Oil-in-water emulsion comprising a semiochemical composition, suitable for administration in the form of a cream
A stable oil-in-water emulsion composition with humectants and emollients addresses the volatility and insolubility issues of semiochemicals, offering a non-toxic, environmentally friendly solution for prolonged semiochemical release.
Patent Information
- Application Number
- FR2024003564
- Authority / Receiving Office
- FR · FR
- Patent Type
- Utility models
- Current Assignee / Owner
- Filing Date
- 2024-04-05
- Publication Date
- 2025-10-10
- Estimated Expiration
- 2034-04-05
AI Technical Summary
Existing semiochemical products face challenges due to physicochemical constraints such as volatility and insolubility in water, necessitating the development of aqueous formulations that are non-toxic and environmentally friendly for topical administration.
A stable and homogeneous oil-in-water emulsion composition is developed, comprising an aqueous phase with humectants and gelling agents, and an oily phase with emollient and emulsifying agents, incorporating semiochemical compounds like methyl linoleate and bis(2-ethylhexyl) adipate, for prolonged release.
The emulsion provides a stable and prolonged release of semiochemicals, addressing regulatory and environmental concerns while maintaining effectiveness for behavioral or protective effects against pests.
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Abstract
Description
Title of the invention: Oil-in-water emulsion comprising a semiochemical composition, suitable for administration in the form of a cream Technical field of the invention
[0001] The invention relates to the field of semiochemical products, and describes in particular a composition in the form of an oil-in-water emulsion comprising an aqueous phase, and an oily phase comprising a semiochemical composition, in particular suitable for administration in the form of a cream, as well as its preparation process. The invention also relates to the non-therapeutic use of the composition according to the invention for topical administration, in particular cutaneous administration to an animal or a human. State of the prior art
[0002] The semiochemicals according to the invention correspond to mixtures of several chemical compounds, described for the first time in particular by Silverstein, RM (1977). Semiochemicals are chemical substances emitted by a plant or an animal which provoke a non-therapeutic behavioral or physiological reaction in another organism. When the semiochemical product affects an individual of the same species (an "intraspecific" semiochemical product), it is called a pheromone (Wyatt TD, 2003). There are several types of pheromones allowing different types of behavioral interactions or communication, for example appeasing pheromones, sex pheromones, territorial marking pheromones and alert pheromones. When the semiochemical product affects an individual of a different species (an "interspecific" semiochemical product), it is called an allelochemical substance.Among allelochemicals, an allomone is an allelochemical that triggers a reaction in the target species, this reaction being favorable to the species that releases the allomone (the opposite is a kairomone).
[0003] Since 1995, specialties whose active ingredients are semiochemical agents have been placed on the market. Some of their uses require the product to be deposited on the animal's skin, for example to achieve the desired effects on an animal in an open environment or to protect it against pests such as parasites or biting insects, or on human skin. The physicochemical constraints of the semiochemical components, and in particular their volatility and insolubility in water, have led to the use of excipients such as ethoxydiglycol in marketed specialties. The use of this type of excipients is today increasingly limited by current regulations, but also by the general public who tends to reject them due to their synthesis methods and their potential direct and environmental toxicity. It therefore appeared necessary to develop aqueous formulations of semiochemical compounds. Presentation of the invention
[0004] The invention aims to develop a composition based on semiochemical products (also called compounds, active ingredients or agents) in a new galenic form, preferably non-toxic and environmentally friendly, in particular in the form of an oil-in-water (O / W) emulsion, preferably in the form of a stable and homogeneous oil-in-water (O / W) emulsion, for topical administration, in particular cutaneous to an animal, in particular a mammal, or a human, or for topical administration, in particular cutaneous to farm animals treated in groups, in particular for prolonged release of the semiochemical composition. Preferably, the topical administration of the composition according to the invention is carried out by punctual or localized deposits at one or more points of the skin, for example by a "spot-on" type deposit, from which the semiochemical composition is released. Summary of the invention
[0005] The invention is defined by the independent claims. The dependent claims define particular or preferred embodiments of the invention.
[0006] According to a first aspect, the invention relates to a composition in the form of an oil-in-water (O / W) emulsion (called O / W composition or composition according to the invention), suitable in particular for the release of semiochemical compounds, comprising: a) an aqueous phase comprising water, at least one humectant chosen from polyols and sugars, and at least one gelling agent chosen from polysaccharides, b) an oily phase comprising at least one emollient agent, at least one emulsifying agent, and a semiochemical composition, wherein said semiochemical composition comprises: - methyl linoleate, methyl oleate and methyl palmitate; or - bis(2-ethylhexyl) adipate and l-isopropyl-2,2-dimethyltrimethylene diisobutyrate.
[0007] According to a second aspect, the invention relates to a process for preparing a composition according to the invention, comprising the following steps: a) said at least one gelling agent is pasted into said at least one humectant; then water is added with stirring and at a temperature between 65°C and 75°C, preferably at a temperature of 70°C, so as to obtain a phase homogeneous aqueous; b) mixing said at least one emollient agent, said at least one emulsifying agent, said semiochemical composition and optionally said at least one additive, with stirring and at a temperature between 65°C and 75°C, preferably at a temperature of 70°C, so as to obtain a homogeneous oily phase; c) the oily phase from step b) is added with stirring to the aqueous phase from step a) so as to obtain an oil-in-water (O / W) emulsion; d) optionally the pH of the emulsion obtained in step c) is adjusted; e) optionally add a perfume; f) the composition is recovered in the form of an oil-in-water (O / W) emulsion, in particular stable and homogeneous, obtained in step c), d) or e).
[0008] According to a third aspect, the invention relates to the non-therapeutic use of a composition according to the invention for topical administration, in particular cutaneous administration to an animal or a human, in particular on the skin of an animal or a human, in particular for prolonged release of the semiochemical composition. Brief description of the figures
[0009] [Fig. 1] represents the analysis of a compress before the deposit of the comparative composition on the skin of the rabbit.
[0010] [Fig.2] represents the analysis of the sample taken 24 hours after the deposit of the comparative composition on the skin of the rabbit.
[0011] [Fig.3] represents the analysis of the extract 2 days after the deposit of the comparative composition on the skin of the rabbit.
[0012] [Fig.4] represents the analysis of the cotton swab extract before the deposition of the composition according to the invention on the skin of the rabbit.
[0013] [Fig.5] represents the analysis of the cotton swab extract rubbed 24 hours after the deposition of the composition according to the invention on the skin of the rabbit.
[0014] [Fig.6] represents a superposition of the chromatograms obtained for the analyses at T=1 day, 4 days, 7 days and 9 days for methyl palmitate (peak between 13.3 and 13.4), methyl linoleate (peak between 16.8 and 16.9) then methyl oleate (peak between 17.0 and 17.1), of the composition according to the invention on the skin of the rabbit. Detailed description of the invention
[0015] The invention is now described in more detail and in a non-limiting manner in the following description. Unless otherwise indicated, all percentages relating to quantities are mass percentages. Any reference to ranges of values in the description and / or the claims implies, unless otherwise stated, that the limits of the ranges are included.
[0016] The invention relates to a composition in the form of an oil-in-water emulsion (O / W), particularly suitable for the release of semiochemical compounds, including: a) an aqueous phase comprising water, at least one humectant chosen from polyols and sugars, and at least one gelling agent chosen from polysaccharides, b) an oily phase comprising at least one emollient agent, at least one emulsifying agent, and a semiochemical composition, wherein said semiochemical composition comprises: - methyl linoleate, methyl oleate and methyl palmitate; or - bis(2-ethylhexyl) adipate and l-isopropyl-2,2-dimethyltrimethylene diisobutyrate.
[0017] In a particular embodiment of the invention, said semiochemical composition comprises: - methyl linoleate, methyl oleate, methyl palmitate, 2-(2-butoxyethoxy)ethanol, dimethyl glutarate, dimethyl adipate, dimethyl succinate and dodecane; or - methyl stearate, methyl linoleate, methyl palmitate, methyl laurate, methyl myristate and methyl oleate; or - methyl laurate, methyl myristate, methyl palmitate, methyl stearate, methyl oleate, methyl linoleate, dimethyl pimelate and dimethyl azelate; or - methyl linoleate, methyl oleate, methyl palmitate, methyl stearate, methyl myristate, methyl pentadecanoate and methyl laurate; or - bis(2-ethylhexyl) adipate and l-isopropyl-2,2-dimethyltrimethylene diisobutyrate; or - methyl oleate, methyl palmitate, methyl linoleate, dioxolane, methyl laurate and methyl myristate.
[0018] In a preferred embodiment of the invention, said semiochemical composition comprises: - from 30% to 40% by weight of methyl linoleate, from 25% to 35% by weight of methyl oleate, from 15% to 25% by weight of methyl palmitate, from 5% to 15% by weight of 2-(2-butoxyethoxy)ethanol, from 2% to 6% by weight of dimethyl glutarate, from 1% to 3% by weight of dimethyl adipate, from 1% to 3% by weight of dimethyl succinate and from 1% to 3% by weight of dodecane; or -from 5% to 15% by weight of methyl stearate, from 10% to 25% by weight of methyl linoleate, from 15% to 25% by weight of methyl palmitate, from 5% to 15% by weight of methyl laurate, from 5% to 15% by weight of methyl myristate and from 25% to 35% by weight of methyl oleate; or - from 2% to 6% by weight of methyl laurate, from 2% to 6% by weight of methyl myristate, from 1% to 5% by weight of methyl palmitate, from 2% to 6% by weight of methyl stearate, from 42% to 50% by weight of methyl oleate, from 4% to 8% by weight of methyl linoleate, from 7% to 13% by weight of dimethyl pimelate and from 6% to 11% by weight of dimethyl azelate; or - from 25% to 35% by weight of methyl linoleate, from 25% to 35% by weight of methyl oleate, from 15% to 25% by weight of methyl palmitate, from 10% to 15% by weight of methyl stearate, from 2% to 7% by weight of methyl myristate, from 2% to 6% by weight of methyl pentadecanoate and from 1% to 3% by weight of methyl laurate; or - from 40% to 60% by weight of bis(2-ethylhexyl) adipate and from 40% to 60% by weight of l-isopropyl-2,2-dimethyltrimethylene diisobutyrate; - from 35% to 45% by weight of methyl oleate, from 20% to 30% by weight of methyl palmitate, from 20% to 30% by weight of methyl linoleate, from 2% to 7% by weight of dioxolane, from 1% to 5% by weight of methyl laurate and from 1% to 4% by weight of methyl myristate; the total sum of the compounds present in said semiochemical composition being equal to 100%. Galenic
[0019] The composition according to the invention is in the form of an oil-in-water (O / W) emulsion, in particular an oil-in-water emulsion which is stable and has a homogeneous appearance, in particular to the naked eye. In particular, the composition is in the form of a cream, preferably in the form of a white cream, having an opaque and thick texture.
[0020] In the context of the invention, the term "emulsion" refers to a mixture of two immiscible liquid substances, such as oil and water. In an oil-in-water (O / W) emulsion, the oil is dispersed in the water in the form of droplets, especially small droplets.
[0021] In the context of the invention, the term "stable emulsion" refers to an emulsion which does not show signs of instability (phase separation, increase in droplet size, etc.), in particular an emulsion which does not release water or oil and which remains in its initial form over time and under different temperature conditions, for example during 3 months of storage at a temperature between 5°C and 40°C.
[0022] In the context of the invention, the term "homogeneous emulsion" refers to an emulsion whose surface is smooth and uniform to the naked eye. Aqueous phase
[0023] The composition according to the invention comprises an aqueous phase, in particular a continuous aqueous phase (also called external phase).
[0024] The aqueous phase of the composition according to the invention comprises water, preferably demineralized water or purified water, and optionally one or more compounds miscible with water or at least partly miscible with water, for example a skin care agent such as ALOE VERA, a hydrosol, urea, an antistatic agent.
[0025] In the context of the invention, the term "skin conditioning agent" refers to an agent for maintaining the skin in good condition, e.g., healthy in appearance.
[0026] In the context of the invention, the term "antistatic agent" refers to an agent that reduces static electricity by neutralizing the electrical charge on a surface.
[0027] In a particular embodiment of the invention, the composition according to the invention comprises from 60% to 95% by weight of water, preferably from 70% to 80% by weight of water, relative to the total weight of the composition.
[0028] In a preferred embodiment of the invention, the composition according to the invention comprises from 62% to 91% by weight of water, preferably from 73.7% to 76% by weight of water, even more preferably 77.9% by weight of water, relative to the total weight of the composition.
[0029] The aqueous phase of the composition according to the invention may comprise water, at least one humectant chosen from polyols and sugars, and at least one gelling agent chosen from polysaccharides. Humectant
[0030] According to a particular embodiment, the aqueous phase of the composition according to the invention further comprises at least one humectant chosen from polyols and sugars. In particular, the aqueous phase of the composition according to the invention further comprises a single humectant chosen from polyols or sugars, preferably polyols. Said at least one humectant is in particular soluble in the aqueous phase.
[0031] In the context of the invention, the term “humectant” (also called moisturizing agent) refers to a compound or mixture of compounds capable of retaining water thanks to their hygroscopic power.
[0032] In the context of the invention, the term “polyol” refers to any organic compound comprising at least two free hydroxyl (-OH) groups such as glycols.
[0033] In the context of the invention, the term "sugar" refers to simple carbohydrates, in particular any organic molecule consisting of one ose (monosaccharide) or two oses (disaccharide).
[0034] In a particular embodiment of the invention, said at least one humectant is chosen from polyols selected from the group consisting of glycerol (also called glycerin), propylene glycol, polyethylene glycols (PEG), xylitol, isomalt, maltitol, mannitol, polydextrose, sorbitol, isomaltitol, lactitol, and mixtures thereof; and / or said at least one humectant is selected from sugars selected from the group consisting of fructose, glucose, lactose, and mixtures thereof.
[0035] In a preferred embodiment of the invention, said at least one humectant is a polyol, in particular glycerol.
[0036] Said at least one humectant, i.e., one or more humectants, preferably a humectant, may be present in the composition in a content ranging from 4% to 12% or 4.5% to 12% by weight, preferably from 7% to 8% by weight, relative to the total weight of the composition.
[0037] Preferably, said at least one humectant is glycerol and is present in the composition in a content ranging from 4.5% to 12% by weight, preferably 7.5% by weight, relative to the total weight of the composition. Gelling agent
[0038] In a particular embodiment, the aqueous phase of the composition according to the invention further comprises at least one gelling agent chosen from polysaccharides. In particular, the aqueous phase of the composition according to the invention further comprises a single gelling agent chosen from polysaccharides. Said at least one gelling agent is in particular soluble in the aqueous phase. Said at least one gelling agent is a hydrophilic gelling agent.
[0039] In the context of the invention, the term “gelling agent” refers to an agent capable of increasing the viscosity of the oil-in-water emulsion, and / or allowing the cohesion of the different constituents of the composition.
[0040] In the context of the invention, the term "polysaccharides" (also called glycans, polyosides or polyholosides) refers to complex carbohydrates formed by the polymerization of oses (monosaccharides) linked together by glycosidic bonds.
[0041] In a particular embodiment of the invention, the polysaccharides are chosen from the group consisting of xanthan gum, guar gum, cellulose, cellulose derivatives, maltodextrin, maltodextrin derivatives, and mixtures thereof, preferably xanthan gum.
[0042] The polysaccharides may be present in the composition in a content ranging from 0.05% to 1% or 0.05% to 0.9% by weight, preferably from 0.1% to 0.6% by weight, relative to the total weight of the composition.
[0043] Preferably, the polysaccharides are xanthan gum and are present in the composition in a content ranging from 0.05% to 0.9% by weight, preferably from 0.2% to 0.5% by weight, even more preferably 0.5% by weight, relative to the total weight of the composition.
[0044] In a particular embodiment of the invention, the aqueous phase of the composition comprises glycerol in a content ranging from 4.5% to 12% by weight, preferably 7.5% by weight, as well as xanthan gum in a content ranging from 0.05% to 0.9% by weight, preferably from 0.2% to 0.5% by weight, even more preferably 0.5% by weight, all of the percentages being given relative to the total weight of the composition. Oily phase
[0045] The composition according to the invention comprises an oily phase, in particular a dispersed oily phase (also called discontinuous or internal phase).
[0046] The oily phase of the composition according to the invention may comprise at least one emollient agent, at least one emulsifying agent, and a semiochemical composition. In particular, said at least one emollient agent, said at least one emulsifying agent, and said semiochemical composition are in particular soluble in the oily phase.
[0047] The oily phase may be present in a content ranging from 3% to 30% by weight, preferably from 15% to 25% by weight, relative to the total weight of the composition. Emollient agent
[0048] According to a particular embodiment, the oily phase of the composition according to the invention further comprises at least one emollient agent. In particular, the oily phase of the composition according to the invention further comprises a single emollient agent. Said at least one emollient agent is in particular soluble in the oily phase.
[0049] In the context of the invention, the term "emollient agent" refers to an agent for softening and making the skin supple during topical administration, in particular cutaneous administration, of the composition according to the invention.
[0050] In a particular embodiment of the invention, said at least one emollient agent is chosen from the group consisting of hydrogenated or non-hydrogenated vegetable oils (vegetable oils comprising triglycerides of unsaturated fatty acids, for example olive oil, rapeseed oil, sunflower oil, sesame oil, linseed oil, hemp oil, walnut oil, hazelnut oil, coconut oil, argan oil, jojoba oil, sweet almond oil, shea butter, castor oil, avocado oil, apricot kernel oil, macadamia oil, etc.), silicone oils (for example dimethicone, etc.), mineral oils and waxes (for example, parrafin, etc.), fatty alcohols (for example, arachidic alcohol, batyl alcohol, alcohol behenyl alcohol, C12-C13 alcohols, cetearyl alcohol, cetyl alcohol, coconut alcohol, isocetyl alcohol, octyldodecanol, palm alcohol, ...), fatty acids and fatty acid esters (e.g., batyl stearate, cetearyl behenate, isononanoate. cetearyl, cetyl esters, coconut acid, ethyl linoleate, ethyl linolenate, ethyl olivate, ethylhexyl cocoate, ethylhexyl myristate, glyceryl caprylate, glyceryl laurate / oleate, glyceryl ricinoleate, isocetyl salicylate, isostearyl alcohol, linoleic acid, linolenic acid, oleic acid, palm kernel acid, palmitic acid, wheat germ acid, ...), glyceride derivatives (e.g., capric / caprylic acid triglycerides, cocoglycerides, palm glycerides, ...) and glycerol derivatives (e.g., glyceryl trioctanoate: Tricaprylin, glyceryl tristearate: Tristearin ...), preferably glyceride derivatives such as fatty acid triglycerides.
[0051] Said at least one emollient agent, i.e., one or more emollient agent(s), is / are present in a content ranging from 0.5% to 8% by weight, preferably from 1% to 3% by weight, relative to the total weight of the composition.
[0052] Preferably, said at least one emollient agent is a glyceride derivative, in particular a fatty acid triglyceride, in particular a caprylic / capric acid triglyceride such as that marketed in particular by the company BASF under the name Myritol 318®, and is present in the composition in a content ranging from 0.5% to 8% by weight, preferably 2% by weight, relative to the total weight of the composition.
[0053] In a particular embodiment of the invention, the aqueous phase of the composition comprises glycerol in a content ranging from 4.5% to 12% by weight, preferably 7.5% by weight, as well as xanthan gum in a content ranging from 0.05% to 0.9% by weight, preferably from 0.2% to 0.5% by weight, even more preferably 0.5% by weight, and the oily phase of the composition comprises a caprylic / capric acid triglyceride such as Myritol 318® in a content ranging from 0.5% to 8% by weight, preferably 2% by weight, all percentages being given relative to the total weight of the composition. Emulsifying agent
[0054] The oily phase of the composition according to the invention further comprises at least one emulsifying agent, preferably one or more emulsifying agent(s). Said at least one emulsifying agent is in particular soluble in the oily phase.
[0055] In the context of the invention, the term "emulsifying agent" (also called emulsifying agent) refers to a small molecule composed of a hydrophilic head soluble in the aqueous phase and a lipophilic tail having an affinity for the oily phase. Said at least one emulsifying agent allows the formation of an interfacial film around the droplets located in the dispersed phase, thus forming the emulsion and providing stability to this formed emulsion.
[0056] Said at least one emulsifying agent may be chosen from non-ionic or ionic (anionic, cationic) surfactants, preferably non-ionic surfactants. ionic.
[0057] In the context of the invention, the term "surfactant" refers to a compound making it possible to reduce the surface tension and promoting a uniform distribution of the composition according to the invention during its use.
[0058] In a particular embodiment of the invention, said at least one non-ionic surfactant has a hydrophilic-lipophilic balance (HLB) of between 8 and 20 at 25°C.
[0059] In a particular embodiment of the invention, said at least one emulsifying agent is an ionic surfactant, preferably an anionic surfactant chosen from sulfated castor oil, sodium dodecyl sulfate (SDS), sodium coco sulfate (INCI Name: Sodium coco sulfate (SCS)), sodium cocoyl isethionate (INCI Name: Sodium cocoyl isethionate (SCI)), sodium lauryl sulfoacetate (INCI Name: Sodium lauryl sulfoacetate (SLSA)), sodium laureth sulfate (INCI Name: Sodium laureth sulfate (SLES)) and sodium lauroyl sarcosinate (INCI Name: Sodium Lauroyl Sarcosinate), or a cationic surfactant chosen from cetearyl alcohol (INCI Name: Cetearyl Alcohol), behentrimonium methosulfate (INCI Name: Be-hentrimonium Methosulfate (BTMS)), Brassica Alcohol (and) Brassicyl Valinate Esylate (INCI Name: Brassica Alcohol (and) Brassicyl Valinate Esylate), Benzalkonium Chlorides (BAC),didecyldimethylammonium chlorides (DDAC), brassicamidopropyl dimethylamine (INCI Name: Brassicamidopropyl dimethylamine), Polyquaternium-7, Polyquaternium-10, Polyquaternium-22 and Polyquaternium-37. In a preferred embodiment of the invention, said at least one emulsifying agent is a non-ionic surfactant, preferably a non-ionic surfactant having an HLB of between 8 and 20 at 25°C, and is in particular chosen from fatty acid esters of polyoxyethylene sorbitan, alkyl polyglucosides, or mixtures of at least one alkyl polyglucoside and at least one fatty alcohol.
[0060] Examples of fatty acid esters of polyoxyethylene sorbitan (also called ethoxylated sorbitan, sorbitan esters) include in particular C8-C24, preferably C16-C22, fatty acid esters of polyoxyethylene sorbitan which may comprise from 1 to 150 oxyethylenated groups, such as polysorbate 20, in particular marketed under the name Tween 20® by the company CRODA, polysorbate 21, in particular marketed under the name Tween 21® by the company CRODA, polysorbate 40, in particular marketed under the name Tween 40® by the company CRODA, polysorbate 60, in particular marketed under the name Tween 60® by the company CRODA, polysorbate 61, in particular marketed under the name Tween 61® by the company CRODA, polysorbate 65, in particular marketed under the name Tween 65® by the company CRODA, polysorbate 80 marketed in particular under the name Tween 80® by the company CRODA,polysorbate 81, notably marketed under the name Tween 81® by the company CRODA and, polysorbate 85, notably marketed under the name Tween 85® by the company CRODA, preferably polysorbate 80 and polysorbate 85.
[0061] Examples of alkyl polyglucosides (APG) are known to those skilled in the art.
[0062] Mixtures of at least one alkyl polyglucoside and at least one fatty alcohol include in particular at least one C12-C20 alkyl polyglucoside and at least one C14-C22 fatty alcohol such as Montanov L® notably marketed by the company SEPPIC, a mixture of myristic alcohol and myristyl glucoside such as Montanov 14® notably marketed by the company SEPPIC.
[0063] In a particular embodiment of the invention, said at least one emulsifying agent, i.e., one or more emulsifying agent(s), is / are present in the composition in a content ranging from 2% to 30% by weight, preferably from 10% to 12% by weight, relative to the total weight of the composition.
[0064] In a preferred embodiment of the invention, the composition according to the invention comprises several emulsifying agents, in particular a mixture of emulsifying agents consisting of fatty acid esters of polyoxyethylene sorbitan, alkyl polyglucosides, and mixtures of at least one alkyl polyglucoside and at least one fatty alcohol, preferably a mixture of emulsifying agents consisting of fatty acid esters of polyoxyethylene sorbitan, and mixtures of at least one alkyl polyglucoside and at least one fatty alcohol.
[0065] Preferably, said emulsifying agents are a C12-C20 alkyl polyglucoside and at least one C14-C22 fatty alcohol such as Montanov L®, notably sold by the company SEPPIC, a mixture of myristic alcohol and myristyl glucoside such as Montanov 14®, notably sold by the company SEPPIC, esters of fatty acid and polyoxyethylene sorbitan such as polysorbate 80, notably sold under the name Tween 80® by the company CRODA, and polysorbate 85, notably sold under the name Tween 85® by the company CRODA, and said emulsifying agents are present in the composition in a content ranging from 2.5% to 28.1% by weight, preferably 11% by weight, relative to the total weight of the composition.In particular, Montanov L® is present in the composition in a content ranging from 1.3% to 8.5% by weight, preferably 5% by weight, relative to the total weight of the composition; and / or Montanov 14® is present in the composition in a content ranging from 0.2% to 5.2% by weight, preferably 2% by weight, relative to the total weight of the composition; and / or polysorbate 80 is present in the composition in a content ranging from 0.5% to 7.2% by weight, preferably 2% by weight, relative to the total weight of the composition; and / or polysorbate 85 is present in the composition in a content ranging from 0.5% to 7.2% by weight, preferably 2% by weight, relative to the total weight of the composition.
[0066] In a particular embodiment of the invention, the aqueous phase of the com position comprises glycerol in a content ranging from 4.5% to 12% by weight, preferably 7.5% by weight, as well as xanthan gum in a content ranging from 0.05% to 0.9% by weight, preferably from 0.2% to 0.5% by weight, even more preferably 0.5% by weight, and the oily phase of the composition comprises a caprylic / capric acid triglyceride such as Myritol 318® in a content ranging from 0.5% to 8% by weight, preferably 2% by weight, as well as a mixture of emulsifying agents consisting of Montanov L® present in the composition in a content ranging from 1.3% to 8.5% by weight, preferably 5% by weight, Montanov 14® in a content ranging from 0.2% to 5.2% by weight, preferably 2% by weight, polysorbate 80 in a content ranging from 0.5% to 7.2% by weight, preferably 2% by weight, and polysorbate 85 in a content ranging from 0.5% to 7.2% by weight, preferably 2% by weight,all percentages being given in relation to the total weight of the composition. Semiochemical composition
[0067] The oily phase of the composition according to the invention further comprises a semiochemical composition as active agent, as defined above. Said semiochemical composition is in particular soluble in the oily phase described here. Particular semiochemical compositions are described above as well as in the preferred embodiments and experimental examples which follow. The semiochemical compositions contained in the compositions according to the invention are in particular intended for non-therapeutic use, for example use for their behavioral or protective effect against pests (parasites, insects, etc.) on the animals to which they are administered or on the animals interacting with the latter, in the form of the O / W composition.
[0068] The semiochemical composition may be present in the composition in the form of an oil-in-water emulsion in a content ranging from 2% to 5% by weight, preferably from 2.2% to 4.2% by weight of said semiochemical composition, relative to the total weight of the O / W composition according to the invention. Additives
[0069] The composition according to the invention may further comprise at least one additive provided that it does not interfere with the desired properties of the composition, in particular with its property of being an O / W emulsion.
[0070] In a particular embodiment of the invention, said at least one additive is chosen from the group consisting of a preservative agent, in particular an antimicrobial agent or an antioxidant agent, a perfume, a masking agent, and mixtures thereof.
[0071] In the context of the invention, the term “preservative agent” refers to an agent protecting the composition according to the invention against the transformation of its physical or chemical state, its color, its odor or even protecting it from contamination or microbial degradation, for example by inhibiting the development of microorganisms during the storage or use time of the composition according to the invention. Such an agent must be compatible with use of the composition according to the invention in contact with an animal or a human, and is advantageously non-irritating to the skin and eyes.
[0072] Examples of preservatives are known to those skilled in the art and include in particular benzyl alcohol, didecyldimonium chloride, caprylyl glycol, phenylpropanol, sodium benzoate, phenyl acetate, sorbic acid, dehydroacetic acid, potassium sorbate, phenoxyethanol, cetrimonium bromide, triclosa, parabens, thiazolinones.
[0073] In the context of the invention, the term “antimicrobial agent” therefore refers to a preservative agent making it possible to slow down the growth of microorganisms (bacteria, fungi, yeasts, molds) and combating the development of microbes in the composition according to the invention, when it is preserved and / or when it is used.
[0074] Examples of antimicrobial agents are known to those skilled in the art and include in particular Glycerin / phenyl alcohol / caprylhydroxamic acid, notably marketed under the name Aromastat® by the company INOLEX.
[0075] The composition according to the invention may comprise from 0% to 4% by weight, preferably from 0.2% to 3.2% by weight, even more preferably 1% by weight of preservative, in particular of antimicrobial agent relative to the total weight of the composition according to the invention.
[0076] In the context of the invention, the term "antioxidant agent" refers to a preservative agent capable of inhibiting reactions promoted by oxygen, thus preventing oxidation.
[0077] Examples of antioxidant agents are known to those skilled in the art and include in particular compounds of the cinnamic acid family and their derivatives, such as pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate in particular marketed under the name Tinogard TT® by the company BASF, vitamin A (retinol), vitamin C (ascorbic acid) and derivatives (ascobate), vitamin E (tocopherol) and derivatives (tocopheryl), preferably Tinogard TT®.
[0078] The composition according to the invention may comprise from 0% to 2% by weight, preferably from 0.02% to 0.3% by weight, even more preferably 0.1% by weight of antioxidant agent, relative to the total weight of the composition.
[0079] In the context of the invention, the term “perfume” or perfuming agent refers to any hydrophobic substance designating a pure body or a mixture insoluble or very slightly soluble in water capable of releasing a pleasant odor.
[0080] The composition according to the invention may comprise from 0% to 3% by weight, preferably from 0.2% to 2.5% by weight, even more preferably 1% or 2% by weight of perfume, relative to the total weight of the composition.
[0081] In the context of the invention, the term "masking agent" refers to an agent that reduces or inhibits the basic odor or taste of the product.
[0082] Examples of masking agents are known to those skilled in the art and include in particular beta sitosterol, citric acid, bisabolol, calendula officenalis flower extract.
[0083] The composition according to the invention may comprise from 0% to 3% by weight, preferably from 0.2% to 2.5% by weight, even more preferably 1% or 2% by weight of a masking agent, relative to the total weight of the composition.
[0084] In a particular embodiment according to the invention, said at least one additive is added to the oily phase, i.e., the oily phase further comprises at least one additive as defined previously.
[0085] In another particular embodiment according to the invention, said at least one additive, for example a perfume, is added after the formation of the oil-in-water emulsion, or after a step of adjusting the pH of the oil-in-water emulsion.
[0086] In a preferred embodiment according to the invention, the oily phase further comprises at least one additive chosen from the group consisting of a preservative, in particular an antimicrobial agent or an antioxidant agent, a perfume, a masking agent, and mixtures thereof, even more preferably at least one additive chosen from the group consisting of a preservative, in particular an antimicrobial agent or an antioxidant agent, a masking agent, and mixtures thereof.
[0087] In another preferred embodiment according to the invention, the composition according to the invention further comprises at least one additive such as a perfume. Said perfume is in particular added after the formation of the oil-in-water emulsion or after a step of adjusting the pH of the oil-in-water emulsion in order to avoid degradation of the perfume or loss of the scent of the perfume.
[0088] In a preferred embodiment of the invention, the composition comprises: a) an aqueous phase comprising water, glycerol and xanthan gum, b) an oily phase comprising at least one C12-C20 alkyl polyglucoside and at least one C14-C22 fatty alcohol (Montanov L® in particular marketed by the company SEPPIC), a mixture of myristic alcohol and myristyl glucoside (Montanov 14® in particular marketed by the company SEPPIC), caprylic / capric acid triglycerides (Myritol 318® in particular marketed by the company BASF), fatty acid esters of polyoxyethylene sorbitan (polysorbate 80 in particular marketed under the name Tween 80® by the company CRODA and polysorbate 85 in particular marketed under the name Tween 85® by the company CRODA), pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate (Tinogard TT® marketed in particular by the company BASF), Glycerin / phenyl alcohol / caprylhydroxamic acid (Aromastat® marketed in particular by the company INOLEX) and a semiochemical composition, the semiochemical composition being present in the composition according to the invention in a content ranging from 2% to 5% by weight, preferably from 2.2% to 4.2% by weight, relative to the total weight of the O / W composition according to the invention.
[0089] In an even more preferred embodiment of the invention, the composition according to the invention comprises:a) an aqueous phase comprising water in a content ranging from 62% to 91% by weight of water, preferably from 73.7% to 76% by weight of water, even more preferably 77.9% by weight, glycerol in a content ranging from 4.5% to 12% by weight, preferably 7.5% by weight, and xanthan gum in a content ranging from 0.05% to 0.9% by weight, preferably from 0.2% to 0.5% by weight, even more preferably 0.5% by weight,b) an oily phase comprising at least one C12-C20 alkyl polyglucoside and at least one C14-C22 fatty alcohol (Montanov L® notably marketed by the company SEPPIC) in a content ranging from 1.3% to 8.5% by weight, preferably 5% by weight; a mixture of myristic alcohol and myristyl glucoside (Montanov 14® notably marketed by the company SEPPIC) in a content ranging from 0.2% to 5.2% by weight, preferably 2% by weight;caprylic / capric acid triglycerides (Myritol 318® sold in particular by BASF) in a content ranging from 0.5% to 8% by weight, preferably 2% by weight; fatty acid esters of polyoxyethylene sorbitan such as polysorbate 80 sold in particular under the name Tween 80® by CRODA in a content ranging from 0.5% to 7.2% by weight, preferably 2% by weight, and polysorbate 85 sold in particular under the name Tween 85® by CRODA in a content ranging from 0.5% to 7.2% by weight, preferably 2% by weight;pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate (Tinogard TT® marketed in particular by BASF) in a content ranging from 0.02% to 0.3% by weight, preferably 0.1% by weight, Glycerin / phenyl alcohol / caprylhydroxamic acid (Aromastat® marketed in particular by INOLEX) in a content ranging from 0.2% to 3.2% by weight, preferably 1% by weight, and a semiochemical composition in a content ranging from 2% to 5% by weight, preferably from 2.2% to 4.2% by weight, the contents being expressed by weight relative to the total weight of the O / W composition according to the invention. ;
[0090] In a particular embodiment of the invention, the composition has a Brookfield viscosity greater than or equal to 4500 mPa.s, in particular between 4500 mPa.s and 5500 mPa.s, preferably 4500 mPa.s, as measured at 25°C. The viscosity within the meaning of the present invention is a Brookfield viscosity measured at room temperature (25°C), preferably after 24 hours, using a viscometer, for example a Brookfield digital viscometer (model LDVI Prime), S 63 spindle and rotation speed 6 RPM.
[0091] In a particular embodiment of the invention, the composition in the form of an oil-in-water (O / W) emulsion has a pH of between 5 and 8, preferably a pH of between 5.5 and 7.5 or a pH of between 7 and 8. Preferably, the composition has a pH value compatible with topical application, in particular cutaneous application of the composition to the skin of an animal or human skin.
[0092] Process for preparing the composition according to the invention
[0093] The invention also relates to a first process for preparing a composition according to the invention, comprising the following steps: a) said at least one gelling agent is pasted into said at least one humectant; then water is added with stirring and at a temperature between 65°C and 75°C, preferably at a temperature of 70°C, so as to obtain a homogeneous aqueous phase; b) mixing said at least one emollient agent, said at least one emulsifying agent, said semiochemical composition and optionally said at least one additive, with stirring and at a temperature between 65°C and 75°C, preferably at a temperature of 70°C, so as to obtain a homogeneous oily phase; c) the oily phase from step b) is added with stirring to the aqueous phase from step a) so as to obtain an oil-in-water (O / W) emulsion; d) optionally the pH of the emulsion obtained in step c) is adjusted; e) optionally add a perfume; f) the composition is recovered in the form of an oil-in-water (O / W) emulsion obtained in step c), d) or e).
[0094] The invention also relates to a second process for preparing a composition according to the invention, comprising the following steps: a) said at least one gelling agent is pasted into said at least one humectant; then water is added with stirring and at a temperature between 65°C and 75°C, preferably at a temperature of 70°C, so as to obtain a homogeneous aqueous phase; b) mixing said at least one emollient agent, said at least one emulsifying agent, said semiochemical composition, with stirring and at a temperature between 65°C and 75°C, preferably at a temperature of 70°C, so as to obtain a homogeneous oily phase; c) the oily phase from step b) is added with stirring to the aqueous phase of step a) so as to obtain an oil-in-water (O / W) emulsion; d) optionally the pH of the emulsion obtained in step c) is adjusted; e) optionally adding said at least one additive; f) the composition is recovered in the form of an oil-in-water (O / W) emulsion obtained in step c), d) or e).
[0095] Preferably, the invention relates to the first process for preparing a composition according to the invention.
[0096] The definitions and / or particular / preferred embodiments mentioned in the following paragraphs are applicable to both the first and second processes for preparing a composition according to the invention.
[0097] In the context of the invention, the term "pasting" means that before adding the water in step a) of the process, said at least one gelling agent is dispersed in said at least one humectant, in order to obtain a smooth and homogeneous paste. This pasting step known to those skilled in the art makes it possible to separate the particles and avoid the formation of lumps.
[0098] In a particular embodiment of the first or second process according to the invention, the pasting step a) is carried out at room temperature; and / or - the homogeneous aqueous phase obtained in step a) is kept stirring at a temperature between 65°C and 75°C, preferably at a temperature of 70°C; and / or - the homogeneous oily phase obtained in step b) is kept stirring at a temperature between 65°C and 75°C, preferably at a temperature of 70°C; and / or - step c) is carried out by mixing the oily phase of step b) in the aqueous phase of step a) at a temperature between 65°C and 75°C, preferably at a temperature of 70°C, and the emulsion is cooled to room temperature; and / or - step d) is carried out by adding a basic solution, for example a NaOH solution, in particular a 1% NaOH solution in order to increase the pH of the emulsion obtained in step c), preferably in order to obtain a pH of between 5 and 8, preferably a pH of between 7 and 8.
[0099] In a particular embodiment of the process according to the invention, the aqueous phase obtained in step a) is in the form of a homogeneous mixture.
[0100] In a particular embodiment of the process according to the invention, the oily phase obtained in step b) is in the form of a homogeneous mixture.
[0101] In the context of the invention, the term “homogeneous mixture” refers to a mixture whose different constituents cannot be distinguished with the naked eye.
[0102] In a particular embodiment of the method according to the invention, the emulsion oil-in-water (O / W) obtained in step c) is a stable and homogeneous emulsion as defined previously.
[0103] In a particular embodiment of the process according to the invention, step d) is mandatory for the preparation of a composition in the form of an oil-in-water (O / W) emulsion, comprising a semiochemical composition comprising (i) from 5% to 15% by weight of methyl stearate, from 10% to 25% by weight of methyl linoleate, from 15% to 25% by weight of methyl palmitate, from 5% to 15% by weight of methyl laurate, from 5% to 15% by weight of methyl myristate and from 25% to 35% by weight of methyl oleate; or (ii) from 2% to 6% by weight of methyl laurate, from 2% to 6% by weight of methyl myristate, from 1% to 5% by weight of methyl palmitate, from 2% to 6% by weight of methyl stearate, from 42% to 50% by weight of methyl oleate, from 4% to 8% by weight of methyl linoleate, from 7% to 13% by weight of dimethyl pimelate and from 6% to 11% by weight of dimethyl azelate;preferably (i) 11% by weight of methyl stearate, 17% by weight of methyl linoleate, 22% by weight of methyl palmitate, 11% by weight of methyl laurate, 11% by weight of methyl myristate and 28% by weight of methyl oleate (CS2); or (ii) 4.50% by weight of methyl laurate, 4.50% by weight of methyl myristate, 13.40% by weight of methyl palmitate, 4.50% by weight of methyl stearate, 46.60% by weight of methyl oleate, 6.50% by weight of methyl linoleate, 11% by weight of dimethyl pimelate and 9% by weight of dimethyl azelate (CS3). ;
[0104] The subject of the invention is in particular a process for preparing a composition according to the invention, in particular a first or second process for preparing a composition according to the invention as described previously, in which the compounds of the aqueous and oily phases are as described above.
[0105] The invention also relates to the use of a composition consisting of an aqueous phase and a composition consisting of an oily phase as described above and exemplified below, for producing a composition according to the invention comprising as active agent a semiochemical composition (associated with the oily phase), in the form of an oil-in-water (O / W) emulsion, in particular an oil-in-water emulsion which is stable and has a homogeneous appearance. In particular, the composition is in the form of a cream, preferably in the form of a white cream, having an opaque and thick texture (not flowing naturally out of the container containing it). Non-therapeutic use according to the invention
[0106] According to another aspect, the invention relates to a non-therapeutic use of a composition according to the invention. According to this use, the composition according to the invention is used to obtain the semiochemical effect(s) expected from the semiochemical composition which it contains. Thus a composition according to the invention is used for improve the management of behaviors or interactions of target animals or their well-being, by the transmission of information or signals vectorized by semiochemical agents.
[0107] A use of the composition according to the invention is for example a use as a tool or means for improving animal breeding. A use of the composition according to the invention is for example a use as a tool or means for adapting the animal to its environment.
[0108] The use of the composition according to the invention comprises the topical administration, in particular cutaneous, preferably localized (spot-on type) of said composition to an animal, in particular a mammal, or to a human, or to animals treated in a group, in particular for a prolonged release of the semiochemical composition.
[0109] In a particular embodiment according to the invention, the composition is administered topically, in particular cutaneously, on the skin of an animal or on human skin, preferably on the skin of an animal.
[0110] In the context of the invention, the term "prolonged release" means that the semiochemical composition according to the invention is released from its pharmaceutical form in a progressive, controlled manner over a more or less extended period of time, as opposed to immediate release where the duration of action is shorter.
[0111] In a preferred embodiment of the invention, the composition has a persistence time of between 5 and 9 days, thus allowing a prolonged release of the semiochemical composition and providing a rate of administration of the composition acceptable to users.
[0112] In a particular embodiment according to the invention, the animal is a domestic animal or a farm animal, in particular a mammal, preferably the animal is chosen from the group consisting of pets such as rabbits, cats, dogs, birds or from the group of farm animals such as horses or production animals such as pigs, cattle, poultry, for example chickens.
[0113] In a particular embodiment according to the invention, the composition comprises a semiochemical composition, in particular comprising a rabbit appeasing pheromone, comprising from 30% to 40% by weight of methyl linoleate, from 25% to 35% by weight of methyl oleate, from 15% to 25% by weight of methyl palmitate, from 5% to 15% by weight of 2-(2-butoxyethoxy)ethanol, from 2% to 6% by weight of dimethyl glutarate, from 1% to 3% by weight of dimethyl adipate, from 1% to 3% by weight of dimethyl succinate and from 1% to 3% by weight of dodecane; and relates to the non-therapeutic use of said composition for topical, in particular cutaneous, administration to rabbits, in particular on the skin of a rabbit, in particular to promote the well-being in rabbits, for example to promote positive emotional states in rabbits, in particular to facilitate adaptation to transport, during examination by the veterinarian, when meeting unknown animals or people, when arriving in an unknown place, or any other circumstance of a rabbit's daily life.
[0114] In a particular embodiment according to the invention, the composition comprises a semiochemical composition, in particular comprising a cat appeasing pheromone, comprising from 5% to 15% by weight of methyl stearate, from 10% to 25% by weight of methyl linoleate, from 15% to 25% by weight of methyl palmitate, from 5% to 15% by weight of methyl laurate, from 5% to 15% by weight of methyl myristate and from 25% to 35% by weight of methyl oleate; and relates to the non-therapeutic use of said composition for topical administration, in particular cutaneous to cats, in particular on the skin of a cat, in particular to prevent social stress in the cat and / or aggressive behaviors induced by encounters with unknown conspecifics, unknown people or animals of other species.
[0115] In a particular embodiment according to the invention, the composition comprises a semiochemical composition, in particular comprising a mixture of feline facial pheromone and cat appeasing pheromone, comprising from 2% to 6% by weight of methyl laurate, from 2% to 6% by weight of methyl myristate, from 1% to 5% by weight of methyl palmitate, from 2% to 6% by weight of methyl stearate, from 42% to 50% by weight of methyl oleate, from 4% to 8% by weight of methyl linoleate, from 7% to 13% by weight of dimethyl pimelate and from 6% to 11% by weight of dimethyl azelate; and relates to the non-therapeutic use of said composition for topical, in particular cutaneous, administration to cats, in particular on the skin of a cat, in particular for preventing and managing stress-induced urine marking behavior in cats.
[0116] In a particular embodiment according to the invention, the composition comprises a semiochemical composition, in particular comprising a dog appeasing pheromone, comprising from 25% to 35% by weight of methyl linoleate, from 25% to 35% by weight of methyl oleate, from 15% to 25% by weight of methyl palmitate, from 10% to 15% by weight of methyl stearate, from 2% to 7% by weight of methyl myristate, from 2% to 6% by weight of methyl pentadecanoate and from 1% to 3% by weight of methyl laurate; and relates to the non-therapeutic use of said composition for topical administration, in particular cutaneous to dogs, in particular on the skin of a dog, in particular to facilitate adaptation and prevent stress induced by encounters with unknown dogs, humans or animals, and / or prevent stress reactions induced by external factors such as fireworks, thunderstorms, loud noises or unusual environments.
[0117] In a particular embodiment according to the invention, the composition comprises a semiochemical composition, in particular comprising an allomone produced by the uropygial glands of the duck, comprising from 40% to 60% by weight of bis(2-ethylhexyl) adipate and from 40% to 60% by weight of l-isopropyl-2,2-dimethyltrimethylene diisobutyrate; and relates to the non-therapeutic use of said composition for topical administration, in particular cutaneous administration to poultry such as chickens, in particular on the skin of poultry such as chickens, in particular as a repellent allomone, in particular for preventing infestation by parasites such as the red poultry mite (Dermanyssus sp. or Omithonyssus sylviarum).Another non-therapeutic use of said composition relates to topical administration, in particular cutaneous to an animal, for example birds or mammals, in particular on the skin of birds or mammals, or to a human, in particular on human skin, in particular to prevent infestation or bites by invertebrates, in particular blood-sucking insects.
[0118] In a particular embodiment according to the invention, the composition comprises a semiochemical composition, in particular comprising an equine appeasing pheromone, comprising from 35% to 45% by weight of methyl oleate, from 20% to 30% by weight of methyl palmitate, from 20% to 30% by weight of methyl linoleate, from 2% to 7% by weight of dioxolane, from 1% to 5% by weight of methyl laurate and from 1% to 4% by weight of methyl myristate; and relates to the non-therapeutic use of said composition for topical, in particular cutaneous, administration to horses, in particular on the skin of a horse, in particular for preventing social stress in the horse and / or aggressive behaviors induced by encounters with unknown conspecifics, unknown people or animals of other species.
[0119] The above-mentioned uses of said composition according to the invention are non-therapeutic uses, and exclude any therapeutic use carried out on the animal or human body. Examples
[0120] The following examples are given for purely illustrative purposes, and should not be interpreted in any way as limiting the invention. Example 1. Oil-in-water emulsions (cream)
[0121] Compositions in the form of an oil-in-water emulsion (cream) according to the invention having the composition shown in the following Table 1 were prepared.
[0122] [Tables 1] Compound Name INCI Function CAS No. Weight Percentage Aqueous Phase Water AQUA 7732-18-5 qsp Glycerol Humectant GLYCERIN 56-81-5 7.5% Xanthan Gum Gelling Agent XANTHAN GUM 11138-66- 2 0.5% Oily Phase Montanov L Emulsifying Agent C14-22 ALCOHOLS & C12-20 ALKYL GLUCOSIDE 5.0% Montanov 14 Emulsifying Agent MYRISTYL ALCOHOL & MYRISTYL GLUCOSIDE 112-72-1 2.0% Myritol 318 Emollient Agent CAPRYLIC / CAPRI C TRI GLYCERIDE 73398-61- 5 2.0% Polysorbate 85 Emulsifying Agent POLYSORBATE 85 9005-70-3 2.0% Polysorbate 80 Emulsifying Agent POLYSORBATE 80 9005-65-6 2.0% Tinogard TT Antioxidant Agent PENTAERYTHRIT YL TETRA-DLT-BUTYL HY-DROXYHYDROCI NNAMATE 6683-19-8 0.1% Aromastat Antimicrobial Agent GLYCERIN / PHEN ETHYL ALCOHOL CAPRYLHYDROX AMIC ACID 56-81-5 60-12-8 7377-03-9 1.0% Semiochemical composition (CS1, CS2, CS3, CS4, CS5 or CS6) / / 2% Perfume (optional) / / 1.0% NaOH solution 1% (only with CS2 or CS3) SODIUM HYDROXIDE 1310-73-2 0.007%
[0123] Semiochemical compositions (CS) used as examples in the formulation of Table 1 - CS1: 35% by weight of methyl linoleate, 29% by weight of methyl oleate, 18% by weight of methyl palmitate, 9.18% by weight of 2-(2-butoxyethoxy)ethanol, 4.32% by weight of dimethyl glutarate, 1.62% by weight of dimethyl adipate, 1.62% by weight of dimethyl succinate and 1.26% by weight of dodecane; or - CS2: 11% by weight of methyl stearate, 17% by weight of methyl linoleate, 22% by weight of methyl palmitate, 11% by weight of methyl laurate, 11% by weight of methyl myristate and 28% by weight of methyl oleate; or - CS3: 4.50% by weight of methyl laurate, 4.50% by weight of methyl myristate, 13.40% by weight of methyl palmitate, 4.50% by weight of methyl stearate, 46.60% by weight of methyl oleate, 6.50% by weight of methyl linoleate, 11% by weight of dimethyl pimelate and 9% by weight of dimethyl azelate; or - CS4: 29% by weight of methyl linoleate, 29% by weight of methyl oleate, 18% by weight of methyl palmitate, 13% by weight of methyl stearate, 5% by weight of methyl myristate, 4% by weight of methyl pentadecanoate and 2% by weight of methyl laurate; or - CS5: 50% by weight of bis(2-ethylhexyl) adipate and 50% by weight of l-isopropyl-2,2-dimethyltrimethylene diisobutyrate; - CS6: from 35% to 45% by weight of methyl oleate, from 20% to 30% by weight of methyl palmitate, from 20% to 30% by weight of methyl linoleate, from 2% to 7% by weight of dioxolane, from 1% to 5% by weight of methyl laurate and from 1% to 4% by weight of methyl myristate.
[0124] Example 2. Process for the preparation of oil-in-water emulsions (cream) according to Example 1
[0125] The oil-in-water emulsions (cream) according to Example 1 were prepared according to the following protocol: STEP 1: Preparation of the mash / aqueous phase 1. In a container suitable for receiving the final volume of the aqueous phase, the glycerin and xanthan gum were weighed and added. The mixture was stirred at room temperature. 2. Once the mashing is done, all the water is added. 3. After homogenization of the aqueous phase (obtaining a homogeneous mixture), the aqueous phase was maintained at 70°C and stirred until step 3. STEP 2: Preparation of the oil phase 4. In another container suitable for receiving the final volume of the oil phase, the compounds of the oil phase, namely Montanov L, Montanov 14, Polysorbate 80, Polysorbate 85, Myritol 318, Tinogard TT, Aromastat and the semiochemical composition, were weighed and added. 5. Once all the compounds were added, the mixture was stirred and heated to 70°C until a homogeneous mixture was obtained. STEP 3: Formation of the oil-in-water emulsion 6. When the two phases (aqueous and oily) were perfectly homogeneous, the oily phase at 70°C was added to the aqueous phase at 70°C. Care was taken to ensure that the emulsion was well stirred throughout this step. The emulsion was then cooled to room temperature after homogenization of the emulsion. STEP 4: Changing the pH only with the above-mentioned compositions CS2 and CS3 7. In the case of compositions comprising the semiochemical composition CS2 or CS3 and in order to increase the pH, a pH adjustment step was carried out by adding a 1% NaOH solution until a pH between 7 and 8 was obtained. STEP 5: Perfume 8. Addition of any perfume while stirring at room temperature STEP 6: Recovery of the oil-in-water (O / W) emulsion The final emulsion obtained was white, opaque and thick.
[0126] Example 3. Organoleptic measurements of oil-in-water emulsions (cream) according to Example 1
[0127] 4 criteria (appearance, color, odor, texture) were selected for the measurements organoleptics. Appearance: Thick cream Color: White Odor: Characteristic odor Texture: rich texture (cream).
[0128] Example 4. pH measurements of oil-in-water emulsions (cream) according to Example 1
[0129] The pH measurements were carried out using an LE 438 IP 67 electrode marketed by Mettler Toledo®. This is a 2-in-1 glass pH electrode with Integrated temperature sensor and liquid electrolyte for rapid laboratory measurements; for aqueous samples, such as acids, bases, etc.
[0130] The specifications of this electrode are mentioned in the following Table 2. [Tables 2] Measuring range pH 0 - 14 Zero point 7.00 ± 0.25 Temperature range 0 - 80 °C Temperature sensor NTC 30 KQ Membrane resistance (25 °C) < 250 MQ Reference electrolyte 3 mol / L KC1 solution saturated with AgCl Reference system Ag / AgCl Reference diaphragm Gel
[0131] Prior to any measurement, the pH meter used was calibrated. Indeed, the nature of the semiochemical composition can cause the pH of the emulsion to change because certain semiochemicals have an acidic pH. In the context of a topical application, in particular cutaneous, it is therefore necessary to measure the pH of each emulsion obtained and possibly adjust the pH in order to obtain a pH between 5 and 8, preferably a pH between 7 and 8.
[0132] pH measurements were carried out after obtaining each emulsion, and are reported below: CREAM with CS1: 5.5 < pH < 7.3 CREAM with CS2: 5.5 < pH < 6.5 CREAM with CS3: 5.5 < pH < 6.5 CREAM with CS4: 5.5 < pH < 7.5 CREAM with CS5: 5.5 < pH < 7.5 CREAM with CS6: 5.5 < pH < 7.5
[0133] In order to get as close as possible to the pH of animal or human skin, and to avoid causing an irritating skin reaction, a pH adjustment was made for the formulations corresponding to CREAM with CS2 and CREAM with CS3. Following this adjustment, new pH measurements were carried out and are reported below: CREAM with CS2: 7.0 < pH < 8.0 CREAM with CS3: 7.0 < pH < 8.0
[0134] For the formulations corresponding to CREAM with CS1, CREAM with CS3 and CREAM with CS4, CREAM with CS6, no pH adjustment step was carried out.
[0135] Example 5. Measurement of the viscosity of oil-in-water emulsions (cream) according to Example 1
[0136] Viscosity is the resistance of a fluid to the sliding of one layer relative to another. For each cream, the viscosity must be checked after each production. Viscosity is influenced by a number of factors including temperature, the measuring device used, the measuring speed used, the time of measurement relative to production (measurements at T0 and T+24h, T+48h). The viscosity measurement must be carried out when the solution is at room temperature, preferably at T+24h.
[0137] The measurement of the viscosity of the oil-in-water emulsions according to example 1 was carried out using the Brookfield digital viscometer (model DV-I Prime), mobile S 63 and at a rotation speed of 6 RPM.
[0138] The DV-I Prime Brookfield viscometer measures the viscosity of fluids at a given velocity gradient. The operating principle consists of rotating a spindle (which is immersed in the liquid to be tested) by means of a calibrated spring. The measuring range (in centipoise or milliPascal-second) is determined by the spindle rotation speed, the size and shape of the spindle, the section where the spindle is rotating and the full scale of the calibrated spring torque.
[0139] The specifications of the DV-I Prime Brookfield viscometer are reported in the following Table 3.
[0140] [Table 3]: Speeds (rpm) 0.0; 0.3; 0.6; 1.5; 3; 6; 12; 30; 60; 0.5; 1; 2; 2.5; 4; 5; 10; 20; 50; 100 Viscosity Range (cP) 15 - 2,000,000 Operating Environment Temperature Range 0°C to 40°C (32°F to 104°F) 20% to 80% RH: Non-condensing Analog Torque Output 0-1 VDC (0 to 100% Torque) Viscosity Measurement Accuracy ±1°C: -of full scale Viscosity Measurement Reproducibility 0.2% of full scale used Spindles Used S61; S62; S63; S64
[0141] Following these measurements, all oil-in-water emulsions (cream) according to example 1 had a viscosity > 4500 cP or mPa.s.
[0142] Example 6. Comparative tests of remanence studies
[0143] The inventors carried out persistence studies on the skin of rabbits by comparing two compositions having two different galenics: (1) a composition according to the invention in the form of an oil-in-water emulsion (cream) having the composition of Example 1 comprising the semiochemical composition CS1, and (2) a comparative composition in liquid form comprising the semiochemical composition CS1 diluted in the solvent diethylene glycol monoethyl ether (petroleum-based solvent).
[0144] Methods used: Both studies were carried out according to the same protocol: - A sampling support (compress or cotton swab) was rubbed on the skin of the rabbits before applying the compositions to check that compounds naturally present on the rabbits did not interfere with the analyses; - The composition according to the invention and the comparative composition were then applied to the rabbits at the nape of the neck (the area which is the most difficult to access for licking); - Each day, a compress or cotton swab was rubbed over the application area on a single rabbit. The "sampled" rabbit was then removed from the test to avoid taking two samples from the same rabbit. - The compress or cotton swab was then extracted with a chemical solvent and the extract was analyzed by gas chromatography with a mass spectrometry detector to determine whether or not the compounds of the semiochemical composition CS1 were present on the rabbit. - For each analysis, so-called “blank” analyses (analysis of solvent alone, extract from compress or cotton swab without composition, extract rubbed on the skin of the rabbits before application of the compositions) were carried out to guarantee that the signal observed in the analyses came only from the product deposited on the rabbit. Results obtained:
[0145] • Study of persistence on the skin of rabbits using the comparative composition in liquid form (diethylene glycol monoethyl ether)
[0146] The following active ingredients of the semiochemical composition CS1 were identified by gas chromatography on the compresses rubbed on the skin of rabbits at the following time intervals: - before filing the comparative composition ([Fig.l]): methyl palmitate and methyl oleate; - 24 hours after deposition of the comparative composition ([Fig.2]): methyl palmitate, methyl oleate, methyl linoleate, dimethyl adipate, 2-(2-butoxyethoxy)ethanol.
[0147] Furthermore, the quantities of the two active ingredients (methyl palmitate and methyl oleate) already present on the compress before application were lower than those present after application of the comparative composition. Therefore, the semiochemical composition CS1 was considered to be present after 24 hours on the skin of the rabbits. - After 2 days ([Fig.3]): only the three most abundant active ingredients (methyl linoleate, methyl oleate, methyl palmitate) were still found; - After 3 days: the quantities of active ingredients found were negligible because they were similar to those already present initially on the compress before depositing the comparative composition.
[0148] Consequently, the inventors identified that the persistence of the comparative composition in liquid form (diethylene glycol monoethyl ether) was 2 days. • Study of persistence on the skin of rabbits using the composition according to the invention in the form of an oil-in-water emulsion (cream)
[0149] The following active ingredients of the semiochemical composition CS1 were identified by gas chromatography on cotton swabs rubbed on the skin of rabbits at the following time intervals: - before filing the composition according to the invention ([Fig.4]): no active ingredient of the semiochemical composition CS1 was found; - 24 hours after depositing the composition according to the invention ([Fig.5]): the most abundant active ingredients (methyl linoleate, methyl oleate, methyl palmitate) were found; - after 4, 7 and 9 days ([Fig.6]): the most abundant active ingredients (methyl linoleate, methyl oleate, methyl palmitate) were found at more or less high intensities.
[0150] Therefore, the inventors identified that the persistence of the composition according to the invention in the form of an oil-in-water emulsion (cream) having the composition of Example 1 comprising the semiochemical composition CS1 was 9 days.
[0151] In conclusion, the results of the persistence studies carried out on two compositions having different galenics (cream vs liquid) showed that the persistence of the composition according to the invention in the form of an oil-in-water emulsion (cream) having the composition of Example 1 comprising the semiochemical composition CS1 was significantly greater (9 days) than that obtained with the comparative composition in liquid form. Thus, the non-therapeutic use of a composition according to the invention in the form of an oil-in-water emulsion (cream) for an admi Cutaneous administration on rabbit skin resulted in sustained release of the semiochemical composition CS1. References
[0152] - Silverstein, RM, 1977. "Complexity, diversity and specificity of behavior- modifying Chemicals; examples from Coleoptera and Hymenoptera," Chemical Control of Insect Behavior:Theory and Application. Editeurs H.H. Shorey & J.J.McKelvey pp.231-251 New York : Plénum Press). - Wyatt T.D., 2003 "Pheromones and Animal Behavior. Communication by smell and taste, pp.1-4 New York: Cambridge University Press.
Claims
Claims
1. A composition in the form of an oil-in-water (O / W) emulsion comprising: a) an aqueous phase comprising water, at least one humectant chosen from polyols and sugars, and at least one gelling agent chosen from polysaccharides, b) an oily phase comprising at least one emollient agent, at least one emulsifying agent, and a semiochemical composition, wherein said semiochemical composition comprises: - methyl linoleate, methyl oleate and methyl palmitate; or - bis(2-ethylhexyl) adipate and 1-isopropyl-2,2-dimethyltrimethylene diisobutyrate.
2. Composition in the form of an oil-in-water (O / W) emulsion according to claim 1, characterized in that said semiochemical composition comprises: - methyl linoleate, methyl oleate, methyl palmitate, 2-(2-butoxyethoxy)ethanol, dimethyl glutarate, dimethyl adipate, dimethyl succinate and dodecane; or - methyl stearate, methyl linoleate, methyl palmitate, methyl laurate, methyl myristate and methyl oleate; or - methyl laurate, methyl myristate, methyl palmitate, methyl stearate, methyl oleate, methyl linoleate, dimethyl pimelate and dimethyl azelate; or - methyl linoleate, methyl oleate, methyl palmitate, methyl stearate, methyl myristate, methyl pentadecanoate and methyl laurate;or - bis(2-ethylhexyl) adipate and l-isopropyl-2,2-dimethyltrimethylene diisobutyrate; or - methyl oleate, methyl palmitate, methyl linoleate, dioxolane, methyl laurate and methyl myristate.;
3. Composition in the form of an oil-in-water (O / W) emulsion according to claim 1 or 2, characterized in that said semiochemical composition comprises: - from 30% to 40% by weight of methyl linoleate, from 25% to 35% by
4. weight of methyl oleate, from 15% to 25% by weight of methyl palmitate, from 5% to 15% by weight of 2-(2-butoxyethoxy)ethanol, from 2% to 6% by weight of dimethyl glutarate, from 1% to 3% by weight of dimethyl adipate, from 1% to 3% by weight of dimethyl succinate and from 1% to 3% by weight of dodecane; or -from 5% to 15% by weight of methyl stearate, from 10% to 25% by weight of methyl linoleate, from 15% to 25% by weight of methyl palmitate, from 5% to 15% by weight of methyl laurate, from 5% to 15% by weight of methyl myristate and from 25% to 35% by weight of methyl oleate; or - from 2% to 6% by weight of methyl laurate, from 2% to 6% by weight of methyl myristate, from 11% to 15% by weight of methyl palmitate, from 2% to 6% by weight of methyl stearate, from 42% to 50% by weight of methyl oleate, from 4% to 8% by weight of methyl linoleate, from 7% to 13% by weight of dimethyl pimelate and from 6% to 11% by weight of dimethyl azelate; or - from 25% to 35% by weight of methyl linoleate, from 25% to 35% by weight of methyl oleate, from 15% to 25% by weight of methyl palmitate, from 10% to 15% by weight of methyl stearate, from 2% to 7% by weight of methyl myristate, from 2% to 6% by weight of methyl pentadecanoate and from 1% to 3% by weight of methyl laurate; or - from 40% to 60% by weight of bis(2-ethylhexyl) adipate and from 40% to 60% by weight of l-isopropyl-2,2-dimethyltrimethylene diisobutyrate; or - from 35% to 45% by weight of methyl oleate, from 20% to 30% by weight of methyl palmitate, from 20% to 30% by weight of methyl linoleate, from 2% to 7% by weight of dioxolane, from 1% to 5% by weight of methyl laurate and from 1% to 4% by weight of methyl myristate; the total sum of the compounds present in said semiochemical composition being equal to 100%. Composition in the form of an oil-in-water (O / W) emulsion according to any one of claims 1 to 3, characterized in that said at least one humectant is chosen from polyols selected from the group consisting of glycerol, propylene glycol, polyethylene glycols (PEG), xylitol, isomalt, maltitol, mannitol, polydextrose, sorbitol, isomaltitol, lactitol, and mixtures thereof; and / or said at least one humectant is chosen from sugars selected from the group consisting of fructose, glucose, lactose; preferably said at least one humectant is glycerol.
5. Composition in the form of an oil-in-water (O / W) emulsion according to any one of claims 1 to 4, characterized in that said at least one humectant is present in a content ranging from 4% to 12% by weight, preferably from 7% to 8% by weight, relative to the total weight of the composition.
6. Composition in the form of an oil-in-water (O / W) emulsion according to any one of claims 1 to 5, characterized in that the polysaccharides are chosen from the group consisting of xanthan gum, guar gum, cellulose, cellulose derivatives, maltodextrin, maltodextrin derivatives, and mixtures thereof, preferably xanthan gum.
7. Composition in the form of an oil-in-water (O / W) emulsion according to any one of claims 1 to 6, characterized in that the polysaccharides are present in a content ranging from 0.05% to 1% by weight, preferably from 0.1% to 0.6% by weight, relative to the total weight of the composition.
8. Composition in the form of an oil-in-water (O / W) emulsion according to any one of claims 1 to 7, characterized in that it comprises from 60% to 95% by weight of water, preferably from 70% to 80% by weight of water, relative to the total weight of the composition, and / or in that it comprises from 2% to 5% by weight, preferably from 2.2% to 4.2% by weight of said semiochemical composition, relative to the total weight of the composition.
9. Composition in the form of an oil-in-water (O / W) emulsion according to any one of claims 1 to 8, characterized in that said at least one emollient agent is chosen from the group consisting of hydrogenated or non-hydrogenated vegetable oils, silicone oils, mineral oils and waxes, fatty alcohols, fatty acids and fatty acid esters, glyceride derivatives, and glycerol derivatives, preferably glyceride derivatives.
10. Composition in the form of an oil-in-water (O / W) emulsion according to any one of claims 1 to 9, characterized in that said at least one emollient agent is present in a content ranging from 0.5% to 8% by weight, preferably from 1% to 3% by weight, relative to the total weight of the composition.
11. Composition in the form of an oil-in-water (O / W) emulsion according to any one of claims 1 to 10, characterized in that said at least one emulsifying agent is chosen from fatty acid esters of polyoxyethylene sorbitan, alkyl polyglucosides, or mixtures of at least one alkyl polyglucoside and at least one fatty alcohol.
12. Composition in the form of an oil-in-water (O / W) emulsion according to any one of claims 1 to 11, characterized in that said at least one emulsifying agent is present in a content ranging from 2% to 30% by weight, preferably from 10% to 12% by weight, relative to the total weight of the composition.
13. Composition in the form of an oil-in-water (O / W) emulsion according to any one of claims 1 to 12, characterized in that the oily phase further comprises at least one additive chosen from the group consisting of a preservative, in particular an antimicrobial agent or an antioxidant agent, a perfume, a masking agent, and mixtures thereof.
14. Composition in the form of an oil-in-water (O / W) emulsion according to any one of claims 1 to 13, characterized in that it is in the form of a cream.
15. Composition in the form of an oil-in-water (O / W) emulsion according to any one of claims 1 to 14, characterized in that it comprises: a) an aqueous phase comprising water, glycerol and xanthan gum, b) an oily phase comprising at least one C 12-C 20 alkyl polyglucoside and at least one C 14-C 22 fatty alcohol, a mixture of myristyl alcohol and myristyl glucoside, caprylic / capric acid triglycerides, polyoxyethylene sorbitan fatty acid esters, pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate, Glycerin / phenyl alcohol / caprylhydroxamic acid, and a semiochemical composition, the semiochemical composition being present in the composition in the form of an oil-in-water emulsion in a content ranging from 2% to 5% by weight, preferably from 2.2% to 4.2% by weight, relative to the total weight of the composition.
16. Process for preparing a composition in the form of an oil-in-water (O / W) emulsion according to any one of claims 1 to 15, comprising the following steps: a) said at least one gelling agent is pasted into said at least one humectant; then water is added with stirring and at a temperature between 65°C and 75°C, preferably at a temperature of 70°C, so as to obtain a homogeneous aqueous phase; b) said at least one emollient agent, said at least one emulsifying agent, said semiochemical composition and optionally said at least one additive are mixed, with stirring and at a temperature between 65°C and 75°C, preferably at a temperature of 70°C, so as to obtain a homogeneous oily phase; c) the oily phase from step b) is added with stirring to the aqueous phase from step a) so as to obtain an oil-in-water (O / W) emulsion; d) optionally the pH of the emulsion obtained in step c) is adjusted; e) optionally a perfume is added; f) the composition is recovered in the form of an oil-in-water (O / W) emulsion obtained in step c), d) or e).
17. Method according to claim 16, characterized in that: - the pasting step a) is carried out at room temperature; and / or - the homogeneous aqueous phase obtained in step a) is kept stirring at a temperature between 65°C and 75°C, preferably at a temperature of 70°C; and / or - the homogeneous oily phase obtained in step b) is kept stirring at a temperature between 65°C and 75°C, preferably at a temperature of 70°C; and / or - step c) is carried out by mixing the oily phase of step b) in the aqueous phase of step a) at a temperature between 65°C and 75°C, preferably at a temperature of 70°C, and the emulsion is cooled to room temperature; and / or - step d) is carried out by adding a basic solution, for example a NaOH solution.
18. Non-therapeutic use of a composition in the form of an oil-in-water (O / W) emulsion according to any one of claims 1 to 15, for topical, in particular cutaneous, preferably localized, administration to an animal, in particular a mammal, or to a human, in particular for prolonged release of the semiochemical composition.