30results about How to "Improve resistance to enzymatic hydrolysis" patented technology

The invention belongs to the technical field of nano-particles, and relates to self-assembly nano-particles of a sulfhydrylation chitosan quaternary ammonium salt and a preparation method and application thereof. The sulfhydrylation chitosan quaternary ammonium salt is prepared from chitosan through quaterisation and sulfhydrylation modifications in turn. The nano-particles are generated from the positively charged sulfhydrylation chitosan quaternary ammonium salt and a negatively charged protein polypeptide medicament or a nucleic acid medicament through polyelectrolyte action. Compared with the prior art, the invention has the advantages that: the preparation process of the nano-particles is simple and easy to control, organic solvent is not needed, and the stability of medicaments can be effectively improved. Compared with the conventional chitosan quaternary ammonium salt nano particles, the nano-particles have better effects of promoting absorption of the protein medicament and promoting cell transfection of the nucleic acid medicament.

The invention provides a collagen-based biomedical material by taking dialdehyde polyethylene glycol as a cross-linking agent and a preparation method thereof. The preparation method disclosed by the invention comprises the following steps of: preparing dialdehyde polyethylene glycol having a certain hydroformylation degree at first, uniformly mixing dialdehyde polyethylene glycol solution with the mass fraction of 0.1-5% with collagen solution with the mass fraction of 0.3-3%, then, pouring into a mould, freezing at -30-0 DEG C for 1-10 days, taking out, and freeze-drying in a freeze-drying machine for 1-2 days to obtain dialdehyde polyethylene glycol-collagen sponge; and repetitively immersing the sponge in water for 2-4 times, each time for 2-10 h to obtain dialdehyde polyethylene glycol-collagen hydrogel. According to the invention, a freezing polymerizing technology and a freeze drying technology are combined; the mechanical property, the thermal stability and the enzymatic degradation resistant property of collagen are improved by the prepared dialdehyde polyethylene glycol collagen sponge or gel; furthermore, the collagen-based biomedical material disclosed by the invention has the advantages of porosity, hydrophilia, water-retaining property, nontoxicity, good biocompatibility and the like, can be used in the biomedical fields, such as biological scaffolds, cell culture, drug release, burn and wound dressing and the like, and has good market application prospect.

The invention discloses a protein coupling method based on catenane. Each second-level component (SpyTag, BDTag and SpyStapler) in a SpyTag-SpyCatcher compound is connected renewedly, a chain entanglement structure designed by labor is introduced, a protein activity template method combining winding and catalyzing is developed, and mechanical key coupling of different target proteins connected in a catenane mode can be realized. The protein coupling method based on the catenane is used for performing heterogeneous catenane on disordered proteins or folding proteins, and the structure and performance of the proteins cannot be affected. The catenane process further can realize intracellular direct expression preparation through a coexpression system. Due to the fact that a catenane structure has a conformation limiting effect and space control on the target proteins, and the stability of the target proteins can be improved. According to the protein coupling method based on the catenane, concise synthesis of protein heterogeneous catenane is realized, and the protein coupling method based on the catenane is a very valuable and novel protein coupling strategy.

The invention provides a biological anti-adhesion material, a preparation method and application thereof. The biological anti-adhesion material is characterized in that the biological anti-adhesion material is prepared by using a small intestinal submucosa tissue material of an animal as a raw material, eliminating immunogenicity and retaining complete extracellular matrix ingredients and comprises a first surface, a second surface and a degradable absorbing structure positioned therebetween, the first surface is a smooth surface, the second surface is a coarse surface, and the degradable absorbing structure is in gradually-varied connection. The coarse surface of the biological anti-adhesion material is conducive to guiding growth of wound surface tissue cells so as to repair the wound surface; the smooth surface is conducive to stopping the cells to be adhered to other tissue so as to effectively prevent adhesion. The biological anti-adhesion material can be used for anti-adhesion treatment of the wound surface in enterocoelia, thorax or pelvic cavity.

The invention discloses an alpha conus polypeptide derivative, amino acid residues of which are shown in sequence 1 in a sequence table. To effectively resist the degradation digestion of partial protease in a human body, and improve the bioavailability and the drug metabolism performance, an N end of the alpha conus polypeptide derivative can be connected with a benzoyl group. The alpha conus polypeptide derivative can also be subjected to cyclization, fattening or PEG modification to strengthen the treatment effect of the alpha conus polypeptide derivative. A big mouse experiment shows that the alpha conus polypeptide derivative shows strong analgesic activity in a neuropathic pain model of a big mouse, and the analgesic activity is remarkably higher than that of control peptide Vc1.1 and shows dose-dependent relation.

The invention belongs to the technical field of medicines and specifically provides a galactose modified sulfhydryl chitosan quaternary ammonium salt nanoparticle, as well as a preparation method and an application of the nanoparticle. The nanoparticle provided by the invention is generated by positively charged galactose modified sulfhydryl chitosan quaternary ammonium salt and an ionic cross linking agent under an ionic cross linking action, and meanwhile is entrapped with protein polypeptide medicine or nucleic acid medicine, wherein the galactose modified sulfhydryl chitosan quaternary ammonium salt is formed by sequentially enabling amino of chitosan to be subjected to quaternization, galactose modification and sulfhydryl modification. The preparation process of the nanoparticle is simple, the organic solvent is not required, and the activity of the protein polypeptide medicine or the nucleic acid medicine can be protected. The nanoparticle is stable in structure, can actively target inflammation macrophage and liver cancer cell, effectively improves small intestine absorption of oral-taken medicine and improves the transfection efficiency of nucleic medicine, has anti-inflammation and anti-tumor effects which are better than those of the existing chitosan nanoparticles, and can be used for preparing an oral-taken medicating system, united medicating system, and the like.

The invention relates to pH-sensitive starch-based micro-capsules embedded with fat-soluble functional factors and a preparation method thereof, and belongs to the field of starch-based hydrogel micro-capsule preparation. The preparation method of the pH-sensitive starch-based micro-capsules embedded with the fat-soluble functional factors comprises the following steps: performing acid hydrolysison starch so as to obtain acid-hydrolyzed carboxymethyl starch; mixing the acid-hydrolyzed carboxymethyl starch with xanthan gum so as to obtain a compound solution of starch and colloid; adding an emulsifier and fat-soluble functional factors, and carrying out emulsification so as to obtain an emulsion; and then, carrying out drying so as to obtain the micro-capsules. The micro-capsules preparedby the preparation method are capable of resisting hydrolysis by gastric acid and enzymes in gastric juice; and thus, bioavailability of core materials, namely the fat-soluble functional factors is improved. The release rate of the fat-soluble functional factors in simulated gastric juice is only 20-40%; and the cumulative release rate of the fat-soluble functional factors in human body digestivetract (simulated gastric juice and simulated intestinal juice) is up to 80-95%. Therefore, the problems of bad water-solubility, liable oxidation, low oral availability and the like of the fat-solublefunctional factors are solved; so that, the micro-capsules can be added into products, such as beverages and the like, as a nutrient fortifier or a food additive. Thus, the micro-capsules have wide application prospects.

The invention belongs to the biotechnological field, and particularly relates to tripolymer TRAIL protein and application thereof.The tripolymer TRAIL recombination protein is prepared through the steps that a 114-281 amino acid sequence of TRAIL and a vector PET are subjected to gene cloning to prepare TRAIL recombination protein (HZ-TRAIL for short) with an N-terminal histidine label and an isoleucine zipper motif recombination gene pET23dw-His-ILZ-hTRAIL114-281; the HZ-TRAIL is modified by polyethylene glycol to enable PEG to be coupled to the N-terminal amino of the HZ-TRAIL protein through a covalent bond, and then the polyethylene glycol-modified TRAIL recombination protein, that is, the PEG-HZ-TRAIL protein is obtained.The TRAIL recombination gene is improved into the novel PEG-HZ-TRAIL through a PEGylation technique to produce the high-activity TRAIL protein of a tripolymer, and the tripolymer TRAIL protein has the advantage of being high in pharmacological efficacy on resisting tumors and rheumatoid arthritis.

The invention relates to an in-situ cross-linking gel forming method of degradable protein. The method comprises the following specific steps: S1, dispersing a degradable biological material taking protein as a main raw material in normal saline or a phosphate buffer solution to prepare a solution A; S2, adding riboflavin or riboflavin derivatives into the solution A, and stirring and mixing to prepare a solution B; S3, filling an injector or a 3D printer with the solution B; S4, performing in-vivo injection filling by using the injector, and irradiating the injected solution B by using an endoscope light source probe during injection; or adopting the 3D printer for printing, and adopting light beams emitted by a light beam generator for irradiating the solution B sprayed out of an ink nozzle of the 3D printer during printing. The gel is formed through in-situ cross-linking under the wet condition, the method is simple and easy to operate, no toxic cross-linking reagent is added, and the prepared gel can effectively improve the enzymolysis resistance of protein and has good biocompatibility.

The invention discloses siRNA for specifically knocking down TNF-alpha gene expression and application thereof.The siRNA sequence provided by the invention can specifically knock down the TNF-alpha transcriptional level, a positive-sense strand is modified through sulfo, on the basis that cytotoxicity is not obviously increased, the anti-enzymolysis capacity in serum is greatly improved, the in-vivo residence time of the siRNA is prolonged, and the siRNA can be used for preparing a medicine for treating the TNF-alpha. And potential application values can be exerted in treatment of various tumor diseases and autoimmune diseases.

The invention provides sodium hyaluronate essence and a preparation method thereof. The sodium hyaluronate essence is prepared from the following components in parts by weight: 4 to 8 parts of modified sodium hyaluronate, 0.5 to 0.8 part of squalane, 0.5 to 1.0 part of propolis, 40 to 50 parts of humectant, 5 to 10 parts of skin conditioner, 3 to 5 parts of traditional Chinese medicine essence extract, 0.1 to 0.5 part of absorption enhancer and 50 to 80 parts of water. The modified sodium hyaluronate is added, so that the enzymolysis resistance of the sodium hyaluronate is enhanced, the function limitation of a single component is avoided, and the prepared essence has a better moisturizing effect and a better free radical scavenging capability.

The invention relates to a method for improving enzymolysis resistance of casein and reducing sensitization, which is used for cross-linking China-hemp seed protein and casein through transglutaminase, and specifically comprises the following steps: (1) preparing a mixed solution of casein and China-hemp seed protein; (2) adding transglutaminase into the mixed solution of the casein and the hemp seed protein, and carrying out cross-linking reaction to obtain a cross-linked casein solution; and (3) placing the cross-linked casein solution in an environment of 3-5 DEG C, and terminating cross-linking. Compared with the prior art, the method has the advantages that the process steps are simple, the novel food resource, namely the hemp seed protein, is fully utilized, the casein is replaced by the hemp seed protein, the sensitization of the casein is further reduced, the enzymolysis resistance of the casein is improved, and the delivery effect of the casein on sensitive substances in the fields of food and pharmacy is improved.

The invention provides a dynorphin A (1-8) and neurotensin (8-13) coupled cyclic hybrid peptide, as well as a synthesizing method and an application thereof, relates to cyclic hybrid peptides, as wellas a synthesizing method and an application thereof, and aims at solving the problems of relatively poor biological stability and poor neuropathic pain relieving effect of existing opioid medicines.The hybrid peptide has an amino acid sequence of Dmt-Gly-c(Cys-NMePhe-Leu-Arg-Arg-Ile-Cys)-Gly-NMeArg-Lys-Pro-Trp-Tle-Leu. The method comprises the following steps: 1, pretreating 'Fmoc' protected Wang resin; 2, removing the 'Fmoc' protective group; 3, performing an amino acid condensation reaction; 4, prolonging a peptide chain; 5, forming a disulfide bond; 6, cutting off the peptide chain from resin; and 7, desalting and purifying crude peptide. The biological stability of hybrid peptide can be enhanced through multi-site unnatural amino acid substitution and cyclic modification, and the cyclic hybrid peptide has an effect of relieving neuropathic pains. The hybrid peptide is used for preparing neuropathic pain relieving medicines.