175 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 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 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 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 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 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.

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.

The invention discloses application of a miR-3960 inhibitor, and belongs to the technical field of biological medicines. The invention aims to find and discover miRNA markers related to AD diagnosis and treatment. Researches on AD pathogenesis discover that expression of the miR-3960 is significantly increased in AD patients, and further cell experiments discover that inhibition of the expression of the miR-3960 significantly improves the influence of A beta1-42 on cell viability, apoptosis, ROS and APP proteins, and the miR-3960 has a significant therapeutic effect on AD. A beta1-42 is a core component of amyloid plaque in the brain of an AD patient, and is widely applied to construction of AD cell models and animal models so as to research pathogenesis and drug evaluation of AD. The miR-3960 inhibitor is used for preparing a medicine for treating the Alzheimer's disease, and the nucleotide sequence of the miR-3960 inhibitor is CCCCCGCCUCCGCCGCCGCC.

This invention belongs to the medical field and establishes a clinically relevant mouse glioblastoma treatment model, obtaining "cured" mice. When these "cured" mice were re-challenged with tumors, the tumors spontaneously regressed, and the animals achieved long-term survival. This indicates that the "cured" mice acquired immunity to the tumor, and these mice are named "cured-immune" mice. Intracranial inoculation of tumor cells into the "cured-immune" mice specifically induced a microglia subset exhibiting high expression of the purinergic receptor P2ry12 gene. High ) and immune-boosting functional characteristics, P2ry12 infusion Hi Small glial subsets significantly prolonged the survival time of glioma-bearing mice. Compared with the control group, P2ry12 in "cured-immune" (LTS) mice was significantly reduced. High Ccl12 low Differentially expressed genes in microglial cell subsets are enriched in signaling pathways that promote immune function, hence P2ry12 High Ccl12 low Microglial cell subsets have therapeutic effects on gliomas.

The invention relates to the technical field of medicines, in particular to application of a neuropeptide Y1 receptor antagonist in preparation of a hereditary polycystic kidney disease treatment medicine. The neuropeptide Y1 receptor antagonist is selected from a compound BIBO3304 which plays a role in blocking combination of neuropeptide Y (NPY) and a Y1 receptor subtype thereof. On the basis that early-stage histopathology, high-throughput sequencing, cytobiology and molecular biology are combined with in-vitro cell culture and in-vivo animal experiments, the potential treatment effect of the neuropeptide Y1 receptor antagonist in preparation of hereditary polycystic kidney disease treatment drugs is provided, and a new basis is provided for hereditary polycystic kidney disease treatment.

The present invention relates to a multifunctional cascade reactive nano - scale ultrasound contrast agent and its preparation method and application. The contrast agent (GHB - NPs) has a core of chitosan loaded with Basigin - siRNA and modified with hyaluronidase, and a shell membrane of phospholipid - polyethylene glycol - 2GSH. Perfluoropentane is encapsulated inside the shell membrane, and the particle size is 106 - 295 nm. For the GHB - NPs prepared by the present invention, DSPE - PEG2k - 2GSH on its surface can react with highly expressed γ - GGT on the surface of tumor cells, resulting in electrostatic repulsion to expose hyaluronidase, enabling GHB - NPs to penetrate deep into tumor tissues, and having targeting and high efficiency for the treatment of tumors. And it can be used in combination with UTMD. By inhibiting the β - catenin / c - Myc pathway, it down - regulates glycolysis - related proteins and reduces the production of lactic acid and ATP, which is beneficial to the treatment of tumor diseases. And the present invention has experimentally proved that GHB - NPs + UTMD has an obvious therapeutic effect on melanoma model mice, and can be used for the preparation of anti - tumor drugs to achieve the integration of tumor diagnosis and treatment.

The invention belongs to the technical field of medicine, and discloses application of SHLP2 in preparation of medicine for relieving and treating acute and chronic inflammatory pain, and the amino acid sequence of SHLP2 polypeptide is MGVKFFTLSTRFFPSVQRAVPLWTNS. After the SHLP2 polypeptide is treated in an intrathecal (5 [mu] g / 10 [mu] g / 20 [mu] g) injection mode, the SHLP2 polypeptide shows a good treatment effect in an acute inflammation pain model induced by formalin and capsaicin and a chronic inflammation pain model induced by carrageenan and a complete Freund's adjuvant. The SHLP2 is utilized to target a mitochondrial genome, the effect of relieving acute and chronic inflammatory pain is achieved in a central sheath injection mode, and a target different from a traditional analgesic drug can be searched for treatment of the acute and chronic inflammatory pain.

This invention discloses the application of substances that inhibit Trx1 nitration in the preparation of drugs for treating Trx1 nitration-related diseases. This invention reveals for the first time that nitration modification of tyrosine residue 49 (Y49) of the Trx1 protein is a key pathological step in diseases such as ischemic stroke and myocardial ischemia-reperfusion injury. Inhibiting nitration at this site can effectively restore Trx1 reductase activity, enhance the binding of Trx1 to ASK1, and block the downstream ASK1-p38 / JNK apoptosis signaling pathway, thereby exerting a therapeutic effect. This invention provides a novel treatment strategy for Trx1 nitration-related diseases.

The application discloses an application of a miR-4680-3p inhibitor and belongs to the technical field of biological medicines.The inventor of the application finds that the expression of miR-4680-3p 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-4680-3p 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 classic model of cerebral apoplexy in vitro in research. The miR-4680-3p inhibitor disclosed by the application is used for preparing a medicine for treating ischemic apoplexy, and the nucleotide sequence of the miR-4680-3p inhibitor is as follows: UAACAACUCUUACAAUUCAGA.

Provided herein are compositions of chimeric shuttle-binder-effector fusion proteins with components related to modulating endogenous cytotoxic effector mechanisms, which are useful for therapeutic effects on predetermined target molecules. These shuttle-binder-effector proteins also have specific epitope binding affinities for these target molecules. Compositions for modified cells expressing these chimeric shuttle-binder-effector fusion proteins are also provided. Methods for the modification of cells to express these chimeric shuttle-binder-effector fusion proteins and for delivering the chimeric shuttle-binder-effector fusion proteins into target cells using the lytic granule cellular mechanisms in these modified cells are also provided.

The invention discloses a Toll-like receptor (TLR) agonist / organic photosensitizer protein nano-composite as well as a preparation method and application of the Toll-like receptor (TLR) agonist / organic photosensitizer protein nano-composite. In order to overcome the defects of short blood half-life period, low bioavailability and the like of the existing TLR agonist, the protein nano-composite is obtained by forming a compound in a protein cavity by using the TLR agonist and an organic photosensitizer, and has tumor and lymph node dual-targeting characteristics. The protein nano-composite is simple in preparation method, mild in condition, free of an organic solvent, uniform in particle size and has a pH-responsive drug release behavior, and the protein nano-composite is prepared by a one-step method with water as a solvent. Based on an active targeting mechanism mediated by an albumin binding receptor and an active uptake mechanism of antigen presenting cells to albumin, the nano-composite has tumor and lymph node dual-targeting characteristics, has immunotherapy and light therapy effects under irradiation of near-infrared light, and has a good application prospect from two aspects of short-term quick action and long-term body immunity improvement. Tumor growth is effectively restrained, and tumors are expected to be radically treated.