2464results about "Antiinfectives" patented technology

Disclosed herein are an engineered immune cell with CD7 gene knock-out and use thereof. According to the present invention, an sgRNA specifically targeting CD7 gene is designed and synthesized, which can accurately target CD7 gene to achieve gene knock-out with high knock-out efficiency. The provided sgRNA can be used for preparing a CD7-targeting engineered immune cell, and can be further used for preparing a CD7-targeting universal CAR-T cell

The invention belongs to the technical field of polypeptides and biological medicines, and particularly relates to a WK7 series antibacterial peptide and application thereof in the aspects of resisting bacteria and preventing and treating diabetic foot, pneumonia and septicemia. According to the invention, a linear peptide WK7-line with an amino acid sequence of WKRWKRW is used as a minimum active unit, and modification is carried out to form a plurality of linear modified peptides; meanwhile, a cyclic peptide WK7-cyl is formed on the basis of the linear peptide WK7-line through cyclization, and the cyclic peptide WK7-cyl is further modified to form an annular modified peptide. The linear peptide WK7-line, the linear modified peptide, the cyclic peptide WK7-cyl and the cyclic modified peptide jointly form the WK7-series antibacterial peptide, and the WK7-series antibacterial peptide is artificially synthesized polypeptide, is small in molecular weight, easy to synthesize, free of cytotoxicity, almost free of hemolysis risk, high in sterilization speed and broad-spectrum antibacterial property and can be used for preparing the antibacterial peptide. The traditional Chinese medicine composition has a certain effect on prevention and treatment of diabetic foot ulcer, pneumonia and septicemia.

The invention discloses a macrophage-targeting inhalable nano material, a preparation method thereof and application of the inhalable nano material in treatment of sepsis myocarditis, and belongs to the technical field of medicines. The nano-material is a nano-liposome, the nano-liposome comprises a mannose modified nano-liposome microsphere, and the mannose modified nano-liposome microsphere comprises a liposome skeleton shell layer, a drug and a targeting layer; the liposome skeleton shell layer comprises soybean lecithin and cholesterol; the medicine comprises quercetin and TPPU (Thermoplastic Polyurethane); and the targeting layer is formed by connecting mannose modified DSPE-PEG2000 to the outer surface of the liposome skeleton shell layer. The nano material can accurately target macrophages at a cardiac inflammation part, has a multi-target-point synergistic effect, is more convenient and faster in administration, remarkably improves the safety and comprehensively improves the treatment effect.

The invention belongs to the field of biological medicines, and relates to a drug-loaded nano-vesicle as well as a preparation method and application thereof. The drug-loaded nano-vesicle comprises a vesicle core and a drug-loaded nano-vesicle, wherein the vesicle core comprises siRNA (small interfering Ribonucleic Acid) capable of specifically targeting and silencing an NR1D1 gene; the vesicle membrane is formed by fusing an erythrocyte membrane, a macrophage membrane, cardiolipin, cholesterol and lecithin. The drug-loaded nano-vesicle can specifically target macrophages in a sepsis immunosuppression stage, has an intracellular response release function, recovers BMAL1 and IGF2BP2-ATP6V1B2 / ATP6V0c axis functions by inhibiting NR1D1 expression, reconstructs a macrophage phagocytosis function and lysosome-dependent bacterium removal capability, and can be used for preparing a drug-loaded nano-vesicle with a specific targeting function. The survival rate of sepsis immunosuppression model animals is obviously improved; and the bacterial load is reduced. Compared with a traditional electroporation method, the preparation method disclosed by the invention has the advantage that the encapsulation efficiency of siRNA is remarkably improved.

The present invention relates to compounds of formula (I) and salts, stereoisomers, tautomers or N-oxides thereof that are useful as modulators of STING (Stimulator of Interferon Genes). The present invention further relates to the compounds of formula (I) for use as a medicament and to a pharmaceutical composition comprising said compounds.

The invention discloses a cationic lipid compound, a lipid carrier containing the same and application, and belongs to the technical field of gene therapy. The cationic lipid compound disclosed by the invention has a structure as shown in a formula I, or an isomer, a pharmaceutically acceptable salt and a prodrug thereof. The lipid nanoparticles have the advantages of stable nanostructure, uniform size distribution, good biological biocompatibility, high in-vivo and in-vitro mRNA delivery efficiency, selective organ targeting and the like. The cationic lipid reaction operation is simple, the raw materials are cheap and easy to obtain, and the cationic lipid has high safety, is beneficial to industrial production and quality control, and has a good application prospect.

The invention relates to the technical field of biological medicines, in particular to Hangzhou white chrysanthemum-derived exosome-like nano-vesicles as well as a preparation method and application thereof. Chrysanthemum morifolium ramat nano-vesicles are prepared from compositae plants through a high-speed centrifugation method, the average particle size of the nano-vesicles is 68 nm, and the Zeta potential is-19.50 + / -1.10 mV. The nano vesicles can effectively protect nerve cells and improve anxiety behaviors and cognitive impairment of SAE mice. The compound has a good application prospect in preparation of medicines for treating neuroinflammation and SAE.

The invention belongs to the field of biological medicine, and relates to an application of an NR1D1 inhibitor in preparation of a medicine for treating sepsis, the NR1D1 inhibitor comprises siRNA capable of specifically silencing an NR1D1 gene in a targeted manner, and can up-regulate BMAL1 and recover IGF2BP2-ATP6V1B2 / ATP6V0c axis, so that sepsis immunosuppression and secondary infection defense are remarkably improved.

As described herein are polypeptides and antibodies having an Fc region and an antigen binding region where the Fc region has an Fc-Fc-enhancing mutation and a C1q binding-enhancing mutation providing for polypeptides or antibodies with increased CDC activity and / or agonistic activity.

The invention relates to the field of biological medicine, and provides an application of a dihydroorotate dehydrogenase inhibitor in preparation of megakaryocytes, and the dihydroorotate dehydrogenase inhibitor is a compound shown as a formula I, a formula II or a formula III, or a pharmaceutically acceptable salt of the compound. According to the technical scheme, the dihydroorotate dehydrogenase inhibitor can promote hematopoietic stem / progenitor cells to differentiate into megakaryocytes and platelets, the platelet generation amount is increased by about 2 times, and a promising strategy is provided for in-vivo and in-vitro megakaryocyte and platelet generation.

The invention provides a compound or an N-oxide, a solvate, a pharmaceutically acceptable salt or a stereoisomer thereof, and also provides a composition containing the compound and application of the compound and the composition to delivery of a therapeutic agent or a prophylactic agent. According to the invention, the types of cationic lipid compounds are enriched, and more choices are provided for effective delivery of nucleic acid drugs, gene vaccines, small molecule drugs, polypeptides or protein drugs. After the lipid nanoparticles are formed with other lipid components, mRNA or drug molecules can be effectively delivered into cells to exert biological functions.

The present invention relates to antibodies, and fragments thereof, that bind and inhibit CD73. The invention also relates to cells producing such compounds; methods of making such compounds, and antibodies, fragments, variants, and derivatives thereof; pharmaceutical compositions comprising the same; methods of using the compounds to diagnose, treat or prevent diseases, e.g., cancer.

Disclosed are Hematopoietic Progenitor Kinase 1 (HPK1) degradation / disruption compounds including a HPK1 ligand, a degradation / disruption tag and a linker, and methods for use of such compounds in the treatment of HPK1-mediated diseases.

The present invention relates to a novel lipid compound for tissue-specific delivery, and a lipid nano-particle (LNP) composition comprising the same, the lipid nano-particle comprising a modified lipid compound as a component, according to the present invention, internal active substances are selectively delivered into cells of specific tissues such as lymph nodes, spleen, retina, cancer, brain, liver and the like in vivo, thereby preventing side effects and safely exhibiting a desired level of effect. The tissue-specific non-viral LNP delivery vectors can be effectively used for prevention of infectious diseases and treatment of rare and refractory (hereditary) diseases (diseases which are effectively and selectively delivered to in-vivo targeted sites, such as macular degeneration, diabetic retinal degeneration, hereditary retinal degeneration, cancer, cerebral diseases, liver diseases and the like).

The present application disclosed a compound of formula (I) and a salt and a stereoisomer thereof, wherein each variable is as defined in the specification. The present application also disclosed a nanoparticle composition comprising the compound or a salt or a stereoisomer thereof, and the use of the nanoparticle composition for delivering active agents.

The invention provides an antibody drug conjugate containing a functional small molecule side chain. The antibody drug conjugate is used for enhancing the targeted therapeutic effect of cancers and refractory diseases. The invention also relates to a preparation method of the conjugate, a pharmaceutical composition and a method for treating refractory diseases.

Several embodiments disclosed herein relate to methods and compositions for enhanced expansion of NK cells in culture, through the repeated co-culturing of NK cells with feeder cells and the selective use of stimulatory interleukins. In several embodiments, the methods utilize one or more soluble interleukins as culture media supplements at one or more time points during expansion of the NK cell, or other immune cell, which results in a highly expanded and highly cytotoxic population of cells, for use in, for example allogeneic cellular immunotherapy.

The present disclosure features, among other things, compounds and related compositions that modulate nucleic acid splicing, eg, pre-mRNA splicing, and methods of their use.

The present invention relates to an antibody-drug conjugate containing two or more functional small molecules for enhancement of targeted treatment of cancers and refractory diseases. The invention also relates to preparation of such conjugate, pharmaceutical compositions, and methods in treatment of cancers and refractory diseases.

The present invention relates to an isolated cellular targeted delivery system comprising a CD45+ leukocyte cell comprising within said cell a complex of one or more iron binding proteins and / or a label as well as methods for producing such isolated cellular targeted delivery system and uses of such system for therapy diagnosis and in particular for diagnosis of cancer, particularly metastatic cancer, in particular for therapy of cancer.

Compositions of particles having at least 95% by weight of cisplatin and a specific surface area (SSA) of at least 3.5 m2 / g. methods for their use. and methods for their production are provided.

Provided herein is a preparation of a stable drug conjugate containing one or two opened ring structures of thiosuccinimides linked to an antibody or an antibody-like protein for enhancement of targeted treatment of cancers and refractory diseases. In particular, provided herein are preparation of such conjugate homogenously, and its pharmaceutical compositions, as well methods in treatment of refractory diseases.

The invention relates to the technical field of traditional Chinese medicine preparations, in particular to a traditional Chinese medicine compound preparation for preventing and treating sepsis based on intestinal treatment and gasification regulation and a preparation method and application of the traditional Chinese medicine compound preparation. The composition is prepared from the following medicinal materials in parts by weight: 3 to 10 parts of rheum officinale, 5 to 10 parts of fructus aurantii, 5 to 10 parts of radix aucklandiae, 10 to 15 parts of fructus gardeniae, 10 to 15 parts of dandelion, 10 to 15 parts of fructus forsythiae, 10 to 15 parts of herba artemisiae scopariae, 10 to 15 parts of rhizoma atractylodis, 10 to 15 parts of poria cocos, 10 to 15 parts of radix paeoniae rubra, 10 to 15 parts of radix salviae miltiorrhizae, 15 to 20 parts of astragalus membranaceus, 10 to 15 parts of rhizoma anemarrhenae, 10 to 15 parts of fructus cannabis, 10 to 15 parts of semen pruni and 3 to 6 parts of raw liquorice. The traditional Chinese medicine compound provided by the invention considers the treatment rules of relaxing bowels, purging heat, promoting qi circulation, removing stagnation, detoxifying, dispersing blood stasis, reinforcing qi, nourishing yin and the like, and also considers the effects of relaxing bowels, regulating qi and supporting healthy qi, various diseases of sepsis patients can be remarkably improved through the synergistic effect of the medicines in the formula, and the traditional Chinese medicine compound especially has an obvious curative effect on gastrointestinal dysfunction. A novel traditional Chinese medicine treatment thought is provided for clinical treatment of sepsis diseases.

An isolated cell having a central memory T-lymphocyte (Tcm) phenotype, the cell being tolerance-inducing cell and capable of homing to the lymph nodes following transplantation, the cell being transduced to express a cell surface receptor comprising a T cell receptor signaling module is described. Methods of generating same and using same are also described.

The invention discloses a medicine composition for inducing fibroblasts to be reprogrammed into pericyte-like cells (PCLCs) through a chemical small molecule combination, and the medicine composition is used for treating sepsis. According to the invention, a chemical reprogramming strategy without genetic modification is adopted, an endogenous signal channel is activated through a time sequence, and fibroblasts from somatic cells are efficiently converted into PCLCs with high expression of genes such as EMILIN3, LAMC3, GDF10, AHR, CD109, AHR, NQO1, QPRT and the like. When applied to treatment of sepsis, the medicine composition can improve pathological symptoms and reduce death rate by synergistically exerting anti-inflammatory, anti-oxidation, immune regulation and tissue barrier protection effects. The invention provides a novel safe treatment strategy based on non-genetically modified cells for sepsis.

The present disclosure relates to a conjugate comprising a STING agonist, linker and antibody or antigen-binding fragment thereof, and uses thereof for the treatment of diseases.

The invention discloses a gamma delta T cell efficient amplification method and application, and belongs to the technical field of cell biology. The amplification method comprises the following steps: separating PBMC (peripheral blood mononuclear cells) by adopting a density gradient centrifugation method, carrying out initial culture through a polylysine coated container, carrying out three-stage dynamic stimulation, combining with an X-VIVO 15 culture medium of 5-8% autoserum, and finally carrying out anti-gamma delta TCR magnetic bead separation to obtain high-purity cells. Through collaborative optimization of stepped factor combination, staged container coating and a low-serum system, the amplification multiple of the gamma delta T cells reaches 150-180 times, the purity is larger than or equal to 90% after purification, the cytotoxicity and the survival ability are remarkably improved, the gamma delta T cells can be efficiently used for immunotherapy of tumors and infectious diseases, and stable technical support is provided for clinical transformation of the gamma delta T cells.

A novel, scalable synthetic method for preparing endokinin-like quinolone compounds of formula (I), wherein R is H, Cl, or F, preferably F, and R is C1-C2 alkyl, preferably C1 alkyl, comprising the process for preparing a compound of formula 4, wherein R is C1-C2 alkyl, preferably C1 alkyl. [Formula 1] TIFF2025538726000078.tif56148

The invention discloses a thiazole compound and medical application thereof, the structure of the thiazole compound is shown as a formula I. The compound shown as the formula I is a potent STING inhibitor and has good pharmacokinetic properties, and the compound shown as the formula I or pharmaceutically acceptable salt thereof can be used for preparing drugs for preventing or treating STING-mediated diseases.

The invention discloses a culture method for improving proliferation and differentiation capacity of NK (Natural Killer) cells based on angelica sinensis-astragalus membranaceus exosomes, which comprises the following steps: firstly extracting exosomes in angelica sinensis and astragalus membranaceus, then adding the exosomes into an NK cell culture system according to a specific concentration, and regulating and controlling an NK cell signal channel by virtue of active ingredients carried by the exosomes so as to improve the proliferation and differentiation capacity of the NK cells. Therefore, the proliferation rate and differentiation maturity of the NK cells are remarkably improved. Experimental results show that compared with a traditional culture method, the proliferation multiple of the NK cells cultured through the method is increased by 28.99%-33.69%, the proportion of differentiated mature cells is increased by 15.91%-28.30%, and the cell killing activity is not remarkably reduced. The method can be widely applied to the field of immune cell treatment, provides a high-quality NK cell source for clinic, effectively solves the problems of slow cell proliferation rate, low differentiation maturity, easy activity reduction after large-scale culture and the like in traditional NK cell in-vitro culture, and has important clinical application value and industrialization prospect.