93 results about "Anthracycline Antibiotics" patented technology

A liposome composition for localizing an anti-tumor compound to a solid tumor via the bloodstream. The liposomes, which contain the agent in entrapped form, are composed of vesicle-forming lipids and between 1-20 mole percent of a vesicle-forming lipid derivatized with hydrophilic biocompatible polymer, and have sizes in a selected size range between 0.07 and 0.12 microns. After intravenous administration, the liposomes are taken up by the tumor within 24-48 hours, for site-specific release of entrapped compound into the tumor. In one composition for use in treating a solid tumor, the compound is an anthracycline antibiotic drug which is entrapped in the liposomes at a concentration of greater than about 50 mug agent / mumole liposome lipid. The method results in regression of solid colon and breast carcinomas which are refractory to anthracycline antibiotic drugs administered in free form or entrapped in conventional liposomes.

The invention discloses an engineering bacterium through anthracene nucleus antibiotic and appliance, which is characterized by the following: inserting or replacing restriction enzymes site of dnmV gene nucleic acid order of sky blue rufus streptomycete with antibiotic against property gene and surface cerubidin synthetic gene; blocking-up engineering bacterium of dnmV gene; or transforming expressing carrier of anthracene nucleus antibiotic synthetic gene to lead streptomycin (S.lividans)TK24; extracting expressing plasmid from S.lividans TK24; leading-in sky blue rufus streptomycete gene only with antibiotic against property gene to block dnmV gene; blocking-up abrupt change bacterium. This invention can produce cerubidin and / or analogue, such as anthracene nucleus antibiotic.

The invention relates to a drug for prevention and treatment of cardiotoxicity induced by anthracycline antibiotics, and an application thereof. Flavone can be adopted for preparing the drug for prevention and treatment of the cardiotoxicity induced by the anthracycline drugs after modifying a plurality of sites such as 3, 5, 6, 7, 3', 4' and the like on the chemical structural formula of the flavone. The experimental results show that: with the flavone compounds, the cardiotoxicity induced by adriamycin can be reduced, myocardial contraction function can be improved, and oxygen radicals can be removed; cardiac tissue overoxidation damage induced by the adriamycin can be reduced, and cardiac function can be improved; the cardiotoxicity to the human body induced by the anthracycline drugs during chemotherapy can be effectively reduced, the pain of the patient undergoing the chemotherapy can be reduced, and the death rate caused by the anthracycline drugs can be reduced.

The invention discloses a two-photon fluorescence probe for detecting peroxynitrite as well as a preparation method and application of the two-photon fluorescence probe. The two-photon fluorescence probe has the structural formula as shown in the description. The two-photon fluorescence probe is named as TPNIR-FP. The two-photon fluorescence probe adopts a Nile red derivative as a fluorescent group and an alpha-keto-amide functional group as an ONOO-reaction group, can rapidly respond to ONOO- (within 10 seconds), and in addition is high in sensitivity and good in selectivity. The two-photon fluorescence probe can be applied to imaging research on ONOO- in antharcycline antibiotic induced cardiac muscle cell and cardiac muscle tissue damage.

The present invention is based, in part, on the discovery that amplification of human chromosome 8q22-23 regions and over-expression of 8q22-23 genes (e.g., LAPTM4B and YWHAZ) is associated with and predictive of resistance to anthracycline-type chemotherapy. Accordingly, the invention relates to compositions, kits, and methods for predicting the response of cancer cells, e.g., breast, prostate, lung, ovarian, pancreatic, liver, and colon malignancies to anthracyclines.

A method for treating multiple myeloma in newly diagnosed or previously treated patients is described. The method comprises administering a composition consisting of a combination of chemotherapeutic agents of an anthracycline antibiothic, preferably entrapped in a liposome, dexamethasone, and thalidomide, and, optionally, a reduced dose of vincristine.

The invention discloses a compound drug-carrying liposome as well as a preparation method and application thereof. The compound drug-carrying liposome comprises a long-circulating liposome and medicinal active ingredients coated by the long-circulating liposome, wherein the long-circulating liposome is a liposome of which the surface is modified by distearoyl phosphoethanolamine-methoxy polyethylene glycol 2000; the medicinal active ingredients refer to anthracycline antibiotics and resveratrol. The preparation method of the compound drug-carrying liposome comprises preparing a liposome source, the distearoyl phosphoethanolamine-methoxy polyethylene glycol 2000 and the medicinal active ingredients into the compound drug-carrying liposome, wherein the medicinal active ingredients refer to anthracycline antibiotics and resveratrol. The compound drug-carrying liposome disclosed by the invention has inhibitory activity on the development of drug-sensitive tumors, can effectively inhibit the development of chemotherapeutic drug-tolerant tumors and is small in side effect, thereby achieving a great clinical application value.

The invention relates to a biosynthesis gene cluster of kosinostatin, and in particular relates to cloning, sequencing, analysis, functional study and application of the biosynthesis gene cluster of the kosinostatin, which is an antharcycline antibiotic with antitumor activity and generated from micromonospora sp.TP-A0468. The whole gene cluster comprises 55 genes in all, that is, 17 II-type polyketone synthetase (PKS) related genes, 8 non-ribosome polypeptide synthetase (NRPS) related genes, 9 glycosyl synthetic related genes, 6 special post-modifying genes, 7 antibiotic genes, 5 conditioning genes and 3 genes without definite functions. Through the genetic manipulation of the biosynthesis genes, the biosynthesis of kosinostatin can be blocked, the output is changed, or novel compounds are produced. The gene cluster can be applied to gene engineering, protein expression, enzymatic catalytic reaction and the like of antharcycline compounds, and can also be used for finding and discovering compounds, genes or proteins for medicines, industry or agriculture.

A gene set, kit and method predict the efficiency of anthracyclines-based treatment of breast cancer.

Anthracyclines-treated tumor cells are particularly effective in eliciting an anti-cancer immune response, where the rDNA-damaging agents, such as etoposide and mitomycin C do not induce immunogenic cell death. Anthracyclines induce the rapid, pre-apoptotic translocation of calreticulin (CRT) to the cell surface. Blockade or knock down of CRT suppressed the phagocytosis of anthracyclines-treated tumor cells by dendritic cells and abolished their immunogenicity in mammals, such as mice. The anthracyclines-induced CRT translocation was mimicked by inhibition of the protein phosphatase1 / GADD34 complex. Administration of recombinant CRT or inhibitors of protein phosphatase1 / GADD34 restored the immunogenicity of cell death elicited by etoposide and mitomycin C, and enhanced their antitumor effects in vivo. These data identify CRT as a key feature determining anti-cancer immune responses and delineate a possible strategy for immunogenic chemotherapy.

A method of synthesizing R1, R2-substituted-4′ (ax. or eq.)-OH anthracyclines and their corresponding salts of Formula (1) from daunorubicin or N-Trifluoroacetyl-4-R1-derivatives of daunorubicin, wherein R1 is defined as H, OH, and 4′-HO is defined as ax[ial]. The method includes producing N-Trifluoroacetyl daunorubicin and treating the N-Trifluoroacetyldaunorubicin or N-Trifluoroacetyl-4-R1-derivatives of daunorubicin, wherein R1 is defined as H, OH, with dimethylsulfoxide activated by different acylating agents. The attained intermediate product is then treated with a strong base (ex. tertiary amines) resulting in the 4′-keto-N-Trifluoroacetyl-4-R1 daunorubicin wherein R1 is defined as H, OH, OMe. The 4′-keto-N-Trifluoroacetyl-4-R1-daunorubicin is reacted with a reducing agent, a derivative of a borohydride of an alkaline metal MHBL3 , to produce N-Trifluoroacetyl-4′-epi-4-R1-daunorubicin. The N-Trifluoroacetyl-4′-epi-4-R1-daunorubicin undergoes hydrolysis in a basic solution to produce a derivate of an anthoacyclin which is halogenized [by complex halogenides] to form a 14-Hal-derivative. This result is then hydrolyzed by well-known methods in the presence of a formate of an alkaline metal to form the desired final compound.

The method for synthesizing 4-R-substituted anthracycline antibiotics and corresponding salts thereof from 4-demethyldaunorubicin comprises the following steps: treating 4-demethyldaunorubicin with a sulfonating agent to form 4-demethyldaunorubicin Methyl-4-sulfonyl-R3-daunorubicin; then in an inert atmosphere, in an aprotic polar solvent, in the temperature range of about 30-100 ° C, in the presence of a transition metal catalyst to make 4- Demethyl-4-R3-sulfonyl-daunorubicin reacts with reducing agent. Then, the protected 4-desmethoxy-4-R-daunorubicin is hydrolyzed in alkaline solution to form 4-R-substituted anthracycline antibiotics. The new method eliminates the step of forming a stereospecific glycoside between the aglycone and the aminoglycoside. The method also increases the yield of the final product by up to 30 to 40%.

The invention discloses a new Chemomycin A and preparing method and drug component and application in the tumour prevention drug, which is characterized by the following: separating Angucycline from Nocardia Mediterranei Var. Kanglensis 1747-64 to obtain the product; displaying excellent anti-tumour activity in the external activity test.

The present invention discloses new and novel substituted anthracyclines with modified alkyl-aromatic ring substitutions on the C-3′ of the sugar moiety or modified or unmodified alkyl-aromatic ring substitutions at the C-4′ of the sugar moiety. It also discloses novel methods for the preparation of sugar substrates and methods for the preparation of anthracycline antibiotics. These anthracycline analogs show high cytotoxicity in vitro against several tumor cell lines.

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.

The invention provides preparation and applications of a pH and ATP response-type nano carrier. The pH and ATP response-type nano carrier comprises a nucleic acid nano carrier and an anti-tumor drug immobilized on the nucleic acid nano carrier; the anti-tumor drug is anthracycline antibiotics; and the nucleic acid nano carrier comprises an ATP aptamer double helix structure and an i-motif stem loop structure. The pH and ATP response-type nano carrier provided by the invention utilizes the characteristics of tumor cell high-concentration ATP to promote dissociation of aptamers and complementarysequences thereof; and utilizes the acidic environment of tumor cells to promote the i-motif conformational change and to realize the efficient and rapid release of drugs in cells.

The present invention relates to a group of novel compound Chemomicin B,C,D and its preparation method, pharmaceutical composition containing Chemomicin B,C,D as active ingredients and its uses of Chemomicin B,C,D in preparing antineoplastic drug. Chemomicin B,C,D is Angucyclinone antibiotic separated from Nocardia Mediterranei Var.Kanglensis 1747-64 culture. In vitro activity test prove Chemomicin B,C,D has strong suppressing activity for human oesophagus cancer cell KYSE150 and has good development prospect as a novel antineoplastic drug.

A method of synthesizing R1, R2-substituted-4′ (ax. or eq.)-OH anthracyclines and their corresponding salts of Formula (1) from daunorubicin or N-Trifluoroacetyl-4-R1-derivatives of daunorubicin, wherein R1 is defined as H, OH, and 4′-HO is defined as ax[ial]. The method includes producing N-Trifluoroacetyl daunorubicin and treating the N-Trifluoroacetyldaunorubicin or N-Trifluoroacetyl-4-R1-derivatives of daunorubicin, wherein R1 is defined as H, OH, with dimethylsulfoxide activated by different acylating agents. The attained intermediate product is then treated with a strong base (ex. tertiary amines) resulting in the 4′-keto-N-Trifluoroacetyl-4-R1 daunorubicin wherein R1 is defined as H, OH, OMe. The 4′-keto-N-Trifluoroacetyl-4-R1-daunorubicin is reacted with a reducing agent, a derivative of a borohydride of an alkaline metal MHBL3 , to produce N-Trifluoroacetyl-4′-epi-4-R1-daunorubicin. The N-Trifluoroacetyl-4′-epi-4-R1-daunorubicin undergoes hydrolysis in a basic solution to produce a derivate of an anthoacyclin which is halogenized [by complex halogenides] to form a 14-Hal-derivative. This result is then hydrolyzed by well-known methods in the presence of a formate of an alkaline metal to form the desired final compound.

The invention discloses an application of anthracene nucleus antibiotic and its pharmaceutical salt for treating ocular inflammation. The invention found that the anthracene nucleus antibiotic and its pharmaceutical salt have good effect on treatment of exogenous ocular inflammation and endogenous ocular inflammation, and especially the anthracene nucleus antibiotics can be prepared to prolonged action preparations such as a nano preparation, a microballoon preparation, liposome and hydrogel, the curative effect can be directly performed on ocular surface and eye ground, the toxicity of anthracene nucleus antibiotic is reduced, administration dosage is simultaneously enlarged through ophthalmic administration by prolonged action preparations, the duration time of drug effect is long, the medicament curative effect is stronger than that of the common preparations of the anthracene nucleus antibiotic, when the ophthalmic administration is carried out, the anthracene nucleus antibiotic has good treatment effect for exogenous and endogenous ocular surface, and eye ground inflammation, and especially has good treatment effect for the ocular surface and eye ground diseases caused by external wound, so that the problems of certain eyes inflammation with long treatment and more severe eye diseases due to eyes inflammation can be solved.

The invention discloses a new compound having an anthracycline antibiotic structure, and a preparation method and an application thereof. The anthracycline antibiotic coupled nonlinear multi-block copolymer has better effects on treatment of oculopathy compared with other forms of drugs or medicaments.

The invention relates to the technical field of traditional Chinese medicines, in particular to a drug composition for preventing and treating cardiotoxicity induced by anthracycline antibiotics and application for the drug composition. Experiments prove that glycyrrhizin can weaken the cardiotoxicity caused by doxorubicin, lower a myocardial enzyme level and improve an inflammatory response, so that the lethality caused by doxorubicin cardiotoxicity is lowered, and the drug composition has the remarkable protective effect to the cardiotoxicity induced by the doxorubicin. The drug compositioncan be used for preventing and lightening the cardiotoxicity induced by anthracycline antibiotics and has the clinical practicability.

The invention provides a targeted anti-tumor drug system and a preparation method thereof. The targeted anti-tumor drug system comprises an aptamer carrier and anti-tumor drugs immobilized onto the aptamer carrier, wherein the anti-tumor drugs are anthracycline antibiotics and porphyrin; and the aptamer carrier is an aptamer subjected to annealing treatment. The targeted anti-tumor drug system andthe preparation method thereof provided by the invention aim to perform targeted loading on dual anti-tumor drugs based on the guiding role and high-selectivity effect of the aptamer, and the aim ofrealizing dual inhibition of tumor proliferation is achieved by combining chemotherapy and photodynamic therapy.

The present invention discloses new and novel substituted anthracyclines with modified alkyl-aromatic ring substitutions on the C-3′ of the sugar moiety or modified or unmodified alkyl-aromatic ring substitutions at the C-4′ of the sugar moiety. It also discloses novel methods for the preparation of sugar substrates and methods for the preparation of anthracyline antibiotics. These anthracycline analogs show high cytotoxicity in vitro against several tumor cell lines.

The invention relates to a novel pharmaceutical composition. Cytosine arabinoside and antharcycline antibiotics are co-encapsulated to prepare the pharmaceutical composition. The provided pharmaceutical composition can stably maintain the ratio of cytosine arabinoside to antharcycline antibiotics to be in a range in human body; the synergistic effect can be exerted maximally; and the pharmaceutical composition is used to treat proliferative diseases of a hematopoietic system, in particular, acute leukemia.

The invention discloses a new use of a series of anthracycline antibiotics and medicinal salts thereof. The new use is the use in the preparation of medicines for treating age-related macular degeneration (AMD). Researches in the invention prove that the AMD symptom treatment effect can be performed through inhibiting HIF-1 after the small-dosage multi-time intraocular administration of the common powder injection of the anthracycline antibiotics and the one-time intraocular administration of a polymer prepared long-acting micro-balloon or nano-preparation and a hydrogel long-acting preparation, and no side effects comprising retinopathy or the like are caused. The medicines can continuously act for two months because the slow release administration effect mode can be applied.

The invention discloses a dendritic polymer grafted with an anthracycline antibiotic structure, and a preparation method and an application thereof. The anthracycline antibiotic-grafted dendritic polymer has better effects on treatment of age-related macular degeneration disease than other forms of drugs or medicaments.

The invention discloses an application of anthracene nucleus antibiotic and its pharmaceutical salt for treating neovascular glaucoma. The invention found that the anthracene nucleus antibiotic and its pharmaceutical salt have good effect on treatment of r neovascular glaucoma, and especially the anthracene nucleus antibiotics can be prepared to prolonged action preparations such as a nano preparation, a microballoon preparation, liposome and hydrogel, the toxicity of anthracene nucleus antibiotic is reduced, and the anthracene nucleus antibiotic enables ophthalmic administration, administration dosage is simultaneously enlarged, the duration time of drug effect is long, the medicament curative effect is stronger than that of the common preparations of the anthracene nucleus antibiotic, when the ophthalmic administration is carried out, the anthracene nucleus antibiotic has good treatment effect for treating retinal vein occlusion, and the blank that no medicine is good for treating neovascular glaucoma can be filled.

The invention discloses application of a flavonoid derivative GL-V9 and anthracycline antibiotics in preparation of a leukemia treatment medicine, and belongs to the technical field of medicines. It is found that the flavonoid derivative GL-V9 combined with low-dose anthracycline antibiotics can significantly inhibit growth of acute myelogenous leukemia (AML) cells, MTT experiments and U937 cell nude mouse transplantation tumor models verify that the GL-V9 and the low-dose anthracycline antibiotics can play a synergistic anti-AML effect, and the application potential of the combined administration mode in treatment of AML is prompted.