DE4434312A1 - Antimycotic cosmetic and dermatological compsns. - Google Patents

Abstract

Use of alkyl-substd. hydroquinones (I) as antimycotically-active agents in cosmetic and dermatological compsns. is new. PREFERRED HYDROQUINONE - (I) is pref. tert.-butyl hydroquinone (TBHQ). (I) may be used in the form of a plant extract, esp. a thyme or rosemary extract.

Description

The present invention relates to antimycotic agents and preparation protected against infestation with mycobionts tion, preferably cosmetic or dermatological accessories horse riding.

Mushrooms, also fungi [fungus = lat. Mushroom], Mycota [mykes = grch. Mushroom] or Mycobionten, belong to the Euca ryonten. Eucaryotes are living things whose cells (eucytes) in contrast to those of the so-called procaryotes (Procyten) via a through nuclear envelope and nuclear membrane from remaining cytoplasm delimited cell nucleus. Of the The nucleus contains the genetic information stored in chromosomes chert.

Representatives of the mycobionts include yeasts, for example (Protoascomycetes), mold (Plectomycetes), powdery mildew (Pyrenomycetes), downy mildew (Phycomycetes) and the Mushrooms (Basidiomycetes).

Mushrooms, not even the Basidiomycetes, are not vegetable Chen organisms, but like this have a cell wall, cell juice-filled vacuoles and a microscopic one Plasma flow. They do not contain photosynthetic pig elements and are C-heterotrophic. They grow under aerobic Conditions and gain energy through oxidation of organic Substances. Some representatives, such as yeasts, are  however, optional anaerobes and for energy production enabled by fermentation processes.

Dermatomycoses are diseases in which certain types of fungi, especially dermatophytes, in the skin and hair follicles penetration. The symptoms of dermatomycoses are for example vesicles, exfoliation, rhagades and erosion, mostly associated with itching or allergic eczema.

Dermatomycoses can essentially be broken down into four Groups are divided into: Dermatophytia (e.g. Epidermo phytia, favus, microsporie, trichophytia), yeast mycoses (e.g. Pityriasis and other pityosporum-related mycoses, Candida Infections, blastomycosis, Busse-Buschke disease, Torulose, piedra alba, torulopsidosis, trichosporosis), Mold mycoses (e.g. aspergillosis, cephalosporidosis, Phycomycosis and scopulariopsidosis), system mycoses (e.g. Chromomycosis, coccidiomycosis, histoplasmosis).

Pathogenic and facultative pathogens include from the group of the yeast Candida species (e.g. Candida albi cans) and those of the Pityrosporum family. Pityrosporum Species, especially Pityrosporum ovale, are for skin diseases such as pityriasis versicolor, seborrhea in the Forms Seborrhoea oleosa and Seborrhoea sicca, which are especially express as seborrhea capitis (= dandruff), seborrheic eczema and pityrosporum folliculitis to make literal.

All areas of human skin can be made from Dermatomy cosen be infected. Dermatophytia almost infest finally skin, hair and nails. Hefemycoses can also Mucous membranes and internal organs are affected, system mycoses extend to entire organ systems on a regular basis.

The areas of the body that are affected are particularly often affected  get wet through clothing, jewelry or footwear activity and heat can accumulate. So the athlete's foot belongs to the best known and most widespread dermatomy cosen. Fungal diseases are still particularly unpleasant the finger and toenail areas.

Furthermore, super infections of the skin by fungi are not Rare.

The healthy human skin is not with a variety pathogenic microorganisms colonized. This so-called Mi Kroflora of the skin is not only harmless, it restores important protection against opportunistic or pathogenic germs.

If there is a primary infection, d. that is, the normal germ settlement of the skin, new infection occurring with high Bacterial counts of one or more often physiological pathogens, for example staphylococci, but often also non-physiological pathogens, for example Candida albicans, can have a negative impact when adverse influences come together "Superinfection" of the affected skin occurs. The normal one Microflora of the skin (or other body organ) thereby literally overgrown by the secondary pathogen.

Such super infections can, depending on germ in question, in favorable cases in unan pleasant skin symptoms (itching, unsightly external appearance Appearance). In unfavorable cases but they can lead to extensive destruction of the skin, in the worst case, culminating in the patient's death.

Superinfections of the type described above are e.g. B. at Full screen of AIDS common secondary diseases. In itself - at least in low germ densities - harmless, but possibly also very pathogenic germs  in this way overgrow the healthy skin flora. With AIDS however, other body organs are also superinfectious ons affected.

Such superinfections are also common in a large number dermatological diseases, e.g. B. atopic eczema, Neurodermatitis, acne, seborrheic dermatitis or Psoriasis observed. Many medical and therapeutic measures, e.g. B. radio or chemotherapy of tumor diseases, caused as a side effect, drug-induced immunosuppression or systemic antibiotic treatment, as well as external chemical or physical influences (e.g. environmental ver dirt, smog), promote the appearance of Superinfections of the external and internal organs, especially the skin and mucous membranes.

In individual cases it is possible without further ado, Superin to fight infections with antibiotics, usually have sol che substances but the disadvantage of unpleasant side effects kungen. For example, patients are often against penicillins allergic, which is why a corresponding treatment is in would prohibit such a case.

Furthermore, topically administered antibiotics have the disadvantage that that they not only get the skin flora from the secondary pathogen free, but also the physiological skin flora severely affect and the natural healing process this way is braked again.

An object of the present invention was the disadvantages the state of the art to eliminate and substances and Preparations containing such substances are available to be cured by using super infections can be, the physiological skin flora none suffered significant losses.  

Furthermore, it was a task of the present one Invention, substances and cosmetic or dermatological Preparations containing such substances are available to face the prophylactic against super infections Act.

Finally, mycobiont infestation can cause preparations especially food, but also cosmetics and the same are destroyed. Protection against infection stretches therefore also on the products themselves.

Dermatomycoses are treated with medication or with others ren methods, for example with light irradiation. Common Medications contain salicylic acid, cresol, 1-menthol and others, all of which are applied externally and regularly bring good healing success.

Nevertheless, the previously known antimycotic have The disadvantage is that they smell unpleasant and / or that additionally irritate affected skin area. In severe Cases of dermatomycoses can even be caused by the drug Pain triggered.

Another object of the present invention was to provide antimycotic agents which do not have the disadvantages of the prior art exhibit. In particular, active ingredients should be made accessible that meet the following conditions:

• 1) The biological processes of the skin must not be affected to be pregnant.
• 2) The active ingredients should not have a distinctive smell have.  
• 3) You should not be in case of overdose or other harmless use.
• 4) You shouldn't get up after repeated use enrich the skin.
• 5) Pathogenic and facultative pathogenic mycobionts should effectively combat the physiological microflora the rest of the skin, however.
• 6) The effective principles should work well in usual cosmetic or dermatological formulations let work.
• 7) The active ingredients should not irritate the skin.
• 8) Preparations containing these active ingredients should also be protected against mycobiont infestation.

It has been found and that is the solution to all of these Tasks that the use of alkyl substituted hydrochi none as an antimycotic active principle in cosmetic or dermatological preparations the disadvantages of the state the technology helps.

It has surprisingly turned out that the Hydroquinone derivatives according to the invention the growth of My Prevent cobionts.

In particular, the hydroquinone derivatives according to the invention enables yeast growth, especially the pi tyrosporum species, namely Pityrosporum ovale, to ver prevent.

It has also been found that the inventive Hydroquinone derivatives the formation of seborrheic Er  prevent symptoms, especially dandruff, and pre-existing seborrheic phenomena, in particular To eliminate dandruff.

A method for controlling is therefore also according to the invention seborrheic symptoms, especially dandruff, as well as prophylaxis against seborrheic symptoms, especially dandruff.

Finally, it has been found that the fiction hydroquinones the spoilage of organic matter, ins special cosmetic and dermatological preparations, can prevent by infestation with mycobionts if they be added to these preparations.

According to the invention are therefore also a method for combating of mycobionts, characterized in that alkylated Hydroquinones, optionally in a suitable cosmos tables or dermatological carriers with which Myco the contaminated area, and a process for protecting organic products from the Infestation with mycobionts, characterized in that this organic products alkylated hydroquinones in effective Amount to be added.

The alkylated hydroquinones according to the invention stand out advantageous due to the following structure:

where R _1-4 are selected independently of one another from the group consisting of hydrogen and the branched and unbranched alkyl groups having 1 to 10 carbon atoms, at least one of the radicals R _{1-4 being} an alkyl radical.

The preferred alkylated hydroquinone has been tert-Bu tylhydroquinone (TBHQ)

proven.

The antioxidant effect of certain alkylated ones Hydroquinones known. EP-A 472 225 and EP-A- 229 561 cosmetic or pharmaceutical preparations described, which may include TBHQ. However, this serves in the above-mentioned. described accessories riding as a stabilizer against the ingress of oxygen.

Preparations for dermatoses are described in RO-A-79 428 wrote which contain unsubstituted hydroquinone can.

The prior art therefore did not deliver the slightest Reference to the use according to the invention as an antimyco operating principle.

It was also surprising that the alky hydroquinones are particularly effective against the germ responsible for the development of dandruff Pityrosporum oval and related germs. A preferred one  Embodiments of the present invention are therefore against Formulations to be used for dandruff, for example Anti-dandruff shampoos.

According to the alkylated hydroquinones before in cosmetic or dermatological compositions used a content of 0.005-50.0 wt .-%, esp Special 0.01-20.0 wt .-%, based on the total weight the composition are preferred. Advantageously included the compositions 0.02-10.0% by weight, especially before add 0.02-5.0 wt .-% of the alkylated invention Hydroquinones, very particularly advantageously 0.5-3.0% by weight, each based on the total weight of the composition.

It is also an advantage rather than a purely inventive one Hydroquinones to use such substances, which are in turn through a content of the invention Mark hydroquinones. Such substances include for example some plant extracts such as rosemary extract and thyme extract.

The alkylated hydroquinones according to the invention can be without difficulty in common cosmetic or dermato Incorporate logical formulations, advantageous in Pump sprays, aerosol sprays, creams, ointments, tinctures, lotions, Nail care products (e.g. nail polishes, nail polish remover, Nail balms) and the like.

The present invention is particularly advantageous alkylated hydroquinones in the form of anti-dandruff shampoos in front.

It is also possible and advantageous if necessary alkylated hydroquinones according to the invention with others Combine active ingredients, for example with antimicro biologically active substances.  

It is advantageous the compositions of the invention buffer. A pH range of 3.5-7.5 is advantageous. It is particularly favorable to adjust the pH in a range of 4.0-6.0 to choose.

The cosmetic and / or dermatological invention Formulations can be composed as usual and to treat the skin and / or hair in the sense of a dermatological treatment or a treatment in the sense serve the care cosmetics. But you can also in Make-up products used in decorative cosmetics will.

The cosmetic according to the invention are used and / or dermatological formulations in the for Kosme tika and dermatics usual way on the skin and / or the Hair applied in sufficient quantities.

Such cosmetic and dermatological are advantageous Preparations in the form of a sunscreen available. These additionally advantageously contain at least a UVA filter and / or at least one UVB filter and / or at least one inorganic pigment.

Protective cosmetic preparations according to the invention The skin from UV rays can come in different forms are present, such as. B. usually for this type of Preparations are used. So you can z. Legs Solution, an emulsion of the type water-in-oil (W / O) or of Type oil-in-water (O / W), or a multiple emulsions, for example of the water-in-oil-in-water (W / O / W) type Gel, a hydrodispersion, a solid stick or even a Represent aerosol.

The cosmetic preparations according to the invention can  Contain cosmetic auxiliaries, as usually in such preparations are used, e.g. B. Conserve agents, bactericides, antioxidants, perfumes, agents to prevent foaming, dyes, pigments, the one have coloring effect, thickener, surface active Substances, emulsifiers, softening substances, moist and moisturizing substances, fats, oils, waxes or other common components of a cosmetic Formulation such as alcohols, polyols, polymers, foam stabilizers lisators, electrolytes, organic solvents or Si liqueur derivatives.

If the cosmetic or dermatological preparation Solution or lotion can be used as a solvent be used:

• - 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 Al low C number alcohols, e.g. B. with isopropanol, Pro pylene glycol or glycerin, or esters of fatty alcohols with low C number alkanoic acids or with fatty acids;
• - Alcohols, diols or polyols with a low C number, and their ethers, preferably ethanol, isopropanol, pro pylene glycol, glycerin, ethylene glycol, ethylene glycol monoethyl or monobutyl ether, propylene glycol mono methyl, monoethyl or monobutyl ether, diethylene glycol monomethyl or monoethyl ether and analog Products.

In particular, mixtures of the aforementioned Lö  means used. With alcoholic solvents can Water can be another ingredient.

According to the invention, all of the following can be used as favorable antioxidants suitable for cosmetic and / or dermatological applications or common antioxidants can be used.

The antioxidants are advantageously selected from the group consisting of amino acids (e.g. glycine, histidine, tyrosine, Tryptophan) and their derivatives, imidazoles (e.g. urocanic acid re) and their derivatives, peptides such as D, L-carnosine, D- Carnosine, L-carnosine and their derivatives (e.g. anserine), Carotenoids, carotenes (e.g. α-carotene, β-carotene, lycopene) and their derivatives, lipoic acid and their derivatives (e.g. Dihydrolipoic acid), aurothioglucose, propylthiouracil and other thiols (e.g. thioredoxin, glutathione, cysteine, Cystine, cystamine and their glycosyl, N-acetyl, methyl, Ethyl, propyl, amyl, butyl and lauryl, palmitoyl, Oleyl, γ-linoleyl, cholesteryl and glyceryl esters) and their salts, dilauryl thiodipropionate, distearyl thiodipropio nat, thiodipropionic acid and its derivatives (esters, ethers, Peptides, lipids, nucleotides, nucleosides and salts) and Sulfoximine compounds (e.g. buthionine sulfoximines, homocy stone sulfoximine, buthionine sulfones, penta-, hexa-, heptathio ninsulfoximine) in very low tolerable doses (e.g. pmol to µmol / kg), also (metal) chelators (e.g. α- Hydroxy fatty acids, palmitic acid, phytic acid, lactofer rin), α-hydroxy acids (e.g. citric acid, lactic acid, Ap rock acid), humic acid, bile acid, bile extracts, bili ruby, biliverdin, EDTA, EGTA and their derivatives, unsaturated saturated fatty acids and their derivatives (e.g. γ-linolenic acid, Linoleic acid, oleic acid), folic acid and its derivatives, ubiquinone and ubiquinol and its derivatives, vitamin C and derivatives (e.g. ascorbyl palmitate, Mg ascorbyl phosphate, Ascorbyl acetate), tocopherols and derivatives (e.g. vitamin E - acetate), vitamin A and derivatives (vitamin A palmitate) and  Konyferyl benzoate of benzoin, rutinic acid and their Derivatives, ferulic acid and its derivatives, butyl hy droxytoluene, butylated hydroxyanisole, nordihydroguajakh resin acid, Nordihydroguajaretic acid, trihydroxybutyrophenon, uric acid and their derivatives, mannose and their derivatives, zinc and its derivatives (e.g. ZnO, ZnSO₄) selenium and its derivatives (e.g. selenium methionine), stilbene and their derivatives (e.g. Stilbene oxide, trans-stilbene oxide) and the invention suitable derivatives (salts, esters, ethers, sugars, nu kleotide, nucleosides, peptides and lipids) of these Active ingredients.

The amount of antioxidants (one or more compounds gen) in the preparations is preferably 0.001 to 30 % By weight, particularly preferably 0.05-20% by weight, in particular 1-10 wt .-%, based on the total weight of the preparation.

Provided that vitamin E and / or its derivatives or the Antioxidants are beneficial, their respective Concentrations in the range of 0.001-10% by weight, based on the total weight of the formulation.

If vitamin A, or vitamin A derivatives, or carotenes or their derivatives represent the antioxidant (s), is advantageous, their respective concentrations from the Range of 0.001-10% by weight based on the total weight the wording to choose.

Emulsions according to the invention are advantageous and contain e.g. B. the said fats, oils, waxes and other fat per, as well as water and an emulsifier, as he usually does is used for such a type of formulation.

Gels according to the invention usually contain alcohols low C number, e.g. B. ethanol, isopropanol, 1,2-propanediol, Glycerin and water or an oil mentioned above in  Presence of a thickening agent that is used in oily-alko Holic gels preferably silicon dioxide or an aluminum minium silicate, for aqueous-alcoholic or alcoholic Gel is preferably a polyacrylate.

Fixed pins according to the invention contain e.g. B. natural or synthetic waxes, fatty alcohols or fatty acid esters. Lip care sticks and deodorant are preferred Pens ("deodorant sticks").

As a propellant for aerosol containers according to the invention sprayable cosmetic or dermatological preparations are the usual well known volatile, liquefied Propellants, e.g. B. hydrocarbons (propane, butane, Isobutane) suitable, alone or in a mixture with each other can be used. Compressed air is also advantageous use.

Of course, the expert knows that it is in itself non-toxic Propellant gases are there, basically for the present Er would be suitable, but nevertheless because of concerns effect on the environment or other accompanying circumstances should be avoided, especially fluorocarbons Hydrocarbons and chlorofluorocarbons (CFCs).

The preparations according to the invention can also preferably Contain substances that absorb UV radiation in the UVB range beers, the total amount of filter substances z. B. 0.1 % By weight to 30% by weight, preferably 0.5 to 10% by weight, in particular is particularly 1 to 6 wt .-%, based on the Ge total weight of the preparation to make cosmetic preparations to provide the skin before the whole Protect the area of ultraviolet radiation. You can also serve as a sunscreen.

Cosmetic preparations according to the present invention  can also contain inorganic pigments, the more common wise in cosmetics to protect the skin from UV rays be used. These are oxides of titanium, Zinc, iron, zirconium, silicon, manganese, aluminum, Cers and mixtures thereof, as well as modifications in which the Oxides are the active agents. Acts particularly preferred are pigments based on titanium dioxide.

Cosmetic preparations for hair care it is, for example, shampoo, Zu Preparations when rinsing the hair before or after the Shampooing, before or after the permanent wave treatment, before or applied after coloring or decoloring the hair be used to blow-dry or lay hair, Preparations for dyeing or decolorizing a hairdressing and treatment lotion, a hair varnish, or by duration corrugating agent.

The cosmetic preparations contain active ingredients and Excipients, such as those commonly used for this type of Preparations used for hair care and hair treatment will.

Preservatives serve as auxiliary substances, surfactants, substances for preventing the Foaming, emulsifiers, thickeners, fats, oils, Waxes, organic solvents, bactericides, perfumes, Dyes or pigments whose job it is to hair or to dye the preparation itself, electrolytes, preparation against hair greasing.

Cosmetic preparations containing a shampoo or represent a washing, shower or bath preparation, preferably contain at least one anionic, non- ionic or amphoteric surfactant or Mixtures thereof, at least one ethoxy according to the invention  lated or propoxylated organic compound in aqueous Medium and aids, as is usually the case be used. The surface-active substance can be in a concentration between 1 wt .-% and 50 wt .-% in the Shampoo, or the washing, showering or bathing preparation, available.

Is the cosmetic or dermatological preparation in Form of a lotion before rinsing and z. B. before or after discoloration, before or after shampooing, between two shampooing steps, before or after the duration Well treatment is applied, so it is e.g. B. to aqueous or aqueous-alcoholic solutions that optionally contain surface-active substances, preferably non-ionic or cationic surface-active Substances whose concentration is between 0.1 and 10% by weight, preferably between 0.2 and 5% by weight. These cosmetic or dermatological preparation can also be a Aerosol with the aids commonly used for this represent.

A cosmetic preparation in the form of a lotion that is not is rinsed out, especially a lotion to insert the Hair, a lotion used to blow-dry hair, a hairdressing and treatment lotion, in general an aqueous, alcoholic or aqueous-alcoholic solution and contains at least one cationic, anionic, non-ionic or amphoteric polymer or mixtures the same, and at least one according to the invention alkylated hydroquinone. The amount of used Hydroquinone derivatives are e.g. B. between 0.1 and 10% by weight, preferably between 0.1 and 3% by weight.

Cosmetic and dermatological preparations for treatment and hair care, at least one according to the invention alkylated hydroquinone can contain as emulsions  are present, which are of the non-ionic or anionic type are. In addition to water, non-ionic emulsions contain oils or fatty alcohols, for example polyethoxylated or can be polypropoxylated, or mixtures of the two organic components. These emulsions contain optionally cationic surface-active substances. Anionic emulsions are preferably of the soap type and contain at least one ethoxylated according to the invention or propoxylated organic compound with anionic or non-ionic in character.

Cosmetic and dermatological preparations for treatment and hair care can be present as gels, alongside at least one alkylated hydroquinone according to the invention and solvents usually used for it organic thickeners, e.g. B. gum arabic, Xanthan gum, sodium alginate, cellulose derivatives, preferably methyl cellulose, hydroxymethyl cellulose, Hy droxyethyl cellulose, hydroxypropyl cellulose, hydroxypro pylmethyl cellulose or inorganic thickeners, e.g. B. Aluminum silicates such as bentonite, or a Mixture of polyethylene glycol and polyethylene glycol stearate or distearate. The thickener is in the gel e.g. B. in an amount between 0.1 and 30 wt .-%, preferred between 0.5 and 15% by weight.

The amount of alky according to the invention is preferably hydroquinones in a hair-destined Average 0.01% by weight to 10% by weight, in particular 0.5% by weight to 5% by weight, based on the total weight of the preparations.

The following examples are intended to represent the embodiment of the illustrate lying inventions. Get the information always refer to% by weight, unless otherwise stated be made.  

example 1

Example 2

Example 3

Example 4

Example 5

Example 6

Example 7

Example 8

Example 9

Example 10

Example 11

Example 12

Example 13

Example 14

Example 15

Example 16

Example 17

Example 18

Example 19

Example 20

Example 21

Example 22

By mixing the respective components together liquid phase obtained is combined with a propane 39: 61 butane mixture (2: 7) in aerosol container bottled.  

Example 23

Example 24

Example 25

Example 26

Proof of effectiveness

The characterization of the antifungal efficacy of TBHQ was carried out using the inhibition test. It became watery Solutions containing increasing concentrations of TBHQ, for their effectiveness against Pityrosporum ovale examined.

The effectiveness corresponds essentially to that of a be knew antimicrobial used in shampoos active substance, the monoethanolamine salt of 1-hydroxy 4-methyl-6- (2,4,4-trimethylpentyl) -2- (1H) pyridone.

Claims (7)

1. Use of alkyl-substituted hydroquinones as antimy cotic active principle in cosmetic or dermatological Preparations. 2. Use according to claim 1, characterized in that the alkylated hydroquinones have the following structure: where R _1-4 are selected independently of one another from the group consisting of hydrogen and the branched and unbranched alkyl groups having 1 to 10 carbon atoms and at least one of the radicals R _{1-4 represents} an alkyl radical. 3. Use according to claim 1, characterized in that the tert-butylhydroquinone as the alkylated hydroquinone is chosen. 4. Use according to claim 1, characterized in that the alkylated hydroquinone or plants in the form of plants Extracts are available. 5. Use according to claim 5, characterized in that as herbal extracts thyme extract and / or Rosemary extract can be chosen. 6. Use according to claim 1, characterized in that the preparations were in the form of anti-dandruff shampoos gene. 7. Use of one or more alkylated hydroquinones to combat fungus-induced Super infections.