WO1994021241A1

WO1994021241A1 - New use of anti-acne agents

Info

Publication number: WO1994021241A1
Application number: PCT/EP1994/000769
Authority: WO
Inventors: Gerhard Sauermann; Franz STÄB
Original assignee: Beiersdorf Ag
Priority date: 1993-03-15
Filing date: 1994-03-11
Publication date: 1994-09-29
Also published as: EP0689431A1; DE4307976A1; JPH08507772A

Abstract

Active agents or preparations that are used or suited for treating acne can be used for prophylaxis or treatment of light-sensitive skin, in particular photodermatoses, and preferably polymorphous photodermatosis.

Description

description

New use of drugs

The present invention relates to active ingredients and preparations which serve for the prophylaxis and treatment of light-sensitive skin, in particular photodermatoses.

The damaging effect of the ultraviolet part of the sun's radiation on the skin is generally known. While rays with a wavelength shorter than 290 nm (the so-called UVC range) are absorbed by the ozone layer in the earth's atmosphere, rays in the range between 290 nm and 320 nm, the so-called UVB range, cause erythema simple sunburn or even more or less severe burns.

The narrower range around 308 nm is given as a maximum of the erythema effectiveness of sunlight.

Numerous compounds are known for protection against UVB radiation, which are derivatives of 3-benzylidene camphor, 4-aminobenzoic acid, cinnamic acid, salicylic acid, benzophenone and also 2-phenylbenzimidazole.

It is also important for the range between about 320 nm and about 400 nm, the so-called UVA range, To have filter substances available because their rays can cause reactions in light-sensitive skin. It has been proven that UVA radiation damages elastic and collagen fibers. it carries connective tissue, which causes the skin to age prematurely, and that it can be seen as the cause of numerous phototoxic and photoallergic reactions. The damaging influence of UVB radiation can be intensified by UVA radiation.

To protect against the rays of the UVA range, certain derivatives of dibenzoylmethane are therefore used, the photostability (Int. J. Cosm. Science j_0, 53 (1988)) of which is insufficient.

However, UV radiation can also lead to photochemical reactions, in which case the photochemical reaction products intervene in the skin metabolism.

Such photochemical reaction products are predominantly free radical compounds, for example hydroxy radicals. Undefined radical photo products which arise in the skin itself can also display uncontrolled subsequent reactions due to their high reactivity. But also singlet oxygen, a non-radical excited state of the oxygen molecule can occur with UV radiation, just as short-lived epoxies and many others. Singlet oxygen, for example, is characterized by increased reactivity compared to the triplet oxygen that is normally present (basic radical state). However, there are also excited, reactive (radical) triplet states of the oxygen molecule. UV radiation also belongs to ionizing radiation. There is therefore a risk that ionic species also develop when exposed to UV rays, which in turn can oxidatively intervene in the biochemical processes.

In order to prevent these reactions, additional antioxidants and / or free radical scavengers can be incorporated into the cosmetic or dermatological formulations.

It has already been proposed to use vitamin E, a substance with a known antioxidative effect, in light protection formulations, but the effect achieved here also falls far short of the hoped-for effect.

The object of the invention is to provide cosmetic, dermatological and pharmaceutical active substances and preparations as well as light protection formulations which are used for the prophylaxis and treatment of light-sensitive skin, in particular photodermatoses, preferably PLD.

This object is achieved by the use of active substances or preparations which serve or are suitable for acne treatment, for the prophylaxis and treatment of light-sensitive skin, in particular photodermatoses and preferably polymorphic light dermatosis.

Further names for polyorpheic light dermatosis are PLD, PLE, Mallorca acne and a large number of other names, such as those used in the literature (e.g. A. Voelckel et al, Zentralblatt Haut- und Sexterlechtenungen (1989), 156, Page 2).

The invention also relates to the mixtures of the active substances and preparations therewith. Preparations according to the invention which contain a UV protective agent are particularly preferred.

Acne agents or acne active ingredients are known in large numbers. It can be cosmetic, dermatological and pharmaceutical active ingredients which e.g. can be administered orally, parenterally or topically. Their effect according to the invention is surprising since there are no indications of an effect in photodermatoses. The term "Mallorca acne" is misleading in this context, since this so-called "acne" is not one of the acne forms.

It was also surprising that the active substances according to the invention would be effective in photochemical oxidation processes relevant in human skin.

The cause of the new acne remedies according to the invention has not yet been completely clarified. However, there may be a connection with the formation of porphyrin by propionibacteria, which are found in the human sebaceous glands, and also with the cleavage of porphyrins by enzymes.

Preferred acne active ingredients are vitamin A and derivatives, antibiotics from the acne treatment spectrum such as clindamycin and tratracyclines, but especially those which have antibacterial activity against propionibacteria, keratolytics such as salicylic acid and alpha-hydroxy acids and preparations, in particular topical preparations with them . Benzoyl peroxide and in particular also topical preparations are particularly preferred.

Benzoyl peroxide and preparations with it, together with an antibacterial agent, are preferred. in particular an antibacterial acne agent used.

When used according to the invention, the acne agents are used in the same way as in the acne treatment and in the preparations known in the process.

The following agents against acne or propionibacteria or comedones are particularly preferred:

Vitamin A acid (all-trans retinoic acid) e.g. in

0.05 to 0.025% by weight solutions, creams or gels,

Benzoyl peroxide, e.g. in topical preparations such as emulsions, gels, creams, preferably with 0.5 to 20 wt .-%, in particular 2.5 to 10 wt .- /. salary

topical antibiotics, such as

Tretracyclines, erythromycin, clindamycin in ointments, creams, gels, solutions with e.g. 1 to 3% by weight of active ingredient, optionally in combination with benzoyl peroxide, tretinoin, zinc acetate,

Salicylic acid, e.g. in topical preparations with 1 to 10% by weight,

Azelaic acid, for example in creams with 1 to 20% by weight, preferably 15 20 6% by weight of active substance, oral antibiotics such as

Tretracyclines, macrolides, e.g. Doxycycline, minocycline, erythromycin, josamycin, e.g. with daily doses of 50 to 1500 mg

Isotretinoin, e.g. with daily doses of 2.5 to 40 mg

Vitamin A (retinol), administered orally e.g. to

40 mg a day

Retinol palmitate, applied topically, e.g. in solutions,

Creams, gels with 0.1 to 5% by weight !. Active substance content

Cyproterone acetate, e.g. with daily doses of 5 to 100 mg.

The acne agents used according to the invention preferably also contain antioxidants.

Preferred antioxidants are thiols, e.g. Cysteine and cysteine derivatives, glutathione, cystine, N-acetylcysteine, lipoic acid, folic acid, ubiquinone, phytic acid, alpha-hydroxy acids such as e.g. Citric acid and lactic acid, zinc sulfate, zinc oxide, vitamin C, vitamin E, carotene.

The cosmetic or dermatological preparations according to the invention contain antioxidants, for example in amounts of 0.01% by weight to 10% by weight, preferably in amounts of 0.5% by weight to 6% by weight, but in particular 2 % By weight to 4% by weight based on the total weight of the preparations. The active substances according to the invention and the preparations obtained therewith have a prophylactic effect in that they protect the light-sensitive skin and prevent or reduce the formation of PLD. For this purpose, they are used before sun exposure.

With e.g. Photodermatoses and manifest PLE take place in the treatment with the active substances and preparations according to the invention, an improvement in the skin conditions and a faster decay, e.g. the PLD or the photodermatosis.

Cosmetic and dermatological preparations which are in the form of a sunscreen are particularly preferred. These preferably additionally contain at least one UVA filter and / or at least one further UVB filter and / or at least one inorganic pigment.

Cosmetic and dermatological preparations according to the invention for protecting the skin from UV rays can be in various forms, such as those e.g. are usually used for this type of preparation. So you can e.g. a solution, an emulsion of the type water-in-oil (W / 0) or of the type oil-in-water (0 / W), or a multiple emulsions, for example of the type water-in-oil-in-water (W / O / W), a gel, a solid stick or an aerosol.

The cosmetic and dermatological preparations according to the invention can contain cosmetic auxiliaries of the kind normally used in such preparations, for example preservatives, bactericides, perfumes, substances for preventing foaming, dyes, pigments which have a coloring effect, Thickeners, surface-active substances, emulsifiers, softening, moisturizing and / or moisturizing substances, fats, oils, waxes or other usual components of a cosmetic or dermatological formulation such as alcohols, polyols, polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives.

If the cosmetic or dermatological preparation is a solution or lotion, ^ .B. used as solvents:

Water or aqueous solutions

Oils, such as triglycerides of capric or caprylic acid, but preferably castor oil;

Fats, waxes and other natural and synthetic fat bodies, preferably esters of fatty acids with alcohols of low C number, e.g. with isopropanol, propylene glycol or glycerin, or esters of fatty alcohols with low C number alkanoic acids or with fatty acids;

Alcohols, diols or polyols of low C number, as well as their ethers, preferably ethanol, isopropanol, propylene glycol, glycerin, ethylene glycol, ethylene glycol monoethyl or monobutyl ether, propylene glycol monomethyl, monoethyl or monobutyl ether, diethylene glycol onomethyl or monoethyl ether and analog products.

Mixtures of the abovementioned solvents are used in particular. Water can also be a component of alcoholic solvents. Emulsions according to the invention, for example in the form of a sunscreen cream or sunscreen milk, are preferred and contain, for example, the fats, oils, waxes and other fat bodies mentioned, as well as water and an emulsifier, as is customarily used for such a type of formulation.

Gels according to the invention usually contain low C number alcohols, e.g. Ethanol, isopropanol, 1,2-propanediol, glycerol and water or an oil mentioned above in the presence of a thickener, which is preferred in the case of oily-alcoholic gels, preferably silicon dioxide or an aluminum silicate, in the case of aqueous-alcoholic or alcoholic gels is a polyacrylate.

Fixed pins according to the invention contain e.g. natural or synthetic waxes, fatty alcohols or fatty acid esters. Lip care sticks are preferred.

Suitable blowing agents for cosmetic deodorants according to the invention which can be sprayed from aerosol containers are the customary, known volatile, liquefied blowing agents, for example hydrocarbons (propane, butane, isobutane), which can be used alone or in a mixture with one another. Compressed air can also be used advantageously.

Of course, the person skilled in the art knows that there are non-toxic propellant gases per se which would in principle be suitable for the present invention, but which should nevertheless be dispensed with, in particular fluorocarbons and chlorofluorocarbons (CFCs), because of their harmful effects on the environment or other associated circumstances. The topical preparations according to the invention can preferably also contain substances which absorb UV radiation in the UVA and / or in the UVB range, the total amount of the filter substances being, for example, 0.1% by weight to 30% by weight, preferably 0.5 to 10 wt. , in particular 1 to 6% by weight, based on the total weight of the preparations, in order to provide cosmetic preparations which protect the skin from the entire range of ultraviolet radiation. They can also serve as sunscreens.

The UVB filters can be oil-soluble or water-soluble. As oil-soluble substances e.g. to call:

- 3-benzylidene camphor derivatives, preferably 3- (4-methylbenzylidene) camphor, 3-benzylidene camphor;

- 4-aminobenzoic acid derivatives, preferably 4- (dimethylamino) benzoic acid (2-ethylhexyl) ester, 4- (dimethylamino) benzoic acid amyl ester;

- Esters of cinnamic acid, preferably 4-methoxycinnamic acid (2-ethylhexyl) ester, 4-methoxycytic acid isopentyl ester;

- esters of salicylic acid, preferably salicylic acid (2-ethylhexyl) ester, salicylic acid (4-isopropylbenzyl) ester, salicylic acid homomethyl ester;

Derivatives of benzophenone, preferably 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone; - Esters of benzalmalonic acid, preferably 4-methoxybenzalmalonic acid di (2-ethylhexyl) ester;

- 2,4,6-trianilino- (p-carbo-2'-ethyl-1'-hexyloxy) -1, 3,5-triazine.

As water-soluble substances e.g. to call:

- Salts of 2-phenylbenzimidazole-5-sulfonic acid such as its sodium, potassium or triethanolammonium salt, and the sulfonic acid itself;

- Sulfonic acid derivatives of benzophenones, preferably 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and its salts;

- Sulfonic acid derivatives of 3-benzylidene camphor, e.g. 4- (2-0xo-3-bornylidenemethyl) benzenesulfonic acid, 2-methy1-5- (2-oxo-3-bornylidenemethyl) sulfonic acid and their salts.

The list of UVB filters mentioned should, of course, not be limiting.

The invention also relates to preparations according to the invention with combinations of a UVA filter with a UVB filter or cosmetic or dermatological preparations according to the invention which also contain a UVB filter.

It can also be advantageous to combine the active substances according to the invention with UVA filters, which have hitherto usually been contained in cosmetic preparations. These substances are preferably derivatives of dibenzoylmethane, in particular 1- (4'- tert-Butylphenyl) -3- (4'-methoxyphenyl) propane-1, 3-dione and 1-phenyl-3- (4 '-isopropylphenyl) propane-1, 3-dione. These combinations or preparations which contain these combinations are also the subject of the invention. It ^• The amounts used for the UVA combination can be used.

Cosmetic and dermatological preparations according to the invention can also contain inorganic pigments which are usually used in cosmetics to protect the skin from UV rays. These are oxides of titanium, zinc, iron, zirconium, silicon, manganese, aluminum, cerium and mixtures thereof, as well as modifications in which the oxides are the active agents. It is particularly preferred to use pigments based on titanium dioxide. These combinations of UVA filter and pigment or preparations containing this combination are also the subject of the invention. The amounts given for the above combinations can be used.

Unless otherwise stated, all quantities, parts and percentages are based on the weight and the total amount or on the total weight of the preparations.

The invention also relates to the process for the production of the cosmetic compositions according to the invention, which is characterized in that the active ingredients according to the invention are incorporated into cosmetic and dermatological formulations in a manner known per se.

The following examples are intended to illustrate the present invention without restricting it. The preparations of the examples show excellent effects in the prophylaxis and treatment of sensitive skin, photodermatoses and PLD.

The preparations are prepared in a manner known per se, in particular by mixing the constituents, if appropriate at elevated temperature. Fat and water phase are produced separately and mixed or emulsified if necessary at elevated temperature.

Example I

W / O type skin cream

Fat phase:% by weight

Benzoyl peroxide 5

Vaseline DAB 9 13

Paraffin oil

(Mineral oil 5E, Shell) 26

Cetearyl alcohol / PEG-40-

Castor Oil / sodium cetearyl sulfate (Emulgade F, Henkel KGaA) 2.5

Water phase:

Glycerin DAB 9 6.3

Water, demineralized 34.4

A mixture of 6.3% by weight of wool wax alcohols and 6.5% by weight of paraffin oil is added to the fat phase at 75 ° C. The fat phase is then added to the 75 ° C warm water phase, stirred and homogenized until a uniform white cream has formed.

Example I has the following final composition:

% By weight

Vaseline DAB 9 13

Glycerin DAB 9 6.3

Water, demineralized 29.7 paraffin oil

(Mineral oil 5E, Shell) 37.5 cetearyl alcohol / PEG-40 Castor Oil / sodium cetearyl sulfate (Emulgade F, Henkel KGaA) 2.5 D

Wool wax alcohols (Eucerit) 6

Benzoyl peroxide 5.0

Example II

W / 0 type skin cream

Fat phase: wt. . -%

Tetracycline HCL 3

POE glycerol sorbitan oleostearate

(Arlacel 581, ICI) 8

Vaseline DAB 2, 8

Paraffin wax / paraffin 1, 8

Ceresin 2, 2

Octyldodecanol

(Eutanol G, Henkel) 10

Total additives (perfume,

Preservation, stabilization) 0.8

Water phase:

Propylene glycol 1

Glycerin 1

Magnesium sulfate 0.7

Water, demineralized 56.65

The fat phase at 75 ° C. is added to the water phase at 75 ° C., stirred and homogenized until a uniform white cream has formed. In game III

Fat phase: wt. -

Salicylic acid 5

Octyldodecanol

(Eutanol G, Henkel KGaA) 9.3

Cetearyl alcohol / PEG-40-

Castor Oil / sodium cetearyl sulfate (Emulgade F, Henkel KGaA) 3.7

Paraffin oil

(Mineral oil eE, Shell) 1.4

Water phase:

Water, demineralized 68.7

Glycerin DAB 9 4.6

The preparation takes place as indicated in Example II.

Example IV

Hydrogel

Benzoyl peroxide 100.0 g 2-phenylbenzimidazo1-5-sulfonic acid,

("Eusolex 232", Merck) 27.0 g

Allantoin 2.0 g

Sorbitol fl. ("Karion F", Merck) 22.0 g

"Carbopol 934", B.F. Goodrich 15.0 g

Tris (hydroxymethyl) aminomethane 27.0 g

Propylene glycol 10.0 g

Ethanol 300.0 g

Water 497.0 g perfume, correctives, additives, Antioxidants, stabilizers at will

A hydrogel is produced in the usual way with the constituents mentioned.

Example V

Aqueous gel% by weight

Polyacrylate,

Carbomer 5984 (B.F. Goodrich) 0.25%

Polyacrylate,

Carbomer 2984 (B.F. Goodrich) 0.45%

PEG-20 monostearate, Myrj 49 (ICI) 2.0%

Benzoyl peroxide 5.0%

Polyethylene glycol 400 5.0 l

Water ad 100%

A gel is produced with the ingredients in the usual way.

Claims

1. Use of active ingredients or preparations which are used or suitable for acne treatment for the prophylaxis and treatment of light-sensitive skin, in particular photodermatoses and preferably polymorphic light dermatosis.

2. Use according to claim 1, characterized in that a UV protection agent such as a UVA blocker and / or a UVB blocker is additionally used.

3. Use according to claim 1 or 2, characterized gekenn¬ characterized in that an antioxidant or more antioxidants are additionally used.

4. Use according to claim 1, characterized in that benzoyl peroxide and preparations are used therewith, optionally in combination with an antibacterial acne agent.