EP3996509A1

EP3996509A1 - Mosquito repellent composition and method for the preparation thereof

Info

Publication number: EP3996509A1
Application number: EP20740284.3A
Authority: EP
Inventors: Claude Grison; Andrii STANOVYCH
Original assignee: Centre National de la Recherche Scientifique CNRS; Universite de Montpellier I; Universite de Montpellier
Current assignee: Centre National de la Recherche Scientifique CNRS; Universite de Montpellier I; Universite de Montpellier
Priority date: 2019-07-10
Filing date: 2020-07-10
Publication date: 2022-05-18
Also published as: BR112022000296A2; FR3098373B1; US20220312763A1; CA3146445A1; WO2021005204A1; FR3098373A1

Abstract

The present invention relates to a natural composition comprising p-menthane-3,8-diol, citronellol and geraniol.

Description

TITLE: Mosquito repellent composition and method of preparation

The present invention relates to a natural composition comprising penthane-3,8-diol, citronellol and geraniol.

The present invention also relates to a process for the synthesis of this composition, as well as to the use of this composition as a repellent agent for insects, in particular mosquitoes.

STATE OF THE ART

The globalization of trade, commercial or passenger, is a major cause of the introduction of invasive insects. Thus, during the last decades, the geographical distribution of blood-sucking insects, and in particular mosquitoes carrying vector-borne diseases, has increased considerably. They represent a major health problem insofar as they transmit pathogens causing alarming epidemics.

Among these invasive insects, the tiger mosquito, or Aedes albopictus, accidentally imported from Southeast Asia, has found favorable ground in Europe, China and the Indian Ocean. Its adaptation is particularly worrying, because it is a potential vector of 20 disabling and even fatal diseases such as chikungunya, dengue and zika.

In the absence of vaccines for most mosquito-borne diseases, the use of repellents is the main measure to avoid human-mosquito contact.

Two types of repellents exist today, synthetic agents and natural products.

Synthetic repellents are the most widely used mosquito repellents. The most active synthetic agent against the tiger mosquito is DEET or N, N diethyl-meta-toluamide. However, if its effectiveness is recognized, its toxicity for the nervous system is also. It inhibits acetylcholisnesterase, an enzyme essential in the synaptic cholinergic transmission of insects but also mammals (Corbel et al., BMC Biol. 2009, 5; 7: 47). This effect is to be compared to that of organophosphate pesticides or carbamates; and repeated use of DEET in combination with other substances is not recommended for children under 12 and pregnant women. These concerns about consumer safety and mosquito resistance of these synthetic repellents have led to a growing demand for natural alternatives.

Among the many existing natural products, only p-menthane-3,8-diol (PMD) has an interesting repellent activity. A 20% PMD formulation has been shown to provide 7 to 8 hour protection against Aedes albopictus, similar to a product containing 15% DEET (Barnard DR, Xue RD, J Med Entomol 2004, 41 (4) : 726-730), while having low toxicity and no adverse effects, with the exception of eye irritation, which is observed for all non-toxic natural active ingredients.

This organic compound can be extracted from the essential oil of lemon eucalyptus (Corymbia citriodora, equivalent to Eucalyptus citriodora), which is endemic to Australia. However, a limited amount (around 1%) of PMD is present in this essential oil. Given the restricted geographical distribution of Eucalyptus citriodora, the development of natural PMD production cannot meet market demand. This is why the majority of PMDs used in repellents come from synthetic processes.

PMD can be synthesized from a natural and abundant raw material: citronellal. This synthesis comprises two steps: 1) the intramolecular ene-carbonyl reaction of citronellal to give isopulegol, followed by 2) the addition of H ₂ 0 to the intermediate isopulegol.

Much work relating to this synthesis has been carried out.

For example, US Pat. No. 5,959,161 describes the aqueous phase synthesis of PMD in the presence of sulfuric acid H ₂ SO ₄ from citronellal. Many variants have also been proposed to promote the production of the cis stereoisomer of PMD, reputed to have better repellent activity than the trans stereoisomer (WO 9202136).

On the other hand, the synthesis of PMD catalyzed by a Lewis acid has been less studied because it is significantly less efficient. For example, the use of Mo (CO) 50Tf) 2 in DME has been described (Kocovsky et al., J. Org. Chem. 1999, 64, 2765-2775). After 48 hours, 80% of cis stereoisomers of the PMD have been obtained, but the preparation of the catalytic complexes used in these syntheses is delicate, dangerous and expensive.

Thus, in general, the methods of producing synthetic PMD involve the use of corrosive reagents, such as H ₂ SO ₄ , and / or the use of toxic solvents such as dichloromethane, toluene, benzene or DME, as well as neutralization and / or purification steps generating waste.

Therefore, the use of natural catalysts has also been tested in order to develop more ecological processes.

EP2862442 describes, for example, the use of citric acid as a catalyst for the reaction to convert citronellal into PMD. However, the solubility of the carboxylic acids in the organic phase necessitated a final treatment of the reaction mixture, which generated waste (solvent and inorganic salts). This neutralization step led to an unsatisfactory Sheldon factor from an ecological point of view (ratio of the mass of waste to the obtained mass of desired product).

Thus, although some syntheses making it possible to obtain PMD are organically inspired, the qualification of "natural" attributed to the PMD obtained according to these methods is very often questionable, because if they are carefully examined, it is evident that these methods are far from being able to be used. '' be respectful of the environment.

AIMS OF THE INVENTION

Thus, there is a need to provide a composition which repels hematophagous arthropods, and in particular mosquitoes, which addresses one or more of the above technical problems, and in particular to provide a natural composition which repels hematophagous arthropods which is effective and efficient. non-toxic compared to existing repellants.

There is also a need to provide a process for preparing a composition which repels hematophagous arthropods, and in particular mosquitoes, which makes it possible to overcome the aforementioned drawbacks.

Thus, an objective of the present invention is to provide a composition comprising p-menthane-3,8-diol, citronellol and geraniol, and to provide a composition which can be used as a repellant against mosquitoes, said repellent agent being more effective than those of the state of the art.

Another object of the present invention is to provide a process for preparing a composition comprising p-menthane-3,8-diol, citronellol and geraniol in an efficient manner and which improves its impact from an ecological point of view. The object of the invention is also to resolve these technical problems by proposing a process and a so-called natural composition, and in particular which can be labeled as natural / natural within the meaning of the regulations, and preferably of the most stringent regulations. Another object of the invention is to resolve these technical problems by proposing a process using only natural reagents and a composition prepared solely from natural reagents.

DETAILED DESCRIPTION OF THE INVENTION

For the purposes of the present application, the term “natural composition” is understood to mean a composition comprising or consisting of one or more compounds, said compound (s) being natural. The term “natural compound” means a compound present in nature or which can be extracted from an element present in nature and which has not undergone any additional chemical transformation not involving elements present in nature or extracted from it. nature, and / or a synthetic compound qualifying as natural according to the EFFA regulations. Preferably, by “natural compound” is meant a compound present in nature or which can be extracted from an element present in nature and which has optionally undergone at least one additional chemical transformation, said additional transformation only involving one or more elements. present in nature or extracted from nature, and / or a synthetic compound qualifying as natural according to the EFFA regulations.

For the purposes of the present invention, p-menthane-3,8-diol (PMD) corresponds to (2-hydroxypropan-2-yl) -5-methylcyclohexan-1 -ol, in the form of at least one of its stereoisomers or any mixture thereof.

PMD exists in the form of eight stereoisomers la, lb, lc, ld, le, lf, I- g, lh of the following formula:

According to the invention, the cis stereoisomers of PMD correspond to a mixture of stereoisomers of PMD comprising at least one stereoisomer chosen from stereoisomers l-a, l-c, l-e and l-g.

According to the invention, the trans stereoisomers of PMD correspond to a mixture of stereoisomers of PMD comprising at least one stereoisomer chosen from the stereoisomers l-b, l-d, l-f and l-h.

For the purposes of the present invention, citronellol corresponds to 3,7-dimethyloct-6-en-1 -ol (CAS number: 106-22-9) in one of its two enantiopure forms or as a racemic mixture.

For the purposes of the present invention, geraniol corresponds to trans-3,7-dimethyl-2,6-octadien-1 -ol (CAS number: 106-24-1).

Preferably, the composition according to the invention is a repellent composition.

For the purposes of the present application, the term “repellent composition” is understood to mean a composition which makes it possible to effectively remove from their “target” (humans or animals) a hematophagous arthropod. Preferably, a repellent composition according to the invention has a repellent activity against hematophagous arthropods, preferably against mosquitoes, advantageously against the Aedes albopictus mosquito, greater than or equal to the ED 50 (equivalent to the EC 50) of p pure menthane-3,8-diol. Preferably, the composition according to the invention further comprises at least one compound chosen from linalool, citronellal, isopulegol, and an acetal, said acetal being produced by reaction between citronellal and p-menthane-3,8 -diol. For the purposes of the present invention, linalool corresponds to the compound 3,7-dimethylocta-1, 6-dien-3-ol, in one of its two enantiopure forms or as a racemic mixture.

For the purposes of the present invention, citronellal corresponds to 3,7-dimethyloct-6-en-1 -al (CAS number: 106-23-0), in one of its two enantiopure forms or as a racemic mixture.

For the purposes of the present invention, isopulegol corresponds to 5-methyl-2-prop-1 -èn-2-ylcyclohexan-1 -ol, in the form of at least one of its stereoisomers or any one of their mixtures.

For the purposes of the present invention, an acetal is a compound produced by an acetalization reaction between the aldehyde function of citronellal and the two hydroxyl functions of PMD.

Preferably, the acetal corresponds to the compound (Ac) of the following formula:

as at least one of its stereoisomers or any mixture thereof.

Preferably, the composition according to the invention comprises, relative to the total number of moles:

- from 40 to 99% by moles, preferably from 50 to 95% by moles, preferably from 70 to 90% by moles of p-menthane-3,8-diol,

- from 0.1 to 40% by moles, preferably from 0.5 to 30% by moles, preferably from 1 to 25% by moles of geraniol, - from 0.5 to 50% by moles, preferably from 1 to 40% by moles, preferably from 2 to 30% by moles of citronellol, and optionally,

- from 0.1 to 15% in moles of linalool, and optionally

- from 0.1 to 40% by moles, preferably from 0.5 to 30% by moles, preferably from 1 to 20% by moles of citronellal, and optionally

- from 0.1 to 30% by moles, preferably from 1 to 20% by moles, preferably from 1 to 15% by moles of isopulegol, and optionally

- from 0.1 to 30% by moles, preferably from 0.5 to 20% by moles, preferably from 1 to 10% by moles of acetal.

The present invention also relates to a composition comprising:

- from 0.1 to 40% by moles, preferably from 0.5 to 30% by moles, preferably from 1 to 25% by moles of geraniol,

- from 0.5 to 50% by moles, preferably from 1 to 40% by moles, preferably from 2 to 30% by moles of citronellol, and optionally,

- from 0.1 to 15% in moles of linalool, and optionally

- from 0.1 to 20% by moles, preferably from 0.5 to 10% by moles, preferably from 1 to 5% by moles of acetal,

said acetal being produced by reaction between citronellal and p-menthane-3,8-diol.

P-menthane-3,8-diol, geraniol, citronellol, linalool, citronellal, isopulegol and an acetal are as defined according to the invention.

Preferably, the composition according to the invention comprises:

- from 70 to 90% by moles of p-menthane-3,8-diol,

- from 1 to 25% in moles of geraniol, and

- from 2 to 30% in moles of citronellol.

Advantageously, the composition according to the invention is natural. The definition of natural composition is as detailed above. Preferably, the composition according to the invention further comprises from 0.1 to 15 mol% of linalool.

Preferably, the composition according to the invention further comprises from 0.1 to 40% by moles, preferably from 0.5 to 30% by moles, preferably from 1 to 20% by moles of citronellal.

Preferably, the composition according to the invention further comprises from 0.1 to 30% by moles, preferably from 1 to 20% by moles, preferably from 1 to 15% by moles of isopulegol.

Preferably, the composition according to the invention further comprises from 0.1 to 20% by moles, preferably from 0.5 to 10% by moles, preferably from 1 to 5% by moles of acetal, said acetal being produced by reaction between citronellal and pementhane-3,8-diol.

Preferably, in a composition of the invention, p-menthane-3,8-diol is present in the form of at least one of its stereoisomers.

The stereoisomers of p-menthane-3,8-diol are as defined above.

Preferably, the composition according to the invention is characterized in that the p-menthane-3,8-diol is present in the form of a mixture of cis and trans stereoisomers, said mixture comprising from 10 to 90% by moles, preferably 20 to 80 mol% of cis stereoisomers, and 10 to 90 mol%, preferably 20 to 80 mol% of trans stereoisomers.

The present invention also relates to a process for preparing a composition according to the invention, characterized in that it comprises a step a) of bringing citronellal into contact with an essential oil comprising geraniol and citronellol, and obtaining of a composition according to the invention.

For the purposes of the present application, the term “essential oil” is understood to mean a volatile odorous substance produced by certain plants and which can be extracted, preferably by hydrodistillation, in the form of a liquid.

Citronellal, geraniol and citronellol are as defined above.

Preferably, the essential oil comprising geraniol and citronellol is chosen from the group consisting of an essential oil of the species Geranium rose, an essential oil of the species Rosa damascena, an essential oil of Rosa gentifolia species, an essential oil of the species Cympogon winterianus and an essential oil of the species Nepata cataria.

The essential oil of the species Geranium rose can also be called the essential oil of the species Pelargonium asperum.

Preferably, the essential oil of the Rose Geranium species comes from China, Reunion or Africa, preferably Reunion or Egypt.

Preferably, the essential oil of the Rosa damascena species comes from Iran, China, Bulgaria or India.

Preferably, the essential oil of the Rosa gentifolia species comes from France, Egypt or Morocco.

Preferably, the essential oil of the species Cympogon winterianus comes from Réunion, Africa, Asia or South America, preferably Réunion, China, Taiwan, Brazil, Argentina or Chile.

Preferably, the essential oil of the species Nepata cataria comes from Europe or North America.

Advantageously, the essential oil comprising geraniol and citronellol is an essential oil of the species Geranium rose.

Preferably, the method according to the invention further comprises the following steps:

b. adding water to the mixture obtained in step a), preferably a volume of water of between 1 times and 10 times the volume of said mixture, and

vs. heating the mixture obtained in step b).

Preferably, step c) of the process according to the invention is carried out at a temperature between 40 ° C and 120 ° C, preferably between 60 ° C and 100 ° C, preferably between 80 ° C and 100 ° C. ° C, for example for a period of between 2 hours and 10 hours, preferably between 4 hours and 8 hours, preferably between 5 hours and 7 hours.

Preferably, the method according to the invention is characterized in that the citronellal is used in the form of an essential oil chosen in particular from the group consisting of essential oils obtained from the species: Eucalyptus citriodora, Cymbogon winterianus or Citrus hystix.

The essential oil of the species Eucalyptus citriodora can also be called the essential oil of the species Corymbia citriodora. Preferably, the essential oil of the species Eucalyptus citriodora comes from Australia, China or South America, preferably Australia.

Preferably, the essential oil of the Citrus hystrix species comes from Réunion or Madagascar.

Advantageously, the essential oil of the species Citrus hystrix is obtained from the leaves of the species Citrus hystrix.

Advantageously, the process according to the invention is characterized in that the mixture obtained in step a) comprises from 30% to 99% by mass of an essential oil comprising citronellal, and preferably of essential oils originating from the species : Eucalyptus citriodora, Cymbogon winterianus or Citrus hystix, and from 1% to 70% by mass of essential oil comprising geraniol and citronellol, and preferably of an essential oil of the species Geranium rosat.

The present invention also relates to the use of the composition according to the invention as a repellent agent for at least one insect.

The present invention also relates to the use of the composition according to the invention as a repellent agent for at least one hematophagous arthropod.

By "at least one insect repellent" is meant within the meaning of the present invention a compound or a composition making it possible to effectively remove an insect from their "target" (humans or animals).

By "repellent agent for at least one hematophagous arthropod" is meant within the meaning of the present invention a compound or a composition making it possible to effectively remove a hematophagous arthropod from their "target" (humans or animals).

According to one embodiment, the repellant is in the form of a lotion, a cream or a spray.

According to one embodiment, the repellant is contained in a bead applicator.

Preferably, in using the composition according to the invention as a repellant for at least one insect, the insect is selected from the group consisting of mosquitoes, ticks and midges.

Advantageously, in the use of the composition according to the invention as a repellent agent for at least one insect, the insect is chosen from among mosquitoes, preferably of the genus Aedes, Anopheles, or Culex, preferably the mosquito is Aedes albopictus.

Preferably, in the use of the composition according to the invention as a repellent agent for at least one hematophagous arthropod, the hematophagous arthropod is selected from the group consisting of mosquitoes, ticks and midges.

Advantageously, in the use of the composition according to the invention as a repellent agent for at least one hematophagous arthropod, the hematophagous arthropod is chosen from mosquitoes, preferably of the genus Aedes, Anopheles, or Culex, preferably the mosquito is Aedes albopictus.

The invention will now be described using the following non-limiting examples.

EXAMPLES

N, N diethyl-meta-toluamide (DEET), commercial PMD cis / trans 75/25, citronellol, geraniol, terpineol, come from Sigma-Aldrich.

The essential oils of Eucalyptus citriodora, Geranium rose, Cymbopogon winteranius or Citrus hystrix come from the Compagnie des Sens.

All essential oils are organic certified according to the COSMOS Organic standard by Ecocert Greenlife and guaranteed 100% pure, natural and integral.

Example 1: Production of PMD from a mixture of essential oils

PMD can be produced from a mixture of two essential oils in the presence of water.

For this, 2 mL of mixture of essential oil (EO) of Eucalyptus citriodora (EC) and essential oil of Geranium rose (GR), in a mass ratio of 50/50, 75/25 or 90/10, are added to 8 mL of water. The mixture is heated at 100 ° C. for 6 h.

The results obtained are presented in the following table:

[Table 1]

The conversion rate corresponds to the percentage of citronellal included in the essential oil which reacted at the end of the reaction, and the selectivity corresponds to the percentage ratio between the amount of PMD obtained over the amount of citronellal converted.

The essential oil of Eucalyptus citriodora can be replaced by essential oil of Cymbopogon winteranius or Citrus hystrix.

Example 2: Behavioral tests of Aedes albopictus vis-à-vis the compositions of the invention

The activity of the compositions obtained by the method according to the invention was tested on the behavior of the tiger mosquito, Aedes albopictus.

The behavioral tests were carried out at the Montpellier vectopôle, which is a WHO collaborating center for the evaluation of insecticides in public health.

The tests were carried out on mosquitoes 5 to 9 days old after their evolution from nymph to adult.

In anticipation of the experiment, the mosquitoes were fed sugar water only the day before, in order to increase their appetite for the test the next day. Each test was carried out during the afternoon, when mosquitoes are most active.

Each cup contains a damp cotton. The female mosquitoes were removed from the cage using a tube allowing their aspiration. They were then placed in each experiment cup (10 mosquitoes per cup).

The tests were carried out on plexiglass racks serving as supports for glass bells called feeders. These are connected to each other by plastic pipes where water circulates at 37 ° C. Pig intestinal skin was used to mimic human skin in the experiment. The pieces of intestinal skin are deposited and stretched over the feeders.

The repellent is diluted in EtOH and is deposited on the skin using a micropipette and spread over the entire surface. The concentration of commercial PMD is that of ED 50 (median effective dose, or “median effective dose” in English, which corresponds to the dose necessary for an active ingredient to be effective for 50% of a population tested), which was established at 200 mg / m ² , i.e. a concentration of 0.02036 mg / pL. If the composition tested is a mixture of at least two compounds, one of which is PMD, said composition is diluted in ethanol at a concentration of 0.02036 mg / pL, or else is diluted in ethanol until to obtain 0.02036 mg / pL of PMD in the solution.

The feeders are turned over, then 300 μL of sheep blood are placed in each feeder. The cups are inserted under each feeder.

Polystyrene plates are inserted between each line of repellent to avoid possible odor interactions. The experiment lasts one hour. The cups are then placed in a freezer at -20 ° C for 40 minutes. After freezing, the contents of a cup are placed between two sheets of paper. Everything is crushed with a plexiglass plate. Counting blood-soaked mosquitoes is done by the number of red dots on the sheet of paper. The results are expressed as a percentage of repellency (100% - X% of gorging). The percentage of engorgement is defined relative to the EtOH negative control. DEET and commercial cis / trans PMD 75/25 at 200 mg / m ² were used as positive controls.

The results obtained were statistically analyzed using R software (R Development Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0, 2013 ) and represent the average of 16 replicates. Percent repellency values are presented as the mean ± standard deviation. The R software also makes it possible to compare two repulsion percentage values by calculating the quantity p. This quantity p is a probability. If p <0.005, the difference observed between the two compared values of percent repellency is statistically significantly different.

The repellent activity of the compositions obtained according to the method of the invention were tested on tiger mosquitoes according to the protocol described above. These activities were compared with those of DEET and commercial PMD, as well as with the activity of mixtures of 50/50, 75/25 or 90/10 mass ratios of essential oil of Eucalyptus citriodora (EC) and of essential oil of Geranium rose (GR) which have not been heated in the presence of water.

The results are presented in the following table:

[Table 2]

The compositions according to the invention are systematically more repellent than mixtures of essential oil of Eucalyptus citriodora (EC) and essential oil of geranium rose (GR) before heating in the presence of water.

From a statistical point of view, compositions 1.1, 1 .2 and 1.3 exhibit the same repellent activity.

These results are all the more remarkable since these compositions correspond to a mixture comprising PMD and other compounds. A composition tested at a concentration of 0.02036 mg / pL therefore contains less PMD than the commercial PMD positive control cis / trans 75/25, also tested at 0.02036 mg / pL (200 mg / m ² in EtOH).

A second series of tests was carried out by adjusting the amount of composition according to the invention deposited so that the skin surface tested contained 200 mg / m ² of PMD.

The results are presented in the following table: [Table 3]

By adjusting the PMD concentration to 200 mg / m ² for each test, all the compositions according to the invention are more repellent than commercial PMD (p <

0.001).

Composition 1 .2 is that which shows the strongest repellent activity. These surprising results may be the consequence of a synergistic effect between three compounds present in the composition according to the invention: PMD, citronellol and geraniol.

To illustrate this phenomenon, the repellent activity of compositions comprising commercial PMD (cis / trans 75/25 mixture) alone or as a mixture with citronellol and / or geraniol were tested on tiger mosquitoes according to the protocol described above. .

In the rest of the results, X% by mass of a compound added to commercial PMD at 200 mg / m ² means that said compound was tested at a concentration of X ^* 200 mg / m ² .

The results are presented in the following tables: [Table 4]

[Table 5]

The addition of citronellol to commercial PMD increases its repellent activity (p = 0.0267). In addition, the joint addition of citronellol and geraniol considerably enhances the repellent activity of PMD; this conclusion is verified regardless of the relative amounts of PMD, citronellol and geraniol (in each case, p <0.001).

[Table 6]

It has also been shown that a two-fold dilution of the composition

PMD / geraniol / citronellol (PMD at 100 mg / m ² ) remains at least as active as PMD twice as concentrated (PMD at 200 mg / m ² ). It can therefore be concluded that the combination of these three compounds makes it possible to reduce by two the amount of PMD while keeping the same repellent activity.

Consequently, the process according to the invention makes it possible to generate, by simple addition of water, a natural composition with a very high repellent activity, allowing the use of small amounts of PMD, citronellol and geraniol and thus limit the risks of skin irritation observed with essential oils used in too high a quantity.

[Table 7]

The addition of commercial PMD to the essential oil of Geranium rose (HE GR) makes it possible to regain the effectiveness of the PMD / citronellol / geraniol combination, which constitutes a clear confirmation of the interest of this association

Likewise, the addition of PMD to the essential oil of Eucalyptus citriodora (HE EC) clearly increases the effectiveness of this essential oil alone or of PMD alone, but the repellent activity of the mixture remains lower than that of two best combinations PMD / citronellol / geraniol or PMD / HE GR.

In conclusion, the PMD / citronellol / geraniol combination is ideal in terms of repellent activity; it can be obtained by mixing the three aforementioned compounds, or by the addition of commercial PMD in the essential oil of Geranium rose, or even more simply and more naturally by the process according to the invention in which the two are mixed. essential oils of Lemon Eucalyptus and Rose Geranium, the composition of which is modified by the addition of water.

Claims

1. A natural repellent composition for at least one hematophagous arthropod, said composition comprising p-menthane-3,8-diol, citronellol and geraniol.

2. Natural repellent composition according to claim 1, characterized in that said composition further comprises at least one compound selected from linalool, citronellal, isopulegol, and an acetal, said acetal being produced by reaction between citronellal and p-menthane-3,8-diol.

3. Natural repellent composition according to one of claims 1 or 2, characterized in that said composition comprises relative to the total number of moles:

- from 0.1 to 15% in moles of linalool, and optionally

4. Composition comprising:

- from 40 to 99% by moles, preferably from 50 to 95% by moles of p- menthane-3,8-diol,

- from 0.1 to 40% by moles, preferably from 0.5 to 30% by moles of geraniol, and

- From 0.5 to 50% by moles, preferably from 1 to 40% by moles of citronellol.

5. Composition according to claim 4, characterized in that said composition comprising:

- from 70 to 90% by moles of p-menthane-3,8-diol,

- from 1 to 25% in moles of geraniol, and

- from 2 to 30% in moles of citronellol.

6. Composition according to claim 4 or 5, characterized in that said composition is natural.

7. Composition according to any one of claims 4 to 6, characterized in that said composition further comprises from 0.1 to 15% by moles of linalool.

8. Composition according to any one of claims 4 to 7, characterized in that said composition further comprises from 0.1 to 40% by moles, preferably from 0.5 to 30% by moles, preferably from 1 to 20. % in moles of citronellal.

9. Composition according to any one of claims 4 to 8, characterized in that said composition further comprises from 0.1 to 30% by moles, preferably from 1 to 20% by moles, preferably from 1 to 15% by moles. moles of isopulegol.

10. Composition according to any one of claims 4 to 9, characterized in that said composition further comprises from 0.1 to 20% by moles, preferably from 0.5 to 10% by moles, preferably from 1 to 5. mol% acetal, said acetal being produced by reaction between citronellal and p-menthane-3,8-diol.

11. Composition according to any one of the preceding claims, characterized in that the p-menthane-3,8-diol is present in the form of at least one of its stereoisomers.

12. Composition according to any one of the preceding claims, characterized in that the p-menthane-3,8-diol is present in the form of a mixture of cis and trans stereoisomers, said mixture comprising from 10 to 90% by moles, preferably from 20 to 80% by moles of cis stereoisomers, and from 10 to 90% by moles, preferably from 20 to 80% by moles of trans stereoisomers.

13. Process for preparing a composition according to any one of claims 1 to 12, characterized in that it comprises a step a) of bringing citronellal into contact with an essential oil comprising geraniol and citronellol, and the obtaining a composition according to any one of claims 1 to 12.

14. The method of claim 13, characterized in that the essential oil comprising geraniol and citronellol is an essential oil of the species Geranium rose.

15. The method of claim 13 or 14, characterized in that it further comprises a step b) of adding water to the mixture obtained in step a), preferably a volume of water between 1 time and 10 times the volume of said mixture, and a step c) of heating the mixture obtained in step b).

16. Method according to any one of claims 13 to 15, characterized in that the citronellal is used in the form of an essential oil chosen in particular from the group consisting of essential oils originating from the species: Eucalyptus citriodora, Cymbogon winterianus or Citrus. hystix.

17. Method according to any one of claims 13 to 16, characterized in that the mixture obtained in step a) comprises from 30% to 99% by mass of an essential oil comprising citronellal, and preferably of essential oils from the species: Eucalyptus citriodora, Cymbogon winterianus or Citrus hystix, and from 1% to 70% by mass of essential oil comprising geraniol and citronellol, and preferably from an essential oil of the species Rosat Geranium.

18. Use of the composition according to any one of claims 1 to 6 as a repellent agent for at least one hematophagous arthropod.

19. Use according to claim 18, characterized in that the hematophagous arthropod is selected from the group consisting of mosquitoes, ticks and midges.

20. Use according to claim 18 or 19, characterized in that the hematophagous arthropod is chosen from mosquitoes, preferably of the genus Aedes, Anopheles, or Culex, preferably the mosquito is Aedes albopictus.