethyl isoleucate, polyethylene glycol-3 acetate (Camodol), whereby ethyl isopropyl isocetyl isocetyl acetate, Oxyethyl isoleucate (Camol) is a mixture of waxy acids, such as polyethylene glycol, or its derivatives, such as CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP, CDP

It is also particularly preferable that the cellulose derivatives are hydroxypropyl cellulose, carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose and their derivatives or mixtures.

In particular, it is also preferable that the acrylate polymers are cross-linked acrylate polymers.

The source material should preferably be single to triple aliphatic alcohols with a chain length of up to 5 carbon atoms or mixtures thereof.

It is also particularly desirable that the aliphatic alcohols of equal value are selected from ethanol, n-propanol and isopropanol or a mixture thereof.

In addition, the invention prefers that the polyoles are selected from glycerol, propylene glycol and 1,2-pentandiol or a mixture thereof.

It is particularly preferable that the carbon dioxide esters are selected from the group of ethylene carbonate, propylene carbonate and other homologues of ethylene carbonate and mixtures thereof.

It is furthermore preferable that the starting product continues to contain diethylene glycol monoethylene ether, polyoxylated caprylic caprylic acid glycerides, dimethyl isosorbide and/or other pharmaceutically compatible solvents or mixtures thereof.

A system according to the invention, with the lipid phase and/or the polymer phase containing active components, is particularly preferable.

It is also preferable that the lipid phase and the polymer phase contain different active ingredients, in particular that the active ingredients are selected from skin care products, skin colouring products, UV protectors, pharmaceutical active substances or combinations thereof.

For example, preferred active ingredients are selected from polydocanol, synthetic tannins, antiseptics such as chlorhexidine and triclosan, antibiotics such as fusidic acid, erythromycin, tetracycline, clindamycin, peptidine antibiotics, antifungals such as imidazold derivatives, terbenafin, cyclopirox, salicylic acid, zinc pyrithione, topical corticosteroids such as methylprednisolone, retroxydrites, clobetasone, mometasone fluorate, topical acids such as tacrolimus and pteroclolimus, oligonucleotides used for the treatment of siRNA analogues and antibodies, ribosomal antibodies, macronutrients such as cyclohexyl, phenylalanol, phenylalanol, and other non-soluble substances such as vitamin B3, and their extracts (such as extracts from fruit oils, citronella, and other essential oils, and extracts from plant extracts such as citronella, and other aromatic oils, and extracts from natural products such as citronella, and other aromatic oils, and extracts from plant extracts such as citronella, and other aromatic oils, and aromatic oils, and other aromatic oils, and minerals, and minerals, and minerals, and minerals, and minerals, and minerals, and minerals, and minerals, and minerals, and minerals, and minerals, and minerals, and minerals, and minerals, and minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals, minerals

It is particularly preferable to use the active substance together with a solubiliser.

A preferred system of the invention shall continue to contain one or more additives useful for a topically applicable composition.

The present invention also relates to the use of a system to produce a pharmaceutical composition for application on the skin, mucous membranes and/or wound surfaces.

The use is preferable for the manufacture of a human or veterinary medicinal product, i.e. for use in humans and animals.

A further subject of the present invention is a method for the preparation of a composition in the form of an anhydrous multiphase gel system consisting of an outer lipid matrix and a polymer-gelled inner phase, characterized by the fact that the lipid phase contains skin-tolerant lipids, further characterized by boiling the soluble polymers or polymer mixtures by means of a source containing OH groups, further characterized by the fact that the source still contains carbon dioxide diester or mixtures of carbon dioxide diester, and further characterized by the fact that the source still contains carbon dioxide diester or mixtures of carbon dioxide diester. (b) mix and homogenise soluble polymers or polymer mixtures to form a polymer phase to be dispersed, the polymer phase comprising the source materials containing OH groups and furthermore carbon dioxide esters or mixtures of carbon diesters;

The preferred method is to add an active substance to the polymer phase, the lipid phase or both.

Surprisingly, the compositions of the invention were found to have particularly beneficial properties, with an occlusion comparable to that of a grease ointment and the positive application properties of a cream, such as a pleasant skin sensation and easy distribution on the skin.

Furthermore, the compositions of the invention have been shown to be particularly suitable as topical vehicles for a wide variety of classes of substances.

The compositions of the invention allow the incorporation of a wide variety of classes of substances in effective amounts. The active substance can be incorporated either into the outer lipid matrix or into the gel-dispersed phase provided by a solution reservoir. Furthermore, different active substances can be contained in a composition of the invention by being incorporated together into a phase or distributed to the two phases of the system.

The penetration of the cosmetic, nursing and/or therapeutic substances contained in the composition of the invention into the skin has also proved to be highly beneficial.

These surprising properties of the compositions of the invention are obviously due to the formation of a stable multiphase gel system.

The advantage of such compartmentalization in the form of a coherent lipid phase and a gel-like dispersed phase which forms a reservoir has been demonstrated, for example, by the fact that the composition of the invention is particularly suitable as a solvent for hydrophobic active substances which are poorly soluble or practically insoluble in hydrocarbons at effective concentrations or which, due to their sensitivity to hydrolysis, cannot come into contact with water (e.g. TIMS (e.g. tacrolimus, pimecrolimus, ascrolimus), corticosteroids and hormones, antibiotics). This has been demonstrated by means of an induced contact matrix.

In particular, the composition of the invention is advantageous in that it allows the stable incorporation of non-aqueous solvents such as propylene carbonate, propylene glycol, glycerin in the system up to concentrations of 30% and the absorption of ethanol and other short-chain alcohols up to 25%.

This provides active substances with a much larger solvent reservoir compared to the state of the art known topical systems with comparable application characteristics.

A major advantage of the multiphase gel composition of the invention is therefore the effective solubilization of hard-soluble active substances, which is usually not possible in conventional hydrocarbon ointments at effective concentrations.

It has also been shown that the special properties of the system of the invention improve the dermal administration of active substances which show only a slight tendency to penetrate the skin from a composition when solvent intermediates or solvent mixtures are used, compared with systems known at the present stage of the technology.

However, according to the state of the art, the use of solvent intermediates or solvent mixtures that increase the saturation solubility of an active substance in the formulation is limited in the case of creams and hydrocarbon ointments known to the state of the art, since only limited amounts of penetration enhancers can be incorporated into the systems without dramatically reducing the stability of the system.

This property was observed in particular when the solvent and active substance were introduced into the internal phase of the system, which is present as a discrete compartment in the composition of the invention.

The system of the invention, on the other hand, creates a separate solvent compartment containing penetration enhancers and active substance in high concentrations and close proximity, which leads to a better solubility of the active substance itself in the system and consequently also to better penetration through the skin.

It is assumed that this increases the concentration gap of the active substance, which at the same time increases the rate of penetration, so that the addition of the penetration enhancers in the system of the invention results in an increased concentration of the active substance in deeper layers of the skin, since these substances in turn diffuse into the skin and reduce the barrier function of the cornea.

The penetration can be increased by choosing the type and amount of solvent, depending on the active substances used and the concentration and loading location of the system.

Thus, the systems of the invention have both essential aspects of enhancing the penetration of active substances into the skin, occlusion effect and penetration enhancement by skin-tolerant solvents that transport the incorporated active substances into the skin.

For the purposes of this invention, a multiphase gel system is a system consisting of two or more phases.

Err1:Expecting ',' delimiter: line 1 column 111 (char 110)

Err1:Expecting ',' delimiter: line 1 column 84 (char 83)

Err1:Expecting ',' delimiter: line 1 column 71 (char 70)

The use of the present invention in the manufacture of water-free solvents is not exclusive to the use of water in the manufacture of other solvents.

The polymers which can be cooled by OH groups can be selected from acrylate polymers or mixtures thereof. The Commission also concluded that the measures at issue in the present case are not imputable to the State and that the measures in question are not liable to affect trade between Member States.

In the context of the present invention, short-chain alcohols refer to one to three-value aliphatic alcohols with up to five carbon atoms.

All steps of the process for the production of the compositions of the invention can be carried out by techniques known to the average professional, such as mixing and homogenising the components in step (b) to produce the dispersed polymer phase by conventional stirring systems and homogenisers.

The viscosity of the polymer phase produced can be adjusted by, for example, heating.

In addition to the components already listed, the composition of the invention may continue to contain one or more additives useful for topical applications, such as colours, fragrances, preservatives and absorption enhancers.

The following are examples of the invention and present research results showing the properties and advantages of the compositions of the invention, also in comparison with conventional topical systems.

Figures 1 to 5 illustrate the experimental results.

It shows: The number of employees Results of a human skin application study (measured: general skin sensation) as shown in Example 7Figure 2 Results of a human skin application study (measured as effect on lesions) as shown in Example 7Figure 3 Results of a human skin application study (measured: total effect) as shown in Example 7Figure 4 Results of an induced contact dermatitis in mice (measured: ear weight) as shown in example 8Figure 5 Results of an induced contact dermatitis in mice (measured by peroxidase) as shown in example 8

The following examples explain the invention without limiting it, and it is expressly claimed that the beneficial effects in the following examples are intended to be illustrative only and not to be exhaustive.

Examples 1 to 5

The following table 1 shows sample formulations (ad 100 g) for the aqueous multiphase gel system of the invention based on semi-solid lipid formulations with gelled mixtures of propylene carbonate and propylene glycol or ethanol. Table 1 shows formulations according to the invention using examples 1 to 5. The first column gives the ingredients used in the manufacture. The second column gives the limits in which the respective ingredient can be present in the finished formula in quantities (in % by weight). Columns 3 to 7 represent selected formulations (in quantities, respectively, in examples 3 and 4 (fifth and sixth)), containing the active ingredients of the invention as asbestos substrate.

Table 1 thus shows that the amounts of the individual constituents are highly variable in order to obtain the composition of the invention with the beneficial properties.

It is therefore easy for the practitioner to establish, with the help of fewer attempts, a formula which also dissolves very hardly soluble active substances in the inventive composition in solution to ensure their application on or through the skin. Tabelle 1

Ascrolimus (Wirkstoff)	0 - 1,0	-	-	1,0	0,1	-
Carbomer Copolymer (Pemulen TR-1/TR-2)	0,1 - 0,6	0,45	0,3	0,15	0,15	0,40
Carbomer (Carbopol 980)	0 - 0,3	0,17	-	-	-	0,17
Hydroxypropylcellulose (Klucel HF)	0 - 0,4	0,12	-	-	-	-
Hydroxyethylmethylcellulose (Tylopur MH 1000)	0 - 0,4	-	0,15	-	-	-
Propylencarbonat	5,0 - 15,0	14,75	9,775	5,0	5,0	-
Ethanol 96%ig	0 - 20	-	-	-	-	19,0
Propylenglykol	5,0 - 15,0	14,75	9,775	5,0	5,0
Diisopropylamin	0 - 0,1	0,075	0,024	-	-	0,05
Weißes Vaselin	40,0 - 80,0	47,685	57,976	65,85	66,75	59,95
Paraffinöl, dickflüssig	0 - 10,0	10,0	10,0	10,0	10,0	10,0
Cyclomethicone	0 - 10,0	3,0	-	-	-	3,0
Bienenwachs (Cera Alba)	0 - 5,0	2,0	5,0	5,0	5,0	2,0
Hartparaffin	0 - 7,0	7,0	7,0	5,0	5,0	7,0
Mikrokristallines Wachs	0 - 5,0	-	-	3,0	3,0	-

Example 6 General manufacturing technology for an EDRS

The following diagram shows the general manufacturing technology for the EDR system of the invention. The active substances to be introduced into the system can, depending on the intended purpose, be introduced into either the lipid or polymer phase or both phases. The temperatures at which the individual manufacturing steps take place can also have an influence. The lipids must almost always be melted down, while the polymer phase is already sufficiently fluid under particular conditions of composition so that a further liquid can remain, for example by heat.

Example7 Human skin study

The following describes a study of the tolerability of the composition of the invention compared with two state-of-the-art formulations. The compositions for the topical treatment of atopic dermatitis were used over a period of one week on a single target lesion. The series of trials was conducted as a double-blind, randomized, single-center two-period crossover study.

18 subjects (male and female, Caucasian type, aged 19-41 years, with at least two 4 cm2 lesions) were enrolled by the end of the study; no statistical distribution was made.

Three preparations were used:

Vehicle A: grease (state of the art) Vehicle B: water-free multiphase gel system (EDRS) of the inventionVehículo C: water-in-oil preparation (state of the art)

The measured values:

Subjects were asked to rate skin sensation including the appearance of itching on a questionnaire, with a range of 0 to 100.2.Subjects were asked to indicate the overall impression of the treatments.3.Subjects' comments of all kinds, spontaneous or on demand (any discomfort, any discomfort, skin irritation, pimple/ rash, skin warmth, cold sensation, stinging, tingling, burning, itching, skin tension, pain, etc.) were collected.4.The overall severity of the lesions was assessed (estimated by the physician: severity of erythema, edema/ population, nausea/ chest pain, coronary artery disease, lichenitis, blood pressure, and was assessed on a 4-P, negative or positive cardiac-export documentation) and was measured by a photoreportation.5.

Results:

The results are shown in Figure 1 and the x-axis shows the mean (bars) and the standard deviation (line) in mm. Subjects were examined for the following parameters: overall impression (GE), penetration into the skin (EH), stiffness (KL), oilyness (FE), itching during treatment (JB), itching upon application (JA), skin stiffness (HT), moisture (FT), odor (GR). It is clear that the composition of the invention (vehicle B) is in most cases comparable to the water-in-oil formulation (vehicle C), which is generally considered to be particularly pleasant on the skin.The results for the three areas of skin irritation, pimple/ rash and itching are shown in Figures 2a to 2c. The results for the size of skin irritation (Figure 2a), pimple/ rash (Figure 2b) and itching (Figure 2c) are shown in Figure 2a. The scoring framework includes a scale (axis) of 0 to 12 and takes into account the sensitivity of the acids and their intensity (1 - 3).The x-axis shows two bars for vehicles A (A), B (B) and C (C), each with the left column indicating sensation before treatment and the right column indicating sensation after treatment with the respective vehicle. It appears that the EDRS (vehicle B) of the invention has achieved significantly better results in all cases, particularly in the treatment of skin irritation and itching.Ad 4. The assessment of the total lesions is shown in Figure 3.The left columns of the pairs of columns show the severity before the treatment, the right columns show the severity of the lesions after the treatment with the respective vehicle, and it is clear that vehicle B (EDRS of the invention) showed the best effect.Ad 5. Subject 1: Bronchitis, unrelated to treatment during the study Subject 2: Urticaria of low intensity, far from the lesions, previously observed in Subject 8: Exacerbation of atopic dermatitis in the treated lesion, presumably due to vehicle C.

In conclusion, the classical water-in-oil formulation is generally preferred by the subjects, however, the EDRS (vehicle B) of the invention has significant advantages over the state-of-the-art formulas, particularly in terms of the therapeutically important properties such as itching, skin irritation and overall effect.

Example 8 DBFB-induced contact dermatitis in mice

A suitable pharmacological model for anti-inflammatory skin therapy is the 'Irritant contact dermatitis (ICD) ' model for anus, which mimics the inflammatory components of eczema. This inflammatory aspect also plays a role in allergic contact dermatitis and atopic dermatitis involving allergen-specific T cells. Therefore, a T-cell-dependent model of allergic contact dermatitis (in response to dinrofluorobol, DNFB) can be used.

Acute and chronic allergic contact dermatitis (ACD) are characterised by a type 1 dominant cytokine profile, which is why the dinitrofluorobenzol (DNFB) induced ACD model was used to assess the activity of the active substance ascrolimus (topical immunomodulator) in vivo.

The mice (NMRI) were sensitized with 0.5% DNFB on day 0 and day 1. On day 5, the mice were re-treated with 0.3% DNFB. The test products containing the active substance ascrolimus were co-applied topically in three different concentrations (0.1, 0.3, 1.0%) in a standard fat ointment and with the EDRS of the invention. After 24 h, the animals were sacrificed to measure the ear weight, elastase and peroxidase activity of ear homogenizers as a parameter for edema and granulocyte infiltration. Each experiment was repeated twice.

The results of the ear weight measurement as a measure of oedema formation show a significant reduction in the concentration-dependent induced inflammatory effects of EDRS-verum ointments compared to standard fat ointments, where no significant reduction in ear weight (y-axis = delta ear weight in mg [mg]) is observed at 1% of ascrolimus concentration compared to placebo (Figure 4).

Peroxidase activity as a measure of granulocyte infiltration (Figure 5) showed (y-axis = delta peroxidase in units per ml [U/ ml]) an equally significant concentration-dependent inhibition when ascrolimus was administered in the EDR system, whereas no significant effect was seen with the standard fat ointment.

Legend of the figures 4 and 5: The test chemical is used to determine the concentration of the active substance in the test chemical. 0,1, 0,3, 1.0% in vehicle A or B = Ascrolimus concentrations in the vehicle Neribas = base (placebo); internal standard Nerisona = standard fatty ointment with diflucorotolone pivalate (glucocorticoid); internal standard

It has been demonstrated by example that the systems of the invention (EDRS) are sufficiently stable and have a high tolerability.

Claims (18)

1. Composition in the form of an anhydrous multiphase gel system consisting of an outer lipid matrix and an inner phase gelled by means of a polymer, characterized in that the lipid phase contains lipids that are compatible with the skin, further characterized in that the polymers or polymer blends that can be swollen are swollen by means of swelling agents containing OH groups, further characterized in that the swelling agent additionally comprises carbonic acid diesters or mixtures of carbonic acid diesters, which phase can be obtained by

   a) melting the lipid phase with the formation of a liquid lipid phase,

   b) mixing and homogenizing polymers or polymer blends capable of swelling with the formation of a polymer phase to be dispersed which comprises swelling agents containing OH groups and additionally carbonic acid diesters or mixtures of carbonic acid diesters,

   c) combining the polymer phase with the liquid lipid phase and homogenizing the phases, and

   d) cold stirring the phase mixture until a solid gel-like mixed structure of the entire system is formed.
2. Composition according to Claim 1, characterized in that the lipids are selected from petrolatum, paraffin, microcrystalline wax, squalene, cetylstearyl octanoate, ethyl oleate, glyceryl tricaprylate/caprate (but not 2 compounds), myristyl myristate, propylene glycol dicaprate, cetyl esters, isopropyl myristate, isopropyl palmitate, mono-, di- and triglycerides, ethoxylated glycerides, polyethylene glycol esters, sorbitan esters, solid lipids (Novata™), dibutyl adipate, ethyl linoleate, propylene glycol isoceteth-3 acetate (crodamols), ethylhexyl cocoate, isocetyl stearate, oleyl oleate (Cetiol™), cetyl palmitate, cetyl palmitate (Cutina CP™), cetyl alcohol, oleyl alcohol, stearyl alcohol, dicaprylyl ether, oleic acid, waxes, jojoba wax, beeswax, cholesterins, polyethylene glycols, lanolin, lanolin alcohols, silicone oils and their mixtures.
3. Composition according to either of the preceding Claims 1 and 2, characterized in that the polymers involve cellulose derivatives, acrylate polymers or their mixture.
4. Composition according to Claim 3, characterized in that the cellulose derivatives involve hydroxypropylcellulose, carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose or their mixture.
5. Composition according to one of Claims 1 to 3, characterized in that the acrylate polymers involve crosslinked acrylate polymers.
6. Composition according to one or more of Claims 1 to 5, characterized in that the swelling agent is a monohydric to trihydric aliphatic alcohol with a chain length of up to 5 carbon atoms or mixtures thereof.
7. Composition according to Claim 6, characterized in that the monohydric aliphatic alcohols are selected from ethanol, n-propanol and isopropanol or mixtures thereof.
8. Composition according to Claim 6, characterized in that the polyols are selected from glycerin, propylene glycol and 1,2-pentanediol or mixtures therof.
9. Composition according to one or more of Claims 1 to 8, characterized in that the carbonic acid diesters are selected from the group: ethylene carbonate, propylene carbonate and other homologs of ethylene carbonate and mixtures thereof.
10. Composition according to one of Claims 6 to 9, characterized in that the swelling agent additionally comprises diethylene glycol monoethyl ether, polyoxylated capryl/capric acid glycerides, dimethyl isosorbide and/or additional pharmaceutically compatible solvents or mixtures thereof.
11. Composition according to one or more of Claims 1 to 10, characterized in that the lipid phase and/or the polymer phase additionally contain active components.
12. Composition according to Claim 11, characterized in that the lipid phase and the polymer phase contain different active components.
13. Composition according to Claim 11 or Claim 12, characterized in that the active components are selected from skin-care substances, skin-coloring substances, UV protectors, pharmaceutically active substances or mixtures thereof.
14. Composition according to Claim 11 or 12, characterized in that the active components are selected from polidocanol, synthetic tanning substances, antiseptics, chlorhexidine, triclosan, antibiotics, fusidic acid, erythromycin, tetracycline, clindamycin, peptide antibiotics, antimycotics, imidazole derivatives, terbenafine, ciclopirox, salicylic acid, zinc pyrithione, topical corticosteroids, methylprednisolone aceponate, clobetasol, mometasone fuorate, topical macrolides, ascrolimus, tacrolimus, pimecrolimus, oligonucleotides for gene therapy, si-RNA, ribozymes, antihistamines, immunosuppressants, cyclosporin, azathioprine, mycophenolate mofetil, anthralines, cignolin, dithranol, vitamin D3 analogs, calcipotriol, topical retinoids, urea, lactic acid, fumaric acid ester, azelaic acid, hydroquinone, benzoyl peroxide, non-steroidal antiphlogistics, sex hormones, estrogens, androgens, cytostatics, UV protectors, stilbene derivatives, plant extracts such as green tea extract, Centella asiatica extract, willow bark extract, birch extract, tea tree oil, olive leaf extract, Aloe vera extract, marigold extract, passion flower extract, Hamamelis extract, chamomile extract, bearberry leaf extract and licorice root extract, 18β-glycyrhetinic acid (Zn combination), fruit acids such as α-hydroxy acids, β-hydroxy acids, polyhydroxy acids or mixtures thereof.
15. Composition according to one of Claims 11 to 14, characterized in that the active component is introduced together with a solubilizing agent.
16. Composition according to one or more of Claims 1 to 15, characterized in that the formulation additionally comprises one or more additives useful for a topically applicable composition.
17. Method for the production of an anhydrous multiphase gel composition consisting of an outer lipid matrix and an inner phase gelled by means of a polymer characterized in that the lipid phase contains lipids that are compatible with the skin, further characterized in that the polymers or polymer blends that can be swollen are swollen by means of swelling agents containing OH groups, further characterized in that the swelling agent additionally comprises carbonic acid diesters or mixtures of carbonic acid diesters, wherein

    a) the lipid phase is melted with the formation of a liquid lipid phase,

    b) polymers or polymer blends capable of swelling are mixed and homogenized with the formation of a polymer phase to be dispersed, wherein the polymer phase comprises the swelling agents containing OH groups and additionally carbonic acid diesters or mixtures of carbonic diesters,

    c) the polymer phase is combined with the liquid lipid phase and the phases are homogenized, and

    d) the phase mixture is cold stirred until a solid, gel-type mixed structure of the system is formed.
18. Method according to Claim 17, characterized in that an active substance is added to the polymer phase, the lipid phase or both phases.