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WO2006021166A1 - Thérapie combinatoire à base de procaïne - Google Patents

Thérapie combinatoire à base de procaïne Download PDF

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Publication number
WO2006021166A1
WO2006021166A1 PCT/DE2004/002259 DE2004002259W WO2006021166A1 WO 2006021166 A1 WO2006021166 A1 WO 2006021166A1 DE 2004002259 W DE2004002259 W DE 2004002259W WO 2006021166 A1 WO2006021166 A1 WO 2006021166A1
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Prior art keywords
procaine
combination therapy
agents
drugs
hair
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PCT/DE2004/002259
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German (de)
English (en)
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Romulus Balaban
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Romulus Balaban
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Priority to DE112004003010T priority Critical patent/DE112004003010A5/de
Publication of WO2006021166A1 publication Critical patent/WO2006021166A1/fr

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    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
    • A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
    • A61K31/245—Amino benzoic acid types, e.g. procaine, novocaine
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00—Anaesthetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • 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 invention relates to the use of procaine, its physiologically acceptable amine derivatives or acid addition salts for the manufacture of a medicament for combination therapy together with analgesics, antirheumatics, antiphologics, migraines, antihypertensives, antiarrhythmics, antiasthmatics, antiallergics, fibrinolytics, antidiabetic agents, lipid lowering agents, gastrointestinal -Means, antidepressants, anti-dementia drugs, antiparkinsonian, neuroleptics, peripheral and centrally acting muscle relaxants, medicines for erectile dysfunction, mitigation-influencing agents, antivirals, cytostatics and / or with hair nutriens is used.
  • Procaine is the diethylaminoethyl ester of para-aminobenzoic acid (PABA) and is hydrolytically cleaved within 20 to 40 minutes by the tissue-derived plasmacholinesterase into the two antihistamine bodies, PABA and the DEAE. About 30% of the procaine is metabolised via the liver and only 2% are excreted unchanged by the kidney. The metabolism of procaine in the liver may be reduced if the concentration of serum cholinesterase is reduced by previous liver diseases. In rare cases, the procaine is not degraded because of a congenital cholinesterase deficiency.
  • PABA para-aminobenzoic acid
  • the p-aminobenzoic acid is an enzyme component (vitamin H 1), an intermediate in the formation of folic acid, it activates the intestinal flora, protects the intestinal walls and the skin from the effects of sunlight. Probably it is also the main active ingredient against pathological sclerosis and hardening of the tissue (scleroderma, vitiligo). Lack of PABA is associated with the formation of gray hair.
  • the second product of hydrolysis, diethylaminoethanol, is a vasodilator that promotes blood pressure and inhibits the synthesis of acetylcholine. Proven is the
  • diethylaminoethanol leads to an improvement in the action of neurostransmitters in the brain, and thus to an increase in brain performance and brain functions (thinking, memory, learning, concentration).
  • diethylaminoethanol elevates mood, promotes a normal sleep pattern and slows down the aging process in the brain due to its antioxidant effect.
  • Procaine blocks acetylcholine formation in the parasympathetic nervous system of pre- and postganglionic neurons as well as acetylcholine formation in the sympathetic system of preganglionic neurons. It normalizes the balance of neurotransmitters in the brain, and procaine acts on those parts of the brain that are linked to the transformation of the stimulus into emotions.
  • procaine In its mode of action as a beta-receptor blocker, procaine is able to eliminate all reactions caused by stress and lowers the catecholamine level in the blood, weakens the effect of the sympathetic, has antiarrhythmic, antifibrilant, oxygen-sparing effect on the myocardium, acts as a coronary dilator, antipektanginous, as well as capillary and vascular sealing.
  • Procain has a lipotropic effect, acts in the coronary artery against arteriosclerotic processes as well as against central, peripheral arteriosclerotic processes. It improves metabolic processes, including cellular respiration. Procaine has a high redox potential of + 290 mV. It has a protective effect on the body cells, stimulates cellular regeneration and regeneration of the matrix.
  • procaine is a pharmacological substance 5 with extensive and complex pharmacological effects and has a very low tendency to develop side effects.
  • a further task was to exploit the very low side effects of procaine in interaction with other active substances from the most relevant indication areas as well as the influence of procain on the course of therapy in comparison to conventional therapies.
  • an activity-increasing activity of procaine has been found in antirheumatics, antiphologics, antihypertensives, antidiabetics, antidepressants, antidementia, antivirals and cytostatics and that the side effects are eliminated, reduced or prevented due to a scientifically hitherto not yet fully elucidated effect can.
  • the two objects are achieved in that the procaine or its physiologically acceptable amine derivatives or acid addition salts together with analgesics, antirheumatics, antipyretics, migraines, antihypertensives, antiarrhythmics, antiasthmatics, antiallergics, fibrinolytics, antidiabetic agents, lipid lowering agents, gastrointestinal agents, antidepressants , Anti-dementia drugs, antiparkinsonian drugs, neuroleptics, peripherally and centrally acting muscle relaxants, medicines for erectile dysfunction, mitechnischsbeeinpoundung agents, antivirals, cytostatics and / or 0 with hair nutriens for the manufacture of a medicament for a Combination therapy is used.
  • the medicament produced according to the invention has an increased efficiency due to the complementary active ingredients in the combination therapy.
  • the procaine is in the form of its hydrochloride or
  • hydrobromids used in the combination therapy may be expedient to use a physiologically tolerated amine derivative, in particular a C1-C4 mono- or di-substituted derivative of the p-aminobenzoic acid- ⁇ -diethylamino derivative.
  • physiological media, the procaine or a derivative may be present in the form of physiologically acceptable acid addition salts, for example as mesylate, besylate or maleate.
  • Procain is particularly in the combination therapy with antidepressants with regular use able to develop synergies. Worldwide is the
  • depression is a common and serious condition, with high rates of recurrence and increased mortality. After several weeks of therapy, there is an improvement in depression, although only half of the patients can achieve a complete remission.
  • Prof. Wolfgang Schreiber from the Deggendorf-Mainkofen district hospital published the results of a meta-analysis of 31 controlled trials of the antidepressant venlafaxine (Trevilor) compared with other psychotropic drugs fluoxetine, paroxetine, sertraline, citalopram, fluroxamine in the double-blind study involving more than 7000 patients Depression participated. The best remission rates were achieved with venlafaxine (41%) with SSWH (36%) and in the placebo group (24%). The most effective antidepressant in 41% of cases is able to completely suppress the depressive symptoms ( ⁇ beauzeitung, February 2004 issue). Overall, the antidepressants have a relatively low effect size.
  • the combination therapy of procaine according to the invention with antidepressants causes a synergistic interaction of the active ingredients.
  • antidepressants such as tricyclic and tetracyclic antidepressants, MAO inhibitors, selective serotonin reuptake inhibitors or herbal antidepressants with procaine can significantly increase the success rate of antidepressant drug therapy. At the same time, the risk of relapse can be reduced and a reduction in side effects is observed.
  • anti-dementia drugs nootropics
  • procaine as a substance which makes the central nervous system less sensitive to harmful stimuli and as a factor for the elimination of Regulation disorders of the cerebral blood vessels, both with plant antidementia example, with extracts of ginkgo biloba leaves, chemically defined anti-dementia agents such as calcium, cholinesterase inhibitors, glutamate modulators or with, dihydroergotoxine, nicergoline, piracetam, pyritinol, vincamine, vinpocetine and organ preparations, such as For example, Actovegin, Cerebrolisin, Anti Focal Solubile can be combined.
  • anti-dementia drugs nootropics
  • procaine as a substance which makes the central nervous system less sensitive to harmful stimuli and as a factor for the elimination of Regulation disorders of the cerebral blood vessels, both with plant antidementia example, with extracts of ginkgo biloba leaves, chemically defined anti-dementia agents such
  • procain with dopaminergic agents such as amantadine, bromocriptine, selegillin, budipin, cabergoline, lisuride,
  • Pramiprexol, pergolide or ropinirole appropriate.
  • i5 procaine can also be used with L-dopa, levodopa and benserazide, levodopa and carbidopa.
  • Procain develops synergies in combination therapy with antidiabetics. With the use of procaine in the treatment of diabetes mellitus, these synergies are achievable because of its metabolic, vascular, anti-inflammatory and antidepressant effects.
  • the aim of the combination therapy of Procain together with antidiabetics is to achieve a close approximation to the range of the standard glycemia, as well as to avoid the acute and chronic complications of the diabetes mellitus.
  • Procaine can improve and stabilize metabolic processes. It suggests that procaine is also the diabetic specific
  • Procain is capable of acting as a ⁇ -receptor blocker and through its action catechol-lowering effect to enhance the effect of oral hypoglycemic agents.
  • Procain can be used in patients with insulin-dependent insulin resistance.
  • Diabetes mellitus reduces insulin resistance as antibody formation against exogenous insulin increases, while enhancing insulin sensitivity
  • Diabetics suffer about twice as often as the normal population from depression. In about 50% of diabetics, depression is not recognized. Depression is a significant barrier to good blood sugar control. The reduction of depressive symptoms is therefore associated with a better metabolism.
  • procaine with oral antidiabetics and / or insulin (all types of insulin) new principles of action have been found that are therapeutically effective in the pathophysiology of diabetes mellitus and their acute and chronic complications.
  • procaine In its mode of action as a beta-receptor blocker, procaine is able to eliminate all reactions caused by sympatikomimetics.
  • Combination therapy with antihypertensive agents is able to potentiate the efficacy of antihypertensive medication while reducing, eliminating or preventing the side effects of antihypertensive agents.
  • Procaine has sympatholytic, lowering catecholamine, has an antiadrenergic effect on blood vessels, has spasmolytic and vasodilatory effect, is sodium antagonist and has diuretic effect renal function, has a beta-blocking effect and improves microcirculation by opening the arteriovenous anastomosis.
  • procaine may be used with all monotherapy-suitable substances such as beta-receptor blockers, calcium channel blockers, inhibitors of the renin-angiotensin system, diuretics, vasodilators, peripherally active anti-adrenergic agents such as ⁇ -receptor blockers, and with centrally acting anti-adrenergic agents be combined with herbal antihypertensives and homeopathic remedies.
  • monotherapy-suitable substances such as beta-receptor blockers, calcium channel blockers, inhibitors of the renin-angiotensin system, diuretics, vasodilators, peripherally active anti-adrenergic agents such as ⁇ -receptor blockers, and with centrally acting anti-adrenergic agents be combined with herbal antihypertensives and homeopathic remedies.
  • procaine may be administered, for example, with H1 antihistamines, with cetirizine, loratadine, terfenadine, hydroxysin,
  • Procain has an antihistaminic, antiallergic, vaso-sealing and antipruritic effect in the combination therapy.
  • the antihistaminic effect results from the reversible blocking of the H1 and H2 receptors, which are competitively inhibited.
  • procaine has an antispasmolytic effect on smooth muscle.
  • procaine Due to the anti-allergic, anti-inflammatory, anticholinergic and antiobstructive as well as bronchospasmolytic effects of procaine, it can significantly improve the therapy of bronchial asthma in combination therapy.
  • combination therapy of procaine against bronchial asthma and expediently against allergies rhinitis allergica and allergic asthma procaine together with vitamin C 1 vitamin B5, ß-carotene, vitamin E, zinc, manganese and / or selenium given.
  • procaine may be conveniently given in combination with betamimetics or cortisone.
  • the procaine can also be used in combination therapy with antirheumatics, anti-inflammatory drugs and analgesics.
  • the procaine is able to work against all components of the inflammatory quatro such as tumor, dolor, rubor, calor (swelling, pain, redness, fever) and function restrictions.
  • procaine has an anti-oedematous, antipyretic, antibacterial and analgesic effect.
  • Procaine inhibits the body's production of interleukin-6 (IL-6) and C-reactive protein; it activates the body's defense.
  • IL-6 interleukin-6
  • analgesics / anti-inflammatory drugs such as steroidal and non-steroidal anti-inflammatory drugs combined
  • the combination therapy of procaine according to the invention with cytostatics is characterized by the fact that the side effects of the cytostatics are markedly reduced, since the procaine protects the healthy body cells during the therapy. At the same time, the procaine is able to inhibit the growth of cancer cells.
  • the combination therapy of procaine with cytostatics is particularly preferred because of the reduction of the toxic side effects as well as the anti-cancer effect of procaine.
  • cytostatic agents in combination therapy all conventional cytotoxic drugs in question, in particular herbal cytostatics, chemically defined cytostatics and antineoplastic agents (cisplatin).
  • the combination therapy of procaine with cytostatics allows the usual dosage of cytotoxic drugs to increase by 2 to 5 times, in particular by 2 to 3 times, more preferably a dosage that is more than 3 times the usual dosage.
  • Combination therapy of procaine, which itself has antiviral activity, with antiviral agents and as part of antiviral combination therapy in HIV patients with antiretroviral agents, can reduce the side effect of antiviral agents and antiretroviral agents.
  • Procaine inhibits in combination therapy with virustatics and antiretroviral agents, the proliferation of viruses and / or their growth (antiviral and viralidal effect).
  • the antivirals acyclovir; Ganciclovir, famciclovir, valganciclovir or foscamet in combination therapy.
  • the combination of procaine with antivirals has proven to be a successful treatment concept in daily practice.
  • the procaine is suitable in the
  • Procaine Recanalization of arteriovenous shunts, acute Myocardtinfarkt and closure of the central vessels of the eye to be used.
  • the combination therapy of Procaine is particularly with the fibrinolytic Actilyse, Corase, Streptase,
  • procaine In combination with hair nutrients, procaine also has an excellent effect in combination therapy.
  • the combination therapy of Procaine with hair nutrients stops hair loss, eliminates dandruff, regenerates the hair growth process and leads to a significantly improved hair volume.
  • the combination of procaine with hair nutrients such as vitamin B1, vitamin B2 (riboflavin), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine), folic acid, biotin, choline inositol, L-cysteine, in the form of tablets, and in particular the Combination therapy of procaine with B1, B2, B6 and L-cysteine as an injection under the head skin has proven to be particularly effective.
  • Procaine blocks cholinesterase, inhibits the excitability of peripheral choline receptors, and simultaneously blocks acetylcholine production at synapses of the central nervous system and motor endplates of the musculature.
  • the procaine has a vegetative balancing effect on gastric secretion. Detected is a musculotropic spasmolytic o effect.
  • chemically defined gastritis-ulcer-H2 receptor blockers such as cimetidine, famotidine, ranitidine, nizatidine or with anticholinergics, such as muscarinic receptor blockers or with spasmolytics / Antichlolinergic agents such as omeprazole, esomeprazole
  • procaine is a Class IA of Nathumantagoriisten and membrane stabilizers.
  • the main mode of action of procaine is aimed at extending the duration of the action potentials. Therefore, the procaine can be used in atrial fibrillation, supraventricular and ventricular tachycardia.
  • procaine can therefore be used in the combination therapy with class IA-A-quinidine-like substances, class IB-A, class IC-A, class II-A (beta-receptor blockers) class III-A (amiodarone and sotalol).
  • Class IV-A calcium antagonists with antiarrhythmic properties such as verapamil, gallopamil or diltiazem are used.
  • the procaine may, with its gentle but complex action against all backgrounds of erectile dysfunction, such as neurogenic, vascular or psychogenic with all chemically defined agents which are active against erectile dysfunction, with Johimbin preparations and / or
  • the combination therapy of Procaine with lipid-lowering agents makes sense.
  • Cheap combination of Procains with lipid-lowering agents are those with HMG-CoA reductase inhibitors, such as simavastatin, fluvastatin, lovastatin, pravastatin or atorvastatin.
  • Combination therapy with fibrates, with bile acid binding Agents, such as colestyramine, colestipol and with nicotinic acid and its derivatives as well as with organ and plant preparations is also useful.
  • procaine Because of its action against changes in cortical neural activity, against disorders of the neurotransmitter equilibrium, against circulatory disorders and probably its action against aseptic, vascular inflammation of the dura mater, procaine can be used particularly well in combination therapy with migraine agents. Procaine is particularly suitable for this combination therapy because it improves the work of the neurotransmitters, supports the microcirculation and has an anti-inflammatory effect.
  • Procaine has a vegetative balancing against neurogenic bladder disorder as well as spasmolytic and anticholinergic.
  • Suitable agents influencing the combination in the treatment with procaine are, for example, oxybutynin, trospium chloride, tolterodine, phenoxybenzamine, propiverine and homeopathics.
  • Procaine is suitable to be used in the combination therapy with neuroeleptics.
  • Procaine can be used with all typical and atypical antipsychotics such as chlorpromazine, reserpine, haloperidol, fluphenazine, thioridazine, clozapine, risperidone, olanzapine, amisulpride, quetiapine, ziprasidone and aripripazole.
  • Procain is able to potentiate the efficacy of neuroeleptics while reducing, eliminating or preventing the side effects of neuroleptics.
  • pharmaceutical compositions for example are pharmaceutical compositions for example, reserpine, haloperidol, fluphenazine, thioridazine, clozapine, risperidone, olanzapine, amisulpride, quetiapine, ziprasidone and aripripazole.
  • Procain is able to potentiate
  • the active substances which can be used according to the invention are from the indication areas of the analgesics,
  • Anti-inflammatory drugs anti-inflammatory drugs, migraines, antihypertensives, and
  • Antiarrhythmics antiasthmatics, antiallergic drugs, fibrinolytics, antidiabetics,
  • Lipid-lowering, gastrointestinal, antidepressants, anti-dementia Lipid-lowering, gastrointestinal, antidepressants, anti-dementia,
  • compositions of the invention further contain physiologically acceptable carrier and toxicological concern.
  • a particularly preferred pharmaceutical composition is an injection or infusion preparation coexistent with suitable pharmaceutically acceptable carriers and excipients.
  • suitable pharmaceutically acceptable carriers and excipients can be present as a parenteral depot medicine form, as an implant or in a retarded form.
  • the parenteral diluent may optionally be packaged separately in the packaging in such a way that mixing of the components contained therein is possible immediately prior to use with a conventional parenterally administrable diluent.
  • compositions can be present in solid, perorally administrable form as a tablet, as a capsule, as a dragee as a sustained-release and / or enteric preparation or as a liquid medicament.
  • the perorally administrable pharmaceutical composition may be a solution or a suspension.
  • effervescent tablets, of tabs or dragees which optionally controlled the active ingredient, for example, delayed or accelerated release.
  • the pharmaceutical composition according to the invention may also be present in the form of an inhalation therapy, as a transdermal therapeutic system for systemic treatment or as a gastrointestinal therapeutic system for systemic treatment in the form of an ointment, suspension, emulsion, patch or in the form of an externally administrable solution.
  • the two combined active ingredients in the pharmaceutical composition are present separately from each other in separate packaging in the drug package.
  • the unit dose of procaine according to the invention in the combination therapy is 0.5 to 3 wt .-% Procaine based on the pharmaceutical composition with single administration. Preference is given to 1 to 2 wt .-% Procaine per single administration.
  • Preferred doses for single administration of procaine hydrochloride are 50 mg to 300 g, especially 100 to 200 mg.
  • the total dose per day is 500 to 600 mg procaine.
  • the patient was in a psychiatric hospital from November 1973 to February 1974 for bipolar psychosis (depressed and manic). Initially inpatient and later outpatient.
  • Antidepressant therapy has been supplemented with 100 mg of procaine injected intramuscularly three times a week since 1993.
  • the dose of saroxan has been reduced to 100 mg / day after three months, and after three more months
  • Procain with St. John's wort extract or Felis 650 which is used twice a day, supplemented. Since then, the combination therapy consisting of two to three weekly injections of 100 mg procaine i.m. and 650 mg of St. John's wort extract taken daily, in addition to Lecitin and Rökan.
  • the patient suffered from a depressive syndrome (numbness, thoughts, loss of drive, loss of libido, anxiety and restlessness, sleep disorders, significant weight loss, pronounced daily fluctuations, thoughts of suicidal thoughts).
  • amitriptyline 100 mg daily and procaine 100 mg three times a week She was treated with amitriptyline 100 mg daily and procaine 100 mg three times a week. The symptoms improved continuously. After six months the amitriptyline dose was reduced to 50 mg daily and after another six months the amitriptyline was slowly discontinued. Thereafter, the patient was treated for 12 months with a combination therapy of procaine and redcurrants. Six months with Felis 650 mg twice daily followed by Felis 650 mg once daily for six months and 100 mg Procain three times a week.
  • the mental health and general health record is consistently good.
  • Impairment, vegetative and somatic disorders, palpitations, constipation, loss of libido and daily fluctuations in mood This group was treated with venlaflaxin (Trevilor) 37.5 mg twice daily and with 100 mg procaine given intramuscularly five times a week. After six weeks an improvement of the mental, vegetative and somatic state was observed. The dose of venlaflaxin was reduced to 37.5 mg daily and after another six weeks the drug was discontinued. Subsequently, the patient group was treated with the following combination therapy. 1300 mg of St. John's wort extract and five times weekly 100 mg of Procaine intramuscularly. The clinical picture of the patients has improved continuously.
  • a 53-year-old type 2 diabetic with a BMI of 33 and liver dysfunction The diabetic herself is not able to change her weight.
  • the prescribed diet is only relatively maintained, walks are made only two or three times a week for almost two hours, no alcohol consumption, no hepatitis in the history.
  • the patient is treated with a combination of Repaglinide 1 mg three times daily and Metformin 500 mg twice daily.
  • the glucose value was 267 and the HbA1c value was 10.1.
  • the patient was additionally treated with 15 ml of Procaine 1% (150 mg) intramuscularly five times a week. Further medication, lifestyle, diet and exercise remained unchanged. During the five-month study, the patient gained more weight.
  • the following table shows how their sugar levels have changed.
  • the clinical picture shows dramatic glycaemia fluctuations from 300 mg up to 5 70 mg within 30 minutes without a specific background, a low blood sugar every night, the leukocyte count has been 22,000 to 23,000 for many years, HbAIc 14 to 16, generalized inflammatory dermatosis (scalp, chest, all extremities), neuropathic symptoms: tingling to the knees on both sides, numbness on touch of the hands and feet, achilles tendon reflex, unreliable on both sides.
  • the patient While maintaining his previous insulin and diet regimen and his previous habits, the patient has been injecting a vial of 5 mg procaine per day for four months.
  • the clinical picture has changed as follows after the four-month combination therapy of procaine and insulin:
  • the medication was (hydrochlorothiazide 12.5 mg and felodipine 5 mg daily and valsartan, respectively 160 mg and hydrochlorothiazide 12.5 mg daily.)
  • 100 mg of procaine were intramuscularly injected five times a week over a period of 10 weeks, and the RR values were measured at 142/152: 85/91 following the six-week treatment. After four more weeks of combination therapy blood pressure values at patients stabilized at this level.
  • the following treatment regimen was used in 18 patients: 100 times per week per 100 mg procaine hydrochloride, diclofenac 50 mg daily or ibuprofen 400 mg twice daily or piroxicam 100 mg daily and vitamin E 400 IU twice daily and magnesium 200 mg as magnesium aspartate per die.
  • the daily dose of diclofenac and ibuprofen could be halved without worsening the
  • Ibuprofen be discontinued.
  • the patients treated with piroxicam were able to discontinue this after six weeks.
  • the patients with rheumatic complaints were treated for a further 10 weeks with the combination therapy consisting of procaine, three times 100 mg i.m. per week, herbal anti-inflammatory drugs, magnesium aspartate 200 mg and vitamin E 800 daily and subsequently 400 mg. In all cases, the symptoms have further improved.
  • hair volume could be within a 6- to 9-month period
  • the dosage of procaine with the named active ingredients can be carried out in a ratio of 10: 1 to 1:10, in particular in a ratio of 5: 1 to 1: 5.
  • Per 100 mg of procaine hydrochloride the usual daily dosing recommendations of the herbal preparations and organ preparations are used. These are usually two to three times daily per tablet, tablet or a dragee. Per 100 mg of procaine hydrochloride are administered 80 to 90% of the usual daily dosage recommendation of the chemically produced drugs. This applies both to solid dosage forms, semi-solid and liquid dosage forms, such as injections and infusions.
  • procaine hydrochloride with antirheumatics is carried out according to the following dosage scheme.
  • Per 100 mg of procaine hydrochloride the usual daily dosing recommendations of the herbal supplements, vitamin E400 IU and 200 mg magnesium in the form of magnesium aspartate are used.
  • procaine hydrochloride Per 100 mg of procaine hydrochloride, 80 to 90% of the usual daily dosage recommendation of the chemically produced active ingredients, vitamin E400 IE and 200 mg of magnesium in the form of magnesium aspartate are used.
  • procaine with antidiabetic agents per 100 mg procaine hydrochloride given the usual oral daily dosage recommendations of the antidiabetics. These are usually two to three times daily per tablet, tablet or a dragee.
  • Procain When Procain is combined with the following types of insulin (short-acting, intermediate-acting, long-acting insulin, human insulin, animal insulin, insulin analogues), daily 100 to 300 mg procaine hydrochloride are administered together with the individually required amount of insulin.
  • procaine hydrochloride which may be in the form of a film-coated tablet, capsule or in the form of an injection solution
  • the usual daily dosage recommendation of cytotoxic agents are used.
  • procaine hydrochloride is added to the recommended daily dose of cytotoxic agents.
  • procaine hydrochloride 100 to 200 mg procaine hydrochloride, in the form of a
  • procaine hydrochloride 100 to 200 mg procaine hydrochloride, in the form of a
  • usual daily dosing recommendations of the viral and antiretroviral agents administered 100 to 200 mg procaine hydrochloride, in the form of a
  • procaine hydrochloride is added to the recommended daily allowance of viral and antiretroviral agents.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth 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)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Epidemiology (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Virology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Dermatology (AREA)
  • Toxicology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Reproductive Health (AREA)
  • Anesthesiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne une forme thérapeutique en mesure de transférer les effets fonctionnels pharmacologiques nombreux et complexes de la procaïne à des domaines d'indications pertinents. Elle concerne l'utilisation de procaïne avec des analgésiques, des antirhumatismaux, des antiphlogistiques, des agents contre la migraine, des antihypertenseurs, des antiarythmiques, des antiasthmatiques, des antiallergiques, des fibrinolytiques, des antidiabétiques, des abaisseurs du niveau de lipides, des médicaments pour le système gastro-intestinal, des antidépresseurs, des médicaments contre la démence, des antiparkinsoniens, des neuroleptiques, des relaxants musculaires périphériques et centraux, des médicaments contre la dysfonction érectile, des médicaments agissant sur la miction, des virostatiques, des cytostatiques et / ou avec des substances nutritives capillaires, ainsi que des compositions pharmaceutiques contenant de la procaïne.
PCT/DE2004/002259 2004-08-21 2004-10-12 Thérapie combinatoire à base de procaïne WO2006021166A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DE112004003010T DE112004003010A5 (de) 2004-08-21 2004-10-12 Kombinationstherapie mit Procain

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DE102004040630A DE102004040630A1 (de) 2004-08-21 2004-08-21 Kombinationstherapie mit Procain
DE102004040630.8 2004-08-21

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WO2006021166A1 true WO2006021166A1 (fr) 2006-03-02

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WO2021233571A1 (fr) 2020-04-30 2021-11-25 Ninoderm Ug (Haftungsbeschränkt) Agent de traitement pour thérapie antivirale, applicateur et procédé de fabrication d'un agent de traitement

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995007103A1 (fr) * 1993-09-07 1995-03-16 The Procter & Gamble Company Compositions contenant un sel d'acide amine d'un agent anti-inflammatoire non steroidien a base d'acide propionique et au moins un decongestionnant ou un expectorant ou un antihistaminique ou un antitussif
JP2001010977A (ja) * 1999-06-29 2001-01-16 Taisho Pharmaceut Co Ltd 経口用組成物

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Publication number Priority date Publication date Assignee Title
DE3940315A1 (de) * 1989-12-06 1991-06-13 Speranta Dr Med Stratulat Muskelrelaxans, insbesondere fuer die gynaekologie
CA2111837A1 (fr) * 1991-06-20 1993-01-07 Bruce W. Miller Composition topique favorisant la cicatrisation des lesions de l'herpes
US5891885A (en) * 1996-10-09 1999-04-06 Algos Pharmaceutical Corporation Method for treating migraine
DE19715594A1 (de) * 1997-04-15 1998-10-22 Bayer Ag Analgetika-Kombination

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995007103A1 (fr) * 1993-09-07 1995-03-16 The Procter & Gamble Company Compositions contenant un sel d'acide amine d'un agent anti-inflammatoire non steroidien a base d'acide propionique et au moins un decongestionnant ou un expectorant ou un antihistaminique ou un antitussif
JP2001010977A (ja) * 1999-06-29 2001-01-16 Taisho Pharmaceut Co Ltd 経口用組成物

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BEKEMEIER H ET AL: "ANTI-INFLAMMATORY EFFECT OF COMBINATIONS OF INHIBITORS OF PHOSPHOLIPASE A-2 CYCLOOXYGENASE AND LIPOXYGENASE OF THE ARACHIDONIC-ACID CASCADE", DIE PHARMAZIE, vol. 41, no. 4, 1986, pages 260 - 262, XP001206706, ISSN: 0031-7144 *
PATENT ABSTRACTS OF JAPAN vol. 2000, no. 16 8 May 2001 (2001-05-08) *

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DE112004003010A5 (de) 2007-08-09

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