Antioxidant and stimulating the growth of nerve cells means

 

The proposed use of derivatives 1-(aminoalkyl)-3-cinoxacin-2-it, in particular derivatives of 1-diethylaminoethyl-3-cinoxacin-2-she is of the formula (I), where R3means hydroxy, methoxy, ethoxy or hydrogen, or their pharmaceutically compatible salts as activitiesthese substances upon receipt of the compositions as antioxidants for the prevention or treatment of diseases caused by free radicals of oxygen-cellular metabolism, stimulate the growth of nerve cells, excitation antagonism of putamadrenicolas and/or stimulate the growth glutamatic nerve cells. The compounds can be administered in any known dosage form. Previously proposed compounds were known, in particular as gastrointestinal antispasmodics, as a means to treat diseases of the blood (EP 0032564). 10 C.p. f-crystals, 6 ill.

The present invention relates to the use of derivatives of 1-(aminoalkyl)-3-cinoxacin-2-it, chastnosti 1-diethylaminoethyl-3-cinoxacin-2-it formulawhere R3means hydroxy, methoxy, ethoxy or hydrogen, or their pharmaceutically compatible salts for new pharmaceutical compositions.

Pharma is ti, 1-diethylaminoethyl-3-(p-methoxybenzyl)-1,2-dihydroquinoxaline-2-it, no nomenclature name of which Caroverine (Caroverin), has been used as an effective gastrointestinal antispasmodic. The effectiveness of this substance explain, in particular, its ability to block calcium, and it blocks the activation of myofibrils ATP (adenosine triphosphate) eposredstvenno through calcium.

In EP-A 0032564 described the use Caroverine and its pharmaceutically compatible salts in many cases, diseases of the circulatory system heart and as a drug for the prevention of clot formation in human blood as a drug to increase blood flow, as well as substances for the treatment of angina, myocardial infarction, hypertensive States and other Action Caroverine specified in the application EP-A 0032564 due to the fact that it represents a specific CA-antagonist and that Caroverine has the ability to reduce the flow of ions of CA2+in cells up to 50%. In "Subsidia med.", 22, 3, pp. 78-85, 1970, Maislinger (reports that Caroverine able to suppress epileptic seizures. Also described cases of application Caroverine if Leche is the use of derivatives of 1-(aminoalkyl)-3-cinoxacin-2-it as a neuroprotective substances, and, in particular, describes their application when induced by glutamate and posredstvennyh glutenfreemom neurotoxic disorders and functional disorders of the Central nervous system, in particular the inner ear and the retina. In the same publication reported about the use of these substances in the treatment of degenerative processes of neurons of the Central nervous system, as, for example, diseases Alzheimer's disease (Alzheimer's), Huntington (Huntington), Parkinson's disease, Wernicke-Korsakov syndrome Jakob-Creutzfeld (Jakob-Creutzfeld). The effect of these special derived finokalia attributed to the selective blocking of NMDA receptors and non-NMDA receptors without affecting other receptors, as a result it seems that described in the publication of the pharmaceutical agents are applicable only when induced by glutamate and posredstvennyh glutenfreemom neurotoxic disorders, such as functional disorders of the inner ear and the retina, and in these degenerative processes.

From "Dervent Abstract, publication number'AN 83-45789 TO know about the action Caroverine, in particular substances 1-(2-dialkylaminoalkyl-3-(p-alkoxybenzyl)-1,2-dehydrogenation here anticancer activity is due to the fact, what anticancer therapeutic agents are transported into cells through the cell membrane. With conventional anti-cancer therapeutic agents, their effects over time weakens, because, on the one hand, cancer cells develop resistance against them and, on the other hand, anti-cancer therapeutic agents are washed away from the cells or gradually out that prevented according to this prior art by appointment admission derivative finokalia, as these derivatives finokalia delay leaching anti-cancer therapeutic agent from the cells and guarantee the safety of its high concentration in the cells.

In DE-a 2521905 describes the medicinal product containing 1-diethylaminoethyl-3-(p-methoxybenzyl)-2,1,2-dihydroquinoxaline-2-it, which has an effect on cerebral vessels and cerebral blood flow.

The aim of the present invention is to provide, along with the above application-specific derivatives of 1-(aminoalkyl)-3-cinoxacin-2-it new pharmaceutical applications, and therefore the invention concerns the use of derivatives of 1-(aminoalkyl)-3-cinoxacin-2-it, in particular derivatives of 1-diethylaminoethyl-3-cinoxacin-2-formula is logically compatible salts as active substances to obtain compositions as antioxidants, intended for the prevention and treatment of diseases caused by free oxygen radicals-cell metabolism, with the purpose of stimulation and growth of nerve cells, excitation antagonism of putamadrenicolas and/or growth stimulation, in particular, glutamatic nerve cells. At the extended studies of the structure of molecules and their possible influence by the applicant, it was found that the applied according to the invention derivatives of 1-diethylaminoethyl-3-cinoxacin-2-it is extremely pronounced in antioxidants and that, therefore, they are characterized, in particular, extremely high ability to trap radicals are primarily responsible for numerous diseases oxylene, peroxyl and peroxynitrite radicals. Action as antioxidants and therefore trap for radicals due to the structural properties of these special substances, which are honokalani rich electrons aromatic cyclic systems containing active redox atoms of oxygen and nitrogen. Due to the high number of electrons in the molecule, it was possible to prove that compounds able to bind free radicals caused by free oxygen radicals-cell metabolism, using special used according to the invention derived from 1-diethylaminoethyl-3-cinoxacin-2-it or prevent such diseases. In addition, unexpectedly discovered a special ability derivatives of 1-(aminoalkyl)-3-cinoxacin-2-it, in particular Caroverine, to cause antagonism of metabotropic putamadrenicolas. Because glutamatergicakie, in particular metabotropic glutamatergicakie, can be considered as accelerators or promoters of intracellular metabolism, in particular, the intracellular metabolism using Caroverine and other derivatives of 1-(aminoalkyl)-3-cinoxacin-2-it can anlagenservice, i.e., much slower.

As used according to the invention derived minoxidin-2-it is known that they can be used in pharmaceutical without noticeable side effects, the research an attempt was made to differentiate or to optimize the scope of the substances used as an antioxidant or traps radicals, by increasing appointed to the dose. During these studies it was unexpectedly found that applied under the picture is of exist and antioxidant effect discovered during the research that led to the creation of the present invention have neuroregeneration effect when taken in high doses. This is so that if you use traps radicals, the radicals are blocked internal neurotrophins, restored the activity of neurotrophins and used according to the invention substances cause neuroregenerative action. Therefore, in the process, suddenly became possible not only to prevent further destruction of damaged nerves and, in particular, neural pathways affected or impaired due to degeneration of neurons in the Central nervous system, as stated in EP-0542689, but also to restore damaged neural pathways so widely that along with known neuroprotective action of such substances unexpectedly achieved and neuroregenerative effect, leading to a marked reduction of symptoms of neurodegenerative diseases and to improve the condition of the patient.

Used according to the invention derived from 1-(aminoalkyl)-3-cinoxacin-2-it is a positive effect was shown, in particular, auxiproizvodnykh 1-diethylaminoethyl-3-(p-oxybenzyl)-1,2-dihydroquinoxaline-2-he methoxypropane study in vitro in high doses without harmful side effects for the studied cells and the in vivo on laboratory animals and patients without harmful side effects.

Based on its strong antioxidant action and, consequently, the ability to capture the radicals used according to the invention derivatives of 1-(aminoalkyl)-3-cinoxacin-2-it is effective, in particular for the prevention or treatment of DNA changes caused by the presence of free radicals, in particular, cancer. This mechanism of action is explained by the fact that one of the major biological actions, in particular, radicals and radicals of the ONO is the oxidation of DNA with biological consequence of mutation of the latest and eventually cancer. This mechanism of action, in particular, radicals was investigated and confirmed in multiple studies. From these studies it follows that due to the carcinogenic effect of radicals on DNA suitable as a means for prevention and treatment of cancer is an effective trap for radicals, i.e., an antioxidant that can slow the oxidative action of the radical in biological material, as proposed in accordance with the invention.

Other preferred steps used according to the invention derived from 1-(aminoalkyl)-3-cinoxacin-2-it is an option for treatment is Alisma, in particular, to suppress HIV replication. In the study of diseases, based on viral caused by free oxygen radicals-cell metabolism replication, it was found that when receiving used according to the invention derived finokalia, in particular Caroverine was markedly decreased HIV replication in educated monocytes macrophages on the basis of application of the substances according to the invention with a strongly manifested properties to capture radicals, in particular Caroverine.

Based on the strong antioxidant properties used according to the invention derived from 1-(aminoalkyl)-3-cinoxacin-2-it is extremely effective and successful was, in particular, their application to the phenomena of aging caused by free radicals of oxygen-cellular metabolism, and/or destruction of cells, in particular of skin aging. This effect is as if caused by chemical oxidative effects on somatic cells of the body and skin cells that have undergone strong oxidative effect, for example, environmental factors, in particular solar radiation.

Allergic reactions, such as allergic disease type I, called the appointment of antihistamines. It has been unexpectedly found that under the action of histamines, cytokines, lipid mediators and neurotransmitters are allocated peroxynitrite radicals and radicals HE and that as a result of the application according to the invention derived from 1-(aminoalkyl)-3-cinoxacin-2-it is on the basis of their antioxidant properties, in particular properties to capture the radicals it is possible to prevent the manifestation of secondary allergic phenomena, as, for example, inflammation, etc. and completely eliminate the primary phenomena, such as sneezing, almost immediately after taking used according to the invention derived from 1-(aminoalkyl)-3-cinoxacin-2-it. Completely unexpected and therapeutically particularly interesting possibility of using derivatives of 1-(aminoalkyl)-3-cinoxacin-2-it is according to the invention is that they stimulate the growth of nerve cells, in particular restore functional ability, in particular, glutamatic nerves after an apoplectic fit, and eliminate violations of swallowing function, articulation disorders, in particular disorders of speech and transverse paralysis, cure Alzheimer's disease, schizophrenia, amyotrophic lateral sclerosis, promote nerve growth in the presence of the cochlear implant is nania or facial nerve.

In studies in which doses used according to the invention derived finokalia taken by patients without pharmaceutically serious side effects, was, as already noted above, unexpectedly found that along with known neuroprotective actions of the agents are, in particular, neurodegenerative actions, so that the use of the compositions according to the invention in the treatment of diseases caused degenerations, in particular, glutamatic nerve cells, allows not only to maintain a stable picture of the disease, as it was shown in the prior art, but according to the invention in any case can be achieved noticeable improvement of this picture and the renewed growth of nerve cells.

Thus, in particular, for example, patients who wear cochlear implant that is used to stimulate nerves in the inner ear, it was found that while receiving used according to the invention derived cinoxacin-2-it, in particular Caroverine, nerve stimulated by the implant, partially regenerated, resulting in significantly improved contacting of the implant, which significantly improved the hearing of the past treatment of the patient.

In cha is s salt when used as antioxidants, in particular as a trap for radicals, are applied at a daily dose of from 3 to 10 mg/kg, in particular from 5 to 10 mg/kg of body weight. After taking this daily dose could significantly reduce or alleviate the symptoms of the disease and it is not accompanied by a simultaneous side-effects due to the dosage of the medication.

When using derivatives of 1-(aminoalkyl)-3-cinoxacin-2-it is according to the invention or their pharmaceutically compatible salts as neuroregenerative agent is preferably a daily dose of from 3 to 20 mg/kg body weight, in particular from 5 to 15 mg/kg body weight.

At lower dosages, particularly when known from the literature dosages of substances, especially Caroverine used as neuroregenerative substances, or as a calcium antagonist, or also as antioxidant substances, as proposed according to the invention, during the experiments, in particular in vitro experiments, it was found that the substance does not have neuroregenerative impact, resulting to achieve possible according to the invention neuroregenerative steps should be applied a higher dose of the substance. During the design almost without side effects.

Used according to the invention derivatives of 1-(aminoalkyl)-3-cinoxacin-2-it can be administered in the form of any known dosage form, in particular, oral, transcutaneous, locally and parenteral, and except for use as a means to prevent premature aging of skin cells, it is preferable to intravenous administration.

Below the invention is explained in more detail on the basis of experiments, respectively, of examples with reference to the accompanying drawings on which is shown: Fig.1 - tone audiogram of the patient is female; Fig.2 - tone audiogram male patient; Fig.3 - tone audiogram another male patient;
Fig.4 - diagram of speech or articulation male patient;
Fig.5 - inhibition of cation radical ABTS using Caroverine;
Fig. 6 is a comparative kinetic study of the reactivity Caroverine against the radicals.

Examples 1, 2 and 3.

Using clinical examples, tested the effectiveness Caroverine - (1-diethylaminoethyl-3-(p-methoxybenzyl)-1,2-dihydroquinoxaline-2-it) - as neuroregenerative substances on two patients in whom there has been a significant sharp pagefunction line shows tone audiogram after a sharp drop of the hearing, stripline shown tonal audiogram directly after treatment and solid line - tone audiogram of the patient two weeks after the beginning of treatment, and treatment of the patient during this period was carried out by receiving high doses Caroverine. Caroverine dissolved in 250 ml of physiological saline, was injected slowly intravenously three times per day for 240 mg.

A noticeable improvement in the hearing of the patient due to at least partial recovery of the auditory nerve.

In Fig. 2 shows a similar example, but related to the patient, while again the dash-dotted line presents the tonal audiogram of the patient after a sharp drop of the hearing, before the course of treatment and to use the cochlear implant, the dashed line shows the chart of the patient's hearing after receiving Caroverine in small doses, the dashed line shows the chart of the patient's hearing after completing two weeks of treatment, accompanied by taking increased doses Caroverine, and a solid line shows again the tonal audiogram of the patient after administration of large doses Caroverine within two weeks after application of the cochlear implant. In Fig.2 clearly prosleeves ability of the patient, moreover, however, this improvement was minor. When the patient was taken four times daily in the amount of 240 mg/250 ml of physiological salt solution Caroverine for two weeks, and additionally he was inserted cochlear implant, was achieved sustained auditory ability, in particular in the range from 0.15 to 2 kHz, which corresponds approximately to the hearing of a healthy person.

In Fig. 3 shows another example for the patient, and again the dash-dotted line shows the tonal audiogram of the patient after a sharp drop of the hearing and before the beginning of treatment and a solid line shows the chart of a patient after treatment for two weeks with the use of high doses Caroverine. The cochlear implant was not used. It is evident from Fig.3 clearly shows that after receiving high doses Caroverine - and in this case were taken daily 300 mg Caroverine in 500 ml of physiological saline for two weeks - there may come a sustainable hearing ability in the frequency range of 0.250 to 8 kHz, which substantially corresponds to the auditory abilities of a healthy person.

From the data shown in Fig. 1, 2 and 3, clearly follows that Caravella and that, in particular, patients using advanced cochlear implant, have significantly better hearing through better engagement of the implant with the auditory nerve.

Example 4.

Two patients aged 70 to 75 years old, suffering from Alzheimer's disease, additionally investigated the effect Caroverine as neuroregenerative funds. The average weight of patients was 75 kg, the treatment was held stationary. Patients were administered three times a day 400 mg Caroverine in physiological salt solution, in the form of infusion for about 2 hours, and these solutions infusion could be blended with conventional additives. In any case, the course of treatment was three weeks.

Before treatment with the use of high doses Caroverine patients suffered from forgetfulness, did not recognize his relatives and was regarded as in need of nursing care. At the end of the treatment course lasting three weeks, two patients noted significant improvement in the state, they could partially unable to feed himself and learned of their loved ones and medical staff. Taking into account the fact that a known substance used in the treatment of Alzheimer's disease, can only stabilizirovannami within a relatively short period of intake of this substance became possible relative recovery of neurological managed functions.

As a result of intravenous Caroverine three times per day 160 mg in 250 ml of physiological saline for three weeks it became possible to improve the condition of patients, the latter was not observed strictly and long, from which it can directly conclude that sustained therapeutic success can be achieved only in the case when there is neuroregenerative action Caroverine.

Example 5.

Four patients, two women and two men ranging in age from 40 to 50 years old, suffering from periodic schizophrenia treated during massive bouts of illness with the use of high doses Caroverine. He was prescribed three reception per day in the amount of 400 mg Caroverine in physiological salt solution, in the form of infusion over 30 minutes. The treatment duration was 7 days, 14 days and 21 days.

Immediately after the start of treatment with the use of high doses Caroverine the behavior of all four of the patients were markedly improved. They became prominent enlightenment of consciousness, almost stopped hallucinations and they were able to recognize the real events and to act in accordance with them, were able Vali.

All four patients it was found that such improvement was maintained during the course of treatment, but the success beyond the course of treatment were achieved only in patients whose treatment duration was 21 days.

Compared with the applied methods of treatment in patients during treatment showed a significant improvement in their behavior, with massive side effects, usually manifested when taking psychotropic drugs, such as the absence of stimulation, weight gain, etc. when eating Caroverine was possible to warn.

As a result of taking 240 mg Caroverine per day or 400 mg Caroverine in combination with 10 mg of Haloperidol (Haloperidol) (neuroleptic tool category butyrophenones), it became possible to obtain similar results as when taking high doses Caroverine, and improvement after discontinuation Caroverine not continued.

Example 6.

Neuroregenerative action Caroverine investigated on two patients suffering from facial paralysis.

Two patients suffering from massive palsy trigeminal nerve, were combined treatment for four weeks with the use of IU, introduced the active principle in the form of depo-patch containing 1,000 mg Caroverine. Depot-the patch is changed once a week. Already after two weeks it was possible to observe each of both patients reduce symptoms of paralysis so that paralyzed half of his face appeared again the beginnings of facial expressions and the patient again had possession of, in particular, for centuries.

Additional extension of the course of treatment with the use Caroverine led to a further reduction of the manifestations of paralysis, however, it was found that full recovery of facial nerve function resulting from the application of only one Caroverine without additional measures not achieved.

Example 7.

The patient with massive speech disorders due to brain haemorrhage was administered intravenously Caroverine for three months in high-dose (160 mg four times a day in a physiological salt solution. As shown in Fig.4 in the Annex, at the beginning of treatment, as indicated by the chart in phantom line, the patient is owned approximately 50% of articulatory abilities, and at the end of treatment articulatory ability has recovered 100% (shown by the solid line in Fig.4) and speech disorders no longer autocallables thanks neuroregenerative effect Caroverine, and as a result became possible full recovery of verbal ability.

Example 8.

In relation to the antioxidant action of derivatives of 1-(aminoalkyl)-3-cinoxacin-2-it, as well as their properties to serve as traps for radicals was performed in vitro experiments using Caroverine and specific, detecting the radicals of the reactant - 2,2'-Azino-bis(3-atives)thiazoline-6-sulfonic acids (ABTS) with the aim of comparing the abilities Caroverine and ABTS to catch radicals. In the presence of highly reactive radicals ABTS is oxidized with the formation of sustainable thiazolin-cation radical ABTS+. The intense green color of this radical was measured photometrically at the main absorption 420 nm. Caroverine was able to suppress the formation of ABTS-cation radical through education exiling and peroxyl radical both in the absence and in the presence of brain homogenate (Fig.5). This Caroverine quickly reacted with the free axiline, peroxyl and ABTS-cation radicals, as noted in the comparative studies using ABTS as in the absence and in the presence of brain homogenate. The reaction rate constant with axiline radicals 0.41-10M/lsince, as already observed in the course of conducting comparative studies with the use of ABTS in the absence and in the presence of brain homogenate (Fig.6). These results indicate that Caroverine suppresses the formation of ABTS-cation radicals and catalyzes the recovery ABTS-cation radicals in the presence and in the absence of a homogenate of the brain, acts as a very effective electron donor at low micromolar concentrations. If this has been mentioned, the use of education and recovery ABTS-cation radicals to study reactions transfer electrons, since this substance because of its color allows direct measurement of the formation and recovery of the radicals.

In the comparative study, it was found that the effectiveness Caroverine at least three times higher than the efficiency of known antioxidants Ascorbate, Trolox and Glutathione (Ascorbat, Trolox, Glutathion). Ability Caroverine to catch radicals was determined that it reaches the ability of Melatonin (Melatonin), which up to the present time is considered to be the most effective electron donor and, as has been established, lovley radicals and damaged biomolecules.

Example 9.

Five patients, two women and three men, suffering from allergies, type I, in particular hay cold, when the primary manifestation of allergic reactions, namely when sneezing, perote throat and nasal discharge treated using Caroverine. They were taken three times a day tablet with a content of 150 mg Caroverine.

All five patients became possible elimination of manifestations of secondary effects allergic reactions, namely redness in the throat, etc. and Also primary reactions such as sneezing, runny nose, etc., completely disappeared after two days of receiving Caroverine, after the disappearance of the primary reactions - to maintain the achieved effect was accepted Caroverine twice daily in small doses during the week.

For comparative purposes, were treated two patients with conventional antihistamines funds as primary manifestations of allergies, and in particular secondary manifestations were not immediately and completely suppressed, resulting in the patients suffered from hay runny nose during the whole time as they were exposed to the cause, namely the action of the pollen of grass. Cancel when the data of the case on its extremely high antioxidant effect, in particular on its ability to capture the radicals, to engage selectively in communication with educated histamine and cytokine radicals HE or ONOO and thus neutralize them. By taking Caroverine allergic cycle is interrupted and further reaction does not occur.

Example 10.

Antioxidant action, in particular the prevention of premature aging of skin cells, was investigated using ointments prepared with a content of 150 mg Caroverine per 100 g of cream. As the basis of the cream was applied glycerin, and other pharmaceutically active additives in the ointment was absent.

Five patients aged from 35 to 45 years old, the skin which on average was characterized by dryness and partly by the presence of already clearly evident manifestations of aging, used the cream based Caroverine for four weeks twice a day as the basis for applying makeup, or just a night cream.

Already after two weeks have been noted, particularly in the younger test persons a noticeable improvement in the skin condition, and significantly decreased, in particular, damage to the skin from the sun and caused by the oxidation of skin redness. In addition, within four weeks, skin art is a cleaner picture, in which, in particular, redness and sun damage have disappeared almost completely.

Example 11.

The use of derivatives of 1-(aminoalkyl)-3-cinoxacin-2-it is as an antagonist of metabotropic putamadrenicolas group I in the ear of the Guinea pig.

The group of six Guinea pigs were injected with in-ear oxyphenisatin as a receptor agonist, the receptor responds in such a way that there is a sharp increase hearing ability of the Guinea-pig. Guinea pigs that were injected oxyphenisatin showed signs of fear already at an extremely quiet noise and nervously ran around the cage, and when the noises, not exceeding their normal level in pharmacochemical laboratory, some Guinea pigs was observed behavior, which allowed to conclude about the pain experienced by animals. Four of the six Guinea pigs were then injected into the ear vein dose of 8 mg/kg of body weight of the Guinea pig and observed behavior. Unexpectedly, it was noted that immediately after the introduction Caroverine Guinea pigs calmed down and no longer reacted with fear to loud noises such as clapping, in the immediate vicinity. So, if clapping directly in front of the cage, they do not obino excited, and, for example, clapping before the cell has led to the fact that they started to run fast back and forth and clearly detected signs of pain and nervousness. Such differences in the behavior of Guinea pigs was also observed after placement of the electrodes on their ears, measurement data, which allows us to easily determine aroused or not aroused animals unexpected noises. Also, measurement data electrodes clearly showed that after the introduction of Caroverine cavies excitation was either absent or present in extremely small degree.

Then examined the inhibitory effect Caroverine on metabotropic glutamatergicakie group I on anesthetized animal by placing microelectrodes on his auditory nerve. From the results of measurements carried out on experimental animals after administration of them Caroverine and comparative experimental animals, which Caroverine was not introduced, it was possible to conclude that anxiety putamadrenicolas group I was massively depressed entered Caroverine.

Based on these comparison results, we can conclude about what Caroverine and, consequently, derivatives of 1-(aminoalkyl)-3-cinoxacin-2-it is able to cause the data 1-(aminoalkyl)-3-cinoxacin-2-it for cancer prevention skin of Guinea pigs.

Guinea pigs, comprising a group of six pieces, shaved area in the occipital part of the head and subjected them to intense UV radiation for at least two hours daily. Ultraviolet radiation contained a certain proportion of ultraviolet rays as the a-side and b - and C-parts. Four of the six Guinea pigs was applied by brush a highly concentrated solution of Caroverine and hydrochloride on the shaved area of the back of his head, it was made sure that the distribution was uniform as possible, and around the irradiated area.

After two weeks of intense radiation on the skin of Guinea pigs from the comparison group appeared clear signs of damage, such as burns, redness and damage to the skin, and in the samples of fabric were already discovered the cancer cells. Four Guinea pigs subjected to processing solution "Caroverine-hydrochloride", after exposure of the same duration had some redness of the skin, however, in the samples of tissue cancer cells were found.

A similar experiment was carried out using 1-diethylaminoethyl-3-(p-oxybenzyl)-1,2-dihydroquinoxaline-2-she developed 1-diethylaminoethyl-3-cinoxacin-2-it is extremely effective antioxidants and traps oxygen radicals-cell metabolism and that due to this property they are able to warn caused by free radicals, changes in DNA, in particular cancer, and as a result are suitable for the prevention, particularly prevention of skin cancer.

Example 13.

Three patients in the age from 19 to 75 years old, suffering from cancer of the colon, along with conventional chemotherapy with the use of Irinotecan and Oxaliplatin (Irinothekam, Oxaliplatin) in a four-week course of chemotherapy was additionally assumed Caroverine, and the first day was administered intravenously increased dose in physiological salt solution, in the following days took 3 x 3 tablets daily.

Due to the extremely high antioxidant action Caroverine when conducting this study it was observed a complete disappearance of cancer of the colon. Two comparative patients who were treated without the use of Caroverine, as a result of chemotherapy had known reduction carcinoma, but it has not disappeared.

Subsequent experiments conducted with patients suffering from advanced tumors of the head and throat, showed similar results, and these patients along with current chemotherapy also took Caroverine. Along with the successful reduction of pain was possible also reduces the size of tumors. The complete disappearance of the tumors was achieved not least the system are derived free radicals oxygen-cellular metabolism and, therefore, may be detained for more sustainable change DNA, causing cancer. Thus it appears that Caroverine can be used not only for cancer prevention, but also is highly effective in its treatment, in particular, some specific types of tumors.


Claims

1. The use of derivatives of 1-(aminoalkyl)-3-cinoxacin-2-it, in particular, derivatives of 1-diethylaminoethyl-3-cinoxacin 2-she formulas

where R3means hydroxy, methoxy, ethoxy or hydrogen,

their pharmaceutically compatible salts as antioxidant funds in compositions for the prevention and treatment of diseases caused by free oxygen radicals-cell metabolism, and as a stimulator of nerve cells, in particular glutamatic nerve cells.

2. Application under item 1, where the derivative 1-(aminoalkyl)-3-cinoxacin-2-use it methoxypropane 1-diethylaminoethyl-3-(p-methoxybenzyl)-1,2-dihydroquinoxaline-2-it or its pharmaceutically compatible salts.

3. Application under item 1, where the derivative 1-(aminoalkyl)-3-cinoxacin-2-it uses hydroxy is by salt.

4. Use one of the PP.1-3 for the prevention or treatment of changes in DNA caused by free radicals HE, in particular, cancer.

5. Use one of the PP.1-3 for the treatment of diseases based on viral replication caused by free oxygen radicals-cell metabolism, in particular, to suppress HIV replication.

6. Use one of the PP.1-3 for the treatment of the phenomena of aging cells and/or destruction of cells caused by free radicals of oxygen-cellular metabolism, in particular, the phenomena of aging.

7. Use one of the PP.1-3 for the treatment of allergic diseases, type 1, caused by free radicals IT and/or free radicals ONOO.

8. Use one of the PP.1-3 to stimulate the growth of nerve cells, in particular, to restore the functional ability of the nerves after an apoplectic fit, and to improve disorders of swallowing function and articulation, in particular, speech disorders and cross paralysis, for the treatment of schizophrenia and amitrofanova lateral sclerosis, to stimulate, in particular, growth glutamatic nerves in the presence of the cochlear implant, as well as with functional disorders of the auditory nerve, nerve ray themes that the derived 1-(aminoalkyl)-3-cinoxacin-2-it or its pharmaceutically compatible salt is used at a daily dose of from 3 to 20 mg/kg body weight, in particular from 5 to 15 mg/kg body weight.

10. Use one of the PP.1-7, characterized in that the derivative of 1-(aminoalkyl)-3-cinoxacin-2-it or its pharmaceutically compatible salt is used at a daily dose of from 3 to 10 mg/kg, in particular from 5 to 10 mg/kg body weight.

11. Use one of the PP.1-10, characterized in that the derivative of 1-(aminoalkyl)-3-cinoxacin-2-it is intended for oral, percutaneous, local, parenteral, particularly intravenous administration.

 

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