1551results about "Antiinfectives" patented technology

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 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 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.

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 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.

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 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.

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 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 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.

The invention belongs to the field of medicines, discloses a polyamino cationic lipid containing a carbamate structure, a composition containing the polyamino cationic lipid and application, and particularly discloses a cationic lipid shown in a formula (I). The cationic lipid provided by the invention can be used for targeted delivery of nucleic acid, and can significantly enhance spleen targeting of nucleic acid drugs while reducing liver enrichment.

Disclosures herein are directed to methods and compositions for predicting high- and low-risk liver disease in patients. Based on the results achieved from the methods and compositions disclosed herein, liver disease patients can be classified into a prognostic risk group, which enables early diagnosis and prevention of HCC and other lethal complications. Methods and compositions disclosed herein substantially improve the poor prognosis of subjects having or at risk for one or more liver diseases.

To provide immunotherapy that prevents or minimizes the failure of immunotherapy treatment due to the emergence of antigen-loss escape mutations in cancer cells, etc. [Solution] A bispecific chimeric antigen receptor comprising (a) an antigen-specific target-directed region containing an antigen-specific single-chain Fv(scFv) fragment that binds to at least two different antigens, (b) an extracellular spacer domain, (c) a transmembrane domain, (d) at least one costimulatory domain, and (e) an intracellular signaling domain, which is to be co-expressed with a therapeutic regulatory substance such as truncated epidermal growth factor receptor (EGFRt).

The application relates to the field of biological medicine, and particularly relates to application of animal bifidobacterium lactis in a medicine for preventing and treating multiple organ injury caused by sepsis. The animal bifidobacterium lactis is used to prevent and treat sepsis and multiple organ injury, and is integrated with anti-inflammation, antioxidation, intestinal barrier repair and immune regulation, can effectively relieve the whole-body inflammation storm, can synchronously protect multiple organs such as lungs, livers and kidneys, can curb the progress of multiple organ dysfunction syndrome, and has more comprehensive and more significant curative effect.

Provided in the present invention are an anti-TLR7 antibody or an antigen-binding fragment thereof, and a pharmaceutical composition thereof. The antibody or the antigen-binding fragment thereof can specifically bind to a human or simian TLR7 antigen and does not bind to murine TLR7, exhibits significant TLR7 antigen-binding activity, and can effectively inhibit various inflammatory cytokines produced upon TLR7 activation. The anti-TLR7 antibody or the antigen-binding fragment thereof can be used, either as a monotherapy or in combination with other drugs, for treating and / or preventing diseases pathologically associated with the TLR7 target, including immune inflammation-related diseases, allergic diseases, infectious diseases, cancers, etc.

Provided is a microorganism characterized in that: it can be used as probiotic for animals such as pigs, it belongs to the genus clostridium, and in that it has the ability to produce isoallolithocholic acid in the presence of bile acid.

The present invention relates to the field of vaccines, and in particular to a novel adjuvant polypeptide sequence and a use thereof. The adjuvant polypeptide sequence provided by the present invention comprises amino acid sequences of tetanus toxoid epitopes P2 and P16 and further comprises amino acid sequences of P30 and / or PX. The adjuvant polypeptide sequence aims to expand the coverage population of immune responses by increasing epitope diversity. In addition, the present invention uses an LNP (lipid nanoparticle) delivery system to introduce an mRNA encoding an adjuvant polypeptide and an initial antigen protein into a human body, thereby improving the immunostimulatory ability of the initial antigen. The adjuvant polypeptide sequence provided by the present invention and the initial antigen sequence are preferably fused, thereby simplifying the composition of mRNA in a nucleic acid vaccine and reducing the complexity of vaccine preparation.

The present disclosure relates to anti-CitH3 (citrullinated histone H3) antibodies, antigen-binding fragments, and uses thereof.

The present disclosure provides thymic cells, thymic organoids, and animal models comprising such thymic cells and thymic organoids. It also provides methods for inducing differentiation of pluripotent stem cells into definitive endoderm (DE), anterior foregut endoderm (AFE), ventral pharyngeal endoderm (VPE), thymic epithelial progenitor (TEP) cells, thymic epithelial cells (TECs) and thymic organoids in vitro and in vivo.

The present disclosure provides a formulation of an IL-12-albumin binding domain (ABD) fusion protein comprising a fusion protein of about 10 μg / mL to about 50 μg / mL, about 25 mM to about 100 mM alanine, about 100 mM to about 400 mM trehalose, about 10 mM to about 50 mM glycylglycine, about 0.01% to about 0.04% polysorbate 20 (v / v), and about 5 μM to about 20 μM diethylenetriaminepentaacetic acid (DTPA), and the formulation has a pH of about 6.8 to about 8.0. Such a formulation may be useful for treating and / or preventing an IL-12 related disease or disorder in a subject in need of treatment of an IL-12 related disease or disorder.

An engineered trophoblast that expresses a cell surface molecule that specifically recognizes NKp46, the cell surface molecule comprising at least an antibody targeting NKp46 and a transmembrane domain. The invention discloses a cell culture medium and a method for amplifying NK cells. Compared with unengineered trophoblasts, the engineered trophoblasts are used for activating NK cells, and the amplification capacity of the NK cells and the killing activity of tumor cells can be enhanced.

The present application relates to a kind of drug composition containing STING agonist and WIP1 inhibitor and its liposome and application.The composition can be co-encapsulated in liposome with STING agonist and WIP1 inhibitor, form stable drug delivery system.The liposome can promote efficient endocytosis of cell, and release two active ingredients in cytoplasm synchronously, block the negative feedback mechanism of STING signal path by WIP1 inhibitor, enhance and prolong the activation level of STING path, to synergistically inhibit tumor growth.Based on the mechanism, the drug composition of the present application can be used for preparing the drug for treating diseases related to STING path (such as tumor).

The present invention provides novel methods for reducing the serine protease and / or serine protease zymogen content of a plasma-derived protein composition. Also provided are methods for manufacturing plasma-derived protein compositions having reduced serine protease and / or serine protease zymogen content. Among yet other aspects, the present invention provides aqueous and lyophilized compositions of plasma-derived proteins having reduced serine protease and / or serine protease zymogen content. Yet other aspects include methods for treating, managing, and / or preventing a disease comprising the administration of a plasma-derived protein composition having a reduced serine protease or serine protease zymogen content.

The invention provides a modified phosphoramidate intemucleotide linkage, referred to herein as a fiuorosulfonyl phosphoramidate (fsP) internucleotide linkage, wherein the fsP intemucleotide linkage has the structure of formula (I) modified oligonucleotides comprising at least one tsP intemucleotide linkage, and methods of using the modified oligonucleotides comprising at least one fsP internucleotide linkage.

The present invention is related to new compounds useful in the manufacture of a medicament for preventing or treating malaria, pharmaceutical compositions, methods of preparation and uses thereof.