33 results about "Ganglioside" patented technology

The application provides a toxicity-enhanced neurotoxin recombinant protein and application thereof, and belongs to the technical field of biological medicine. The recombinant protein comprises a botulinum toxin type A receptor binding domain and at least one GM1 binding peptide inserted into the botulinum toxin type A receptor binding domain, and the recombinin protein can recognize and bind to ganglioside GM1. The short peptide sequence capable of binding to ganglioside GM1 is introduced into the botulinum toxin type A receptor binding domain to obtain the recombinant protein, the binding capacity of the recombinant protein to ganglioside GM1 is enhanced, the target recognition and binding capacity of the recombinant protein to the nerve cell membrane are improved, the overall affinity and endocytosis efficiency of the recombinant protein to the nerve cell are improved, and the neurotoxicity of the botulinum toxin is enhanced. The application not only improves the binding efficiency of BoNT / A in the in-vitro nerve cell model, but also shows a higher toxicity level in the functional verification, and shows a good clinical conversion prospect.

The invention discloses application of miR-6340 in preparation of a medicine for treating cerebral ischemia. Metabolism of GM1 in MCAO / R rats and metabolism of ganglioside GM1 in microglial cells after OGD / R can be inhibited by down-regulating expression of Glb1. It is found that upstream miRNA (miR-6340) of a Glb1 protein coding gene and mir-6340 / Glb1 promote the autophagy process of microglial cells through metabolism of GM1. According to the application, a new view angle is provided for the neuroprotective effect of GM1 on OGD / R induction by reducing autophagy.

The present invention relates to the field of biotechnology and immunooncology. The invention discloses a bispecific antibody. The bispecific antibody comprises an antibody, an antibody fragment or a single-chain variable fragment for recognizing NGcGM3 ganglioside on tumor cells and an antibody, an antibody fragment or a single-chain variable fragment for recognizing a CD3 antigen on human immune effector cells. These bispecific antibodies are characterized in that they are capable of mediating selective cytotoxicity against NGcGM3-positive tumor cells, rather than normal cells capable of expressing the gangliosides, and allow recruitment of not only T lymphocytes but also NKT. The bispecific antibodies of the invention, as well as the nucleic acids encoding them, are useful for the treatment of lymphoproliferative diseases and solid tumors expressing NGcGM3.

The invention provides a method for detecting amino acid in a compound encephalokinin injection by using an LC-MS (Liquid Chromatography-Mass Spectrometry) method, which has the characteristics of simplicity and convenience in operation, and good precision, stability and recovery rate. The method can be used for detecting the content of 13 amino acids in the compound brain peptide injection, including histidine, phenylalanine, lysine, tyrosine, asparagine, methionine, valine, leucine, serine, arginine, proline, alanine and isoleucine. The detection method is high in detection sensitivity and can be applied to internal quality component research, intermediate component control and quality identification of the product. The detection method can also be used for evaluating the inherent quality of the compound encephalokinin injection, further ensuring the stability of the inherent quality of the product and providing technical reference.

This invention provides a sea cucumber ganglioside extract nanoliposome with neuroprotective activity and its preparation method. The preparation steps are as follows: thawed frozen ready-to-eat sea cucumber, chopped, freeze-dried, pulverized, and sieved to obtain freeze-dried powder. The powder is then extracted using supercritical CO2 extraction and rotary evaporation to remove the solvent. This powder is then dissolved in anhydrous ethanol with soybean lecithin and β-sitosterol as the oil phase, mixed with PBS buffer, stirred, and hydrated to obtain a proemulsion. After centrifugation, the precipitate is resuspended and sonicated to obtain the product. This invention uses supercritical CO2 extraction, and the extract contains 59.70 μg / g of gangliosides, with glycosphingolipids accounting for 96.372% of sphingolipids, resulting in enrichment of the target components. Simultaneously, these nanoliposomes significantly delay Aβ1-42-induced paralysis. The 30 μg / mL group showed a 2.75-fold increase in motor ability and a 30% increase in reproductive function compared to the control group, and a 47% reduction in ROS levels. The neuroprotective effect is superior to that of the unencapsulated extract, providing a new approach for adjuvant intervention in neurodegenerative diseases such as Alzheimer's disease, and has broad application prospects in the functional food field.

Disclosed is a single-domain antibody specifically binding to ganglioside GD2, which can specifically bind to GD2 glycan. The present application provides a single-domain antibody that can be used for targeting and / or treating several cancers (such as neuroblastoma, glioma, etc.) associated with GD2-overexpressing cells. The present application also relates to a recombinant nucleic acid sequence encoding the above-mentioned single-domain antibody, as well as an expression vector and a host cell.

This invention discloses a chimeric antigen receptor (CAR), microglia expressing the CAR differentiated from human pluripotent stem cells, and their applications. The chimeric antigen receptor CAR provided by this invention is a bisialic acid ganglioside-based chimeric antigen receptor, and its amino acid sequence is shown in SEQ ID NO.1. This invention also provides a method for preparing microglia expressing the CAR differentiated from human pluripotent stem cells, comprising the following steps: infecting human pluripotent stem cells with the lentivirus; screening for positive clones, selecting positive clones for culture and identification; differentiating the human pluripotent stem cells expressing the CAR into microglia, thereby obtaining the microglia expressing the CAR. The microglia expressing the CAR differentiated from human pluripotent stem cells provided by this invention have unique advantages such as non-immunogenicity and no immune rejection issues in human treatment.

Aspects of the disclosure relate to compositions and methods for the treatment of lysosomal storage disorders, such as GM1 gangliosidosis, Tay Sachs disease, and Sandhoff disease. In some embodiments, the compositions comprise viral vectors encoding beta-galactosidase. In some embodiments, the compositions comprise viral vectors encoding beta-hexosaminidase subunits (e.g. HEXA, HEXB, or combinations thereof).

A persistent encapsulation structure capable of preventing the degradation of bioactive substances, which encapsulation structure comprises a variety of encapsulation structure bodies (10), characterized by that the respective encapsulation structure body (10) has a polysaccharide structure (11) by which a plurality of bioactive substances (12) are encapsulated, wherein the bioactive substance (12) is selected from a group consisting of a bioactive fatty substance (121) and a bioactive non-fatty substance (122); that the polysaccharide structure (11) comprises at least one polysaccharide, wherein the at least one polysaccharide is first thoroughly mixed, then sheared at high pressure or homogenized at high speed and finally atomized dried, such that the polysaccharide structure (11) forms branched polysaccharides and linear polysaccharides which form a multitude of network structures; that the bioactive fatty substance (121) is selected from a group consisting of glycerophospholipids, sphingophospholipids, gangliosides, L-α- / glycerylphosphorylcholines, phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositol, phosphatidylserines, phosphatidic acids, phosphatidylglycerol, ceramides, glucocerebrosides, glycolipids, cholesterols and fatty acid substances; and that the bioactive nonfatty substance (122) is selected from a group of coenzymes, vitamins, carotenes, carotenoids, curcuminoids, curcumin, curcumin extract, polyphenols, saponins, glycosides, terpenoids, ergothioneine, minerals, acid substances, functional polysaccharides, carbohydrates, functional proteins, peptides, amino acids and their derivatives.

The invention provides a toxicity-enhanced neurotoxin recombinant protein and application thereof, and belongs to the technical field of biological medicines. The recombinant protein comprises an A-type botulinum toxin receptor binding domain and at least one GM1 binding peptide inserted into the A-type botulinum toxin receptor binding domain, and the recombinant protein can recognize and bind to ganglioside GM1. The oligopeptide sequence capable of being combined with the ganglioside GM1 is introduced into the A-type botulinum toxin receptor binding structural domain, and the recombinant protein is obtained, so that the combining capacity of the A-type botulinum toxin receptor binding structural domain to the ganglioside GM1 is enhanced, the targeting recognition and combining capacity of a nerve cell membrane of the A-type botulinum toxin receptor binding structural domain is further improved, the overall affinity and endocytosis efficiency of the A-type botulinum toxin receptor binding structural domain and the nerve cell membrane are improved, and the aim of treating the neurotoxin is achieved. The neurotoxicity of the carnotoxin is enhanced. According to the invention, not only is the binding efficiency of BoNT / A in an in-vitro nerve cell model improved, but also a higher toxicity level is shown in functional verification, and a good clinical transformation prospect is shown.

Provided herein is a method in which venglustat is administered to a patient with a ganglioside storage disorder, e.g. a GM2 gangliosidosis such as Sandhoff disease or Tay-Sachs disease, GM1 gangliosidosis, or sialidosis. The method is designed to reduce the levels of disease related biomarkers in the patient.

In various embodiments, provided herein are host cells, methods, and pharmaceutical compositions, including complex sphingolipids, such as monosialic acid ganglioside 1 (GM1), monosialic acid ganglioside 2 (GM2), and monosialic acid ganglioside 3 (GM3). In some embodiments, the present disclosure provides biological production of glycosphingolipids. In still further embodiments, the present disclosure provides for the biological production of gangliosides.

The invention provides a medicine for preventing and relieving Alzheimer's disease and a preparation method thereof. Comprising a capsule-shaped medicine main body, and three coatings are arranged in the capsule-shaped medicine main body and are respectively a first coating section, a second coating section and a third coating section from outside to inside; the pharmaceutical composition comprises antioxidants such as SOD, vitamin C, vitamin E and anthocyanin, nerve repairing components such as nervonic acid, ganglioside and vitamin B12 and neurotransmitter regulators such as arginine, tryptophan and asparaginic acid, can block multiple pathogenic links of the Alzheimer's disease at the same time, remarkably improves the curative effect, adopts a three-stage coating technology, and is free of toxic and side effects. According to the present invention, different components are ensured to be accurately released at the specific site and within the specific time, the mutual interference among the components is avoided, the drug activity is maximized, the ROS in the body is cleared through the SOD, the vitamin E and the like, the antioxidant activity is stabilized by the anthocyanin, the nerve cell repair is promoted by the nervonic acid and the ganglioside, and the brain function is significantly improved;

The present invention relates to a novel glycosynthase, especially an endoglycoceramide synthase, and to a method for the glycosylation of sphingolipids.

In various embodiments, host cells, methods, and pharmaceutical compositions comprising complex sphingolipids such as monosialoganglioside 1 (GM1), monosialoganglioside 2 (GM2), and monosialoganglioside 3 (GM3) are provided herein. In some embodiments, the disclosure provides the bioproduction of sphingoglycolipids. In yet another embodiment, the disclosure provides the bioproduction of gangliosides.

Provided herein is a method of stabilizing the 9-HPT, 25-FWT, and / or FARS-neuro test score (a measure of neurologic impairment) in a human subject suffering from GM1 gangliosidosis, juvenile GM2 gangliosidosis, or sialidosis. The method comprises administering to the subject an effective amount of venglustat or a pharmaceutically acceptable salt thereof.

The present invention is based on the surprising discovery that a lipid nanoparticle (LNP) bearing sialic acid residues on the surface can withstand nebulization and maintain its integrity. The invention provides an LNP composition comprising a lipid bearing, or substituted by, a sialic acid (SA) residue such as a ganglioside, a ganglioside derivative, a mimetic, a SA-bearing entity or a combination thereof. The lipid nanoparticles described herein can incorporate nucleic acid molecules, or cargos, withstanding nebulization, and delivering the cargos to the lung via a nebulization-mediated delivery. The present invention also provides methods of using the LNP compositions described herein for pharmaceutical applications. For example, the LNPs provided herein are useful for the treatment of various pulmonary diseases. The LNPs provided herein are also useful for prophylactic applications including vaccines for infectious diseases, allergies, autoimmune diseases and cancer.

The invention discloses a sphingolipid ceramide N-deacylase mutant. The mutant is formed by amino acid mutation in sphingolipid ceramide N-deacylase as shown in SEQ ID NO.1, and the amino acid mutation is selected from one or more of mutation of the 232 site Tyr, mutation of the 254 site Asn, mutation of the 416 site Phe and mutation of the 592 site Leu. The invention also discloses application of the mutant in preparation of ganglioside derivative molecules by efficient enzymatic synthesis. The stability of the sphingolipid ceramide N-deacylase SCDase mutant is improved, and the pyrolysis chain temperature Tm of the mutant is improved by 5.79 DEG C compared with that of a wild type; the sphingolipid ceramide N-deacylase SCDase mutant provided by the invention enhances the enzyme preparation efficiency of ganglioside, especially for short-chain fatty acids (carbohydrate chain length lt; and 4) the synthetic activity is improved by more than two times, and the result broadens the practical application value of the SCDase enzyme.

The present invention relates to antibodies directed against ganglioside tumor antigens which can be obtained in Phaeodactylum tricornutum, said antibodies presenting an increased FcRn affinity and an increased direct cytotoxicity activity; their uses as medicament and for cancer treatment more specifically.

The invention discloses a substance with remarkable maintenance and protection effects on brain health of old people. The substance is acidic human milk oligosaccharide, preferably comprises 6 '-sialic acid lactose, and can directly and quickly penetrate through the blood-brain barrier to enter brain cells to directionally deliver exogenous sialic acid to the brain. The composition has the key characteristics of protecting nerve cells, maintaining a cognitive function, preventing decline of cognitive ability and occurrence of cognitive impairment and relieving or treating cognitive impairment, and the cognitive ability can be remarkably improved by protecting cerebral neurons. In addition, the substance is also suitable for treating or preventing cognitive competence decline and / or disorder caused by insufficient supply or generation of sialic acid in the brain. The substance rapidly passes through the blood brain barrier, enhances brain plasticity, promotes neurodevelopment, reduces inflammatory response caused by microglial cells, and protects neuronal cells in the brain by enhancing polysialylation of nerve cell adhesion molecules on nerve cells and the expression of ganglioside, thereby enhancing the cognitive competence of the elderly.

The application discloses a blood marker combination and kit for neurodegenerative diseases of lysosome function axis, and relates to the technical field of biomedical detection. The marker combination is composed of seven markers in three categories: glucocerebrosidase and cathepsin D; sphingolipids and gangliosides; and phosphorylated tau-217 protein, neurofilament light chain protein and glial fibrillary acidic protein. The application also provides an in-vitro diagnostic kit containing specific reagents for detecting the above markers, and constructs a risk assessment model based on a logistic regression or random forest algorithm. The marker combination and kit can be used for early screening, differential diagnosis, disease progression prediction and drug efficacy monitoring of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and neurogenic Gaucher disease, and have the advantages of high sensitivity, high specificity and minimally invasive detection.

The application belongs to the technical field of biological medicine, and particularly relates to an immune liposome targeting ganglioside GD2 and mitochondria as well as a preparation method and application thereof. The application couples LX3 and thiolated daratumumab to DSPE-PEG2000 respectively to obtain DSPE-PEG2000-LX3 and DSPE-PEG2000-aGD2, and then is compounded with DSPC and cholesterol to obtain the immune liposome, which has good dispersity, excellent stability and cannot induce cytotoxicity. Cell combination and uptake analysis shows that the immune liposome can specifically target ganglioside GD2 positive tumor cells and then further reach mitochondria thereof. Compared with existing liposomes, the immune liposome provided by the application has double targeting functions of ganglioside GD2 and mitochondria, and can selectively deliver an anti-tumor drug into mitochondria of neuroblastoma cells.

An infant formula milk powder is rich in milk fat globule membrane protein, phospholipids, and oligosaccharides. A preparation method includes using raw cow milk as raw material, cleaning and pre-sterilizing raw cow milk, adding MFGM-rich whey protein powder, α-lactalbumin powder, galactooligosaccharides, polyfructoses and other ingredients into the pre-sterilized raw cow milk, and performing pre-sterilization, homogenization, sterilization, concentration, and spray drying. By means of formula adjustment, the contents of biologically active substances having special functional components such as MFGM-protein, lactoferrin, α-lactalbumin, total galactooligosaccharide, total polyfructose, sialic acid, total phospholipid, sphingomyelin, lecithin, phosphatidylserine, phosphatidylethanolamines, phosphatidylinositol, ganglioside, triglyceride and diglyceride in the infant formula milk powder are increased, thereby facilitating the colonization of probiotics in the intestinal microbiota of an infant, especially significantly enriching lactic acid bacteria in an intestinal tract, while reducing unclassified bacterial family and other miscellaneous bacteria.

The present invention relates to a liposome composition for use in a method of treating Parkinson's disease. The present invention relates to a liposome composition comprising sphingomyelin and a therapeutically effective amount of monosialotetrahexosyl ganglioside (GM1) in a lipid bilayer wherein a therapeutically effective amount of the liposome composition is administered at most every 4 days in a predominant administration manner, at least three days between each administration; preferably, the medicine is administered every 6 days at most in a main administration mode, and the time interval between every two times of administration is at least 5 days; most preferably, the medicament is administered at most every 7 days in a main administration mode, and the interval between every two administration is at least 6 days.

The invention provides ganglioside spraying equipment for catgut embedding production, and relates to the field of ganglioside spraying equipment. The ganglioside spraying equipment is characterized in that a net rack is provided with a cleaning mechanism, the cleaning mechanism comprises a water tank, the outer side of the net rack is provided with a plurality of water storage bins, each water storage bin is provided with an atomizing nozzle, the net rack is provided with a brush head, and the brush head is provided with a water inlet and a water outlet; and a plurality of slotted holes are formed in the brush head. The automatic cleaning device has the advantages that by arranging corresponding mechanisms, an automatic cleaning method is used for replacing manual operation, impurities such as ganglioside attached to the surface of the spray head can be quickly removed, the cleaning time is remarkably shortened, the production efficiency is improved, meanwhile, the physical burden of manual cleaning is avoided, the labor intensity is reduced, the consistency of the cleanliness of the spray head is ensured, and the production efficiency is improved. Therefore, the spraying uniformity of the ganglioside and the quality stability of a thread embedding product are guaranteed, and finally efficient and accurate automatic production of the nerve repairing material is achieved.

This disclosure relates to novel glycosynthase enzymes for the engineering of antibody-drug conjugates (ADCs). The enzyme variants, designated EndoSd-D232M and EndoSz-D234M, contain glycan conjugation and / or modification activity at the conserved N297 glycosylation site in the Fc region of exemplary antibodies. The glycosynthase activity of EndoSd-D232M and EndoSz-D234M was demonstrated to be applicable to various mAbs targeting various receptors, including, but not limited to, Globo H, SSEA-4, and SSEA-3 series receptors (OBI-888; Globo H ganglioside), Herceptin (Her 2 receptor), Perjeta (Her 2 receptor), and Vectibix (EGFR receptor). Both mAb-GlcNAc and mAb-GlucNAc(F) were found to be suitable substrates for EndoSd-D232M and EndoSz-D234M.

The invention relates to a method for improving the detection sensitivity of ganglioside GM1, which comprises the following steps: S1, diluting GM1 recombinant protein by using a coating solution, spraying the diluted GM1 recombinant protein on a nitrocellulose membrane, and drying; s2, carrying out sealing treatment on the nitrocellulose membrane by adopting a sealing solution, and cutting to form a detection membrane strip; s3, carrying out sample incubation on the detection membrane strip and a sample together, cleaning, adding an enzyme conjugate for incubation, adding a substrate for incubation, and carrying out result judgment in a result judgment template; by optimizing the pH value of the coating liquid and adding the modified trehalose, carboxymethyl cellulose and beta-cyclodextrin, the stability and binding efficiency of the recombinant protein on the nitrocellulose membrane are improved. Experimental data show that the positive coincidence rate is increased to 96% from 88% of a conventional method.

The invention relates to the field of analytical chemistry and the field of lipidomics research, in particular to a method for omics analysis of acidic glycosphingolipids in animal brain tissues. The group analysis method comprises the following steps: firstly, extracting ganglioside and thioglycoside from animal brain tissues, carrying out C18 solid-phase extraction and enrichment, then carrying out qualitative analysis by using Nano-LC-Chip-Q-TOF-MS, carrying out analysis in combination with a QSRR model, and then carrying out quantitative analysis by using Nano-LC-Chip-QQQ-MS. The group analysis method is based on a Chip technology, combines C18 solid-phase extraction segmented enrichment and a QSRR model, greatly avoids ion inhibition and signal interference, has high resolution, high sensitivity and high accuracy, can accurately distinguish isomeride and same-weight elements, remarkably improves the detection efficiency and the structural identification and unknown substance prediction and quantification capability, and has a good application prospect. The defects of low-abundance component loss, narrow dynamic range and the like in the prior art are overcome.

Highly pure, highly homogeneous ganglioside compositions are provided in addition to methods of making and using these compositions. An exemplary ganglioside composition is a GM1 composition.

The invention provides a nasal-absorbed stem cell exosome preparation and a preparation method thereof, the nasal-absorbed stem cell exosome preparation comprises an exosome and a matrix solution, and the matrix solution comprises 0.9% of sodium chloride injection, 5-10% of human serum albumin, 10-20% of dextran 40 glucose injection, 20-30% of glycerin fructose sodium chloride injection, 20-50 [mu] g / ml of ganglioside sodium and 4-8 [mu] g / ml of edaravone injection. The stem cell exosome preparation prepared from the stem cell exosome and the matrix solution can be preserved at-20 DEG C for 12 months, and can be preserved at 2-8 DEG C for 15 days after thawing, the number of the exosomes, surface protein expression and the form of vesicles can be well maintained, and the stem cell exosome preparation is clear and safe in component. Exosome administration is carried out through nasal mucosa to enter brain tissue parts, endogenous neural stem cells of organisms are activated and nourished, a regeneration microenvironment is established, nerve injury repair is promoted, and the exosome is used for preventing, treating and improving cognitive impairment and traumatic brain injury of senile dementia. The preparation is simple and convenient to prepare, small in toxic and side effects and convenient to dose.