WO2011050871A1

WO2011050871A1 - Use of menthyl ethers as anti-bacterial, anti-mycotic or anti-viral active substances

Info

Publication number: WO2011050871A1
Application number: PCT/EP2010/004556
Authority: WO
Inventors: Kathrin Thiesen; Bernd Traupe
Original assignee: Beiersdorf Ag
Priority date: 2009-10-27
Filing date: 2010-07-26
Publication date: 2011-05-05
Also published as: EP2493463A1; BR112012009730A2; DE102009050854A1

Abstract

The invention relates to the use of menthyl ethers with a structure (I), in which R represents a branched or unbranched alkyl group, optionally monosubstituted or polysubstituted with hydroxy groups and comprising up to 10 carbon atoms, as anti-bacterial, anti-mycotic or anti-viral active substances.

Description

Beiersdorf Aktiengesellschaft

description

Use of menthyl ethers as antibacterial, antimycotic or antiviral agents

The present invention relates to the use of substances known per se as active against bacteria, mycota and viruses substances. In particular embodiments, the present invention relates to cosmetic and dermatological preparations containing such substances.

The healthy warm-blooded organism, especially the healthy human skin, is populated with a variety of non-pathogenic microorganisms. This so-called microflora of the skin is not only harmless, it represents an important protection against opportunistic or pathogenic germs.

Bacteria belong to the prokaryotic unicellular organisms. They can be roughly distinguished according to their shape (sphere, cylinder, curved cylinder) and the structure of their cell wall (gram-positive, gram-negative). Finer subdivisions also take into account the physiology of the organisms. There are aerobic, anaerobic and facultative anaerobic bacteria. Some individuals are of medical importance in their capacity as pathogenic agents, while others are completely harmless.

Against bacteria active substances have been known for some time. The term "antibiotics", for example, which is not applicable to all antimicrobial substances, can be dated to the year 1941, although the first findings on penicillin were already found in 1929. Antibiotics in the modern sense are not for all medical, even not suitable for cosmetic applications, since often the warm-blooded organism, so for example the diseased patient, at

CONFIRMATION COPY Application is impaired in any way in its metabolic functions.

It was therefore an object of the present invention to enrich the state of the art in this direction, in particular to provide substances which are active against gram-positive and / or gram-negative bacteria, without an unacceptable impairment of health with the use of the substances the user would be connected.

Gram-negative bacteria are, for example, Escherichia coli, Pseudomonas species and Enterobacteriaceae, such as Citrobacter.

Gram-positive bacteria also play a role in cosmetics and dermatology. In the case of impure skin, for example, bacterial secondary infections of etiological importance are, among other influences. One of the most important microorganisms associated with impure skin is Propionibacterium acnes.

Impure skin and / or comedones affect the well-being of those affected but even in mild cases. Since virtually every adolescent or person is affected by blemished skin of some kind, many people need to remedy this condition.

A particular object of the present invention was therefore to find a substance or combination of substances which is effective against impure skin or Propionibacterium acnes.

The present invention relates in a further embodiment cosmetic deodorants. Such formulations serve to eliminate body odor, which arises when the per se odorless fresh sweat is decomposed by especially gram-positive microorganisms. Microorganisms that are responsible for the formation of odor are Coryneform bacteria, staphylococci, propionibacteria, micrococci and anaerobic bacteria. The usual cosmetic deodorants are based on different active principles. Both known and customary are liquid deodorants, for example aerosol sprays, roll-ons and the like, as well as solid preparations, for example deodorant sticks ("sticks"), powders, powder sprays, intimate cleaners, etc.

In so-called antiperspirants can be prevented by astringents - mainly aluminum salts such as aluminum hydroxychloride (Aluchlorhydrat) - the formation of sweat.

By using antimicrobial substances in cosmetic deodorants, the bacterial flora on the skin can be reduced. Ideally, only the odor causing microorganisms should be effectively reduced. In practice, however, it has been found that the entire microflora of the skin can be affected.

The sweat flow itself is not influenced by this, ideally only the microbial decomposition of the sweat is temporarily stopped.

The combination of astringents with antimicrobial substances in the same composition is also common. However, the disadvantages of both classes of active ingredients can not be completely eliminated in this way.

Finally, body odor can also be masked by fragrances, a method that is least in line with the consumer's aesthetic needs, as the mixture of body odor and perfume smells rather unpleasant.

However, most cosmetic deodorants, as well as most cosmetics as a whole, are perfumed even if they contain deodorizing agents. Perfuming can also serve to increase the consumer acceptance of a cosmetic product or to give a product a certain flair.

The perfuming of active ingredient-containing cosmetic agents, in particular cosmetic deodorants, however, is often problematic because active ingredients and perfume ingredients can occasionally react with each other and make each other ineffective. Deodorants should fulfill the following conditions:

1) They should cause a reliable deodorization.

2) The natural biological processes of the skin must not be impaired by the deodorants.

3) The deodorants must be harmless in case of overdose or other improper use.

4) They should not accumulate on the skin after repeated use.

5) They should be well incorporated into common cosmetic formulations.

Another object of the present invention was therefore to develop cosmetic deodorants which do not have the disadvantages of the prior art. In particular, the deodorants should protect the microflora of the skin largely, but selectively reduce the number of microorganisms that are responsible for the body odor.

Furthermore, it was an object of the invention to develop cosmetic deodorants, which are characterized by good skin compatibility. In no case should the deodorizing principles of action accumulate on the skin.

A further object was to develop cosmetic deodorants which harmonize with the widest possible variety of customary cosmetic auxiliaries and additives, in particular with the perfume ingredients which are especially important in deodorizing or antiperspirant formulations.

Yet another object of the invention was to provide cosmetic deodorants which are effective over a prolonged period, on the order of at least half a day, without noticeably reducing their effect.

Finally, it was an object of the present invention to develop deodorizing cosmetic principles which can be incorporated as universally as possible into the most diverse dosage forms of cosmetic deodorants, without being limited to one or a few special dosage forms. Mushrooms, also called fungi [fungus = lat. Fungus], Mycota [μυκης = common fungus] or mycobionts, count as eucaryotes in contrast to the bacteria. Eucaryotes are organisms whose cells (Eucytes), unlike those of the so-called procaryotes (Procytes), have a nucleus delimited by the nuclear envelope and the nuclear membrane from the rest of the cytoplasm. The nucleus contains the genetic information stored in chromosomes.

Representatives of mycobionts include, for example, yeasts (Protoascomycetes), molds (Plectomycetes), mildew (Pyrenomycetes), downy mildew (Phycomycetes), and wild mushrooms (Basidiomycetes).

Dermatomycoses are diseases in which certain types of fungi, in particular dermatophytes, invade the skin and hair follicles. The symptoms of dermatomycoses include blisters, exfoliation, rhagades and erosion, usually associated with itching or allergic eczema.

Dermatomycoses can be subdivided essentially into the following four groups: dermatophytoses (eg, epidermophytia, favus, microsporia, trichophytia), yeast mecoses (eg, pityriasis and other myrotic pityrosporum, candidal infections, blastomycosis, Busch-Buske disease, torulosis, Piedra alba, torulopsidosis, trichosporosis), mold mycoses (eg aspergillosis, cephalosporidosis, phycomycosis and scopular isopidemia), systemic mycoses (eg chromomycosis, coccidiomycosis, stroke stop masmosis).

The pathogenic and facultative pathogens include, for example, from the group of yeasts Candida species (eg Candida albicans) and those of the family Malassezien. These are responsible for skin diseases such as pityriasis versicolor, seborrhoea in the forms Seborrhoea oleosa and Seborrhoea sicca, which manifest themselves mainly as seborrhoea capitis (= dandruff), seborrheic dermatitis and pityrosporum folliculitis. Participation of Malassezien in the development of psoriasis is discussed by experts. All areas of human skin can be affected by dermatomycoses. Dermatophytoses almost exclusively affect the skin, hair and nails. Yeast mycoses can also affect the mucous membranes and internal organs, systemic mycoses regularly extend to whole organ systems.

Particularly often the body areas are affected, on which through clothing, jewelry or footwear moisture and heat can accumulate. So the athlete's foot belongs to the most well-known and most widespread Dermatomycosen. Especially unpleasant are further fungal diseases of the finger and toenail areas (onychomycoses).

Furthermore, superinfections of the skin by fungi and bacteria are not uncommon.

The object of the present invention was to eliminate the disadvantages of the prior art and to provide substances and preparations containing such substances, by the use of which superinfections can be cured, wherein the physiological skin flora suffers no significant loss.

In contrast to the prokaryotic and eukaryotic cellular organisms, viruses are biological structures that require a host cell for biosynthesis. Extracellular viruses (also called "virions") consist of a single- or double-stranded nucleic acid sequence (DNA or RNA) and a protein coat (called capsid), optionally surrounded by an additional lipid-containing envelope (Envelope). The classification of the viruses was classed according to clinical criteria, but nowadays mostly according to their structure, their morphology, but in particular according to the nucleic acid sequence.

Viruses of dermatological importance are, for example, herpes viruses (herpes simplex type 1 and 2, varicella zoster) and papillomaviruses.

Viruzide, ie virus killing substances in the true sense does not exist because viruses do not have their own metabolism. It was therefore also discussed whether viruses should be classified as living things. At any rate, pharmacological interventions without damaging the unaffected cells are difficult. possible The primary mechanisms of action in the fight against the viruses are primarily the disruption of their replication, for example by blocking the enzymes that are important for replication and which are present in the host cell. Furthermore, the release of the viral nucleic acids into the host cell can be prevented. Within the scope of the disclosure presented here, terms such as "antiviral" or "effective against viruses", "virucidal" or the like are understood to mean the property of a substance, a single or multicellular organism against harmful consequences of a viral infection, be it prophylactically or therapeutically regardless of what the actual mechanism of action of the substance is in an individual case.

The state of the art, however, lacks anti-virus substances, which also do not damage the host organism or not to a reasonable extent.

An object of the present invention was therefore to remedy this situation, that is to say to find substances which effectively protect a monocellular or multicellular organism from harmful consequences of a viral infection, be it prophylactically or therapeutically.

It has surprisingly been found, and therein lies the solution of all these objects that the use of menthyl ethers of the structure

where R represents a branched or unbranched alkyl radical having up to 10 carbon atoms which is optionally mono- or polysubstituted by hydroxyl groups, as antibacterial, antimycotic or antiviral active compounds, which remedies the disadvantages of the prior art. The individual active ingredients used according to the invention are particularly suitable for use as a deodorizing agent in cosmetic deodorants as well as against blemished skin and mild forms of acne.

Finally, it has been found that the individual active ingredients used according to the invention can prevent spoilage of organic substances, in particular cosmetic and dermatological preparations, by infestation with Gram-positive and Gram-negative bacteria, mycobionts and viruses when added to these preparations.

The preferred ester used according to the invention is the glycerol ether of the menthol having the structure

also called menthoxypropanediol.

According to the invention, the menthyl esters used in accordance with the invention are preferably used in cosmetic or dermatological compositions in a content of 0.005-50.0% by weight, in particular 0.01-20.0% by weight, based on the total weight of the composition. The compositions advantageously contain 0.02-10.0% by weight, more preferably 0.02-5.0% by weight, of one or more menthyl esters used in accordance with the invention, very particularly preferably 0.3-3.0% by weight. %, in each case based on the total weight of the composition.

The individual active ingredients used according to the invention can be incorporated without difficulty into common cosmetic or dermatological formulations. The individual active ingredients used according to the invention are very particularly advantageously present in the form of cosmetic deodorants, for example as aerosols from aerosol containers, squeeze bottles or preparations which can be sprayed by a pump device or in the form of liquid compositions which can be applied by means of roll-on devices, as deodorant sticks (deodorant sticks) ) or in the form of W / O or O / W emulsions which can be applied from normal bottles and containers, for example creams or lotions.

Further, the cosmetic formulations may advantageously be in the form of tinctures, wipes, personal cleansers, shampoos, shower or bath preparations, powders or powder sprays, as well as nail care products (e.g., nail polishes, nail polish removers, nail balms).

It is also possible and optionally advantageous to combine the individual active ingredients used according to the invention with other active ingredients, for example with other antimicrobial, antimycotic or antivirally active substances.

It may also be advantageous to buffer the compositions according to the invention. A pH range of 3.5 to 7.5 is advantageous.

The cosmetic and / or dermatological formulations according to the invention may be composed as usual and used for the treatment of the skin and / or the hair and / or the nails in the sense of a dermatological treatment or a treatment in terms of nourishing cosmetics. But they can also be used in make-up products in decorative cosmetics.

For use, the cosmetic and / or dermatological formulations according to the invention are applied in sufficient quantities to the skin and / or the hair and / or the nails in the manner customary for cosmetics and dermatological agents.

The cosmetic preparations according to the invention may contain cosmetic adjuvants conventionally used in such preparations, for example preservatives, antioxidants, perfumes, foaming inhibitors, colorants, pigments which have a coloring effect, thickeners, surface-active substances, emulsifiers, softening substances, moisturizing and / or moisturizing substances, preservatives, anti-inflammatory substances, additional active substances such as vitamins or proteins, light stabilizers, salts, proteolytic or keratinolytic substances, fats, oils, waxes or other customary constituents of a cosmetic formulation such as alcohols, polyols, polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives.

Emulsions are advantageous according to the invention and contain e.g. the said fats, oils, waxes and other fatty substances, as well as water and an emulsifier, as commonly 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 above-mentioned oil in the presence of a thickening agent which is preferably silica or an aluminosilicate in oily-alcoholic gels, in aqueous-alcoholic or alcoholic gels, preferably a polyacrylate.

Fixed pins according to the invention contain e.g. natural or synthetic waxes, fatty alcohols or fatty acid esters. Preference is given to lip balms and deodorant sticks ("deodorant sticks").

Suitable propellants for cosmetic or dermatological preparations which can be sprayed from aerosol containers according to the invention are the customary known highly volatile, liquefied propellants, e.g. Hydrocarbons (propane, butane, isobutane) suitable, which can be used alone or in combination with each other. Also, compressed air is advantageous to use.

Cosmetic preparations which are a shampoo or a washing, shower or bath preparation preferably comprise at least one anionic, nonionic or amphoteric surfactant or mixtures thereof, at least one dialkyl substituted carboxylic acid in the aqueous medium and adjuvants conventionally used therefor , The following examples are intended to illustrate the embodiments of the present inventions. The information always refers to weight%, unless otherwise stated.

example 1

Transparent microemulsion - roll-on

Weight%

Glycerol monoisostearate 1, 00

Polyoxyethylene (20) isocetyl ether 3.00

Di-n-octyl carbonate 3.00

2-octyldodecanol 2.00

Glycerol 3.00

Jojoba oil 0.10

Menthoxypropanediol 0.50

2-ethylhexyl glycerol ether 0.50

Perfume, Antioxidants q.s.

Water, ad ad 100

Example 2

Translucent microemulsion - atomizer

Weight%

Polyoxyethylene (20) cetyl stearyl ether 2.00

Polyoxyethylene (12) cetylstearyl ether 1, 00

Glycerol stearate 2.50

Cetylstearyl alcohol 0.50

Cetyl palmitate 0.50

Caprylic capric acid ester 4.00

Di-n-octyl ether 8.00

Glycerol 3.00

Menthoxypropanediol 0.40

Pentanediol 2.50

Perfume, Antioxidants q.s.

Water, ad ad 100 Example 3

Example 4

Macro emulsion - cream

Weight%

Glycerol monostearate 5.00

Polyethylene glycol (2000) monostearate 2.00

Stearyl alcohol 3.00

Cyclometicone 4.00

Paraffin oil 6,00

EDTA 0.20

Menthoxypropanediol 1, 00

2-methylpropanediol 3.00

2-ethylhexyl glycerol ether 0.50

Perfume, Antioxidants q.s.

Water, ad ad 100 Example 5

Alcoholic solution - roll-on

Weight%

Alcohol denate. 30.00

2-octyldodecanol 0.10

Hydroxyethylcellulose 0.50

Citric acid 0.05

Polyethylene glycol 400 2.00

Polyethylene glycol (2000) hydrogenated castor oil 2.00

Menthoxypropanediol 2.00

Aluminum chlorohydrate 5.00

Perfume, Antioxidants q.s.

Water Ad 100

Claims

claims:

1. Use of menthyl ethers of the structure

where R represents a branched or unbranched alkyl radical having up to 10 carbon atoms optionally substituted one or more times by hydroxyl groups, as antibacterial, antimycotic, antiparasitic or antiviral agents.

2. Use according to claim 1, characterized in that the menthyl ether of the glycerol ether of the menthol having the structure

also menthoxypropanediol called, is selected.

3. Use according to one of the preceding claims, characterized in that the menthyl ether (s) are present in a content of 0.005-50.0% by weight, in particular 0.01-20.0% by weight, where 0.02- 10.0 wt .-%, particularly preferably 0.02 to 5.0 wt .-% of one or more menthyl ethers, very particularly preferably 0.3 to 3.0 wt .-% are preferred, each based on the total weight of Composition.