175results about How to "Prolong circulation time in the body" patented technology

The invention provides ABA type triblock biodegradable polyurethane with amino side chains and a preparation method and uses thereof, belongs to the field of biomedical materials and solves the problem that the existing biodegradable polyurethane has molecular weight uncontrollable, wide molecular distribution index and complexity in self-assembly. The ABA type triblock biodegradable polyurethane with amino side chains is shown as in a structural formula I or II. The ABA type triblock biodegradable polyurethane is controllable in polymer molecular weight and wide in molecular weight distribution and can serve as a drug carrier; drug molecules, target molecules or fluorescence molecules are grafted to active side groups of the polyurethane by means of physical encapsulation or chemical bonding, so that a carrier drug system having one or multiple of functions such as being untargeted, being targeted, pH sensitivity, photosensitivity, enzyme sensitivity and fluorescence probing is constructed.

The invention relates to a self-assembled nano-system of unsaturated fatty acid-anti-tumor drug conjugates as well as a preparation method and application thereof. (1) Unsaturated fatty acid-anti-tumor drug conjugates can be self-assembled in water to form spherical nano-particles with uniform particle sizes and good stability; and (2) in a preparation process, an amphiphilic polymer material such as DSPE-PEG can be optionally added, so that the particle sizes of the self-assembled nano-particles can be further reduced, and the stability of the self-assembled nano-particles can be further enhanced. The self-assembled nano-system of unsaturated fatty acid-anti-tumor drug conjugates, provided by the invention, is simple in preparation method and easy in industrial production and has the advantages of high drug loading capacity, strong stability, good safety and the like; and growth inhibition tests of tumor cells in vitro prove that the self-assembled nano-system has favorable anti-tumor effects on multiple tumor cells.

The invention discloses a mesoporous silica drug-loaded nanoparticle. Mesoporous silica is used as a drug carrier, and is wrapped with a polydopamine layer; through a Schiff base addition reaction, the raw material is connected to tumor-directed osmotic peptide iRGD and poly (2-ethyl-2-oxazoline) so as to obtain the mesoporous silica drug-loaded nanoparticle MSN (at) PDA-PEOz-iRGD. The invention also discloses a preparation method of the above drug-loaded nanoparticle. By loading the prepared drug-loaded nanoparticle on an anti-cancer drug, the drug has obvious pH-responsive release, obvious tumor cell targeting ability and good photothermal treatment effect and good antitumor effect in vivo and in vitro, and provides theoretical basis for the research of novel targeted drug delivery system.

The invention provides a pH and Redox dual-response amphiphilic block copolymer as well as a preparation method and application thereof. The molecular formula of the copolymer provided by the invention is MPEG-Linker-PAE-ss-PLGA and the copolymer has a structure as shown in the formula I and can be prepared through the following steps of performing reaction to modify macromonomer methoxypolyethylene glycols (MPEG), thereby obtaining hydrophilic macromonomer (MPEG-Linker) with pH responsiveness; performing reaction to modify macromonomer polylactic acid-poly lactic-co-glycolic acid (PLGA) by use of disulfide bonds, thereby obtaining a hydrophobic macromonomer (PLGA-Cys) with Redox responsiveness; and performing michael addition reaction through a one-step method so as to obtain the copolymer. The copolymer provided by the invention can be used in systems for loading water-insoluble drug micelle, is capable of controlling slow release of loaded drugs in normal tissues, is low in release amount accumulated for a long time, and can be enriched and rapidly released in focus tissues, thereby improving the bioavailability and treatment effect of the medicaments.

The invention provides a nano catalyst for tumor treatment, and a preparation method and application thereof. The nano catalyst provided by the invention comprises an erythrocyte membrane, and a composite nano enzyme and a photosensitizer which are coated in the erythrocyte membrane, wherein the composite nano enzyme comprises glucose oxidase and iron nanoparticles which are coated in an inner cavity of the glucose oxidase. The nano catalyst is preferentially accumulated at a target tumor site through targeted biomimetic delivery, and release of the composite nano enzyme is realized under irradiation of near infrared light. Based on high glucose uptake and a weakly acidic environment at the tumor site, glucose oxidase converts glucose into H2O2, induces iron nano particles to start an in-situ Fenton reaction, generates hydroxyl free radicals after sequential catalysis, induces tumor cells to be subjected to oxidative damage, and further kills the tumor cells. The nano catalyst not onlycan realize high-efficiency loading of the catalyst, but also can effectively prolong in-vivo circulation time, so that accurate and sustained release on a tumor focus part is realized, and a new thought and platform are provided for tumor treatment.

The invention falls into the biomedical field and relates to an electrostatic coating based non-viral nucleic acid ternary complex system (TCS) and the preparation method thereof. The TCS is prepared by autonomous compression of plasmid DNA or siRNA through cation polymer poly(beta-amino ester) to form a binary complex, and physical modification of the binary complex with multi-carboxyl polymer through electrostatic interaction. The invention can effectively compress and pack plasmid DNA or siRNA, enhance the lysosome escape of the TCS, and protect the plasmid from degradation in cell, thereby improving the efficiency of gene transfection and expression.

The invention relates to an anti-tumor medicine coupler decorated with saturated fatty acid and a self-assembling nanometer system and preparation method of the coupler. Firstly, the coupler obtained by decorating the structure of the anti-tumor medicine with different types of saturated fatty acid can be self-assembled into spherical nanoparticles uniform in granularity and high in stability in water; secondly, after any amphiphilic polymer material such as DSPE-PEG is added in the preparation process, the granularity of the self-assembled nanoparticles can be decreased, and the stability of the nanoparticles can be improved. By means of the method, the anti-tumor medicine where nanoparticles can hardly be self-assembled can be endowed with the self-assembling capacity, only one step of reaction is needed during synthesis, and the method is easy and convenient to implement; meanwhile, compared with a traditional carrier dependence type nanometer system and an amphiphilic prodrug micelle system, the self-assembling system has higher medicine loading capacity and higher stability; the preparation method is easier to implement and beneficial to industrial production and provides a new concept for design and establishment of nanometer medicines.

The invention a bionic acid-sensitive nano drug as well as a preparation method and an application method thereof. The bionic acid-sensitive nano drug comprises an inner core and an outer shell, wherein the outer shell comprises a targeted modified red blood cell membrane. The bionic acid-sensitive nano drug has immune-free natural biological characteristics, and can greatly prolong in-vivo circulating time of the nano drug; and the inner core comprises a carrier with a sensitive bond on a side chain, and can effectively release the drug to achieve the purpose of targeted treatment of tumors.The preparation method for the bionic acid-sensitive nano drug is simple, is suitable for large-scale production, is suitable for preparing the targeted treatment drug, is preferably suitable for preparing the tumor targeted treatment drug, and is especially suitable for preparing a brain glioma targeted treatment drug, and effectively solves the key problems that the existing nano-drug is short in in-vivo circulating time, has difficulty in crossing BBB, is low intake amount by tumor cells, is low in release at a focus, and the like.

The invention relates to a reduction-sensitive activated photodynamic nano-drug preparation and a preparation method and application thereof. The nano-drug preparation comprises a carrier GQD-SS-PEG and a photosensitizer loaded on the GQD-SS-PEG, wherein loading amount of the photosensitizer is 5-9wt%. The nano-drug preparation is prepared by the following steps: (A), adding EDC into a GQD solution for ultrasonic treatment, adding PEG-SS-NH2, stirring at room temperature for reaction, and removing impurities in a reaction product to obtain a GQD-SS-PEG water solution; (B), adding a photosensitizer DMSO solution into the GQD-SS-PEG water solution, mixing before ultrasonic treatment, and stirring for reaction at room temperature and in darkness; (C), centrifugally separating the reaction product of the step (B), subjecting supernate to ultrafiltration to remove unloaded photosensitizer to obtain a final target product. The nano-drug preparation is mainly used for inhibiting tumor growth. Compared with the prior art, the nano-drug preparation has the advantages that the photosensitizer is high in targeting ability, and the nano-drug preparation is high in treatment effectiveness and has selective killing characteristic.

The invention belongs to the field of medicinal preparations, and relates to preparation and application of a cytomembrane biomimic lipoprotein targeted nanometer drug delivery system. An anti-obesitydrug is embedded with a reconstituted high-density lipoprotein (rHDL) in a lipoprotein family to form a drug loading core, P3 peptide is modified with a cytomembrane to form a bionic shell, a bionictargeted nanoparticle used for obesity treatment is constructed, and the nanoparticle has the following characteristics: (1) the P3 peptide modified cytomembrane bionic shell has good biocompatibilityand adipose tissue targeting, so that the conditioning and phagocytosis effects of an immunity system for the nanoparticle can be reduced, the body circulation time of the drug is prolonged, and theaccumulation of the drug in adipose tissues is increased; (2) an rHDL core drug carrier has high safety and good carrying property, a lipid soluble drug can be loaded in a core embedding manner, and the lipid soluble drug can be biologically degraded completely without causing an immune reaction; and (3) the adopted anti-obesity drug can stimulate adipose tissue angiogenesis and increase white adipose tissue browning, so that the obesity is cured through synergy of the mechanism.

The invention discloses an adriamycin nano drug delivery system as well as a preparation method and application thereof. The drug delivery system comprises the following components in percentage by weight: 0.02%-1.5% of active ingredient containing adriamycin, 1%-20% of solid lipid, 0.1%-20% of liquid lipid, 0.5%-20% of emulsifier and 0.1%-5% of isoosmotic adjusting agent, wherein the solid lipid and the liquid lipid form nanoparticles to cover the active ingredient containing the adriamycin. The preparation method comprises the following steps: (1), uniformly dispersing the active ingredient containing the adriamycin, the solid lipid, the liquid lipid and fat-soluble emulsifier in an organic solvent, evaporating the organic solvent to obtain an oil phase; (2), uniformly dispersing other emulsifiers and the isoosmotic adjusting agent in water to obtain a water phase; (3), adding the water phase into the oil phase for emulsifying drop by drop; (4), homogenizing under high pressure; (5), cooling and degerming. The adriamycin nano drug delivery system disclosed by the invention can be used for realizing co-transporting of the adriamycin and a chemosensitizer, so that the killability of the adriamycin on liver cancer cells is strengthened.

The invention relates to double-pH-response amphiphilic copolymer, the molecular formula of the double-pH-response amphiphilic copolymer is MPEG-Dliable-PAE-g-Chol, and the structure of the double-pH-response amphiphilic copolymer is as shown in formula I. The double-pH-response amphiphilic copolymer is copolymerized by hydrophilic block methoxy polyethylene glycol, hydrophobic cholesterol and pH response block poly(beta-amino ester). The double-pH-response amphiphilic copolymer has the advantages that the double-pH-response amphiphilic copolymer can self-assemble in an aqueous solution to obtain a nanoscale micellar system, the inner layer of the nanoscale micellar system is a hydrophobic core modified by cholesterol, the middle of the nanoscale micellar system is a pH-sensitive-response PAE layer, the shell of the nanoscale micellar system is hydrophilic block MPEG, the hydrophilic shell is connected sensitive middle layer through a pH-sensitive benzimide bond, the cell intake of a micelle drug-loading system is increased effectively while the requirements of high entrapment performance, stable system structure, long in-vivo circulation time, stability under neutral conditions and controllable drug release under weak acid conditions of hydrophobic drugs are satisfied, and accordingly drug bioavailability is increased, and a tumor treatment effect is optimized.

The invention discloses a preparation method of a multi-stimulation-response cooperative anti-tumor polymer prodrug. The preparation method comprises the following steps: based on beta-cyclodextrin, modifying a double-sulfur-bond camptothecin monomer CPT-SS, 2-(diisopropylamino)ethyl methacrylate DPA and polyethylene glycol methacrylate OEGMA on an initiator by utilizing atom transfer radical polymerization reaction (ATRP), so as to obtain an amphiphilic polymer prodrug beta-CD-P (CPT-co-DPA-co-OEGMA). The obtained amphiphilic polymer prodrug can be directly self-assembled in a water phase toform a single-molecule medicine micelle and also can be used for physical embedding an anti-cancer drug, i.e., adriamycin. Double sulfur bonds of the single-molecule prodrug are opened under the stimulation of a tumor microenvironment condition, amphiphilic performance is changed and the anti-tumor drug is synchronously released to kill tumor cells. Therefore, the method has the advantages that the loading amount of a hydrophobic drug is improved and the selectivity of the anti-tumor drug is also increased; the cooperative treatment effect is remarkable and the safety is high.

The invention relates to a method for synthesizing mono pegylation-thymopentin (mPEG-TP5) by solid phase and liquid phase combination. The method comprises the following steps of: connecting modified polyethylene glycol (mPEG-SCM) to side chain amino of lysine protected by amino by adopting liquid-phase synthesis technology; synthesizing mPEG-TP5 by adopting solid-phase synthesis technology; analyzing and purifying high-efficiency liquid phase through dialysis; and identifying the product structure through nuclear magnetism and mass spectrum. The mono pegylation-thymopentin synthesized by themethod improves the defect that the conventional parent medicament thymopentin has quick biodegradation, poor digesting stability, short biological half-life and the like, and has good application prospect.

The invention discloses a polyethylene glycol modified glycyrrhetinic acid and curcumin compound used for resisting hepatic carcinoma, and a preparation method thereof. The preparation method comprises the following steps: (1), the preparation of methoxy polyethylene glycol-tosylate (mPEG-OTs); (2), the preparation of methoxy polyethylene glycol-phthalimide (mPEG-PI); (3), the preparation of single-ended amino methoxy polyethylene glycol (mPEG-NH2); (4), the preparation of methoxy polyethylene glycol-glycyrrhetinic acid (mPEG-18beta-GA); (5), the preparation of polyethylene glycol modified glycyrrhetinic acid and curcumin compound (mPEG-GA and CUR compound), wherein the yield of the mPEG-OTs can reach 84.54 percent or above, the yield of the mPEG-PI can reach 88.96 percent or above, the yield of the mPEG-NH2 can reach 88.72 percent or above, and the yield of the mPEG-18beta-GA can reach 82.43 percent or above. The purity of the mPEG-OTs can reach 95.74 percent or above, the purity of the mPEG-PI can reach 96.88 percent or above, the purity of the mPEG-NH2 can reach 99.51 percent or above, the purity of the mPEG-18beta-GA can reach 99.65 percent or above, the yield of the mPEG-GA and the CUR compound can reach 83.31 percent or above, and the purity of the mPEG-GA and the CUR compound can reach 99.78 percent or above.

The invention discloses a targeted drug delivery system for a brain glioma, as well as a preparation method and use of the targeted drug delivery system for the brain glioma. The drug delivery system comprises targeting molecules, a polymer carrier and a drug, wherein the targeting molecules are aptamers AS1411, the polymer carrier is PGG (polyclonal gamma globulin), and the drug is PTX (paclitaxel); PGG and PTX are combined to a PGG-PTX covalent bond complex through a covalent bond; the aptamers AS1411 are covalently linked with carboxyls on the surface of PGG-PTX through primary amino modified by the 5'ends of the aptamers AS1411 to form an AS1411-PGG-PTX covalent bond complex modified by the aptamers AS1411 which has a structure of the following formula. The targeted drug delivery system disclosed by the invention can target brain glioma tissues and neovascular endothelial cells simultaneously to effectively improve the drug accumulation in tumor sites and increase the drug concentration in tumor cells so as to enhance the antitumor treatment effect of the drug. The targeted drug delivery system is easily and automatically assembled into nanoparticles to improve the accuracy of PTX chemotherapy and reduce side effects of PTX in clinical application.

The invention belongs to the field of macromolecule polymers, in particular to a triple disulfide-bond linked polyethylene glycol-polycaprolactone triblock copolymer as well as a preparation method and application thereof. The weight-average molecular weight of the triblock copolymer is 6000 to 26000 Da; the triblock copolymer is obtained via mutual reaction between activated polyethylene glycol and polycaprolactone which is provided with living functional groups and obtained via ring-opening polymerization. The triblock copolymer is high in biocompatibility and biodegradability and low in toxicity, has the characteristic of intelligent responsive release when being used as an anticancer drug carrier, and also has the advantages of being good in stability, long in circulating time in a body and strong in cell uptake.

The invention discloses zinc glutamate-coated Prussian blue nanoparticles with triphenylphosphine-clonidamine coated with cancer cell membrane and a preparation method thereof. The nanoparticle comprises Prussian blue nanocore, wherein a surface of the Prussian blue nanocore is coated with at least one zinc glutamate layer, and a surface of the zinc glutamate layer at the outermost layer is provided with a loading layer loaded with triphenylphosphine-clonidamine, and the loading layer is coated with a tumor cell membrane layer. The nanoparticle has an ability to target tumor cells, has a longcirculation time in a body, can gather in mitochondria and cause dysfunction, reduces synthesis of ATP, down-regulates synthesis of a variety of heat shock proteins, causes cell apoptosis, and effectively enhances efficacy of tumor low-temperature photothermal therapy.

The invention relates to a multifunctional synergistic pharmaceutical composition based on adriamycin. According to the pharmaceutical composition, natural hydrophobic small molecules having a conjugated structure are covalently coupled with a polysaccharide skeleton to form an anti-angiogenesis drug, the anti-angiogenesis drug is physically mixed with the conjugated structure-modifying mitochondria damage peptide derivative and adriamycin, and the pharmaceutical composition of a nano size is assembled by virtue of various supramolecular driving forces. The pharmaceutical composition has the advantages of simultaneously regulating a tumor micro environment and tumor cells, reversing the anti-apoptosis characteristics of tumor cells, and maximizing the antitumor effect of the adriamycin. Inaddition, the multifunctional synergistic pharmaceutical composition has the advantages of the adriamycin such as high load, high stability and high targeting. The multifunctional synergistic pharmaceutical composition based on the adriamycin is compatible with corresponding medicinal auxiliary materials to prepare antitumoar drug preparations for injection, oral administration or external use. The multifunctional synergistic pharmaceutical composition is prepared by virtue of a multi-component supramolecular combination construction, so that the operation is simple, and the industrialized production is easy to realize.

The invention discloses a lovastatin silicon plastid of a targeted breast cancer stem cell and a preparation method thereof.The lovastatin silicon plastid is prepared from, by weight, lovastatin 2%-30%, organic-inorganic compound lipid 20%-70%, phosphatidyl ethanolamine-polyethylene glycol 2000 1%-20% and distearoyl phosphatidylcholine 10%-60%.The lovastatin silicon plastid overcomes the shortcoming that the bioavailability of lovastatin drugs in the prior art is low.

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 discloses a cholesterol grafted pH-response tri-block amphiphilic copolymer and a preparation method and application thereof. Through Michael addition, a pH-response macromonomer poly (beta-amino ester) (PAE) is prepared; through Michael addition, a pH-response tri-block amphiphilic intermediate product PAE-b-PEG-b-PAE is prepared; and finally cholesterol is grafted onto PAE-b-PEG-b-PAE to obtain the cholesterol grafted pH-response tri-block amphiphilic copolymer Chol-g-PAE-b-PEG-b-PAE-g-Chol. The cholesterol grafted pH-response tri-block amphiphilic copolymer is applied in the preparation of a micelles system for loading poorly water-soluble drugs. The micelles system can be self-assembled in an aqueous solution to form nano-micelle with a stable structure and can efficiently coat and load poorly water-soluble drugs. By adjusting the ratio of different blocks in the polymer, pH response range can be effectively adjusted. Then, micelle can rapidly and accurately respond to pH changes of an environment, and burst release also can be effectively relived to control drug release rate.