57 results about "Botulinum toxin" patented technology

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 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.

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 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 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.

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 provides a recombinant botulinum toxin and a method for producing the same. A nucleic acid encoding the recombinant botulinum toxin comprises: a first nucleic acid fragment, a second nucleic acid fragment, a first modified tag, and a second modified tag; wherein the first nucleic acid fragment codes for the heavy chain of the botulinum toxin, and the second nucleic acid fragment codes for the light chain of the botulinum toxin; the first modified tag codes for a His tag; and the second modified tag codes for a GST tag or an MBP tag.

Dietary supplement comprising at least one zinc compound and phytase, to enhance the effect of botulinum toxin and / or prolong its duration of action.

1. The name of the design product: microfluidic photochemical luminescence automatic detection instrument. 2. The use of the design product: the design product belongs to the technical field of immune analysis detection instrument, and is applied to analysis and detection of toxins, pathogens and the like, for example, detection of botulinum toxin. 3. The design points of the design product: in shape. 4. The picture or photo best indicating the design points: perspective view.

The invention relates to the technical field of biological medicines, in particular to a recombinant E-type botulinum toxin precursor protein and application thereof. The recombinant E-type botulinum toxin precursor protein is prepared by utilizing a prokaryotic expression system, has complete structural conformation and biological function activity under the condition of not needing protease inception, and can be used for medical cosmetology or disease treatment. And the recombinant E-type botulinum toxin precursor protein single-chain molecule can form a crystal with a spherical structure, and has the characteristics of stability, safety and controllable quality. A novel tool molecule, a nerve cell delivery carrier and a candidate drug are provided for development and application of E-type botulinum toxin protein molecules, a basis is provided for further research and development of the functional effect of botulinum toxin and wider medical application, and the E-type botulinum toxin protein molecules have wide application prospects.

The invention relates to the technical field of massage instruments, in particular to a muscle relieving massage instrument for inhibiting stiffness after a botulinum toxin operation and a control method.The muscle relieving massage instrument comprises a shell, a massage assembly is arranged in the shell and comprises a vibration base and a massage hammer, the vibration base is movably connected to the shell, and the massage hammer is fixedly connected to the vibration base; a binding assembly is arranged on the shell, the binding assembly comprises connecting belts, binding belts, sticking belts and primary and secondary stickers, the two connecting belts are fixedly connected to the shell, the two binding belts are fixedly connected with the two connecting belts respectively, the two sticking belts are fixedly connected between the two binding belts, and the primary and secondary stickers are arranged on the two binding belts; the limb massager can be bound on the limbs of a patient, and then the limb muscles of the patient can be massaged without being held by hands, so that the patient can be automatically massaged by the massager while working and resting.

The application belongs to the technical field of biotechnology, and particularly relates to a purification method of type A recombinant botulinum toxin. The purification method comprises the following steps: collecting a fermentation liquor, crushing a bacterial body to obtain a crushing liquor; adding a flocculating agent to the crushing liquor to clarify, centrifuging to remove impurities to obtain a clarified liquor; adding the clarified liquor to an ion chromatography column to perform ion chromatography to obtain an ion chromatography liquor; adding thrombin to the ion chromatography liquor to perform enzymatic cutting to obtain an enzymatic cutting liquor; adding the enzymatic cutting liquor to a hydrophobic chromatography column to perform hydrophobic chromatography to obtain a hydrophobic chromatography liquor; performing ultrafiltration concentration on the hydrophobic chromatography liquor to obtain an ultrafiltration concentrated liquor; adding the ultrafiltration concentrated liquor to a molecular sieve chromatography column to perform molecular sieve chromatography to obtain the purified type A recombinant botulinum toxin. Compared with the prior art, the purification method can effectively remove impurity proteins, does not affect the integrity of light chains and heavy chains, has an amino acid sequence coverage of 100%, and does not affect the amino acid sequence coverage of 100%.

This invention relates to a microstructure preparation technique for botulinum toxin. The microstructure preparation technique of this invention allows for precise control of the botulinum toxin concentration, reducing pain during administration and ensuring accurate injection at the target site. Therefore, this technique is expected to be widely used in the safe and convenient medical application of botulinum toxin.

This invention relates to the field of biotechnology, and more particularly to recombinant rBoNT protein, its precursor, preparation methods, and applications. The recombinant protein (rBoNT) obtained by deleting variable structural regions (1-15 amino acids from the C-terminus of the light chain and 1-3 amino acids from the N-terminus of the heavy chain) exhibits extremely strong biological activity. The recombinant strain constructed by this invention can achieve soluble expression of rBoNT, and it can be specifically activated by enzymatic cleavage, is not easily affected by protease cleavage similar to precursor toxin hydrolases, significantly improving the purity and uniformity of the target precursor polypeptide. This invention combines membrane ultrafiltration with hydrophobic and ion exchange, which, compared to traditional affinity chromatography, not only simplifies the process and reduces costs while ensuring the yield and purity of the recombinant protein, but also significantly reduces biosafety risks, facilitating the scale-up of botulinum toxin industrial production and providing a solid foundation for the large-scale production of botulinum toxin.

The invention belongs to the technical field of protein engineering, and relates to transmembrane anti-wrinkle protein as well as expression and application thereof. The cell-penetrating wrinkle-removing protein is a nerve cell targeting cell-penetrating peptide-carnotoxin light chain recombinant protein, and is a protein formed by connecting a nerve cell targeting cell-penetrating peptide to an N terminal or a C terminal of a carnotoxin light chain protein. The transmembrane wrinkle removal protein has efficient nerve cell targeting, can efficiently remove wrinkles, and is higher in safety and easier to express; research results show that the recombinant genetically engineered bacterium has a significantly high secretion level of the nerve cell targeting cell-penetrating peptide-carnotoxin light chain recombinant protein.

The application discloses a non-toxic genetically engineered toxoid molecule antigen vaccine based on a protective antigen functional domain structure and a preparation method and application thereof. It is determined that botulinum toxin and tetanus toxin both have two key protective antigen molecules, i.e. a receptor binding region Hc and a light chain-transmembrane region L-HN. Based on the important role of the functional domain in immunoprotective efficacy, a non-toxic genetically engineered toxoid or chimeric toxoid multivalent vaccine molecule is designed and prepared by using a biosynthesis technology. The vaccine has two important protective antigens of biological toxins, can produce strong complete protection at a low dose and a small number of immunization times, and can be used as a high-efficiency genetically engineered toxoid vaccine to replace formaldehyde inactivated toxoids for biological toxin prevention. The vaccine has important protective antigens of two different biological toxins, can produce protective efficacy against a plurality of different toxin biological agents, and can be used as a broad-spectrum multivalent vaccine for biological toxin prevention.

The present application belongs to the technical field of cosmetic product ingredient identification, and particularly relates to a method for identifying and detecting counterfeit ingredients of counterfeit botulinum toxin cosmetic products. The present application prepares a test sample into a test solution, detects it according to high performance liquid chromatography mass spectrometry, takes telencephalin, acetyl hexapeptide-1 and snake venom-like tripeptide as key indicators for distinguishing counterfeit ingredients of counterfeit botulinum toxin products, and ensures the safety and effectiveness of the botulinum toxin products. The present application only needs to use standard control samples of counterfeit ingredients when the method is established for the first time, and does not need to use control samples in the subsequent routine detection process to accurately determine whether the sample is counterfeit. Moreover, the present application first establishes a method for quantitatively analyzing telencephalin by using liquid chromatography-tandem mass spectrometry. The present application is simple in operation, good in repeatability, high in sensitivity, fast in separation speed, high in detection flux, reliable in results, and effectively ensures the safety and effectiveness of the botulinum toxin products.