204 results about "Hepatitis B" patented technology

This invention discloses a monoclonal antibody against human hepatitis B e antigen and its application, relating to the field of hepatitis B detection technology. In the heavy chain variable region of the monoclonal antibody, the amino acid sequences of the complementarity-determining regions (CDR1-3) are as shown in SEQ ID NO. 1-3 or have at least 95% homology with the sequences shown in SEQ ID NO. 1-3; in the light chain variable region, the amino acid sequences of the complementarity-determining regions (CDR1 and CDR3) are as shown in SEQ ID NO. 4 and 5 or have at least 95% homology with the sequences shown in SEQ ID NO. 4 and 5, and the amino acid sequence of the complementarity-determining region (CDR2) is FAS. The monoclonal antibody provided by this invention can effectively recognize natural hepatitis B e antigen, and the titer of the supernatant from B cell culture can reach 1:10000, making it fully applicable to the detection and research of human hepatitis B e antigen. The chemiluminescent reagent prepared using the monoclonal antibody described in this invention has advantages such as high specificity, strong anti-interference ability, high detection sensitivity, and good stability, with almost no missed detections, and can replace imported reagents.

The present disclosure related to compounds that can be useful as inhibitors of PD-1, PD-L1 or the PD-1 / PD-L1 interaction. Also disclosed herein are pharmaceutical compositions of that can include a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and uses of or methods of using a compound of Formula (I), or a pharmaceutically acceptable salt thereof, for the treatment of PD-L1 related diseases including but not limited to liver diseases, cancer, hepatocellular carcinoma, viral diseases, or hepatitis B.

The invention relates to the technical field of biological medicines, in particular to a vaccine for treating or preventing hepatitis B virus infection. The vaccine comprises a hepatitis B surface antigen and a composite adjuvant, wherein the composite adjuvant is prepared from CpG oligodeoxynucleotide and saponin QS-21, and the composite adjuvant is prepared from CpG oligodeoxynucleotide and saponin QS-21; the nucleotide sequence of the CpG oligodeoxynucleotide is as shown in SEQ ID NO. 1. According to the vaccine provided by the invention, an HBsAg antibody can be generated in a normal mouse body, and HBV in an HBV-carrier mouse can be effectively eliminated, so that the vaccine has the effect of treating or preventing hepatitis B virus infection. According to the vaccine provided by the invention, two adjuvants, namely CpG oligodeoxynucleotide and saponin QS-21, are adopted, so that the vaccine can be used for synergistically activating an immune effect, enhancing the activation of B cells and permanently transforming into plasma cells, and meanwhile, the vaccine can be used for resisting immune tolerance of T cells, realizing the removal of hepatitis B viruses and realizing functional cure of clinical hepatitis B treatment.

The invention belongs to the field of biological medicines, and particularly relates to an antigen-antibody compound for enhancing immune response of hepatitis B patients as well as a preparation method and application of the antigen-antibody compound. The antigen-antibody compound preparation prepared from the HBsAg and the anti-HBsAg monoclonal antibody is superior to an antigen-antibody compound preparation prepared from a polyclonal antibody in the aspect of continuously inducing the immune response of a chronic hepatitis B patient, and an antigen-antibody compound for inducing the immune response of the hepatitis B patient is developed for the first time; in the compound, the hepatitis B surface antigen is combined with the anti-HBsAg monoclonal antibody, and the compound formed by the hepatitis B surface antigen and the anti-HBsAg monoclonal antibody in a certain mass ratio can induce immune response of chronic hepatitis B patients and can also prevent and / or treat chronic hepatitis B.

Disclosed are antibodies to anti-hepatitis B surface antigen (HBsAg) (especially humanized antibodies), nucleic acid molecules encoding same, methods for preparing same, and pharmaceutical compositions containing same. The antibodies have higher affinity for HBsAg at neutral pH than at acidic pH, thereby significantly enhancing the virus clearance efficiency and prolonging the virus inhibition time. The antibodies and the pharmaceutical compositions can be used for preventing and / or treating HBV infections or diseases related to HBV infections (e.g., hepatitis B), for neutralizing the virulence of HBV in a subject (e.g., a human), for reducing the serum level of HBV DNA and / or HBsAg in the body of the subject, or for activating the humoral immune response of the subject (e.g., a chronic HBV infected or chronic hepatitis B patient) against HBV.

The present disclosure provides methods for treating HBV infection using combination therapies, and related kits and compositions for use. The components of the combination therapies include an inhibitor of HBV gene expression or an agent that reduces HBV antigenic load, and an anti-HBV antibody.

The invention provides a Mongolian medicine composition for treating hepatitis B and a preparation method of the Mongolian medicine composition. The composition is prepared from the following components in parts by weight: 75 to 85 parts of saffron, 75 to 85 parts of trogopterus dung, 65 to 75 parts of gardenia jasminoides, 45 to 55 parts of cortex phellodendri, 45 to 55 parts of dianthus chinensis, 55 to 65 parts of gypsum, 55 to 65 parts of scabiosa, 55 to 65 parts of calamine, 55 to 65 parts of caulis akebiae, 25 to 35 parts of rhizoma coptidis, 25 to 35 parts of fructus gardeniae, 25 to 35 parts of calomel, 25 to 35 parts of bunge corydalis herb, 45 to 55 parts of elecampane, 45 to 55 parts of rose and 55 to 65 parts of calculus bovis factitius. The Mongolian medicine composition for treating hepatitis B is prepared from multiple raw materials, meanwhile, the added coptis chinensis and rose flowers are treated through a specific extraction mode and a specific fermentation mode, and the prepared Mongolian medicine composition for treating hepatitis B has an excellent hepatitis B treatment effect.

The invention provides a polypeptide for activating cellular immunity in chronic hepatitis B and application of the polypeptide, and belongs to the technical field of biological medicine. A polypeptide library is designed and synthesized on the basis of a preS1 structural domain for coding HBV large HBsAg, a full-length core protein Core, a polymerase protein fragment rich in T cell epitopes and an mRNA-PreS1CPX holoantigen sequence (as shown in SEQ ID NO.1) of full-length X protein HBX, and peptide fragments capable of activating T cell immunity are screened by utilizing ELISPOT and flow cytometry. Experimental results show that the polypeptide sequences as shown in SEQ ID NO.2-15 can promote HBV antigen specific immune response by stimulating CD8 + T lymphocytes to secrete IFN-gamma, so that immune activation treatment of hepatitis B is realized.

The present application relates to derivatives of STOPS™ antiviral compounds having enhanced helicity, wherein the compounds are S-antigen transport inhibiting oligonucleotide polymers. This application further relates to processes for making the compounds and methods of using them to treat diseases and conditions. In some embodiments, the diseases and conditions are related to hepatitis B and / or hepatitis D.

2'-Fluoro-6'-methylene-carbocyclic adenosine (FMCA, 21) and its phosphoramidate prodrug (FMCAP, 31) have demonstrated potential anti-HBV activity against both adefovir- resistant as well as lamivudine-resistant double (rtL180M / rtM204V) mutant hepatitis B virus (HBV). In addition, in vitro, these molecules have reinstated a significant activity against lamivudine / entecavir triple mutants (L180M+S202G+M204V). This invention is directed to compounds, pharmaceuticals and methods of treating HBV infections, especially including infections caused by resistant and multiple resistant HBV. Pursuant to the present invention, a complete structure-activity relationship (SAR) of 2'-fluoro-6'-methylene-carbocyclic derived nucleos(t)ides has been evaluated and that analysis is presented herein. Pursuant to the present invention, the synthesis and antiviral evaluation of purine and pyrimidine-derived nucleosides have been reported against wild-type and various HBV mutants. Guanosine analog (FMCG, 25) demonstrated an EC50 value of 0.217μM and cytosine analog (FMCC, 41) expressed a potent EC50 value of 0.0025 μM compared to entecavir (EC50 = 0.0029) against wild-type HBV. Additionally, FMCC (41) maintains its antiviral potency against various HBV mutants. Furthermore, chiral pure FMCAP Sp (34) isomer demonstrated an EC50 value of 1.3 nM and was more potent against several HBV mutants than entecavir.

The application discloses a low-cost hepatitis B (HBV) virus nucleic acid rapid detection method based on a functionally modified paper base, and can realize rapid detection of HBV virus nucleic acid.The method comprises the following steps: (1) pre-amplifying HBV virus nucleic acid to obtain Texas red-labeled nucleic acid; (2) capturing and enriching the Texas red-labeled nucleic acid by using a functionally modified paper base; and (3) performing signal detection.The functionally modified paper base is modified with a fusion protein containing a TR512 polypeptide.The protein functionally modified paper base is simple in preparation, fast in nucleic acid detection time and low in detection cost.

The present application relates to the technical field of knowledge graph, in particular to a multi-task hepatitis B drug screening method and system based on knowledge graph assistance, comprising the following steps: based on hepatitis B virus genotype sequence data recorded over time, patient drug use records and drug sensitivity. In the present application, multi-dimensional dynamic time series data such as virus genotype sequence data, patient drug use records and drug sensitivity are integrated, the interaction events between entities are marked by time stamp, the dynamic characteristics such as virus variation track and drug efficacy change are embedded in the graph node attributes, so that the knowledge representation can reflect the time dependence in the real scene. Based on biological pathway annotation information and protein interaction data, the hyperedge connection multi-entity set is defined, the limitation of traditional knowledge graph which only supports binary relationship is expanded, the drug combination and multi-target synergistic mechanism are explicitly modeled, and the misjudgment of combination effect caused by the simplification of interaction relationship is avoided.

The present invention discloses an antibody-drug conjugate and a preparation method and application thereof, in particular, a conjugate of an anti-PD-L1 antibody and a TLR7 and / or TLR8 agonist and a pharmaceutical composition, preparation method and application thereof. The present invention obtains a modified anti-PD-L1 antibody with a mutant cysteine ​​by gene editing, which basically retains the structure of the original antibody and can be used for the construction of an antibody-drug conjugate. Through anti-tumor experiments, it was found that the obtained antibody-drug conjugate has better activity, such as strong anti-tumor activity, can significantly improve the survival rate of tumor-bearing animals, and has significantly reduced toxicity, less burden on the body of experimental animals, greatly reduces the minimum effective dose of small molecule drugs when used alone, expands its therapeutic window, and is expected to be used in the development of therapeutic drugs for various diseases (such as tumors, viral diseases such as hepatitis B, etc.), with good application prospects and value.

Provided are a combination comprising a drug for treating hepatitis B and an antiviral agent, and a use thereof. The drug for treating hepatitis B comprises a nucleic acid or nucleic acid combination (e.g., an mRNA combination) encoding an antigen of hepatitis B virus. The combined use of the drug for treating hepatitis B and the antiviral agent can significantly reduce the number of liver HBV Core positive cells in an infected subject, greatly improve the HBV-specific T cell response level in the subject, and shows no obvious rebound of HBsAg after drug withdrawal.

The invention discloses application of 5 beta-cholanic acid (5 beta-CA) in enhancement of NK cell functions and preparation of antiviral drugs. The NK cell function of a chronic hepatitis B (CHB) patient is depleted, it is found that the intracellular 5beta-CA level is reduced by screening differential metabolites of peripheral blood NK cells of the CHB patient, and the NK cell function of the CHB patient can be enhanced by exogenous supplementation of 5beta-CA; the function of NK cells of HBV persistently infected mice can be enhanced, and the level of virology indexes such as serum HBV related antigens and the like can be reduced. Specifically, the 5beta-CA enhances the NK cell function by activating a TGR5-cAMP-mTOR signal channel so as to play an anti-HBV role. The research finds that the improvement of the 5beta-CA level is expected to become a new thought for enhancing the NK cell function of a CHB patient, and a new technical means is provided for the treatment of CHB.

The present disclosure relates to compounds that can be useful as inhibitors of PD-1, PD-Ll or the PD-1 / PD-Ll interaction. Also disclosed herein are pharmaceutical compositions of that can include a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and uses of or methods of using a compound of Formula (I), or a pharmaceutically acceptable salt thereof, for the treatment of PD-L1 related diseases including, but not limited to, liver diseases, cancer (for example, hepatocellular carcinoma) and / or viral diseases, such as hepatitis B.

The invention discloses vidarabine monophosphate lipidosome freeze-dried powder injection and a preparation method and application thereof, and belongs to the technical field of medicine, and the lipidosome is composed of vidarabine monophosphate, phospholipid, cholesterol, pegylated phospholipid and a freeze-drying protective agent (such as trehalose). By optimizing a formula and a preparation process, the liposome disclosed by the invention has excellent placement stability and freeze-drying stability, and can still keep good encapsulation efficiency and particle size distribution after long-term storage. By introducing polyethylene glycol (PEG), the retention time of liposome in systemic circulation is remarkably prolonged, and passive targeting enrichment of liver and spleen is reduced, so that the toxicity of immune organs is reduced, and the accumulation of drugs at focus parts is facilitated. The liposome has an excellent slow release characteristic, can improve the antiviral ability and cell entry ability of drugs and reduce toxic and side effects, and is suitable for treating viral infectious diseases, such as hepatitis B, herpes and the like.

Disclosed are a class of drugs and combinations for treating hepatitis B, which specifically relate to a compound of formula (I) for treating hepatitis B, and combinations with other drugs for treating hepatitis B and administration methods, as well as uses of the compound and the drug combinations in the preparation of a drug for treating hepatitis B.

The application belongs to the technical field of medicine, and discloses application of SERPINE1 protein or a coding gene thereof as a new target for hepatitis B virus treatment. The application first discloses that SERPINE1 promotes autophagy flux by directly combining PIKfyve protein, thereby significantly inhibiting HBV replication and HBsAg expression. Based on this, the application establishes a multi-dimensional target verification platform, and first discovers that a natural compound, betulinic acid, is a high-affinity agonist (KD=1.46 µM) of SERPINE1. In-vivo and in-vitro experiments prove that betulinic acid can effectively reduce the levels of HBsAg and HBV DNA, and has good safety. In addition, betulinic acid and entecavir show a synergistic antiviral effect (CI<1). The application provides a new target and treatment strategy for realizing functional cure of hepatitis B.

According to the application of the E3 ligase UFL1 modified by the Especially in clearing the SHBs / HBsAg, the SHBs / HBsAg can be cleared by inhibiting the expression of the E3 ligase UFL1 modified by the Especially, so that the effect of treating HBV infection or HBV related diseases is achieved. The strategy of the invention is to directly target and remove the existing SHBs / HBsAg protein, and the action is more direct and rapid. According to the present invention, the inherent protein mass control system (proteasome pathway) of cells is utilized, such that the high biocompatibility and the low off-target toxicity can be provided; and the combination of the strategy and the existing antiviral drugs is expected to further significantly improve the functional cure rate of hepatitis B.

An endocyclic thiamidoamide-arylamide compound and a pharmaceutical composition comprising said compound are described, as well as the use of the same or of the pharmaceutical composition in the treatment of hepatitis B. In particular, a compound that can be used as an inhibitor of HBV replication and that has the structure shown in chemical formula (L), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, is described.

The invention relates to the technical field of bioinformatics, and relates to a construction method and application of a children chronic hepatitis B prediction model based on machine learning. The construction method comprises the following steps: S1, acquiring corresponding information and data of a research object, and preprocessing the acquired data; s2, screening and determining characteristic indexes of chronic hepatitis B of children; s3, constructing a prediction model; s4, evaluating and comparing the model of the children chronic hepatitis B prediction algorithm; and S5, generating a network calculator and calculating the prediction probability of the chronic hepatitis B of children. The constructed prediction model can predict the probability that children suffer from chronic hepatitis B, the network calculator generated according to the model can be applied to medical electronic cases, children suffering from chronic hepatitis B can be recognized more effectively clinically, effective early intervention can be achieved, and therefore potential hazards caused by chronic hepatitis B to children health are reduced.

The invention discloses an application of hsa-miR-17-3p in the prevention and / or treatment of hepatic fibrosis. Through clinical sample sequencing, it is found for the first time that expression of hsa-miR-17-3p (SEQ ID NO.1) in hepatitis B related hepatic fibrosis tissue is remarkably reduced. Furthermore, a dual luciferase reporter gene experiment proves that the hsa-miR-17-3p can be directly combined with a 3'untranslated region of the TGFBR1 in a targeting manner to inhibit mRNA and protein expression of the TGFBR1, so that activation of hepatic stellate cells is effectively inhibited, and secretion of I-type and III-type collagen is remarkably reduced. The discovery not only reveals a new mechanism of hepatic fibrosis, but also provides a theoretical basis and candidate molecules for developing novel targeted therapeutic drugs based on miRNA, and has important clinical application value and wide prospects in the aspects of early intervention, treatment and diagnosis of hepatic fibrosis.

The present disclosure related to compounds that can be useful as inhibitors of PD-1, PD-Ll or the PD-1 / PD-Ll interaction. Also disclosed herein are pharmaceutical compositions of that can include a compound as described herein, or a pharmaceutically acceptable salt thereof, and uses of or methods of using a compound as described herein, or a pharmaceutically acceptable salt thereof, for the treatment of PD-L1 related diseases including, but not limited to, liver diseases, cancer, hepatocellular carcinoma, viral diseases, or hepatitis B.

The application relates to the field of biological medicine, in particular to application of TDF in serum cholesterol regulation and a verification method. The application discloses that tenofovir disoproxil fumarate (TDF) can inhibit intestinal cholesterol absorption by specifically down-regulating the expression level of NPC1L1 protein in the intestinal tract, so as to reduce serum cholesterol. The regulation has tissue specificity, and TDF has no significant influence on the expression of key genes of liver cholesterol metabolism. The application also provides a method for verifying the regulation of TDF on serum cholesterol, which is evaluated by detecting blood lipid indexes and the gene and / or protein expression level of NPC1L1 in duodenal tissue. The application provides a treatment scheme with antiviral and cholesterol-lowering effects for patients with chronic hepatitis B combined with hypercholesterolemia, and provides a new idea for developing a lipid-lowering strategy targeting intestinal cholesterol absorption.

To identify novel nucleic acid molecules that can inhibit the expression of both PAPD5 and PAPD7 in vivo and in vitro.SOLUTION: The present invention provides a nucleic acid molecule that is complementary to both PAP-related domain-containing 5 (PAPD5) and PAP-related domain-containing 7 (PAPD7), and inhibits the expression of both PAPD5 and PAPD7 when using a single nucleic acid molecule. The present invention also provides PAPD5 and PAPD7 specific nucleic acid molecules used for the treatment and / or prevention of HBV infections, especially chronic HBV infections. Also included in the present invention are pharmaceutical compositions for use in the treatment and / or prevention of HBV infections.SELECTED DRAWING: Figure 3

The present application provides a compound of formula (I), or an optical isomer thereof, a pharmaceutically acceptable salt, a solvated form, or a prodrug. The compound may modulate NTCP function for the prevention and / or treatment of HBV / HDV and hepatitis virus-related diseases, bile acid-related cholestasis disorders, metabolic disorders, and / or liver diseases. Additionally, the present application relates to a pharmaceutical composition comprising such a compound and a method for modulating NTCP.

The application discloses a DNA methylation site marker for detecting hepatocellular carcinoma, a multiplex dPCR kit and a diagnostic model construction method. The DNA methylation site marker comprises cg02829688, cg13080379, cg03760839, cg10703826, cg12664119, cg16990168 and cg23371746 sites. The application designs a primer probe group for the above sites, constructs a multiplex dPCR kit of a double reaction system, realizes quantification of target DNA methylation sites, takes the methylation levels of the 7 sites as characteristic variables, adopts an XGBoost algorithm and / or an LR algorithm to construct a diagnostic model. Experimental verification shows that the model can effectively distinguish hepatocellular carcinoma patients from liver cirrhosis, chronic hepatitis B, metabolic dysfunction-related fatty liver disease patients and healthy individuals, especially shows good efficiency in auxiliary diagnosis of early hepatocellular carcinoma, and provides a new technical scheme for clinical diagnosis and screening of hepatocellular carcinoma.

The invention discloses a plasma near-infrared spectrum mode recognition method for detecting latent hepatitis B. The method comprises the following steps: S1, collecting spectral data of a plasma sample to be tested in a near-infrared band; s2, acquiring multi-repetition near infrared spectrum data of each sample, and constructing a spectrum data set; s3, grouping samples of a latent hepatitis B infection group and a normal control group in the spectral data set; s4, constructing an OBI-normal control spectrum discrimination model of the plasma sample based on a classifier primitive algorithm; s5, preprocessing parameters are optimized based on the discriminant performance of the classifier; s6, constructing an optimal wavelength combination; and S7, checking the optimal model. Compared with the prior art, the plasma near infrared spectrum mode recognition method for detecting the latent hepatitis B has the advantage that a solution can be provided for developing a small special blood analyzer for detecting latent hepatitis B infection.