88 results about "Botulinum neurotoxin" patented technology

The invention discloses a detection method for B-type botulinum neurotoxin and application. The method disclosed by the invention is short in detection time, high in sensitivity as a qualitative detection method, capable of reaching a pictogram level, and obvious in detection advantage on trace toxin samples. Compared with an animal method using antiserum detection, the monoclonal antibody has high detection specificity, is beneficial to accurate decision-making when being used for scientific research detection and food hygiene inspection, and has small error compared with the animal method. In addition, the produced botulinum neurotoxin double-antibody sandwich reaction characteristic peak can be used for stability detection of botulinum neurotoxin, and plays a role which cannot be replaced by other methods in botulinum toxin product production, quality control, new product research and development, quality control and monitoring of standard substances for verification and market supervision. Therefore, the method can be used for guiding establishment of toxin immunodetection standard substances and promoting a capillary immunodetection technology to become a novel botulinum toxin detection standard method.

The present application provides stable peptide-based Botulinum neurotoxin (BoNT) serotype A capture agents and methods of use as detection and diagnosis agents and in the treatment of diseases and disorders. The application further provides methods of manufacturing BoNT serotype A capture agents using iterative on-bead in situ click chemistry.

The invention discloses a detection kit and a detection method for B-type botulinum neurotoxin. According to the method, qualitative detection of various suspected botulinum neurotoxin poisoning cases can be completed in a short time, evidence support is provided for assisting doctors in diagnosis and timely performing treatment decision making, and the method has important significance in the aspect of social health safety. Meanwhile, the detection method disclosed by the invention can be used for remarkably improving the specificity of toxin protein, avoiding the problem of long time and the like caused by animal experiments such as serotype identification and the like, and can be applied to research, development and production processes of botulinum neurotoxin products. In addition, quality control can be carried out on the stability, the shelf life and the like of the botulinum neurotoxin standard substance.

The invention relates to the field of botulinum toxin analysis, in particular to an anti-botulinum toxin antibody HPCE fingerprint construction method and application thereof.According to the method, a capillary immunoelectrophoresis reaction is carried out on botulinum neurotoxin, and a capillary immunoelectrophoresis reaction is carried out on each subunit of a botulinum toxin compound. The capillary immunoelectrophoretogram of the botulinum neurotoxin and the capillary immunoelectrophoretogram of each subunit of the botulinum toxin compound are obtained, the spectrograms obtained through the method can be compared with botulinum toxin compound detection, and the detection precision of the botulinum toxin compound is improved to the pg level.

Serotype E botulinum neurotoxin (BoNT / E) is one of the major causes of human botulism and paradoxically also a promising therapeutic agent. However, the molecular mechanism by which BoNT / E recognizes synaptic vesicle glycoprotein 2A (SV2.A) and 2B (SV2B), but no closely related SV2C, as its neuronal receptors has been challenging to resolve. The Inventor, surprisingly, was able to obtain crystal structures of the receptor-binding domain of BoNT / E (HCE) in complex with SV2.A. These structures reveal that HCE engages both specific peptide fragments and an N-glycan of SV2A, as well as SV2B in a similar manner. Structure-based mutagenesis and functional studies demonstrate that both the peptide- and glycan-based associations are essential for SV2A / 2B-mediated cell entry of BoNT / E and for its potent neurotoxicity. Thus, the engineering of BoNT / E variants for new clinical applications is described herein.

The present invention relates to aqueous saline solutions comprising dantrolene and optionally at least one additional active ingredient, such as botulinum neurotoxin, and their use for various therapeutic and / or aesthetic purposes. The solutions can be administered in any suitable manner, but have the advantage of being particularly well-suited for intramuscular injection.

The present invention relates to a method for preparing a composition comprising (A) a cross-linked material comprising one or more polysaccharide moieties covalently cross-linked with each other through ester bonds using one or more triazine-based activating agents, and (B) at least one botulinum toxin. Furthermore, the present invention relates to the composition obtainable by said method, and therapeutic and aesthetic uses of such composition.

The present invention relates to a novel alternative material to botulinum neurotoxin and a method for producing the same, specifically, to a myricetin acetyl derivative that has a dramatically improved stability of the substance, including stability in the body, and has the ability to inhibit the formation of the SNARE complex and thereby inhibit acetylcholine secretion, and a method for producing the same.

The present invention relates to methods of treating headache disorders with Botulinum neurotoxin type A (BoNT / A).

The present invention relates to aqueous compositions comprising dantrolene and optionally also at least one additional active principle, such as botulinum neurotoxin, and their use for various therapeutic and / or aesthetic / cosmetic purposes. The compositions can be administered in any suitable way but are advantageous in that they are particularly well adapted to intramuscular injection, subcutaneous injection and / or intradermal injection.

The present invention discloses a detection kit and a detection method for type B botulinum neurotoxin. The present invention can complete qualitative detection of various suspected cases of botulinum neurotoxin poisoning in a short time, provide evidence support for assisting doctors in diagnosis and timely treatment decisions, and is of great significance in social health and safety. At the same time, the detection method of the present invention can significantly improve the specificity of toxin proteins, avoid the time problems caused by animal experiments such as serotype identification, and can be applied to the research and development and production process of botulinum neurotoxin products. In addition, the present invention can perform quality control on the stability and shelf life of botulinum neurotoxin standards.

Products, pharmaceutical compositions, methods of use, and kits are provided for treating a patient suffering from botulinum neurotoxin intoxication. Featured are single-domain variable heavy-chain (VHH) polypeptides (antibodies) that target and neutralize the light chain (LC) protease domains of botulinum neurotoxin (BoNT), i.e., BoNT LC / A and BoNT LC / B, and that advantageously provide late and post-exposure therapy for botulism patients. The LC / A toxin-binding and LC / B toxin-binding VHH polypeptides, which can be recombinantly produced, specifically bind to the LCs of the botulinum neurotoxins to inhibit toxin activity and treat intoxication.

Compositions and methods for improved cell-based methods of characterizing botulinum neurotoxins are provided. Cells utilized in these methods include a reporting construct that is cleaved following uptake and processing of botulinum neurotoxin by the cell, resulting in proteolysis of the portion of the reporting construct that is released following cleavage. The released portion includes a fluorophore and amino acid substitutions or sequences that enhance the rate of proteolysis. A pair of reporting constructs can be utilized in which one member of the pair is modified to resist cleavage by the botulinum neurotoxin while co-localizing with the remaining member of the pair.

Disclosed herein are methods of treatment of moderate to severe and very severe glabellar lines and lateral canthal lines using liquid botulinum neurotoxin compositions. Also disclosed are liquid compositions of botulinum neurotoxin.

Form-specific cell based assays for the characterization of Clostridia botulinum neurotoxins and genetically modified cells utilized in such assays are described. Such assays and genetically modified cells can discriminate between complexed and non-complexed forms of botulinum neurotoxin having the same serotype, for example serotype E. Methods are also provided for generating and identifying cell lines that can be utilized in such cell based assays.

The present invention is directed to a modified botulinum neurotoxin A (BoNT / A) for use in treating a facial dystonia, including blepharospasm and hemifacial spasm, wherein the unit dose of the modified BoNT / A is greater than 240 pg (or greater than 8000 pg) of modified BoNT / A, wherein the modified BoNT / A is administered by intramuscular injection to an affected muscle of a subject, wherein the total dose administered during the treatment is greater than 24,000 pg (or greater than 82500 pg) and up to 264,000 pg (e.g. up to 240,000 pg) of the modified BoNT / A, and wherein the modified BoNT / A comprises a BoNT / A light- chain and translocation domain (HN), and a BoNT / B receptor binding domain (Hc domain).

The present disclosure relates to a botulinum toxin composition which has an effect of reduced diffusion and / or an effect of extended duration.

The present invention is directed inter alia to the treatment of pain. For example, there is provided a chimeric clostridial neurotoxin for use in treating pain by inhibiting the release of a pain mediator from a neuron comprising an Aδ nerve fiber or a C nerve fiber, wherein the chimeric clostridial neurotoxin binds to the neuron comprising the Aδ nerve fiber or the C nerve fiber, respectively, and wherein the chimeric clostridial neurotoxin comprises a botulinum neurotoxin A (BoNT / A) light-chain and translocation domain (HN domain), and a BoNT / B receptor binding domain (HC domain). Also provided are methods, uses, kits, and unit dosage forms.

Provided are a composition for stabilizing botulinum neurotoxin, a botulinum neurotoxin formulation including the same, and a polypeptide for use therein.

Methods for the isolation and purification of a botulinum neurotoxin protein (BONT) or a polypeptide comprising a BONT receptor-binding domain from a solution are disclosed here. The method comprises contacting the solution containing the protein or polypeptide with a matrix bound to it by a non-toxic non-hemagglutinin (NTNHA) under appropriate conditions for binding, washing the matrix to remove unbound materials, and eluting the protein or polypeptide with a solution that dissociates the bound protein from the NTNHA. Appropriate conditions for binding are a pH less than 7.5 (e.g., 6). Appropriate conditions for dissociation are a pH greater than or equal to 7.5 (e.g., 8). Specific compositions for the methods are also described.

The present invention is directed inter alia to the treatment of pain. For example, there is provided a chimeric clostridial neurotoxin for use in treating pain by inhibiting release of a pain mediator from a neuron comprising an Aδ nerve fiber or a C nerve fiber, wherein the chimeric clostridial neurotoxin binds to the neuron comprising the Aδ nerve fiber or the C nerve fiber, respectively, and wherein the chimeric clostridial neurotoxin comprises a botulinum neurotoxin A (BoNT / A) light-chain and translocation domain (HN domain), and a BoNT / B receptor binding domain (HC domain). Also provided are methods, uses, kits, and unit dosage forms.

The invention relates to the technical field of bioengineering, in particular to recombinant botulinum toxin and a preparation method thereof. The nucleotide sequence of the coding gene of the recombinant botulinum neurotoxin is as shown in SEQ ID NO: 1; the amino acid sequence of the toxin is as shown in SEQ ID NO: 2. The clostridium botulinum neurotoxin sequence optimization method realizes soluble expression of clostridium botulinum neurotoxin protein by escherichia coli; meanwhile, the purity of the botulinum neurotoxin protein is improved by a novel purification process technology, and the double-chain botulinum neurotoxin with relatively high biological activity is obtained; according to the method, the process operation steps of the botulinum neurotoxin are reduced, the biological safety risk is remarkably reduced, industrial production amplification of the botulinum neurotoxin is facilitated, a solid foundation is provided for large-scale production of the botulinum neurotoxin, and the method can be effectively applied to preparation of medical, beauty and health-care products.

A botulinum neurotoxin serotype E (BoNT / E) for use in treating a disorder or a cosmetic condition, wherein the BoNT / E provides a maximum inhibition of neurotransmitter secretion from a target cell or tissue 13 days or less after administration to a human subject and the inhibition is reduced but is greater than 25% at day 14 following administration. A method for treating a disorder or a cosmetic condition, the method comprising administering the aforementioned BoNT / E.

Disclosed herein are compositions and methods for therapeutic procedures. The use of "fast-acting" botulinum toxins for cosmetic treatments and / or to prevent or reduce scarring. "Fast-acting" refers to botulinum toxins that produce effects in patients more quickly than effects produced by, for example, botulinum neurotoxin type A. "Fast-acting" botulinum toxins, such as botulinum neurotoxin type E.

The present invention is directed to a modified botulinum neurotoxin A (BoNT / A) for use in treating a facial dystonia, including blepharospasm and hemifacial spasm, wherein the unit dose of the modified BoNT / A is at least 240 pg of modified BoNT / A, wherein the modified BoNT / A is administered by intramuscular injection to an affected muscle of a subject, wherein the total dose administered during the treatment is greater than 24,000 pg and up to 82,500 pg (e.g. up to 75,000 pg) of the modified BoNT / A, and wherein the modified BoNT / A comprises a BoNT / A light-chain and translocation domain (HN), and a BoNT / B receptor binding domain (HC domain).

This invention provides libraries of Botulinum neurotoxin A (BoNT / A) protease variants for stepwise evolution of the enzyme to generate BoNT / A variants that can specifically cleave a desired cleavage site in a target protein. Related methods for performing stepwise evolution of BoNT / A with the BoNT / A variant libraries and simultaneous stepwise evolution of a desired substrate sequence in a target protein are also provided by the disclosure. Additionally provided in the disclosure are specifically evolved BoNT / A variant enzymes and conjugate proteins that specifically degrade intrinsically disordered proteins (IDPs) that are involved in human deceases, e.g., a-Synuclein. Polynucleotide sequences encoding the engineered BoNT / A proteases, expression vectors and related pharmaceutical compositions are also provided in this disclosure. Further encompassed by the invention are therapeutic methods that utilize the engineered BoNT / A enzymes in the treatment of various synucleinopathies.

The present invention discloses a detection method and application for type B botulinum neurotoxin. The method of the present invention has a short detection time and is highly sensitive as a qualitative detection method, reaching the picogram level, and has obvious advantages in detecting trace toxin samples. Compared with the animal method using antiserum detection, the use of monoclonal antibodies has high detection specificity, which is conducive to accurate decision-making whether it is used for scientific research detection and food hygiene inspection, and has a small error compared to the animal method. In addition, the characteristic peak of the botulinum neurotoxin double antibody sandwich reaction produced by the present invention can be used for the stability detection of botulinum neurotoxin, and plays a role that cannot be replaced by other methods in the production of botulinum toxin products, quality control, new product development, quality control and monitoring of calibration standards, and market supervision. Therefore, the present invention can be used to guide the establishment of toxin immunoassay standard substances and promote capillary immunoassay technology to become a new standard method for botulinum toxin detection.

Provided herein are solid compositions comprising Clostridium botulinum neurotoxin serotype A (BoNT / A) and human serum albumin (HSA), wherein the solid compositions comprise a low amount of HSA aggregates. Further provided herein are methods of producing solid compositions comprising BoNT / A and HSA by drying a solution comprising BoNT / A in a manner such that the solution does not undergo freezing during drying.

The present invention relates to a novel botulinum neurotoxin (BoNT) Heavy Chain Binding domain (He / TAB) adapted to synergistically bind to a synaptotagmin (Syt) receptor, a synaptic associated vesicle 2 (SV2) receptor and a ganglioside (Gang) receptor, as well as polypeptides comprising said novel He / TAB, vectors encoding said polypeptides, and uses thereof.