WO2012031987A2

WO2012031987A2 - Octenidine dihydrochloride as co-emulsifier in microemulsions

Info

Publication number: WO2012031987A2
Application number: PCT/EP2011/065211
Authority: WO
Inventors: Stefan Biel; Maren Meyer; Nicole Tschierske
Original assignee: Beiersdorf Ag
Priority date: 2010-09-09
Filing date: 2011-09-02
Publication date: 2012-03-15
Also published as: DE112011103003A5; DE102010044785A1; WO2012031987A3

Abstract

The invention relates to cosmetic or dermatological preparations which, formulated as microemulsions comprising octenidine dihydrochloride, display improved transparency.

Description

Octenidine dihydrochloride as a coemulsifier in microemulsions

The invention comprises cosmetic or dermatological preparations based on a microemulsion comprising octenidine dihydrochloride as co-emulsifier.

Emulsions are thermodynamically unstable dispersions of two immiscible liquids. The inner (discontinuous) phase is distributed in the form of droplets in the outer (continuous) phase. If the inner phase is the lipophilic phase, then it is an oil-in-water emulsion (O / W emulsion). For a water-in-oil (W / O) emulsion, the lipophilic phase is the outer phase. There are too

Multiple emulsions of the type W / O / W and O / W / O known.

Another distinguishing feature for emulsions is the classification into micro- and macroemulsions. Many documents also describe nanoemulsions, which in turn constitute a subgroup of microemulsions. Distinguishing criterion of the micro and macroemulsion is the droplet size. Thus, macroemulsions appear white because the droplet size is larger than the wavelength of visible light. As droplet diameters decrease, the emulsions become increasingly translucent, all the way to transparent micellar solutions.

The "macroemulsion" is a white emulsion which can be prepared, for example, with a steareth-2 / steareth-21 emulsifier system which forms liquid-crystalline structures or with polyglyceryl-3-methylglucose distearate The emulsion is self-thickening.

Due to their solid state properties, liquid crystals show abnormalities in

different examination methods. They are birefringent and therefore im

polarized light visible. By means of scattering and diffraction methods, e.g.

X-ray small angle scattering, the aggregation form can be determined. The magnetic anisotropy of the liquid crystals leads to broadening of signals and to baseline curvatures in the NMR spectrum. Rheological parameters provide information about the strength of the structures and thus about the strength of intermolecular interactions.

By contrast, microemulsions are thermodynamically stable emulsions with a large oil / water interface. Because of this, they require high amounts of

Emulsifiers. The result is translucent to transparent emulsions

Drop sizes from 10 to 50 nm. They are subject to very high dynamics in terms of their internal structure. The "microemulsion" is a translucent, for example, by a PIT process (English: β-phase inversion temperature) emulsion prepared, for example, with a

Associative thickener (PEG-150 distearate) can be thickened.

To distinguish between the two types of emulsion, the determination of the

Drop sizes. For droplet sizes in the range 0.02 to 2000 μηι laser diffraction is a suitable method. In this area of the monomer droplets are the macroemulsions. For emulsions with droplet sizes from 1 to 1000 nm, the

Photon correlation spectroscopy uses the area in which the microemulsions lie.

Thus, emulsions with a monomer droplet size of 1 to 10 μιη apply

Macroemulsions and emulsions with a droplet diameter of 0.005 to 0, 1 μηι as a microemulsion (Römpp-Chemie Lexikon, March 2002). This division is also used according to the invention.

An emulsion with a droplet size distribution in the transition region between 0.1 to 1 μηπ is inventively defined depending on the other distinguishing criteria either as micro or macroemulsion.

In principle, besides the droplet size, the criteria opacity and formation of liquid-crystalline structures are used for classification as micro- or macroemulsion.

Microemulsions are translucent to transparent emulsions. Macroemulsions have liquid-crystalline phases, while the microemulsion shows no superstructures.

According to the invention, of course, the transparency or translucency without the addition of coloring or refraction influencing additives to assess.

To provide completely transparent or translucent emulsions requires a high formulation effort. Fully transparent formulations are known only as thickened aqueous and / or aqueous / alcoholic systems.

It is therefore desirable to provide cosmetic or dermatological preparations based on a microemulsion which has improved transparency compared with the known microemulsions. The choice of emulsifiers and thickeners and their proportion should not increase.

Cosmetic antiperspirants or deodorants / deodorants serve to

To eliminate body odor or to reduce its formation. Body odor through perspiration occurs when the odorless fresh sweat is decomposed by microorganisms. The usual cosmetic deodorants are based on different active principles. In common usage, there is not always a clear distinction between the terms "deodorant" and "antiperspirant". Rather, especially in the

German-speaking countries - products for use in the underarm area generally referred to as deodorants or "deodorants." This is irrelevant to the question of whether an antiperspirant effect is present.

Antiperspirants (AT) are antiperspirants that - in contrast to the

Deodorants, which generally prevent microbial decomposition of already formed sweat - to prevent the secretion of sweat at all.

In contrast to the antiperspirants pure deodorants cause no active

Influencing the sweat secretion, but only the control or influence of the body or armpit odor (odor control agent). Common mechanisms of action are antibacterial effects, as shown by non-colloidal silver,

Odor neutralization (masking), influencing of bacterial metabolisms, the pure perfuming as well as the use of precursors of certain perfume components, which are converted by enzymatic reactions to fragrant substances. In addition to the actual antiperspirant active ingredients (AT-Wrker), preparations may additionally contain substances which inhibit the microbial degradation of the perspiration, such as e.g. Triclosan. Triclosan has an effect against gram-positive and gram-negative bacteria as well as against fungi and yeasts, which results in a deodorizing, but no antiperspirant effect, since no influence on the sweat secretion can be deduced from the influence on the bacterial skin flora.

Sweat odor consists to a large extent of branched-chain fatty acids, which are released by bacterial enzymes from odorless sweat. Classic deodorant ingredients counteract this by reducing the growth of bacteria. Frequently, however, the substances used for this purpose also act nonselectively against useful skin germs and can lead to skin irritations in sensitive individuals.

Octenidine dihydrochloride, CAS 70775-75-6 (N, IM ^' - (1, 10-decanediyldi-1 [4H] -pyridinyl-4-ylidenes) bis- (octanamine) dihydrochloride, octenidine HCl, octenidine) of the structure ^■ ^■ NH (CH ₂₎ io ⁺ H- 1 CGH 7

2C1

C 8 ⁿ 1 7 NH N- {CH ₂ ) io- i ^"f H CgH 1 7

C ₃ 6H62N ₄ - 2HCi

r: 623.8

is known as a surface-active, amphiphilic, antimicrobial substance (Skin Pharmacol Physiol 2010; 23, 244-258).

An anti-biofilm efficacy of octenidine HCl is also described above.

Mixtures of ethylhexylglycerol, octenidine HCl and propylene glycol are known under the trade name Sensidin DO.

From DE 4240674 C1 it is known that glycerol monoalkyl ethers of the formula

ROCH ₂ CHOHCH ₂ OH have a good deodorizing effect. Preference is given to using 1- (2-ethylhexyl) glycerol ether (commercial product Sensiva® SC 50, Schülke & Mayr GmbH). From this patent specification, inter alia, a Deoformulierung is known, the 58 wt .-% water, 40 wt .-% ethanol and 1, 0 wt .-% 1, 2-propylene glycol, 0.9 wt .-% 2-Ethylhe- xylglycerinether and 0, 1 wt .-% Bispyridiniumalkan (eg Octenidindihydrochlond). This formulation is not sufficiently stable on storage. It can contribute to the formation of

Peroxides and as a result, the formation of degradation products, such as low molecular weight volatiles and unpleasant-smelling alcohols, such as 2-ethylhexanol. In addition, the content of volatile substances (VOC, such as ethanol) and the active ingredient content in the finished preparation are comparatively high.

DE 10 2008 011 692 A1 discloses clear, colorless, water- or alcohol-containing solutions with bispyridiniumalkanes, such as octenidine dihydrochloride, which can be used in deodorant formulations. Preferred embodiments of the preparations for topical application are emulsions (eg creams, lotions), gels, solutions,

Called liniments, ointments, sprays or powders. The concrete use of octenidine dihydrochloride in microemulsions is not disclosed.

DE 10 2005 002 644 A1 discloses compositions for hygienic

Hand disinfection or hand washing, the composition

Glycerolmonomethylether, one or more Bispyridiniumalkane and optionally one or more polyols and / or one or more surfactants.

The water solubility of glycerol monomethyl ether is herein by addition of the

Bispyridinium alkane, especially octenidine dihydrochloride, significantly improved.

The use of octenidine dihydrochloride in microemulsions is not disclosed.

It is desirable to provide a cosmetic or dermatological deodorant preparation which can be formulated optically attractive, transparent and at the same time has a sufficiently good deodorizing activity

Surprisingly, it has now been found that octenidine dihydrochloride in microemulsions leads to improved transparency of the preparation.

The invention comprises cosmetic or dermatological preparations based on a microemulsion, i. for example, with a drop size in the range of about 0.005 to 0.1 μηι, comprising octenidine dihydrochloride.

The invention also relates to the use of octenidine dihydrochloride for improving the transparency of microemulsion-based cosmetic or dermatological preparations.

As a particularly advantageous feature, the microemulsion relating to the invention has no superstructures and is not self-thickening, so that use as an atomizer (liquid) up to the roll-on applicator (viscous) is possible.

The decisive criterion in addition to the drop size is that the microemulsion-based preparations according to the invention do not form a liquid-crystalline system, as are characteristic of macroemulsions.

Advantageously, the cosmetic or dermatological preparations are therefore based on a microemulsion, wherein the drop size diameter of the emulsion drops in the range of 0.005 to 0.1 μηι and the emulsion does not form a liquid-crystalline system. The emulsion according to the invention forms a microemulsion even without octenidines. The formation is supported by octenidines as a so-called coemulsifier but according to the invention.

Microemulsions are known to have a certain translucency.

Surprisingly, the addition of octenidines, in particular with increasing concentration, makes the microemulsion more transparent than comparable systems without octenidines. This use according to the invention of octenidine, which is known per se merely as antimicrobial agent, surprisingly leads to improved, more transparent microemulsions. Octenidine is known to be incorporated in the oil / water interface. These

Incorporation in the interface of the microemulsion leads to the formation of smaller droplets. The smaller the droplets of a microemulsion, the more translucent / transparent the formulation becomes.

In accordance with the invention, a proportion of octenidines has been found to be optimally improved by optimally improving the transparency of a microemulsion.

This proportion ranges from about 0.01% to 0.1% by weight of octenidines, as illustrated in FIG.

Optimal for PIT microemulsions is the proportion of octenidine by about 0.01 wt.%, Based on the total mass of the preparation. In these areas, the distribution of drop size is narrow, but smaller than in microemulsions without octenidine.

Figure 1 shows the drop size of a microemulsion (measured with

Photon correlation spectroscopy, Horiba LB-550) with different proportions of octenidines.

A is placebo microemulsion with 0 wt% octenidine,

B microemulsion with 0.01% octenidines,

C microemulsion with 0.05% octenidines,

D microemulsion with 0.1% octenidines,

E microemulsion with 0.5% octenidine and

F microemulsion with 1% octenidine.

Certain emulsifiers (such as PEGs) promote by their temperature-dependent properties, the formation of a microemulsion according to the PIT process. The higher the temperature rises during the production of the emulsion, the more they shift

Characteristics of the emulsifiers from O / W to W / O. That that at the beginning

Joining the hot oil and water phase initially produces a w / o emulsion with large drops. During subsequent cooling with stirring, the Emulator again more to O / W, so it comes at the PIT point to a change from W / O to O / W. This turnover produces very small droplets that have a translucent appearance.

With increased addition of octenidines, the PIT is less white when merging the phases. U.U. the PIT range shifts or the PIT method does not work properly anymore.

According to the invention, it was found that the more octenidine added in the production, the smaller the drops become. Octenidine does not have the same properties as a PIT or PEG emulsifier, so it does not disturb the emulsification, but rather promotes it. Octenidine thus serves as a co-emulsifier.

In the suspension test (Figure 2) it was also shown that with an increasing concentration of octenidines not only the transparency of the emulsion increases, but also an improved release of the active substance occurs. The more octenidine added, the better the antimicrobial performance.

Particularly advantageously, the proportion of octeniding in the range of at least 0.03 wt.% (Graph D, increasing concentration to H) is selected, in which a release is achieved, which ensures good efficacy in vivo.

In the suspension test Figure 2 mean A - control preparation, microemulsion without octenidine and the preparations B to H microemulsion with increasing concentration of octenidines, B - 0.01 wt.%, C - 0.02 wt.%, D - 0.03 wt. %, E - 0.04% by weight, F - 0.05% by weight, G - 0.075% by weight, H - 0, 1% by weight, in each case based on the total mass of the preparation.

In the suspension tests presented, 500 mg of a bacterial suspension (S. epidermidis) were given 250 mg of the formulation to be tested (in the positive control only 250 mg of the bacterial medium). These mixtures are filled with medium to 1000μΙ_. The suspension then contains approximately 1 * 10 ⁶ CFU / mL (CFU: colony-forming units). The batches are incubated at 37 ° C with rotation for three hours. After 0, 20, 60 and 180 minutes samples are taken, diluted and plated on agar plates. These are incubated for 24 h at 37 ° C to grow the remaining germs. Good and in vivo effective deodorant formulations reduce the germ count already after 20 minutes

Detection limit of 100 cfu / mL.

According to the invention, this results in a double benefit from the addition of octenidines in microemulsions: on the one hand, a significantly more transparent system is obtained and on the other hand, a sufficiently active concentration in the water phase and thus a sufficient Deowireffizienz from a microemulsion, which is not effective and less transparent without octennidine.

Octenidines and its effects on the microemulsion were further investigated indirectly by determining viscosity and droplet size determination.

Microemulsions show viscosities of 372 mPa * s. By adding 0.5% by weight

Octenidine HCl / ethylhexylglycerol showed an increase in viscosity to 568 mPa * s. That the higher viscosity means a more stable structure.

Droplet size determination of the microemulsion yielded 34.5 ± 2.5 nm (d ₅₀ ). Addition of 0.5% by weight of octenidine HCl / ethylhexylglycerol gave drop sizes of 17.1 ± 1.9 nm (d ₅₀ ). That is, the droplets were smaller. Smaller drops are more stable.

Accordingly, the cosmetic or dermatological according to the invention include

Preparations based on a microemulsion, i. in particular with a droplet size in the range of 0.005 to 0.1 μm, comprising octenidine dihydrochloride, preferably in an amount of 0.005 to 3% by weight, particularly preferably in the range of 0.01-1% by weight.

Ethylhexylglycerin is advantageously added to a proportion of 0.001 to 1 wt.%, Preferably 0.01 to 0.2 wt.%, Particularly preferably 0.05 to 0.1 wt.%, Each based on the

Total mass of the preparation.

According to the invention, the use of octenidines, preferably in a proportion of 0.005 to 3 wt.%, Particularly preferably in the range of 0.01 to 1 wt.%, Particularly advantageously in the range of 0.03 to 1 wt.%, In each case to the total mass of the preparation, to improve the transparency of microemulsion-based cosmetic or dermatological preparations.

In a particular embodiment, the preparations according to the invention comprise deodorant formulations.

Advantageously, antimicrobial active ingredients can be added to the preparations according to the invention for further support of the deodorizing active power. Here, preference is given to choosing nature-identical raw materials such as butyloctanoic acid or propylene glycol.

Preference is given to preparations according to the invention antiperspirant active substances such as vicinal diols (as described in DE 10 2009 004 269 A1), preferably 1, 2-propylene glycol, and / or salts of 1, 1-dimethyl-piperidinium or 1, 1-dimethyl pyrrolindium compounds such as 4 - [(2-cyclopentyl-2-hydroxyphenylacetyl) oxy] -1, 1-dimethyl-piperidinium bromide or other salts, 4 - [(2-cyclohexyl-2-hydroxyphenylacetyl) oxy] -1, 1-dimethyl piperidinium bromide or other salts, 4 - [(3-methyl-2-hydroxyphenylpentanoyl) oxy] -1, 1-dimethylpiperidinium bromide or other salts, 4 - [(3-methyl-2-phenylpentanoyl) oxy] -1, 1- dimethyl-piperidinium bromide or other salts, or 3 - [(2-cyclopentyl-2 ~

hydroxyphenylacetyl) oxy] -1, 1-dimethylpyrrolidinium bromide.

In addition to octenidines, the preparations according to the invention preferably also include propylene glycol, ethylhexyl glycerol and butyloctanoic acid, advantageously in the stated proportions.

The proportion of butyloctanoic acid is advantageously from 0.01 to 2% by weight, preferably from 0.01 to 0.5% by weight, particularly preferably 0.1% by weight, in each case based on the total mass of the preparation.

The proportion of vicinal diols, especially 1,2-propylene glycol, is advantageously 10 to 50% by weight, preferably 15 to 30% by weight, particularly preferably 20% by weight, in each case based on the total mass of the preparation.

The microemulsion according to the invention can be known to those skilled in the art from those known to it

Make ingredients. As preferred emulsifiers for the preparation of

microemulsions according to the invention lsoceteth-20 and / or glyceryl isostearate are selected.

These emulsifiers are advantageously used in a proportion of 1 to 10% by weight, in particular in the range of 2 to 8% by weight, based on the total mass of the preparation.

The preparation preferably does not comprise any antiperspirant active aluminum salts, such as aluminum chlorohydrates.

The cosmetic or dermatological preparations according to the invention may further contain cosmetic adjuvants and other active ingredients, such as are commonly used in such preparations, for. Preservatives, preservatives, bactericides, anti-foaming agents, dyes and color pigments, thickeners, moisturizing and / or moisturizing substances, fats, oils, waxes or other common ingredients of a cosmetic or dermatological formulation such as alcohols, polyols, polymers, foam stabilizers, Electrolytes, organic solvents or silicone derivatives, provided the additive meets the required properties

not impaired in terms of deodorising and / or transparency. The preparations according to the invention preferably comprise one or more further antimicrobially active agents.

It is also preferred to dispense with the addition of preservative, preservative aid. The formulations are then according to consumer wishes

preservative-free.

Known preservatives are the compounds known as parabens, in particular 4-hydroxybenzoic acid and its esters, methylparaben, ethylparaben,

Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, Phenylparaben.

Furthermore, phenoxyethanol, ethylene glycol monophenyl ether, phenyl glycol, phenoxetof are known for the preservation of cosmetic products.

These substances can preferably be dispensed with according to the invention.

Cosmetic or dermatological preparations preferred according to the invention are to be formulated in the form of roll-on, atomizers and aerosols as a microemulsion comprising octenidines.

Preferred are W / O microemulsion forms.

Propane, propene, n-butane, isobutane, isobutene, n-pentane, n-pentene, isopentane, isopentene, methane, ethane, dimethyl ether, nitrogen, air, in the preferred aerosol according to the invention are preferably propane. Oxygen, nitrogen oxides, nitrous oxide, 1, 1, 1, 3-tetrafluoroethane, heptafluoro-n-propane, perfluoroethane, monochlorodifluoromethane, 1, 1-difluoroethane used individually or in combination. Also hydrophilic propellants, such. As carbon dioxide, can be used advantageously in the context of the present invention, when the proportion of hydrophilic gases is selected low and lipophilic propellant gas (eg., Propane / butane) is present in excess.

Propane, butane, isobutane or mixtures of these propellant gases are particularly preferred. For the purposes of the present invention, the gases mentioned can be used individually or in any desired mixtures with one another. Preference is given to using mixtures with pressure stages from 2.0 to 3.5 bar. Very particular preference is given to a pressure stage of 2.7 bar.

The following examples are intended to further describe the invention without being limiting.

The proportions relate to parts by weight, based on the total mass of the preparation, unless otherwise disclosed. Examples

5 6 7

Dicaprylyl ether 3.0000 3.0000

Paraffinum Liquidum 3.0000

Glyceryl isostearates 2.4000 2.4000 2.2000 lsoceteth-20 4.8000 4.8000 5.0000

Butylene glycol 3.0000 3.0000 3.0000

Propylene Glycol 0.4350 1.3440 0.3850

Ethylhexylglycerol 0.0500 0.2400 0.1000

Octenidine HCl 0.0150 0.0160 0.0150

PEG-150 Distearate 0.7000

Butyloctanoic acid 0.0500

Perfume 1.1000 1.0000

Aqua 85.1500 85.2000 84.6000

Claims

Claims. Cosmetic or dermatological preparations based on a micro-emulsion comprising octenidine dihydrochloride.

2. Preparation according to claim 1, characterized in that the proportion of

Octenidine dihydrochloride in the range of 0.005 to 3 wt.%, Particularly preferably in the range of 0.01 to 1 wt.%, In particular in the range 0.03 to 1 wt.%, In each case based on the total mass of the preparation is selected.

3. Preparation according to one of the preceding claims comprising one or more further antimicrobially active agents.

4. Preparation according to one of the preceding claims comprising butyloctanoic acid, propylene glycol and / or ethylhexylglycerol.

5. Preparation according to one of the preceding claims comprising no antiperspirant effective aluminum salts.

6. Preparation according to one of the preceding claims comprising none

Preservatives and / or preservatives, in particular no compounds known as parabens, in particular 4-hydroxybenzoic acid and its esters, methylparaben, ethylparaben, propylparaben, isopropylparaben, butylparaben, isobutylparaben, phenylparaben, and also no phenoxyethanol,

Ethylene glycol monophenyl ether and / or phenyl glycol.

7. Preparation according to one of the preceding claims as an aerosol.

8. Use of octenidine dihydrochloride to improve the transparency of microemulsion-based cosmetic or dermatological preparations.