Composition, especially for use in the treatment of veisalgia

Abstract

Composition, in particular pharmaceutical composition, especially for use in the prophylactic and / or therapeutic (symptomatic) treatment of veisalgia (alcohol intoxication, hangover), wherein the composition is in the form of a fixed dosage (fixed dosage form) for oral administration, and wherein the composition comprises an effective, in particular pharmaceutically and / or therapeutically effective, amount of active substances from the drug classes (i) non-steroidal anti-inflammatory drug (NSAID), (ii) H1 antihistamine and (iii) calcium channel antagonist, wherein the active substances are selected from Class (i): Acetylsalicylic acid, ibuprofen, dexibuprofen, flurbiprofen, naproxen, ketoprofen, tiaprofenic acid, diclofenac, indomethacin, acemetacin, flufenamic acid, mefenamic acid, piroxicam, tenoxicam, meloxicam, lornoxicam, nabumetone and / or mixtures thereof, Class (ii): Dimenhydrinate, and Class (iii): Cinnarizine.

Description

[0001] The present invention relates to the field of medicine and in particular to the technical (i.e. medical-pharmaceutical) field of the treatment or therapy of veisalgia (alcohol intoxication, hangover).

[0002] In particular, the present invention relates to a composition, especially a pharmaceutical composition, which is particularly suitable or intended for use in the prophylactic or therapeutic (symptomatic) treatment of veisalgia (alcohol intoxication, hangover).

[0003] The indication veisalgia, i.e., the state of alcohol intoxication, also known as a "hangover," describes the condition or a rather broad spectrum of symptoms following excessive alcohol consumption, which typically sets in several hours after the acute effects of intoxication have subsided. Common symptoms include headache, nausea, fatigue, dizziness, increased sensitivity, and a general physical and mental impairment.

[0004] The underlying pathophysiology is multifactorial and not yet fully understood. Several mechanisms contributing to the aforementioned symptoms can be identified, with alcohol metabolism playing a central role. Furthermore, alcohol has a diuretic effect, and alcohol-induced hypoglycemia, particularly on an empty stomach, can also contribute to the symptoms described above. The potential for hangovers is further increased by congeners found especially in dark spirits such as whiskey and rum. Finally, alcohol also disrupts sleep architecture.

[0005] There is currently no causal therapy available for hangovers; treatment is symptomatic. The primary focus is on measures such as increased fluid intake, consuming carbohydrate-rich foods to stabilize blood sugar levels, and physical recovery. Medication can be used as a supplement or preventative measure, although there are limitations due to potential adverse effects on organs, and real health risks beyond the intoxication itself may arise.

[0006] For example, patent document EP 0 426 479 B1 discloses a composition proposed for treating the symptoms of overindulgence, particularly after excessive consumption of alcoholic beverages and / or food. The formulation described therein preferably combines an analgesic or antipyretic, e.g., paracetamol, with a gastric acid-reducing agent, such as cimetidine, ranitidine, famotidine, or omeprazole.

[0007] From a pharmacological and toxicological perspective, this combination is particularly problematic for treating hangovers. Paracetamol, for example, undergoes hepatic biotransformation, which, especially after alcohol consumption, leads to reactive intermediates via cytochrome P450-dependent metabolism (CYP2E1). With reduced glutathione reserves, as is typical after alcohol consumption, the detoxification of these intermediates may be insufficient, resulting in hepatotoxic effects.

[0008] Furthermore, the concurrently administered acid-reducing agent can delay gastric emptying and thus the absorption and metabolism of food and alcohol residues. The proposed H2 blockers and proton pump inhibitors lead to an increase in intragastric pH and a decrease in proteolytic activity, thereby slowing the natural breakdown of food components. This can prolong the residence time of residual alcohol or fusel alcohol metabolites in the stomach and thus prolong or intensify hangover symptoms.

[0009] Furthermore, the altered pH situation in the stomach can influence the absorption kinetics of the analgesic or antipyretic and lead to uneven plasma levels, causing the desired analgesic effect to occur late or be weakened.

[0010] The proposed combination of active ingredients is therefore ultimately unsuitable or potentially contraindicated for the treatment of veisalgia, particularly with regard to safety and the physiological regeneration process after alcohol overdose. Currently, no suitable systematic or specifically tailored (symptomatic) therapies are available for the consequences of excessive alcohol consumption, especially the treatment of veisalgia or hangovers.

[0011] Against this background, one object of the present invention is to provide a concept that eliminates or at least mitigates the previous disadvantages or shortcomings of existing approaches to the treatment or reduction of veisalgia or hangovers.

[0012] The present invention is based in particular on the objective of providing a reliable treatment concept that specifically and in combination addresses the symptoms of veisalgia or hangovers, especially with a reduced risk of side effects.

[0013] To solve the problem described above, the present invention therefore proposes – according to a first aspect of the present invention – a composition, particularly pharmaceutical, for use in the prophylactic and / or therapeutic (symptomatic) treatment of veisalgia (alcohol intoxication, hangover) according to claim 1. Advantageous further developments and embodiments of this aspect of the invention are the subject of the respective dependent claims.

[0014] Further aspects of the present invention include the use of a particularly pharmaceutical composition according to the present invention for the manufacture of a drug or medicament for the prophylactic and / or therapeutic (symptomatic) treatment of veisalgia, as well as a corresponding drug or medicament according to the related independent claim.

[0015] It goes without saying that embodiments, designs, advantages and the like, which are listed below for one aspect of the invention only to avoid repetition, naturally also apply to the other aspects of the invention without requiring separate mention.

[0016] Furthermore, it goes without saying that the following specifications of values, numbers and ranges are not to be understood as limiting; it is self-evident to the person skilled in the art that deviations from the specified range or specifications are possible in individual cases or depending on the application, without leaving the scope of the present invention.

[0017] Furthermore, it should be noted that for all relative or percentage-based quantity specifications mentioned below, especially those related to weight, these specifications must be selected or combined by a person skilled in the art in such a way that the total always results in 100% or 100% by weight, possibly including further components, ingredients, additives, or constituents, particularly as defined below. This is self-evident to a person skilled in the art.

[0018] Furthermore, it should be noted that all values ​​or parameters mentioned below, or the like, can generally be determined using standardized or explicitly specified determination methods, or using determination methods that are generally familiar to those skilled in the field.

[0019] Furthermore, for the purposes of describing the present invention, the features of the present invention cited in connection with specific embodiments, configurations, advantages, examples, or the like are also considered disclosed in combination. Thus, higher-order combinations of individual or multiple features cited for specific embodiments, configurations, application examples, or the like are also considered disclosed.

[0020] In particular, with regard to the features characterizing the invention, all possible combinations of these features shall be deemed disclosed, with embodiments of comparable or corresponding preference of the various features in their combination being preferred (e.g. quantities or quantity ranges of the relevant active ingredients and components of the same preference or the like).

[0021] It is particularly important to note that for the quantities listed below relating to the various active ingredients or components of the composition according to the invention, especially relative or absolute quantities of the same preference or level of preference, the respective combinations relating to the various active ingredients or components with the corresponding preference or level of preference are also disclosed. Likewise, all other combinations (i.e., combinations based on different preferences or levels of preference) are also disclosed.

[0022] Having said that, the present invention will now be explained in detail below: The subject matter of the present invention – according to a first aspect of the present invention – is a composition, in particular a pharmaceutical composition, especially for use in the prophylactic and / or therapeutic (symptomatic) treatment of veisalgia (alcohol intoxication, hangover), wherein the composition is in the form of a fixed dosage (fixed dosage form) for oral administration, and wherein the composition comprises an effective, in particular pharmaceutically and / or therapeutically effective, amount of active substances from the drug classes (i) non-steroidal anti-inflammatory drug (NSAID), (ii) H1 antihistamine and (iii) calcium channel antagonist, wherein the active substances are selected from Class (i): Acetylsalicylic acid, ibuprofen, dexibuprofen, flurbiprofen, naproxen, ketoprofen, tiaprofenic acid, diclofenac, indomethacin, acemetacin, flufenamic acid, mefenamic acid, piroxicam, tenoxicam, meloxicam, lornoxicam, nabumetone and / or mixtures thereof, Class (ii): Dimenhydrinate, and Class (iii): Cinnarizine.

[0023] Within the scope of this application, the specification of an active substance, in particular as above, under its generic name or generic name, shall include all pharmaceutically acceptable forms of this active substance, in particular salts, esters, amides, solvates, hydrates, polymorphic modifications, isomers, enantiomers and prodrugs, insofar as these have the same or a functionally equivalent pharmacological activity.

[0024] The terms "salt" and "ester", as used here with regard to the active ingredients or components, refer in particular to the respective pharmaceutically compatible or physiologically compatible or harmless salts or esters of the active ingredients or components listed.

[0025] Furthermore, the term “composition” or “pharmaceutical composition”, as used in the context of the present invention, is to be understood broadly and includes not only pharmaceutical preparations or pharmaceuticals and medicinal products as such, but also so-called medical devices, homeopathic remedies and food supplements, etc.

[0026] With regard to the present invention, the applicant has found in a completely surprising way that the combination of active substances from the classes of (i) non-steroidal anti-inflammatory drug (NSAID), (ii) H1 antihistamine and (iii) calcium channel antagonist yields, in particular, pharmaceutical compositions with an action profile optimized for the treatment of veisalgia or hangovers.

[0027] The active substances of class (i) are compounds with analgesic, antipyretic, and anti-inflammatory effects that exert their pharmacological activity primarily by inhibiting cyclooxygenase enzymes (COX-1 and / or COX-2), thereby inhibiting the biosynthesis of prostaglandins, prostacyclins, and thromboxanes. For the intended indication, they represent a pharmacologically safe, rapidly acting, and physiologically compatible class of drugs. In particular, these active substances are characterized by broad efficacy against the symptoms to be treated, comparatively low hepatic burden, and optimized integration into formulations, especially those that are gentle on the stomach.

[0028] These active ingredients can be used individually or in combination. The selection of the respective active ingredient generally depends on the desired potency, pharmacokinetics, tolerability, and the intended indication. According to the invention, preferred representatives are ibuprofen, dexibuprofen, and / or naproxen due to their favorable tolerability profile and broad therapeutic application.

[0029] Diclofenac is also preferred, as it has a pronounced anti-inflammatory effect. Acetylsalicylic acid is particularly advantageous due to its analgesic and antipyretic effects.

[0030] The H1 antihistamine (ii) dimenhydrinate used according to the invention is a salt of diphenhydramine and 8-chlorotheophylline and thus combines two active ingredients. Diphenhydramine blocks histamine H1 receptors and therefore acts on the central nervous system. In this way, it can be effective against nausea and vomiting and also as a sedative. 8-Chlorotheophylline, from the xanthine chemical class, acts as a stimulant with caffeine-like physiological effects. In this way, it reduces the sedative effect of diphenhydramine and, moreover, contributes to alleviating hangover symptoms through its stimulating effect.

[0031] Dimenhydrinate is conventionally used to treat motion sickness. Motion sickness occurs when conflicting information from the sensory organs converges in the brain. The resulting sensory conflict overwhelms the brain, which can lead to activation of the vomiting center and symptoms such as nausea. In this respect, the conventional use of dimenhydrinate, and the intended symptom relief, differs significantly from the treatment of veisalgia envisioned according to the invention, which is based on a state of intoxication and thus an actual physical impairment.

[0032] According to the invention, cinnarizine is used as a calcium channel antagonist (iii). It is traditionally used to treat disorders of cerebral and peripheral circulation as well as balance problems (dizziness). It is a piperazine derivative that regulates cellular calcium overload and can thereby, among other things, promote vasodilation.

[0033] The combination of active ingredients provided within the scope of the invention advantageously addresses inflammatory, neurovegetative, and vascular mechanisms simultaneously. Such mechanisms are involved in complex symptom states, such as those that occur particularly in connection with veisalgia or hangovers, and are typically complex or difficult to address.

[0034] Within the scope of the invention, the proposed combination of active ingredients advantageously achieves a multimodal and synergistic pharmaceutical effect without pharmacologically redundant overlaps. The synergistic effect results from peripheral pain and inflammation inhibition, while histamine-mediated symptoms and neurovegetative reactions are modulated, and vascular and neuronal excitation processes are inhibited by a blockade of voltage-dependent calcium channels. 2+ -Channels are stabilized.

[0035] In detail, NSAIDs (i) can reduce prostaglandin synthesis via cyclooxygenase (COX-1 / COX-2) inhibition, thereby decreasing peripheral inflammation, pain receptor sensitivity, and vascular dilation. The calcium channel antagonist (iii) can complement this effect by inhibiting calcium-mediated neurotransmitter release, thus attenuating neurogenic inflammatory and pain components. This combination allows for a potentiated analgesic effect with potentially lower NSAID dosages, which reduces gastrointestinal burden.

[0036] Furthermore, the combination of H1 antihistamine (ii) and calcium channel antagonist (iii) can achieve an increased blockade of vestibular impulse conduction, thereby stabilizing the system against movement- and alcohol-induced irritations.

[0037] Furthermore, many hangover symptoms are based on vascular dysregulation (e.g., dilation of cerebral vessels, increased permeability). The calcium channel antagonist (iii) can reduce intracellular calcium in these cases. 2+ Inhibit influx-mediated vasodilation, while the NSAIDs (i) contribute to a reduction in prostaglandin-dependent vascular permeability. In this combination, the active ingredients beneficially normalize vascular tone and reduce vascular headaches. The H1 antihistamine (ii) further contributes to this effect by stabilizing the endothelial barrier and inhibiting histamine-mediated vasodilation.

[0038] By having the drug classes (i) to (iii) act on different, complementary target structures as explained above, a low pharmacodynamic overlap is advantageously achieved, which also advantageously allows for mutual dose reduction while maintaining the same efficacy.

[0039] In addition, stomach irritation can be alleviated and a uniform peripheral blood flow, which improves general absorption and distribution, can be achieved.

[0040] Overall, the combination of active ingredient classes (i) to (iii) provided for in the invention, particularly based on the specifically provided active ingredients, advantageously allows for multimodal treatment of complex symptomatic conditions resulting from the toxic effects of alcohol intoxication or veisalgia. Due to the different yet complementary mechanisms of action, analgesic, anti-inflammatory, vasostabilizing, and antiemetic effects can be advantageously achieved overall – and this is particularly true with comparatively high tolerability and a potentially reduced dose of each individual active ingredient. This results in an unexpected synergistic mode of action of the composition according to the invention for the intended indication, so that the invention advantageously enables targeted and improved treatment of hangovers.

[0041] The following further information is provided regarding the active ingredients and any other ingredients of the claimed composition: The composition according to the invention contains the active ingredients of classes (i) and (ii) preferably in weight-based ratios of class (i) : class (ii) in the range of 1 : 2 to 20 : 1, in particular 2 : 1 to 15 : 1, preferably 5 : 1 to 10 : 1. Equally preferably, the composition contains the active ingredients of classes (i) and (iii) in weight-based ratios of class (i) : class (iii) in the range of 1 : 1 to 30 : 1, in particular 3 : 1 to 25 : 1, preferably 10 : 1 to 20 : 1. Good results with regard to the realized spectrum of activity of the composition according to the invention are also obtained if the composition contains the active ingredients of classes (ii) and (iii) in weight-based ratios of class (ii) : class (iii) in the range of 5 : 1 to 1 : 1, in particular 3 : 1 to 1 : 1.25, preferably 2.5 : 1 to 1.5 : 1, contains. In a preferred embodiment of the invention, the composition contains the active ingredients of classes (i), (ii) and (iii) in weight-based ratios of class (i) : class (ii) : class (iii) in the range of 30 : 3 : 1 to 3 : 1 : 1, in particular 25 : 2.5 : 1 to 10 : 1.25 : 1, preferably 20 : 2.5 : 1 to 15 : 1.5 : 1.

[0042] For this design, an optimal combination of active ingredients from classes (i) to (iii) is achieved, so that effective and lasting treatment of hangover symptoms is possible.

[0043] For compositions according to the invention with amounts of the active ingredients of classes (i) to (iii) in the aforementioned ratio ranges, the advantageous effects of the composition according to the invention described at the outset are realized to a particularly high degree.

[0044] Furthermore, it has proven advantageous if the active ingredient of class (i) is selected from acetylsalicylic acid, ibuprofen, dexibuprofen, naproxen, diclofenac, and / or mixtures thereof. The active ingredient of class (i) is preferably ibuprofen. The aforementioned NSAIDs are characterized by an established analgesic and anti-inflammatory effect, which is particularly reliable in the context of the indication veisalgia. At the same time, the risk of pharmacological and toxicological effects is minimized or tolerable, especially when higher doses of the aforementioned active ingredients are taken.

[0045] The composition according to the invention contains the active ingredients preferably in amounts in the range of 40 wt.% to 98 wt.%, in particular 45 wt.% to 96 wt.%, preferably 50 wt.% to 95 wt.%, based on the total composition.

[0046] For effective action and treatment of hangover symptoms, it has also proven beneficial if the composition contains active ingredients of class (i) in amounts in the range of 30 wt.% to 75 wt.%, in particular 40 wt.% to 70 wt.%, preferably 50 wt.% to 65 wt.%, based on the total composition.

[0047] Active ingredients of class (ii) are preferably included in the composition according to the invention in amounts in the range of 4 wt.% to 20 wt.%, in particular 5 wt.% to 15 wt.%, preferably 6 wt.% to 10 wt.%, based on the total composition.

[0048] For active substances of class (iii) it has proven advantageous with regard to the treatment of the desired symptoms if they are included in the composition in amounts in the range of 0.5 wt.% to 7 wt.%, in particular 1.5 wt.% to 5 wt.%, preferably 2 wt.% to 4 wt.%, based on the total composition.

[0049] Particularly good effects are achieved according to the invention for appropriately composed formulations. Likewise, a favorable or application-oriented dosage can be implemented, which can be advantageous with regard to acceptance and adherence.

[0050] In a further preferred embodiment, the composition according to the invention can contain one or more adjuvants, in particular in amounts in the range of 0.1 wt.% to 50 wt.%, in particular 3 wt.% to 30 wt.%, preferably 5 wt.% to 15 wt.%, based on the total composition.

[0051] Within the scope of the invention, adjuvants serve to improve the pharmacological efficacy, stability, bioavailability, or sensory acceptability of the preparation and can be of either natural or synthetic origin. The adjuvants are preferably selected to be chemically and physically compatible with the active pharmaceutical ingredient(s). Furthermore, they can contribute to positively influencing the release characteristics, taste, shelf life, or tolerability of the composition.

[0052] In a preferred embodiment, the composition comprises flavoring and / or organoleptic adjuvants, which serve in particular to improve taste, mask unpleasant taste notes, or create a cooling or refreshing mouthfeel. These include, for example, menthol, thymol, eucalyptol, peppermint oil, citric acid, lactic acid, lactate, sucralose, xylitol, and maltitol. These adjuvants can also advantageously contribute to adjusting the pH value, improving solubility, or stabilizing hygroscopic components.

[0053] In a further preferred embodiment, the composition contains phytotherapeutic adjuvants or plant extracts that can exert complementary pharmacological effects. Particularly suitable phytotherapeutics or plant extracts include ginger extract, which contains gingerols or shogaols and has antiemetic and gastroprotective properties; ginseng extract with adaptogenic and tonic effects; guarana extract and green tea extract with stimulating and antioxidant properties; and aloe vera extract, which exhibits a mild anti-inflammatory and epithelial-regenerating effect. Other suitable plant adjuvants are curcumin, resveratrol, quercetin, lutein, and / or lycopene, which act as polyphenolic antioxidants and can prevent oxidative degradation processes of sensitive active ingredients in the matrix.In addition, essential oils, in particular from peppermint, fennel, chamomile, rosemary or eucalyptus, may be included in the composition according to the invention, which, through their spasmolytic and aromatic effect, improve both the sensory and functional properties of the composition.

[0054] In a further preferred embodiment, the composition may contain vitamins, coenzymes, and / or redox-active adjuvants that enhance the oxidative stability and physiological benefits of the formulation. Particularly preferred are vitamin B6, vitamin C (ascorbic acid), vitamin E (tocopherol), niacin, pantothenic acid, folic acid, vitamin B12 (cyanocobalamin), coenzyme Q10, biotin, and riboflavin. These substances can be used individually or in combination with plant polyphenols to achieve synergistic antioxidant effects and reduce oxidative stress in the pharmaceutical matrix.

[0055] Furthermore, the composition may contain amino acids, particularly peptides or biogenic derivatives thereof, which exhibit antioxidant, cell-protective, or metabolism-modulating properties. These include, in particular, DL-carnitine, DL-theanine, DL-lysine, taurine, glutathione, and allantoin. Such components can improve the bioavailability of lipophilic or sensitive active ingredients and support the user's physiological energy balance.

[0056] Furthermore, it has proven beneficial if the composition contains one or more electrolytic or mineral adjuvants. These can preferably be selected from physiologically compatible salts of sodium, potassium, calcium, magnesium, and mixtures thereof. Potassium chloride, sodium chloride, sodium citrate, calcium citrate, magnesium citrate, and mixtures thereof are particularly preferred. These adjuvants advantageously contribute to a balanced supply or restoration of the supply balance for minerals and electrolytes, which in turn can contribute to an improvement in hangover symptoms. The aforementioned salts support homeostasis after fluid or electrolyte loss, such as can occur with fatigue, dehydration, or alcohol consumption. In the form of their citrates, the salts, especially magnesium and calcium salts, can additionally act as pH-regulating buffers and mild alkalinizers.Magnesium and calcium ions also support neuromuscular stability and circulatory regulation, while potassium ions counteract fatigue of the cardiovascular system.

[0057] Furthermore, good results in alleviating hangover symptoms are achieved when the formula contains one or more sugar-containing or glucose-stabilizing adjuvants. Sugars (sucrose), dextrose (glucose), or other mono- or disaccharide carbohydrates, as well as their derivatives, are preferred in this context. These sugars serve as a readily available energy source and support physiological regeneration after hypoglycemic or alcohol-induced states.

[0058] In a further embodiment, caffeine-containing or stimulating adjuvants may be included, in particular caffeine, guarana extract, theobromine, pseudoephedrine, and taurine. These substances can have a central stimulating effect and, in combination with the active ingredients provided according to the invention, which have, among other things, analgesic, adaptogenic, or anti-fatigue effects, serve as functional enhancers.

[0059] The aforementioned adjuvants can be used individually or in any combination. A suitable combination of the adjuvants, particularly in conjunction with the active ingredients of the composition according to the invention, can achieve a synergistic effect that improves both the therapeutic efficacy and the user acceptance of the composition according to the invention.

[0060] In particular, the combination of the adjuvants lysine (DL-lysine 1:1), pseudoephedrine, and / or caffeine with the active ingredients of classes (i) to (iii) of the composition according to the invention, especially with the active ingredients ibuprofen, dimenhydrinate, and cinnarizine, is particularly preferred within the scope of the invention, as this has proven to be particularly advantageous with regard to accelerating or improving the intended effect in the treatment of veisalgia or hangovers. In particular, this combination allows for improved bioavailability, a faster onset of action, and physiological support of circulatory function. Lysine, in particular, improves the solubility and gastric tolerability of acidic active ingredients (e.g., ibuprofen), while caffeine can enhance the analgesic effect and reduce fatigue, and pseudoephedrine contributes a tonic and vasoconstrictive component.A corresponding composition thus advantageously achieves synergistic analgesia and performance stabilization while simultaneously improving tolerability.

[0061] Regarding the dosage form of the composition according to the invention, it has proven advantageous for the composition to comprise a solid matrix, particularly as a pharmaceutical carrier for the active ingredients. Specifically, the composition, which is available in the form of a fixed dosage (solid dosage form) for oral administration, can be in the form of a tablet, particularly a chewable tablet, film-coated tablet, coated tablet, and / or sustained-release tablet, a capsule, particularly a hard capsule, and / or as granules and / or powder, particularly for the preparation of aqueous suspensions. The preferred form is that of a tablet, particularly a chewable tablet, film-coated tablet, coated tablet, and / or sustained-release tablet, and / or a capsule, particularly a hard capsule. In this context, an enteric-coated formulation has also proven particularly advantageous.

[0062] The composition according to the invention can further comprise a matrix, in particular a solid matrix, which contains or embeds the active ingredients and thus serves as a carrier, release, and stabilization system. Preferably, the composition contains the matrix in amounts ranging from 2 wt.% to 60 wt.%, in particular 4 wt.% to 55 wt.%, preferably 5 wt.% to 50 wt.%, based on the total composition.

[0063] The matrix preferably contains one or more pharmaceutically acceptable excipients (auxiliaries), in particular selected from the group of fillers, binders, disintegrants, lubricants and / or lubricants, humectants and / or flow regulators, film formers, gelling agents and / or structuring agents, lipophilic components, and / or mixtures thereof, or is preferably formed from these.

[0064] This allows the desired technological and biopharmaceutical properties of the dosage form to be controlled or optimized.

[0065] In a preferred embodiment, the matrix comprises as an excipient one or more polymeric components selected from the group consisting of cellulose derivatives such as hydroxypropyl methylcellulose, hydroxyethylcellulose, or ethylcellulose, as well as polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycols, polylactides, polyglycolides, or their copolymers. Depending on the desired release characteristics, these substances can function as film formers, gelling agents, or structure-enhancing agents and contribute to the mechanical strength of the solid unit.

[0066] To control drug release, the matrix can additionally contain lipophilic components such as saturated or unsaturated fatty acids, waxes, glycerides, or hydrogenated vegetable oils. These create a delayed release through diffusion or erosion mechanisms within the compact matrix structure. Alternatively or additionally, hydrophilic fillers, for example, lactose, mannitol, sorbitol, xylitol, or microcrystalline cellulose, can be used to modulate the disintegration and water absorption properties.

[0067] In addition, the matrix can contain one or more binders as an excipient, including polyvinylpyrrolidone (povidone), modified starches, gelatin or sugar alcohol derivatives, which increase the cohesion of the powder particles during shaping and improve tabletability.

[0068] To selectively control disintegration and degradation, the matrix may contain disintegrants, in particular croscarmellose sodium, sodium starch glycolate, crospovidone, or microcrystalline cellulose. These promote the rapid disintegration of the dosage form after oral administration and enable a uniform release of the active ingredient.

[0069] To improve flowability, reduce friction during tableting, and optimize surface finish, one or more lubricants and / or lubricants can be used. Preferred examples include magnesium stearate, stearic acid, talc, and highly dispersed silica.

[0070] The matrix may also contain humectants and / or flow regulators, in particular polyethylene glycols, glycerol, sorbitol, or mannitol. These contribute to the stabilization of hygroscopic active ingredients and positively influence the plasticity and compressibility of the tablet mixture. For delayed-release or controlled-release systems, the matrix may additionally contain swelling or pore-forming components. Particularly suitable are sodium carboxymethylcellulose, cross-linked polyacrylic acids, alginates, carrageenans, or polysaccharide complexes, which form a gel or network upon contact with aqueous media, thus enabling a gradual release of the active ingredient.

[0071] To stabilize sensitive active ingredients, the matrix may also contain pH buffers, antioxidants, moisture regulators, or complexing agents. Preferred examples are ascorbic acid, butylhydroxytoluene, silica gel, mannitol, or cyclodextrins. These additives contribute to maintaining the chemical and physical integrity of the active ingredients during storage and use.

[0072] In a preferred embodiment, the matrix is ​​homogeneously dispersed, with the active ingredient present in molecularly dissolved or finely dispersed form. Alternatively, the active ingredient can be embedded in a multiphase structure consisting of a diffusion-inhibiting outer layer and an erodible or soluble core. By appropriately selecting and combining the matrix components, release profiles ranging from immediate to delayed (sustained) drug release can be achieved.

[0073] The matrix can also contain functional coatings or coverings that serve as a moisture barrier, flavor mask, or pH-dependent protective layer. Suitable polymers include, in particular, Eudragit® types, cellulose acetate phthalate, or poly(meth)acrylates, which are applied in solution or dispersion.

[0074] Overall, the selection and combination of the described excipients and matrix components enables targeted control of the mechanical strength, disintegration, drug release and stability of the solid pharmaceutical preparation, with the composition advantageously designed so that all components are pharmacologically safe and compatible with the active ingredients.

[0075] Furthermore, it has proven advantageous if the composition, particularly in a solid dosage form, has a total weight per dose in the range of 0.25 g to 5 g, particularly in the range of 0.4 g to 4 g, preferably in the range of 0.5 g to 3.5 g.

[0076] For an optimized relationship between single dose and efficacy, it has proven advantageous if the composition, particularly in a fixed dosage form, contains per dose class (i) active ingredients in amounts ranging from 25 mg to 900 mg, particularly 100 mg to 800 mg, preferably 150 mg to 650 mg, and / or if the composition contains per dose class (ii) active ingredients in amounts ranging from 10 mg to 100 mg, particularly 20 mg to 70 mg, preferably 30 mg to 50 mg, and / or if the composition contains per dose class (iii) active ingredients in amounts ranging from 5 mg to 50 mg, particularly 10 mg to 30 mg, preferably 15 mg to 25 mg. Within the aforementioned amount ranges for the respective active ingredients, the advantageous effects described above are particularly well realized.

[0077] Furthermore, good results regarding the relief of hangover symptoms are obtained when the composition, based on the total active ingredients, is administered at a daily dose in the range of 50 mg / day to 2,000 mg / day, in particular 250 mg / day to 1,600 mg / day, preferably 400 mg / day to 1,400 mg / day, and / or when the composition is formulated as a fixed dosage form, based on the total active ingredients, for administering a daily dose in the range of 50 mg / day to 2,000 mg / day, in particular 250 mg / day to 1,600 mg / day, preferably 400 mg / day to 1,400 mg / day.

[0078] According to a preferred embodiment of the present invention, the present invention further comprises, in particular, such a composition, especially for use in the prophylactic and / or therapeutic treatment of veisalgia, each comprising an effective, in particular pharmaceutically and / or therapeutically effective, amount of active substances from the drug classes (i) non-steroidal anti-inflammatory drug, (ii) H1 antihistamine and (iii) calcium channel antagonist, wherein the active substances are selected from Class (i): Acetylsalicylic acid, ibuprofen, dexibuprofen, flurbiprofen, naproxen, ketoprofen, tiaprofenic acid, diclofenac, indomethacin, acemetacin, flufenamic acid, mefenamic acid, piroxicam, tenoxicam, meloxicam, lornoxicam, nabumetone and / or mixtures thereof, Class (ii): Dimenhydrinate, and Class (iii): Cinnarizine, and which further includes adjuvants selected from the group of flavoring and / or organoleptic adjuvants, phytotherapeutic adjuvants, plant extracts, vitamins, coenzymes, redox-active adjuvants, amino acids, caffeine-containing adjuvants, stimulating adjuvants and / or mixtures thereof, and / or which is in the form of a fixed dosage (fixed dosage form), especially for oral administration and / or wherein the composition comprises a solid matrix, especially as a pharmaceutical carrier for the active ingredients.

[0079] The aforementioned respective advantages and special features apply equally to this preferred embodiment of the present invention.

[0080] For further details on this aspect of the invention, reference can be made to the explanations of the other aspects of the invention, these explanations applying equally to the present aspect of the invention.

[0081] A further subject matter of the present invention – according to a second and third aspect of the present invention – is the use of a composition, in particular a pharmaceutical composition, according to the present invention for the manufacture of a medicinal product or drug for the prophylactic and / or therapeutic treatment of veisalgia, as well as a medicinal product or drug for the prophylactic and / or therapeutic treatment of veisalgia comprising a composition according to the present invention.

[0082] For further details on this aspect of the invention, reference can be made to the explanations of the other aspects of the invention, these explanations applying equally to the present aspect of the invention.

[0083] Further embodiments, modifications and variations as well as advantages of the present invention are readily apparent and achievable for the person skilled in the art when reading the description, without leaving the scope of the present invention.

[0084] The following embodiments serve only to illustrate the present invention, but without limiting the present invention to them. EXAMPLES OF EXECUTION:

[0085] To evaluate the effect of the composition according to the invention, a controlled, single-blind comparative study was carried out with volunteer subjects. Experimental setup:

[0086] Two groups (Group A (verum group) and Group B (comparison group)) with 20 subjects each aged between 25 and 55 years were formed.

[0087] Before the start of the experiment, all subjects were asked about their general well-being and then reported any discomfort such as headaches, fatigue, general lethargy, nausea or mild to moderate gastrointestinal complaints.

[0088] After documenting their well-being over the course of an evening (approx. 3 to 5 hours) and prior to taking the composition according to the invention, all test subjects consumed a predetermined amount of alcohol, tailored to their individual body weight, under supervision.

[0089] After alcohol consumption, the subjects were given the following dosage for oral administration in tablet form: 1. Group A (Verum Group): The subjects in group A received a single dose of the composition according to the invention, containing 400 mg ibuprofen lysine (DL 1:1), 20 mg cinnarizine, 40 mg dimenhydrinate, 200 mg matrix components according to the invention. The medication was taken in the late evening, immediately before going to bed, about 30 to 60 minutes after the last alcohol intake, with 200 ml of water. After taking the medication, the participants entered a rest or sleep phase. Their subjective well-being was documented by the participants upon waking the following morning using a qualitative positive / negative scale. 2. Group B (comparison group): The subjects in group B received no therapeutic agent and were only given the option, upon request, to self-medicate using conventional painkillers such as paracetamol, ibuprofen or metamizole (Novalgin). ® to resort to. If medication was taken, it was administered late in the evening, immediately before bedtime, approximately 30 to 60 minutes after the last alcohol consumption, with 200 ml of water. About 20% of the participants used this method of self-medication. The participants entered a rest or sleep phase approximately 60 to 90 minutes after their last alcohol consumption. Their subjective well-being was documented by the participants upon waking the following morning using a qualitative positive / negative scale. 3. Evaluation method The subjects were asked to describe their well-being upon waking the following morning in relation to five main symptoms: ▪ Headache / pressure in the head ▪ Nausea / stomach upset ▪ General well-being / alertness ▪ Circulatory stability / dizziness ▪ Mood / Willingness to perform The evaluation was carried out by self-assessment using the following symbols: “++” = significantly better symptoms than usual, “+” = better symptoms than usual, “-” = worse symptoms than usual, “0” = unchanged symptoms. The evaluations were documented and then analyzed anonymously. 4. Results Upon waking the next morning, over 80% of the subjects experienced at least two positive changes (“+” or “++”) compared to the hangover symptoms usually expected individually, while in comparison group B hardly any comparable improvement was reported. In particular, group A showed a combined improvement in symptoms such as headache or pressure in the head and nausea or stomach upset, as well as circulatory stability or dizziness, i.e., an overall significantly less fatigued feeling than usual, while in group B, predominantly only an improvement in essentially one of the symptoms was observed (headache or pressure in the head, especially in the case of the subjects who had taken a conventional painkiller). Further observation throughout the day revealed that over 85% of participants in the verum group reported a positive or significantly positive feeling ("+" or "++"), while the control group reported only a moderate improvement, essentially following their usual hangover symptoms. In group A, a stable or progressively increasing improvement in symptoms was also observed throughout the day, particularly with regard to general well-being, alertness, mood, and performance. 5. Further investigations The comparative study was repeated for the composition according to the invention, with the subjects in the verum group A taking the composition approximately 30 minutes after waking up the following morning. A noticeable improvement in hangover symptoms was observed, which was particularly pronounced than the improvement achieved with conventional painkillers alone. Comparing the administration regimens, an improved effect of the composition according to the invention was found when it was taken 30 to 60 minutes after the last alcohol consumption. In this case, more comprehensive relief of hangover symptoms was observed. However, especially in cases of pronounced hangover symptoms, a combined administration regimen of taking the composition according to the invention before bedtime and again after waking up the following morning is advantageous. The comparative study was also repeated for a composition according to the invention that additionally contains caffeine as an adjuvant. Comparable results were achieved, with a particularly significant improvement reported with regard to the criteria of general well-being, alertness, mood, and performance readiness. QUOTES INCLUDED IN THE DESCRIPTION

[0000] This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Cited patent literature

[0000] EP 0 426 479 B1

[0006]

Claims

[1] Composition, in particular pharmaceutical composition, especially for use in the prophylactic and / or therapeutic (symptomatic) treatment of veisalgia (alcohol intoxication, hangover), wherein the composition is in the form of a fixed dosage (fixed dosage form) for oral administration, and wherein the composition comprises an effective, in particular pharmaceutically and / or therapeutically effective, amount of active substances from the drug classes (i) non-steroidal anti-inflammatory drug (NSAID), (ii) H1 antihistamine and (iii) calcium channel antagonist, wherein the active substances are selected from Class (i): Acetylsalicylic acid, ibuprofen, dexibuprofen, flurbiprofen, naproxen, ketoprofen, tiaprofenic acid, diclofenac, indomethacin, acemetacin, flufenamic acid, mefenamic acid, piroxicam, tenoxicam, meloxicam, lornoxicam, nabumetone and / or mixtures thereof, Class (ii): Dimenhydrinate, and Class (iii): Cinnarizine. [2] Composition according to claim 1, wherein the composition contains the active ingredients of classes (i) and (ii) in weight-based ratios of class (i) : class (ii) in the range of 1 : 2 to 20 : 1, in particular 2 : 1 to 15 : 1, preferably 5 : 1 to 10 : 1, and / or wherein the composition contains the active ingredients of classes (i) and (iii) in weight-based ratios of class (i) : class (iii) in the range of 1 : 1 to 30 : 1, in particular 3 : 1 to 25 : 1, preferably 10 : 1 to 20 : 1, and / or wherein the composition contains the active ingredients of classes (ii) and (iii) in weight-based ratios of class (ii) : class (iii) in the range of 5 : 1 to 1 : 1, in particular 3 : 1 to 1 : 1.25, preferably 2.5 : 1 to 1.5 :

1. [3] Composition according to claim 1 or 2, wherein the composition contains the active ingredients of classes (i), (ii) and (iii) in weight-based proportions of class (i) : class (ii) : class (iii) in the range of 30 : 3 : 1 to 3 : 1 : 1, in particular 25 : 2.5 : 1 to 10 : 1.25 : 1, preferably 20 : 2.5 : 1 to 15 : 1.5 :

1. [4] Composition according to any one of the preceding claims, wherein the active ingredient of class (i) is selected from acetylsalicylic acid, ibuprofen, naproxen, diclofenac and / or mixtures thereof, in particular ibuprofen. [5] Composition according to any of the preceding claims, wherein the composition contains the active ingredients in total amounts in a range of 40 wt.% to 98 wt.%, in particular 45 wt.% to 96 wt.%, preferably 50 wt.% to 95 wt.%, based on the total composition. [6] Composition according to any one of the preceding claims, wherein the composition contains active ingredients of class (i) in amounts in the range of 30 wt.% to 75 wt.%, in particular 40 wt.% to 70 wt.%, preferably 50 wt.% to 65 wt.%, based on the total composition, and / or wherein the composition contains active ingredients of class (ii) in amounts in the range of 4 wt.% to 20 wt.%, in particular 5 wt.% to 15 wt.%, preferably 6 wt.% to 10 wt.%, based on the total composition, and / or wherein the composition contains active substances of class (iii) in amounts in the range of 0.5 wt.% to 7 wt.%, in particular 1.5 wt.% to 5 wt.%, preferably 2 wt.% to 4 wt.%, based on the total composition. [7] Composition according to any one of the preceding claims, wherein the composition contains one or more adjuvants, in particular wherein the composition contains adjuvants in amounts in the range of 0.1 wt.% to 50 wt.%, in particular 3 wt.% to 30 wt.%, preferably 5 wt.% to 15 wt.%, based on the total composition. [8] Composition according to any of the preceding claims, wherein the adjuvants are selected from the group consisting of flavoring and / or organoleptic adjuvants, phytotherapeutic adjuvants, plant extracts, vitamins, coenzymes, redox-active adjuvants, amino acids, caffeine-containing adjuvants, stimulating adjuvants and / or mixtures thereof. [9] Composition according to any of the preceding claims, wherein the composition comprises a solid matrix, in particular as a pharmaceutical carrier for the active ingredients. [10] Composition according to any of the preceding claims, wherein the composition contains the matrix in amounts in the range of 2 wt.% to 60 wt.%, in particular 4 wt.% to 55 wt.%, preferably 5 wt.% to 50 wt.%, based on the total composition, and / or wherein the matrix contains one or more pharmaceutically acceptable excipients, in particular selected from the group consisting of fillers, binders, disintegrants, lubricants and / or lubricants, humectants and / or flow regulators, film formers, gelling agents and / or structuring agents, lipophilic components, and / or mixtures thereof, and in particular is formed thereof. [11] Composition according to any of the preceding claims, wherein the composition is in the form of a solid dosage form as a tablet, in particular a film-coated tablet, an uncoated tablet or an enteric-coated tablet, and / or wherein the composition, in particular as a solid dosage form, has a total weight per dose in the range of 0.25 g to 5 g, in particular in the range of 0.4 g to 4 g, preferably in the range of 0.5 g to 3.5 g. [12] Composition according to any one of the preceding claims, wherein the composition, in particular as a solid dosage form, contains per dose class (i) active substances in amounts in the range of 25 mg to 900 mg, in particular 100 mg to 800 mg, preferably 150 mg to 650 mg, and / or wherein the composition per dose contains class (ii) active substances in amounts in the range of 10 mg to 100 mg, in particular 20 mg to 70 mg, preferably 30 mg to 50 mg, and / or wherein the composition per dose contains class (iii) active substances in amounts in the range of 5 mg to 50 mg, in particular 10 mg to 30 mg, preferably 15 mg to 25 mg. [13] Composition according to any of the preceding claims, wherein the composition, based on the total active ingredients, is administered with a daily dose in the range of 50 mg / diem to 2,000 mg / diem, in particular 250 mg / diem to 1,600 mg / diem, preferably 400 mg / diem to 1,400 mg / diem, and / or wherein the composition is prepared as a fixed dosage form, based on the total active ingredients, for administering a daily dose in the range of 50 mg / diem to 2,000 mg / diem, in particular 250 mg / diem to 1,600 mg / diem, preferably 400 mg / diem to 1,400 mg / diem. [14] A medicinal product or drug, in particular for the prophylactic and / or therapeutic treatment of veisalgia, comprising a composition according to one or more of the preceding claims.