WO2006021166A1

WO2006021166A1 - Procaine combination therapy

Info

Publication number: WO2006021166A1
Application number: PCT/DE2004/002259
Authority: WO
Inventors: Romulus Balaban
Original assignee: Romulus Balaban
Priority date: 2004-08-21
Filing date: 2004-10-12
Publication date: 2006-03-02
Also published as: DE112004003010A5; DE102004040630A1

Abstract

The invention relates to a form of therapy which is capable of transferring the extensive and complex pharmacological action functions of procaine to relevant indications. The invention also relates to the use of procaine in combination with analgesics, antirheumatics, antiphlogistics, migraine analgesics, antihypertensive agents, antiarrhythmics, antasthmatics, antiallergics, fibrinolytic agents, antidiabetics, lipid reducers, gastrointestinal agents, antidepressants, antidementia drugs, antiparkinson drugs, neuroleptics, peripheral and central muscle relaxants, drugs against erectile dysfunction, miction-influencing agents, virostatics and/or with hair nutrients, and to pharmaceutical compositions containing the same.

Description

Combination therapy with procaine

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.

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

^■ Spasmolytic effect on tonic vessels and the influence on the

.Vegetative sympathetic and parasympathetic structures and the stimulating effect on the central nervous system. Furthermore, 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). In addition, 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.

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.

In addition, 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.

After many years of own experience in the treatment of patients with procaine, it has been found that procaine is a pharmacological substance 5 with extensive and complex pharmacological effects and has a very low tendency to develop side effects.

^'It has therefore set itself the task of developing a form of therapy that is.-Capable of extensive and complex pharmacological action functions of procaine transmitted to relevant indications to lo, and to make available therein.

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.

Surprisingly, 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.

According to the invention, 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, miktionsbeeinflussung 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.

Usually, the procaine is in the form of its hydrochloride or

5 hydrobromids used in the combination therapy. It 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-β-diethylamino derivative.

- to use ethyl ester. To improve the solubility in aqueous or

, 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. By the use according to the invention for the production of a medicament for the combination therapy of Procain with further customary active substances, it is possible by using the effectiveness of the individual components (addition and potentizing effect) to strengthen (widen) and widen the main effect of the Kombinations¬ partner and a To reduce the toxicity. Procain is able to synergize in combination therapy and increase the efficacy of the combination therapy combination at lower dosages.

o Some diseases seem to be associated with inflammatory processes; As diabetes mellitus, arteriosclerosis and Alzheimer's. Procaine is known for its anti-inflammatory effect. It inhibits the inflammatory processes and exerts an attractant effect (chemotaxis) on immune cells and has an activating effect on the specific and non-specific defense. The use of antiinflammatory active substances in the new combination therapy results in improved therapeutic success.

The use according to the invention of the procaine for the production of a medicament which is used in combination therapy together with analgesics, o antirheumatics, antiphologics, migraines, antihypertensives, antiarrhythmics, antiasthmatics, antiallergics, fibrinolytics, antidiabetics, lipid lowering agents, gastrointestinal agents, antidepressants, antidementia agents, Antiparkinsonian medicines, neuroleptics, peripherally and centrally acting muscle relaxants, drugs for erectile dysfunction, antifungals, antivirals, cytostatics and / or hair nutrients can reduce, eliminate or prevent the side effects of these medicines.

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 (Ärztezeitung, 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. The combination of 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.

The combination therapy according to the invention of anti-dementia drugs (nootropics) with 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.

^" Because of the anticholinergic effect of Procains are also combinations

, between procaine and Parkinson's agents and other agents against extrapyramidal disorders and centrally acting anti-acetylcholinergics such as

Biperiden, Bornaprin, Metixen, Procyclidin, Trihexyphenidyl expedient.

In addition, the combination therapy of procain with dopaminergic agents such as amantadine, bromocriptine, selegillin, budipin, cabergoline, lisuride,

Pramiprexol, pergolide or ropinirole appropriate. According to the invention, 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 has a variety of positive effects on the clinical picture and on the

25 complications of diabetes mellitus. As a result of diabetes mellitus, for example, in Germany annually 31,000 amputations of the lower

Extremities are performed and 4,000 diabetics go blind each year

Germany. Procaine can improve and stabilize metabolic processes. It suggests that procaine is also the diabetic specific

30 micro- and macroangiopathies that may reduce or delay cardiovascular and renal risk as well as diabetic retinopathy. Procain is capable of acting as a β-receptor blocker and through its action catechol-lowering effect to enhance the effect of oral hypoglycemic agents.

It is known that there is a link between inflammation and diabetes mellitus as well as arteriosclerosis. Furthermore, a high concentration of inflammatory markers in the plasma is often associated with a

Associated with insulin resistance. Procain can be used in patients with insulin-dependent

Diabetes mellitus reduces insulin resistance as antibody formation against exogenous insulin increases, while enhancing insulin sensitivity

- the peripheral tissue.

An increasing comorbidity is observed in diabetes mellitus with depression. The comorbidity of both diseases worsens the possibilities of metabolic control, leads to more micro- and macrocascular complications and overall deteriorates the prognosis of the disease process. 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.

The inventive combination of 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.

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. In combination therapy, 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 α-receptor blockers, and with centrally acting anti-adrenergic agents be combined with herbal antihypertensives and homeopathic remedies.

In the combination therapy with antiallergic drugs, procaine may be administered, for example, with H1 antihistamines, with cetirizine, loratadine, terfenadine, hydroxysin,

Clemastine hydrogen fumarate, misolastine with allergen extracts such as Depigoid or

Phostal as well as with anti-allergic homeopathic remedies are combined. The

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. Furthermore, procaine has an antispasmolytic effect on smooth muscle.

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. In the 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. For non-allergic asthma, procaine may be conveniently given in combination with betamimetics or cortisone.

According to the invention, 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. Furthermore, 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.

Due to the anti-inflammatory effect of Procains this can expediently also with herbal analgesics / antirheumatics, such as Brennesel, devil's claw, willow bark and / or with vitamins of the B group, with high-dose vitamin E, with enzyme preparations

Homeopathic and chemically defined analgesics / anti-inflammatory drugs, such as steroidal and non-steroidal anti-inflammatory drugs combined

^• become. The combination therapy of procaine according to the invention with analgesics and / or antirheumatics is characterized by a reduction,

Eliminate or prevent the side effects of these

Indications usual agents. In particular, the

Side effects, the non-steroidal anti-inflammatory drugs significantly reduced.

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. As 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. By using the

Effectiveness of both drugs in the combination therapy, an addition and potentiation effect is achieved. Procaine inhibits in combination therapy with virustatics and antiretroviral agents, the proliferation of viruses and / or their growth (antiviral and viralidal effect). Conveniently, 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.

Due to its fibrinolytic effect, the procaine is suitable in the

_, Combination therapy with other fibrinolytics to eliminate

Vascular occlusions caused by fresh or older clots in case of o pulmonary embolism, venous thrombosis, acute arterial thrombosis,

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,

Urokinase displayed.

5 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.

5 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. As a result, the procaine has a vegetative balancing effect on gastric secretion. Detected is a musculotropic spasmolytic o effect. Combination therapy of procaine with chemically defined antacid aluminum-magnesium silicate hydrate or bismuth, as well as with herbal gastritis ulcers, 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, lansoprazole, rabeprazole and / or pantoprazole and gastrointestinal enzyme preparations can improve its tolerability.

^'The combination of procaine with antiarrhythmic drugs seems appropriate because 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. According to the invention, 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.

According to the invention, 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

Homeopathic remedies are used in combination therapy. Appropriately, the usual drugs that act against erectile dysfunction are used. They are sold under the trade names Caverject, Caverject Impuls, Cialis,

Levitra, Ixense, Uprima, Viagra, Viridal distributed.

Because of the lipotrophic effect and the therapeutic effect against arteriosclerotic processes, 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.

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.

In the combination therapy of procain with migraine agents according to the invention, the combinations of procaine with all conventional triptans or with ergotamine, the derivatives of ergotamine, with ibuprofen, acetylsalicylic acid or even with paracetamol and with herbal migraine remedies and homeopathics.

Also in the combination therapy with miktionsbeeinflussenden means 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.

Because of its effect in a dysbalance of cerebral neurotransmission to shift these towards a physiological balance, the 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. According to the invention are pharmaceutical compositions for

Provided procaine, the physiologically acceptable

Amine derivatives or acid addition salts and one or more common

Contains active substances from the following indication areas, 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,

Antiarrhythmics, antiasthmatics, antiallergic drugs, fibrinolytics, antidiabetics,

Lipid-lowering, gastrointestinal, antidepressants, anti-dementia,

^{"Antiparkinsonian,} antipsychotic drugs, peripheral and centrally acting - muscle relaxants, drugs for erectile dysfunction, voiding influencing agents, antivirals, cytostatics and / or Hair nutriens The pharmaceutical compositions of the invention further contain physiologically acceptable carrier and toxicological concern.

Excipients.

A particularly preferred pharmaceutical composition is an injection or infusion preparation coexistent with suitable pharmaceutically acceptable carriers and excipients. Appropriately, these can be present as a parenteral depot medicine form, as an implant or in a retarded form. If the pharmaceutical composition is in the form of a concentrate, powder or lyophilisate, 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.

Further expedient pharmaceutical 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. In this case, the perorally administrable pharmaceutical composition may be a solution or a suspension. Also conceivable is the use of 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. In a particularly preferred embodiment, 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 following studies and results with persons substantiate the effects according to the invention.

Study 1: Combination therapy of procaine with antidepressants:

Over a period of 15 years, a group of patients with all forms of depression symptoms was cared for and observed.

First case study (today 84 years old):

The patient was in a psychiatric hospital from November 1973 to February 1974 for bipolar psychosis (depressed and manic). Initially inpatient and later outpatient.

Over a period of 20 years, 150 g of Saroten were taken daily. Intermetierend the dose was reduced to 100 g daily, because of a worsening of the symptoms, the dose had to be increased again to 150 mg daily. In 1993, the patient was treated for depressive moods, non-objective anxiety, lack of drive, mood swings, inhibition of thinking, lack of concentration, constipation, cardiac arrhythmias, occasional collapse conditions, increase in liver enzyme activity. The latter four symptoms are associated with side effects caused by years of treatment with Saroten.

^{■ * "} 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

Months to 50 mg. The general and mental

Status of the patient has improved continuously. 12 months after the start of the combination therapy with sarats and procaine, the amitriptyline was completely discontinued. Following was a combination therapy of

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 health status of the patient and his mental performance are age-appropriate to describe as very good, his depressive and manic phases have only very discrete manifestations.

Second case study (48 years):

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).

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.

Third case study (72 years):

o A patient who experiences reactive depression (depressive mood, anxiety, difficulty concentrating, sleeping disorders, hopelessness) due to very stressful living conditions was initially treated with five weekly doses per 100 mg procaine i.m. together with twice 650 mg St. John's wort extract, which was taken daily, treated 5. This combination therapy lasted for six months. It was possible to avoid a worsening of depressive symptoms and the patient was able to work during the entire disease phase. The procaine treatment was then continued and the administration of St. John's wort extract reduced to 450 mg daily. The man has a permanently o balanced state of health.

Further case studies:

Over a period of 18 months, five patients between 40 and 45 years of age were treated and observed with depressive syndrome. They are exposed to permanent psychosocial stress, have a hypersensitive personality structure, feel tired and without energy, live with anxiety and worry about the future. Other symptoms include difficulty concentrating, falling asleep and staying asleep,

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.

After an average four to six-week incapacity for work, they were able to progressively resume their work.

The combination therapy was continued as follows:

650 mg daily of St. John's wort extract and procaine 100 mg intramuscularly two to three times a week.

Study 2: Combination therapy of anti-dementia drugs (nootropics) with procaine.

Case Studies:

In the last 14 years, a total of 20 patients (both male and female) aged 58-78 years were treated with a combination of procaine and an extract of Ginkgo biloba leaf (Tebonin, Rökan) and in two cases with a combination of Procain Piracetam as a preventive measure against a possible Alzheimer's dementia, treated against the degradation of mental and physical performance. Patients with incipient disturbances of concentration, dizziness, and depressed mood were included in this group, which are not based on a specific underlying disease. Eight patients have had arterial hypertension for many years, which is well adjusted to medication. This group of patients received Tebonin Intens 120 mg or Rökan novo 120 mg twice daily or Piracetam 1600 mg daily and 100 mg Procain intramuscularly three times a week. A patient aged 93 years has now passed away, the youngest is now 72 years, the oldest 92 years, most patients are between 78 and 85 years old. It was found that the initial pathological processes did not worsen over the years, but were consistently or significantly delayed.

The positive effect on the clinical picture, consistent cognitive performance and unrestricted daily activity can be attributed to 14 years of treatment with procaine in combination with ginkgo biloba extract or procaine in combination with piracetam. A female patient, 82 years old, had her dizziness aggravated, possibly due to hydrocephalus diagnosed four years ago.

Study 3: Combination therapy of procaine with antidiabetics

First case example:

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. Thereafter, in addition to the above-mentioned medication, 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. Monthly glucose HbAlc value

1st month 267 10.1

2nd month 196 9,3 s 4th month 160 8,8

6th month 119 8.0

^" Third case study:

A 44-year-old patient (normal body weight, insulin-dependent for 34 years, very experienced diabetic, no endogenous insulin production) who has used the following insulin therapy over the last o years:

Long-acting insulin Protafan three times a day 16 IU in the morning, 15 IU at 6 pm, 9 IU at 2 am. Short-acting insulin: 3 IU for one BE at all meals.

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. 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:

5 The fluctuations in glycaemia and nocturnal hypoglycaemia no longer occur. The patient requires less short-acting insulin (the ratio 3: 1 only exists for the morning, otherwise the ratio is 1) IE: 1 BE for the rest of the day. The HbAIc dropped from 14 to 16 to 9.8. The leukocyte count has reduced from 22,000 to 23,000 to the current 12,000. The neuropathic symptoms have receded and all inflammatory dermatoses healed.

Study 4: Combination therapy of procaine with antihypertensive agents

Case Description:

^" A 10-person group of patients older than 60 years treated with diuretics and calcium antagonists had RR values of 150/160: 92/98 mm Hg despite this hypotensive therapy. The medication was (hydrochlorothiazide 12.5 mg and felodipine 5 mg daily and valsartan, respectively 160 mg and hydrochlorothiazide 12.5 mg daily.) In addition, 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.

Study 5: Combination therapy with procaine for the treatment of bronchial asthma

With a combination therapy of procaine with vitamin C ₁ vitamin B5, beta-carotene, vitamin E, zinc, manganese and selenium, a group of patients (50 patients) could successfully be treated without the allergy test, desensitisation and cortisone.

Study 6: Combination therapy of procaine with analgesics / antirheumatics

Case Description:

For the treatment of acute and chronic arthrides, rheumatoid arthritis and soft tissue rheumatism, 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.

After six weeks of therapy, the clinical picture has changed as follows: The

Pain of patients decreased, swelling and the raised local temperature of joints considerably decreased and

Agility has improved. After another six weeks increasing

- analgesic and antiinflammatory effect, the daily dose of diclofenac and ibuprofen could be halved without worsening the

To observe symptoms. After another four weeks Diclofenac and

Ibuprofen be discontinued. The patients treated with piroxicam were able to discontinue this after six weeks.

Subsequently, 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.

Study 7: Combination therapy of procaine with antivirals

Case Description:

In 28 cases a complete healing success could be achieved by injecting procaine directly into the zona zoster areas or in areas infected with herpes simplex virus. In three cases of zona zoster in the facial area, a healing process was induced by the combination therapy of procaine with acyclovir as an infusion and by injection of procaine directly into the zona zoster areas.

Study 8: Combination therapy of procaine with hair nutrients Fallbθschreibung:

The combination of Procaine with Hair nutrients 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 the combination therapy of procaine with B1, B2, B6 and L-cysteine, among which

Kopfschwarte was injected, resulted in a patient group consisting of

32 patients to stop the constant hair loss process.

In addition, hair volume could be within a 6- to 9-month period

■ continuous therapy (once or twice a week) may be increased two to three times. In all patients a complete

Healing from dandruff can be achieved.

Doses of the active ingredients in the combination therapy of Procaine with analgesics, antirheumatics, antiphologics, migraines, antihypertensives, antiarrhythmics, antiasthmatics, antiallergics, fibrinolytics, antidiabetics, lipid-lowering, gastrointestinal, antidepressants, antidementia, antiparkinsonian, neuroleptics, peripherally and centrally acting muscle relaxants , Erectile dysfunction drugs, anti-viral agents, antivirals, cytostatics and / or hair nutrients. 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.

Doses of the active ingredients in the combination therapy of Procaine with analgesics, antiphologics, migraines, antihypertensives, antiarrhythmics, antiasthmatics, antiallergic drugs, fibrinolytics, lipid lowering, gastrointestinal, antidepressants, antidementia, antiparkinsonian, neuroleptics, peripherally and centrally acting muscle relaxants, medicines for erectile Dysfunction, miktionsbeeinflussenden means and / or with Hair nutriens.

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.

The dosage of 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.

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.

For the dosage of 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.

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.

In the combination therapy of procaine with cytostatics per 100 mg of 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. Using an infusion solution, 200 mg procaine hydrochloride is added to the recommended daily dose of cytotoxic agents.

In the combination treatment of procaine with viral and antiretroviral agents 100 to 200 mg procaine hydrochloride, in the form of a In addition, the usual daily dosing recommendations of the viral and antiretroviral agents administered.

Using an infusion solution, 200 mg procaine hydrochloride is added to the recommended daily allowance of viral and antiretroviral agents.

Claims

claims

1. Use of procaine or its physiologically acceptable amine derivatives or acid addition salts for the manufacture of a medicament

5 for combination therapy together with analgesics, antirheumatics, antiphologics, migraines, antihypertensives, antiarrhythmics, antiasthmatics, antiallergics, fibrinolytics, antidiabetics, lipid lowering agents, gastrointestinal, antidepressants, antidementia, antiparkinsonian, neuroleptics, peripherally and centrally acting muscle relaxants, medicines against erectile dysfunction, treatment-influencing agents, antivirals, cytostatics and / or with hair nutriens.

2. Use according to claim 1, characterized in that procaine is used as procaine hydrochloride or procaine hydrobromide in the combination therapy.

5 3. Use according to any one of claims 1 or 2, characterized in that procaine in the combination therapy with analgesics, anti-inflammatory drugs, antipyretic, migraine, antihypertensives, antiarrhythmics, antiasthmatics, antiallergic drugs, 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, miktions¬ influencing agents, antivirals, cytostatics and / or with hair nutriens, the side effects, the drugs commonly used in these indications, eliminated or prevented.

4. Use according to one of claims 1 to 3, characterized in that in the synergistic combination therapy Procaine is used together with anti-inflammatory drugs, anti-inflammatory drugs, antihypertensives, antidepressants, anti-dementia drugs or.

5. Use according to one of claims 1 to 3, characterized in that in the synergistic combination therapy procaine is used together with antidiabetics to achieve a standard glycemic value and / or reduces the acute and chronic complications of diabetes mellitus.

6. Use according to one of claims 1 to 3, characterized in that procaine is used in the combination therapy with antiviral and antiretroviral agents.

7. Use according to one of claims 1 to 3, in particular for injection under the Kopfschwarte, characterized in that in the synergistic combination therapy procaine is used together with hair nutriens and stops the hair loss, regenerates the hair growth process and / or increases the volume of hair.

8. Use according to one of claims 1 to 3, characterized in that procaine in the combination therapy reduces, eliminates or prevents the side effects of the cytostatics, in which it protects the healthy body cells.

9. Use according to claim 8, characterized in that procaine inhibits the growth of cancer cells in the combination therapy with cytostatics.

10. Use of procaine according to claim 9, characterized in that the medicament for the combination therapy with procaine contains the cytostatic in the two- to five-fold dosage of the usual dosage with single administration.

11. Pharmaceutical composition, characterized in that it comprises procaine, its physiologically acceptable amine derivatives or acid addition salts and one or more conventional active substances from the therapeutic indication of analgesics, antirheumatics, antiphologics, migraines, antihypertensives, antiarrhythmics, antiasthmatic agents, antiallergic drugs,

Fibrinolytics, antidiabetics, lipid lowering agents, gastrointestinal agents, antidepressants,

Antidementia drugs, antiparkinsonian drugs, neuroleptics, peripheral and central-acting

Muscle relaxants, medicines for erectile dysfunction,

^" affecting agents, antivirals, cytostatics and / or with Hair nutriens in ..- a ratio of 10: 1 to 1:10 and physiologically acceptable

Contains carrier and toxicologically harmless excipients.

12. A pharmaceutical composition according to claim 11, characterized in that it is in the form of an injection or infusion preparation together with suitable, pharmaceutically acceptable excipients and Hiifsstoffen, optionally in retarded form or as a parenteral Depotarzneiform or implant or as a concentrate, powder or lyophilisate is present and optionally the parenteral diluent separately packaged in the package so that the mixing of the components contained therein in each case immediately before use with a conventional parenterally administrable diluent is possible.

13. Pharmaceutical composition according to claim 11, characterized in that it can be administered in solid, perorally administrable form, as a tablet, capsule, dragee, as a sustained-release and / or enteric preparation, as a liquid medicine, for example as a perorally administrable solution, suspension, effervescent tablet Form of tabs or dragees, is present, which optionally retards the active ingredient, accelerated and / or released controlled.

14. A pharmaceutical composition according to claim 11, characterized in that it is in the form of an inhalant, in the form of a transdermal therapeutic system for systemic treatment, in the form of a gastrointestinal therapeutic system for systemic Treatment in the form of an ointment, suspension, emulsion, a patch or in the form of an externally administrable solution.

15. A pharmaceutical composition according to any one of claims 11 to 14, characterized in that the combined active ingredients are contained separately in separate packaging in the drug package.

16. Pharmaceutical composition according to one of claims 11 to 15, characterized in that a dosage unit for

Single administration 0.5 to 3% -gew. Procaine contains.

17. A pharmaceutical composition according to any one of claims

11 to 16, characterized in that a unit dose for single administration contains 50 mg to 300 g procaine hydrochloride, in particular 100 mg procaine hydrochloride.

18. Use of procaine to increase the efficacy and / or tolerability of analgesics, antirheumatics, antiphologics, migraine medications,

Antihypertensives, antiarrhythmics, antiasthmatics, antiallergic drugs, fibrinolytics,

Antidiabetics, lipid-lowering, gastrointestinal, antidepressants,

Muscle relaxants, medicines for erectile dysfunction, anti-influenza agents, antivirals, cytostatics and / or with hair nutriens.