2010 results about "Therapy medication" patented technology

The invention discloses multifunctional hydrogel and application thereof, and belongs to the technical field of biological medicine. According to the multifunctional hydrogel, ketal mercaptan with two hydrazide ends and oxidized dextran are cross-linked to form a cross-linked network containing dynamic covalent bonds. The preparation method comprises the following steps: dissolving ketal mercaptan with two hydrazide ends in deionized water to obtain a ketal mercaptan solution, dissolving oxidized dextran in deionized water to obtain an oxidized dextran solution, mixing the ketal mercaptan solution with the oxidized dextran solution, and standing to obtain the multifunctional hydrogel. The multifunctional hydrogel has pH / ROS dual responsiveness, can respond to inflammation microenvironment and low pH of infectious wounds, remove active oxygen, release therapeutic drugs, regulate macrophage polarization and relieve bacterial infection, thereby playing a key role in inflammation, proliferation and remodeling stages of wound healing to accelerate wound healing. The curcumin-encapsulated liposome is added into the multifunctional hydrogel, so that the antibacterial effect can be further improved.

The present invention discloses a pharmaceutical composition comprising a circular RNA and a drug delivery carrier. Compared with traditional linear 1 * siRNA and annular 1 * siRNA, the number of repeated series connection of positive-sense strands is increased to include but not limited to two or more, it is accidentally found that the silence effect is remarkably enhanced, the expression level of the PCSK9 gene can be remarkably reduced, and degradation of mRNA of PCSK9 protein is mediated. The nano-particles are used for delivering oligonucleotide, so that the stability is improved, the immunogenicity is reduced, the effects of lowering cholesterol, reducing aortic plaque load and resisting atherosclerosis are improved, and the nano-particles are safe and free of obvious liver and kidney toxicity and have a wide application prospect in the aspect of preparing medicines for treating hypercholesterolemia and coronary heart disease.

The invention discloses a medical developing marker and a manufacturing method thereof, and relates to the field of medical instruments, the medical developing marker comprises a closed tube, the outer wall of the closed tube is provided with a bionic barb structure, the bionic barb structure is distributed in a flexible zigzag convex manner, and the bionic barb structure and the closed tube are integrally formed through an injection molding process; a closed cavity is arranged in the closed tube, four developing strips are symmetrically arranged in the tube wall of the closed cavity, the tube wall of the region where the developing strips are located is etched to form a weak band, and a developing material layer and a sustained-release medicine layer are sequentially deposited at the weak band. The developing material layer and the sustained-release drug and / or marked nano-particle layer are alternately deposited to form a functional composite layer, and the functional composite layer can directionally rupture to release the therapeutic drug under the action of implantation pressure. The marker integrates the functions of precise development, tissue anchoring and drug sustained release, is adaptive to multi-mode imaging such as ultrasonic imaging, X-ray imaging, CT imaging, MRI imaging and PET-CT imaging, and has remarkable clinical value in precise positioning treatment of solid tumors such as breast cancer and liver cancer.

The invention provides a construction method of a predictive cell senescence model, a method for predicting the senescence state of a tissue sample based on the senescence model, a method for screening potential therapeutic drugs, equipment, a medium and a program product, and relates to the field of intelligent medical treatment. The model construction method comprises the following steps: acquiring a training set sample expression profile data set; identifying a key senescence gene set from the data set by using a feature selection algorithm; inputting the key senescence gene set into a machine learning model to fit a prediction model, and determining an optimal hyper-parameter to obtain a cell senescence model containing the weight of a single gene in the key senescence gene set; the cell senescence model is a senescence score obtained by calculating the sum of the product of the expression quantity of a single gene and the regression coefficient thereof. The cell senescence model, namely PreCSenM, is constructed by integrating a plurality of senescence characteristic gene sets and a gene scoring algorithm, the accuracy in CS evaluation is superior to that of 10 existing methods, and the application of CS from biological research to clinical scenes is also realized.

Provided is a pharmaceutical composition, comprising a circular RNA and a drug delivery carrier. It is surprisingly found that compared with conventional linear 1 x siRNAs and circular 1 x siRNAs, increasing the number of tandem repeats in the sense strand to two or more significantly enhances the silencing effect, significantly reduces the expression level of the PCSK9 gene, and mediates the degradation of the PCSK9 protein mRNA. The use of nano-particles for delivering oligonucleotides features improved stability, reduced immunogenicity, improved cholesterol-lowering, aortic plaque load-reducing and anti-atherosclerotic effects, good safety, no significant liver and kidney toxicity, and therefore good prospects in preparing medicaments for treating hypercholesterolemia and a coronary heart disease.

The invention discloses a polypeptide drug for resisting gram-negative bacteria and application, and belongs to the technical field of biological medicine. The MIC of the antibacterial peptide obtained through screening on escherichia coli, salmonella typhimurium, pseudomonas aeruginosa, klebsiella pneumoniae, shigella sonnei and stenotrophomonas maltophilia is 16 [mu] g / mL, 2 [mu] g / mL, 16 [mu] g / mL, 4 [mu] g / mL, 2 [mu] g / mL and 4 [mu] g / mL respectively, and the antibacterial peptide has broad-spectrum antibacterial performance. The hemolytic activity and toxicity of the compound are lower than therapeutic concentration threshold values, and the compound can be used for preparing drugs or medical products for treating multi-drug-resistant bacterium infection.

The invention provides a neurosteroid derivative solid dispersion, a preparation method and application thereof, and a medicine containing a hot-melt extrusion solid dispersion, and belongs to the technical field of pharmacy. The preparation method comprises the following steps: carrying out melt extrusion on a raw material mixture at 125-160 DEG C to obtain the neurosteroid derivative solid dispersion, the mixed material comprises an active component, a plasticizer and a carrier material in a mass ratio of 10: (1-15): (10-90); the active component comprises at least one of a neurosteroid derivative (with a structure as shown in a formula 1), an isomer, a solvate and a pharmaceutically acceptable salt thereof; the plasticizer is selected from one or more of polyethylene glycol, poloxamer and Tween, and the average molecular weight of the polyethylene glycol is 1t; 6000, 6000; active components in the neurosteroid derivative solid dispersion exist in an amorphous state. The neurosteroid derivative in the neurosteroid derivative solid dispersion disclosed by the invention has relatively high oral bioavailability. # imgabs0 #

The invention belongs to the technical field of biological medicines, and particularly relates to application of an expression inhibitor of an NR4A1 gene in preparation of a medicine for treating wine-dependent withdrawal. It is found that after wine-dependent withdrawal, mice have anxiety behaviors, the NR4A1 level of the prefrontal lobe is increased, and apoptosis-related protein in the prefrontal lobe is increased. Knockout of the forehead NR4A1 gene intervenes the expression level of the NR4A1 gene in the forehead lobe of the mouse, it can be proved that down-regulation of the expression of the forehead lobe NR4A1 gene can rescue apoptosis and damage, caused by alcohol, of cortical neurons of the forehead lobe, relieve anxiety behaviors caused by alcohol withdrawal of the mouse, and have the effect of protecting the brain of the mouse; the inhibitor DIM-C-pPhOH of the NR4A1 protein can reduce the expression of the NR4A1 gene of the prefrontal lobe of an alcohol withdrawal mouse and anxiety-like behaviors caused by alcohol withdrawal, and provides related therapeutic targets and new therapeutic drugs for anxiety dysfunction caused by clinical alcohol dependence and alcohol dependence withdrawal.

The invention discloses an intelligent tumor microenvironment analysis and drug screening method based on multi-modal data, and relates to the field of tumor research. The method comprises the following steps: obtaining a plurality of prognosis image features according to preoperative magnetic resonance images of the brain of a plurality of glioblastoma patients; identifying a key image genomics gene set for each prognostic image feature; analyzing biological reasons of prognosis differences of high-risk patients and low-risk patients by using a transcriptome method; analyzing biological functions of prognosis image features; utilizing Fisher to accurately test and determine a cell population associated with the prognostic image features; determining a functional state of the cell population based on the scRNA-seq data of the cell population; constructing an image-gene-cell population-functional state association; potential therapeutic drugs for cell populations associated with prognostic image features are parsed using chi-square test. According to the invention, the tumor heterogeneity of glioblastoma can be depicted from the perspective of images, and potential therapeutic drugs can be identified.

The invention relates to the technical field of medicines, in particular to novel application of orifice-opening and deafness-removing pills in preparation of anti-dizziness medicines. Experiments prove that the administration group can remarkably shorten the standing time consumption of a vertigo mouse caused by movement on the horizontal rod and reduce the vertigo response index, so that the movement vertigo model mouse can stand stably on the horizontal rod more quickly; abnormal changes of indexes such as ACTH, NE and CREB in mouse serum and BDNF, CREB, 5-HT and DA in brain caused by motion vertigo can be remarkably reversed. Therefore, the orifice-opening and deafness-removing pill has an obvious anti-dizziness effect, can be used as an active ingredient for preparing the anti-dizziness medicine, and is an effective treatment medicine especially for dizziness induced by movement. According to the invention, new indications of the orifice-opening and deafness-removing pill except deafness, tinnitus and otitis media are expanded. In anti-dizziness treatment, compared with dizziness stop, the traditional Chinese medicine composition can avoid digestive system reaction, cardiovascular reaction, central nervous system reaction and other side effects caused by dizziness stop.

The invention belongs to the technical field of gene engineering, and provides shRNA (short hairpin Ribonucleic Acid) for knocking down BST2 gene expression, a recombinant vector and application of the shRNA, and the shRNA comprises Bst2-shRNA-1 or Bst2-shRNA-2; the Bst2-shRNA-1 comprises a positive-sense strand of which the nucleotide sequence is as shown in SEQ ID NO. 1 and an antisense strand of which the nucleotide sequence is as shown in SEQ ID NO. 2; the Bst2-shRNA-2 comprises a positive-sense strand of which the nucleotide sequence is as shown in SEQ ID NO. 3 and an antisense strand of which the nucleotide sequence is as shown in SEQ ID NO. 4. The shRNA disclosed by the invention plays an important role in inhibiting non-infectious aseptic inflammation, can effectively delay the ALS attack time and protect motor neurons, has a very good application prospect, and also provides a direction and a technical basis for searching, researching and developing new therapeutic drugs for treating ALS.

Disclosed in certain embodiments is a method of treating a drug overdose comprising administering to a patient in need thereof a therapeutically effective amount of a respiratory stimulant, wherein the overdosed drug comprises an α2 adrenergic receptor agonist.

The invention discloses an engineered bionic nucleic acid nano-vesicle as well as a preparation method and application thereof, relates to the technical field of nano biomedicine, and aims at solving the problems that in-vivo targeting efficiency and immunogenicity of a traditional cationic lipid nano-carrier are limited due to deletion and cleavage obstacles of GSDMD expression in tumor cells. The technical key point of the invention is as follows: the engineered bionic nucleic acid nano-vesicle is provided and is prepared by wrapping a cationic lipid nucleic acid drug with an exosome derived from engineered macrophages; wherein the exosome from the engineered macrophage is the exosome from the macrophage with high expression of PD1, which is as shown in SEQ. ID. NO.1. The exosome from the engineered macrophage is the exosome from the macrophage with high expression of PD1; the lipid nucleic acid medicine is prepared by loading GSDMD-N mRNA (messenger Ribonucleic Acid) shown on the basis of SEQ.ID.NO.2 on a cationic liposome. The engineered bionic nucleic acid nano-vesicle is used for preparing an oral squamous cell carcinoma diagnostic kit and a therapeutic drug.

The invention belongs to the technical field of biotechnology and animal models, and discloses a double-person-derived mouse model for simulating a tumor immune microenvironment and a construction method and application thereof. The method comprises the following steps: firstly, pretreating NSG immunodeficient mice by adopting low-dose whole-body irradiation in combination with double-antibody targeted bone marrow depletion, and transplanting CD34 + hematopoietic stem cells from the same human donor to complete human immune system reconstruction; separating tumor primary cells, tumor-related fibroblasts and tumor vascular endothelial cells of the same donor, performing three-dimensional co-culture to obtain homologous human tumor organs, and performing in-situ inoculation to immune reconstruction mice to obtain a target model. The core defects of MHC mismatching, low immune reconstruction efficiency, poor tumor immune microenvironment simulation degree, low clinical consistency and the like of an existing model are overcome, and the method can be used for tumor immune treatment drug screening, microenvironment mechanism research and personalized tumor treatment scheme verification.

The invention belongs to the technical field of damage assessment, and particularly relates to a construction method of a rat traumatic brain injury model caused by explosive shock waves. By protecting other important visceral organs except the brain, interference of damage of visceral organs such as the lung to brain injury is avoided, the overall function stability of the body is maintained, the caused brain injury can more truly reflect the characteristics of explosive traumatic brain injury, and the credibility and repeatability of experimental data are improved. The construction method simulates loading of explosion shock wave parameters in a real environment, constructs an animal traumatic brain injury model through live ammunition explosion, is closer to an actual combat environment, and can truly reflect physical parameters related to explosion and a complex action process generated by interaction of the physical parameters. And a support is provided for developing molecular mechanisms of explosive traumatic brain injury, clinical diagnosis, screening of therapeutic drugs and the like.

Disclosed herein are heterocyclic compounds that activate GLP-1R pathways. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the GLP-1R agonists are disclosed, alone or in combination with other therapeutic agents, for the treatment of diabetes, obesity, and other diseases or conditions dependent on GLP-1R pathways.

The invention relates to an application of an intervention SNRK-MTA1 signal channel axis in preparation of a non-small cell lung cancer targeted therapy drug. The nucleotide sequences of the mRNA of the SNRK gene and the mRNA of the MTA1 gene are respectively as shown in SEQ ID NO.1-2. The invention innovatively provides a strategy for treating the non-small cell lung cancer through double-target combined intervention. According to the strategy, SNRK gene expression is improved through exogenous gene overexpression plasmids, and meanwhile MTA1 gene expression is silenced through the siRNA technology. In a non-small cell lung cancer model, the strategy of combined application of the SNRK-OE plasmid and siMTA1 can specifically up-regulate the SNRK mRNA level and knock down the MTA1 mRNA level at the same time, and the combined strategy shows a better anti-tumor effect than single intervention, and can more effectively inhibit the growth and migration of tumor cells. Based on the discovery, the SNRK-MTA1 signal pathway axis can be developed into a novel therapeutic target for non-small cell lung cancer, and is used for designing a drug combination scheme or a composite targeted drug.

The invention discloses an anti-tumor medicine composition combined with a PARG inhibitor and application. Through natural product library screening and CCK-8 experiments, it is found that PARG knockout gastric cancer cells show significantly enhanced sensitivity to ginsenoside CK. Further clone formation experimental analysis shows that PARG knockout significantly enhances the inhibitory effect of ginsenoside CK on gastric cancer cell proliferation. In in-vivo experiments, a CDX model is utilized to verify that PARG knockout can significantly enhance the anti-tumor activity of ginsenoside CK on gastric cancer. The discovery provides an important experimental basis for clinical application of PARG as a gastric cancer treatment target and ginsenoside CK as a potential treatment drug. The research finds that the PARG inhibitor and ginsenoside CK are combined to achieve a better killing effect on other various cancer cells, and it is indicated that improvement of the effect is broad-spectrum.

The present invention provides anticancer agents comprising as an active ingredient a bispecific antibody that comprises a domain comprising a glypican 3-binding antibody variable region, a domain comprising a T cell receptor complex-binding antibody variable region, and common L chains that can enhance the affinity for the two antigens, as well as pharmaceutical compositions comprising the bispecific antibody as an active ingredient, the compositions being for use in combination with other anticancer agents. The bispecific antibodies are novel molecules which are produced with high efficiency and have strong anti-tumor activity as well as safety and excellent pharmacodynamics. The bispecific antibodies can be expected to be applied to various cancers.

The present disclosure provides compositions and methods related to the delivery of therapeutic medicines to the heart for treating a cardiac injury, such as those that occur due to a myocardial infarction (MI). In particular, the present disclosure provides novel hydrogel-based compositions that safely and effectively deliver a therapeutic agent to the pericardial cavity of the heart to treat the cardiac injury.

The invention discloses a construction method and application of a mouse model for specifically tracing heart valve cells, and belongs to the technical field of animal model construction. The model construction method comprises the following steps: (1) constructing a Wid1-Cre hybrid mouse before inserting a Cre recombinase coding gene into a termination codon of a mouse Wid1 gene; and (2) hybridizing the Wid1-Cre hybrid mouse with the Rosa26-tdTomato homozygous report mouse, so as to obtain the double transgenic mouse which simultaneously carries the Wid1-Cre gene and the Rosa26-tdTomato gene. According to the invention, on the basis of the expression characteristic that Wif1 is only limited to a valve area in the heart, Wif1-Cre is constructed; according to the Rosa26-tdTomato mouse model, specific tracing of heart valve cells is achieved, and an important experimental tool is provided for mechanism research of heart valve diseases and development of therapeutic drugs.

The invention discloses application of a small-molecule inhibitor of stress particles in preparation of tumor treatment drugs, and relates to the technical field of biological medicines. According to the present invention, the high throughput screening is performed on the 'ChemDiv Protein-Protein Interaction (PPI) Library', such that the small molecule inhibitor of the stress particle, i.e., the compound UA-0007373, is obtained; the research finds that the small-molecule inhibitor can effectively inhibit the formation of cell stress particles caused by G3BP1, so that the drug resistance of tumor cells is reduced. Cell experiments prove that the small-molecule inhibitor can effectively inhibit the formation of stress particles induced by anti-cancer drugs. Therefore, a brand new auxiliary compound is provided for chemical drug treatment of cancers, and a new technical thought can be provided for research and development of cancer drugs.

The invention provides a biomarker for sepsis encephalopathy and application of the biomarker. The biomarker is selected from any one or a combination of more than two of 5-HTP, 5-HIAA or 5-HIAA / 5-HT according to a ratio of 5-HTP to 5-HIAA to 5-HT. The biomarker has the advantages of high sensitivity and high precision, and development and utilization of the key biomarker have important value in precise diagnosis, prognosis, subsequent treatment and drug screening of sepsis encephalopathy.

The invention discloses a big data mining system based on a traditional Chinese medicine diabetes database in the technical field of big data, and the system comprises an acquisition unit and a construction unit, and the construction unit is used for obtaining the age, gender, pathogenesis, illness, traditional Chinese medicine diagnosis and traditional Chinese medicine symptom type of a patient according to the features of the patient, and obtaining the drug type according to a prescription; constructing a matrix of different drug types and the age, gender, pathogenesis, disease symptoms, traditional Chinese medicine diagnosis and traditional Chinese medicine symptom types of the patient, thereby constructing the association between the different drug types and the age, gender, pathogenesis, disease symptoms, traditional Chinese medicine diagnosis and traditional Chinese medicine symptom types of the patient, and establishing a special diabetes disease knowledge graph; an input unit; and the mining unit is used for mining required treatment drugs from the special diabetes disease knowledge map according to the age, the gender, the pathogenesis, the diseases, the traditional Chinese medicine diagnosis and the traditional Chinese medicine symptom type so as to solve the problem that in the prior art, the drug combination in the prescription is difficult to flexibly adjust according to the physique and the symptom of the patient, so that the mined prescription is relatively weak in pertinence.

The invention discloses a Zhejiang anoectochilus roxburghii polysaccharide and application thereof in preparation of cartilage injury repair medicine.The Zhejiang anoectochilus roxburghii polysaccharide is characterized in that a crude polysaccharide AZJP is extracted from the Zhejiang anoectochilus roxburghii polysaccharide through a hot water extraction method, an anion exchange column DEAE-celluse-52 and a gel permeation chromatographic column Sephadex G-200 are used for separating the AZJP, and the Zhejiang anoectochilus roxburghii homogeneous polysaccharides AZJP-1a, AZJP-2a, AZJP-2b and AZJP-2c are obtained; measuring UV (ultraviolet), IR (infrared), molecular weight, monosaccharide composition, methylated sugar residues, NMR (nuclear magnetic resonance) signals, triple helix structures, SEM (scanning electron microscope) and AFM (atomic force microscopy) surface microstructures and cartilage repair activity; the four homogeneous polysaccharides have remarkable cartilage repair activity on transgenic zebrafish, are superior to a positive drug alendronate sodium, and have application prospects in development of drugs for treating osteoarticular cartilage injuries.

The invention discloses platycodon grandiflorum inulin polysaccharide as well as a preparation method and application thereof in preparation of a medicine for treating psoriasis, the structure of the platycodon grandiflorum inulin polysaccharide is as shown in formula I, the platycodon grandiflorum inulin polysaccharide contains fructose and glucose, and the weight-average molecular weight of the platycodon grandiflorum inulin polysaccharide is 2-10KD. The platycodon grandiflorum inulin polysaccharide disclosed by the invention is remarkable in psoriasis resisting effect, safe, non-toxic and good in biocompatibility, and is expected to be developed into a novel treatment medicine for treating psoriasis. # imgabs0 #

The invention discloses an application of a benzotriazolyl piperazine compound or a salt thereof in preparation of a medicine for treating pulmonary arterial hypertension, and belongs to a new application of the benzotriazolyl piperazine compound. 3-[4-[4-(1H-benzotriazole-1-yl) butyl] piperazine-1-yl] benzisothiazole hydrochloride (PH-001) is subjected to an in-vivo animal experiment; mainly based on pharmacological experiments in a rat pulmonary arterial hypertension model induced by monocrotaline, it is found that the right ventricular systolic pressure (RVSP), the right ventricular hypertrophy index (RVHI) and the pulmonary arterial wall thickness (PAWT) of a rat are all remarkably reduced after intervention of a test sample PH-001, and the technical scheme opens up a new way for clinical application in the field of pulmonary arterial hypertension treatment. Therefore, PH symptoms and disease course development are effectively relieved, a theoretical basis is provided for clinical development, and the traditional Chinese medicine composition is expected to become a new effective treatment strategy.

To identify lipid metabolites that control Th17 cell differentiation and lipid biosynthetic enzymes involved therein, and based on that, to provide a screening method for a therapeutic agent for diseases caused by excessive Th17 cell responses.SOLUTION: Provided is 1-oleoyl-lysophosphatidylethanolamine (LPE(1-18:1)) as a lipid metabolic product that controls Th17 cell differentiation. Since LPE(1-18:1) binds to RORγt with high specificity and promotes differentiation into Th17 cells, a candidate compound for a therapeutic agent for diseases caused by excessive Th17 cell responses can be obtained by selecting a compound that inhibits the binding of LPE(1-18:1) to RORγt. Also provided are five lipid metabolic enzymes (Gpam, Gpat3, Lplat1, Pla2g12a, and Scd2) that are responsible for the biosynthesis of LPE(1-18:1) and control Th17 cell differentiation. By selecting a compound that inhibits the activity or expression of these lipid metabolic enzymes, a candidate compound for a therapeutic agent for diseases caused by excessive Th17 cell responses can be obtained.SELECTED DRAWING: None

The invention discloses design and synthesis of a series of brain-targeted ginsenoside Rg1 derivatives and application of the brain-targeted ginsenoside Rg1 derivatives in treatment of Alzheimer's disease. According to the invention, ginsenoside Rg1 and polyethylene glycol with a specific chain length are covalently linked to successfully construct the derivative capable of enhancing the penetrating power of the blood-brain barrier. The series of derivatives provided by the invention not only solve the problems of poor brain targeting and insufficient stability of natural Rg1, but also can inhibit neuroinflammation by regulating and controlling an NLRP3 / caspase-1 signal channel in an LPS-induced neuroinflammation model, and finally, the learning and memory ability is remarkably improved. The product is simple and convenient in preparation process and good in biological safety, and a new candidate compound is provided for developing a new generation of Alzheimer disease treatment medicines.

The invention discloses application of a Lys35 site of a PC4 protein as a target spot in preparation of tumor diagnosis and treatment products. The invention provides application of a Lys35 site of a PC4 protein as a target spot in preparation of a tumor diagnosis product. The research shows that the Lys35 site methylation of the PC4 protein can promote the cell cycle progress of tumor cells and promote the proliferation growth and malignant progression of the tumor cells, and the scheme for inhibiting the site methylation can be used for developing tumor treatment drugs. Therefore, the Lys35 site of the PC4 protein can be used as a key target to be applied to development of tumor diagnosis products and targeted therapy drugs. The invention further develops the PC4 protein Lys35 methylation antigen peptide and the antibody capable of specifically recognizing the PC4 protein Lys35 methylation site, and the PC4 protein Lys35 methylation antigen peptide and the antibody can be applied to regulation and control of tumor cell proliferation or growth, can be used for developing diagnostic products and targeted therapy drugs for clinical tumor diseases, and have good clinical application value.