Sodium arsenite-containing pharmaceutical composition for treatment of malignant tumor

FIELD: medicine, oncology, chemical-pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to a pharmaceutical composition used in treatment of solid tumors, for example, large intestine tumor, stomach tumor, breast tumor, ovary tumor, prostate tumor and kidney tumor, and these tumors are sensitive to effect of sodium meta-arsenite. Proposed composition comprises meta-arsenite (AsO2-) salt taken in the pharmaceutically effective dose and pharmaceutically acceptable accessory agent. Also, invention relates to using this composition in treatment of solid tumors in a patient, and to a method for treatment of solid tumor showing sensitivity to effect of sodium meta-arsenite. Invention provides enhancing effectiveness in treatment of solid tumors.

EFFECT: valuable medicinal property of pharmaceutical composition, enhanced effectiveness of treatment.

13 cl, 1 tbl

 

The present invention relates to pharmaceutical compositions for the treatment of malignant tumors, which includes arsenic.

Pharmaceutical compositions containing arsenic, a known cancer therapy. For example, in the review S.Waxman and others in The Oncologist 6 (suppl.2), 2001, SS-10 describes the use of the disulphide of arsenic trisulde arsenic trioxide and arsenic in the above-mentioned composition comprising the salt of meta-arsenite (AsO2-and pharmaceutically acceptable auxiliary agent.

Due to their inherent toxicity and the emergence of good alternatives of interest to arsenic compounds still remained low.

The basis of the invention was based on the task to provide a pharmaceutical composition for the treatment of malignant tumors, which allows to treat solid tumors. The pharmaceutical composition can be used for the treatment of solid tumors for which there is no universally accepted treatment, or as an alternative or additional treatment of solid tumors.

In response to the latter, the pharmaceutical composition of the present invention differs in that it is a pharmaceutical composition for the treatment of solid malignant tumor selected from the group represented by the tumor of the colon, stomach tumor, tumor m is Nochnoi gland, tumor of the ovary, prostate cancer and kidney tumors; this composition includes a salt of meta-arsenite (AsO2-and pharmaceutically acceptable auxiliary agent.

It was found that certain types of tumors are unusually sensitive to salt meta-arsenite. In salt counter-ion meta-arsenite can be any pharmaceutically acceptable counter-ion.

In the above article Waxman cited article G.S. Tarnowski and others in Cancer Research, 26, 1966, cc.181-206, where it was studied the effect of 14 different anticancer chemical compounds in relation to the 8 types of tumors. The potassium arsenite had effect only on the growth of ascitic Ehrlich tumor. Regarding tumors of this type it is noted that it is more sensitive in ascitic form than in solid. This underlines the surprising discovery of the present invention.

In a preferred embodiment of the present invention apply salt of alkali or alkaline earth metal. In a more preferred embodiment of the present invention the salt is a sodium salt.

These salts dissolve easily and quickly respond to their antitumor activity.

The invention also relates to the use of salts of meta-arsenite (AsO2-to create a pharmaceutical composition intended for lecheniyena malignant tumors, selected from the group consisting of tumors of the colon, cancer of the stomach, mammary gland tumors, tumors of the ovary, prostate tumors and tumors of the kidney.

It was found that the solid forms such tumors belonging to the group consisting of tumors of the colon, breast tumors, prostate tumors and kidney tumors, especially sensitive.

The present invention also relates to a method of treatment of humans suffering from a solid malignant tumor selected from the group consisting of tumors of the colon, cancer of the stomach, mammary gland tumors, tumors of the ovary, prostate tumors and kidney tumors, pharmaceutically effective dose of a salt of meta-arsenite (AsO2-).

For a better understanding of the invention provides an example that illustrates but does not limit described by the present invention.

Example

Various tumor cells were grown at 37°C in humidified atmosphere (95% air, 5% CO2in monolayer cultures in RPMI medium 1640 with phenol red (firm Life Technologies, Karlsruhe, Germany) and with the addition of fetal calf serum. Cells were treated with trypsin and perseval weekly.

The study of cytotoxicity

For research antiproliferative activity of the studied compounds were used a modified method with IP is the use of iodide of propidium (based on the method W.A.Dengler and other in Anti-Cancer Drugs, 6, 1995, cc.552-532. In brief, the method consists in the following. Cells were harvested in exponential growth phase culture medium RPMI 1640 with the addition of 10% fetal calf serum, were treated with trypsin, counted and placed in 96-well plates to micrometrology with flat-bottomed wells (140 μl of cell suspension, 8×10 cells/ml). After 24 h of incubation to achieve cells exponential growth in the wells was added to 10 μl of culture medium (6 test holes on the plate) or culture medium containing the test drug. Each concentration of drug was investigated in a three-fold repetition. After 4 days of incubation the culture medium was replaced with an aqueous solution of iodide of propidium (6 µg/ml). Tablets for micrometrology kept at -18°C for 24 h, which resulted in total cell death. After thawing of the plates was measured by fluorescence using a Millipore Cytofluor 2350 reader for microplankton (excitation 530 nm, emission 620 nm), to determine the total number of cells. The analysis included untreated and positive controls (5-FU and vindesine).

Growth inhibition was expressed with regard to the experience/control × 100 (or About/To%). Values IR50and IR70was calculated by comparing the concentration of the substance in relation to the number to ATOC. Average values IR50and IR70was calculated by the formula:

where x = a definite line of tumor cells and n = total number of investigated cell lines. If IR50and IR70cannot be installed within the study area doses for counting used the lowest or the highest studied concentration.

Tests were considered significant only if the positive control (5-FU) resulted in inhibition of tumor growth About/To<30% and solvent-treated control cells had fluorescence intensity>500 units.

Results

The results are summarized in table, which shows that, in particular, tumor cell line, such as a stomach tumor, a tumor of the ovaries and, in particular, prostate cancer, tumor, breast cancer, kidney cancer and colon were sensitive to compounds meta-arsenite. In comparison with them promyelocyte leukemia, which is known to respond to arsenic trioxide, showed the value IR70=6,82 µg/ml Therefore, tumor cells, to which pertains the present invention, almost 2-20 times more sensitive to the connection meta-arsenite.

TumorCell lineIR70 (µg/ml)
ColonDLD10,48
StomachGXF251Lis 3.08
Breast cancerMXAF401NL0,32
OvarianOVCAR33,02
ProstateRS0,85
KidneyRXF486L0,63

1. Pharmaceutical composition for treatment of solid malignant tumor selected from the group consisting of tumors of the colon, cancer of the stomach, mammary gland tumors, tumors of the ovary, prostate tumors and kidney tumors, including meta-arsenite (AsO2-) sodium and pharmaceutically acceptable auxiliary substance.

2. Meta-arsenite (AsO2-) sodium to obtain a pharmaceutical composition for the treatment of solid malignant tumor selected from the group consisting of tumors of the colon, cancer of the stomach, mammary gland tumors, tumors of the ovary, prostate tumors and tumors of the kidney.

3. The method of treatment of a person suffering from a solid malignant tumor selected from the group consisting of tumors of the colon, cancer of the stomach, mammary gland tumors, tumors of the ovary, prostate tumors and kidney tumors, providing use is of pharmaceutically effective doses of metaarsenite (AsO 2-) sodium.

4. The method according to claim 3, in which the tumor is a tumor of the colon.

5. The method according to claim 3, in which the tumor is a tumor of the stomach.

6. The method according to claim 3, in which the tumor is a tumor of the breast.

7. The method according to claim 3, in which the tumor is a tumor of the ovary.

8. The method according to claim 3, in which the tumor is a prostate tumor.

9. The method according to claim 3, in which the tumor is a tumor of the kidney.

10. Pharmaceutical composition for treatment of solid malignant tumors, despite the fact that the composition includes metaarsenite (AsO2-) sodium and pharmaceutically acceptable auxiliary substance.

11. The method of treatment of a patient suffering from a solid malignant tumor, involving the administration to a patient pharmaceutically effective dose of a composition comprising metaarsenite (AsO2-) sodium.

12. Pharmaceutical composition for treatment of solid malignant tumor selected from the group consisting of tumors of the colon, cancer of the stomach, mammary gland tumors, tumors of the ovary, prostate tumors and kidney tumors, despite the fact that the said composition essentially includes metaarsenite (AsO2-) sodium and pharmaceutically acceptable auxiliary materials is inoe substance.

13. The method of treatment of a patient suffering from a solid malignant tumor, involving the administration to a patient pharmaceutically effective dose of a composition essentially containing metaarsenite (AsO2-) sodium.



 

Same patents:

FIELD: pharmaceutical industry.

SUBSTANCE: invention relates to application of 2-hydroxyoleic acid and analogs thereof in production of drugs useful in diseases associated with G-proteins and mediated by membrane structure transition from lamellar structure to hexagonal one. Discribed is application of compounds of general formula I: COOH-CHR-(CH2)m-CH=-CH-(CH2)n-CH3, wherein R represents OH or NH2; m and n = 1-6 in production of drugs useful in treatment of cancer; as well as compounds of formula I, wherein R represents H, OH, NH2 or CH3, useful in treatment of hypertension and obesity.

EFFECT: drugs with increased effectiveness.

8 cl, 11 dwg, 3 tbl, 11 ex

FIELD: biopharmacology and medicine.

SUBSTANCE: disclosed is method for production of mononuclear blood cells, namely activated lymphocytes (ACL) and dendrite cells (DC). Claimed method includes a) isolation of mononuclear leucocytes (MNL) from blood and marrow of patient suffering from malignant neoplasm, or infective disease, or immunodeficient condition; d) incubation of isolated mononuclear lymphocytes in cultural medium; c) separation of MNL cultural bottles adhering to plastic and non-adhering thereto.; d) treatment of adhering MNL with growth factors to produce dendrite cells therefrom; e) treatment of DC with lysates from patient tumor; f) cultivation of non-adhered lymphocytes with interleukine-2 to produce ACL-cells. Also disclosed is method for treatment and prophylaxis malignant and infective diseases and immunodeficient conditions in patients by combined application of ACL-cells and dendrite cells.

EFFECT: new method for treatment and prophylaxis of malignant, infective diseases and immunodeficient conditions.

3 cl

FIELD: medicine, oncology.

SUBSTANCE: invention relates to using 2-chloroethylphosphonic acid sodium salt as an antitumor agent that displays enhanced effectiveness in treatment of different tumors, reduced toxicity and less adverse effects in comparison with many other antitumor agents.

EFFECT: valuable medicinal properties of agent.

4 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to biologically active substances displaying perspective using medicine, veterinary science, cosmetics and dairy industry. Agent comprises polyoxyarylene ester and hydroquinone in their ratio from 83:17 to 5:95, respectively. Agent comprises 2-(1-oxy-4-hydroxyphenylene)benzoquinone or 4-hydroxyphenylene-2,4-dioxybenzene as a polyoxyarylene ester. Method for preparing agent involves mixing polyoxyarylene ester with hydroquinone and wearing the prepared mixture up to formation of the uniform mass. Invention provides creature of a novel agent of the broad spectrum of effect, namely: antioxidant, antihypoxic, antitumor, radioprotective, immunostimulating and biocide effects.

EFFECT: valuable properties of agent.

7 cl, 20 tbl, 16 ex

FIELD: organic chemistry, pharmaceuticals.

SUBSTANCE: invention relates to compounds of general formula I and pharmaceutically acceptable salt thereof, wherein R1, R3, R4, R5, and R10 are independently H, halogen, C1-C4-alkyl, etc.; R2 is H, halogen, NO2, etc.; R6 is H, C1-C6-alkyl, C1-C6-alkoxy-substituted C1-C4-alkyl, etc.; R7 is H, C1-C4-alkyl or C2-C4-alkenyl, optionally substituted with halogen; R8 and R9 are H, R11 and R12; meanings of the rest substituents are as define in specification.

EFFECT: new compounds with value biological properties and useful as drug having activity in relates to progesterone receptor.

15 cl, 3 tbl, 80 ex

FIELD: organic chemistry, pharmaceuticals.

SUBSTANCE: invention relates to compounds of general formula I , wherein Z is -NH-; X is radical; E is phenyl optionally monosubstituted with halogen; T is -O(CH2)m-, -S(CH2)m-; L is phenyl etc.; G1, G2, G3, and G4 are independently hydrogen, C1-C6-alkoxy, R2NH; R7 is -J; M is >NR6; W is direct bond; Het is pyrrolidine optionally monosubstituted at R6, hydroxy; each R6 is independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl; R2 is ; each R3 is , etc; J are independently hydrogen, chlorine, bromine or iodine; a = 0 or 1; n = 0 or 1; M = 1; p = 2-4; r = 1-4; u = 4 and pharmaceutically acceptable salts thereof. Also disclosed are methods for treatment, growth inhibiting or combating of neoplasm and other disorders and pharmaceutical composition having activity of EGF-R and HER2 kinase inhibitors, as well as method for production of abovementioned compounds.

EFFECT: new compounds with useful biological properties.

31 cl, 3 tbl, 10 ex

FIELD: medicine, chemical-pharmaceutical industry.

SUBSTANCE: agent possessing antioxidant, antitumor, anti-inflammatory, antibacterial, hypotensive, immunomodulating and adaptogenic effect comprises complex of active substances isolated from aqueous extract of peach leaves and involving flavonoids, tannic substances, coumarins, phenylcarboxylic acids, phenolglycosides, saponins, complex of active substances isolated from plant eyebright (Euphrasia) aqueous extract and involving flavonoids, phenolcarboxylic acids, steroid saponins, glycosides, carotinoids wherein the ratio of complexes is 1:1 or 1;2, or 2;1, and also biologically active components chosen from group: glucose, lactose, ascorbic acid, vitamins A and B, vegetable cellulose and accessory substance taken in the definite ratio. Agent is designated for oral using as drops, powders, tablets, lozenges and capsules. Agent doesn't possess toxicity, mutagenic, embryotoxic and teratogenic effects. Invention can be used in treatment and prophylaxis of inflammatory diseases being among them eyes, tumor processes, cardiovascular system diseases, secondary immunodeficient states and as a general tonic agent. Invention expands spectrum of effect the preparation, provides the development of a novel medicinal preparation based on substances of vegetable origin and possessing antioxidant, antitumor, anti-inflammatory, hypotensive, immunomodulating and adaptogenic effect by combination of two aqueous purified concentrated extracts from peach leaves and plant eyebright (Euphrasia).

EFFECT: improved, enhanced and valuable medicinal effects of agent.

3 cl, 5 tbl, 4 ex

FIELD: medicine, oncology.

SUBSTANCE: the second fraction of Dorogov's antiseptic stimulant (DAS-f2) in 5%-novocain solution at 1:5 ratio should be dissolved with water at 1:200. The preparation should be introduced perorally at the dosage of 0.1-0.5·10-3 mg/kg body weight once daily in the morning about 20-30 min before meals. Moreover, the intake of the preparation suggested should be started from the lowest limit of dosages; range. The prophylaxis should be carried out before, during and after chemotherapy. The innovation in question enables to increase the reserve blood alkalinity, create the conditions for neutralization of acidic products and decrease unfavorable side effects of chemotherapy that leads to cheaper cost of therapy conducted.

EFFECT: higher accuracy and efficiency of prophylaxis.

1 cl, 4 ex, 4 tbl

FIELD: medicine, oncology, biology, pharmacy.

SUBSTANCE: the claimed invention involves using inhibitors. Invention relates to using cyclopamine and its pharmaceutically acceptable salts for preparing a pharmaceutical agent for induction of apoptosis of tumor cells that use transfer of Hedgehog/Smoothened signal for prophylaxis of apoptosis. Cyclopamine causes apoptosis by not genotoxic mechanism and therefore it distinguishes from radiation therapy and most of the modern anticancer chemotherapeutic agent that effect inducing DNA damages. These new effects early not achieved in cancer chemotherapy provide using cyclopamine as to be very desirable in cancer therapy, in treatment of BCC (basal cell carcinoma) and other tumors that use way of signal transduction of hedgehog/smoothened protein for proliferation and prophylaxis of apoptosis.

EFFECT: valuable medicinal properties of cyclopamine.

6 cl, 1 tbl, dwg 7

FIELD: chemistry of polymers, medicine.

SUBSTANCE: invention describes a micelle-formed composition including hydrophobic core covered by hydrophilic envelope and a therapeutic agent as a component of micelle said wherein hydrophobic core is chosen from group consisting of poly-(ortho-ester), polyanhydride, pseudopoly-(amino acid) prepared from tyrosine, polyphosphazene or poly-(β-benzyl-L-aspartate) and their combinations, or polyester chosen from group consisting of poly-(glycolic acid), poly-(lactic acid), poly-(D-lactic acid), poly-(D,L)-lactic acid), copolymers of lactide/glycolide, polycaprolactone and their derivatives and wherein hydrophilic envelope represents poly-(N-vinyl-2-pyrrolidone). Indicated composition can be easily dispersed or dissolved repeatedly after addition of water or aqueous solution to a form obtained after sublimation drying the indicated micelle-formed composition. Using hydrophilic envelope allows avoiding aggregation of micelles. Also, invention provides simplifying stages in preparing micelles.

EFFECT: improved and simplified preparing method.

10 cl, 4 tbl, 1 ex

FIELD: medicine, oncology, chemical-pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to a pharmaceutical composition used in treatment of solid tumors, for example, large intestine tumor, stomach tumor, breast tumor, ovary tumor, prostate tumor and kidney tumor, and these tumors are sensitive to effect of sodium meta-arsenite. Proposed composition comprises meta-arsenite (AsO2-) salt taken in the pharmaceutically effective dose and pharmaceutically acceptable accessory agent. Also, invention relates to using this composition in treatment of solid tumors in a patient, and to a method for treatment of solid tumor showing sensitivity to effect of sodium meta-arsenite. Invention provides enhancing effectiveness in treatment of solid tumors.

EFFECT: valuable medicinal property of pharmaceutical composition, enhanced effectiveness of treatment.

13 cl, 1 tbl

FIELD: medicine.

SUBSTANCE: invention belongs to veterinary. "ЭВЛ-Se КОМПОЗИЦИЯ" is administered to whole flock with free drinking in water once a day during 10 days in single dose 0.02 ml per capita.

EFFECT: method improves hens' insemination efficiency, hatchability and survival rate of poults.

2 tbl, 2 ex

FIELD: agriculture.

SUBSTANCE: invention refers to the sphere of poultry keeping. Method includes application of preparation "EVL-Se COMPOSITION" solution, which is administered to chickens once by group method through unrestricted bottle-feeding with water once per day for 10-20 days in a single dose of 0.02 ml per head.

EFFECT: application of method makes it possible to reduce losses, to increase weight gains, to improve immune response in vaccinations.

4 tbl, 2 ex

FIELD: medicine, veterinary science.

SUBSTANCE: method involves application of EVL-Se COMPOSITION solution, which is introduced to animal inside orally by a group method with water (milk or imitation milk) once a day for 10 days in single dosage 1.0 ml per a head.

EFFECT: application of the method allows reducing disease incidence and recovery time, increasing average daily weight gains, ensures more rapid microflora formation and has no by-effects.

2 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed group of inventions relates to medicine, namely to oncology, and can be used for treatment of metastatic neoplastic disease. Claimed is treatment method which includes introduction of therapeutically efficient quantity of sodium meta-arsenite. Additionally introduction of other chemotherapeutical substance is carried out. Claimed is composition, containing sodium meta-arsenite. Claimed is set for inhibition of abnormal cell growth, which includes therapeutically efficient quantity of pharmaceutical composition, containing sodium meta-arsenite, and other chemotherapeutical substance.

EFFECT: group of inventions ensures possibility of metastatic neoplastic disease treatment with alternative compound with anticancer activity, as well as treatment safety.

2 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmacy, namely to creation of complexes for treatment of chronic fatigue syndrome (CFS). Four naturopathic complexes for CFS treatment contain herbal mixtures and homeopathic medications.

EFFECT: intake of naturopathic complexes ensures high therapeutic effect throughout the treatment without negative side effects and disease recurrences.

5 cl, 4 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of veterinary. Method consists in the following: applied is "EVL-Se-COMPOSITION" solution which is introduced into animals by group method with water one time per day in single dose 0.05 ml during 10 days, 5 days before weaning and 5 days after weaning.

EFFECT: application of claimed method makes it possible to realise prophylaxis of gastrointestinal diseases, increase average daily weight gain, does not cause side effects.

3 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry and represents the use of sodium metaarsenite in preparing an oral dosage form of a pharmaceutical composition for inflammation treatment in a mammal.

EFFECT: use of sodium metaarsenite in preparing the oral dosage form of the pharmaceutical composition for inflammation treatment in a mammal.

6 cl, 7 ex, 1 dwg

FIELD: medicine.

SUBSTANCE: invention refers to veterinary science and aims at treating a gastrointestinal pathology of non-infectious aethiology in calves. Acupuncture points are exposed to a remote therapeutic massage electrode No.1 of DiaDENS-PC apparatus in the 'Therapy' regimen with alternating frequencies of 77 Hz and 10 Hz on the acupuncture points located along the median sagittal line between the spinous processes of the thoracic spine, for 5 minutes, followed by introducing the medicine 'Liarsin' in a dose of 0.5 ml in the area of a biologically active point located between the spinous processes of the last thoracic and first lumbar vertebrae.

EFFECT: method has the high therapeutic efficacy and eliminates local allergic reactions, causes no anxiety in an animal.

1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a kit for lung cancer cell sensitisation to cisplatin. The declared kit comprises a first composition containing a therapeutically effective amount of sodium metaarsenite, and a second composition containing a therapeutically effective amount of cisplatin. Also, the invention refers to using the therapeutically effective amount of sodium metaarsenite for lung cancer cell sensitisation in a patient treated with cisplatin.

EFFECT: invention provides increasing the therapeutic effectiveness with a reduced risk of side effects.

10 cl, 4 tbl, 3 dwg, 1 ex

Up!