Method of treating patients with rheumatoid arthritis

FIELD: medicine.

SUBSTANCE: composite application of therapeutic preparations is combined with a laser therapy. A basic anti-inflammatory preparation is presented by methotrexate administered subcutaneously in a dose of 15mg once a week, and folic acid administered orally in a dose of 5mg a week. Movalis is additionally prescribed in the form of intramuscular injections in a dose of 15mg once a day. The laser therapy is differentiated depending on a degree of the disease, a degree of endothelial dysfunction manifestation, namely a von Willebrand factor (vWF), haemostasis system activity indices, namely activated partial thromboplastin time (APTT), prothrombin time (PTT), thrombin clotting time (TCT), antithrombin III (AT III), protein C. If observing the degree I of the disease, APTT 30.6±1.5 sec or more, PTT 19.2±0.9 sec or more, TCT 15.1±0.7 sec or more, AT III 92.8±7.6% or more, protein C 0.92±0.02 or more, vWF 108.9±9.6% or less, 6-8 daily procedures of the intravenous laser blood irradiation, on the first day for 15 minutes at wavelength 0.365mcm, on the following day for 5 minutes at wavelength 0.405mcm, radiant power at a light guide end 1.5-2.0mV in a continuous mode; the procedures are alternated every second day. The degrees II and III of the disease, APTT 22.2±5.5 sec or less, PTT 12.8±1.7 sec or less, TCT 11.2±0.9 sec or less, AT III 85.4±1.1% or less, protein C 0.84±0.02 and less, vWF 133.5±2.2% or more, require performing 10 daily procedures of the intravenous laser blood irradiation, on the first day for 15 minutes at wavelength 0.365mcm, on the following day for 5 minutes at wavelength 0.405mcm, radiant power at the light guide end 1.5-2.0mV in a continuous mode; the procedures are alternated every second day.

EFFECT: method enables reducing the clinical manifestations of the disease, provides higher effectiveness of the drug therapy by involving the pathological processes in the haemostasis system.

1 tbl, 3 ex

 

The invention relates to medicine, namely to "rheumatology", and for the treatment of patients with rheumatoid arthritis.

Today rheumatoid arthritis is a serious medical and social problem, due to the high prevalence, the steady increase in morbidity and early disability of working age population. (Balabanova P. M. Rheumatoid arthritis. 2007) Increased risk of premature mortality in RA patients is associated with non-articular (systemic) symptoms, as well as the activity of the inflammatory process and seropositivity for rheumatoid factor (I.e Century Popkov, D. S. Novikov, E. L. Nasonov. Cardiovascular risk factors in rheumatic diseases: relationship with inflammation, Consilium medicum 2010 No. 2). In recent years, the clinic became a widely used new physical treatment factors, among which the most widespread are low-intensity laser radiation. Literature data suggest that the effectiveness of the use of laser radiation in the treatment of many diseases. It is shown that laser radiation has anti-inflammatory, immunomodulatory, antioxidant, antihypoxic and many other effects.

Modern laser devices allow you to apply the methods of laser therapy in L. the treatment of many diseases and pathological conditions. In the early 80-ies of the last century there was a method of intravenous laser irradiation of blood, based on blood irradiation of laser light directly in Vienna, which was considerably more efficiently and economically less costly.

Laser radiation in the treatment of rheumatic diseases applied for more than three decades, but until now many pathogenetic mechanisms of action of low-intensity laser radiation in rheumatic diseases remain unclear.

The closest to the essential features of the claimed invention is a method for the treatment of patients with rheumatoid arthritis, using the contact laser therapy, taken as a prototype (A. L. o Alavi, S. K. Nutrinova. The influence of laser radiation on the performance of the blood coagulation system in patients with rheumatoid arthritis. - Physiotherapy, balneology, rehabilitation. No. 3, S. 40-43), which includes the use of basic drugs and percutaneous laser wavelength of 0.89 μm, the pulse frequency 80-1500 Hz, at a rate of 10-12 sessions. Daily for one session influenced the affected joints, the exposure time is 2-5 minutes on one field, one procedure was irradiated up to 4-5 fields.

The prototype of the invention has the following essential features: simultaneous complex is th use of drugs, such as the basic anti-inflammatory drugs, and laser therapy.

However, the disadvantage of the prototype is that laser therapy is prescribed cutaneous method not given the opportunity to assign intravenous blood irradiation. It is known that rheumatoid arthritis is a disease that affects not only the joints, but many organs and systems, including the hemostatic system and microcirculation, with this in mind, the most expedient is the use of intravenous irradiation of blood.

Not taken into account using the method for correction of abnormalities in endothelial dysfunction, namely the level of von Willebrand factor, violations in the hemostatic system, namely, activated partial thromboplastin time, thrombin time, prothrombin time, protein C, as well as the most important indicators of anticoagulant - anti-thrombin III.

The claimed invention is directed to solving the challenge in creating a treatment for patients with rheumatoid arthritis.

The solution to this problem provides a positive effect on pathological processes in the hemostatic system, reduces clinical manifestations of the disease, medication reduces the burden on the patient, increases the effectiveness of drug therapy and gives a rationale for the efficacy of laser therapy in the complex treatment of rheumatoid arthritis.

To achieve this, the technical result of the claimed invention of the method for the treatment of patients with rheumatoid arthritis includes the following significant features - simultaneous complex application of laser radiation and drugs: a basic anti-inflammatory, nonsteroidal anti-inflammatory drugs and laser therapy that is prescribed for differentially, depending on the degree of disease activity, severity of endothelial dysfunction, namely, von Willebrand factor, level of activity indicators of hemostasis, namely the level of activated partial thromboplastin time, prothrombin time, thrombin time, anti-thrombin III, protein C, With I degree of disease activity, the level of activated partial thromboplastin time, equal to or more 30,6±1.5 seconds, prothrombin time, equal and more of 19.2±0.9 sec, thrombin time, equal and more of 15.1±0.7 sec, anti-thrombin III equal and more of 92.8±7,6%, protein C (BUT) equal to or more 0,92±0,02, von Willebrand factor equal to and less 108,9±9.6% of spend 6-8 daily procedures of intravenous laser irradiation of blood, the first day for 15 minutes wavelength 0,365 μm, on the next day within 5 minutes of wavelength 0,405 μm, the radiation power at the end of the fiber 1,5-2,0 mW, continuous the m mode radiation, treatments alternated every other day, at II and III degree of disease activity, the level of activated partial thromboplastin time, equal to and less of 22.2±5.5 sec, prothrombin time, equal to and less of 12.8±1,7 sec, thrombin time, equal to and less of 11.2±0.9 sec, anti-thrombin III, equal and less 85,4±1.1%, protein C (BUT) equal to and less 0,84±0,02, von Willebrand factor, equal and more to 133.5±2.2%, and perform 10 daily procedures of intravenous laser irradiation of blood, on the first day for 15 minutes wavelength 0,365 μm, on the next day within 5 minutes of wavelength 0,405 μm, the radiation power at the end of the optical fiber of 1.5-2.0 mW, CW mode, procedure alternate through the day.

Between the features and the technical result is the following causal relationship: the use of alternating irradiation of blood by laser light with a wavelength of 0,365 μm and 0,405 μm marked positive effect on the hemostatic system, improving the quality of treatment, reduces the treatment time.

According to the authors ' knowledge, the set of essential features that characterize the essence of the claimed invention, is not known, which allows to make a conclusion about conformity of the invention, the criterion of "novelty".

According to the authors, the essence of the claimed invention should not be obvious to the contraction in the om of the known level of medicine, as it has not detected above the method of treatment according to the method of alternating laser light with a wavelength of 0,365 μm and 0,405 μm, which differ from the prototype of the claimed invention, which allows to make a conclusion on compliance with a criterion of "inventive step".

The set of essential features that characterize the invention, can be used repeatedly in medicine with the technical result consists in increasing the effectiveness of laser therapy in patients with rheumatoid arthritis, which allows to make a conclusion about conformity of the invention, the criterion of "industrial applicability".

This method is as follows.

All patients with rheumatoid arthritis is a complex drug therapy (basic anti-inflammatory, non-steroidal anti-inflammatory drugs), while use of a course of intravenous laser therapy.

The proposed method of treatment of patients with rheumatoid arthritis were used in 132 patients, aged 18 to 85 years (mean age 50,33+3,22 year). All patients were divided into 2 groups - control (30 people) and the core (102). The comparison group consisted of 20 healthy individuals, matched by gender and age, which were surveyed to obtain average normal values is issleduemykh indicators. All patients received standard medical therapy - basic anti-inflammatory-drugs - methotrexate 15 mg / week subcutaneously, folic acid 5 mg / week orally, and nonsteroidal anti-inflammatory drugs - Movalis 15 mg 1 time per day intramuscularly. In the 1st (control) group (30 people) were used for treatment of traditional medical therapy, patients of the 2nd group (102 people) along with drug therapy has received a course of intravenous laser therapy that is prescribed for differentially, depending on the degree of disease activity, severity of endothelial dysfunction, namely, von Willebrand factor, level of activity indicators of hemostasis, namely the level of activated partial thromboplastin time, prothrombin time, thrombin time, anti-thrombin III, protein C, With I degree of disease activity, the level of activated partial thromboplastin time, equal to or more 30,6±1.5 seconds, prothrombin time, equal and more of 19.2±0.9 sec, thrombin time, equal and more of 15.1±0.7 sec, anti-thrombin III, equal and more of 92.8±7,6%, protein C (BUT) equal to or more 0,92±0,02, von Willebrand factor, equal to and less 108,9±9.6%, and - spend 6-8 daily procedures of intravenous laser irradiation of blood, on the first day within 15 minutes of the lengths of the wave 0,365 μm, the next day, within 5 minutes the wavelength 0,405 μm, the radiation power at the end of the optical fiber of 1.5-2.0 mW, CW mode, procedure alternate every other day, at II and III degree of disease activity, the level of activated partial thromboplastin time, equal to and less of 22.2±5.5 sec, prothrombin time, equal to and less of 12.8±1,7 sec, thrombin time, equal to and less of 11.2±0.9 sec, anti-thrombin III, equal and less 85,4±1.1%, protein C (BUT) equal to and less 0,84±0,02, von Willebrand factor, equal and more to 133.5±2.2%, and perform 10 daily procedures of intravenous laser irradiation of blood, the first day for 15 minutes wavelength 0,365 μm, on the next day within 5 minutes of wavelength 0,405 μm, the radiation power at the end of the optical fiber of 1.5-2.0 mW, CW mode, procedure alternate through the day.

The effectiveness of laser therapy was evaluated on the basis of the dynamics of changes in clinical status, indicators of hemostasis (table 1).

Dynamics of plasma hemostasis in patients with RA before and after treatment

Thus, comparison of the data shows that the inclusion in the complex therapy of patients with rheumatoid arthritis intravenous laser therapy has a positive normalizing effect n the indices of hemostasis.

Thus, from the above it follows that a positive effect on the rheological properties of blood, anti-inflammatory effect of combination therapy with a course of laser treatment using alternating laser light with a wavelength of 0,405 μm and 0,365 microns superior to conventional drug therapy.

As an illustration of the method of treatment of patients, including the use of drugs and laser therapy, as well as normalizing effect on parameters of hemostasis here is a brief extract from a case history No. 1604.

Example 1.

Patient S., 44 years old, was admitted to the rheumatology Department of the Clinical hospital of the North-Ossetian State medical Academy diagnosed with:

Rheumatoid arthritis seropositive deployed stage, activity 2 (DAS28=4,5), erosive (x-ray stage III), HACCP (+), Functional Class 3.

Complaints: pain and limitation of movements in the small joints of the hands, feet, morning stiffness in the small joints, continuing to dining hours, increased body temperature up to 38 degrees, General weakness.

From the anamnesis of illness: sore rheumatoid arthritis for about 4 years. The onset of disease with arthritis metacarpophalangeal joints of the hands. Onset with nothing in common. The patient was examined in the outpatient setting. The survey was in the manifest: ESR - 61 mm/h, WBC - 15,6*109/l RF - 55 E, CRP+++ rengenografii brushes: single racemose enlightenment, narrowing of joint cracks, hardening of the articular surfaces. The patient was recommended inpatient treatment and receiving methotrexate 10 mg/week, but after taking the drug effect was not noted. Over time, arthritis symptoms began to grow, began to increase body temperature. The patient was examined at the Institute of Rheumatology of RAMS, where the diagnosis was confirmed and assigned to methotrexate at a dose of 15 mg/week in/m

Deterioration after exposure to cold, when it began to increase body temperature, increase the pain in the joints, morning stiffness.

From the anamnesis of life: growing and developing according to age. Of illness notes Botkin's disease in childhood.

Objectively: the state of moderate severity, clear consciousness, the normal power supply. The skin and the regular color, clean. Mucous pink, pure. Lymph nodes are not enlarged.

Articular status: arthritis wrist joints (swelling, hyperthermia, limiting the amount of active and passive movements), the impossibility of complete constriction of the hands in a fist, tenderness, severe swelling, limitation of range of motion of the proximal interphalangeal, metacarpophalangeal joints. Symptom transverse compression of the brush is good on both sides. The compression force 2 points. There is expansion of the left border of the heart is determined in the fifth intercostal space, at 1.5 cm outwards from the left srednechrochnoy line. Heart sounds somewhat muffled, regular rhythm, weakened 1 tone. BP - 120/80 mm RT.art., HR - 94 in 1 minute. The chest is involved in the act of breathing evenly across all departments. Percussion sound clear lung, vesicular breathing. The abdomen is soft, painless. Liver at the edge of the costal arch, spleen not palpated. Symptom tapping - negative on both sides.

Patients: in General, the analysis of blood draws attention leukocytosis is 16.5×109/l, the shift of leukocyte formula to the left, accelerated ESR - 34 mm/L. Immunological blood tests: RF - 46 E, ACCP - 38 U/ml

The hemostatic system: activated partial thromboplastin time, with 18.1 seconds, prothrombin time of 10.6 seconds, thrombin time of 11.1 seconds, protein C (BUT) - 0,88, the von Willebrand factor - 135%, antithrombin III - 83%.

The patient in patients receiving drug therapy (methotrexate subcutaneously at a dose of 15 mg 1 time a week, folic acid into 5 mg per week, Movalis intramuscularly at a dose of 15 mg 1 time per day) had a course of intravenous therapy, which is produced daily for 10 days, the first day for 15 minutes wavelength 0,365 μm, on the next day within 5 minutes of wavelength 0,405 μm, the power radiated by the I at the end of the fiber 1,5-2,0 mW, in the CW mode, the procedure is alternated every other day.

Patient on day 3 procedures vlok noted a decrease in pain, decreased swelling in the joints, improved sleep.

After completing the course of therapy: the level of activated partial thromboplastin time of 31.2 seconds, prothrombin time - 19,6 sec, thrombin time is 15.7 seconds, von Willebrand factor - 106,8%, anti-thrombin III - 99,8%, the activity of protein C (BUT) - 0,99.

Thus, in the process of treatment was normalizing effect of intravenous laser therapy on the hemostatic system.

Example 2. (extract from the history of the disease 1905)

Patient G., aged 45, was admitted to the rheumatology Department KB SOHMA diagnosed with:

Rheumatoid arthritis seropositive deployed stage, erosive (Rst.III), activity 3 (DAS 28 - 5,3), HACCP (+), functional class III (three).

Complaints: pain in small joints of hands, feet, wrist, elbow, shoulder, hip, knee, and ankle joints; swelling, deformity, limitation of range of motion, joint stiffness in the morning, continuing throughout the day, expressed General weakness.

From the anamnesis of the disease: pain in the joints bother about 7 years. The onset of arthritis in the joints of the hands on the background of morning stiffness. Onset with nothing in common. the 2008 surveyed in the rheumatology Department of the KB SOHMA, diagnosed with seropositive rheumatoid arthritis, and as a basic therapy assigned methotrexate 15 mg/week with a positive effect.

Objectively: the state of moderate severity. Clear consciousness. Moves with additional support. Color skin pale pink. Peripheral lymph nodes are not enlarged. Peripheral edema no.

Status localis - deformity of the proximal interphalangeal, metacarpophalangeal, wrist, elbow, shoulder, metatarsophalangeal, interphalangeal joint of the foot, ankle, knee joints due to exudative-proliferative effects. Palpation of the articular painful cracks. YOUR pain is 70 mm Symptom transverse compression brushes - positive. Motion range is limited. The force of compression in the fist 3 points.

In the lungs - vesicular respiration, wheezing no. NPV 17 in 1 minute

The region of the heart and large vessels is not changed. Apical impulse in the fifth intercostal space at l.mediacl. The borders of relative cardiac dullness is shifted to the left by 1 see Auscultatory - the muted colours, the rhythm correct. HR - 87 beats per 1 minute of HELL 130/80 mm RT.article The abdomen is soft, painless. Liver at the edge of the costal arch, the edge of the liver rounded. Symptom tapping on the lumbar region is negative on both sides.

During examination: RF-40E, DRR+++, ACCP - 121 IU/ml

The hemostatic system: activated partial comboplus the new time - 19,6 seconds, prothrombin time of 10.9 seconds, thrombin time of 10.5 seconds, protein C (BUT) is 0.84, the von Willebrand factor - 140%, antithrombin III - 84,1%.

Sick in patients receiving drug therapy (methotrexate subcutaneously at a dose of 15 mg 1 time a week, folic acid into 5 mg per week, Movalis intramuscularly at a dose of 15 mg 1 time per day) had a course of intravenous therapy, which was carried out daily for 10 days, the first day for 15 minutes wavelength 0,365 μm, on the next day within 5 minutes of wavelength 0,405 μm, the radiation power at the end of the optical fiber of 1.5-2.0 mW, CW mode, procedure alternate through the day.

The patient on day 5 of the procedures noted a decrease in pain, swelling in the joints.

After completion of treatment, the patient noted the relief of pain, increased activity in the joints.

Dynamics: activated partial thromboplastin time - 30,9 seconds, prothrombin time is 20.1 seconds, thrombin time of 15.2 seconds, the von Willebrand factor - 106,4%, antithrombin III - 84%, protein C (BUT) - 0,98.

Thus, in the process of treatment was normalizing effect of intravenous laser therapy on the hemostatic system and intercellular interaction.

Example 3. (extract from history 2697)

Patient R., 21, enrolled in the rheumatology Department of the KB SIGMA with the diagnosis of the m:

Rheumatoid arthritis seropositive, early stage, neurosignal (Rst.II) activity 1 (DAS 28-3,1), HACCP (-), Functional class II (two).

Complaint: pain in the joints of the hands, wrist, ankle joints; swelling, deformity, limitation of range of motion, joint stiffness in the morning, continuing to dining hours.

From the anamnesis of the disease: pain in the joints concerned about 2 years. The onset of arthritis in the joints of the hands on the background of morning stiffness. Onset with nothing in common. In 2011, examined in the rheumatology Department of the KB SOHMA diagnosed seropositive rheumatoid arthritis. Received methotrexate 7.5 mg/day. In 2012 received treatment in R & d RAMS, the dose of methotrexate was increased to 15 mg/week orally.

Objectively: the patient is in satisfactory condition. Color skin pale pink. Peripheral lymph nodes are not enlarged. Peripheral edema no.

Articular status: incomplete tightening of the left hand into a fist, tenderness, severe swelling, limitation of range of motion of the proximal interphalangeal, metacarpophalangeal joints. Heart sounds somewhat muffled, regular rhythm, weakened 1 tone. AD - 110/60 mm RT.article, HR - 61 in 1 minute. The chest is involved in the act of breathing evenly across all departments. Percussion sucasny lung, the vesicular breathing. The abdomen is soft, painless. Liver at the edge of the costal arch, spleen not palpated. Symptom tapping negative on both sides.

During examination: RF-31E, CRP negative, ACCP - 51 IU/ml

The hemostatic system: activated partial thromboplastin time were 31.9 seconds, prothrombin time - of 20.9 seconds, thrombin time of 15.2 seconds, protein C (BUT) - 0,96, the von Willebrand factor - 105%, Antithrombin III-99,9%.

Sick in patients receiving drug therapy was conducted by a course of intravenous therapy, which was performed daily for 6 days, the first day for 15 minutes wavelength 0,365 μm, on the next day within 5 minutes of wavelength 0,405 μm, the radiation power at the end of the optical fiber of 1.5-2.0 mV, a pulse frequency of 80 Hz in CW mode, procedure alternate through the day.

Sick on day 3 of the procedures noted a decrease in pain, swelling in the joints.

After completion of treatment, the patient noted the relief of pain, increased activity in the joints.

Dynamics: activated partial thromboplastin time - to 33.6 seconds, prothrombin time - 21,0 sec, pribinova time of 16.4 seconds. the von Willebrand factor - 106,9%, antithrombin III - 101,3%, protein C (BUT) - 0,99. Thus, in the process of treatment was normalizing effect of intravenous laser therapy n the hemostasis system.

Clinical and laboratory studies of the proposed method for the treatment of patients with rheumatoid arthritis compared with the known method (prototype) showed the effectiveness of the proposed method of treatment, the possibility of correcting the changes occurring in this disease, improving the results of ongoing drug therapy, reducing treatment time.

A method for the treatment of patients with rheumatoid arthritis, including simultaneous integrated use of drugs and laser therapy, characterized in that as the reference anti-inflammatory drug used methotrexate subcutaneously at a dose of 15 mg 1 time per week, as well as folic acid into 5 mg per week, appoint Movalis intramuscularly at a dose of 15 mg 1 time per day, laser therapy is prescribed differentially, depending on the degree of disease activity, severity of endothelial dysfunction, namely, von Willebrand factor, level of activity indicators of hemostasis, namely the level of activated partial thromboplastin time, prothrombin time, thrombin time, anti-thrombin III, protein C, With I degree of disease activity, the level of activated partial thromboplastin time equal to or more 30,6±1.5 seconds, prothrombin time, equal and more of 19.2±0.9 sec is to, thrombin time, equal and more of 15.1±0.7 sec, anti-thrombin III, equal and more of 92.8±7,6%, protein C (BUT) equal to or more 0,92±0,02, von Willebrand factor, equal to and less 108,9±9.6%, and - spend 6-8 daily procedures of intravenous laser irradiation of blood, the first day for 15 minutes wavelength 0,365 μm, on the next day within 5 minutes of wavelength 0,405 μm, the radiation power at the end of the optical fiber of 1.5-2.0 mW, CW mode, procedure alternate through the day, at the II and III degree of disease activity, the level of activated partial thromboplastin time, equal to and less of 22.2±5.5 sec, prothrombin time, equal to and less of 12.8±1,7 sec, thrombin time, equal to and less of 11.2±0.9 sec, anti-thrombin III, equal and less 85,4±1.1%, protein C (BUT) equal to and less 0,84±0,02, von Willebrand factor, equal and more to 133.5±2.2%, and perform 10 daily procedures of intravenous laser irradiation of blood, the first day for 15 minutes wavelength 0,365 μm, the next day, within 5 minutes the wavelength 0,405 μm, the radiation power at the end of the optical fiber of 1.5-2.0 mW, CW mode, procedure alternate every other day.



 

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3 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula IV, VIII-A and X, and to their pharmaceutical acceptable salts possessing the inhibitory activity on PI3-kinase (phosphoinositide-3-kinase). In compounds of formula IV and IX and Wd is specified in a group consisting of, , , and each of which can be substituted. In formula VIII-A, the group Wd represents the group or , wherein Ra is hydrogen, R11 is amino; in compound IV, Wa2 represents CR5; Wa3 represents CR6; Wa4 represents N or CR7; in compound IX, Wa1 and Wa2 independently represent CR5, N or NR4, and Wa4 independently represents CR7 or S, wherein no more than two neighbouring atoms in a ring represent atom or sulphur; Wb5 represents N; B represents a grouping of formula II, as well as in case of compound IV, B means C1-C10alkyl, C3-C10cycloalkyl, C3-C10heterocycloalkyl having one to six ring heteroatoms specified in N, O and S; in case of compound IX, B also means C1-C10alkyl, C3-C10cycloalkyl or 6-merous heterocycloalkyl having nitrogen atom; Wc represents C6-C10aryl or 5-18-merous heteroaryl having one or more ring heteroatoms specified in N, O and S, or phenyl or 6-merous heteroaryl respectively is equal to an integer of 0, 1, 2, 3 or 4; X is absent or represents -(CH(R9))z-, respectively; z is equal to 1; Y is absent. The other radical values are specified in the patent claim.

EFFECT: compounds can be used for treating such diseases, as cancer, bone disorders, an inflammatory or immune disease, diseases of the nervous system, metabolic disorders, respiratory diseases, thrombosis or cardiac diseases mediated by PI3-kinase.

68 cl, 11 dwg, 7 tbl, 55 ex

FIELD: medicine.

SUBSTANCE: composition 16-21ml consisting of a mixture of therapeutic preparations: Dona glucosamine sulphate 3.0 ml; ChondroGuard, or Mucosatum, or Chondrolon chondroitin sulphate - 2.0 ml; Alflutop 2.0 ml; Actovegin 4.0-5.0 ml; glucocorticosteroids Depo-Medrol 1.0-2.0 ml in the concentration of 40 mg/ml, or Diprospane 1.0-2.0 ml in the concentration of 7 mg/ml, or Metipred 1.0-2.0 ml in the concentration of 62.5 mg/ml; vitamins B1, B6, B12 Combilipen 2.0 ml, or Milgamma 2.0 ml, or Neurobion 3.0 ml; 95% or 70% ethanol 2.0-4.0 ml, is administered into a pathologically changed region. That is immediately followed by exposing the pathologically changed region and adjoining segments to a session of A shock-wave therapy in the following mode: pressure 1.2 - 4.0 bar, frequency 7-12 Hz, beat quantity 8000-14000 for 20-40 minutes. The complex procedures are performed within the course of 1-6 times every 7-10 days.

EFFECT: method enables the direct exposure on the pathologically changed region to achieve the optimum concentration of drug preparations therein with avoiding systemic prescription and preventing a risk of side effects.

3 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds of general formula [1] or their pharmaceutically acceptable salts, which possess properties of an inhibitor of the JAK2 thyrokinase activity. In general formula radicals are selected from group (I) or (II). In group (I) X represents CH or N; R1 represents a halogen atom and R2 represents H, a halogen atom, CN, or is selected from the groups of formulas

,

or a group -ORP or 5-6-membered heteroaryl, containing 1-4 nitrogen atoms and optionally additionally containing an oxygen or sulphur atom or containing an oxygen atom as a heteroatom, optionally substituted; or (II) X represents -CRA; and RA represents a group of formula , RB represents (a) amino, optionally substituted with one or two groups, selected from the group, consisting of C1-6alkyl, C3-6cycloalkyl, (C3-6cycloalkyl)C1-6alkyl and C1-3alcoxyC1-3alkyl, (b) C1-3alcoxy, (c) hydroxy or (d) a 5-6-membered saturated cyclic amino group, which additionally can contain a heteroatom, selected from an oxygen atom; R1 represents a halogen atom and R2 represents H; R3 -R5 have values given above. Other values of the radicals are given in the invention formula.

EFFECT: compounds can be applied for the prevention or treatment of cancer, for instance hematologic cancer disease or a solid form of cancer, inflammatory disorder, for instance, rheumatoid arthritis, inflammatory intestinal disease, osteoporosis or multiple sclerosis and angiopathy, for instance, pulmonary hypertension, arteriosclerosis, aneurism or varicose veins.

14 cl, 19 tbl, 234 ex

FIELD: veterinary medicine.

SUBSTANCE: method of treatment of intervertebral disk disease in dogs comprises intravenous injection of 3-5.5% aqueous solution of lithium chloride based on 2.5-3.5 mmol/kg of animal body weight, and additionally subcutaneously 10-30% aqueous solution of polyethylene glycol-4000 based on 2-4 ml/kg of animal body weight every second day for 5-7 days.

EFFECT: increased efficiency and simplification of the method.

4 ex

FIELD: veterinary medicine.

SUBSTANCE: method of treatment of intervertebral disk disease in dogs comprises administering the medicinal product, and the medicinal product is used as 10-30% aqueous solution of polyethylene glycol-4000, which is administered subcutaneously in an amount of 2-4 ml/kg of animal body weight every second day for 5-7 days.

EFFECT: improvement of efficiency of the method.

1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I), possessing an activity with respect to cytokines, versions of based on them pharmaceutical compositions and their application. Formula (I) compounds can be applied for treatment or prevention asthma, COPD, ARDS, rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis or gouty arthritis. In general formula (I) L is selected from the group, consisting of -C(O)-, -CH2-, Ar1 represents a mono-, di- or trisubstituted phenyl ring, where substituents are independently selected from the group, consisting of a halogen and -C1-4alkyl; Ar2 represents an optionally substituted thiadiazolyl ring, where the substituent represents -C1-4alkyl, -C3-5cycloalkyl, -methylcyclopropyl, phenyl or a 5- or 6-membered monocyclic heteroaromatic ring or a bicyclic heteroaromatic ring with 9 or 10 atoms, with the said heteroaromatic ring containing 1, 2 or 3 heteroatoms, selected from the group, consisting of S, O and N, where the said phenyl or heteroaromatic ring is optionally mono- or disubstituted with substituents, independently selected from the group, consisting of a halogen, -C1-6alkyl, optionally substituted with 1-4 fluorine atoms, -O-C1-6alkyl, -CF3 and oxo.

EFFECT: increased efficiency of the application of the compounds.

16 cl, 1 tbl, 46 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to traumatology and orthopaedics, and can be used for treating patients with epicondylitis. That is ensured by applying a complex of measures, in particular a restraint of motions in the involved segment, physiotherapy and drug treatment. A pain syndrome is pre-evaluated by a visual analogue scale (VAS). A proximal forearm is immobilised with an epicondylic bandage in the daytime for 7-10 days in sportsmen, and for 2-3 weeks in common patients. Therapeutic exercises (TE) are prescribed from the first day of treatment. The first part of TE consisting of isometric and static exercises aiming at strengthening arm muscles is done before noon. The second part of TE comprising relaxing exercises is performed in the late afternoon or after any physical loads. The patient continues with the therapeutic exercises after the bandage is removed and to be used for professional or sports loads only. Electric stimulation is conducted daily for 7-10 days with using TENS apparatus or its analogues generating electrical signals covering the enthesis and the involved forearm muscles. Arthrofoon is administered with underlying electric stimulation. If the pain syndrome value according to the VAS is less than 4 points, the preparation is administered as a monotherapy in a dose of 4 weeks a day for three months. If the pain syndrome according to the VAS is more than 4 points, Arthrofoon is administered in a dose of 8 tablets a day in a combination with a selective non-steroid anti-inflammatory preparation in a therapeutic dose for no more than 10 days. The therapeutic regimen also contains Sirdalud 2-4 mg one hour before bedtime for 2 weeks. There are also administered vasodilators improving microcirculation of the involved segment, intramuscularly for 10 days. The therapeutic complex is also added with Milgamma B 2 ml, 5 injections, and another 5 injections triduan. Wobenzyme is administered for 3-4 weeks. Calcemine or Calcemine-advance, the preparations of calcium are administered for six months. The therapeutic course according to the presented regimen is repeated half a year later. The physical exercising for the arm muscles strengthening are to be further done two or three times a week on the average for min. 30 minutes for the life term if suffering high loads or doing any top-class sports for the purpose of maintaining the forearm tonus. The segment of interest is fixed with an orthesis when suffering a load. The therapy with the TENS or similar apparatus of the forearm muscles of interest and the enthesis follow a pronounced load 2-3 hours before bedtime and shall be accompanied with a session of relaxing exercises.

EFFECT: method provides the evident and stable clinical effect characterised by the complete recurrence-free recovery by the physical restoration of the tissue structure within the inflammation with the high quality of life and a surgical intervention avoided.

1 dwg, 2 ex

FIELD: biotechnologies.

SUBSTANCE: invention proposes a molecule that is specifically combined with CD37 and that contains the following from N-end to C-end: (a) CD37-specific scFV containing the following from N-end to C-end: (i) humanized variable region of a heavy chain, which contains CDR1 GYNMN, CDR2 NIDPYYGGTTYNRKFKG and CDR3 SVGPFDS, (ii) linker having 5 to 30 aminoacids inclusive, and (iii) humanized variable region of an easy chain containing CDR1 RASENVYSYLA, CDR2 FAKTLAE and CDR3 QHHSDNPWT; (b) a link region; and (c) immunoglobulin regions CH2 and CH3. The following is described: The following is described: nucleic acid coding the above binding molecule; an expression vector containing the above nucleic acid; and a host cell for production of a binding molecule, which contains the above vector. The invention proposes use of the above binding molecule to obtain a medicinal agent to reduce the number of B-cells, treatment of a disease or an illness, which is related to abnormal activity of B-cells. Besides, the invention describes compositions containing effective number of the above binding molecule to reduce the number of B-cells, treatment of a disease or an illness related to abnormal activity of B-cells.

EFFECT: invention allows obtaining scFV molecule binding CD37, having orientation of variable regions VHVL, with high yield and efficiency in comparison to scFV molecule against CD37, which has orientation of variable regions VLVH.

31 cl, 17 dwg, 13 tbl, 12 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to biotechnology and represents a pharmaceutical composition applicable for treating a rheumatic disease and containing the humanised anti-CD4 antibody able to activate CD4+CD25+ regulatory T-cells, and methotrexat. The present invention also discloses a kit and a method of treating the rheumatic disease with using the above pharmaceutical combination and the above kit.

EFFECT: invention enables implementing more effective methods of treating the rheumatic diseases, including rheumatoid arthritis.

57 cl, 8 dwg, 2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine. What is described is a biological material containing: a) a liquid carrier containing a viscous solution containing at least one natural and/or semisynthetic polysaccharide and having a dynamic viscosity measured at 20°C and at shear rate D=350 s-1, within the range of 100 to 250 centipoise and/or kinematic viscosity within the range of 99 to 248 centistokes (measured in the same environment); b) a autologous or heterologous mesenchymal cell culture and/or c) platelet rich blood product.

EFFECT: material in form of viscous liquid is particularly applicable for the therapy of osteoarthritis, ligament injuries and administered intra-articularly, intradermally or applied in situ without change of the properties of the mesenchymal stem cells and/or its platelets.

11 cl, 5 ex

FIELD: medicine.

SUBSTANCE: composition of 5,10,15,20-tetrakis(N-methyl-3'-pyridyl)chlorine and 5,10,15,20-tetrakis(N-methyl-3'-pyridyl)bacteriochlorine is administered into a tumour tissue as a photosensitiser in an amount of 0.5-10mg per 1g of tumour tissue depending on a degree of tumour differentiation. The laser exposure starts 20-40 minutes later at wave length 760-762 nm. The cytological examination follows 6-7 days later, and if observing signs of persistent tumour growth, the presented therapeutic session is repeated.

EFFECT: gradual depression of the malignant tumour tissue up to the complete elimination of its cell and structural abnormalities, lower rate of metastasis or progression prevention that makes it possible to avoid surgical intervention in some cases.

4 cl, 3 dwg, 3 ex

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