89 results about "Neurotoxin" patented technology

The invention discloses a method for predicting peripheral neurotoxicity induced by treatment of colorectal cancer through oxaliplatin, and relates to the technical field of drug application, and the method comprises the following steps: obtaining pre-drug patient information before treatment of a patient with oxaliplatin and clinical feature data after use; processing and feature analysis are carried out based on pre-drug patient information and clinical feature data, and a core feature data set related to neurotoxin is determined; and based on the core feature data set, predicting the oxaliplatin-induced peripheral neurotoxicity of the patient by adopting a pre-trained gradient boosting decision tree model, and outputting a prediction risk result. According to the method, the occurrence risk of peripheral neurotoxicity can be accurately predicted according to clinical indexes so as to guide clinical accurate medication.

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 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 is directed to cell-free methods, such as those for determining the clostridial neurotoxin activity of a composition, determining whether or not a composition comprises clostridial neurotoxin polypeptides, and / or determining whether or not clostridial neurotoxin polypeptides or portions thereof comprised in a composition comprise an activity-altering property. The invention is also directed to an isolated capture substrate for a clostridial neurotoxin, use of the same, therapeutic or cosmetic clostridial neurotoxin compositions, and methods for producing the same.

The application belongs to the technical field of pesticide mite-killing, and discloses a mite-killing composition and application thereof, wherein the mite-killing composition comprises active ingredient A and active ingredient B; the active ingredient A is a compound shown in formula I; and the active ingredient B is selected from any one of a mitochondrial respiration inhibitor mite-killing agent, a growth inhibitor mite-killing agent, a neurotoxin mite-killing agent and other mite-killing agents. The mite-killing composition has obvious synergistic effect, has good control effect on common leaf mite family harmful mites of crops, can effectively control the harm of mite pests, reduces the use dose of pesticides and reduces the cost of agricultural production.

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 is directed to cell-free methods, such as methods for determining the clostridial neurotoxin activity of a composition, determining whether a composition contains a clostridial neurotoxin polypeptide, and / or determining whether a clostridial neurotoxin polypeptide or portion thereof contained in a composition contains an activity-altering characteristic. The present invention is also directed to isolated capture substrates for clostridial neurotoxins, uses thereof, therapeutic or cosmetic clostridial neurotoxin compositions, and methods for making same.

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.

This invention provides a method for producing Clostridium neurotoxins containing an exogenous activation loop, modified Clostridium neurotoxins, and pharmaceutical compositions. [Solution] A method for proteolytically processing a single-chain Clostridium neurotoxin into a corresponding double-chain Clostridium neurotoxin, comprising: providing a single-chain Clostridium neurotoxin; and contacting the single-chain Clostridium neurotoxin with enterokinase or factor Xa, wherein the single-chain Clostridium neurotoxin has the polypeptide sequence Cys-(Xaa) a -Ile-Asp / Glu-Gly-Arg-(Yaa) b - A method in which an activation loop containing Cys (SEQ ID NO: 1) is present, a=1 to 10, b=4 to 15, and enterokinase or factor Xa hydrolyzes the peptide bond of the activation loop, thereby producing a double-stranded Clostridium neurotoxin.

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.

The present disclosure relates to methods of producing a 900 kDa BoNT / A complex, wherein the method does not comprise a step of precipitation during the purification process. Further provided herein are methods of preparing a Clostridium botulinum working cell bank (WCB).

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 invention relates to a spider neurotoxin tail peptide with a cell transmembrane function and application of the spider neurotoxin tail peptide. The amino acid sequence of the spider neurotoxin tail peptide with the cell penetrating function is as shown in SEQ ID NO: 2. The invention also provides application of the cell-penetrating peptide in preparation of a carrier which is used for delivering bioactive molecules and can penetrate cell membranes. The invention further provides a fusion protein composed of the spider neurotoxin tail peptide and spider neurotoxin omega-Pp1b and application of the fusion protein in preparation of insecticides. The invention also provides an amphiphilic peptide and application thereof in preparation of a carrier which is used for delivering bioactive molecules and can penetrate through a cell membrane. The invention also provides a nano-composite and application of the nano-composite in preparation of a preparation for insect cell gene silencing. The invention also provides a pesticide composition. The invention is a novel cell-penetrating peptide derived from an insect system, and has important significance for promoting the development of peptide biological insecticides and RNA pesticides.

The present invention relates to a pharmaceutical composition. The pharmaceutical composition comprises cobra cardiotoxin (CDX) and a pharmaceutically acceptable carrier thereof. The pharmaceutical composition is further characterized by comprising use of cobra cardiotoxin (CDX) in combination with any one or both of the following drugs for treating migraine: cobra phospholipase A2 (PLA2) and cobra neurotoxin (NTX). The pharmaceutical composition can be used for preventing and treating migraine and down-regulating the concentration of nitric oxide (NO) in migraine patients. The pharmaceutical composition is of great significance for the treatment of migraine.

The present application relates to the field of biopharmaceuticals and specifically provides a neurotoxin-containing freeze-dried powder and a nasal formulation. The freeze-dried powder comprises a neurotoxin, and further comprises a stabilizer and an excipient. The excipient comprises one or more of acidic gelatin, alkaline gelatin, and sucrose. The stabilizer comprises one or more of block polyether F-68, block polyether F-127, and Tween 80. The use of the stabilizer comprising one or more of block polyether F-68, block polyether F-127, and Tween 80 and the excipient comprising one or more of acidic gelatin, alkaline gelatin, and sucrose produces a synergistic effect, such that the stability of the neurotoxin at room temperature is significantly improved, thereby slowing down the degradation of the neurotoxin, and significantly extending the period during which the bioactivity of the neurotoxin is maintained at 95% or higher. Moreover, the formulation can be nasally administered to increase the delivery of the neurotoxin across the blood-brain barrier and greatly reduce the toxicity.

Present invention relates to a method of treating a disorder by administering an effective amount of a pharmaceutical composition comprising a therapeutic agent bound to a p80 neurotoxin associated polypeptide (NAP) derived from Clostridium Botulinum Type E (BoNT / E). The p80 is bound to a therapeutic agent, comprising one or more of: drugs, dyes, small molecules, biomolecules, proteins or a combination thereof. P80 enhances the transportation of the therapeutic agent into the bloodstream for increased bioavailability because thep80 is a tight junction modulator to enhance the permeability of the intestinal epithelium so as to facilitate drug delivery.

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.

The present invention relates to a nucleic acid molecule for modulating neuromuscular transmission, said nucleic acid molecule comprising a sequence encoding one or more motor endplate receptors or fragments thereof. The present invention further relates to a fusion protein, preferably comprising one or more features of one or more of the foregoing Claims, said fusion protein comprising a motor endplate receptor and / or fragments thereof, wherein said motor endplate receptor is an acetylcholine receptor (AChR), a muscle-specific tyrosine kinase (MuSK) receptor, and / or a glutamate receptor, and / or fragments thereof, and / or a neurotoxin, wherein said neurotoxin is botulinum toxin (BoNT) and / or tetanus toxin.

The application discloses a Parkinson's disease model animal, a method for establishing the Parkinson's disease model animal, and application of the Parkinson's disease model animal. In the Parkinson's disease model animal, a mouse Citrobacter rodentium (C.R) and / or a dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3.6-tetrahydropyridine (MPTP) is given to the animal. The phenotype of the Parkinson's disease model animal is stable, and the Parkinson's disease model animal can be used for researching the pathology of Parkinson's disease and screening and developing a therapeutic drug for Parkinson's disease caused by intestinal infection.

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

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.

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.

To provide means for inactivating intrinsic toxicity of tetanus toxin and producing safe and effective vaccines.SOLUTION: Provided herein are engineered non-catalytic, non-toxic tetanus toxin variants and methods of using such engineered tetanus toxin variants as low dose, protective vaccines that are non-toxic and more potent than their respective chemically inactivated toxoids. In addition, provided herein are conjugate-vaccine carriers comprising engineered tetanus toxin variants and methods of using such conjugate-vaccines to elicit T-cell dependent immune memory responses which can target a broad spectrum of microbial pathogens as a single vaccine.SELECTED DRAWING: Figure 1

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.

As botulinum toxin has recently been attempted as a therapeutic agent for various indications, the demand for botulinum toxin in the medical and cosmetic fields has rapidly increased. However, there is no stable and highly reproducible cell-based assay method for measuring the potency of botulinum toxin. Since botulinum toxin is a very potent neurotoxin protein, the development of highly specific and sensitive cells is particularly required for accurate cell-based measurement of the potency of botulinum toxin. The present invention is directed to a neuronal cell line with altered gene expression. The transformed cell line according to the present invention has significantly increased sensitivity to botulinum toxin, and thus is expected to be very effectively used for cell-based determination of botulinum toxin activity or cell-based detection of botulinum toxin.

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.