78 results about "Gemcitabine" patented technology

The application discloses a LYTAG-Gem compound for enhancing the anti-tumor effect of gemcitabine and application thereof, relates to the technical field of biological medicine, and particularly relates to a gemcitabine (Gem) targeted delivery system based on a lysosome targeting chimera (LYTAC) and application thereof in enhancing the anti-tumor process. 2+ The system is assembled from heavy chain ferritin, Ni 2+ , NTA-PEG5000-DBCO and a targeting ligand TPP-1-N3 in a specific mass percentage, can efficiently load Gem and form a nano compound with a particle size of about 59-79 nm, the system targets tumor cells through heavy chain ferritin, and realizes site-specific release of Gem in cells by means of an endocytosis-lysosome pathway mediated by the LYTAC structure, in-vivo pharmacodynamic experiments show that the LYTAC-Gem compound can significantly inhibit the tumor growth of a KPC pancreatic cancer mouse model, molecular mechanism research further reveals that the LYTAC-Gem compound can down-regulate the expression of PD-L1 protein in tumor tissues, and it is indicated that the LYTAC-Gem compound has the potential to activate an anti-tumor immune response, and the application provides a novel targeted delivery strategy for overcoming the toxic side effects and tumor drug resistance of gemcitabine.

The present invention provides methods for treatment of high-risk non-muscle invasive bladder cancer that is unresponsive to BCG therapy by locally administering gemcitabine to the bladder. Also provided herein are kits and articles of manufacture for treating high-risk non-muscle invasive bladder cancer that is unresponsive to BCG.

The present disclosure provides double stranded nucleic acid compositions incorporating uracil, gemcitabine, and methotrexate (MTX). More specifically, the present disclosure reveals that modification of a double-stranded microRNA nucleotide sequence with 5-fluorouracil, gemcitabine, and methotrexate (MTX) enhances the therapeutic efficacy and tumor specificity of tumor suppression. Thus, the present disclosure provides various nucleic acid (e.g., microRNA) compositions having 5-fluorouracil, gemcitabine, and methotrexate (MTX) incorporated into their nucleic acid sequences, as well as methods of using the same. The disclosure further provides pharmaceutical compositions (e.g., formulations) comprising the modified nucleic acid compositions, and methods for treating cancer, e.g., pancreatic cancer. The method is a platform technology which can be applied to other tumor suppressor genes miRNA and siRNA.

The invention provides a drug-loaded gelatin nanogel, a bionic nanogel, a preparation method of the drug-loaded gelatin nanogel, a preparation method of the bionic nanogel, a combined drug and application of the bionic nanogel, and belongs to the technical field of biological medicine. According to the invention, all-transretinoic acid, pirfenidone and gelatin react to form drug-loaded gelatin nanogel, and the drug-loaded gelatin nanogel can synergistically inhibit the activation of pancreatic stellate cells and block a fibrosis-promoting signal channel, so that the reversion of a pancreatic cancer fibrosis microenvironment is realized; meanwhile, the activated pancreatic stellate cell membrane is coated with the drug-loaded gelatin nanogel to construct the bionic nanogel, so that the bionic nanogel has active targeting property, and the delivery efficiency and the treatment effect of the drug are remarkably improved; and the drug-loaded gelatin nanogel, the bionic nanogel and the chemotherapeutic drug are combined for treating pancreatic cancer, so that a remarkable anti-tumor effect is achieved, and the combined treatment of the bionic nanogel and gemcitabine has a synergistic anti-tumor effect. The gel provided by the invention realizes effective regulation and control of a pancreatic cancer dense fibrosis microenvironment, and provides a feasible new strategy for treatment of pancreatic cancer.

The invention relates to a gemcitabine prodrug nano assembly as well as a preparation method and application thereof, and belongs to the field of new auxiliary materials and new dosage forms of pharmaceutical preparations. The gemcitabine-vitamin E prodrug is obtained by connecting gemcitabine and vitamin E by taking thiodiglycolic anhydride as a connecting chain, and the specific structure is as shown in a general formula (I). The prodrug disclosed by the invention can construct and form a gemcitabine-vitamin E prodrug nano assembly with good self-assembly stability and chemical stability based on a Core-matured technology, and specifically releases gemcitabine in a high-oxidation environment in tumor cells, so that the curative effect of gemcitabine is effectively improved, the toxic and side effects of gemcitabine are reduced, and the preparation method is suitable for clinical application. And a new strategy and choice are provided for developing a high-efficiency and low-toxicity chemotherapy preparation.

The present invention is directed to polymer-drug conjugates and / or compositions and / or nanoparticles comprising anti-cancer agents. The present invention is also directed to polymer- drug conjugates and / or compositions comprising docetaxel and the administration of docetaxel derivatives for the treatment of a number of diseases. The present invention is also directed to polymer-drug conjugates and / or compositions comprising gemcitabine or combretastatin A4 for the treatment of a number of diseases.

The present invention provides methods, devices and kits relating to treating lower tract urothelial carcinomas with an antimetabolite (such as gemcitabine). In some aspects the methods, devices and kits relate to treating lower tract urothelial carcinomas with an antimetabolite (such as gemcitabine) and an immunomodulatory agent.

The invention provides a pharmaceutical composition for preventing and / or treating pancreatic cancer and application, and belongs to the technical field of biological medicine. According to the pharmaceutical composition, through combination of amentotaxus biflavone and gemcitabine, the prevention and treatment effect of gemcitabine or amentotaxus biflavone on pancreatic cancer can be further improved, and the pharmaceutical composition has a synergistic interaction effect. Research results show that the combination of amentoflavone and gemcitabine not only can significantly inhibit the growth of pancreatic cancer cells, but also can inhibit the migration ability of pancreatic cancer cells. The pharmaceutical composition disclosed by the invention provides more choices for clinically preventing and treating pancreatic cancer.

A method for treating a tumor, characterized by administering to an individual having a tumor immune effector cells expressing a receptor recognizing a tumor antigen and gemcitabine. A kit for treating a tumor, characterized by comprising: 1) immune effector cells expressing a receptor recognizing a tumor antigen; 2) gemcitabine; 3) a container for containing the above 1) and 2); and 4) a written notice for treating a tumor using the kit.

The application provides a candidate drug for promoting embryo implantation efficiency of a patient with endometrial microcirculation disorder type RIF, and belongs to the technical field of embryo implantation. In order to solve the problem of how to find a potential intervention drug for the pathological mechanism of microcirculation disorder type RIF, a five-step high-efficiency drug screening strategy based on an in-vitro implantation model of endometrial microcirculation disorder type repeated embryo implantation failure is adopted to ensure the reliability and functional correlation of the screening result. The candidate drug screened by the five-step high-efficiency drug screening strategy includes any one of the following drugs: phenylbutazone, ferulic acid, L-proline, indinavir, solfazone, teneligliptin and gemcitabine. Among the candidate drugs, phenylbutazone, ferulic acid and L-proline are the best three drugs for promoting the implantation efficiency of the patient with endometrial microcirculation disorder type RIF.

A method for treating a tumor, characterized by administering to an individual having a tumor immune effector cells expressing a receptor recognizing a tumor antigen and gemcitabine. A kit for treating a tumor, characterized by comprising: 1) immune effector cells expressing a receptor recognizing a tumor antigen; 2) gemcitabine; 3) a container for containing the above 1) and 2); and 4) a written notice for treating a tumor using the kit.

The present invention belongs to the technical field of cancer pharmaceuticals, and specifically relates to the use of AZD1152 and gemcitabine in the preparation of a drug for treating cholangiocarcinoma. AZD1152 and gemcitabine exhibit a synergistic effect in the treatment of cholangiocarcinoma. The combination of AZD1152 with gemcitabine can significantly inhibit cholangiocarcinoma cell proliferation and tumor growth, with efficacy superior to that of AZD1152 or gemcitabine alone.

The application discloses a kind of endoplasmic reticulum of tumor cell can be targeted N -(2-hydroxypropyl) methacrylamide (HPMA) polymer-drug conjugate. The chemotherapeutic drug carried by the HPMA polymer is at least one of doxorubicin, epirubicin, pirarubicin, cisplatin, oxaliplatin, camptothecin, paclitaxel, gemcitabine, methotrexate, vinblastine, mitoxantrone, irinotecan, and the linker for connecting the drug and the HPMA polymer is at least one of hydrazone bond, amide bond, ester bond, disulfide bond, and ketosulfenyl bond. The HPMA polymer-drug conjugate targets the drug to the endoplasmic reticulum through receptor-ligand interaction, can cause severe endoplasmic reticulum stress, thereby transporting a large amount of calnexin to the tumor cell membrane surface, greatly improving the immunogenicity of tumor cells, and promoting tumor immunotherapy.

The invention discloses a pharmaceutical composition for inhibiting tumor drug resistance and application thereof. The pharmaceutical composition comprises an exosome inhibitor, nintedanib and gemcitabine, the exosome inhibitor, the nintedanib and the gemcitabine are used in a combined manner, so that the cell viability of the CTS can be remarkably reduced, and the proportion of apoptotic cells in the CTS can be remarkably increased; the pharmaceutical composition interferes with the mutual transformation process between normal fibroblasts and CAFs, and inhibits secretion and release of EVs and reduces formation of new CAFs while restoring the CAFs existing in TME to normal fibroblasts, thereby successfully reversing the drug resistance of tumors.

The invention provides a novel human distal bile duct cancer cell line with TP53 missense mutation and application, the novel human distal bile duct cancer cell line CBC3T-3 is established, the cell line is preserved in the China Center for Type Culture Collection (the preservation number is CCTCC NO: C202555), the uniqueness and stability of the cell line are proved through STR typing and karyotype analysis, and the TP53 missense mutation novel human distal bile duct cancer cell line has the advantages that the TP53 missense mutation novel human distal bile duct cancer cell line CBC3T-3 can be used for preparing the TP53 missense mutation novel human distal bile duct cancer cell line CBC3T-3; and a plurality of driver gene mutations including TP53 missense mutation are carried. The CBC3T-3 has strong proliferation, invasion and migration capabilities, has high tumor formation rate in immunodeficient mice, is resistant to cis-platinum and sensitive to paclitaxel and gemcitabine, and provides an experimental basis for selection of clinical chemotherapy regimens. According to the model, the TP53 missense mutation type distal bile duct cancer in-vitro model is successfully established, and a key experimental platform is provided for deeply researching the drug resistance mechanism of the TP53 missense mutation type distal bile duct cancer and developing an individualized treatment strategy aiming at the subtype of the TP53 missense mutation type distal bile duct cancer.

This invention relates to a liposomal formulation based on myeloid cell regulation and chemotherapy enhancement, along with its preparation method and antitumor applications, belonging to the technical field of pharmaceutical formulations. The liposomal formulation uses liposomes as carriers to co-load the CD11b agonist leukadherin-1 (LA1) prodrug (DSPE-PEG2000-Azo-LA1) and the gemcitabine prodrug Gem-SS-Chol. DSPE-PEG2000-Azo-LA1 contains a hypoxia-responsive azobenzene linker, and Gem-SS-Chol contains a glutathione-responsive disulfide bond, enabling precise drug release within the tumor microenvironment. This formulation exhibits uniform particle size and good stability, synergistically exerting chemotherapeutic and immunomodulatory effects. It effectively inhibits the proliferation and migration of pancreatic cancer tumor cells, enhances tumor cell immunogenic cell death, regulates the phenotype of myeloid immune cells in the tumor immunosuppressive microenvironment, and improves the therapeutic effect of pancreatic cancer. This invention provides a novel and highly efficient liposomal formulation for pancreatic cancer treatment, focusing on myeloid cell regulation and chemotherapy enhancement.

The invention discloses a preparation method and application of a multistage rocket structure nanometer material in the technical field of biomedical materials. Mesoporous silicon dioxide (MSNs) serves as a core, gemcitabine (GEM) is wrapped in the core, the outer layer of the core is coated with calcium carbonate to form a middle layer, halofuginone (HF) is loaded on the middle layer, and the outermost layer is connected with targeting molecules to form a core-shell structure; the nano material has pH and GSH dual responsiveness, calcium carbonate on the outer layer is disintegrated in a subacid environment with the pH being 6.2-6.5, and mesoporous silica (MSNs) on the inner layer is further disintegrated in a 10mM GSH environment; the synthesis method provided by the invention is simple and easy to operate, and the nanoparticles have the advantages of large specific surface area, uniform particle size, good biocompatibility and the like.

The present invention provides CIP3M, a SN38 / gemcitabine conjugate that is useful as an anti-cancer agent. The present invention also provides pharmaceutical composition comprising CIP3M, and the use of CIP3M and pharmaceutical compositions thereof, as therapeutic agents, in particular in the treatment of cancers, including metastatic cancers and chemoresistant cancers.

The invention discloses application of an IGF2BP2-m6A-VCAN-TLR2 (Insulin-like Growth Factor 2BP2-m6A-VCAN-TLR2) signal axis in preparation of a medicine for treating lymphatic metastasis of intrahepatic cholangiocarcinoma. Aiming at the problems of unknown lymphatic metastasis mechanism and lack of effective targets of intrahepatic cholangiocarcinoma, the invention discovers and verifies that mRNA binding protein 2 of insulin-like growth factor 2 is modified by m6A to regulate and control the expression of pluripotent proteoglycan so as to activate a Toll-like receptor 2 signal, promote macrophages to secrete vascular endothelial growth factor C and drive a brand new pathway of lymphatic metastasis. Based on this, the invention provides an inhibitor targeting the signal axis, especially a small molecule compound 8010-8498. Experiments show that the compound can significantly inhibit migration, invasion and epithelial-mesenchymal transition of bile duct cancer cells, reduce macrophage secretion of vascular endothelial growth factors C, effectively inhibit tumor growth and lymphatic metastasis in a nude mouse popliteal lymph node metastasis model and a spontaneous bile duct cancer model, and present a synergistic effect when combined with gemcitabine and cis-platinum.

To provide: novel small molecule-drug conjugates (SMDCs) for using in the treatment or prevention of cancer or other proliferative conditions characterized by cells expressing cytochrome P4501B1 (CYP1B1) and allelic variants thereof; pharmaceutical compositions comprising one or more such compounds for use in the treatment or prevention of cancer or other proliferative conditions in medical therapy; and methods for treating cancer or other conditions in human or non-human patients.SOLUTION: Compounds of formula (I) are provided.SELECTED DRAWING: Figure 1a

This invention belongs to the field of ovarian cancer cell inhibitor technology, specifically relating to a reagent for inhibiting the proliferation of ovarian cancer cells, its preparation method, and its application. The reagent for inhibiting the proliferation of ovarian cancer cells is composed of the following raw materials: gemcitabine, vitamin B6, and a decoction of *Rhizophora stylosa* leaves, with a mass ratio of 0.4~0.7:5~10:1000. This invention utilizes vitamin B6 and *Rhizophora stylosa* leaf decoction to enhance the inhibitory effect of gemcitabine on ovarian cancer cells, showing significant killing effects on OVCAR3 and ES-2 cells, while exhibiting weak killing effects on normal human ovarian epithelial cells IOSE-80, suggesting that the reagent of this invention has anti-ovarian cancer activity.

The invention belongs to the technical field of biological medicines, and particularly relates to a bladder cancer targeted nano-drug and a preparation method thereof. The drug is constructed by taking a chemotherapeutic drug gemcitabine-loaded poly (lactic-co-glycolic acid) nanoparticle as a core and assembling two functional components, namely a gadolinium-doped zinc-aluminum layered double hydroxide folic acid conjugate and a bismuth-tellurium alloy nano-cluster hyaluronic acid compound, on the surface of the nanoparticle. During preparation, the drug-loaded nanoparticles are prepared by adopting a multiple emulsion solvent evaporation method, and then the two functional compounds are co-assembled on the surfaces of the drug-loaded nanoparticles by utilizing electrostatic interaction to form the multifunctional hybrid shell layer. The nano-drug integrates multiple functions such as active targeting, microenvironment response drug release, multi-mode imaging, chemotherapy and chemical kinetics combined treatment and radiotherapy sensitization, enrichment and permeation of the drug at a bladder tumor part can be remarkably improved, efficient synergistic treatment is achieved, system toxicity is reduced, and the nano-drug is particularly suitable for perfusion treatment in the bladder.

The invention relates to a proportion-locked in-situ gel for tumor chemoimmunotherapy as well as a preparation method and application of the proportion-locked in-situ gel. The in-situ gel comprises a pharmaceutical composition and sodium alginate (ALG), wherein the pharmaceutical composition is composed of gemcitabine (GEM), oxaliplatin (OXA) and cytidine deaminase inhibitor chidauridine (CDZ), and the sodium alginate (ALG) is used as a carrier. The in-situ gel is subjected to intratumor injection and then gelation is triggered by Ca < 2 + > in a tumor, so that local retention and synchronous slow release of the medicine are realized. Metabolic inactivation of GEM is inhibited through CDZ, the optimal treatment proportion of GEM and OXA is maintained at the tumor site, and meanwhile the in-situ gel solves the problems of systemic toxicity and proportion imbalance caused by traditional intravenous administration. The synergistic effect of the pharmaceutical composition not only enhances direct cytotoxicity, but also synergistically activates anti-tumor immune response through OXA-induced immunogenic cell death and GEM-mediated regulatory T cell depletion. The invention realizes safe and efficient local chemical immunotherapy, and has a good clinical application prospect.

This utility model discloses a distillation apparatus for producing gemcitabine. Upon opening the valve, the apparatus begins a reaction. An evaporation chamber is fixedly connected to the end of a first conduit. A reboiler is fixedly connected to the left side of the evaporation chamber via a pipe. A reflux conduit is located at the lower end of the reboiler, and a bottom liquid pump is fixedly connected to its rear surface. A column bottom receiving device is fixedly connected to the right side of the bottom liquid pump. The liquid enters the reboiler through the bottom reflux conduit for further heating. Sediment forms at the bottom of the evaporation chamber; this sediment is pumped out by the bottom liquid pump and enters the column bottom receiving device. A third conduit is fixedly connected to the upper right end of the evaporation chamber. A condenser is located at the upper end of the second conduit. A reflux tank is fixedly connected to the rear side of the condenser. A buffer tank is fixedly connected to the inlet of the reflux tank, and a finished product storage tank is fixedly connected to the other side of the filter screen. A reflux vessel is located at the lower end of the reflux tank, allowing for cyclical and repeated evaporation, thus improving utilization.

The application provides a Her-2 antibody-polyethylene glycol-reverse phospholipid, a gemcitabine reverse phospholipid liposome preparation and a preparation method and application thereof, and belongs to the technical field of biological medicines. The Her-2 antibody-polyethylene glycol-reverse phospholipid provided by the application has a structure shown in formula I. The Her-2 antibody-polyethylene glycol-reverse phospholipid is used to prepare a gemcitabine reverse phospholipid liposome coupled with a Her-2 antibody by simultaneously compounding a reverse phospholipid as a main auxiliary material, so that the gemcitabine can be accurately targeted to Her-2 positive breast cancer cells and kill the Her-2 positive breast cancer cells, and the gemcitabine has excellent Her-2 positive breast cancer treatment effect.

The invention relates to siRNA targeting TRIM29, the sequence of the siRNA is shown as SEQ ID NO.1. Through cell level and animal level experiment detection, the siRNA can inhibit expression of the TRIM29, and the sensitivity of gallbladder cancer to gemcitabine is remarkably improved; the invention further relates to gemcitabine and TRIM29 siRNA co-loaded lipid nanoparticles and a preparation method and application thereof, the preparation method comprises the steps that firstly, gemcitabine and TRIM29 siRNA wrapped lipid nanoparticles are constructed, then the gemcitabine and TRIM29 siRNA are co-incubated to obtain GSL, the GSL is oval in microcosmic shape and good in stability, through cell level and animal level experiment detection, the GSL has a good anti-tumor effect, and the GSL has a good anti-tumor effect on the gemcitabine and TRIM29 siRNA co-loaded lipid nanoparticles. The GSL can significantly reduce the protein expression level of TRIM29, significantly improve the sensitivity of gallbladder cancer to gemcitabine, inhibit tumor growth, and inhibit STAT3 pathway, and the GSL prepared by the method has good biological safety, and opens up a new channel for treatment of gallbladder cancer.

The application discloses an IGF2BP2-m6A-VCAN-TLR2 signal axis in the preparation of a drug for treating intrahepatic cholangiocarcinoma lymphatic metastasis. In view of the problems of unknown intrahepatic cholangiocarcinoma lymphatic metastasis mechanism and lack of effective target, the application finds and verifies a new pathway that from insulin-like growth factor 2 mRNA binding protein 2, m6A modification regulates the expression of multi-functional proteoglycan, and then activates Toll-like receptor 2 signal, promotes macrophage secretion of vascular endothelial growth factor C and drives lymphatic metastasis. Based on this, the application provides an inhibitor targeting the signal axis, in particular, a small molecule compound 8010-8498. Experiments show that the compound can significantly inhibit cholangiocarcinoma cell migration, invasion and epithelial mesenchymal transition, reduce macrophage secretion of vascular endothelial growth factor C, and effectively inhibit tumor growth and lymphatic metastasis in a naked mouse popliteal lymph node metastasis model and a spontaneous cholangiocarcinoma model. The compound presents a synergistic effect in combination with gemcitabine and cisplatin.

The present invention relates to a method using low intensity pulsed ultrasound (LIPUS) in order to improve drug delivery efficiency in a hypoxic tumor microenvironment (TME) of cholangiocarcinoma (CCA), and more specifically, to a method for confirming the drug permeability and cancer cell apoptosis of cholangiocarcinoma through the irradiation of low intensity pulsed ultrasound (LIPUS) under a tumor microenvironment, and a combination regimen, of gemcitabine and cisplatin with low-intensity pulsed ultrasound, for inhibiting cholangiocarcinoma growth. To this end, provided is the method for confirming the drug permeability and cancer cell apoptosis of cholangiocarcinoma through the irradiation of low intensity pulsed ultrasound (LIPUS) under a tumor microenvironment, the method comprising: a step (S100) for administering a drug and a fluorescent material to cholangiocarcinoma (CCA) under a tumor microenvironment; a step (S120) for allowing a predetermined time to elapse; a step (S140) for irradiating the cholangiocarcinoma (CCA) low intensity pulsed ultrasound (LIPUS); a step (S160) for acquiring a 3D image by performing tissue-clearing on the cholangiocarcinoma (CCA); and a step (S180) for confirming the in vivo drug permeability of a drug and a fluorescent material from the 3D image.

The need for improved drug delivery methods and systems for treating bladder cancer remains. It exists as such. [Solution] Gemcitabine is administered intravesically into the bladder of patients requiring treatment for bladder cancer, and then absorbed into the bladder tissue. A sustained concentration of gemcitabine sufficient to produce the above-mentioned therapeutically effective concentration By obtaining mucitabine in the urine of the bladder, the above patients can be administered gemcitabine. A drug delivery device and method are provided. In an embodiment, local delivery into the bladder of the patient. The administration is based on the average dose of gemcitabine (FBE) mentioned above, ranging from 1 mg / day to approximately 300 mg / day. That is the case.

The invention discloses application of polyporus polysaccharide in prevention and treatment of drug-induced liver injury (DILI) caused by antitumor drugs, and belongs to the field of new application of traditional Chinese medicines. Aiming at the clinical pain point of lack of effective prevention and treatment means for liver injury caused by anti-tumor drugs in the prior art, the prevention effect of polyporus polysaccharide on liver injury caused by anti-tumor drugs is verified for the first time by constructing mouse liver injury models with single use of cis-platinum and oxaliplatin and combined use of cis-platinum and oxaliplatin and paclitaxel and / or gemcitabine. Experiments show that compared with a model group, the serum ALT and AST levels of a drug delivery group are remarkably reduced, the T-SOD activity of liver tissues is improved, the GSH-Px activity is improved, the MDA content is reduced, and definite dose dependence is shown. The invention provides a safe and effective traditional Chinese medicine solution for the prevention and treatment of liver injury by antitumor drugs, and has the advantages of clear mechanism and clinical applicability.