[go: up one dir, main page]

EP2432471A1 - Nouveaux concepts thérapeutiques pour le traitement de fibromyalgies - Google Patents

Nouveaux concepts thérapeutiques pour le traitement de fibromyalgies

Info

Publication number
EP2432471A1
EP2432471A1 EP10737496A EP10737496A EP2432471A1 EP 2432471 A1 EP2432471 A1 EP 2432471A1 EP 10737496 A EP10737496 A EP 10737496A EP 10737496 A EP10737496 A EP 10737496A EP 2432471 A1 EP2432471 A1 EP 2432471A1
Authority
EP
European Patent Office
Prior art keywords
quinine
fibromyalgia
pain
active ingredient
prophylactic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
EP10737496A
Other languages
German (de)
English (en)
Inventor
Harald Greve
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Maria Clementine Martin Klosterfrau Vertriebs GmbH
Original Assignee
Maria Clementine Martin Klosterfrau Vertriebs GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Maria Clementine Martin Klosterfrau Vertriebs GmbH filed Critical Maria Clementine Martin Klosterfrau Vertriebs GmbH
Publication of EP2432471A1 publication Critical patent/EP2432471A1/fr
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/49—Cinchonan derivatives, e.g. quinine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to the field of medicine, in particular the field of prophylactic and / or therapeutic (curative) treatment of diseases or diseases occurring in human or veterinary medicine, which are caused by a malfunction of the pain stimulus or by the inhibition of the pain stimulus are treatable, especially fibromyalgia.
  • the present invention relates to the use of quinine or its salts, isomers, derivatives or prodrugs as active ingredient for the prophylactic and / or therapeutic treatment of diseases caused by a malfunction of the pain stimulus and / or by the inhibition of the pain irritation treatable diseases or for the production of a drug for the prophylactic and / or therapeutic treatment of disorders caused by misdirection of pain stimulation and / or treatable by the inhibition of pain stimulation.
  • the present invention further relates to the use of quinine or its salts, isomers, derivatives or prodrugs as active ingredient for the prophylactic and / or therapeutic treatment of fibromyalgia or rheumatic diseases, in particular fibromyalgia, or for the preparation of a medicament for prophylactic and / or therapeutic treatment of fibromyalgia or rheumatic diseases, especially fibromyalgia.
  • the present invention relates to the use of quinine or its salts, isomers, derivatives or prodrugs for improving and / or influencing a dysregulation of the body's own pain stimulation (pain transmission) or for producing a drug for improving and / or influencing a dysregulation of the body's pain stimulus (pain transmission).
  • the present invention relates to the use of quinine or its salts, isomers, derivatives or prodrugs for the inhibition of endogenous pain stimulus conduction (pain transmission) or for the production of a medicament for the inhibition of the body's pain stimulus conduction (pain transmission).
  • the present invention relates to the use of an active ingredient for improving and / or influencing a dysregulation of the body's pain stimulus (pain transmission) for prophylactic and / or therapeutic treatment of fibromyalgia or rheumatic diseases, especially fibromyalgia, or for the preparation of a medicament for prophylactic and / or therapeutic treatment of fibromyalgia or rheumatic diseases, especially fibromyalgia.
  • the present invention relates to the use of an active ingredient for the inhibition of endogenous pain stimulation (pain transmission) for the prophylactic and / or therapeutic treatment of fibromyalgia or rheumatic diseases, especially fibromyalgia, or for the manufacture of a medicament for the prophylactic and / or therapeutic treatment of fibromyalgia or Rheumatic diseases, especially fibromyalgia.
  • the present invention also relates to a pharmaceutical composition or a medicament for the prophylactic and / or therapeutic treatment of fibromyalgia (antifibromyalgia agent), wherein the medicament in addition to a pharmaceutical excipient (carrier) as the active ingredient quinine or at least one salt, isomer, derivative or prodrug of quinine contains.
  • a pharmaceutical excipient carrier
  • the present invention also relates to a drug combination, wherein the drug combination comprises on the one hand the aforementioned pharmaceutical composition of the invention or the above-mentioned inventive drug and on the other hand, at least one further pharmaceutical active ingredient, wherein the further pharmaceutical active ingredient is in particular selected from the group of analgesics, antidepressants and their combinations
  • the present invention relates to a method for the prophylactic and / or therapeutic treatment of caused by a false control of the pain stimulus and / or treatable by the inhibition of pain stimulation diseases or a method for the prophylactic and / or therapeutic treatment of fibromyalgia or rheumatic diseases, especially fibromyalgia, the method comprising preferably oral administration of quinine or its salts, isomers, derivatives or prodrugs.
  • Fibromyalgia is a chronic, non-inflammatory pain disorder, which is not to be equated with the term of so-called soft tissue rheumatism.
  • the fibromyalgia syndrome (FMS) can in the broadest sense be attributed to the rheumatic disease, if the term rheumatism is understood as a painful disease of the locomotor system, often associated with restricted mobility.
  • the outdated designation is among other things also “generalized Tendomy opathie”, abbreviated “GTM”. Synonyms are “fibromyalgic syndrome”, “fibromyalgia syndrome”, “fibrosis syndrome” or the like.
  • AWMF Association of the Scientific Medical Societies
  • the main symptoms are chronic pain in various parts of the body, persistent fatigue, general weakness, difficulty concentrating and the like to exhaustion (so-called "fatigue syndrome") and sleep disorders;
  • the back, neck, chest and the joints in the arms and legs are particularly affected by the pain.
  • the symptoms should occur over a period of at least three months.
  • Common concomitant symptoms include swelling in the hands, feet, or face, morning stiffness, irritable bowel, irritable stomach, headache, dryness, etc. Hypersensitivity of the mucous membranes as well as increased anxiety and depression.
  • various vegetative complaints may also occur, such as cardiac arrhythmias, sensitive skin (eg excessive reactions in case of contact with near people, etc.), increased venous signs, hair loss, difficulty in breathing, diffuse chest pain in connection with shortness of breath , Susceptibility to infection, slightly elevated temperature, numbness, restless legs, leg muscle cramps, shaking hands, irritable bladder, irritable bowel, period pain, diminution of sexual interest, impotence, hoarseness, difficulty in swallowing, lumping sensation in throat, toothache, pain in the masticatory muscles, disorders of the sense of hearing, blindness, tinnitus (ear noises), tendencies to increased perspiration, water retention, irritability, mood swings, word finding disorders, pain in the spinal area, alternating pain (eg pain on right hand and left foot on one day, on the f left leg on left arm and right leg etc.).
  • sensitive skin eg excessive reactions in case of contact with near people, etc.
  • increased venous signs eg.
  • the onset of the disease is insidious and inconspicuous: In the beginning there are usually nonspecific complaints, such as fatigue, insomnia or gastrointestinal discomfort. Later there is pain in the lumbar spine or - less often - the Cervical spine added. Only then will the typical pain in the arms and legs and other accompanying symptoms and symptoms develop. As a rule, the disease does not worsen continuously. Violent pain attacks are replaced by painless intervals. Cold, wet or external stress can lead to aggravation. It takes an average of seven to eight years to develop the full picture of the condition. The individual relapses and acute phases do not follow a specific pattern and are therefore difficult to predict, but they are particularly common after acute infectious diseases (eg, flu, pneumonia, Lyme disease, etc.).
  • acute infectious diseases eg, flu, pneumonia, Lyme disease, etc.
  • Fibromyalgia itself usually does not lead to a disease-related destruction of the bones - such as rheumatoid arthritis, however, the sometimes massive movement restriction can lead to capsular shrinkage and other irreparable consequences in the articular apparatus, which is very rare.
  • fibromyalgia The diagnosis of fibromyalgia is quite difficult, since both X-ray images and laboratory values are not clear. A diagnosis can not always be guaranteed. Usually, so-called “tender points” (English for “sensitive areas”) are used (see classification criteria of the American College of Rheumatology, 1990): If there are 1 1 or more of 18 tender points, there is an increased tenderness the suspicion of fibromyalgia. These diagnostic points are usually close to the joints of the tendon-muscle approaches. Often the diagnosis is made after eight to ten years, so that it has already come to a full picture of the disease before the patient is treated properly.
  • the diagnostic criteria for fibromyalgia include spontaneous pain in the muscles or in the course of tendons and tendons, which are present for at least three months in three different regions, a tender tenderness of tender points (see above) and accompanying vegetative and functional symptoms (eg sleep disturbances, tiredness, headache or migraine, cold hands / feet, dry mouth, hyperhydrosis or excessive sweat production, circulatory Running difficulties, dizziness, gastrointestinal discomfort or gastrointestinal discomfort, Globe feeling, functional respiratory problems, sensations such. Tingling, functional cardiac complaints, dysuria and / or dysmenorrhoea).
  • vegetative and functional symptoms eg sleep disturbances, tiredness, headache or migraine, cold hands / feet, dry mouth, hyperhydrosis or excessive sweat production, circulatory Running difficulties, dizziness, gastrointestinal discomfort or gastrointestinal discomfort, Globe feeling, functional respiratory problems, sensations such. Tingling, functional cardiac complaints, dysuria and / or dysmenorrhoea).
  • Fibromyalgia patients often have difficulty recognizing that they are incapacitated because of the problematic diagnosis, which often leads to great social or financial difficulties. Although the disease is not fatal, it can lead to a massive impairment of quality of life. Both the cause (aetiology) of fibromyalgia and the mechanisms of pathogenesis (pathogenesis) are unclear. There are a variety of findings concerning genetic, hormonal, neurophysiological, mental and other factors. In the synopsis of the findings is currently mainly a disorder of pain-processing systems in the central nervous system with the consequence of a low pain threshold discussed.
  • Psychiatric disorders such as depression and anxiety are more prevalent in patients with fibromyalgia. It is unclear and the subject of scientific discussions to what extent these mental disorders are themselves the result of chronic pain or the symptoms of fibromyalgia reflect an underlying mental disorder.
  • examinations revealed a more frequent occurrence of physical ill-treatment and sexual abuse in the past.
  • About 0.6 to 4% of the population in the Federal Republic of Germany is affected by the disease, and 85 to 90% of them are women.
  • the disease usually begins at the end of the twentieth year of life and is fully developed at about the middle of the thirtieth year of life and has a frequency peak in and after the climacteric. Children and adolescents are also less affected by the disease; In old people, the disease can often be falsely subsumed under "age complaints".
  • Typical are so-called "patient careers", d. H.
  • the affected persons visited a large number of doctors until the diagnosis was made and had to undergo many different, sometimes superfluous diagnostic and / or therapeutic measures.
  • Fibromyalgia is not curable by medical procedures in general. Basically, there is a risk of drug abuse to the drug addiction and the risk of unpredictable consequential damage through continuous medication with various painkillers.
  • a treatment concept today is the so-called multimodal therapy according to the findings of modern pain research.
  • the aim of all measures here is to maintain and improve the functionality in everyday life and thus the quality of life as well as the reduction and / or alleviation of symptoms.
  • This can generally be a lifelong symptom of the condition, it is especially recommended that treatment be self-administered by individuals ("self-management") with no or little side effects and their long-term efficacy.
  • self-management the Federal Association of the German Fibromyalgia Association (DFV eV) publishes a patient guideline based on these guidelines.
  • fibromyalgia is a descriptive exclusion diagnosis, other defined diseases must necessarily be excluded. A careful psychiatric clarification is also important here, since, for example, depression is often overlooked.
  • fibromyalgia are generally inadequate and are essentially limited to alleviating the symptoms, especially the pain.
  • drug therapies are often inefficient: As described above, drug therapies of fibromyalgia are limited in particular to the administration of antidepressants, serotonin reuptake inhibitors, muscle relaxants and analgesics as well as local anesthetics. Occasionally herbal preparations and homeopathic remedies are also used.
  • fibromyalgia The therapeutic options for the treatment of fibromyalgia are therefore to date generally considered unsatisfactory. Since the causes of the development of fibromyalgia are not yet known in detail, there are currently no targeted therapeutics available. Those drugs that can at least alleviate the symptoms of fibromyalgia are often limited in clinical use by side effects.
  • the object of the present invention to provide an efficient therapy or an efficient therapeutic concept or an efficient or effective drug for the prophylactic and / or therapeutic (curative) treatment of diseases or diseases occurring in human or veterinary medicine be provided by the inhibition of pain stimulation, especially of fibromyalgia, provide, whereby the above-mentioned, occurring in connection with the prior art disadvantages and side effects should be at least partially avoided or at least partially mitigated.
  • the invention has for its object to provide medicines or drugs available, which in particular for the prophylactic and / or therapeutic (curative) treatment of human or veterinary diseases or diseases, which caused by a malfunction of the pain stimulus or are treatable by the inhibition of pain irritation, in particular of fibromyalgia, are suitable.
  • the pharmaceutical or medical preparation provided in this context according to the invention should be well tolerated by the patients in question, in particular lead to no or only slight side effects or side effects, or at least to be essentially non-toxic.
  • the present invention proposes - according to a first or second aspect of the invention - the use of quinine or its salts, isomers, derivatives or prodrugs according to claim 1 or 2 before; Further advantageous embodiments of these aspects of the invention are the subject of the relevant subclaims.
  • Another object of the present invention - according to a third or fourth aspect of the invention - is the use of quinine or its salts, isomers, derivatives or prodrugs according to claim 14 or 15; Further advantageous embodiments of these aspects of the invention are the subject of the relevant subclaims.
  • Yet another object of the present invention - according to a fifth or sixth aspect of the invention - is the use of quinine or its salts, isomers, derivatives or prodrugs according to claim 19 or 20; Further advantageous embodiments of these aspects of the invention are the subject of the relevant subclaims.
  • quinine including its derivatives and isomers, and salts of quinine (ie pharmaceutically or pharmacologically or acceptably acceptable salts of quinine, such as, for example, quinine sulfate), for the treatment of diseases or disorders, which are caused by a malfunction of the pain stimulation or are treatable by the inhibition of pain stimulation, in particular fibromyalgia, are effective in an efficient way or suitable, in particular by alleviating the symptoms caused by these diseases or completely disappear.
  • quinine including its derivatives and isomers, and salts of quinine (ie pharmaceutically or pharmacologically or acceptably acceptable salts of quinine, such as, for example, quinine sulfate)
  • quinine as used in the context of the present invention, is to be understood very broadly not only the substance quinine as such, but rather also its salts of all kinds, their derivatives of all kinds (eg esters, ethers etc ), their isomers of all kinds (eg stereoisomers, structural isomers, etc.) and their prodrugs of all kinds (eg suitable precursors, which are able to generate quinine in vivo or under physiological conditions, etc.).
  • this term refers to quinine and its salts, esters, ethers and stereoisomers.
  • quinine quinine, quinine salts, quinine derivatives, quinine isomers and quinine prodrugs
  • quinine-based active substance or simply as active substance.
  • the quinine is an alkaloid of the following structural formula:
  • Quinine was first isolated in 1820 by Pierre Joseph Pelletier and Joseph Binaime Caventou by extraction with alcohol from the cinchona bark. The extract was diluted with potassium hydroxide solution to give a yellowish, amorphous, very bitter-tasting precipitate. Pelletier and Caventou named the dried substance quinine.
  • the pharmacist Friedrich Koch in Oppenheim quinine was the first to be produced on an industrial scale from the bark of Cinchona species.
  • Zdenko Hans Skraup, Wilhelm Königs and Paul Rabe explained the structure of quinine.
  • quinine was formally totally synthesized by Robert B. Woodward, but the actual total synthesis did not reach Uskokovic until 1970.
  • Quinine is used in the art for the treatment of malaria, especially in the case of malaria tropica, because it inhibits nucleic acid synthesis in the asexual forms of the pathogen.
  • quinine painkillend in the immediate vicinity anesthetic and antipyretic. In China, it is mixed in small doses and means for the treatment of influenza due to the antipyretic and analgesic effect.
  • quinine has a stimulating effect on the uterine musculature and thus promotes labor.
  • quinine was also used as a labor-promoting agent because of its stimulating effect on the uterine musculature.
  • the bitter-tasting quinine is also added in small quantities (about 70 mg / l) in the food and food industry to so-called bitter lemon and tonic water drinks.
  • quinine is also a popular bittering agent in the food industry and can also be found, for example, in Magenbittern.
  • Magenbittern since it is a pharmacologically active substance, the use in Germany must always be identified in foods.
  • the present invention is associated with a variety of advantages, improvements and particularities which distinguish the present invention from the prior art:
  • the present invention provides an efficient therapy or an efficient therapeutic concept or an efficient or effective drug for the prophylactic and / or therapeutic (curative) treatment of diseases or diseases occurring in human or veterinary medicine, which are caused by a malfunction of the pain stimulus line caused or by the inhibition of the pain irritation are treatable, in particular of fibromyalgia, ready, whereby the previously described, occurring in connection with the prior art disadvantages and side effects should be at least partially avoided or at least partially mitigated.
  • the present invention for the first time drugs or medicines available, which are particularly for the prophylactic and / or therapeutic (curative) treatment of human or veterinary diseases or diseases that are caused by a malfunction of the pain stimulus or by the inhibition of pain irritation are treatable, in particular of fibromyalgia, are suitable.
  • the pharmaceutical or medical preparation provided according to the invention in this context is well tolerated by the patients in question and leads, in particular, to no or at most minor side effects or concomitant symptoms and is at least essentially non-toxic.
  • the effectiveness of quinine or its salts, derivatives, isomers and prodrugs in the context of the present invention may explain the following, as follows: Applicant's recent investigations into the pathophysiology of fibromyalgia provide an explanation of the aetiology of fibromyalgia. It is known that the neurotransmitter serotonin increases pain stimuli from the body periphery in the context of pain transmission. After repeated pain stimuli it could be demonstrated in the animal model that corresponding neurons are also spon- tan and thereby enlarge corresponding pain-processing areas of the cerebral cortex.
  • the increased sensitivity in fibromyalgia patients is attributed to a disturbance of the body's own pain inhibition.
  • These are signals that, starting from the brain, affect pain-processing neurons in the spinal cord.
  • the system is under the control of superior brain areas in the frontal brain, which assess the importance of pain to the organism. If such a pain signal is overrated, the pain inhibition system is slowed down. The result is that the pain is felt more strongly than in healthy people.
  • the fibromyalgia patients experience a constant false alarm, which leads to a vicious circle (circulus vitiosus) for the fibromyalgia patient.
  • the present invention - according to a first aspect of the present invention - is thus the use of quinine or its salts, isomers, derivatives or prodrugs as active ingredient for the prophylactic and / or therapeutic treatment of caused by a misdirection of the pain stimulus and / or by the inhibition theischen Sontechnisch treatable diseases or for the manufacture of a medicament for the prophylactic and / or therapeutic treatment caused by a malfunction of the pain stimulus and / or treatable by the inhibition of pain stimulation diseases.
  • Another object of the present invention - according to a second aspect of the present invention - is the use of quinine or its salts, isomers, derivatives or prodrugs, in particular according to the first aspect of the invention, as an active ingredient for the prophylactic and / or therapeutic treatment of fibromyalgia or rheumatic diseases, in particular Fibromyalgia, or for the manufacture of a medicament for the prophylactic and / or therapeutic treatment of fibromyalgia or rheumatic diseases, especially fibromyalgia.
  • this active ingredient may preferably be in the form of (pure) quinine, a quinine ester, quinine ether or quinol mono-isomer, preferably in the form of a quinine salt, more preferably in the form of a quinine sulfate, be used.
  • a particularly preferred quinine salt according to the invention is quinine sulfate.
  • a dosage form suitable for oral administration contains, for example, 200 mg of quinine sulfate per application unit, in particular per tablet, capsule, pill, dragee etc., corresponding to 165.7 mg of quinine.
  • the quinine-based active substance is preferably administered systemically or topically, preferably systemically.
  • the active ingredient is preferably prepared in a systemically or topically administrable form, preferably in a systemically administrable form.
  • the active substance can be administered according to the invention orally, rectally, intramuscularly, subcutaneously, intraarticularly or intravenously, preferably orally, ie. H. in other words, the active ingredient is prepared according to the invention in an oral, rectal, intramuscular, subcutaneous, intraarticular or intravenously administrable form, preferably in an orally administrable form.
  • the active ingredient is applied in the form of tablets, dragees, pills, capsules, solutions, dispersions, injections, ointments, creams, inhalation preparations, aerosols or suppositories, preferably in the form of tablets, dragees, pills or capsules when the active ingredient is formulated as tablets, dragees, pills, capsules, solutions, dispersions, injections, ointments, creams, inhalation preparations, aerosols or suppositories, preferably as tablets, dragees, pills or capsules.
  • the active ingredient is formulated in a form suitable for oral administration, in particular solid form, preferably as tablets, dragees, pills or capsules.
  • the pharmaceutical preparations or drugs of the quinine-based active substance used according to the invention can be formulated in a known manner using one or more pharmaceutically acceptable excipients and optionally further ingredients or additives. As described above, these preparations can be formulated, for example, for oral, parenteral, rectal, intranasal, etc. administration or, for example, in a manner suitable for administration by inhalation, insufflation, etc.
  • compositions for oral administration which are suitable according to the invention can be used, for example, in the form of tablets, dragees, pills or capsules, which are prepared by methods known per se with pharmaceutically acceptable excipients and optionally further ingredients or additives (eg diluents, binders, fillers , Lubricants, disintegrants, wetting agents, etc.) and are also available as such in the trade (though, mind you, for a completely different medical indication, as described).
  • the preferably oral administration forms according to the invention in particular in the form of tablets, dragees, pills, capsules, etc., can optionally be coated by methods known per se. This is readily apparent to those skilled in the art.
  • Liquid preparations for oral administration may be in the form of, for example, aqueous or oily solutions, syrups, elixirs, emulsions or suspensions, or alternatively they may be present as a dry product for constitution with water or other suitable vehicle before use.
  • Such liquid preparations can be prepared by methods known per se with pharmaceutically acceptable excipients and optionally other additives, such. As suspending agents, emulsifiers, non-aqueous vehicles and preservatives.
  • the liquid preparations may also contain per se known buffers, flavoring or flavoring agents, dyes, sweeteners, etc., as needed.
  • the formulations may be formulated especially for injections, preferably for intravenous, intramuscular or subcutaneous injections.
  • the preparations for the injections may be in forms intended for single dosing, such as. As ampoules, or for the multiple dosage forms such. B. so-called multi-dose containers usually present with an added preservative.
  • the preparations may be in this embodiment in the form of suspensions, solutions or emulsions in oily or aqueous vehicles and optionally also auxiliary formulation such. As suspending, stabilizing and / or dispersing agents and / or means for adjusting the tonicity of the solution containing.
  • the contained active ingredient may be constituted with a suitable carrier, e.g. Sterile pyrogen-free water, before use. Rectal preparations such as suppositories may also be formulated for use, eg. For example, those containing per se known suppository bases.
  • the compounds may be administered as liquid sprays, e.g. B. in the form of drops and / or as Schnupfpulver used.
  • the active ingredient may be in particular in the form of an aerosol spray, for. B. from a pressurized pack, in particular using suitable propellant or in a sputtering device, are discharged.
  • the dosage unit may be determined by providing a valve which will release an appropriate amount.
  • capsules and cartridges for use in an inhaler or insufflator may be formulated to contain a powder mix of a quinine-based active agent and a suitable powder base material of the present invention, such as the like. As lactose or starch.
  • the relevant pharmaceutical preparations or medicaments with the quinine-based active ingredient are administered as needed.
  • the dosage as such is not critical in this regard and may in principle be a function of the severity of the disease, the weight of the patient to be treated, the route of administration, the frequency of Administration and the duration of treatment can be varied slightly by the doctor.
  • a dosage has proven effective according to which the active compound is more preferably 50 to 600 mg, more preferably 50 to 600 mg, even more preferably 10 to 2000 mg, more preferably 10 to 2000 mg, more preferably 20 to 1000 mg, even more preferably 25 to 750 mg 75 to 500 mg, more preferably 100 to 400 mg, calculated in each case as quinine, or after which the active ingredient in a for a daily dosage of 5 to 5000 mg, especially 10 to 2000 mg, preferably 20 to 1000 mg, particularly preferred 25 to 750 mg, most preferably 50 to 600 mg, even more preferably 75 to 500 mg, even more preferably 100 to 400 mg, each calculated as quinine, suitable or specific form prepared.
  • a dosage has proven particularly advantageous, according to which the active ingredient is administered in an intake daily dose of 100 to 1000 mg, in particular 200 to 750 mg, preferably 250 to 600 mg, in each case calculated as quinine, preferably distributed over at least two daily doses, in particular over a time dream of 7 Days to 6 months, preferably 2 weeks to 4 months, more preferably 3 weeks to 3 months, followed by a maintenance daily dose reduced by 20% to 80%, in particular 30% to 60%, compared to the intake dose, in particular a maintenance daily dose of 50 to 600 mg, especially 75 to 450 mg, preferably 100 to 350 mg, each calculated as quinine.
  • a dosage has proven particularly useful, according to which the active ingredient is prepared for administration in an input daily dose of 100 to 1000 mg, in particular 200 to 750 mg, preferably 250 to 600 mg, in each case calculated as quinine, preferably distributed on at least two daily doses, in particular over a period of 7 days to 6 months, preferably 2 weeks to 4 months, particularly preferably 3 weeks to 3 months, is applied, followed by a 20% to 80%, especially 30% to 60% reduced maintenance daily dose compared to the input daily dose, in particular a maintenance daily dose of 50 to 600 mg, especially 75 to 450 mg, preferably 100 to 350 mg, each calculated as quinine.
  • the quinine-based active substance can be administered in combination with at least one further pharmaceutical active substance or, according to the invention, the quinine-based active substance can be prepared for combined administration with at least one further pharmaceutical active substance.
  • the further pharmaceutical active substance may in particular be an active substance which is used for the symptomatic treatment of fibromyalgia, in particular as already used in this context in the prior art.
  • the further active pharmaceutical ingredient may be selected from the group of analgesics, antidepressants and combinations thereof.
  • the additional pharmaceutically active agent may be spatially separated from the quinine-based drug and / or administered (i.e., as a separate drug so as to result in a so-called "kit-of-parts").
  • Yet another object of the present invention - according to a third aspect of the present invention - is the use of quinine or its salts, isomers, derivatives or prodrugs to improve and / or influence a dysregulation of the body's pain stimulus (pain transmission) or for the preparation of a medicament for the improvement and / or influence of a dysregulation of the body's pain stimulus line (pain transmission).
  • Yet another object of the present invention - according to a fourth aspect of the present invention - is the use of quinine or its salts, isomers, derivatives or prodrugs for the inhibition of endogenous pain stimulation (pain transmission) or for the preparation of a medicament for the inhibition of the body's pain stimulus (pain transmission).
  • an extension of the refractory period by, in particular, a direct effect on the muscle fiber and / or a reduction in the excitability of the motor end plate and / or a positive influence on the distribution of calcium in the muscle fiber and / or an increase in the threshold for a muscle reaction to a single maximum stimulus.
  • the use for prophylactic and / or therapeutic treatment caused by a misdirection of the pain stimulus and / or treatable by the inhibition of pain stimulation diseases or for the preparation of a medicament for prophylactic and / or therapeutic treatment of disorders caused by misdirection of pain irritation and / or treatable by inhibition of pain conduction is also possible.
  • the third and fourth aspects of the invention also make use in particular for the prophylactic and / or therapeutic treatment of fibromyalgia or rheumatic diseases, in particular fibromyalgia, or for the preparation of a medicament for the prophylactic and / or therapeutic treatment of fibromyalgia or Rheumatic diseases, especially fibromyalgia.
  • Yet another object of the present invention - according to a fifth aspect of the present invention - is the use of an active substance for the improvement and / or influencing of a dysregulation of the body's pain stimulation (pain transmission) for the prophylactic and / or therapeutic treatment of fibromyalgia or rheumatic diseases, in particular fibromyalgia, or for the manufacture of a medicament for the prophylactic and / or therapeutic treatment of fibromyalgia or rheumatic diseases, in particular fibromyalgia.
  • a likewise further object of the present invention - according to a sixth aspect of the present invention - is the use of an active ingredient for the inhibition of endogenous pain stimulation (pain transmission) for the prophylactic and / or therapeutic treatment of fibromyalgia or rheumatic diseases, in particular fibromyalgia, or for producing a Medicament for the prophylactic and / or therapeutic treatment of fibromyalgia or rheumatic diseases, especially fibromyalgia.
  • quinine or its salts, isomers, derivatives or prodrugs are administered as the active ingredient.
  • Yet another object of the present invention - according to a seventh aspect of the present invention - is an antifibromyalgia agent (ie a pharmaceutical composition or a medicament for the prophylactic and / or therapeutic treatment of fibromyalgia), wherein the antifibromyalgia agent - in addition to a pharmaceutical excipient patients or carriers - as the active ingredient contains quinine or at least one salt, isomer, derivative or prodrug of quinine.
  • an antifibromyalgia agent ie a pharmaceutical composition or a medicament for the prophylactic and / or therapeutic treatment of fibromyalgia
  • the antifibromyalgia agent - in addition to a pharmaceutical excipient patients or carriers - as the active ingredient contains quinine or at least one salt, isomer, derivative or prodrug of quinine.
  • the antifibromyalgia agent may be formulated in the form of tablets, dragees, pills, capsules, solutions, dispersions, injections, ointments, creams, inhalants, aerosols or suppositories, preferably in the form of tablets, dragees, pills or capsules.
  • the antifibromyalgia agent is preferably formulated in a particularly solid form suitable for oral administration, preferably as tablets, dragees, pills or capsules.
  • the antifibromyalgia agent contains quinine or at least one salt, isomer, derivative or prodrug of quinine in pharmaceutically effective amounts.
  • the antifibromyalgia agent is for administration of the quinine or at least one salt, isomer, derivative or prodrug of quinine in a daily dose of 5 to 5000 mg, especially 10 to 2000 mg, preferably 20 to 1000 mg, most preferably 25 to 750 mg, whole more preferably 50 to 600 mg, more preferably 75 to 500 mg, even more preferably 100 to 400 mg, each calculated as quinine prepared.
  • the antifibromyalgia agent contains quinine or at least one salt, isomer, derivative or prodrug of quinine per application unit, in particular per tablet, dragee, pill or capsule, in amounts of 10 to 1000 mg, in particular 25 to 750 mg, preferably 50 to 500 mg, each calculated as quinine.
  • Yet another object of the present invention - according to an eighth aspect of the present invention - is a drug combination, wherein the drug combination on the one hand an antifibromyalgia (ie, a pharmaceutical composition or a drug for the prophylactic and / or therapeutic treatment of fibro-myalgia), as described above, and on the other hand comprises at least one further pharmaceutical active substance.
  • an antifibromyalgia ie, a pharmaceutical composition or a drug for the prophylactic and / or therapeutic treatment of fibro-myalgia
  • the further active pharmaceutical ingredient may in particular be an active ingredient which is used for the symptomatic treatment of fibromyalgia, in particular as already used in the prior art in this context.
  • the further active pharmaceutical ingredient may be selected from the group of analgesics, antidepressants and combinations thereof.
  • the additional pharmaceutically active agent may be spatially separated from the quinine-based drug and / or administered (i.e., as a separate drug so as to result in a so-called “kit-of-parts").
  • Another object of the present invention - according to a ninth aspect of the present invention a method for the prophylactic and / or therapeutic treatment caused by a misdirection of the pain stimulus and / or treatable by the inhibition of pain stimulation diseases or a method for prophylactic and or therapeutic treatment of fibromyalgia or rheumatic diseases, in particular fibromyalgia, which process comprises the preferably oral administration of quinine or its salts, isomers, derivatives or prodrugs.
  • the active ingredient quinine sulphate in the form of a perorally administered drug was administered orally as tablets (200 mg quinine sulphate equivalent to 165.7 mg quinine per tablet) and taken at a dose of 2 tablets daily for several weeks. After three to six weeks there was a significant improvement in the overall clinical picture of the treated patients with fibromyalgia.
  • ACR American American Rheumatologist
  • fibromyalgia Applicant's recent investigations into the pathophysiology of fibromyalgia provide an explanation of the etiology of fibromyalgia. It is known that the neurotransmitter serotonin increases pain stimuli from the body periphery in the context of pain transmission. After repeated painful stimuli, it could be demonstrated in the animal model that corresponding neurons also become spontaneously active, thereby increasing corresponding pain-processing areas of the cerebral cortex. The findings gained correlate with the clinical investigations in fibromyalgia patients.

Landscapes

  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne de nouveaux concepts pour le traitement prophylactique et/ou thérapeutique (curatif) de maladies, notamment de fibromyalgies, survenant dans la médecine humaine ou vétérinaire, provoquées par un dysfonctionnement de la transmission de stimuli douloureux ou pouvant être traitées par l'inhibition de la transmission de stimuli douloureux.
EP10737496A 2009-09-01 2010-07-12 Nouveaux concepts thérapeutiques pour le traitement de fibromyalgies Ceased EP2432471A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102009039546A DE102009039546A1 (de) 2009-09-01 2009-09-01 Neue therapeutische Konzepte für die Behandlung von Fibromyalgien
PCT/EP2010/004214 WO2011026536A1 (fr) 2009-09-01 2010-07-12 Nouveaux concepts thérapeutiques pour le traitement de fibromyalgies

Publications (1)

Publication Number Publication Date
EP2432471A1 true EP2432471A1 (fr) 2012-03-28

Family

ID=42829609

Family Applications (1)

Application Number Title Priority Date Filing Date
EP10737496A Ceased EP2432471A1 (fr) 2009-09-01 2010-07-12 Nouveaux concepts thérapeutiques pour le traitement de fibromyalgies

Country Status (6)

Country Link
EP (1) EP2432471A1 (fr)
DE (2) DE102009039546A1 (fr)
EA (1) EA021912B1 (fr)
GE (1) GEP20146191B (fr)
UA (1) UA104773C2 (fr)
WO (1) WO2011026536A1 (fr)

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB189820721A (en) * 1898-10-01 1898-11-19 David Gillies Medicinal Preparation for the Cure of Rheumatic Affections.

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2011026536A1 *

Also Published As

Publication number Publication date
EA201200407A1 (ru) 2012-09-28
WO2011026536A1 (fr) 2011-03-10
EA021912B1 (ru) 2015-09-30
UA104773C2 (ru) 2014-03-11
DE102009039546A1 (de) 2011-03-10
GEP20146191B (en) 2014-11-10
DE202009012983U1 (de) 2010-10-28

Similar Documents

Publication Publication Date Title
DE60119534T2 (de) Verwendung von hydroxyethylrutosiden zur behandlung von erkältungssymptomen, symptomen der allergischen rhinitis und atemwegsinfektionen
DE2920739C2 (fr)
DE69829112T2 (de) Butyrate Derivate zur Behandlung von Fibromyalgia und chronischem Müdigkeits-Syndrom
DE69828881T2 (de) Zusammensetzung zur linderung von störungen der stimmungslage bei gesunden individuen
CN106999467A (zh) 治疗认知减退的方法
DE60111025T2 (de) Verwendung von Topiramat zur Behandlung und Diagnostizierung von Atemstörungen während des Schlafens und Mittel zur Durchführung der Behandlung und Diagnose
DE3850154T2 (de) Verwendung von Gepiron zur Herstellung eines pharmazeutischen Präparats zur Behandlung atypischer Depression.
DE69730214T2 (de) Zusammensetzung und verfahren zur behandlung von herpes simplex
DE2824165A1 (de) Arzneimittel mit angstneurosen und angstaehnliche neurosen beseitigender wirkung und verfahren zum zubereiten des arzneimittels
EP1513533A2 (fr) Combinaison d'agents actifs pharmaceutiques et utilisation
DE10163667A1 (de) Verwendung von Desoxypeganin zur Behandlung der klinischen Depression
EP2432471A1 (fr) Nouveaux concepts thérapeutiques pour le traitement de fibromyalgies
Sharma et al. DOUBLE BLIND STUDY TO ASSESS THE EFFICACY OF SEPTILlN IN ACUTE RHINITIS
DE3116859A1 (de) Therapeutische zubereitungen fuer die behandlung einer tardiven dyskinesie
EP0358683A1 (fr) Substance pharmaceutique
DE2831728C2 (de) Arzneimittel zur Behandlung von Kopfschmerzen
CN118078936B (zh) 十六味杜鹃花丸防治神经痛的用途
Kumawat et al. Anti-post-traumatic stress potential of Strawberry (Fragaria) and Carissa carandas leaves: A review
EP2548564B1 (fr) Produit pharmaceutique, alimentation d'un patient et procédé de réduction du poids
DE10248601A1 (de) Pharmazeutisches Mittel zur endonasalen Applikation bei der Behandlung von Krankheiten und Störungen des zentralen Nervensystems
Kalam Evaluation of anticonvulsant activity of Aqer Qerha (Anacyclus pyrethrum DC) root in experimental animals
EP1725229B1 (fr) Utilisation de desoxypeganine pour traiter des psychoses schizophrenes
CN107569577A (zh) 一种药物组合物在制备治疗三叉神经痛的药物中的应用
Joshi et al. AYURVEDIC REVIEW ARTICLE ON KUCHLA
Sizer et al. Effects of Anatolian Propolis and Hypertonic Saline Combination Nasal Spray on Allergic Rhinitis Symptoms

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20111222

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME RS

17Q First examination report despatched

Effective date: 20121107

REG Reference to a national code

Ref country code: DE

Ref legal event code: R003

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN REFUSED

18R Application refused

Effective date: 20140128