Agent having cytostatic and apoptosis-inducing activity

FIELD: pharmaceutical industry, in particular agent having cytostatic and apoptosis-inducing activity.

SUBSTANCE: claimed agent represents β-Asparagine, obtained by extraction of ground burdock roots having specific particle size with heated water in specific raw materials/extractant ratio; decoction, extract separation, concentration up to dry residue in concentrate, filtering, and double recrystallization.

EFFECT: agent with high cytostatic and apoptosis-inducing (anti-tumor) activity.

5 dwg, 2 tbl

 

The invention relates to medicine and can be used as medicinal products from vegetable raw materials with cytotoxic and apoptosis inducing (anticancer) activity.

It is known that the main drawback used in oncological clinic cytostatic drugs of plant origin or synthetic is their high toxic effects on the body and on normal cells [Medmaravis. Medicinal product. A manual for physicians, volume 2, str. Moscow: OOO "New wave". Publisher Sbelow, 2002].

Closest to the present invention is vinblastine (rozevin) - a drug used in adjuvant cancer chemotherapy in combination with other anticancer drugs. It is contained in the plant pink periwinkle (Vinca rosea L.), as well as in the plant katarantus (Catharanthus roseus L). [Medmaravis. Medicinal product. A manual for physicians, volume 2, str. Moscow: OOO "New wave". Publisher Sbelow, 2002]. However, its toxicity is high enough.

The objective of the invention is the creation of funds from vegetable raw materials with cytotoxic and apoptosis inducing (anticancer) activity and does not have a toxic effect on the body.

The technical result consists in the manifestation of apoptosisinducing cytotoxic activity of the substance, isolated from the concentrated extract of burdock root.

Burdock root is harvested in the spring in ecologically clean regions, thoroughly washed and sterilized by briefly immersing in boiling water. Then clean the burdock root is crushed to particle sizes less than 1 mm, the resulting mass add heated to 60-70°With water in a mass ratio of 1:3 and infused for 25-30 minutes the extract Obtained is separated from the cake by filtration and centrifugation. Then the extract was concentrated to solids content of the concentrate 75-80%. Within 10-20 days in the concentrated extract is the loss of solid, which is filtered from the extract through a grid of stainless wire with mesh size less than 200 microns.

After filtration and double recrystallization from water the substance is a colorless precipitate (yield up to 10% in terms of concentrated extract), consisting of large rhombic crystals, melting at a temperature above 200°With decomposition. A dedicated connection is not soluble in organic solvents (hydrocarbons, alcohols, acetone, dimethylsulfoxide), soluble in water, in dilute acids and alkalis. Identified physical properties characteristic of amino acids and their derivatives. The ninhydrin reaction on the amino acid gave a positive result. When is the agrevanie aqueous solution of the selected crystals with alkali released ammonia, what is characteristic of amides.

According to elemental analysis the substance contains %: 35,20, N 22,60, N 6.48 in. C4H8N2O3(CHN elemental analyzer HP-185). Calculated, %: C 36,36; N The 6.06; N 21,21.

Molecular formula calculated according to the elemental analysis corresponds to the formula asparagine - monoamide aspartic acid. Depending on the position of the amino group relative to the amide distinguish αand β-asparagine

1 - aspartic acid; 2 - α-asparagine; 3 - β-asparagine.

Because α-asparagine produced synthetically, and in animal and plant tissues contain β-asparagine mainly in the L-form, we can assume that from the juice of the roots of burdock selected β-asparagine. Proof of its structure held by spectral methods.

The IR spectrum (figure 1) have absorption bands, confirming the presence in the structure of the compounds functional groups:

In the region of stretching vibrations of N-H primary amines have had exhibits bands 3455 and 3382 cm-1. Amide group is manifested in the spectrum band of stretching vibrations of NH at 3111 cm-1and deformation vibrations of NH at 1644 cm-1(Amide II band), characteristic Pervin the x amides, the second area of occurrence of these oscillations lies in the region of lower frequencies, at 1429 cm-1band Amide III). The stretching vibrations of the carbonyl group (C=O) amides found at 1682 cm-1(Amide I band). Region 1500-1700 cm-1contains the number of intense bands attributed, as mentioned above, the Amide bands I, II, III, band 1578 cm-1corresponds to the stretching vibrations of C=O in the ionized carboxyl amino acids that indicates zwitter-ion structure of asparagine. Band deformation vibrations in NH+NH3group at 1528 cm-1also confirms zwitter-ion structure. Broadened absorption band at 669 cm-1corresponds to the deformation vibrations of N-H in amines have had.

In the PMR spectrum of compound (2) showed resonance signals of protons of the amino group with a 7.85 ppm, protons of amide groups at 7,60 & 6.86 ppm ppm Doublet of doublets with a chemical shift of 4.0 ppm (J1=4 Hz, J2=8 Hz) refers to the methine proton. It multipletness indicates neweventnotify adjacent methylene protons. The calculation of the spectrum related to the methylene protons gave the following parameters: the signal of one of the methylene protons have a chemical shift to 2.94 ppm (J1=4 Hz), the second - 2,84 ppm (J2=8 Hz), the absolute value of the constant of spin-spin interaction between the methylene protons of the composition is scored 17 Hz.

Thus, the first selection of asparagine from the roots of burdock. The chemical composition of burdock root has been studied adequately, including amino acid composition, but to our research asparagine has not been detected.

Testing the cytotoxic action of aspartic acid selected from concentrate burdock root in comparison with vinblastine held in suspension cultures of tumor cells of Ehrlich carcinoma (2,5·105cells/ml) inclusion of3H - thymidine, followed by analysis on a beta counter Mark-III, as well as in the reaction of blast transformation of human lymphocytes stimulated by phytohemagglutinin (PHA) after exposure to the drug in the concentration range from 0.4·10-3up to 75·10-3M. evaluation of the effect of drugs on lymphocyte proliferative activity in spontaneous and induced PHA test conducted in accordance with the methodological recommendations of farmkomiteta of the RF Ministry of health (Protocol No. 10 from running from 10.12.1998)

The results are shown in table 1.

The data obtained show that the claimed product has a dose-dependent effects on tumor cells, with concentrations of the order of 37.8·10-3M 3,78·10-3M and 0,378·10-3M inhibited the proliferation of malignant cells to 56.2%-71,8% of control (tumor cells without preparation is tov), but lower doses had no inhibitory effect on the proliferation of tumor cells. The obtained results show that the proposed tool has antibioticsbuy properties.

The results of the test products in the reaction of blast transformation of lymphocytes is presented in figure 3. As of similar used commercial product of plant origin - vinblastine.

As a result of researches it is established that the claimed product has a dampening effect on PHA induced lymphocyte proliferative activity. Draws attention to the emergence of cells with the phenomena of necrobiosis, which together can serve as a confirmation of his antibioticheskih actions on cells. In contrast to the claimed means of the use of vinblastine was accompanied by a more profound suppression of cell proliferation lymphoblastic cells and their destruction, which is associated with the presence of immunosuppressive properties of vinblastine.

Testing the apoptosis inducing effects of the proposed drug held in the tumor cells of Ehrlich carcinoma according to the method of S. Orlov N., Dam .V., J. Trembly et al. // Biochem. Biophys. Res. Commun. 1996. Vol.221. P.708-715.

The results are shown in figure 4.

The data obtained show that the proposed tool has a dose-dependent apoptosis inducing effect on SDA is Olivia cells, the most pronounced at a concentration of about 4·10-3M (induction of apoptosis 87%) from control (tumor cells without drugs), which proves its apoptosis inducing activity.

The results of the toxicity studies of the proposed drug compared with vinblastine and other devices used in the treatment are presented in table 2.

Of materials table 2 shows that the inventive tool (asparagine) in contrast to the known anticancer drugs is not toxic and does not cause the death of experimental animals. Thus, the inventive tool (asparagine) shows cytotoxic and apoptosis inducing (anticancer) activity, but does not have an adverse toxic effect on the organism.

Table 1
Cytotoxic effect of the drug on tumor cells of Ehrlich carcinoma.
The drug concentrationThe control (cells without the influence of the drug)37,8·10-3M3,78·10-3M0,378·10-3M
The number of viable cells (%)8656,27071,8

Table 2.
Name of productDose mg/kgThe number of animals (white outbred mouse)The number of dead animals (white outbred mouse)
The inventive tool (asparagine)200050
100050
50050
Vinblastine200055
100055
50055
Cyclophosphamide200055
100055
50055
6-mercaptopurine200055
100055
50055

The agent with cytotoxic and apoptosis inducing activity, characterized by the fact that it is a β-asparagine, obtained by extraction crushed to particle sizes less than 1 mm burdock heated to 60-70°With water at the ratio of raw material : solvent 1 : 3, fabrication of separation of the extract concentration to dry on the TATKO in concentrate 75-80%, filtration, double recrystallization.



 

Same patents:

FIELD: medicine, oncology.

SUBSTANCE: method involves carrying out lumbal puncture to a patient in post-operative period, subarachnoid space is catheterized, and 5 ml of liquor is removed followed by incubation of liquor with nimustine taken in the dose 5 mg in vitro at temperature 38°C for 30 min, and liquor is administrated into subarachnoid space through catheter. Procedure is carried out 2 times with interval for 7 days. Since the second day after onset of this procedure distant gamma-therapy on bed of removed tumor is carried out up to the total focus dose 60 Gr. Method provides stable remission, decreasing toxicity of chemopreparation, frequency of adverse by-side effects and significant reducing the cost of chemotherapy. Invention can be used in carrying out the adjuvant chemoradiation therapy of brain malignant glial tumors.

EFFECT: improved method of chemoradiation therapy, enhanced effectiveness of method.

1 ex

FIELD: medicine, oncology, gynecology.

SUBSTANCE: method involves trepanopuncture of flank bone wing, aspiration of bone marrow suspension in the amount 150-200 ml followed by incubation of suspension with chemopreparations cisplatin and cyclophosphan at temperature 37°C for 40 min in doses above therapeutic ones. Doxorubicin is not incubated with bone marrow suspension and chemopreparations are administrated separately by intravenous route, by drops in indicated order in day when the bone marrow suspension has been taken, and this procedure is repeated with interval for 3-4 weeks but totally 4 times per one treatment course. Proposed method provides attaining the stable anti-tumor effect up to the complete tumor regression in this category of patients showing high tolerance to chemotherapy, and in practical absence of adverse toxic responses. Invention can be used in treatment of patients with relapses of ovary and uterus body cancer in case absence effectiveness of other methods of treatment or in case of their low effectiveness.

EFFECT: improved method of treatment.

2 ex

FIELD: medicine, oncology.

SUBSTANCE: method involves administration of bleomycin and erythropoietin simultaneously in patients. Invention can be used for decreasing pulmonary cytotoxicity in patients treated with bleomycin. Invention provides improving functioning lung in patients of this category.

EFFECT: valuable medicinal properties of erythropoietin.

4 cl, 2 dwg, 2 ex

FIELD: medicine, oncology, pharmacology, pharmacy.

SUBSTANCE: invention relates to methods and medicinal formulations used in antitumor treatment and enhancing oral biological availability of taxanes. Method involves administration of taxane in combination with agent enhancing biological availability of taxane in oral administration in subject wherein concentrations of taxane attain levels of therapeutic activity in subject. Ketoconazol representing inhibitor of cytochrome P-450 is used as agent enhancing oral biological availability of taxane. Invention provides enhancing bioavailability of taxane in its oral administration in subject in subtherapeutic doses that results to decreasing toxicity of treatment.

EFFECT: improved and valuable medicinal properties of drug.

33 cl, 42 dwg, 10 tbl, 12 ex

FIELD: chemistry, medicine.

SUBSTANCE: invention relates to hemin-peptide of general formula I , wherein R1 is ArgTrpHisArgLeuLysGlu(OMe)OH; R2 is -OH; Y is Cl; Me is Fe, or pharmaceutically acceptable salts thereof having virulicidal and anti-viral activity, including activity against herpes virus and HIV, and capability for destroying of λ fag, herpes and HIV DNA. Hemin-peptide fragment also is disclosed.

EFFECT: new anti-viral agent.

2 cl, 5 tbl, 5 ex

FIELD: organic chemistry, biochemistry, medicine.

SUBSTANCE: invention relates to derivatives of 2-aminonicotine amide of the formula (I): , to methods of their synthesis and a pharmaceutical composition based on thereof inhibiting activity of receptor tyrosine kinase vessel endothelial growth factor (VEGF) and to corresponding method for inhibition of activity of VEGF-receptor tyrosine kinase. It is suggested that this activity will allow offering the curative effect in proliferative diseases associated with angiogenesis, in particular, in treatment of tumors, retinopathy or age degeneration of yellow (corneal) spot.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

9 cl, 42 ex

FIELD: medicine, ophthalmology, ophthalmooncology.

SUBSTANCE: one should intravenously inject a photosensitizer photosens at 0.1-1.0 mg/kg patient's body weight. In about 48-72 h since the moment of photosens injection it is important to detect the presence of preparation's therapeutic dosage in the tumor. For this purpose one should specify the coefficient of contrast degree between the tumor and healthy adjacent tissues. Planning of photodynamic therapy should be fulfilled individually by orienting to concrete values of the coefficient of contrast degree in a concrete patient. At the value of coefficient of contrast degree being ≥4, but under 10 it is necessary to irradiate with low single dosages (ranged 80-150 mW/sq. cm) by increasing the number of seances conducted (up to 10). At the value of the above-mentioned coefficient being ≥10.0 irradiation should be carried out once or during 2-3 seances at high single radiation dosages (ranged 150-800 mW/sq. cm). The innovation enables to optimize therapy in patients with intraocular tumors.

EFFECT: higher efficiency of therapy.

2 ex

FIELD: organic chemistry, medicine, oncology.

SUBSTANCE: invention relates to using dicarboxylic acids of the general formula (2): R-CONH-OH (2) wherein R means -HO-HNCO, -HO-NHCOCH-(OH)CH(OH), -HOOC-CH2CH2, -HO-OCCH=CH as inhibitors of metastasis and agents enhancing chemotherapeutic activity of antitumor preparations. Also, invention relates to a method for enhancing effectiveness of cytostatics in carrying out cytostatic chemotherapy of tumors. Method is carried out by using cytostatics in combination with derivatives of dicarboxylic acids of the formula (2). Also, invention relates to a method for inhibition of metastasizing process. Method is carried out by effect of the known cytostatics and derivatives of dicarboxylic acid of the formula (2) on tumor. Proposed substances provide enhancing antitumor and anti-metastatic activity of known cytostatics based on using derivatives of dicarboxylic acids.

EFFECT: valuable medicinal properties of agents and preparations, enhanced effectiveness of metastasizing inhibition.

4 cl, 4 dwg, 7 ex

FIELD: medicine.

SUBSTANCE: method involves impregnating sterile gauze napkins with Tactivin solution, in the amount of 100 mcg per each napkin, and imposing it on mammary gland. Then, variable magnetic field treatment is applied. When applying the procedure one day and one hour prior to operation the napkins are arranged on both sides with respect to nodular formation, 3 cm far from it. When carrying out the procedure at the third day after operation, napkins are placed directly onto zone under operation.

EFFECT: reduced risk of complications in postoperative period.

FIELD: medicine.

SUBSTANCE: method involves concurrently giving Cyclopheron and Licopid under immunogram control at traditional doses and courses. Thus, if even one of parameters of immunogram, carried out in 2 months after treatment, does not reach normative limits, additional Licopid administration is applied under traditional preventive scheme.

EFFECT: enhanced effectiveness of immunocorrective and immononormalizing treatment; reduced risk of complications.

FIELD: medicine, surgery.

SUBSTANCE: during the period of 5 d before operation and 10 d after it is important to prescribe the intake of ADP-37 preparation for patients at the dosage of 6 capsules/d. The innovation enables to decrease traumatism of prophylactic procedures carried out at pre- and post-surgical stages.

EFFECT: higher efficiency of prophylaxis.

2 ex

FIELD: medicine, stomatology, in particular agents for oral cavity care.

SUBSTANCE: claimed agent contains natural-origin active substance such as amberant; target additives such as silica, glycerol and/or sorbitol, sodium carboxymethylcellulise, sodium lauryl sulfate, sweetener, water as carrier. According to set of used target additives and appropriate carrier agent may be produced in various forms, namely in form of gel transparent tooth-paste gel non-transparent tooth-paste; chalky tooth-paste, liquid rinse, resorbable films. Target additives and carrier agent provide stability, convenient application and effective action of produced forms. Healthy agent of present invention has sufficient anti-inflammatory effect, effectively scales dental plaque, and removes angiostaxis.

EFFECT: agent for treatment and/or prophylaxis of parodontum diseases having no contraindications and allergic response.

5 cl, 5 tbl

FIELD: medicine, stomatology, in particular agents for oral cavity care.

SUBSTANCE: claimed agent contains natural-origin active substance such as amberant; target additives such as silica, glycerol and/or sorbitol, sodium carboxymethylcellulise, sodium lauryl sulfate, sweetener, water as carrier. According to set of used target additives and appropriate carrier agent may be produced in various forms, namely in form of gel transparent tooth-paste gel non-transparent tooth-paste; chalky tooth-paste, liquid rinse, resorbable films. Target additives and carrier agent provide stability, convenient application and effective action of produced forms. Healthy agent of present invention has sufficient anti-inflammatory effect, effectively scales dental plaque, and removes angiostaxis.

EFFECT: agent for treatment and/or prophylaxis of parodontum diseases having no contraindications and allergic response.

5 cl, 5 tbl

FIELD: medicine, stomatology, in particular agents for oral cavity care.

SUBSTANCE: claimed agent contains natural-origin active substance such as amberant; target additives such as silica, glycerol and/or sorbitol, sodium carboxymethylcellulise, sodium lauryl sulfate, sweetener, water as carrier. According to set of used target additives and appropriate carrier agent may be produced in various forms, namely in form of gel transparent tooth-paste gel non-transparent tooth-paste; chalky tooth-paste, liquid rinse, resorbable films. Target additives and carrier agent provide stability, convenient application and effective action of produced forms. Healthy agent of present invention has sufficient anti-inflammatory effect, effectively scales dental plaque, and removes angiostaxis.

EFFECT: agent for treatment and/or prophylaxis of parodontum diseases having no contraindications and allergic response.

5 cl, 5 tbl

FIELD: medicine, stomatology, in particular agents for oral cavity care.

SUBSTANCE: claimed agent contains natural-origin active substance such as amberant; target additives such as silica, glycerol and/or sorbitol, sodium carboxymethylcellulise, sodium lauryl sulfate, sweetener, water as carrier. According to set of used target additives and appropriate carrier agent may be produced in various forms, namely in form of gel transparent tooth-paste gel non-transparent tooth-paste; chalky tooth-paste, liquid rinse, resorbable films. Target additives and carrier agent provide stability, convenient application and effective action of produced forms. Healthy agent of present invention has sufficient anti-inflammatory effect, effectively scales dental plaque, and removes angiostaxis.

EFFECT: agent for treatment and/or prophylaxis of parodontum diseases having no contraindications and allergic response.

5 cl, 5 tbl

FIELD: medicine, stomatology, in particular agents for oral cavity care.

SUBSTANCE: claimed agent contains natural-origin active substance such as amberant; target additives such as silica, glycerol and/or sorbitol, sodium carboxymethylcellulise, sodium lauryl sulfate, sweetener, water as carrier. According to set of used target additives and appropriate carrier agent may be produced in various forms, namely in form of gel transparent tooth-paste gel non-transparent tooth-paste; chalky tooth-paste, liquid rinse, resorbable films. Target additives and carrier agent provide stability, convenient application and effective action of produced forms. Healthy agent of present invention has sufficient anti-inflammatory effect, effectively scales dental plaque, and removes angiostaxis.

EFFECT: agent for treatment and/or prophylaxis of parodontum diseases having no contraindications and allergic response.

5 cl, 5 tbl

FIELD: medicine, stomatology, in particular agents for oral cavity care.

SUBSTANCE: claimed agent contains natural-origin active substance such as amberant; target additives such as silica, glycerol and/or sorbitol, sodium carboxymethylcellulise, sodium lauryl sulfate, sweetener, water as carrier. According to set of used target additives and appropriate carrier agent may be produced in various forms, namely in form of gel transparent tooth-paste gel non-transparent tooth-paste; chalky tooth-paste, liquid rinse, resorbable films. Target additives and carrier agent provide stability, convenient application and effective action of produced forms. Healthy agent of present invention has sufficient anti-inflammatory effect, effectively scales dental plaque, and removes angiostaxis.

EFFECT: agent for treatment and/or prophylaxis of parodontum diseases having no contraindications and allergic response.

5 cl, 5 tbl

FIELD: cosmetology, dermatology, in particular remedial, prophylaxis, and/or cosmetic preparations.

SUBSTANCE: claimed emulsion represents water-in-oil invert emulsion wherein as stabilizer and simultaneously source of bioactive substances it contains Sal carolinum factitium in concentration of 0,1-0,5 % and concentration of organosilicones is 20-95 %. Method for production of said emulsion includes simultaneous blending of all components, followed by generous mixing in ultrahigh-speed mixer and homogenization in homogenizer under pressure of 600-800 atm.

EFFECT: emulsion of high stability and improved application performances.

2 cl, 15 ex

FIELD: cosmetology, dermatology, in particular remedial, prophylaxis, and/or cosmetic preparations.

SUBSTANCE: claimed emulsion represents water-in-oil invert emulsion wherein as stabilizer and simultaneously source of bioactive substances it contains Sal carolinum factitium in concentration of 0,1-0,5 % and concentration of organosilicones is 20-95 %. Method for production of said emulsion includes simultaneous blending of all components, followed by generous mixing in ultrahigh-speed mixer and homogenization in homogenizer under pressure of 600-800 atm.

EFFECT: emulsion of high stability and improved application performances.

2 cl, 15 ex

FIELD: medicine.

SUBSTANCE: the present innovation deals with the product for teeth whitening that contains a strip of material its size sufficient to cover anterior surface of one of several teeth and a soft cloth being adjacent to anterior dental surface. Thin layer of composition for teeth whitening is located on the above-mentioned strip. Composition for teeth whitening contains peroxide active substance at concentration being above approximately 7.5% weight of composition for teeth whitening, and composition for teeth whitening has got peroxide density being less than approximately 1.3 mg/sq. cm. The suggested product for teeth whitening is of higher efficiency against those applied nowadays flexible strip-based products for teeth whitening along with maintaining acceptable tolerance of soft tissues (the degree up to which a user has got feelings often described as burning).

EFFECT: higher efficiency.

20 cl, 15 dwg

FIELD: medicine, surgery.

SUBSTANCE: during the period of 5 d before operation and 10 d after it is important to prescribe the intake of ADP-37 preparation for patients at the dosage of 6 capsules/d. The innovation enables to decrease traumatism of prophylactic procedures carried out at pre- and post-surgical stages.

EFFECT: higher efficiency of prophylaxis.

2 ex

Up!