FR2495471A1 - COMPOSITIONS FOR THE TREATMENT OF ACNE - Google Patents

Abstract

THE INVENTION RELATES TO A PHARMACEUTICAL COMPOSITION. THE PROBLEM TO BE SOLVED IS TO AVOID ANY IRRITATION AS WELL AS LOSS OF KERATOLYTIC POWER. THE COMPOSITION CONTAINS, AS ACTIVE INGREDIENTS, A PEROXIDE OF AN ORGANIC ACID AND AN ERYTHROMYCIN COMPOUND CHOSEN FROM ERYTHROMYCIN, ITS STEARATE AND ITS GLUCOHEPTONATE OR THE PEROXIDE CONSISTS OF 0.5 TO 30 TIMES THE WEIGHT OF THE SAID COMPOUND ERYTHROMYCIN, THIS COMPOSITION MAY BE PRESENT IN CONTAINERS 7, 8 CONTAINED IN A PACKAGING 5. THE COMPOSITION IN QUESTION MAY BE USED FOR THE TREATMENT OF ACNE.

Description

"Compositions for the treatment of acne" The present invention relates to

  pharmaceutical preparations and, more particularly, ingredients

  active ingredients that are suitable for the topical treatment of acne.

  The invention also relates to the use of prepa-

  pharmaceutical rations and the aforementioned ingredients

  to treat acne medically in humans.

  Acne is a common inflammatory disease whose skin areas or sebaceous glands are the largest, the most numerous and the most active. In its most milder forms, acne is a more

  or less superficial, which is manifested by slight irritation

  Punctual rites and ordinary hygiene of the skin is a satisfactory treatment. However, in

  types of acne more inflammatory; a bacterial invasion

  of or around the pilo-sabacea follicles

  duals and pustules, infected cysts and, in extreme cases, inflamed and infected pockets, these lesions may become

  and leave permanent disfiguring scars

your.

  Acne is very common at puberty and at least 80% of teenagers feel distressed. We know that eruptions

  facials cause psychological shocks in many

  teenagers that they find it difficult to make personal adaptations and, therefore,

  symptoms of retrenchment and self-pity

  even manifest themselves. The victim of acne can be

  aware of obvious facial imperfections.

  For these reasons, a medicinal product and

  with the help of the latter are of obvious interest

  and may eliminate the need for a p.

  therapy. Previously, various forms of medication have been applied topically to the skin to reduce the severity of acne. Antibacterial soaps were used for this purpose, as were bactericidal agents, such as

- - 2495471

  as sulfur and resorcinol. Other topical compositions separately contained benzoyl peroxide, hexachlorophene, erythromycin or neomycin sulfate. None of these prior preparations have been fully effective.

  U.S. Patent No. 3,535,722 discloses

  describes a therapeutic composition for the treatment of acne, which comprises a uniform dispersion of benzoyl peroxide in a liquid medium containing water and

at least one organic emollient.

  U.S. Patent No. 4,056,611 discloses

  discloses a therapeutic composition for the treatment of acne, which comprises a stable dispersion of finely divided particles of benzoyl peroxide in a single phase aqueous alcoholic vehicle. The single phase of the

  The composition is alipidic and contains a surfactant

  non-ionic active agent which is soluble in the alcoholic carrier

aqueous liquefaction.

  In the description of the U.S. patent application

  No. 60,392, filed July 25, 1979, of the Applicant, which is hereby incorporated by reference, the use of sodium dioctyl sulfosuccinate as a stabilizing agent or compositions based on benzoyl peroxide is disclosed, as well as the increased stability of the

  benzoyl peroxide in micronized form. Compositions

  The peroxide-based compositions of the prior art, which simply contain finely divided peroxide particles in a water emulsion and some selected emollients, suffer from the disadvantage that when the water content of the emulsion is reduced by evaporation, it remains

  most organic emollients and large

  of benzoyl peroxide on the surface of the skin

  neighborhood and in contact with acne sites, which may

  to express an irritation. Moreover, the use of large amounts of nonionic surfactants in such compositions, unless extremely fine particles of peroxide are

  probability of irritation caused by peroxide.

  In the same way, because of the powerfully oxy-

  components of the peroxide component, the inclusion of this

  stance in a conventional emulsion or ointment or with other active ingredients,

  unstable people who rapidly manifest an unacceptable loss

table of keratolytic power.

  In accordance with the present invention, it has been found that a mixture on the skin of a peroxide, especially benzoyl, and erythromycin is particularly beneficial, since these compounds exert a statistically significant potentiating effect. Benzoyl peroxide inhibits the formation of free fatty acids in the skin, mainly through the inactivation of extracellular (oxidation) lipase required for splitting

  triglycerides in free fatty acids and glycerol.

  Erythromycin effectively reduces the concentration of

  Corynebacterium acnes (that is to say P. acnes), a bac-

  normal anaerobic serum which is the main source

  lipase. Instead of benzoyl peroxide which constitutes

  kills the preferred peroxide, one can also use other

  peroxides of organic acids, such as peroxide of

  royle. Instead of erythromycin, which is the preferred compound, derivatives may be substituted for it

  erythromycin, such as glucoheptonate or

spleen erythromycin.

  Both of these ingredients can be applied to the skin,

  as a mixture or they can be applied separately.

  on the skin. When proceeding in the manner indicated last, it is preferable to apply first

  erythromycin on the skin and then apply the

  oxidize immediately or shortly thereafter. We can just as well reverse the order of application. If the mixture is first to be prepared and then applied to the skin, it is best to mix at the time of your application.

  application or use the mixture within 24 hours.

who follow his making.

  The prompt use of a premix has its raison d'être in the relative incompatibility of the two active agents and, because of this characteristic, it is advisable to introduce the two agents in bottles, vials or bottles. other separate containers. However, according to one of its features, the subject of the present invention is a new vehicle for the active ingredients, such that the mixture of the ingredients has a

  amazing pot life and stability in the

  usually used for the preservation of eritromycin solutions; in addition, the new vehicle produces a more uniform dispersion of ingredients

assets.

  The therapeutic gel composition according to

  The present invention must contain a sufficient amount of peroxide to be therapeutically effective and may contain no more peroxide than may be uniformly dispersed throughout the vehicle to form an easy to spread composition. Such conditions require that the composition contain at least 1% and not more than

  % by weight of peroxide and, preferably, that the

  The composition contains about 2.5 to 15% by weight of peroxide.

  The peroxide which forms one of the constituents of the

  sition must be of high purity and be in the form of finely divided crystalline particles, preferably micronized

  average particles less than 35 microns. The utilisa-

  peroxide which has been micronized gives a longer shelf life and better stability - to the composition, when used in combination

  with sodium dioctylsulfosuccinate as a

  active. The composition in the form of a gel according to the

  The present invention may advantageously comprise an additional wetting agent, such as polyol esters of sugars, condensation products of ethylene oxide and fatty acids, aliphatic alcohols, long-chain alkylphenols, long-lived mercaptans and the like. chain, long-chain amides, polyethers of polyhydroxylated aliphatic alcohols and alkylpolyglycol ethers in an amount

at about 6% by weight.

  It has been noted, not without surprise, that in a vehicle

  aqueous alcoholic type, the use of a peroxide

  and an erythromycin compound in combination with dioctyl-

  sodium sulphosuccinate as a surfactant,

  should be a composition exhibiting total stability

  as regards the constituent peroxide, even when subjected to

  erations higher than those normally encountered during the ordinary use of the product. Similarly, the mixture according to the present invention allows by evaporation a uniform release of the peroxide, so as to overcome the burns and erythema generated with

other harder compositions.

  The aqueous gel composition according to the present invention

  vention contains from about 1% to about 30% and,

  from about 5% to 15% by weight of peroxide plus

  particularly, micronized benzoyl peroxide pos-

  sedating a particle size of less than about 150 microns, with an average particle diameter of less than about 35 microns. Sodium dioctylsulfosuccinate

  which acts as a surfactant while ensuring stability

  increased composition, is present in the

  from about 0.1% to 2% by weight relative to

  composition. The composition can also be advantageous

  contain an additional wetting agent in an amount of from about 1.0% to about 6.0% by weight and

preferably 3% to 6% by weight.

  Other Objects and Advantages of the Present Invention

  appear more clearly on reading the description of the

  detailed description which follows, with reference to the following illustrative drawings in which:

  FIG. 1 represents a perspective view of an em-

  2 containing a container, one for each active agent, - Figure 2 shows a section along line 2-2 of Figure 1, - Figure 3 shows a section taken along the line 3-3 of the figure 2 and

  FIG. 4 represents a perspective view of an em-

  a ballad containing a single container.

  An affected area of the skin can be lightly sprinkled with a mixture of the two active ingredients approximately

  in the same way that an ordinary powder would be applied

  for the face. This may consist either of an application of the premix shown in FIG. 4, or of the successive applications of the separated agents in the two containers represented in FIG. 1, or the application of a premix of the two agents represented

  in Figure 1, prepared at the time of application. How-

  However, it is possible to dilute the mixture with a vehicle which can be a powder, a semisolid vehicle of the consistency of a cream, or a liquid, such as an aqueous emulsion or with an organic solvent, in particular an aqueous mixture. containing sodium dioctylsulfosuccinate

as a surfactant.

  On a weight basis, the selected erythromycin and

  peroxide chosen must be determined in such a way that

  when applied to the skin, the peroxide is from about 1 to about 30 times the weight of erythromycin, preferably from about 1 to about 5 times the weight of erythromycin. In a premix composition

  comprising a diluent to be applied to the skin, erythro-

  - selected mycine must be present in a varying proportion

  from 0.5% to 5.0% w / w and the peroxide chosen must be

  in a proportion ranging from 1.0% to 30% w / w. The preferred concentration ranges from about 2% to about 3% of the selected erythromycin and from about 5% to about 10%

selected peroxide.

  Since erythromycin has limited solubility, the preferred dermatological solvents are alcohol or acetone, but the composition is not limited to these liquids at all. Erythromycin degrades rapidly in solution, even at normal temperature. Refrigeration extends the pot life of such solutions somewhat. A preferred vehicle or diluent consists of a hydroalcoholic gel system, but emulsions and liquid suspensions, as well as creams, ointments

  and powders are also acceptable. We can have

  conventional pharmaceutical processes to pre-

  counter these common forms of topical medicinal compositions. For example, a premix can be placed in a conventional capsule or capsule-like ointor as encapsulated in FIG. 4, and this minimizes the problem of stability. It is necessary

  instruct the patient that he must refrigerate the preparation.

  Ordinarily, the bottle 9 can be introduced into a

  cardboard box or similar packaging 10.

  In view of the commercial preparation, it is most appropriate of. produce a cardboard package 5 with a lid 6, which contains 2 capsulated containers and

  the drawings represent it. One of the containers

  should contain only erythromycin and be of a

  - sufficient to accommodate all other ingredients

  that one must subsequently mix with its contents.

  The other container could contain an aqueous gel composition of benzoyl peroxide, with or without a solvent for erythromycin, as well as all other ingredients

  intended for the preparation of the topical composition. How-

  However, it has been surprisingly found that the use of

  sodium dioctylsulfosuccinate as a surfactant

  the stability of the composition.

  The gelling agent used for the purpose of the present invention may be selected, both in type and quantity so as to obtain products of various viscosities. According to the preferred embodiment of the invention, the gelling agent is chosen so as to generate an elegantly formed and stable gel. A variety of gelling agents may be used for the purpose of this invention. However, the preferred gelling agents are hydroxypropylmethylcellulose,

  colloldal magnesium aluminum silicate and the

  pure microcrystalline cellulose, as well as vinyl polymers known as hydroxylated polymers, more particularly those described in US Pat. No. 2,798,053. Among the hydroxylated vinyl polymers which are of special interest for the purposes of the present invention, mention may be made of , all in all those described in the aforementioned patent as interpolymers of a monomeric monoolefinic acrylic acid and from about 0.1% to about 10% by weight, based on the total monomer, of a polyether monomer of a oligosaccharide in which the hydroxyl groups which are modified are esterified by a / bile groups, said polyether containing at least

  two allyl ether groups per oligosaccharide molecule.

  As interpolymers of this type commercially available, those sold under the trade name Carbopol may be used. These compounds are described as being crosslinked acrylic acid polymers with about 1%

  polyallyl ether of sucrose having a medium of

  about 5.8 allyl groups for each sucrose molecule. These polymers have a molecular weight of an order of magnitude equal to one million. These polymers are sold by B.F. Goodrich Chemical Company and are placed on the market under the trademarks of factories.

  Carbopol 934, Carbopol 940 and Carbopol941.

  The amount of gelling agents that the compositions according to the invention may contain may also vary somewhat. Ordinarily this amount is from about 0.1% to about 15% by weight and preferably from about 0.5% to about 3% by weight, based on

  basis of the total weight of the finished composition.

  As mentioned above, the simplest topical preparation consists of a mixture of erythromycin and powdery benzoyl peroxide, without diluent, but it must be applied sparingly to the skin. Instead of applying such a mixture of the active compounds, one can first be applied to the skin and then apply the other with a

  slight friction so as to mix them on the skin.

  An appropriate simplified preparation is one that corresponds to the following formula:

EXAMPLE 1

  Benzoyl peroxide 1 - 35 w / w Calcium phosphate 63 - 98.5 w / w Erythromycin 0.5 - 5 w / w These ingredients are intimately mixed together and the affected area of the skin is sprinkled with 1 to 4 times a day. This mixture can be sold in

  the container 9 as shown in Figure 4.

  If it is desired to obtain a liquid preparation, a simplified composition is given below which can be prepared and applied to the skin from 1 to 4 times a day, as if it were an ordinary lotion for the face. We could sell it in one of the bottles represented

  in FIG. 1, with or without the carton 5.

EXAMPLE 2

  Ethanol up to 100 w / w Erythromycin 0.5 - 5 w / w Benzoyl peroxide 1 30 w / w Other examples that illustrate the present invention are as follows:

EXAMPLE 3

3.5 Lotion.

  In a first container 7 are introduced the ingredients

  following factors, in proportions by weight:

Ethyl cetyl stearyl alcohol

  xylated 7.00% Cetyl alcohol 0.75% Isopropyl myristate 5.00% Hydroxyanisole butylated 0.10% Polyoxyl 40 stearate 0.25% Water, deionized or distilled 68.80% Propylene glycol 3.00% Peroxide of benzoyl 5.00% Acetone 10.00% Dioctyl sulfosuccinate 0.15% In a second container 8, the following ingredient is introduced, the container being of sufficient capacity to adapt to a quantity of solvent, preferably, ethanol or acetone, in the proportion of 3 cc / 20 g

  of the composition contained in the container 7.

Erythromycin 2% w / w

content of the

  The two containers are introduced into a single salable package, such as that represented by reference numeral 5, with the instruction that the container contents 8 should be added to the container 7 and then intimately mixed. In the container 8 containing erythromycin, it is also possible to introduce 3 cc of ethanol per 20 g of material contained in the container 7.

  The solution of erythromycin in ethanol is then

  troduced in the container 7 and the whole is vigorously mixed. This can be done by both the pharmacist and the patient. The patient must apply the lotion

  on the skin as if it were an ordinary rash

from 1 to 4 times a day.

  A variant of Example 3 consists in diluting

  Vantage the contents of the container 8 with the same solvent, so that a certain amount of the contents of the container 7 is first applied to the skin and that some

  quantity of the contents of the container 8 is then applied

  on the skin, so that the mixture is

  comfortable on the skin in question. This eliminates the losses

  due to the lack of pot life or the

the mixture.

EXEXPLE 4

  Cream. In a first container 7, the following ingredients are introduced in the following proportions, in weight proportions: ethoxylated cetyl-stearyl alcohol 15.00% Cetyl alcohol 1.25% Isopropyl myristate 5.00% Hydroxyanisole butylated 0.10% Polyoxyl 40 stearate 0.25% Water, deionized or distilled 60, 60% Propylene glycol 3.00% Benzoyl peroxide 5.00% Acetone 10.00% Dioctyl sodium sulfosuccinate 0.10% In a second container 8, the next ingredient, the container being large enough to accommodate a quantity of a solvent, preferably ethanol or acetone, in the proportion of

  3 cc / 20 g of the composition contained in the container 7.

Erythromycin 3% w / w

of the content of the

please 7.

  The explanation for sales and employment that we have

  spoken in example 3 also applies to this cream.

  Since the preparation is of crisp consistency

  meuse, the containers 7 and 8 must have bottlenecks

  large enough to facilitate the mixing and pre-

removing the cream.

EXAMPLE 5

Gel.

  The container 7 comprises the following ingredients, in weight proportions: Water, deionized or distilled 54.65% Colloidal bentonite 2, 50% Carboxyvinyl polymer (arid form) 1.00% Dioctyl sodium sulfosuccinate 1.00% Diisopropanolamine 0, 75% Ethyl alcohol, 200 35.00% Hydroxyanisole butylated.0, I 5, Benzoyl peroxide (micronized) 5.00% Container 8 contains only the following ingredient: Erythromycin 3% w / w content of

container 7.

  The explanation for the packaging in wide mouth containers and their mixing at the time of use as it is shown in Example 4 also applies to this gel.

EXAMPLE 6

  Suspension. The container 7 contains the following ingredients, in weight proportions: Water, deionized or distilled 56.97% Bentonite colioldale 1.50 5 Carboxyvinyl polymer (acid form) 0.25% Dioctyl sodium sulfosuccinate 1.00% Diisopropanolamine 0.18% Ethyl alcohol, 200 35.00% Butylated hydroxylisole 0.10% Benzoyl peroxide (micronized) 5.00% Container 8 contains only the following ingredient: Erythromycin 2% w / w

container 7.

  The explanation described in Example 3 also applies

this suspension.

EXAMPLE 7

  The amount of benzoyl peroxide in any of Examples 3 to 6 is reduced or increased between the limits of 1% to 30% w / w of the contents of the container 7, the amount of water being proportionally increased or reduced. The amount of erythromycin in the container 8 should be titrated to a level of one fifth to two times w / w, the proportion of peroxide

of benzoyl.

EXAMPLE 8

  In any of the above examples, another peroxide of organic acid is substituted for

of benzoyl.

EXAMPLE 9

  In any of Examples 3 to 6, water and / or a lower alkanol, such as methanol, are substituted.

ethanol, etc. with acetone.

EXAMPLE 10

  In any of the above examples,

  substitutes an erythromycin derivative for erythromycin.

  These examples are only illustrations of

  the present invention and not limit it in any way.

  So, for example, we can substitute some of the

  the aforementioned ingredients to other ingredients which are well known to those skilled in the manufacture of dermatological preparations. Various quantities of other ingredients or other excipients can be added or interchanged with one another without leaving the

  framework and spirit of the invention. The use of

  tone or alcohol may also be required to vary according to

that the preparer wishes.

EXAMPLE 1

  (A) 495.0 mg of purified water were stirred and

  15.0 mg of Carbopol 940 (a carboxyvinyl polymer, acid form, from B.F. Goodrich Co.) is stirred in. Stirring of the mixture was continued for 45 min. Then 4 095 mg of sodium hydroxide in 4.91 ml of purified water was added. Stirring of the mixture was continued for 10 minutes, then 150.0 mg of ethyl alcohol, 0.50 mg of perfume and 0.50 mg of methyl salycilate were added. To the stirred mixture was then added a mixture of 210.0 mg peroxide of

  moist micronized benzoyl (50% benzoyl peroxide)

  % water), 2.0 mg sodium dioctyl sulfosuccinate, 41.0 mg alkylpolyglycol ether and 41.0 mg purified water. The mixture was stirred for 30 minutes until a mixture formed

smooth and elegant gel.

  (B) Three samples of the gel composition of the Apesant portion of approximately 20.0 g were mixed with 0.8 g of erythromycin in 3.0 ml of absolute ethanol to give a total weight of 23 g. 25 g. Each gram

  sample contained 34.40 mg of erythromycin.

  On the initial day of the experiment (time-0) 3 samples of 20.0 g of gel were mixed with the erythromycin-EtOH solution for 3 minutes, using a plastic spatula and allowed to to rest

  mix for approximately 15 minutes.

  A sample of 1.0 double gen of

  each of the three samples and then we first

  MeOH troduct and secondly a buffer of 0.1 M P04 pH 8.0 to obtain a total volume of 200 ml. This mixture was introduced into a low speed mixer for 3 minutes at room temperature. The solution was allowed to stand for 5 minutes to lose its foam layer and then a 1.0 ml sample was taken and brought to a volume of 109 ml with 0.1 P04 buffer. PH 8.0. This mixture was placed in stainless steel bottles which had been previously placed on seeded agar plates. The upper 4 ml seed layer contained 1.5 ml of S. lutea stock (at 25% light transmission in a 1:40 dilution of solution).

  standardized) per 100 ml of the agar.

  Plates also had appropriate reference standards of pg / ml of erythromycin solution

in other bottles.

  Plates for standard curve, as well as test plates were incubated at 35 C for 18 hours. The bottles were removed and the caliber

  areas and compared to the calibres of the standard areas

sting.

EXAMPLE 12

  (A) 536.0 mg of purified water were stirred and

  produced, while stirring, 15.0 mg of Carbopol 940 (one

  carboxyvinyl polymer, acid form of B.F.

  Goodrich Co.) The stirring of the mixture was continued for 45 minutes. Then 4.095 mg of sodium hydroxide in 4.91 ml of purified water was introduced. Stirring of the mixture was continued for 10 minutes and then 150.0 mg of ethyl alcohol, 0.50 mg of perfume and 0.50 mg of methyl salicylate were added. To the stirred mixture was then added a mixture consisting of 210.0 mg wet micronized benzoyl peroxide (50% benzoyl peroxide-50% water), 2.0 mg sodium dioctyl sulfosuccinate and 41, 0 mg of water

  purified. The mixture was stirred for 30 minutes

* to obtain a mixture consisting of a smooth gel

and elegant. (B) Samples of the gel composition of Part A were mixed;

  weighing approximately 20.0 g, 0.5 g of erythromycin in 3.0 ml of ethanol, so as to obtain a total weight of 22.87 g and the compositions thus obtained were introduced into containers. Each

  sample contained approximately 21.85 mg of erythrocyte

  thromycine. The product thus obtained is suitable for use

  for the treatment of acne.

EXEIMPLE 13

  Repeating the procedure described in Example 12, the following gel composition was prepared: Benzoyl peroxide (micronized) Erythromycin Ethyl alcohol

Polyoxy lauryl ether

  Ethylene Magnesium silicate-colloidal aluminum Hydroxypropyl methylcellulose Citric acid Dioctyl sodium sulfosuccinate Water, 46% by weight 2.00 44.10% by weight% by weight 6.00% by weight

2.50%

1.00%

0.05%

0.02%

in en in weight weight weight weight

until the

desired.

  The product thus obtained had good stability

  and was effective for the treatment of acne.

Claims (10)

  1. Composition for the topical treatment of acne,   characterized in that it contains, as an ingredient   a peroxide of an organic acid and an erythromycin compound selected from the group consisting of erythromycin and its stearate and glucoheptonate and that the above-mentioned peroxide forms from about 0.5 to about 30 times the weight of the erythromycin compound in question.   2. A composition according to claim 1, characterized in that the peroxide is selected from the group consisting of   benzoyl peroxide and lauroyl peroxide.   3. Composition according to any one of the   1 and 2, characterized in that it comprises a   pharmaceutically acceptable excipient.   4. Composition according to claim 3, characterized   ridiculous in that it is a gel composition comprising   sodium dioctyl sulphosuccinate as a stabilizing agent biliser and surfactant.   5. Composition according to any of the claims   cations 1 and 3, characterized in that the peroxide   from about 1.0% to about 30% of the weight of the   and the above-mentioned erythromycin compound   from about 0.5 to about 5% of the weight of the position.   6. Composition according to any one of the   cations 1 and 3, characterized in that the peroxide is micronized benzoyl peroxide.   7. Composition according to any one of the   cations 1 and 3, characterized in that the erythrocyte Thromycin is erythromycin.   8. Aqueous alcoholic therapeutic gel composition   A tick suitable for the treatment of acne, characterized in that it comprises: a) from about 1% to about 30% by weight of micronized benzoyl peroxide having a particle size of less than 150 microns with a mean particle size in said composition less than 35 microns, b) from about 2.0% to about 5.0% by weight of an erythromycin compound, c) from about 0.1 to about 6.0% by weight of dioctyl sodium sulfosuccinate, d) from about 1.0 to about 6.0% by weight of another wetting agent, e) from about 0.5% to about 15% by weight of a gelling agent, and ) from about 10% to about 80% of a lower alkyl alcohol and g) water.   9. Aqueous aqueous alcoholic gel composition   The present invention is characterized in that it comprises: a) from about 1% to about 30% by weight of micronized benzoyl peroxide having a particle size of less than about 500 microns with a mean particle size in the range of said composition less than about 35 microns, b) from about 2.0 to about 5.0% by weight of an erythromycin compound, c) from about 0.1% to about 6.0% by weight of dioctyl sodium sulfosuccinate and d) a gelling agent.   10. Composition according to any one of the   8 and 9, characterized in that the gelling agent   is selected from the group consisting of magnesium silicate   sium-colloidal aluminum, hydroxypropyl methylcellulose, microcrystalline cellulose and hydroxylated vinyl polymers.