Method for manufacturing an active-loaded polymer matrix using a gas, product and associated use.

Abstract

Gas-assisted incorporation process within a polymer matrix, product, and associated use. The present invention relates to the field of polymer matrices loaded with active ingredients and, in particular, to processes for obtaining said loaded matrices. More specifically, the invention concerns a process for incorporating an active ingredient into a polymer matrix by means of a gas, the product obtained from this process, and its use. Figure for the abstract: [Fig 2]

Description

Title of the invention: Process for manufacturing a polymer matrix loaded with active ingredients using a gas, product and associated use.

[0001] The present invention relates to the field of polymer matrices loaded with active ingredients and in particular to the processes for obtaining said matrices.

[0002] More specifically, the invention relates to a method for manufacturing a polymer matrix loaded with active ingredients using a gas, the use of the latter and the product obtained from this method.

[0003] The process according to the invention aims to produce matrices loaded with active ingredients intended for various applications, in humans or in the veterinary field where plastics processing is often used for the production of diffusion devices.

[0004] These diffusion devices often take the form of necklaces or bracelets for topical application for antiparasitic or insecticidal purposes and can also allow the diffusion of other active ingredients such as essential oils.

[0005] Among the plastics processing methods used for the creation of these diffusion devices, we find in particular, but not exclusively, extrusion and injection molding processes.

[0006] Extrusion is a continuous transformation process. The polymer, in the form of granules or powder, is fed into a heated barrel equipped with a screw in the case of a single-screw extruder, or with two counter-rotating or co-rotating screws in the case of a twin-screw extruder. The material is conveyed, homogenized, and plasticized before passing through a die of the desired shape.

[0007] Generally, injection molding is a manufacturing process in which a molten material is injected into a pre-prepared mold and then allowed to cool. During cooling, the material solidifies and takes the shape of the mold before being ejected.

[0008] Generally speaking, polymers can be classified into two categories. We distinguish between thermoplastics and thermosets.

[0009] Thermoplastics comprise linear macromolecular chains made up of monomers, capable of inducing a reversible physical state depending on the heating or cooling of the material.

[0010] They exist in two forms, an amorphous form or a semi-crystalline form. The amorphous form is characterized by the glass transition temperature (Tg); indeed, when the temperature of the thermoplastic polymer is below this temperature, it is more brittle and is said to be glassy. Conversely, When the temperature of the thermoplastic polymer is above the Tg, the macromolecular chains are more mobile and the material is in a rubbery state.

[0011] Regarding the semi-crystalline form, when such a polymer is heated, its structure will break down and the material will become fluid. This phenomenon is called melting, and the melting temperature (Tf) is associated with this state. For semi-crystalline polymers, crystalline regions coexist with amorphous regions.

[0012] Thermosetting materials, on the other hand, are characterized by a three-dimensional network. They contain polycondensed, polymerized, or cross-linked macromolecular motifs which mean that when the material is in its final form, it is in an irreversible state.

[0013] The polymers of interest within the meaning of the invention are chosen from thermoplastic polymers.

[0014] For the purposes of this invention, the term "matrix" should be understood as an element capable of receiving or being impregnated with a substance and diffusing that substance over time. Therefore, the polymer matrix constitutes, for the purposes of this invention, a reservoir of the active ingredient and will be able to release it over a prolonged period.

[0015] The term "active ingredient reservoir" refers to the polymer matrix loaded with the active ingredient, in which the active ingredient is homogeneously distributed during the incorporation process. It should be understood that the invention does not involve compartmentalizing the active ingredient within the matrix.

[0016] The term incorporation can be defined in the context of the invention as the act of incorporating or introducing a liquid or solid active ingredient into a polymer matrix as defined above.

[0017] The terms diffusion, migration, release, or leaching, which refer to the exit of the active ingredient from the polymer matrix, from the inside to the outside of the latter, can also be used interchangeably. In the remainder of this application, the terms matrix, polymeric matrix, polymer matrix, solid matrix, thermoplastic matrix, or polymer will be used interchangeably to define the polymer matrix according to the invention.

[0018] A method for incorporating active ingredients within a polymer matrix is ​​known from the prior art. This method addresses the problem of incorporating temperature-sensitive active ingredients within a polymer matrix. In this context, a method is proposed consisting of heating polymers 1°C to 5°C above their glass transition temperature in order to incorporate a composition of temperature-sensitive active ingredients at room temperature. The disclosed polymers are ethylene-vinyl acetate (EVA) copolymers or polyether block amides (PEBA), and the latter are described as having transition temperatures glassy (Tg) temperatures between 20°C and 80°C. However, this process does not allow for satisfactory incorporation conditions for several reasons.

[0019] Indeed, EVA and PEBA type polymers have very low and negative Tg values, and it is not possible to properly incorporate active ingredients by repeating the steps of this process as described in the prior art. Furthermore, this process is not applicable to other matrix-active ingredient pairs; that is, the reproducibility of this incorporation process on other polymers or with other active ingredients is not guaranteed.

[0020] There are also other problems inherent in the use of these polymer matrices. One such problem is the product's long-term effectiveness. Indeed, it is necessary to have a stable product with prolonged effectiveness that does not lose its incorporation capacity over time.

[0021] Regarding the use of gases on polymers, the prior art contains numerous documents on foaming or expansion techniques for thermoplastics with the aim of lightening the final material. This is not relevant to the field of the present invention or the related issues of incorporating active ingredients.

[0022] However, a process for impregnating thermoplastic polymers using a gas as a volatile blowing agent exists in the prior art. This process consists of a first step involving the dissolution of an active ingredient in said volatile blowing agent under supercritical or near-supercritical conditions. The thermoplastic of interest is then brought into contact with the volatile blowing agent containing the active ingredient to be incorporated at very high pressures (2500 psi or 173 bar). The volatile blowing agent serves both to dissolve the active ingredient and to inflate the thermoplastic for incorporation, which is carried out exclusively under supercritical or near-supercritical conditions. This document further describes only a process in which incorporation within the polymer is performed simultaneously with impregnation and under very high pressure conditions.

[0023] Nevertheless, the incorporation rates with this type of process remain very low; less than 6.5% of the active ingredient is found in the finished product obtained from this process using supercritical or near-supercritical CO2. This process does not offer solutions for improving the incorporation of active ingredients using a gas compared to conventional incorporation processes.

[0024] There is therefore a need to provide a process for achieving better incorporation of active ingredients within a polymer matrix in a stable and prolonged manner, which can overcome the aforementioned drawbacks, regardless of the nature of the matrix or the active ingredients used. There is also a need, in some cases, to accelerate the process of incorporating active ingredients into the matrices. Furthermore, In some cases, asset incorporation proves impossible, therefore there is also a need to make said incorporation feasible.

[0025] The terms maximum incorporability, maximum incorporation, and maximum incorporation rate can be defined as equivalent and relate to the capacity of a matrix according to the invention to incorporate assets. This should be understood as a notion of maximum achievable.

[0026] One object of the invention is thus to provide a method for incorporating an active ingredient into a polymer matrix using a gas that is not in a supercritical fluid state, thereby improving the maximum incorporation rate of a polymer, accelerating the incorporation process, or making incorporation possible. The invention also relates to the product obtained by this method and to the use of a gas to improve the incorporation rate of a polymer matrix. The supercritical conditions of a fluid or gas are well known to those skilled in the art and are defined by precise temperature and pressure pairs. For carbon dioxide, in particular, they correspond to the precise temperature / pressure pair of 31°C / 73 bar, i.e., very high pressure conditions. For nitrogen, the supercritical conditions correspond to a precise temperature / pressure pair of -147°C / 34 bar, i.e., extreme temperatures.By non-supercritical gas, usable according to the invention, we therefore mean a gas whose temperature and pressure pairs used are lower than the thresholds of said pairs of values ​​known to those skilled in the art defining their critical point.

[0027] The applicant has developed a process in which the steps of impregnating the polymer matrix with a gas that is not in a supercritical fluid state and the step of incorporating the active ingredient into the polymer matrix are separated. Furthermore, the use of a gas in a non-supercritical state is a significant advantage with regard to the ease of implementation of the process.

[0028] The process according to the invention makes it possible, on the one hand, to obtain a polymer matrix with a better capacity for incorporating active ingredients, and on the other hand, to ensure that said polymer matrix retains its capacity for incorporation even after storage. There is thus an effective and lasting increase in the incorporation capacity over time thanks to the process according to the invention. The applicant therefore proposes, through the present invention, to address these issues by improving the maximum incorporation rate of active ingredients in a polymer matrix, or by accelerating its incorporation, or by making incorporation possible, and this on several types of polymers through a pretreatment of the polymers with a non-supercritical gas.

[0029] In the remainder of this description, it shall be understood that the term "polymer" shall refer to the polymers of interest mentioned above, namely thermoplastics in an undifferentiated manner.

[0030] The method of incorporating an active ingredient into a polymer matrix using a gas according to the invention comprises the following steps: a. Impregnation of a polymer using a gas in a non-supercritical state, b. Incorporation of the active ingredient.

[0031] In the remainder of this description, it is understood that, by "impregnation", we mean the step of impregnating a polymer with a fluid, preferably a gas, in a non-supercritical state; by incorporation, we mean the step of incorporating an active ingredient into the polymer matrix.

[0032] The polymers constituting the solid matrix are chosen from among non-biodegradable thermoplastic polymers, selected from the group formed by: - Polyolefins and their derivatives selected from polyethylenes (PE), polypropylenes (PP), ethylene-vinyl acetate (EVA) copolymers, ethylene butyl acrylates, - Polyamides, copolyamides and their derivatives. - Other vinyl polymers such as poly(vinyl chloride (PVC) or styrenics and their derivatives selected from polystyrene-poly(ethylene-butylene)-polystyrene (SEBS) copolymers, polystyrene-polyisoprene-polystyrene (SIS) copolymers, polystyrene-polybutadiene-polystyrene (SBS) copolymers. - Other thermoplastic elastomers such as thermoplastic polyurethanes (TPU), block ether amides (PEBA), ethylene-propylene-diene (EPDM) or their derivatives (PP / EPDM). - Polyesters such as polyethylene terephthalate (PET), butylene polyethylene terephthalate (PBT) or trimethylene polyethylene terephthalate (PTT).

[0033] Alternatively, the polymer constituting the solid matrix is ​​a bio-based and / or biodegradable thermoplastic polymer which may be: - a polyester or copolyester, chosen from polycaprolactones, polylactides (PLA), polyesteramides, aliphatic and aromatic copolyesters, - an agropolymer chosen from polysaccharides, starch and its derivatives, cellulosic compounds and their derivatives, milk protein derivatives or a mixture of all these polymers.

[0034] polymers from microbial synthesis such as polyhydroxyalkanoates (PHA), poly([3-hydroxybutyrate) (PHB) or all their derivatives.

[0035] In a preferred embodiment, the polymers that can be used as a matrix in the invention are preferably chosen from ethylene-vinyl acetate (EVA), polyamides, bio-based or thermoplastics, polyether block amide (PEBA), polypropylenes (PP), polyethylenes (PE), thermoplastic polyurethanes (TPU), polyvinyl chlorides (PVC), polystyrenes such as polystyrene-b-polybutadiene-b-polystyrene (SEBS) or polystyrene-b-polyisoprene-b-polystyrene (SIS), polyesters, polylactic acids (PLA) or even biodegradable polymers, agropolymers and their derivatives.

[0036] The active ingredients used for the invention are liquid active ingredients. Preferably, the active ingredients are lipophilic in nature.

[0037] By lipophilic actives, it is understood that the actives may have been previously solubilized in a fatty or oily phase, or that they have an affinity with fatty or oily phases.

[0038] The active ingredients that can be incorporated into the polymer matrix according to the process of the invention can be chosen from active ingredients known to those skilled in the art, such as pharmaceutical active ingredients, insecticides or repellents, antiparasitics, painkillers, essential oils, plasticizers or mixtures thereof.

[0039] Pharmaceutical actives can be chosen from among the actives known to those skilled in the art and usable in the veterinary field.

[0040] Insecticides or repellents may be chosen from plant pyrethrum, pyrethroids, pyrethrins and their derivatives, carbamates, formamidines, carboxylic esters, N,N-diethyl-3-methylbenzamide (DEET), icaridin, phenylpyrazoles, organophosphate compounds, organohalogen compounds, neonicotinoids, avermectins and their derivatives, spinosyns, nootkatone and its derivatives, isoxazolines or mixtures thereof.

[0041] Antiparasitic agents may be chosen from among anthelmintics, endectocides, isoxazolines, or mixtures thereof. Although having a systemic action against parasites, some endectocides may also have an insecticidal effect.

[0042] Painkillers or sedatives can be chosen from among the active ingredients known to those skilled in the art for these activities, and can in particular be chosen from cannabinoid-type derivatives devoid of tetrahydrocannabinol (THC), such as cannabidiol (CBD) devoid of THC or cannabigerol (CBG) devoid of THC or their mixture.

[0043] In one embodiment, the active ingredient comprises at least one essential oil.

[0044] Essential oil is understood to mean a plant extract concentrated in volatile aromatic compounds such as, but not limited to, geraniol, limonene, menthol, the linalool, citriodiol, citronellal, lactones without prejudice to the presence of other constituents of essential oils or their mixture.

[0045] The essential oil is preferably chosen from the essential oil of lavandin, lavender, orange, margosa, eucalyptus, citronella, lavender, neem, peppermint, spearmint, pennyroyal, field mint, wintergreen, basil, rosemary, cedar, citronella, clove, geranium, thyme or a mixture thereof.

[0046] For the purposes of this application, it is understood that the aforementioned assets may be used in a mixture within a specific formulation and that the applicant does not intend to limit itself to only one of these categories. It is also understood that the asset used may also be a mixture of assets, and in particular a mixture of the aforementioned assets.

[0047] In one embodiment, the active ingredient is a mixture comprising at least one essential oil and vegetable pyrethrum, which may also be referred to as pyrethrum in the rest of the application.

[0048] In a preferred embodiment, the active ingredient is a mixture comprising at least one essential oil, vegetable pyrethrum and an auxiliary oil.

[0049] This auxiliary oil is a vegetable oil which may preferably but not exclusively be chosen from almond oil, linseed oil, rapeseed oil, macadamia oil or hemp oil, or CBD, devoid of THC.

[0050] Although the prior art discloses a method for cold loading an active ingredient into a polymer matrix, the applicant has advantageously succeeded in increasing the maximum incorporation or the speed of incorporation of an active ingredient into a polymer matrix by adding upstream an impregnation step of said matrix with a non-supercritical fluid, preferably a gas in a non-supercritical state.

[0051] Thus the applicant proposes a new incorporation process in two successive stages comprising a first stage of impregnation of the matrix, then a second stage of incorporation.

[0052] Indeed, among diffusion devices such as collars, for example, it is necessary to obtain a homogeneous matrix to ensure optimal diffusion and even distribution of the active ingredient within it. Regarding the use of liquid active ingredients to be incorporated into the matrix, these require absorption under mechanical agitation. In an effort to improve the incorporation of active ingredients into matrices, the applicant has therefore attempted to combine, in a single step, the impregnation of the matrix with a non-supercritical fluid and the incorporation of said active ingredients.

[0053] It was found that the incorporation was not improved compared to a conventional process and that the contribution of an impregnation thus carried out simultaneously with the incorporation was negligible.

[0054] In this same approach, the applicant observed that when impregnation was carried out in the absence of active ingredients, prior to an incorporation step, it resulted in a higher matrix incorporation rate than conventional processes. Even more surprisingly, the applicant also demonstrated that using an impregnation step with a non-supercritical fluid improved the polymer's incorporability, and that this polymer retained its greater incorporation capacity over time. Indeed, a lasting effect of the modification induced by impregnation on the polymer was observed, which advantageously allows the impregnated matrices to be preserved or stored before incorporation.

[0055] The first step of the process according to the invention is thus that of impregnating the polymer matrix with a non-supercritical fluid.

[0056] Impregnation can be defined as the process by which a polymer is subjected to the pressure of a gas, under specific pressure and temperature conditions, these conditions allowing it to enter into the polymer network.

[0057] In one embodiment, the non-supercritical fluid is a gas in its non-supercritical state, preferably carbon dioxide (CO2) or nitrogen (N2) in its non-supercritical state. Indeed, the applicant does not exploit the capacity of these gases in the supercritical state, namely their solvent properties, since this impregnation step according to the present invention does not serve to solubilize the active ingredient. Furthermore, this solvent effect of the supercritical fluid on the active ingredient would only be obtained in a process where impregnation is simultaneous with incorporation, but the applicant has observed that simultaneous impregnation with the incorporation of liquid active ingredients into the matrix does not solve the problem posed by the present invention.In the process according to the invention, improving the incorporation of the active ingredient into the matrix requires carrying out the impregnation in a step upstream of the incorporation, and at temperature and gas pressure values ​​below those known for the supercritical state.

[0058] During this impregnation step, the polymers are placed in a hermetically sealed, pressure-resistant reactor equipped with an opening flange. This opening flange is itself connected to a gas inlet valve, allowing control of gas inlets into the reactor. The entire assembly is then connected to a gas source and includes means for controlling pressure, temperature, and evaluation of other necessary physico-chemical variables known to a person skilled in the art.

[0059] The polymers used in the impregnation step of the invention are in the form of granules, beads, powders, or any other form known to those skilled in the art that is suitable for agitation in an incorporation tank. Impregnation according to the process of the invention is not carried out on molded or pre-formed parts. Accordingly, any form of blowing of the material with the gas from the impregnation step is also excluded; therefore, there is no volatile blowing agent, and the invention is not intended to cause the matrix to foam.

[0060] Once the polymer is placed in the reactor, the next step is to pressurize the reactor. The impregnation step thus takes place in the presence of a pressurized gas.

[0061] The applicant was able to determine that the improvement in the matrix incorporation rate and the changes caused by the non-supercritical fluid were obtained from a pressure equivalent to 5 bar.

[0062] A pressure range within which the gas increased the maximum incorporation into the matrix was thus evaluated. Unexpectedly, the applicant was able to demonstrate that by applying a pressure between 5 and 50 bar, the maximum incorporation of the polymer increased with pressure. Above 50 bar, the effect on incorporation appears to reach a plateau and is no longer significant, while below 5 bar, changes in incorporation are not detectable.

[0063] In one embodiment, the pressure ranges that can be used during the impregnation step of the process can be between 5 and 50 bar, preferably between 25 and 35 bar, more preferably at a pressure of 30 bar.

[0064] Another important factor in the impregnation step, in addition to pressure, is temperature. Indeed, the applicant has shown that the maximum incorporation obtained for the same matrix at the same pressure can vary depending on the gassing temperature. This gassing temperature can be defined as the temperature at which the matrix is ​​placed in the presence of gas in the reactor. Furthermore, the gassing or pressurization temperatures are defined as the temperature applied to the entire system formed by the polymer matrix and the gas within the reactor.

[0065] In the case of the polymers and thermoplastics of the invention, it could be assumed that the higher the temperature, the more the polymer network would tend to relax and leave more spaces or cavities. The spaces thus created could then allow for better incorporation following the impregnation step.

[0066] Surprisingly, in the process according to the invention, the applicant was able to demonstrate that the pressure application temperatures must be relatively low for a polymer. Indeed, the temperatures that can be used during the impregnation step of the process are between 15 and 50°C, preferably between 20°C and 30°C, with the best results obtained at 25°C. Consequently, the effect of the pressure application temperature on the maximum matrix incorporation rate is all the more significant the lower the temperature.

[0067] Regarding the impregnation time, notwithstanding the time required for the system to reach pressure, the latter is inversely proportional to the applied pressure. Indeed, the higher the pressure applied to the system, the shorter the impregnation time of the polymer with the non-supercritical fluid, and vice versa.

[0068] For a pressure range between 5 and 50 bar, the impregnation time can be between 150 min and 5 min respectively.

[0069] The second step of the process is a step of incorporating the polymer matrix. Impregnation can then be considered as a pre-treatment step of the matrix before its incorporation.

[0070] During the incorporation step, the impregnated matrix is ​​placed in a stirring tank equipped with a heating method known to those skilled in the art. Surprisingly, the applicant found that the incorporation rate of the previously impregnated matrix was always higher than that of the same unimpregnated matrix, regardless of the incorporation temperature.

[0071] At the end of this incorporation step, the matrix can be defined as an incorporated matrix, or loaded with active ingredients, ready for shaping according to known plastics techniques.

[0072] The incorporation temperatures are dependent on the nature of the polymers, and more particularly on the active-matrix pairs, but for the polymers of the invention it is appropriate to work at an incorporation temperature higher than the Tg but nevertheless lower than the melting temperature of the polymer.

[0073] We thus find a transition state at the molecular scale where the amorphous part of the polymers is fluidized, that is to say that the chains which constitute the polymer network are more mobile when this temperature is reached.

[0074] The best results were thus obtained for an incorporation temperature ranging from 30°C to 100°C, preferably from 35°C to 65°C.

[0075] In these temperature ranges, the use of the pre-impregnation step of the matrix with the non-supercritical gas of the invention makes it possible to improve the maximum incorporation of the matrix independently of the incorporation temperature. It is therefore possible to reduce the temperature Incorporation rate for a predetermined and known incorporation rate using the process according to the invention. On an industrial scale, such a process would then be less energy-intensive thanks to the matrices impregnated according to the process of the invention.

[0076] In addition to improving the maximum incorporation of a given polymer, the applicant has demonstrated that impregnation also reduces the duration of the incorporation step compared to a conventional loading process, and that this effect is even more pronounced with EVA. Thus, the process used is faster, therefore less expensive and more efficient for incorporating the active ingredients.

[0077] On the other hand, for a similar incorporation time for a given polymer, the applicant's process always shows an increase in the maximum incorporation rate compared to a conventional process, even on matrices described as difficult to incorporate.

[0078] Without being exhaustive, these difficult matrices may for example belong to the class of polypropylenes (PP) or polyethylenes (PE).

[0079] The process according to the invention also makes it possible to obtain a polymer matrix that maintains a high incorporation rate over time, even after the matrix has been stored following the impregnation step, without having incorporated any active ingredient. This results in a sustained effect of the impregnation step over time, allowing for a better incorporation rate.

[0080] The applicant has thus been able to develop a process for manufacturing a polymer matrix loaded with an active ingredient, said process comprising an impregnation step prior to an incorporation step. The loaded matrix obtained at the end of the process thus benefits from a better incorporation rate of the active ingredient compared to processes conventionally used in this field.

[0081] A first object of the invention therefore relates to a process for manufacturing a polymer matrix loaded with at least one lipophilic liquid active ingredient using a gas comprising the following steps:

[0082] - impregnation of the polymer with a gas in the non-supercritical state;

[0083] - incorporation of said active ingredient(s) at a temperature between 30°C and 100°C.

[0084] Preferably, the gas for the impregnation step is chosen from dioxide of carbon (CO2) or dinitrogen (N2).

[0085] According to the invention, the impregnation step can be carried out under a pressure between 5 bar and 50 bar.

[0086] In one embodiment, the impregnation step is carried out at a temperature between 15°C and 50°C.

[0087] In another embodiment, the duration of the impregnation step is between 5 min and 150 min.

[0088] In a preferred embodiment of the process according to the invention, the polymer is a thermoplastic.

[0089] The invention also relates to a polymer matrix loaded with active ingredients obtained according to the previous process, its variants or embodiments.

[0090] In one embodiment, said matrix is ​​characterized in that the active ingredient comprises at least one essential oil.

[0091] In a preferred embodiment, said matrix is ​​characterized in that the active ingredient comprises an essential oil and vegetable pyrethrum.

[0092] The invention also relates to the use of a gas in a non-supercritical state to improve the incorporation of an active ingredient within a polymer matrix.

[0093] In a preferred mode, the gas is chosen from carbon dioxide (CO2) or nitrogen (N2).

[0094] The process of the invention will be better understood through the following non-limiting examples and figures.

[0095] [Fig-1] shows the result of comparative tests of the process according to the invention with a conventional incorporation process for multiple active-matrix pairs

[0096] [Fig.2] shows the comparative test between the process of the invention and a conventional process for assets considered difficult to incorporate.

[0097] [Fig.3] shows the maintenance over time of the matrix incorporation rate after impregnation

[0098] [Fig.4] shows the study of the influence of CO2 on the maximum incorporation as a function of the incorporation temperature.

[0099] Example 1: Carrying out the process according to the invention on an EVA polymer matrix.

[0100] Matrix impregnation:

[0101] EVA granules devoid of active ingredients are placed in an impregnation reactor supplied with a CO2 source. In order to maintain this gas in a non-supercritical state, the temperature is set at 25°C and the pressure applied to the granules is 30 bar. The granules are then maintained under these conditions for a period of 120 min before being subjected to the incorporation step.

[0102] Incorporation of the matrix:

[0103] The now impregnated EVA granules are then incorporated with the active ingredient.

[0104] To do this, the granules are placed in an incorporation reactor in the presence of the active ingredient at a fixed temperature of 61°C. This reactor is subjected to agitation for an incorporation period of 2h30 at the end of which granules loaded with the active ingredient are obtained; said granules at the end of this step constitute the loaded or incorporated matrix.

[0105] The granules can then be subjected to injection by a press or other means known to those skilled in the art in order to form an active object of the desired shape, ready for use. Kinetic and dosage studies on a standardized form then make it possible to compare the effects of the process according to the invention on the incorporation of the active ingredient within the matrix.

[0106] Example 2: Comparative testing of the process according to the invention with a conventional incorporation process for several active-matrix pairs.

[0107] Several tests were conducted to compare the incorporation rate of the asset within the matrix. The incorporation rate was evaluated by a weighing calculation; it corresponds to the ratio between the mass of asset added and the sum of the total masses (matrix and asset). It is determined from the incorporated matrix.

[0108] Several active-matrix pairs were studied. The applicant's tests were compared with a conventional incorporation process. This conventional incorporation process consists only of the incorporation step and does not include an impregnation step. In other words, the conventional incorporation tests replicate only, but entirely, the conditions of the incorporation step of the process according to the invention.

[0109] It is understood that these conditions may vary depending on the nature of the active ingredient-matrix combination and that the applicant has been able to adapt them. The tests were carried out for different polymers, with a mixture of active ingredient A or B, which are mixtures of active ingredients with different compositions.

[0110] Active ingredient A comprises linseed oil, vegetable pyrethrum and lavandin essential oil.

[0111] Active ingredient B comprises sweet almond oil, peppermint essential oil and cedar essential oil.

[0112] The tests follow the same protocol as Example 1; only the incorporation parameters may change depending on the nature of the active-matrix pair. Test 1:

[0113] Active couple / matrix: active A, EVA.

[0114] Impregnation parameters: CO2, 25°C, 30 bar, 120 min.

[0115] Incorporation parameters: 61°C, 2h30min. Test 2:

[0116] Active / matrix couple: active B, Polyamide.

[0117] Impregnation parameters: CO2, 25°C, 30 bar, 120 min.

[0118] Incorporation parameters: 70°C, 3h. Test 3:

[0119] Active pair / matrix: active A, PE.

[0120] Impregnation parameters: CO2, 25°C, 30 bar, 120 min.

[0121] Incorporation parameters: 90°C, 3h. Test 4:

[0122] Active / matrix pair: active A, Biodegradable casein-based polymer.

[0123] Impregnation parameters: CO2, 25°C, 30 bar, 120 min.

[0124] Incorporation parameters: 30°C, 5h. Test 5:

[0125] Active pair / matrix: active A, PEBA.

[0126] Impregnation parameters: CO2, 25°C, 30 bar, 120 min.

[0127] Incorporation parameters: 61°C, 3hl5min. Test 6:

[0128] Active pair / matrix: active A, PP.

[0129] Impregnation parameters: CO2, 25°C, 30 bar, 120 min.

[0130] Incorporation parameters: 61°C, 2h30min. Test 7:

[0131] Active couple / matrix: active A, Polyester.

[0132] Impregnation parameters: CO2, 25°C, 30 bar, 120 min.

[0133] Incorporation parameters: 70°C, 2h30min. Results :

[0134] For each of these tests, the applicant was able to demonstrate that the use of a gas in a non-supercritical state to impregnate the matrix prior to the incorporation of the active ingredient, made it possible to have a higher rate of incorporated active ingredients in the matrix from the process according to the invention compared to a matrix from the conventional process, and this regardless of the active ingredient-matrix pair chosen.

[0135] The complete results are presented in [Fig.1].

[0136] The overall results show a percentage increase in the incorporation rate of active ingredients of at least 15% and up to 100% depending on the nature of the polymers.

[0137] Example 2 _ j. _ Test with assets that are difficult to incorporate

[0138] In these tests, the active ingredients are chosen from neem oil, icaridin or oil sweet almond (HAD). The process described in Example 1 is followed for incorporation into an EVA-based matrix. These active ingredients are incorporated individually, not in a mixture, and are described as being difficult to incorporate in their pure form into a polymer.

[0139] The comparative results [Fig. 2] show that the process according to the invention allows for a much better incorporation of these active ingredients by total weight of the loaded matrix compared to a conventional incorporation process. The impregnation step of the process The applicant's [solution] therefore allows for a significant gain on the incorporation of these difficult assets.

[0140] Indeed, even with these assets which are difficult to incorporate, the increase in the rate of incorporation of the assets using the process according to the invention is at least 20%.

[0141] Example 3: Maintaining the matrix incorporation rate over time after impregnation

[0142] In order to determine whether the effect of the impregnation step was transient, the applicant was able to assess the durability of the impregnation of the matrix.

[0143] To this end, maximum incorporation evaluation tests according to Examples 1 and 2 were carried out on a batch of EVA granules previously impregnated according to the process of the invention. The same active ingredients A and B were tested, but also an active ingredient C comprising lavandin, geraniol, and pyrethrum.

[0144] The protocol used is as follows:

[0145] After choosing the polymer matrix, the impregnation step is carried out with carbon dioxide (CO2) or nitrogen (N2) at a temperature of 25°C and a pressure of 30 bar.

[0146] Once the matrix is ​​impregnated, a fraction of said matrix is ​​taken to carry out an incorporation test denoted t0. The remainder of the impregnated material is stored in an open container, allowing the total desorption of the chosen gas.

[0147] Once incorporation has been carried out at t0, the incorporation rate is evaluated as a total weight of the loaded matrix. This incorporation rate corresponds to the maximum incorporation of the matrix as a percentage of the total weight of the loaded matrix obtained. This test is repeated once a week for a period of 4 to 5 weeks, each time taking a new fraction of the matrix from the open container used for storage.

[0148] The applicant was thus able to demonstrate that once the matrix was impregnated, the resulting positive effects on incorporation remained unchanged and were even improved compared to a conventional process. Indeed, linearity can be observed across the different incorporation tests for various active ingredient-matrix pairs. The impregnated matrices can therefore be stored and preserved after this first step, and will maintain improved incorporability over time for at least 30 days after the impregnation step.

[0149] Figure 3 illustrates these results.

[0150] Example 4: Study of the influence of CO2 as a function of the incorporation temperature.

[0151] In order to study the influence of CO2 in the non-supercritical state on the incorporation temperature, the applicant carried out several tests in which an evaluation of the maximum incorporation according to the process of the invention was made.

[0152] These tests were carried out with the following active-matrix pair: Active A - EVA.

[0153] The maximum incorporation rate was evaluated as a function of temperature, and four tests were carried out at the respective temperatures of 35°C, 40°C, 50°C, and 63°C. These four tests were performed on a matrix impregnated with CO2 and on a non-impregnated matrix in order to study the influence of CO2 on the incorporation of the active ingredient.

[0154] Figure 4 shows that impregnating the matrix with CO2 improves the incorporation rate, regardless of the incorporation temperature. Therefore, a given and defined incorporation rate can be achieved at a lower temperature, if necessary, if the process according to the invention is used.

Claims

Demands

1. A method for manufacturing a polymer matrix loaded with at least one lipophilic liquid active ingredient using a gas comprising the following successive steps: a) impregnation of the polymer with said gas in the non-supercritical state selected from carbon dioxide (CO2) and nitrogen (N2), under a pressure between 25 bar and 35 bar and at a temperature between 20°C and 30°C; b) incorporation of the active ingredient at a temperature between 30°C and 100°C.

2. A method according to claim 1, wherein the duration of the impregnation step is between 5 min and 150 min.

3. A method according to any one of the preceding claims wherein the polymer is a thermoplastic.

4. A process according to claim 3, characterized in that the polymer is a thermoplastic selected from ethylene-vinyl acetate (EVA), polyamides, bioplastics or bio-based thermoplastics, polyether block amides (PEBA), polypropylenes (PP), polyethylenes (PE), thermoplastic polyurethanes (TPU), polyvinyl chlorides (PVC), polystyrenes such as polystyrene-b-polybutadiene-b-polystyrene (SEBS) or polystyrene-b-polyisoprene-b-polystyrene (SIS), polyesters, polylactic acids (PLA) or biodegradable polymers or agropolymers.

5. A method according to any one of claims 1 to 4, characterized in that the incorporated active ingredient is selected from pharmaceutical active ingredients, insecticides or repellents, antiparasitics, painkillers, essential oils, plasticizers or mixtures thereof.

6. Active-loaded polymer matrix obtained according to the process of claims 1 to 5, characterized in that the incorporation rate of said active is increased by at least 15% compared to the incorporation of said active carried out in said matrix according to a process without a gas impregnation phase.

7. Matrix according to claim 6, characterized in that the active ingredient comprises an essential oil and vegetable pyrethrum.

8. Use of a gas in a non-supercritical state, selected from carbon dioxide (CO2) or nitrogen (N2) to improve the incorporation of an active ingredient within a polymer matrix, characterized in that the matrix is ​​obtained by the process according to any one of claims 1 to 5.

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