178results about How to "Prolong blood circulation time" patented technology

The invention provides a targeted photothermal black phosphorus nano-preparation, which is prepared from a black phosphorus nano-slice, polyethylene glycol absorbed on the surface of the black phosphorus nano-slice by means of electrostatic attraction, and folic acid connected to the polyethylene glycol by means of an amide bond, wherein one end of the polyethylene glycol is amino, and the other end of the polyethylene glycol is imino; nitrogen atom of the imino and carbonyl carbon atom of the folic acid are connected with each other so as to form the amide bond; the folic acid is exposed at the outermost layer of the nano-preparation. The targeted photothermal black phosphorus nano-preparation is high in stability, good in target recognition ability and excellent in light-heat property, is capable of effectively killing cancer cells, and can be used for performing targeted photothermal treatment on cancers at the cellular level. The invention also provides a preparation method and application of the targeted photothermal black phosphorus nano-preparation.

The invention relates to a method for preparing a computed tomography (CT) / magnatic resonance imaging (MRI) bimodal imaging contrast agent based on dendrimers. The method comprises the following steps of: (1) adding DOTA-N-hydroxy succinimide (NHS) solution into the fifth generation of poly(amidoamine) (PAMAM) dendrimer solution, adding methoxy poly(ethylene glycol) (mPEG)-COOH solution which is subjected to 1-ethy 1-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC) activation, reacting with stirring, and thus obtaining functionalized dendrimer solution; (2) adding chloroauric acid solution and sodium borohydride solution into the functionalized dendrimer solution, reacting with stirring, adding gadolinium nitrate solution, stirring, adding triethylamine and acetic anhydride, andreacting with stirring for 8 to 24 hours; and (3) dialyzing the solution obtained in the step (2), performing freeze drying treatment, and thus obtaining the contrast agent. The method has a simple preparation process, and experimental conditions are realized at normal temperature and under normal pressure; and the CT / MRI bimodal imaging contrast agent prepared by the method has a good CT / MRI effect, and a favorable foundation is laid for the development of a novel multifunctional contrast agent.

The invention relates to a nanomicelle of magnetic tumor double-targeting polymer and a preparation method thereof. The nanomicelle of magnetic tumor double-targeting polymer is a nuclear shell structure; the surface of an outer shell is connected with targeted ligand, an inner core is enclosed with nano-particles of super paramagnetic ferriferrous oxide and anticarcinogen with hydrophobic property; in virtue of the physical effect of an external magnetic field and induction of the targeting ligand, the tumor double-targeting function of the nanomicelle is realized. The invention also provides the preparation method of the nanomicelle of magnetic tumor double-targeting polymer: polyethylene glycol with end capping by folacin, and poly Epsilon-caprolactone or sandwich copolymer of poly propiolactone are taken as raw materials and enclosed with the nano-particles of super paramagnetic ferriferrous oxide and the anticarcinogen with hydrophobic property, and then dialysed to obtain the nanomicelle of magnetic tumor double-targeting polymer. The drug carrier system of the nanomicelle reinforces the treatment effect of the anticarcinogen with hydrophobic property on tumor, prolongs the circulating time of the anticarcinogen in human body, intensifies the targeting action of drugs, improves the release efficiency and partial concentration of drugs, and reduces the dosage and toxic and side effect of drugs.

The invention discloses a nanometer micelle capable of intelligently releasing medicine as well as a preparation method and an application thereof. The nanometer micelle provided by the invention comprises the components of polyethylene glycol-poly (aspartate-cysteine)-poly (aspartate-diisopropyl ethanediamine). The preparation method comprises the following steps of: firstly, synthesizing PEG-PBLA-N3 and PA-PAsp (DIP); then, taking cuprous bromide / pentamethyldiethylenetriamine as a catalyst system, and synthesizing PEG-PBLA-PAsp (DIP) through a click reaction of PEG-PBLA-N3 and PA-PAsp (DIP); and finally, carrying out an aminolysis reaction on 2-aminoethyl mercaptan to obtain the final polymer PEG-PAsp (MEA)-PAsp (DIP). The nanometer micelle provided by the invention can be used as a hydrophobic medicine carrier. The nanometer micelle is sensitive to pH value, the disulfide bond in the intermediate cross-linking layer is sensitive to a reducing agent, and the nanometer micelle has the characteristic of intelligently releasing medicine.

The invention discloses a degradable acid-sensitive amphipathic segmented copolymer and a preparation method and application thereof. The hydrophilic and hydrophobic sections of the amphipathic segmented copolymer consist of polyethylene glycol of which the molecular weight is more than 1,000 and acid-sensitive radicals respectively, wherein the corresponding segmentation ratio is 5:1-75. The degradable acid-sensitive amphipathic segmented copolymer is prepared by initiating ring-opening polymerization on N-dicarboxylic acid ahhydride of L-alanine benzyl ester with an active side group by single amine-terminated poly(ethylene glycol), and reacting the product with activated diisopropyl aminoethanol after debenzylation protection so as to perform acid-sensitivity modification. The copolymer of the invention has good acid sensitivity, biocompatibility and biodegradability, can self-assemble in aqueous solution and form a nano-grade medicament carrier, and has important research value and application prospect in the fields of targeted therapy and diagnosis.

The invention relates to the field of biologic medicines, and discloses an albumin indocyanine green paclitaxel compound as well as a preparation method and an application thereof. The albumin indocyanine green paclitaxel compound consists of indocyanine green, paclitaxel and human serum albumin, wherein the indocyanine green and the paclitaxel are absorbed onto human serum albumin through a hydrophobic force. The compound is good in water solubility, biocompatibility and dispersity, can generate heat in laser radiation, can promote more material cells, can kill tumor cells, is further high in fluorescence property, and can instruct joint treatment of photo-thermal therapy and chemotherapy in a fluorescence imaging mode. The preparation of the albumin indocyanine green paclitaxel compound is simple to operate and can be applied to on-scale preparation of the albumin indocyanine green paclitaxel compound, and the raw materials are easily available.

The invention belongs to the field of pharmaceutical preparations, and relates to preparation of a novel target nano carrier and application of the novel target nano carrier in a camptothecin drug targeting delivery system. The system can be represented as PAMAM-HA / drug, wherein PAMAM is polyamide amine-amine arboraceous macromolecules of different generations, HA is hyaluronic acid of different molecular weights, and the drug is one or more of camptothecin anticancer drugs such as camptothecin, 10- hydroxycamptothecine, topotecan and the like. The carrier is used for wrapping the camptothecin drugs, and has the actions of prolonging the drug blood circulation time, improving the drug bioavailability, reducing the non-tumor part concentration of the drug, reducing the drug cytotoxicity, and simultaneously protecting the lactonic rings of the camptothecin drugs from damage, thereby improving the tumor treatment efficiency from multiple aspects. The nano carrier provided by the invention has important significance in promoting the safe delivery of the camptothecin drugs and the effective treatment of tumor.

The present invention relates to a quercetin long-acting liposome powder injection and its preparation method. Said powder injection is formed from quercetin, polyethylene glycol-ethanolamine phosphoglycerides, lecithin, cholesterol and excipient. Said invention also provides the concrete steps of its preparation method.

The invention relates to compositions that comprise dendrimers useful in medical and veterinary applications that provide controlled release of drugs, such as peptides, nucleic acids and small molecules. The drugs are covalently coupled to the dendrimer through a linkage that releases the drug or a prodrug through controlled beta elimination.

The invention discloses a magnetic tumor targeting polymer nano-capsule which contains the following ingredients by weight portion: 5-20 portions of amphiphilic copolymer of folic acid terminated polyethylene glycol and polylactic acid, one portion of paramagnetic nano-particles, a portion of hydrophilic anticancer medicine. The invention also discloses the preparation method of the nano-capsule; the preparation method adopts amphiphilic copolymer of folic acid terminated polyethylene glycol and polylactic acid as the raw material; ferroferric oxide nano-particles and hydrophilic anticancer medicine are encapsulated to obtain the nano-capsule through the ultrasonic emulsifying method. The nano-capsule can further improve the release efficiency and local concentration of the medicine, reduce the medicine dosage, the toxic and side effects. The magnetic tumor targeting polymer nano-capsule has excellent magnetic resonance imaging characteristic and has great research values and application prospects in the treatment and early diagnosis fields of cancer.

The invention relates to the technical field of biomedicine, in particular to a hydrogen peroxide-responsive liposomal nanoprobe and a preparation method and application thereof. The liposomal nanoprobe comprises a liposome, HRP and ABTS, wherein a hydrophilic cavity of the liposome is loaded with HRP, and a hydrophobic layer of the liposome is loaded with ABTS. The hydrogen peroxide-responsive liposomal nanoprobe prepared by the invention has very good hydrogen peroxide responsiveness, and can realize the detection of nano hydrogen peroxide. Compared with the traditional method for detecting hydrogen peroxide by fluorescence or bioluminescence, the photoacoustic imaging detection can significantly improve the depth of penetration of tissues to achieve the hydrogen peroxide imaging of deep tissues; the photoacoustic imaging of the liposome nanoprobe can monitor the occurrence and development of inflammation in real time, and the liposome nanoprobe can react with hydrogen peroxide in a tumor microenvironment to achieve the photoacoustic imaging of tumors.

The invention relates to a zwitter ion modified dendritic macromolecular composite material, as well as preparation and application thereof. The composite material is dendritic macromolecular, and ismodified with zwitter ions and a targeting reagent RGD and chelated with gadolinium ions on the surface, and a gold nanoparticle is wrapped therein. The composite material is prepared by the followingsteps: preparing a G5-DOTA-(PEG-RGD) aqueous solution, adding an HAuCl4 solution and NaBH4 for reduction, adding dropwise a gadolinium nitrate solution, performing stirring for 12 h, adding dropwise1,3-PS, performing reaction for 24 h, and performing dialysis and lyophilization. The method is simple and has industrial and commercial potential, and the prepared nanoparticle is long in blood half-life in a mouse, and has a tumor CT / MRI dual-mode tomographic function at the animal level.

The invention discloses an acid-responsive nanometer micelle for drug loading, a preparation method and an application thereof. The nano-micelles were self-assembled from hydrophilic segment polyethylene glycol (PEG) and hydrophobic segment pH-sensitive polyaspartyl diisopropylethylenediamine / di-n-butylethylenediamine (PAsp (DIP / DBA)). The nano-micelles can prolong the drug circulation time, aggregate in the tumor site, increase the local drug concentration, and respond to the micro-acid environment of the tumor tissue. As a drug carrier of stimulation response, the nano-micelles can rapidly release the loaded chemotherapeutic drug adriamycin in the tumor site, and play a significant anti-tumor effect. At the same time, the nano-micelles loaded with magnetic resonance contrast agent superparamagnetic iron oxide can be used for tumor magnetic resonance imaging and monitoring drug uptake and aggregation. This method utilizes nano-drug aggregation at tumor site and acid responsiveness ofcarrier to realize rapid drug release to improve tumor therapeutic effect, and endows nano-micellar MRI visualization function, which provides a promising innovative strategy for cancer diagnosis andtreatment, and has broad application prospects.

The invention relates to a preparation method of amphoteric ion modified ultra-fine iron oxide particles. The preparation method comprises the following steps: dissolving trivalent ferric salt in solvents, adding sodium citrate, stirring, adding anhydrous sodium acetate, stirring, reacting for 3 to 4 hours at the temperature of 190 to 200 DEG C, cooling, carrying out centrifugation and drying to obtain ultra-fine Fe3O4 nanoparticles, then dispersing the nanoparticles in ultrapure water, performing ultrasound, and EDC and NHS activation, dropwise adding to the ultrapure aqueous solution of Mal-PEG-NH2, reacting for 60 to 72 hours to obtain an aqueous solution of Fe3O4-PEG-Mal, and then dropwise adding the ultrapure aqueous solution of L-cysteine, reacting for 60 to 72 hours, dialyzing and freeze-drying to obtain the amphoteric ion modified ultra-fine iron oxide particles. The method disclosed by the invention is simple, and the prepared nanoparticles are long in half-life periods of blood in mouse bodies, and can realize blood pool angiography in animal levels and enhance imaging for subcutaneous transplanted tumors T1 of HeLa cells, so that the preparation method of the mphoteric ion modified ultra-fine iron oxide particles has potentials of industrialization and commercialization.

The invention relates to a tumor-targeted multifunctional nano probe with MRI (Magnetic Resonance Imaging) / SPECT (Single Photon Emission Computed Tomography) bimodal images as well as a preparation method and application thereof. The nano probe comprises an MNPs-DSPE-PEG-RGD nano probe composed of Fe@Fe3O4 nano particles and liposome DSPE-PEG-RGD and liposome DSPE-PEG which are coupled on the surface layer of the Fe@Fe3O4 nano particles, and radionuclide I125 can also be marked on the MNPs-DSPE-PEG-RGD nano probe to form an MNPs-DSPE-PEG-RGD-I125 nano probe. The preparation method comprises the following steps: dissolving DSPE-PEG-RGD and DSPE-PEG in an organic solvent, adding an Fe@Fe3O4 nano particle solution, and mixing uniformly to obtain the MNPs-DSPE-PEG-RGD nano probe; and marking with I125 by a chloramine-T method to obtain the MNPs-DSPE-PEG-RGD-I125 nano probe. The prepared MNPs-DSPE-PEG-RGD nano probe is used for MRI of human brain glioma, and the prepared MNPs-DSPE-PEG-RGD-I125 nano probe is used for SPECT. Compared with the prior art, the probe provided by the invention has the advantages of strong targeting property and the like, and multiple molecular imaging probes can be achieved on the same molecule.

The invention relates to a multi-mode targeted probe for early hepatic fibrosis diagnosis and a preparation method thereof. The multi-mode targeted probe for the early hepatic fibrosis diagnosis is characterized by comprising a vector, and the vector is connected with a fluorescence group and a magnetic resonance imaging group and can be connected with a targeted compound group, which can be combined with a receptor on the surface of a hepatic stellate cell in hepatic fibrosis / cirrhosis, through a bridging group. The preparation method comprises the steps of: connecting the targeted compound group, which can be combined with the receptor on the surface of the hepatic stellate cell in the hepatic fibrosis / cirrhosis, with the bridging group, and sequentially connecting the targeted compoundgroup, the fluorescence group and the magnetic resonance imaging group on the vector. The targeted probe has higher sensitivity when being used for diagnosing and evaluating the fibrosis diagnosis.

The invention relates to a functionalized dendrimer-based SPECT-CT bimodal imaging contrast agent and a preparation method thereof. The functionalized dendrimer-based SPECT-CT bimodal imaging contrast agent is obtained by pegylation modified fifth polyamide-amine dendrimer as a polymer carrier material; connecting diethylenetriaminepentaacetic acid on the dendrimer surface through covalent grafting; coating gold nanoparticles through an in-situ synthesis method; carrying out acetylation or hydroxylation on residual surface amino groups; and marking <99m>Tc. The functionalized dendrimer-based SPECT-CT bimodal imaging contrast agent has a very good SPECT / CT imaging effect, realizes SPECT / CT imaging of different in-vivo tissue sites of a mouse, lays good foundation for development of multi-functional tissue specific contrast agent, and has wide application prospects.

The invention belongs to the field of pharmaceutic preparations, and discloses the preparation and pharmaceutical application of a protein adsorption-resistant photic sensitivity-enhanced anoxic stress cationic carrier. A cationic polymer is taken as a skeleton to modify a zwitter-ion glycine betaine monomer so as to weaken the adsorption to protein in an organism of the polymer; further modifyingthe intermediate with a hydrophobic connecting arm containing an anoxic stress azobenzene structure and a photosensitizer, so as to construct an amphipathic polymer carrier. The cationic modifier form a nanoparticle through self assembling in a water solution, can be directly applied to photodynamics therapy, can also be used for loading hydrophobic chemical drugs or nucleic acid drugs and applied to photodynamics and antineoplastic drug combination therapy. According to the invention, the photodynamics therapy of the photosensitizer is used for constructing a high-anoxic tumor microenvironment to stimulate nanometer disassembly, thus promoting drug release and improving the utilization ratio; in addition, through the sensitivity-enhanced antineoplastic drug therapeutic effect generated by the photodynamic active oxygen, the high-efficient synergistic treatment on tumour is realized.

Novel acoustically sensitive drug carrying particles comprising non-lamellar forming lipids are disclosed, as well as uses and methods thereof. The drug carrying particles accumulate in the diseased target tissue and efficiently release their pay-load upon exposure to acoustic energy.

The invention belongs to the field of medical imaging contrast agents, and provides a pegylated polyethyleneimine macromolecular magnetic resonance imaging contrast agent and a preparation method of the contrast agent. The preparation method comprises the following steps: first, modifying a gadolinium ion chelating agent DTPA (Diethylenetriamine Pentaacetic Acid) on the surface of PEI (Polyethyleneimine) to prepare PEI-DPTA; second, modifying a composite material by pegylation to prepare PEI-DTPA-mPEG; and finally, chelating gadolinium ions to prepare PEI-DTPA (Gd III)-mPEG, and acetylating residual amino groups on the surface of PEI. The pegylated polyethyleneimine macromolecular magnetic resonance imaging contrast agent obtained by the invention realizes in vivo MR (Magnetic Resonance) blood vessel and kidney imaging of a mouse as well as passive targeted MR imaging detection of tumor tissues. The contrast agent is wide in application prospect.

The invention discloses a polymer, which has a narrow molecular weight distribution, which is less than 1.3, and has a general formula of B-z-H, P-B-H and P-H-B. In the general formula, B represents a block for bonding a drug, H represents a hydrophilic block, P represents a PEG block, and z represents having or not having environment-responsive chemical bond connection. The polymer forms a micelle with small particle size in water, the micelle can spontaneously aggregate to form an aggregation having a large particle size, and the aggregation has superior tumor specific enrichment than an ordinary drug carrier. The polymer has long body circulation time, and has the feature of being enriched on a tumor. The polymer can carry a drug through a covalent bond and / or a non-covalent bond, and the obtained product can further couple to a targeting molecule and / or a labelled molecule for preparing an administration system or a detection reagent.

The invention provides a preparation method of convertible surface charge nano-gel. The preparation method includes the steps: A) dissolving an initiating agent with a morpholinyl group and L-glutamic acid polyethylene glycol single methyl ether-N-carboxyanhydride into an organic solvent for reaction to obtain mixed solution; B) mixing a compound with a formula (I) structure, a compound with a formula (II) structure and the mixed solution obtained in the step A) for reaction to obtain reaction solution; C) mixing and filtering the reaction solution obtained in the step B) and the organic solvent to obtain the convertible surface charge nano-gel. A convertible surface charge nano-gel drug-loaded particle has no toxic and side effects on human bodies and has excellent water solubility, stability and biocompatibility.

The invention discloses dual-mode imaging nano-micelle which comprises a CT (Computed tomography) contrast medium, red fluorescent molecules NPAPF (N-(2-naphthyl)phenylamino)phenyl)-fumaronitrile) and a carrying material for carrying the CT contrast medium and the NPAPF into the dual-mode imaging nano-micelle. The invention further discloses a preparation method and an application of the dual-mode imaging nano-micelle. The dual-mode imaging nano-micelle combines fluorescent imaging and CT imaging, achieves targeted dual-mode imaging of living tumor and organs and meanwhile is long in action time, intensive in detection signal and very small in toxicity.

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 discloses a chitosan-based fluorescence probe suitable for long circulation of blood. The chitosan-based fluorescence probe has a structure as shown in formula (1). A preparing method for the chitosan-based fluorescence probe comprises the steps of grafting polyethylene glycol onto chitosan to obtain polyethylene glycol-chitosan suitable for long circulation of blood, and then marking tetraphenyl ethylene fluorescent molecules on a chitosan link to obtain the chitosan-based fluorescence probe which has an aggregation-induced emission property and is suitable for long circulation of blood. The prepared fluorescence probe has the advantages that sensitivity and light stability are high, quenching is avoided when concentration is high, and fluorescence spectrum shift is avoided, is suitable for long circulation of blood, and has broad application prospects in the fields including cell tracing, tumor diagnosis and drug metabolism detection.

The invention relates to a preparation method of tree-like macromolecular and stable ultra-small ferroferric oxide / gold nano-flowers. The preparation method comprises the following steps: mixing FeCl3, sodium citrate and anhydrous sodium acetate and reacting to obtain ultra-small Fe3O4NPs; carrying out activation treatment to obtain activated ultra-small Fe3O4NPs; enabling a G5 solution to react with a chloroauric acid solution to obtain G5-Au NPs; enabling the G5-Au NPs to react with the ultra-small Fe3O4NPs, so as to obtain G5-Fe3O4-Au NPs; enabling the chloroauric acid solution, an AgNO3 solution and an ascorbic acid AA solution to react, so as to obtain a G5-Fe3O4-AuNFs solution; carrying out acetylation treatment to obtain a product. Nanoparticles prepared by the preparation method have excellent biocompatibility and a good MR / CT / PA imaging function; the nanoparticles can be used for photothermal therapy of tumors; a photothermal therapy effect is improved through radiotherapy andthe nanoparticles can be used for a potential tumor multi-modal imaging contrast agent and combined therapy and have a wide application prospect.

Using liposomes to deliver bioactive agents to cancer or tumor cells and compositions of specific lipids that form liposomes to deliver a biologically active agent.

The invention discloses an amphiphilic chitosan derivative drug-loaded nano-micelle and a preparation method and belongs to the field of pharmaceutical preparations. Amphiphilic chitosan derivatives form the micelle by means of self assembling, vitamin E succinate serves as a kernel, and thiolated chitosan serves as a shell; the hydrophobic kernel is used for entrapping a hydrophobic anti-HIV drug, the shell carrying positive charges is used for adsorbing cytomembrane, the loaded drug can be stably released in vivo, the hydrophilic shell is used for enhancing the solubility of the micelle and maintaining the stability of the micelle in a solution, and then the blood circulation time of the micelle after systematic administration is prolonged. The micelle can stably exist in all kinds of body fluid for more than 10 hours after particles are formed, the particle size is smaller than 200 nanometers, and it is beneficial for controlling the micelle particles to enter cells without being removed by macrophages. The delivery system can keep stability under the condition that serums exist, the drug is delivered into the cells, and good biocompatibility is achieved.

Novel use of ultrasound sensitive drug carrying particles comprising an alcohol is disclosed, as well as products and methods thereof. The drug carrying particles accumulate in the diseased target tissue and efficiently release their payload upon ultrasound exposure.

The invention relates to compositions that comprise dendrimers useful in medical and veterinary applications that provide controlled release of drugs, such as peptides, nucleic acids and small molecules. The drugs are covalently coupled to the dendrimer through a linkage that releases the drug or a prodrug through controlled beta elimination.