25 results about "Microsome" patented technology

The present invention provides methods for treating patients suffering from familial hypercholesterolemia, including both HeFH and HoFH. The methods of the invention provide for lowering at least one lipid parameter in the patient by administering a therapeutically effective amount of an antibody or antigen-binding fragment thereof that specifically binds to ANGPTL3 in combination with a therapeutically effective amount of a statin, a first lipid lowering agent other than a statin, and a second lipid lowering agent other than a statin. The first non-statin lipid lowering agent is an agent that inhibits cholesterol uptake (e.g. ezetimibe) and the second non-statin lipid-lowering agent is an inhibitor of microsomal triglyceride transfer protein (e.g. lomitapide). The combination therapy is useful in treating hypercholesterolemia, as well as hyperlipidemia, hyperlipoproteinemia and dyslipidemia, including hypertriglyceridemia, chylomicronemia, and to prevent or treat diseases or disorders, for which abnormal lipid metabolism is a risk factor, such as cardiovascular diseases.

The antioxidant activity of alpha-tocopherol polyethylene glycol 1000 succinate (TPGS) and of alpha-tocopherol succinate (TS) has been examined in isolated hepatocytes and microsomal fractions from rat liver. Both TPGS and TS require esterase activity to yield free alpha-tocopherol and, hence, antioxidant activity. TPGS and TS consistently exerted a more effective antioxidant protection than an equivalent amount of directly-added free alpha-tocopherol. The low antioxidant efficiency of directly added free alpha-tocopherol in such water-based experimental systems as used here seems to be due to its extreme hydrophobicity. TPGS, on the other hand, is an extremely hydrophilic compound which is being examined as a useful source of alpha-tocopherol in certain clinical situations and is here shown to be a convenient and effective source for experimental studies into lipid peroxidation and antioxidant mechanisms.

The present invention relates to pharmaceutical composition(s) comprising particles comprising one or more compounds which are inhibitors of microsomal triglyceride transfer protein and / or apolipoprotein B (Apo B) secretion, wherein at least 50% of the particles are characterized by a volume particle fraction less than 10 μm, more preferably less than 5 μm, more preferably less than 2.5 μm. The pharmaceutical composition can be useful for the prevention and treatment of various diseases, particularly atherosclerosis and its clinical sequelae, for lowering serum lipids, and related ailments. The invention further relates to methods of treating diseases, such as hypertriglyceridemia, hyperchylomicronemia, atherosclerosis, obesity, and related conditions using the compounds. A method for decreasing apolipoprotein B (apo B) secretion is also provided.

The present application relates to a kind of ganoderma lucidum spore as carrier paclitaxel ganoderma lucidum spore oil self-nanoemulsion composite microparticle and its preparation method, belong to medical technology field.The pretreated ganoderma lucidum spore (GLS) is obtained by process screening, and it is used as drug carrier, and the paclitaxel ganoderma lucidum spore oil self-nanoemulsion (PGS) is loaded therein, and paclitaxel composite microparticle (PGS@GLS) is obtained.Release curve in vitro shows that PGS@GLS has the characteristics of slow release after reaching intestinal tract;In vivo pharmacodynamics experiment shows that PGS@GLS can significantly inhibit the development and metastasis of colorectal cancer in mice;Tumor tissue section immunofluorescence analysis shows that PGS@GLS can effectively exert the therapeutic effect on colon cancer.Paclitaxel self-nanoemulsion ganoderma lucidum spore composite microparticle promotes cancer immune cycle by inducing immunogenic cell death and immune regulation, significantly improves the treatment effect of colon cancer, and has good biological safety.

The invention provides an antiviral drug screening marker and application of a microsome triglyceride transfer protein inhibitor in preparation of an antiviral drug, and finds new application of the microsome triglyceride transfer protein inhibitor in antiviral infection for the first time compared with the prior art. Experiments prove that the expression level of the microsome triglyceride transfer protein in the process of infecting cells with vesicular stomatitis virus is remarkably increased, and the microsome triglyceride transfer protein is used as an antiviral drug screening marker. The invention provides a new target spot for the treatment of virus infection, and the lomitapide as a marketed drug has verified safety, can be quickly transformed and applied, and has a wide application prospect. The invention has broad spectrum potential of targeting host factors or being effective to various viruses (such as coronavirus and influenza virus).

FIELD: clinical gastroenterology.SUBSTANCE: intended to predict the risk of relapse of autoimmune hepatitis after discontinuation of immunosuppressive therapy. The patient undergoes a clinical and biochemical examination and the relapse risk probability index is determined using the formula: PI RR = –0.394×(IGA≥ 9) + 1.252×(AT) + 0.915×(a-SLA / LP) + 0.555×(a-LKM1) – 0.692×(IgG norm) + 0.316×(obesity), where PI RR is the prognostic index of recurrence risk; HAI is the histological activity index of more than 9 according to Knodell (binary indicator: HAI ≥ 9 corresponds to the multiplier “1”; HAI < 9 corresponds to the multiplier “0”); AB – the presence of autoantibodies (binary indicator: detection of at least 1 corresponds to the multiplier “1”; absence of autoantibodies corresponds to the multiplier “0”); a-SLA / LP – antibodies to soluble liver / kidney antigen (binary indicator: presence – corresponds to the multiplier “1”; absence – corresponds to the multiplier “0”); a-LKM1 – antibodies to liver and pancreas microsomes (binary indicator: presence corresponds to the multiplier “1”; absence corresponds to the multiplier “0”); IgG – immunoglobulin G (binary indicator: normal Ig G level corresponds to the multiplier “1”; elevated IgG level corresponds to the multiplier “0”); obesity (BMI ≥ 30) – (binary indicator: presence of BMI ≥ 30 corresponds to a multiplier of “1”; BMI < 30 corresponds to the multiplier “0”). With the value of PI RR < 0.93 – low probability of relapse, PI RR > 0.93 – high probability of relapse.EFFECT: increased accuracy in predicting the risk of recurrence of autoimmune hepatitis after discontinuation of immunosuppressive therapy.1 cl, 2 ex

The invention relates to production and application of ganoderic acid based on acetyltransferase GlAT, which comprises the following steps: transforming acetyltransferase GlAT in ganoderma lucidum into a corresponding saccharomyces cerevisiae strain for heterologous expression, and implementing heterologous biosynthesis of ganoderic acid TN (GA-TN), ganoderic acid X (GA-X) and ganoderic acid T-Q (GA-T-Q) through fermentation culture, furthermore, GlAT yeast microsomes are prepared to perform in-vitro enzymatic reaction, so that the production of ganoderic acid R (GA-R), ganoderic acid P (GA-P), ganoderic acid Mk (GA-Mk), ganoderic acid T (GA-T) and ganoderic acid T1 (GA-T1) is realized. According to the invention, acetyltransferase participating in ganoderic acid biosynthesis is excavated and identified and is subjected to heterologous expression in saccharomyces cerevisiae, and a plurality of ganoderic acid compounds are obtained through fermentation culture or microsome reaction.

A high-throughput screening for at least one ligand of at least one transmembrane protein (TP) of interest that is embedded in a lipid bilayer of at least one endogenous microsome derived from plant-based endoplasmatic reticulum (ER). The screening includes providing at least one endogenous microsome that includes at least one lipid bilayer embedded TP or at least one endogenous microsomal fragment that includes at least one lipid bilayer embedded TP, and providing at least one analyte of interest, contacting of the at least one TP with the at least one analyte and detection of interaction between the at least one analyte and the at least one TP. The screening is suitable for high multiplex grades of TPs and analytes and for a fast and reproducible identification of ligands as potential drug candidates. All essential products, consumables and kits for use in the high-throughput screening are described.

The invention discloses application of a gene expression enhancer in promotion of neuronal growth. The invention provides and verifies that the growth of neurons can be promoted by enhancing the expression of the microsome glutathione S transferase 3 gene for the first time, and the regeneration of a nervous system after injury and the recovery of sensory and motor functions are realized. The microsome glutathione S transferase 3 can be used as a new target of related drugs for diseases caused by nerve injury and neurodegenerative diseases, and has an excellent clinical application prospect.

The application provides an antiviral drug screening marker and an application of a microsomal triglyceride transfer protein inhibitor in preparation of an antiviral drug, and compared with the prior art, the application firstly finds a new use of the microsomal triglyceride transfer protein inhibitor in antiviral infection. The application proves by experiments that the expression level of the microsomal triglyceride transfer protein is significantly increased in the process of vesicular stomatitis virus infection of cells, and the microsomal triglyceride transfer protein is used as an antiviral drug screening marker. The application provides a new target for treatment of viral infection, and lomitapide is an already-marketed drug, the safety of which has been verified, can be quickly converted for application, and has wide application prospect. Moreover, the application has broad-spectrum potential: targeting a host factor, or being effective for multiple viruses (such as a coronavirus and an influenza virus).

The invention discloses a liver / mitochondria dual-targeting carboxylesterase fluorescent probe as well as a preparation method and application thereof, and belongs to the technical field of medicines. The probe is a compound LDM-CA, has the liver and mitochondria dual-targeting characteristic, and shows high selectivity, sensitivity and strong binding affinity to CEs. In-vitro cell experiments show that the LDM-CA has excellent mitochondrial targeting ability in the HCC cells and specific fluorescence opening response to CEs in the cells, and can clearly distinguish the HCC cells from normal liver cells or non-liver cancer cells. In-vivo imaging of a mouse model shows that no matter in-tumor injection or intravenous injection, the LDM-CA can effectively visualize the HCC tumor and draw the edge of the tumor, has the prospect of serving as a powerful molecular tool for early HCC diagnosis and image-guided surgery, and also provides a valuable means for studying the action of mitochondrial CEs activity in HCC pathogenesis at the subcellular level.

The present invention discloses a Hibiscus tiliaceus active ingredient compound and a preparation method thereof, belonging to the field of compound technology. The compound has the general structural formula: wherein: R1 is an alkyl group or hydrogen; R2 is a hydroxyl group, a carboxyl group, an ether bond, or hydrogen; and R3 is a hydroxyl group, a carboxyl group, an ether bond, or hydrogen. The present invention incubates tansyl in a liver microsomal incubation system, followed by silica gel column chromatography and semi-preparative high-pressure liquid separation to obtain new compounds GDX 3, named tanacetinometin A, and GDX 7-3, named tanacetinometin C.

The invention discloses a C-Met targeted proteolysis chimera for treating gastric cancer as well as a preparation method, a pharmaceutical composition and application of the C-Met targeted proteolysis chimera, belongs to the technical field of chemical medicines, and solves the druggability problems of complex preparation, low C-Met degradation efficiency, insufficient in-vivo and in-vitro antitumor activity, poor oral bioavailability, poor plasma stability and the like of an existing C-Met inhibitor. The preparation process is simple and easy to implement, the prepared proteolysis targeted chimera or the pharmaceutically acceptable salt thereof has the effect of efficiently degrading C-Met in a targeted manner, a C-Met degrading agent is obtained, and the C-Met degrading agent has high in-vivo and in-vitro anti-tumor activity; all the prepared compounds show the inhibition capability on human gastric cancer cells SNU-620 and Hs746T, and all the prepared compounds show the degradation effect on C-Met protein in the SNU-620 cells; the prepared compound liver microsome is relatively good in stability and shows certain oral bioavailability. In addition, the compound has good plasma stability and good patent medicine potential and is suitable for development of drugs for treating cancers such as gastric cancer.

The application discloses a C-Met targeted proteolysis chimera for treating gastric cancer and a preparation method, a pharmaceutical composition and application thereof, and belongs to the technical field of chemical medicines. The C-Met inhibitor preparation is complex, the C-Met degradation efficiency is low, the in-vivo and in-vitro anti-tumor activity is insufficient, the oral bioavailability is poor, and the plasma stability is poor, and the like, and the problems of the prepared medicine are solved. The preparation process is simple and easy to implement, the prepared proteolysis targeted chimera or pharmaceutically acceptable salt thereof has the effect of high-efficiency targeted degradation of C-Met, a C-Met degradation agent is obtained, and the in-vivo and in-vitro anti-tumor activity is high. All the prepared compounds show the inhibition ability on human gastric cancer cells SNU-620 and Hs746T, and show the degradation effect on C-Met protein in SNU-620 cells. The liver microsomal stability of the prepared compound is relatively good, and a certain oral bioavailability is shown. In addition, the compound has good plasma stability, has good medicine potential, and is suitable for the development of medicines for treating gastric cancer and other cancers.

The application discloses a method for synthesizing 2,2',4,5,5'-pentachloro-4-biphenyl alcohol based on a pig liver microsome incubation system, which comprises the following steps: establishing a pig liver microsome incubation system, and adding a substrate 2,2',4,5,5'-pentachlorobiphenyl; the 2,2',4,5,5'-pentachlorobiphenyl is metabolically converted by pig liver microsomes to form 2,2',4,5,5'-pentachloro-4-biphenyl alcohol; after termination of the incubation, isopropyl alcohol, dichloromethane and n-hexane are added to the incubation solution, and after oscillation and centrifugation, the organic phase is transferred and volatilized under high-temperature and reduced-pressure conditions; the 2,2',4,5,5'-pentachloro-4-biphenyl alcohol is directly converted, the lipid impurities are removed through concentrated sulfuric acid sulfonation reaction, the residual 2,2',4,5,5'-pentachlorobiphenyl is separated by using a silica gel column, and thus the purified 2,2',4,5,5'-pentachloro-4-biphenyl alcohol is obtained, and the method has the advantages of simple operation, high conversion efficiency, no interference of isomers, and high purity of target products.

The inventors have now succeeded in developing new astatoaryl compounds, as well as a method for synthesizing said astatoaryl compounds comprising the step of reacting aryl compounds carrying a leaving group with astatine. These astatoaryl compounds have the advantage of having one hydrogen bond donor in the At environment which improves stability against oxidative deastatination and a second hydrogen bond donor which further improves this stability. In particular, benzylic alcohol functions in ortho position to At successfully leads to improved stability compared to the gold standard astatobenzoate in KMnO4 solution or human and rat microsomes. The present invention relates to astatoaryl compounds, a method for synthesizing astatoaryl compounds comprising the reaction of an aryl compound carrying a leaving group with astatine. The invention also concerns a method of synthesizing an astatolabelled biomolecule and / or vector using said astatoraryl compound.

The present application relates to the technical field of biological medicine, and more particularly to the application of virus modified micro-gel electrospun scaffold in nerve injury by inducing in-situ reprogramming of fibroblasts. The present application provides a micro-gel electrospun scaffold which is modified with a polydopamine coating and grafted with a shPTB lentivirus vector; the matrix of the scaffold is prepared from brain-derived neurotrophic factor, poly-L-lactic acid and hyaluronic acid. The present application also provides a preparation method and use of the scaffold. Compared with conventional nerve injury biomaterial therapy, the micro-gel electrospun scaffold system can improve multiple characteristics such as a large number of inflammatory factors generated in the microenvironment after injury, lack of neurotrophic factors, and scar tissue proliferation.

The invention provides a C24-site hydroxylase gene CYP7140E67 of stamen eugenin C, a CYP7140E67 protein and application of the C24-site hydroxylase gene CYP7140E67 and belongs to the technical field of genes. According to the invention, the key enzyme for catalyzing hydroxylation of the C24 site of the stamen eugenin C is successfully found and identified, the blank of research on the catalytic enzyme in aesculus chinensis is filled, and a key gene and a protein coding sequence are provided for biosynthetic pathway analysis and synthetic biology research of the original aescin and derivatives thereof. Moreover, the proaescin is heterogeneously synthesized by expressing the CYP714E67 in the Bensi tobacco leaves, a living body biosynthesis system is constructed, the CYP714E67 is heterogeneously expressed by utilizing saccharomyces cerevisiae, and the in-vitro synthesis of the proaescin is realized by virtue of yeast microsomes, so that a flexible path is provided for industrial production; the problem of resource supply of aescin A is solved, and a solid foundation is laid for promoting cultivation of new varieties of high-yield plants and industrial biosynthesis.

The present invention relates to pharmaceutical composition(s) comprising particles comprising one or more compounds which are inhibitors of microsomal triglyceride transfer protein and / or apolipoprotein B (Apo B) secretion, wherein at least 50% of the particles are characterized by a volume particle fraction less than 10 μm, more preferably less than 5 μm, more preferably less than 2.5 μm. The pharmaceutical composition can be useful for the prevention and treatment of various diseases, particularly atherosclerosis and its clinical sequelae, for lowering serum lipids, and related ailments. The invention further relates to methods of treating diseases, such as hypertriglyceridemia, hyperchylomicronemia, atherosclerosis, obesity, and related conditions using the compounds. A method for decreasing apolipoprotein B (apo B) secretion is also provided.

The invention discloses an application of microsome glutathione S transferase 3 in preparation of a medicine for treating diseases caused by excessive growth of neurite. The invention provides and verifies that the microsome glutathione S-transferase 3 inhibitor can effectively inhibit the growth of neurite for the first time, and provides a new direction for research and development of drugs for treating diseases caused by excessive growth of neuronal axons of a peripheral or central nervous system.

Indole carboxamide compounds of Formula (II) or pharmaceutically acceptable salt thereof have activity of inhibiting production of prostaglandin E2 (PGE2) through inhibition of microsomal prostaglandin E2 synthase-1 (mPGES-1). The indole carboxamide compounds and salts can be effectively used in treating or preventing inflammation, arthritis, high fever, pain, cancer, stroke or brain diseases such as Alzheimer's disease. A pharmaceutical composition contains the indole carboxamide compound as an active ingredient.

The invention relates to the technical field of medicines, in particular to application of lomitapide mesylate and combination of lomitapide mesylate and gemcitabine in preparation of a medicine for treating pancreatic cancer. The invention finds that a single drug of lomitapide mesylate is screened from more than 70000 compounds and can be used for treating pancreatic cancer when being combined with gemcitabine, and verifies the in-vivo and in-vitro pancreatic cancer resisting efficacy of the lomitapide mesylate, and the lomitapide mesylate is a microsome triglyceride transporter inhibitor. The composition has been used in the treatment of familial hypercholesterolemia. The clear pharmacokinetic characteristics and safety data provide a favorable basis for the subsequent research and development of antitumor drugs.

The invention discloses a preparation method of three Venetoclax analogues and an activity research result of the three Venetoclax analogues. The three analogues are designed by replacing cyclohexene fragments in a Venetoclax structure with a bioisostere structure, namely, a tricyclic diene skeleton, a tricyclic monoene skeleton and a high cubic alkane skeleton. The invention provides a simple preparation method of the three Venetoclax analogues, raw materials used for synthesis are commercially available reagents, and a representative synthesis route is shown in the claims. Cellular level activity research shows that the three Venetoclax analogues are close to a Venetoclax standard sample in the aspects of physical and chemical properties and mouse liver microsome stability, and meanwhile, the preliminary result of the tumor inhibitory activity on HL60 cells is equivalent to that of the standard sample.

The present invention relates to microsomes bound to magnetizable beads and their use in studying or determining drug metabolism. Compositions, methods, kits and systems involving the magnetizable bead-bound microsomes are described herein.

The invention provides siRNA for inhibiting MTTP gene expression and application of the siRNA. Specifically, the invention provides siRNA, a siRNA conjugate and a pharmaceutical composition thereof for inhibiting the expression of a microsome triacylglycerol transferase (MTTP) gene, and a method for reducing the expression of the MTTP gene by using the siRNA, the siRNA conjugate and the pharmaceutical composition thereof. The siRNA, the siRNA conjugate and the pharmaceutical composition of the siRNA can be used for preventing and / or treating MTTP gene mediated diseases or symptoms.