THC-based TTS formulations

Abstract

Disclosed is a transdermal therapeutic system comprising an active agent-impermeable backing layer, at least one adhesive layer comprising at least 70% by weight of at least one polysiloxane polymer, at least one tetrahydrocannabinol (THC), and at least one solubilizing agent, and optionally a protective layer that is removed prior to use, a method for its preparation, and its use as a pharmaceutical.

Description

[Technical Field]

[0001] The present invention relates to a transdermal therapeutic system based on a polysiloxane polymer containing at least one active agent selected from the group of cannabinoids, a method for preparing the same, and the use of the same as a pharmaceutical product. [Background technology]

[0002] Transdermal therapy systems (TTSs) are drug delivery systems applied directly to the skin. The active drug is released into the skin and dispersed throughout the body via the bloodstream. Transdermal therapy systems are widely known for administering a wide variety of active drugs. However, the application of active drugs through the skin presents problems such as insufficient absorption of the active drug, resulting in only a limited number of commercially successful drugs being administered via transdermal routes.

[0003] With the exception of a few special forms, TTSs can be basically classified into two distinct types: those known as matrix systems and those known as reservoir systems. In the simplest example, a matrix system, the active agent may be dissolved in a self-adhesive layer, or suspended or dispersed in the adhesive in crystalline form. In a reservoir system, there is typically a compartment filled with the active agent in liquid form, from which the agent is released into the skin via a permeable membrane, which may be improved with an adhesive layer for adhesion to the skin.

[0004] The liquid microreservoir TTS combines the two basic forms of a reservoir system, where the active agent exists in liquid form, and the matrix system, where the active agent is dispersed throughout the matrix in the form of tiny droplets.

[0005] This has the effect that, in a liquid microreservoir TTS, the majority of the active agent is present in the liquid microreservoir, which is embedded in one or more matrix polymer layers, rather than in the polymer components of the system. In its simplest form, the liquid microreservoir is embedded in a self-adhesive polymer layer.

[0006] In terms of appearance, the liquid microreservoir TTS designed in this way is indistinguishable from a conventional matrix system. However, microscopic examination reveals the heterogeneous structure of the microreservoir and the resulting adhesive layer.

[0007] Microreservoir TTS can also be constructed using polymer matrix systems, but in such cases, they are either not self-adhesive or have insufficient self-adhesion. In such systems, the lack of adhesion can be compensated for, for example, by applying an additional self-adhesive layer to the matrix layer, which plays a role in fixing the system to the skin. Similarly, adhesives may be used to improve the adhesion of the backing layer to the matrix system containing active agents.

[0008] Negative attitudes toward cannabinoids as drugs have changed in recent years, and with the official approval of cannabinoid-based active drugs as pharmaceuticals, there is a growing demand for drug delivery systems for administering cannabinoids as active drugs.

[0009] Because cannabinoids are rapidly metabolized in the body, when administered via conventional routes, the concentration level of the active drug in the bloodstream decreases rapidly. This makes cannabinoids a promising candidate for transdermal application, as it allows for the administration of precise doses of the active drug over long periods, thereby maintaining a relatively constant concentration level of the chemical in the bloodstream. On the other hand, an obstacle to using cannabinoids is that they are highly lipid-soluble and have a strong tendency to bind to tissues and proteins, making transdermal application difficult.

[0010] Patent Document 1 describes a system for transdermal delivery of cannabidiol (CBD), which includes a membrane or has an integrated design. In the latter, cannabidiol is mixed with polyisobutylene, an acrylic adhesive, or a silicone adhesive to prepare an active ingredient-containing layer. [Prior art documents] [Patent Documents]

[0011] [Patent Document 1] U.S. Patent No. 10,272,125 B2 [Overview of the Initiative] [Problems that the invention aims to solve]

[0012] An objective of the present invention was to provide a stable TTS formulation for the application of tetrahydrocannabinol as a cannabinoid active agent. Despite the somewhat unfavorable properties of tetrahydrocannabinol (i.e., high hydrophobicity), the TTS formulation should provide stable and sustained drug delivery through the patient's skin over a long period, preferably up to 7 days. [Means for solving the problem]

[0013] Remarkably, the TTS formulation described in claim 1, in particular a transdermal therapeutic system comprising i) an active drug-impermeable backing layer, ii) at least one adhesive layer comprising at least 70% by weight of at least one polysiloxane polymer, at least one tetrahydrocannabinol (THC), and at least one solubilizer, and optionally iii) a removable protective layer, has now been found to solve the above objectives.

[0014] The transdermal treatment system of the present invention therefore includes i) a backing layer impermeable to active drugs, ii) at least one adhesive layer comprising at least 70% by weight of at least one polysiloxane polymer, at least one tetrahydrocannabinol, and at least one solubilizer, and optionally iii) a protective layer that can be removed before use. [Modes for carrying out the invention]

[0015] In the context of this invention, the terms "transdermal treatment system" and "TTS" are used interchangeably.

[0016] In the transdermal treatment system described above, the polysiloxane polymer forms a matrix in which tetrahydrocannabinol is incorporated. In a preferred embodiment, in order to form a microreservoir TTS as described above when forming the transdermal treatment system, the tetrahydrocannabinol is sufficiently insoluble in the polysiloxane polymer so that the polysiloxane polymer and the tetrahydrocannabinol are separated, at least to some extent. In such a microreservoir system, the tetrahydrocannabinol is mainly present (i.e., at least 60 wt.-%, particularly at least 75 wt.-%, preferably at least 90 wt.-%, most preferably at least 95 wt.-%) in the microreservoir formed within the polysiloxane polymer.

[0017] As described above, the transdermal treatment system of the present invention includes, as a first component, a backing layer that is impermeable to active drugs. Suitable materials for the backing layer include, for example, polyethylene, polypropylene, polyester such as polyethylene terephthalate, copolymers of ethylene and vinyl acetate (EVA), and polyvinyl chloride films. Such films may consist of laminations of different polymers and may further include a color layer and / or coloring pigments. This type of film is well known to those skilled in the art, and the optimal film for a particular purpose can be found without difficulty.

[0018] The transdermal treatment system according to the present invention comprises at least one adhesive layer containing at least 70% by weight, preferably at least 75% by weight, and more preferably at least 80% by weight of at least one polysiloxane polymer. The maximum amount of the polysiloxane polymer is not particularly limited, other than that it must allow for the presence of an effective amount of tetrahydrocannabinol and a solubilizer in the adhesive layer. As a suitable maximum amount of the polysiloxane polymer, amounts of up to 95% by weight, preferably up to 90% by weight, and most preferably up to 86% by weight may be mentioned.

[0019] The polysiloxane polymer of the TTS according to the present invention is preferably an amine-resistant polysiloxane polymer. This means that the polysiloxane does not have free silanol groups (Si-OH) that can participate in further condensation reactions in the presence of a basic active agent.

[0020] Suitable polysiloxane polymers are polycondensation products of silanol-terminated polydimethylsiloxanes using soluble silicate resins, such as those commercially available from Dow Corning under the trade name BIO-PSA®. These polysiloxanes are typically supplied as solutions in various solvents. For the purpose of preparing the TTS of the present invention, solutions of low-boiling alkanes, particularly n-heptane or ethyl acetate, have been found to be particularly suitable.

[0021] Particularly suitable standard silicone adhesives or amine-compatible silicone adhesives such as BIO-PSA (registered trademark) polymers include BIO-PSA4101, BIO-PSA4201, BIO-PSA4301, BIO-PSA4102, BIO-PSA4202, BIO-PSA4302, BIO-PSA4401, BIO-PSA4402, BIO-PSA4501, and BIO-PSA4502 (all from Dow Corning).

[0022] Furthermore, the polysiloxane polymer of the TTS according to the present invention is preferably self-adhesive. This has the advantage that no additional adhesive needs to be applied to adhere the TTS to the patient's skin, and no additional adhesive needs to be applied to adhere the adhesive layer to the backing layer impermeable to the active drug. Polysiloxanes are usually extremely poorly miscible with tackifier additives. Nevertheless, in individual cases, it can be advantageous to improve the tack by adding a small amount of an adhesive such as a polyterpene, a resin derivative, or a silicone oil.

[0023] The adhesive layer can comprise a single polysiloxane polymer or can comprise a mixture of two or more polysiloxane polymers. Since a mixture allows for more precise fine-tuning of the final properties, it is preferred that the adhesive layer comprises a mixture of polysiloxane polymers, particularly a mixture of two polysiloxane polymers. In this case, the ratio of the two polysiloxane polymers is preferably in the range of 1:9 to 9:1, more preferably in the range of 2:8 to 8:2.

[0024] In a particularly preferred embodiment of the present invention, the adhesive layer comprises a mixture of a high-tack silicone adhesive and a medium-tack or low-tack silicone adhesive. The tackiness of the silicone polymer depends on the resin-to-polymer ratio, i.e., the ratio of silanol-terminated polydimethylsiloxane to the silicate resin, which is preferably in the range of 70:30 to 50:50, and more preferably in the range of 65:35 to 55:45. The tackiness increases with increasing the amount of polymer relative to the resin. A high-tack silicone polymer is defined herein as having a resin-to-polymer ratio of up to 57:43, preferably about 55:45; a medium-tack silicone polymer has a resin-to-polymer ratio from above 57:43 to 63:37, preferably about 60:40; and a low-tack silicone polymer has a resin-to-polymer ratio above 63:37, preferably about 65:35. The highly adhesive amine-compatible silicone polymer has a complex viscosity of 0.01 radians / second and at 30°C, preferably about 5 × 10⁻¹⁶. 6 The poise, medium-viscosity amine-compatible silicone polymer has a complex viscosity of 0.01 radians / second and at 30°C, preferably about 5 × 10⁻¹⁶. 8 The poise, low-tack, amine-compatible silicone polymer has a complex viscosity of 0.01 radians / second and at 30°C, preferably about 5 × 10⁻¹⁶. 9 It's Poise.

[0025] Most preferably, the adhesive layer contains a mixture of a medium-tack silicone polymer and a high-tack silicone polymer, particularly a medium-tack amine-compatible silicone polymer and a high-tack amine-compatible silicone polymer, in a ratio of 1:9 to 9:1, preferably 2:8 to 8:2, and most preferably 3:7 to 7:3.

[0026] Polysiloxanes have low solubility for active agents. As a result, in the absence of additives, the active agent in the polysiloxane exists mainly in a dispersed state and is not present in the solution within the polymer.

[0027] The transdermal therapy system according to the present invention further comprises at least one tetrahydrocannabinol as an active agent.

[0028] In the transdermal therapy system of the present invention, tetrahydrocannabinol may be naturally occurring, but may also be partially or completely synthesized. For example, as a completely synthesized tetrahydrocannabinol, R-(6a,10a)-Δ9-tetrahydrocannabinol is suitable for administration in the transdermal therapy system of the present invention.

[0029] Cannabis extracts and cannabis oils, particularly extracts and oils of Cannabis sativa or Cannabis indica, can be similarly used as active agents in the transdermal therapeutic system of the present invention. Cannabis extracts or cannabis oils contain, among other things, tetrahydrocannabinol (mainly Δ9-tetrahydrocannabinol, and relatively less Δ8-tetrahydrocannabinol) as pharmacologically active agents.

[0030] The TTS according to the present invention comprises at least one tetrahydrocannabinol (THC) selected from the group including Δ8-tetrahydrocannabinol, Δ9-tetrahydrocannabinol, and R-(6a,10a)-Δ9-tetrahydrocannabinol, but does not include any prodrugs, derivatives, and analogs of THC.

[0031] The amount of at least one tetrahydrocannabinol in the TTS according to the present invention is preferably 0.1 to 20% by weight, more preferably 1 to 15% by weight, and most preferably 3 to 10% by weight, based on the total weight of the at least one adhesive layer.

[0032] As a third component of the adhesive layer, the transdermal treatment system of the present invention includes at least one solubilizing agent. In the context of the present invention, the solubilizing agent (i.e., a solubilizing agent) is a substance that contributes to the dissolution of the tetrahydrocannabinol in the polymer and facilitates its dissolution.

[0033] Suitable solubilizers for use in the present invention include saturated or unsaturated fatty acids or fatty acid esters such as pentanoic acid, capric acid, caprylic acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, linoleic acid, lignoceric acid, isovaleric acid, neoheptonic acid, neonanonic acid, isostearic acid, pentanoic acid, hexanoic acid, ricinoleic acid, octanoic acid, nonanoic acid, decanoic acid, lauric acid, oleic acid, arachidonic acid, galloleic acid, erucic acid, methyl valerate, diethyl sebacitetate, methyl laurate, ethyl oleate, isopropyl decanoate, isobutyric acid, isobutyric acid, isopropyl myristate, isopropyl palmitate, and / or isopropyl oleate. Among these, amphiphilic molecules, i.e., molecules having dual amphiphilicity and containing both a hydrophilic and a lipophilic portion, are preferred. In particular, amphiphilic molecules are the acids mentioned above. Isopropyl myristate and lauric acid are the most preferred.

[0034] Other suitable solubilizers include polyethylene glycol monolaurate (e.g., commercially available under the trade name Lauroglycol 90), polyethylene glycol dodecyl ether / polyoxyethylene(4) lauryl ether (e.g., commercially available under the trade name Brij L4), polyoxyethylene(2) cetyl ether (e.g., commercially available under the trade name Brij C2), PEG-6 monoesters and diesters of oleic acid (commercially available as mixtures with mono-, di-, and triglycerides, e.g., under the trade name Labrafil® M1944 CS), and glyceryl monooleate (e.g., commercially available under the trade name Citrol® GMO HP).

[0035] In preferred embodiments, fatty acids (i.e., C2-C20 saturated or unsaturated aliphatic carboxylic acids), polyethylene glycol, isopropyl myristate, and isopropyl palmitate are excluded as solubilizers in the transdermal therapeutic system of the present invention.

[0036] The inventors of the present invention have also found that certain polymers exhibit suitable properties as solubilizers. Polymers that have proven advantageous as solubilizers include, for example, polyvinylpyrrolidones such as polyvinylpyrrolidone 30 (40,000 Mw) and polyvinylcaprolactam- / polyvinyl acetate- / polyethylene glycol copolymers (e.g., commercially available under the trade name "Soluplus").

[0037] In a preferred embodiment, the TTS according to the present invention is characterized in that at least one solubilizer is a polymer or an amphiphilic molecule having an HLB of less than 6. The HLB value (HLB = hydrophilic-lipophilic balance = hydrophilic-lipophilic ratio) is primarily a measure of the water-soluble or oil-soluble nature of a nonionic surfactant and the stability of the emulsion. The HLB value is given by the following equation:

number

[0038] An HLB value of 1 indicates a lipophilic compound, while a chemical compound with an HLB value of 20 contains highly hydrophilic substances. Values ​​between 3 and 8 are classified as water-in-oil (w / o) solubilizers / emulsifiers, and values ​​between 8 and 18 are classified as oil-in-water (o / w) solubilizers / emulsifiers.

[0039] Particularly preferred solubilizers in the TTS of the present invention are selected from the group comprising polyvinylpyrrolidone 30, PEG-6 monoesters and diesters of lauric acid, caprylic acid, and oleic acid, polyethylene glycol dodecyl ether / polyoxyethylene(4) lauryl ether, and polyvinylcaprolactam- / polyvinyl acetate- / polyethylene glycol-copolymer.

[0040] The amount of at least one solubilizer in the TTS according to the present invention is preferably in the range of 0.1 to 12% by weight, more preferably in the range of 0.5 to 10% by weight, based on the total weight of the at least one adhesive layer.

[0041] The TTS according to the present invention more preferably comprises at least one translocation enhancer. A translocation enhancer, as used in the present invention, is a compound that facilitates the transfer of the active agent across the skin. Any compound known to a skilled practitioner to possess the required properties can be used as a translocation enhancer. In the context of the present invention, preferred translocation enhancers are, for example, propylene glycol, dipropylene glycol, or 2-(2-ethoxyethoxy)ethanol (commercially available as "Transcutol").

[0042] For example, some of the above-mentioned solubilizers, such as PEG-6 monoesters and diesters of oleic acid (commercially available as mixtures with mono-, di-, and triglycerides, for example under the trade name Labrafil® M1944 CS), or glycerin monooleate (commercially available under the trade name Cithrol® GMO HP), or polyethylene glycol monolaurate (commercially available under the trade name Lauroglycol 90), also possess suitable properties as permeation enhancers. Therefore, in one embodiment, the compounds of the solubilizer and the permeation enhancer may be the same.

[0043] The amount of the at least one permeation enhancer is preferably in the range of 0.1 to 20% by weight, more preferably 1 to 15% by weight, and most preferably 2 to 10% by weight, based on the total weight of the at least one adhesive layer.

[0044] In a preferred embodiment, the TTS of the present invention does not contain DMSO, which is frequently used as a permeation enhancer in transdermal treatment systems. DMSO in the body is metabolized to some extent to dimethyl sulfide, which has an unpleasant odor even at very low concentrations. Furthermore, according to the present invention, it is preferable that the adhesive layer does not contain a permeation enhancer selected from the group consisting of terpenes such as cineole.

[0045] It has been further found that, in the present invention, it is not essential to incorporate a compound with an HLB value of 6 or higher (calculated according to Davies' method) into the TTS. Therefore, in one embodiment, the adhesive layer of the present invention substantially lacks a compound with an HLB value of 6 or higher (i.e., a content of less than 1 wt.-%, preferably less than 0.5 wt.-%, and more preferably less than 0.1 wt.-%). Most preferably, the adhesive layer has an HLB value of 6 and does not contain any intentionally added compounds.

[0046] The TTS according to the present invention more preferably comprises at least one antioxidant. The antioxidant is a chemical compound that prevents or reduces the undesirable oxidation of other substances, particularly the active substance, which is mainly caused by oxygen, thereby counteracting the degradation of the TTS. In the embodiment of the present invention, preferred antioxidants are, for example, tocopherol (vitamin E), ascorbyl palmitate, ascorbic acid, or butylhydroxytoluol.

[0047] The at least one antioxidant is preferably present in an amount of 0.005 to 2% by weight, preferably 0.01 to 0.7% by weight, based on the total weight of the adhesive layer.

[0048] The transdermal treatment system according to the present invention further includes, optionally, a protective layer that is removed before use. A removable protective layer, in particular a suitable material for a silicone adhesive, is a polyethylene terephthalate film. The use of such a protective layer that is removed before use has the advantage of simplifying the packaging and storage of the TTS according to the present invention.

[0049] In a preferred embodiment, the TTS according to the present invention is a microreservoir TTS, the maximum size of which the microreservoir does not exceed 80% of the thickness of its adhesive layer. In an additional preferred embodiment, the TTS according to the present invention is a microreservoir, the average diameter of which the microreservoir is 5 to 50 μm, preferably 5 to 35 μm (measured by microscopic observation).

[0050] In another preferred embodiment, the TTS according to the present invention is an integrated TTS in which the active ingredient (THC) is incorporated into a layer that is in direct contact with the skin during use (i.e., this layer contains at least 70 wt.-%, preferably at least 90 wt.-%, of the THC in the TTS).

[0051] The TTS according to the present invention may further include conventional auxiliary additives such as solvents, crystallization inhibitors, viscosity modifiers, pH adjusters, fillers, colorants, gelling agents, or any combination thereof.

[0052] The TTS according to the present invention has an adhesive layer with a weight of 20-300 g / m². 2 This is a characteristic feature. Preferably, the weight of the adhesive layer is 50 to 250 g / m². 2 The range is most preferably 100-200 g / m 2 It is within the range.

[0053] The typical size of the adhesive layer in TTS according to the present invention is 1 to 150 cm². 2 Preferably, 5-80cm 2 That is the case.

[0054] Furthermore, the TTS according to the present invention preferably contains an active agent in a total amount of 1 to 120 mg, preferably 5 to 100 mg, more preferably 8 to 90 mg, and even more preferably 10 to 60 mg.

[0055] In a further embodiment, the present invention relates to a method for preparing a transdermal treatment system as described above: a) A step of preparing a mixture comprising at least one polysiloxane polymer, at least one active agent selected from the group of tetrahydrocannabinols, and at least one solubilizer; b) The step of placing the mixture from a) on top of the protective layer that is removed before use, c) A step of placing an active drug-impermeable backing layer on top of the layer of mixture prepared in step b). Regarding methods including

[0056] The mixture prepared in step a) preferably contains a suitable solvent for dissolving the at least one active agent and at least one solubilizer to enable uniform distribution of the active agent in the polysiloxane polymer. If the mixture in step a) contains a solvent, it is preferable that at least a portion of the solvent be removed or distilled off before the active agent-impermeable backing layer is placed in step c).

[0057] In a further embodiment, the present invention relates to TTS obtainable by the method described above.

[0058] In further embodiments, the present invention relates to the use of TTS as described above or as available by the above methods for use as a pharmaceutical. The pharmaceutical is applicable for the treatment of any condition that is alleviated or cured by the application of tetrahydrocannabinol, in which case the treatment of nausea, vomiting, neuropathic pain, fibromyalgia, anorexia, cachexia, multiple sclerosis, traumatic cross-sectional disorders, dystonia, bronchial asthma, epileptic seizures, alcohol withdrawal symptoms, benzodiazepine and opioid dependence, Parkinson's disease, dementia, Alzheimer's disease, arthritis, glaucoma, migraine, dysmenorrhea, or Tourette syndrome is preferred.

[0059] Therefore, in a further embodiment, the present invention relates to a TTS as described above, which is available by the above method for use in the treatment of nausea, vomiting, neuropathic pain, fibromyalgia, anorexia, cachexia, multiple sclerosis, traumatic transverse lesions, dystonia, bronchial asthma, epileptic seizures, alcohol withdrawal symptoms, benzodiazepine and opioid dependence, Parkinson's disease, dementia, Alzheimer's disease, arthritis, glaucoma, migraine, dysmenorrhea, or Tourette syndrome. Preferably, the TTS is for use in the treatment of neuropathic pain, fibromyalgia, and / or Tourette syndrome.

[0060] The present invention is described in the following embodiments, which are provided for illustrative purposes only and should not be considered as limiting in any way. [Examples]

[0061] Tetrahydrocannabinol-based transdermal therapy system The transdermal treatment systems Thc0103, Thc104, Thc105, Thc0109, Thc0112, and Thc0114 according to the present invention were prepared using only the adhesive layer as a reference system. The components and amounts of the adhesive layer are shown in Table 1 below.

[0062] [Table 1]

[0063] The in vitro human skin permeability of the system listed in Example 1 was measured using a Franz cell. For the measurement, the adhesive layer was adhered to the skin (dermatomalized skin 400 μm) in the donor compartment. The acceptor compartment was filled with a buffer solution or other solution. The permeability of the substance through the skin over a selected period was tracked by regular sampling from the acceptor compartment. The effect of the penetration enhancer on the permeability of the substance was also tested using this system. The use of a Franz cell as a diffusion model is mainly suitable for predicting the transport (= permeability) of drugs through human skin, and this transport corresponds to systemic availability.

[0064] In this case, 400 μm of dermatomalized skin having a diffusion area of about 1,191 cm 2 was incubated with the topical treatment system. 0.1% Na - azide and 1% Tween 20 were added to an aqueous isotonic phosphate buffer pH = 5.5. 0.1% 2 - hydroxypropyl - β - cyclodextrin with an acceptor medium filling volume of 10 mL was added to 1% ascorbic acid. The permeability measurement was carried out at a temperature of 32 °C and measured at 8, 24, 32, 48, 56, 72, 80, 144, 152, and 168 hours later (n = 3).

[0065] From this data, in addition to the cumulative active drug permeated after 168 hours (see Figure 1), the human skin permeation flow rate after 168 hours (see Figure 2) was determined. Furthermore, in addition to the residual amount of the active drug in the skin, the utilization rate of the active drug was calculated. Finally, the TTS was visually inspected for its color and tactilely tested for its adhesiveness and cohesion. The results are summarized in Table 2.

[0066]

Table 2

Brief Description of the Drawings

[0067] [Figure 1]This figure shows the cumulative amount of active drug that has permeated after 168 hours. [Figure 2] This figure shows the human skin permeability and fluid flow rate after 168 hours.

Claims

1. It is a transdermal treatment system, i) A backing layer that is impermeable to active drugs, ii) comprising at least one adhesive layer containing at least 70% by weight of at least two polysiloxane polymers, at least one tetrahydrocannabinol (THC), and at least one solubilizer, The aforementioned at least one solubilizer is selected from the group consisting of polyvinylpyrrolidone, pentanoic acid, capric acid, caprylic acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, linoleic acid, lignoceric acid, isovaleric acid, isostearic acid, pentanoic acid, hexanoic acid, ricinoleic acid, octanoic acid, nonanoic acid, decanoic acid, lauric acid, arachidonic acid, erucic acid, polyethylene glycol monolaurate, PEG-6 monoesters and diesters of oleic acid, polyethylene glycol dodecyl ether / polyoxyethylene (4) lauryl ether, and polyvinylcaprolactam- / polyvinyl acetate- / polyethylene glycol-copolymer. The aforementioned polysiloxane polymer is amine-resistant, The adhesive layer comprises a mixture of a highly tacky silicone polymer and a medium-tacky or low-tacky silicone polymer. Furthermore, the transdermal treatment system contains propylene glycol as a penetration enhancer. Transdermal treatment system.

2. The transdermal treatment system according to claim 1, wherein the polysiloxane is self-adhesive.

3. The transdermal treatment system according to claim 1 or 2, wherein the at least one tetrahydrocannabinol is selected from Δ8-tetrahydrocannabinol, Δ9-tetrahydrocannabinol, and R-(6a,10a)-Δ9-tetrahydrocannabinol.

4. The transdermal treatment system according to any one of claims 1 to 3, wherein the at least one tetrahydrocannabinol is present in an amount of 0.1 to 20% by weight based on the total weight of the at least one adhesive layer.

5. The transdermal treatment system according to any one of claims 1 to 4, wherein the at least one solubilizer is selected from the group consisting of polyvinylpyrrolidone, lauric acid, caprylic acid, polyethylene glycol monolaurate, PEG-6 monoesters and diesters of oleic acid, polyethylene glycol dodecyl ether / polyoxyethylene (4) lauryl ether, and polyvinylcaprolactam- / polyvinyl acetate- / polyethylene glycol-copolymer.

6. The percutaneous treatment system according to any one of claims 1 to 5, wherein the at least one solubilizing agent is present in an amount of 0.1 to 12% by weight based on the total weight of the at least one adhesive layer.

7. The transdermal treatment system according to any one of claims 1 to 6, wherein the transdermal treatment system does not contain a compound having an HLB of 6 or higher.

8. A transdermal treatment system according to any one of claims 1 to 7, further comprising at least one antioxidant.

9. A method for preparing a transdermal treatment system according to any one of claims 1 to 8: a) A step of preparing a mixture comprising at least two polysiloxane polymers, at least one tetrahydrocannabinol, at least one solubilizer, and propylene glycol as a permeation enhancer; b) The step of placing the mixture from a) on top of the protective layer that is to be removed before use, c) A method comprising the step of placing an active drug-impermeable backing layer on top of the layer of mixture prepared in step b).

10. A transdermal treatment system according to any one of claims 1 to 8, for use as a pharmaceutical product.

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