Method of treating slow methotrexate elimination following high-dose infusion accompanying cerebral tumours in children |
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IPC classes for russian patent Method of treating slow methotrexate elimination following high-dose infusion accompanying cerebral tumours in children (RU 2516924):
 Method for determining non-small cells lung cancer sensitivity to preparations reactivating protein p53 / 2509808
Invention refers to oncology and molecular biology. What is presented is a method for determining the non-small cells lung cancer sensitivity to the preparations reactivating protein p53, involving the recovery of RNA from samples, the synthesis of complementary DNA of the genes CDKN1A, BTG2 and E2F1 by reverse transcription and real-time polymerase chain reaction, and the determination of a relation of the amount of complementary DNA of the gene E2F1 to the amount of complementary DNA of the gene CDKN1A or the gene BTG2, wherein if observing the relation of E2F1/CDKN1A>3 or E2F1/BTG2>1.5, the non-small cells lung cancer cells are considered to be sensitive to the preparations reactivating protein p53.
Method for preparing vaccine of living nematode larvae of species trichinella railliet (1895) for immunising animals and humans, using milk of animal immunised by this vaccine as agent for prevention and treatment of immune disorders, method for preparing blood serum of immunised animals, and method for prevention and treatment of immune disorders using this serum / 2506088
Group of inventions relates to biotechnology. A method for preparing the vaccine provides crossing of two different species of the four: T.spiralis, T.nativa, T.pseudospiralis and T.britovi, and selecting the line having the lower pathogenic and higher immunogenic properties by infecting with murine Trichinella larvae and controlling the embryogenesis; 1.5-2 months later, infected mouse's muscular tissue is separated, and the invasion larvae are recovered to be used for re-infection in a dose of 200-300 larvae; a degree of infection is determined, while the vaccine is prepared of the Trichinella line that leads to a mildest disease, while the re-infection causes no disease. Milk of the animals immunised with the vaccine prepared as described above is used for the purpose of prevention and treatment of the immune disorders. The vaccine described above is also used to prepare the serum. The vaccine is orally administered in a dose of 5000 to 20000 living larvae starting from the 10-14th day from the administration of the preparation; a usual therapeutic correction is required as that for trichinellosis, while the blood is sampled 30 days after the administration of the preparation. The prepared serum is administered into an individual according to the following schedule: either orally starting from 0.05 ml per one intake 3 times a day and increased to 1.2 ml by adding 0.05 ml to each intake, and then decreased in reverse order, or in the form of injections parenterally in a dose of 1-2 ml every 2 days, and in a dose of 10-15 ml into an animal three times to prevent and treat the immune disorders.
 Hydroxylated pyrimidylcyclopentanes as protein kinase (akt) inhibitors / 2504542
Invention concerns novel hydroxylated pyrimidylcyclopentanes of general formula I and pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition containing an effective amount of a compound of formula I, use of the compounds to produce a drug for therapy of protein kinase AKT mediated pathological conditions such as a hyperproliferative disease, particularly cancer. In formula (I):
 Nonapeptide with antitumour activity / 2503685
Invention refers to peptides or peptide-like molecules of the following formula: CCLLCCLLC (I) (SEQ ID NO: 1) or CLLCCLLCC (III) (SEQ ID NO:3), where C is cationic aminoacid and L is aminoacid with lipophile group R, in which one of the aminoacids, which has lipophile group R, represents genetically uncoded aminoacid. This compound is probably in the form of pharmaceutically acceptable salt, ester or amide, and refers to their use in therapy, and namely as antitumour agents.
Method for prediction of success rate of infectious complication prevention in premature infants / 2502995
Disadvantages of the known methods are the absence of usage data in premature infants, including for the purpose of prevention, as well as a low accuracy degree. What is presented is predicting a success rate of the prevention of any infectious complications in premature newborns in the period of hospital nursing by taking into consideration the perinatal history, clinical-laboratory data, and by prescribing a probiotic. The above probiotic is a liguid form of E. faecium L3; the values of linear classification functions LCF1 (the absence of infectious complications) and LCF2 (the presence of infectious complications) are determined by formulas: LCF1=-12.2-1.29X1-0.27X2-0.87X3+4.75X4+3.13X5+10.68X6, LCF2=-8.78+0.74X1+0.93X2-0.15X3+3.78X4+ +2.77X5+7.6X6, wherein: X1 - burdened maternal obstetric and gynecological history (0 - no; 1 - yes), X2 - mother's chronic nicotine intoxification (0 - no; 1 - yes), X3 - cesarean section (0 - no; 1 - yes), X4 - high eosinophil count as shown by infant's complete blood count (0 - no; 1 - yes), X5 - infant's feces Escherichia count by real-time polymerase chain reaction (1 - insufficient; 2 - normal; 3 - increased), X6 - use of the probiotic form of E. faecium L3 in the integrated therapy of the premature infant (1 - no; 2 - yes); the LCF1 and LCF2 are compared, and the success rate is predicted if observing LCF1>LCF2.
 Heterocyclic mek inhibitors and methods for use thereof / 2500673
Invention describes a compound of formula
Method of treating degenerative and dystrophic retinal diseases / 2495669
Invention refers to ophthalmology and may be used for treating degenerative and dystrophic retinal diseases. That is ensured by subcutaneous introduction of the preparation Coenzyme compositum 0.5 ml within the mastoid process, the preparation Lymphomyosot - within the temporal fossa, as well as by parabulbar introduction of the preparation Placenta compositum. The course is 10 sessions every second day 1-2 days a year. The introductions are double-sided if the retina in both eyes is involved.
 Method of preventing respiratory diseases in calves / 2494749
Invention refers to veterinary science. The method for preventing respiratory diseases in calves involves the immunisation by subcutaneous injections of donor animals' hyperimmune blood serum containing antihemagglutinin in titres to herpes virus -3 1:1280, to rednose virus - min. 1:256, to viral diarrhoea -1:1024 and to adenovirus -1:128; besides, 20-30 minutes before feeding, a pytopreparation of an alcohol tincture prepared of purple echinacea (Echinacea purpurea L) herb and blossom, common pine (Pinus sylvestris) buttons, horseheal (Inula helenium) roots and rhizomes, common liquorice (Glycyrrhiza glabra L.) roots and harmala shrub (Peganum harmala) herb taken in relation 1:1:1:1:0.5 in the amount of 7-8% of aqueous solution is administered in a dose of 2.0-2.5 ml/kg of body weight for 15 days every 24 hours.
Method of treating non-hodgekin lymphomas / 2493858
Invention refers to medicine, namely oncology, and may be used for treating non-Hodgkin lymphomas. That is ensured by sampling an intramedullary suspension 100-200 ml into a bottle containing the haemopreserving agent Glugicirum 50-70 ml. The prepared suspension is added with the chemopreparation doxorubicin 50 mg/m2. It is incubated at t +37°C for 40 minutes. Then it is introduced intravenously drop-by-drop. The intramedullary suspension is sampled during the second and fourth chemotherapeutic course.
Method for prevention of mycotoxicosis in animals / 2491942
Invention refers to microbiology and mycotoxicology, and aims at prevention of mycotoxicosis. The method involves the intake of a microbial preparation presented by the strain Bacillus subtilis-93 in a dose of 6-10 ml containing 1 bln microbial cell/ml for 10 days.
 Pyrimidopyridazine derivatives applicable as p38 map kinase / 2516466
Invention refers to a compound of formula
 Some chemical structures, compositions and methods / 2513636
Invention refers to new compounds of structural formula I that possess inhibitory activity on phosphatidyl inositol-3-kinase (PI3-kinase). In formula
 Implanted risperidone delivery system and methods for using it / 2510266
Invention refers to using a polyurethane polymer as a drug delivery system to provide the biologically active risperidone delivery at a constant speed for a relatively long period of time, as well as to methods for using it.
 Long-term devices with polyurethane polymers for drug delivery and preparing them / 2508089
Invention refers to medicine. What is described is an implanted drug delivery device on the basis of polyurethane for the delivery of biologically active compounds at a constant speed for a long period of time, and a method for preparing it. The device is high biocompatible and bioresistant, and applicable as an implant for patients (human and animals) for the delivery of biologically active compounds to tissues and organs.
 Antiviral compounds / 2505540
Invention pertains to new compounds that have the properties of HCV virus replication inhibitor. In expression I:
 Method for maintaining induced remission / 2505288
There are presented a method for maintaining the induced remission of rheumatoid arthritis by administering methotrexate, involving the replacement of methotrexate by a compound presented by one of formulas 1 and 2, after the remission of rheumatoid arthritis has been induced by methotrexate, and using the compounds of one of formulas
 Oxazolopyrimidines as agonists of edg-1 receptor / 2503680
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.
 Heterocycle-substituted piperazino-dihydrothienopyrimidines / 2500681
Invention relates to dihydrothienopyrimidinesulphoxides of formula 1, and pharmaceutically acceptable salts thereof
Mixed dosage form of cmf (cyclophosphan-methotrexate-5-fluorouracil), method for preparing mixed dosage form of cmf (cyclophosphan-methotrexate-5-fluorouracil) (versions) and method for lymphotropic interstitial administration of mixed dosage form of cmf (cyclophosphan-methotrexate-5-fluorouracil) for treating tumours / 2500405
Invention refers to medicine, namely to clinical lymphology, pharmacology and oncology. A mixed dosage form of CMF (cyclophosphan-methotrexate-5-fluorouracil) for lymphotropic interstitial administration in chemotherapy contains cyclophosphan, methotrexate, 5-fluorouracil, normal saline NaCl, and if necessary, novocaine, in weight ratio to provide pH of the mixture equal to physiological pH of the interstitial tissue within the range of 6.9 to 7.2. There are also described 2 versions of the method for preparing the mixed dosage form of CMF. Treating the tumours involves lymphotropic interstitial administration of the mixed dosage form of CMF in the amount of 3 to 10 units either in the lymphatic region of the tumour, or peritumourally (next to the tumour) two-three times a day, 8 to 12 injections a month.
 Method for integrated treatment of cervical pregnancy / 2514548
Uterine arteries are embolised, and methotrexate is administered intra-arterially, while a gestational sac is evacuated with a vacuum excochleator assisted with a transabdominaal ultrasonography. The uterine arteries are embolised using Embosphere® and HepaSphere™ microspheres. Methotrexate is administered intra-arterially from a primary blood supply of the gestational sac in a dose of 25 mg with embolysate microparticles using HepaSphere™ microparticles.
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FIELD: medicine. SUBSTANCE: dose of leucovorin is determined 24 hours after the 24-hour infusion of methotrexate and further every 6 hours depending on the concentration of blood serum methotrexate, and a time from the beginning of the 24-hour infusion of methotrexate in a dose of 5 g/m2, as follows: if the concentration of blood serum methotrexate is ≥151 µmole/l 24 hours after the beginning of the infusion, a dose of leucovorin makes 100 mg/m2, 30-42 hours after the infusion - 200 mg/m2, 48 hours and more after the infusion - 2,000 mg/m2; if the concentration of methotrexate is 101-150 µmole/l 24 hours after the beginning of the infusion, leucovorin is not administered, 30-54 hours after the beginning of the infusion, a dose of leucovorin makes 200 mg/m2, 60 hours and more after the infusion - 2,000 mg/m2; if the concentration of methotrexate is 21-100 µmole/l 24 hours after the beginning of the infusion, leucovorin is not administered, 30 hours after the beginning of the infusion, a dose of leucovorin makes 15 mg/m2, 36-66 hours - 30 mg/m2; 72 hours and more - 200 mg/m2; if the concentration of methotrexate is 4-20 µmole/l 24-30 hours after the beginning of the infusion, leucovorin is not administered, 36-66 hours after the beginning of the infusion, a dose of leucovorin makes 15 mg/m2, 72 hours and more - 30 mg/m2; if the concentration of methotrexate is 0.2-3.9 µmole/l 24-42 hours after the beginning of the infusion, leucovorin is not administered, 48 hours and more after the beginning of the infusion, a dose of leucovorin makes 15 mg/m2; leucovorin is administered until the concentration of blood serum makes not less than 0.2 µmole/l. EFFECT: method enables reducing a toxic effect of methotrexate on the body by selecting an optimum individual dose of leucovorin. 1 dwg, 2 tbl, 1 ex
The invention relates to medicine, namely to Oncology and oncidiinae, and can be used to speed up delayed elimination of methotrexate in the treatment of brain tumors in children after high-dose infusions. Drug antifolate activity - methotrexate (MTX - methotrexate) - violates the metabolism of folic acid by competitive inhibition digidrofolatreduktazy and other enzymes. Standard doses of this medicine is widely used in the treatment of oncological and non-oncological diseases (psoriasis, rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease). Range of tumors, therapy regimens using different dose methotrexate, high, and today, in addition to hematological malignancies, include solid tumors, as osteogenic sarcoma, and brain tumors. When last used dose intensification regimes of chemotherapy methotrexate. Delayed elimination of methotrexate from plasma is a rare disease, occurring in isolated cases. The half-life of methotrexate is about 6-7 hours with a deviation of from 3 to 17 hours. Considerably longer period of excretion in patients with polyserositis (pleural effusion, ascites). Product is excreted through the kidneys by glomerular filter is tion and secretion in the proximal tubules. About 5-20% of methotrexate and 1-5% 7-hydroxymethotrexate eliminated via the biliary route. Among the complications of treatment with high-dose methotrexate allocate nephro-, hepato-, gastrointestine and myelotoxicity. The use of MTX leads to death in 6% of cases, 80% of them due to severe myelosuppression and as a consequence, sepsis and hemorrhagic syndrome, the remaining 20% of renal insufficiency. The severity of complications associated with age: the younger the patient, paranoimia toxicity, while in patients older complications occur in the severe and often associated with a fatal outcome. Infusion of high doses methotrexate became possible after the introduction in ekologicheskuu practice antagonist antifolates leucovorin (calcium folinata). In the majority of treatment programs using high doses methotrexate included calcium folinate as a drug that reduces the toxicity of the latter. In the mechanism of transformation of leucovorin in tetrahydrofolate dihydrotetrazolo, inactivated methotrexate and its metabolite, does not participate, so the process of repair and replication of DNA and RNA with the use of calcium folinata quickly restored. Dose leucovorin range from 10 mg/m2every 6 h up to 1000 mg/m2every 3 hours Single me the Oia about the modes of introduction of calcium folinata not. A known way of expediting delayed elimination of methotrexate in the treatment of brain tumors in children after high-dose infusion, including the use of nomograms doses of leucovorin appointed after high doses of methotrexate. (E. Dombrowsky, Jayaraman Century, Narayan M. and J.S. Barrett Evaluating performance of the decision support system to improve methotrexate pharmacotherapy in children and yang adults with cancer // Ther. Drug Monit. - 2011. No. 1. - P. 99-107). This nomogram difficult to use: on the x-axis and y-projected time after infusion (20, 40, 60 h, and so on) and the concentration of drug in serum (10-8, 10-7, 10-6mol), respectively, values which are not convenient in clinical practice. In addition, it does not take into account the specific mode of methotrexate (dose and duration) and morphological variant of the tumor. Different modes of administration of the drug (dose of 0.5 g/m2when non-Hodgkin lymphoma to 12 g/m2for osteogenic sarcoma, a duration of 4 h for osteogenic sarcoma to 24 h with brain tumors and hematological malignancies), as well as the Genesis and localization of the tumor already predetermine individual clearance of methotrexate and its metabolites. The technical result of the invention is to optimize individual doses of leucovorin in children with brain tumors, the treatment of which is applied a 24-hour infusion of methotrexate in to the e 5 g/m 2in order to reduce the toxic effects on the body and prevent or reduce the depth and duration of various complications of treatment. This technical result is achieved by the fact that in the known method the acceleration of delayed elimination of methotrexate in the treatment of brain tumors in children after high-dose infusion by infusion of leucovorin, according to the invention, the dose of leucovorin determined 24 hours after the beginning of the 24-hour infusion of methotrexate and thereafter every 6 hours depending on the concentration of methotrexate in the blood serum and the time elapsed from the start of the 24-hour infusion of methotrexate in a dose of 5 g/m2as follows: when the concentration of methotrexate in serum ≥151 mol/l 24 hours after beginning infusion dose administration of leucovorin 100 mg/m2through 30-42 hours - 200 mg/m2after 48 hours and more or 2000 mg/m2; when the concentration of methotrexate 101-150 mol/l 24 hours after start of infusion leucovorin not enter through 30-54 hours after beginning infusion dose leucovorin 200 mg/m2through 60 hours and over - 2000 mg/m2; when the concentration of methotrexate 21-100 mol/l 24 hours after start of infusion leucovorin not impose, 30 hours after the start of infusion, the dose of leucovorin is 15 mg/m2through 36-66 the aces - 30 mg/m2; after 72 hours and more than 200 mg/m2; when the concentration of methotrexate 4-20 mol/l after 24-30 hours after the start of infusion leucovorin not enter through 36-66 hours after the beginning of infusion, the dose of leucovorin is 15 mg/m2through 72 hours and more than 30 mg/m2; when methotrexate concentration of 0.2-3,9 mol/l through 24-42 hours after the start of infusion leucovorin not enter, after 48 hours or more after the start of infusion, the dose of leucovorin is 15 mg/m2, and leucovorin administered up until the concentration of methotrexate in serum is less than 0,2 mol/L. As a result of the research was to define the optimal dose leucovorin, administered every 6 hours, depending on the concentration of methotrexate after his 24-hour infusion at a dose of 5 g/m (see table 1).
* after 120 h of observation with delayed elimination of methotrexate dose leucovorin match table for 120 h, the drug is administered up until the concentration of MTX in serum will not be <0,2 mol/L. Material for the compilation of the table was the information about the concentration of methotrexate in serum obtained after conducting 34 cycles of chemotherapy with methotrexate high doses (from 5 to 12 g/m2) in 13 patients. Mn is I time, since the beginning of the infusion of high-dose methotrexate, and its concentration in serum at a given hour, you can use table 1 to determine the dose of leucovorin required for inactivation of the drug. The use of the proposed method to accelerate the excretion of toxic metabolites of methotrexate and the drug, thereby preventing their adverse impact on the child's body, reducing the length of hospitalization and reducing the risk of disability of patients. Comparative analysis of the prototype shows that the use of individual doses of leucovorin, based on the individual values of the concentration of methotrexate - time", it is more practical to use and applicable in children with brain tumors, therapy which used 24-hour infusion of methotrexate in a dose of 5 g/m2. The invention is illustrated by the image in Fig., where is a diagram of doses of leucovorin (mg/m2) with delayed elimination of methotrexate after his 24-hour infusion at a dose of 5 g/m2in brain tumors, based on the individual profile of the concentration of methotrexate - time", built in accordance with table 1, with the standard (positive) rectangular coordinate system on the plane, on which the abscissa axis in accordance with the selected scale projects the I time, elapsed after the start of infusions of methotrexate at 24 h intervals for 6 h; volume horizontal rectangles represent the range of possible values of the concentration of methotrexate in the blood serum of the patient; on the y-axis projected need individual dose leucovorin, calculated on the surface area, administered every 6 hours. The method is as follows. 24 hours after the beginning of the 24-hour infusion of methotrexate in a dose of 5 g/m2and then every 6 hours to determine the concentration of methotrexate in serum. On the initial concentration of methotrexate in serum and the time passed from the beginning of the infusion, in accordance with table 1, or a chart (Fig.) determine the individual dose leucovorin, administered every 6 or 3 hours. For example, if after 30 h after the start of infusions of methotrexate in a dose of 5 g/m2the concentration in the serum was 105 mol/l, the dose of leucovorin in table 1 should be 100 mg/m2every 3 hours or 200 mg/m2entered every 6 hours. The drug is administered up until the concentration of MTX in serum will not be less than 0.2 mol/L. If treatment delayed elimination of methotrexate will be more than 120 hours, the dose of leucovorin correspond to the values for 120 hours. The invention is illustrated by the following clinical example. Example. Patient, 6 months, received on the treatment of morphologically verified primitive neuroectodermal tumors of the sellar region of the brain. After suffering ARD mother noted the deterioration of appetite, left-sided ptosis. On the advice of a neurologist and an ophthalmologist performed brain MRI, which showed a mass education of sellar region with supra-procellarum growth, size 17×21×25 mm, nakaplivalsya contrast agent. Was performed microsurgical intervention using a surgical microscope, intraoperative navigation and neurophysiological studies with intracerebral tumors brain, osteoplastic craniotomy in the left frontal region with calling for the middle line, submontana revision of the Foundation of the anterior and middle cranial fossa, the partial removal of the tumor. Immunohistochemistry: Chromogranin+, CD99+, S100+, NB weakly focal+, Synaptophysin individual cells+, NSE-, GFAP-, Ki67 Express about 45% of the cells. MRI brain was preserved residual tumor size 20×25 mm, MRI of the cervical, thoracic and lumbosacral spine showed diffuse accumulation of contrast agent in the region of the membranes of the spinal cord. The level of creatinine in serum and clearance were in before the lah reference values. Specific drug therapy is started as a life-saving program HIT-2000 (branch MET-HIT 2000-BIS4 for primitive neuroectodermal tumors) with a reduction of the doses of drugs. The cycle consisted of vincristine (0.005 mg/kg) and carboplatin (25 mg/kg) on day 1, Vepesid (2 mg/kg) and cyclophosphamide (65 mg/kg) in 2-3 days, methotrexate (5 g/m2in the 5th day. The estimated dose of methotrexate was 1.8, Before, before and during the administration of MTX was conducted infusion therapy glucose-salt preparations, as well as the alkalinity of the body using a 5% solution of soda (NaHCO4). Infusion, according to the Protocol lasted 24 hours. The water balance was adequate, hourly urine output was 1.6-2.0 ml/kg/h without diuretics. In the control analysis after 24 h the observed high concentration of MTX in serum (522 mol/l), the dose of leucovorin was calculated by table 1. Table 2 contains the individual values of the dose leucovorin for the patient depending on the concentrations of methotrexate in serum and time from start of infusion of methotrexate.
Monitoring of serum methotrexate was conducted to his values less than 0.5 mol/HP When it reaches this level leucovorin was administered 11 more times every 6 h at the dose of 15 mg/m2. When using the proposed method, based on the individual values of the concentration of methotrexate-time", was carried out selection of doses of leucovorin for a particular patient with a brain tumor, was able to completely eliminate methotrexate and its products is the products of metabolism. The proposed method for the acceleration of delayed elimination of methotrexate in the treatment of brain tumors in children after high-dose infusion was used after 11 cycles of chemotherapy with a 24-hour infusion of methotrexate in a dose of 5 g/m24 patients with brain tumors. The invention allows to choose the optimal individual dose leucovorin in children with brain tumors, the treatment of which is applied a 24-hour infusion of methotrexate in a dose of 5 g/m2, thereby reducing the toxic effects on the body, preventing and reducing various complications of treatment. The way to accelerate delayed elimination of methotrexate in the treatment of brain tumors in children after high-dose infusion by infusion of leucovorin, wherein the dose of leucovorin determined 24 hours after the beginning of the 24-hour infusion of methotrexate and thereafter every 6 hours depending on the concentration of methotrexate in the blood serum and the time elapsed from the start of the 24-hour infusion of methotrexate in a dose of 5 g/m2as follows:
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