DE2751391A1 - PREPARATION FOR THE PROPHYLAXIS AND TREATMENT OF ACNE - Google Patents

Description

PATENT LAWYERS

DR. WALTER KRAUS DIPLOMAL CHEMIST ■ DR.-IN G. ANN EKÄTE WEISERT DIPL.-ING. SPECIALIZATION CHEMISTRY IRMGARDSTRASSE 15 · D-BOOO MUNICH 71 · TELEPHONE 08 9/79 70 77-79 70 78 ■ TELEX O5-212156 kpat d

TELEGRAM CRAUS PATENT

1688 WK / rm

PHARMACIA AB
Uppsala / Sweden

Preparation for the prophylaxis and treatment of acne

809821/0892

Description £ / 51391

The invention relates to new hygienic-cosmetic preparations which are applied to the skin for the treatment of acne that has already developed or, if desired, for the prophylaxis Formation of acne can be applied. The invention also relates to a method for producing such Preparation and the use of this preparation for the treatment of skin and in particular for the treatment of acne.

For example, from US Pat. No. 3,806,593, agents against acne are already known which contain 2 to 50 parts by weight of a lactic acid ester, in particular ethyl lactate, and preferably up to 10 wt .- # contain glycerine and / or propylene glycol, with the remainder of the preparation, which is essentially anhydrous, consists essentially of ethyl and / or isopropyl alcohol. These agents, and especially those that contain a combination of ethyl lactate and ethyl alcohol, have proven themselves as effective for the prophylaxis and reduction of acne, in particular the less severe forms of acne, e.g. of blackheads and surface pimples with a diameter of less than 2 mm, the surrounding reddening of which is not much are strongly pronounced. These funds also have the advantage that there are practically no undesirable side effects appear. The anti-acne agents disclosed in U.S. Patent 3,806 however, have some disadvantages and limitations. In particular, these remedies are not active enough to treat the more severe forms of acne, for example larger pimples or pustules, deep-seated, large infiltrates, unrelated to each other, isolated cysts and the like.

It is also known that it is possible to treat acne by the topical application of agents containing retinoic acid (vitamin Α acid). It is generally believed

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that such means to be sufficiently active, at least must contain about 0.05% by weight of retinoic acid. Although the end results are satisfactory after prolonged treatment the skin can be obtained with agents which contain retinoic acid in concentrations of at least about 0.05 Contained by weight-96, however, is a major disadvantage of these agents that as the initial result of the treatment the skin turns red due to inflammation. This inflammation disappears later despite further use of the remedy, but can sometimes be quite pronounced and prohibit further treatment. Applying this Agents used to treat acne often cause serious side effects, such as pronounced irritation or dehydration, an erythema, an eczema, an edema, a burning sensation, an itching and the like. The initial stage of inflammation, during which the treated person's skin often looks worse than before treatment, generally lasts some weeks. Because acne and similar skin conditions common in teenagers often cause severe mental health problems effect is the initial period of inflammation that occurs when treated with conventional agents, which is about 0.05% by weight Containing retinoic acid is very bothersome and may discourage the patient from carrying out the treatment.

Surprisingly, it has now been found that acne and similar skin disorders can be effectively prevented and existing conditions can be improved by treatment with agents which contain 2 to 50 wt combination with lower M _e nts, for example of only from 0.005 to 0.020 parts by weight 96, retinoic acid, a lower alkyl thereof and / or retinaldehyde in a medium consisting of ethyl alcohol, isopropyl alcohol, or mixtures

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of which, contains. With the new means according to the invention the disadvantages of the known agents against acne are eliminated or considerably reduced.

Another unexpected advantage of the preparation according to the invention is the more rapid occurrence of the anti-acne effect Compared to the above-mentioned retinoic acid products, despite the fact that the treatment is less violent can and should be carried out when using the known retinoic acid products. Actually show already after one or two weeks most patients experience a definite improvement, which increases during the following weeks, which is in contrast to the known retinoic acid preparations, where the improvement usually occurs much more slowly. This is clearly evident from the results Comparative tests, as summarized, for example, in Table II below.

The lower tendency to strong side reactions together with the considerably faster onset of improvement the preparation according to the invention is considerably more attractive for the patient. It is very likely that the excellent dissolving properties of the ethyl lactate-alcohol mixture also enable the retinoic acid component to penetrate more quickly and deeply into the skin, resulting in a combined simultaneous effect on several components that cause acne. The known retinoic acid preparations do not have this effect.

The preferred ester component which is used in the agent according to the invention is ethyl lactate, which is derived from both Derive racemic and optically active lactic acid

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can. It is of course also possible to use mixtures of the above To use esters.

It is preferred that the alcohols used be anhydrous or virtually anhydrous in order to hydrolyze the ester component to prevent already in the preparation. It has been shown that so-called absolute alcohol, e.g. alcohol with a purity of 99.5% »is very suitable for the purposes of the invention. The presence of alcohol also has the advantage that the hydrolysis of the ester already present in the preparation is prevented, because the alcohol shifts the hydrolysis equilibrium towards ester formation.

It is well known that high concentrations of alcohol can cause the skin to dry out. In order to counteract this effect of the above-mentioned preparations, a moisture-retaining agent, for example a low polyol, preferably propylene glycol or glycerine, can be added. The amount of the moisture-retaining agent in the preparation according to the invention can be 0 to 25% by weight, preferably up to 10% by weight and most preferably 1 to 5% by weight. High polyol contents tend to make the preparation greasy after application to the skin and should therefore not be used. The moisturizing agent is preferably anhydrous or substantially anhydrous, but it is also possible to use agents which contain water. The total water content of the preparation should not, however, exceed 20% by weight and preferably not be higher than about 10% by weight. According to a preferred embodiment of the invention, the preparation or the agent contains no more than about 5% by weight of water.

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According to a preferred embodiment of the invention, the new preparations contain 5 to 30% by weight of the lactic acid ester component, 0 (005 to 0.015% by weight of the retinoic acid component) and 1 to 10 wt .-% moisturizer. The preferred preparation contains about 10% by weight of ethyl lactate, about 0.007 to 0.012 parts by weight of retinoic acid and about 5 parts by weight of 96 Glycerine, the remainder being essentially 99.5% ethanol.

Although the preparations according to the invention preferably contain retinoic acid, it is also possible to use the corresponding Cj ^ -alkyl esters, e.g. the methyl, ethyl, propyl and isobutyl ester or retinaldehyde and mixtures thereof to be used as the retinoic acid component.

The preparations according to the invention preferably also contain a small amount (for example about 0.001 to 0.02% by weight ) of one or more antioxidants in order to stabilize the retinoic acid component, for example butylated hydroxytoluene and the like. The preparations can also contain small amounts of additives that are conventionally used in skin treatment agents, such as perfume, etc.

The invention also includes the use of the preparation according to the invention for the treatment of skin, in particular for Treatment of acne, in which the preparation is applied to the skin. The preparation can be applied in a conventional manner, for example by bathing. Excellent results will be in the treatment of acne by applying it once or several times a day or in less severe cases or in those that have already become have improved every two days or even less according to the need and demands in the special case received.

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AO

According to a preferred embodiment of the invention, the preparation is impregnated by means of a so-called or a compress or bandage with medical additives applied. Such a compress usually exists from a fiber-containing pillow that is impregnated with the preparation according to the invention and in a vapor-proof Sheath is enclosed, which is usually made of aluminum foil or a similar material. When the pillow is to be used, the cover is opened, by cutting, for example, along three edges with scissors and the pillow that is firmly in the Sheath is arranged, is pressed with the hand against the skin area to be treated. When applying this way the preparation does not evaporate as quickly as it would otherwise, and good penetration is ensured, which is further intensified by the temperature increase in the preparation, which is due to a lack of evaporation and is due to a warming effect on the skin and hand.

The invention also provides a process for the preparation of the new anti-acne agents, which is characterized in that 2 to 50 wt. -% retinoic acid, a C ^ a-alkyl ester thereof, of Retinsäurealdehyd or a mixture thereof, and preferably up to 25 parts by weight of 96, especially up to 10 wt -.%, and particularly 1 to 5 parts by weight 96, a Moisture-retaining agent, such as glycerine or propylene glycol, mixed with ethyl alcohol and / or isopropyl alcohol, which essentially forms the remainder of the preparation.

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The invention is illustrated in the examples. Examples 1 to 9

The components listed in Table I were mixed in the indicated proportions and the mixture was stirred until a homogeneous product is obtained. Clinical tests have shown that a significant anti-acne effect is achieved with these preparations, once or applied to the skin several times a day.

Example 10

The preparation of Example 1, which in the form of a with 10 ml of the preparation impregnated bandage was used, was compared in clinical tests with a commercially available anti-acne cream, which 0.05 wt .- # retinoic acid as Active ingredient contained.

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9 - 43

A total of 79 acne patients were treated. The pads and cream were applied once a day in the afternoon. The observation period was six weeks with a control after two weeks of treatment. The effect of the treatment was evaluated according to the following scheme, which is a modification of the method of Juhlin and Lidfen in "Br. J. Derm.", 81 (1969), Pages 154-158.

Degree unit 1/2: blackheads, open or closed, without inflammatory Changes (without any erythema).

Degree unit 1: Degree unit 2:

Degree unit 3:

Blackheads with surrounding erythema. Superficial pimples or pustules, their purulent Parts had a diameter of 2 mm or less and the surrounding erythema did not were very pronounced.

Pimples or pustules with a diameter of more than 2 mm, their surrounding erythema were pronounced.

Deep-seated, large infiltrates that don't were in contact with each other, with or without pimples or pustules. Cysts too.

The test results, expressed as the percentage of total sprinkling, are given in Table II. In particular, the preparation according to Example 1 showed a significant one after two weeks better effect than a cream with 0.0596 retinoic acid .

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- 8 - Table I.

Components example no. (The amounts are given in weight-96)

1234 5 6 78

Ethyl lactate 1096 ΙΟ * 1596 596 TÖ96 2096 3096 1096 Glycerol dilactate ----- - - - Retinoic acid 0.01296 0.00796 0.00996 0.01996 0.01296 0.00796 0.00996 0.01296 0.01596 Propylene Glycol - 296 2096 1096 -

anhydrous glycerine 596 596 - - - 196 796 -

ο butylated hydroxytoluene 0.01296 0.01296 0.01096 0.02096 0.01296 0.01296 0.01096 0.01296 0.0296

<° Ethanol, 99.596 to 10096 to 10096 to 10096 to 10096 to 10096 to 10096 to 10096 to 10096 to 10096

n> perfume q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s.

ro -j cn

Table II

Overall product improvement - average values

after two weeks after six weeks

Example 1 23,496 44,996

Cream with 0.0596

Retinoic acid - 4,196 39,496

The side effects of the two preparations were also examined and divided as follows:

a) Minor complaints: slight irritation, moderate dryness (which can be achieved by simply using a bold Skin cream or the like can be avoided);

b) Moderate discomfort: more pronounced irritation and dryness;

c) Main complaints: erythema, eczema, edema, pain, Itch.

42,596 of the patients who had been treated with the cream with 0.0596 retinoic acid, but only 28,296 those with the preparation of Example 1 showed major and moderate type side effects.

Example 11

In a further clinical test, the preparation of Example 2 was used with a corresponding preparation without Retinoic acid component compared. Both preparations were applied twice a day in the form of sanitary napkins that came with 10 ml of the respective preparation were impregnated. The observation period was six weeks. The results were

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evaluated as in example 10. The test results that are summarized in Table III, indicate that the preparation according to Example 2 is superior to the corresponding retinoic acid-free preparation. In particular, should the very good effect against the more severe grades (grades 2 and 3) of acne should be noted. Both preparations were practically no undesirable side effects were observed.

Table III Product average relative Besse

tion grades 1/2 and 1 grades 2 and 3

Preparation of Example 2 5596 5996

dto. without retinoic acid 2896 3896

End of description.

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Claims (10)

Claims 1. Preparation for the prophylaxis and treatment of acne and similar skin conditions, characterized in that it contains 2 to 50% by weight of a lactic acid ester component and 0.005 to 0.020% by weight of a retinoic acid component in a medium consisting of ethanol, Isopropyl alcohol or mixtures thereof, the milk acid ester component being ethyl lactate, isopropyl lactate, Is glycerol monolactate, glycerol dilactate or a mixture thereof and the retinoic acid component is retinoic acid (vitamin A acid), a C ^^ - alkyl ester thereof, retinaldehyde or a Mixture of it is. 2. Preparation according to claim 1, characterized in that it also contains up to 23 wt. preferably up to 10% by weight, one moisture retaining Contains means. 3. Preparation according to claim 2, characterized in that the moisture-retaining agent is a lower polyol such as propylene glycol or glycerin. 4. Preparation according to one of claims 1 to 3 »characterized in that it also contains an antioxidant to stabilize the retinoic acid component. 809821/0892 ORIGINAL INSPECTED 5. Preparation according to one of claims 1, 2, 3 or 4, characterized in that it a) 5 to 30% by weight of lactic acid ester component, b) 0.007 to 0.015 wt .- # retinoic acid ester component and c) 1 to 10 wt .-% moisture retaining agent contains, the remainder consisting essentially of ethanol and / or isopropanol. 6. Preparation according to one of the preceding claims, characterized in that it is about 10 96 wt% ethyl lactate, about 0.012 wt% retinoic acid, and about Contains 5% by weight glycerol and the remainder consists essentially of ethanol. 7. Preparation according to one of claims 1 to 6, characterized in that it is 0.001 to 0.02 Contains% by weight of an antioxidant. 8. Medical pillow for the prophylaxis or treatment of acne and similar skin conditions, characterized by a fibrous tissue, which is impregnated with any preparation according to any one of the preceding claims and enclosed in an evaporation-proof envelope is. 9. A method for producing a preparation according to claim 1, characterized in that 2 to 50 wt. % Ethyl lactate, isopropyl lactate, glycerol mono- 809871/0892 lactate, glycerol dilactate or a mixture thereof and 0.005 to 0.020% by weight of retinoic acid, a Cj ^ -alkyl ester thereof, of retinaldehyde or a mixture thereof and preferably also up to 25% by weight , in particular up to 10% by weight, of one Moisturizing agent mixed with ethyl alcohol and / or isopropyl alcohol, which essentially forms the remainder of the preparation. 10. Use of the preparation according to one of claims 1 to 7 for the treatment of acne and similar skin conditions, applying an effective amount of this preparation to the acne or similar lesion of the skin of a person suffering from it brings up. 809821/0892