88 results about "Botulinum toxin" patented technology

The invention provides a preparation method, application and the like of large intestine expression recombinant A-type botulinum toxin (BONT / A). The recombinant BONT / A nucleic acid expression cassette comprises a tag, a restriction enzyme cutting site and a BONT / A nucleic acid sequence, and an exogenous protease recognition site is not introduced between a BONT / A light chain and a BONT / A heavy chain. The invention also provides a recombinant vector containing the nucleic acid expression cassette, a recombinant bacterium, a coded and expressed protein and the like, the prepared recombinant BONT / A does not introduce exogenous amino acid or only introduces two amino acids at one position, and the consistency of the recombinant BONT / A with the natural A-type botulinum toxin is ensured to the greatest extent. Through novel molecular design and preparation process, the recombinant reBONT / A with higher toxicity and low immunogenicity is efficiently obtained, and wide industrial application is facilitated.

Aspects of the disclosure relate to Botulinum toxin X (BoNT X) protein variants. The variants provided herein have been evolved to cleave GTP cyclohydrolase 1 (GCH1). Some of the variants provided herein were evolved from a procaspase-1 cleaving polypeptide. Further aspects of the disclosure relate to nucleic acids encoding the GCH1 cleaving polypeptides described herein and expression vectors comprising the nucleic acids, as well as host cells and fusion proteins comprising the GCH1 cleaving polypeptides described herein, and kits comprising the GCH1 polypeptides, fusion proteins, nucleic acids, expression vectors, or host cells described herein. Further aspects of the disclosure relate to methods of producing BoNT X variants and methods of using the BoNT X protein variants, for example, to reduce pain.

The present invention provides a botulinum toxin protein composition, mainly comprising botulinum toxin protein, a saccharide, a salt, and human serum albumin. The botulinum toxin protein composition of the present invention features good activity and stable properties, and can maintain the activity of the botulinum toxin protein at a high level after long-term storage.

The invention provides a method for improving the expression level of a meat toxin light chain. The method comprises the following steps: connecting a dissolution-promoting tag to an N end or a C end of meat toxin light chain protein to form soluble meat toxin light chain recombinant protein; the dissolution-promoting tag is a wild dissolution-promoting tag NT11 or a mutant protein mut7 of the wild dissolution-promoting tag NT11, enzyme digestion removal is not needed, the activity of a meat toxin light chain is hardly influenced and interfered, and the fusion protein can keep 93% of substrate enzyme digestion activity. The method further comprises overexpressing a molecular chaperone htpG in the genome of the host bacterium. According to the invention, a BoNT / A-LC high-efficiency expression system is constructed through multi-strategy optimization, so that the yield of BoNT / A-LC is increased by nearly 20% compared with that of wild type NT11-Lc, the yield reaches 647 mg / L through overexpression of a molecular chaperone htpG, and after combinatorial optimization, the yield is 8.5 times that of only expressed BoNT / A Lc, 1.79 times that of NT11-Lc and 1.43 times that of Mut7-Lc.

The present disclosure relates to a composition comprising a recombinant botulinum toxin protein with improved stability. The composition according to the present disclosure comprises a sugar alcohol as a stabilizer. More specifically, the present disclosure provides a composition comprising a botulinum toxin type A light chain protein or a functional fragment thereof, and comprising, as a stabilizer, a sugar alcohol having six or fewer carbon atoms and / or a solubility in water of 150 mg / mL or more at 20°C. The composition of the present invention can achieve the effect of maintaining the biological activity of the recombinant botulinum toxin light chain protein at a usable level while sufficiently ensuring the stability of the botulinum toxin protein through the stabilizer.

The invention discloses a precise regulation and control injection device for extraocular muscle toxin, and belongs to the technical field of medical instruments. The precise regulation and control injection device for extraocular muscle toxin comprises a microneedle assembly, a handle, a suction head and an injection regulation and control part, wherein the injection regulation and control part is used for controlling the microneedle assembly to be connected with the suction head. When the precise regulation and control injection device for the extraocular muscle toxin is used, the micro-needle assembly can be in suction connection with the suction head arranged at the tail end of the handle through adjustment of the injection regulation and control part, so that in the process that an operator injects the extraocular muscle toxin to a patient, it is ensured that a micro-needle does not deviate or loosen in the injection process, and the injection efficiency is improved. The precise positioning of an injection part is ensured; and the injection regulation and control part can regulate the action range of the microneedle on the microneedle assembly to be more concentrated, so that the concentration of the action range of the medicine and the accurate delivery of the medicine to the target muscle layer can be ensured, the out-of-control diffusion of the medicine is avoided, and the risk of penetrating through the sclera is reduced.

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 liquid formulation containing botulinum toxin and stabilizing agent, and preparation method therefor. A liquid formulation containing botulinum toxin and stabilizing agent according to the present invention be can easily store and distribute. AND it was proved a significant effect on the stabilization of botulinum toxin under suitable conditions according to the temperature and pH of the human body. Thus, it is expected that the pharmaceutical composition of the present invention will greatly contribute to the safe and convenient medical use of botulinum toxin.

The invention relates to the technical field of biological medicines, in particular to a botulinum toxin protective agent and a preparation method of a botulinum toxin freeze-drying preparation. The non-protein botulinum toxin protective agent is characterized by comprising the following components: a polypeptide polymer containing an RGD (arginine-glycine-aspartic acid) sequence and having a mass volume concentration of 0.001%-0.005%; a non-reducing disaccharide having a mass volume concentration of 5%-15%; a nonionic surfactant with a mass volume concentration of 0.01% to 0.1%; the buffer agent with the mmol concentration of 5-25mM is used as the buffer agent; and the balance of water. According to the botulinum toxin protective agent disclosed by the invention, a botulinum toxin freeze-drying preparation can be stably stored for at least 18 months under the condition of 4 DEG C; the redissolved botulinum toxin solution can be stably stored for at least 14 days at 4 DEG C, so that the freezing storage stability of the botulinum toxin is remarkably improved, the safety is higher, and the use is more convenient.

The present invention relates to a composition comprising (A) a crosslinked material comprising one or more silk fibroin moieties and one or more polysaccharide moieties covalently bound to each other, (B) a botulinum toxin. Furthermore, the present invention relates to therapeutic and cosmetic uses of such a composition.

To provide a method for treating a subject in need of treatment, the method comprising administering a large agent (for example, a biologically active large agent, such as a biologic therapeutic, for example, botulinum toxin) to the subject.SOLUTION: A method of treating a subject in need of treatment is provided, the method comprising a step of administering, in combination with microneedle skin conditioning (MSC), a plurality of doses of a composition that delivers a large agent having a molecular weight of 100,000 Da or greater to a site on skin of the subject according to a dosing regimen in which at least two successive doses are separated from one another by a time period of at least one month.SELECTED DRAWING: None

Provided are a botulinum toxin stabilization composition, a botulinum toxin preparation containing the same, and a polypeptide for use therein.

The present technology relates to commercial-scale methods for purifying botulinum toxin compositions obtained from cell cultures. Purification methods according to the present disclosure are based on a series of filtration and chromatographic separation steps that produce a high-purity botulinum toxin composition, which comprises botulinum toxin protein molecules (˜150 kDa) in solution, which is free, essentially free, or substantially free of botulinum toxin complexes and animal products, and without precipitating or lyophilizing botulinum toxin protein molecules. The purification method according to the present disclosure uses no precipitation, lyophilization, or centrifugation steps, permitting production of highly pure, highly active, free botulinum toxin protein molecules (˜150 kDa) in solution, without the need for reconstitution by the end user.

A method for injection of drugs into a patient, the method including a) marking on a skin of the patient indicators to identify locations for drug injections: b) taking an image of the skin with the markings thereon; c) after obtaining a customized cover with openings in the cover, inserting a marking device through the openings to mark the skin for injection locations.

The present invention provides a botulinum toxin pre-filled syringe dosage form which is easy to control the discharge speed and is stable.

The present invention relates to a method for purifying botulinum toxin (BTX). More specifically, the method is performed in the order of purification steps using cation exchange chromatography (CEX), hydrophobic interaction chromatography (HIC), and mixed mode chromatography (cation exchange (phosphate) and affinity (calcium)), the method further comprising the step of treating trypsin to activate the botulinum toxin. Therefore, the method can purify botulinum toxin having excellent purity and activity and thus can be useful in producing botulinum toxin.

The present disclosure relates to the treatment of a skin condition in a subject, including but not limited to one or more of luminosity, brightness, skin pore size, skin pore count, sebum production, sebum composition, overall skin quality, eyelid laxity, fine lines under the eye, fine lines on the face, laxity on the face, perioral rhytids, moderate to severe facial folds and wrinkles such as nasolabial folds, moderate to severe facial wrinkles such as smile lines or marionette lines, age-related midface contour deficiencies, dorsal hand to correct volume deficit, glabellar lines, correction of facila depressions, either due to injury or age-related, perioral wrinkles, lip commissures, crow's feet, facial rhytides, and forehead wrinkles, comprising applying to the skin of the subject a first composition derived from one or more sponges, and a second composition comprising one or more botulinum toxins. Also provided are compositions for use in the treatment of a skin condition in a subject, including but not limited to hyperhidrosis, comprising a first composition and a second composition, wherein (a) the first composition comprises Spongilla; and (b) the second composition comprises one or more botulinum toxins. Also provided are kits, including kits for the treatment of a skin condition in a subject including but not limited to hyperhidrosis, comprising a first composition and a second composition, wherein the first composition comprises Spongilla, and the second composition comprises one or more botulinum toxins.

The present invention relates to a liquid composition for stabilizing botulinum toxin, and it was confirmed that a stabilizer comprising a non-ionic surfactant, an amino acid, and disaccharides as active ingredients can significantly increase the stability of botulinum toxin. Specifically, in the present invention, polysorbate 20, histidine, and disaccharides are combined, and the concentration conditions of each ingredient were established to prepare the optimal stabilizer through the combination. Thus, it is possible to prepare a botulinum toxin liquid formulation with low cytotoxicity and increased stability without containing animal-derived substances, and therefore the present invention can be used in various fields using botulinum toxin.

The invention relates to the use of an animal-protein-free botulinum toxin composition to treat a disease, disorder or condition in a patient in need thereof whereby the animal-protein-free botulinum toxin composition exhibits a longer lasting effect in the patient compared to an animal-protein-containing botulinum toxin composition.

The present invention relates to a method for producing botulinum toxin in a recombinant manner by using a soluble partner and intein. In the present invention, it was confirmed that HC having low solubility can be expressed in a soluble form by attaching a soluble partner. It was also confirmed that a soluble partner is generally a protein having a very high molecular weight, and when intein is used in the present invention, the soluble partner can be easily removed.

The present invention relates to a liquid formulation comprising (i) botulinum toxin, (ii) human serum albumin (HSA), (iii) hyaluronic acid, (iv) algitol, and optionally (v) an isotonic agent and / or (vi) a buffering agent. In a preferred embodiment, the HSA is used as a chelating agent. Furthermore, the present invention relates to the use of the liquid formulation in the treatment of therapeutic and cosmetic indications.

The present invention provides methods for cleaving a SNARE protein by administering an RNA molecule that encodes the light chain of botulinum toxin. The invention also provides pharmaceutical compositions and formulations for administering the therapeutic molecules of the invention. In one embodiment the therapeutic molecule can be an RNA molecule encoding the light chain of botulinum toxin comprised in a lipid nanoparticle, liposome, or solid lipid nanoparticle. The methods can administer the compositions for a variety of therapeutic and cosmetic purposes. The invention also provides methods of synthesizing a toxic substance, for example botulinum toxin.

A food supplement for oral administration, comprising: - a zinc compound, preferably zinc bisglycinate, - at least one amino acid from the group consisting of L-histidine and L-methionine, - a magnesium compound, preferably magnesium citrate, - vitamin C, wherein the composition serves to enhance and prolong the effect of botulinum toxin applications.

The invention relates to a method for producing botulinum toxin by utilizing a solubilizing partner and GP41.1 intein, in particular to a method for producing the botulinum toxin by utilizing the solubilizing partner and the GP41.1 intein in a recombination manner. The present invention confirms that the receptor binding domain (HC) of the heavy chain of botulinum toxin, which is less soluble, can be expressed in a soluble form in Escherichia coli by adding a solubilizing partner (Soluble Partner). Moreover, the solubilizing partner is usually a protein having a very high molecular weight, but the present invention confirms that the solubilizing partner can be easily removed using the GP41.1 intein.

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.

The present disclosure provides a light chain variant of botulinum toxin type E, in which a specific lysine residue is substituted with arginine. The light chain variant of botulinum toxin type E according to the present disclosure exhibits a significantly increased in vivo half-life due to the suppression of degradation via the ubiquitin-proteasome pathway.

The present invention relates to a prefilled glass container, such as a prefilled glass syringe, comprising an aqueous botulinum toxin formulation. The aqueous botulinum toxin formulation in the prefilled container is stable at low to ambient temperature for a prolonged time period. Furthermore, the present invention relates to a kit comprising the botulinum toxin prefilled container, and to the use of the botulinum toxin prefilled container in therapeutic and cosmetic applications.

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.