205results about How to "Extended half-life" patented technology

The invention discloses a polypeptide derivative with a GCGR, GIPR and GLP-1R triple targeting agonistic effect as well as a preparation method and application of the polypeptide derivative, the polypeptide derivative is shown as a formula (I), (II) is a branched chain modification structure of a peptide chain, and the group definition is detailed in the specification. The polypeptide derivative compound and the pharmaceutically acceptable salt thereof provided by the invention can be used for treating metabolic related diseases such as diabetes mellitus, weight loss, MASH and the like, cardiovascular and cerebrovascular diseases and / or neurodegenerative diseases. Tyr-Aib-Gln-Gly-Thr-Ph-Thr-Ser-Asp-Tyr-Ser-Xaa12-Xaa13-Leu-As-Lys-Xaa17-Ala-Gln-Xaa24-Xaa25-Leu-Leu-Xaa28-Gly-Ala-Pro-Pro-Ser-NH2 (I) # imgabs0 #

The invention discloses a bispecific cytokine fusion protein, which comprises an amino acid sequence of a type I cytokine and an amino acid sequence of a type II cytokine, and the amino acid sequence of the type I cytokine and the amino acid sequence of the type II cytokine are directly connected through a connecting peptide or are connected in series or in parallel through a fusion partner and the connecting peptide. Amino acid sequences of type I and type II cytokines are connected in series or in parallel to form the bispecific cytokine fusion protein, and the fusion protein can synergistically activate precursor depleted CD8 + T cells and terminal depleted CD8 + T cells, improve immunosuppression of a solid tumor complex microenvironment and release the potential of tumor immunotherapy. The invention further discloses nucleic acid, a carrier, a cell, a medicine or a medicine composition related to the bispecific cytokine fusion protein. The invention also discloses application of the bispecific cytokine fusion protein in preparation of drugs for treating cancers.

The invention relates to the technical field of medicine, and discloses an artificial exosome and application thereof in drug delivery, the artificial exosome is prepared into an oil phase based on PLGA and DOTAP, and a water phase based on OCT4 protein and siTrim28; mixing the two phases to obtain a primary emulsion, and adding a PVA aqueous solution to obtain a double emulsion; stirring the double emulsion and volatilizing the solvent to form an emulsified solution, and centrifuging to obtain PLGA nanoparticles; the lipid mixture is prepared from lipid, DPPE-PEG2000, alpha-tocopherol and alpha-lactalbumin, and a lipid film is formed after a solvent is evaporated; the preparation method comprises the following steps: mixing PLGA nanoparticles, a lipid film and membrane protein, uniformly mixing and heating to obtain a film-coated solution, and finally extruding through a cellulose acetate film to obtain the artificial exosome. The artificial exosome disclosed by the invention combines the stability of the PLGA nanoparticles and the biocompatibility of the lipid membrane, and provides new possibility for a drug delivery system.

The invention provides a novel platform for tumor immunotherapy. The platform is formed by self-assembly of full-heavy-chain human ferritin which can be jointly fused and expressed by a polypeptide prodrug mask which can be activated by protease and a mitochondrial disrupting peptide, and can specifically target a tumor microenvironment and induce ICD death of tumors. Meanwhile, an ion channel is formed in a protein shell of the platform, so that immunocompetence metal ions can be loaded in a cavity of the platform, and time-space synchronous anti-tumor immune activation can be carried out in cooperation with ICD. As the mitochondrial disrupting peptide and the metal ions can be optimized according to tumor types, the platform can be used for treating various tumors.

The invention relates to multi-element modified nano SiO2 particles, a method for constructing a high-efficiency CO2 foaming agent and the CO2 foaming agent, temperature-resistant and salt-resistant particles with a foam stabilizing effect are prepared by carrying out two-step chemical modification on the nano SiO2 particles, and the high-efficiency CO2 foaming agent is constructed by the temperature-resistant and salt-resistant particles and a low-concentration betaine and alpha-olefin sulfonate composite surfactant. The nano SiO2 particles are subjected to multi-element modification such as chemical modification and physical modification, so that the nano SiO2 particles are adsorbed on the gas-liquid surface and are tightly arranged to form a firm interfacial film. The half-life period of CO2 foam formed by a foaming system composed of modified nano SiO2 particles, a betaine active agent and alpha-olefin sulfonate under the conditions that the temperature is 80 DEG C, the pressure is 10 MPa and the salt content in water is 3 * 10 < 4 > mg / L is 9 times or above longer than that of pure modified nano particles, and the half-life period of CO2 foam is 6 times or above longer than that of alpha-olefin sulfonate.

The invention discloses a beta < + >-gamma-gamma coincidence positron annihilation lifetime-momentum correlation spectrometer, and belongs to the technical field of nuclear detection. The spectrometer comprises a positron annihilation life detection module, a positron annihilation gamma photon energy detection module, a signal acquisition module and a control and analysis module, and the positron annihilation life detection module is used for acquiring a life part in an AMOC spectrum; the positron annihilation gamma photon energy detection module is used for acquiring a momentum part in an AMOC spectrum by detecting gamma photons generated by positron annihilation; the signal acquisition module is used for acquiring signals generated by the positron annihilation life detection module and the positron annihilation gamma photon energy detection module; the control and analysis module is used for controlling the signal acquisition module and obtaining an AMOC spectrum based on signals acquired by the signal acquisition module. According to the method, the coincidence counting rate can be effectively improved, good coincidence time resolution and extremely low source components are achieved, and the construction cost of a spectrometer can be reduced.

The invention provides an aromatic fused ring compound, a pharmaceutical composition containing the compound and application of the aromatic fused ring compound, and relates to the technical field of medicines. The aromatic fused ring compound disclosed by the invention has a structure as shown in a formula (I): # imgabs0 # or a stereoisomer and pharmaceutically acceptable salt thereof, wherein the structural unit # imgabs1 # is selected from # imgabs2 # or # imgabs3 #, and each substituent group is defined in the specification. The aromatic fused ring compound has a strong inhibition effect on SIKs enzyme activity, has a positive regulation effect on TNF-alpha and IL-10 in serum of mice with acute inflammation, has a longer half-life period and a higher oral exposure amount, has a remarkable inhibition effect on NF-kappa B gene expression of THP-1 cells under MDP stimulation, and can be used for preparing medicines for treating acute inflammation. The traditional Chinese medicine composition has a remarkable weight recovery promoting effect on cachexia induced by cis-platinum.

The invention belongs to the field of biological catalysis, and particularly relates to a method for preparing oxidized nicotinamide adenine dinucleotide phosphate through double-enzyme coupling. According to the invention, through construction and optimization of a one-pot double-enzyme coupled catalytic system, a genetically engineered bacterium containing nicotinamide mononucleotide adenosine transferase NMNAT and a genetically engineered bacterium containing NAD kinase are used as a whole-cell catalyst, nicotinamide mononucleotide NMN is used as a starting substrate, adenosine triphosphate, polyphosphate and divalent metal ion salt are added, and the whole-cell enzyme is prepared through a one-pot method. The oxidized nicotinamide adenine dinucleotide phosphate NADP < + > is efficiently and catalytically synthesized by a one-pot method, and the whole-cell catalytic reaction liquid is separated and purified to obtain the NADP < + >. The double-enzyme catalysis method disclosed by the invention is short in reaction route, high in atom economy, capable of reducing the existing production cost, short in production period, easy for downstream separation and purification, and suitable for large-scale and large-scale production of NADP < + >.

The invention relates to application of an antioxidant liposome in preparation of a medicine for preventing and / or treating inner ear injury caused by active oxygen accumulation, and belongs to the field of medical technologies and biological medical materials. The antioxidant lipidosome is rutin-entrapped lipidosome, and the inner ear injury is preferably cis-platinum induced inner ear injury. The antioxidant liposome disclosed by the invention is used for inhibiting active oxygen accumulation, mitochondrial injury and cell apoptosis in cells; the compound is used for inhibiting auditory hair cell mitochondrial injury in cochlea. The antioxidant liposome disclosed by the invention can be used for effectively packaging medicines and improving the bioavailability and the stability of the medicines; the limitation of a tympanic membrane barrier and other biological barriers can be overcome, so that the medicine can effectively reach the inner ear part; precise targeted delivery of the medicine can be achieved, and it is ensured that the medicine is intensively released at the needed position.

The invention belongs to the technical field of exosome modification, and particularly relates to an exosome modification method for connecting a target protein to the surface of an exosome by utilizing NHS-PEG-NHS to achieve a targeting or treatment effect, and application of the exosome modification method in targeted central nervous system demyelination disease treatment. In particular to a technology for modifying an exosome to enable the exosome to have targeting property and a preparation method of the exosome. NHS-PEG-NHS is used as a connecting substance, and protein, polypeptide and substances with primary amine groups on the surface can be connected to the surface of an exosome membrane. The modified exosome can load drugs and can be accurately delivered to tissues expressing specific proteins or polypeptides through oral administration, so that the bioavailability and the treatment effect of the drugs are remarkably improved. Taking the NG2 antibody modified cow milk exosome as an example, the NG2 antibody is connected to the surface of the cow milk exosome to target the central demyelination focus area, so that the effective therapeutic dose of the drug in the central focus area is achieved through oral delivery.

The invention discloses a novel polypeptide, a polypeptide derivative and application thereof, and belongs to the technical field of biological medicine. The invention specifically relates to a specific sequence, a discovery process, a specific anti-tumor type, a long-acting modification mode and application of the novel polypeptide. The tumors comprise one or more of brain glioma, neuroblastoma, head and neck cancer, esophagus cancer, thyroid cancer, lung cancer, liver cancer, kidney cancer, breast cancer, cervical cancer, uterine cancer, ovarian cancer, colon cancer, small intestinal cancer, ileocecum cancer, stomach cancer, bladder cancer, pancreatic cancer, prostate cancer, bile duct cancer, melanoma, sarcoma, myeloma, lymphoma and leukemia; the compound has the specific effect of inhibiting proliferation and / or metastasis of tumor cells, is wide in treatment spectrum and has important treatment value in various tumors.

The invention relates to the technical field of genetic engineering biology, and particularly discloses a GLP-1 analogue fusion protein as well as a preparation method and application thereof. According to the application, fGLP-1 and a mutant thereof are respectively fused with FSA, IgG4-Fc and a mutant thereof through connecting peptides to form a GLP-1 analogue fusion protein with the effects of high biological activity, long half-life period, high stability and the like, and meanwhile, after pichia pastoris codon is optimized and modified, an efficient pichia pastoris methanol-induced secretory expression system is utilized for expression; the problems of short half-life period, low biological activity, poor thermal stability, potential immunogenicity, complex production process, high purification and preparation cost and the like of the GLP-1 analogue prepared by the existing expression system and related biotechnology are solved.

The invention belongs to the technical field of biological medicine, and particularly relates to an iron ion carrier and a preparation method and application thereof. The iron ion carrier disclosed by the invention has the advantages that the iron ion carrier disclosed by the invention can have relatively good binding activity with iron ions and ferrous ions, and has relatively low cytotoxicity and relatively long in-vivo drug half-life period.

The invention provides a preparation method and application of a platelet-based targeting oncolytic virus delivery preparation, effective loading of oncolytic viruses is realized by infecting platelets with the oncolytic viruses, and meanwhile, the cellular structure of the platelets can be used as a physical barrier, so that the platelet-based targeting oncolytic virus delivery preparation is prepared. The tumor targeting drug delivery system shields the neutralizing and removing effects of in-vivo neutralizing antibodies / complements / removing cells on the oncolytic viruses, so that the oncolytic viruses can enter the body in a systematic drug delivery mode, tumor targeting drug delivery of the oncolytic viruses is achieved through the tumor targeting capacity of platelets, and the success of intravenous drug delivery and tumor targeting of the oncolytic viruses is achieved. The invention provides a technical support and a new idea for wider and more effective treatment of cancers, and has a good application prospect.

The invention provides a nucleic acid aptamer agonist conjugate as well as a preparation method and application thereof. The nucleic acid aptamer agonist conjugate is prepared by coupling a nucleic acid aptamer, a connexon and an STING agonist, the nucleic acid aptamer agonist conjugate can be used as a medicine to recognize a target spot on the surface of a tumor cell in a targeted manner and enter the cell to start a cGAS-STING signal channel so as to realize an anti-tumor effect. The variety of STING agonists and the variety of connexons are also screened, so that the aptamer agonist conjugate not only has the advantages of easiness in transmembrane and cell entry, strong tumor permeability, long half-life period, small toxic and side effects and the like, but also has a strong inhibition effect on triple-negative breast cancer. The aptamer agonist conjugate can also be combined with an immune checkpoint blocking therapy to further realize long-acting and efficient inhibition of tumor growth.

The invention belongs to the field of biological medicine, and relates to siRNA for inhibiting PLN gene expression and a conjugate, the siRNA comprises a positive-sense strand and an antisense strand, the positive-sense strand comprises a nucleotide sequence I, and the antisense strand comprises a nucleotide sequence II; each nucleotide in the nucleotide sequence I and the nucleotide sequence II is modified or unmodified nucleotide; the nucleotide sequence I and the nucleotide sequence II are at least partially reversely complementary to form a double-stranded region; the nucleotide sequence I is basically consistent with a first section of nucleotide sequence, and the first section of nucleotide sequence is a section of nucleotide sequence with the length of at least 19 nucleotides in mRNA expressed by the PLN gene. The siRNA and the conjugate and the pharmaceutical composition thereof disclosed by the invention can effectively prevent and / or treat diseases associated with PLN expression, such as heart failure, cardiomyopathy, arrhythmia and the like, and have a good patent medicine prospect.

The invention provides a self-replicating mRNA molecular combination and application thereof, the self-replicating mRNA molecular combination comprises a first mRNA molecule for coding a self-replicating enzyme, and the first mRNA molecule comprises an ORF sequence for coding the self-replicating enzyme; and, at least one second mRNA molecule encoding a protein of interest. According to the self-replicating mRNA molecular combination, a nucleotide sequence of a functional region is reasonably optimized, so that a first mRNA molecule for coding replicase protein has a relatively high yield, and a second mRNA molecule for coding a target gene is further efficiently and massively replicated, so that the self-replicating mRNA molecular combination has a longer half-life period, the existence duration and the yield of the target protein are greatly improved, and the self-replicating mRNA molecular combination has a good application prospect. And a wide application prospect is provided. The self-replicating mRNA molecular combination can be used for preparing a pharmaceutical composition for treating, diagnosing or preventing diseases.

The invention belongs to the technical field of oil exploitation, and particularly relates to a foaming agent for nitrogen foam fracturing and a preparation method and application thereof. The preparation method comprises the following steps: adding 2, 4, 6-trimethyl-3, 5-diaminobenzene sulfonic acid, xylene and a catalyst into a high-pressure reactor, fully stirring, purging a pipeline and a reaction kettle with nitrogen for 5-10 minutes, vacuumizing, stirring, heating to 70-80 DEG C, stopping vacuumizing, adding epoxypropane, heating to 170-190 DEG C, reacting for 2-10 hours, and cooling the system to 70-80 DEG C; continuously stirring the mixed solution, introducing ethylene oxide, heating to 180-200 DEG C after the ethylene oxide is completely introduced, continuously reacting, and cooling the system to room temperature; and adjusting the pH value to 8-9 with hydrochloric acid, filtering, and carrying out reduced pressure distillation to obtain a viscous solid, namely the foaming agent product. The foaming agent has the advantages of large foaming volume and long half-life period.

The invention relates to a medicinal salt used as a tyrosine kinase inhibitor, a crystal, a preparation method and application thereof, in particular to a medicinal salt of (E)-4-(dimethylamino)-N-(7-(2-ethoxyethoxy ether)-4-((3-ethynyl phenyl) amino)-6-quinazoline)-2-buteneamide, a crystal form and a preparation method thereof. The invention also relates to a pharmaceutical composition containing a therapeutically effective amount of the crystal form and application of the crystal form in cancer treatment.

The invention discloses compound enzyme nanogel as well as a preparation method and application thereof. The compound enzyme nanogel is prepared from the following components in parts by weight: 12 to 1310 parts of compound protease; 5-210 parts of a monomer polymer material; 12 to 120 parts of an adhesive; and 12-120 parts of a cross-linking agent. The compound enzyme nanogel disclosed by the invention improves the loading capacity of protein, and is high in stability and good in safety; in addition, due to the stability of the nanogel structure, the protease has a relatively long half-life period, an enzyme cascade effect can be continuously and effectively carried out, and meanwhile, the administration concentration and the administration frequency are reduced.

The invention relates to dexcamphanol or fenchol ester derivatives of 2-hydroxynicotinic acid and pharmaceutical application of the dexcamphanol or fenchol ester derivatives, and belongs to the technical field of biological medicine. The structural general formula of the derivative disclosed by the invention is # imgabs0 #, wherein R1 is selected from-H,-Cl, alkyl with 1 to 8 carbon atoms,-CF3,-CF2H,-CN,-SCH3,-OH,-CHO,-CH2OH,-CH2NH2,-COOH, halogenated phenyl or-NR4R5; r4 and R5 are independently selected from-H or-CH3; r2 is selected from-H, alkyl with 1-6 carbon atoms, and acyl or carbamoyl with 2-7 carbon atoms; r3 is selected from # imgabs1; # X is selected from-CH = or-N =. The derivative disclosed by the invention has a good inflammation inhibition effect; and under the condition of high concentration, the compound has lower cytotoxicity and is safer. The compound can be used for preparing medicines for treating inflammation and inflammation-related diseases such as cerebral apoplexy, neuropathic pain, depression and senile dementia.

The invention belongs to the technical field of oil-gas field development, and particularly relates to a foaming agent and a synthesis method and application thereof. The synthesis method comprises the following steps: adding 1-amino-3, 6, 9, 12, 15, 18-hexaoxaheneicosan-21-acid and ethanol into a high-pressure reaction kettle, stirring and dissolving, adding 4-(2-bromoethyl) sodium benzenesulfonate, continuously stirring, adjusting the pH value to 8-9 by using sodium hydroxide, heating and preserving heat, and adjusting the pH value to 8-9 by using sodium hydroxide during the period; and adding bromotetradecane into the solution, heating and refluxing, adjusting the pH value to 8-9 by using sodium hydroxide during heating and refluxing, carrying out reduced pressure distillation to obtain a viscous solid, and recrystallizing by using normal hexane to obtain a product, namely the foaming agent. The foaming agent provided by the invention has the advantages of strong foaming power, good stability and low interfacial tension.

The invention discloses a programmable multi-modified long-acting slow-release elastin-like protein (ELP) vector and an application thereof. A programmable biosynthesis method is utilized to construct a series of ELPs with different structures and properties consisting of different amino acids, including a composite characteristic positive charge series ELP (IVK), a composite characteristic negative charge series ELP (IVE), a composite characteristic benzene ring series ELP (IVF), a composite characteristic hydroxyl benzene ring series ELP (IVY) and a structure chimeric characteristic series ELP (IVYIVE). After subcutaneous injection, the ELP carrier is subjected to in-situ phase change under the triggering of body temperature and forms a drug reservoir, and the drug is slowly released from the reservoir to an in-vivo circulatory system, so that the effective action time of single injection of the drug is remarkably prolonged, pharmacokinetic parameters are improved, and the compliance of a patient is improved. The programmable slow-release ELP has wide application potential and is suitable for delivery of various drugs such as proteins, nucleic acids, polypeptides, antibodies and small molecule drugs.

The invention provides an oxytetracycline injection and a preparation method thereof, and belongs to the technical field of medicine preparation, the preparation method comprises the following steps: uniformly mixing 35-50 parts by weight of polyethylene glycol 400 and water, sequentially adding 0.4-0.6 part by weight of sodium formaldehyde sulfoxylate and 1.6-1.8 parts by weight of magnesium oxide, heating, adding 18-22 parts by weight of oxytetracycline, carrying out a complex reaction, adding monoethanolamine to adjust the pH value to 8.4-8.6, and uniformly stirring to obtain the oxytetracycline injection. And fixing the volume and filtering to obtain the oxytetracycline injection. The oxytetracycline injection prepared from the oxytetracycline can effectively improve the stability and the drug effect, prolong the half-life period of the drug and reduce the irritation.

The invention relates to the technical field of biology, in particular to a mirror image coupled protein nanoparticle conjugate and application thereof. The conjugate comprises: ii) a functional protein labeled by a first peptide tag, and ii) a scaffold protein labeled by a second peptide tag, the first peptide tag and the second peptide tag being composed of D-amino acid residues; the first peptide tag and the second peptide tag form a peptide partner pair, and the first peptide tag and the second peptide tag are coupled and combined through an isopeptide bond. The conjugate provided by the invention is easier to escape from the recognition of protease, can obviously prolong the half-life period in a biological system, is not easy to cause unnecessary immunoreaction, and has good biological stability and safety.

The invention discloses a long-acting slow-release lyotropic liquid crystal gel preparation and a preparation method and application thereof, the preparation comprises a matrix material, a cosolvent and a raw material medicine, the preparation has a hexagonal phase microstructure, shows a slow-release effect of more than 72 h and even up to 170 h, can prolong the half-life period of the medicine by nearly 10 times, and can realize analgesia or analgesia and anti-inflammatory dual curative effects.

The invention relates to the technical field of nano materials, in particular to a CoMo-BTNT anode, a preparation method and application thereof, and the preparation method comprises the following steps: preparing a Ti substrate; preparing a titanium dioxide nanotube array by using a Ti substrate; co-Mo oxide layer deposition liquid is deposited on the surface of TNA through a direct-current electrodeposition method, then annealing heat treatment is conducted, and CoMo-TNA is prepared; preparing a CoMo-BTNT anode by taking CoMo-TNA as a cathode and a Pt sheet as an anode; the invention also provides an application of the CoMo-BTNT anode in degradation of antibiotics in water. According to the invention, TNA is used as a base layer, an active CoMo oxide layer is deposited on the TNA base layer, the TNA base layer has good electrical conductivity and electro-catalytic performance, the electrical conductivity of the anode is improved, an effective electrically-assisted activated PMS degradation tetracycline system is constructed, and a new solution thought is provided for treatment of tetracycline wastewater.

The present invention belongs to the field of bioengineering technology, and specifically relates to a human growth hormone fusion protein and its application. The fusion protein hGH-linker-HSA and the hGH mutant fusion protein hGHmutF31Q / V90E-linker-HSA are constructed by connecting hGH and HSA through a connecting peptide. Mouse experiments show that hGHmutF31Q / V90E-linker-HSA can improve the metabolic stability of hGH, prolong the half-life of hGH, and enhance the administration effect of hGH, and has a broad application prospect in clinical practice.

The invention provides a high-strength self-assembly gel foam oil displacement agent and a preparation method thereof, and belongs to the field of chemical oil displacement. The high-strength self-assembly gel foam oil-displacing agent is prepared from the following components: a ternary amphiphilic hydrophobic association copolymer, a zwitterionic surfactant, a nonionic surfactant, heat-resistant polybasic acid, a counter-ion compound, a chelating agent and formation water. According to the self-assembly gel foam oil-displacing agent, quadruple interaction is formed among molecules of all the components, the strength of foaming liquid is remarkably improved, generated nitrogen foam is fine, rich and good in stability, large cracks and karst caves can be blocked in a fracture-cavity type oil reservoir, the swept volume can be effectively enlarged, the crude oil recovery rate of the fracture-cavity type oil reservoir can be remarkably increased, and the oil-displacing effect is good. The foaming agent does not generate precipitates with calcium and magnesium ions, and does not separate out due to salt.