Device in the form of a cannabinoid-based polymer matrix

Abstract

The present invention relates to a device for topical application in the form of a polymer matrix containing at least one active ingredient from the cannabinoid family, alone or in a mixture with other active ingredients. The present invention relates to the device, preferably in the form of a collar, its use for improving the health and mobility of animals to which the device is applied, and a process for manufacturing the device.

Description

[Technical field]

[0001] The present invention is in the field of treatment for relieving various symptoms related to pain or stress.More specifically, the present invention relates to a device for topical application in the form of a polymer matrix, which contains at least one active ingredient of the cannabinoid family, alone or in a mixture with other active ingredients.The present invention relates to a device, preferably in the form of a collar, its use method for improving the health and mobility of the animal to which the device is applied, and the process for manufacturing the device.

[0002] The use of cannabis for medicine has been known for a long time. Many of the currently known therapeutic effects of cannabis are due to the psychoactive molecules present in cannabis, the cannabinoids, and in particular cannabinol (CBN), delta-9-tetrahydrocannabinol (THC) or cannabidiol (CBD). THC is mainly responsible for the euphoric, psychotropic properties and gives cannabis the drug state. More recently, the administration of cannabidiol (CBD) (also known as hemp), one of the main active compounds of cannabis, has been commercialized. Thus, hemp varieties that do not have narcotic properties (do not have THC) can be used for industrial and commercial purposes, subject to three cumulative conditions: - The approved hemp varieties are listed in France's public health law. - Only seeds and fibers may be used, except for flowers, which are prohibited. -The plant must have a delta-9-tetrahydrocannabinol (THC) content of less than 0.2%. - Any amount of THC present in CBD-based products is prohibited.

[0003] The THC-free cannabinoids have been used since ancient times to improve the quality of life of people and animals affected by conditions such as pain, stress, anxiety, epilepsy, convulsions, arthritis, nausea, or skin diseases. The cannabinoids are basically administered orally or sublingually. For topical administration, cannabidiol oil is formulated either in semi-solid form (ointments, creams, gels) or in liquid form (milks, emulsions, lotions). The above-mentioned galenics for topical application require repeated application to produce the expected systemic effect. Moreover, in the veterinary field, the application of such topical products is neither easy nor optimal for effectively penetrating the animal's fur or for long-term treatment.

[0004] One of the objectives of the present invention is to propose a more advantageous local administration method for the local treatment of pain or stress, which can be used for longer treatment, while limiting the known systemic side effects of oral methods.In the field to which the present invention pertains, it has been observed that when compositions are applied locally, some of the ingredients may disappear due to their volatility, oxidative decomposition, exposure to ultraviolet light, or washing.This results in up to 40% of the available effective dose of active ingredient passing through.The bioavailability of the active ingredient is not optimal, which results in its reduced effectiveness in relieving pain or stress.

[0005] In order to overcome the above-mentioned various drawbacks and improve the passage of the active ingredient through the skin, the applicant proposes to use a solid polymer matrix as a vehicle for topical and / or transdermal application of cannabinoids, alone or in combination with other active ingredients, which allows to obtain a composition with a stably incorporated active ingredient. Stability according to the invention should be understood as the physical stability of the device and the chemical stability of the active ingredient in the device. Physical stability means the absence of exudation that confirms the correct incorporation of the active phase and the mechanical strength of the device, in particular the resistance to deformation, flexibility or hardness required for the final use. Chemical stability means the absence of degradation of the main active ingredient or ingredients, which may be less than 10% of the amount initially introduced into the device. The device according to the invention may be stable against the risk of evaporation and loss, in particular through leaching, provision during use, and continuous, controlled, effective and gradual release of the active ingredient to be treated.

[0006] One of the objectives of the present invention is also to propose a device whose manufacturing method is easy to carry out and which is transferable to an industrial scale. In the prior art in the field of polymers, it is described that it is difficult to incorporate active ingredients into said polymers. This is because it is necessary to enable the active ingredient to be fully and stably incorporated into the polymer, avoiding uncontrollable release or delivery. In response to these problems, the prior art describes various solutions, such as adding a number of specific ingredients to enable the incorporation of the active ingredient, or proposing to incorporate the active ingredient into a particle structure that produces different degrees of complexation. The method for obtaining the device according to the present invention allows the incorporation of liquid active ingredients into the structural polymer of the matrix, without the use of specific ingredients or the need to incorporate the active ingredient in a particulate form.

[0007] The device according to the present invention can be defined as a topical application, and is for local use, where the device is applied to the skin or covering of the subject to be treated.The device according to the present invention can also meet the definition by those skilled in the art of a transdermal device, and is formed from a polymer matrix that is used as a support for the active ingredient, and is produced to allow the active ingredient to be released for delivery to the subject to be treated, so that the active ingredient can reach the cannabinoid receptor.In the remainder of this application, the terms "topical" and "transdermal" are applied interchangeably to the device according to the present invention.

[0008] Transdermal systems containing cannabinoid derivatives have been described in the prior art. However, they all describe reservoir or matrix type systems, which are composed of at least two or multiple layers of different materials with diverse functions. The transdermal systems are composed of at least one adhesive layer for attaching the device to the subject, a reservoir layer containing one or more active ingredients to be delivered, and an impermeable outer layer. The prior art does not describe a non-adhesive single layer system that allows cannabinoid active ingredients to be easily incorporated and delivered, as proposed in the present invention. Moreover, the systems described are complex to manufacture and are not suitable for use on furry animal subjects.

[0009] Thus, in the present invention, the applicant proposes to use at least one cannabinoid, alone or in association with other active ingredients, as an active sedative or anti-stress agent in a polymer matrix of a single-layer monopolymer not described in the prior art. A single-layer polymer matrix according to the present invention should be understood as a matrix composed of a single polymer layer, not the juxtaposition of several layers as generally described in the prior art. A monopolymer according to the present invention should be understood as a matrix composed of the same polymer. The same polymer may be a homopolymer or a copolymer. A homopolymer is a polymer derived from a single (real, implied or hypothetical) monomer species. The repeat units of a homopolymer are all of the same chemical nature. A copolymer is a polymer derived from at least two different monomers, known as comonomers, and contains at least two types of repeat units. [Brief description of the drawings]

[0010] [Figure 1] 1 shows the CBD release kinetics from a device according to one embodiment of the present invention according to Example 10. [Diagram 2] 1 shows the CBD release kinetics from devices according to embodiments of the present invention according to Examples 5 and 11.

[0011] Cannabinoids, more specifically cannabidiol (CBD), Isolate It has been found that by incorporating cannabinoid-rich oil derived from hemp in the form of essential oils, either as the sole active ingredient or preferably in combination with essential oils in the solid polymer matrix described in the present invention, the result is a stable composition that effectively relieves pain or stress in a human or animal subject treated by the device according to the present invention.Therefore, there is a need for the present invention that helps to relieve pain or stress and increases the stability of the composition while ensuring the bioavailability of the ingredient, resulting in a more effective analgesic or stress-relieving effect and long-term effectiveness.

[0012] Thus, a first object of the present invention is to provide a method for the preparation of a hemp extract or cannabis oil, either alone or in association with other active ingredients, Isolate The device comprises a solid polymer matrix containing a composition of active ingredients containing at least a first active ingredient formed by a cannabinoid in the form of a solid polymer matrix. The active ingredient used in association with the cannabinoid active ingredient according to the invention may be selected from analgesic, anti-inflammatory, sedative or anesthetic active ingredients. According to one embodiment, the cannabinoid active ingredient may also be associated with an insecticidal or pest control active ingredient.

[0013] According to the invention, the cannabinoids used are preferably in the form of a powder, liquid, solution, oil or Isolate, or cannabidiol (CBD), which may be used in the form of a hemp plant extract. CBD oil is understood as an oil rich in cannabinoids, more specifically rich in phytocannabinoids and terpenes, preferably identified in the hemp gene. The oil is in particular an oil derived from the Cannabis sativa, Cannabis indica and Cannabis ruderalis plants. Preferably, the CBD oil used contains 50% to 95% cannabidiol (CBD), preferably 80% to 90% CBD, in addition to various terpenes. In certain embodiments where a specific medical treatment is indicated, the CBD oil used according to the invention may contain THC (also known as full spectrum CBD). However, in a preferred embodiment according to the invention, the oil used is an oil known as broad spectrum oil, the THC content of which is less than 0.2%, preferably THC-free, and still serves to relieve pain or stress, or any other related pathology. In the remainder of this specification, the terms "CBD oil" or "CBD-rich hemp oil" are used indiscriminately to refer to CBD in the form of oil extracted from hemp rich in cannabidiol (CBD) and with a THC content of less than 0.2% p / p. In the composition according to the invention, the CBD oil is present in an amount of 0.01% to 10% p / p, preferably 0.1% to 5%, relative to the total weight of the device. The cannabidiol and terpene purification and extraction system may be based on, but is not limited to, patented technology that preserves the terpenes and lipids of the plant while being free of undesirable compounds such as delta-9-THC, waxes and chlorophyll, as specifically described in U.S. Patent Application No. 2018 / 0333446, the entirety of which is incorporated herein by reference.

[0014] In a particularly preferred method, the CBD used is Isolate The present invention is in the form of Isolate is to be understood in particular as a crystalline powder obtained by extraction from the hemp plant and having a CBD concentration of 99% or more. In a preferred embodiment, the CBD used in the composition Isolateis present in an amount of 0.01% to 10% p / p, preferably 0.1% to 5% p / p, more preferably 0.5% to 2.5% p / p of the composition.

[0015] In a preferred embodiment according to the present invention, the active ingredient that can be used in combination with cannabinoid is an essential oil, or a monoterpene acid alcohol, aldehyde or ester derivative of an essential oil.Preferably, the active ingredient is selected from linalool, menthol or essential oil of peppermint, lavender, lavandin, Italian helichrysum, cedar, lemon, citronella, carrot, ginger, niaouli, sweet orange, clove, eucalyptus citriodora, eucalyptus radiata, geranium, valerian, neptet cataria, chamomile, ylang-ylang, clary sage, mandarin, sandalwood, bergamot, marjoram, frankincense, geranium, thyme, juniper, or mixtures thereof.Preferably, CBD oil or CBD oil is selected from linalool, menthol or essential oil of peppermint, lavender, lavandin, Italian helichrysum, cedar, lemon, citronella, carrot, ginger, niaouli, sweet orange, clove, eucalyptus citriodora, eucalyptus radiata, geranium, valerian, neptet cataria, chamomile, ylang-ylang, clary sage, mandarin, sandalwood, bergamot, marjoram, frankincense, geranium, thyme, juniper, or mixtures thereof. Isolate is associated with menthol, linalool, essential oils of peppermint, eucalyptus citriodora, lavender, lavandin, valerian or nepeta cataria. More preferably, in the sedative device according to the invention, the active ingredient is CBD. Isolate or CBD oil and peppermint or Eucalyptus citriodora essential oil, combined with the sedative and / or analgesic properties of CBD. In the device according to the invention, the active ingredient in the form of an essential oil or a compound of essential oils is present in an amount between 0.5% and 20% p / p, preferably between 0.5% and 15% p / p, more preferably between 0.5% and 6%, relative to the total weight of the device.

[0016] According to a first variant, the polymer matrix is ​​composed of a thermosetting or thermosetting polymer chosen from cast polyurethanes, reactive silicones and epoxy resins, preferably cast polyurethanes. The cast polyurethane matrix according to the invention is described in its entirety in French patent No. 2 992 325, which is incorporated herein by reference.

[0017] According to a second preferred variant of the device according to the invention, the polymer forming the solid matrix is ​​selected from thermoplastic polymers, which may or may not be biodegradable, selected from the group consisting of polyolefins and their derivatives, ethylene butyl acrylate, polyamides, copolyamides and their derivatives, polyvinyl chloride (PVC), polyurethanes (TPU) and their derivatives, styrene and its derivatives, vulcanized thermoplastics, agricultural polymers and their derivatives, polyesters and their derivatives, or selected alone or in a mixture. The polyolefins and their derivatives may in particular be selected from polyethylene (PE), polypropylene (PP), ethylene and vinyl acetate copolymers (EVA). The styrenes and their derivatives may in particular be selected from polystyrene-poly(ethylenebutylene)-polystyrene copolymers (SEBS), polystyrene-polyisoprene-polystyrene copolymers (SIS) or polystyrene-polybutadiene-polystyrene copolymers (SBS). The copolyamides and their derivatives may in particular be selected from ether block amides (EBA). The agropolymers and their derivatives may in particular be chosen from polysaccharides, starches, cellulose and derivatives or proteins.

[0018] Preferably, the thermoplastic polymers that may be used according to the invention are selected from polyolefins and their derivatives, or polyurethanes and their derivatives. More preferably, the polymer matrix forming the device according to the invention is a thermoplastic consisting of ethylene and vinyl acetate copolymer (EVA) or polyether or polyester unit polyurethane (TPU). The applicant has demonstrated that these two preferred polymers impart optimal loading and release properties of the active ingredient. The two polymers allow both the mechanical properties of elasticity and hardness required for use in the device, and optimal incorporation and release capacity of the active ingredient, using methods that are easily implemented on an industrial scale. Preferably, for devices with a transparent, translucent appearance, TPU is preferred. The polymer represents 40% to 99% by weight of the device. Preferably, the polymer matrix is ​​in an amount sufficient to account for 100% (qs100%) of the composition of the device.

[0019] According to a particularly preferred embodiment, when the device is a collar for an animal, the thermoplastic polymers that may be used according to the invention are non-adhesive, since adhesive devices are not suitable for application to the fur of animals.

[0020] According to particularly preferred embodiments, in order to meet the objective of maintaining the stability and integrity of the device for long-term treatment of a subject, the thermoplastic polymers that may be used according to the present invention are not water-soluble.

[0021] Furthermore, it is specified that unlike polymer matrices found in the prior art formed from polymer mixtures and / or multiple layers or sequences of polymers, the matrices forming the devices according to the present invention are only single-layer monopolymer matrices and are not formed by the association of multiple sequences of different polymers.

[0022] In the present invention, the skilled person may add other additives to the formulation of the device. As non-exhaustive examples, formulation additives may be dispersants, solvents, vectorizers, penetration enhancers, plasticizers, stabilizers, colorants, or fragrances for addition to the composition according to the present invention, depending on the effect desired.

[0023] Examples of dispersants, solvents, vectorizers, or propenetrators may include oils of organic, synthetic, mineral, or vegetable origin, esters such as mixtures of succinic acid, glutaric acid, and adipates, omega-3 polyunsaturated fatty acids, fatty acid esters, glycol ethers, or squalene, and derivatives thereof.

[0024] A preferred embodiment of the device according to the invention comprises a vectorizer or penetration enhancer capable of facilitating the vectorization of the active ingredient on the skin or fur of the subject and / or the transdermal passage of the active ingredient. In a preferred embodiment, the vectorizer or penetration enhancer is a lipophilic compound. Indications include coconut oil, jojoba oil, hemp oil, macadamia oil, linseed oil, sweet almond oil, krill oil, diethylene glycol monoethyl ether, isopropyl myristate, commercially available under the name Transcutol V, or a derivative of squalene, preferably 2,6,10,15,19,23-hexamethyltetracosane, also known as perhydrosqualene or dodecahydrosqualene, commercially available under the name squalene. The component is present in an amount of 0.1-30% p / p, preferably 0.5-15% p / p, more preferably 1-6% based on the total weight of the device.

[0025] According to the invention, the device also comprises a plasticizing compound. This is because the applicant has surprisingly found that the plasticizer plays a role in the release of the active ingredient from the polymer matrix, making it possible for the nature and concentration of the plasticizer to modulate the release of the active ingredient. As plasticizers that may be used in the device according to the invention, mention may be made of ethylhexyl diphenyl phosphate, dioctyl adipate, diisooctyl adipate, dibutyl adipate, dimethyl adipate, dimethyl glutarate or dimethyl succinate, either alone or as a mixture. According to a particular embodiment, a plasticizer mixture consisting of dimethyl adipate, dimethyl glutarate and dimethyl succinate is used in the form of a commercial mixture known as Coasol. Preferably, the plasticizer is different from phthalates, the use of which is controversial due to their toxicity. In a preferred embodiment according to the invention, the plasticizer or plasticizer mixture is present in an amount of 0% to 50% by weight of the composition, preferably 5% to 35% by weight. Moreover, plasticizers make it possible to give the matrix the plasticity properties required for its use.According to the present invention, plasticizers also have the role of softener of the polymeric material used to give the device a selected flexibility or hardness.This is because, as a preferred embodiment, one of the objects of the present invention is a device in the form of a collar for animals.The collar therefore needs to be flexible enough to fit the shape of the animal's neck while retaining the necessary shape and structure as well as the desired active ingredient release properties.According to a particularly preferred embodiment according to the present invention, in particular when the polymer used is TPU, the polymeric matrix according to the present invention comprises at least one plasticizer.

[0026] In certain embodiments, the stabilizer and / or antioxidant may be added to the composition of the device according to the invention at a concentration of 0% to 5% by weight of the composition, preferably 0% to 1.5% by weight. Preferred examples may include vitamin E or tocopherol, which is present at 0.5% to 1.5% by weight relative to the total weight of the composition.

[0027] Not only fragrances, but also colorants can be added to the composition.Colorants can be in liquid or solid form.As examples of perfumes, the perfumes can be selected from vanilla, green lemon, lavender, violet, apple, apricot, patchouli, or green bamboo leaf, and can be adapted to the indication and the user.

[0028] One skilled in the art can select formulation additives so as not to interfere with the properties desired for the composition according to the invention.

[0029] According to a variant, the device according to the invention comprises, as a percentage by weight of the device: -0.01% to 10% CBD Isolate Or CBD oil -0.5%~20% of complementary active ingredients, -0.1%~30% of vectorizing additives -0%~50% of plasticizing additives; - Consists of a solid polymer matrix of qs100% by weight selected from EVA or TPU.

[0030] According to a particular embodiment, the device according to the invention comprises, as a percentage by weight of the device: -0.01% to 10% CBD Isolate Or CBD oil -0.5%~20% of complementary active ingredients, -0.5% to 15% vector additives, -0% to 1.5% antioxidant additives, -qsConstituted as a 100% by weight solid EVA polymer matrix.

[0031] According to another particular embodiment, the device according to the invention comprises between -0.1% and 5% CBD, by weight of the device. Isolate , -0.5% to 15% by weight of active ingredients in the form of essential oils and / or essential oil compounds, -0.5% to 15% of vectoring additives, -5% to 35% plasticizing additives, -qs100% by weight of TPU solid polymer matrix.

[0032] According to a more preferred embodiment, the device according to the invention comprises, as a percentage by weight of the device: -0.1% to 5% CBD Isolate , -0.5% to 15% by weight of active ingredients in the form of essential oils and / or essential oil compounds; -1% to 6% of vectorizing additives; -5% to 35% plasticizing additives, -qs100% by weight of TPU solid polymer matrix.

[0033] According to a second more preferred embodiment, the device according to the invention comprises, as a percentage by weight of the device: -0.1% to 5% CBD Isolate , - 0.5% to 15% by weight of active ingredients in the form of essential oils and / or essential oil compounds, more preferably peppermint essential oil, - 1% to 6% of a vectoring additive, more preferably squalane, - 5% to 35% of a plasticizer, preferably a mixture of ethylhexyl diphenyl phosphate, dimethyl adipate, dimethyl glutarate and dimethyl succinate or dimethyl glutarate, -Constituted as a solid polymer matrix with qs100 wt% composed of TPU.

[0034] According to one embodiment, the device is presented in the form of a collar, a bracelet, a medallion, a single-layer patch or a textile coating.Preferably, the device is manufactured in the form of a collar or a bracelet.In a preferred embodiment, the method for obtaining the device is an injection molding method.In a particularly preferred embodiment, the device is a collar for pets, in particular a collar for dogs or cats.

[0035] A second object of the present invention is to provide a compound comprising at least one CBD oil for use in the treatment or alleviation of pain or stress in a human or animal subject. IsolateOr a device consisting of a solid polymer matrix incorporating a solution of an active ingredient containing CBD oil. More specifically, taking into account the properties of CBD in combination with one or more other active ingredients according to the invention, the application of the device can regulate pain, especially caused by inflammatory disorders, with or without immune induction. By way of example, the device makes it possible to regulate skin pain or itch, muscle pain, joint pain, tendonitis and rheumatic pain, such as arthropathy or arthritis, in human or animal subjects. The device according to the invention can also be used to regulate stress in human or animal subjects.

[0036] The present invention therefore relates to a device for topical / transdermal application in a thermoplastic polymer matrix loaded with an active ingredient, in particular cannabidiol, for use in relieving pain or stress in a human or animal being treated. The device is characterized in that it is placed in contact with the skin and / or fur. According to a preferred embodiment, the device serves to ensure the relief of pain or stress in animals, characterized in that it is applied in the form of a collar in contact with the skin and / or fur. Thus, the active ingredient is released from the collar and penetrates the skin by topical application, being transported in particular by sebum. The present invention therefore relates to a device for use in improving the mobility and health of a subject, more particularly an animal.

[0037] Another object of the invention is to administer the device according to the invention, used to administer cannabidiol, and any other active ingredient incorporated in the device, transdermally. This delivery route therefore offers the advantage of reducing any metabolic effects previously obtained during oral administration of the active ingredient and increasing the bioavailability of the active compound. Furthermore, the use of the transdermal device according to the invention has the advantage of delivering the active ingredient gradually, continuously, in a measured manner and over a longer period of time. The application time required for the device according to the invention is from 30 minutes for a quick effect to several months for a long-lasting effect. According to a preferred embodiment, the device according to the invention is applied for 1 day to 60 days, preferably 28 days (4 weeks). This is because, according to a preferred embodiment, said time of 4 weeks is necessary and sufficient to treat pain or stress in a human or animal subject before a new application, if necessary.

[0038] Another object of the invention is a method for producing the device according to the invention, since, surprisingly, the process, and in particular the choice of mixing temperature, makes it possible to carry out the manufacturing process in a few steps, without relying on the addition of specific components or particle structures to aid the incorporation of the active ingredient into the polymer matrix.

[0039] According to the invention, the method for producing the device according to the invention comprises four main steps: heating the polymer, preparing the active phase, mixing the active phase with the polymer, and molding the device.

[0040] Thus, the first step of the method consists of placing the polymer in a reactor that has been preheated to the required temperature depending on the nature of the polymer. In a preferred embodiment, the polymer is heated to a temperature 10-15°C below its melting point, sufficient to give the polymer a structure that allows the network to open up to facilitate the incorporation of the active ingredient without reaching the melting point of the polymer.

[0041] By way of example, if the polymer used is polyurethane (TPU), in a particular mode according to the invention, the reactor is heated to 80-90° C., preferably 90° C.-95° C. In another particular embodiment according to the invention, if the polymer used is ethylene vinyl acetate copolymer (EVA), the reactor is heated to 45-90° C., preferably 70° C.-75° C. The reactor is then stirred.

[0042] The second step of the method is the following protocol: weighing and measuring the plasticizing and vectorizing components; Transparent It consists of preparing a liquid active phase by stirring to obtain a homogenous mixture.The active ingredient is then added with stirring at ambient temperature until a marginal, translucent and homogenous mixture is obtained.

[0043] The third step of the method consists of gradually adding the active phase to the polymer until the target temperature selected for incorporation is reached. Agitation is maintained until the active ingredient is completely incorporated into the polymer. It is cooled to ambient temperature while stirring. Colorants or other additives are added to the reactor. The reactor is then emptied and then a fourth and final injection molding step is carried out to obtain the desired shape of the device by injection molding methods known to those skilled in the art.

[0044] Another object of the invention is the product obtained by the process defined above.

[0045] In summary, the present invention relates to a device for topical application formed from a monolayer polymer matrix, characterized in that the polymer is selected from the group consisting of ethylene vinyl acetate copolymers and polyurethanes, said matrix also comprising at least one cannabinoid derivative and at least one essential oil or monoterpene derivative of an essential oil, in an amount ranging from 0.5% to 20% by total weight of the matrix.

[0046] The invention more particularly relates to devices in which the polymer is characterised by its non-adhesive properties.

[0047] The invention more particularly relates to devices characterized in that the polymer is an ethylene-vinyl acetate copolymer or a polyurethane.

[0048] The present invention relates to such a device, characterized in that the cannabinoid derivative is cannabidiol, preferably free of delta-9-tetrahydrocannabinol.More preferably, the device is characterized in that the cannabidiol is CBD. Isolate or in the form of CBD oil, Isolate contains at least 90% CBD, and the CBD oil is characterized by containing 80% to 90% CBD.

[0049] The invention also relates to such a device, characterized in that it comprises at least one essential oil or monoterpene derivative of an essential oil selected from linalool, menthol, or the essential oils of lavender, lavandin, Italian helichrysum, cedar, lemon, citronella, carrot, ginger, niaouli, sweet orange, clove, Eucalyptus citriodora, Eucalyptus radiata, peppermint, geranium, valerian, nepeta cataria, chamomile, ylang ylang, clary sage, mandarin, sandalwood, bergamot, marjoram, frankincense, geranium, thyme, juniper, or mixtures thereof.

[0050] The device according to the invention is also characterized in that it comprises a vectorizing compound chosen from oils of organic, synthetic, mineral or vegetable origin, esters such as mixtures of succinic acid, glutaric acid and adipates, oils such as omega-3 polyunsaturated fatty acids, fatty acid esters, glycol ethers, or squalene and their derivatives.

[0051] In the case of certain polymers, and in particular when the polymer used is TPU, the device is characterized in that it also comprises a plasticizing compound selected from ethylhexyl diphenyl phosphate, dioctyl adipate, diisooctyl adipate, dibutyl adipate, dimethyl adipate, dimethyl glutarate or dimethyl succinate, either alone or in a mixture.

[0052] According to the invention, the device is also characterized in that it is presented in the form of a collar, a bracelet, a patch, a medallion or a textile coating, preferably in the form of a collar.

[0053] More specifically, the present invention relates to a device for topical application in a thermoplastic polymer matrix, loaded with an active ingredient for use in the relief of pain or stress in an animal, the device being placed in contact with the skin and / or fur, and comprising at least one cannabidiol free of delta-9-tetrahydrocannabinol. Isolate The present invention relates to a device comprising at least one essential oil or compound of essential oils and at least one non-stick thermoplastic polymer selected from polyurethanes or ethylene vinyl acetate copolymers.

[0054] The invention also relates to a device as defined above for use in the relief of stress, or muscle, joint or rheumatic pain, such as tendonitis, arthritis or arthropathy.

[0055] The present invention also relates to a method of using a device according to the invention, characterized in that it allows to regulate the release and delivery of cannabidiol to a human or animal subject, topically or transdermally.

[0056] The present invention also provides a method for producing a device comprising a thermoplastic polymer matrix comprising at least one non-tacky thermoplastic polymer selected from polyurethane or ethylene vinyl acetate copolymer, wherein the active ingredient is at least one cannabidiol free of delta-9-tetrahydrocannabinol. Isolate and 0.5% to 20% p / p of at least one essential oil or compound of essential oils, characterized in that the method comprises heating a polymer to a selected temperature, preparing an active phase, mixing the active phase with the polymer, and then molding the device, wherein the method does not include a step of adding specific excipients or particle structures to help incorporate the active ingredient into the polymer matrix.

[0057] The present invention also relates to the products obtained by the above-mentioned process.

[0058] The above examples serve to illustrate the present invention without limiting its scope. Also, manufactured and defined in a specific shape (collar, bracelet, etc.), the compositions of the following examples may be adapted to different end forms. Only the final injection molding method is changed and adapted according to the final shape.

[0059] Example 1: Pain Relief Collar Fabrication of the collar as an ethylene vinyl acetate copolymer (EVA) matrix formulated with CBD-rich hemp oil. [Table 1]

[0060] The active ingredients, i.e. hemp oil enriched with cannabinoids and peppermint oil, are placed in a beaker at ambient temperature. Linseed oil is added and the mixture is homogenized, then Transcutol V is added as a penetration enhancer. This is gently stirred using a bar magnet to obtain a homogenous mixture that forms the analgesic active ingredient solution.

[0061] Then, a cylindrical mixer is preheated to 70°C in an oil bath. EVA pellets (Alcudia® PA-538) are placed in it, with gentle stirring, until the temperature measured on the pellets is close to 70°C. Then, the solution already obtained is placed in the mixer, still with gentle stirring. It is stirred until all the liquid is completely absorbed by the polymer, and then the temperature is reduced to 25°C. The mixer is emptied and the compound thus obtained is stored in a sealed package that is impermeable to air and moisture. "Compound" refers to the term well known to those skilled in the art to designate a polymer that is compounded with an active ingredient.

[0062] The polymer containing the active ingredient obtained above is injected into the nozzle outlet to form a collar of about 41 g with a length of 75 cm. The collar is applied to dogs to relieve pain in various types of arthropathy. of It is meant to be worn around the neck.

[0063] Example 2: Pain Relief Collar [Table 2] The three active ingredients, namely hemp oil, linalool, and menthol, are placed one after the other in a beaker at ambient temperature. Refined linseed oil is added to better disperse the active ingredients, and then isopropyl myristate is added as a penetration enhancer. This is gently stirred using a bar magnet to obtain a homogenous mixture that forms a solution of the analgesic active ingredient.

[0064] The cylindrical mixer is then preheated to 70° C. in an oil bath. EVA pellets (Alcudia® PA-538) are introduced with gentle stirring until the temperature measured on the pellets is close to 70° C. The previously obtained solution is then introduced into the mixer, which is further stirred gently. This is stirred until all the liquid is completely absorbed by the polymer, after which the temperature is reduced to 25° C. The mixer is emptied and the obtained compound is stored in an air- and moisture-tight sealed package.

[0065] The polymer containing the active ingredient obtained above is injected at the nozzle outlet into a collar of 41 g and 75 cm in length. The collar is used to treat dogs with various types of arthropathy to relieve pain. Wrapped around the neck This is the intention.

[0066] Example 3: Anti-Stress Medallion [Table 3] The active ingredients, i.e. hemp oil enriched with cannabinoids and valerian essential oil, are placed in a beaker at ambient temperature and then Transcutol V is added as a penetration enhancer. This is gently stirred using a bar magnet to obtain a homogenous mixture that forms a solution of the relaxing anti-stress active ingredients.

[0067] The cylindrical mixer is then preheated to 70° C. in an oil bath. EVA pellets (Alcudia® PA-538) are introduced with gentle stirring until the temperature measured on the pellets is close to 70° C. The previously obtained solution of active ingredient is then introduced into the mixer, which is further stirred gently. This is stirred until all the liquid is completely absorbed by the polymer, after which the temperature is reduced to 25° C. The mixer is emptied and the obtained compound is stored in an air- and moisture-tight sealed package.

[0068] The polymer loaded with the active ingredient obtained above is injected at the nozzle outlet as a medallion weighing 15 g, intended to be worn as a dog collar to calm the dog in case of a potentially stressful situation.

[0069] Example 4: Pain Relief Bracelet [Table 4] Example 4 is the preparation of an active monopolymer matrix that can be injected in the form of a bracelet. The manufacturing method is the same as that of Examples 1 to 3 above.

[0070] Example 5: Sedative Collar [Table 5] The polymer is placed in a reactor preheated to the required temperature depending on the type of polymer (in this case, for TPU, about 90 °C to 95 °C), sufficient to impart to the polymer a structure that allows the network to open up to incorporate the active ingredient within it, with gentle stirring.

[0071] The liquid active phase is prepared according to the following protocol. - The plasticizing and vectorizing components are weighed and mixed, stirred to homogenize, to obtain a limit mixture. -CBD as the first active ingredient, with stirring at ambient temperature Isolate Add and continue stirring until a marginally translucent mixture is obtained. -Add the co-active ingredient, in this case peppermint essential oil, and homogenize to obtain a homogenous translucent mixture.

[0072] Once the polymer has reached the target temperature, the previously prepared active ingredient mixture is slowly added.

[0073] Stirring is continued until the active phase is incorporated into the polymer.

[0074] Cool to ambient temperature and continue stirring.

[0075] The colorant is added and the mixture is homogenized.

[0076] The reactor is emptied and an injection molding step is carried out to obtain the desired shape of the device.

[0077] The embodiment according to the invention is tested for physical and chemical stability as defined in the application above. The results of the device are as follows: [Table 6] The results show that the device is stable and allows for the effective incorporation of the required active ingredients, including CBD.

[0078] Example 6: Calming Bracelet [Table 7] The polymer is placed in a reactor preheated to the temperature required depending on the type of polymer (in this case, for EVA, about 70°C), sufficient to give the polymer a structure that allows the network to open up to incorporate the active ingredient therein, and gently stirred.

[0079] The liquid active phase is prepared according to the following protocol. - The plasticizing and vectorizing components are weighed and mixed, stirred to homogenize, to obtain a limit mixture. -CBD as the first active ingredient, with stirring at ambient temperature Isolate Add and continue stirring until a marginally translucent mixture is obtained. -Add the co-active ingredient, in this case peppermint essential oil, and homogenize to obtain a homogenous translucent mixture.

[0080] Once the polymer has reached the target temperature, the previously prepared active ingredient mixture is slowly added.

[0081] Stirring is continued until the active phase is incorporated into the polymer.

[0082] Cool to ambient temperature with stirring.

[0083] The colorant is added and the mixture is homogenized.

[0084] The reactor is emptied and an injection molding step is carried out to obtain the desired shape of the device.

[0085] Example 7: Pain Relief Bracelet [Table 8] The manufacturing method is the same as in Example 6 above.

[0086] Example 8: Pain Relief Bracelet [Table 9] The manufacturing method is the same as in Example 5 above.

[0087] Example 9: Sedative Collar [Table 10] The manufacturing method is the same as in Example 6 above.

[0088] Example 10: Sedative Collar [Table 11] The manufacturing method is the same as in Example 5 above.

[0089] Example 11: Sedative Collar [Table 12] The manufacturing method is the same as in Example 5 above.

[0090] The stability results for this device are as follows: [Table 13] The results show that the device is stable and allows for the effective incorporation of the required active ingredients, including CBD.

[0091] Example 12: In vitro study of the kinetics of CBD release from a device according to the invention. In order to be able to verify that the active ingredients stably incorporated in the device according to the invention can be effectively delivered over a period of at least four weeks to treat the subject to which the device is applied, an in vitro test has been developed by the applicant.

[0092] The choice of kinetics in oil simulates contact of the device with sebum from the skin or fur, allowing the active ingredient to be released to treat the subject.

[0093] Examples of dog collars made according to the above examples have been previously tested, with some testing still ongoing as of the filing date of this application.

[0094] The method of operation for this analysis of various examples of collars is as follows. 1) Remove the sheet that keeps the collar rolled up before use. 2) Weigh and record the initial weight of the collar. 3) Place the collar into a 250ml flask. 4) Add olive oil until the collar is completely submerged and measure. 5) Continue stirring throughout the kinetic test. 6) At each determined time for analysis (e.g. D1, D3, D7, D10, D14, D21, D28), take oil samples. 7) Extract the CBD from this oil sample using a suitable solvent. 8) The extracts are analyzed using HPLC to quantify the amount of CBD released into the medium. Amounts are given as mg or percentage of the amount initially incorporated. Analysis is performed using reversed-phase HPLC with external calibration from a certified CBD standard. 9) Plot the CBD release curve in oil over time.

[0095] Results are obtained by averaging the values ​​of three similar devices tested.

[0096] A) Results of CBD release from collars according to Example 10: [Table 14] The device according to the present invention according to Example 10 in the form of a collar can effectively and stably incorporate the necessary active ingredients, including CBD. The above results and the corresponding curves in Figure 1 show that CBD is gradually released over time for long-term treatment of subjects such as dogs. It is noted that at 28 days, no plateau has been reached and release continues.

[0097] B) Results of CBD release from collars according to Example 5 [Table 15] The device according to the present invention according to Example 5 in the form of a collar was able to effectively incorporate the necessary active ingredients, including CBD. The above results and the corresponding curves in Figure 2 show that CBD is gradually released over time. In the ongoing test, the release can be evaluated over a period of 10 days. It is understood that the test is ongoing and the slope of the curve can be easily estimated for continued release over time.

[0098] C) Results of CBD release from collars according to Example 11 [Table 16] The device according to the present invention according to Example 11 in the form of a collar was able to effectively incorporate the necessary active ingredients, including CBD. The above results and the corresponding curves in Figure 2 show that CBD is gradually released over time. In the ongoing test, the release can be evaluated over a period of 10 days. It is understood that the test is ongoing and the slope of the curve can be easily estimated for continued release over time.

[0099] The curves of figure 2 also make it possible to compare the release kinetics of the devices according to examples 5 and 11. These two devices according to the invention differ only in the amount of plasticizer in their composition.

[0100] These results show that the level of plasticizing compound in the composition makes it possible to modulate the active ingredient release kinetics of the device according to the invention.

Claims

1. A device for topical application formed from a monolayer polymer matrix characterized in that the polymer is selected from the group consisting of ethylene vinyl acetate copolymers and polyurethanes, said matrix also comprising at least cannabidiol (CBD) free of delta-9-tetrahydrocannabinol (THC) and 0.5% to 20% of an essential oil or a monoterpene derivative of an essential oil by total weight of said matrix.

2. The device of claim 1 , wherein the polymer is non-adhesive.

3. 3. The device according to claim 1 or 2, characterized in that the polymer is an ethylene vinyl acetate copolymer.

4. 3. The device according to claim 1, wherein the polymer is a polyurethane.

5. 5. The device according to any one of claims 1 to 4, characterized in that the essential oil is chosen from the following essential oils: lavender, lavandin, Italian helichrysum, cedar, lemon, citronella, carrot, ginger, niaouli, sweet orange, clove, Eucalyptus citriodora, Eucalyptus radiata, peppermint, geranium, valerian, nepeta cataria, chamomile, ylang ylang, clary sage, mandarin, sandalwood, bergamot, marjoram, frankincense, pelargonium, thyme, juniper, or mixtures thereof.

6. A device according to any one of claims 1 to 5, characterized in that the monoterpene derivatives of essential oils are selected from linalool, menthol, or mixtures thereof.

7. 7. A device according to any one of claims 1 to 6, characterized in that it comprises a penetration enhancer chosen from oils of organic, synthetic, mineral, vegetable origin, esters such as succinates, glutarates and adipates mixtures, omega-3 polyunsaturated fatty acid oils, fatty acid esters, glycol ethers, squalene and squalene derivatives.

8. 8. The device according to claim 1, characterized in that it comprises a plasticizing compound selected from ethylhexyl diphenylphosphate, dioctyl adipate, diisooctyl adipate, dibutyl adipate, dimethyl adipate, dimethyl glutarate, dimethyl succinate, or mixtures thereof.

9. A device according to any one of claims 1 to 8, characterized in that it is presented in the form of a collar, a bracelet, a medallion or a textile coating.

10. A device according to any one of claims 5 to 9, characterized in that the cannabidiol is present in the form of CBD isolate or CBD oil.

11. 1. A device for topical application formed from a single layer of a thermoplastic polymer matrix loaded with an active ingredient for use in relieving pain or stress in an animal, said device being placed in contact with the skin and / or fur, said polymer matrix comprising at least one non-adhesive thermoplastic polymer selected from polyurethane or ethylene vinyl acetate copolymer, and said active ingredient comprising at least one cannabidiol isolate free of delta-9-tetrahydrocannabinol, or a THC-free cannabidiol oil, and 0.5% to 20% of at least one essential oil or essential oil compound by total matrix weight.

12. 12. A device as claimed in claim 11 for use in the relief of stress or muscle, joint or rheumatic pain, such as tendonitis, arthritis and arthropathy.

13. 1. A method for manufacturing a device consisting of a single layer of a thermoplastic polymer matrix comprising one non-tacky thermoplastic polymer selected from polyurethane or ethylene vinyl acetate copolymer, wherein the active ingredients comprise at least one cannabidiol isolate free of delta-9-tetrahydrocannabinol or a cannabidiol oil free of delta-9-tetrahydrocannabinol and at least one essential oil or compound of essential oils in an amount between 0.5% and 20% of the total matrix weight, said method comprising the steps of heating the polymer to a selected temperature, preparing an active phase, mixing the active phase with the polymer and then shaping the device, characterized in that said method does not include the step of adding specific excipients or particle structures to help incorporate the active ingredient into the polymer matrix.

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