14 results about "Microsome" patented technology

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.

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 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 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 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.

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.