Microcolloidal solution of propofol for anaesthesia
SUBSTANCE: aqueous composition for anaesthesia is proposed, which comprises propofol as an active agent, the PEG-660-12-hydroxystearate as a solubiliser, benzyl alcohol, or chloroethanol or parabens as preservative, the tocopherol and arginine or glycine at a specific content of components wt %. The GABA agonists can be additionally added to the composition, e.g. aminophenyl-butyric acid, local anesthetics such as lidocaine, alpha-2-adrenoceptor agonists such as xylazine. The method is proposed for implementing anaesthesia comprising administering to a patient of an effective amount of the claimed composition.
EFFECT: invention provides low toxicity of dosage form and high efficiency.
5 cl, 3 tbl, 1 ex
The invention relates to the field of medicine and veterinary medicine and can be used for induction and maintenance of anesthesia.
Propofol (2,6-diisopropylphenol) - short-acting anesthetic used for induction and maintenance of General anesthesia and sedation with local surgical intervention. Preparations of propofol administered in a single intravenous dose or in repeated dose bolus may also continuous infusion introduction.
Propofol first obtained in the research division of the Corporation ICI (UK) via chemical synthesis. In 70-80 years of the last century Corporation ICI received several patents on compositions and the use of propofol as an anesthetic funds - US Pat. 4056635 "2,6-Diisopropylphenol as an anaesthetic agent, US Pat. 4452817 "Anesthetic composition containing 2,6-Diisopropylphenol", US Pat. 4798846 "Pharmaceutical compositions". In these patents the claimed compositions in water-organic base containing as a solubilizer Cremophor EL (polyoxyethylene castor oil), or other similar connection.
Subsequently, when the widespread use of drugs on the basis of removerow, and large numbers of patients were marked by numerous anaphylactic (allergic) reactions and these drugs were withdrawn from the practice of medicine.
The main prerequisite bioavailability and the effect is vnesti dosage forms of propofol - the solubility in water. Propofol hydrophobic substance and can be mixed with water only in the presence of solubilization (surfactants). However, most surface-active substances (surfactants) are not compatible with humans and animals, so the development was carried out only with Awami permitted by the pharmacopoeias.
The most famous composition of the medicinal product on the basis of propofol contains as an emulsifier/solubilizer mixture of soybean oil and egg lecithin and has the following composition:
Propofol - 1%; Soybean oil cleaned - 10%; egg Lecithin - 12%; Glycerol - 22,5%; sodium Hydroxide to pH 8.5; Water to 100%. When mixing these substances with water it turns opaque white emulsion is very sensitive to temperature changes.
In 1986 the company Astra-Zeneca (UK) has introduced this recipe to medical and veterinary market under the commercial name "Diprivan" for veterinary use "Rabinovich". This drug was widely used in world practice anaesthetics, but already in the first years of use has been identified the main drawback of this drug is non-resistant to microbial contamination and, as a consequence, the threat of a General infection of the patient. The reason for this instability in the large sensitivity of the emulsion to the presence of ionic and hydrophob what's connections, so as it breaks the surface energy of droplets of the emulsion and causes delamination of the solution. Therefore, the developers have refrained from having the formulation of preservatives, antioxidants and other substances that affect the physical and chemical stability of the drug.
Further, employees of the company Astra-Zeneca tried to improve this recipe in the following patents: Patent RF №2147432 "Emulsion of the type oil-in-water containing propofol and edentate and US Pat. 7125909 "Sterile parenteral nutrition compositions". In these patents resistant to microbial contamination was increased to 24 hours due to the introduction of the formulation of the edetate sodium (EDTA), but it is also insufficient due to the large consumption of the drug and weak antimicrobial activity of EDTA.
Known patents, in which as a solubilizer used poloxamer (pluronic): RF patent №2250101 "Anesthetic formulations", US Pat. 4798846 "Pharmaceutical compositions", US Pat. 6623765 "Microemulsion and micelle systems for solubilizing drugs", US Pat. 7915317 "Aqueous 2,6-diisopropylphenol pharmaceutical compositions", US Pat. 6743436 "Anesthetic composition for intravenous injection comprising propofol", WO/2003/017977 "Anaesthetic formulations of propofol". In these patents shows the formulation of the dosage form of propofol following composition: propofol of 0.1 - 10%; poloxamer 407/188/237/108/234 (in different proportions) is 5-20%; preservatives (EDTA) - 0,005-0,1%; water for injection to 100%. The example above is typical of all of these patents, USPat. 6623765 "Microemulsion and micelle systems for solubilizing drugs added simulatory (polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycols, polyoxyethylene esters).
The compounds presented in the above patents, meet the essential criteria of the physico-chemical stability adopted for drugs. However, these compounds have appreciable viscosity, which makes them difficult parenteral administration. In addition, a colloidal solution of propofol in the aqueous poloxamer sensitive to the introduction of additional components, antioxidants, preservatives, biologically active substances that affect the bioavailability and reduce the toxicity of propofol. The introduction of these substances is needed to improve the pharmacological properties of the drug, but leads to a sharp drop physico-chemical stability of dosage forms containing poloxamer.
Patent US Pat. 7138387 " Clear aqueous composition comprising propofol and hydroxypropyl-beta-cyclodextrin and EP 1928412 "Aqueous anaesthetic compositions comprising propofol" the claimed dosage forms on the basis of a complex of cyclodextrin with propofol following composition: Propofol - 1 g; 2-hydroxypropyl-beta-cyclodextrin - 30 g; Glycerol - 2.25 g; Edetate sodium - 0.005 g; Water to 100 ml.
In the practical reproduction of this composition in the laboratory, it is found that the complex formation is strongly dependent on the characteristics of si is thesis of the original substance cyclodextrin (used commercial substance cyclodextrin different manufacturers) and the content of propofol in a stable dosage forms did not exceed 0.3%, that is not enough for effective anesthesia.
Closest to the proposed solution are dosage forms that are claimed in the patent US 7326735 "Formulations for anaesthetic use". This patent describes the formulation of the dosage form of propofol following composition: propofol - 0,5-1,5%; solvent glucotrol) - 10-30%; the co-solvent (Solutol HS 15 (PEG-660 12-hydroxystearate), esters of polyethylene glycol and 12-hydroxystearate acid) is 5-20%; a viscosity modifier (ethanol) is 0.5 - 5%; preservatives (EDTA) - 0,005-0,1%; benzyl alcohol and 0.1 - 10%; water for injection to 100%.
In the proposed dosage form required the presence of solvent (glucotrol), which leads to increased cost of the drug. Also, the authors of the invention have not announced the introduction of the biologically active substances that improve pharmacological properties and reduce the toxicity of the solvent, the authors of the patent claim by the pharmacological action of the proposed dosage form is similar to Diprivan (Astra-Zeneca).
The present invention is the design of injectable anesthesia on the basis of propofol with low toxicity, high efficiency (bioavailability) and high physical and chemical stability with the introduction of biologically active substances which improve the above-mentioned parameters.
the technical result is lower toxicity dosage forms and high efficiency in comparison with the known compounds.
The problem is solved in that the aqueous composition for anesthesia containing propofol as active-active substance, PEG-660-12-hydroxystearate as a solubilizer, benzyl alcohol, or chlorate, or parabens as a preservative, according to the invention additionally contains tocopherol and arginine or glycine at the following content, wt.%:
|preservative||0.1 to 2|
|arginine or glycine||0,1-10|
|water for injection||rest|
The composition may further contain GABA agonists, for example, aminophenylalanine acid in an amount of from 0.01 to 10 wt.%, as well as local anesthetics, such as lidocaine in an amount of from 0.05 to 5 wt.%. In addition, the composition can be added to the alpha 2-adrenoceptor agonist, e.g., xylazine in an amount of from 0.01 to 10 wt.%.
The problem is solved also by the fact that the means of implementing the anesthesia includes introduction what their patient an effective amount of a composition of the above composition.
The problem is solved in that the dosage form is a sustained (physico-chemically stable) microcolloidal solution of propofol in the water, as a solubilizer is used PEG-12-hydroxystearate, physico-chemical stability of the solution is achieved by a certain ratio of propofol/solubilizer/preservative/water, low toxicity and high bioavailability is achieved through the introduction to dosage form of tocopherol and arginine or glycine.
Below is a pharmacological parameters (toxicity and efficacy of sedation (anesthesia)) the most stable dosage forms of propofol (tables 1 and 2). The basis was taken dosage form of propofol with an optimal ratio of propofol/solubilizer/preservative/water (basic LF). This part is the most physico-chemically stable and resistant to microbial contamination. The number of basic components LF shown in example 1.
|The parameters of acute toxicity of compositions (dosage forms) of propofol when vnutribruchinnom introduction to white mice|
|Name of the component||Mr. the R variant of the dosage form|
Component content, %
|Water for injection||100||100||100||100||100||100||100||100||100|
Introduction to basic pharmaceutical form of propofol components such as tocopherol or amino acids arginine/glycine, reduces the acute toxicity of the anesthetic composition (LD50in 1.1 and 1.2 times respectively. Simultaneous inclusion of basic pharmaceutical form of propofol tocopherol with amino acid has a synergistic effect on the reduction of toxicity of the anesthetic composition is from 1.5 to 1.8 times (options VI, VIII, IX).
Introduction basic LF of propofol with tocopherol, but without amino acids etc which has led to a significant increase in such index, as a stand without support, 4,50 vs. 1.25 and 1.75 for formulations of propofol containing amino acids arginine and glycine, respectively. The remaining indicators in rats groups that received LF of propofol without amino acids, such as a front pillar, a short grooming, the number of crossed squares, in the center, unreliable were higher than in groups, which was introduced propofol in combination with amino acids. The level of anxiety in groups of animals, which was introduced basic dosage form of propofol with tocopherol and tocopherol and amino acids (argmin/glycine) was significantly lower levels of anxiety in the control group.
Below is the technology of preparation of dosage forms of propofol and the most significant examples of the compounds.
Technology of preparation of dosage forms of propofol following.
In a suitable container of glass is placed a portion PEG-12-hydroxystearate (solutol), heated to melt, add a shot of propofol and preservative and mix until a homogeneous mixture. The temperature of the mixture +40-50°C.
In a separate container placed a portion of water for injection and add a sample of other ingredients, mix until dissolved.
Then add the mixture solutol-propofol-preservative in the container of aqueous solution with constant stirring. Received about is this at all slightly opalescent solution is filtered through a membrane filter of 0.22 μm and filled into sterile glass vials.
The basic composition of the dosage form of propofol, and the optimal number of other prerequisites
|Name of the component||Basic LF|
Component content, %
Component content, %
|Water for injection||100||100|
Table 3 provides examples that illustrate the limits of the physico-chemical stability of the compositions LF of propofol, as well as variants of excipients that can be and is used in LF.
|Examples of compositions (dosage forms) of propofol.|
|Name of the component||Example No.|
Component content, %
|Water for injection||100||100||100||100||100||100||100||100||100|
Composition I. the Maximum content of arginine (when using glycine occur similar processes). Further increase in the content of arginine or glycine leads to physico-chemical system instability (stratification and the turbidity of the solution).
Composition II. The increase in the content of propofol to 2.0% leads to an increase in the concentration of the solubilizer, which makes the solution more viscous, especially at temperatures below +20°C.
Compositions III and IV. Further increase in the content of propofol (10%) leads to a sharp increase in viscosity and instability of the solution. For such LF necessary the introduction of the organic solvent, which has a negative effect on the pharmacological properties of the drug. To reduce the side effects of an organic solvent to increase the concentration of lidocaine, resulting in limiting ways of entering data LF (only intramuscularly or subcutaneously). Increasing the concentration of tocopherol acetate partially neutralizes the adverse effects of high concentrations of lidocaine.
Composition V. the Maximum content of glycine. With further increase of the content of glycine is the stratification of the solution.
Composition VI. The minimum content of solubilizer (PEG-660-12-hydroxystearate). In this composition is also reduced content of propofol and tocopherol in connection with the physico-chemical instability of this LF at elevated concentrations of the above components.
Composition VII, VIII. The maximum content of substances that increase the efficiency of anesthesia (GABA agonists and alpha-2-adrenoceptor agonist). With further increase of the content of these substances physico-chemical stability of the solution decreases sharply (precipitation, stratification).
Composition IX. The maximum content of preservative. The increase in the concentration of preservative leads to unacceptable toxicity dosage forms.
1. Aqueous composition for anesthesia containing propofol as active-active substance, PEG-660-12-hydroxystearate as a solubilizer, benzyl alcohol, or chlorate, or parabens as a preservative, characterized in that it further comprises tocopherol and arginine or glycine at the following content, wt.%:
|preservative||0.1 to 2|
|arginine or glycine||0,1-10|
|water for injection||rest|
2.The composition according to p. 1, characterized in that it added GABA agonists, such as aminophenylalanine acid in an amount of from 0.01 to 10 wt.%.
3. The composition according to p. 1, characterized in that it added to local anesthetics, such as lidocaine in an amount of from 0.05 to 5 wt.%.
4. The composition according to p. 1, characterized in that it added the alpha 2-adrenoceptor agonists such as xylazine in an amount of from 0.01 to 10 wt.%.
5. The manner of exercise of anesthesia, including an introduction to the patient an effective amount of a composition according to any one of paragraphs.1-4.
SUBSTANCE: radionuclide indicator is administered to record the dynamics of its distribution in limb tissues by a radionuclide method. The examination is performed at rest and during a load test. The load test represents an epidural block by gradual administration of bupivacaine 25-30 mg between L2-L3 vertebrae for 5-7 minutes. That is followed by measuring a blood flow as a percentage of its value to the same level in an analogous segment of a collateral limb.
EFFECT: qualitative assessment of the circulation reserve in various categories of patients, including disabled ones by inhibiting sympathetic and minimally sensory activity with maintaining the patients' motor activity.
2 dwg, 2 ex
SUBSTANCE: invention refers to medicine, namely to abdominal surgery and anaesthesiology, and can be used where it is necessary to anaesthetise after the prosthetic hernioplasty for median postoperative ventral hernias. That is ensured by placing an endoprosthesis under the aponeurosis, a polyvinylchloride catheter is placed into the formed spaced around the periphery of a postoperative wound in the form of an oval above the endoprosthesis plane at 2.5-3 cm from its edges. Along its full length, the catheter has multiple side holes. Single openings are created in a projection of a lower corner of the wound, and the catheter ends are brought out onto the skin. An inlet of the catheter is attached to a local anaesthetic dosage device by means of a cannula. That is followed by a controlled prolonged irrigation with 2.5% Ropivacaine 20 ml every 6-8 hours during 2-3 days.
EFFECT: method enables the adequate postoperative anaesthesia, as well as the length of the postoperative intestinal distention by providing the uniform controlled administration of the local anaesthesia solution.
7 dwg, 1 ex
SUBSTANCE: invention relates to medicine, namely to anaesthesiology and surgery, and can be used in case of anaesthesia necessity in patients after herniorrhaphy with inguinal access in case of inguinal hernias. For this purpose after the main stage of operation - hernioplasty, before suturing of the aponeurosis of the external oblique abdominal muscle, through subcutaneous adipose cellular tissue a puncture of 1 cm more medially and 1 cm higher than the anterior-superior iliac spine is made. A multiperforated catheter is introduced through the puncture under finger and visual control in such a way that its distal end is near the pubic tubercle. The catheter is placed under the aponeurosis of the external oblique abdominal muscle in the inguinal canal above and parallel to the spermatic cord in men or the round ligament of uterus in women. All the side holes of the catheter must be located in the subaponeurotic space. The first 48 hours of the post-operation period the local anaesthetic is continuously introduced by drop infusion at a rate of 2-4 ml/h or by bolus introduction in a dose of 10 ml each 4-6 hours through the catheter. After 48 hours the catheter is removed.
EFFECT: method provides adequate anaesthesia in the said category of patients in the post-operation period without application of additional anaesthetic preparations due to blockade of ilioinguinal, ilioceliac and hollow branch of genitofemoral nerves.
2 dwg, 2 ex
SUBSTANCE: group of inventions refers to medicine, and may be used in treating the patients suffering headaches and facial pains. There are presented versions of a drug delivery device comprising an injector a first end of which is left outside patient's nasal passages. Another end of the injector comprises one or more holes for spraying a drug upwards, and/or to the side, and/or to the front towards a sphenopalatine ganglion, an input device interacting with a patient's nostril and comprising a canal for receiving the injector. Additionally, the device can comprise a handle connected to the input device and provided for receiving the canal of the input device. The injector can move between a storage position before the interaction, and an interaction position related to the interaction. There are also presented versions of the method of using the above device that involve introducing the injector through the nasal passage into median and/or posterior and/or inferior region in relation to the patient's sphenopalatine ganglion, and spraying the drug.
EFFECT: group of inventions provides faster and more effective headache and facial pain relief by safe and accurate drug delivery of the therapeutic substances blocking the sphenopalatine ganglion.
49 cl, 4 dwg, 30 ex
SUBSTANCE: invention relates to a novel biologically active 2,6-dimethylanilide of N-cyclohexylpyrrolidine-2-carboxylic acid, having surface, infiltration and conduction anaesthesia activity, considerably better than bupivacaine and ropivacaine with the same or less toxicity.
EFFECT: improved compounds.
FIELD: medicine, pharmaceutics.
SUBSTANCE: what is presented is a pharmaceutical composition in the form of a spray for treating a damage by non-lethal irritants (e.g. pelargonic acid morpholide), containing pediphene in the following proportions, wt/volume %: pediphene hydrochloride 0.01-10.0; sodium chloride 0.1-10.0; water for injections up to 100 ml. What is shown is the efficacy of pediphene in compliance with the declared application ensured by the local anaesthetic effect of the drugs.
EFFECT: drug preparation has no allergenic and immunotoxic properties.
3 dwg, 40 tbl
SUBSTANCE: invention refers to medicine, namely anesthesiology, intensive therapy and endosurgery, and may be used in patients in need of endoscopic transpapillary intervention. That is ensured by an intravenous infusion therapy with crystalloid solutions in the amount of 800-1200 ml. An epidural space is punctured and catheterised at the level of Th VIII - Th IX with the catheter moved by 4-5 cm in the cranial direction. A local anaesthetic solution and Clopheline 100 mcg are introduced through the epidural catheter at the level of Th V - Th X 20 minutes before the endoscopic transpapillary intervention. It is followed by pre-medication enabled by introducing 0.1% atropine 0.5-1 ml and 0.5% relanium 1-2 ml, and the patient is wheeled into a catheterisation laboratory. After the endoscopic transpapillary intervention completed, the patient is transferred into an intensive therapy unit wherein prolonged epidural analgesia is enabled by introducing 0.5-1% lidocaine 10 ml into the epidural space every 4 hours. If observing no clinical manifestations of postoperative pancreatitis, the epidural catheter is removed, and the patient is transferred into a department of surgery for symptomatic treatment.
EFFECT: method enables preventing acute postoperative pancreatitis following such interventions due to action of a general mechanism of pathogenesis of the given pathology.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a pharmaceutical vaginal composition for reducing or relieving uterine dysrhythmia. The composition contains an antidysrhythmia drug in the concentration of 1 wt % to 12.5 wt % and a pharmaceutically acceptable carrier providing prolonged release. The carrier contains a bioadhesive, water-swellable, water-insoluble, cross-linked polycarboxylic acid polymer such as polycarbophil. The drug is specified in prilocaine, mepivacaine, bupivacaine, ropivacaine, ethidocaine, mexiletine, procainamide, moracizin, propaphenone and flecainide.
EFFECT: invention provides reducing or relieving uterine dysrhythmia with prolonged release of said drugs with creating adequate local concentrations and low blood concentrations.
9 cl, 33 ex
SUBSTANCE: after performing main stage of surgery, under visual control needle puncture is performed into retroperitoneum space of right iliac fossa perpendicularly to skin, 1 cm inward from anterior superior iliac spine. Needle is passed inward, downward and frontward to the depth 6-8 cm, sliding on internal surface of iliac bone. Conductor is introduced through needle lumen and polyethylene catheter, through which after the end of operation, after 4-6 and 10-12 hours introduced is naropin in dose 2.5 mg/ml in 0.9% sodium chloride solution, is installed.
EFFECT: method makes it possible to ensure adequate and safe anesthetics in post-operative period due to accuracy of introduction of anesthetic directly in the zone of surgery.
SUBSTANCE: puncture point is anaesthetised by 0.5% bupivacaine. It is followed by puncture of a subdural space with the use of a spinal needle at the level of L3-4, L4-5 from a medial approach. A local anaesthetic is presented by hyperbaric 0.5% bupivacaine 0.8-1.2 ml. The patient is kept seating for 10 minutes.
EFFECT: method enables adequate anaesthesia with ensured maximum perineal myorelaxation combined with decreased drug-induced load on mother's and foetus's bodies.
SUBSTANCE: what is involved is infusion therapy with crystalloid solutions at 15 ml/kg of a patient's body weight. That is followed by puncturing and catheterising an epidural space at the level of ThVII-ThVIII according to the standard practice and introducing a test dose of 2% lidocaine 3 ml. If observing no signs of intrathecal introduction of local anaesthetics 10 minutes later, a basic dose containing 0.75-1% naropin 10 ml or 0.25-0.5% marcaine 10 ml and clofelin 3-5 mcg/kg is introduced. Total intravenous anaesthesia follows 20 minutes after pre-medication with atropine 0.01 mg/kg, 1% diphenylhydramine 1 ml and relanium 10 mg and urethral catheterisation. A narcosis is induced with propofol in a dose of 2 mg/kg. Anaesthesia is maintained with propofol 2-4 mg/kg·h. After that, within the first hour following the detoxification, naloxone 12 mg is introduced intravenously; a naloxone measurement rate is supposed to make 0.8 mg/h for 4-5 following hours of general anaesthesia. The repeated introduction of 0.75-1% naropin 6 ml or 0.25-0.5% marcaine 6 ml and clofelin 2-3 mcg/kg into the epidural space is performed 90 minutes later. After the procedure is terminated, and the patient recovers, prolonged epidural analgesia is conducted by introducing 0.2% naropin 10 ml and clofelin 1 mcg/kg into the epidural space every 4 hours for 24-48 hours.
EFFECT: method provides safety of ultrafast opioid detoxification and prolongs the remission in the given category of patients.
SUBSTANCE: invention refers to medicine, namely to anaesthesiology and resuscitation, and may be used in epidural anaesthesia. That is ensured by administering slowly intravenously a basic dose of the local anaesthetic: 0.2-1% naropin or 0.2-0.5% marcaine, or 1-2% lidocaine; 1% Sol. Nicotini acidi 1% - 0.5-1 ml into the epidural space 10-20 minutes later. After 5-10 minutes, nicotine test results are visually evaluated by determining a clear interface of skin colour - hyperemic and normal - along an axillary line from both sides. The normal skin interface corresponds to the sympathetic block.
EFFECT: method provides higher accuracy and simplification of measuring the sympathetic block.
SUBSTANCE: thoracic epidural analgesia is conducted by puncturing and catheterisation of an epidural space at ThVIII - ThIX before the expiry of 24 hours from the onset of a disease after a moderate intravenous infusion therapy in the amount of 15-20 mg/kg of crystalloid solutions. 20 minutes before an expected endoscopic papillosphincterotomy, a catheter is moved 4-5 cm in a cranial direction. At ThV-ThX, 0.4% naropin 10-12 ml or 0.2% Marcaine 10-12 ml and clonidine 100 mcg are administered through a catheter. That is followed by a pre-medication by administering 0.1% atropine 0.5-1 ml and 0.5% relanium 1-2 ml. Thereafter, the patient is taken to an X-ray operation room to conduct the endoscopic papillosphincterotomy without an endoscopic retrograde cholangiopancreatography with general pancreatic duct stenting. After the operation has been completed, the patient is taken to an intensive care unit wherein an extended epidural analgesia is conducted by administering 0.2% naropin 10-12 ml or 0.15% marcaine 10-12 ml into the epidural space every 4 hours until the patient is taken to a department of surgery.
EFFECT: early intestinal motility recovery, increased pancreatic secretion, prevented spasm of the gastrointestinal sphincter ensured by a pathological complete blockade of sympathetic impulsing.
SUBSTANCE: group of inventions refers to medicine, and can be used in need of the delivery of therapeutic compositions for local application, including for local analgesic therapy. That is ensured by a system comprising a container having a first chamber with a therapeutic composition for local application with at least one active ingredient, and a second chamber containing a coating composition. The composition for local application and the coating composition is dispensed through a valve and supplied through one nozzle gradually. The delivery can be also gradual by dispensing the composition for local application by pressing a first release button, while the coating composition is dispensed from the system by pressing a second release button.
EFFECT: invention provides the most convenient delivery of the therapeutic compositions ensured by the gradual release of the two compositions having different consistence through the same nozzle.
SUBSTANCE: invention refers to medicine, namely to paediatric anaesthesiology, and may be used for executing the surgical operations of neck and head cancers in children. A pre-operative Kerdo index is determined. If observing an initial sympathicotonia, the anaesthesia is induced by sevoflurane inhalations and potentiated by administration of 1% propofol to be followed by sevoflurane inhalations.
EFFECT: method enables optimising the course of anaesthesia, achieving the normotonic sympathovagal balance and providing the haemodynamic stability by taking into account the individual vegetative response, as well as the separate and sequential administration of propofol and sevoflurane.
2 tbl, 2 ex
SUBSTANCE: invention refers to medicine, namely to anaesthesiology, and may be used as an anaesthesia care of a surgical intervention for carotid endaterectomy or internal carotid artery resection after pathological deformation thereof. That is ensured by general anaesthesia in a combination with deep and superficial cervical plexus blockade. Pre-medication is used the day before the operation and on the operative day in the morning. Diazepam is introduced intramuscularly 30 minutes before the operation in a combination with phentanyl; the introduction is followed by ECG monitoring and heart rate count, plethysmography with arterial blood saturation, non-invasive blood pressure measurement and neuromonitring according to a bispectral index or entropy. Catheterisation of patient's peripheral or central vein is followed by an infusion therapy, an ionotropic therapy, a cardiotropic therapy, peripheral resistance maintenance. If heart rate is no more than 80 beats per minute, the anaesthesia is induced to reach an anaesthetic depth according to the bispectral index or entropy within 40-60 units. Analgesia is provided by the intravenous introduction of 0.005% phentanyl; myoplegia is ensured by the intravenous introduction of a myorelaxant. After tracheal intubation, the patient is transferred to forced volumentic artificial pulmonary ventilation with the CO2 level within 35-45 mm Hg according to capnography. The anaesthesia is maintained by supplying an inhalation anaesthetic to the steam level of 0.8-1.0 MAK 0.8-0.9 litre of the air and oxygen flow containing 50% oxygen with controlling the inhalation anaesthetic volume by the level of the anaesthetic depth according to the bispectral index or entropy. That is followed by deep cervical plexus blockade. A tubercle of the VI cervical vertebra (a carotid tubercle) and a mastoid process are localised; thereafter a line connecting the above reference points is drawn on skin. The second line is drawn 1 cm below the first one in parallel. To verify an injection point of a local anaesthetic, the spines of IV, III, II cervical vertebras being at 1.5 cm from each other are palpated, and the reference point is the VI cervical vertebra. The needle is inserted perpendicularly to the skin and slightly in the caudal direction to reach the spines. The anaesthetic is introduced in a dose of 5-7 ml in each point C4, C3, C2. Another 5-7 ml of the anaesthetic is introduced in a point found in an apex of the mastoid process. The superficial cervical plexus blockade requires introducing he fan-shaped introduction of the anaesthetic solution in a dose of 15 ml in a point found in the middle of a lateral crus of the nodding muscle under the above muscle, 4-5 ml in each direction from the same point; the first and following injections are performed at a depth of a usual intramuscular needle perpendicularly to nodding muscle.
EFFECT: method provides the adequate and safe anaesthesia ensured by avoiding linear blood velocity reduction in the medial cerebral artery during the surgical intervention, preventing intracranial pressure increase, reducing cerebral perfusion pressure in a combination with providing adequate protection against surgical invasion with maintaining stroke volume and arterial pressure.
4 cl, 3 ex
SUBSTANCE: invention refers to medicine, namely anaesthesia, and may be used as a postoperative anaesthesia accompanying low- and medium-injury operations. For this purpose, at the stages of anaesthetising and de-anaesthetising, nonsteroidal anti-inflammatory compounds (NSAICs) are introduced intravenously. The NSAIC dose is equivalent to ketorol 0.5-3.0 ml. The introduction is performed 1-3 times.
EFFECT: method provides the complete prevention of developing postoperative pain syndrome ensured by the intravenous introduction of the NSAIC at the specific stages of anaesthesia in certain doses.
1 tbl, 5 ex
SUBSTANCE: presented group of inventions refers to anaesthesiology, and may be used in performing X-ray endovascular heart, aorta and other great vessel surgeries in infants and young children. For this purpose, 10-12 hours before the surgery, a patient is pre-medicated by administering benzodiazepine, antihistamine and blocker H2. The anaesthetic administration is enabled by fast induction of sevoflurane before the first surgical stage. Then, a two-flap laryngeal mask is used, its drainage duct is used to pass a gastric probe a correct placement of which is monitored by X-ray, and the gastric contents is evacuated. The probe is removed, and the same duct is used to insert an echocardiographic probe. The anaesthesia is maintained by infusion of propofol in a dose of 6-8 mg/kg/h and bolus introduction of an opioid analgesic. The artificial pulmonary ventilation is conducted through the laryngeal mask, and the patient is transferred to unassisted respiration with a dose of propofol to be reduced to 4-5 mg/kg/h. The principal stage of the surgery and ultrasonic control, or control with introducing a contrast agent, the echocardiographic probe is removed. Infusion of propofol is terminated after suturing and compression hemostasis. In the period of escaping the anaesthesia with the laryngopharyngeal reflexes recovered, air is evacuated from a cuff of the laryngeal mask, and after adequate respiration recovered, the same mask is removed.
EFFECT: group of inventions ensures the adequate anaesthesia in these patients by means of the developed method of lung ventilation using no myorelaxants, and prevented regurgitation of the gastric contents.
8 cl, 3 ex
SUBSTANCE: invention refers to medicine, in particular to anesthesiology and intensive care, and may be used if preoperative preparation of the patients with chronic pancreatitis and manifested pain syndrome required. For this purpose, back skin of a sitting patient is treated within a puncture at the Th7-Th8 level. Then, an epidural space is punctured, and a puncture catheter needle is introduced therein, and the catheter is pushed forward in the cranial direction to a depth of 3 cm. The needle is removed, and the catheter is placed along the spine and is brought out to the subclavian region while strapped all over. Thereafter, a test dose of 2% lidocaine 3.0 ml is introduced. If observing no effects of spinal block, prolonged permanent introduction of 0.2% ropivacaine at rate 4-5 ml/hour 3 times a day. With underlying it, 30 minutes before a meal, fractional introduction of 0.75% ropivacaine 3.0 ml and 0.005% fentanyl 1.0 ml for 4-5 days is performed.
EFFECT: method provides the adequate preparation of the patients for pancreatic surgery due to pain relief that enables supplying proteins and eliminating hypovolemia, as well as due to improved pancreatic-duodenal microcirculation.
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to new derivatives of ((phenyl)imidazolyl)methylheteroaryl of formula wherein A represents pyridyl or thienyl having 0 or 1 substitute; B represents phenyl having 0, 1 or 2 substitutes; wherein each substitute independently represents alkyl having 1 to 8 carbon atoms, -F, -Cl, -Br or -CF3. Also, the invention refers to the use of the declared compounds for the purpose of preparing a therapeutic agent, a pharmaceutical composition on the basis of the declared compounds, and to a kit containing the pharmaceutical composition above.
EFFECT: there are prepared new derivatives of ((phenyl)imidazolyl)methylheteroaryl effective in pain management.
10 cl, 1 tbl, 2 ex
SUBSTANCE: composition containing curcumine, an acid specified in a group consisting of citric acid, malic acid, acetic acid, tartaric acid, lactic acid, alginic acid or a mixture thereof, and an edible emulsifying agent with specific characteristics and taken in a certain amount wherein the above composition is applicable as a therapeutic agent. The composition containing curcumine, the edible emulsifying agent or a mixture thereof, the acid specified in a group consisting of citric acid, malic acid, acetic acid, tartaric acid, lactic acid, alginic acid or a mixture thereof taken in certain proportions, and additionally encapsulated into a gelatine capsule, wherein the above composition is applicable for treating or preventing an inflammation and/or diseases caused by the inflammation.
EFFECT: compositions improve the curcumine bioavailability effectively.
13 cl, 1 tbl, 6 ex