The agent with antidepressant and neuroprotective activity
(57) Abstract:The invention relates to medicine, namely to pharmacology. The proposed means of N-acetyl-DL-aspartic acid, which has antidepressant and neuroprotective activity, which can be used as a medicine in the treatment of mental illness. table 4. The invention relates to the chemistry of amino acids and their derivatives, namely N-acetyl-DL-aspartic acid formula
HOOC-CHOH which the disodium salt has antidepressant and neuroprotective activity.Known antidepressant and neuroprotective drugs used currently for the treatment of mental illness, have a number of significant drawbacks.For example, drug hydrochloride formula
is one of the most effective antidepressants that also provides additional psychoactive effect. However, imipramine cause numerous side effects: headaches, dizziness, ataxia, cardiac arrhythmias, skin allergic reactions, constipation, etc. [Mashkovsky M. D. Pharmacology of antidepressants. M. Medicine, 1983, S. 174; Mashkovsky M. D. Medicines, T. 1, M Medicine, 1986, S. 94]
Known nootropic agent piracetam [Mashkovsky M. D. Medicines. So 1. M. Medicine, 1986, S. 117] formula
is not sufficiently effective for the correction memory in persons of old age, suffering from degenerative and sclerotic lesions of the brain [Heise, G. A. Trends Pharmacol. Sciene, 1987, v. 8, R. 65-68] This is reflected in the experimental studies, which show that piracetam does not eliminate memory impairment model scopolamine amnesia corresponding to memory impairment in persons in old age [Petkov V. Vuglenova Y. Acta physiol. pharmacol. Bulg. 1985, v. 11. p 37; Tobe A. Yamaguchi T. Nagai R. Egava M. Jap. J. Pharmacol, 1985, v. 39, R. 153-161]
Aspartic acid and some of its derivatives exhibit high biological activity.-Alkalemia esters of aspartic acid and its 2-alkyl derivatives of General formula
HOOC-CH2-)-COO-R2where R1, R2H, alkyl
used as antihypertensive drugs [U.S. Pat. USA N 4065572 (1977), CL 424/273 R]
A dipeptide of aspartic acid, e.g/112.5 R (1982)] or other lower alkalemia ester-L-aspartyl-L-phenylalanine [U.S. Pat. USA N 4332718, CL 260/112.5 R (1982)] are used as sweeteners.The diamide N-acylaminoacyl, including aspartic acid of General formula
(CH3)2N--(CH2offered as an oral anti-ulcer drug [jap. application N 57-134452, class C 07 C 103/84, A 61 K 31/165 (1983)]
N-phosphonacetyl-L-aspartic acid formula
HOOC-CH disodium or TETRANITRATE salts inhibit the biosynthesis of pyrimidine nucleotides and shows antitumor activity [U.S. Pat. USA N 4267126, CL 260/942 (1981); the Application of Germany N 2752287, class C 07 C 101/22 (1979)]
N-Acetylaspartate acid is a product of the metabolism of nerve tissue and is found in large quantities in the brain [Trackenmiller M. E. J. Neurochem. 1985m c. 45, p. 1658-1662] However, the functional role of N-acetylcarnosine acid metabolism in brain tissue remains unclear. It has been suggested that N-acetylcarnosine acid involved in the biosynthesis of acetylcholine and myelin in neurons, promotes the release of excitatory amino acids-mediators. The content of N-acetylcarnosine acid in the brain changes in traumatic brain injury and other pathological effects [Crafts M. W. Exchange wiseana glutamatergic synapses. L. Science, 1987, S. 50] Information about pharmacological effects, in particular, on the study of the antidepressant and neuroprotective activity of N-acetylcarnosine acids are missing.As the base object for the antidepressant activity of selected drug imipramine widely used in the depressed state of various etiologies, for example, endogenous depression, involutional menopause depression, depression with personality disorder, neurosis, as well as with alcoholic depression. A significant drawback of imipramine are numerous side effects: headaches, dizziness, ataxia, arrhythmia, skin allergic reactions, constipation, retention of urine, sweating, accommodation disorder, insomnia, etc. [Mashkovsky M. D. Medicines. So 1, M Medicine, 1986, S. 94]
As the base object for nootropic activity of selected drug is piracetam used for memory impairment, cerebral blood flow insufficiency, chronic alcoholism, head injuries, and so on [Mashkovsky M. D. Medicines. So 1. M: Medicine, 1986, S. 117] the Disadvantage of piracetam is its low efficiency in the correction memory in individuals old the completion of the present invention is to develop a new low-toxic psychotropic drug with the antidepressant and neuroprotective activity.The essence of the invention lies in the use of N-acetyl-DL-aspartic acid disodium salt as a psychotropic agent with antidepressant and neuroprotective activity.Synthesis of N-acetyl-DL-aspartic acid is performed by the acetylation of DL-aspartic acid with acetic anhydride in the environment of glacial acetic acid at 80-100aboutC.P R I m e R 1. N-Acetyl-DL-aspartic acid. 20,0 g (0,150 mol) of DL-aspartic acid and 17.5 ml (0,185 mole) of acetic anhydride and 150 ml of glacial acetic acid is stirred at a temperature of 80-90aboutC for 4 h, cooled, filtered off the insoluble impurities, acetic acid and excess acetic anhydride is distilled off in a boiling water bath in a vacuum, getting to 24.6 g of vitreous light-yellow substance, the yield of 93.5%
PMR-spectrum , M. D. 1,90 (3H), 2,89 d (7 Hz, 2H); 4,89 kV (7 Hz, 1H); (Tesla BS-A, 100 MHz, 20% solution in dimethylformamide D7).P R I m m e R 2. N-Acetyl-DL-aspartic acid, 25,0 g (0.147 mol) of the hydrochloride DL-aspartic acid, 12.5 g (0,152 mol) of sodium acetate, 17.5 g (0.185 mol) of acetic anhydride and 150 ml of glacial acetic acid is strong acid and excess acetic anhydride is distilled off in vacuum on a boiling water bath, the release of N-acetyl-DL-aspartic acid 23.7 g (92.1 per cent).P R I m e R 3. The disodium salt of N-acetyl-DL-aspartic acid (ACAC). 10.0 g (0,057 mol) of N-acetyl-DL-aspartic acid and 4.5 g (0,113 mol) of sodium hydroxide dissolved under cooling in 50 ml of water and adjusted pH to 11-12 by adding 20% sodium hydroxide solution. Add 2 g of activated carbon, stirred for 10 min at room temperature, filtered, the filtrate was poured with stirring into 250 ml of acetone emitted yellow oil three times triturated with 50 ml of anhydrous acetone and dried in vacuum at a residual pressure of 1-2 mm RT.article and a temperature of 100-120aboutWith getting 12.2 g of light yellow crystalline hygroscopic product, deliquescent in the air.We investigated the antidepressant and neuroprotective activity of disodium salt of N-acetyl-DL-aspartic acid (ACAC). The study of psychotropic activity of ACAC were carried out on outbred rats-males weighing 150-200 g and mice-males 18-20 g, were obtained from the nursery of AMS USSR "White moss".The influence of Azak on spontaneous locomotor activity and orienting-exploratory behavior of animals studied in the open-field test. Installing the open field was krupppresta conducted under illumination platform 60 Lux and recorded the following indicators of animal behavior: the number of crossed squares (locomotor activity), the number of stevani on his hind legs and zaglyadyvanie in holes (approximately research activity) and the number of defecations (emotionality). After 1 h after intraperitoneal administration of Azak at doses of 10 and 50 mg/kg had no effect on the behavior of rats in the open-field test, and in a dose of 100 mg/kg increased orienting-exploratory activity (number of stevani on his hind legs) and emotional level (the number of defecations) animals (table.1).For the study of the antidepressant activity of ACAC used method [Porsolt R. D. Bertin A. Yalfre M. Arch. Int. Pharmacodyn. Ther. 1977, v. 229, p. 327-333] modification [Schmidt J. Biomed. Biochim. Acta. 1985, v. 44, p. 755=761] according to which the main indicator of "behavioral despair" of mice is the time of immobilization (negative finding a way out of the vessel filled with water). The reduction in the duration of immobilization was regarded as a manifestation of the antidepressant activity of the substance. The results of the study of the antidepressant activity of ACAC test "behavioral despair in mice are presented in table.2. ACAC at doses of 1, 50 and 100 mg/kg significantly reduced the duration of immobilization of animals that can be considered by increasing the activity of mice in search of an exit from aversive situations is nteu activity ACAC as the comparison drug was selected antidepressant imipramine, widely used currently in clinical practice. Test "behavioral despair", which is most often used to evaluate the antidepressant activity, imipramine has a strong antidepressant effect in the dose of 10 mg/kg, which is about 1/7 of the LD50. ACAC shows antidepressant activity, 3-4 times larger than the activity of imipramine, in doses of 1, 50 and 100 mg/kg, which is only 1/2660-1/26 from LD50, i.e., in doses of 3.7 380 times less toxic than the reference drug.The study of the neuroprotective activity of ACAC conducted on the model of the violation of the conditional reaction passive avoidance (passive avoidance reaction). As amnestic effects used the introduction of M-cholinolytic of scopolamine dose of 1.5 mg/kg over 30 min to play passive avoidance reaction [Tobe A. Yamaguchi T. Nagai R. Egawa M. Jap. J. Pharmacol, 1985, v. 39, p. 153-161] Evaluation antiamnesic effect of tested compounds was carried out according to two indicators of passive avoidance reaction latency period of time in the dark compartment and the time spent in the dark compartment. The comparison of the neuroprotective properties of ACAC conducted with the reference drug piracetam, widely used in the clinic as a neuroprotective agent. Data about the antiamnesic effect of piracetam taken from the property.The introduction of scopolamine dose of 1.5 mg/kg over 30 min to play passive avoidance reaction caused memory impairment in animals, which was reflected in the reduction of latency period of time in the dark compartment and increase the time spent in the dark compartment. ACAC at a dose of 10 mg/kg had no effect, and at a dose of 50 mg/kN increased the latent period of time in the dark compartment and reduced the time spent on it compared to a group of animals, which were introduced only scopolamine (PL.3). This suggests that Azak has antiamnesic effect on the model scopolamine amnesia. This model is often used to study the neuroprotective activity of the compounds [Methodical recommendations for a pilot study of drugs with neuroprotective action type. M. Medicine, 1986, S. 11] and adequate memory impairment in humans during aging [Bartus R. T. Dean, R. L., Beer, B. A. S. Lippa Science, 1982, v. 217, p. 408-414] the Reference drug piracetam dose of 100 mg/kg, which is 2-5 times higher than therapeutic doses, does not resolve the amnesia passive avoidance reaction caused by scopolamine (PL.3).The results of determination of the acute daily toxicity (LD50) studied substances on white outbred mice with intraperitoneal injection method Prozorovsky Century B. [Prozorovsky Century B. Prozorovskaya M. P. FA is it toxic, than imipramine, surpasses it in 3-4 times the antidepressant activity at doses of 1-100 mg/kg, and at a dose of 50 mg/kg exceeds piracetam for nootropic activity model violations passive avoidance reaction, with the introduction of scopolamine. The combination of expressed antidepressant and neuroprotective properties of N-acetyl-DL-aspartic acid makes it possible to consider this compound is promising for the treatment of a wide range of mental illnesses. The use of N-acetyl-DL-aspartic acid as an agent with antidepressant and neuroprotective activity.
HOOC-CH2-CH2-COHCH2-C6H4-COOC2H5< / BR>(I) with antiviral activity that involves its use in medical practice
FIELD: medicine, narcology.
SUBSTANCE: one should detect satisfaction insufficiency syndrome due to performing genetic analysis by the presence of, at least, one of the genes coding the exchange of neuromediators being the constituents of human satisfaction system. One should compensate satisfaction insufficiency due to performing, at least, one complex of physical exercises. Moreover, in case of availability of pathological gene allele of dopamine D2 receptor and/or protein gene of reverse dopamine capture in patient one should apply the complex of physical exercises including those to provide sedative effect, and in case of availability of pathological gene allele of dopamine-beta-hydroxylase protein one should apply the complex of physical exercises including those that induce an activating effect. In case of availability of pathological gene allele of dopamine D2 receptor and/or protein gene of reverse dopamine capture one should apply additional food biologically active additives based upon amino acids being the precursors of neuromediators, such as taurine, D-, L-phenylalanine in combination with 5-hydroxytryptophan, hypericin and vitamin B6, and in case of pathological gene allele of dopamine-beta-hydroxylase protein one should additionally apply food biologically active additives based upon amino acids being the precursors of neuromediators, such as: taurine, tyrosine and/or dimethylaminoethanol, lecithin and group B-vitamins. The present innovation enables to take into account pathological disease mechanism.
EFFECT: higher efficiency of prophylaxis.
14 cl, 5 ex
FIELD: medicine, oncology, amino acids.
SUBSTANCE: invention relates, in particular, to the development of an antitumor preparation based on natural substances. Invention relates to an amino acid preparation comprising at least one modified essential amino acid obtained by treatment of amino acid by ultraviolet radiation (UV) at wavelength 250-350 nm for 12-80 h at temperature 15-30oC or with ozone at temperature 15-25oC. The modified amino acid has no toxicity for health cells. Also, invention relates to a method for preparing such preparation. Invention provides the development of an antitumor preparation based on modified amino acids and expanded assortment of antitumor preparations being without cytotoxicity for normal cells.
EFFECT: valuable medicinal antitumor properties of preparation.
8 cl, 4 tbl, 2 dwg, 4 ex
FIELD: organic chemistry, medicine.
SUBSTANCE: invention relates to compounds designated for applying in photochemotherapy or diagnosis and indicated compounds represent 5-aminolevulinic acid aryl-substituted esters, their derivatives or pharmaceutically acceptable salts. In particular, invention provides preparing compounds of the general formula (I): R
EFFECT: valuable medicinal properties of compounds.
18 cl, 17 dwg, 2 tbl, 3 ex
SUBSTANCE: method involves carrying out analysis of clinical manifestations in patients having satisfaction deficiency syndrome. Clinical manifestations like obsessive compulsive disorders occurring, physical training exercises acting upon visceral organs as a result of abdominal wall muscle and inferior and superior small pelvis diaphragm muscle contraction. Clinical manifestations like irritation and aggressiveness being observed, physical training exercises like slow diaphragm-type breathing with deep muscle relaxation or alternating hyperventilation and deep diaphragm-type breathing are to be done. Clinical manifestations like hyperactivity taking place, physical dynamic exercises causing activating action are done in combination with slow deep breathing. Clinical manifestations like emotional disorders being observed, physical training exercises causing sedative action are applied. The exercises are based on alternating muscle and tendon extension and following relaxation. Dietetic low hydrocarbon content nutrition is additionally applied with one of the following diets: low hydrocarbon content diet having animal proteins and saturated with fat, or vegetarian diet having mainly vegetable proteins, moderate hydrocarbon content and large amount of vegetable fibers, or ketogenic diet being protein-and-fat diet containing large amount of fat with fatty acids like triglycerides of chain having not more than 12 carbomers.
EFFECT: enhanced effectiveness of prophylaxis and correction procedures.
FIELD: cosmetic industry.
SUBSTANCE: the present innovation deals with preparations to fix, strengthen, restructure, restore or stabilize keratin fibers, especially damaged fibers. For this purpose one should apply creatine, creatinine and/or their salts to provide improves glare, volume or combing capacity of one's hair, as well. Earlier these preparations had been known as hair moisturizers.
EFFECT: higher efficiency of application.
12 cl, 9 ex
SUBSTANCE: preparation is a crushed and UV-radiation activated β-(3-indolyl)-α-aminocapronic acid obtained by treating dry initial preparation (native aminocapronic acid) crushed to 1-5 mcm large particles with UV-radiation during 12-18 h to the moment the substance decomposition starts. Method involves crushing dry substance of β-(3-indolyl)-α-aminocapronic acid by means of vibration mill with 1500-3000 oscillations per min to 1-5 mcm large particles, activating the crushed product by exposing it to UV-radiation of 250-280 nm wavelength during 12-18 h to the moment the initial substance decomposition starts. The moment is determined by 3-5% large initial mass loss.
EFFECT: enhanced effectiveness of the preparation with no adverse side effects.
6 cl, 3 tbl
FIELD: medicine, dermatology.
SUBSTANCE: one should apply an applicator onto affected parts of skin that contains 5-aminolevulinic acid at concentration of 5-20%. After keeping and removing the applicator it is necessary to irradiate with light at wave length being 630 ± 10 nm and energy density of 10-1200 J/sq. cm. Control should be carried out due to evaluating the concentration of photosensitizer at affected parts of skin due to fixing fluorescence ranges at all basic stages of photodynamic therapy. The method enables to adjust skin relief and achieve scars' whitening and their regression.
EFFECT: higher efficiency of therapy and control.
6 cl, 2 dwg, 3 ex
FIELD: medicine, gynecology, anesthesiology.
SUBSTANCE: invention concerns to a method for carrying out the anesthesiology assistance for woman in childbirth with accompanying bronchial asthma. Method involves administration of atropine, dimedrol, analgin and clophelin. Method involves additional intravenous administration of transamine for 5-7 min. Transamine is administrated in doses 12-14 and 15-17 mg/kg in woman in childbirth with body mass 75 kg and above and 74 kg and less, respectively. Method provides enhancing quality and safety of anesthesia in this class of woman in childbirth.
EFFECT: improved assistance method.
7 tbl, 4 ex
FIELD: pharmaceutical chemistry.
SUBSTANCE: invention relates, in particular, to a composition for interaction of ligands wherein the composition comprises a noncovalent associate of multiple separate conjugates being each of that comprises a head group and a tail group wherein tail groups of conjugates form hydrophobic aggregate. Conjugates are mobile within the associate and in the presence of ligand at least two head groups are places by a method corresponding to the epitope formation that is able to interact with ligand stronger as compared with each separate head group. Invention provides applying conjugates in combinatory approach for detecting effective combinations to induce the desirable interaction in binding in receptor-specific treatment of patients.
EFFECT: valuable properties of epitopes.
31 cl, 2 dwg, 4 ex
FIELD: medicine, pharmacy.
SUBSTANCE: physiologically acceptable sodium salt is dissolved in purified apyrogenic water in the concentration 5-10 g/100 ml and colloidal substance of polymeric nature is added at temperature of solution 40-70C at stirring up to disappearance of polymer solid phase from the surface solution. Solution is stirred for 30-60 min and then subjected for high-temperature treatment at 90-100°C for 15-30 min and successive filtration through micro- and sterilizing filters of pores diameters 0.8 and/or 0.45 and then 0.22 mcm, respectively, and in gradual increasing the pressure value from 0.5 to 3.0 atm and final packaging. Invention provides preparing microimpurity-free hypertonic colloidal solution that is stable in storage and effective in using. Invention can be used in methods for preparing preparations used in reanimatology, intensive therapy and in emergency medicine.
EFFECT: improved preparing method, valuable medicinal properties of preparation.
8 cl, 3 ex