18 results about "Norcantharidin" patented technology

The invention belongs to the field of biological medicine, and particularly discloses a method for preparing nanoparticles NCTD-LpEV-cRGD by adopting bacterial extracellular vesicles (LpEV) derived from lactobacillus paracasei to entrap tumor chemotherapeutic drug norcantharidin (NCTD) and modifying tumor targeting peptide cRGD on the surface of the LpEV. An anti-colorectal cancer effect test research shows that the NCTD-coated LpEV-cRGD nanoparticle can simultaneously exert a colorectal cancer cell targeting effect and an anti-colorectal cancer proliferation and metastasis effect, so that the anti-colorectal metastasis curative effects of chemotherapeutic drugs norcantharidin and bacterial extracellular vesicles are remarkably enhanced, and the NCTD-coated LpEV-cRGD nanoparticle has good safety. The NCTD-coated LpEV-cRGD nanoparticles prepared by the preparation method disclosed by the invention can be used for preparing medicines for resisting colorectal metastasis.

The application discloses a norcantharidin derivative, a preparation method and application, and belongs to the technical field of medicine preparation. Norcantharidin and aminobenzene boronic acid are dissolved in a proper amount of dry tetrahydrofuran to obtain a crude product; ethyl acetate is added, and white solid is obtained through rotary evaporation under reduced pressure; ethyl acetate and acetone are added for stirring, and white powder norcantharidin derivative is obtained after filtration. The carboxyl of norcantharidin lactone after ring opening is connected with the amino of aminobenzene boronic acid to obtain norcantharidin derivative, which is combined with a chemotherapy drug or used as a preoperative drug to antagonize leukopenia caused by the chemotherapy drug. The norcantharidin derivative synthesized by the application has the advantages of simple method, high yield, low cost, remarkable effect of increasing white blood cells, effective reduction of the toxic side effect of norcantharidin, high oral bioavailability and improved curative effect.

The invention provides a cross-linked astragalus polysaccharide-platinum drug polymer as well as a preparation method and application thereof, and belongs to the field of drug polymer synthesis. The cross-linked astragalus polysaccharide-platinum drug polymer provided by the invention has a chemical structure as shown in a formula I which is described in the specification. The cross-linked astragalus polysaccharide-platinum drug polymer contains the astragalus polysaccharide unit and the cis-platinum-norcantharidin unit, and the astragalus polysaccharide unit improves the enrichment capacity of the polymer on tumor cells and prolongs the residence time; the cis-platinum-norcantharidin unit improves the anti-cancer effect of the polymer and reduces the toxic and side effects of a platinum drug. The toxicity of the cross-linked astragalus polysaccharide-platinum drug polymer provided by the invention is lower than that of cis-platinum and a cis-platinum-norcantharidin small-molecule prodrug; the cross-linked astragalus polysaccharide-platinum drug polymer has IC50 of 23.65 [mu] g / mL and 15.37 [mu] g / mL on two cancer cells A549 and HepG2 respectively, and has relatively low toxic and side effects and good anti-cancer activity.

The invention relates to the technical field of synthetic biology, and discloses a recombinant plasmid and a recombinant bacterium for producing nortetracycline as well as a construction method and application of the recombinant plasmid and the recombinant bacterium. In order to heterologously produce the nortetracycline, the invention provides a recombinant plasmid for producing the nortetracycline, a starting plasmid of the recombinant plasmid is pOxy2, and the recombinant plasmid is obtained by knocking out oxyS and oxyR genes in the starting plasmid pOxy2, then knocking out oxyF genes and introducing ctcN and ctcM genes in an aureomycin biosynthesis pathway to the position of an oxyF original reading frame. The recombinant plasmid prepared by the invention is used for selecting a host which is rapid in growth and simple and convenient in genetic manipulation as a nortetracycline industrial production strain, so that biological synthesis of nortetracycline is realized, and no other tetracycline by-products exist.

The invention discloses a gold nano-enzyme composite material MAuN-coated HA and a preparation method and application thereof, the preparation method of the MAuN-coated HA comprises the following steps: growing gold nanoparticles on MIL-88 (Fe), specifically, uniformly dispersing the MIL-88 (Fe) in water, adding tetrachloroauric acid trihydrate of which the mass is 0.8-1.2 times of that of the MIL-88 (Fe), uniformly mixing, adding a reducing agent into the system, and reacting for 2-5 hours to obtain MAu; then, norcantharidin is loaded on the MAu, and MAuN is obtained; and modifying hyaluronic acid on the surface of the MAuN to obtain the product. According to the composite material disclosed by the invention, through chemotherapy, chemokinetic therapy, enhancement effect of gold atom nano-enzyme on activity of CAT / POD / OXD-like enzyme and multi-catalytic mechanism of Russell effect, remarkable chemotherapy / CDT synergistic therapy is realized, and the problem of low efficiency of traditional CDT therapy is solved.

The present application provides the application of Rabdosia serra extract in the preparation of drugs for treating atrophic gastritis and precancerous lesions of gastric cancer, wherein the Rabdosia serra extract includes Rabdosia serra aerial part extract, Rabdosia serra underground part extract, Rabdosia serra total part extract and eluate thereof, etc. The present application also provides the application of compounds in Rabdosia serra in the preparation of drugs for treating atrophic gastritis and precancerous lesions of gastric cancer, wherein the compounds in Rabdosia serra are selected from oridonin, rabdosin C, norcantharidin, raxofelone and rabdosiin A. The present application proves that Rabdosia serra extract and the compounds in Rabdosia serra have good activity of reversing precancerous lesions of gastric cancer by constructing a cell model (MC cell model) of atrophic gastritis and precancerous lesions of gastric cancer by stimulating GES-1 cells with MNNG.

The application belongs to the technical field of biological medicine, and particularly relates to a multi-hydrogen bond cross-linked outer membrane inner core type norcantharidin lipid nanoparticle and a preparation method and application thereof. In order to improve the encapsulation rate of norcantharidin (Nor), solve the problems of poor water solubility, insufficient targeting, low stability and strong toxic and side effects of the existing Nor preparation, the application provides a multi-hydrogen bond cross-linked outer membrane inner core type norcantharidin lipid nanoparticle (Man-Nor-NLCs). Compared with the existing nanoparticles for delivering Nor, the Man-Nor-NLCs of the application not only has enhanced structural stability, but also can realize precise targeting and intelligent controlled release, and has specific, rapid and efficient accumulation capacity in tumor tissues. Meanwhile, the preparation raw material is biodegradable and non-toxic, and is easy to industrialize, so the application has wide application prospect.

The invention provides a cantharidin-alkannin derivative as well as a preparation method and application thereof, and relates to the field of drug synthesis and application, two active structures of alkannin and norcantharidin are spliced into a norcantharidin-alkannin anti-tumor monomer, the two active structures are combined to generate a synergistic anti-tumor effect, and the anti-tumor activity of the norcantharidin-alkannin anti-tumor monomer is improved. According to the present invention, with the application of the traditional Chinese medicine composition, the adverse reactions such as the improvement of the water solubility of the alkannin, the reduction of the irritation of the norcantharidin to the gastrointestinal tract and the like can be possibly reduced in the aspects of tumor cell killing effect enhancing, treatment efficiency improving and toxic-side effect reducing, such that the tolerance and the compliance of the patient are improved, and the more effective treatment scheme is provided for the cancer patient; a foundation is laid for developing a novel anti-tumor drug with the characteristics of high efficiency and low toxicity.

The invention belongs to the technical field of medicines, and relates to a vincristine sulfate liposome freeze-dried product as well as a preparation method and application thereof, in particular to a vincristine sulfate liposome or sialic acid modified vincristine sulfate liposome freeze-dried product as well as a preparation method and application thereof in preparation of antitumor drugs. The vincristine sulfate liposome modified by sialic acid is a vincristine sulfate liposome modified by a sialic acid lipid derivative. The vincristine sulfate liposome is prepared by taking (NH4) 4EDTA (Ethylene Diamine Tetraacetic Acid) as a hydration medium and adopting an ethylenediamine tetraacetic acid amine (DTA-NH4) gradient method. And preparing a vincristine sulfate liposome freeze-dried product by taking a combination of disaccharide and monosialotetrahexosyl ganglioside (sodium salt) as a freeze-drying protective agent. The vincristine sulfate liposome freeze-dried product disclosed by the invention has good in-vivo and in-vitro stability, tumor active targeting property and excellent anti-tumor effect. And the compound can be combined with norcantharidin to improve the anti-tumor activity.

The invention discloses a traditional Chinese medicine engineered core-shell structure gold nanoparticle and a preparation method and application thereof.The preparation method comprises the steps that D1-miR155 modified gold nanoparticles, D2-miR155 modified gold nanoparticles, polyethylene glycol modified norcantharidin and a tumor cell membrane are mixed to be uniform, extrusion is conducted through a lipidosome extruder, and the core-shell structure gold nanoparticle is obtained; the traditional Chinese medicine engineered core-shell structure gold nanoparticles are obtained. The prepared gold nanoparticles can capture oncogene miR155 overexpressed in tumor cells to activate the photothermal conversion effect, induce apoptosis of the tumor cells and cause the process of immunogenic death (ICD). Meanwhile, a key signal molecule STAT3 of a tumor can be regulated and controlled by reducing miR155 so as to enhance immunogenicity of the tumor, a Tregs inhibitor-norcantharidin (DMC and traditional Chinese medicine small molecules) is effectively delivered to inhibit immune escape of the tumor, and stronger photothermal-immunotherapy activity is achieved together with an ICD process caused by photothermal.

The invention belongs to the field of medicinal chemistry, and particularly relates to tripterine-nojirimycin derivatives as well as a preparation method and application thereof. The tripterine-nojirimycin derivative provided by the invention not only overcomes the defects of high toxicity, low bioavailability, poor water solubility and the like of tripterine, but also has good hypoglycemic and lipid-lowering activity, has lower toxicity compared with tripterine, and has good clinical application potential.

This invention discloses a pH-sensitive norcantharidin solid self-microemulsion, its preparation method, and its applications, belonging to the field of pharmaceutical technology. It comprises the following components in parts by weight: 0.1–3 parts norcantharidin, 1–10 parts pH-sensitive polymer, 30–80 parts solid adsorbent, and 87–98.9 parts blank self-microemulsion. The pH-sensitive norcantharidin solid self-microemulsion of this invention can improve the solubility and permeability of the drug. Due to the amide bond cleavage of the pH-sensitive polymer under acidic conditions, the drug is released systematically from the interior of the nano-solid self-microemulsion, resulting in targeted release at the tumor site. Animal experiments show that the pH-sensitive norcantharidin solid self-microemulsion of this invention can effectively improve the absorption rate constant and apparent permeability coefficient of norcantharidin at the colon tumor site, thereby enhancing its ability to inhibit tumor growth, migration, and invasion, and thus significantly improving the therapeutic effect of colon tumors.

The application discloses a doxorubicin-quadruple platinum drug-norcantharidin three-drug combination nano drug and a preparation method and application thereof, and belongs to the technical field of medical materials. 2+ The application constructs a novel nano drug through coordination of doxorubicin and a quadruple platinum drug modified by norcantharidin, and then polymerizes polydopamine with a mild photothermal effect to prepare a nano drug for the three-drug combination of doxorubicin, the quadruple platinum drug and norcantharidin. The nano drug has the ability of controlled release of drugs under acidity and reduction, can realize photothermal conversion to generate a mild photothermal effect under laser irradiation, has a better tumor cell killing effect, has the ability of consumption of glutathione and generation of hydroxyl radicals, can enter cancer cells through an endocytosis mode and release DOX, and provides a new idea for multi-drug combination, chemotherapy-chemical kinetics treatment-photothermal treatment multi-mode combined treatment.

The application provides a norcantharidin emulsion and a preparation method and application thereof, and belongs to the technical field of pharmaceutical preparations.The norcantharidin emulsion is prepared from the following components by weight: 0.2-0.3 parts of norcantharidin, 2.0-3.0 parts of phospholipid, 0.5-0.75 parts of a membrane stabilizer, 10-15 parts of an oil phase matrix, 0.05-0.1 parts of a co-emulsifier, 1.2-1.8 parts of an emulsifier, 6.5-7.5 parts of a gel matrix, 3.0-3.25 parts of a humectant and 950-1000 parts of water.The norcantharidin emulsion has high stability, uniform drug distribution and low irritation, can effectively isolate or relieve the direct contact irritation of the raw drug to the skin, promote the penetration of the drug through the stratum corneum of the skin, increase the retention amount of the drug in the target skin layer, reach a local effective concentration and achieve the goal of reducing irritation and increasing curative effect.

This invention discloses the preparation and application of a ternary carrier-free injectable hydrogel co-assembled from glycyrrhizic acid, norcantharidin, and copper ions. The hydrogel forms a gel without the addition of excipients and possesses excellent gel material properties such as injectability, thermosensitivity, and stability, making it an ideal anti-tumor drug for clinical application. This hydrogel induces tumor cell apoptosis, copper death, and anti-inflammation, synergistically regulating the tumor microenvironment; combined with laser irradiation to enhance the Fenton-like effect, it achieves chemokinetic therapy of tumors. In the Hepa1-6 hepatocellular carcinoma mouse model, this hydrogel exhibits excellent anti-tumor activity, with significantly better efficacy than individual drug groups. Furthermore, this hydrogel has good biocompatibility and is a novel anti-tumor hydrogel that is simple to prepare, green, and has potential for clinical translation.

The application discloses a norcantharidin derivative, a synthetic method and application thereof, and belongs to the technical field of medicine preparation. Norcantharidin and aminobenzene boronic acid are dissolved in an ice acetic acid solution, after reaction, the obtained white filter residue is dried to obtain a crude product; then the crude product is dissolved in methanol and repeatedly recrystallized to obtain transparent needle-like crystalline norcantharidin derivative. The amino group of aminobenzene boronic acid is used to connect norcantharidin and aminobenzene boronic acid to obtain the norcantharidin derivative, which can antagonize leukopenia caused by chemotherapy drugs on the basis of retaining the anticancer activity. The synthetic method is simple, the yield is high, the cost is low, the toxic and side effects of norcantharidin in treating liver cancer can be effectively reduced, the oral bioavailability is high, and the curative effect is improved.

The application provides a culture method of macrophages and application thereof, and the culture method comprises the following steps: using human PBMCs, adding an induction culture medium to induce differentiation into macrophages, wherein the induction culture medium comprises a basic culture medium, serum, M-CSF and 5-15 muM norcantharidin, wherein liquid supplementing or replacing is performed every 2-3 days; 100 U / mL IFN-gamma is added to the induction culture medium on the fifth day to induce macrophages; the macrophages are continuously cultured for 2 days, and corresponding macrophages are obtained; the cells and supernatant are obtained by centrifugation, and the cells and supernatant are detected. By using the method, M1 polarization of macrophages can be inhibited, and a new application prospect of anti-inflammation of macrophages is provided.

The invention provides a macrophage culture method and application thereof, the culture method comprises the following steps: human PBMC is adopted, an induction medium is added for induced differentiation into macrophages, the induction medium comprises a basic medium, serum, M-CSF and 5-15 [mu] M norcantharidin, and liquid supplementation or liquid replacement is carried out every 2-3 days; on the fifth day, 100 U / mL of IFN-gamma is added into the induction culture medium to induce macrophages; and continuously culturing for 2 days to obtain corresponding macrophages, centrifuging to take cells and supernate, and detecting the cells and the supernate. By adopting the method, the M1 type polarization of the macrophages can be inhibited, and a new application prospect is provided for the anti-inflammation of the macrophages.