36 results about "Daunorubicina" patented technology

This invention is in the field of chemical restructuring of pharmaceutical agents known to cause tissue toxicity as a side effect, by producing their orotate derivatives. More particularly, it concerns orotate derivatives of the anthracyclines, doxorubicin and daunorubicin, that are found to reduce levels of the pharmaceutical agent in noncancerous tissues. These orotate derivatives are equally efficacious in inhibiting the SCCAKI-1 kidney tumor in animals and the reduction in the heart tissue of doxorubicin compared with doxorubicin HCl suggests a reduction in toxicity induced by free radical generation by the anthracyclines.

Methods of treatment and pharmaceutical combinations are provided for the treatment of acute leukemia, such as acute myelogenous leukemia, and myelodysplastic syndrome. The methods of treatment and pharmaceutical combinations employ an anti-CD33 cytotoxic conjugate in combination with at least one compound selected from the group consisting of an anthracycline and a pyrimidine or purine nucleoside analog. Preferred methods of treatment and pharmaceutical combinations employ gemtuzumab ozogamicin, daunorubicin, and cytarabine.

The present invention relates to a marker gene for screening a drug inducing toxicity in human and a screening method using the same. More precisely, the invention relates to a microarray on which marker genes up-or down-regulated specifically by 16 drugs inducing pulmonary toxicity, teratogenicity, nephrotoxicity, cardiotoxicity or mutation (Methotrexate, Nitrofurantoin, Amiodarone, Carbamazepine, Valproic acid, Thalidomide, Cisplatin, Gentamycin, Amphotericine, Furylfuramide, N-nitroso-N-methylurea, methylmethanesulfonate, 4-nitroquinoline-N-oxide, 2-nitrofluorene, Doxorubicin and Daunorubicin) are integrated, a kit comprising the said microarray, and a screening method of a drug inducing toxicity in human using the same. The DNA microarray containing the marker gene of the present invention facilitates the construction of Toxtarget Array for screening a drug inducing toxicity in human using drug-specific genes, suggesting that this chip can be effectively used for monitoring drugs or chemicals carrying toxicity to human or determining risks thereof and also it can be used as a tool for examining mechanisms of toxicity / side effects caused by the drugs.

The invention provides a daunorubicin C-14 hydroxylase mutant and a production method of genetically engineered bacteria thereof. In a C-14 hydroxylase sequence coded by genes of the daunorubicin C-14 hydroxylase mutant, the glutamic acid at the 121 position is mutated into valine; through directed evolution technology, a target gene is subjected to random mutation, and a C-14 hydroxylase mutant with improved enzyme activity is obtained through a high-throughput screening method; the safety is better, the production rate is higher, and the method is environment-friendly.

A method of treating a cancer comprising administering to a subject in need thereof an effective amount of a glycylcycline, for example tigecycline in combination with a chemotherapeutic such as daunorubicin or cytarabine.

The invention discloses a gene blocking mutant for streptomyces coeruleorubidus and a preparation method thereof. In the gene blocking mutant for streptomyces coeruleorubidus, a dauW gene is blocked. In the technical scheme, the dauW gene in streptomyces coeruleorubidus is blocked through homologous recombination exchange, the yield of daunorubicin of streptomyces coeruleorubidus is greatly improved after the dauW gene is blocked and has increased by five times, and the effect is much better than that of blocking other genes, e.g. dnrX, dnrH and the like, the yield of which only can be increased by three times. Therefore, the blocking of the dauW gene substantially improves the fermentation unit of daunorubicin.

The invention discloses a preparation method of a double-targeting acid-sensitive prussian blue drug delivery system and an application thereof, which can effectively solve the problems of leukemia drug resistance and liver and spleen infiltration. According to the technical scheme, the preparation method comprises the following steps: firstly, adsorbing acid-sensitive polyethylene glycol-polyethyleneimine macromolecules on the surfaces of Prussian blue nanoparticles through electrostatic interaction and hydrogen-bond interaction; secondly, the CXCR4 antagonistic polypeptide (E5) and hyaluronic acid are connected with polyethyleneimine molecules on the surfaces of the prussian blue nanoparticles through chemical bonds; thirdly, daunorubicin is adsorbed to the surfaces of the prussian bluenanoparticles through hydrogen bond interaction. The preparation method is simple and mild, materials are safe and easy to obtain, good biocompatibility is achieved, a prepared carrier has the blood long-circulation capacity, the tumor cell double-targeting capacity, the lysosome escape capacity and the acid-sensitive drug release capacity, the mouse leukemia treatment effect can be effectively enhanced, and bone marrow homing and liver and spleen infiltration are inhibited.

A lipid injection of Zhengdingmycin or zhengdingmycin hydrochloride is prepared from Zhengdingmycin or zhengdingmycin hydrochloride, neutral phosphide, negative-charge phosphide, cholesterol, antioxidizing agent, organic acid, alkali, sugar, buffer and the water for injection through preparing liposome, homogenizing coating, purifying, solidifying, and sterilizing. Its advantages are high stability and low toxic by-effect.

The invention provides an application of a compound represented by a formula (I), and pharmaceutically acceptable salts or solvates of the compound in the preparation of drugs for treating multi-drugresistant cancers. A pharmaceutical composition comprises the compound represented by the formula (I) or pharmaceutically acceptable salts or solvates of the compound, and a chemotherapeutic drug picked from taxol, docetaxel, doxorubicin, 5-fluorouracil, and daunorubicin.

The invention relates to a preparation method of a nano delivery system of a double-pH sensitive supported chemotherapy drug daunorubicin (DNR). The preparation method comprises specific steps as follows: DNR and p-alkynyl benzaldehyde react to produce imine-DNR; then, a macromolecular carrier POEGMA-poly(p-azido benzyl methacrylate-co-AMA is prepared, and amphipathic blocks, azido and amino are introduced; alkynyl of the imine-DNA and the azido of the macromolecular carrier are subjected to a click chemical reaction to obtain a DNR polymer predrug intermediate; and amino of the macromolecularpredrug intermediate and 2,3-dimethyl maleic anhydride react to obtain a DNR macromolecular predrug, and self-assembly is carried out to obtain polymeric micelle. The polymeric micelle prepared by the method can realize charge reverse in normal systemic circulation and cancer cell environments according to different pH conditions, improve target property, realize precise delivery of drugs, reducetoxic and side effects of drugs and enhance antitumor therapeutic effects.

The invention discloses a preparation method of a CdTe quantum dot nanometer medicine carrying system carrying daunorubicin and gambogic acid, and relates to a preparation technology of a nanometer medicine carrying system carrying antitumor drugs and tumor multidrug resistance reversal drugs. The method comprises the steps that functional modification is conducted on CdTe through high-molecular polymer polyethylene glycol; BMPH is dropwise added in a DMF solution for dissolving daunorubicin, a stirring reaction is conducted at room temperature, and DNR carbamyl maleimide is obtained; a modified CdTe solution is added for conducting oscillating incubation, filtration and purification are conducted, and a PH sensitive novel medicine carrying system CdTe-DNR is obtained; a CdTe-DNR solution and a gambogic acid (GA) solution are mixed according to a certain proportion, after a reaction in a dark place is conducted, centrifugation is conducted, precipitation is washed through water, and the CdTe quantum dot nanometer medicine carrying system carrying daunorubicin and gambogic acid is obtained.

The invention relates to compositions and methods for treating patients with hematological proliferative disorders who are ineligible for treatment with standard intensive chemotherapy, using low intensity treatment with CPX-351, a liposomal composition of daunorubicin and cytarabine.

Compositions which comprise an anthracycline agent, and a cytidine analog are encapsulated in liposomal carriers. The preferred anthracycline agent is selected from the group of daunorubicin, doxorubicin, and idarubicin, while the preferred cytidine analog is selected from the group of cytarabine, gemcitabine, or 5-azacytidine. The combination of the anthracycline agent and cytidine analog encapsulated in said liposomal carriers are useful in achieving a drug retention and a sustained drug release for each therapeutic agent.

Provided are compositions and methods for the treatment of hematological conditions, in particular CD99+ acute myelogenous leukemias (AML) and myelodysplastic syndromes (MDS), which comprise one or more antibody that (a) binds to the extracellular domain of CD99, (b) ligates AML and / or MDS cell-surface expressed CD99, (c) promotes the capping / clustering / aggregation AML and / or MDS cell-surface expressed CD99, and (d) induces apoptosis in and consequent cytotoxicity of antibody-ligated CD99+ AML and / or MDS cells. Disclosed methods include methods for identifying AML and MDS patients that are susceptible to treatment with an anti-CD99 antibody by detecting the elevated expression of CD99 in a tissue sample or cell from an AML or MDS patient and for treating an AML and / or MDS patient exhibiting elevated CD99 gene and or cell-surface protein expression by administering a composition comprising an anti-CD99 antibody, either alone or in combination with one or more additional component such as a mobilizing agent, a transmigration blocking agent, and an AML and / or MDS chemotherapeutic agent, such as daunorubicin, idarubicin, cytarabine, 5-azacytidine, and decitabine.

The invention belongs to the technical field of medicines for preventing and treating cardiotoxicity, and particularly relates to application of bioactive peptide in preparation of a medicine for preventing and treating anthracycline cardiotoxicity, wherein the bioactive peptide is albumin peptide, wheat oligopeptide, soybean peptide or corn oligopeptide; and the anthracycline medicine is adriamycin or daunorubicin. The biological functions of the albumin peptide, the wheat oligopeptide, the soybean peptide and the corn oligopeptide except for oxidation resistance and tumour resistance are found in the invention; the application range of the bioactive peptide is expanded; and the bioactive peptide in the invention has a remarkable effect on preventing and treating the anthracycline cardiotoxicity and has no side effect.

The invention provides the application of Hsp90 inhibitor 17-DMAG in the preparation of medicines for inhibiting children's acute lymphoblastic leukemia, which belongs to the field of medical biotechnology. Experiments have verified that the combination of Hsp90 inhibitor 17-DMAG and cytarabine can synergistically promote the apoptosis of leukemia cells, but it cannot achieve similar effects when combined with daunorubicin and etoposide. It provides a basis for establishing the rational application of 17-DMAG combined with cytarabine chemotherapy in children ALL chemotherapy, and provides the possibility to improve the chemotherapy effect of leukemia patients and improve drug resistance; The application of DMAG and cytarabine as active ingredients in the preparation of drugs for inhibiting children's acute lymphoblastic leukemia.

The present invention discloses a nucleotide sequence which roots in an anthracycline and produces the partial gene dnrX1 and the gene fragment dnrX 2 of the dnrX 1 of streptomyces coeruleorubidus (Streptomyces coeruleorubidus), and an express vector containing the sequences. The present invention also discloses a gene disruption engineering strain which disrupts the treptomyces coeruleorubidus of the dnrX gene by adopting the express vectors with an exchange and homologous recombination method. When the gene disruption engineering strain is used to produce the anthracycline, the acidizing treatment is not required, adriacin which is not produced by a wild fungus can be produced, and the output of the adriacin and the daunorubicin can be greatly increased.

This invention relates to methods and compositions for treatment of inv(16) leukemia and particularly to treatment of acute myeloid leukemia. Disclosed is a method of treating inv(16) leukemia comprising the step of administering to a subject in need thereof a therapeutically effective combination of a) a compound of the formula (1) and b) a chemotherapeutic agent selected from the group consisting of pirarubicin, aclarubicin, mitoxantrone, doxorubicin, daunorubicin, idarubicin, epirubicin, cytarabine, pharmaceutically acceptable salts and mixtures thereof. The therapeutically effective combination synergistically inhibits proliferation of inv(16) leukemia cells. This invention also relates to pharmaceutical compositions comprising a therapeutically effective combination of the compound of formula (1) and the chemotherapeutic agent and a pharmaceutically acceptable excipient.

This invention discloses a genetically engineered strain of streptomyces coeruleorubidus highly producing epi-daunorubicin, which is a genetically engineered strain to block dnmV gene and express aveBIV (avermectins keto-reductase) by inserting a first foreign gene containing aveBIV gene in the dnmV gene of a wild strain of the streptomyces coeruleorubidus or changing the dnmV gene of the wild strain of the streptomyces coeruleorubidus into the first foreign gene containing aveBIV gene. A second foreign gene is further integrated in the genome of the genetically engineered strain, and the first and second foreign genes are chain segments of a promoter and the aveBIV gene. The constructed genetically engineered strain does not contain any resistance marker and is convenient for further genetic engineering construction. The yield of epi-daunorubicin is preferably 70mg / L and is far greater than that of the epi-daunorubicin made by existing methods; through continuous passage, the yield of epi-daunorubicin is very stable with good repeatability.

The invention discloses engineering streptomycete for producing daunorubicin and a construction method of the engineering streptomycete. Streptomyces albus ZD11 is used as an original strain, and through in-vitro fishing of large fragments of a genome, engineering transformation of a pathway specific activation protein gene promoter, deletion of a synthetic branch and blocking of a competitive synthetic pathway, an engineering streptomycete strain ZD11-M4 capable of heterologously synthesizing the daunorubicin is constructed, and the shake-flask fermentation yield of the daunorubicin reaches 22.62 mg / g and is doubled compared with that of an original strain. According to the engineering streptomycete provided by the invention, heterologous expression of daunorubicin synthetic gene clustersis realized for the first time, and a technical foundation is laid for industrial production of the daunorubicin. Besides, an efficient expression method of a polyketone compound in a heterologous host provided by the invention has important research and application values for exploring novel polyketone antibiotics, reducing the fermentation cost and increasing the yield.

The invention provides a daunorubicin hydrochloride bacterium and a yield increasing method thereof. The method comprises the following steps: Q1, preparing protoplast; Q2, regenerating the protoplast; Q3, performing ultraviolet mutagenesis of the protoplast; Q4, performing ion implantation mutagenization treatment of the prepared protoplast suspension according to the following steps; Q5, performing genome shuffling treatment by using bacterial colonies respectively treated in Q3 step and cultured in Q4 step as parents with different genetic backgrounds; Q6, culturing heterozygous regenerated offspring mycelia; Q7, preparing heterozygous offspring protoplast and performing protoplast fusion; Q8, performing multi-time fusion and regeneration of offspring protoplast, that is, performing multi-time repeated fusion and of offspring according to Q1-Q7, and screening to obtain a mutant strain with greatly increased daunorubicin yield.

The present invention relates to a method for pharmacological treatment of accidental extravasation of topoisomerase II poisons, such as anthracyclines. In particular, the invention relates to the use of a topo II catalytic inhibitor, such as the bisdioxopiperazine ICRF-187, for the treatment of an accidental extravasation of a topoisomerase II poison. A method for treatment of such extravasation of a topoisomerase poison such as the anthracyclines, daunorubicin, doxorubicin, epirubicin, or idarubicin is disclosed.

The invention relates to application of zogta in preparation of drugs for enhancing the anticancer activity of daunorubicin in vivo and in vitro, belonging to the technical field of drug preparation.The invention provides the application of the zogta in preparation of the drugs for enhancing the anticancer activity of the daunorubicin in vivo and in vitro. According to the invention, a daunorubicin anticancer monomer drug is combined with zogta nanoparticles for in-vitro administration, which proves that the zogta can promote enrichment of the daunorubicin in different cancer cells. Meanwhile, the apoptosis promoting effect of the drugs can be enhanced.

The invention discloses a preparation method and application of a dual-target acid-sensitive Prussian blue drug-carrying system, which can effectively solve the problems of leukemia drug resistance and liver and spleen infiltration. The technical solution is, firstly, the acid-sensitive polyethylene glycol-polyethyleneimine polymer is adsorbed on the surface of Prussian blue nanoparticles through electrostatic and hydrogen bonding; secondly, CXCR4 antagonistic polypeptide (E5) and hyaluronic acid are chemically bonded to Polyethyleneimine molecules on the surface of Prussian blue nanoparticles are connected; again, daunorubicin is adsorbed on the surface of Prussian blue nanoparticles through hydrogen bonding. The preparation method of the present invention is simple and mild, the material is safe and easy to obtain, and has good biocompatibility. The prepared carrier has long-term blood circulation ability, tumor cell double-targeting ability, lysosome escape ability, and acid-sensitive drug release ability, and can effectively Enhance the therapeutic effect of leukemia in mice and inhibit the homing of bone marrow and the infiltration of liver and spleen.

The invention relates to the field of reconstruction of drug chemical structure by preparation of orotate derivatives, and the drug is known to have side effect to cause tissue toxicity. More specifically, the invention relates to anthracycline, doxorubicin and daunorubicin orotate derivatives, and the orotate derivatives which and can reduce drug levels in non cancer tissues. The orotate derivatives are equally effective in inhibiting animal SCCAKI-1 renal tumor, and compared with doxorubicin hydrochloride, doxorubicin reduction in heart tissue shows that toxicity induced by production of anthracycline free radicals is reduced.

The application of the invention provides a daunorubicin-containing medicine, a preparation method of the daunorubicin-containing medicine, a medical composition and an application of the daunorubicin-containing medicine. The medicine comprises nucleic acid nanometer particles and daunorubicin, wherein the daunorubicin is mounted on the nucleic acid nanometer particles, the nucleic acid nanometerparticles comprise nucleic acid structural domains, the nucleic acid structural domains include an a sequence, a b sequence and a c sequence, the a sequence includes an a1 sequence or a sequence obtained in a manner that one or more basic groups of the a1 sequence are inserted, deleted or replaced, the b sequence includes a b1 sequence or a sequence obtained in a manner that one or more basic groups of the b1 sequence are inserted, deleted or replaced, and the c sequence includes a c1 sequence or a sequence obtained in a manner that one or more basic groups of the c1 sequence are inserted, deleted or replaced. According to the daunorubicin-containing medicine provided by the application of the invention, after the nucleic acid structural domains are subjected to target head modification, the daunorubicin-containing medicine has better target properties, can steadily deliver the daunorubicin, and is high in reliability.

The present invention relates to a preparation method of magnetic nano medicine for curing leukemia. Said preparation method uses surface-functional monodisperse magnetic nano particle Ni or Fe2O3 or Fe3O4 as carrier, on the surface of carrier the doxorubicin or daunorubicin or other medicine for curing leukemia can be loaded. Under the condition of externally-applied magnetic field it can be used for making auxiliary therapy, and can greatly raise medicine concentration in leukemia cell interior of tumor zone, and can reduce the hazard due to medicine resistance of cell to obtain the action of controlling and effectively killing cancer cell.