Methods for treating a bladder dysfunction by injecting a clostridial derivative to a target site below the bladder midline are described.

The present invention relates to a vial that is at least partially filled with an aqueous formulation of a neurotoxin, preferably botulinum toxin, to the manufacture of the vial and to the use thereof. The aqueous formulation of a neurotoxin is stable in the vial for a prolonged period of time.

Microneedle arrays for introducing an active ingredient through a skin surface of a patient can include a base layer, a plurality of microneedles projecting from the base layer, and a shell layer having an active ingredient. Each of the microneedles includes an elongate body having a proximal portion and a distal portion, in which the proximal portion is attached to the base layer. Each of the microneedles can also include at least one dissolvable polymer. The active ingredient is incorporated in the shell layer, which extends around at least a portion of the elongate body.

The present invention relates to a botulinum toxin pharmaceutical composition comprising tannic acid as an active ingredient. The botulinum toxin pharmaceutical composition comprising tannic acid provided in one aspect of the present invention improves the activity of the botulinum neurotoxin itself, allows the botulinum neurotoxin to stay in the injected place, and prevents the botulinum neurotoxin from spreading to the blood due to the properties of tannic acid. Therefore, the composition of the present invention has an effect of minimizing the side effects of the conventional Botox caused by the spread of the botulinum neurotoxin.

The invention provides methods for producing soluble di-chain BoNT/A protein.

Methods and apparatus are provided for applying an fragment of a neurotoxin such as the active light chain (LC) of the botulinum toxin (BoNT), such as one of the serotype A, B, C, D, E, F or G botulinum toxins, via permeabilization of targeted cell membranes to enable translocation of the botulinum neurotoxin light chain (BoNT-LC) molecule across the targeted cell membrane to the cell cytosol where a therapeutic response is produced in a mammalian system. The methods and apparatus include use of catheter based delivery systems, non-invasive delivery systems, and transdermal delivery systems.

Methods for the formulation of biodegradable microparticles for delivery of protein drugs, such as botulinum toxin, have been developed. The methods include the steps of precipitating and washing proteins with organic solvent to remove water prior to dispersing in polymer-dissolved organic solvent to prevent exposure to water/solvent interfaces and maintain bioactivity of the protein drugs and fabrication of microparticles by either template or emulsion method. Biodegradable microparticles, formed of one or more biodegradable polymers having entrapped in the polymer one or more protein agents, such as botulinum toxin, are also provided. Precipitated botulinum toxin and botulinum toxin-loaded microparticles can also be formulated into thermogels or crosslinked hydrogels. The stability of the protein within these microparticles, as well as the controlled release of the entrapped agents, provides for sustained efficacy of the agents.

The present invention provides a modified botulinum neurotoxin A (BoNT/A) L-chain protease that demonstrates enhanced cleaveage of human SNAP-23 (hSNAP-23) relative to unmodified (wild-type) BoNT/A L-chain protease, together with the use thereof for cleaving hSNAP-23.

Polyhydric polymers may be converted to derivatives thereof by reaction with divinyl sulfone to provide vinyl sulfone substituted polymers, where the polymers may additionally be further derivatized, including crosslinked, and the crosslinked and non-crosslinked derivatives may be used in biomedical and other applications.

The present disclosure provides a nanoparticle containing hydrophobic substance and manufacturing process and use thereof, wherein the nanoparticle containing the hydrophobic substance includes an emulsified layer containing an emulsified hydrophobic substance; and an outer layer containing an alginate and a hyaluronic acid; wherein the outer layer is deposited on an outer side of the emulsified layer.