EP3236917A1 - Use of octenidine as active deodorant ingredient - Google Patents

Abstract

At a weight fraction of 0.1 to 0.5 wt%, octenidine displays a deodorant effect and can be used as an active deodorant ingredient in cosmetic preparations. The combination of octenidine and ethylhexylglycerol in an octenidine-to-ethylhexylglycerol ratio of 0.4:1 to 10:1 by weight exhibits very good deodorizing activity, moreover.

Description

 description

Use of octenidine as a deodorizing agent

The invention is the use of octenidine as a deodorant active ingredient in cosmetic or dermatological preparations.

The invention moreover relates to the use of a mixture of octenidine and ethylhexylgylcerol in specific weight ratios to one another and a certain proportion by weight of the mixture in a cosmetic or dermatological preparation. The mixture can be used as a deodorizing agent.

Octenidine dihydrochloride or shortened octenidine (A / octyl-1- [10- (4-octyliminopyridin-1-yl) decyl] pyridin-4-imine, A /, / \ '- (decane-1, 10-diyldi- 1 (4 - /) - pyridyl-4-ylidene) bis (octylammonium) dichloride)) is known as a broad-spectrum antiseptic for the disinfection of skin and mucous membranes as well as for wound disinfection.

Octenidine acts bactericidal against both gram-positive and -negative bacteria, virucidal against lipophilic viruses such as the herpes simplex virus and the hepatitis B virus. It also acts fungicidal, but not against spores.

Octenidine is used in combination with phenoxyethanol, 1-propanol or 2-propanol as disinfectants, mouthwashes or wound gels.

Ethylhexyglycerol is a known cosmetic ingredient.

Sensidin® DO from Schuelke & Mayr is known, comprising ethylhexylglycerol and octenidine HCl, as also described by way of example in DE 10028638 A1 and DE 601 29 705 T2.

In DE 10 2008 01 1692 A1, a combination of active substances comprising at least 1, 0 wt .-% 1- or 2- (C1 to C24 alkyl) glycerol ether (Glycerinmonoalkylether), at least 0.2 wt .-% Bispyridiniumalkan, at least 1, 5 wt .-% polyol and at least 0.0005 wt .-% antioxidants disclosed. DE 4240674 C2 describes the combination of ethylhexylglycerol and other deowir core.

In this case, the ratio of glycerol monoalkyl ether to the other deodorant composition constituents is in the range from 50: 1 to 1:50, preferably 10: 1 to 1:10 and particularly preferably in the range from 5: 1 to 1: 1.

WO 2009106467 A2 discloses compositions comprising octenidine and stabilizers, e.g. Antioxidants, EDTA or UV filters, and adjuvants, e.g. Emulators, described in aqueous preparation.

US 2009076084 A1 describes alcoholic preparations comprising octenidine.

WO 9820095 A2 describes combinations of octenidine with alcohols and hydroxycarboxylic acids.

EP 1982696 A1 discloses antiseptic gels based on poloxamers comprising octenidine and / or polihexamide as active ingredients.

DE 10 2005 002644 A1 discloses disinfecting compositions which comprise a) one or more 1- or 2- (C 1 - to C 24 -alkyl) -glycerol ethers,

b) one or more bispyridiniumalkanes and

c) one or more polyols and / or one or more surfactants selected from the group c1) comprises nonionic surfactant and c2) quaternary ammonium compound.

DE 102010044787 A1 discloses macroemulsions with octenidine. In this case, the macroemulsion has as a particularly advantageous feature a liquid-crystalline system whose liquid crystals, also called mesophases, possess properties of liquid and solid states. The emulsion forms a liquid-crystalline system even without octenidine. This system is not destroyed by the addition of octenidine, so that is obtained by incorporation of octenidine in a macroemulsion such a liquid-crystalline system or generated. Antiperspirants (AT) or deodorants (deodorants) are used to eliminate or prevent body odor that results 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 German-speaking countries, products for use in the armpit area are referred to as deodorants or "deodorants", irrespective of the question of whether an antiperspirant effect is also present.

Antiperspirants (AT) are antiperspirants that, in contrast to the deodorants which generally prevent microbial decomposition of already formed perspiration, are said to prevent the secretion of sweat at all.

In contrast to the antiperspirants pure deodorants cause no active influence on the sweat secretion, but only the control or influence of the body or underarm odor (odor control agent). Sweat odor consists to a large extent of branched-chain fatty acids, which are released by bacterial enzymes from odorless sweat. Classic deodorizing agents counteract this by reducing the growth of bacteria.

Basically, antimicrobial agents do not per se also deodorant.

A deodorizing effect is only present when the active ingredient, after application to the skin, leads to a reduction in the substances responsible for the malodor, such as bacteria, in particular Corynebacterium jeikeium (C. jeikeium).

It is known that substances present on the skin, such as, for example, skin lipids, proteins, etc., can have an inhibiting effect on putative active substances and lead to these substances not causing any deodorant action on the skin. It is therefore not clear that, for example, antimicrobial substances automatically deodorant act.

One challenge therefore is to identify active ingredients that, in addition to being skin friendly, are deodorising and can be used as a deodorizer. Applicable means that a skin irritation or other impairments are avoided.

Another challenge is to provide a non-perfumed base recipe for deodorizing cosmetics that have deodorant activity. That It is desirable to provide cosmetic deodorizing preparations which do not require perfume ingredients.

Reason for this is u.a. that perfume or its components can lead to incompatibilities.

Furthermore, it is desirable when using perfume ingredients, if possible in small quantities and especially flexible, i. various perfumes, to be able to work. This has not succeeded with the previously known blends of known active ingredients.

According to the invention, the use of octenidine as a deodorant active in cosmetic or dermatological preparations, wherein the proportion of octenidine in the range of

0, 1 wt.% Up to 0.5 wt.%, In particular in the range of 0, 15 wt.% To 0.25 wt.%, Preferably in the range to 0.2 wt.%, Based on the total mass of the preparation , is elected.

In this case, octenidine is preferably used in combination with ethylhexylglycerol in a weight ratio of octenidine to ethylhexylglycerol of 0.35 to 1 to 10 to 1, in particular in the range of 0.7 to 1 to 3 to 1, preferably in the range of 1.7 to 1 to 2.5 to 1 selected.

The combination of octenidine and ethylhexylglycerol is preferably provided in the following blends or combinations.

(1) Mixture of octenidine and ethylhexylglycerol in a suitable solubilizer such as propylene glycol or glycerol.

 According to the invention, the use of the combination of octenidine and ethylhexylglycerol in the claimed ratio and proportions by weight in cosmetic or dermatological preparations is preferred

 (2) Preparations in the form of alcoholic solutions or emulsions

 or as

(3) propellant-containing preparations, aerosols. In the case of proportions relating to the total mass of the preparation, the proportion to the mass of the preparation without propellant gases (3) is meant, unless otherwise specified.

As a preferred blend (1.), The inventive combination of octenidine and ethylhexylglycerol in mixtures with propylene glycol is provided.

Ideally, the proportions by weight of these blends are in the range of 9 to

1 1 wt.% Ethylhexylglycerin, 18 to 22 wt.% Octenidine dihydrochloride and 67 to 73 wt.% Solubilizer, preferably propylene glycol, in each case based on the total mass of the mixture (1.).

Propylene glycol has no effect on the deodorant activity of octenidine and does not show itself any desodoriende effect, as is clear for example from the studies of Figures 2 and 4.

In contrast, ethylhexylglycerol surprisingly exhibits an effect on the deodorizing activity of octenidine.

The prior art describes cosmetic preparations, for example as deodorants or antiperspirants, which comprise octenidine and / or ethylhexylglycerol. However, this does not disclose that octenidine is present in the proportions according to the invention and in particular in the claimed weight ratios to ethylhexylglycerol. Above all, there is a lack of recognition that octenidine per se acts as a deodorant active in these ratios and proportions.

The invention is therefore also the use of octenidine to a certain weight proportion and preferably in combination with Ethylhexylglycerin in a certain weight ratio as a deodorant active ingredient.

Octenidine is preferably used as a deodorant active ingredient in cosmetic or dermatological preparations.

The preparations may comprise one or more further deodorant and / or anti-perspirant substances. However, it is preferred that the preparations used according to the invention comprise no further antiperspirant substances, in particular no aluminum salts.

Furthermore, the preparations of the invention are free of additional Deowirkern, especially free of perfume ingredients.

"Free from" means that the proportion of these substances is below 0.01% by weight, based on the total mass of the preparation, as a result of which accidentally introduced impurities of possibly deodorizing or antiperspirant substances are included, which, however, due to their low content, do not contain any Have effects.

As known from the prior art, there are mixtures of octenidine and Ethylhe- xylglycerin, which can be used as a disinfectant. However, a sufficient deodorizing effect has not been known.

Surprisingly, studies have shown that octenidine has deodorizing properties and that this surprisingly depends advantageously on the ratio to ethylhexylglycerol as well as on the total amount used.

Thus, a mixture of octenidine hydrochloride and ethylhexylglycerol in a weight ratio of 0.1 to 1 showed inadequate activity, so that this mixture can not be used in this concentration in order to achieve in particular a 48h deodorant activity from unscented aerosol spray formulations.

It was found in the investigations carried out that proportions of ethylhexylglycerol over 15 wt.%, Based on the total mass of the mixture comprising octenidine, ethylhexylglycerol and suitable solubilizers, adversely affect the efficacy of octenidine.

That there is still a mixture with octenidine, which develop a deodorizing effect, was therefore not expected.

For this purpose, comparative experiments were carried out by means of a pig skin infection assay. Initially, pure octenidine and mixtures B and C with different concentrations were tested against control K + (water) using a pigskin assay (Figure 1, 2 and 3).

In the test procedure, the bacterium C. jeikeium (DSM 7171) is spread from a cryotube according to EN 12353 on a corresponding agar plate (C + T agar) and incubated at 30 ° C for 48 hours. From the grown bacteria, a second passage as liquid culture (AC medium), which was incubated for 8 h at 30 ° C, applied.

The liquid culture is adjusted to 0.1 after an OD determination and diluted 1: 8 with thickened medium (AC medium + 0.2% agar). This bacterial suspension was then used for the test.

For this purpose, 25μΙ bacteria are applied to the skin (bacterial count of 1 ^* 10 ⁵ / cm ² ) and evenly distributed with a spatula. After a drying phase, 10 mg of the active substance mixtures (A) are likewise pipetted onto the skin and distributed. 2 punches are mixed with 500μΙ Abspülpuffer and with the spatula for 30 sec. rinsed. The bacteria are plated by means of a spiral plater. The plate with the pig skin is for 20 min. incubated at 30 ° C and a humidity of about 90%. After the time, all skin punches are covered with 500μΙ Abspülpuffer and for 1 min. sonicated in an ultrasonic bath. 200μΙ of the rinsed solutions are pipetted to 800μΙ disinhibition medium. These dilutions were plated out by means of a spiral plate on agar plates and incubated at 30 ° C for 48 hours, then the bacterial count was determined by means of the countermate. Hints can also be found in: LW Bush, LM Benson and JH White "Pig Skin as Test Substrate for Evaluating Topical Antimicrobial Activity" Journal of Clinical Microbiology, Sept. 1986, p. 343-348.

The investigations demonstrate a potency of octenidine to a weight fraction of 0.1 to 0.2 wt.%, Based on the total mass of the preparation, which consists only of octenidine, ethylhexylglycerol, propylene glycol and water.

Interestingly, 0.15% by weight of octenidine in the tested concentration series experienced an apparent deterioration in potency (see Figure 1).

However, this onset of activity was not observed in pure octenidine (0.15 wt% pure octenidine, see Figure 2). Pure octenidine, which was examined as before for the mixture with ethylhexylglycerol with respect to the bacterial reduction of the Corynebacterium jeikeium, showed an activity in the range from 0.1 to 0.15% by weight, based on the total mass of the preparation, which was only octenidine, Propylene glycol and water.

It has been suggested that there is interaction between the components of the mixture which leads to a decrease in deodorant activity.

Further efficacy studies led to further improved results and the first approaches of the inventively most preferred proportions and weight ratios. It turned out that it could be promising to reduce the ethylhexylglycerol content.

For this purpose, differently concentrated mixtures B, comprising 19.8% octenidine, 19.8% ethylhexyl glycerol, the remainder propylene glycol, based on the total mass of mixture B, were tested against control K + (water) by means of a pig skin assay (FIG. 1).

1% of mixture B comprises thus 0.198% by weight of octenidine, 0.198% by weight of ethylhexylglycerol and 0.604% by weight of propylene glycol, based on the total mass of the tested preparation comprising mixture B and solvent water (then to 99% by weight).

Similarly, 0.75% blend B comprises 0.1485 weight% octenidine, 0.5% blend B contains 0.099% octenidine, and 0.25% blend B comprises 0.0495% octenidine.

The weight ratio of octenidine to ethylhexylglycerol in Blend B is 0.198% by weight to 0.198% by weight, i. 1 to 1.

A further reduction of the Ethylhexylglycerin content and a ratio of octenidine to Ethylhexyglycerin of about 2 to 1 (C) showed an inventively particularly preferred embodiment of the mixture octenidine / Ethylhexylglycerin. An active collapse as in Figure 1 could no longer be observed here at 0.15% octenidine use concentration (see Figure 3).

Mixtures C comprise 20% octenidine, 10% ethylhexyl glycerol, balance propylene glycol, based on the total mass of the mixture C. Figure 3 shows the results of the pigskin assay of mixtures C versus control K + (water).

1% of mixture C comprises thus 0.2% by weight of octenidine, 0.1% by weight of ethylhexylglycerol and 0.7% by weight of propylene glycol, based on the total mass of the tested preparation comprising mixture A and solvent water (then to 99% by weight) ).

Correspondingly, 0.75% mixture C comprises 0.15% by weight octenidine, 0.5% mixture C 0.1% octenidine and 0.25% mixture C comprises 0.05% octenidine.

The weight ratio of octenidine to ethylhexylglycerol in the mixture C is 0.2 to 0.1, i. 2 to 1.

A reduction of C. jeikium on pig skin by a factor of 1000 (99.9%) after 20 minutes with 0.2% octenidine corresponds to an antimicrobial activity in the armpit by a factor of 10 (90%).

That 90% of the bacteria are reduced. Thus, a deodorizing activity, i. a bacterial reduction on the skin, evidenced.

The investigations show that a bacterial reduction on the skin after 20 minutes at a value of 1000 CFU / ml shows an effective deodorizing effect.

The results of the preparations with a lower concentration of octenidine (<0.1% by weight, eg 0.05% by weight pure octenidine (Figure 2), 0.25% mixture B, 0.25% mixture C) show a lower bacterial reduction ,

Thus, the influence according to the invention of the proportion of octenidine of at least 0.1% by weight, based on the total mass of the preparation, is evident.

In addition, however, the investigations also show that the ratio by weight to ethylhexylglycerol should also be taken into account to advantage. Thus, with a proportion of octenidine of 0.2% by weight or 0.15% by weight and a ratio to ethylhexylglycerol of 1: 1 or 2: 1 (Figures 1 and 3), a particularly advantageous bacterial reduction can be observed and thus a particularly preferred deodorant activity. Octenidine can thus be used only in the proportions according to the invention and in particular in the particular weight ratios to ethylhexylglycerol as a deodorant active ingredient in cosmetic or dermatological preparations.

These optimized mixtures of octenidine according to the invention also show very good and significant effects in the in-vivo sniff test against an untreated control.

The sniff test (SNK) is used to determine an i.d.R. 48-hour deodorant efficacy of cosmetic formulations after single use. The application of the test product and the measurement of the effectiveness take place in the user-relevant area, the armpit. The target is the odor intensity of the armpit sweat.

An aerosol spray preparation according to Example 1 without the addition of perfume was tested.

The measurement is performed as described below.

The determination of the deodorizing activity is realized by the use of valid and accepted measurement methods and evaluation methods.

The study design is designed so that deodorizing activities can be demonstrated as follows:

^■ at least simply allied and randomized in terms of test samples and open to untreated control

^■ Comparison to untreated control => Proof of active substance and formulation.

The measurement is made by a subjective, olfactory assessment of the intensity of armpit sweat through a sniffer panel. As a rule, the odor intensity of the armpit sweat is evaluated for a comparative assessment of the odor samples according to the absolute scale values from 0 (no sweat odor) to 5 (very strong sweat odor). During the pre-test phase, the score "X" for foreign smells (eg cigarette smoke, perfume, etc.) is assigned in pairs for each L (left) and R (right) pairs of glasses R and L of a test person are opened one after the other and then only then is an assessment given for each sample. A coded test sample (coding according to Wl 7 MAT 100) in a contralateral comparison against the untreated control is tested.

The sniff test results are shown in Table 1.

Table 1 :

The results show that on the treated side a scent of 0.37 odor units is achieved which shows a significant deodorizing effect.

The cosmetic or dermatological preparations according to the invention may further contain cosmetic adjuvants and active ingredients such as are commonly used in such preparations, for. As agents, preservatives, preservatives, bactericides, lipids, substances for preventing foaming, dyes and color pigments, thickeners, moisturizing and / or moisturizing substances or other conventional ingredients of a cosmetic or dermatological formulation such as polyols, polymers, foam stabilizers, organic solvents or silicone derivatives if the additive does not impair or preclude the required properties with regard to their effectiveness.

Preferred preparations comprising the combination of octenidine and ethylhexylglycerol are to be selected from:

 alcoholic solutions, preferably ethanol

 Emulsions, preferably water in oil

 propellant-containing preparations, in particular W / O aerosols, or oil-containing aerosols

The preparations according to the invention are preferably provided as atomizer formulations with an alcohol content, preferably ethanol, between 30 and 99% by weight, based on the total mass of the preparation without propellant gases.

This formulation, provided as a body spray, allows a pleasing and pleasing application, avoiding the influence of additional formulation ingredients. In this case, the mixing ratio of the alcoholic solution or W / O emulsion, summarized as preparation (2.), with propellant preferably in the range of 20 to 40 wt.%, In particular 30 wt.%, Active substance solution to 60 to 80 wt. %, in particular 70 wt.%, propellant to choose. According to the invention, these propellant-containing preparations (3.) furthermore contain octenidine in the range from 0.1% by weight up to 0.5% by weight, based on the total mass of the preparation without propellant gas.

The weight ratio of the octenidine-containing preparations (2) to propellant gas is preferably selected in the range from 10% by weight to 90% by weight to 70% by weight to 30% by weight, based now on the total mass of the propellant-containing preparation (3. ).

Advantageously, the ratio is in the range of 15% preparation to 85% propellant, or 30% to 70% and in particular 60% preparation to 40% propellant gas.

Furthermore, preference can be given to the addition of perfume or perfume ingredients or their proportion can be reduced and still achieves an acceptable Desodo- ration.

The proportion of perfume or perfume ingredients is therefore preferably selected in the range of less than 0.5 wt.%, In particular less than 0.2 wt.%, Advantageously less than

0.01 wt.%., Based on the total mass of the preparation.

The following examples illustrate preparations according to the invention. The figures are parts by weight based on the total mass of the preparation without propellant gases, unless stated otherwise.

Examples

 Aerosol spray alcoholic:

The liquid phase (2.) obtained by mixing together the respective constituents is filled with a propane-butane mixture (2: 7) in a ratio of 39:61 into aerosol containers.

Aerosol spray suspension:

The liquid phase obtained by mixing together the respective components is filled with a propane-butane mixture (2: 7) in the ratio 17:83 in aerosol containers. Aerosol spray W / O

The liquid phase obtained by mixing together the respective components is filled with a propane-butane mixture (2: 7) in the ratio 39:61 in aerosol containers.

pump sprayer:

 7 8

Ethanol 55.00 45.00

 PEG-40 Hydrogenated castor oil

 2.00 2.00

Glycerol 1, 00 1, 00

Perfume q.s. q.s.

 1 1% ethylhexylglycerol, 18% octenidine dihydrochlo¬

1, 00 1, 5

 and 71% propylene glycol

Aqua ad 100.00 ad 100.00 Roll-on gel:

Roll-on: macro-emulsion:

 11 12 13

Aluminum chlorohydrate - 10.00 2.00

Polypropylene glycol (15) stearyl ether 5.00 5.00 3.00

Steareth-2 3.00 1.00 2.50

Steareth-21 4,00 2,00 1,50

11% ethylhexylglycerol, 18% octenidine dihydrochloride 1.00

 1.00 1.25

 and 71% propylene glycol

 Perfume, preservatives q.s. q.s. q.s.

Propylene Glycol - - 3.00

Aqua ad 100.00 ad 100.00 ad 100.00 Roll-on: micro-emulsion:

Deodorant Pen Soap Gel:

 17 18

Sodium stearate 7.00 7.00

1, 2-propylene glycol 48.00 20.00

PEG-8 + Aqua 20.00 30.00

1 1% ethylhexylglycerol, 19% octenidine dihydrochloride

 1, 00 1, 25 and 70% propylene glycol

 Perfume, preservatives q.s. q.s.

Aqua ad 100.00 ad 100.00 Deodorant stick suspension

 19 20

1 1% ethylhexylglycerol, 18% octenidine dihydrochloride and

 1.00 2.00 69% propylene glycol

 Stearyl Alcohol 20,00 15,00

Paraffinium Liquidum 15.00 10.00

PPG-14 butyl ether 10.00 15.00

Tale 5,00 7,00

Aluminum Starch Octenylsuccinate + Aqua 3.00 5.00

Glyceryl Stearate SE 2.00 1.00

Perfume, preservatives q.s. q.s.

Cyclomethicone ad 100.00 ad 100.00

Claims

claims 1. Use of octenidine as a deodorant active ingredient in cosmetic or dermatological preparations, characterized in that octenidine in a proportion of 0, 1 to 0.5 wt.%, In particular in the range of 0, 15 to 0.25 wt.%, Based on the Total mass of the preparation is included. 2. Use according to claim 1, characterized in that in the preparation Ethylhexylglycenn in a weight ratio of octenidine to Ethylhexylglycerin of 0.35 to 1 to 10 to 1 in the preparation is present. 3. Use according to claim 2, characterized in that the weight ratio of octenidine to Ethylhexylglycerin in the range of 0.7 to 1 to 3 to 1, preferably in the range of 1, 7 to 1 to 2.5 to 1, is selected. 4. Use according to one of claims 1 to 3, characterized in that the preparation contains less than 0.01% by weight, in particular 0% by weight, of perfume or perfume constituents, based on the total mass of the preparation. 5. Use according to one of claims 1 to 4 characterized in that in the preparation less than 0.01 wt.%, In particular 0 wt.% Antiperspirant and / or deodorizing agents, preferably none of the two substance groups are included except octenidine, based on the total mass of the preparation.