Urease application for malignant cells inhibition

FIELD: medicine; pharmacology.

SUBSTANCE: invention can be applied for tumours treatment and diagnostics. This composition contains urease enzyme and target fragment directly conjugated with urease, and optionally weak-base antitumor compound.

EFFECT: improved enzyme delivery to tumour cells is provided as composition is injected.

6 cl, 6 ex, 3 tbl, 5 dwg

 

The text descriptions are given in facsimile form.

1. The pharmaceutical composition intended for use in the inhibition of growth of tumor cells in the mammal is a human subject, comprising the enzyme urease, the target fragment, directly conjugated with the indicated enzyme urease selected from the group consisting of antibodies to anti-tumor antigen antibody to anti-hCG and ligand capable of specific binding to the surface receptors of tumor cells, and the specified target fragment can effectively enhance the delivery of the enzyme to the tumor cells upon introduction of the composition to a subject, and optionally, a weakly basic anticancer compound, the efficiency of which decreases in a gradient higher intracellular/lower extracellular pH in solid tumors.

2. The composition according to claim 1, comprising a hybrid protein consisting of the target fragment and farms the NTA urease.

3. The composition according to claim 1, in which the urease is a plant or bacterial urease.

4. The composition according to claim 1, in which the anticancer compound selected from the group consisting of doxorubicin, daunorubicin, mitoxantrone, epirubicin, mitomycin, bleomycin, Vinca alkaloids (Vinca), such as vinblastine and vincristine, alkylating agents such as cyclophosphamide and mechlorethamine hydrochloride, and antitumor derivatives of purine and pyrimidine.

5. The use of a composition according to claim 1 in the manufacture of a medicinal product for the treatment or diagnosis of a tumor in the mammal subject.

6. The use according to claim 5, in which the antitumor compound selected from the group consisting of doxorubicin, daunorubicin, mitoxantrone, epirubicin, mitomycin, bleomycin, Vinca alkaloids (Vinca), such as vinblastine and vincristine, alkylating agents such as cyclophosphamide and mechlorethamine hydrochloride, and antitumor derivatives of purine and pyrimidine.



 

Same patents:

FIELD: pharmacology.

SUBSTANCE: refers to application of compounds of common formula 1 for production of medicinal agent for inhibition of cdc25-phosphatases and/or CD45- phosphatase, medicinal agent for inhibition of cdc25-phosphatases or CD45- phosphatase, pharmaceutical formulations for inhibition of cdc25-phosphatases or CD45-phosphatase; invention also refers to compounds of formula 1 and provides high-degree inhibition of cdc25-phosphatases and/or CD45- phosphatase.

EFFECT: high degree of inhibition.

22 cl, 1 dwg, 3 tbl, 131 ex

FIELD: medicine; immunotherapy.

SUBSTANCE: indications for adjuvant immunotherapy of primary and metastatic malignant unresectable liver tumours are determined. For this purpose within surgical process incision biopsy of tumour and healthy liver tissue is performed. Then immediately after operation lymphocytes of tumour tissue, healthy tissue and peripheral blood by markers CD4+, CD8+, CD16+, CD56+ are immunophenotyped. In case lymphocyte marker levels CD4+, CD8+ and NK-cells levels CD16+ and CD56+ are lowered more than 10% for tumour tissue and peripheral blood in comparison with healthy tissue and peripheral blood, postoperative intraportal prolonged introduction of rhoncoleukin is indicated.

EFFECT: provides accurate direct evaluation of local immunity condition; enables to improve treatment results.

12 dwg, 4 tbl, 1 ex

FIELD: medicine; immunotherapy.

SUBSTANCE: indications for adjuvant immunotherapy of primary and metastatic malignant unresectable liver tumours are determined. For this purpose within surgical process incision biopsy of tumour and healthy liver tissue is performed. Then immediately after operation lymphocytes of tumour tissue, healthy tissue and peripheral blood by markers CD4+, CD8+, CD16+, CD56+ are immunophenotyped. In case lymphocyte marker levels CD4+, CD8+ and NK-cells levels CD16+ and CD56+ are lowered more than 10% for tumour tissue and peripheral blood in comparison with healthy tissue and peripheral blood, postoperative intraportal prolonged introduction of rhoncoleukin is indicated.

EFFECT: provides accurate direct evaluation of local immunity condition; enables to improve treatment results.

12 dwg, 4 tbl, 1 ex

FIELD: medicine; carcinology.

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EFFECT: reduced tumour mass, provided epithelisation of skin ulcer, prevented by-effect toxicity of chemotherapy and metastases.

2 dwg, 1 ex

FIELD: medicine; carcinology.

SUBSTANCE: method includes 2-4 presurgical chemotherapy courses within 14 days implying intravenous injections of adriamycin of daily dose 30 mg/m in 1st and 8th day and intramuscular injections of cyclophosphan of daily dose 100 mg/m2 during 14 days. Intervals between courses are 28 days. In addition course implies oral introduction of xeloda of daily dose 2000 mg/m2 twice a day. Method ensures reduction of total chemotherapy toxicity owing to selective activation of medicines directly inside of tumour tissue, and makes possible to perform organ preserving surgical treatment.

EFFECT: reduction of total chemotherapy toxicity; organ preserving surgical treatment.

3 ex

FIELD: medicine; carcinology.

SUBSTANCE: method includes anti-oxidant therapy implying preoperative intramuscular injection of tocopherol acetate of dose 300 mg and intravenous injection of mexidol of dose 200 mg. Then during operation 45-50 minutes before intraoperative radiation therapy (IORT) mexidol is reinjected dosed 400 mg, and within antienzyme therapy gordox is introduced dosed 100 000 units. Within 3-7 days after operation tocopherol acetate is injected dosed 300 mg every 8 hours and mexidol is injected dosed 200 mg every 6 hours. Method enables to make favourable conditions for IORT and reduce number of complications caused by hemorheologic damages and hypercoagulation.

EFFECT: making of favourable conditions for IORT and reduced number of complications caused by hemorheologic damages and hypercoagulation.

6 tbl, 2 ex

FIELD: medicine.

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EFFECT: proliferation inhibition of vein endotheliocytes and proliferation inhibition stimulated by vascular endothelial growth factor.

3 cl

FIELD: medicine; pharmaceutics.

SUBSTANCE: invention refers to medicine and pharmaceutics. Dry granulated pharmaceutical formulation containing atorvastatin or its pharmaceutically acceptable salt, in combination with at least one other active medicinal agent, method of specified formulations production, sets including such formulations, and treatment of hypercholesterolemia and/or hyperlipidemia, osteoporosis, benign prostate hyperplasia (BPG) and Alzheimer's disease by using pharmaceutical formulation in amount providing therapeutic effectiveness. Offered pharmaceutical formulation of atorvastatin is characterised with good solubility, bioavailability, dosage homogeneity, and method of atorvastatin production with low content of impurities and adequate stability.

EFFECT: production of atorvastatin formulation, characterised with good solubility, bioavailability, dosage homogeneity, and method of atorvastatin production with low content of impurities and adequate stability.

6 cl, 6 ex, 5 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to heterocyclic compounds with general formula (I) or its pharmaceutically acceptable salts; and including its any stereoisomer forms;X and Y are independently N or CR1; Z represents S, O, NR1 or CR12;every R1-R6 represent independently H or not influencing substitute, which is alkyl (C1-10), allkenyl (C2-10), alkynil (C2-10), aryl ("C'5-12), arylalkyl, arylalkenyl or arylalkynil, each of which can not obligatorily contain one or more heteroatoms selected from O, S and N and each of which can be substituted further one; or not obligatorily substituted forms of acyl, arylacyl, alkyl,alkenyl alkynyl or arylsulphonyl or their forms which contain heteroatoms in alkyl,alkynyl or aryl fragments or representing OR, SR, NR2, COOR, CONR2, where R is N or alkyl alkenyl, alkynyl, or aryl not obligatorily substituted, as defined above, when C is a substituted atom not influencing substitute can be a halohen, OOCR, NROCR, where R is H or its substitute shown above, or can equal 0; nl is equal to 0-4; n2 is equal to 0-1, where * means that CR5=CR5 can be substituted by C=C; n3 is equal to 0-4;where nl+n2+n3 exceeds or equals 2; b is equal to 0-2; where the following combinations of R-groups can be associated with cycle formation, which can saturated or unsaturated R2-R2, one R2+R3, R3+ one R4, R4+R4, one R5 + the other R5, one R5 + one R6 and R6+R6; where cycle can not be aromatic, when the cycle formation components are represented by two R5; and where, when n2 is unity 1, neither of n1 nor n3 can be equal to 0, the invention also relates to pharmaceutical composition, based on these compounds, possessing a modulating ability relative to CXCR4- and/or CCRS-receptor; to modulation method CXCR4- and/or CCRS-receptor; to method of treatment of a statec described by unusual activity CXCR4- and/or CCR5-receptor and application of the described compounds for production of pharmaceutical.

EFFECT: new compounds feature useful biological properties.

36 cl, 171 ex

FIELD: medicine; oncology.

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EFFECT: improvement of tumour therapy quality.

5 cl, 1 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine, specifically to conjugates of hydroxyalkyl starch and allergen, in which at least one hydroxyalkyl starch is covalent bonded with allergen for hyposensitisation. Conjugates HAS-allergen provide epitope profile comparable to natural, that enables to increase immunotherapy efficiency.

EFFECT: increasing of immunotherapy efficiency.

14 cl, 5 dwg

FIELD: chemistry.

SUBSTANCE: activated polymer derivatives of bicin are described as well as conjugates obtained with the aid of the derivates. Also modes of obtaining and application of the bicin derivatives are described.

EFFECT: obtaining of bicin derivatives.

24 cl, 11 dwg, 2 tbl, 21 ex

FIELD: medicine.

SUBSTANCE: composition contains: a. core composition including therapeutically active agent, swelling agent and capillary agent; b. coating composition including water-insoluble polymer and water-soluble polymer.

EFFECT: composition releases therapeutically active agent in pulse mode at preset time.

21 cl, 15 tbl, 7 ex

FIELD: medicine, polymers, pharmacy.

SUBSTANCE: invention relates to a copolymer or its pharmacologically acceptable salt that comprises the following components as elemental links forming their: (a) one or some structural elemental links describes by the formula (I) given in the invention description, and (b) one or some structural links describes by the formula (II) given in the invention description. Disposition of these structural elements represented by the formulae (I) and (II) is chosen from the following sequences: (i) sequence with alternation "head-to-head"; (ii) sequence with alternation "head-to-tail"; (iii) mixed sequence with alternation "head-to-head" and "head-to-tail"; (iv) random sequence and taking into account that the ratio between structural links of the formula (I) and structural links of the formula (II) in indicated copolymer is in the range from 10:1 to 1:10. Also, the invention relates to a copolymer or its pharmacologically acceptable salt synthesized by addition of one or some links of carboxylic acid anhydride described by the formula (III) given in the invention description that comprises as elemental links: (a) one or some structural elemental links described by the formula (I), and (b) structural link comprising carboxylic acid anhydride link described by the formula (III) for one or some reactions chosen from the group consisting of: (i) hydrolysis; (ii) ammonolysis; (iii) aminolysis, and (iv) alcoholysis. Also, invention relates to a pharmaceutical composition used for prophylaxis or treatment of osseous metabolism disorder and comprising an acceptable excipient or carrier, at least one of above indicated copolymers or their pharmaceutically acceptable salts and at least one protein representing osteoclastogenesis inhibition factor (OCIF) or its analogue, or variant. Also, invention relates to a modifying agent comprising above said copolymers, to a complex between of one of above said copolymers and protein or its analogue, or variant, to a pharmaceutical composition comprising this complex. Also, invention relates to a method for time prolongation when OCIF is retained in blood stream after intake by a patient a complex between protein and at least one of above said copolymers. Also, invention relates to a method for treatment or prophylaxis of disorders of osseous metabolism involving intake by a patient the effective amount of complex comprising complex including OCIF or its analogue or variant and bound with at least one of the claimed copolymers. Also, invention relates to use of the complex comprising OCIF bound with at least one of the claimed copolymers designated for preparing a drug designated for prophylaxis or treatment of disorder of osseous metabolism and showing sensitivity to the protein effect. Modifying the protein, namely OCIF, by the claimed copolymers results to formation of complex possessing uniform properties being especially characterizing by reduced formation of disordered structure cross-linked with protein, improved retention of the protein activity and the excellent retaining protein in blood after intake of the indicated complex.

EFFECT: improved and valuable medicinal and pharmaceutical properties of agents.

110 cl, 13 tbl, 3 dwg, 40 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to drugs and concerns sustained-release oral compositions. Agent comprises micelle-forming water-soluble main drug showing a positive charge at physiological pH value, polymer showing an opposite charge chosen from group consisting of polyacrylic acid, carboxymethylcellulose, xanthane gum, hellane gum, guara gum, dextran-sulfate and carragheenan, polyethylene oxide and if necessary a hydrophilic base. Also, invention proposes a method for sustained-release of micelle-forming drug.

EFFECT: improved and valuable medicinal and pharmaceutical properties of agent.

20 cl, 4 tbl, 24 dwg, 13 ex

FIELD: pharmacy, peptides.

SUBSTANCE: invention relates to a pharmaceutical composition that comprises an oligopeptide preparation and comprising oligopeptide of the formula (I): cyclo-(n-Arg-nGly-nAsp-nD-nE) and esterified β-cyclodextrin, and to a method for preparing an aqueous pharmaceutical preparation. Invention provides significant increasing solubility of oligopeptide and stability of the preparation for relatively prolonged time.

EFFECT: improved and valuable pharmaceutical properties of preparation.

13 cl, 6 tbl, 5 ex

FIELD: medicine, oncology, pharmacy.

SUBSTANCE: invention relates to drugs and concerns an antitumor composition for injection. Agent comprises derivative of anthracycline possessing the antitumor activity as an active component, and block-copolymer formed by derivative of polyethylene oxide and derivative of polyaspartic acid. The composition comprises additionally saccharide and a base represented by sodium hydrocarbonate, sodium hydrophosphate, sodium citrate and sodium hydroxide with pH value in the range 4-9. Also, invention proposes a composition based on block-copolymer micelles, solution of block-copolymer micelles with pH value in the range 4-9, and a solid composition for injection prepared by drying a micellar solution. Compositions show stability for a prolonged period and possess the improved capacity for repeated dissolving.

EFFECT: improved and valuable pharmaceutical properties of preparation.

15 cl, 2 tbl, 10 ex

FIELD: chemical-pharmaceutical industry and technology, pharmacy.

SUBSTANCE: invention relates to a composition in form of microemulsion concentrate designated for oral using, for example, in gelatin capsule. Proposed pharmaceutical composition provides high bioavailability of preparation. Pharmaceutical composition in form of microemulsion concentrate comprises ciclosporin and accessory components: (a) propanediol monocaprylate as a solvent; (b) monocaprylate glyceryl; (c) polyethylene glycol 40, hydrogenated castor oil and linoleic acid glycerides polyethylene glycol as surfactants; (d) 1,2-propylene glycol as a hydrophilic component; (e) alpha-tocoferol acetate as an antioxidant wherein in dilution microemulsion concentrate forms microemulsion to be easily dosed with particles size 15-20 nm.

EFFECT: improved and valuable properties of pharmaceutical composition.

1 tbl, 5 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to polyalkylene glycolic acids and their binding with therapeutically effective biopharmaceutical preparations, such as polypeptides, sugars, proteins and therapeutically active low-molecular compounds in aims for preparing therapeutically active conjugates of polyalkylene glycol with indicated biopharmaceutical preparations. Invention claims compounds of general formulae (I-A) and (I-B) wherein X means -NH-, and compounds of the general formula (I-C) wherein X means -O- or -NH-. Also, invention claims methods for synthesis of these compounds that involve the condensation reaction of compound of the formula: RO-PAG-V (for compounds of formulae (I-A) and (I-B)) or compound of the formula: RO-PAG1-O-(CH2)k-V (for compound of the formula (I-C)) wherein V means -OH or -NH2 with corresponding halide, hydrolysis of prepared ester to form a corresponding acid and, if necessary, interaction of indicated free acid with halogen in an activated leaving group in the presence of a condensing agent to form indicated activated ester. Also, invention claims conjugates of the general formula that are given in the invention description. Indicated reagents show enhanced stability in aqueous medium and they can be used for site-specific modification of protein. Claimed compounds possess higher activity and prolonged biochemical half-life index.

EFFECT: improved method of synthesis, valuable properties of additives.

19 cl, 9 ex

FIELD: pharmaceutical technology, pharmacy.

SUBSTANCE: invention relates to a method for preparing the inclusion compound of piroxicam with β-cyclodextrin. Method involves freezing process of aqueous solution of two components before drying at very high rate. Prepared products show physicochemical properties and technological and biopharmaceutical properties that display advantage properties as compared with properties prepared by methods of preceding practice. Solubility of piroxicam in tablets prepared by the proposed method is ≥90% for 10 minutes. Prepared products are useful for preparing pharmaceutical compositions for oral administration.

EFFECT: improved preparing method, improved properties.

13 cl, 2 dwg, 2 ex

FIELD: medicine.

SUBSTANCE: described humanised and chimeric CD20 antibodies are designed for treatment of CD20-positive malignant and autoimmune diseases. Antibody is effective with respect to depletion of B-cells of mammals in vivo, contains in variable region of H-chain of CDR3- sequence from antibody to human CD20 and practically all remains of consensus frame region (FR) of human H-chain of subgroup 111. According to invention antibody is used in composition or product, binding CD20. Besides, antibody is used for apoptosis induction, treatment of CB20-positive cancer, autoimmune disease, and rheumatic arthritis. Invention contains nucleic acid (NA) coding antibody, expression vector containing specified NA, and host cell producing recombinant antibody, as well as method of specified antibody production. According to invention antibodies are characterised by minimum antigenicity or no antigenicity at all, that enables to use them for continuous treatment overcoming limits of existing therapeutic compositions application.

EFFECT: enables to use for continuous treatment.

83 cl, 32 dwg, 12 tbl, 16 ex

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