503 results about "Biopharmaceutical" patented technology

The invention discloses a site for stably expressing protein in a CHO cell gene NW023276806.1 and application of the site, and belongs to the technical field of biological genes. The site belongs to a fixed position in a CHO cell genome, different protein genes are introduced based on a micro-homologous end connection mechanism through a CRISPR / Cas9 tool, and stable expression is carried out. By adopting a site-specific integration method, a target gene is integrated to a stable expression area in a site-specific manner, repeated high-expression monoclonal screening is effectively avoided, and an MMEJ mechanism is introduced to integrate a donor fragment, so that the research and development time for constructing a stable expression cell strain in biological pharmacy can be effectively shortened, and the cost is reduced.

The present invention belongs to the field of biopharmaceutical technology, and specifically relates to a method for preparing GLP-1 or its analogs. The present invention provides a leader peptide, and a fusion protein comprising the leader peptide. The leader peptide or fusion protein is used to prepare a semaglutide precursor polypeptide, and the results show that the yield of the prokaryotic expression fusion protein can reach 26g / L, and the purity of the precursor polypeptide obtained after enzyme cleavage is higher than 95%. The precursor polypeptide is further side-chain modified and connected with a dipeptide to efficiently prepare semaglutide.

The invention provides a biopharmacy downstream process optimization method and system based on machine learning. The method comprises the following steps: acquiring process parameters, process parameters and key quality attributes from a historical production process; preprocessing the technological parameters, the process parameters and the key quality attributes, performing feature construction, and selecting feature data; training a plurality of pre-acquired machine learning models based on the feature data, identifying key process parameters, evaluating the trained machine learning models according to a preset dimension, and selecting at least one optimal machine learning model according to an evaluation result; and performing parameter combination based on the key process parameters and a preset constraint range, inputting the combined parameters into at least one optimal machine learning model, and selecting a key process parameter combination meeting a preset quality standard according to an output result. According to the method, the problem that the key quality attributes are difficult to accurately predict and optimize in the existing biopharmacy downstream process is solved.

The invention provides a composition capable of penetrating an intestinal barrier by oral administration. The composition contains a carrier or an auxiliary material of a targeted Microflod cell Dectin-1 receptor, and one or / and a plurality of medicinal components / components, wherein the carrier or the auxiliary material of the target Microflood cell Dectin-1 receptor is beta-glucan, and the carrier or the auxiliary material of the target Microflood cell Dectin-1 receptor is beta-glucan. The effective components / components are traditional Chinese medicine effective components / components, or / and probiotics, or / and chemical medicine components, or / and biological medicines. The invention relates to a composition capable of realizing oral administration and penetrating through an intestinal barrier, which is based on the discovery of the inventor that the composition reaches colon through gastrointestinal tracts, targets colon Microflood cells, is taken by the Microflood cells, penetrates through the intestinal barrier and enters immune tissue Colonic Patches of a colon submucosa. Based on the research, the composition disclosed by the invention can be used for treating various diseases, such as ulcerative colitis, Crohn's disease, colon cancer, rheumatoid arthritis or bacterial pneumonia after being orally taken and absorbed by rectum.

The invention provides an AS01 derivative adjuvant, a preparation method thereof and application of the AS01 derivative adjuvant in preparation of vaccines or anti-tumor drugs, and belongs to the technical field of biological drugs or products. The AS01 derivative adjuvant is prepared from the following components in parts by mass: 0.5 to 1.0 part of cholesterol, 2.0 to 4.0 parts of dioleoyl lecithin and at least one of the following components in parts by mass: 0.1 to 0.2 part of monophosphoryl lipid A, 0.1 to 0.2 part of QS-21, 0.36 to 0.72 part of 3M-052, 0.4 to 0.8 part of muramyl dipeptide and 0.2 to 0.4 part of oligodeoxynucleotide. According to the AS01 derived adjuvant, a novel synergistic adjuvant system is developed by integrating various immunomodulators, so that the immunogenicity of a vaccine is enhanced. The HPV vaccine is prepared on the basis of the AS01 derived adjuvant, so that the immunogenicity can be enhanced, and good anti-tumor activity can be achieved. Therefore, the invention provides a new strategy for immunotherapy of HPV-related tumors.

A series of viscosity-reducing and stabilizing formulations for high concentration protein formulations, which are meticulously tailored to significantly decrease the viscosity and increase the stability of high concentration biopharmaceuticals. The viscosity-reducing and stabilizing formulations can be used in high concentration biopharmaceutical products and can bring considerable potential for enhancing the stability during preparation and storage and elevating the feasibility of high concentration biopharmaceutical products.

The invention discloses a serum-free full-suspension MDCK (Madin-Darby Canine Kidney) cell and application thereof in preparation of influenza vaccines, and belongs to the field of virology and biological medicines. The serum-free full-suspension MDCK cell is preserved in the China Center for Type Culture Collection, is classified and named as a canine kidney cell MDCK-JHS, and has a preservation number of CCTCC NO: C2024373. The invention further provides a method for culturing the influenza virus by using the cell line, high-titer amplification of the influenza virus can be realized, and the method is suitable for industrial production.

The invention relates to the field of biological medicine preparation, and provides a semi-synthesis preparation method of semeglutide and a preparation method of a semeglutide side chain, the semi-synthesis preparation method comprises the following steps: 1, in the presence of a first base catalyst, mixing a compound SMG-1 solution with a compound III solution, reacting to obtain a compound IV, and filtering to obtain a compound III; wherein the addition amount of the first base catalyst is such that the pH value of the SMG-1 solution is 11.2-11.6; 2, in the presence of a coupling agent and a second base catalyst, a compound IV solution and a compound SMG-3 solution are mixed and coupled to obtain a compound V, and the pH value in the step 2 is 9.5-10.0; and 3, carrying out deprotection on the compound V by using a deprotection agent to finally obtain the semeglutide. The method provided by the invention has the advantages of few reaction steps, reduced cost, high semeglutide purity and high yield, and is suitable for large-scale industrial production.

The invention belongs to the technical field of biological medicine, and particularly relates to a novel deuterated JAK2 inhibitor or pharmaceutically acceptable salt thereof. Compared with the prior art, the compound or the pharmaceutically acceptable salt thereof provided by the invention has better JAK2 inhibition activity, and the JAK2 inhibition target selectivity of the compound or the pharmaceutically acceptable salt thereof is obviously superior to that of the existing compound, so that the compound or the pharmaceutically acceptable salt thereof has better druggability.

The invention belongs to the technical field of biological pharmacy, and relates to a method for preparing tremella aurantialba polyphenol by utilizing tremella aurantialba TA58.21 fungus chassis cell fermentation, which comprises the following steps: adding a cooked soybean meal culture medium and a tremella aurantialba seed solution into a fermentation tank, introducing sterile oxygen, controlling the stirring rotating speed of the fermentation tank and the culture temperature to be 25-30 DEG C, continuously culturing for 5-8 days, and when the fermentation liquor becomes red, stopping the fermentation; when a large amount of foam is generated, closing an exhaust valve, keeping the tank pressure at 0.1 MPa, increasing the fermentation temperature to 50 DEG C, continuing to culture for 24 hours, increasing the stirring rotating speed of the fermentation tank, heating the fermentation liquor to 80-90 DEG C, keeping the temperature for 4-8 hours, stopping stirring, continuing to heat to 120 DEG C, and keeping the temperature for 30 minutes; centrifuging the fermentation liquor to remove precipitates and mycelia; collecting supernate, and pre-treating macromolecular substances and thallus fragments; collecting permeate liquid, and intercepting through a nanofiltration membrane to obtain a concentrated solution; and carrying out spray drying or freeze drying treatment on the concentrated solution to obtain a high-purity product. According to the invention, the tremella aurantialba polyphenol product with good water solubility, heat resistance, acid resistance and molecular weight of less than 10000 Da can be obtained.

The invention belongs to the field of biological medicines, and discloses an application of a protein polymer in preparation of a medicine for treating Alzheimer's disease, a production process of the protein polymer comprises the following steps: S1) using ultraviolet irradiation to stimulate mesenchymal stem cells and culturing; and S2) splitting the mesenchymal stem cells, separating and purifying to obtain the protein polymer. According to the present invention, the mesenchymal stem cells are stimulated to express the protein with the nerve repair function through the ultraviolet irradiation stress mode, and the protein polymer is obtained through further separation and purification, such that the protein polymer can be adapted to diversified application modes, can improve the abnormal conditions of the Alzheimer's disease related biomarkers, and can provide the significant treatment effect on the Alzheimer's disease.

Use of PGLYRP2 gene and a related drug thereof. The present invention relates to the field of biopharmaceuticals, and in particular, to use of the PGLYRP2 gene and the related drug thereof. The present invention aims to solve the problem that existing drugs can only inhibit the replication of hepatitis B virus and cannot eliminate viral cccDNA. The PGLYRP2 gene is used for preparing a drug for treating a hepatitis B virus infection. The PGLYRP2 gene is used for preparing a drug for eliminating hepatitis B virus cccDNA. Also provided is a gene therapy vector for eliminating hepatitis B virus. The gene therapy vector comprises a promoter, an intron, an enhancer, and a PGLYRP2 gene encoding region. The HBV virus inhibition function and the cccDNA-eliminating effect of the PGLYRP2 protein are defined, so that the elimination of HBV in liver cells and a mouse liver can be significantly promoted.

The invention belongs to the technical field of biological medicines, and particularly relates to a combined preparation of chlorbuconazole or pharmaceutically acceptable salt thereof and a proline hydroxylase inhibitor medicine. The combined use of the chlorbuconazole and the proline hydroxylase inhibitor drug can activate the expression of the downstream target gene of the HIF-2alpha, and a synergistic effect is shown. In a cisplatin-induced renal anemia model, the chlorprazole acid can enhance the effect of the proline hydroxylase inhibitor on treating renal anemia.

The invention belongs to the field of biological medicines, and discloses a stress-induced mesenchymal stem cell extract and a preparation method and application thereof.The preparation method comprises the steps that S1, mesenchymal stem cells are cultured under the high-temperature condition, swelling and cracking are conducted on the mesenchymal stem cells, or supernate obtained after culture of the mesenchymal stem cells is taken and filtered, and filtrate is obtained; the temperature of the high temperature ranges from 37.0 DEG C to 42.0 DEG C; s2, purifying the mesenchymal stem cell extract by adopting a molecular sieve exclusion chromatography method or a reverse chromatography method. Specific high-temperature stimulation is adopted to induce the mesenchymal stem cells, a purification method is combined, protein expression is promoted, the purity of the mesenchymal stem cell extract is improved, the prepared and obtained purified Alibitumen is used in a cell oxidative damage model, and the cell oxidative damage rate is increased. It is found that all the Aribitua derived from high-temperature stress culture has high oxidative damage repairing capacity.

This invention belongs to the field of biopharmaceuticals and provides a keratin YK93-6, its encoding nucleic acid molecule, an expression vector containing the nucleic acid molecule, a host cell containing the expression vector or whose genome integrates the nucleic acid molecule, as well as a preparation method and a pharmaceutical composition thereof. It also provides the application of the above-mentioned keratin YK93-6 and other products in the preparation of drugs for treating benign prostatic hyperplasia, lymphoma, melanoma, analgesia, lactation, breast cancer, lung cancer, uterine fibroids, coagulation, etc.

The invention discloses a dust-free environment purification method for biological pharmacy. Comprising the following steps: constructing three layers of metal filter screens, realizing particle interception through a conical micro-column array, an Al2O3 / TiO2 composite ceramic layer and a diamond-like carbon film, fixing lysozyme by adopting a crystal face regulated ZIF-8 crystal, and realizing dual inactivation of microorganisms by combining dielectric barrier discharge of a spiral plasma channel. The electrostatic adsorption HEPA filter paper adopts a BaTiO3-graphene quantum dot composite electret substrate, and a TiO2 / graphene heterojunction catalytic layer is decomposed by a Pt-Co bimetallic nanocluster and a photocatalysis-plasma-ozone-thermocatalysis quadruple oxidation system; and 0.1 mu m organic aerosol triggers graded reverse pulse cleaning based on differential pressure integration and a particle concentration threshold value, and the honeycomb flow guide structure drives a shutter and a gradient density sintering metal flow guide plate through piezoelectric ceramics to maintain laminar flow uniformity. According to the scheme, the limitation of a traditional technology is broken through, the purification efficiency of 0.1 micron particles is improved, and a high-stability solution is provided for a biopharmaceutical clean room.

The invention belongs to the field of biological medicines, and discloses an application of a protein polymer in preparation of a medicine for treating spinal cerebellar ataxia disease, a production process of the protein polymer comprises the following steps: S1) using ultraviolet irradiation to stimulate mesenchymal stem cells and culturing; and S2) splitting the mesenchymal stem cells, separating and purifying to obtain the protein polymer. An ultraviolet irradiation stress mode is adopted, mesenchymal stem cells are stimulated to express protein with a neural repair function, the protein polymer is obtained through further separation and purification, the cell gene expression pathway is regulated, the cell stress state is relieved, the cells are promoted to recover normal forms and functions, meanwhile, the preparation mode is relatively simple, and the preparation method is suitable for large-scale production. And quality and yield monitoring is facilitated, and the method can be adapted to diversified application modes.

The invention belongs to the field of biological pharmacy, and relates to an alpha-amylase inhibitory peptide and application thereof. Specifically, the provided unreported peptide fragment LDKFLWT can effectively inhibit the activity of alpha-amylase, and animal experiments prove that the newly designed polypeptide has the effects of reducing blood sugar, reducing blood fat, improving insulin resistance and the like through polypeptide intervention; compared with a traditional hypoglycemic drug, the alpha-amylase inhibitory peptide disclosed by the invention has remarkable safety.

The invention relates to the field of biological medicine preparation, and particularly provides liraglutide precursor peptide tandem recombinant fusion protein, polynucleotide, recombinant expression plasmid, engineered host cell and a method for preparing target polypeptide. The recombinant fusion protein is fusion peptide-target polypeptide-(linker peptide-target polypeptide) n from the N terminal to the C terminal, n is a positive integer from 4 to 6, the fusion peptide is SEQ ID NO.1, the target polypeptide is liraglutide precursor peptide, the linker peptide comprises a spacer peptide and a protease restriction enzyme cutting site, the spacer peptide is SEQ ID NO.2, the isoelectric point of the recombinant fusion protein is 4.6-4.7, and the average hydrophilic value is-0.780--0.765. The proportion of the target polypeptide in the recombinant fusion protein is high, use of solvents under extreme conditions is avoided in the production process, the enzyme digestion efficiency is high, and the product purity and yield are high.

The invention relates to the field of computational biology and bioinformatics, in particular to an RNA (Ribonucleic Acid) sequence screening and promoter function predicting and screening method based on machine learning, which comprises the following steps of: firstly, adopting a novel sequence algorithm based on a sliding window and a position weight matrix, and combining technologies such as k-mer frequency analysis and conservative motif recognition; candidate RNA sequences are efficiently identified from genomic sequences. Then, an integrated prediction model fusing deep learning and traditional machine learning is established, and multi-dimensional information such as sequence features, structural features, functional features and evolution features is extracted; and carrying out batch prediction on the candidate RNA sequences, outputting a function intensity score and providing credibility evaluation. And finally, screening an RNA sequence with an optimal prediction result based on a multi-objective optimization strategy, and designing an experimental verification scheme. According to the method, the prediction accuracy and the screening efficiency are improved, the experiment cost can be remarkably reduced, and an efficient promoter screening tool is provided for the fields of synthetic biology, gene therapy, biological pharmacy and the like.

This invention belongs to the field of biopharmaceuticals and provides a keratin YK93-8, its encoding nucleic acid molecule, an expression vector containing the nucleic acid molecule, a host cell containing the expression vector or whose genome integrates the nucleic acid molecule, as well as a preparation method and a pharmaceutical composition thereof. It also provides the application of the above-mentioned keratin YK93-8 and other products in the preparation of drugs for treating benign prostatic hyperplasia, lymphoma, melanoma, breast cancer, lung cancer, analgesia, lactation, uterine fibroids, coagulation, etc.

The invention relates to the field of biological pharmacy, and discloses a preparation method of an MPL adjuvant, which comprises the following steps: dissolving an MPL raw material in a buffer solution to obtain an MPL solution; adding a freeze-drying protective agent into the MPL solution to form a stable liquid system; carrying out pre-freezing treatment of cooling by stages on the obtained solution; freezing and drying the pre-freezing system under a temperature control condition to obtain freeze-dried powder; and sealing the freeze-dried powder in a treated packaging material to form a final product, the freeze-drying protective agent is prepared from trehalose, a polyethylene glycol-polylactic acid segmented copolymer (PEG-PLA) and L-methionine. A dynamic temperature regulation and control technology is adopted, the temperature of the shelf is adjusted in real time, the sample temperature is kept in a subcritical interval of-42 DEG C to-38 DEG C, the sublimation rate is ensured to be stable, lipid heat stress caused by too high temperature is avoided, and it is also prevented that the drying efficiency is affected by too low temperature.

The invention relates to the field of biological medicine preparation, and particularly provides canagliflozin precursor peptide tandem recombinant fusion protein, polynucleotide, recombinant expression plasmid, engineered host cell and a method for preparing target polypeptide. The recombinant fusion protein is a fusion peptide-target polypeptide-(linker peptide-target polypeptide) n from an N terminal to a C terminal, n is a positive integer of 4-6, the fusion peptide is SEQ ID NO.1 or SEQ ID NO.2, the target polypeptide is a canagliptin precursor peptide, the linker peptide comprises a spacer peptide and a protease restriction enzyme cutting site, the spacer peptide is SEQ ID NO.3, the isoelectric point of the recombinant fusion protein is 5.5-6.5, and the average hydrophilic value is-0.85--0.96. The invention creatively provides a method for preparing the canagliflozin precursor peptide by using a gene recombination technology, the proportion of the target polypeptide in the recombinant fusion protein is high, the use of a solvent under extreme conditions is avoided in the production process, the enzyme digestion efficiency is high, and the product purity and yield are high.

The present invention belongs to the field of biopharmaceuticals and specifically relates to a composition for detoxifying alcohol and preventing hangovers and its preparation method, comprising the following steps: 1) adding a portion of yeast extract to purified water to obtain solution A, adding curcumin to anhydrous ethanol to obtain solution B, and mixing solution A and solution B to obtain a mixed solution; 2) adjusting the pH of the mixed solution to 5-6; 3) placing the mixed solution in a -25°C cold trap and allowing it to stand for 16-32 hours until crystals precipitate; 4) filtering at 4°C to obtain a filter cake and a filtrate; 5) pulverizing the filter cake to obtain a crystalline powder; and 6) uniformly mixing the crystalline powder, another portion of yeast extract, dihydroquercetin, and excipients, and then tableting to obtain the composition for detoxifying alcohol and preventing hangovers. The present invention utilizes a complex formed by precipitating the yeast extract and curcumin cocrystals, which expands the application range of the composition and improves the solubility and bioavailability of curcumin.

The invention provides a lung stem cell peptide for treating pulmonary nodule as well as a preparation method and application thereof, and belongs to the technical field of biological pharmacy. The method comprises the following steps: performing induced differentiation on iPSC to obtain lung stem cells; lung stem cells are cultured and centrifuged, supernatant is collected, and a lung stem cell crude solution is obtained; mixing the lung stem cell crude liquid with protease, performing enzymolysis, centrifuging, concentrating, and performing spray drying to obtain the lung stem cell peptide for treating pulmonary nodule. By optimizing the composition of each culture medium, the iPSC is induced and differentiated into the lung stem cells, then the lung stem cell peptide is extracted and separated from the lung stem cells, and the extracted lung stem cell peptide migrates to the lung in a vein reinfusion mode, so that the generation of lung tumor nodules can be effectively inhibited, the number of the lung tumor nodules is greatly reduced, and the lung tumor nodules can be effectively inhibited. Toxic and side effects and adverse reactions are avoided.

As a series of viscosity-reducing and stabilizing formulations for high-concentration protein formulations, they are finely tuned to significantly reduce the viscosity of high-concentration biopharmaceuticals and increase their stability. Viscosity-reducing and stabilizing formulations can be used for high-concentration biopharmaceutical products and have significant potential to improve stability during manufacturing and storage, thereby increasing the feasibility of high-concentration biopharmaceutical products.

The invention relates to an SR-B1 targeted polypeptide compound and application thereof in preparation of antitumor drugs and immunotherapy sensitizers, and belongs to the technical field of biological drug manufacturing. In order to solve the problems that an existing PD-L1 inhibitor is single in action mechanism and immune system dysfunction is easily caused, the invention provides an SR-B1 targeted polypeptide compound which is composed of SR-B1 targeted polypeptide and Resiquimod. The SR-B1 targeting polypeptide comprises an SR-B1 targeting peptide fragment, a self-assembly peptide fragment and a hydrophobic molecule which are connected in sequence. The SR-B1 targeting polypeptide can recognize overexpressed SR-B1 in tumor cells, block cholesterol uptake, inhibit tumor progression and inhibit expression of PD-L1 at the same time. The polypeptide compound accurately delivers Resiquimod to a tumor site, anti-tumor immune response is activated, and sensitivity of tumor immunotherapy is greatly enhanced through combination of cholesterol metabolism regulation and immunotherapy.

The application discloses application of O-acyl-alpha-hydroxy acid compounds in weight loss and lipid reduction, and belongs to the fields of biological medicine manufacturing, biological medicine use and functional food development. The O-acyl-alpha-hydroxy acid compounds can inhibit weight growth of high-fat diet-induced obese model mice and reduce body fat. Compared with GLP-1 receptor weight loss drugs which achieve the effect of reducing weight by inhibiting appetite, the O-acyl-alpha-hydroxy acid compounds are not dependent on appetite inhibition, and can reduce side effects such as gastrointestinal discomfort and muscle loss caused by inhibiting appetite. When combined or sequentially administered with GLP-1 drugs, the O-acyl-alpha-hydroxy acid compounds can maintain or enhance the weight loss effect while improving the side effects caused by GLP-1, and can prevent the risk of significant weight rebound after stopping GLP-1 by maintaining body weight. The application provides a safe and effective new strategy for weight loss and lipid reduction.

Provided are poly(ethylene glycol)-polyoxazoline (PEOZ) copolymers. In some cases, the PEOZ polymer has a repeat unit of structure –CH2N(C(O)R)CH2CH2OCH2CH2–. The PEOZ copolymers can be used in a variety of applications, e.g., to increase the solubility of various compounds, such as drugs, dyes and biopharmaceuticals. Also provided are methods of making the PEOZ copolymers, which in some cases can generate monodisperse compositions of PEOZ copolymers.

The present application relates to the technical field of biopharmaceuticals, and in particular, polypeptides or derivatives thereof, pharmaceutically acceptable salts thereof based on artificial intelligence design and applications thereof are provided, wherein the amino acid sequence of the polypeptides is shown as SEQ ID NO:1.The polypeptides or derivatives thereof, pharmaceutically acceptable salts thereof can simultaneously bind to PD-1 and CTLA-4, can effectively block the binding between PD-1 and CTLA-4 and their ligands respectively, release the inhibition of immune checkpoint proteins PD-1 and CTLA-4 on immune cells, and significantly enhance the anti-tumor immune response of the body. The polypeptides or derivatives thereof, pharmaceutically acceptable salts thereof can be used for detecting PD-1 and / or CTLA-4, and can also be used for treating or preventing diseases related to PD-1 and / or CTLA-4.