2431 results about "Covalent modifier" patented technology

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.

The invention belongs to the technical field of biological medicines, and particularly discloses an epidermal growth factor-linker polypeptide-collagen, and the linker polypeptide has an amino acid sequence as shown in SEQ ID No.1. The linker polypeptide capable of connecting the EGF and the collagen is designed and synthesized, the N end of the linker polypeptide simulates an EGF receptor structure and can be combined with the EGF, and the linker polypeptide is connected with the EGF through non-covalent Van der Waals force, so that the structure of the EGF cannot be damaged; the C terminal of the linker polypeptide is rich in lysine residues, and can be covalently crosslinked to collagen through glutamine transaminase to form EGF-linker polypeptide-collagen. The protein solution taking EGF-linker polypeptide-collagen as active ingredients is low in cytotoxicity and high in biological safety, and meanwhile, the action time of the epidermal growth factor can be remarkably prolonged. In addition, a stable repairing microenvironment can be formed on the surface of the endometrium, and the endometrium injury repairing effect is remarkably improved.

The invention relates to a dynamic-covalent hybrid cross-linked hydrogel material as well as a preparation method and application thereof. The preparation method comprises the following steps: dissolving a component A-phenylboronic acid modified polymer derivative in a biocompatible medium to obtain a solution A; dissolving a component B, namely a macromolecular derivative containing a vicinal diol group, into a biocompatible medium to obtain a solution B; dissolving a component C-double bond group modified polymer derivative in a biocompatible medium to obtain a solution C; and mixing the solution A, the solution B and the solution C with certain concentrations for a certain time, and performing illumination under a photoinitiator for a certain time to obtain the dynamic-covalent hybrid cross-linked hydrogel material. Compared with single dynamic bond crosslinking or covalent bond crosslinking, the prepared hydrogel material has machinability and mechanical stability; the hydrogel material has plasticity, shear thinning, self-repairing property and the like in the early stage of crosslinking; enough mechanical strength and long-term stability are realized in the later stage of crosslinking.

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.

β-Ketoenamine covalent organic frameworks (COFs) provide remarkable water sorption capabilities and stable adsorption–desorption cycling, particularly under low relative humidity (RH) conditions.

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).

The invention discloses a method for preparing a high internal phase emulsion and delivering curcumin by using transglutaminase mediated casein-carboxymethyl chitosan covalent substances, aims to improve the stability and bioaccessibility of curcumin, and belongs to the field of food processing. The method comprises the following steps: firstly, carrying out ultrasonic treatment on sodium caseinate for a certain time, and carrying out transglutaminase cross-linking reaction on sodium caseinate and carboxymethyl chitosan to obtain a casein-carboxymethyl chitosan covalent substance; and then adding the mixture into the curcumin-loaded corn oil according to a certain proportion, and homogenizing to obtain the curcumin-loaded high internal phase emulsion. The emulsion has good interface characteristics and can effectively encapsulate curcumin. The preparation process is simple, efficient, green and environmentally friendly, the prepared high internal phase emulsion has high stability and good biological accessibility, a new technical means is provided for delivery of curcumin, and the high internal phase emulsion has wide application prospects in the field of food.

The present invention relates to magnetic, catalytically active, and radiosensitizing nanoparticles (NanoXcats) and the method for their production. A method is disclosed for the production of functionalized greigite nanoparticles with a narrowband size distribution (10-30 nm) for use in multimodal cancer therapy. NanoXcats are superparamagnetic Fe3S4 nanoparticles whose surfaces are equipped with polar functional groups. The surface structures of NanoXcats are suitable for conjugation with, or for covalent or electrostatic binding of, active substances, which may be cancer drugs, cell growth inhibitors, or NO donors. Due to the EPR effect, NanoXcats are preferentially internalized by tumor cells. The targeted accumulation of NanoXcats in tumor tissue is achieved by an external inhomogeneous magnetic field. NanoXcats exhibit enhanced catalytic activity in tumor cells.The catalytic activity of intracellular NanoXcats can be triggered, controlled, and enhanced by low-dose X-rays. Surface-bound drugs are additionally activated in tumor cells by the catalytic activity of NanoXcats. NanoXcats act as superoxide dismutase, nitric oxide synthase, and Fenton catalyst. They catalyze, for example, reactions of the superoxide anion radical to hydrogen peroxide, of L-arginine to NO, and of hydrogen peroxide to the hydroxyl radical.

The invention belongs to the technical field of membrane separation, and aims to provide a preparation method and application of a covalent organic framework bipolar membrane. The method comprises the following steps: combining at least one amine, hydrazide or aldehyde monomer containing ionic groups with a monomer without ionic groups, and respectively synthesizing covalent organic framework COF nanosheets with positive charges and negative charges through a one-pot method under the condition of coexistence of an acid catalyst and an organic solvent; sequentially depositing COF nanosheets with positive and negative charges on the surface of the porous carrier by a hot solvent evaporation method; by constructing two COF separation layers with regular pore channels and opposite electrical properties, the covalent organic framework bipolar membrane with charge asymmetry is finally obtained. The product provided by the invention has high selectivity, can realize efficient separation of protons and metal cations, and significantly improves the extraction and recovery purity of hydrochloric acid; through charge repulsion and pore size screening mechanisms, separation of different anions can be further realized, and selective recovery of acid molecules is enhanced.

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 beta-lactoglobulin fluorescent probe as well as a preparation method and application thereof, the structural formula of the probe is (C30H25N4I), the probe is combined with beta-lactoglobulin through non-covalent interaction, a fluorescence signal is triggered to be remarkably enhanced, and low-background fluorescence detection of the beta-lactoglobulin is realized. The probe has low cytotoxicity and excellent mitochondrial targeting ability, and provides a powerful tool for visualization of beta-lactoglobulin in living cells. After being combined with beta-lactoglobulin, a sample can generate obvious color change under the irradiation of an ultraviolet lamp, and the change can be used for evaluating the content of active beta-lactoglobulin in the sample, so that the rapid detection of the milk protein level in a beverage is realized. The beta-lactoglobulin fluorescent probe disclosed by the invention has a wide application prospect in the fields of biological imaging, milk protein detection, beverage quality control and the like.

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 provides a whole-process targeting polypeptide, a drug compound thereof, a drug delivery system and application of the whole-process targeting polypeptide. The whole-process targeting polypeptide comprises pHA and VAP which are covalently connected through a bridging structure; the VAP is LVAP, a reverse sequence polypeptide of the LVAP, DVAP or SVAP; wherein the amino acid sequence of the LVAP is as shown in SEQ ID NO: 1; the SVAP is a D-configuration polypeptide of the LVAP; the DVAP is a D-configuration polypeptide of the LVAP inverted sequence polypeptide; the bridging structure is amino-monoethylene glycol-carboxylic acid or a derivative thereof. The whole-process targeting polypeptide not only can cross a blood-brain barrier, target tumor neovascularization, cross a blood-tumor barrier, target tumor mimicry vessels, tumor cells and stem cells thereof, but also has better tumor cell affinity, anti-tumor treatment and in-vivo safety effects. Meanwhile, the drug compound or the drug delivery system has a synergistic effect after being combined with a chemotherapeutic drug, and the anti-tumor drug effect can be remarkably improved.

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 provides a preparation method of a recombinant collagen dressing, and belongs to the technical field of medical dressings. According to the technical scheme, stacked short sequences and continuous human collagen amino acid short sequences are repeatedly combined for multiple times to form recombinant collagen with specificity, and high similarity of the recombinant collagen with human collagen is ensured. On the basis, 4-FPBA is used as a cross-linking agent to respectively form a Schiff base bond responsive to pH and a boric acid ester bond responsive to glucose with CMCS and two kinds of HA with different molecular weights, and then the double-dynamic covalent cross-linked network adhesive hydrogel is synthesized. The triple-helix structure of the recombinant collagen is combined with a specific receptor on a cell membrane, and cell behaviors are regulated and controlled by inducing signal transduction through a cytoskeleton, so that skin microcirculation can be effectively improved, and a skin barrier can be repaired; the hydrogel dressing matrix has the effects of resisting inflammation, resisting oxidation, resisting bacteria, promoting healing and the like, the biological performance of the dressing is remarkably improved, and a better curative effect is achieved.

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 provides a triphenylamine derivative as well as a preparation method and application thereof in killing gram-positive bacteria. The preparation method comprises the following steps: firstly, synthesizing an intermediate molecule 4-di-p-methoxyanilino benzaldehyde (s); the s respectively reacts with 3-pyridylacetonitrile and 4-pyridylacetonitrile to generate intermediate molecules a and b; the intermediate molecules a and b respectively react with methyl iodide to generate triphenylamine derivatives 1 and 2, and the intermediate molecules a and b respectively react with 9-bromomethyl anthracene to generate triphenylamine derivatives 3 and 4. The prepared triphenylamine derivative has a donor-acceptor structure and is a D-pi-A structure, the modified triphenylamine is used as a donor, a carbon-carbon double bond is used as a covalent bridge, and cyano and N positive ions have electron withdrawing property. As all the components contain positive ions, the components can be anchored on a bacterial membrane to kill bacteria; and the compound has a short alkyl chain and can be combined with gram-positive bacteria, so that the bacteria are killed.

The invention provides a covalent organic framework composite membrane as well as a preparation method and application thereof. The preparation method of the covalent organic framework composite membrane comprises the following steps: (1) dissolving 2, 4, 6-triformyl phloroglucinol in an organic solvent to obtain a 2, 4, 6-triformyl phloroglucinol solution; slowly adding a buffer layer of deionized water or alkali liquor to the top of the 2, 4, 6-triformyl phloroglucinol solution; dropwise adding a solution containing a diamine ligand onto the buffer layer, reacting at 25-35 DEG C for 3-10 days, collecting nanosheets, and dialyzing and purifying the nanosheets to obtain the covalent organic framework nanosheets, (2) taking hydroxyl carbon nanotubes, adding an organic solvent, and carrying out ultrasonic dissolution to obtain a hydroxyl carbon nanotube solution; taking a hydroxyl carbon nanotube solution, mixing the hydroxyl carbon nanotube solution with the covalent organic framework nanosheet obtained in the step (1), performing uniform ultrasonic treatment, performing vacuum pressurization, assembling the mixture onto a nylon membrane, and performing drying to obtain the covalent organic framework composite membrane. The membrane material has excellent properties such as relatively high rejection rate and good antifouling property.

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 belongs to the field of novel environment-friendly materials, and particularly relates to a modified covalent organic framework material for simultaneously adsorbing multiple heavy metal ions as well as a preparation method and application of the modified covalent organic framework material. The preparation method of the material comprises the following steps: dissolving 1, 3, 5-tri (4-aminophenyl) benzene and 2, 5-dihydroxy terephthalaldehyde in a mixed solvent, and standing and reacting at room temperature to obtain a mixed solution; adding scandium trifluoromethanesulfonate into the obtained mixed solution, carrying out standing reaction at room temperature, after the reaction is finished, separating insoluble substances from the reaction solution, and washing and drying the insoluble substances to obtain a covalent organic framework base material; a covalent organic framework base material prepared by adopting a neutral solution is subjected to ultrasonic modification treatment, and then the modified base material is washed and dried to obtain the modified covalent organic framework material. The material modified by the neutral solution shows a good adsorption effect on multiple heavy metal mixed ions in water, and has a good application prospect in the aspect of adsorbing and removing heavy metal ions in a water environment.