Oral thin film formulation containing adrenaline

Abstract

An oral thin film agent comprising one or more layers, wherein at least one layer contains adrenaline or a pharmaceutically acceptable salt thereof and at least one polymer, and the adrenaline is not substantially dissolved in the at least one polymer. A method for producing the oral thin film agent, comprising: a) producing a solution containing a solvent in which the at least one polymer and adrenaline or a pharmaceutically acceptable salt thereof are substantially insoluble; b) adding adrenaline; c) spreading and drying the suspension obtained in step (b) to obtain a single-layer oral thin film agent. Also provided is the use of the oral thin film agent for the treatment of allergic reactions for use as a medicament and for use as a medicament.

Description

【Technical Field】 【0001】 The present invention is directed to oral thin film agents, methods for their manufacture, and their use as medicaments. 【Background Art】 【0002】 An oral thin film agent (OTF) is a thin film agent that contains at least one pharmaceutically active substance and is dispensed directly into the oral cavity or applied to the oral mucosa, where it dissolves. In particular, these are polymer-based thin film agents containing an active ingredient, and when applied to the mucosa, particularly the oral mucosa, they release the active ingredient directly onto the oral mucosa. The very good blood circulation of the oral mucosa ensures the rapid transfer of the active ingredient into the blood circulation. This administration system has the advantage of avoiding the "first-pass effect" associated with tablet forms, which are conventional dosage forms of active ingredients, since most of the active ingredient is absorbed through the mucosa. 【0003】 Problems associated with adrenaline administration, particularly in dissolved form in oral thin film agents, are that the active ingredient first dissolves or partially dissolves during the process of manufacturing the oral thin film agent and partially recrystallizes when the solvent evaporates. However, recrystallization is undesirable because it can cause morphological changes in the active ingredient and also have a negative impact on the chemical stability of the active ingredient. In particular, a non-uniform appearance can occur on the surface, which appears as spots and / or accumulations of crystals / crystals visible under a microscope. In addition, recrystallization can also have a negative impact on the mechanical properties of the oral thin film agent. 【0004】 The decomposition of adrenaline to adrenochrome leads to strong coloring, but the decomposition mechanisms to D-adrenaline and adrenaline sulfonic acid are responsible for the largest amount of decomposition quantitatively. This is planar sp 2This occurs through the stabilization of the transition state by activated aromatics. The reaction of the transition state with water leads to the formation of D-adrenaline and L-adrenaline in a 1:1 ratio, which in the long term leads to racemization of the starting material. Current commercial products use large amounts of sodium metabisulfite, and sulfite (SO3 2- ) and adrenaline (S N This leads to a reaction with (1) reaction. Therefore, at the end of the shelf life, known commercially available products contain up to 15% adrenaline sulfonate. 【0005】 Patent Document 1 discloses a pharmaceutical composition for adrenaline administration in which adrenaline is partially dissolved in the composition. 【0006】 Further oral film formulations are disclosed in Patent Documents 2 and 3. Foamed film formulations are disclosed in Patent Document 4. [Prior art documents] [Patent Documents] 【0007】 [Patent Document 1] US2018 / 0125977A1 [Patent Document 2] WO2022 / 195521A1 [Patent Document 3] WO2021 / 001461A1 [Patent Document 4] WO2018 / 224591A1 [Overview of the Initiative] [Problems that the invention aims to solve] 【0008】 The fundamental problem of the present invention is to overcome the disadvantages of the prior art described above. In particular, the problem of the present invention is to provide an oral thin-film formulation for administering adrenaline or a pharmaceutically acceptable salt thereof, in which uncontrolled recrystallization of adrenaline or a pharmaceutically acceptable salt thereof is largely prevented. Furthermore, adrenaline or a pharmaceutically acceptable salt thereof should exist in a chemically stable state in the oral thin-film formulation so as to prevent the degradation or racemization of pharmaceutically active L-adrenaline without the need to use large amounts of antioxidants, particularly sodium metabisulfite. Moreover, the oral thin-film formulation should be easy and inexpensive to manufacture. [Means for solving the problem] 【0009】 This problem is solved by an oral thin film agent according to claim 1, comprising one or more layers, wherein at least one layer contains adrenaline or a pharmaceutically acceptable salt thereof and at least one polymer, and the adrenaline is substantially insoluble in at least one of the polymers. 【0010】 This dosage form makes it possible to eliminate the aforementioned disadvantages. In particular, because adrenaline remains crystalline throughout the entire manufacturing process, uncontrolled or partial recrystallization, which would lead to the aforementioned disadvantages, does not occur during the manufacturing or storage of the oral thin-film formulation. 【0011】 Due to the polymer matrix of the oral thin-film formulation, the active ingredient adrenaline is well protected from oxygen and exogenous moisture. Since adrenaline in crystalline form is also very chemically stable, this largely prevents racemization of L-adrenaline, eliminating the need to rely on large amounts of antioxidants, especially sodium metabisulfite. [Modes for carrying out the invention] 【0012】 "Substantially undissolved" means that more than 95% by weight, preferably more than 98%, of adrenaline is present without dissolving, i.e., it is crystalline. 【0013】 Preferably, adrenaline is at least partially soluble in at least one polymer at a temperature of 15°C to 25°C. The definitions of different solubility grades are shown below. 【0014】 [Table 1] 【0015】 Therefore, adrenaline is preferably present as a solid suspension in at least one polymer. That is, adrenaline is present as particles dispersed in an oral film matrix / polymer. As further disclosed herein, the oral thin film agent comprises one or more layers, at least one of which contains adrenaline or a pharmaceutically acceptable salt thereof and at least one polymer, wherein the adrenaline or a pharmaceutically acceptable salt thereof is present as fine particles, preferably having a particle size distribution d(99) < 10 μm. 【0016】 Adrenaline, or epinephrine, is a hormone produced in the adrenal medulla and belongs to the catecholamine group. Adrenaline is also found in the central nervous system, where it exists as a neurotransmitter in adrenaline neurons. Adrenaline mediates its effects by activating adrenaline receptors, which are G protein-bound receptors. 【0017】 Adrenaline is also known by the IUPAC systematic name 4-[1-hydroxy-2-(methylamino)ethyl]benzene-1,2-diol. Only the L-enantiomer is pharmaceutically active. 【0018】 Therefore, the oral thin film agent according to the present invention is preferably characterized in that adrenaline or a pharmaceutically acceptable salt thereof exists as an L-enantiomer, i.e., the film agent contains L-adrenaline or a pharmaceutically acceptable salt thereof. 【0019】 Adrenaline is particularly preferably in the form of adrenaline bitartrate, especially L - adrenaline bitartrate, which is also referred to as L - adrenaline hydrogen tartrate. Additionally, L - adrenaline hydrochloride can be an available salt. 【0020】 The oral thin film agent according to the present invention is more preferably characterized in that adrenaline or a pharmaceutically acceptable salt thereof is present as fine particles in the oral thin film agent. The fine particles can be characterized by having a particle size distribution with d(99)<10 μm. The particle size distribution is preferably determined by laser diffraction that determines a volume - based particle size distribution such as dv(99), and the fine particles can have a particle size distribution with dv(99)<10 μm. 【0021】 The property of d(99) or dv(99) means that 99% of the particles are smaller than 10 μm. In some cases, dv(99) can be even smaller, in the small micro range such as <9 μm, <8 μm, <5 μm, or even <3 μm, <2 μm, <1 μm. 【0022】 The particle size distribution of adrenaline or a pharmaceutically acceptable salt thereof can be controlled / determined by laser diffraction technology before suspending in at least one polymer. 【0023】 Alternatively, the size and shape of adrenaline particles can be determined by optical microscopy. This method can be used to control the particle size of adrenaline or a pharmaceutically acceptable salt thereof in the oral thin film agent as well. 【0024】 The particle size distribution can also be determined according to the 10th edition of the European Pharmacopoeia (Ph.Eur.). 【0025】 The particle size distribution is preferably such that the largest particles do not exceed a size of 12 μm and are not smaller than a size of 0.5 μm. 【0026】 The use of micronized active ingredients increases the dissolution rate in the finished film, which can be advantageous in terms of absorption, and also allows for processing into a homogeneous film. 【0027】 The oral thin film agent according to the present invention is more preferably characterized in that at least one polymer comprises at least one water-soluble polymer. 【0028】 Water-soluble polymers include chemically distinct, natural or synthetic polymers that share the common characteristic of solubility in water or aqueous media. A prerequisite is that these polymers have a sufficient number of hydrophilic groups for water solubility and are not crosslinked. Hydrophilic groups can be nonionic, anionic, cationic, and / or zwitterionic. 【0029】 Preferably, at least one polymer in the oral thin film preparation of the present invention is selected from the group consisting of starch and starch derivatives, dextran, carboxymethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxypropylethylcellulose, sodium carboxymethylcellulose, cellulose derivatives such as ethyl or propylcellulose, polyacrylic acid, polyacrylate, polyvinylpyrrolidone, polyvinyl alcohol, polyvinylpyrrolidone / polyvinyl acetate copolymer, polyethylene oxide polymer, polyacrylamide, polyethylene glycol, polyvinyl alcohol / polyethylene glycol copolymer, gelatin, collagen, alginate, pectin, pullulan, tragacanth, chitosan, alginic acid, arabinogalactan, galactomannan, agar, agarose, carrageenan, natural rubber, and mixtures thereof. 【0030】 Hydroxypropyl cellulose, polyvinylpyrrolidone, polyvinylpyrrolidone / polyvinyl acetate copolymer, polyvinyl alcohol, polyvinyl alcohol / polyethylene glycol copolymer and / or pectin (amylopectin) are particularly preferred. 【0031】 The most preferred polymers are hydroxypropylcellulose and polyvinylpyrrolidone / polyvinyl acetate copolymer. 【0032】 The oral thin film agent according to the present invention is preferably characterized by containing less than 1% by weight, preferably less than 0.5% by weight, and more preferably less than 0.1% by weight, of an antioxidant relative to the total weight of each layer of the oral thin film agent, or relative to the total weight of the oral thin film agent. 【0033】 Known antioxidants or stabilizers used include, in particular, tocopherols and their esters, sesamol derived from sesame oil, coniferous benzoates derived from benzoin resin, gallic acid esters (including methyl, ethyl, propyl, amyl, butyl, and lauryl gallates), butylated hydroxyanisole (also known as BHA / BHT or butyl-p-cresol), ascorbic acid and its salts and esters (e.g., ascorbyl palmitate), erythorbic acid (isoascorbic acid) and its salts and esters, monothioglycerin, sodium formaldehyde sulfoxylate, sodium metabisulfite, sodium bisulfite, sodium sulfite, potassium metabisulfite, butylated hydroxyanisole, butylated hydroxytoluene (BHT), and / or propionic acid. 【0034】 The absence of antioxidants, either largely or completely, has the advantage of eliminating the possibility of antioxidants reacting with the active ingredients to form undesirable compounds. Furthermore, antioxidants can cause allergic reactions. Therefore, the absence or reduction of antioxidants is advantageous. 【0035】 In particular, it is advantageous that the oral thin film agent of the present invention contains less than 1% by weight, preferably less than 0.5% by weight, and more preferably less than 0.1% by weight, of a metabisulfite such as sodium metabisulfite or potassium metabisulfite relative to the total weight of each layer of the oral thin film agent, or relative to the total weight of the oral thin film agent. 【0036】 In particular, it is advantageous to have only a small amount of sodium metabisulfite, or even none at all, because sodium metabisulfite can cause allergic reactions and can react with adrenaline to form sulfonate adrenaline. 【0037】 The oral thin film agent according to the present invention is preferably characterized by containing an antimicrobial substance in an amount of less than 5% by weight, preferably less than 4% by weight, preferably less than 3% by weight, preferably less than 2% by weight, preferably less than 1% by weight, preferably less than 0.5% by weight, and more preferably less than 0.1% by weight, relative to the total weight of each layer of the oral thin film agent, or relative to the total weight of the oral thin film agent. 【0038】 Since antimicrobial agents can be toxic to patients or cause allergic reactions, the absence of antimicrobial agents has advantages. This risk is reduced by omitting antimicrobial agents whenever possible. 【0039】 Known antimicrobial substances include, in particular, plant extracts. 【0040】 Therefore, the oral thin film agent according to the present invention is preferably characterized by containing less than 5% by weight, preferably less than 4% by weight, preferably less than 3% by weight, preferably less than 2% by weight, preferably less than 1% by weight, preferably less than 0.5% by weight, and more preferably less than 0.1% by weight of a plant extract, relative to the total weight of each layer of the oral thin film agent, or relative to the total weight of the oral thin film agent. 【0041】 The oral thin film agent according to the present invention is preferably characterized by containing less than 10% by weight, preferably less than 9% by weight, preferably less than 8% by weight, preferably less than 7% by weight, preferably less than 6% by weight, preferably less than 5% by weight, and more preferably less than 3% by weight of water, relative to the total weight of each layer of the oral thin film agent, or relative to the total weight of the oral thin film agent. 【0042】 To determine the water content, the oral thin-film preparation is typically dissolved in 5 mL of dimethyl sulfoxide by shaking in a laboratory shaker at approximately 1200 rpm for 10 minutes, and then analyzed using Karl Fischer coulometric titration. Thus, the water content can be determined by Karl Fischer titration. 【0043】 However, the oral thin film agent according to the present invention may contain up to 10% by weight, preferably up to 4% by weight, of an organic solvent such as ethanol and / or acetone, relative to the total weight of each layer of the oral thin film agent, or relative to the total weight of the oral thin film agent. 【0044】 The oral thin film agent according to the present invention is preferably characterized by containing at least 40% by weight, preferably at least 45% by weight, and more preferably at least 50% by weight of adrenaline or a pharmaceutically acceptable salt thereof (as defined above) relative to the total weight of each layer of the oral thin film agent, or relative to the total weight of the oral thin film agent. 【0045】 Preferably, the oral thin film preparation according to the present invention is characterized by containing 40% to 65% by weight, preferably 45% to 60% by weight, more preferably 50% to 56% by weight of adrenaline or a pharmaceutically acceptable salt thereof (as defined above) relative to the total weight of each layer of the oral thin film preparation, or relative to the total weight of the oral thin film preparation. 【0046】 The oral thin film agent according to the present invention is preferably characterized by containing at least 30% to 60% by weight, preferably 33% to 55% by weight, preferably 35% to 50% by weight, and preferably 38% to 44% by weight of at least one polymer, relative to the total weight of each layer of the oral thin film agent, or relative to the total weight of the oral thin film agent. 【0047】 A blend of several polymers can also be used. In this case, the total amount of all polymers used is preferably 30% to 60% by weight, preferably 35% to 55% by weight, preferably 38% to 51% by weight, and preferably 39% to 50% by weight, relative to the total weight of each layer of the oral thin film agent, or relative to the total weight of the oral thin film agent. 【0048】 The oral thin film agent according to the present invention is preferably characterized by further comprising at least one excipient selected from the group consisting of colorants, flavoring agents, sweeteners, taste masking agents, emulsifiers, enhancers, pH adjusters, humectants and / or preservatives. 【0049】 Each excipient can be present in the oral thin film in an amount of about 0.001 to 10% by weight, preferably 0.01 to 5% by weight, preferably 0.01 to 2% by weight, relative to the total weight of each layer of the oral thin film, or relative to the total weight of the oral thin film. 【0050】 The oral thin film agent according to the present invention is more preferably 20 to 400 g / m² 2 Preferably 100-350 g / m² 2 It is characterized by having a mass per unit area. 【0051】 The oral thin film agent according to the present invention is preferably characterized by comprising at least two layers. 【0052】 The two layers are preferably identical, but they may also have different compositions. 【0053】 The oral thin film agent according to the present invention may also have more than two layers. In this case as well, the composition of each layer may be the same or different. 【0054】 Preferably, the oral thin-film agent of the present invention comprises at least two layers, each containing adrenaline or a pharmaceutically acceptable salt thereof, and at least one polymer, wherein the adrenaline is substantially insoluble in at least one of the polymers. 【0055】 The oral thin film agent according to the present invention is more preferably characterized in that multiple layers are bonded together by a pharmaceutically acceptable adhesive. 【0056】 Several layers, preferably two layers, can also be joined by other methods familiar to those skilled in the art. These include, for example, sealing or heat sealing, direct coating, or lamination of the first and second layers. 【0057】 The oral thin film agent according to the present invention is preferably characterized in that multiple layers are bonded together by a pharmaceutically acceptable adhesive, the pharmaceutically acceptable adhesive preferably comprises at least one water-soluble polymer and at least one plasticizer. 【0058】 The multilayer oral thin film agent of the present invention is more preferably characterized in that at least one water-soluble polymer in the adhesive contains shellac, vinylpyrrolidone / vinyl acetate copolymer, polyvinylcarbrolactam / polyvinyl acetate / polyethylene glycol copolymer, hydroxypropyl cellulose or hydroxypropyl methylcellulose and / or polyvinylpyrrolidone. 【0059】 Preferably, the oral thin film agent according to the present invention is characterized in that at least one plasticizer in the adhesive contains glycerin, polyethylene glycol, particularly polyethylene glycol 200, sorbitol and / or tributyl citrate. 【0060】 In particular, at least one plasticizer in the adhesive includes glycerin, polyethylene glycol 200, and / or tributyl citrate. 【0061】 By using at least one water-soluble polymer and at least one plasticizer, preferably as a mixture, a viscous mixture is produced, which can preferably be used as an adhesive layer in the oral thin film agent according to the present invention after drying. 【0062】 The weight ratio of at least one water-soluble polymer to at least one plasticizer in the adhesive is preferably about 85:50 to about 15:50, preferably 85:65 to about 15:35, more preferably about 80:60 to about 20:40, more preferably about 80:50 to about 20:50, more preferably about 82:68 to about 18:32, and most preferably about 80:70 to about 20:30. 【0063】 Too little or too much plasticizer can result in a mixture that is either not viscous or impossible to process. 【0064】 Even special mixtures of two polymers have been shown to be sufficiently viscous and usable as adhesives. In this case, a mixture of 5-15% by weight of polyvinylpyrrolidone / polyvinyl acetate copolymer and 35-45% by weight of hydroxypropyl cellulose has proven useful. 【0065】 The present invention also relates to a method for producing an oral thin film preparation according to the present invention. The method is as follows: a) A step of preparing a solution comprising a solvent in which at least one polymer and adrenaline or a pharmaceutically acceptable salt thereof are substantially insoluble, b) Adding adrenaline or a pharmaceutically acceptable salt thereof, c) A step in which the suspension obtained in step (b) is spread and dried to obtain a single layer of oral thin film agent. Includes. 【0066】 When manufacturing a multilayer oral thin film formulation, the above method is as follows: d) The first layer obtained in c) is coated with a pharmaceutically acceptable adhesive and applied to a further, preferably identical, second layer to obtain a two-layer oral thin film agent. It also includes. 【0067】 Similarly, and naturally, additional layers can be applied to obtain oral thin-film preparations having any number of layers. 【0068】 All of the above preferred embodiments for oral thin-film formulations are similarly applicable to the methods according to the present invention. 【0069】 Solvents in which adrenaline or a pharmaceutically acceptable salt thereof is substantially insoluble preferably include ethanol, ethyl acetate, methanol, propanol, and / or isopropanol. 【0070】 These solvents have the advantage that common polymers are sufficiently soluble in them, while adrenaline is essentially insoluble. 【0071】 Essentially insoluble, as defined in the table above, means having solubility of at least "slightly insoluble" or less in at least one polymer at temperatures between 15°C and 25°C. 【0072】 The present invention also covers oral thin film preparations that can be obtained by the method described above. 【0073】 All of the above preferred embodiments of oral thin film preparations and methods for obtaining oral thin film preparations are similarly applicable to oral thin film preparations that can be obtained by the methods according to the present invention. 【0074】 The present invention further relates to oral thin-film preparations, which can be obtained as described above or by the methods described above, for use as pharmaceuticals, particularly in the treatment of allergic reactions, in the treatment of shock conditions, in emergency medicine, for example, in resuscitation, in the treatment of respiratory diseases and / or local vasoconstriction. [Examples] 【0075】 The present invention can be further illustrated by non-limiting examples. [Examples] 【0076】 Oral thin-film formulations containing micronized adrenaline were manufactured using the excipients listed in Table 1. 【0077】 [Table 2] 【0078】 HPC was dissolved in ethanol, the process solvent. Subsequently, Kollidon VA64, sodium metabisulfite, and adrenaline bitartrate were added. 【0079】 This suspension was applied to a silicone-treated liner and dried. 【0080】 We also manufactured adhesives for the compositions listed in Table 2. 【0081】 [Table 3] 【0082】 For this purpose, Kollidon VA64 was dissolved in ethanol, the process solvent. Then glycerin was added. 【0083】 A coating was applied to a silicone-treated liner, and then dried to obtain an adhesive layer. 【0084】 Next, a multilayer oral thin film formulation was manufactured. For this purpose, a laminated piece of the adhesive layer was attached to a laminated piece of the active ingredient layer, and a laminated piece of another active ingredient layer was attached to the other side of the adhesive layer. 【0085】 The advantages of this multilayer oral thin film formulation include improved adrenaline stability (see also Example 2), the absence of the acetate odor often present in formulations using dissolved adrenaline, and the absence of uncontrolled recrystallization. [Examples] 【0086】 A single-layer oral thin film formulation 197Adr0100 was prepared in the same manner as in Example 1. 【0087】 Formulations 197Adr0086, 197Adr0078, 197Adr0091, and 197Adr0084 were manufactured as follows: 【0088】 The production of oral thin-film formulations can be carried out by mass production techniques known to those skilled in the art, for example, by stirring / mixing the contained components using an agitator motor and a suitable stirring tool. 【0089】 Next, gas was added to the resulting mass by stirring, for example, using a whisking machine. The foamed mass could then be coated onto a coating carrier to a certain thickness using suitable equipment (roller applicator, doctor blade, coating box, etc.). The resulting foam contains cavities. 【0090】 A fully temperature-stable network material that can remove a dried film may be used as a coating support. This can be achieved by selecting the material of the coating support (different surface tensions between the foam mass and the substrate), or by a suitable non-adhesive coating of the coating support, for example, using silicone or a fluoropolymer. 【0091】 The process solvent contained, usually water or a mixture of water and an organic water-miscible solvent, is removed by drying. From the resulting solid foam layer, the oral thin film material can be cut or die-cut to the appropriate size. 【0092】 [Table 4] 【0093】 Formulation 197Adr0100 corresponds to the oral thin film formulation according to the present invention. 【0094】 Other formulations are equivalent to the original formulation in which the active ingredient is partially dissolved. 【0095】 The degradation of L-adrenaline and racemization to D-adrenaline after storage at 25°C and 40°C were measured by HPLC, respectively. The results are summarized in Tables 4 and 5. The measurements were performed by comparing the relative peak sizes of the peaks resulting from the L-enantiomer and D-enantiomer using HPLC. 【0096】 [Table 5] 【0097】 [Table 6] 【0098】 When OTF in a sealed aluminum pouch is stored at 40°C, the amount of adrenaline decreases only slightly after 5 months (values ​​show the change from the initial value). 197Adr0100: 0.09% decrease in adrenaline, of which 0.03% was racemization. 197Adr0086: 1.32% decrease in adrenaline, of which 0.83% was racemized. 197Adr0078: 1.89% decrease in adrenaline, of which 1.18% was racemized. 197Adr0084: 1.79% decrease in adrenaline, of which 1.27% was racemized. 【0099】 The OTF according to the present invention exhibits the lowest levels of decomposition and racemization.

Claims

[Claim 1] An oral thin film preparation comprising one or more layers, wherein at least one layer contains adrenaline or a pharmaceutically acceptable salt thereof and at least one polymer, more than 95% by weight of the adrenaline exists undissolved in the at least one polymer, the adrenaline or a pharmaceutically acceptable salt thereof exists as an L-enantiomer, and each oral thin film preparation contains at least 40% by weight of adrenaline or a pharmaceutically acceptable salt thereof relative to the total weight of each layer of the oral thin film preparation, or relative to the total weight of the oral thin film preparation. [Claim 2] The oral thin film preparation according to claim 1, wherein adrenaline or a pharmaceutically acceptable salt thereof is present in the form of fine particles having a particle size distribution of d(99) < 10 μm. [Claim 3] The oral thin film agent according to claim 1, wherein at least one polymer is selected from the group consisting of starch, dextran, carboxymethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxypropylethylcellulose, sodium carboxymethylcellulose, ethyl or propylcellulose, polyacrylic acid, polyacrylate, polyvinylpyrrolidone, polyvinyl alcohol, polyvinylpyrrolidone / polyvinyl acetate copolymer, polyethylene oxide polymer, polyacrylamide, polyethylene glycol, polyvinyl alcohol / polyethylene glycol copolymer, gelatin, collagen, alginate, pectin, pullulan, tragacanth, chitosan, alginic acid, arabinogalactan, galactomannan, agar, agarose, carrageenan, natural rubber, and mixtures thereof. [Claim 4] The oral thin film agent according to claim 1, wherein each layer of the oral thin film agent contains less than 1% by weight of an antioxidant relative to the total weight of the oral thin film agent, or relative to the total weight of the oral thin film agent. [Claim 5] The oral thin film agent according to claim 4, wherein the antioxidant is metabisulfite. [Claim 6] The oral thin film agent according to claim 1, comprising at least 35% by weight of the at least one polymer based on the total weight of the oral thin film agent. [Claim 7] The oral thin film agent according to claim 1, further comprising at least one excipient selected from the group consisting of colorants, flavoring agents, sweeteners, taste masking agents, emulsifiers, enhancers, pH adjusters, humectants, and / or preservatives. [Claim 8] The oral thin film agent according to claim 1, comprising at least two layers each containing adrenaline or a pharmaceutically acceptable salt thereof, and at least one polymer, wherein more than 95% by weight of the adrenaline is present undissolved in at least one of the polymers. [Claim 9] The oral thin film agent according to claim 1, wherein multiple layers are bonded together with a pharmaceutically acceptable adhesive. [Claim 10] The oral thin film agent according to claim 9, wherein the pharmaceutically acceptable adhesive comprises at least one water-soluble polymer and at least one plasticizer. [Claim 11] A method for producing an oral thin film agent according to any one of claims 1 to 10: a) A step of preparing a solution comprising at least one polymer and a solvent containing ethanol, ethyl acetate, methanol, propanol and / or isopropanol, b) the step of adding adrenaline or a pharmaceutically acceptable salt thereof, c) A step of spreading the suspension obtained in step (b) and drying it to obtain a single layer of oral thin film agent. A method that includes this. [Claim 12] A step of coating the first layer obtained in d) and c) with a pharmaceutically acceptable adhesive and applying a further second layer to obtain a two-layer oral thin film agent. The method according to claim 11, further comprising: [Claim 13] The method according to claim 12, wherein the second layer is identical to the first layer. [Claim 14] An oral thin film preparation according to any one of claims 1 to 10, for use as a pharmaceutical. [Claim 15] An oral thin film preparation according to any one of claims 1 to 10, for use as a pharmaceutical in the treatment of allergic reactions.

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