85results about How to "Tumor targeting" patented technology

The invention provides medicinal compositions of taxol medicaments and pharmaceutically acceptable biological carriers and preparation method thereof. The medicinal compositions of the taxol medicaments and carrier proteins are nano mixed suspensions prepared from the carrier proteins, organic phases, stabilizers, freeze drying protective agents and the taxol medicaments. The weight volume percentconcentration of the taxol medicaments is 0.075 to 1.0. The taxol medicament nano particles prepared by using high-pressure homogenization can reduce adverse reaction aroused by the taxol medicamentsand improve the safety of the clinical administration of the taxol medicaments. The preparation process of the nano mixed suspensions is simple and feasible and is suitable for large-scale preparation and industrial production.

The invention discloses a redox-sensitive core-crosslinked Pulullan nano particle having dual-targeting property and a preparation method thereof, preparation of a drug carrying nano particle with the compound as a carrier, and in-vitro releasing researching of the drug carrying nano particle. The method includes the steps of: 1) performing esterification reaction to lipoic acid and Pulullan to convert the water-soluble Pulullan into a hydrophobic polymer, which is beneficial to preparation of nano particles and entrapment of a hydrophobic medicine; 2) conjugating the polymer with folic acid to form a folic acid-Pulullan-lipoic acid conjugate, and performing crosslinking to inner cores of the nano particles in DTT in catalytic quantity to prepare stable and reversible folic acid-Pulullan-lipoic acid (FA-Pull-LA) nano particles having dual-targeting property. The drug carrying nano particle is prepared with paclitaxel as a model medicine in a dialysis manner, wherein stability and reduction sensitivity of the drug carrying nano particle are inspected through an in-vitro releasing test. A result proves that the dialysis method for preparing the FA-Pull-LA nano particles is simple and has good repeatability, is easy to achieve expanded production and has high drug carrying rate. The nano particle is stable in vitro and can quickly release the drug in an intracellular reductive environment.

The invention belongs to the field of pharmaceutical preparations, and provides a pharmaceutical albumin nanoparticle, a preparation method and application of the nanoparticle to tumor targeting therapy. The nanoparticle is made from two types of proteins, namely avidin and albumin, encapsulating slightly-soluble antitumor drugs. The electrostatic interaction exists between avidin and albumin, and avidin in the nanoparticle can be combined with biotin. Avidin can target the nanoparticle encapsulating the drugs on a biotin enrichment part. Before the application of the nanoparticle, a biotinylated antibody is used for pre-targeting on a tumor part, and can improve the distribution of a nanoparticle preparation in the tumor part. The biotinylated antibody and the nanoparticle preparation are combined for therapy, thereby playing better antitumor effect than the effect played by the combination of a monoclonal antibody and an albumin nanoparticle without avidin.

A transgenic carrier with deal targets (fibroblast growth factor receptor and integrant) is composed of the polypeptide CR16 specifically linked with alkaline fibroblast growth factor receptor, the polypeptide CP9 specifically linked with integrant, and the transgenic non-virus carrier system of CR16/CP9/cationic polymer PEI/exogenous DNA. Said carrier can effectively introduce the exogenous DNA to the tumor cell line and tumor tissue with high expression of FGFRs, so suppressing the growth of tumor. It can be used to preparation of the medicine for treating tumor and other diseases.

The invention discloses a tumor-targeting albumin nano-lyophilized powder injection preparation and a preparation method thereof. The preparation comprises the following components: an insoluble antitumor drug (for example, taxol), albumin, tricaprylin, tributyrin, polyethylene glycol-12-hydroxy stearate and phospholipid. The tumor-targeting albumin nano-lyophilized powder injection preparation provided by the invention can spontaneously form a nanoemulsion with the particle size of about 100nm after being diluted by normal saline, and the drug can target the tumor tissues after intravenous injection, thus improving the effectiveness and safety. In addition, the tumor-targeting albumin nano-lyophilized powder injection preparation provided by the invention is simple in preparation process and suitable for industrialized production.

The invention relates to a composite drug-loading sustained release microsphere system entrapped with quantum dots and a preparation method of the composite drug-loading sustained release microsphere system. The quantum dots and an anti-cancer medicament are entrapped in a polylactic-co-glycolic acid microsphere, and a cationic macromolecular liposome prepared from arginine-glycine-aspartic acid (RGD) peptide-modified octadecyl-quaternized lysine modified chitosan and cholesterol is coated outside the polylactic-co-glycolic acid microsphere to form a core-shell drug-loading microsphere system. The composite drug-loading microsphere system entrapped with the quantum dots and the anti-cancer medicament has the particle size being between 300 and 400nm, positive surface Zeta potential and high stability, and can be stored for at least two months after being freeze-dried. The composite drug-loading sustained release microsphere system entrapped with the quantum dots and the anti-cancer medicament has the characteristics of uniform and controllable particle size, high stability, RGD peptide modification on surface, simple preparation process and the like, and is suitable for batch production.

The invention relates to methoxy polyethylene glycol-poly-N-isopropyl acrylamide-metal tetramino phthalocyanine and a preparation method therefor and belongs to the field of photodynamic therapy. Methoxy polyethylene glycol-poly-N-isopropyl acrylamide-metal tetramino phthalocyanine is used for solving the problem that the existing phthalocyanine photosensitizer is poor in water solubility and low in tumor targeting performance and the application in the photodynamic therapy is limited by unstable PI-PI accumulative action. Methoxy polyethylene glycol-poly-N-isopropyl acrylamide-metal tetramino phthalocyanine disclosed by the invention has the skeleton symbol of MPEG-PNIPAM-MTAPc, wherein MPEG means methoxy polyethylene glycol, PNIPAM means poly-N-isopropyl acrylamide, and MTAPc means metal tetramino phthalocyanine. The preparation method disclosed by the invention comprises the steps: firstly, preparing an ATRP (Atom Transfer Radical Polymerization) initiator MPEG-X from MPEG-OH and a halogenated substance; secondly, initiating an NIPAM (N-isopropyl acrylamide) monomer to subject to ATRP by the initiator, so as to obtain a temperature-sensitive diblock copolymer MPEG-PNIPAM-X; then, carrying out terminal group functionalization on the MPEG-PNIPAM-X with MA (Maleic Anhydride), so as to obtain MPEG-PNIPAM-MA-X; and finally, bonding MTAPc to the MPEG-PNIPAM-MA-X, thereby obtaining the MPEG-PNIPAM-MTAPc. The prepared photosensitizer is good in water solubility and high in tumor targeting performance, is not liable to aggregation in aqueous solutions and is a phthalocyanine photosensitizer with development potential.

The invention relates to a docetaxel liposome sterile lyophilized preparation and preparation method thereof, and the docetaxel liposome sterile lyophilized preparation comprises docetaxel, natural lecithin, PEG-DSPE, cholesterol, a protective agent for lyophilization, and buffer salts. The natural lecithin, PEG-DSPE, cholesterol, and docetaxel are dissolved in a organic solvent; a buffer solution containing the protective agent for lyophilization is added into mixed solution; the solution is incubated for 10-60 min for decreasing the average particle size of the liposome to 50-200 nm; and the preparation is obtained after bacilli-eliminated filtration and lyophilization. The docetaxel liposome prepared by the invention has the advantages of less toxic and side effect and higher curative effect when compared with commercially available ordinary injections at present. The preparation method of the invention is simple and practical, and is applicable to industrial production; and the prepared docetaxel liposome has high encapsulation efficiency and good stability.

The invention relates to the technical field of preparing a contrast agent by utilizing a hyperbranched polymer. A preparing method of the hyperbranched polymer includes reacting a lysine salt and caustic alkali in a mole ratio of 100:80-90 at 140-160 DEG C for 40-50 h in a protective atmosphere; mixing a hyperbranched polylysine skeleton and diethylenetriaminepentaacetic acid according to a mass ratio of at least 1:5 in water; reacting the mixture at room temperature for 6-8 h; mixing the first hyperbranched polylysine molecule and a gadolinium compound in water; reacting the mixture at 37-42 DEG C for 6-12 h, with the mass ratio of the first hyperbranched polylysine molecule to the gadolinium compound being 1:1-1:2; and mixing and reacting the second hyperbranched polylysine molecule and folic acid in a carbonate the pH value of which is 8-10 for 5-12 h. The hyperbranched polylysine contrast agent has good biocompatibility, low toxicity and a high relaxation rate and can be metabolized in vivo.

The invention was involved in the polymine modified vector of fibroblast growth factor receptor, containing peptide YC25 which could specially bind to the alkaline fibroblast growth factor receptor, peptide YC25/positive ion PEI/exogenous DNA.The exogenous DNA could be effectively introduced to the cancer clone and system of high expression of FGFRs to inhibit the growth of tumor. But there was low effect to the tumor tissue and cell liens without expression of FGFRs, so the vector system was tumor-targeting. The non-virus vector system could transfer the exogenous DNA and its size ranged from tens bp to thousands kb to overcome the limit of the size of exogenous gene. So, it could be used to produce the medicament to cure tumor by combined transfer of multi-gene and also to produce gene drug for other disease.

The invention discloses synthesis and application of a type of folate (FA)-conjugated polyethylene glycol polycyanoacrylate (PEG - PHDCA) (FA-PEG-PHDCA for short). The type of polymer is an amphiphilic block copolymer obtained through the Michael addition reaction of folate-polyethylene glycolcyano acetate and alkyl cyanoacetate in the presence of formaldehyde and dimethylamine. The type of polymer can be self-assembled into nano-particles or micelles in water, wherein hydrophobic alkyl segments are aggregated to a core, while hydrophilic polyethylene glycol segments form a hydrophilic shell.Meanwhile, due to excellent surface activity of the polymer and the tumor targeting property of folate, the polymer can also be applied to the modification of solid lipid nano-particles, liposomes, submicroemulsion and other nano-particle preparations. The polymer can be used for intravascular administration, intramuscular injection and oral administration, and is applicable to water-soluble and water-insoluble medicaments. The preparation method has the advantages of mature process and suitability for large-scale continuous production.

The invention relates to a construction method and applications of targeting oncolytic-adenovirus carier Ad-TD-gene. The carrier of the oncolytic-adenouirus is Ad5, the adenovirus-5 in Subcategory C;three internal genes of the adenovirus, including E1A-CR2, E1B19K and E3gp-19K, are deleted; an E3B gene is retained, and an E3gp-19K promoter expression exogenous therapeutic gene is retained; and any antigen gene which is helpful to treating tumors or used for infectious disease vaccines can be inserted into the carrier. The Ad-TD-gene has the advantages of specificity, high safety and high efficiency, can carry various antigen genes treating tumors, and can be used for treating various solid tumors. By utilizing the human chemotactic factor CCL 21 gene as the therapeutic gene, the Ad-TD-hccL21 has the effects of tumor targeting and tumor resistance, lays foundation for introducing targeting genetic engineering medicines towards clinical applications, and provides an effective therapy for patients with tumors.

The invention discloses an imaging method of tumor targeting based on enhancement effect of zinc ion effects. When the imaging method of the tumor targeting based on the enhancement effect of the zinc ion signals is applied at the cellular level, a zinc saline solution is manufactured firstly. Then the saline solution is arranged into a cell incubator together with cancer cells or cancer tissues for incubation. After high resolution fluorescence microscopic imaging and Raman imaging are carried out, qualitative and quantitative analysis is performed on the structure or chemical constituents of the cancer cells or the cancer tissues through the signal data of a fluorescence spectrum and a Raman spectrum. When the imaging method of the tumor targeting based on the enhancement effect of the zinc ion signals is applied at the animal model level, a tumor animal model is constructed and the zinc saline solution is manufactured, after part of the tumor location of an experimental animal is injected with the zinc saline solution, a confocal fluorescence microscope, an ultrasonic imaging device, a fluorescence imaging device, a Raman spectrometer or a Raman microscope are used for monitoring the signal information of the tumor cells or the cancer tissues and processing and analyzing the signal information. Due to the fact that the zinc ions are adopted as the imaging signal enhancer, the imaging method of the tumor targeting based on the enhancement effect of the zinc ion signals has small toxicity on a living body, and has tumor targeting capability.

The invention discloses an active targeted gene delivery nanoparticle, and a preparation method and application thereof. The active targeted gene delivery nanoparticle consists of a cationic polymer,hyaluronic acid and a negatively charged gene. The cationic polymer and the negatively charged gene form a composite core; the hyaluronic acid coats on the surface of the composite core by charge action and chemical bond bonding; and the cationic polymer is one of PAsp (EDA), PAsp (DET), PAsp (TET) and PAsp (TEP), or one of chemically modified derivatives of the PAsp (EDA), PAsp (DET), PAsp (TET)and PAsp (TEP). The hyaluronic acid used in the invention has excellent biocompatibility, not only reduces the cytotoxicity caused by the cationic polymer, but also actively targets a hyaluronic acid-specific receptor which is highly expressed on surfaces of tumor cells, theeby more efficiently delivering exogenous source genes into the tumor cells, and increasing cellular uptake and transfectionefficiency.

The invention discloses a construction method of a tumor specific adenovirus vector carrying a p21ras single-chain antibody gene and application of the tumor specific adenovirus vector to CIK (cytokine induced killer) cells by loading. The prepared conditionally replicating tumor specific adenovirus has double targeting and can infect the CIK cells. The tumor specific adenovirus KGHV500 carrying the p21ras single-chain antibody gene is prepared by cloning a p21ras single-chain antibody and a GFP (green fluorescent protein) gene into a recombinant adenovirus shuttle plasmid pXC2P simultaneously. The prepared recombinant adenovirus can specifically recognize tumor cells and has low toxicity towards normal cells. The p21ras single-chain antibody gene carried by the virus can be expressed for a long term along with virus replication, and the virus shows good anti-tumor effects through in vitro and vivo experiments. The tumor specific adenovirus vector can be used for researching and developing drug preparations of related tumors caused by p21ras protein over-expression, such as breast tumors and the like.

The invention relates to folic acid modifying chitosan nano particles as well as preparation and application thereof. The preparation method comprises the following steps: adding folic acid FA, EDC and NHS into a solvent, stirring, and obtaining a mixed solution; and adding the mixed solution into a prepared aqueous solution of chitosan temperature-sensitive segmented copolymer CS-g-PNIPAM, stirring, dialyzing, and freeze drying, thus obtaining the folic acid modifying chitosan nano particles. By adopting the RAFT method, the reaction is stable, no implosion occurs, and a reaction product is low in molecular weight dispersion width.

The invention discloses an Lf-HA-DOX macromolecule prodrug compound, a constructing method thereof and an application of the Lf-HA-DOX macromolecule prodrug compound to treating glioma. According to the Lf-HA-DOX macromolecule prodrug compound, lactoferrin (Lf) serves as ligand for targeting modification, Doxorubicin (DOX) serves as a therapeutic drug, hyaluronic acid (HA) serves as a carrier skeleton, tumor targeting of the HA is used, and the double-targeting macromolecule prodrug compound is obtained. The Lf-HA-DOX macromolecule prodrug compound can penetrate through blood brain barriers, and further has quite good glioma targeting; meanwhile, the effect of slowly releasing the drug can be achieved, and the Lf-HA-DOX macromolecule prodrug compound has the quite good application prospects in treatment of glioma.

The invention discloses a pH-sensitive degradable polymer, and a preparation method and application thereof. The polymer is the compound with the following structure as shown in figure, n is not larger than 410 and not smaller than 140, and n is an integer. The pH-sensitive polymer as a medicine carrying micelle has the characteristics that (1), nanoscale is truly realized (smaller than 200nm), and uniformity and stability are high; (2) a multi-targeting technology is realized (defects of mono-targeting are overcome), and comprises natural targeting of long circulation nano particles and pH-sensitive physical chemistry targeting, and tumor targeting is fully obtained; (3) medicine carrying amount is larger, stability is good, treatment cost is reduced and side effects generated by release of free medicine are reduced; (5) the polymer has little distribution in normal tissues due to high tumor targeting, and has very small side effects; even a small amount of polymer arrive at a non-tumor position, the medicine is barely released or very small in release rate due to pH sensitivity and the side effects are very small.

The invention relates to an expressed superantigen gene of targeted prostate tumor, in particular to a method for preparing dual-regulated oncolytic adenovirus for the expressed superantigen gene of the targeted prostate tumor, and belongs to the technical field of gene therapy. The preparation method comprises the following steps of: by applying the genetic engineering technology, cloning staphylococcus aureus enterotoxin A genes into an oncolytic adenovirus vector so as to limit the proliferation and expression of the genes in prostate tumor cells only and fulfill the aim of killing target prostate tumor cells; and regulating a tumor specific proliferous adenovirus vector by using a prostate specific antigen promoter and a telomerase reverse transcriptase promoter, carrying the staphylococcus aureus enterotoxin A gene fragment, and naming as SG504-SEA. The expressed superantigen gene has the advantages of specific proliferation in tumor cells and high cytotoxic T lymphocyte irritating capacity.

The invention relates to a Frizzled7 targeted humanized antibody and a preparation method and application thereof. The Frizzled7 targeted humanized antibody has a heavy chain variable region and a light chain variable region, wherein the amino acid sequence of the heavy chain variable region is as shown in SEQID No.11, and the amino acid sequence of the light chain variable region is as shown in SEQID No.12. The Frizzled7 targeted humanized antibody SHH002-hu1 disclosed by the invention reserves high affinity (the KD values of a mouse-derived monoclonal antibody SHH002 and a recombinant humanFzd7 protein are both smaller than 1*10<-12>M) of the mouse-derived monoclonal antibody SHH002 and the recombinant human Fzd7 protein, is specifically combined with Fzd7, and does not have cross reactions with other receptors in a Fzd family, so that the target missing risk of the antibody in possible clinical application is reduced. The SHH002-hu1 can be combined with Fzd7 on the surfaces of tumor cells to block a Wnt signal channel, can be effectively combined with Fzd7 in tumor tissue of a patient, has potential tumor targeting properties, and is a new candidate medicine for anti-tumor treatment in the future.

The invention discloses a tumor-targeting drug-resistant O6-thiophenemethyl guanine-indolequinone-chloroethyl nitrosourea combined molecule and a preparation method thereof, and relates to the field of pharmacy. According to the compound, indolequinone serves as a hypoxia activation pharmacophore, and under the tumor hypoxia condition, indolequinone is reduced to generate an imine substance with cytotoxicity; the CENUs pharmacophore is decomposed to generate chloroethyl carbocations, so that DNA interstrand cross-linking is caused; and meanwhile, an AGT inhibitor O6-TMG derivative is released, and an AGT inhibition effect is achieved. Therefore, the compound disclosed by the invention not only can play a dual anti-tumor effect, but also has drug resistance and tumor hypoxia targeting property, and has high-efficiency and low-toxicity anti-cancer activity.

The invention relates to the field of medicinal materials and discloses a synthetic method and application of a glucan/indometacin graft. According to the synthetic method and the application, the problem that certain drugs have serious toxic and side effects is solved. 4-dimethylaminopyridine (DMAP) is taken as a catalyst, carbodiimide (EDC) is taken as a dehydrating agent, glucan and indometacin are respectively taken as a hydrophilic skeleton and a hydrophobic chain segment, and hydroxide radicals in a chemical structure of glucan (Dex) generate esterification reaction with carboxyl in a chemical structure of indometacin (Indo) to generate an amphipathic compound, namely the glucan/indometacin graft. A drug delivery system which is prepared from the glucan/indometacin graft and loaded with an indissolvable drug polymer nanoparticle solution has relatively high drug loading capacity and encapsulation efficiency, presents hypotoxicity and can be used as a drug carrier.