NL8102997A - PHARMACEUTICAL PREPARATION. - Google Patents

Description

. N.0. 30.2If 1! Pharmaceutical preparation. The invention relates to pharmaceutical preparations and in especially on active ingredients, which are useful for the

! pical treatment of acne. These pharmaceutical preparations and ingredients I

| parts are intended for the medicinal treatment of acne in humans.

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; ; Acne is a common inflammatory disease! in skin areas, where the sebaceous glands are the largest, most numerous, and most active. In its milder forms, it is a somewhat superficial ailment, manifested by minor blotchy irritations, in which case the usual skin hygiene is a satisfactory treatment. In the more inflammatory types of acne, a bacterial invasion occurs in or near the hair root sacs and | pustules, infected cysts and, in extreme cases, channel formation of inflamed and infected sacs. These lesions can be 15; cover a significant area and leave permanent disfiguring scars.

Acne is very common in puberty and at least 80% of teens are infected with it. It is known that facial rashes occur in many more mature juveniles can cause such psychological trauma that they find it difficult to adjust personally so that an individual then withdraws and feels sorry for themselves. The acne sufferer may be constantly aware of the easily occurring facial damage. For these reasons, a medicinal preparation and treatment is definitely of advantage and therefore the need for psychotherapy can be avoided.

To reduce the more severe forms of acne, various forms of medicaments have already been applied topically to the skin. Antibacterial soaps have been used, as have bactericidal agents such as sulfur and resorcinol. Other topical formulations individually contain benzoyl peroxide, hexachlorophene, erythromycin or neomycin sulfate as active ingredient. None of these known preparations were

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completely effective.

For example, U.S. Pat. No. 3,535,422 discloses a therapeutic composition for the treatment of acne consisting of an even dispersion of benzoyl peroxide in a liquid medium containing water and at least one organic emollient.

U.S. Pat. No. 4,056,611 describes a therapist 81 02 9 9 7 v> 2 "........ ~ Ί ................ ..... .......... ....... .....! Acne treatment for acne treatment, which consists of a stable dispersion of finely divided particles of benzoyl peroxide in a aqueous alcohol, which forms a single phase The single phase of the composition is non-fat and contains a nonionic surfactant which is soluble in the aqueous alcohol used as the carrier.

j: In U.S. Patent Application Serial No. 60,392 filed 25; July 1979, the content of which is to be regarded as inserted by its bare mention, the use of sodium dioctylsulfo | 10; succinate as a stabilizer for benzoyl peroxide formulations and the increased stability of benzoyl peroxide in a very finely divided form, as obtained when grinding in a jet mill, is described | ven.

Known peroxide preparations, which are simply finely divided peroxide-15; particles in an aqueous emulsion and certain selected emollient; parts have the drawback that if the water content of the emulsion evaporates, most of the organic emollients and large benzoyl peroxide particles remain on the surface of the skin near and in contact with the acne sites, which may cause irritation.

In addition, the use of large amounts of nonionic surfactants in such formulations, unless extremely fine peroxide particles are used, will increase the likelihood of peroxide irritation.

Due to the strong oxidizing properties of the peroxide component, the inclusion of this substance in a conventional ointment or emulsion or in combination with other active ingredients gives rise to unstable preparations which soon deteriorate unacceptably | of its keratolytic effect.

According to the invention, it has been found that a mixture on the skin of a peroxide, in particular benzoyl peroxide, and erythromycin, is particularly advantageous because they exert a statistically significant synergistic effect. Benzoyl peroxide inhibits the formation of free fatty acids in the skin primarily by deactivating extracellular acids. 35 1 of lipase (via oxidation) which is necessary for splitting triglycerides into free fatty acids and glycerol. Erythromycin lowers; Effectively, the concentration of Corynebacterium acnes (ie P. acnes) is a normal anaerobic bacterium, which is the major source of the lipase. Instead of the preferred benzoyl peroxide, other peroxides of organic acids 8102997 3 I can also be used, such as lauroyl peroxide. Instead of erythromycin, that j | erythromycin derivatives, such as erythromycin stearate or glucoheptonate, may be used instead.

These two ingredients can be applied to the skin as a mixture or can also be applied separately to the skin.

! i | | ; In the latter case, it is preferable to use the erythromycin apply to the skin immediately or shortly afterwards followed by it! | applying the peroxide. The order of application could also be reversed 1. If a mixture must first be prepared,; 10; it is best to apply it to the skin afterwards, it is best that the mixture is prepared at the time of application or that it! ! mixture is used within 24 hours.

| | The prompt use of a premix is related to the rela-; Inactive incompatibility of the two active ingredients and because of this it is recommended to include the two active ingredients in separate jars, bottles or other containers. However, as an aspect of the invention, a novel carrier for the active agent; ingredients, whereby the mixture of ingredients has surprising stability and service life at temperatures commonly used to store erythromycin solutions; in addition, the new carrier provides a more uniform dispersion of the active ingredients. ! j

The therapeutic gel preparation according to the invention must have a; ! contain sufficient amount of peroxide to be therapeutically effective; 25 and should not contain more peroxide than can be uniformly dispersed in the carrier to form a smooth-spreadable composition. From such considerations, it follows that the composition should contain at least 1 wt% and no more than 30 wt% peroxide, and that the composition preferably contains about 2.5 to 15 wt% peroxide. The peroxide component of the preparation should be very pure and be in the form of finely divided crystalline particles, preferably particles milled in a jet mill with an ! the particle size of less than 35 µm. The use of a peroxide ground in a jet mill increases the stability -35; and shelf life given to the preparation when used in combination with surfactant sodium dioctyl sulfosuccinate dust. The gel preparation according to the invention can advantageously contain a further wetting agent, such as the esters of polyols and sugars, the condensation products of epoxyethane with fatty acids, fatty alcohols, alkyl-40; long alkyl chain phenols, long chain mercaptans, am 81 0 2 9 9 7 4 y! long chain pine, polyethers and polyhydroxylated fat; | | I 1 alcohols and alkyl polyglycol ethers, in an amount from about 3 to about 6% by weight.

| ! Surprisingly, it has been found that in an aqueous-alcoholic 5 'gel as carrier the use of a peroxide and an erythromycin verifier. Bonding in combination with sodium dioctyl sulfosuccinate as surfactant gives rise to a composition which is completely stable; 1] exhibits lity with respect to the peroxide compound even if J is exposed to higher temperatures than the temperatures | 10: would normally be used in the ordinary use of the product! wait. In addition, the mixture according to the invention makes on evaporation i! | ; allows uniform delivery of the peroxide, avoiding combustion and erythema, as with other coarser preparations | 1 can occur. i I! The aqueous gel preparation according to the invention contains about 1 i! up to about 30 wt.%, preferably about 5 to 15 wt.%, peroxide, especially jet milled benzoyl peroxide having a particle size of less than 150 µm at an average particle size of less than about 35 µm. Sodium dioctyl sulfosuccinate, which acts as a surfactant and additionally for imparting the j | high stability of the composition is present in an amount of 0.1 to 2% by weight of the composition. The composition may also advantageously contain a further wetting agent in an amount of from about 1.0 to about 6.0 wt.%, And preferably from about 3 to 6 wt.%.

Further advantages and objects of the invention will become more apparent from the following description and the accompanying drawing, in which j

Fig. 1 shows a perspective view of a package containing two containers, one for each active ingredient; FIG. 2 is a section along line 2-2 in FIG. 1, FIG. 3 is a section along line 3-3 in FIG. 2, and | Figure 4 shows a perspective view of a package containing only a single jar. j j35 The mixture of the two active ingredients may be slightly on the

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! ! affected skin surfaces are stewed substantially in the same manner as would be used for powdering the face. This would apply either the pre-mix as shown in Figure 4; either of the sequentially applied separate means in 140 'may be the two containers of FIG. 1, but may also be a premix of the 810997. two means of Fig. 1, which is being prepared at the time of application. However, it is possible to dilute the mixture with a carrier which is a powder, a semi-solid carrier of creamy consistency or; a liquid, such as an aqueous emulsion, can be or with an organ 5: niseb solvent, in particular an aqueous mixture, which is used as surfactant contains sodium dioctyl sulfosuccinate.

| On a weight basis, the selected erythromycin and the selected | peroxide to be dosed in such a way that the peroxide is on the; skin is applied in an amount from about 1 to about i '; | 10 | 30 times the weight of erythromycin, preferably one! amount of peroxide from about 1 to about 5 times the amount of J of the erythromycin. In a premix composition to be applied to the skin, containing an excipient, the selected erythromyclic i i | ne to be present in an amount of 0.5 to 5.0% (w / w) and! The selected peroxide should be present in an amount of from 1.0 L to 30% (w / w). Preferred is a concentration of about 2 to about 3% of the selected erythromycin and from about 5 to about 10% of the selected peroxide.

Since erythromycin has limited solubility, alco-! Hollow or acetone is preferred as dermatological solvents although the composition is not limited to these liquids. In solution, erythromycin is subject to rapid degradation even at normal room temperature perature. The service life of such solutions can be slightly extended by refrigeration.

. An excipient or carrier which, respectively, that; preferred is an aqueous-alcoholic gel system, but liquid suspensions and emulsions as well as creams, ointments and powders are acceptable. Conventional pharmaceutical techniques can be used in formulating these conventional forms of medicinal topical preparations. For example, a premix can be placed in a conventional ointment jar or similar container fitted with a lid ! as shown in Fig. 4, as this could minimize the stability problem. The patient instruction should then include that the preparation should be stored in the refrigerator. The pot 9 will usually be in a cardboard or similar package 10.

For a commercial preparation it is best that it consists of a cardboard package 5 with a lid 6 containing two lidged containers, as shown in the accompanying drawing in fig.

40 1 to 3. One container will then only contain the erythromycin and 81 0 2 9 9 7 6! I large enough to contain all other ingredients as well j | j ten, which will be mixed with this later. The other holder will use the benzo-; yl peroxide in the form of an aqueous gel preparation already contain! | not in combination with the solvent for the erythromycin as well as the other ingredients for preparing the topical composition. Verj | ; It has been found, however, that the use of sodium di-ethyl sulfosuccinate as a surfactant imparts stability to the composition.

| The gelling agent used in the invention can be selected in terms of both type and amount such that products of different viscosities are obtained. In the preferred embodiment I of the invention, the gelling agent is so; ] I chose to have an elegantly shaped and stable gel. | : purchase. Various gelling agents can be used for the present purpose. Preferred gelling agents, however, are pure microcrystalline cellulose, colloidal magnesium aluminum silicate, | hydroxypropylmethylcellulose and the so-called hydroxylated vinyl po-; lymers, especially the polymers described in U.S. Patent 2,798,053. Hydroxylated vinyl polymers of particular interest here include those generally described as interpolymers of a monomerically monounsaturated acrylic acid and from about 0.1% to about 10% by weight, based on the total amount of monomer, of a monomeric polyether of an oligosaccharide, wherein the modified hydroxyl groups are etherified with allyl groups, the polyether containing at least two allyl ether groups per oligosaccharide molecule. Commercially available interpolymers of this type are marketed under the brand name Carbopol Φ. These are described as poly; acrylic acid mers cross-linked with about 1% of a polyallyl ether of sucrose with an average of about 5.8 allyl groups per sugar. : crose molecule. These polymers have a molecular weight on the order of 1,000,000. Such polymers are used by B.F.

Goodrich Chemical Company marketed under brand names such as Carbopol® 934, Carbopol® 940 and Carbopol® 941.

The amount of gelling agent which can be included in the compositions may vary slightly. Usually, the gelling agent will comprise from about 0.1 to about 15% by weight, and preferably from about 0.5 to about 3% by weight, based on the total weight of the finished composition.

40 As mentioned above, the simplest topical preparation is 81 02 9 9 7 7

; '"ΐ ................................ I

I a mixture of powdered benzoyl peroxide and erythromycin without any i | adjuvant but this should be applied sparingly to the skin j

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j brought. Instead of applying a premix, you can! 1 | ; one of which is first applied to the skin and then rubbed the other under light to mix both on the skin. A suitable suitable simplified preparation is the following: j

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! ! Example I

! Benzoyl Peroxide 1 - 35% (w / w) i Calcium Phosphate 63 - 98.5% (w / w) 10 | Erythromycin 0.5-5% (w / w) | These ingredients are intimately mixed with one to four years ; stewed on the affected skin surface several times a day. The preparation ; could be sold in the holder 9, as shown in Fig. 4! If a liquid formulation is desired, the following is a simplified formulation, which can be prepared and applied to the skin one to four times a day as if it were an ordinary one.

! vision lotion. It could be sold in one of the bottles, as shown in Fig. 1 with or without the cardboard package 5. Example II

20 Ethanol q.s. - 100% (w / w)

Erythromycin 0.5 - 5% (w / w)

Benzoyl Peroxide 1 - 30% (w / w)

Other examples representative of the invention include the following:

; 25 | Example III

Lotion! '

The following standing parts are placed in a first holder 7: I cw wt.%

Oxethylated cetyl stearyl alcohol 7.00 30 Cetyl alcohol 0.75

Isopropyl myristate 5.00

Butylated hydroxyanisole 0.10

Polyoxyl 40 stearate 0.25 l 1; j Deionized or distilled water 68.80 35 'Propylene glycol 3.00

Benzoyl peroxide 5.00

Acetone 10.00

Sodium dioctyl sulfosuccinate 0.10

The following component 40 is introduced as such into a second container 8, the container being large enough to store an amount of dissolved 81 0 2 9 9 7 8

... i ........................................ ...... ο I

agent, preferably ethanol or acetone, in a ratio of 3 car / 20 µg of the preparation in the container 7.

Erythromycin 2% by weight, based on the weight of | ! 5: the content of the i; container 7 I Both containers are placed in a single salable package, such as i: 5, with instructions that the contents of container 8 be delivered to the container. ; ! contents of container 7 must be added and must therefore be thoroughly cleaned 10: mixed. The vessel 8 with the erythromycin can also contain 3 cnP ethanol; per 20 g of the material in the container 7 are added. The erythromycin in ethanol solution is then added to the contents of the container; ; \ 7 and mixed thoroughly. This can be done either j '. i by the pharmacist or by the patient. The patient should apply the lotion j '15! apply to the skin one to four times a day as if it were a ordinary lotion.

! According to a variation of example III, the content of the container; of the 8 further diluted with the same solvent, so that a portion of the contents of the container 7 must first be applied to the skin and then a portion of the contents of the container 8 to form the mixture on the skin . This avoids losses due to the useful life or durability of the mixture. t Example IV; Cream; 25 The following components are placed in a first container 7:

Oxethylated Cetyl Stearyl Alcohol 15.00 wt%

Cetyl alcohol 1.25 wt

Isopropyl myristate 5.00 wt%; '!

Butylated hydroxyanisole 0.10 wt% i30 Polyoxyl 40 stearate 0.25 wt%

Deionized or distilled water 60.60 wt% propylene glycol 3.00 wt% benzoyl peroxide 5.00 wt%! Acetone 10.00% by weight | 35; Sodium dioctyl sulfosuccinate 0.10 wt%!

In the second container 8, the next component as such! the container being large enough to receive an amount of a solvent, preferably ethanol or acetone, in an amount of 3 cm / 20 g of the preparation in the container 7.

40 Erythromycin 3% by weight based on the 81 02 9 9 7 9! weight of the contents of

| the holder 7 I

; i Notes on sales and use, soj

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I as indicated in example III also apply to this cream. Since the composition has the consistency of a cream, the containers 7 and 8 must have a wide opening for mixing and removing the | cream. !

; Example V

i Gel i 10! The container 7 has the following contents: 1 l of deionized or distilled water 54.65 wt.% Colloidal bentonite 2.50 wt.% I carboxyvinyl polymer (acid form) 1.00 wt.% Sodium dioctyl sulfosuccinate 1.00 wt.% 15 'diisopropanolamine 0.75% by weight | ethyl alcohol, 200 ° 35.00 wt% butylated hydroxyanisole 0.10 wt% benzoyl peroxide (ground in the jet mill) 5.00 wt%;

The container 8 contains only the following: Erythromycin 3% by weight based on the weight of the contents of the container 7 | The comments regarding packaging in wide-opening containers and mixing immediately before use, as indicated in Example IV, also apply to this gel.

Example VI Suspension

The container 7 has the following contents: deionized or distilled water 56.97 wt.% Colloidal bentonite 1.50 wt.%! ! '! carboxyvinyl polymer (acid form) 0.25 wt% sodium dioctyl sulfosuccinate 1.00 wt% diisopropanolamine 0.18 wt%! ethyl alcohol, 200 ° 35.00% by weight i 35 butylated hydroxyanisole 0.10% by weight benzoyl peroxide (ground in the jet mill) 5.00% by weight | . i

The holder 8 contains only the following:];

Erythromycin 2% by weight based on the weight of the contents of the container 7 8102997 10 ''; i .............. ...................

The explanation regarding the use in example III

i also applies to this suspension.

1 Example VII

In each of Examples III to VI, the amount of benzo-5-yl peroxide is reduced or increased within the range of 1 to 30 yl; % by weight, based on the weight of the contents of the container 7 and! the amount of water increased or decreased proportionately. The amount of erythromycin in container 8 should be measured to correspond to one-fifth to two times the weight amount of; The benzoyl peroxide. j i: i

; Example VIII

In each of the above examples, the benzoyl peroxide j is replaced with a peroxide of another organic acid.

! | Example IX

i 15! The water is replaced in each of Examples III to VI! by acetone and / or an alkanol with a small number of carbon atoms, such as methanol, ethanol, etc.

Example X.

In each of the above examples, the erythromycin 20 is replaced with an erythromycin derivative.

These examples are given to illustrate the invention and are not to be construed as limiting it. So can

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For example, some of the above ingredients are replaced by other ingredients which are well known to those skilled in the art of dermatological preparations. Varying amounts of other ingredients or other excipients may be added or used in place of the aforementioned as would be obvious to one skilled in the art, which of course is within the scope of the invention. The use of acetone or alcohol can also be changed depending on the wishes of the person skilled in the art.

Example XI

(A) 495.0 mg of purified water was mixed and 15.0 mg of CarbopolÖP940! (an acidic carboxyvinyl polymer from B.F. Goodrich Co.)

Added to the water with stirring. Stirring of the mixture was continued for 45 minutes. Subsequently, 4.095 mg of Na- | ; Trium hydroxide in 4.91 mg of purified water. Stirring of the mixture was continued for 10 minutes, after which 150.0 mg of ethanol, 0.50 mg of perfume and 0.50 mg of methyl salicylate were added. To the mixture i was then added, with stirring, a mixture consisting of 210.0 mg 40 jet milled benzoyl peroxide in wet form (50% benzoyl- 81 02 9 9 7 11 peroxide - 50% water), 2.0 mg sodium dioctyl sulfosuccinate 41.0 mg of alkyl polyglycol ether and 41.0 mg of purified water. The mixture was still! Stirred for 30 minutes until a smooth and elegant gel mixture was obtained; ! gene. | (B) Three samples of the gel preparation of part A weighing j

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{! about 20.0 g of gel were added with 0.8 g of erythromycin in 3.0 ml of absolute j i; ethanol mixed into a preparation with a total weight of 23.25 g.

1 per gram of a sample contained 34.40 mg of erythromycin.

On the first day of the experiment (time 0), three samples of 10 | 20.0 g of the active gel for 3 minutes with the erythromycin I | ! ethanol solution mixed with a plastic spatula and mixed i. left for about 15 minutes.

! A 1.0 g sample was taken from each of the three samples in duplicate, after which the first sample was charged with methanol and the second with a 0.1 µl PO4 buffer with a pH of 8.0 to a total ! I volume of 200 ml. This mixture was mixed with a small speed mixer at room temperature for 3 minutes. The foam layer of the solution was allowed to disappear by waiting 5 minutes, after which a 1.0 ml sample was taken, which was made up to 109 ml, supplemented with the 0.1 µ PO4 buffer with a pH of 8.0. This was put into grafted stainless steel cylinders; agar plates. The top 4 ml of the seed layer contained 1.5 ml of S. lutea material (at 25% light transmission in a 1:40 dilution of the standardizing solution) per 100 ml of the agar.

The plates also had appropriate reference standards of µg / ml erythromycin solution in other cylinders.

! The standard curve plates as well as the test plates were incubated at 35 ° C for 18 hours. The cylinders were then removed and the I dimensions of the zones were measured and compared with the I30 dimensions of the zones of the standard.

I:;

Example XII

j (A) 536.0 mg of purified water was mixed and 15.0 l was added with stirring. mg Carbopol® 940 (a carboxyvinyl polymer, acid form, from B.F.

I Goodrich Co.) to the water. Stirring of the mixture was continued for 45 minutes. Then, 4.095 mg of sodium hydroxide in 4.91 ml of purified water were added. Stirring of the mixture was continued for 10 minutes, after which 150.0 mg of ethanol, 0.50 mg of perfume and 0.50: mg of methyl salicylate were added. To the mixture was then added, with stirring, a mixture consisting of 210.0 mg jet-milled mill of wet benzoyl peroxide (50% benzoyl peroxide - 50% water), 2.0 mg sodium dioctyl sulfosuccinate and 41.0 mg of purified water. j! The mixture was stirred for an additional 30 minutes until a smooth and elegant gel mixture was obtained.

I (B) Samples of the gel formulation of Part A weighing approx. 20.0 g of gel were mixed with 0.5 g of erythromycin in 3.0 ml of ethanol! to a mixture with a total weight of 22.87 g and placed in containers I brought you. About 21.85 mg erythromycin was present per gram of the sample. The resulting plug was suitable for use in the treatment of acne.

Example XIII

Using the rule of Example XII, the! ! I

the following gel preparation was prepared: 1 benzoyl peroxide (ground in the jet mill) 5.46% by weight | Erythromycin 2.00 wt.% 151 ethanol 44.10 wt.%! polyoxyethylene lauryl ether 6.00 wt% colloidal magnesium aluminum silicate 2.50 wt% hydroxypropylmethylcellulose 1.00 wt% j citric acid 0.05 wt% j 20 sodium dioctyl sulfosuccinate 0.02 wt% water q.s. j

The product obtained had good stability and was effective for use in the treatment of acne.

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! j! 0 r /. '· -'-' 8102997 i i

Claims (12)

Preparation for the topical treatment of acne, characterized in that as active ingredients a peroxide of an organic acid i; and an erythromycin compound consisting of erythromycin itself and / or stearate and / or glucoheptanate derivatives thereof are present, the peroxide being present in an amount from about half to about thirty times the weight of the erythromycin compound . ! i 2. Preparation according to claim 1, characterized in that the peroxygen i is the benzoyl peroxide and / or lauroyl peroxide. Preparation according to claim 1 or 2, characterized in that the peroxide is benzoyl peroxide. Preparation according to one or more of the preceding claims, characterized in that the peroxide ground benzoyl peroxide milled in the jet mill. I i is. I 15 Preparation according to one or more of the preceding claims, characterized in that the erythromycin compound is erythromycin. i; Preparation according to one or more of the preceding claims, characterized in that the peroxide constitutes from about 1.0 to about 30% by weight of the composition and the erythromycin compound from about 0.5 to about 20% by weight of the composition. Preparation according to one or more of the preceding claims, characterized in that it contains a pharmaceutically acceptable carrier. 8. A composition according to any one or more of the preceding claims, characterized in that it is a gel preparation containing sodium dioctyl sulfosuccinate as stabilizing agent and surfactant. Preparation according to claims 1 and 8, characterized in that the preparation is an aqueous-alcoholic gel preparation with (a) about 1 to about 30% by weight of benzo | ground in a jet mill. yl peroxide with a particle size of less than 150 µm and an average 30 | particle size in the preparation of less than 35 µm! (b) about 2.0 to about 5.0 wt% of an erythromycin compound I: (c) about 0.1 to about 6.0 wt%, especially about 0.1 µl to about 3.0 wt% sodium dioctyl sulfosuccinate, I (d) about 1.0 to about 6.0 wt% of a further wetting 35; agent,; (e) about 0.5 to about 15% by weight of a gelling agent, i (f) about 10 to about 80% of an alkanol with a small number of carbon atoms and, i (g) water. 10. A composition according to claims 1 and 8, characterized in that the 8102997, "14" 1 i preparation is an aqueous gel preparation with! | ; (a) about 1 to about 30% by weight, of a jet mill ground benzoyl peroxide with a particle size of less than about 150 / nn and i | ! an average particle size in the preparation of less than approximately | 5 35 µm | j i | (b) about 2.0 to about 5.0 wt% of an erythromycin compound, j [(c) about 0.1 to about 6.0 wt%, especially about 0.1! up to about 3.0 wt% sodium dioctyl sulfosuccinate, i; j (d) a gelling agent, especially about 0.5 to about 10% by weight of a gelling agent and (e) water. ; I; 11. A composition according to claim 9 or 10, characterized in that the gelling agent is colloidal magnesium aluminum silicate, hydroxypropylmethylcellulose, microcrystalline cellulose and / or hydroxylated vinyl-polymer. !; ! j Preparation according to one or more of claims 1 to 7, with the | ---------— - ... -! characterized in that the preparation is a two-component preparation. -HI I I I I I I I I! ! ! j 1 j! ; i | 81 02 99 f