27 results about "Long circulating" patented technology

The invention relates to the technical field of biological medicines and vaccines, in particular to a nano-selenium modified liposome as well as a preparation method and application thereof. The nano-selenium modified lipidosome disclosed by the invention comprises a lipidosome and nano-selenium. Wherein the nano-selenium is modified on the surface of the liposome; the liposome is composed of cholesterol, phospholipid, and distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000. The nano-selenium modified liposome can be suitable for different treatment scenes, becomes a multifunctional drug delivery platform, has the characteristics of long circulation, good biocompatibility, high drug loading rate, good stability, increase of retention time of a treatment drug in a body and the like, can be directly entrapped with an antigen, can also be cooperatively combined with a drug and a vaccine, and has a wide application prospect. The defects of low bioavailability, poor stability, toxic and side effects and the like of the existing medicinal preparation are overcome, and the immunotherapy effect is remarkably enhanced while the treatment medicine in the liposome is promoted to achieve a remarkable slow release effect.

The invention relates to the technical field of biomedicine nanotechnology, in particular to a high-stability engineered exosome based on rigid hydrophobic anchoring and micelle disassembly and purification as well as a preparation method and application of the high-stability engineered exosome. According to the invention, a ternary surface structure of rigid hydrophobic anchoring-hydrophilic polymer spacer arm-targeting ligand (L-S-T) is constructed, cholesterol hemisuccinate or multi-branched lipid is selected as an anchoring group, and the problem that conventional phospholipid modification is easy to fall off in vivo and in an albumin-containing preparation is obviously solved; a technology of'micellar insertion after temperature control 'combined with'CMC critical concentration adjustment and purification' is adopted, lossless insertion of functional molecules is realized by utilizing thermodynamic driving force, and residual micelles are induced to be disintegrated into monomers by adjusting the concentration of a system to be lower than the concentration of critical micelles, so that efficient removal of free impurities is realized through conventional ultrafiltration. The engineered exosome has the advantages of long circulation, high targeting and excellent storage stability, and has important clinical application and commercial transformation prospects.

The application discloses a naphthalene phthalocyanine copper liposome and a construction method and application thereof, and belongs to the technical field of liposome preparations. The naphthalene phthalocyanine copper liposome can improve the problems of poor water solubility and insufficient stability of existing sonosensitizers by wrapping naphthalene phthalocyanine copper and catalase in the liposome. Meanwhile, the naphthalene phthalocyanine copper liposome has the function of catalyzing the production of O2 by excessive H2O2 in the microenvironment of brain glioma to supply the continuous production of ROS in the sonodynamic therapy (SDT), enhances the sonodynamic performance, improves the treatment effect of brain glioma, has the advantages of good biological safety, low immunogenicity and long circulation in the body, can effectively penetrate the blood-brain barrier and be delivered to the tumor site, solves the problems that drugs are difficult to penetrate the blood-brain barrier and cannot reach an effective concentration in the traditional treatment method of brain glioma, and provides a new strategy for the treatment of brain glioma.

The invention belongs to the technical field of drug delivery and tumor immunotherapy, and particularly relates to an oncolytic virus vesicle as well as a preparation method and application thereof. The preparation method comprises the following steps: co-incubating oncolytic adenovirus and platelets in a buffer system containing prostaglandin E2, and inducing to form an inner membrane encapsulation body; and activating and releasing the vesicles under the conditions of 36-38 DEG C and 4-6% CO2, and carrying out gradient centrifugal collection of 300g, 2000g, 10000g and 100000g. The particle size of the oncolytic virus-loaded vesicle is 50-200nm, the surface of the oncolytic virus-loaded vesicle contains CD41, CD61 and P-selectin, and the oncolytic virus-loaded vesicle can realize long circulation and lung targeting delivery of oncolytic viruses, is suitable for preparing drugs for treating breast cancer and breast cancer lung metastasis, and has a remarkable tumor inhibition effect.

Described herein are novel compositions comprising lipid-poly(ethylene glycol) (lipid-PEG) molecules or lipid-PEG-like molecules, and methods of use thereof, e.g., for sustained delivery of therapeutic agents such as nucleic acids, proteins, and small molecules.

The invention discloses an ergosterol peroxide composite sustained-release agent as well as a preparation method and application thereof, and belongs to the technical field of medical antitumor drug preparations. The invention discloses a preparation method of an ergosterol peroxide composite sustained-release agent, which comprises the following steps: compounding ergosterol peroxide powder and soybean lecithin (Soybean lecithin, SPC, purity gradegt, 90%) through methanol, and sequentially carrying out the steps of normal hexane washing, reduced pressure rotary evaporation, filtration and ultrasonic treatment, so as to obtain the ergosterol peroxide composite sustained-release agent. Compared with the anti-tumor effect of pure ergosterol peroxide, the ergosterol peroxide has the characteristics of long circulation, low toxicity, strong targeting property, better treatment effect and the like.

The invention provides a liver function diagnosis and treatment integrated nano preparation and a preparation method thereof. By exploring co-assembly conditions of ICG and small molecule drugs, the prepared nano-preparation is co-assembled under certain conditions (such as a specific mass ratio) through acting forces such as intermolecular hydrogen bonds, hydrophilicity and hydrophobicity, pi-accumulation and the like, and the nano-preparation passively targets the liver through a specific size effect, so that the preparation has a good application prospect. Meanwhile, the nano-particles enhance the uptake of the cells to the medicine, so that the long circulation of the medicine in the body is further caused, and the bioavailability is enhanced. Surprisingly, when the specific small molecule medicine is adopted, the ICG diagnosis window is effectively expanded, and the ICG clearance rate can be increased from 15 min to 60 min. And the error value of clinical operation is effectively reduced. The nano preparation integrating diagnosis and treatment provides a direction for diagnosis and treatment of hepatic fibrosis.

The invention belongs to the technical field of separation and purification, and particularly relates to a composition for selectively extracting and purifying a long-circulating antibody from various sample matrixes, a kit and application of the composition and the kit. According to the method, a magnetic nano material with a macroporous structure, a hydrophilic outer surface layer and an FcRn extracellular domain fixed on the surface is used as a magnetic solid phase extraction (MSPE) adsorbent, meanwhile, the operation characteristics of step-by-step combination and elution of the MSPE technology are utilized, the target antibody is accurately extracted from a sample when the pH value is 6.0 + / -0.2, the target antibody is eluted from the surface of the material when the pH value is 7.2 + / -0.2, and the detection result is accurate. Therefore, the long-circulating antibody component in the sample is selectively extracted, but not all antibodies are extracted. Compared with a traditional extraction and purification mode, the method has the advantages that the interference of large-size impurities and hydrophobic impurities in a sample is remarkably reduced, and meanwhile, only the long-circulating antibody can be selectively extracted from various antibody components.

Embodiments of the present disclosure pertain to an active agent carrier that includes a disc-shaped membrane with a plurality of self-assembled amphiphilic block copolymers encased by membrane stabilizing agents, where the amphiphilic block copolymers include hydrophilic blocks and hydrophobic blocks, and where at least one active agent is associated with the disc-shaped membrane. Tunable numbers of targeting agents may also be associated with the disc-shaped membrane. Additional embodiments pertain to methods of delivering one or more active agents to a subject by administering to the subject an active agent carrier of the present disclosure. Further embodiments pertain to methods of making an active agent carrier of the present disclosure.

The invention belongs to the technical field of biological medicines, and discloses a fusion polypeptide of tachyplesin antibacterial peptide and carrier protein and a preparation method of the fusion polypeptide. The fusion polypeptide is formed by sequentially connecting an N-terminal tachyplesin antibacterial peptide, an intermediate microenvironment response type connection module and a C-terminal carrier protein, wherein the connection module is a GFLGVR sequence with both acid sensitivity and MMP-9 cleavability or a chemical equivalent structure of the GFLGVR sequence. Through a bionically designed double-response connection module, the fusion polypeptide is highly stable under physiological conditions, active components are efficiently released in an infected microenvironment, and the therapeutic index is remarkably improved; the in-vivo half-life period of the tachyplesin antibacterial peptide is prolonged from the minute level to the hour level by utilizing the natural long-cycle characteristic of the carrier protein, so that the defect of rapid removal of the tachyplesin antibacterial peptide is overcome; lesion targeted activation is realized by depending on infection microenvironment specific signals, and whole body exposure and potential toxicity are reduced; the preparation process is mature and controllable, is suitable for large-scale production, and lays a foundation for clinical transformation.

The invention relates to the field of medicine and health, in particular to a composition with modified gamma-aminobutyric acid and a preparation method thereof.The preparation method comprises the following steps that S1, modified gamma-aminobutyric acid, soybean phosphatidylcholine, cholesterol and modified polyethylene glycol monomethyl ether are added into anhydrous chloroform, the temperature is increased to 30-40 DEG C, the rotating speed is 100-200 rpm, stirring is conducted for 15-25 min, reduced pressure distillation is conducted, and a mixture is obtained; a liposome film is obtained; according to the invention, gamma-aminobutyric acid and L-leucine are chemically bonded to prepare a prodrug, and autonomously synthesized modified polyethylene glycol monomethyl ether 2000 and other materials are utilized to construct a long-circulating liposome to wrap the prodrug, so that the core defects that natural gamma-aminobutyric acid is difficult to penetrate through a blood-brain barrier and the oral bioavailability is low are overcome; the invention provides a new solution for treating anxiety, insomnia and neurodegenerative diseases, and has a wide application prospect.

The invention discloses a preparation method of highly acetylated phospholipid type euphausia superba oil, and belongs to a preparation method of euphausia superba oil phospholipid modification. According to the method, the high acetylated phospholipid type euphausia superba oil is prepared by modifying euphausia superba oil phospholipid with acetic anhydride, and the high acetylated phospholipid type euphausia superba oil is screened under the preparation conditions (reaction temperature, reaction time and acetic anhydride dosage) and can be used as a raw material of lipidosome, so that the high acetylated phospholipid type euphausia superba oil can be used for preparing the high acetylated phospholipid type euphausia superba oil. The preparation method is simple in process, is used for enhancing liposome stability, prolonging circulation time, precisely controlling drug release, reducing toxicity, improving targeted delivery capacity and remarkably optimizing comprehensive performance of a drug delivery system, the preparation process is simple, and the industrial thought of valuable utilization of marine food is developed to a certain extent.

The application discloses star-shaped polyamino acid nanoparticles with long circulation properties and a preparation method and application thereof, and belongs to the technical field of biological medicines.The nanoparticles are of a star-shaped structure with polyamide-amine dendrimers as a core and copolyamino acids as arms;the nanoparticles are prepared through random copolymerization reaction of polyamide-amine as an initiator, first N -carboxylic acid cyclic anhydride and second N -carboxylic acid cyclic anhydride monomers, and the reaction is carried out in an organic solvent; wherein the organic solvent is a mixed solvent of low-polarity halogenated alkane and high-polarity amide or cyclic ether, and the volume ratio of the two is 9:1, and the preparation method is simple and efficient.The application proves that the star-shaped topological structure and glutamic acid / lysine side chains play a key role in realizing long circulation by regulating the types of amino acids, the charge and the topological structure of the nanoparticles, and the nanoparticles have wide application prospects in the field of preparing tumor treatment drugs.

The application provides a coordination nanometer assembly of a chiral cyclic peptide and a manganese ion, a preparation method and application thereof, the method of the application combines a manganese superoxide dismutase protein domain with a unique tumor microenvironment of a melanoma high tyrosinase, and first designs polypeptide sequences with different chirality L‑ Y D‑ h L‑ D D‑ h、 L‑ Y L‑ H L‑ D L‑ H and D‑ y D‑ h D‑ d D‑ h, regulates polypeptide chirality, improves in-vivo circulation stability and cell entry efficiency of the nanometer assembly, coordinates self-assembly of manganese and the chiral cyclic peptide, simulates in-situ oxidation of the tumor microenvironment for photothermal therapy, and coats cell membranes. The method of the application is simple, the experimental conditions are mild, and the method is easy to operate, the cell membrane coated nanometer assembly prepared by the method not only has long circulation stability and high cell entry efficiency, but also can realize mild photothermal therapy through in-situ oxidation, release manganese ions to activate the CGAS-STING pathway for tumor immunotherapy, and has potential application value in the field of tumor combination therapy.

The application discloses a kind of response type micelles for loading hydrophobic positively charged drug and preparation method thereof, it is related to the field of biomedicine and nanomaterials.This carrier is based on polyethylene glycol and introduces stimulus-responsive disulfide bond and crosslinkable group, and the efficient loading and control release of drug are carried out.Through multi-step organic synthesis "ABA" type triblock structure polymer, four hydroxyl PEG is prepared first, and then coupled and photocrosslinking with undecanethiol undecanoic acid and sulfonated molecule in turn through disulfide bond at four hydroxyl ends, and finally obtain amphiphilic polymer with triblock structure.The polymer can efficiently load hydrophobic drug using its hydrophobic micro area, and promote the loading of positively charged drug by means of its hydrophobic end connected sulfonic group negative group, and realize good water solubility and long cycle by means of the hydrophilicity of PEG segment;The disulfide bond contained therein can be broken under high-concentration glutathione environment in tumor cells, to realize the intelligent control release of drug.

This invention discloses a star-shaped polyamino acid nanoparticle with long-cycle properties, its preparation method, and its applications, belonging to the field of biomedical technology. The nanoparticles of this invention have a star-shaped structure with a polyamide-amine dendritic macromolecule as the core and copolymerized amino acids as arms; the nanoparticles are first initiated by polyamide-amine as an initiator. N -Carboxylic acid ring anhydride and second N The nanoparticles are prepared by random copolymerization of anhydride monomers within a carboxylic acid ring in an organic solvent. The organic solvent is a mixture of a low-polarity haloalkane and a high-polarity amide or cyclic ether solvent in a volume ratio of 9:1. This preparation method is simple and efficient. This invention, by controlling the types of amino acids, the charge of the nanoparticles, and their topological structure, demonstrates that the star-shaped topology and glutamic acid / lysine side chains play a crucial role in achieving long-term cycling. These nanoparticles have broad application prospects in the preparation of therapeutic tumor drugs.

The present invention discloses a preparation method and application of a pH-responsive Cecropin B antimicrobial polypeptide. The preparation method comprises the following steps: S1. reacting 2,3-dimethylmaleic anhydride and 1-hydroxybenzotriazole as raw materials in the presence of an acid-binding agent and a catalyst to obtain a ring-opening condensation product; and S2. grafting the ring-opening condensation product with cecropin B as raw materials, followed by purification and dialysis to obtain the pH-responsive Cecropin B antimicrobial polypeptide. The pH-responsive Cecropin B antimicrobial polypeptide can release the Cecropin B antimicrobial polypeptide at a specific point after long circulation, has high stability, and does not produce drug resistance.

The invention relates to a DMPE-PEG and ROS response unit targeted synergistic drug delivery system as well as a preparation method and application thereof. The DMPE-PEG and ROS response unit targeted synergistic drug delivery system comprises a nano-micelle formed by self-assembly of an amphiphilic compound and a therapeutic agent entrapped in the nano-micelle, wherein the nano-micelle comprises a hydrophobic chain segment, a hydrophilic chain segment and an ROS response unit; the hydrophobic chain segment is dimyristoyl phosphatidyl ethanolamine, the hydrophilic chain segment is polyethylene glycol, and the ROS response unit is selected from at least one responsive group of a phenylboronic acid ester group, a thioether group and a selenide group; the therapeutic agent comprises siRNA or a small molecule inhibitor. Through high ROS microenvironment specific response of the focus, precise targeting of the focus is realized; the action time of the medicine on the focus part can be prolonged in cooperation with the long circulation effect of the PEG chain; the DMPE has higher membrane fluidity and fusion capability, so that the delivery efficiency of the drug in cells is further promoted.

This invention belongs to the field of biopharmaceutical nanoparticle formulations and provides an anti-AQP5 arginine deiminase nanocarrier complex and its preparation method. The invention utilizes a PLGA-PEG-maleimide copolymer to self-assemble into core-shell nanoparticles with a particle size of 50-200 nm. The shell layer is cross-linked by pH-sensitive hydrazone bonds formed by diacylhydrazide and glutaraldehyde, maintaining structural and storage stability under neutral conditions. Under acidic tumor / endosome environments, it can partially dissociate to release and restore the protein conformation. The anti-AQP5 antibody-arginine deiminase is covalently fixed to the shell surface via thio-maleimide addition, achieving a synergistic effect of high protein loading and enzyme activity maintenance, long PEGylation cycling and AQP5-mediated active targeting, and a dynamic balance between stable encapsulation and acid-triggered deactivation. In vitro uptake by AQP5-highly expressing tumor cells is significantly superior to non-targeting carriers, and the in vivo plasma half-life is significantly prolonged, making it suitable for tumor metabolic therapy.

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to gemcitabine liposome as well as a preparation method and application thereof. According to the method, the osmotic pressure of the water phase is adjusted by adopting phosphate, so that the oil phase is injected into the water phase with high osmotic pressure for hydration, and the safety is high. According to the invention, liposome preparation and incubation drug loading are completed at the same time in one step, and the obtained gemcitabine liposome has high drug-lipid ratio, stable quality and long circulation effect. The gemcitabine liposome prepared by the invention can significantly prolong the in-vivo circulation time of gemcitabine, can reduce the dosage of gemcitabine by dozens of times, improves the anti-tumor curative effect, and reduces side effects.

The invention discloses a novel compound as shown in a formula (1) and pharmaceutically acceptable salt, solvate, polymorph or isomer thereof for a long-circulating drug coupling system. The invention also discloses a carrier or antibody covalently or non-covalently bound compound represented by the formula (J), the formula (X) and the formula (Y), and pharmaceutically acceptable salts, solvates, polymorphs or isomers thereof. The invention also discloses a synthesis method of the compound and a preparation method of the compound in a small molecule coupling drug and polypeptide coupling drug system. The invention also discloses an application of the compound in preparation of antitumor drugs, and an application of the compound in preparation of albumin binding type micromolecule coupling drugs and polypeptide coupling drug systems. The invention innovatively proposes that the functional fragment in the compound is connected to a prodrug main body through a Y-shaped branch chain, and the functional fragment can be changed according to different drug coupling systems. The method has a wide application prospect.

The invention discloses a magnesium monatomic nano-enzyme with multienzyme activity and a preparation method and application thereof, the magnesium monatomic nano-enzyme takes a nitrogen-doped carbon material loaded magnesium monatomic as a core, and the surface of the magnesium monatomic nano-enzyme is connected with a brain-targeted ligand through polyethylene glycol as a connector to obtain the magnesium monatomic nano-enzyme modified by the brain-targeted ligand. According to the invention, monatomic magnesium is used as a catalytic activity center, and an oxidative stress treatment mechanism of multienzyme activity induction tumor microenvironment response, PEG-mediated long circulation and ligand-guided active targeting are integrated, so that the drug can accurately reach and be enriched in the most stubborn glioma stem cell area; and the glioblastoma can be efficiently removed through specific catalytic action, so that the problems of high recurrence rate and short lifetime in the current treatment of glioblastoma are expected to be solved.

The invention discloses a responsive micelle for loading a hydrophobic positively charged drug and a preparation method thereof, and relates to the field of biological medicines and nano materials. The carrier is based on polyethylene glycol, stimuli-responsive disulfide bonds and crosslinkable groups are introduced, and efficient loading and controlled release of drugs are carried out. The preparation method comprises the following steps: performing multi-step organic synthesis on an ABA type three-block structure polymer, firstly preparing tetrahydroxy PEG, and then sequentially performing functional coupling and photo-crosslinking on four hydroxy ends, undecanol undecanoic acid and sulfonated molecules through disulfide bonds, thereby obtaining the amphiphilic polymer with the three-block structure. According to the polymer, hydrophobic drugs can be efficiently entrapped by using hydrophobic micro-regions of the polymer, loading of positive charge drugs is promoted by virtue of sulfonic acid group negative electricity groups connected to hydrophobic ends of the polymer, and good water solubility and long circulation are realized by virtue of hydrophilicity of PEG chain segments; the disulfide bond contained in the drug can be broken in tumor cells in a high-concentration glutathione environment, so that the intelligent controlled release of the drug is realized.

The invention relates to the technical field of biological medicines, and discloses a GPX4 mimic phospholipid-like material, and a liposome and application thereof. The general structural formula of the GPX4 simulated phospholipid-like material is shown in the specification, wherein X is a phospholipid head group and is choline, ethanolamine, serine, glycerol or inositol; sn-1 and sn-2 positions are ester bonds or ether bonds, and are respectively covalently connected with R1 and R2 groups at the tail part; r1 and R2 are respectively one of an aliphatic chain, an organic selenium compound simulating GPX4 or a derivative thereof. The aliphatic chain is a saturated aliphatic chain or a monounsaturated aliphatic chain; the organic selenium compound for simulating the GPX4 function is ebbeselenene or a derivative thereof. The ferroptosis inhibition liposome prepared by adopting the GPX4 simulation type phospholipid-like material has the capabilities of removing lipid peroxide and inhibiting cell ferroptosis, has the characteristics of high stability and long cycle, and can be used for preparing medicines for relieving and / or treating dry age-related macular degeneration (AMD).

The application relates to the technical field of medicines, in particular to preparation and application of an immunogenic phospholipid nano delivery system. The nano particle comprises 1,2-dimyristoyl-rac-glycerol-3-polyethylene glycol (DMG-PEG 2k ), cholesterol (Chol) and an immunogenic lipid. The purpose is to solve the inflammatory reaction caused in the process of cationic lipid delivery of genes or drugs, and meanwhile, the hydrophilic lipid 1,2-dimyristoyl-rac-glycerol-3-polyethylene glycol (DMG-PEG 2k ) in the immunogenic lipid composition can successfully shield protein adsorption, and the long circulation effect in the body is realized.

The invention relates to a method for inducing sex reversal of larimichthys crocea based on estradiol carried by nano-liposome, which comprises the following steps: preparing the nano-liposome (E2-NLC) carried with 17beta-estradiol, the nano-liposome is prepared from structural lipid, a membrane stabilizer, a long circulating material and 17beta-estradiol; the nano-liposome is mixed with a feed to prepare the nano-liposome medicinal bait, and the dosage of the 17 beta-estradiol in the medicinal bait is 0.3-0.7 mg / kg of the feed. The hormone dosage can be greatly reduced, so that toxic and side effects on fish bodies can be relieved or eliminated; the bioavailability and the induction efficiency of hormones are improved, and the sex reversal rate of 100% is ensured; effective treatment time is shortened, and breeding efficiency is improved.