140 results about "Chronic hepatitis" patented technology

The invention discloses an application of a combination of entecavir, an ASO drug, an mRNA therapeutic vaccine and / or interferon in preparation of drugs for treating chronic hepatitis B. Entecavir and interferon have an antiviral effect, the ASO drug reduces hepatitis B surface antigen titer, and the mRNA therapeutic vaccine is high in immunization speed, so that the entecavir, ASO drug, mRNA therapeutic vaccine and / or interferon combination can inhibit virus replication, and can be used for treating chronic hepatitis B. The composition strikes hepatitis B virus from multiple angles and multiple levels, achieves a good, lasting and non-rebound antiviral effect, and can cure hepatitis B to a certain extent.

The invention provides a construction method and system of a chronic hepatitis B liver tissue inflammation grading prediction model and application. The construction method of the chronic hepatitis B liver tissue inflammation grading prediction model comprises the following steps: S1, screening out a plurality of patients which are diagnosed as chronic hepatitis B through liver tissue biopsy pathology and have clear liver tissue inflammation grading according to inclusion and exclusion standards, and collecting clinical data and serum samples of the patients; s2, performing serum protein N-carbohydrate chain fingerprint spectrum difference analysis on the serum samples of the patients with different ALT levels by adopting an N-carbohydrate fingerprint spectrum technology; s3, on the basis of conventional biochemical indexes and / or N-sugar markers, constructing liver tissue inflammation grading evaluation models under different ALT levels by adopting a binary logistic regression analysis method; and S4, respectively evaluating and selecting the model with the optimal efficiency as a chronic hepatitis B liver tissue inflammation grading prediction model. The chronic hepatitis B liver tissue inflammation grading method can be used for quickly, accurately and noninvasively grading the chronic hepatitis B liver tissue inflammation.

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 invention relates to an HBV infection degree prediction formula and a determination method thereof, and relates to the field of biomedicine. The invention relates to an HBV (Hepatitis B Virus) infection degree prediction formula, which is characterized in that the HBV infection degree prediction formula comprises # imgabs0 #. According to the method, after detection data of healthy people, chronic hepatitis B patients, liver cirrhosis patients and liver cancer patients are collected to obtain multi-dimensional mitochondrial indexes, six strong correlation difference indexes are screened through difference analysis and random forest analysis, a principal component calculation formula is obtained through further PCA dimension reduction analysis, and then an MOPLS (PCA) value is obtained; calculating a calculation formula of the MOPLS value according to the calculated MOPLS (PCA) value, and determining an optimal calculation formula of the MOPLS value through ROC analysis; the method aims at simplifying the calculation process of the MOPLS (PCA) value and obtaining the optimal MOPLS value calculation formula through screening.

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 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 application relates to a detection method of anti-preS1 antibody, an anti-preS1 antibody detection kit and application, the application carries out multi-sequence comparison and conservation analysis on preS1 sequences of different genotypes (A, B, C, D and CD mixed type) of HBV, takes type A (AB697487.1), type C (FJ032351.1) and type D (LC519808.1) as reference sequences, based on the sequence consistency standard of 85% of full length and 90% of the key region of functional antibody binding, a highly conservative preS1 full-length antigen sequence is systematically screened out in natural variation, the sequence can cover antigen variation of A-D type HBV, and the sequence is taken as a coating antigen to establish an indirect ELISA detection system, a good linear relationship is presented in the range of 4.88-625 ng / mL, and the Cut-off value is 33.6 ng / mL; clinical verification shows that the method can effectively distinguish chronic hepatitis B patients from healthy control groups, compared with detection methods based on partial fragments or overlapping short fragments, the false negative rate can be significantly reduced, and the method is suitable for HBV infection immune state evaluation, anti-virus curative effect monitoring and prognosis analysis.

The present invention relates to anti-HBsAg antibodies, antibody fragments, and their uses for the prevention and treatment of hepatitis D virus infection and associated diseases. A method of neutralizing a hepatitis D virus infection comprising administering via injection or infusion to a patient in need an effective amount of the antibody, wherein said antibody or antigen binding fragment, is provided.

The liver-protecting health-care tea comprises 20 parts of Pu'er tea, 10 parts of centella asiatica leaves, 10 parts of nutgall, 20 parts of dried longan, 10 parts of chrysanthemum, 10 parts of penthorum chinense pursh, 10 parts of dendrobe and 10 parts of Chinese dates. The tea is prepared into tea bags, and each bag is 30g. The traditional Chinese medicine composition is simple in process and low in cost, has a remarkable treatment effect on acute and chronic hepatitis, cholestatic hepatitis, alcoholic hepatitis, fatty liver and the like, and also has the effects of clearing fat, losing weight, inducing diuresis, promoting alcohol metabolism, protecting liver after drinking and the like; the liver health tea bag provided by the invention is rich in nutritional ingredients, very convenient to drink for a long time, high in appearance grade, convenient to use, strong, mellow, sweet and fragrant in taste and worthy of being well developed and utilized, and the products are placed in the tea bag in proportion.

Described are methods for treating alpha-1 antitrypsin deficiency (AATD) in a human patient in need of treatment, using pharmaceutical compositions that include AAT RNAi agents. The pharmaceutical compositions disclosed herein that include AAT RNAi agents, when administered to a human patient in need thereof, treat liver diseases associated with AAT deficiency such as chronic hepatitis, cirrhosis, increased risk of hepatocellular carcinoma, transaminitis, cholestasis, fibrosis, fulminant hepatic failure, and other liver-related diseases.

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 relates to a traditional Chinese medicine composition for treating liver diseases such as chronic hepatitis, liver cirrhosis, liver cancer and the like, a preparation method and application in preparation of medicines for treating liver diseases. The traditional Chinese medicine composition is prepared into pills or granules, powder, capsules and the like from 0.15-36 parts by weight of sliced white aconite and 0.3-6 parts by weight of ligusticum wallichii according to the conventional preparation process of Chinese patent medicines. The effective rates of the traditional Chinese medicine composition for treating chronic hepatitis, cirrhosis and liver cancer respectively reach 87%, 75% and 70% or above. The traditional Chinese medicine composition has the characteristics of simple medicine composition, prominent curative effect, low production cost, simple and mature preparation process and the like.

Provided herein are methods for administering a hepatitis B virus surface antigen (HBsAg) to subjects with chronic hepatitis B to distinguish between responder subjects who respond to the HBsAg administration with an increase in an HBV antibody levels and non-responder subjects, and treating chronic hepatitis B in the responder subjects with an HBV therapy. Methods of excluding non-responder subjects from a clinical study are also provided.

The invention provides preparation of a novel mRNA vaccine and application of the novel mRNA vaccine in a medicine composition for treating hepatitis B virus diseases. Specifically, the invention provides a chronic hepatitis B infection therapeutic mRNA vaccine, which comprises mRNA for coding a large protein (L protein) region of hepatitis B virus surface antigen, and simultaneously comprises two mRNA for respectively coding a middle protein (M protein) region of hepatitis B virus surface antigen and a small protein (S protein) region, or comprises mRNA for coding the small protein (S protein) region. The mRNA therapeutic vaccine provided by the invention can break the immune tolerance state in chronic hepatitis B infection, and has the potential of functionally curing chronic hepatitis B infection clinically.

The invention relates to a compound and application thereof in treatment of chronic hepatitis B, hepatic fibrosis and liver cancer. Specifically provided are compounds represented by formula O, or stereoisomers, prodrugs, pharmaceutically acceptable salts or pharmaceutically acceptable solvates thereof, # imgabs0 # of the compounds, or stereoisomers, prodrugs, pharmaceutically acceptable salts or pharmaceutically acceptable solvates thereof

The present invention relates to a dry granulation process for preparing a solid pharmaceutical composition comprising Tenofovir alafenamide or pharmaceutically acceptable salts thereof, and one or more pharmaceutically acceptable excipients, and its use in the treatment of for the treatment of chronic hepatitis B (CHB). The pharmaceutical composition comprises at least a disintegrant as pharmaceutical acceptable excipient for increasing the stability of the Tenofovir alafenamide and tablet coating material comprising hypromellose and hydroxypropyl cellulose, thus surprisingly improved impurity values and also improved dissolution profile has been obtained.

The invention discloses an application of an epoxidase type II inhibitor, the application is the application in preparation of drugs for treating liver injury, hepatitis, hepatic fibrosis, or liver function decline or complications thereof, and the application discovers that the existing COX-2 selective inhibitors such as celecoxib and the like and a novel efficient COX-2 selective inhibitor 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, the 2, 8-deuterated dimethyl-2-(trifluoromethyl)-2H-benzopyran-3-carboxylic acid disclosed by the invention has the effects of remarkably relieving liver injury, reducing necrosis focus and inflammatory cell infiltration of liver cells and resisting cholestatic hepatic fibrosis; in addition, hepatocyte lipid accumulation and ballooning induced by high fat diet can be reduced, and the progress of lipid hepatitis is remarkably inhibited; it is found for the first time that the traditional Chinese medicine composition can significantly reduce the concentration of serum bilirubin and play a role in relieving hyperbilirubinemia caused by liver injury or liver insufficiency; the traditional Chinese medicine composition can be used for treating neonatal jaundice, congenital bile duct atresia, cholestatic cirrhosis, acute toxic hepatic failure, bilirubin increase caused by acute attack of chronic hepatitis, chronic hepatic failure or hepatic encephalopathy and the like; therefore, the method has obvious economic benefit and clinical application value.

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.

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 present invention relates to a pharmaceutical composition, a pharmaceutical combination preparation, and a combination preparation kit, each of which contains an oral antiviral drug as an active ingredient and a therapeutic vaccine containing a lipopeptide and a poly (I: C) adjuvant. When the pharmaceutical composition, the pharmaceutical combination preparation, and the combination preparation kit are administered / used in hepatitis B patients, a significant synergistic effect occurs in the therapeutic index of chronic hepatitis B, compared with patients who have received standard treatment including administration of conventional antiviral drugs, showing the possibility of completely curing the disease.

The present disclosure relates to double stranded RNA agents targeting the hepatitis B virus (HBV) genome, and methods of using such agents to inhibit expression of one or more HBV genes and methods of treating subjects having an HBV infection or HBV-associated disorder, e.g., chronic hepatitis B infection.

The invention discloses a construction method of a metabolism-related fatty liver disease and chronic hepatitis B-related hepatocellular carcinoma model, and belongs to the technical field of disease animal models. The construction method comprises the following steps: S1, linearizing an HBV genome, and injecting the linearized HBV genome into a fertilized egg of a C57BL / 6 mouse to establish an HBV transgenic mouse; and S2, feeding the HBV transgenic mouse in the step S1 with D09100310 feed to obtain the mouse model of metabolism-related fatty liver disease combined with chronic hepatitis B-related hepatocellular carcinoma. According to the construction method of the metabolism-related fatty liver disease combined chronic hepatitis B related hepatocellular carcinoma model, HBV-Tg mice are selected as experimental animals, the D09100310 mouse feed is utilized to construct the metabolism-related fatty liver disease combined chronic hepatitis B related hepatocellular carcinoma model, the stability and repeatability are good, objectiveness and simplicity are achieved, operability is high, and the model is suitable for being used for the clinical application. And other possible interference factors are reduced.

Provided in the present invention are a liver-cancer-related serum microRNA marker and a new method for diagnosing liver cancer. The liver-cancer-related serum microRNA marker is composed of hsa-miR-122, hsa-miR-21, hsa-miR-2115, hsa-miR-221, hsa-miR-27 and hsa-miR-4499. The relative expression level of each liver-cancer-related serum microRNA marker in serum is detected by means of a real-time PCR method, and the detection reagent comprises primers of the above-described liver-cancer-related serum microRNA markers. The present invention can be used for diagnosing hepatocellular carcinoma, especially early hepatocellular carcinoma; or for distinguishing serum of at least one hepatocellular carcinoma patient from serum of at least one healthy individual, serum of at least one chronic hepatitis B patient or serum of at least one liver cirrhosis patient.

Provided herein are methods for administering hepatitis B virus surface antigen (HBsAg) to a subject suffering from chronic hepatitis B to differentiate between responder subjects and non-responder subjects that the administration of HBsAg results in an increased response to HBV antibody levels, and treating chronic hepatitis B in responder subjects using HBV therapy. Also provided are methods of excluding unresponded subjects outside a clinical study.

To provide RNAi agents for inhibiting expression of the α-1 antitrypsin (AAT) gene, compositions including the AAT RNAi agents, and methods of using the same.SOLUTION: Also there are disclosed pharmaceutical compositions including one or more AAT RNAi agents together with one or more excipients capable of delivering the RNAi agents to living cells in vivo. The delivery of the AAT RNAi agents to liver cells in vivo inhibits AAT gene expression and treats diseases associated with AAT deficiency such as chronic hepatitis, cirrhosis, hepatocellular carcinoma, transaminitis, cholestasis, fibrosis, and fulminant hepatic failure.SELECTED DRAWING: Figure 9

The present invention relates to a film-coated swallowable tablet comprising eltrombopag bis(monoethanolamine) and pharmaceutically acceptable excipients comprising calcium silicate as diluent. The invention further relates to the use of said tablet as a medicament, particularly in the treatment of immune thrombocytopenia (ITP), thrombocytopenia in patients with chronic hepatitis C virus (HCV) and severe aplastic anaemia (SAA).

The present invention relates to compositions and methods for therapeutic immunization for treatment of chronic hepatitis B virus (CHB). Methods of the invention include a method generating a high titer hybrid-hepatitis B virus (HBV) vector, methods of treating and / or preventing HBV infection and / or CHB, and methods of inducing a memory T and B cell immune response against HBV infection in a subject administered the VLV composition produced thereby. Furthermore, the invention encompasses a pharmaceutical composition for vaccinating a subject to protect the subject against infection with HBV.

The present invention relates to the field of pharmaceutical synthesis. Disclosed is a long-lasting hepatitis virus entry inhibitor. The long-lasting hepatitis virus entry inhibitor of the present invention is used for preparing a pharmaceutical composition for treating diseases, the pharmaceutical composition being used for treating chronic hepatitis B and hepatitis D.

The application discloses application of a low-dose anti-PD-1 antibody in a limited course of treatment in treatment of hepatitis B. Anti-PD-1 antibody treatment is carried out on a chronic hepatitis B patient receiving nucleoside analogue or nucleotide analogue treatment, 100 mg is injected intravenously each time, once every three weeks, and the course of treatment is ended after 12 weeks or 24 weeks. The application blocks the combination of the PD-1 receptor highly expressed on the surface of T cells of the CHB patient with a ligand by blocking the CHB patient T cell surface high expression of the PD-1 receptor, thereby reversing the T cell exhaustion state, enhancing the HBV specific T cell immune response, and promoting HBsAg clearance. The application uses a limited course of treatment and a low-dose alpha PD-1 to enhance the HBV specific T cell immune response of the patient and promote the clearance of HBsAg while ensuring good safety. Compared with the traditional 48-week Peg-IFN alpha or several years or even decades of NAs treatment of the CHB patient, the 12-week or 24-week course of alpha PD-1 is shorter and has a smaller economic burden on the patient.