46results about How to "Passive targeting" patented technology

The invention discloses a pH-responsive polyethylene glycol-anticarcinogen conjugate, and a synthetic method and application thereof. After anticarcinogen molecules and polyethylene glycol are covalently linked through pH-sensitive phenylimide linkage, the conjugate is formed, wherein, anticarcinogen can be doxorubicin, epirubicin, daunorubicin, demethoxydaunorubicin or hydrochlorides of the above-mentioned anticarcinogens. The phenylimide linkage is stable under the condition of a normal physiological pH value but undergoes hydrolysis under the condition of a slightly acidic pH value, e.g., a solid tumor cell external pH value and a cell endosome and lysosome pH value; that is, the phenylimide linkage is sensitive to changes of pH values in a range of 7.4 to 4.5 or to below 4.5. The polyethylene glycol-anticarcinogen conjugate has amphiphilic nature and can form nanometer-scale micelle in a saline solution through self-assembly; the micelle can be used as a drug carrier to carry hydrophobic drugs and form a nanometer micelle preparation cladded with drugs, thereby realizing synergy therapy of a plurality of drugs.

The invention relates to the technical field of medicines, and relates to design, preparation and application of vesicle nanoparticles of insoluble medicines. The invention comprises the following aspects: (1) a model medicine is dissolved in a good solvent to form a medicinal solution, and a functional stabilizer is dissolved in another solvent to form a poor medicinal solution; and (2) the medicinal solution is mixed with the poor solvent, and vesicle nanocrystal suspension of which the average effective particle size of less than 1 mu m is formed through self-assembly. A micromolecular material with high compatibility is selected, and a macromolecular polymer stabilizer is synthesized by a covalent binding technology; by microsedimentation, self-assembly and surface modification technologies, the medicine is stabilized in the poor solvent in a form of pure nanocrystals, and a problem that the insoluble medicines are hardly prepared into solution preparations and the problems of dumping and passivity of the traditional nanoparticles are solved; and compared with the traditional preparations, the vesicle nanoparticles have the advantages that the adverse reaction is reduced, toxic and side effects are reduced, the bioavailability is improved, and the vesicle nanoparticles have controlled-release and active targeting functions, and are convenient to use.

The invention discloses a photosensitizer phospholipid compound, a preparation method of the photosensitizer phospholipid compound, a pharmaceutical composition and application of the photosensitizer phospholipid compound. The pharmaceutical composition is the photosensitizer phospholipid or a combined pharmaceutical composition of the photosensitizer phospholipid and a pharmacologically acceptable carrier, and the pharmaceutical composition is in the form of a liquid preparation, a solid preparation, a semisolid preparation, a capsule, granules, a gel or an injection. The photosensitizer phospholipid compound or a liposome of the photosensitizer phospholipid is applicable to the photodynamic therapy of tumors; the photosensitizer phospholipid compound or the liposome of the photosensitizer phospholipid compound can be rapidly taken by cells and can release a photosensitizer crude drug, and under laser action, the photosensitizer phospholipid compound or the liposome of the photosensitizer phospholipid compound can rapidly release active oxygen to take a strong anti-tumor effect. The photosensitizer phospholipid compound and a liposome nanoparticle thereof can serve as a liquid preparation, a solid preparation, a semisolid preparation, a sterilized preparation and a sterile preparation; and the photosensitizer phospholipid compound and the liposome nanoparticle are low in toxicity and are applicable to the efficient treatment of various tumors.

The invention discloses a preparation method of starch nanometer microspheres based on ionic liquid-type surfactant microemulsion system. The method comprises the following steps: firstly adding dried soluble starch into a sodium hydroxide solution and stirring and heating and stirring to be dissolved completely; cooling the obtained solution to room temperature and then adding cyclohexane, an ionic liquid-type surfactant and an auxiliary surfactant until the solution is clear, so as to prepare a water-in-oil ionic liquid microemulsion; adding epoxy chloropropane into the formed water-in-oil ionic liquid microemulsion to react at 40-60 DEG C for 2-6 hours, cooling the solution after completion of the reaction, adding absolute ethyl alcohol to deposit, centrifuging, removing supernate, washing deposits and drying to obtain the starch nanometer microspheres. The starch nanometer microspheres are small in particle sizes, large in surface areas, high in colloid stability and excellent in adsorption performance. Furthermore, the starch nanometer microspheres are also excellent in degradation performance and biocompatibility, so that the starch nanometer microspheres are applicable in fields of drug carrier materials and cosmetics.

The invention discloses a folic acid mediated antitumor drug superparamagnetic tumor targeted nanoparticle. A superparamagnetic iron oxide nanoparticle is adopted as the carrier, and high temperature thermal decomposition method is employed to synthesize polyethylene glycol-polyethyleneimine modified uperparamagnetic iron oxide nanoparticle, then a folic acid ligand is grafted on the surface of iron oxide by chemical method, and then an antitumor drug is loaded into the iron oxide nanoparticle by electrostatic adsorption and hydrogen bonding, thus obtaining the folic acid mediated antitumor drug superparamagnetic tumor targeted nanoparticle. According to the invention, the dual targeting effect can strengthen the anti-tumor effect of the antitumor drugs, and the folic acid mediated antitumor drug superparamagnetic tumor targeted nanoparticle has small toxic and side effect, thus being a tumor treatment nanoparticle preparation with substantial development value.

The present invention discloses a docetaxel pH-sensitive liposome which is composed of the following raw materials: docetaxel, phosphatidylethanolamine, cholesterol and oleic acid. The particle size of the pH-sensitive liposome is 277+/-2nm-303+/-1nm. A preparation method of the docetaxel pH-sensitive liposome comprises the following steps: weighing 30mg of phosphatidylethanolamine, 20mg of cholesterol and 30mg of oleic acid, dissolving in 15ml of organic solvent, performing pressurizing and evaporating for the mixed solution until a layer of uniform lipid film is formed; then adding 2ml of docetaxel solution, after dissolving, performing ultrasonic treatment for forming uniform suspension, performing hydration at a 37 DEG C water bath state for 30 min, and obtaining the docetaxel pH-sensitive liposome. The preparation method of the docetaxel pH-sensitive liposome has the following advantages: simple preparation process, higher envelope rate and stable performance of the prepared liposome medicine. The prepared docetaxel pH-sensitive liposome has the following remarkable characteristics: passive targeting performance, intelligent controlled release, etc. Furthermore the docetaxel pH-sensitive liposome has the following advantages: high storage stability, high therapeutic index, low toxic and side effect, and capability of being used for treating various neoplastic diseases, etc.

The invention relates to a three-arm star hydrophilic copolymer, and a synthesis method and application thereof. The synthesis method comprises the following steps: initiating gamma-benzyl-L-glutamate-N-carboxy-alpha-amino acid anhydride ring-opening polymerization reaction by using a three-element primary amine inner core, and bonding small-molecule RAFT polymeric chain transfer agent to three terminated amino groups of the star polymer through a carbodiimide method, thus obtaining large-molecule RAFT chain transfer agent; and performing RAFT polymerization by using N-(3-dimethylaminopropyl) and N-hydroxymethyl acrylamide as monomers, finally reacting the hydroxyl group of the N-hydroxymethyl acrylamide component in the copolymer with isocyanated methyl-terminated polyethyleneglycol to realize connection to the polyethyleneglycol via a disulfide bond, and performing hydrazinolysis treatment to obtain the required three-arm star hydrophilic copolymer. According to the method, the molecular weight and chain length of each polymer component can be flexibly controlled, the reaction conditions are mild, and the raw materials are accessible; the synthesized polymer can improve the drug effect and reduce the toxic or side effect; and meanwhile, when loading amycin and gene-based drugs, the polymer realizes the synergic antitumor treatment effect.

The invention relates to an anti-tumor pH-sensitive liposome, a freeze-dried powder injection preparation thereof and a preparation method thereof. The anti-tumor pH-sensitive liposome mainly consists of the following raw materials in parts by weight: 1 part of an anti-tumor active pharmaceutical ingredient , 1-20 parts of phospholipids, 1-20 parts of cholesterol and 0.5-10 parts of oleic acid, the phospholipids are one of phosphatidylethanolamine, dioleoylphosphatidylethanolamine and hydrogenated phospholipids. The present invention uses phosphatidylethanolamine as phospholipid, and the polar group of this phospholipid is protonated in an acidic environment, thereby causing changes in the structure of liposomes. Better release effect.

The invention discloses a PLGA-PEG-ZOL drug-loaded nano-material specifically targeting bone tissues. The shell surface of PLGA is coupled with zoledronic acid, so the obtained PLGA has the in vivo targeting ability to actively target the bone tissues, and the PLGA has a treatment effect on osteoporosis and osteolysis, so the obtained PLGA can be used as a drug carrier shell to encapsulate a therapeutic drug in order to delay the initial burst release dose of the drug, prolong the half-life of the drug and increase the stability and the solubility of the drug, and enables nanoparticles to havea certain sustained release effect and a passive targeting property, that is, the PLGA-PEG-ZOL drug-loaded nano-material can be loaded with different drugs and target the drugs to the bone tissues according to different treatment demands in order to increase the drug concentration of the drugs in bone tissues, thereby the nano-material has the potential to be suitable for multiple skeletal systemdiseases. The invention also discloses a preparation method of the drug-loaded nanomaterial. The preparation method has the advantages of simple process, and easiness in operation.

A lipid nanoparticle (size 100-200nm) of glyceride behenate is prepared by the combination of solvent-fusion method and high-pressure emulsifying, where the mixture of ATO and soybean phosphatide is used as carrier and the poloxamer 188 is used as suspending aid to make the medicine is wrapped by lipid nanoparticle to form uniform dispersed system in water. Its advantages are high biological utilization rate and stable absorptivity.

The invention relates to the technical field of medicine, pharmaceuticals and analysis detection, particularly relates to an in-situ tumor nondestructive detection kit and a preparation method thereof. The in-situ tumor nondestructive detection kit is characterized in that the kit comprises chitosan micelle phosphoric acid buffer solution, wherein hydrophobic lead sulfide quantum dots are embedded inside the chitosan micelles. The in-situ tumor nondestructive detection kit provided by the invention is simple for operation and tumor-targeting, has the characteristics of high light quantum yield, strong light stability, good biocompatibility and increased solubility of hydrophobic quantum dots, and can conduct nondestructive in-situ real-time monitoring, so that the kit is more suitable for in-situ imaging and detection of tumors.

The invention relates to a lipid nano-scale ultrasound contrast agent for targeting tumor-associated macrophages as well as a preparation method and application thereof. The lipid nano-scale ultrasound contrast agent for the targeting tumor-associated macrophages disclosed by the invention takes lipids as a shell membrane material, and wraps low-molecular-weight hyaluronic acids and gaseous fluorocarbon in the shell membrane; and the lipids consist of dipalmitoyl-phosphatidylcholine (DPPC), distearoyl-phosphatidylethanolamine (DSPE) and distearyl phosphatidylethanolamine-polyethylene glycol-folic acids (DSPE-PEG-FOL). The lipid nano-scale ultrasound contrast agent has a particle size of 255-497 nm, and is capable of passing through vascular wall space of tumor tissue so as to achieve tumortreatment effects with passive targeting and high efficiency; PEG chain is utilized so as to have coupled folic acids located outside the lipids shell membrane and the low-molecular-weight hyaluronicacids wrapped in the contrast agent, so that it is ensured that the lipid nano-scale ultrasound contrast agent for the targeting tumor-associated macrophages can actively target the tumor-associatedmacrophages by a folic acid-folic acid receptor way; and the low-molecular-weight hyaluronic acids act on the tumor-associated macrophages, so that the tumor-associated macrophages can be transformedfrom type-M2 macrophages into type-M1 macrophages.

The invention provides a drug carrying microsphere with a tumor chemoradiotherapy synergistic sensitization effect and a preparation method thereof. The method comprises the following steps: carryingout amidation reaction on a polyacrylic acid PAA and polyethylene glycol PEG with two end amination under action of a first activating agent to obtain a PAA-PEG block polymer; carrying out esterification reaction on the PAA-PEG block polymer and 1-ethoxy-2-methyl-5-nitroimidazole MN under the action of a second activating agent to obtain a MN-PAA-PEG polymer microsphere; and carrying out self-assembly on the MN-PAA-PEG polymer and doxorubicin DOX to obtain a doxorubicin-loaded DOX/MN-PAA-PEG microsphere. The drug carrying microsphere can be obtained only through three steps of an acylation reaction, an esterification reaction and self-assembly, the method has characteristics of a simple process, mild reaction conditions and easiness in operation.

The invention discloses a medical phospholipid compound and a medical composition and application thereof. The phospholipid compound is a compound as shown in the following general formula (1) or pharmaceutically acceptable salt prepared from the compound as shown in the general formula (1) and counterions; and in the formula (1), m is a positive integer from 2-10, n is a positive integer from 5-10, X is a medicine, and L is 2-aminoethyl cations and 2-trimethylamine ethyl cations. The medical composition comprises the medical phospholipid compound, or the medical phospholipid compound and a pharmaceutically acceptable carrier. The application of the medical phospholipid compound to preparation of antitumor medicines lies in that the medical phospholipid compound or the pharmaceutically acceptable salt thereof, and the pharmaceutically acceptable carrier are prepared into a medicament. The medical phospholipid compound and liposome nanometer particles thereof can be used as a liquid preparation, a solid preparation, a semisolid preparation, a sterilizing preparation and a sterile preparation, and liposomes can be formed under a water-phase system.

The invention discloses fenofibrate-containing nano-liposome as well as a preparation method and application thereof. The fenofibrate-containing nano-liposome comprises fenofibrate and nano-liposome, wherein the nano-liposome is composed of phospholipid and cholesterol, and the mass ratio of the cholesterol to the phospholipid is equal to 1: (3-15); the mass ratio of the fenofibrate to the phospholipid is equal to 1: (4-40). The preparation method comprises the following steps: (1) dissolving the phospholipid, the cholesterol and the fenofibrate into a solvent, mixing, and then removing the solvent to obtain a mixture; (2) hydrating the mixture obtained in the step (1) with a buffer solution to obtain a nano-liposome system; (3) carrying out probe ultrasonic processing on the nano-liposome system obtained in the step (2), and then filtering to obtain the fenofibrate-containing nano-liposome. The fenofibrate-containing nano-liposome is applied to preparation of medicine for treating non-alcoholic fatty liver disease. The fenofibrate-containing nano-liposome can improve the bioavailability of fenofibrate oral administration.

The invention provides a targeted photosensitizer and a preparation method and application thereof, and an anti-tumor drug comprising the targeted photosensitizer, and relates to the field of photosensitizers. The targeted photosensitizer takes folic acid as a tumor target group; a photoactive effector molecule and the folic acid are connected through a carbonate ester bond, a disulfide bond and apeptide chain in sequence; after the targeted photosensitizer enters a tumor cell, the photoactive effector molecule is released through exchange reaction of sulfydryl and the disulfide bond and molecular nucleophilic substitution reaction in a strong reductive environment, so as to exert an effect of photodynamically killing a tumor under the illumination. The preparation method of the targetedphotosensitizer comprises simple steps and is easy to operate; furthermore, no large-sized or complicated instruments are needed, and the preparation method is suitable for expanding large-scale production and preparation.

The invention discloses a preparation method of CPZ-coupled MS2 protein nanoparticles and an application thereof in breast cancer resistance. The CPZ is coupled on the surface of MS2 protein nanoparticles by covalent coupling, so that the MS2 protein nanoparticles have the characteristics of good water solubility, high drug loading rate, uniformity and stability. Hydrophobicity of phthalocyanine compounds leads to aggregation of the compounds in physiological environment, which affects photophysical (reduced 1O2 formation), chemical (reduced solubility) and biological (insufficient tumor localization) properties of the compounds and reduces the photodynamic therapy (PDT) efficacy of the compounds. Through the nano covalent coupling, the drug effect of ZnPc on breast cancer is improved, nanoparticles can obviously improve the solubility of monocarboxylic groups, provide appropriate particle size and surface properties, and prolong blood circulation, thereby allowing selective accumulation of tumors through enhanced permeability and retention effect (EPR), so that the nanoparticles have a good effect in the application of breast cancer.