Method for decreasing ceramide content, set comprising antiretroviral medicinal agent
FIELD: medicine, virology, pharmacy.
SUBSTANCE: invention relates to treatment of HIV-infection and AIDS and involves a method for decreasing the content of ceramides in a patient suffering these diseases and a set for its realization. Method involves administration in a patient the medicinal preparation comprising L-carnitine or acyl-L-carnitine wherein a linear or branched acyl group comprises 2-6 carbon atoms, or their pharmacologically acceptable salts in combination with an antiretroviral medicinal preparation taken among the group of nucleoside-like inhibitors of reverse transcriptase, non-nucleoside inhibitors of reverse transcriptase, inhibitors of HIV protease. A set for decreasing the content of the content of ceramides involves an antiretroviral medicinal agent taken among the abovementioned group and enhancing agent taken among the group consisting of L-carnitine or acyl-L-carnitine wherein linear or branched acyl group comprises 2-6 carbon atoms, or their pharmacologically acceptable salts or mixtures. Invention provides enhancing activity of antiretroviral agents and to protect immune system due to decreasing the concentration of ceramides that results to inhibition of HIV expression and cellular apoptosis.
EFFECT: improved and valuable medicinal properties of agent.
20 cl, 2 tbl, 2 ex
The present invention relates to a method for reducing the content of ceramides with HIV and AIDS through injection of L-carnitine, its derivatives and pharmacologically suitable salts in combination with antiretroviral drugs to treat HIV infection and AIDS. In more detail, the present invention relates to a method using L-carnitine, acyl-L-carnitine, where acyl group, a linear or branched, has 2-6 carbon atoms, and their pharmaceutically acceptable salts in combination with nucleocytoplasmic reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors and HIV protease inhibitors for reducing the content of ceramides and increasing the activity of these antiretroviral drugs in HIV-infected patients.
Most of the pathogenic mechanisms that contribute to the progression of the infection caused by the human immunodeficiency virus 1 and 2 (HIV-1, HIV-2), directly or indirectly related to the state General activation of the immune system.
Chronic activation of the immune system activates viral replication through the secretion of several cytokines, favoring the expression of HIV, and by the conservation reserve activated immune cells that act as targets for HIV and promote its replication.
In addition to the, the steady state activation of the immune system induces pathology of this nature (for example, increased apoptosis), leading to the weakening of immune responses.
Thus, we have a vicious circle: the progressive loss of the normal functioning of the immune system → viral disseminirovanne - reduced elimination of the virus → chronic activation of the immune system. This process can last for years until until is specified depletion of the immune system that leads to uncontrolled viral replication and attack opportunistic infections or the development of acquired immunodeficiency syndrome (AIDS).
On the basis of the above pathogenic mechanisms it is clear that we need to be aware of any anti-HIV treatment that reduces viral replication and blocking the depletion of the immune system.
With regard to antiretroviral therapy, unfortunately, HIV is characterized by a high degree of genetic variability, occurring mainly at a very significant disadvantage of reverse transcriptase. Retroviral enzyme deprives enzymatic system control possible errors of transcription. The result is the emergence of virus variants is beyond the range that is a function of viral replication is responsible for the progressive immune deviation si is theme and resistance to antiretroviral drugs. In the case of zidovudine (zidovudine - AZT, ZDV) loss of clinical efficacy in situations monotherapy is widely recognized. Even open recently antiretroviral agents, for example, zalcitabine [ddc], didanosine [ddI] and lamivudine [3TC] suffer from such a disadvantage.
Recently it was demonstrated that ceramide stimulates HIV-expression. Moreover, ceramide is one of the factors able to induce cell apoptosis, a phenomenon that is enhanced in people with HIV infection and which contributes to the reduction in the number of TCD4 and TCD8 cells. Thus, it is clear that changes in the concentration or metabolism of ceramide may affect viral load and cell apoptosis in HIV-infected patients (Papp Century and others, AIDS, Res. Hum.Retrovirus, 10(7), 775-80).
To my surprise, found that L-carnitine, its derivatives, namely acyl-L-carnitine, in which acyl group, a linear or branched, has 2-6 carbon atoms, and their pharmaceutically suitable salts inhibit the synthesis of ceramide, at least 25%, and when used in combination with antiretroviral drugs, such as AZT, stavudine [4dT], fertility [FLT], isidorean [Azdu], Vospominanie acyclic nucleosides [RMAA], HIV-1 specific oligonucleotides [TSAO]zalcitabine [ddC], didanosine [ddI] and lamivudine [3TC], diperiodic epiney, tetrahydroxybenzophenone, pyridone or L - medicines, bis-heteroarylboronic, derivatives of alpha-anilinoquinazoline, derivatives finokalia, Ro-31-8959, U-81749, INSTITUTE of 227, SC-52151, HOE/BAY 793 and the like, increase potency and protection of the immune system, which is affected by these drugs.
Pharmaceutically acceptable salts of L-carnitine or acyl-L-carnitine include, in addition to internal salts of any salt of these substances with acids, which do not cause unwanted toxic or side effects. Such acids are well known in the art pharmacology and experts in pharmaceutical technology.
Non-limiting examples of suitable salts include chloride; bromide; iodide; aspartate, in particular, acid aspartate; citrate, in particular, acid citrate; tartrate; phosphate, in particular, acid phosphate; fumarate, in particular, acid fumarate; glycerol; phosphate glucose; lactate; maleate, in particular, acid maleate; orotate; oxalate, in particular, acid oxalate; sulphate, in particular, acidic sulfate; trichloroacetate; triptorelin and methanesulfonate.
Particularly preferred L-carnitine, acetyl, propionyl, butyryl, valeryl and isovaleryl-L-carnitine.
Co-administration of L-carnitine and its derivatives, as defined above, together with antiretroviral agent Oba is but perform oral or parenteral way in a daily dose of from 1 to 500 mg/kg, particularly preferred doses from 20 to 100 mg/kg, with a ratio of L-carnitine and its derivatives defined above and antiretroviral agent in the range from 1:40 to 40:1, particularly preferably a ratio of from 1:10 to 10:1.
Usually the drug is administered in the form of standard dosage forms, including both active ingredient, which may also include fillers and additional active ingredients, well known in the art, such as, for example, dextran, TNF-alpha inhibitors (e.g, pentoxifylline), glutathione and other antioxidant drugs (e.g., acetylcysteine, immunomodulatory drugs, immunosuppressive or chemotherapeutic agents, vitamins and trace elements.
Finally, it should be noted that, apparently, other basic amino acids, particularly lysine, acyl derivatives of basic amino acids and their pharmaceutically acceptable salts can reduce the content of ceramides and to increase the activity of antiretroviral drugs for the treatment of HIV infection and AIDS.
The purpose of the following examples is to illustrate the present invention, they should not be construed as limiting in any way the scope of the invention.
Evaluated the effect of combining L-carnitine (8 g per day orally for 4 weeks) in order Luce AZT (600 mg / day orally) in 13 patients, suffering from AIDS, with normal serum and intracellular levels of carnitine and azetilcarnitin, which were treated with AZT (600 mg per day orally) for at least 6 months.
Determination was performed before treatment combination, when patients took only AZT (t0), after 4 weeks of therapy with combination of L-carnitine-AZT (T1) and one month after stopping treatment with L-carnitine (T2), leaving patients only AZT therapy. Measured TCD4 lymphocytes by flow cytometry using specific monoclonal antibodies (number of lymphocytes / mm3and lost lymphocytes by flow cytometry after staining propylimidazol, quantification of cells with hypodiploid cores (the number of lymphocytes at 50,000 cells). Viral load (the number of viral particles per ml of serum) were determined by quantitative determination of HVI-1 RNA using polymerase chain reaction (detection system Roche: Amplicor HIV detection system by Roche). The statistical analysis used the Wilcoxon test.
The results are shown below in table 1.
|Patient||TCD4 lymphocytes/mm3||Lost lymphocytes / 50,000 cells||HIV (viral particles per ml)|
the same patients the levels of lymphocyte-ceramide, measured by examining DAG (diacylglycerol/protein kinase (Cifone M.G. and others, J.Exp. Med., 180(4), 1547-52), decreased from 48±8 picomoles/106lymphocytes [measured before treatment combination (t0)] to 27±5 picomoles/106lymphocytes (T1) (P<0.01), and again increases to 38±9 picomoles/106lymphocytes month after termination of the introduction of L-carnitine (T2).
These results clearly show that treatment only AZT, even lasting more than 6 months (t0), cannot give such immunological and virological improvements that can be achieved with the combination of L-carnitine-AZT for 4 weeks (T1). These improvements tend to decline after the end of treatment (T2).
Four patients with AIDS treated, giving 600 mg of AZT daily oral. Two of them also took L-carnitine for 3 grams per day. The total duration of treatment was 6 months. Before and after treatment was performed muscle biopsy. The content of ceramide in the cells of the muscles was determined before and after treatment after cell disruption by ultrasound and homogenization of biopsy material. Viral load was determined in the same homogenates as described in Example 1.
The results are presented below in table 2.
|Before treatment ceramide peak is moles/mg protein)||After ceramide treatment (picomoles/mg protein)||To treat HIV (VIR. particles/mg protein)||After the treatment of HIV (VIR. particles/mg protein)|
|Patient 1 (AZT)||89||95||3800||4100|
|Patient 2 (AZT)||95||103||5900||5800|
|Continuation of table 2|
|The RMS. off.||4||6||1485||1202|
|The statistics. value||no stat.||no stat.|
|Patient 3 (AZT+L-carnitine)||129||39||10200||3200|
|Patient 4 (AZT+L-carnitine)||79||27||5100||1300|
|The statistics. value||0,01||005|
It is clear that treatment with the combination of L-carnitine-AZT significantly more effective in reducing viral load and content of ceramide, also content in muscle, compared with treatment with AZT alone.
1. The method of reducing the content of ceramides with HIV and AIDS by injecting the patient with medication that includes L-carnitine or acyl-L-carnitine, in which acyl group, a linear or branched, has 2-6 carbon atoms, or their pharmacologically acceptable salts in combination with antiretroviral drug selected from the group nucleocytoplasmic reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, HIV protease inhibitors.
2. The method according to claim 1, wherein the administered L-carnitine.
3. The method according to claim 1, characterized in that the acyl-L-carnitine is isovaleryl-L-carnitine.
4. The method according to claim 1, wherein the patient to be treated has a normal serum and intracellular content of carnitine and azetilcarnitin.
5. The method according to claim 1, characterized in that L-carnitine or acyl-L-carnitine, azidothymidine enter at least for 4 weeks, and the daily dose of L-carnitine or acyl-L-carnitine, or azidothymidine is from 1 to 500 mg/kg
6. The method according to claim 5, characterized in that L-carnitine, acyl-L-carnitine vodadone in the amount of 8 g/day, at least for 4 weeks.
7. The method according to claim 6, characterized in that patients previously for at least 6 months were treated only antiretroviral drug.
8. The method according to claim 7, characterized in that the antiretroviral drug selected from the group consisting of nucleocytoplasmic reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and HIV protease inhibitors.
9. The method according to claim 8, characterized in that the antiretroviral drug is azidothymidine.
10. The method according to claim 1 to reduce the content of ceramides in the muscles of a patient suffering from AIDS, including the introduction of a specified patient antiretroviral drug and L-carnitine for 4 weeks.
11. The method according to claim 6, characterized in that L-carnitine, acyl-L-carnitine is administered in an amount of 3 g/day for 6 months.
12. The method according to any one of claims 1 to 11, characterized in that the amount of L-carnitine or acyl-L-carnitine is such that the daily dose of his or antiretroviral drugs is from 1 to 500 mg/kg and the ratio of L-carnitine or acyl-L-carnitine and antiretroviral drug ranges from 1:40 to 40:1.
13. Set for reducing the content of ceramides with HIV and AIDS, VK is uchumi antiretroviral drug and amplifying means, selected from the group consisting of L-carnitine, acyl-L-carnitine, in which the acyl group has 2-6 carbon atoms, and their pharmacologically acceptable salts or mixtures.
14. Set according to item 13, wherein the antiretroviral drug selected from the group consisting of nucleocytoplasmic reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and HIV protease inhibitors.
15. Set according to item 13, wherein the antiretroviral drug is azidothymidine.
16. Set according to any one of p-15, characterized in that the antiretroviral drug and/or reinforcing means presents at least with a pharmacologically acceptable excipient.
17. Set according to any one of p-16, characterized in that the number of amplifying means such that the daily dose amplified or antiretroviral drugs is from 1 to 500 mg/kg, and the ratio between the amplifying means and antiretroviral drug ranges from 1:40 to 40:1.
18. Set according to any one of p-16, characterized in that the number of amplifying means such that the daily dose amplified or antiretroviral drugs ranges from 20 to 100 mg/kg, and the ratio between strengthening the m tool and antiretroviral drug ranges from 1:10 to 10:1.
19. Set according to any one of p-18, characterized in that the antiretroviral drug and/or reinforcing means shown in the form for oral or parenteral administration.
20. Set according to any one of PP-19, characterized in that the antiretroviral drug and/or reinforcing means are presented together with at least one component selected from the group consisting of dextran, inhibitors of alpha-TNF, anti-oxidant drugs, immunomodulators, immunosuppressants, chemotherapeutic agents, vitamins and trace elements.
SUBSTANCE: one should perform the following stages: a) removal of contaminants out of plant; b) plant's reducing; c) treatment of reduced plant with laser radiation; d) suspending the mixture obtained at stage c) in water; e) maceration of suspension obtained at stage d) and f) separation of liquid developed. Composition should be obtained due to this technique. It should be applied at treating hepatitis C as an aqueous extract. It should be applied as aqueous extract as immunostimulant. Pharmaceutical preparation includes aqueous extract as an active constituent.
EFFECT: increased biological activity of the product.
43 cl, 16 ex, 1 tbl
SUBSTANCE: the suggested treatment should be performed due to introducing a compound of total formula I.
EFFECT: increased efficiency of therapy.
17 cl, 1 dwg, 7 ex, 8 tbl
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new derivatives of isoquinoline carboxamide of the formula (I):
and to their pharmaceutically acceptable salts wherein R1 means hydrogen atom, hydroxy-group or -NHR2 wherein R2 means alkyl, arylalkyl, heterocyclylalkyl that comprises one or some heteroatoms taken among nitrogen, oxygen and sulfur atoms, cycloalkyl, alkylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, heterocyclylcarbonyl that comprises one or some heteroatoms taken among nitrogen, oxygen and sulfur atoms, arylalkylcarbonyl, heterocyclylalkylcarbonyl that comprises one or some heteroatoms taken among nitrogen and oxygen atoms, alkyloxycarbonyl, arylalkyloxycarbonyl, heterocyclylalkyloxycarbonyl that comprises one or some heteroatoms taken among nitrogen atom, heterocyclyl that comprises one or some heteroatoms taken among nitrogen and sulfur atoms, alkylsulfonyl, arylsulfonyl or the group of the formula:
R3 and R4 mean alkyl independently of one another; R5 means alkyl; or R4 and R5 in common with carbon and sulfur atoms to which they are bound form a heterocycle; R6 means alkyl; R13 means hydrogen atom or the group of the formula:
R15 means aryl under condition that if R3, R4 and R5 form methyl, R6 forms tert.-butyl then R13 means hydrogen atom, and if R15 means phenyl then R2 doesn't mean benzyloxycarbonyl and 2-quinoline carbonyl (other values of radicals are given in cl. 1 of the invention claim). Also, invention relates to a medicinal agent based on these compounds used in treatment of HIV-mediated diseases. Invention provides preparing new compounds and a medicinal agent based on thereof in aims for treatment of HIV-mediated diseases.
EFFECT: valuable medicinal properties of compounds and medicinal agent.
14 cl, 11 tbl, 173 ex
FIELD: organic chemistry, vitamins, medicine, pharmacy.
SUBSTANCE: invention relates to a new compound of the formula (I): wherein X means hydrogen atom or hydroxy group; R1 and R2 that can be similar or different mean hydrogen atom, (C1-C4)-alkyl; R3 means hydrogen atom, methyl group, fluorine or chlorine atom. Also, invention relates to its esters able to hydrolysis in vivo in combination with pharmaceutically acceptable acids. Also, invention relates to a pharmaceutical composition eliciting the inhibitory activity with respect to proliferation and promoting differentiation of cells and comprising the effective dose of compound of the formula (I) in common with pharmaceutically acceptable carriers and/or excipients. Also, invention relates to applying compound of the formula (I) for preparing a medicine used in treatment and prophylaxis of disease characterizing by abnormal differentiation of cells and/or proliferation of cells.
EFFECT: valuable medicinal properties of compounds.
13 cl, 3 sch, 3 tbl, 6 ex
SUBSTANCE: method involves treating hepatitis C virus infection or hepatitis B virus infection by introducing carboxamidine of formula 1 or its pharmaceutically permissible salt at a dose of 0.1-40.0 mg/kg of body mass. Α-interferon is also introduced. Compound of formula 1 is in D-configuration.
EFFECT: enhanced effectiveness of treatment.
7 cl, 5 dwg
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new derivatives if azaindole of the formula (I)
or its pharmaceutically acceptable salts wherein the formula is taken among the group consisting of , , and and wherein each among R1, R2, R3 and R4 is taken independently among the group consisting of hydrogen atom (H), (C1-C6)-alkyl, (C2-C6)-alkenyl, halogen atom, cyano-group (CN), phenyl, nitro-group, -OC(O)R15, -C(O)R15, -C(O)OR16, -OR19, -SR20 and NR21R22 wherein R15 is taken independently among the group including hydrogen atom (H),(C1-C6)-alkyl and (C2-C6)-alkenyl; each among R16, R19 and R0 is taken independently among the group including hydrogen atom (H), (C1-C6)-alkyl or (C1-C6)-alkyl substituted with from 1 to 3 halogen atoms; each among R21 and R22 is taken among the group including hydrogen atom(H), hydroxy-group (OH), (C1-C6)-alkyl; R5 represents the group (O)m wherein m = 0 or 1; n = 1 or 2; R6 is taken among the group including hydrogen atom (H), (C1-C6)-alkyl, -C(O)R24 and -C(O)OR5 under condition that carbon atoms comprising carbon-carbon double bond of indicated (C3-C6)-alkenyl are not the addition point to nitrogen atom to which R6 is joined; R24 is taken among the group consisting of hydrogen atom (H), and (C1-C6)-alkyl; R25 represents (C1-C6)-alkyl; each among R7, R8, R9, R10, R11, R12, R13 and R14 is taken independently among the group including hydrogen atom (H) and (C1-C6)-alkyl; Ar is taken among the group including:
, and . Compounds of the formula (I) inhibit HIV-1 that allows proposing their applying in medicine.
EFFECT: valuable medicinal and antiviral properties of compounds.
22 cl, 13 sch, 2 tbl
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to a pharmaceutical composition used in treatment or prophylaxis of HIV-infection in humans that comprises effective amount of β-D-D4FC or its pharmaceutically acceptable salts or a prodrug being optionally in a pharmaceutically acceptable carrier in combination with effective amount of compound being optionally in pharmaceutically acceptable carrier that is taken among the group consisting of indinavir, nelfinavir, saquinavir, amprenavir, efaverenza, delavirdin, nevirapin and abacavir as a single preparation and to a method for treatment or prophylaxis of HIV-infection in humans that involves administration of effective amount of this composition. Pharmaceutical composition elicits the preferred or improved pharmacokinetic parameters, parameters of biological distribution, metabolic parameters, parameters of resistance and other parameters as compared with administration of β-D-D4FC only.
EFFECT: improved method for treatment and prophylaxis, valuable properties of composition.
17 cl, 6 tbl, 2 dwg
FIELD: organic chemistry, pharmaceutical compositions.
SUBSTANCE: invention relates to substituted 3-oxo-1,2,3,4-tetrahydroxinoxalines of general formula 1 , wherein R1 represents substituted sulfanyl or substituted sulfonyl group, containing as substituent optionally substituted C1-C4-alkyl, optionally substituted C3-C8-cycloalkyl, aryl-(C1-C4)alkyl optionally substituted in aril or alkyl group, heterocyclyl-(C1-C4)alkyl optionally substituted in heterocycle or alkyl group; R2 and R3 independently represent hydrogen, halogen, CN, NO2, optionally substituted hydroxyl, optionally substituted amino group, optionally substituted carboxylic group, optionally substituted carbamoyl group, optionally substituted arylcarbonyl group or optionally substituted heterocyclylcarbonyl group; R4 and R5 independently represent hydrogen or inert substituent. Claimed compounds are high effective kaspase-3 inhibitors and are useful in production of pharmaceutical compositions for treatment of diseases associated with excess apoptosis activation, as well as for experimental investigations of apoptosis in vivo and in vitro. Also disclosed are pharmaceutical composition in form of tablets, capsules or injections in pharmaceutically acceptable package, as well as method for production thereof and therapy method.
EFFECT: pharmaceutical composition for apoptosis treatment and investigation.
6 cl, 3 dwg, 8 ex, 1 tbl
FIELD: chemical engineering; pharmaceutical engineering.
SUBSTANCE: method involves applying substances of macrolide group showing high inhibition degree with respect to protein of tyrosine kinase.
EFFECT: enhanced effectiveness in suppressing infection and proliferation of human immune deficiency virus in macrophages.
4 cl, 25 dwg
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new aminobenzophenones of the formula (I):
or their pharmaceutically acceptable salts. These compounds elicit properties of inhibitors of cytokines secretion, in particular, 1β-interleukin (IL-1β) and tumor necrosis α-factor (TNF-α) and to secretion of polymorphonuclear superoxide that are useful for treatment of inflammatory diseases, for example, skin diseases, such as psoriasis, atopic dermatitis. In the formula (I) R1 is taken among the group consisting of halogen atom, hydroxy-, mercapto-group, trifluoromethyl, amino-group, (C1-C3)-alkyl, (C2-C3)-olefinic group, (C1-C3)-alkoxy-, (C1-C3)-alkylthio-, (C1-C6)-alkylamino-group, (C1-C3)-alkoxycarbonyl, cyano-group, carbamoyl, phenyl or nitro-group under condition that when R1 means a single substitute then it at ortho-position, and when R1 means more one substitute then at least one substitute of R1 is at ortho-position; R2 means one substitute at ortho-position being indicated substitute is taken among the group consisting of (C1-C3)-alkyl, (C1-C3)-alkoxy-group; R3 means hydrogen, halogen atom, hydroxy-, mercapto-group, trifluoromethyl, amino-group, (C1-C3)-alkyl, (C2-C3)-olefinic group, (C1-C3)-alkoxy-, (C1-C3)-alkylthio-, (C1-C6)-alkylamino-group, (C1-C3)-alkoxycarbonyl, phenyl, cyano-, carboxy-group or carbamoyl; R4 means hydrogen atom or (C1-C3)-alkyl; Q means a bond or -SO2-; Y means (C1-C15)-alkyl, (C3-C10)-carbocyclic group or phenyl being each of them can be substituted optionally with one or some similar or different substitutes designated by the formula R5; R5 means halogen atom, (C1-C4)-alkyl, amino-, (C1-C3)-alkoxy-group, (C1-C3)-alkoxycarbonyl or -COOH; X means oxygen or sulfur atom. Also, invention relates to a pharmaceutical composition and to a method for treatment and/or prophylaxis of inflammatory diseases.
EFFECT: valuable medicinal properties of compounds and composition.
9 cl, 2 sch, 2 tbl, 29 ex
< / BR>where R represents isopropyl, neopentyl or cyclohexyl,
containing pharmaceutical compositions
FIELD: medicine, surgery.
SUBSTANCE: one should study functional state of hemostasis system based upon electro- and biochemical coagulogram, and at availability of a friable clot: the value of minimal amplitude of electrocoagulogram being above 0.6 c.u. - it is necessary to introduce dicynon per 250 mg intravenously 4 times daily and additionally in case of hypothrombinemia one should carry out infusion of freshly frozen plasma intravenously at the dosage of 3-6 ml/kg patient's body weight, and at availability of hyperactivation of fibrinolysis one should introduce inhibitors of proteases: at first intravenously by bolus technique, and then - as intravenous continuous infusion; moreover, in case of medicinal correction of hemostasis system with anticoagulants in case of hypothrombinemia their dosages should be decreased till achieving normocoagulation. The present innovation enables to restore body hemostasis system due to individually matched therapeutic tactics that, in its turn, enables to prevent postoperational complications.
EFFECT: higher efficiency and accuracy of prophylaxis.
1 cl, 1 dwg, 3 ex, 1 tbl