231 results about "Therapeutic action" patented technology

A compound, as shown in Formula I, is a multi-heterocyclic compound. It has been verified that the compound provided by this invention integrates a novel compound targeting the calcitonin gene-related peptide (CGRP) based on ephedrine. Upon contact with the skin, due to photoactivated cell biological function regulation and the blocking effect of the multi-heterocyclic compound I structure on serotonin receptors, it achieves therapeutic effects on cutaneous vascular malformations and telangiectasia, improves the effectiveness of phototherapy in improving chronic cutaneous vascular diseases, and promotes skin wound healing.

The present invention relates to the field of tumor treatment and immunology biology. Provided are a pharmaceutical combination containing an anti-PD-1-anti-VEGFA bispecific antibody, and the use thereof. Specifically, the pharmaceutical combination comprises at least one bispecific antibody and at least one PARP inhibitor, wherein the bispecific antibody comprises a first protein functional region for targeting PD-1 and a second protein functional region for targeting VEGFA; and according to the EU numbering system, the heavy chain constant region of an immunoglobulin contained in the bispecific antibody is mutated at two sites, i.e. site 234 and site 235, and after mutation, the affinity constant of the bispecific antibody to FcγRI, FcγRIIa, FcγRIIIa and / or C1q is reduced compared with the affinity constant of the bispecific antibody thereto before mutation. The combined administration of the PARPi and the bispecific antibody has a significantly better therapeutic effect on tumors than the individual use of the PARPi or the bispecific antibody; and the present invention has good application prospects.

The invention relates to polypeptide gold nanoparticles modified by trace cigarette extract CSE (0.1%-1%) and application of the polypeptide gold nanoparticles in preparation of drugs for treating chronic obstructive pulmonary diseases. The polypeptide-modified gold nanoparticle is a polypeptide-modified gold nanoparticle as shown in a sequence SEQ ID NO: 1. It is confirmed for the first time that polypeptide (CLPFFD, SEQ ID NO: 1) gold nanoparticles modified by trace CSE (0.1%-1%) can antagonize mtDNA synthesis and inhibit mitochondrial ROS generation so as to inhibit activation of macrophage NLRP3 inflammasome, induce depolarization of macrophage and target lung macrophage in vivo to achieve anti-inflammatory activity, and the polypeptide (CLPFFD, SEQ ID NO: 1) gold nanoparticles can be used for preparing anti-inflammatory drugs. The compound has an obvious treatment effect in a COPD acute exacerbation model and a stable phase model, so that the compound can be used for preparing medicines for treating COPD. The medicine has the advantages of being remarkable in curative effect, capable of acting on specific cells in a targeted mode, convenient to track in vivo and the like, and a new treatment means is provided for COPD.

The present invention relates to a nitrogen-containing heterocyclic compound and its use, which has a significantly superior therapeutic effect on tumors having low expression, no expression, low activity or inactivity of the mitochondrial membrane permeability transition pore and / or low expression, no expression, low activity or inactivity of peptidylprolyl isomerase F. In particular, the present invention provides a compound of formula I, or an optical isomer or racemate thereof, or a solvate thereof, or a pharma- ceutically acceptable salt thereof, or a deuterated compound thereof. JPEG2025509622000598.jpg75147

The invention relates to a small extracellular vesicle containing Klotho protein and / or mRNA as well as a preparation method and application of the small extracellular vesicle. The preparation method of the small extracellular vesicle comprises the following steps: S1, constructing a recombinant expression vector containing a Klotho protein coding gene; s2, introducing the recombinant expression vector into recipient cells to obtain a receptor cell strain with stable expression of the Klotho gene; and S3, culturing the receptor cell strain, collecting a culture supernatant, and extracting the small extracellular vesicles from the culture supernatant. The small extracellular vesicles containing the Klotho protein and / or mRNA can regulate and control the expression of endogenous Klotho, the expression profile of bioactive molecules in the small extracellular vesicles is also changed, the small extracellular vesicles are rich in various kidney protective proteins, miRNA and other bioactive molecules, and the treatment effect on AKI and AD is remarkably enhanced.

The invention provides application of an aromatic sulfonamide compound in preparation of a medicine for preventing and treating liver injury. The aromatic sulfonamide compound BC2059 provided by the invention can be used for inhibiting transcription and protein synthesis of related genes of Fibronectin and CollagenI in hepatic stellate cells, and plays a role in treating liver injury mice induced by bile duct ligation and carbon tetrachloride. The invention provides a potential drug molecule with a new action mechanism for treating liver injury.

The invention discloses a nerve cell senescence resisting medicine containing p-hydroxybenzaldehyde and application thereof.The p-hydroxybenzaldehyde is adopted as the only active substance, and the p-hydroxybenzaldehyde can reduce accumulation of DNA damage in cells, reduce activity of beta-galactosidase in the cells and slow down reduction of cell metabolic capacity, so that the nerve cell senescence resisting medicine is obtained. Therefore, the senescence of nerve cells is effectively slowed down, the cognitive function is improved, and a potential treatment effect is achieved in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.

The invention discloses a frontalon tooth healing targeting nano preparation and a preparation process thereof, belongs to the technical field of nano medicines, and aims to solve the problems that the natural regeneration capacity of teeth is limited and the combination of ethnic drugs and modern biotechnology is caused due to the lack of a targeting inhibition means for USAG-1. Comprising an anti-USAG-1 monoclonal antibody, ethnic drug components and a nano-carrier, the anti-USAG-1 monoclonal antibody is connected to the surface of the nano-carrier through covalent bonds, the ethnic drug components are loaded in the nano-carrier through physical action, and the nano-carrier is a polylactic acid-glycolic acid copolymer or chitosan; the anti-USAG-1 monoclonal antibody is used as a targeting ligand, is high in targeting property, can accurately reach a tooth focus, improves the drug utilization rate, enhances the curative effect, integrates multiple ethnic drug components, exerts a synergistic effect, can increase the contact area between the ethnic drug components and a biological membrane, promotes the absorption and transport of the drug, and improves the bioavailability of the drug. And the medicine can better play a treatment role.

The invention discloses a monatomic iron nano-enzyme with a targeting effect as well as a preparation method and application thereof. The preparation method specifically comprises the following steps: (1) mixing and stirring water, absolute ethyl alcohol and stronger ammonia water, adding a polyphenol substance aqueous solution, stirring again, adding a ferric salt ethanol solution, continuously stirring, centrifuging, washing and freeze-drying; (2) calcining and grinding; and (3) ultrasonically dispersing in water, stirring, adding an NH2-PEG-iRGD solution, continuously stirring, centrifuging, washing, and freeze-drying, thereby obtaining the product. The monatomic iron nano-enzyme with the targeting effect prepared by the invention has very good peroxidase-like activity and photothermal conversion property, can simultaneously play the therapeutic effects of CDT and PTT, and can greatly improve the therapeutic effect of tumors through a combined therapy.

The invention belongs to the field of biological medicine, and particularly relates to a varicella-zoster virus gB protein mutant and application thereof. According to the gB protein mutant of the varicella-zoster virus, provided by the invention, proline mutation, shearing of N-terminal and C-terminal structural domains, release of electrostatic repulsive force in the protein, mutation of a Frelin enzyme cutting site and the like are carried out in a process of converting a gB protein fusion precursor into a fusion afterbody conformation, so that the gB protein mutant of the varicella-zoster virus is obtained. The conformation before fusion can be stabilized, and the expression quantity and the stability of the antigen protein are improved. As a vaccine component, the mutant has good immunogenicity, activates autoimmunity of animals and plays a role in prevention or treatment of vaccines.

The present disclosure relates to Machado-Joseph disease (MJD), or spinocerebellar ataxia type 3 (SCA3), an autosomal dominantly inherited neurodegenerative disorder that is caused by an over-repetition of the polyglutamine-codifying region in the ataxin-3 (ATX7V3) gene. Expanded ATXN3 is prone to aggregate and disturbs diverse cellular systems, ultimately leading to cell dysfunction and death in specific neuronal populations. To date, no treatment able to reverse or stall MJD / SCA3 progression has been developed. Strategies based on the suppression of the deleterious gene products have demonstrated promising results in pre-clinical studies. Nonetheless, these strategies do not target the root cause of the disease, producing an incomplete and / or transient therapeutic effect in target cells or tissues. Recently, gene-based therapeutics, including the bacterial clustered regularly interspaced short palindromic repeat (CRISPR) systems for gene edition, have been successfully used to permanently inactivate and correct disease-related genes, holding promise for the development of a definitive cure for inherited diseases.

The invention discloses application of (20S)-ginsenoside Rh1 in preparation of drugs for preventing and / or improving cerebral arterial thrombosis, and relates to the technical field of medical application of natural drugs. The invention verifies that (20S)-ginsenoside Rh1 up-regulates the expression of an anti-apoptosis gene by promoting STAT3 phosphorylation and translocation to a cell nucleus, so that the (20S)-ginsenoside Rh1 plays a role in protecting neuronal injury induced by sugar oxygen deprivation. In MCAO model mice, the (20S)-ginsenoside Rh1 obviously relieves the symptom of ischemic cerebral apoplexy and has positive influence on neurodegenerative events related to cerebral infarction, and the anti-apoptosis and neuroprotection effects are most prominent. Mechanism research shows that (20S)-ginsenoside Rh1 plays a therapeutic role in PC12 cell and MCAO model mice by activating a JAK2 / STAT3 signal channel.

The present invention relates to the field of drug delivery, and in particular to an extracellular vesicle (EV) delivery platform loaded with a target protein or polypeptide and a use thereof. The present invention provides a plasmid combination for preparing an EV loaded with a target protein or polypeptide, wherein the plasmid combination comprises a pCAG-GOI plasmid and a pMD2.G plasmid, and the GOI refers to a gene sequence corresponding to the target protein or polypeptide. According to the EV delivery platform loaded with the protein or polypeptide provided by the present invention, target proteins or polypeptides can be efficiently loaded into EVs by applying double-plasmid co-transfection cells, the use of EVs as carriers to deliver target substances such as proteins or the polypeptides to exert therapeutic effects into clinical practice is further promoted, and by means of the good structural stability, the innate advantages of transporting biologically active substances and excellent biocompatibility of the EVs, the systemic toxic and side effects caused by conventional delivery carriers are reduced.

The invention provides application of sclareol in preparation of a medicine for preventing and treating varicella-zoster virus infection. A series of biological experiments show that the sclareol can obviously relieve the cytopathic effect caused by VZV infection under the concentration without obvious cytotoxicity; the gene expression quantity of VZV characteristic genes including an immediate early gene ORF62, an early gene ORF21 and a late gene ORF68 and the expression of an early protein IE62 and a late protein gE can be remarkably inhibited, so that the effect of resisting VZV infection is achieved. The results show that sclareol has obvious prevention and treatment effects on VZV, has small toxic and side effects, is safe and effective, and has an application prospect in preparation of drugs for treating and / or preventing VZV.

The invention relates to application of mesenchymal stem cells of overexpressed Numb genes in preparation of drugs for treating chronic liver diseases. The invention also provides a mesenchymal stem cell modified by genetic engineering, and the mesenchymal stem cell modified by genetic engineering is a mesenchymal stem cell of an overexpressed Numb gene. The invention provides a novel human umbilical cord mesenchymal stem cell (hUC-MSC) for treating chronic and acute hepatic failure, hepatic fibrosis and liver cirrhosis. The hUC-MSCs overexpressing the Numb gene can inhibit liver inflammatory response and hepatic fibrosis progress in a dose-dependent manner; biliary duct reaction is inhibited in a dose-dependent manner, and cholestasis is improved; the liver cell proliferation can be promoted in a dose-dependent manner, and the content of serum albumin is increased. And the treatment effects are better than those of the same dose of hUC-MSCs. The hUC-MSCsNumb-OE can be directly used as a cell for treating chronic and acute hepatic failure, hepatic fibrosis and cirrhosis, and also can be used as a tool for screening biological or chemical medicines for treating hepatic fibrosis and cirrhosis.

Provided are methods and compositions for obtaining functionally enhanced immune cells, and derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. Also provided are derivative cells having stable and functional genome editing that delivers improved or enhanced therapeutic effects. Further provided are therapeutic compositions and the use thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors in combination therapies.

The present invention relates to a nitrogen-containing heterocyclic compound and its use, which has a significantly superior therapeutic effect on tumors with low or no expression of NNMT gene, high expression of DNA methyltransferase, high expression of UHRF1, hypermethylation of nucleotide sites in the NNMT gene and / or hypermethylation of DNA CpG sites in the NNMT gene region. The present invention provides a compound of formula I, or an optical isomer or racemate thereof, or a solvate thereof, or a pharma- ceutically acceptable salt thereof, or a deuterated compound thereof. TIFF2025509620000598.tif83150

The invention belongs to the technical field of biological medicine manufacturing, and particularly provides a preparation method of an engineered exosome capable of loading mitochondria for treating pulmonary fibrosis and the engineered exosome. The method comprises the following steps: constructing fusion plasmids for expressing mitochondrial targeting peptide fragment-therapeutic protein genes, dissolving the fusion plasmids in non-enzyme ultrapure water, adding the fusion plasmids into a lipid nano-preparation, and fully mixing to obtain a nano-preparation containing the therapeutic protein genes; the nano preparation is delivered into alveolar epithelial cells and is efficiently transfected, so that the homeostatic balance of the injured alveolar epithelial cells in the development of pulmonary fibrosis is effectively regulated and controlled, the secretion of an exosome with a therapeutic effect is promoted, and the engineered exosome is further obtained through mannose modification. The exosome can effectively load mitochondria and sequentially and accurately target macrophage mitochondria on the basis of a mannose target head and a mitochondrial targeting peptide fragment, so that macrophage mitochondrial homeostatic balance is effectively regulated and controlled, the purpose of reverse treatment of pulmonary fibrosis is achieved, and the exosome has high clinical application value.

The application provides a preparation of a sema7A monoclonal antibody 8A12 and a treatment effect of the sema7A monoclonal antibody 8A12 on lupus nephritis, wherein the CDR-H1 of the heavy chain variable region of the monoclonal antibody 8A12 is an amino acid sequence shown in SEQ ID No. 1, the CDR-H2 of the heavy chain variable region is an amino acid sequence shown in SEQ ID No. 2, and the CDR-H3 of the heavy chain variable region is an amino acid sequence shown in SEQ ID No. 3; the CDR-L1 of the light chain variable region of the monoclonal antibody 8A12 is an amino acid sequence shown in SEQ ID No. 4, the CDR-L2 of the light chain variable region is an amino acid sequence shown in SEQ ID No. 5, and the CDR-L3 of the light chain variable region is an amino acid sequence shown in SEQ ID No. 6. The monoclonal antibody 8A12 can effectively inhibit the expression up-regulation of IL-1beta, TNF-alpha and IL-6 caused by Sema7A recombinant protein, can effectively inhibit the macrophage inflammatory response induced by Sema7A, and can continuously and effectively reduce serum anti-double-stranded DNA antibodies and kidney damage of lupus mice. The monoclonal antibody 8A12 can be used for preparing a pharmaceutical composition for preventing and / or treating systemic lupus erythematosus and / or lupus nephritis thereof.

The present invention relates to immunoglobulin single variable domains (ISVDs) for the treatment of diseases by the enteral, e.g. oral, delivery. In particular, the present invention provides ISVDs comprising sequences with a high percentage of sequence identity to SEQ ID NO: 1 for such enteral administration. Such sequences were identified as extraordinarily stable in the gastrointestinal tract, which prevents their degradation and thereby allows them to exert a strong therapeutic effect.

The invention discloses application of fraxinellone as a cGAS-STING signal channel inhibitor in preparation of a medicine for treating inflammatory bowel disease, and belongs to the technical field of biological medicine. Aiming at the problem that the specific action mechanism between fraxinellone and the inflammatory bowel disease is not clear, the invention researches the specific action mechanism of fraxinellone for exerting the treatment and protection effects on the inflammatory bowel disease from the in-vivo and in-vitro aspects. Results show that the FRA can significantly inhibit the increase of the ROS level of IEC-6 cells caused by LPS, improve the mitochondrial membrane potential, significantly improve the pathological characteristics of DSS-induced mouse weight loss, DAI index increase, red, swollen and shortened colon, damaged colon tissue structure and the like, and inhibit the expression level of inflammatory factors. According to the present invention, it is found that the FRA can up-regulate the TJ tight junction protein and recover the intestinal barrier function by regulating the expression of cGAS-STING signal channel related proteins such as cGAS, STING, p-TBK1, NF-kappa B and the transcriptional level of mRNA, such that the IBD treatment effect is provided, and the basic basis is provided for the development of the new IBD treatment drug or strategy.

The present invention provides a flow cytometer-based kit for detecting PD-1 in tumor patients. The kit, through antibody reagents containing PD-1-PE and Anti-IgG4-PE, can not only detect the PD-1 expression level in tumor patients, but also detect the PD-1 expression level in tumor patients who have been injected with anti-PD-1 monoclonal antibodies, providing better guidance for clinical medication and therapeutic effects. By adding a blocking agent to the diluent, a one-step incubation method is implemented for detection, shortening the detection time and improving the detection efficiency. At the same time, the Anti-IgG4-PE in the antibody reagent and the blocking agent and antioxidant in the diluent are optimized to improve the specificity and stability of the detection, thereby improving the accuracy of the detection. Using this kit for PD-1 detection has the advantages of simple operation, fast and convenient detection process, and accurate test results.

The invention discloses an application of chloroquine in preparation of a medicine for treating glutamine deficiency type tumors, the chloroquine promotes IFN-gamma signal transduction by up-regulating IFNGR1 protein expression, so that the therapeutic effect of immunotherapy on the glutamine deficiency type tumors, ASCT2 low expression tumors or autophagy-lysosomal pathway active tumors is enhanced. The invention provides a new thought and an effective means for solving the problem of immunotherapy drug resistance caused by glutamine metabolism limitation, and has important theoretical significance and potential clinical application value.

The invention discloses a nucleotide for inhibiting expression of ILKAP (Interleukin-7-Kinase Associated Protein) related circular RNA (Ribonucleic Acid) and application of the nucleotide, and the nucleotide is characterized in that the nucleotide sequence is CGUCAGUACUCGGGUUUCA, and the expression level of hsacirc0001116 can be specifically and obviously reduced. Experimental results prove that the nucleic acid molecule can effectively interfere with the expression of hsacirc0001116 in human non-small cell lung cancer A549 cells, and can significantly inhibit the survival of lung cancer cells. In addition, when the nucleic acid molecule is combined with an existing antitumor drug for use, a synergistic treatment effect can be generated.

The application discloses a kind of preparation and application of multi-target small nucleic acid drug based on small activation RNA technology, and is related to the field of biotechnology.The preparation method of the multi-target small nucleic acid drug includes the following steps: (1) selecting at least two anti-disease genes according to target disease;(2) intercepting the sequence of 1000 base pairs of the promoter region upstream of the coding region of the anti-disease gene;(3) according to the promoter sequence, avoid CpG island and locate the segment of species conservation, and cut a sequence containing 19 base length as a sense strand;(4) design an antisense strand according to the sense strand, and the 19 base of the antisense strand and the sense strand are completely complementary;(5) add two deoxythymine or uracil to the 3' end of each chain.The multi-target small nucleic acid drug has good therapeutic effect on heart failure, and has strong cancer cell killing ability and inhibition ability of cancer cell migration, and has wide application prospect.

The invention provides modRNA (Ribonucleic Acid) for treating obliterated bronchitis, and belongs to the technical field of bioengineering. The modRNA for treating obliterated bronchitis provided by the invention is composed of an IL-10 modRNA (Interleukin-10) and an IFN (Interferon)-alpha modRNA (Interferon-alpha) modRNA. The BO treatment effect is achieved by inhibiting bronchial epithelial cell epithelial-mesenchymal transition (EMT), the expression of alpha-SMA and Vimentin in lung tissue can be remarkably reduced, the expression of E-cadherin and Cytokeratin 5 can be up-regulated, microbronchial epithelial injury is repaired, collagen deposition is reduced, and the lung function is improved. The synergistic effect of the two is better than that of single gene therapy, the safety is high, and the controllability is strong.

The present invention discloses an application of FN-1501 and its pharmaceutical composition in the preparation of drugs for preventing and / or treating liver injury, specifically including drugs for preventing and treating autoimmune hepatitis, viral hepatitis or drug-induced liver injury, especially drugs for preventing and treating autoimmune hepatitis. It can achieve multiple pharmacological effects of improving liver tissue structure damage, liver inflammation, reducing serum transaminase, serum lactate dehydrogenase and mRNA levels of inflammatory factors, and can play a therapeutic role at the gene level, molecular level and tissue level. There are no toxic side effects in the body, and the preparation form used is wide. The appropriate drug dosage form can be selected according to the clinical application scenario, which provides a new development strategy for targeted drugs for the prevention and treatment of liver injury.

An antibody-conjugated liposome, particularly a nanoparticle. The surface of the nanoparticle contains antibodies. The number of the antibodies is 5-60, preferably 5-50, and more preferably 5-40. The nanoparticle, for example, a liposome, can more effectively exert a therapeutic effect on tumor and improve multidrug resistance of tumor, thereby overcoming the technical prejudice that it is commonly considered that the more antibodies on a surface of a liposome, the better the target cell binding effect, and laying a foundation for further clinical development.An antibody-conjugated liposome, particularly a nanoparticle, the surface of which contains antibodies, and the number of the antibodies is 5-60, preferably 5-50, and more preferably 5-40. The nanoparticle, such as a liposome, can more effectively exert a therapeutic effect on tumors and reduce the multidrug resistance of tumors. This overcomes the generally accepted technical bias that more antibodies on the surface of a liposome lead to better binding with target cells, thereby laying the foundation for further clinical development.

The application discloses application of a miR-8069 inhibitor and belongs to the technical field of biological medicines.The inventor of the application finds that the expression of miR-8069 in the plasma of IS patients is abnormally increased in the research on the pathogenesis of IS, and through further cell experiments, it is found that inhibiting the expression of miR-8069 can effectively improve the adverse effects of OGD / R treatment on cell viability, apoptosis and ROS, and has a significant therapeutic effect on IS. Cell damage induced by OGD / R is often used as a model of cerebral stroke in vitro in research. The miR-8069 inhibitor disclosed by the application is used for preparing a medicine for treating cerebral stroke, and the nucleotide sequence is as follows: ACCGCCGACCGCCCCCAACCAUCC.

The invention discloses application of tenuifolin in preparation of a medicine for treating multiple sclerosis, and belongs to the technical field of biological pharmacy. Aiming at the problem that the treatment effect and the specific action mechanism of TEN on the multiple sclerosis disease are not clear yet, an EAE model group of a mouse is used for simulating the multiple sclerosis disease, meanwhile, a TEN intervention group is set for simulating the multiple sclerosis disease and then TEN intervention is carried out, and it can be found through experimental comparison that compared with mice of the EAE model group, the mice of the TEN intervention group are more obvious in effect. The average neurological function score is obviously reduced, the clinical symptoms and the demyelination degree are alleviated, the MBP expression is increased, and the inflammatory infiltration is reduced; in addition, TEN intervention can significantly reduce the increase of TLR4 / NF-kappa B protein in mouse spinal cord tissues of an EAE model group. The TEN can inhibit activation of a TLR4 / NF-kappa B pathway to effectively relieve demyelination and abnormal behaviors of mice of an EAE model group and slow down inflammatory response, so that the TEN plays a role in treating the mice of the EAE model group.