Encapsulated form of acyzol
FIELD: chemical and pharmacological industry.
SUBSTANCE: invention relates to encapsulated form of Acyzol containing Acyzol and pharmaceutically acceptable fillers in specific component ratio.
EFFECT: encapsulated mass with high technological characteristics, high biological availability and effectiveness of Acyzol component.
5 tbl, 3 dwg
The present invention relates to a new pharmaceutical form of Alzola (bis(1-vinylimidazole)zinc diacetate), used as an antidote.
Currently known only dosage form of this drug is 6%solution in 0.5%aqueous solution of procaine hydrochloride for intramuscular injection (Patent RF №2038079).
The disadvantage of this known dosage form is its invasive route of administration, as well as its limitations due to the inability of the patients allergic to novocaine.
The objective of the invention is the creation of oral dosage forms, devoid of the disadvantages of the known dosage forms Alzola.
The problem is solved capsulated form of composition, wt.%:
It should be noted that the attempt to fill the capsule substance in the absence of auxiliary substances is not possible, because the powder is hygroscopic, crumpled and not filled.
The addition of lactose in these quantities leads to loose weight, lower amounts of lactose shown below is about impairs the flowability, increasing the lactose content above this limit does not improve the flowability of the mixture.
The presence of other components allow to obtain high technological characteristics of the capsule mass (moisture resistance, flowability while maintaining uniformity of dosing, dilution, etc.
The applicant notes that this ratio was found as a result a great deal of experimental work, which is undoubtedly due to the unique structure of arizola.
Held at the Institute of toxicology health Ministry studies have shown high efficiency of the dosage form of alzola in the form of capsules in the treatment of poisoning by carbon monoxide and other products of thermal destruction.
1. The effectiveness of alzola poisoning carbon monoxide (CO)
Initially, in a special series of experiments were installed toxicometric parameters for mice and rats with static priming with exposure time of 30 minutes This exposure time was chosen based on the actual conditions of exposure to toxic chemicals on humans when performing emergency measures emergency response and rescue.
The values of experimentally determined toxicometric indicators of carbon monoxide for white rats and mice are presented in table 1.
After testing the technique of priming expertise is mental animals and determine toxicometric parameters investigated the effect of intragastric administration of Alzola in the range of doses from 60 to 160 mg/kg (for this purpose from the contents of the capsules alzola were prepared in 0.01% aqueous solution) with an interval of 20 mg/kg on the survival of mice with acute 30 minute seeds WITH a concentration of 8.5 g/m3. Such conditions seed provided the effect of carbon monoxide on the level LC84-LC100. The aggregated results of these experiments are shown in table 2.
Studies show that after intragastric administration of Alzola mice its threshold dose in relation to carbon monoxide is 80 mg/kg Area of the protective action of Alzola is in the range of doses from 100 to 160 mg/kg Maximum efficacy is observed at a dose of 120 mg/kg figure 1 shows the curve "dose of Alzola effect (survival rate, %)".
Similar experiments were carried out on white rats under static 30 minute seeds WITH concentration to 9.70 g/m3that also corresponds to the level LC84-LC100for this species. Graphical representation of dependence "dose of Alzola effect (survival rate, %)for white rats are presented in figure 2.
The results of these studies evaluating the efficacy of prophylactic use of increasing doses of Alzola presented in table 2.
When this threshold dose of Alzola in for this species is 30 mg/kg, the area of the protective action of the drug is in the dose range of 50-80 mg/kg, and the maximum protective effect nabludaetsa.pri dose of 60 mg/kg
The results of experiments conducted on two species of laboratory animals suggests that in conditions of acute inhalation exposure to carbon monoxide at concentrations close to the LC100with an exposure time of 30 minutes, the values of the dose required to achieve the maximum protective effect after intragastric administration of Alzola, is 120 mg/kg for white mice and 60 mg/kg for white rats. Thus, according to the criterion of survival of an effective protective dose of Alzola intragastric application of twice the effective protective dose prescribed for parenteral administration of the drug.
The experimental results indicate a relatively greater efficiency of Alzola when its internal use in smaller concentrations, but relatively long duration of action (up to 3.5 hours)than at high concentrations, but less exposure. This fact is important, since the use of Alzola in the dosage form for oral administration (capsules) are more focused on the protection of rescuers and people for quite a long time in conditions of high, but not lethal concentrations of carbon monoxide.
When evaluating the effectiveness of Alzola indicators of the dynamics of excretion with exhaled air used is whether the experimental model of intraperitoneal administration WITH white rats. Method intraperitoneal injection WITH white rats allows precise metering of the quantity of gas introduced into the body of the animal, and to adequately simulate the conditions of short duration (up to 20 minutes) non-fatal seed. Intraperitoneal administration WITH white rats produced on the assumption of 2.5 ml of gas per 100 g of body weight. 90 minutes before the injection of gas animals intragastrically injected drug Arizol. Exhaled air from animals collected in special samplers individually for each animal. The concentration of CO in expired air was determined using a gas analyzer PGA-VPM using indicator tubes production "Hemamali". The air sampling and investigation of concentrations was carried out during the first hour with an interval of 15 minutes and thereafter every 60 minutes for 3.5 hours. The results of the experiment are presented in table 3.
Our data indicate that acute intoxication WITH causes in the body unprotected animals the development of decompensated metabolic acidosis, as evidenced by a sharp decrease in pH, plasma bicarbonate and a shortage of buffer bases. The introduction of Alzola reduces the severity of metabolic acidosis reduces the severity of intoxication and can accelerate recovery from poisoned zhivotnyh table 4 presents data on the elimination of carbon monoxide. Figure 3 graphically depicts the dynamics of the concentration of carbon monoxide in exhaled air.
The data obtained indicate a more intensive process of elimination of carbon monoxide from the body poisoned by carbon monoxide animals for prophylactic use of Arizola.
Thus, experimental studies have shown that Azizol when used inside an effective protective tool that allows you to provide the necessary level of resistance of the organism to the toxic effects of CO in a wide range of concentrations and time of action of the poison. Identified protective dose intragastric application of Alzola in experiments 2 species. In experiments on white rats start time, end time, and duration of the protective effect of Alzola when it intragastric introduction of the criterion of survival of animals subjected to acute effects. It is shown that a single oral administration of Alzola in effective dose allows to increase the protective action of the antidote in 2-2 .5 times compared to parenteral administration of the drug.
Research of parameters of acid-base balance in the blood of white rats have shown that prophylactic oral administration of Alzola not only provides less manifestation of intoxicate the indicators of the severity of metabolic acidosis, but can accelerate recovery from poisoned animals. In addition, the positive effect of Arizola on the dynamics of the parameters characterizing blood gases (pO2, SAT), and its impact on the acceleration of processes of elimination FROM blood and tissue depot, which is probably largely related to the mechanism of the protective effect of Alzola in respect of carbon monoxide.
2. Study the protective efficacy of Alzola under the action of combustion products
Experiments to study the protective efficacy of Alzola the combined action of CO and other products of thermo-oxidative degradation, the most typical fires, performed on a special installation with radiant panel and a closed circuit gases according to the method developed by the St. Petersburg branch of the research Institute FOR the Ministry of internal Affairs of the Russian Federation.
Installation with running a tubular furnace with a certain amount of combustible material was subjected to thermal decomposition, and the resulting toxic products was applied in the seed chamber type B. Kurland volume of 0.45 m3equipped with radiation panel to create the conditions for uniform homogenization of aerosol environment, with there animals. Drug tests were conducted on adult outbred white rats-males weighing 180-220 g function Of the CSOs capsules alzola were prepared in 0.01% aqueous solution. Experimental animals the drug was administered intragastrically once 45 minutes before priming dose of 60 mg/kg in aqueous solution in a volume of 1.0 ml per 100 g body weight. The control group was administered intragastrically saline in the same volume. For burning used pine wood and polymer material based on phenol-formaldehyde resin foam stamps "Vilares-5".
Synthetic materials, such "Vilares-5", widely used as finishing and insulating materials. When combustion and thermo-oxidative degradation in addition to the oxide and carbon dioxide, are formed of a high concentration of hydrogen chloride, hydrogen cyanide, acetone and other toxic substances. Pine wood was selected as the reference source two-component mixture of volatile products of thermal destruction, as by burning it emits mainly WITH carbon dioxide and a small amount of tar.
Evaluation of the protective efficacy of the drug Arizol for products thermo-oxidative degradation of combustible materials produced by calculating the protection factor (KS):
where HL50the mass of the sample material, the combustion of which 1 m3confined space eye-catching products cause the death of 50% of the animals./p>
Generalized data on the estimates of the toxicity of combustion products of the tested materials protected Etizolam and unprotected white rats and the values of the coefficients protection are presented in table 5.
Thus, preventive intragastric administration of white rats Alzola at a dose of 60 mg/kg exerts a protective effect not only isolated effects of carbon monoxide, but also the combined effect of CO and other toxic combustion products formed during thermo-oxidative degradation of wood and synthetic non-metallic materials like "Vilares-5", used as a finishing and insulating materials.
The clinical study capsules alzola at the St. Petersburg medical Academy of postgraduate education (GOU DPO SPb. Maps of the RF Ministry of health) also showed high efficiency of the drug Arizol in the pharmaceutical form Capsules 120 mg. The drug is recommended to use as antidote and remedy for poisoning by carbon monoxide and other products of thermal destruction.
Thus, the results of preclinical and clinical trials have shown that the pharmacological activity of alzola when kapsulirovanie saved. Capsulated form Alzola has good tolerability.
The following examples which shows how to obtain a capsulated form of alzola according to the invention.
Example 1. In the mixer, gradually introducing the components, mix 120 g alzola, 214 g of milk sugar, 8,91 g of talc and 3.59 g of Aerosil and 3.5 g of calcium stearate to obtain a homogeneous granular mass. The resulting mixture was Packed in capsules. Get 1000 capsules with a mass of capsules 0,35 gaderene active substance in one capsule of 120 mg
Sources of information
1. Report on the study of specific pharmacological activity of the dosage form (capsules) drug "AZIZA", Institute of toxicology, Russian Federation Ministry of health, 2004, Saint-Petersburg.
2. Manual on experimental (preclinical) study of new pharmacological substances. - M.: the Ministry of health of the Russian Federation, "Remedium", pp.33-38.
3. Manual on experimental (preclinical) study of new pharmacological substances. - M.: the Ministry of health of the Russian Federation, "Remedium", s.257-263.
4. Report on experimental pre-clinical study safety dosage form (capsules) drug "AZIZA", Institute of Toxicology MH RF, Saint-Petersburg, 2003
5. Report on the clinical study. Evaluation of the pharmacokinetics, safety of use and impact on physical and mental health of a healthy person of the drug arizol in the pharmaceutical form capsules, 120 mg, is presented as the antidote and remedy for poisoning by carbon monoxide and other products of termed the year. GOU St. Petersburg medical Academy of postgraduate education of the Ministry of health of the Russian Federation, 2004, Saint-Petersburg.
Toxicometric parameters for mice and rats with static seed
|Animal||The number of animals||Duration||Concentate CO, g/m3|
The influence of Arizola on the survival of mice following acute inhalation exposure WITH
|Dose Alzola mg/kg||The number of animals in the group||Including||Survival, %|
|* - the difference significantly compared with control at p<0.05|
|** - the difference significantly compared with control at p<0.025|
Indicators of acid-base balance in the blood of white rats at different times after acute intoxication WITH at a concentration of 5.0 g/m3with an exposure time of 30 minutes
|Indicators||The measurement time after the seed||Groups of animals (n=6)|
|Control (unprotected)||Experience (protection Etizolam)||Intact animals|
|p CO2, mm Hg||0 min||33.15±0.69||31.95±0.46||48.23±1.98|
|PO2, mm Hg||2-5 min||32.72±2.46||At 42.25±0.24*||75.76±1.67|
|3 hours||At 74.77±1.88||78.77±1.88||78.77±1.88|
|The HCO3, mol/l||2-5 min||7.35±0.22||8.70±0.22*||24.83±1.06|
|1 hour||At 23.84±0.46||23.65±0.91|
|T CO2, mol/l||2-5 min||8.65±0.15||9.70±0.22||At 26.17±1.22|
|ABE, mol/l||2-5 min||-22.00±1.29||-20.45±0.20||-1.03±0.61|
|SAT %||2-5 min||53.37±1.95||58.05±0.51*||89.93±1.22|
|Note: * - the difference significantly relative to the control (p<0,05)|
Toxicity of the products of thermo-oxidative degradation of the material "Vilares-5" and pine for protected Etizolam (experience) and unprotected (control) white rats
|Material type||The group of animals||The number of animals in the group||HCL50, g/m3||The protection factor|
|* - the difference significantly compared with control at p<0.05|
Capsulated form Alzola, characterized in that it contains, wt%:
FIELD: veterinary science.
SUBSTANCE: in case of dioxine intoxication animals should be prescribed with dimephosphon at the dosage of about 50-150 mg/kg body weight daily for 10-30 d. The innovation provides decreased embryonic lethality in animals.
EFFECT: higher efficiency of therapy.
3 ex, 1 tbl
FIELD: medicine, toxicology.
SUBSTANCE: invention proposes applying 15% aqueous solution of 1-methyl-5-[2'-(benzyldimethylammonio)ethyl]carbamoyl pyridinium-2-aldoxime dichloride that exceeds the 15% solution of dipiroxime (TMB-4, trimedoxime bromide) used in native medicinal practice by the curative effectiveness. Invention can be used in urgent treatment of acute poisoning with organophosphorus poisonous substances eliciting neuroparalytic effect.
EFFECT: enhanced effectiveness, valuable medicinal properties of agent.
FIELD: medicine, immunology.
SUBSTANCE: method involves administration of derivatives of mono- and disaccharides taken in therapeutically effective doses or pharmaceutical composition based on thereof that provides the effective stimulation of immune system based on the selective modulating effect on cytokines producing. Invention can be used in treatment and prophylaxis of infectious, autoimmune or allergic diseases.
EFFECT: improved method of prophylaxis and treatment.
38 cl, 2 tbl, 9 dwg, 6 ex
FIELD: medicine, immunology, pharmacy.
SUBSTANCE: invention relates to methods for treatment of autoimmune, rheumatic diseases, immune disorders associated with rejection of transplant and involves administration to patient mutant molecules of a soluble CTLA4. These molecules can be administrated in common or successively with the second agent that is chosen from the group consisting of corticosteroid, nonsteroid anti-inflammatory agent, azathioprine, methotrexate, blocker or antagonist of TNFα, hydroxychlorokin, sulfasalazin, gold salt, anakinra, cyclophosphamide and leflunomide. CTLA4 molecule represented in Fig. 23 given in the invention description comprises mutation in position +104 CTLA4 wherein leucine is substituted with glutamic acid, and mutation in position +29 CTLA4 wherein alanine is substituted with tyrosine. CTLA4 molecule can comprise an extracellular domain and involves a sequence shown in Fig. 19 given in the invention description beginning from methionine in position +1 or from alanine in position -1 and terminating by aspartic acid in position +124. CTLA4 molecule can represent L104EA29YIg beginning from methionine in position +1 or from alanine in position -1 and terminating by lysine in position +357 as shown in Fig. 19. Invention provides blocking the immune interaction between T- and B-cells and prevention of activation of B-cells based on binding B7 molecule by using indicated CTLA4 molecule wherein mutations in its molecule result to positive changes in avidity binding with B7.
EFFECT: improved method of treatment.
31 cl, 3 tbl, 33 dwg, 4 ex
FIELD: chemical and pharmaceutical industry.
SUBSTANCE: invention relates to natural immunocorrective preparation Tactivine in spray form. Claimed agent contains Tactivina, vitamin C and 0.14 M sodium chloride solution as solvent in specific component ratio.
EFFECT: agent of improved effectiveness and storage stability.
2 cl, 5 tbl, 4 dwg, 4 ex
SUBSTANCE: method involves introducing anti-staphylococcus-proteus-blu-pus-bacillus vaccine twice: once before and once after an operation with 7-10 days long interval. Antibiotic and vaccination therapy is administered in combination with immunomodulator introduced. The immunomodulator is selected from a group composed of immunomodulator of microbial origin, synthetic chemical substance immunomodulator, immunomodulator obtained from marrow and nucleic acid-based immunomodulator. The treatment is continued by administering probiotics combined with biologically active nutrient additive selected from a group composed of blackberry syrup with Echinacea, Echinacea with vitamin C added and Immunostat E, given beginning from 5th-10th day.
EFFECT: enhanced effectiveness in restoring soft tissue structure in postoperative wound region.
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to 2-thio-substituted derivatives of imidazole of the formula (I) , their optical isomers and physiologically acceptable salts wherein R1, R2, R3 and R4 have values given in claim 1 of the invention. Compounds possess immunomodulating and/or inhibitory effect on cytokine release and can be useful in treatment of diseases associated with the immune system disorder. Also, invention relates to a pharmaceutical agent inhibiting release of cytokines based on compounds of the formula (I) and using these compounds for preparing a pharmaceutical agent inhibiting release of cytokines for treatment of diseases associated with the immune system disorder.
EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.
13 cl, 1 tbl, 88 ex
FIELD: medicine, oncology.
SUBSTANCE: invention relates to immunomodulator representing pentapeptide of formula Val-Val-Tyr-Pro-Asp and drug in liquid and dry forms based on the same. Both pentapeptide and pharmaceutical composition containing the same have antitumor activity in small doses and have no side effects.
EFFECT: new low molecular peptide with immunomodulating activity and antitumor preparation based on the same.
2 cl, 6 ex, 4 tbl
FIELD: pharmaceutical industry in particular immunology.
SUBSTANCE: invention relates to bioactive supplement to prevent suppression of primary and secondary immune response associated with stress. Claimed supplement contains tincture of chamomile inflorescence, vitamin C and β-carotene as antioxidants and Eleuterococus extract or pantocrin extract as adaptogene in specific component ratio.
EFFECT: effective agent to prevent suppression of primary and secondary immune response associated with stress.
3 cl, 3 tbl
FIELD: proteins, chemical-pharmaceutical industry.
SUBSTANCE: dry alpha-fetoprotein (AFP) is isolated from blood serum. Method involves fractionation of proteins with ethyl alcohol of ammonium sulfate, or sodium sulfate. After separation of supernatant the latter is dialyzed against sodium chloride solution and applied on affinity sorbent in sodium chloride solution with the concentration 0.1-1.0 mole/l and Triton X-100 with the concentration 0.01-0.5%. Sorbent is washed out with phosphate-saline buffer and AFP bound with sorbent is eluted by using glycine-HCl buffer solution. Eluate is neutralized and applied on Sepharose with antibodies raised to human IgG used as the second affinity sorbent followed by sterilizing filtration and lyophilization. Invention provides enhancing yield of AFP and its purity.
EFFECT: improved preparing method.
FIELD: medicine, in particular surgery, oncology.
SUBSTANCE: claimed method includes immunotherapy, namely on day before operation reaferonum-EC-lipint in dose of 1000-15000 U/kg is perorally administrated to patient. Then in postoperative period blood sampling, extracorporal incubation of leucocytes with imunofan, and intravenous drop administration are carried out. Further for 5 days after operation reaferonum-EC-lipint is perorally administrated to patient dose of 1000-15000 U/kg one time per day. Method of present invention may be used in treatment of patients after radiotherapy in postoperative period. Furthermore method makes it possible to decrease of therapy time by 1.6 times, to reduce total accident number by 2.3 times and decrease of mortality by 2 times.
EFFECT: improved method for rectal cancer treatment.
3 ex, 1 tbl
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to substituted glutarimides of the general formula (I): wherein X means group of the formula -(CH2)n-(CR8R9)p-Z-(CR8R)m wherein Z means sulfur (S) or oxygen (O) atom, SO- or SO2-group, residue -NR8 (optionally as N-oxide) or the group -CR8R9; m and p mean 0 or 1; n means 0, 1, 2 or 3, and m, n and p can't mean 0 simultaneously; R1 and R2 mean carboxyl, ester or acyl group and others; R3 means hydrogen atom, hydroxyl group and others; R4 means hydrogen atom, (C1-C3)-alkyl group, fluorine atom, trifluoromethyl group; R8 and R9 means hydrogen atom, benzyl, alkyl and others, and to their physiologically acceptable salts also. Compounds of the formula (I) possess immunomodulating effect and can be used in treatment of angiopathy and/or oncohematological diseases.
EFFECT: improved preparing method, valuable medicinal properties of compounds.
15 cl, 1 tbl, 20 ex
FIELD: medicine, infectious diseases.
SUBSTANCE: method involves carrying out the conventional antibacterial, pathogenetic and symptomatic therapy of acute tick borreliosis (ATB) in standard doses. Since the first day of treatment the preparation "yantar antitoks" is prescribed orally in the dose 1 tablet, 2-3 times per 24 h after eating for 25-30 days; before 5-7 days from onset of anthelmintic therapy the preparation "allohol" is prescribed in the dose 1 tablet, 2-3 times per 2 4 h and the preparation No-Spa in the dose 0.04-0.08g, 2-3 times per 24 h; biltricid is prescribed in the first day after termination of antibacterial therapy of ATB in the dose 60 mg/kg of body mass for 3 intakes with break for 4 h for 24 h and 15 after eating. Invention promotes to prophylaxis of borrelia persistence and opisthorchia, reducing intoxication syndrome for the shortest period and decreasing adverse effects of antibacterial therapy. Invention can be used in treatment of ATB on background of chronic opisthorchosis.
EFFECT: improved and enhanced method of treatment.
8 tbl, 4 ex
SUBSTANCE: invention is intended to treat pseudoallergic rhinosinusopathy against a background of parasitic invasion of hepatobiliary system. Elimination of parasites is effected simultaneously with administration of hepatoprotectors and all-purpose membrane stabilizers until clinical is achieved, while cryoconchotomy is performed not later than elimination of parasites is ended.
EFFECT: achieved complete restoration of nasal respiration, reduced incidence of parasitic malady recurrences, and reliably eliminated symptoms of rhinosinusopathy owing to combination of cryoconchotomy and purposive action on hepatobiliary system.
5 cl, 2 ex
FIELD: internal diseases.
SUBSTANCE: patient is administered diet including 0.3-0.5 g/kg/day animal for 10 days followed by increase to dose 0.8-1 g/kg/day during 1 month, after which 5% glucose solution is administered intravenously in dose 400-500 ml for 1 weak, lactulose in dose 60-90 ml divided into 2-3 intakes for 4 weeks, and probiotics over a 2-weak period 30 min before meal time. Simultaneously, L-ornithine-L-aspartate is given during 10 days in dose 30-40 g a day divided into 2-3 intakes followed by dose 5-7 g thrice a day during 10 days.
EFFECT: achieved involution of neurological and psychical manifestations of encephalopathy, reduced hepatic coma development incidence, and increased protein tolerance in patients.
4 cl, 3 ex
FIELD: medicine, hepatology, immunology.
SUBSTANCE: invention proposes using an opioid peptide DSLET of the formula: Tyr-D-Ser-Gly-Phe-Leu-Thr used for stimulation of reparative regeneration of liver and correction of immune reactivity under conditions of toxic hepatopathy. Opioid peptide DSLET is administrated by parenteral route (intaperitoneally) in the dose 50 mcg/kg of body mass in 0.1 ml of physiologically solution in course for 10 doses with break for 24 h between injections to experimental animal (rat) with toxic hepatopathy. The advantage of invention involves the possibility for using this peptide in toxic hepatopathy. Invention can be used for stimulation of regeneration of hepatocytes and correction of immune reactivity in experimental toxic hepatopathy.
EFFECT: valuable medicinal properties of agent.
2 tbl, 2 ex