2070 results about "Covalent modifier" patented technology

The invention discloses a probiotic-polyphenol nanoparticle colon-targeted co-delivery system as well as a preparation method and application thereof, and belongs to the field of biological medicines. The FCPs and hyaluronic acid (HA) are combined through non-covalent interaction, so that the hydrogel has colon targeting property and mucosal adhesion at the same time, and delivery of probiotics is facilitated. The hydrogel (HF) based on polysaccharide has good biocompatibility, and can be used for effectively encapsulating the probiotics and the natural products. Then, the PDA-TH NPs and BA are incorporated into the polysaccharide chain network of HF, and finally the BA-HF-PDAT targeted co-delivery system is constructed. The BA (at) HF-PDAT targeted co-delivery system can protect BA from serious gastrointestinal stress, and is jointly assembled with PDT-TH NPs to realize dual slow release of thymol (Thy), so that the treatment effect of BA and Thy is improved, and the BA (at) HF-PDAT targeted co-delivery system contributes to treatment of clostridium difficile infection (CDI).

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes comprising an oligonucleotide (e.g., useful for targeting DMPK) covalently linked to an antibody (e.g., anti-TfR1 antibody).

Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes comprising an oligonucleotide (e.g., useful for targeting DMPK) covalently linked to an antibody (e.g., anti-TfR1 antibody).

The invention belongs to the technical field of genetic engineering and biological medicine, and particularly discloses a cascade response type nano-particle with a microenvironment remodeling function and a preparation method and application of the cascade response type nano-particle. The nanoparticle provided by the invention adopts a bionic hybrid membrane engineering strategy: an inner core is formed by loading an exosome inhibitor on a nano material, and the surface is covalently coupled with M2 type macrophage specific targeting peptide; the outer layer coats a macrophage membrane and active oxygen response type liposome composite membrane layer through a co-extrusion technology, and is loaded with a TLR agonist. Animal experiments show that after being injected through caudal vein, the nano-particles are enriched at a tumor site in a targeted manner through homing receptors such as membrane surface integrin alpha4beta1 and the like, and outer membrane cracking is triggered in a high-ROS tumor microenvironment, so that space-time controlled release of a TLR agonist and targeted phagocytosis of an exosome inhibitor by macrophages guided by a targeted peptide are realized. The anti-tumor synergistic effect is achieved through multiple regulation and control mechanisms, and an effective treatment strategy is provided for tumor immunotherapy.

The invention discloses a double-crosslinking network hydrogel film for treating oral ulcer, a preparation method and application, and relates to the technical field of biomedical materials. According to the hydrogel film, a dual-network synergistic enhancement structure is constructed through covalent / non-covalent bi-crosslinking, the adhesion to oral mucosa is remarkably enhanced by adopting dopamine (DA) modified hyaluronic acid (HA), and the mechanical property is greatly improved by utilizing a bi-crosslinking network system of disulfide bond / double bond crosslinking (chitosan and CS) and hydrogen bond / catechol self-crosslinking (hyaluronic acid and HA); the antioxidant and anti-inflammatory characteristics of lipoic acid (LA) and the natural antibacterial property of chitosan (CS) are combined to play a synergistic effect, so that the antibacterial and anti-inflammatory effects are remarkably improved. Meanwhile, multifunctional modified materials such as metacrylic acid ester are introduced, so that the functionality and the application range of the hydrogel film are expanded. The preparation technology is optimized, it is ensured that the material is safe and effective, large-scale production is easy, and an efficient and reliable novel material is provided for oral ulcer treatment.

The invention discloses a covalent organic framework membrane and a preparation method thereof, and belongs to the technical field of organic porous materials and membrane materials. The preparation method of the covalent organic framework membrane comprises the following steps: S1, respectively dissolving an amine compound containing a plurality of amino groups and a compound containing a plurality of aldehyde groups in a mixed solution of trifluoroacetic acid and water to respectively obtain a first monomer solution and a second monomer solution; in the mixed solution, the volume ratio of trifluoroacetic acid to water is (95-96): (4-5); s2, mixing the first monomer solution and the second monomer solution, and performing ultrasonic treatment to obtain a reaction solution; and heating the reaction liquid at 95-100 DEG C to react for 3-5 minutes to form the covalent organic framework film. In addition, the invention also provides the covalent organic framework film which is prepared by the preparation method. The COF film which is complete in structure, excellent in crystallinity and flexible can be prepared in a short time through a simple method.

The invention discloses an enzyme response type KRAS targeted protein degradation chimera as well as a preparation method and application thereof, and belongs to the technical field of tumor targeted therapy. The enzyme response type KRAS targeted protein degradation chimera disclosed by the invention is obtained by covalently linking three parts, namely a KRAS targeted protein degradation chimera, an enzyme response type amino acid sequence and a cell penetrating peptide amino acid sequence, wherein the KRAS targeted protein degradation chimera is obtained by linking a KRAS targeted peptide and a VHL E3 ligase ligand through succinic acid. The enzyme response type KRAS targeted protein degradation chimera releases the KRAS targeted protein degradation chimera under the action of ATG4 enzyme shearing, and shows a relatively strong lung cancer resisting effect in vitro and in vivo. The invention has significant advantages in the aspect of antitumor drugs, and opens up a new field for the development of targeted protein degradation chimera drugs. Enzyme response type KRAS targeted protein degradation chimera molecular structural formula as follows: # imgabs0 #

The invention relates to a ligand-effector moiety provided with at least one saponin and antibody-effector moiety provided with at least one saponin. An aspect of the invention is a composition comprising the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention. The invention also relates to an antibody-drug conjugate comprising covalently linked saponin and to an antibody-oligonucleotide conjugate comprising covalently linked saponin. An aspect of the invention relates to a pharmaceutical composition comprising the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention, and optionally further comprising a pharmaceutically acceptable excipient. The invention also relates to the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin, for use as a medicament. The invention also relates to the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention for use in the treatment or prophylaxis of a cancer.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

The invention discloses an immunosensor for detecting cytokine interferon gamma through electrochemiluminescence as well as a preparation method and application of the immunosensor. The immunosensor comprises a three-electrode system consisting of an immunoelectrode, a reference electrode and a counter electrode, the immunoelectrode is a VMSF modified electrode confined to cerium dioxide nano enzyme and platinum nano particles, and is obtained by covalently immobilizing an IFN-gamma antibody and closing a non-specific site; when the immunosensor is used for detection, a solution containing luminol is used as an electrolyte. The CeO2 and the PtNPs which are confined in the nano channel show a remarkable synergistic catalysis effect. Compared with direct modification on a plate electrode, CeO2-PtNPs has higher catalytic activity and stability. The sensor provided by the invention is used for INF-gamma detection, has the advantages of high sensitivity, low detection limit and wide detection range, does not need complex pretreatment and separation processes during detection, reduces the detection cost, is simple to operate, and is suitable for large-scale application.

The invention relates to the field of immobilized enzymes, in particular to immobilized lipase with graft-modified amino resin as a carrier and a preparation method thereof.The method comprises the steps that firstly, the amino resin is modified through the oxidative auto-polymerization characteristic of tannic acid, and first modified amino resin is obtained; and modifying the first modified amino resin by using fatty amine as a hydrophobic modifier to obtain second modified amino resin. Then lipase is fixed on the second modified amino resin through physical adsorption, the lipase is subjected to interfacial activation on an amphiphilic interface on the second modified amino resin, and a part of lipase is covalently bound with quinonyl in an activated state, so that the immobilized lipase with high activity and stability is obtained. The method is easy to operate, green and non-toxic, the prepared immobilized lipase is good in enzyme activity and stability, and the method can be used for preparing the immobilized lipase on a large scale, can be applied to the field of food and has industrial application potential.

The invention discloses a gradient frame membrane and separation application thereof. An integrated gradient membrane material is constructed in a mode of functional group sharing, metal node sharing or skeleton interpenetration, and target molecule recognition sites are designed by utilizing the advantage that a framework material is easy to modify, so that the separation performance is remarkably improved. The gradient film structure comprises a metal organic-metal organic framework gradient film, a metal organic-covalent organic framework gradient film and a covalent organic-metal organic framework gradient film. The invention introduces a new structure of a metal organic framework-covalent organic framework gradient film and a construction strategy thereof in detail. The preparation method comprises the steps of preparing a bottom layer film structure from bottom to top, then preparing a top layer film structure on the bottom layer film structure, performing post-modification and the like. By designing a specific asymmetric porous structure and adsorption sites, the membrane shows excellent ethylene / ethane, propylene / propane, ion screening and organic matter dehydration separation performance under the dual action of adsorption selection and shape-selective screening.

Aspects of the disclosure relate to methods of reducing expression or activity of DUX4 (e.g., DUX4 protein and / or mRNA) and / or methods of treating facioscapulohumeral muscular dystrophy (FSHD) in a subject. In some embodiments, the methods comprise administering to the subject a composition comprising complexes (e.g., muscle targeting complexes) comprising an oligonucleotide (e.g., an RNAi oligonucleotide such as an siRNA) covalently linked to an antibody (e.g., anti-TfRl antibody).

The invention relates to the field of biological medicine, in particular to a hair follicle targeted delivery system and hair growth and hair loss prevention cosmetics, the hair follicle targeted delivery system comprises: a lipid nanoparticle core which is internally loaded with a bioactive component with hair growth and hair loss prevention effects; the hair follicle targeting molecule can specifically recognize and bind to a receptor on the surface of a hair follicle cell; a targeting anchoring conjugate composed of a linker covalently linked to the hair follicle targeting molecule and an anchoring lipid; wherein the targeting anchoring conjugate is embedded into the lipid bilayer of the lipid nanoparticle core through the anchoring lipid, so that the hair follicle targeting molecule is displayed on the surface of the lipid nanoparticle core. According to the application, through an innovative targeted anchoring conjugate structure, the targeting property and enrichment efficiency of hair growth and hair loss prevention active ingredients on hair follicle tissues can be remarkably improved, and the effect that a medicine accurately acts on a focus part is ensured, so that the number of hair follicles at an alopecia areata modeling part can be remarkably increased.

The invention discloses an enzyme immobilization method based on charge directed crosslinking, and belongs to the technical field of enzyme immobilization. The method sequentially comprises the following steps: reacting an enzyme with a modifier containing an anionic group to generate an electronegative modified enzyme; dissolving a protonated amino carrier in an acidic buffer solution to form a first solution, and dispersing a dissociation anion group-containing carrier and a modification enzyme in an alkaline buffer solution to form a second solution; mixing the two solutions, and constructing a gel network immobilized enzyme through electrostatic crosslinking; and finally, strengthening the gel network by using a multivalent metal ion solution. Directional anchoring of the enzyme in the gel is achieved through charge matching, the network stability and the enzyme microenvironment are synchronously optimized in combination with metal ion coordination, use of a covalent cross-linking agent is avoided in the whole process, conformation damage of an enzyme active center is avoided, the activity retention rate, the operation half-life period and the substrate mass transfer efficiency of the immobilized enzyme are remarkably improved, and the immobilized enzyme has good application prospects. The method is suitable for efficient immobilization of industrial enzymes such as beta-glucosidase, and has high biocompatibility and industrial potential.

Aspects of the disclosure relate to complexes comprising an anti-TfR1 antibody covalently linked (e.g., via a linker such as a peptide linker) to a lysosomal enzyme (e.g., an acid alpha glucosidase enzyme), and methods of making and using the fusion complexes to treat a lysosomal storage disease (e.g., Pompe disease).

Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes comprising an oligonucleotide (e.g., useful for targeting DMPK) covalently linked to an antibody (e.g., anti-TfR1 antibody).

The invention provides bioactive conductive hydrogel as well as preparation and application thereof. The hydrogel comprises a dynamic non-covalent cross-linked network which is composed of natural macromolecules and at least comprises a reversible and environment-responsive cross-linking mode; the responsive conductive component is connected with the dynamic non-covalent cross-linked network through a covalent bond or a coordinate bond, the electrical property of the responsive conductive component changes along with the change of the wound surface microenvironment, and electrical signal feedback of the wound surface state is provided through the change of the electrical property; and the active substance is connected to the dynamic non-covalent cross-linked network through a responsive chemical bond, and the responsive chemical bond is broken under specific conditions of a wound surface microenvironment to release the active substance. Compared with the prior art, the integrated design of active oxygen monitoring and drug release is realized for the first time, the wound healing time (about 30-40%) can be remarkably shortened, the complication risk is reduced, and an innovative solution is provided for wound management in an intelligent medical mode.

The invention relates to an acylhydrazone bond-connected covalent organic framework material, in particular to an acylhydrazone bond-connected covalent organic framework material as well as a preparation method and application thereof, and aims to overcome the defects of various materials for adsorbing Pd (II) in one aspect or the defects of poor stability and durability in high-acidity and high-radioactivity environments. Or the adsorption selectivity on Pd (II) is not strong. As an emerging crystalline organic porous polymer, the covalent organic framework is mainly formed by connecting pure organic structural units through dynamic covalent bonds, has the advantages of permanent high porosity, low density, high chemical stability, high thermal stability and the like, and is expected to realize Pd (II) adsorption in strong acid and ray irradiation environments.

The invention discloses starch-collagen composite hydrogel as well as a preparation method and application thereof. Collagen is catalyzed by microbial transglutaminase to form a covalent cross-linked network, and meanwhile, hydroxypropyl starch is introduced to construct a physical interpenetrating network through molecular chain penetration and hydrogen-bond interaction; and chondroitin sulfate is further integrated to strengthen the network structure and biological activity through electrostatic interaction. The method is mild in condition and does not need a toxic chemical cross-linking agent, the obtained composite hydrogel has an interpenetrating double-network structure and has excellent mechanical properties, enzymatic degradation resistance and cell affinity, the compression modulus of the composite hydrogel is remarkably improved, the composite hydrogel can keep structural stability for a long time in a collagenase environment, cell adhesion and proliferation can be effectively promoted, and the composite hydrogel has a good application prospect. The hydrogel can be widely applied to tissue engineering scaffolds, wound dressings, drug sustained-release carriers and cartilage repair materials.

The invention discloses immobilized lipase based on bifunctional silicon dioxide as well as a preparation method and application of the immobilized lipase. Hydrophobic modification and covalent modification are performed on the surface of mesoporous silicon dioxide to obtain a bifunctional silicon dioxide carrier; the hydrophobic modification is any one of methylation modification, octylation modification, octadecyl alkylation modification, esterification modification and bromopropylation modification. The dual-functionalized silicon dioxide carrier is used for immobilization of lipase, and the prepared immobilized lipase can be used for production of biodiesel. The immobilized lipase provided by the invention is mild in enzyme reaction condition, good in biocompatibility, relatively high in enzyme activity, and excellent in stability and repeatability. In addition, by changing the ratio of the covalent modifier to the hydrophobic modifier, the catalytic activity and stability of the immobilized enzyme and the biodiesel yield are remarkably improved.

The invention provides a covalent organic framework material as well as a preparation method and application thereof, 1, 3, 6, 8-tetra (4-aminophenyl) pyrene is selected as a central construction unit, and a trap state is realized in a covalent organic framework (COFs) by regulating and controlling the symmetry of active sites (benzothiadiazole, BT). Compared with a centrosymmetric counterpart in the COFs, by breaking the symmetry of the center BT core, the trap state density in the COFs can be remarkably reduced, and the service life of the shallow trap state can be prolonged to 1160.02 picoseconds. Therefore, more photo-induced electrons can participate in the photocatalytic reaction, and the remarkable performance (greater than 99%) of photocatalytic reduction of uranium (VI) is finally realized. According to the invention, the key effect of symmetric breaking in inhibition of excited state decay of COFs is clarified for the first time, and a profound solution is provided for understanding how to improve the photocatalytic performance of COFs in environmental restoration.

The invention discloses an oligonucleotide intracellular nano delivery system based on polypeptide modification and application thereof. The system is composed of a periostin targeting sequence (SDSSD), a matrix metalloproteinase 2 (MMP2) response sequence (GPAGLLG), a cell penetrating sequence (RRRRRRRR, R9), a reactive oxygen species (ROS) scavenging and adhesion enhancing group (Gly-DOPA)) and a terminal dibenzocyclooctyne (DBCO) modified engineered polypeptide SDSSD-PEG5-YGFGG-GPAGLLG-R9-(G-DOPA) 3-K4-C-DBCO, and a target oligonucleotide miRNA-26a-A5-Azido modified by 5-polyadenylic acid (AAAAA) and an azide group (Azido), and the target oligonucleotide miRNA-26a-A5-Azido, the target oligonucleotide and assembling through a click chemical reaction and a non-covalent interaction. The nano system has good bone targeting, enzyme responsiveness, intracellular delivery effect and biological safety, can realize stable and efficient delivery of therapeutic oligonucleotides in vivo, and significantly improves the utilization efficiency and therapeutic potential of oligonucleotides. The oligonucleotide intracellular nano delivery system has a wide application prospect in the fields of clinical transformation and precise treatment of oligonucleotide drugs.

A pharmaceutical composition comprises a GPCR agonist fusion protein in which a GPCR agonist peptide is covalently coupled to albumin via a linker in a manner that is resistant to a retro-Michael addition. Advantageously, compositions presented herein avoid decoupling of the agonist form the albumin while retaining the agonist in a steric relationship to the albumin that allows for effective binding and activation of the GPCR while also enabling gp60-mediated transcytosis and FcRn-mediated albumin recycling. These properties enable ultra-low dosages for the GPCR agonist fusion protein to give a therapeutic effect while substantially reducing or even entirely avoiding adverse effects otherwise commonly associated with unbound agonists. Such retro-Michael resistant composition is generally achieved by conformational modification of the albumin, resulting in stereoselective coupling of the linker to the albumin.

Provided in the present invention are a preparation method for a crown ether covalent organic framework material, and the use thereof in iodine adsorption. In the present invention, an 18-crown-6-ether group is introduced into the structure of a covalent organic framework (COF) material for iodine adsorption work. The covalent organic framework material can form a one-dimensional pore channel structure in order, and the 18-crown-6-ether can be selectively complexed with iodine molecules, thereby achieving the purpose of efficient iodine adsorption. The material can perform specific iodine adsorption from high-temperature iodine steam, and the iodine steam adsorption capacity of the COF material is as high as 5.56 g / g. The COF material has a high adsorption capacity, is easy to prepare and simple to operate, has a high adsorption efficiency, and is particularly suitable for adsorbing and separating radioactive iodine in the nuclear industry.

The invention discloses a covalent organic framework with oxidation-reduction activity and a bionic nano-channel structure as well as a preparation method and application of the covalent organic framework, and belongs to the technical field of environmental protection. According to the preparation method, 2, 4-dihydroxybenzene-1, 3, 5-tricarboxaldehyde and 2, 5-bis (allyloxy) terephthaloyl hydrazine are taken as raw materials, a two-dimensional covalent organic framework with oxidation-reduction activity is synthesized, and then a sulfonic acid group with negative charges is covalently grafted, so that a functional material with a bionic nano-channel structure is formed. The material has regular porous channels and rich functional sites, the porous channels provide efficient mass transfer paths and adsorption spaces for uranyl ions, and the functional sites realize specific recognition of the uranyl ions through oxidation-reduction reaction and electrostatic interaction, so that the material shows synergistic advantages of strong selectivity, high adsorption capacity and rapid adsorption kinetics on uranium. The method is simple and low in cost, and the prepared material is clear in structure, good in hydrophilicity, capable of efficiently adsorbing uranyl ions and good in application prospect.