RU2820587C2 - Repellent composition for repelling arthropods - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to means of protecting humans and animals from arthropods. Repellent composition for repelling arthropods contains: (i) icaridin (1-(1-methylpropoxycarbonyl)-2-(2-hydroxyethyl)piperidine) in amount of 2.5 wt.% to 40 wt.% based on the total weight of the composition, (ii) optionally at least one additional compound having repellent activity on arthropods, selected from PMD (para-menthane-3,8-diol), DETA (N,N-diethyl-m-methylbenzamide), IR3535 (ethyl-3-acetyl butylaminopropanoate) or ethyl anthranilate (ethyl-2-aminobenzoate), and (iii) at least a methyl glucose ether PPG-20 in amount of 0.1 wt.% to 1.5 wt.% based on the total weight of the composition, and, optionally, at least one additional polyol selected from methylglucose ether PPG-10, propylene glycol, butylene glycol and pentylene glycol. Repellent composition is used to repel insects and/or ticks from contact with a person or an animal and/or from a bite.

EFFECT: disclosed repellent composition is safe for humans and animals, highly effective, non-coloring, non-greasy, long-acting, has balanced solubility.

15 cl, 1 tbl, 9 ex

Description

The present invention relates to an arthropod repellent composition providing long-term protection, in particular against insects and ticks.

As used herein, the term "arthropods" is used to refer to species of insects, arachnids and millipedes, particularly insects and arachnids, preferably mosquitoes and ticks of any type.

The term “insect repellent composition” means a composition that exhibits an insect repellent effect or an insecticidal effect, or both an insect repellent effect and an insecticidal effect.

Repellents are expected to satisfy several basic requirements such as commercial availability, low cost, absence of unpleasant odor, non-irritating and non-toxic materials, high stability and acceptable evaporation rate coupled with adequate repellent action of long-term effectiveness. Solving the latter problem, that is, maintaining the effective release rate of the repellent from the formulation, is a major challenge facing the repellent industry. In addition, volatile insect repellents are known to disappear relatively quickly when applied to the skin. They are also easily washed off by water, such as rain, sweating, swimming or showering. The evaporation of the repellent directly depends on the ambient temperature, body temperature and wind speed.

Another concern is that approximately 50 percent of a topically applied dose is absorbed by the skin in six hours, with peak plasma levels reaching after 1 hour (Lurie et al., Pharmacokinetics of insect repellent N, N-diethyl toluamide. Med. Parazitol., 47, 72, 1979). It is known that ethanol, often used as a co-solvent, can significantly increase and accelerate the penetration of active ingredients into the skin. This, on the one hand, leads to the loss of the active substance on the surface of the skin, and on the other hand can lead to skin irritation and allergic reactions. For this reason, alcohols are sometimes at least partially replaced by surfactants in modern formulations. However, there are also hidden disadvantages to using surfactants, such as possible skin irritation or allergic reactions.

Some developments have proposed the use of physical barriers to control the release of repellents. Incorporating volatile repellents into polymers, encapsulating the volatile repellent into a material forming the shell or walls of a capsule, and using porous and/or layered materials as carriers of volatile active ingredients are examples of attempts to create controlled release repellent formulations.

One commonly used insect repellent is N,N'-diethyltoluamide, better known as DEET. Other known volatile insect repellents include ethylhexanediol; 2-(octylthio)ethanol; dimethyl phthalate; di-n-propyl-2,5-pyridinedicarboxylate; 1,5a,6,9,9a,9b-hexahydro-4a(4b)-dibenzofurancarboxaldehyde; citronellal; citronellol; geraniol; nerol; linalool. Formulation of such insect repellents is particularly problematic due to the oiliness of many repellents and, in particular, the staining of clothing with the compound DEET, damage to plastics and wash-off in wet or rainy weather or when the person using the repellent takes part in water sports such as swimming or fishing. . In addition, the lack of retention of insect repellents due to water is also influenced by the perspiration of the individual user.

Mehr et al (Laboratory Evaluation of Controlled-Release Insect Repellent Formulations, J. Am. Mosq. Control Assoc., 1,143, 1985) evaluated several microencapsulated controlled-release formulations of DEET and hydrophilic vinyl polymers such as polyvinylpyrrolidone . The product using polyvinylpyrrolidone was not superior to pure DEET in repelling mosquitoes.

Reifenrath et al (Evaporation and Skin penetration characteristics of mosquito repellent formulations. J. Am. Mosq. Control Assoc., 5, 45 1989) tested silicone polymers, acrylate polymers, fatty acids and repellent mixtures and assessed their evaporation and skin penetration. There were no differences in evaporation and skin penetration of polymer-containing formulations and pure DEET or a mixture of dimethyl phthalate and DEET.

EP 2439188 A1 describes the incorporation of an active substance into a cellulose matrix, US Patent 4474081 discloses the use of maleic anhydride/alpha-olefin polymers and terpolymers to provide slow release contact insect repellents when applied to the surface of the skin.

US Patent No. 4,774,082 discloses the use of maleic anhydride/alpha-olefin polymers and terpolymers to provide slow release of volatile insect repellents when applied to the surface of the skin.

Chemical Abstracts 110, 207847s (1989) discloses mosquito repellent compositions that contain the active ingredient and a fat-soluble, water-insoluble acrylate polymer containing acrylic acid, stearyl methacrylate and isooctyl acrylate.

In addition, derivatives were considered to increase the duration of action. Accordingly, for example WO2004/006674 A describes the preparation of Cg-so PMD esters. In addition, JP 31335906 A describes an insect repellent that contains N,N-diethyltoluamide (DEET) and a p-menthane derivative such as, for example, p-menthane-3,8-cis-diol monocarboxylic acid or sulfonate.

WO2017/199145 A describes a combination of at least a first compound and a second, different compound, wherein at least the first compound is an insect repellent, and the first compound and the second compound are capable of together forming a negative pseudoazeotrope with a vapor composition at atmospheric pressure and temperature at which the first compound is present in a sufficiently high concentration to provide an insect repellent effect. This application combined several known compounds that are insect repellents, but were found to be unsuitable because they do not form a negative pseudoazeotrope.

WO2018/50211 A discloses an insect repellent composition comprising insect repellents or an insecticide and a cyclodextrin or a cyclodextrin derivative, in which the proportion of the insect repellent/insecticide content is significantly greater than the proportion of the content of said cyclodextrin (its derivative). In all preparations shown in this application, the alcohol content is at least 80% by weight.

It is an object of the present invention to provide an insect repellent preparation for mammals that is non-irritating, highly effective, non-staining, non-greasy, slightly sticky, long-lasting, and has balanced solubility and penetration of the repellent compound into the skin.

This purpose is achieved by an arthropod repellent composition comprising (i) icaridin (1-(1-methylpropoxycarbonyl)-2-(2-hydroxyethyl)piperidine), (ii) optionally at least one additional repellent compound arthropods, selected from PMD (p-menthane-3,8-diol), DEET (N,N-diethyl -m -methylbenzamide), IR3535 (ethyl-3-acetylbutylaminopropanoate), KBR 3023 ((RS)-sec-butyl- (RS)-2-(2-hydroxyethyl)piperidine-1-carboxylate) or ethyl anthranilate (ethyl 2-aminobenzoate), and (iii) at least one polyhydric alcohol (polyol) selected from PPG-20 methyl glucose ether, PPG-10 methyl glucose ether, propylene glycol, butylene glycol and pentylene glycol.

The present invention relates to compositions comprising (i) the arthropod repellent compound icaridin (1-(1-methylpropoxycarbonyl)-2-(2-hydroxyethyl)piperidine); and (optionally, but preferably) (ii) at least one other compound that is an arthropod repellent selected from PMD (para-menthane-3,8-diol), DEET (N,N-diethyl-meta-methylbenzamide) , IR3535 (ethyl 3-acetylbutylaminopropanoate), KBR 3023 ((RS)-sec-butyl-(RS)-2-(2-hydroxyethyl)piperidine-1-carboxylate) or ethyl anthranilate (ethyl 2-aminobenzoate). Preferably, the composition includes, in addition to icaridin, at least PMD, especially preferably, the composition includes both of these compounds in combination.

In addition to the repellent compounds (i) and (ii) mentioned, the composition may contain at least one other compound known in the art to have an arthropod repellent effect, for example N-butylacetanilide, repellent MGK 264, N-methylneodecanamide, AI3-35765 , AI3-37220 (SS220), repellent MGK 326, thymol, eugenol, spatulenol, dibutyl phthalate (DBP), dimethyl phthalate (DMF), dimethyl carbate (DMC), dioctyl phthalate, benzyl benzoate, indalone, nepetalactone, methyl anthranilate, 2-butyl-2-ethyl -1,3-propanediol, Rutgers 612, citronella oil, eucalyptus oil, camphor oil, margosa seed oil, lemongrass oil, citral, geraniol, citronellol, citronellal, piperitone or a pyrethroid such as, but not limited to, empentrin, profluthrin , transfluthrin, furamethrin, metofluthrin, allethrin, prallethrin, phenothrin or permethrin, however the additional compound is not necessary.

Each of the repellent compounds (i) and (ii) mentioned above may independently be present in the composition in an amount of from 2.5% by weight. up to 40% wt., preferably from 5% wt. up to 30% wt., more preferably from 8% wt. up to 20% by weight, respectively, and the total amount in the composition of compounds (i) and (ii), which have repellent activity against arthropods, ranges from 10% by weight. up to 80% wt., preferably from 20% wt. up to 60% wt., more preferably from 25% wt. up to 50% wt., based on the total weight of the composition.

Preferably, icaridin is present in the composition in an amount of 10 to 30 wt%, preferably 15 to 25 wt%, more preferably 18 to 22 wt%. Preferably, PMD is also present in the composition, in particular in an amount of from 5 to 20% by weight, preferably from 7 to 15% by weight, more preferably from 8 to 12% by weight. Icaridin is available under the brand name Saltidin® from Lanxess (Germany), and PMD can be obtained as an emulsion concentrate (50% solution) Galea EC concentrate CP 680 from Citrefine (UK). It should be noted that the oil of eucalyptus citriodora, marketed as Citriodiol ^® by Citrefine, also contains p-menthane-3,8-diol, but in a water-insoluble form.

According to the invention, the total content of repellent compounds (i) and (ii) in the composition is from 10% by weight. up to 80% wt., preferably from 20% wt. up to 60% wt., more preferably from 25% wt. up to 50% wt., based on the total weight of the composition. If icaridin and PMD are combined from the above list of repellent compounds (i) and (ii), the total content of these two compounds in the composition is preferably from 10% by weight. up to 80% by weight, in particular from 15% by weight. up to 50% wt., preferably from 20% wt. up to 40% wt., more preferably from 25% wt. up to 35% wt. based on the total weight of the composition.

If icaridin and PMD are present in the composition, their weight ratio in the composition is preferably from 3:1 to 1:2, preferably from 2.5:1 to 1:1.5, more preferably from 2.2:1 to 1:1 ,2, most preferably about 2:1.

Another ingredient of the composition of the present invention is (iii) a polyol selected from PPG-20 methyl glucose ether, PPG-10 methyl glucose ether, propylene glycol (propanediol), butylene glycol (butanediol) and pentylene glycol (pentanediol). Preferably, the composition includes (iii) at least PPG-20 methyl glucose ether. If additional polyol (iii) is present, the composition preferably includes at least one of the polyhydric alcohols of propylene glycol and pentylene glycol, optionally both of these polyols.

Each of the polyols (iii) is independently present in the composition in an amount of from 0.1 wt%. up to 10% wt., preferably from 0.2% wt. up to 8% wt., more preferably from 0.3% wt. up to 7% wt., most preferably from 0.4% wt. up to 6% wt., respectively, and the total amount of these polyhydric alcohols (iii) in the composition is from 0.2% wt. up to 20% wt., preferably from 0.4% wt. up to 16% wt., more preferably from 0.5% wt. up to 12% wt., based on the total weight of the composition. Preferably, the composition includes at least PPG-20 methyl glucose ether, for example available as ^Glucam® P-20 from Lubrizol (Ohio, USA), preferably in an amount of from 0.1 wt%. up to 1.5% wt., more preferably from 0.2% wt. up to 1% wt., even more preferably from 0.25% wt. up to 0.8% wt., even more preferably from 0.3% wt. up to 0.7% wt. and most preferably from 0.4 wt%. up to 0.6% wt. In addition, if additional polyol (iii) is present, the composition preferably includes at least one of propylene glycol and pentylene glycol polyols, both of which are added independently of each other in an amount of from 2 to 10% by weight, preferably from 3 to 8% by weight ., more preferably from 4 to 6% by weight, respectively.

In a preferred embodiment of the invention, the composition comprises (i) icaridin, (ii) PMD and (iii) PPG-20 methyl glucose ether. The composition may also contain an additional polyol (iii) selected from PPG-10 methyl glucose ether, propylene glycol, butylene glycol and pentylene glycol. If additional polyol (iii) is present, the composition preferably further includes at least one of propylene glycol and pentylene glycol, optionally both.

It has been found that the addition of polyol(s) (iii) to a composition containing (i) repellent compound(s) and, optionally, (ii) results in an increase in the effectiveness of the formulation, as well as a significant increase in the duration of the period of effective action the specified repellent(s) component(s). In particular, the addition of PPG-20 methyl glucose ether significantly increases the duration of effective action of the composition comprising (i) icaridin. A composition containing both icaridin and PMD and additionally containing at least PPG-20 methyl glucose ether and optionally at least one of propylene glycol and pentylene glycol shows an increase in effectiveness and an increase in the duration of effective action well beyond expected values.

To obtain the optimal ratio of solubility and the ability and degree of penetration of repellent compounds into the skin, the maximum content of any C ₁ -C ₅ alcohol is preferably 30% by weight. Thus, the total C _1-5 alcohol content in the composition is preferably no more than 30 wt%, preferably no more than 25 wt%, no more than 20 wt%, no more than 15 wt%, no more than 10 wt%. no more than 8% mass. or no more than 5% of the mass. (total content of all added C _1-5 alcohols), more preferably no more than 3% by weight, even more preferably no more than 2% by weight. However, it is preferable to add at least one C _1-5 alcohol from methanol, ethanol, propanol or isopropanol, n- or tert-butanol or pentanol to increase the solubility of organic compounds in an aqueous medium. Thus, the composition may include a C _1-5 alcohol in an amount of from 0.02 to 30 wt%, preferably at least 0.1 wt%, more preferably at least 0.5 wt%, even more preferably at at least 1% of the mass. C _1-5 alcohol, in particular ethanol (optionally denatured or mixed with isopropanol and/or butanol) or isopropanol.

In addition, since surfactants also increase the penetration of the repellent compound(s) (i) and/or (ii) into the skin, it is particularly preferable that the composition contains less than 5% by weight. any surfactant. In a preferred embodiment, the composition includes less than 4 wt.%, preferably less than 3 wt.%, even more preferably less than 2.5 wt.%. any surfactant, and less than 2% by weight, preferably less than 1.5% by weight, more preferably less than 1% by weight, even more preferably less than 0.5% by weight. anionic, amphoteric or cationic surfactants, and preferably the composition does not contain a surfactant selected from anionic, amphoteric or cationic surfactants. Thus, if a surfactant is present, it is preferable that said surfactant be a non-ionic surfactant. Preferably, the surfactant, when present, serves as an emulsifying agent.

Examples of such nonionic emulsifiers/surfactants are the following compounds:

addition reaction products of 2 to 30 mol of ethylene oxide and/or 0 to 5 mol of propylene oxide to linear C _8-22 fatty alcohols, C _12-22 fatty acids and alkylphenols containing from 8 to 15 carbon atoms in the alkyl group;

mono- and diesters of 12/18 fatty acids and addition products of 1 to 30 mol of ethylene oxide to glycerol;

mono- and diesters of glycerol and mono- and diesters of sorbitan and saturated and unsaturated fatty acids containing from 6 to 22 carbon atoms, and products of addition of ethylene oxide to them;

addition products of 15 to 60 mol of ethylene oxide/polyethylene glycol to castor oil and/or hydrogenated castor oil;

polyhydric alcohol esters, in particular polyglycerol esters, such as, for example, polyglycerol polyricinoleate, polyglycerol poly-12-hydroxystearate or polyglycerol dimerate isostearate; mixtures of compounds from several of these classes are also suitable;

addition products of 2 to 15 mol of ethylene oxide to castor oil and/or hydrogenated castor oil;

partial esters based on linear, branched, unsaturated or saturated C6 _/22 fatty acids, ricinoleic acid and 12-hydroxystearic acid and glycerol, polyglycerol, pentaerythritol, dipentaerythritol, sugar alcohols (e.g. sorbitol), alkyl glucosides (e.g. methyl glucoside, butyl glucoside , lauryl glucoside) and polyglucosides (for example, cellulose);

mono-, di- and trialkylphosphates and mono-, di- and/or tri-PEG-alkylphosphates and their salts;

wool wax alcohols;

polysiloxane/polyalkyl polyether copolymers and their corresponding derivatives;

mixed esters of pentaerythritol, fatty acids, citric acid and fatty alcohol and/or mixed esters of C _6-22 fatty acids, methyl glucose and polyols, preferably glycerol or polyglycerol;

polyalkylene glycols; And

glycerol carbonate.

To provide a pleasant sensation when the composition is applied to the skin, the composition preferably does not include a polymer compound containing more than 100 monomer units, preferably a polymer compound containing more than 80 monomer units. Excluding polymer compounds containing more than 100 monomer units from the composition significantly reduces the effect of a “film” feeling on the skin. However, if it is preferable to ensure water resistance of the composition, a film-forming polymer may be included in the formulation. Film-forming polymers are well known in the art and include, but are not limited to, VP-eicosene copolymer (eg, Antaron V-220 from Ashland or Unimer U-15 from Givaudan), VP-hexadecene copolymer (eg, Unimer U-151 from Givaudan ), Triacontanyl PVP (for example, Unimer U-6 from Givaudan), a copolymer of styrene and acrylates (for example, Dermacryl E from Nouryon).

In addition, in order to cause as little damage as possible to the protective hydrolipidic barrier of the skin, the pH value of the composition is preferably in the range of 4 to 7, preferably 4.5 to 6. To adjust the pH value of the composition, any suitable compound can be used, such as, but not limited to , low molecular weight carboxylic acids such as citric acid, tartaric acid, succinic acid, maleic acid, lactic acid or NaOH, any amine such as MEA (monoethyleneamine), TEA (triethyleneamine) or tetrahydroxypropylethylenediamine.

Another suitable and preferred ingredient of the present composition is any polyethylene glycol (PEG), wherein said PEG is added in addition to the polyols (iii) mentioned above. A suitable PEG also contains less than 80 ethoxy monomers (EO units). Preferably, the added PEG contains no more than 30 EO units, more preferably no more than 20 EO units, even more preferably no more than 15 EO units, and most preferably no more than 10 EO units, but preferably at least 3 EO units, preferably at least 4 , at least 5 or at least 6 EO units, for example 6, 7, 8 or 9 EO units. A particularly preferred polyethylene glycol is PEG-8, for example Pluracare® E 400 from BASF. The amount of said polyethylene glycol(s), if present, may be from 2.5 to 40% by weight, preferably from 3.5 to 30% by weight, more preferably from 5 to 20% wt.

In addition to the above components, the composition may contain other commonly used ingredients.

The composition of the present invention may optionally contain one or more fragrances as at least one additional ingredient. Fragrance may be added to the composition to improve or tailor the organoleptic properties of the product as desired. Suitable fragrances/flavoring agents may include, but are not limited to, for example, natural flavorings, including extracts of flowers (lily, lavender, rose, jasmine, neroli, ylang-ylang), stems and leaves (geranium, patchouli, petitgrain), fruit (anise, coriander, cumin, juniper), fruit peel (bergamot, lemon, orange), roots (nutmeg, angelica, celery, cardamom, costus, iris, calmus), wood (pine, sandalwood, guaiac wood, cedar, rosewood), plants and herbs (tarragon, lemongrass, sage, thyme), pine needles and branches (spruce, fir, pine, dwarf pine), resins and balsams (galbanum, elemia, benzoin, myrrh, olibanum, opoponax). Raw materials of animal origin, such as civet and beaver, can also be used. Typical synthetic fragrances include ester, ester, aldehyde, ketone, alcohol and hydrocarbon types. Examples of ester type fragrances include benzyl acetate, phenoxyethyl isobutyrate, para-tert-butyl cyclohexyl acetate, linalyl acetate, dimethyl benzyl carbinyl acetate, phenyl ethyl acetate, linalyl benzoate, benzyl formate, ethyl methyl phenyl glycinate, allyl cyclohexyl propionate, styralyl propionate and benzyl salicylate. . Ethers include, for example, benzylethyl ether, while aldehydes include, for example, linear alkanals containing from 8 to 18 carbon atoms, citral, citronellal, citronellyl acetaldehyde, cyclamenaldehyde, hydroxycitronellal, lilial and burgeonal. Examples of suitable ketones are ionones, alpha-isomethyl ionone and methylcedryl ketone. Suitable alcohols include anethole, citronellol, eugenol, isoeugenol, geraniol, linalool, phenylethyl alcohol and terpineol. Hydrocarbons mainly include terpenes and balms. However, it is preferable to use mixtures of different fragrances that together create a pleasant aroma. Other suitable perfume oils are essential oils with relatively low volatility, which are primarily used as aroma components. Examples are sage oil, chamomile oil, clove oil, lemon balm oil, peppermint oil, cinnamon leaf oil, linden blossom oil, juniper berry oil, vetiver oil, olibanum oil, galbanum oil, labolan oil and lavendin oil. It is preferable to use bergamot oil, dihydromyrcenol, lilial, lyral, citronellol, phenylethyl alcohol, alpha-hexylcinnamaldehyde, geraniol, benzyl acetone, cyclamenaldehyde, linalool, Boisambrene Forte, ambroxan, indole, hedione, sandelice, citrus oil, individually or in mixtures. mandarin oil, orange oil, allylamyl glycolate, cyclovertal, lavendin oil, nutmeg oil, beta-damascone, bourbon with geranium oil, cyclohexyl salicylate, Vertofix Coeur, Iso-E-Super, Fixolide NP, evernil, iraldein-gamma, phenylacetic acid, geranyl acetate , benzyl acetate, rose oxide, romillate, irotyl and floramate. Fragrances that have a deodorizing effect can also be used.

The composition of the present invention may be presented in the form of a liquid, cream, lotion or gel, but preferably in the form of a liquid composition, in particular an aqueous composition, a water-in-oil emulsion or an oil-in-water emulsion. Preferred is an aqueous liquid composition. The water content in the composition can be at least 5% by weight. up to 65% wt., preferably at least 8% wt. up to 60% wt., more preferably at least 10% wt. up to 55% wt., based on the total weight of the composition.

Preferably, the (kinetic) viscosity of said composition is in the range from 0 to 200 Pa*s at 20°C, preferably from 0.5 to 100 Pa*s, more preferably from 0.8 to 50 Pa*s at 20°C, which is measured in accordance with DIN EN ISO 2555:2018 using a Brookfield DV-II viscometer with L2 spindle at 100 rpm. and 20°C.

If the composition is presented in the form of a cream or lotion, it is preferred that it includes any suitable oily or fatty compound, for example Guerbet alcohols based on fatty alcohols containing from 6 to 18, preferably from 8 to 10, carbon atoms, esters of linear C ₆ - C ₂₂ fatty acids with linear or branched C ₆ -C ₂₂ fatty alcohols or esters of branched C ₆ -C ₁₃ carboxylic acids with linear or branched C ₆ -C ₂₂ fatty alcohols, such as, for example, myristyl myristate, myristyl palmitate, myristyl stearate, myristyl isostearate , myristyl oleate, myristyl behenate, myristyl erucate, cetyl myristate, cetyl palmitate, cetyl stearate, cetyl isostearate, cetyl oleate, cetyl behenate, cetyl erucate, stearyl myristate, stearyl palmitate, stearyl stearate, stearyl isostearate, stearyl oleate, stearyl behenate, erucate, isostearyl myristate, isostearyl palmitate, isostearyl stearate, isostearyl isostearate, isostearyl oleate, isostearyl behenate, isostearyl oleate, oleyl myristate , oleyl palmitate, oleyl stearate, oleyl isostearate, oleyl oleate, oleyl behenate, oleyl erucate, behenyl myristate, behenyl palmitate, behenyl stearate, behenyl isostearate, behenyl oleate, behenyl behenate, behenyl erucate, erucyl myristate, erucyl palmitate, erucyl stearate, arate, erucyl oleate, erucyl behenate and erucyl erucate. Also suitable are esters of linear C ₆ -C ₂₂ fatty acids with branched alcohols, in particular 2-ethylhexanol, esters of C ₁₈ -C ₃₈ alkyloxycarboxylic acids with linear or branched C ₆ -C ₂₂ fatty alcohols, in particular dioctyl malate, esters linear and/or branched fatty acids with polyhydric alcohols (such as, for example, propylene glycol, dimerdiol or trimertriol) and/or herbet alcohols, triglycerides based on C ₆ -C ₁₀ fatty acids, liquid mixtures of mono-/di-/triglycerides based on C ₆ -C ₁₈ fatty acids, esters of C ₆ -C ₂₂ fatty alcohols and/or herbet alcohols with aromatic carboxylic acids, in particular benzoic acid, esters of C ₂ -C ₁₂ dicarboxylic acids with linear or branched alcohols containing from 1 up to 22 carbon atoms, or polyhydric alcohols containing from 2 to 10 carbon atoms and from 2 to 6 hydroxyl groups, vegetable oils, branched primary alcohols, substituted cyclohexanes, linear and branched carbonates of C ₆ -C ₂₂ fatty alcohols, such as, for example , dicaprylyl carbonate (Cetiol®CC), herbet carbonates based on fatty alcohols containing from 6 to 18, preferably from 8 to 10, carbon atoms, benzoic acid esters with linear and/or branched C ₆ -C ₂₂ alcohols (e.g. Finsolv ®TN), linear or branched, symmetric or asymmetric dialkyl ethers containing from 6 to 22 carbon atoms per alkyl group, such as, for example, dicaprylyl ether (Cetiol®OE), ring-opening reaction products of epoxidized fatty acid esters with polyhydric alcohols , silicone oils (cyclomethicones, grades of silicone methicones, etc.), aliphatic or naphthenic hydrocarbons, such as, for example, squalane, squalene or dialkylcyclohexanes, and/or mineral oils.

Preferably, the viscosity of the repellent composition of the present invention is so low that the composition can be sprayed; thus, the composition can be provided in a container equipped with a spray device. Said spray device may be a spray or an aerosol spray device, and both types of spray device are capable of dispersing said repellent composition in the form of fine droplets, where the term "fine droplets" means that the composition is provided in the form of droplets with a size ranging from 5 nm to 500 μm , preferably from 50 nm to 200 µm, more preferably from 100 nm to 100 µm, even more preferably from 500 nm to 50 µm and most preferably from 1 to 50 µm.

Accordingly, it is preferable that the repellent composition of the present invention is provided in a spray container with an atomizer or an aerosol can. If an aerosol can is used, said can or said composition preferably further contains a suitable gaseous propellant, for example propane and/or butane.

The repellent composition of the present invention is suitable for use in repelling insects and/or ticks from contact with human or animal skin and, therefore, preventing human or animal bites. Due to the special combination of components, the repellent composition of the present invention provides longer-lasting protection against various arthropods compared to compositions currently offered on the market. Therefore, the repellent composition described herein can be used in less quantity and/or should not be used less frequently than compositions known on the market. The present repellent composition can, for example, be applied once in the morning and once in the evening, for example before going to bed, due to its effective protection for 12 hours. Protection is preferably achieved by applying an evenly distributed composition, for example by spraying, to bare human or animal skin.

Examples

The following examples show the effectiveness of the compositions of the present invention (E) in repelling Aedes aegypti mosquitoes from biting a human volunteer compared to compositions not covered by the invention (V).

Female Aedes mosquitoes were reared according to a standard protocol at 27.5±0.5°C, 65-85% relative humidity with a 12:12 hour light-dark period. The photoperiod (450 lux) is set from 8:00 to 20:00. After hatching, the larvae are kept in water tanks (30 × 30 × 10 cm) filled with a 1:1 mixture of deoxygenated tap water and deionized water and fed fish food flakes (Tetra Min®Lux). Before departure, adult pupae are transferred to a cage (40x30x20 cm). Adult mosquitoes are given a sugar solution (10% dextrose) and used between 5 and 15 days of age for repellent testing.

30 mosquitoes are placed in each of the experimental cages with a volume of 27,000 cm ³ (41 × 41 × 16 cm). Tests in cages are carried out in a climate chamber (4.5 × 4.5 × 2.5 m) without windows at a temperature of 27.5 ± 0.5 °C and a relative humidity of 65 ± 5% RF. Illumination is 450 lux.

For the examples, aqueous compositions are prepared containing, in addition to water and the following ingredients, a suitable amount of PEG-8 (10 to 25% by weight) and ethanol.

The amount of the respective compositions, which is determined in Table 1 below, is applied to a specific area of the volunteers' forearm (test repeated three times, n=3). Before this, the skin is washed with unscented soap, rinsed with water and wiped with 50% isopropyl alcohol. Mark an area that is larger than the test window to ensure that exposed skin is completely treated with repellent. The area of the marked area is approximately 100 cm ² .

Test drugs are applied to a specific area on one forearm of each volunteer. Before each individual performance test, null control tests are carried out, and the exact time at which up to 10 insect landings are recorded is recorded. Taking into account the obtained time value, protection from repellents on the treated hand is calculated using the following formula:

Defense (in %)=100 - Ʃ results on treated skin per unit of time × 100 Ʃ results on untreated skin per unit of time

The effectiveness of the repellent is checked first immediately after application of the product, and then again at regular intervals of 30 minutes for a maximum of 8 hours (example V2 12 hours) or until the repellent disappears. Each individual test lasts 2 minutes, during which time the number of mosquito landings and bites on the treated skin is recorded.

The effectiveness of the repellent is assessed using the following indicators: 1) time to the first bite; 2) time until bite protection is reduced to 95% compared to untreated skin (multiple bites over the same period of time).

A value of <95% represents the end of the time of full protection and is used as a criterion for aborting repellent testing.

The tests are carried out with three volunteers. All volunteers are attractive to the mosquito species being tested, which meets the requirements for participation in repellent effectiveness studies. Each volunteer receives his own personal fish tank. Cages are connected to an air ventilation system between single tests (null control and potency test) to avoid accumulation of host odors and active ingredients within the cage. Mosquitoes that begin to draw blood during the test are replaced with new mosquitoes to ensure that the number of host-seeking females remains constant throughout the test day.

Table 1

Example Number of PMDs ⁽¹⁾ Amount of Icaridin ⁽²⁾ Glucam quantity ⁽³⁾ Application First
bite
[watch] <95% [hours] V1 10% 1.67 mg/ ^cm2 2.5 +/- 0.5 V2 10% 4 mg/ ^cm2 3.5 +/- 0.5 V3 10% 0.5% 1.67 mg/ ^cm2 2.8 +/- 0.62 3.5 +/- 1.71 V4 10% 0.5% 4 mg/ ^cm2 4.2 +/- 1.03 V5 25% 2.0% 4 mg/ ^cm2 4.5 +/- 0.6 V6 10% 1.67 mg/ ^cm2 2.83 +/- 0.24 7.0 +/- 1.1 E1 10% 0.5% 1.67 mg/ ^cm2 4.5 +/- 2.68 7.33 +/- 0.62 V7 20% 1.67 mg/ ^cm2 4.0 +/- 1.3 8 +/- 1 E2 10% 20% 0.5% 1.67 mg/ ^cm2 8.0 +/- 0 ⁽⁴⁾ 12 ⁽⁵⁾

(1)(1-(1-methylpropoxycarbonyl)-2-(2-hydroxyethyl)piperidine

(2) para-menthane-3,8-diol

(3) methyl glucose ether PPG-20

(4) no bite within 8 hours, next value obtained after 12 hours

(5) the experiment is stopped after 12 hours

As can be seen from the examples, the addition of PPG-20 methylglucose ether to the repellent icaridin provides a marked increase in the time of protection of the skin from the first insect bite (see V6 regarding E1), in fact the addition increases the time to the first bite in such a way that it exceeds the time recorded with using twice the amount of icaridin (E1 relative to V7). However, little effect was observed when PPG-20 methyl glucose ether was added to PMD repellent (see V1 versus V3, and V2 versus V4). Even when combining significantly larger amounts of PPG-20 methylglucose ether and PMD (V5 relative to V4), a significant effect cannot be obtained.

If PPG-20 methyl glucose ether is added to a formulation containing a combination of icaridin and PMD, the time to first insect bite and the time for repellent protection to decline to below 95% of baseline may be significantly increased (see E2) compared to all others. compositions. This effect was not predicted since in E2 both repellents are present on the skin at the same time, so one would expect that the combination of these two repellents should produce an effective time comparable to that provided by icaridin alone (which is clearly greater than the effective time of PMD) . Thus, the combination of three ingredients: icaridin, PMD and PPG-20 methyl glucose ether results in a repellent that is superior to single repellents.

Claims (31)

1. A repellent composition for repelling arthropods, containing: (i) icaridin (1-(1-methylpropoxycarbonyl)-2-(2-hydroxyethyl)piperidine) in an amount ranging from 2.5% by weight to 40% by weight, based on the total weight of the composition, (ii) optionally at least one additional compound having arthropod repellent activity selected from PMD (para-menthane-3,8-diol), DEET (N,N-diethyl-m-methylbenzamide), IR3535 (ethyl- 3-acetylbutylaminopropanoate) or ethylanthranilate (ethyl-2-aminobenzoate), and (iii) at least PPG-20 methyl glucose ether in an amount of from 0.1 wt% to 1.5 wt%, based on the total weight of the composition, and, optionally, at least one additional polyol selected from PPG-10 methyl glucose ether, propylene glycol, butylene glycol and pentylene glycol. 2. Repellent composition for repelling arthropods according to claim 1, including (i) icaridin, (ii) optionally PMD and (iii) at least PPG-20 methyl glucose ether and, optionally, at least one additional polyol selected from PPG-10 methyl glucose ether, propylene glycol, butylene glycol and pentylene glycol. 3. Repellent composition for repelling arthropods according to claim 1, including (i) icaridin, (ii) PMD and (iii) at least PPG-20 methyl glucose ether and, optionally, at least one additional polyol selected from PPG-10 methyl glucose ether, propylene glycol, butylene glycol and pentylene glycol. 4. The arthropod repellent composition of any one of the preceding claims, comprising at least icaridin, PMD, PPG-20 methyl glucose ether, and optionally at least one additional polyol selected from propylene glycol and pentylene glycol. 5. The arthropod repellent composition according to any one of the preceding claims, wherein the amount of each of the repellent compounds (i) and (ii) independently may be from 5 wt% to 30 wt%, more preferably from 8 wt% to 20 wt.%, respectively, and in which the total amount of compounds having repellent activity against arthropods is in the range from 10 wt.% to 80 wt.%, preferably from 20 wt.% to 60 wt.%, more preferably from 25 wt.% to 50 wt.%, based on the total weight of the composition. 6. The arthropod repellent composition according to any of the preceding claims, wherein the amount of each of the additional polyhydric alcohols (iii) is independently from 0.1 wt% to 10 wt%, preferably from 0.2 wt% to 8 wt .%, more preferably from 0.3 wt.% to 7 wt.%, most preferably from 0.4 wt.% to 6 wt.%, respectively, and in which the total amount of said polyhydric alcohols is in the range of 0.2 wt.% to 20 wt.%, preferably from 0.4 wt.% to 16 wt.%, more preferably from 0.5 wt.% to 12 wt.%, based on the total weight of the composition. 7. A repellent composition for repelling arthropods according to any of the previous paragraphs, containing icaradin and PMD in a mass ratio of 3:1 to 1:2, preferably in a mass ratio of 2.5:1 to 1:1.5, more preferably in a mass ratio of in a ratio of 2.2:1 to 1:1.2, most preferably in a weight ratio of about 2:1. 8. An arthropod repellent composition as claimed in any one of the preceding claims, comprising PPG-20 methyl glucose ether in an amount of 0.2 wt% to 1 wt%, preferably 0.25 wt% to 0.8 wt .%, more preferably from 0.3 wt.% to 0.7 wt.% and, most preferably from 0.4 wt.% to 0.6 wt.%, based on the total weight of the composition. 9. A repellent composition for repelling arthropods according to any of the previous paragraphs, which contains: (i) not more than 30% by weight, or not more than 25% by weight, or not more than 20% by weight, or not more than 15% by weight, or not more than 10% by weight, or not more than 8% by weight, or not more than 5 wt.%, preferably not more than 3 wt.%, more preferably not more than 2 wt.% of any C _1-5 alcohol and/or (ii) does not contain a polymer compound containing more than 100 monomer units, preferably does not contain a polymer compound containing more than 80 monomer units, and/or (iii) contains less than 5% by weight of any surfactant. 10. A repellent composition for repelling arthropods according to any of the previous claims, satisfying at least one of the following conditions: (i) the composition is a liquid, cream, lotion or gel, preferably a liquid, (ii) the composition contains water in an amount of at least 5 wt% to 65 wt%, preferably at least 8 wt% to 60 wt%, more preferably at least 10 wt% to 55 wt.%, based on the total weight of the composition, (iii) the viscosity of the composition is in the range from 0 to 200 Pa*s at 20°C, preferably from 0.5 to 100 Pa*s, more preferably from 0.8 to 50 Pa*s at 20°C. 11. The arthropod repellent composition according to any of the previous claims, containing in addition to the polyols (iii) an additional polyethylene glycol consisting of a maximum of up to 80 EO units, preferably in an amount ranging from 2.5 wt.% to 40 wt.%, preferably from 3.5 wt% to 30 wt%, more preferably 5 wt% to 20 wt%. 12. The arthropod repellent composition according to any of the preceding claims, the pH value of which is in the range of 4 to 7, preferably 4.5 to 6. 13. The arthropod repellent composition according to any of the preceding claims, wherein the composition is contained in a container with a spray device capable of spraying said composition in the form of fine droplets. 14. The use of a repellent composition to repel arthropods according to any one of paragraphs. 1-13 to repel insects and/or ticks from contact with a person or animal and/or from being bitten. 15. A method for repelling insects or ticks from contact with the skin of a person or animal and/or from a bite, including applying a repellent composition according to any one of claims. 1-13 on the skin of a specified person or animal.