26 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 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 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 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.

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.

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 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.

The invention belongs to the field of biological detection, and relates to a quality control method of a biological medicine. The establishment of the invention obviously expands the research and development possibility of a botulinum toxin detection method, has important application value in the aspects of food and environment safety screening, laboratory diagnosis of clinical suspected cases and the like, and also can provide sequence reference for the development of recombinant antibodies.

This invention discloses a targeted microneedle loaded with botulinum toxin, its preparation method, and its application. The targeted microneedle comprises a base and a plurality of needles arranged in an array on the base. Each needle includes a needle matrix bonded to the base and a needle tip bonded to the needle matrix. The raw material forming the needle tip includes: a therapeutically effective amount of botulinum toxin; a targeting molecule, which is compounded with botulinum toxin through a non-covalent interaction; and a first soluble polymer matrix. The targeted microneedle can precisely deliver botulinum toxin to peripheral subcutaneous nerve endings and has good punctureability. Simultaneously, it can enhance the therapeutic effect while reducing the dosage and side effects (such as facial stiffness).

The present invention relates to a vacuum drying method for botulinum toxin, and specifically to a vacuum drying method for botulinum toxin, comprising the steps of: a) first drying of a solution containing botulinum toxin at a temperature of 5° C. to 30° C. under a pressure of 0.01 to 2 mmHg; b) a second drying of the first-dried product obtained in step a) at a temperature of 5° C. to 20° C. under a pressure of 0.01 to 1 mmHg; and c) final drying of the second-dried product obtained in step b) at a temperature of 5° C. to 30° C. under a pressure of 0.01 to 0.5 mmHg. The present invention can advantageously improve yield, stability and manufacturing efficiency, compared to conventional methods for vacuum drying botulinum toxin by freeze-drying.

The present invention relates to the use of botulinum toxins for the treatment of hyperpigmentation conditions. The use includes intracutaneously injecting botulinum toxin into the skin of a patient with hyperpigmentation at a specific depth, volume and dose to specifically target the epidermal layer and the upper dermal layer. For example, an intradermal injection of botulinum toxin according to the invention may be used to treat chloasma.

Provided is a light chain variant of botulinum toxin obtained by substituting a certain lysine with arginine in the light chain of botulinum toxin, which shows the suppression of degradation by the ubiquitin-proteasome system and thus a significantly increased in vivo half-life.

A composition may increase a rate of endometrial blood flow and a composition for increasing implantation potential, including botulinum toxin or a salt thereof, and a pharmaceutical composition may preventing or treating subfertility or infertility, including botulinum toxin or a pharmaceutically acceptable salt thereof. Such compositions can increase a rate of endometrial blood flow and improve embryonic implantation potential just by being applied to the endometrium, and thus may be helpful to patients with subfertility or infertility, especially those who have repetitive failures in embryonic implantation. Since the compositions include botulinum toxin which is a substance that has been widely applied to the human body for cosmetic purposes, studies on human toxicity may have a shortened period, and thus the disclosure is very useful in economical and industrial aspects.

The invention provides a botulinum toxin A1 type recombinant protein as well as a preparation method and application thereof, and belongs to the technical field of recombinant proteins. The amino acid sequence of the botulinum toxin A1 type recombinant protein is as shown in SEQ ID NO. 1. The invention designs a novel botulinum toxin A1 type recombinant protein with 10 His tags and Strep tags, and the botulinum toxin A1 type recombinant protein can realize soluble expression in escherichia coli. The invention also provides a preparation method and a purification method of the botulinum toxin A1 type recombinant protein, and large-scale production of the botulinum toxin A1 type recombinant protein can be realized. The invention provides technical support for the application of the botulinum toxin A1 type.

A botulinum toxin injector with a syringe has a volume marking scale that is scaled by 4 units per 0.1 mL. The volume marking scales enable unit conversion to be easy, and the possibility of excessive or insufficient botulinum toxin can be reduced. The syringe may also include additional volume marking scales configured to be interchangeably used for administration of insulin or botulinum toxin. The syringe may also include additional volume marking scales configured to be interchangeably used for administering different types of botulinum toxins.

The present invention relates to a liquid formulation comprising (i) a botulinum toxin, (ii) human serum albumin (HSA), (iii) hyaluronic acid, (iv) a sugar alcohol, and optionally (v) a tonicity agent and / or (vi) a buffer. In a preferred embodiment, the HSA has been treated with a chelating agent. Furthermore, the present invention relates to the use of said liquid formulation in the treatment of therapeutic and cosmetic indications.

Compositions and methods for preventing or reducing the occurrence of headache disorders in a subject in need thereof comprising administering to the subject an effective amount of a pharmaceutical composition comprising a nontoxic engineered protein derived from a botulinum toxin complex. The headache disorder may be selected from episodic migraine headaches, tension-type headaches, cluster headaches, hemiplegic migraine headaches, or retinal migraine headaches.

A decompression drying device includes, in addition to a conventional release valve for introducing external air to restore the inside of a drying chamber to a normal pressure after drying has been completed, a separate external air introduction means for introducing external air into the drying chamber when the pressure inside the drying chamber has reached near a target pressure during a decompression drying process. The decompression drying device is used for drying a pharmaceutical product and, in particular, is used for manufacturing a botulinum toxin dried cake. By introducing external air while finely adjusting its inflow amount when the pressure inside the drying chamber reaches near the target pressure during the decompression drying process, it is possible to prevent a phenomenon in which the pressure inside the drying chamber, particularly the pressure around a vial containing a liquid sample, rises and decreases significantly.