(57) Abstract:The invention relates to medicine, namely to the use of new anti-inflammatory drugs from the class alkanolammonium salts hetarylthioacyl acids, specifically to indolyl-3-diacetate Tris/2-hydroxyethyl/ammonium. The substance has a high anti-inflammatory activity in acute aseptic inflammation and can be used in drug therapy for traumatic tissue damage, myocardial infarction in the postoperative period. 5 Il. The invention relates to a new anti-inflammatory agent, representing Tris/2-hydroxyethyl/ammonium salt of 3-IntelliTouch acid, which can be used in medicine for treatment of inflammation in acute aseptic inflammation.Anti-inflammatory properties of Tris/2-hydroxyethyl/ammonium salt of 3-IntelliTouch acid are not described in literature.Currently used in clinical practice a wide range of anti-inflammatory drugs with different mechanisms of action. One of the most powerful anti-inflammatory drugs are considered glucocorticoid hormones. Their protivovospalitiona reduce vascular permeability, phagocytic activity of neutrophils and macrophages and inhibit all processes of reparative phase: the growth and division of fibroblasts, collagen synthesis, neovascularization and scarring. These effects of glucocorticoid hormones restrict their scope only aseptic inflammatory and only in that case if you want to suppress the process of scarring. For example, glucocorticoids are widely used in eye diseases, bursitis, or inflammation of the joints, etc., Despite a pronounced anti-inflammatory steroid drugs cannot be considered as optimal anti-inflammatory drugs, since their use is accompanied by a significant number of side effects and complications.Of non-steroidal drugs that have anti-inflammatory effect, the most widely used indometacin, acetylsalicylic acid and other actions aimed at the suppression of prostaglandin synthetase. However, these drugs have side effects, caused by disturbance of the synthesis of prostaglandins in the body, causing damage to the gastric mucosa, gastric bleeding, exacerbation of chronic diseases of the stomach and intestines. In addition, Inga is The closest anti-inflammatory action and structure to the claimed drug is indomethacin /derived indole/, which we have chosen as a prototype. Indometacin highly effective drug and is widely used in clinical practice, however, noted a number of shortcomings: the drug is highly toxic, causes allergic reactions and dizziness, while long-term treatment it is observed damage of the gastric mucosa, gastric bleeding, exacerbation of chronic diseases of the stomach and intestines, etc. because the product is aimed at suppressing prostaglandines. In addition, this drug is not soluble in water, difficult to access, is not produced in Russia.The aim of the invention is the creation of a drug having anti-inflammatory activity at a low dose, non-toxic to warm-blooded animals, water-soluble, which is aimed at optimizing the inflammatory process.This goal is achieved by a new anti-inflammatory agent, representing Tris/2-hydroxyethyl/ammonium salt of 3-IntelliTouch acid, internal cipher VM-2-84.Anti-inflammatory properties are not described in literature.Tris/2-hydroxyethyl/ammonium salt of 3-IntelliTouch acid obtained 0oC and a 1:1 ratio when heated for 5 min according to the scheme:
< / BR>Connection VM-2-84 is a yellow color crystalline substance, with a weak odor, infinitely soluble in water, alcohol, aqueous acetone and dioxane, insoluble in ether and hydrocarbons. The composition and structure of its proven method of IR spectroscopy, elemental analysis. In the IR spectrum of VM-2-84 contains absorption bands in the region 1610/COO-/, 3220/NH hetaryl/, 3300 / / 2990/CH alkyl/, 3430/OH/ cm-1.A method of producing a drug based on available industrial raw materials: large-capacity product triethanolamine and available indolyl-3-teoksessa acid. It is simple to implement, does not require the use of catalysts, special equipment, expensive and scarce solvents, selection of target products is carried out by known methods with a high output.Study of anti-inflammatory activity of Tris/2-hydroxyethyl/ammonium salt of 3-IntelliTouch acid.Testing anti-inflammatory activity conducted on 100 white rats-males. Aseptic inflammation modeled by the introduction into the skin of the lower leg sterile celloidin plates standard size animal for each time of observation. The dynamics of inflammation were studied in histological preparations stained with hemotoxin-eosin. In inflammation measured the thickness of the cell shaft around the foreign body, calculated density of cells /number of cells per 1000 µm2/, as well as the number of layers of fibroblast fibroblast capsule. In the peripheral area of inflammation was calculated the number of undifferentiated fibroblast 5000 μm2reflecting from proliferative activity. In preparations stained with pikrofusin by van gieson, morphometric /using an ocular grid was determined by the amount of collagen in fibroblast capsule /gg of Avtandil. Medical morphometry. M. 1990/. The research results are statistically processed and presented in the form of a test report and graphs.In Fig. 1 shows the dynamics of the concentration of cellular elements in the cell shaft and the number of layers of fibroblast in the capsule in the control group, where 1 is the concentration of neutrophils, 2 the concentration of macrophages, 3 the concentration of fibroblast, 4 the number of layers of fibroblast in the capsule of Fig. 2 the dynamics of the density of cells in the cell shaft in the development of aseptic inflammation, occurring against the background of the introduction of VM-2-84 in the dose of 10 mg/kg; about the infusion of BM-2-84 at a dose of 2 mg/kg; in Fig. 4 - the dynamics of the concentration of undifferentiated fibroblast in the peripheral zone of inflammation in the control group animals /1/, in the conditions of introduction VM-2-84 at a dose of 2 mg/kg /2/ and 10 mg/kg /3/ of Fig. 5 trends in the number of collagen and fibroblast in fibroblastic capsule in the control and experimental groups of animals.The effect of the substance VM-2-84 depends on the dose. With the introduction of money in the dose of 10 and 2 mg/kg every 2 h after the onset of inflammation marked anti-inflammatory effect. In the dose of 2 mg/kg anti-inflammatory action of the claimed compounds aimed at optimizing the course of the inflammatory process, which is manifested in the following:
reducing the intensity of leukocyte infiltration, means at a dose of 2 mg/kg limits the alteration of tissue in inflammation caused by proteolytic enzymes and peroxide radicals, sekretiruemyi by leukocytes;
keeping the phagocytic activity of neutrophils and macrophages at a high level, makes it possible phagocytosis of debris smaller number of phagocytes;
suppressing proliferative processes that hinder the transition of acute inflammation in the chronic form;
stimulating the differentiation of fibroblast and kleemola compounds at a dose of 2 mg/kg is the limit of the acute phase and stimulation of reparative process.At a higher dose of 10 mg/kg single administration of the drug after 2 h after the onset of inflammation anti-inflammatory effect of VM-2-84 is expressed in a significant suppression of all cellular reactions of the inflammatory process, including a decrease in phagocytic activity of neutrophils and macrophages and the inhibition of the process of fibrosis and is complicated by the excessive redness of inflammation with impaired integrity of the microvascular bed.Side processes using substances VM-2-84 at a dose of 2-10 mg/kg were found.Thus, the claimed substance VM-2-84 has a pronounced anti-inflammatory action, aimed at the optimization of the inflammatory process, and has a wider scope, because in a dose of 2 mg/kg did not reduce the phagocytic activity of cells, but reduces the intensity of the acute phase, did not inhibit the reparative phase, but rather stimulates it.The study of toxicity. Carried out on outbred white mice weighing 20-22 g intraperitoneal, reg. 3. the introduction of the drug. Studied resorptive action of the drug and chronic toxicity. Intraperitoneal injection LD503000 mg/kg, with the introduction through the mouth LD504466 /3937-5001/ mg/kg. m drug use VM-2-84 for 5 months.at doses of 40 and 70 mg/kg noted certain changes in the tissues of the heart, liver, lungs, kidneys, which are less noticeable in the structures of the cerebral cortex and spleen of mice when compared to control.In the chronic experience with the drug in a dose of 10 mg/kg not detected abnormalities in the tissues of animals.Thus, the claimed connection refers to practically non-toxic substances.The data obtained indicate that it is possible to consider the claimed connection is promising for the creation of drugs anti-inflammatory agents for the treatment of traumatic tissue damage, myocardial infarction and other aseptic inflammations. Anti-inflammatory agent, characterized in that it is a Tris(2-hydroxyethyl)ammonium salt of 3-IntelliTouch acid.
< / BR>as a highly effective protective means in cardiogenic shock and toxic stress
SUBSTANCE: it is suggested to apply tris-(2-hydroxyethyl)ammonium salt of 1-benzylindolyl-3-thioacetic acid earlier known as a stabilizer of cell membrane as preparation to treat autoimmune diseases. The property of the above-mentioned salt to inhibit T-dependent activation of B-lymphocytes, under conditions of decreased medullary function and body leukopenia should enable to develop new pharmacological preparation for treating autoimmune diseases, such as, for example, systemic lupus, rheumatoid polyarthritis, transplant's detachment at transplanting either organs or bony marrow.
EFFECT: higher efficiency of application.
4 ex, 3 tbl
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new derivatives of indol-3-yl of the formula (I):
wherein each A and B represents independently of one another oxygen atom (O), NH, CONH, NHCO or a direct bond; X means (C1-C2)-alkylene or a direct bond; R1 means hydrogen atom (H); R2 means hydrogen atom (H); R3 means NHR6, -NR6-C(=NR6)-NHR6, -C(=NR6)-NHR6, -NR6-C(=NR9)-NHR6, -C(=NR9)-NHR6 or Het1; each R4 and R5 represents independently of one another hydrogen atom (H); R7 means -(CH2)o-Ar, Het, OR6; R6 means hydrogen atom (H); R7 means (C1-C10)-alkyl, (C3-C10)-cycloalkyl; R8 means Hal, NO2 (nitro-group), CN (cyano-group), Z, -(CH2)o-Ar, COOR1, OR1, CF3, OCF3, NHR1; R9 means CN or NO2; Z means (C1-C6)-alkyl; Ar means aryl that can represent unsubstituted, monosubstituted, or polysubstituted R8; Hal means F, Cl, Br, J; Het means saturated, partially or completely saturated monocyclic or bicyclic heterocyclic radical comprising from 5 to 10 ring members wherein 1 or 2 nitrogen atom (N) and/or 1 or two sulfur atom (S) present, and heterocyclic radical can be monosubstituted with phenyl; Het1 means saturated, partially or completely unsaturated monocyclic or bicyclic heterocyclic radical comprising from 5 to 10 ring members and from 1 to 4 nitrogen atoms (N) that can be unsubstituted or monosubstituted NHX, or oxo-group; n = 0, 1 or 2; m = 0, 1, 2, 3, 4, 5 or 6; o means 0, 1 or 2; and their physiologically acceptable salts and solvates. Compounds of the formula (I) elicit intergin-inhibitory effect that allows their using as components of pharmaceutical composition. Also, invention describes intermediate compounds.
EFFECT: valuable medicinal properties of compounds.
11 cl, 4 sch, 1 tbl, 34 ex
FIELD: medicine, arthrology, pharmacy.
SUBSTANCE: agent comprises glucosamine salt as saccharide, dimethylsulfoxide, ointment base and ibuprofen or nimesulide, or piroxicam, or meloxicam, or diclofenac salt, or indometacin, or ketoprofen as a nonsteroid anti-inflammatory agent. Glucosamine hydrochloride, glucosamine sulfate sodium, potassium or calcium salt is used as glucosamine, and diclofenac potassium or sodium salt is used as diclofenac salt. New ointment shows high perfusion rate of active substances to the articulation zone and enhanced effectiveness. Invention expands assortment of agents used in treatment of articulations.
EFFECT: improved, enhanced and valuable medicinal properties of agent.
2 cl, 14 ex
FIELD: medicine, arthrology, pharmacy.
SUBSTANCE: invention relates to agents of topical applying used in treatment of articulation diseases. Proposed agent comprises mixture of chondroitin sulfate and glucosamine salts as a saccharide, the compound taken among the group nonsteroid anti-inflammatory agents, in particular, ibuprofen or nimesulid, or piroxicam, or meloxicam, or diclofenac salt, or indometacin, or ketoprofen, dimethylsulfoxide and an ointment base taken in the definite ratio of components. Invention provides enhancing effectiveness due to the content a mixture of low-molecular and high-molecular saccharides in it that results to increasing diffusion rate of active component to the articulation zone and also the compound taken among the group of nonsteroid anti-inflammatory agents. The combined using these agents provides the curative synergetic effect.
EFFECT: improved and valuable medicinal properties of agent.
2 cl, 14 ex
FIELD: chemical-pharmaceutical industry, pharmacy.
SUBSTANCE: invention relates to manufacturing solid medicinal formulations of preparations. Invention proposes a medicinal formulation consisting of a core comprising the following components: indometacin, lactose, calcium phosphate, hydroxypropylcellulose, magnesium stearate, sodium croscarmellose and envelope comprising collicute MAE 100P, propylene glycol, pigment titanium dioxide, talc, collidon-30, brown sycovite-70. Also, invention discloses a method for preparing the formulation. Invention provides enhancing stability of envelope to effect of stomach juice, rapid and complete release of active substance, simultaneous simplifying the process of applying the envelope for a single step.
EFFECT: improved and valuable pharmaceutical properties of formulation.
3 cl, 1 tbl
FIELD: medicine, neurooncology.
SUBSTANCE: one should carry out chemotherapy and irradiation till radical dosage. Moreover, 2-3 d before the onset of radiation therapy and during the whole course of irradiation one should indicate the intake of indometacin at daily dosage being 300 mg, and 8-14 d before the end of therapy course or the stage of radiation therapy it is necessary to conduct chemotherapeutic cycle with vincristine at total dosage being 4 mG and lomustine at total dosage 160-240 mg. At performing a split course of irradiation the intake of indometacin should be indicated between the stages. The innovation enables to increase radio sensitivity of malignant tumor, suppress angiogenesis, proliferative activity and increased cytotoxic activity of chemopreparations.
EFFECT: higher efficiency of therapy.
1 cl, 3 ex
SUBSTANCE: method involves intragastrically introducing indometacin to rats at a dose of 4.5-5 mg/kg of mass after holding the animals without food and water during 5 days.
EFFECT: enhanced effectiveness of bleeding and perforating ulcer formation.
FIELD: medicine, pharmacology, pharmacy.
SUBSTANCE: invention relates to composition possessing an anti-inflammatory effect and useful for oral administration in form of emulsion preliminary concentrate. Composition comprises NO-releasing nonsteroid anti-inflammatory drug, surface-active substance, oil or semisolid fat and forms in situ emulsion of type oil-in-water after contact with aqueous medium, such as gastroenteric fluid. Also, invention relates to a medicinal formulation based on thereof, oral emulsion, set based on thereof and a method for treatment of inflammation and pain. Proposed compositions possess the improved availability.
EFFECT: improved and valuable properties of composition.
40 cl, 1 tbl, 20 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new amide derivatives of carboxylic acid that are antagonists of NMDA receptors of the formula (I): , wherein one radical among R1, R2, R3 and R4 represents -OH or NH2-group and others are hydrogen atoms; or two adjacent groups R1, R2, R3 and R4 in this case in common with one or more similar or different additional heteroatoms and -CH= and/or -CH2-groups form 5-6-membvered homo- or heterocyclic ring but preferably pyrrole, pyrazole, imidazole, oxazole, oxooxazolidine or 3-oxo-1,4-oxazine ring; two other groups among R1, R2, R3 and R4 radicals represent hydrogen atoms; R5 and R6 in common with nitrogen atom between them form saturated or unsaturated 4-6-membered heterocyclic ring that is substituted with phenoxy-, phenyl-[(C1-C4)-alkoxy]-, phenoxy-[(C1-C4)-alkyl]-, benzoyl-group optionally substituted in aromatic ring with one or more halogen atoms, (C1-C4)-alkyl or (C1-C4)-alkoxy-group; X and Y mean independently oxygen, nitrogen atom or group -CH=, and to their salts formed with acids and bases. Also, invention relates to a method for preparing compounds of the formula (I) and pharmaceutical compositions showing activity as selective antagonists of NR2B receptor based on these compounds. Invention provides preparing new compounds and pharmaceutical compositions based on thereof for aims in treatment of the following diseases: chronic neurodegenerative diseases, chronic painful states, bacterial and viral infections.
EFFECT: improved preparing method, valuable medicinal properties of compounds and compositions.
11 cl, 2 tbl, 27 ex
FIELD: pharmaceutical technology, pharmacy.
SUBSTANCE: method involves addition sugar-alcohol and/or saccharide showing melting point by 5°C lower or above as compared with the first mentioned sugar-alcohol and/or saccharide to sugar-alcohol and/or saccharide followed by combined treatment of prepared powder by pressing and heating. Invention allows preparing medicinal compositions decomposing in mouth cavity rapidly being without water and showing light using owing to the presence of sufficient strength in preparing, transport in usual using. Method involves mixing, pressing and heating components that represent two or more sugar-alcohol and/or saccharide and active component wherein difference between melting points of one among two or more indicated sugar-alcohol and/or saccharide that shows the higher content and any remaining indicated two or more sugar-alcohol and/or saccharide is 5°C or above. Invention provides preparing strength rapidly soluble tablets.
EFFECT: improved preparing method, improved pharmaceutical properties of composition.
30 cl, 12 tbl, 28 ex