Active ingredient with a nicotinic acetyl-cholinergic agonistic effect for use in the treatment of long-covid diseases

Abstract

The present invention relates to the prevention and / or the therapeutic treatment of a disease from the group comprising: Long Covid disease, myalgic encephalomyelitis / chronic fatigue syndrome, fibromyalgia, dementia, neoplastic disease, autoimmune disease, schizophrenia, seizure disorder, hyperinflammatory disease, chronic inflammatory bowel disease, rheumatism, obesity, hyperuricaemia, diabetes mellitus (IDDM / NIDDM), acute viral diseases, amyotrophic lateral sclerosis (ALS), bronchial asthma, atopic-allergic diseases, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), autistic spectrum disorders, autoimmune diseases / antibody-associated diseases, bipolar disorder, celiac disease (CD), chronic obstructive pulmonary disease (COPD), chronic inflammatory bowel disease (CIBD) (i. e. Chron's disease, ulcerative colitis), cystic fibrosis / mucoviscidosis, depression, endometriosis, polycystic ovary syndrome, eating disorders, anxiety disorders, addictions, cardiovascular diseases in the general sense, Alzheimer's, Parkinson's, meningitis, multiple sclerosis (MS), muscular dystrophy, neurodermatitis, peripheral arterial occlusive disease (PAOD), pneumonia, post-vaccination syndrome and vaccination damage in the broadest sense, post-viral syndromes, psoriasis, pulmonary hypertension, restless legs syndrome, restrictive lung diseases, rheumatoid arthritis (RA), schizoaffective disorder, sepsis, scleroderma, systemic lupus erythematosus (SLE) and unfulfilled desire to have children, wherein an active ingredient with a nicotinic acetylcholinergic agonistic effect and / or an active ingredient with a muscarinic acetylcholinergic agonistic and / or muscarinic acetylcholinergic antagonistic effect is used. Very efficient prevention and / or therapeutic treatment of these diseases is thus provided. This prevention and / or treatment are additionally very easily tolerated, cost-effective and easily implemented.

Description

[0001] ACTIVE INGREDIENT WITH NICOTINE ACETTYLCHOLINERG AGONIST EFFECT FOR USE IN THE THERAPY OF LONG-COVID DISEASES

[0002] Prevention and / or therapeutic treatment of a disease from the group comprising: Long Covid disease, myalgic encephalomyelitis / chronic fatigue syndrome, fibromyalgia, dementia, neoplastic disease, autoimmune disease, schizophrenia, seizure disorder, hyperinflammatory disease, chronic inflammatory bowel disease and rheumatic disease, obesity, hyperuricemia, diabetes mellitus (IDDM / NIDDM), acute viral diseases, amyotrophic lateral sclerosis (ALS), bronchial asthma, atopic-allergic diseases, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), autism spectrum disorders, autoimmune diseases / antibody-associated diseases, bipolar disorder, celiac disease (CD), chronic obstructive pulmonary disease (COPD), Chronic inflammatory bowel diseases (IBD) (ie Mb.Chron, ulcerative colitis), cystic fibrosis / mucoviscidosis, depression, endometriosis, polycystic ovary syndrome, eating disorders, anxiety disorders, addiction disorders, frontotemporal dementia (Pick's disease), Graves' disease (GD), cardiovascular diseases in the general sense, Alzheimer's disease, Parkinson's disease, meningitis, multiple sclerosis (MS), muscular dystrophy, neurodermatitis, peripheral arterial occlusive disease (PAD), pneumonia, post-vaccination syndrome and vaccine damage in the broadest sense, post-viral syndromes, psoriasis, pulmonary hypertension, restless legs syndrome, restrictive lung diseases, rheumatoid arthritis (RA), schizoaffective disorders.

[0003] Disorder, Sepsis, Sjögren's syndrome (SS), Scleroderma, Systemic Lupus Erythematosus (SLE) and Infertility

[0004] The present invention relates to the technical (i.e., medical-pharmaceutical) field of the prevention and / or therapeutic treatment of a disease from the group comprising: Long Covid disease, Myalgic Encephalomyelitis / Chronic Fatigue Syndrome, Fibromyalgia, Dementia, Neoplastic Disease, Autoimmune Disease, Schizophrenia, Seizure Disorder, Hyperinflammatory Disease, Chronic Inflammatory Bowel Disease, and Rheumatic Disease. Furthermore, the present invention also relates to the technical (i.e.,Medical (pharmaceutical) field of prevention and / or therapeutic treatment of a disease from the group comprising: obesity, hyperuricemia, diabetes mellitus (IDDM / NIDDM), acute viral diseases, amyotrophic lateral sclerosis (ALS), bronchial asthma, atopic-allergic diseases, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), autism spectrum disorders, autoimmune diseases / antibody-associated diseases, bipolar disorder, celiac disease (CD), chronic obstructive pulmonary disease (COPD), chronic inflammatory bowel diseases (IBD) (e.g., Crohn's disease, ulcerative colitis), cystic fibrosis / mucoviscidosis, depression, endometriosis, polycystic ovary syndrome, eating disorders, anxiety disorders, addiction disorders, frontotemporal dementia (Pick's disease), Graves' disease (GD), cardiovascular diseases in the general sense, Alzheimer's disease, Mb.Parkinson's disease, meningitis, multiple sclerosis (MS), muscular dystrophy, atopic dermatitis, peripheral arterial occlusive disease (PAD), pneumonia, post-vaccination syndrome and vaccine damage in the broadest sense, post-viral syndromes, psoriasis, pulmonary hypertension, restless legs syndrome, restrictive lung diseases, rheumatoid arthritis (RA), schizoaffective disorder, sepsis, Sjögren's syndrome (SS), scleroderma, systemic lupus erythematosus (SLE), infertility.

[0005] In particular, the present invention relates to an active ingredient and a medicament or a composition, each for use in the prevention and / or therapeutic treatment of a disease from the group comprising: long-COVID disease, myalgic encephalomyelitis / chronic fatigue syndrome, fibromyalgia, dementia, neoplastic disease, autoimmune disease, schizophrenia, seizure disorder, and hyperinflammatory disease. Within the scope of the present invention, the active ingredient used is an active ingredient with a nicotinic acetylcholinergic agonist effect and / or an active ingredient with a muscarinic acetylcholinergic agonist and / or muscarinic acetylcholinergic antagonist effect, as further defined and described in the following description and in the claims of the present invention.

[0006] In the context of the present invention, "active ingredient with muscarinic acetylcholinergic agonistic and / or muscarinic acetylcholinergic antagonistic effect" means that there are active ingredients that have only one of the two effects, i.e., either muscarinic acetylcholinergic agonistic effect or muscarinic acetylcholinergic antagonistic effect, as well as that there are active ingredients that have both muscarinic acetylcholinergic agonistic effect and muscarinic acetylcholinergic antagonistic effect. The coronavirus SARS-CoV-2 triggered a pandemic catastrophe and took a toll on the world's population, claiming 6 million lives within 30 months (COVID-19 disease). Unprecedented scientific efforts led to a better understanding of virus structure, transmission routes, and pathological patterns, ultimately contributing to the development of sufficiently protective vaccines.

[0007] However, it is now becoming increasingly clear that even after recovery from an acute COVID-19 illness, the suffering is not over in many cases. Symptoms such as chronic fatigue, dizziness, palpitations, photosensitivity, acoustic intolerance, mild fever, loss of the sense of smell (anosmia), memory lapses, loss of the sense of taste (ageusia), muscle weakness, diarrhea and vomiting, difficulty concentrating and sleeping, mood disorders, headaches, cognitive impairment, motor deficits, new-onset diabetes and hypertension, shortness of breath, and exercise intolerance are summarized as post-COVID-19 syndrome. The occurrence of these symptoms weeks or even months after the acute phase of the SARS-CoV-2 infection is independent of the severity of the initial course of the disease. The incidence is estimated at 35% (outpatients) and 87% (inpatients) of all persons with a SARS-CoV-2 infection.Furthermore, the duration of symptoms is unpredictable. After six months, people suffering from long-COVID-19 report an average of 14 persistent symptoms.

[0008] According to the currently applicable nomenclature, up to 4 weeks after the acute infection, the term post-acute COVID-19 disease (PACS) is used; from 4 weeks after the acute infection has subsided up to 12 weeks thereafter, the term post-COVID syndrome is used; and from 12 weeks thereafter, the term long COVID-19 disease is used. For the purposes of this document, post-COVID syndrome and long COVID-19 disease are referred to collectively as "long COVID disease" and "LC," respectively.

[0009] These facts underscore the enormous significance of post-COVID-19 and long-COVID-19 syndrome for global societies in terms of public health, as well as the political, sociopolitical, and financial burdens on the respective systems. The individual physical and psychological hardship of each suffering patient is not to be forgotten. In the majority of cases of long-COVID-19, there is no sign of improvement, so the chronic form of COVID-19 infection persists for years. The severity of this disease can even lead to permanent bed confinement.

[0010] Therefore, an inevitable aftershock for healthcare systems from this chronic form of COVID-19 is to be feared. While many more infected patients will recover from the acute phase of COVID-19, treatment and rehabilitation capacities will be needed for large segments of the population to alleviate the symptoms of the chronic phase of the disease.

[0011] Since there is currently no explanation for the pathophysiology of this phenomenon, there is no satisfactory treatment concept for the significant number of people affected.

[0012] In addition, most of the currently offered purely ameliorative therapies (plasmapheresis, hyperbaric oxygen therapy, numerous pharmacological supplements) do not lead to lasting symptom improvement and are not feasible for individual patients due to their high costs. If health insurance companies were to cover such expenses (currently, this is not comprehensive), the result would be a systemic burden on the healthcare system of unimaginable proportions.

[0013] In this context, reference should also be made to myalgic encephalomyelitis / chronic fatigue syndrome (hereinafter referred to as "ME / CFS"), which is a severe neuroimmunological chronic disease characterized by exceptionally rapid physical and mental exhaustion, which in extreme cases can lead to extensive disability and the need for care.

[0014] In addition to severe fatigue (physical weakness) that significantly limits activity levels, ME / CFS sufferers also suffer from neurocognitive, autonomic, and immunological symptoms. A characteristic of ME / CFS is post-exertional malaise (PEM), a pronounced and persistent exacerbation of all symptoms after minor physical or mental exertion. Post-exertional malaise leads to pronounced weakness, muscle pain, flu-like symptoms, and a deterioration in general health. It typically occurs after even minor exertion, such as walking a few steps.

[0015] In addition to post-exertional malaise, those affected suffer from symptoms of the autonomic nervous system such as palpitations, dizziness, lightheadedness, and blood pressure fluctuations. Many sufferers are therefore no longer able to stand or sit for extended periods. In medical terms, this is referred to as orthostatic intolerance.

[0016] In addition, there are immunological symptoms such as a strong feeling of illness, painful and swollen lymph nodes, sore throat, respiratory infections and an increased susceptibility to infections.

[0017] Many sufferers also suffer from severe pain, such as muscle and joint pain and a new type of headache. Added to this are muscle twitches and cramps, severe sleep disturbances, and neurocognitive symptoms such as difficulty concentrating, remembering, and finding words (often referred to as "brain fog"), as well as hypersensitivity to sensory stimuli. Severely affected individuals therefore often have to lie in darkened rooms and can only communicate with relatives in whispers.

[0018] ME / CFS often begins after an infectious disease. Various pathogens are known to trigger it, such as the Epstein-Barr virus and influenza. After the SARS pandemic of 2002 / 2003, a portion of those affected developed ME / CFS. The current COVID-19 pandemic shows that a subgroup of those affected by LC is developing ME / CFS. Therefore, a significant increase in the number of ME / CFS patients is expected.

[0019] In addition, there are numerous other clinical pictures, such as fibromyalgia (chronic pain disorder that manifests itself through pain in various parts of the body), dementia (patterns of symptoms of different diseases, the main feature of which is a deterioration of several mental (cognitive) abilities compared to the previous state), neoplastic disease (benign and malignant tumor diseases), autoimmune disease (general term for diseases that are based on a disturbed self-tolerance of the organism), schizophrenia (also called "schizophrenic psychosis", is a severe mental illness characterized by temporary, fundamental disturbances of thinking, perception and experience with impairments up to and including loss of contact with reality), seizure disorder (epilepsy and non-epileptic seizures), hyperinflammatory disease (e.g.chronic inflammatory bowel disease and rheumatic disease), the pathogenetic origin of which is also still unclear.

[0020] Against this background, one object of the present invention is to provide an effective prevention and / or therapeutic treatment of a disease from the group comprising: long-term COVID-19 disease, myalgic encephalomyelitis / chronic fatigue syndrome, fibromyalgia, dementia, neoplastic disease, autoimmune disease, schizophrenia, seizure disorder, and hyperinflammatory disease. This prevention or treatment should, in particular, be easily tolerated, cost-effective, and / or easy to apply.

[0021] This object is achieved with the active ingredient according to the invention according to claim 1, the transdermal delivery device according to the invention according to claim 15 and the medicament or drug according to the invention according to claim 17. Advantageous further developments are specified in the respective dependent claims and in the following description.

[0022] The inventors have recognized that this problem can be solved in a surprising and particularly simple manner by using an active ingredient with nicotinic acetylcholinergic agonistic effect and / or an active ingredient with muscarinic acetylcholinergic agonistic and / or antagonistic effect for use in the prevention and / or therapeutic treatment of a disease from the group comprising: long Covid disease, myalgic encephalomyelitis / chronic fatigue syndrome, fibromyalgia, dementia, neoplastic disease, autoimmune disease, schizophrenia, seizure disorder and hyperinflammatory disease.The inventor hypothesized that nicotinic acetylcholine receptors (hereinafter referred to as "nAChRs") play a central role in the chronic form of the disease and that their blockade by SARS-CoV-2 can be reversed by transcutaneous nicotine application (nicotine patches), which could lead to a re-establishment of physiological cholinergic signaling (neurotransmission). This hypothesis was confirmed in the cases studied. nAChRs are receptors that occur on almost every human cell membrane and primarily function to adapt the specific metabolic performance of the cell to the current needs of the organism. They thus ensure effective cooperation among the approximately 10 trillion cells of the human body with regard to energy consumption, energy supply, and, last but not least, the coherence of all metabolic pathways.

[0023] Given the central role of nAChRs in interneuronal communication and their involvement in almost every synaptic signaling pathway, it is possible that SARS-CoV-2 binds to these nAChRs. The fact that this binding occurs on a large scale in a non-intrinsic manner (i.e., not stimulating the receptor, but rather blocking it) is a plausible explanation for the diverse LC symptoms. By competitively inducing a reduced effect of its natural ligand (acetylcholine, abbreviated to "ACh"), viral blockade of these receptors leads to a profound impairment of cholinergic neurotransmission. Thus, most LC-related deficits can be attributed to such neuromodulatory impairment.

[0024] This hypothesis explains, without exception, all symptoms associated with LC and ME / CFS (both post-viral), as well as the individual differences in disease presentation and severity of symptoms.

[0025] Nicotine as an active ingredient has already been tested and established for its safety and side effects in its transcutaneous form of administration (nicotine patch). Therefore, no incalculable risks are seen in its introduction for the treatment of LC and ME / CFS. More specifically, apart from the use of transcutaneous nicotine application as a substitute for smoking cessation, the transcutaneous application of this substance has been investigated in clinical trials to evaluate its therapeutic effects on neurological or gastrointestinal disorders in non-smoking patients. These studies showed no significant side effects. However, the use of very high doses of nicotine (up to 107 mg / day) led to frequent nausea and vomiting in almost every patient using more than 90 mg / day.Nevertheless, all subjects in a study investigating the ameliorative effect of nicotine on Parkinson's disease showed improved motor performance under reduced dopaminergic treatment. In contrast to the known addictive potential associated with chronic nicotine inhalation, none of the studies demonstrated nicotine dependence after discontinuation of transcutaneous nicotine application.

[0026] Since nicotine has an approximately 30-fold higher affinity for the nAChRs and thus triggers a 30-fold increase in the acetylcholine effect, it is assumed that the nicotine molecule is capable of competitively overcoming the viral blockade. The released viral load is eradicated after a reasonable reaction time of the humoral immune system, which explains the initial deterioration in the sense of a mild infection. No COVID reinfections have been observed to date.

[0027] In the meantime, numerous self-users have reported a significant improvement in symptoms, even reaching complete recovery.

[0028] Instead of nicotine, other active substances with nicotinic acetylcholinergic agonistic effects can also be used, so that the invention is not intended to be limited to nicotine.

[0029] However, since some users experience only unsatisfactory clinical improvement in symptoms, it is suspected that the muscarinic acetylcholine receptors (hereinafter referred to as "mAChRs") may also be affected by the blockade. This blockade can be reversed by an alkaloid active ingredient (scopolamine) in a similar manner to that used for nAChRs. It should be noted that in the case of mAChRs, the active ingredient scopolamine does not exert an agonistic but rather an antagonistic (blocking) effect, which, however, equally leads to the displacement of the residual viral load and, due to the short half-life of the active ingredient itself, results in physiological cholinergic neurotransmission.

[0030] Since this active ingredient has already been tested and established in the long term with regard to its safety and side effects in its transcutaneous administration form (rice sickness patch), no incalculable risks are seen in its introduction for the treatment of LC and ME / CFS.

[0031] Instead of scopolamine, other active substances with muscarinic acetylcholinergic agonistic and / or muscarinic acetylcholinergic antagonistic effects can also be used, so that the invention is not intended to be limited to scopolamine.

[0032] To achieve the above-described object, the present invention therefore proposes, according to a first aspect of the present invention, an active ingredient with nicotinic acetylcholinergic agonistic effect and / or an active ingredient with muscarinic acetylcholinergic agonistic and / or muscarinic acetylcholinergic antagonistic effect for use in the prevention and / or therapeutic treatment of a disease from the group comprising: Long Covid disease, myalgic encephalomyelitis / chronic fatigue syndrome, fibromyalgia, dementia, neoplastic disease, autoimmune disease, schizophrenia, seizure disorder, hyperinflammatory disease, chronic inflammatory bowel disease, rheumatic disease, obesity, hyperuricemia, diabetes mellitus (IDDM / N IDDM), acute viral diseases, amyotrophic lateral sclerosis (ALS), bronchial asthma, Atopic-allergic diseases, attention deficit disorder (ADD),Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorders, Autoimmune / Antibody-Associated Disorders, Bipolar Disorder, Celiac Disease (CD), Chronic Obstructive Pulmonary Disease (COPD), Chronic Inflammatory Bowel Disease (IBD) (e.g., Chron's Disease, Ulcerative Colitis), Cystic Fibrosis / Music Fibrosis, Depression, Endometriosis, Polycystic Ovarian Syndrome, Eating Disorders, Anxiety Disorders, Addiction Disorders, Frontotemporal Dementia (Pick's Disease), Graves' Disease (GD), Cardiovascular Diseases in the General Sense, Alzheimer's Disease, Parkinson's Disease, Meningitis, Multiple Sclerosis (MS), Muscular Dystrophy, Atopic Dermatitis, Peripheral Arterial Occlusive Disease (PAD), Pneumonia, Post-Vaccination Syndrome and Vaccination Damage in the Broadest Sense, Post-Viral Syndromes, Psoriasis, Pulmonary Hypertension, Restless legs syndrome, Restrictive lung diseases, Rheumatoid arthritis (RA), Schizoaffective disorder, Sepsis, Sjögren's syndrome (SS), Scleroderma,Systemic lupus erythematosus (SLE) and infertility.

[0033] The wording "active ingredient with nicotinic acetylcholinergic agonist effect and / or active ingredient with muscarinic acetylcholinergic agonist and / or muscarinic acetylcholinergic antagonist effect" includes both individual active ingredients and mixtures of active ingredients with the corresponding effect.In other words, it can be a) only one active ingredient with nicotinic acetylcholinergic agonist effect, b) only one active ingredient with muscarinic acetylcholinergic agonist and / or muscarinic acetylcholinergic antagonist effect, c) only one active ingredient with both nicotinic acetylcholinergic agonist effect and muscarinic acetylcholinergic agonist and / or muscarinic acetylcholinergic antagonist effect, d) a mixture of active ingredients with only nicotinic acetylcholinergic agonist effect, e) a mixture of active ingredients with only muscarinic acetylcholinergic agonist and / or muscarinic acetylcholinergic antagonist effect or f) a mixture of active ingredients with both nicotinic acetylcholinergic agonist effect and muscarinic acetylcholinergic agonist and / or muscarinic acetylcholinergic antagonist effect.

[0034] J.-P. Changeux et al. (Changeux JP, Amoura Z, Rey FA, ​​M iyara M . A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications. Comptes Rendus Biologies 2020; 343: 33-9) had already pointed out, with reference to the acute COVID-19 disease, the high similarity between a specific section (toxin-like region = PRRA motif) of the viral spike glycoprotein (SGP), which generally generates viral contact with human cells, and various cholinergic toxins (bungarotoxin, cobratoxin, and others), whose toxic effect consists in blocking the nAChRs and mAChRs. However, this only concerned the acute phase of COVID-19 disease. It is the inventor's special achievement to have discovered that nicotine (and possibly other alkaloids) can also be used to treat the chronic form of COVID-19 disease.

[0035] Also for the following diseases: Fibromyalgia, dementia, neoplastic disease, autoimmune disease, schizophrenia, seizure disorder, hyperinflammatory disease, inflammatory bowel disease, rheumatic disease, obesity, hyperuricemia, diabetes mellitus (IDDM / NI DDM), acute viral diseases, amyotrophic lateral sclerosis (ALS), bronchial asthma, atopic-allergic diseases, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), autistic spectrum disorders, autoimmune diseases / antibody-associated diseases, bipolar disorder, celiac disease (CD), chronic obstructive pulmonary disease (COPD), chronic inflammatory bowel disease (IBD) (e.g., Crohn's disease, ulcerative colitis), cystic fibrosis / mucoviscidosis, depression, endometriosis, polycystic ovary syndrome, eating disorders, anxiety disorders, addiction disorders, frontotemporal dementia (Mb. Pick), Graves' disease (GD),The actual cause of cardiovascular diseases in the general sense, Alzheimer's disease, Parkinson's disease, meningitis, multiple sclerosis (MS), muscular dystrophy, atopic dermatitis, peripheral arterial occlusive disease (PAD), pneumonia, postvaccination syndrome and vaccine damage in the broadest sense, postviral syndromes, psoriasis, pulmonary hypertension, restless legs syndrome, restrictive lung diseases, rheumatoid arthritis (RA), schizoaffective disorder, sepsis, Sjögren's syndrome (SS), scleroderma, systemic lupus erythematosus (SLE), and infertility remains unclear. Since chronic impairment of cholinergic neurotransmission could be a highly plausible explanatory model for these clinical pictures as well, it is suspected thatthat the inventive use of the active ingredient with nicotinic acetylcholinergic agonistic effect and / or the active ingredient with muscarinic acetylcholinergic agonistic and / or muscarinic acetylcholinergic antagonistic effect for use in the prevention and / or therapeutic treatment of a disease from the group comprising: fibromyalgia, dementia, neoplastic disease, autoimmune disease, schizophrenia, seizure disorder, hyperinflammatory disease, chronic inflammatory bowel disease, rheumatic disease, obesity, hyperuricemia, diabetes mellitus (IDDM / N IDDM), acute viral diseases, amyotrophic lateral sclerosis (ALS), bronchial asthma, atopic-allergic diseases, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), autistic Spectrum disorders, autoimmune diseases / antibody-associated diseases, bipolar disorder, celiac disease (CD),Chronic obstructive pulmonary disease (COPD), chronic inflammatory bowel disease (IBD) (e.g., Crohn's disease, ulcerative colitis), cystic fibrosis, depression, endometriosis, polycystic ovary syndrome, eating disorders, anxiety disorders, addiction disorders, frontotemporal dementia (Pick's disease), Graves' disease (GD), cardiovascular diseases in the general sense, Alzheimer's disease, Parkinson's disease, meningitis, multiple sclerosis (MS), muscular dystrophy, atopic dermatitis, peripheral arterial occlusive disease (PAD), pneumonia, postvaccination syndrome and vaccine damage in the broadest sense, postviral syndromes, psoriasis, pulmonary hypertension, restless legs syndrome, restrictive lung diseases, rheumatoid arthritis (RA), schizoaffective disorder, sepsis, Sjögren's syndrome (SS), Scleroderma, systemic lupus erythematosus (SLE) and infertility will also be helpful.

[0036] In an advantageous further development, the active ingredient contains an alkaloid. This allows for a particularly good effect on the respective acetylcholine receptors.

[0037] In an advantageous embodiment, the active ingredient is an active ingredient with selective nicotinic acetylcholinergic agonist activity (nAChRs) and / or an active ingredient with selective muscarinic acetylcholinergic agonist and / or muscarinic acetylcholinergic antagonist activity (mAChRs). This allows undesirable side effects (in the case of an alkaloid with a muscarinic acetylcholinergic antagonist effect) to be mutually reduced to a large extent.

[0038] In an advantageous embodiment, the active ingredient comprises a toxin, preferably a plant toxin, a fungal toxin, a snake toxin, or a frog toxin, with the active ingredient particularly comprising a substance from the group consisting of nicotine and scopolamine. These active ingredients are particularly effective. In an advantageous embodiment, the active ingredient is administered transcutaneously and / or is prepared in a dosage form suitable for transcutaneous administration. This results in particularly few undesirable side effects.

[0039] In an advantageous development, the active ingredient is administered using a transdermal delivery device (transdermal therapeutic system / TTS), preferably using a therapeutic patch (drug patch), and / or the active ingredient is prepared for administration in a transdermal delivery device (transdermal therapeutic system / TTS), which preferably has a therapeutic patch (drug patch). This results in particularly few undesirable side effects, and such therapeutic patches are particularly well-tested.

[0040] Therapeutic patches administer the active ingredient transcapillary directly into the venous bloodstream without entering the digestive system. They typically have a self-adhesive layer applied to a carrier layer, such as a fabric. The active ingredient can be incorporated into the adhesive layer itself or into a separate active ingredient layer. In addition, such patches usually have a removable protective film on the adhesive layer.

[0041] In an advantageous further development, the active ingredient is administered in pharmaceutically effective or therapeutically effective amounts and / or the active ingredient is prepared for administration in pharmaceutically effective or therapeutically effective amounts. This makes prevention or treatment particularly effective.

[0042] In an advantageous further development, the active ingredient is administered at a daily dosage of between 0.50 mg / day and 24.00 mg / day and / or the active ingredient is prepared for administration at a daily dosage of between 0.50 mg / day and 24.00 mg / day. These dosages have demonstrated particularly good efficacy. The (daily) dosages specified here and below each refer to an individual active ingredient. They may differ for the active ingredient with nicotinic acetylcholinergic agonist action and the active ingredient with muscarinic agonist and / or muscarinic acetylcholinergic antagonist action.

[0043] For nicotine, for example, a daily dosage of 1.25 to 24.00 mg / diem is recommended, with a daily dosage of 1.25 to 5.00 mg / diem being recommended for children weighing between 30 kg and 65 kg, a daily dosage of 3.50 to 20.00 mg / diem for adult non-smokers and a daily dosage of 7.00 to 24.00 mg / diem for adult smokers.

[0044] For example, for scopolamine, a daily dosage of 0.50 to 1.00 mg / day is recommended. If scopolamine is administered alone, it could also be administered at a dosage in the range 1.50 mg / 72h to 3.00 mg / 72h.

[0045] In an advantageous further development, the daily dosage is increased after treatment lasting 1 to 5 days, preferably 2 to 4 days, and especially 3 days. This further increases the effectiveness.

[0046] In an advantageous further development, after a treatment period of 5 to 10 days, preferably 6 to 8 days, in particular 7 days, a drug-free break of 5 to 9 days, preferably 6 to 8 days, in particular 7 days, is introduced. After the break, the daily dosage preferably remains the same or is increased. The effect is thus even more effective, with the break being explained by the dynamic conformational change that begins with continuous stimulation, in the sense of desensitization of the nAChRs or mAChRs.

[0047] In an advantageous further development, it is provided that the active ingredient is administered for use in adult smokers (aged 16 and over) at a daily dosage of between 7.00 mg / day and 24.00 mg / day and / or that the active ingredient is prepared for use in smokers at a daily dosage of between 7.00 mg / day and 24.00 mg / day. These dosages have proven particularly effective in smokers. In an advantageous further development, it is provided that the active ingredient is administered for use in children at a daily dosage of between 1.25 mg / day and 5.00 mg / day and / or that the active ingredient is prepared for use in children at a daily dosage of between 1.25 mg / day and 5.00 mg / day. These dosages have proven particularly effective in children.

[0048] In an advantageous further development, the active ingredient is administered for use in adult non-smokers at a daily dosage of between 3.50 mg / day and 20.00 mg / day, and / or the active ingredient is prepared for use in non-smokers at a daily dosage of between 3.50 mg / day and 20.00 mg / day. These dosages have proven particularly effective in non-smokers.

[0049] In an advantageous further development, the active ingredient for use in adult smokers is administered at a daily dose of 7.00 mg / day for 3 days, followed by a daily dose of 14.00 mg / day for 7 days, followed by a 7-day drug-free break, and then a daily dose of 24.00 mg / day for a specific period. These dosages have proven particularly effective in non-smokers.

[0050] In an advantageous further development, the active ingredient is administered to adult non-smokers at a daily dose of 3.50 mg / day for 3 days, followed by a daily dose of 7.00 mg / day for 7 days. This is followed by a 7-day drug-free break, and then a daily dose of 14.00 mg / day is administered for a specific period. These dosages have proven particularly effective in non-smokers.

[0051] In an advantageous further development, the active ingredient for use in children is administered at a daily dosage of 1.25 mg / day for 2 days, followed by a daily dosage of 3.50 mg / day for 2 days, and then a daily dosage of 5.00 mg / day for 6 days. This is followed by a 7-day drug-free break, after which a daily dosage of 5.00 mg / day is administered for a specific period. These dosages have proven particularly effective in children.In an advantageous development, it is provided that a specific daily dosage of the active ingredient administered using a transdermal patch and / or prepared for administration in a transdermal patch is adjusted by providing the transdermal patch with a higher daily dosage than the specific daily dosage with a corresponding partial, drug-impermeable adhesive covering the active ingredient surface of the patch. This allows for particularly simple dosage adjustment.

[0052] In an advantageous development, it is provided that a specific daily dosage of the active ingredient administered using a transdermal patch and / or prepared for administration in a transdermal patch is set by cutting off a corresponding partial area of ​​the active ingredient surface of the patch from the transdermal patch with a daily dosage higher than the specific one. This also allows for particularly simple dosage adjustment.

[0053] In an advantageous further development, the active ingredient is available as a combination preparation with selective nicotinic acetylcholinergic agonist action and selective muscarinic acetylcholinergic agonist and / or muscarinic acetylcholinergic antagonist action. The advantage of such a combination preparation lies not only in comprehensive prevention or causal treatment of the clinical picture, but also in the mutual reduction of side effects caused by the individual active ingredients through co-administration of the active ingredients. In particular, scopolamine would reduce or eliminate the side effects of nicotine such as nausea, vomiting, palpitations, and nightmares.

[0054] To achieve the above-described object, the present invention proposes, according to a second aspect of the present invention, a transdermal delivery device comprising an active ingredient with nicotinic acetylcholinergic agonist action and / or an active ingredient with muscarinic acetylcholinergic agonist and / or muscarinic acetylcholinergic antagonist action, for use in the prevention and / or therapeutic treatment of a disease from the group comprising: Long Covid disease, Myalgic Encephalomyelitis / Chronic Fatigue Syndrome, Fibromyalgia, Dementia, Neoplastic Disease, Autoimmune Disease, Schizophrenia, Seizure Disorder, Hyperinflammatory Disease, Chronic Inflammatory Bowel Disease, Rheumatic Disease, Obesity, Hyperuricemia, Diabetes Mellitus (IDDM / IDDM), Acute Viral Diseases, Amyotrophic Lateral Sclerosis (ALS), Asthma bronchial,Atopic-allergic diseases, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), autism spectrum disorders, autoimmune diseases / antibody-associated diseases, bipolar disorder, celiac disease (CD), chronic obstructive pulmonary disease (COPD), chronic inflammatory bowel diseases (IBD) (e.g., Crohn's disease, ulcerative colitis), cystic fibrosis / mucoviscidosis, depression, endometriosis, polycystic ovary syndrome, eating disorders, anxiety disorders, addiction disorders, frontotemporal dementia (Pick's disease), Graves' disease (GD), cardiovascular diseases in the general sense, Alzheimer's disease, Parkinson's disease, meningitis, multiple sclerosis (MS), muscular dystrophy, atopic dermatitis, peripheral arterial occlusive disease (PAD), pneumonia, post-vaccination syndrome and vaccine damage in the broadest sense, post-viral syndromes, psoriasis, pulmonary hypertension, restless legs syndrome, restrictive lung diseases, rheumatoid arthritis (RA),Schizoaffective disorder, sepsis, Sjögren's syndrome (SS), scleroderma, systemic lupus erythematosus (SLE), and infertility.

[0055] In an advantageous further development, it is provided that the active ingredient is designed as the active ingredient according to the invention.

[0056] To achieve the above-described object, the present invention proposes, according to a third aspect of the present invention, a pharmaceutical composition or medicament for use in the prevention and / or therapeutic treatment of a disease from the group comprising: Long Covid disease, Myalgic Encephalomyelitis / Chronic Fatigue Syndrome, Fibromyalgia, Dementia, Neoplastic Disease, Autoimmune Disease, Schizophrenia, Seizure Disorder, Hyperinflammatory Disease, Chronic Inflammatory Bowel Disease, Rheumatic Disease, Obesity, Hyperuricemia, Diabetes Mellitus (IDDM / IDDM), Acute Viral Diseases, Amyotrophic Lateral Sclerosis (ALS), Bronchial Asthma, Atopic-Allergic Diseases, Attention Deficit Disorder (ADD), Attention Deficit Hyperactivity Disorder (ADHD), Autistic Spectrum Disorders, Autoimmune Diseases / Antibodies associated diseases, bipolar disorder,Celiac disease (CD), chronic obstructive pulmonary disease (COPD), chronic inflammatory bowel disease (IBD) (e.g., Crohn's disease, ulcerative colitis), cystic fibrosis, depression, endometriosis, polycystic ovary syndrome, eating disorders, anxiety disorders, addiction disorders, frontotemporal dementia (Pick's disease), Graves' disease (GD), cardiovascular diseases in the general sense, Alzheimer's disease, Parkinson's disease, meningitis, multiple sclerosis (MS), muscular dystrophy, atopic dermatitis, peripheral arterial occlusive disease (PAD), pneumonia, postvaccination syndrome and vaccine damage in the broadest sense, postviral syndromes, psoriasis, pulmonary hypertension, restless legs syndrome, restrictive lung diseases, rheumatoid arthritis (RA), schizoaffective disorder, sepsis, Sjögren's syndrome (SS), scleroderma, systemic lupus erythematosus (SLE) and infertility, where the drug or medication,contains an active ingredient with nicotinic acetylcholinergic agonist effect and / or an active ingredient with muscarinic acetylcholinergic agonist and / or muscarinic acetylcholinergic antagonist effect.

[0057] In an advantageous further development, it is provided that the active ingredient is designed as the active ingredient according to the invention.

[0058] The features and further advantages of the present invention will become clear below from the description of preferred embodiments.

[0059] patients

[0060] A woman (32 years old) and three men (19, 41, and 52 years old, respectively) were examined. Following a PCR-confirmed SARS-CoV-2 infection with a mild course of disease, they suffered from numerous symptoms suggestive of post-COVID-19 syndrome. The patients described weakness, dyspnea, sleep disturbances, dizziness, total ageusia and anosmia, as well as a variety of other symptoms. With the exception of the youngest, the patients were unable to continue activities of daily living compared to the period before the SARS-CoV-2 infection. Since these multiple nonspecific symptoms did not improve over a period of time without evidence of acute COVID-19 infection, they consulted the inventor at his outpatient clinic.

[0061] Procedure After carefully explaining the hypothesis described above, as well as the expected effects of nicotine and possible side effects, the patients were advised to use a standard nicotine patch. Since all included individuals were nicotine-naive, they were instructed to use the lowest available dosage (7.5 mg / 24 h) and to administer the patch once daily (in the morning). All patients followed these instructions, with the exception of the 41-year-old patient. He mistakenly purchased the patches at a higher dosage (15 mg / 24 h) than recommended. In all cases, the patients were asked to record their symptoms starting four days before using the nicotine patch and to rate the severity of their symptoms daily on a scale of zero to five.

[0062] Case 1

[0063] The 19-year-old, otherwise healthy patient was diagnosed with SARS-CoV-2 infection on March 26, 2021, through a positive PCR test. The patient reported a mild course of the acute infectious disease with symptoms such as mild fever, sore throat, and weakness, which completely resolved within 10 days. Approximately three weeks after the detection of the infection, the patient noticed a sudden loss of his sense of smell and taste, as well as general fatigue. These symptoms persisted over the next few months, with only minimal fluctuations in symptom severity.

[0064] Upon presentation to the inventor's outpatient clinic in November 2021, the nicotine-naive patient was counseled about the apparent manifestation of post-COVID-19 syndrome and informed about the challenging diagnostic and therapeutic approach to the described symptoms. The patient consented to the off-label use of percutaneous nicotine application and began 24-hour application of nicotine patches (7.5 mg / 24 h) for seven days on November 23, 2021.

[0065] In the days prior to nicotine use, weakness was noted at the two highest possible levels (levels four to five), and anosmia and ageusia were reported at the highest possible level (level five).

[0066] During nicotine treatment, recovery from weakness occurred most rapidly. A daily reduction in symptom severity was achieved, so that stage two was reached on the third day of treatment and maintained for another three days. Stage one was reported on the sixth day, and by the ninth day, the patient reported no longer experiencing weakness.

[0067] The loss of taste decreased by one level on the first day of treatment, dropped to level three on the third day, decreased further to level two on the tenth day, and reached level one on the thirteenth day. On the 16th day of treatment, the patient reported complete recovery of his sense of taste.

[0068] A similarly sustained symptom reduction was observed in anosmia. Beginning on day three, the patient experienced a decline from stage five to stage four, further declining to stage three on day seven, to stage two on day ten, and reaching stage one on day thirteen. By day sixteen, the patient reported being able to smell as well as before his SARS-CoV-2 infection.

[0069] In a follow-up interview approximately six months after the intervention, the patient reported being free of symptoms.

[0070] Upon initiating nicotine administration, the patient suffered from diarrhea for two days, which resolved spontaneously and was classified by the patient as mild (stage one). This symptom is interpreted as a classic side effect of nicotine. No further intervention was required.

[0071] Case 2

[0072] The 31-year-old patient presented to the inventor's outpatient clinic on December 17, 2020, after experiencing an acute SARS-CoV-2 infection, which was confirmed by a positive PCR test on November 21, 2020. Moderate symptoms included fever, reduced sense of smell and taste, loss of appetite, headache, pain in the limbs, reduced memory, listlessness, and a runny nose, as well as neck, limb, and back pain. The acute phase of infection lasted until December 5, 2020, when recovery was confirmed by a negative PCR test. From this point on, she experienced numerous symptoms, such as chronic fatigue (stage four), loss of smell and taste (stage one), pronounced concentration difficulties (stage four), headache (stage four), and significant exercise intolerance (stage four).

[0073] The otherwise healthy, nicotine-naive patient received all information, explanation, informed consent and nicotine therapy as described for Case 1 (7.5 mg / 24 h).

[0074] From the second day after initiating nicotine therapy, the patient reported a reduction in fatigue of one level per day. By the fourth day, the fatigue had completely disappeared. However, from the sixth day onward, the patient experienced a recurrence of fatigue to a lesser extent (level three), which then progressed as follows: day thirteen (level two), day twenty (level one), and day twenty-three (level zero).

[0075] The patient's impaired memory was perceived as very severe before and at the beginning of treatment (level four). From the third day after nicotine administration, it decreased significantly (level two) and was no longer noticeable by the fourth day.

[0076] Likewise, the ability to concentrate was impaired until the concentration level perceived before SARS-CoV-2 was regained from the fourth day after the start of nicotine therapy.

[0077] Likewise, the significantly impaired exercise tolerance (level four) decreased significantly on the third day (level one), became unreproducible on the fourth day, but increased slightly again on days five (level two) and six (level three), before declining continuously from day eight onward. From day 24 after nicotine use, the patient reported a full recovery of her physical performance.

[0078] From the second day onward, the patient experienced a very unpleasant feeling of tightness in the chest area, which she reported persisting until the thirteenth day after starting nicotine therapy (levels three to five). From then on, it decreased continuously (level three on day fourteen, level two on day nineteen, level one on day twenty-two) until complete remission was achieved on day twenty-three.

[0079] This symptom of tension, which began immediately upon initiating nicotine therapy, is attributed to a side effect of the active ingredient nicotine. The patient also assumed that these symptoms were related to nicotine, which is why she decided to discontinue nicotine therapy on the sixth day rather than continuing until the seventh day, as recommended by the inventor. The reason for this decision was the otherwise very good symptom remission up to the fourth day of nicotine therapy (all symptoms at zero level). In a telephone interview after approximately six months, the patient confirmed that her symptoms had not recurred.

[0080] Case 3

[0081] A 41-year-old male patient visited the inventor's outpatient clinic on December 20, 2022, suffering from a moderate SARS-CoV-2 infection (confirmed on November 13, 2020). His symptoms included weakness, fever, chills, headache, coughing fits, loss of smell and taste, shortness of breath, exercise intolerance, persistent fatigue, and a marked feeling of weakness. At the time of presentation, he was suffering from various persistent symptoms: chronic fatigue (stage three), shortness of breath (stage three), anosmia (stage five), loss of taste (stage five), muscle weakness (stage four), sleep disturbances (stage one), and headache (stage two). The nicotine-naive patient consented to the off-label use of nicotine patches as previously described.

[0082] Unfortunately, the patient did not administer the recommended dose of 7.5 mg / 24 h, but inadvertently doubled it (15 mg / 24 h), resulting in unbearable vomiting (stage five) and diarrhea (stage five) within seven hours. The patient discontinued therapy after ten hours.

[0083] Despite cessation of nicotine use, chronic fatigue decreased significantly on the second day after nicotine use (stage two), decreased further on the third day (stage one), and was no longer detectable on the fourth day.

[0084] Similar to the previously described cases, the symptoms of anosmia and loss of taste showed a rather protracted but continuously decreasing course. The reduction of these two symptoms occurred simultaneously in this particular case. On the eleventh day after nicotine use, there was a slight decrease in both symptoms (level four), which then decreased to level three on the twelfth and thirteenth days. After a decrease to level two on the 14th day, the patient was able to fully perceive all olfactory and gustatory qualities on the 15th day.

[0085] The mild sleep problems reported by the patient (stage one) disappeared permanently (stage zero) on the first day after application of the nicotine patch.

[0086] Regarding the feeling of weakness, the patient described a daily reduction of one level, reaching level one on the third day. This continued for another day and reached final remission (level zero) on the fifth day.

[0087] The persistent headache (level two) reported by the patient disappeared completely (level zero) on the second day after nicotine administration.

[0088] This patient also reported that the described symptoms did not recur after a period of six months.

[0089] Case 4

[0090] A 52-year-old male patient presented to the inventor's outpatient clinic on April 1, 2022, and reported suffering from persistent symptoms such as chronic fatigue (level two), shortness of breath (level two), difficulty concentrating (level one), sleep disturbances (level three), mood swings (level two), chest tightness (level two), and palpitations (level two) since a PCR-positive SARSCoV-2 infection on March 3, 2022.

[0091] After ruling out a persistent acute SARS-CoV-2 infection through a negative PCR test, the patient was informed of the apparent presence of post-COVID syndrome. The nicotine-naive and otherwise healthy patient agreed to a treatment trial with a nicotine patch (7.5 mg / 24 h). Without consultation and contrary to the inventor's recommendation, the patient increased the nicotine dose to 15 mg / 24 h on the third day of therapy. He subsequently discontinued use on the fourth day after almost complete symptom remission. He stated that he had not experienced any side effects from nicotine use, which is why he doubted its effectiveness and therefore applied two nicotine patches of 7.5 mg / 24 h starting on the third day. Chronic fatigue increased slightly on the second day of nicotine use (stage three) and then decreased significantly on the fifth day (stage one). No further fatigue was reported on the sixth day.

[0092] Complaints of shortness of breath subsided on the fifth day (stage one) and were no longer reported from the seventh day onwards (stage zero).

[0093] The patient reported that the concentration difficulties ceased on the first day of nicotine use (level zero).

[0094] Sleep disturbances and mood swings persisted until the fourth day (stage two) and were no longer detectable by the fifth day (stage zero).

[0095] The perceived tightness in the chest (stage two) subsided on the fifth day (stage one) and was no longer detectable on the following day (stage zero).

[0096] The intermittent palpitations (stage one), which were perceived as mild, only appeared two days after starting nicotine use. On the third day of therapy, the patient again noticed episodes of palpitations (stage two), which continued at this level for two days. On the third day of nicotine administration, these symptoms (stage one) subsided and disappeared completely on the fourth day.

[0097] This recurrence of palpitations is interpreted as a classic side effect of nicotine. It stopped spontaneously and required no further treatment.

[0098] In an interview three months after the procedure, the patient confirmed that he had not noticed any recurrence of the symptoms that had led to his initial consultation.

[0099] discussion

[0100] Each of the four presented cases showed significant relief from their persistent symptoms. Improvement was achieved either immediately after application of the nicotine patch or in rapid succession after initiating treatment. There were marked differences in the patterns and durations of symptom relief among the four cases. It is also worth noting that the course of symptom improvement in each of the presented cases was independent of the significantly different duration and progression prior to nicotine therapy.

[0101] In each case, symptoms of exhaustion such as fatigue, weakness, breathlessness and exercise intolerance improved rapidly and comprehensively after nicotine exposure (at the latest by the sixth day).

[0102] In cases with impairment or loss of the sense of taste and smell, improvement has been observed over a longer period of time, with full recovery of these senses occurring within thirteen to sixteen days.

[0103] The perceived chest tightness and rapid heartbeat (palpitations) were described as severe (stage two) and resolved on the second day after their onset (day three after the start of nicotine administration). Regarding the chest tightness described in Case 2, the patient stated that she did not experience any impairment in performance. This made a coronary and / or vascular origin of the problem unrealistic from the inventor's perspective. The patient documented a complete recovery from this side effect on the 22nd day after the start of nicotine therapy.

[0104] The amount of virally blocked AChR can vary greatly from person to person, which certainly influences the course of symptom reduction. This may require individualized nicotine doses and application intervals tailored to the individual patient.

[0105] All described cases were observed in non-smokers. Severe side effects were observed only in the patient who inadvertently used twice the recommended nicotine dose. Severe nausea associated with sweating and repeated vomiting are classic side effects of nicotine and the reason for discontinuation of therapy in this patient. However, with continued nicotine abstinence after this dosing error, all COVID-19-related symptoms previously documented by the patient diminished until restitutio ad integrum was achieved on the fifteenth day after nicotine use. From the inventor's perspective, this development supports the underlying hypothesis, as the displacement of SARS-CoV-2 from nAChR binding sites should follow a specific dose-response relationship.

[0106] In the case of the patient who independently doubled the recommended dose from the third day onwards (case four), it is suspected that the administration of the recommended dose may have led to a habituation reaction, which helped to reduce possible side effects of the higher dosage.

[0107] Release of the SARS-CoV-2 virus from nAChR receptors can lead to short-term viremia with signs of acute SARS-CoV-2 infection at the start of nicotine therapy. However, this viral load should be neutralized within a short time by the humoral component of the immune system due to the SARS-CoV-2 antibodies produced during the acute phase of infection.

[0108] Transcutaneous administration of nicotine ensures constant serum levels without significant peaks. Thus, no development of nicotine dependence was observed during nicotine patch therapy. From the inventor's perspective, this is not to be expected. The overwhelming similarity between the large number of symptoms of LC syndrome and the known central and peripheral symptoms of central anticholinergic syndrome encourages the inventor to assume that LC must be a profound cholinergic signaling disorder. Caused by a significantly higher affinity of SARS-CoV-2 for the nAChR compared to its natural ligand ACh, its displacement of AChRs and subsequent blockade of the intrinsic activity of ACh on the nAChR helps to plausibly explain the myriad typical symptoms.

[0109] The presented cases describe patients who had no comorbidities besides their LC syndrome. Therefore, the indiscriminate use of nicotine patches is not advisable in patients with relevant cardiovascular or respiratory diseases, or in patients taking existing medication. For such patients, nicotine administration under inpatient conditions is safer. In a telephone follow-up with the patients three to six months after the intervention, no symptom-related relapses were observed.

[0110] Although the exemplary embodiments only describe the use of nicotine patches, the invention is not limited to these nicotine patches. Furthermore, the invention is not limited to the use of active ingredients with nicotinic acetylcholinergic agonist effects; rather, active ingredients with muscarinic acetylcholinergic agonist and / or muscarinic acetylcholinergic antagonist effects may also be used alternatively or additionally.

[0111] Even if the embodiments only describe the use of the present invention in the context of the treatment of a disease, the invention is not limited to treatment, but can also be used for prevention.In addition, the invention can also be used for the disease from the group comprising: fibromyalgia, dementia, neoplastic disease, autoimmune disease, schizophrenia, seizure disorder, hyperinflammatory disease, inflammatory bowel disease, rheumatic disease, obesity, hyperuricemia, diabetes mellitus (IDDM / NI DDM), acute viral diseases, amyotrophic lateral sclerosis (ALS), bronchial asthma, atopic-allergic diseases, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), autistic spectrum disorders, autoimmune diseases / antibody-associated diseases, bipolar disorder, celiac disease (CD), chronic obstructive pulmonary disease (COPD), chronic inflammatory bowel diseases (IBD) (ie M b.Chron, ulcerative colitis), cystic fibrosis / mucoviscidosis, depression, endometriosis, polycystic ovary syndrome, eating disorders, anxiety disorders, addiction disorders, frontotemporal dementia (Pick's disease), Graves' disease (GD), cardiovascular diseases in the general sense, Alzheimer's disease, Parkinson's disease, meningitis, multiple sclerosis (MS), muscular dystrophy, neurodermatitis, peripheral arterial occlusive disease (PAD), pneumonia, post-vaccination syndrome and vaccine damage in the broadest sense, post-viral syndromes, psoriasis, pulmonary hypertension, restless legs syndrome, restrictive lung diseases, rheumatoid arthritis (RA), schizoaffective disorder, sepsis, Sjögren's syndrome (SS), scleroderma, systemic lupus erythematosus (SLE) and infertility.According to a particularly preferred embodiment of the invention, combination preparations are used, wherein a first active ingredient has a nicotinic acetylcholinergic agonist effect and / or a muscarinic acetylcholinergic agonist and / or antagonist effect, and a second active ingredient is used to alleviate known side effects of the first active ingredient. Ideally, the combination preparation combines a first active ingredient with a nicotinic acetylcholinergic agonist effect with an active ingredient with a muscarinic acetylcholinergic agonist and / or antagonist effect, wherein one of the two active ingredients, in particular the second active ingredient, alleviates the known side effects of the other active ingredient.

[0112] From the above description it has become clear that the present invention provides a very efficient prevention and / or therapeutic treatment of a disease from the group comprising: Long Covid disease, Myalgic Encephalomyelitis / Chronic Fatigue Syndrome, Fibromyalgia, Dementia, Neoplastic Disease, Autoimmune Disease, Schizophrenia, Seizure Disorder, Hyperinflammatory Disease, Chronic Inflammatory Bowel Disease, Rheumatic Disease, Obesity, Hyperuricemia, Diabetes Mellitus (IDDM / N IDDM), Acute Viral Diseases, Amyotrophic Lateral Sclerosis (ALS), Bronchial Asthma, Atopic-Allergic Diseases, Attention Deficit Disorder (ADD), Attention Deficit Hyperactivity Disorder (ADHD), Autistic Spectrum Disorders, Autoimmune Diseases / Antibody-Associated Diseases, Bipolar Disorder, Celiac Disease (CD), Chronic obstructive pulmonary disease (COPD),Chronic inflammatory bowel diseases (IBD) (e.g., Crohn's disease, ulcerative colitis), cystic fibrosis / mucoviscidosis, depression, endometriosis, polycystic ovary syndrome, eating disorders, anxiety disorders, addiction disorders, frontotemporal dementia (Pick's disease), Graves' disease (GD), cardiovascular diseases in the general sense, Alzheimer's disease, Parkinson's disease, meningitis, multiple sclerosis (MS), muscular dystrophy, atopic dermatitis, peripheral arterial occlusive disease (PAD), pneumonia, postvaccination syndrome and vaccine damage in the broadest sense, postviral syndromes, psoriasis, pulmonary hypertension, restless legs syndrome, restrictive lung diseases, rheumatoid arthritis (RA), schizoaffective disorder, sepsis, Sjögren's syndrome (SS), scleroderma, systemic lupus erythematosus (SLE) and unfulfilled desire for children. This prevention and treatment are also easily tolerated,Cost-effective and easy to apply. Given the significant burden on healthcare systems and the expected high incidence of LC syndrome, as well as the currently exceptionally long treatment durations and their unpredictable outcomes, but also considering the significance of the other diseases mentioned, it is worthwhile to pursue this treatment approach. There is minimal therapeutic effort and easily manageable side effects for such a drug patch with known active ingredients. This treatment approach is far superior to the time-consuming, often disappointing, costly, and complex rehabilitation measures currently available to these patients.

[0113] The claims filed now with the application and those filed later are without prejudice to the attainment of further protection.

[0114] Should a closer examination, particularly of the relevant prior art, reveal that one or another feature is beneficial to the purpose of the invention but not crucially important, then, of course, a formulation will be sought that no longer contains such a feature, particularly in the main claim. Such a subcombination is thus also covered by the disclosure of this application.

[0115] The references cited in the dependent claims indicate the further development of the subject matter of the main claim through the features of the respective subclaim. However, these are not to be understood as a waiver of independent, objective protection for the features of the referenced subclaims.

[0116] It should also be noted that the refinements and variants of the invention described in the various embodiments can be combined with one another as desired. Individual or multiple features are interchangeable. These feature combinations are also disclosed. Features disclosed only in the description or individual features from claims comprising a plurality of features can be incorporated into the independent claim(s) at any time as essential to the invention for the purpose of distinguishing them from the prior art, even if such features were mentioned in conjunction with other features or achieve particularly favorable results in conjunction with other features.

[0117] Thus, all features presented in the general description of the invention, the description of the embodiments and the following claims can be essential to the invention both individually and in any combination.

[0118] Features or combinations of features can each constitute an independent invention, the right to claim which is expressly reserved. Individual features from the description of an embodiment do not necessarily have to be combined with one or more or all of the other features specified in the description of this embodiment; in this respect, each subcombination is expressly disclosed. Furthermore, physical features of an active ingredient can be reformulated and used as process features, and process features can be reformulated and used as physical features of an active ingredient. Such a reformulation is therefore automatically disclosed.

Claims

Patent claims 1. Active ingredient with nicotinic acetylcholinergic agonist effect and / or active ingredient with muscarinic acetylcholinergic agonist and / or muscarinic acetylcholinergic antagonist effect for use in the prevention and / or therapeutic treatment of a disease from the group comprising: Long Covid disease, myalgic encephalomyelitis / chronic fatigue syndrome, fibromyalgia, dementia, neoplastic disease, autoimmune disease, schizophrenia, seizure disorder, hyperinflammatory disease, chronic inflammatory bowel disease, rheumatic disease, obesity, hyperuricemia, diabetes mellitus (IDDM / N IDDM), acute viral diseases, amyotrophic lateral sclerosis (ALS), bronchial asthma, atopic-allergic diseases, attention deficit disorder (ADD), Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorders, Autoimmune / Antibody-Associated Diseases,Bipolar disorder, celiac disease (CD), chronic obstructive pulmonary disease (COPD), chronic inflammatory bowel disease (IBD) (e.g., Crohn's disease, ulcerative colitis), cystic fibrosis, depression, endometriosis, polycystic ovary syndrome, eating disorders, anxiety disorders, addiction disorders, frontotemporal dementia (Pick's disease), Graves' disease (GD), cardiovascular diseases in the general sense, Alzheimer's disease, Parkinson's disease, meningitis, multiple sclerosis (MS), muscular dystrophy, atopic dermatitis, peripheral arterial occlusive disease (PAD), pneumonia, postvaccination syndrome and vaccine damage in the broadest sense, postviral syndromes, psoriasis, pulmonary hypertension, restless legs syndrome, restrictive lung diseases, rheumatoid arthritis (RA), schizoaffective disorder, sepsis, Sjögren's syndrome (SS), scleroderma, systemic lupus erythematosus (SLE), and infertility.

2. Active ingredient for use according to claim 1, characterized in that the active ingredient comprises an alkaloid and / or that the active ingredient is an active ingredient with selective nicotinic acetylcholinergic agonistic effect and / or an active ingredient with selective muscarinic acetylcholinergic agonistic and / or muscarinic acetylcholinergic antagonistic effect.

3. Active ingredient for use according to one of claims 1 or 2, characterized in that the active ingredient comprises a poison, preferably a plant poison, a fungal poison, a snake poison or a frog poison, wherein the active ingredient in particular comprises a substance from the group nicotine and scopolamine.

4. Active ingredient for use according to one of the preceding claims, characterized in that the active ingredient is administered transcutaneously and / or that the active ingredient is prepared in a dosage form for transcutaneous administration.

5. Active ingredient for use according to claim 6, characterized in that the active ingredient is administered using a transdermal delivery device, preferably using a therapeutic patch, and / or that the active ingredient is prepared for administration in a transdermal delivery device, which preferably comprises a therapeutic patch.

6. Active ingredient for use according to one of the preceding claims, characterized in that the active ingredient is administered in pharmaceutically effective or therapeutically effective amounts and / or that the active ingredient is prepared for administration in pharmaceutically effective or therapeutically effective amounts.

7. Active ingredient for use according to one of the preceding claims, characterized in that the active ingredient is administered at a daily dosage of between 0.50 mg / diem and 24.00 mg / diem and / or that the active ingredient is prepared for administration at a daily dosage of between 0.50 mg / diem and 24.00 mg / diem.

8. Active ingredient for use according to one of the preceding claims, characterized in that that after a treatment of 1 to 5 days, preferably 2 to 4 days, in particular 3 days, the daily dosage is increased, and / or that after a treatment of 5 to 10 days, preferably 6 to 8 days, in particular 7 days, an active ingredient-free break of 5 to 9 days, preferably 6 to 8 days, in particular 7 days is inserted, wherein after the break the daily dosage preferably remains the same or is increased.

9. Active ingredient for use according to one of the preceding claims, characterized in that the active ingredient is administered for use in smokers at a daily dosage of between 7.00 mg / diem and 24.00 mg / diem and / or that the active ingredient is prepared for use in smokers for administration at a daily dosage of between 7.00 mg / diem and 24.00 mg / diem.

10. Active ingredient for use according to one of the preceding claims, characterized in that the active ingredient is administered for use in children with a daily dosage of between 1.25 mg / diem and 5.00 mg / diem and / or that the active ingredient is prepared for use in adult non-smokers for administration with a daily dosage of between 1.25 mg / diem and 5.00 mg / diem.

11. Active ingredient for use according to one of the preceding claims, characterized in that the active ingredient is administered for use in adult non-smokers at a daily dosage of between 3.50 mg / diem and 20.00 mg / diem and / or that the active ingredient is prepared for use in adult non-smokers for administration at a daily dosage of between 3.50 mg / diem and 20.00 mg / diem.

12. Active ingredient for use according to any one of the preceding claims, characterized in that the active ingredient for use in adult smokers is administered with a daily dosage of 7.00 mg / diem for 3 days and then with a daily dosage of 14.00 mg / diem for 7 days, followed by a 7-day drug-free break is inserted and then a daily dose of 24.00 mg / day is administered for a specific period of time, and / or that the active ingredient for use in adult non-smokers is administered at a daily dose of 3.50 mg / day for 3 days and then at a daily dose of 7.00 mg / day for 7 days, followed by a 7-day drug-free break and then a daily dose of 14.00 mg / day is administered for a specific period of time, and / or that the active ingredient for use in children is administered at a daily dose of 1.25 mg / day for 2 days, then at a daily dose of 3.50 mg / day for 2 days and then at a daily dose of 5.00 mg / day for 6 days, followed by a 7-day drug-free break and then a daily dose of 5.00 mg / day for a specific period of time becomes.

13. Active ingredient for use according to one of the preceding claims, characterized in that a specific daily dosage of the active ingredient which is administered using a transdermal patch and / or which is prepared for administration in a transdermal patch is set in that the transdermal patch with a higher daily dosage than the specific daily dosage is provided with a corresponding partial active ingredient-impermeable adhesive covering of the active ingredient surface of the patch, and / or in that a specific daily dosage of the active ingredient which is administered using a transdermal patch and / or which is prepared for administration in a transdermal patch is set in that a corresponding partial area of the active ingredient surface of the patch is cut off from the transdermal patch with a higher daily dosage than the specific daily dosage.

14. Active ingredient for use according to one of the preceding claims, characterized in that the active ingredient is present as a combination preparation with selective nicotinic acetylcholinergic agonist effect and with selective muscarinic acetylcholinergic agonist and / or muscarinic acetylcholinergic antagonist effect.

15. A transdermal delivery device comprising an active ingredient with nicotinic acetylcholinergic agonist action and / or an active ingredient with muscarinic acetylcholinergic agonist or muscarinic acetylcholinergic antagonist action, for use in the prevention and / or therapeutic treatment of a disease from the group comprising: Long Covid disease, Myalgic Encephalomyelitis / Chronic Fatigue Syndrome, Fibromyalgia, Dementia, Neoplastic Disease, Autoimmune Disease, Schizophrenia, Seizure Disorder, Hyperinflammatory Disease, Chronic Inflammatory Bowel Disease, Rheumatic Disease, Obesity, Hyperuricemia, Diabetes Mellitus (IDDM / N IDDM), Acute Viral Diseases, Amyotrophic Lateral Sclerosis (ALS), Bronchial Asthma, Atopic-Allergic Clinical pictures, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD),Autism spectrum disorders, autoimmune diseases / antibody-associated diseases, bipolar disorder, celiac disease (CD), chronic obstructive pulmonary disease (COPD), chronic inflammatory bowel diseases (IBD) (e.g., Crohn's disease, ulcerative colitis), cystic fibrosis / mu coviscidosis, depression, endometriosis, polycystic ovary syndrome, eating disorders, anxiety disorders, addiction disorders, frontotemporal dementia (Pick's disease), Graves' disease (GD), cardiovascular diseases in the general sense, Alzheimer's disease, Parkinson's disease, meningitis, multiple sclerosis (MS), muscular dystrophy, atopic dermatitis, peripheral arterial occlusive disease (PAD), pneumonia, postvaccination syndrome and vaccine damage in the broadest sense, postviral syndromes, psoriasis, pulmonary hypertension, restless legs syndrome, restrictive lung diseases, Rheumatoid arthritis (RA), schizoaffective disorder, sepsis, Sjögren's syndrome (SS), scleroderma,Systemic lupus erythematosus (SLE) and infertility.

16. A transdermal delivery device comprising an active ingredient with nicotinic acetylcholinergic agonist action and / or an active ingredient with muscarinic acetylcholinergic agonist and / or muscarinic acetylcholinergic antagonist action, for use according to claim 15, characterized in that the active ingredient is designed according to any one of claims 2 to 14.

17. Medicinal product or medicament for use in the prevention and / or therapeutic treatment of a disease from the group comprising: Long Covid disease, Myalgic Encephalomyelitis / Chronic Fatigue Syndrome, Fibromyalgia, dementia, neoplastic disease, autoimmune disease, schizophrenia, seizure disorder, hyperinflammatory disease, inflammatory bowel disease, rheumatic disease, obesity, hyperuricemia, diabetes mellitus (IDDM / NI DDM), acute viral diseases, amyotrophic lateral sclerosis (ALS), bronchial asthma, atopic-allergic diseases, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), autism spectrum disorders, autoimmune diseases / antibody-associated diseases, bipolar disorder, celiac disease (CD), chronic obstructive pulmonary disease (COPD), chronic inflammatory bowel diseases (IBD) (e.g., M. b. Chron, ulcerative colitis), cystic fibrosis / mucoviscidosis, depression, endometriosis, polycystic ovary rial syndrome, eating disorders, anxiety disorders, addiction disorders, frontotemporal dementia (Mb.Pick), Graves' disease (GD), cardiovascular diseases in the general sense, Alzheimer's disease, Parkinson's disease, meningitis, multiple sclerosis (MS), muscular dystrophy, neurodermatitis, peripheral arterial occlusive disease (PAD), pneumonia, post-vaccination syndrome and vaccine damage in the broadest sense, post-viral syndromes, psoriasis, pulmonary hypertension, restless legs syndrome, restrictive lung diseases, rheumatoid arthritis (RA), schizoaffective disorder, sepsis, Sjögren's syndrome (SS), scleroderma, systemic lupus erythematosus (SLE) and infertility, where the medicinal product or drug contains an active ingredient with nicotinic acetylcholinergic agonist effect and / or an active ingredient with muscarinic agonist and / or muscarinic acetylcholinergic antagonist effect.

18. A medicinal product or medicament for use according to claim 17, characterized in that the active ingredient is formed according to one of claims 2 to 14.