Method for controlled mexidol-induced platelet aggregation decrease in experiment
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine, particularly to experimental pharmacology, and concerns methods for controlled platelet aggregation decrease in vitro. That is ensured by administering mexidol to plasma containing 200-220 thousand/mcl of platelets immediately after plasma sampling. Mexidol is used in the concentration of 0.1 to 0.8 mg/ml of an incubation mixture. The incubation is conducted for 10-15 minutes at room temperature.
EFFECT: method provides platelet aggregation to a desired value.
The invention relates to medicine, namely to experimental pharmacology.
Known application of three sodium citrate, a mixture of sodium citrate and Epsilon aminocaproic acid solution SDA hypersecreting solution, sodium oxalate, potassium oxalate solution Wintrobe, two sodium salt of ethylenediaminetetraacetate, lithium oxalate, Florida sodium to suppress spontaneous platelet aggregation in vitro . It is known that Mexidol exhibits antiplatelet properties in vivo . However, Mexidol, possess antioxidant properties , has not been used for controlled lowering of the aggregation activity of platelets in vitro.
The purpose of the invention - expanding Arsenal of tools to reduce aggregation activity of platelets necessary to the experimental values.
This goal is achieved by applying etilmetilgidroksipiridina succinate (Mexidol) as a means of having the ability to reduce aggregation activity of platelets in a dose-dependent manner.
The invention reduces aggregation activity of platelets in experimental limits.
The method is as follows.
Mexidol is introduced into the platelet-rich plasma directly after its receipt at a concentration of platelets 200-220 thousand/ál. In the incubation with the art creates a concentration of Mexidol from 0.1 mg/ml to 0.8 mg/ml Incubated for 10 to 15 min at room temperature. Get the plasma rich in platelets in which the platelets have required the experimenter activity.
When applying Mexidol identified the following change indicators aggregation activity of platelets (table 1) in comparison with control 1 (control 1 taken as 100%). Control 1 was intact plasma rich in platelets, control 2 plasma rich in platelets, which were administered the same volume of solvent for Mexidol (NaCl 0.85 per cent, pH 7.4).
|Group||The degree of aggregation||The rate of aggregation||Time aggregation|
|Control 1 (intact)||100%||100%||100%|
|Control 2 (saline)||105%||102%||102%|
|Mexidol 0.002 mg/ml||104%||104%||139%|
|Mexidol 0,010 mg/ml||108%||124%||88%|
|Mexidol 0,020 mg/ml||97%||101%||123%|
|Mexidol 0,040 mg/ml||99%||111%||90%|
|Mexidol 0,080 mg/ml||95%||106%||117%|
|Mexidol 0.100 mg/ml||97%||96%||88%|
|Mexidol 0,200 mg/ml||80%||89%||56%|
|Mexidol 0,400 mg/ml||47%||73%||26%|
|Mexidol 0,600 mg/ml||0%||39%||24%|
|Mexidol 0.800 to mg/ml||0%||0%||0%|
|Mexidol 1,000 mg/ml||0%||0%||0%|
|Mexidol 1,200 mg/ml||0%||0%||0%|
1. Thus, the introduction of Mexidol in the dose of from 0.400 mg/ml or more in platelet-rich plasma causes a significant decrease in maximum platelet aggregation and a significant (p<0.001) decrease in the rate of aggregation, completely suppressing the aggregation in a dose of more than 8,000 mg/ml
2. When the concentration of Mexidol in platelet-rich plasma from 0.400 mg/ml or more, significantly (p<0.001) reduced the time of platelet aggregation.
The proposed method can be used in scientific research to finding and developing new effective ways of reducing aggregation activity. You can use this method to create the necessary level of aggregation activity of platelets in the study of various properties of platelets or influence of drugs on platelets.
1. Laboratory methods of hemostasis. Edited by Professor D. of Golberg. -Tomsk, 1980. - 292 S.
2. Zrazhevskaya YEAR Use of Mexidol in the treatment of preeclampsia: author. Diss.... Kida. the honey. Sciences. - Irkutsk - 2001. - 22 S.
3. Klebanov GI, Lubicky O., Vasilyev, O.V., Klimov J.V., Benzolive O., tiplyashin A.S., Thick LM, Promience VK Vladimirov, Y.A. Antioxidant properties of derivatives of 3-oksipiridina: Mexidol, emoxipin and proxipen// Questions of medicines is some chemistry. - 2001, UDC 615.849.19.
The method of controlled lowering of the aggregation activity of platelets, characterized by the fact that in the plasma, containing 200-220 thousand/μl platelets, immediately after its receipt, enter Mexidol in a concentration of from 0.1 to 0.8 mg/ml of incubation mixture, and the incubation carried out for 10-15 min at room temperature.
SUBSTANCE: method involves an intraperitoneal administration of N-acetyl-β-1-O-heptylmuramyl-L-alanyl-D-isoglutamine 20 mcg in 0.9% NaCl 0.1 ml per female laboratory mouse. The preparation is administered on the 5th day of pregnancy in a period of blastocyst implantation and on the 7th day in the beginning of a placentation period.
EFFECT: high level of embryo resorption, high model reproducibility and applicability of linear and non-linear animals.
3 ex, 3 tbl
SUBSTANCE: dermal flap is simulated in laboratory animals on the second day of experiment. Resveratrol is administered ingragastrically in a daily dose of 2.0 mg/kg from the first experimental days every 46 hours.
EFFECT: method is non-toxic, has minimum contraindications, provides the dermal flap survival growth in the reduced circulation, by activating a pre-conditioning process.
1 tbl, 1 ex
SUBSTANCE: invention refers to a field of use of plant objects for control of toxic effect of several medical preparations. The method involves complex evaluation of morphophysiological violations observed in phytotests. Each preparation is tested separately, as well as their liquid mixtures of different concentrations are tested. Morphophysiological violations are found out on garden cress seeds (Lepidium sativum). With that, indices of morphophysiological violations are represented with reduction of germination capacity, reduction of total average length of germs and change of average dry weight of germs. After statistical processing of results a potential toxic effect of a mixture of medical preparations is forecasted.
EFFECT: possible preliminary screening of medical preparations prior to clinic tests.
6 ex, 6 tbl, 1 dwg
SUBSTANCE: skin is excised to subcutaneous tissue in the form of a circle of the diameter of 20 mm, and a purse suture applied on the periphery of the wound. Fasciocutaneous interrupted sutures are formed. Subcutaneous tissue is excised on the surface of the wound bottom by perpendicular cuts to form cells 5×5 mm.
EFFECT: method enables simulating trophic wounds with reproducing local hypoxia and disturbed microcirculation.
1 dwg, 1 ex
SUBSTANCE: respiratory phantom impactor comprises cascade elements placed in a sample bowl built in a body with a pipe fitting attached to an upper part of the body by a threaded connection. Each cascade element, without the last one, consists of a nozzle plate 4, 8, 12, 16, 20, 24, with nozzle holes, a collector plate 6, 10, 14, 18, 22, 26 with a viscous substance coating its surface, and a spacer ring 7, 9, 15, 17, 19, 25, 27; a filter 28 is used as the last cascade element. The seven cascade elements are provided for the gravity sedimentation of aerosols in the respiratory organs. The collector plates 6, 10, 14, 18, 22, 26 are provided for the gravity sedimentation of an aerosol size fraction sedimentary in various parts of the respiratory tract.
EFFECT: assessing the tissue and respiratory distribution of an internal radiation dose after inhalations of the radioactive aerosols.
3 cl, 6 dwg
SUBSTANCE: white rat offspring behaviour after a toxic exposure is studied with an open-field test. The number of sniffing, locomotion, in-place acts are recorded. A prognostic index is calculated by formula: P=1/(1+e-y), wherein P is the prognostic index that is a probability of genetic variations; e is a mathematical constant equal to 2.72; y is a regression equation: y=7.04-0.65X1+1.45X2-0.64X3, wherein numerical values are constants and regression coefficients; X1 is the number of sniffing acts; X2 is the number of locomotion acts; X3 is the number of in-place acts. If P is more than 0 and less than 0.5, a probability of the genetic variation is stated as minimal, while P more than 0.5 and less than 1 shows a probability of the genetic variations stated as high.
EFFECT: method extends the range of methods for assessing the genetic disorders in experimental animals.
1 tbl, 2 ex
SUBSTANCE: fulminant sepsis is simulated by inducing a mixed infection with underlying a burning injury. For this purpose, a thermal injury of the area of 12-23% of the body surface in anaesthetised rabbits is applied by immersing the back and sides into water at temperature 90° for 10 seconds. That is followed by the subcutaneous introduction of the non-culturable culture Staphylococcus aureus 1.0 ml in the concentration of 105 microbial cells in 1 ml. Then 60 minutes later, the non-culturable culture Pseudomonas aeruginosa is subcutaneously introduced in the amount of 1.0 ml in the concentration of 105 microbial cells in 1 ml.
EFFECT: method enables studying the effect of the non-culturable mixed infection on the development of an infectious process caused in a susceptible organism, and developing the new laboratory diagnostic techniques; methods for treatment and prevention of fulminant sepsis in the environment of non-culturable bacteria circulation.
2 tbl, 2 ex
SUBSTANCE: infected oral mucosa wound is simulated on an internal surface of an animal's lower lip along the midline. That is ensured by applying original retractor clamps according to cl. 2 on the lower lip skin and mucosa. Branches of a Bilroth's hemostatic forceps are used to fix an oral mucosa area 2 mm2 to be turned about a longitudinal axis at an angle of 360°. The mucosa is detached towards the operator. The prepared wound is covered with a cultured bacterial suspension in the amount of 2 ml. The method is implemented with using a device that is the original retractor clamps comprising two plates placed on the lower lip skin and mucosa, coupled with a spring hinge and merging into retractor clamps levers. The plate placed onto the lower lip mucosa has a sharp edged hole of the diameter of 5 mm. The plate placed onto the lower lip skin has a knop having the diameter of 3.5 mm and the height of 2 mm. The inventions may be also used in experimental medicine to study the efficacy of new pharmaceutical preparations on the oral mucosal wound process in experimental animals.
EFFECT: inventions enable simulating the natural oral mucosal wound process in the animals, make the studied area anatomically accessible, and normalise the wound surface.
2 cl, 2 ex, 1 dwg
SUBSTANCE: complex phytoadaptogenic preparation phytomix-40 (phm-40) in the form of 10% solution with drinking water is administered into CBA male mice suffering the high-frequency spontaneous hepatocarcinoma formation form the first month of the postnatal development, including a period to the completion of hepatic tissue differentiation.
EFFECT: prolonging the life expectancy, median survival, reducing the spontaneous tumour frequency, improving the animal's life quality.
SUBSTANCE: pedicle skin flap survival is corrected in laboratory animals is corrected by modelling a flap on the second experimental day. On the first and fourth day of the experiment, nicorandyl is introduced intraperitoneally in a daily dose of 1.3 mg/kg in two stages.
EFFECT: higher skin flap survival in the reduced blood circulation environment ensured by opening the ATP-dependent potassium channels and providing the nitrate-like effect of nicorandyl in the specific experimental environment.
1 ex, 1 tbl
SUBSTANCE: invention relates to biotechnology and can be used to produce biologically active collagen peptides from marine hydrobionts. Patiria pectinifera starfish is dehydrated with 96% ethyl alcohol and then demineralised with 1-2 N solution of an inorganic acid with ratio of the raw material to inorganic acid of 1:(3-5) for 1-3 days. The demineralised raw material is washed from traces of acid and water-soluble impurities with distilled water, after which the material is hydrolysed with an alkali solution with ratio of raw material to the alkali solution of 1:(3-5) in order to remove non-collagen proteins and washed with distilled water at temperature of 2-4°C. The obtained starfish collagen shells are homogenised. The homogenate is diluted with distilled water; pH of the suspension is brought to a value equal to 8.0-8.5 with an alkali solution and hydrolysed with 1% collagenase solution with ratio of homogenate to enzyme of (100-200):1 and temperature of 30-40°C for 3-5 hours, pH 8.5-7.0. The enzyme is inactivated at 80-90°C for 10-15 minutes. The hydrolysate solution is filtered to remove non-hydrolysed collagen, subjected to ultra-filtration through a 30 kD membrane filter to remove the inactivated enzyme; the end product, having antitumour, anticoagulant, wound-healing, anti-inflammatory, antioxidant activity, capacity to inhibit collagenase and angiotensin converting enzyme and which is a complex of collagen peptides with a high-molecular weight component weighing 22-23 kD, is concentrated in a vacuum and lyophilised.
EFFECT: obtaining a product, having antitumour, anticoagulant, wound-healing, anti-inflammatory and antioxidant activity.
2 cl, 7 tbl, 2 ex
SUBSTANCE: invention relates to medicine, namely to therapy and pulmonology, and can be used for selection of tactics of treating thromboembolism of pulmonary artery. For this purpose computered tomography with bolus enhancement is performed to patient, areas of affection located more distally than thrombotic embolus are examined and number of respiratory movements per minute is taken into account. Presence of occluded vessel or vessels in examined areas is identified. Occlusion of segmental branch of pulmonary artery, located more distally than embolus, is assessed in one point irrespective of degree of vessel occlusion. Occlusion of each of lobar branches in case of affection of right middle lobar, left middle- and upper lobar branches of pulmonary artery is assessed in 2 points. Occlusion of upper lobar branch of pulmonary artery on the right, lower lobar branch of pulmonary artery on the left is assessed in 3 points. Occlusion of right lower lobar branch of pulmonary artery is assessed in 4 points. Occlusion of left main pulmonary artery is assessed in 7 points. Occlusion of right main pulmonary artery is assessed in 9 points. Occlusion of both main pulmonary arteries and/or pulmonary trunk is assessed in 17 points. After that, points are summed up. If the sum of points is from 1 to 6, anticoagulation therapy is performed with heparin. If the sum of points constitutes from 7 to 10 at rate of respiratory movements (RRM) lower than 18, another anticoagulation therapy is performed, at RRM more than 18 - thrombolytic therapy is performed. If the sum of points constitutes from 11 to 17, thrombolytic therapy is performed.
EFFECT: method provides possibility of operative objective assessment of degree of pulmonary bed affection and beginning of required therapy in due time.
5 dwg, 1 tbl, 4 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutical industry, namely an agent possessing anticoagulant activity. A method for preparing a dry fucus extract possessing anticoagulant action by the complex treatment of Fucus vesiculosus. The dry fucus extract possessing anticoagulant activity representing a polysaccharide complex containing fucoidan having the following composition: neutral monosaccharides - fucose, xylose, mannose, galacose, glucose, uronic acid; as well as polyphenols and sulphates in specific amount. The anticoagulant ointment containing the dry fucus extract.
EFFECT: agents described above possess pronounced anticoagulant action.
4 cl, 4 ex
SUBSTANCE: invention refers to cyclohexyl ammonium salt of 2-[3-methyl-7-(1,1-dioxotiethanyl-3)-1-ethyl xanthenyl-8-tio]acetic acid of the following formula: .
EFFECT: obtaining a new compound that shows antithromboembolic action and can be used in medicine.
2 cl, 2 tbl, 3 ex
SUBSTANCE: invention refers to derivatives of oxazolopyrimidine in any of their stereoisomeric forms, or in the form of a mixture of stereoisomeric forms specified in Claim 1.
EFFECT: oxazolopyrimidine derivatives having agonistic activity in relation to Edg-1 receptor.
5 tbl, 319 ex
SUBSTANCE: invention relates to N-carb(glutaminyl)oxymethylimidazo[4,5-e]benzo[1,2-c; 3,4-c']difuroxane of formula .
EFFECT: obtaining a novel compound which can be used as a medicinal preparation which inhibits thrombocyte aggregation.
1 dwg, 1 tbl
SUBSTANCE: invention relates to compounds of formula (I) and/or stereoisomeric forms thereof and/or mixtures of said forms in any ratio and/or a physiologically tolerant salt of the compound of formula , where: X denotes -C(O)- or -SO2-, U denotes an oxygen atom or -(C0-C4)alkylene, A denotes an oxygen atom, -C(O)-NH-, -NH-C(O)- or -(C0-C4)alkylene, V denotes: 1) -(C2-C9)alkylene, where alkylene is unsubstituted or mono-, di- or tri-substituted, independently of each other, by an -OH group, 2) -(C3-C9)alkenylene, D denotes -(C1-C2)alkylene, Y denotes: 1) a covalent bond, 2) -(C6-C14)arylene-, or 3) Het, where Het denotes pyridyl or imidazolyl, R1 denotes: 1) a hydrogen atom, 2) -(C1-C6)alkyl, R3 denotes: 1) -(C2-C6)alkylene-NH2, 2) -(C1-C4)alkylene-SO2-(C1-C4) alkylene-NH2 or 3) -(C0-C4) alkylene-Het, where Het denotes pyridyl or piperidyl, where Het is unsubstituted or substituted with -NH2, R6 denotes: 1) a hydrogen atom, 2) -(C1-C6) alkyl, where the alkyl is unsubstituted or substituted, independently of each other, by a R16 group, 3) -(C0-C4) alkylene-Het, where Het denotes pyridyl, where -(C0-C4) alkylene and Het are unsubstituted or substituted, independently of each other, by a R16 group, 4) -(C0-C4) alkylene-phenyl, where -(C0-C4) alkylene and phenyl are unsubstituted or substituted, independently of each other, by a R16 group, or 5) -(C0-C4) alkylene-(C3-C8)cycloalkyl, R7 denotes a hydrogen atom, halogen or -(C1-C6)alkyl, R8 denotes a hydrogen atom or -(C1-C6)alkyl, R9 denotes a hydrogen atom, and R16 denotes -NH2, which are inhibitors of the active thrombin-activated fibrinolysis inhibitor, as well as a method for production thereof, a medicinal agent based thereon and use for prevention, secondary prevention and treatment of one or more disorders associated with thrombosis, embolism, hypercoagulation or fibrosis changes.
EFFECT: improved properties of compounds.
7 cl, 1 tbl, 9 ex
SUBSTANCE: described are novel triazolopyridazines of general formula , stereoisomeric or tautomeric forms thereof and physiologically acceptable salts thereof, where Q1 denotes H, -C1-6alkyl, optionally substituted with fluorine, or -C3-6cycloalkyl; Q2 and Q3 independently denote H, -C1-6alkyl; R1-R3 independently denote H, -C1-6 alkyl, -C3-6cycloalkyl, -O-C3-6cycloalkyl, -O-C1-8alkyl, a heterocyclic residue etc; R4-R8 independently denote H, -C1-6 alkyl, -OH, -O-C1-8 alkyl, halogen, SF5 etc, a method for production thereof and use as medicinal agents.
EFFECT: compounds have antithrombotic activity and particularly inhibit the protease-activated receptor.
6 cl, 2 tbl, 242 ex
SUBSTANCE: present invention refers to medicine, particularly to pharmacology, and describes a method for correction of disturbed functional activity of platelets, consisting in using Melaxen as a corrector for the disaggregation and hyperaggregation state of the platelets to be orally administered into white non-linear mature rats in a dose of 1 mg/kg once a day within the 7-day therapeutic course.
EFFECT: invention aims at extending the range of preparations having an ability to control the aggregation properties of platelets depending on the nature of the haemostatic disorders.
4 tbl, 4 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to anticoagulant compounds of formula (I) : and pharmaceutically acceptable salts thereof, wherein R represents C1-C8 alkyl substituted by at least one halogen specified in chlorine or fluorine.
EFFECT: invention refers to pharmaceutical compositions containing the compounds and salts thereof, as well as to using the compounds and salts thereof for treating bleeding disorders, to a method of treating, inhibiting epoxyredutase, vitamin K and coagulation factor synthesis.
31 cl, 3 tbl, 11 ex, 10 dwg
SUBSTANCE: invention relates to novel compounds, particularly novel pyridinone derivatives of formula (I) or stereochemically isomeric forms thereof, where R1 is C1-6alkyl or C1-3alkyl, substituted with C3-7cycloalkyl; R2 is a halogen, trifluoromethyl, C1-3alkyl or cyclopropyl; X is a covalent bond, O or O-CH2; Ar is an unsubstituted phenyl or phenyl substituted with n radicals R4, where n equals 1, 2 or 3; where each R4 is a halogen; or pharmaceutically acceptable addition salts or solvates thereof. The invention also relates to a pharmaceutical composition, having the activity of positive allosteric modulators of the metabotropic glutamate receptor subtype 2, based on compounds of formula I and use of compounds of formula I to prepare a medicinal agent for treating or preventing neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved.
EFFECT: novel compounds which can be useful in treating and preventing neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved are obtained and described.
15 cl, 4 ex, 1 tbl