138 results about "Doxorubicin" patented technology

The invention relates to a preparation method and application of dynamic borate bond hydrogel loaded with adriamycin and an alphaOX40 antibody, and belongs to the technical field of tumors. According to the invention, the dynamic borate bond hydrogel loaded with adriamycin and an alphaOX40 antibody is prepared, and the hydrogel is constructed on the basis of dynamic crosslinking of phenylboronic acid modified hyaluronic acid (HA-PBA) and tannic acid (TA) through a borate bond, and has excellent tissue adhesion and programmed drug release characteristics.

The invention discloses a construction method and application of an animal model for evaluating cardiotoxicity of antitumor drugs, sodium carboxymethyl cellulose (CMC-Na) with extremely low cost is adopted to replace matrigel, a tumor-bearing mouse model with high stability can be constructed at low cost, and experimental verification shows that 4T1 cells are resuspended by using a 0.7% CMC-Na solution, and the tumor formation rate of subcutaneous inoculation reaches gt; 95%. The tumor microenvironment-mediated cardiac injury critical period is accurately captured, and the constructed tumor-bearing mouse model is the optimal tumor-bearing mouse model for evaluating the cardiotoxicity of an antitumor drug (adriamycin) in the tumor microenvironment in the third week after the mouse has a 50mm < 3 > tumor.

The invention relates to the technical field of biomedical engineering and drug delivery, and particularly discloses a novel targeted drug delivery system based on rose fruit extracellular vesicles, which comprises the following steps: preparing rose fruit source extracellular vesicles; preparing a medicine carrying vesicle; preparing targeted modified drug-loaded vesicles; according to the application disclosed by the invention, a stem related pathway is specifically down-regulated through the components of the rose fruits, and meanwhile, conventional tumor cells are killed by using adriamycin, so that a complementary treatment mechanism is formed, and the tumor recurrence risk is fundamentally reduced. The phenylboronic acid group of DSPE-PEG-PBA is used for specifically recognizing sialic acid over-expressed on the surface of a tumor cell, so that the enrichment of the medicine in tumor tissues is remarkably improved, and meanwhile, the distribution of normal tissues is reduced. By means of the natural biocompatibility and low immunogenicity of the RHNVs and in combination with the long circulation characteristic of a PEG chain, the delivery efficiency is guaranteed, the systemic toxicity is reduced to the maximum extent, and particularly the cardiotoxicity and myelosuppression of adriamycin are relieved.

The application discloses a kind of 2-substituted benzylhydrazine-4-indole pyrimidine-5-carbonitrile derivatives and preparation method and application thereof.The derivative has general formula (I) structure: wherein R is hydroxyl or C1-C4 alkoxy, n=1~3.Preferred compound is 2-hydroxy, 4-hydroxy-3-methoxy, 2,3-dihydroxy or 2,4-dihydroxy substituted benzylhydrazine derivative.The application also provides key intermediate 2-hydrazine-4-(1H-indole-3-carbonyl) pyrimidine-5-carbonitrile and preparation method thereof.In vitro antitumor activity shows that the derivative has excellent inhibitory activity on human gastric cancer cell MGC-803, and the inhibition rate is up to 96.3% at 10 μmol / L, which is better than positive control doxorubicin.In vivo combination test shows synergistic effect with 5-fluorouracil or anti-PD-1 antibody.The compound of the application has mild synthesis route, high yield, various preparation forms, good safety, and can be applied in the preparation of anti-gastric cancer drugs.

The invention provides a DNA (Deoxyribose Nucleic Acid) nano-structure carrier. The DNA nano-structure carrier provided by the invention has an EGFR (epidermal growth factor receptor) aptamer structure and is used for loading a connecting sequence of siRNA; moreover, after the siRNA is loaded, the DNA nano-structure carrier can further load a chemotherapeutic drug such as adriamycin, so that a DNA nano-drug based on the DNA nano-structure carrier is obtained. Through the target gene expression knock-down effect of siME3, the cytotoxicity of adriamycin and the targeting property of the EGFR aptamer structure, the DNA nano-drug provided by the invention can effectively inhibit pancreatic cancer, especially the growth of ME2 deletion type pancreatic cancer cells.

The present application relates to the technical field of biological medicine, and discloses inhalable aptamer modified molybdenum disulfide nanoflower compound and application thereof.The compound comprises a molybdenum disulfide nanoflower core, a dendritic polylysine modification layer attached to the surface of the molybdenum disulfide nanoflower, doxorubicin loaded on the molybdenum disulfide nanoflower and / or the dendritic polylysine modification layer, and AS1411 aptamer combined on the outer surface of the dendritic polylysine modification layer by electrostatic assembly.The compound can be delivered to a lung lesion by atomization inhalation or aerosol inhalation, and undergoes responsive structural change under the action of hydrogen peroxide in a tumor microenvironment, generates active oxygen, and promotes the release of doxorubicin, so as to realize the synergistic antitumor effect of chemotherapy and chemical dynamic therapy.The compound has good colloidal stability, drug loading capacity, active targeting ability and lung local delivery potential, and can be used for preparing inhalation preparations or local administration preparations for treating lung cancer.

This invention discloses a hydrogel for tumor treatment based on improving the tumor microenvironment to trigger gas therapy combined with chemotherapy, belonging to the field of biomedical technology. The hydrogel drug delivery system utilizes lipopolysaccharide (LPS) to induce local inflammatory stimulation, thereby altering the tumor microenvironment of breast cancer and promoting nitric oxide (NO) production. The NO donor arginine (L-Arg) and the chemotherapy drug doxorubicin (DOX) are transported using sodium alginate (ALG), achieving combined gas therapy and chemotherapy to inhibit breast tumor growth. The drug delivery system of this invention not only enhances the effect of chemotherapy but also simultaneously achieves precise drug delivery and reduces drug dosage. The preparation method of the drug delivery system of this invention is simple, safe, and without toxic side effects, showing promising application prospects in tumor treatment and possessing significant clinical value.

Disclosed are an anthracycline compound, a preparation method therefor, an intermediate, and a use thereof. The present invention provides an anthracycline compound as shown in formula I or a pharmaceutically acceptable salt thereof. The anthracycline compound provided by the present invention has antitumor activity comparable to existing anthracycline drugs (such as nemorubicin) or greater than that of existing anthracycline drugs doxorubicin and daunorubicin, and does not form an oxazole ring structure during metabolism, thereby improving the clinical safety of such drugs.

A combination therapy for the treatment of cancer, particularly soft tissue sarcoma, is described, which includes low doses of lurbinectedin and doxorubicin.

This application provides a method for preparing pH-responsive polyamino acid drug-loaded nanoparticles based on sarcosine and their application. Sar-NNCA, L-lysine-NCA, and L-phenylalanine-NCA are dissolved in anhydrous DMF and polymerized under argon protection with a hexamethyldisilazine initiator to obtain a polyamino acid block copolymer Sar-NNCA. 80 -Lys(Cbz) n -Phe 10 The crude product was deprotected under HBr / acetic acid and loaded with DOX to obtain Sar. 80 -Lys n -Phe 10 -DOX. This application describes the preparation of a pH-responsive polymer nanoplatform, Sar, by encapsulating doxorubicin in polysarcosine-polylysine-polyphenylalanine nanoparticles via Schiff base bonds. 80 -Lys n -Phe 10 -DOX is used for tumor treatment. These polyamino acid nanoparticles are spherical with an average particle size of approximately 200 nanometers, exhibiting pH-responsive properties, excellent cellular uptake capacity, and anti-tumor effects. In vitro experiments show that Sar... 80 -Lys n -Phe 10 The carrier material exhibits excellent biocompatibility. The newly synthesized Sar... 80 -Lys n -Phe 10 -DOX nanomicelles show promise as a drug delivery system for cancer treatment.

The application discloses a doxorubicin scavenger for protecting ovarian fertility and a preparation method thereof, comprising a DNA complex wrapped by a red blood cell membrane, wherein the red blood cell membrane is surface-modified by an anti-Mullerian duct antibody alphaAMH; the doxorubicin scavenger is specifically combined with AMH which is highly expressed in ovarian tissues through alphaAMH, is enriched in the ovarian part in a targeted manner, adsorbs doxorubicin through a DNA fragment in the DNA complex, reduces toxic damage of doxorubicin to ovarian cells, and further protects ovarian fertility. The doxorubicin scavenger can adsorb injected doxorubicin Dox, reduce side effects of doxorubicin Dox on ovarian granulosa cells, and further protect ovarian function and fertility.

The invention belongs to the technical field of biological material preparation, and particularly relates to a copper-based metal organic framework nanoparticle as well as a preparation method and application thereof. The invention relates to a copper-based metal organic framework nano-particle which is obtained by carrying out hydrothermal reaction on a mixed solution, polyvinylpyrrolidone, 1, 3, 5-benzene tricarboxylic acid and a copper compound, the mixed solution is obtained by mixing deionized water, absolute ethyl alcohol and N, N-dimethylformamide; the ratio of the polyvinylpyrrolidone to the mixed solution is (70mg-90mg): 9mL; the ratio of the 1, 3, 5-benzene tricarboxylic acid to the copper compound to the mixed solution is (7g-14g): 7g: 1500mL. The particle size of the copper-based metal organic framework nano-particles is 167 nm, the loading rate of the copper-based metal organic framework nano-particles to adriamycin within 24 h reaches 78.3%, the copper-based metal organic framework nano-particles have the pH response drug release characteristic in a tumor microenvironment with the pH being 5.2, the cumulative release rate within 72 h reaches 54.75%, and the cumulative release rate is increased by 6.3 times compared with the physiological condition with the pH being 7.4. Complete cell internalization is realized within 6 hours, and acid-triggered drug release is promoted.

The invention relates to the technical field of molecular imprinting and biological medicine, in particular to doxorubicin molecular imprinting hydrogel and a preparation method thereof, and the doxorubicin molecular imprinting hydrogel is prepared by taking DOX as a template and adopting N-isopropylacrylamide and N-[3-(dimethylamino) propyl] methacrylamide as bifunctional monomers through free radical polymerization. According to the method, efficient and specific separation of DOX in a complex biological system is achieved through the functional monomer ratio, the cross-linking agent concentration and the solution pH value, and the defects in the prior art are overcome.

This invention belongs to the field of precision oncology diagnosis and treatment technology, specifically involving a nanomedicine delivery system with tumor microenvironment regulation capabilities, its preparation method, and its application. S1: An organic phase is prepared by dissolving ionizable lipids, helper phospholipids, cholesterol, and functionally modified lipids in a solvent at a molar ratio of 50:38.5:10:1.5. S2: Capsaicin is dissolved in the organic phase obtained in S1, and doxorubicin is dissolved in the solvent to prepare an aqueous phase. The organic and aqueous phases are rapidly mixed in a microfluidic device at a volume ratio of 3:1 to obtain a mixture. S3: The mixture obtained in S2 is placed in a dialysis bag and immersed in Tris buffer for magnetic stirring and dialysis, followed by concentration to obtain (C+D)@LNPPRT. This invention significantly enhances the precision detection of tumors, enables efficient early tumor detection and targeted chemotherapy, and improves treatment efficacy.

The application provides application of Trapidil in preparation of a drug for preventing and / or treating doxorubicin-induced organ toxicity, and belongs to the technical field of biological medicines.The application discloses that Trapidil plays an organ protection role by activating a cAMP / PKA / CREB signal axis and driving two parallel downstream effect channels: on the one hand, up-regulating an NRF2-GPX3 positive feedback loop to inhibit doxorubicin-induced myocardial cell pyroptosis and glomerular podocyte pyroptosis; and on the other hand, activating an NRF2 / HO-1 channel to inhibit myocardial cell apoptosis and glomerular podocyte apoptosis.In-vivo and in-vitro experiments prove that Trapidil can improve doxorubicin-induced cardiac dysfunction and kidney function damage, reduce histopathological damage, reduce the level of oxidative stress, inhibit the pyroptosis and apoptosis of myocardial cells and glomerular podocytes, and does not affect the antitumor effect of doxorubicin.The application provides a new drug strategy for doxorubicin chemotherapy-induced multi-organ toxicity.

The present invention relates to a pharmaceutical composition for preventing or treating anticancer drug-resistant cancer, containing rucaparib camsylate as an active ingredient. Rucaparib camsylate can function as an immune checkpoint inhibitor by blocking the binding of PD-1 and PD-L1, and thus can be effectively used in pharmaceuticals for the prevention or treatment of cancer. In addition, rucaparib camsylate according to the present invention has an excellent anticancer effect against uterine sarcoma cancer that exhibits resistance to doxorubicin, and thus can be very effectively used for the prevention or treatment of resistant cancer.

The invention discloses a drug delivery system containing loaded adriamycin as well as a preparation method and application of the drug delivery system. The drug delivery system comprises poly (beta-amino ester) coupled with adriamycin, wherein the surface of the poly (beta-amino ester) is coated with dextran sulfate, and the poly (beta-amino ester) takes a fourth-generation lysine dendritic molecule Lys-G4 as a core. The drug delivery system has a pH-dependent drug release characteristic, has remarkable toxicity to C6 and U87MG glioma cells, has the capabilities of inducing apoptosis, inhibiting migration and targeting subcellular localization, and can effectively penetrate through a blood-brain barrier model and 3D tumor spheres. The delivery system is compounded with PLA-PEG-PLA thermosensitive hydrogel, and the thermosensitive hydrogel with a drug storage function is successfully constructed. Good tumor inhibition effect and biocompatibility are shown in nude mouse subcutaneous and in-situ glioma models. The invention not only provides a new strategy for overcoming the blood brain barrier, but also can effectively reduce the systemic toxicity, and opens up a new research thought and method for glioma treatment.

The application discloses a high-safety tumor treatment preparation based on a prodrug-enzyme-neutralizing antibody three-system, and a preparation method and application thereof. The preparation comprises three core components: (a) a prodrug, which is coupled by an anti-tumor drug (such as doxorubicin) and cephalosporin; (b) an activating enzyme, such as beta-lactamase, which is specifically expressed in the tumor by phage, catalyzes the hydrolysis of the prodrug, and releases the active drug; and (c) a neutralizing antibody, such as an anti-doxorubicin monoclonal antibody, which can specifically bind and neutralize the active drug overflowing into the blood circulation. The application first integrates the precise killing strategy of "prodrug-local activation" and the safety strategy of "neutralizing antibody-systematic protection" into a complete treatment closed loop, utilizes the "differential neutralization" characteristics of the anti-doxorubicin antibody, effectively protects normal tissues from toxic damage under the premise of not affecting the local efficacy of the tumor, and significantly improves the therapeutic index of the chemotherapy drug, reduces the side effects such as cardiotoxicity and bone marrow suppression, and provides a new paradigm with high efficiency and safety for tumor treatment.

The application discloses a kind of mitochondrial quality control detection methods, the present application relates to mitochondrial quality control detection technical field, operating steps include preparation sample cell suspension, fluorescent dye labeling, cardiomyocyte separation, establish myocardial cell damaged model and detect mitochondrial membrane potential situation.This mitochondrial quality control detection method can simultaneously carry out multi-parameter, rapid quantitative analysis and sorting, measure fast, measure the multi-parameter characteristics of each cell, while carrying out cell characteristic analysis, can separate out the cell of specified characteristics, so as to further culture, cloning, observation or carry out mitochondrial fragmentation test to specific cell, establish myocardial cell damaged model using doxorubicin, the mitochondrial membrane potential situation of normal myocardial cell and damaged myocardial cell obtained by using JC-1 mitochondrial membrane potential fluorescent probe detection is verified the detection quality of this mitochondrial quality control detection method.

The application of BAHCC1 gene in preparing acute myeloid leukemia drugs belongs to the technical field of biological medicine. In order to solve the problems of treating acute myeloid leukemia and reducing its recurrence and drug resistance, the present application significantly inhibits the proliferation and clonogenic ability of acute myeloid leukemia by knocking down BAHCC1, and significantly induces the apoptosis of acute myeloid leukemia and promotes cell differentiation. The three-dimensional spatial structure of BAHCC1 protein is predicted by using AlphaFold software, small molecule compounds targeting BAHCC1 are screened in the three-dimensional spatial structure domain of BAHCC1 protein, and AML cells are treated by using the small molecule compounds targeting BAHCC1. The small molecule compounds targeting BAHCC1 are screened by molecular docking and cell experiments, including 8OK. The small molecule compounds targeting BAHCC1 are combined with cytarabine AraC, daunorubicin DNR or doxorubicin DOX.

The present invention belongs to the technical field of pharmaceutical carriers for targeting tumors, and specifically relates to a targeted tumor carrier based on lactic acid bacteria vesicles, and its preparation method and application. The targeted tumor carrier based on lactic acid bacteria vesicles of the present invention comprises lactic acid bacteria vesicles and DSPE-PEG2000-cRGD anchored on the surface of the lactic acid bacteria vesicles. The targeted tumor carrier of the present invention can effectively and actively deliver SR-18292 and doxorubicin into tumor cells, thereby effectively inhibiting tumor cell apoptosis, significantly inhibiting tumor cell migration and invasion, and thus exerting a significant anti-tumor therapeutic effect. In addition, the tumor drug delivery system of the present invention has good biosafety.

The invention discloses application of a BAHCC1 gene in preparation of acute myelogenous leukemia drugs, and belongs to the technical field of biological medicines. In order to treat the acute myelogenous leukemia and reduce the recurrence and drug resistance of the acute myelogenous leukemia, the knock-down BAHCC1 disclosed by the invention has the advantages that the proliferation and clone formation capabilities of the acute myelogenous leukemia are remarkably inhibited, the apoptosis of the acute myelogenous leukemia is remarkably induced, and the cell differentiation is promoted. AlphaFold software is used for predicting the three-dimensional space structure of the BAHCC1 protein, a small molecule compound targeting BAHCC1 is screened in the three-dimensional space structure domain of the BAHCC1 protein, and the small molecule compound targeting BAHCC1 is used for treating AML cells. A small molecule compound, including 8OK, targeting BAHCC1 is screened through molecular docking and cell experiments. The small molecular compound targeting BAHCC1 is combined with cytarabine arabinoside AraC, daunorubicin DNR or doxorubicin DOX for use.

The invention relates to the technical field of medicine, in particular to application of parishin E in preparation of medicine for preventing and / or treating mitochondrial dysfunction heart failure, and the heart failure particularly refers to chronic heart failure induced by anthracycline antitumor drugs and related to mitochondrial dysfunction. In-vitro experiments prove that the parishin E can remarkably improve the mitochondrial function of myocardial cells damaged by adriamycin and improve basic respiration, ATP (adenosine triphosphate) synthesis and maximum respiration capacity of the myocardial cells. In an animal model, the parishin E effectively improves heart function indexes and relieves pathological injuries such as myocardial fiber arrangement disorder and cavity enlargement. The invention provides a natural small molecule which is novel in mechanism and has development potential for clinically preventing and treating anthracycline cardiotoxicity.

The invention belongs to the technical field of medicines, and provides application of fritillaria alkaloid in preparation of a medicine for treating cardiomyopathy induced by chemotherapeutic drugs. The fritillaria alkaloid is fritillaria pallidiflora alkaloid; the chemotherapeutic drug is an anthracycline chemotherapeutic drug; the anthracycline chemotherapeutic drug is adriamycin. The fritillaria pallidiflora alkaloid can prevent and / or treat doxorubicin-induced cardiomyopathy by resisting myocardial fibrosis and relieving myocardial damage. The fritillaria pallidiflora alkaloid is a natural fritillaria pallidiflora alkaloid, through a multi-target action mechanism, cardiac function decline and cardiomyopathy damage caused by adriamycin are effectively relieved, and a novel candidate drug with potential and a treatment strategy are provided for preventing or treating chemotherapy drug induced cardiomyopathy.

The application belongs to the field of gene drugs, and particularly relates to CTRTS, an analog thereof and application thereof. The CTRTS has a nucleotide sequence as shown in SEQ ID NO. 1. The CTRTS analog is CTRTS Agomir, and has a nucleotide sequence as shown in SEQ ID NO. 2. The present application finds that the expression level of CTRTS is reduced when doxorubicin induces cardiotoxicity; overexpression of CTRTS can significantly inhibit doxorubicin-induced cardiotoxicity, and plays an important role in the regulation of myocardial cell death. The existing drug has limited therapeutic effect, therefore, CTRTS plays an important role in the regulation of myocardial cell death, can regulate the doxorubicin-induced cardiotoxicity treatment by participating in the regulation of the myocardial cell death process, so as to improve the clinical prognosis effect.

Described herein are compounds that block the activity of LOX family members having good IC50 values, no cellular toxicity below 10 μM, induce sensitization of the cells to doxorubicin, strong activity in a recombinant LOX / LOXL2 activity, and a chemical structure that is drug-like and does not have a PAINS flag, as well as, methods of treatment using the compounds with respect to cancer, organ fibrosis, neurodegenerative and cardiovascular diseases.

The application belongs to the technical field of biological medicine, and particularly relates to a cysteine-doxorubicin conjugate as well as a preparation method and application thereof. First, doxorubicin and 3-(2-pyridyl dithio) propionic acid are dissolved in dichloromethane, then 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride is added, and after stirring and dissolving at room temperature, heating and stirring reaction is performed. After the reaction is completed, the solvent is spun dry, and the 3-(2-pyridyl dithio) propionic acid doxorubicin ester is obtained through column chromatography separation and purification. Then, the 3-(2-pyridyl dithio) propionic acid doxorubicin ester is dissolved in N,N-dimethylformamide, cysteine is added, and after stirring and dissolving at room temperature, heating and stirring reaction is performed. After the reaction liquid is cooled to room temperature, it is added to a dialysis bag and dialyzed in ultrapure water. After freeze-drying, the cysteine-doxorubicin conjugate is obtained.

This invention discloses a nano-aluminum formulation of doxorubicin / zoledronic acid, its preparation method, and its application. The preparation method includes the following steps: S1: Adding an aqueous solution of zoledronic acid with a pH of 4-6 to the aqueous solution of nano-aluminum, stirring to obtain zoledronic acid-nano-aluminum; S2: Adding an aqueous solution of doxorubicin to the aqueous solution of zoledronic acid-nano-aluminum, stirring to obtain the doxorubicin / zoledronic acid nano-aluminum formulation. The DOX / ZA-Al-nano formulation of this invention can effectively inhibit tumor cell growth by promoting greater entry of doxorubicin into cells and rapid entry into the cell nucleus, and can be used for the combination therapy of osteosarcoma. Furthermore, the preparation method of this invention is simple, the reaction conditions are mild, and it is easy to operate, optimizing the preparation process and application scheme of nano-aluminum, and has the prospect of industrialization.

This invention discloses a novel class of peptides for targeted cancer therapy and their corresponding drug or fluorescent dye conjugates, belonging to the field of biomedical technology. These peptides are designed based on the optimized structure of natural LHRH-III, enabling them to specifically bind to and efficiently internalize into tumor cells overexpressing luteinizing hormone-releasing hormone receptor (LHRH-R). After fluorescent conjugation, their targeting ability against 4T1 cells is comparable to that of the classic peptide [D-Lys]. 6 The [-LHRH-I] peptide exhibits comparable to or superior performance and significantly improves cellular internalization efficiency. In vivo distribution studies have shown that its liver accumulation is significantly reduced compared to the control group, effectively lowering the risk of hepatotoxicity. Furthermore, by conjugating the targeting peptide with antitumor drugs (such as camptothecin or doxorubicin) via disulfide linkers, the resulting peptide-drug conjugates (PDCs) demonstrate excellent responsive drug release characteristics and good in vitro and in vivo antitumor activity. The peptides and conjugates provided by this invention have potential application value in cancer targeted therapy and diagnosis with high specificity and low toxicity.

This invention relates to the field of biomedical technology, specifically disclosing a biomimetic exosome derived from tumor cell membranes, its preparation method, and its applications. The preparation method of the biomimetic exosomes derived from tumor cell membranes provided by this invention includes the following steps: mixing LLC-derived cell membranes with doxorubicin and resveratrol solutions, and preparing biomimetic exosomes derived from tumor cell membranes by extrusion. The preparation method provided by this invention has advantages such as wide availability of raw materials, simple and controllable process, low technical threshold, and suitability for industrial-scale production. The biomimetic exosomes provided by this invention can effectively induce a specific immune response against tumor cells, achieving the purpose of inhibiting the progression of primary tumors and prolonging the survival of tumor-bearing mice. It can also promote the polarization of macrophages from a pro-tumor M2 phenotype to an anti-tumor M1 phenotype, laying a favorable foundation for the efficient implementation of subsequent immunotherapy and possessing broad application prospects.