Soothing Composition for Animals, Comprising at Least One Fatty Acid and Nepetalactone

Abstract

The invention relates to novel soothing compositions for animals, particularly for cats. It specifically relates to soothing compositions for non-human mammals, comprising between 1% and 50% w/w of at least one fatty acid comprising between 5 and 22 carbon atoms and between 0.01% and 5% w/w of nepetalactone, such that said at least one fatty acid and said nepetalactone are dissolved in a solvent. Said compositions are characterised in that they exhibit soothing properties for stressed animals and are stable for the entire period of use thereof.

Claims

1. A soothing composition for non-human mammals, comprising between 1% and 50% by weight/weight of at least one fatty acid comprising between 5 and 22 carbon atoms and between 0.01% and 5% by weight/weight of nepetalactone, wherein the fatty acid(s) and the nepetalactone are dissolved in a solvent.

2. The composition as claimed in claim 1, wherein the non-human mammal is a feline.

3. The composition as claimed in claim 2, wherein the feline is a domestic cat.

4. The composition as claimed in claim 1, wherein the content of fatty acid is between 1% and 20% by weight/weight.

5. The composition as claimed in claim 1, wherein the fatty acids are selected from the group consisting of oleic, linoleic, linolenic, palmitic, myristic, azelaic, pimelic, capric and lauric acid, and a mixture of at least two thereof.

6. The composition as claimed in claim 1, wherein the fatty acids are among the fatty acids which constitute the F3 fraction of the cat facial pheromones.

7. The composition as claimed in claim 1, wherein the solvent is selected from the group consisting of pure alcohols, alcohols mixed with water, aliphatic paraffins, glycol ethers, polyglycol ethers, and a mixture of at least two thereof.

8. The composition as claimed in claim 7, wherein the aliphatic paraffins, the glycol ethers and the polyglycol ethers have a boiling point of between 200° C. and 330° C.

9. The composition as claimed in claim 7, wherein the polyglycol ethers are selected from the group consisting of mono-, di-, tri- and polypropylene glycol methyl, ethyl, propyl or butyl ethers.

10. The composition as claimed in claim 1, where the nepetalactone used is of synthetic origin or introduced in the form of a plant extract.

11. The composition as claimed in claim 10, wherein the nepetalactone used is derived from an extract of Nepeta cataria.

12. A method for diffusing a composition as claimed in claim 1, comprising adding the composition to an electric diffuser or vaporizer.

13. A method for preventing urine marking and scratching non-human mammal, comprising exposing the mammal to a diffused composition as claimed in claim 1.

14. A method for reducing signs of stress or anxiety in a non-human mammal, consisting of exposing the non-human mammal to a composition as claimed in claim 1.

15. A method for preventing and reducing urine marking and scratching by a cat, consisting of exposing the cat to a composition as claimed in claim 1.

16. A method for facilitating the adaptation and the socialization of kittens, or for increasing their social interactions, consisting of exposing the kittens to a composition as claimed in claim 1.

17. A process for manufacturing a composition as claimed in claim 1, consisting of dissolving the fatty acid(s) in the solvent under hot conditions, and then, when the mixture is homogeneous, introducing nepetalactone of synthetic origin or in the form of a plant extract into the mixture at room temperature, until a homogeneous composition is obtained.

18. The composition as claimed in claim 4, wherein the content of fatty acid is between 1% and 15% by weight/weight.

19. The composition as claimed in claim 7, wherein the aliphatic paraffins, the glycol ethers and the polyglycol ethers have a boiling point of between 230° C. and 310° C.

Description

FIGURES

[0063] FIG. 1 is a graph comprising curves illustrating the degradation over time (in days) of nepetalactone at 40° C. for examples 4 to 7.

[0064] FIG. 2 is a histogram representing the percentage reduction in behavioral scores evaluated during an episode of stress in cats exposed to the composition prepared according to example 5, standardized to the positive control as described in example 9.

EXAMPLES

[0065] The stability of nepetalactone is monitored by gas chromatography (GC). The samples are kept in a ventilated oven at 40° C. and aliquots are analyzed regularly. The product is considered to be sufficiently stable when the half-life of the nepetalactone in the mixture at 40° C. is greater than 20 days (which equates to 30 days at 25° C.).

[0066] The results are expressed as weight percentage of nepetalactone relative to the initial amount. The analyses were carried out under the following conditions: Hewlett Packard GC apparatus (5890 Series II), fitted with a FID detector (Flame Ionization Detector) and an HP5 column (Agilent J&W) 30 m×0.53 mm, film 0.88 μm, with a helium pressure of 11 psi, an injector temperature of 250° C. and a detector temperature of 280° C. The following were also used: an initial oven temperature of 100° C., an initial time of 3 min; a ramp 1 of 30° C./min, a final temperature 1 of 170° C. and a stage time 1 of 3 min; a ramp 2 of 5° C./min, a final temperature 2 of 250° C.; a ramp 3 of 20° C./min, a final temperature of 280° C. and a final stage time of 4 min.

[0067] The samples to be analyzed were prepared by diluting 600 mg of stabilized sample in ethanol (QSP 20 ml). The volume of sample injected into the GC is 1 μl.

[0068] The nepetalactone used for illustrating the invention is obtained commercially from Berjé in the form of an extract of Nepeta cataria which contains approximately 80% nepetalactone.

Example 1

Analysis of the Stability of 0.8% Nepetalactone in Linoleic Acid

[0069] 100 mg of extract of Nepeta cataria is added to 9.9 g of linoleic acid. This solution is placed in an oven at 40° C. Aliquots are taken at 14.5 h, 24 h and 45 h.

[0070] The analysis of the stability at 40° C. of a 0.8% solution of nepetalactone in linoleic acid is presented in table I below.

TABLE-US-00001 TABLE I stability at 40° C. of a 0.8% by weight solution of nepetalactone in linoleic acid % degradation of Time (days) nepetalactone 0 — 0.5  4.4% 1   15% 2 19.5%

[0071] This example shows that, at a content of 0.8% by weight in linoleic acid, after only 1 day, the composition lost 15% of its nepetalactone content, which makes such a composition unusable since the effect of the nepetalactone would decrease too quickly over the duration of use of the composition as soothing agent for non-human mammals. The half-life of this composition is estimated at only 12 days.

Example 2

Analysis of the Stability of Nepetalactone in a 85/15 Linoleic Acid/Extract of Nepeta cataria Mixture

[0072] 1.5 g of extract of Nepeta cataria are added to 8.5 g of linoleic acid. This solution is placed in an oven at 40° C. Aliquots are taken regularly for analysis.

[0073] The analysis of the stability at 40° C. of a solution at 12% by weight, relative to the total weight of the solution, of nepetalactone in linoleic acid is presented in table II below.

TABLE-US-00002 TABLE II stability at 40° C. of a 12% solution of nepetalactone in linoleic acid % degradation of Time (days) nepetalactone 0 — 0.5  4.4% 1  7.5% 2 11.7%

[0074] Approximately 12% of nepetalactone is degraded after 2 days. This gives a half-life of 13 days, which makes this mixture unsuitable for the desired application. Moreover, the slower kinetics than in example 1 suggests that the degradation of the nepetalactone is governed by the fatty acid content.

Example 3

Analysis of the Stability of Nepetalactone in the Presence of a Synthetic F3 Fraction of Cat Facial Pheromone

a) Synthetic Replica of an F3 Fraction of Cat Facial Pheromone

[0075] The replica F3 fraction of cat facial pheromones corresponds to that used in the product sold by CEVA under the brand name Feliway®. More specifically, the authors used GCMS to analyze products sold under the brand name Feliway® containing the synthetic F3 fraction.

[0076] The composition identified in the samples and reproduced for the tests is as follows:

TABLE-US-00003 Composition of Amount of the F3 fraction components used according to to manufacture analysis of the 100 g of replica F3 commercial fraction of cat product facial pheromone Compound Feliway ® (g) (g) Pimelic acid 3.04 3.05 Ethyl pimelate 2.88 2.89 Diethylpimelate 0.42 0.42 Azelaic acid 3.4 3.4 Monomethylnonanedioate 2.7 2.7 Decanoic acid 0.15 0.16 Ethyl decanoate 0.12 0.12 Lauric acid 2.9 2.89 Ethyl laurate 0.8 0.81 Palmitic acid 10.85 10.86 Ethyl palmitate 4.6 4.59 Cis-13-octadecenoic acid 40 40 Ethyl oleate 27 27

[0077] Formulation is carried out at 45° C., starting by introducing the oleic derivatives so as to entirely dissolve all the components. Stability of nepetalactone in the F3 fraction

b) Stability of Nepetalactone in the F3 Fraction

[0078] 100 mg of nepetalactone in the form of extracts of Nepeta cataria are added to 9.9 g of the F3 fraction thus obtained at 70% in ethanol. This solution is placed in an oven at 40° C. Aliquots are taken at different time intervals. The analysis of the stability at 40° C. of a 70% solution of F3 fraction, containing 0.8% by weight, relative to the total weight of the solution, of nepetalactone, is presented in table III below.

TABLE-US-00004 TABLE III stability at 40° C. of a 0.8% by weight solution of nepetalactone in an F3 fraction obtained at 70% in ethanol % degradation of Time (days) nepetalactone 0 — 1  7.4% 2 19.7%

[0079] A similar degradation is observed to that observed in example 1; again, it makes such a composition unusable since the nepetalactone content decreases too quickly. The faster kinetics than in test 2 show that the F3 fraction degrades the nepetalactone more quickly than linoleic acid.

Example 4a-c

Preparation of Alcoholic Solutions of Linoleic Acid and Extract of Nepeta cataria in a 95/5 Ratio

[0080] General procedure: 9.5 g of linoleic acid are dissolved in a volume of isopropanol at 40° C., then after returning to room temperature 0.5 g of nepetalactone in the form of extract of Nepeta cataria is added.

[0081] The solutions prepared are characterized by the volume of isopropanol used and summarized in the following table IV.

TABLE-US-00005 TABLE IV alcoholic solutions 4a, 4b and 4c of linoleic acid and extract of Nepeta cataria in a 95/5 ratio Linoleic Extract of Nepeta acid (g) cataria (g) Isopropanol (g) (%) (% nepetalactone) (%) Example 4a 9.5 (47.5%) 0.5 (2%) 10 (50%) Example 4b 9.5 (31.7%) 0.5 (1.36%) 20 (66%) Example 4c 9.5 (19%) 0.5 (0.8%) 40 (80%)

Example 5

Preparation of Alcoholic Solutions of F3 Fraction and Nepetalactone According to the Invention

[0082] The procedure as in example 3 is carried out, mixing 10 g of F3 fraction with 90 g of denatured water-ethanol (10/90) mixture, then 0.5 g of extract of Nepeta cataria is added. These mixing operations are carried out at room temperature, and the final mixture is homogeneous. The initial content of nepetalactone measured (relative to the chromatographic area and in comparison with a pure nepetalactone standard) is 0.4% by weight relative to the total weight of the solution.

Example 6

Preparation of Paraffinic Solutions of F3 Fraction and Nepetalactone

[0083] The F3 fraction is prepared as in example 3, mixing 2 g of F3 fraction in 97.5 g of paraffin at 45° C. The mixture is left to return to room temperature, then 0.5 g of nepetalactone is added. After brief stirring, a translucent mixture is obtained. The nepetalactone in the mixture is assayed relative to an external standard.

Example 7

Preparation of Polyglycolic Solutions of F3 Fraction and Nepetalactone

[0084] The F3 fraction is prepared as in example 5, mixing 2 g of F3 fraction in 97.5 g of dipropylene glycol propyl ether at 35° C. The mixture is left to return to room temperature, then 0.5 g of nepetalactone is added. After brief stirring, a translucent mixture is obtained.

Example 8

Analysis of the Stability of the Compositions of Examples 4 to 7

[0085] All the samples are packaged in climatic chambers at 40° C. and 75% moisture, upside-down for the sprays (in order to guarantee the leaktightness of the bottles and avoid side reactions which could lead to the presence of air).

[0086] The results of the analysis of stability are presented in table V below.

TABLE-US-00006 TABLE V Change in the content of nepetalactone over time relative to initial content (in % remaining) (values greater than 100 are due to measurement precision; values in italics are extrapolated over a trend curve with a correlation coefficient of greater than 99%) number of days 0 1 2 7 45 90 Example 4a 100 98 95 83 40 15 Example 4b 100 100 96 87 50 25 Example 4c 100 100 97 89 53 30 Example 5 100 100 100 100 96 83 Example 6 100 100 100 100 100 105 Example 7 100 100 100 103 103 100

[0087] All these examples have a half-life of the nepetalactone in the mixture, at 40° C., of greater than 20 days. As expected, it can be seen that the degradation kinetics slow down as a function of the reduction in concentration. The change in kinetics as a function of concentration indicates that the limit of composition which makes it possible to have a half-life at 40° C. of greater than 20 days is approximately 45% isopropanol, 50% linoleic acid and 5% extract of nepetalactone.

Example 9

Study of Effectiveness of the Compositions According to the Invention

[0088] The study is carried out with a group of 24 healthy adult cats, at least 12 months old at the start of the study, divided into four groups. Arterial pressure was never measured on any of the cats: this act of handling is the event which causes the stress in the animal, in this example.

[0089] Two products were tested: [0090] the composition resulting from the present invention, prepared according to example 5 in a 20 ml vaporizer; [0091] the commercial product Feliway® in a 20 ml vaporizer (Ceva, France), which contains a synthetic analog of the F3 fraction (10%), and ethanol q.s.p. 20 ml, and which represents the positive control which makes it possible to standardize the results obtained with the composition prepared according to example 5.

[0092] The study comprises a period of administration of 5 days and a period of withdrawal of at least 9 days. 2 groups of 6 cats received the product tested first, and the 2 others received the positive control. All the cats then changed, taking the other product, such that each product was tested by the 24 cats.

[0093] The arterial pressure of each cat was measured at the start and at the end of the period of exposure to the composition. The latter was sprayed for three consecutive days following the day on which the first measurement of arterial pressure was taken and the day on which the second measurement of arterial pressure was taken. All the products were sprayed in 5 applications (volume of product of 0.15 ml per application) in each corner of each study room 3 times daily.

[0094] Acceptance of the arterial pressure measurement and of the overall procedure was evaluated by taking into account different somatic attitudes (which are characteristic of aggressive, wary and soothed behaviors) and the intensity of these behaviors. This evaluation enables a behavioral well-being score to be obtained, which is reflected in a low score when the cat is sensitive to stress, and a high score when the cat is soothed.

[0095] These behavioral observations were carried out at different times:

[0096] 30-40 minutes before handling, during handling, 30 to 40 minutes after handling, and 4-5 hours after handling.

[0097] In order to evaluate the impact of the novel composition, the mean of the scores for stress obtained with each product (product tested and Feliway® positive control) was calculated at the different times mentioned above, during day 1 and again at day 5.

[0098] The difference in the scores between day 1 (before exposure to the composition) and 5 (at the end of the period of exposure) was then compared for the composition prepared according to example 5, standardized using the positive control at the evaluation points in order to identify the impact of the novel composition.

[0099] The study results showed a difference between the positive control and the product tested according to the invention at different times (FIG. 2). During the central stressing event (measurement of arterial pressure), the product tested according to the invention provided a statistically significant reduction in the stress index compared to the positive control. 4 to 5 hours after the measurement of arterial pressure, a very small numerical difference was noted, without statistical significance.

[0100] The combination of the synthetic analog of the F3 fraction and nepetalactone enables better management of stress in domestic cats than with the F3 fraction alone (Feliway®). Such a combination may be a novel tool for managing moderate behavioral disorders, especially in the case of immediate or acute stress. This composition may also be used for facilitating the adaptation and the socialization of non-human mammals, in particular kittens, and for increasing social interactions and playful behavior.