Patent Description:
Injections are a common method of introducing materials, for example therapeutic materials, into patients. However, such injections carry the risk of unwanted dispersion or dissipation of the materials beyond a desired treatment site. For example, adverse effects can result when neurotoxin injections spread beyond a treatment site; in the case of glabellar line or "crows feet" injections, eye droop or "ptosis" can occur. Neck weakness or difficulty swallowing can occur as a result of injections to the head. Further, immune response can be increased when injected materials spread from desired treatment sites. In the case of dermal filler injections, the injected material can spread beyond the treatment site, causing unwanted cosmetic effects, for example when treating the lip or cheekbones.

It is known that electrical stimulus can affect the movement of molecules, biologics, etc., and that electromagnetic forces including electric currents, charges, fields, magnetic fields, etc., can be used therapeutically.

For example, <CIT> discloses an apparatus for the delivery of a therapeutic agent, which includes a delivery orifice and a plurality of skin penetrating electrodes arranged at a predetermined spatial relationship relative to the orifice to improve uptake of the agent. However, while the use of skin penetrating electrodes may be suitable for use when delivering agents through the arm or leg, they would be far less desirable in regions of the head and face, where the tissue is much more shallow and near vital organs such as the eyes.

Another example is iontophoresis, which is a process of transdermal drug delivery by use of a voltage gradient on the skin. Molecules (for example, drugs or biologics) are transported across the stratum corneum by electrophoresis (the motion of dispersed particles relative to a fluid under the influence of a spatially uniform electric field) and electro-osmosis (the motion of liquid induced by an applied potential across a porous material). During iontophoresis, a small electric current is applied to an iontophoretic chamber placed on the skin, containing a charged active agent and its solvent vehicle. Another chamber or a skin electrode carries the return current. One or two chambers are filled with a solution containing an active ingredient and its solvent vehicle. The positively charged chamber, called the anode, will repel a positively charged chemical species, whereas the negatively charged chamber, called the cathode, will repel a negatively charged species into the skin.

It is known that low-voltage iontophoresis equipment can safely "drive" molecules over <NUM> into the tissue beneath the skin, using safe, well-tolerated voltages and currents. Such depths are suitable for methods disclosed herein, as many injected materials are administered just below the skin or at a minimum depth intramuscularly. Therefore, these safe, well-tolerated voltages and currents used in iontophoresis can also be used to control material dissipation by, rather than using a repellant force to drive a material into the skin, using that repellant force to "fence" or limit the material to a desired treatment area. In addition to the repellant force, an attractive force can also be used to localize an administered material.

Iontophoresis provides an alternative to injection. However, iontophoresis does not offer the precision of other administration modes, for example a needle. Therefore, an object of the instant Specification is to provide a device for use in combination with traditional administration methods such as injection, which applies electromagnetic forces such as electric charges, fields, and currents to control post-administration dissipation for the treatment of glabellar lines. In embodiments, an electric charge can be used to attract or repel an administered material- an "attractive" force can be used to increase localization of an injected material, for example by applying an attractive force to a treatment area, while a "repellant" force can be used to decrease dissipation of an administered material, for example by "fencing" the treatment area or aspects thereof with the repellant force.

Embodiments comprise systems, and devices for localizing or minimizing the spread or dissipation of injected materials, for example injected pharmaceutical compositions. Embodiments comprise the use of, for example, an energy field, for example an electromagnetic field (EMF) such as an electric field, an electric charge, an electric current, a magnetic field, or combinations thereof, to localize injected compositions. Injected compositions can comprise, for example, neurotoxins.

Embodiments comprise systems, and devices for increasing the spread or dissipation of injected materials, for example injected pharmaceutical compositions. Embodiments comprise the use of, for example, an energy field, for example an electromagnetic field (EMF) such as an electric field, an electric charge, an electric current, a magnetic field, or combinations thereof, to dissipate injected compositions. Injected compositions can comprise, for example, neurotoxins.

Embodiments comprise systems, and devices for directing the spread or dissipation of injected materials, for example injected pharmaceutical compositions. Embodiments comprise the use of, for example, an energy field, for example an electromagnetic field (EMF) such as an electric field, an electric charge, an electric current, a magnetic field, or combinations thereof, to localize injected compositions. Injected compositions can comprise, for example, neurotoxins.

Localizing the injected materials can eliminate or reduce the spread or dissipation of the materials, thereby eliminating or reducing the risk of unwanted effects, as well as minimizing the "immunogen footprint" that can result from an injection. Localizing the materials can increase the effect duration of injected materials, for example the effect duration of a neurotoxin injection. Localizing the materials can increase the effect intensity of injected materials, for example the effect intensity of a neurotoxin injection.

In embodiments, a material is injected subcutaneously to, for example, between <NUM> and <NUM> depth, then an attractive force comprising an electric charge is applied to the injection site. The order of this operation can be reversed, such that the force is applied before or after the administration.

In embodiments, a material is injected subcutaneously to, for example, between <NUM> and <NUM> depth, then a repellant force comprising an electric charge is applied around or partially around the treatment site. The order of this operation can be reversed, such that the force is applied before or after the administration.

In embodiments, a material is injected subcutaneously to, for example, between <NUM> and <NUM> depth, then an attractive force comprising an electric charge is applied to the injection site, and a repellant force comprising an electric charge is applied around or partially around the treatment site, wherein the attractive and repellant forces comprise opposite electric charges. The order of this operation can be reversed, such that the force is applied before or after the administration. In embodiments, the attractive and repellant forces establish an electric field. In embodiments wherein there is electrical conductivity between the attractive and repellant forces, an electric current can be established.

Embodiments can comprise neurotoxin administrations to treat, for example, cosmetic concerns. For example, to treat cosmetic concerns, an attractant force, for example the attractant electrode (determined based upon the physical properties of an injected material) of a TENS device can be placed on top of or in the vicinity of the injection site of a neurotoxin, with the repellant electrode of the device placed, for example, an inch or less from the attractant electrode. Clinically, TENS is applied at varying frequencies, intensities, and pulse durations of stimulation. By means of electrodes, electric flow from TENS unit is converted into an ionic current flow in the living tissue. During TENS therapy, pulsed electrical current is generated either by A. mains or using batteries (usually 9V) and delivered across the intact skin surface via electrodes. In the case of methods utilizing TENS, the attractant electrode can be placed over the injected material treatment site.

Disclosed embodiments comprise "active" devices that utilize a power source such as AC or DC power or pulsed RF or pulsed current, such as high voltage pulsed current, or "passive" devices that do not require external power. For example, in passive embodiments, the electrical energy can be derived from dissimilar metals creating a battery, for example wherein the dissimilar metals are located on a separate dressing or bandage, whereas those embodiments with an external power source can require conductive electrodes in a spaced apart configuration to predetermine the electric field shape and strength. In active devices, AC or DC current can be used. For example, an exemplary active device suitable for use with disclosed embodiments comprises a TENS device.

Aspects disclosed herein comprise bioelectric devices that comprise electrodes. Such matrices can include an electrode formed from a first conductive material, the material including a metal species, and a second electrode formed from a second conductive material, the material including a metal species capable of defining at least one voltaic cell for spontaneously generating at least one electrical current with the metal species of the first electrode when said first and second electrodes are connected via an electrolytic solution such as that within the body, and said first and second electrodes are not in physical contact with each other. Certain aspects utilize an external power source such as AC or DC power or pulsed RF or pulsed current, such as high voltage pulsed current.

Further disclosed embodiments can comprise articles of manufacture that include packaging material and an amount of a chemo-denervating agent, for example a neurotoxin. The chemo-denervating agent can be a Clostridial neurotoxin, for example a botulinum toxin such as botulinum toxin A (BoNT/A), botulinum toxin B (BoNT/B), botulinum toxin E (BoNT/E), botulinum toxin F (BoNT/F), combinations thereof, and devices as disclosed herein. These articles of manufacture can comprise kits, for example comprising a neurotoxin or combinations thereof, disclosed devices, and instructions for use.

Disclosed embodiments comprise articles of manufacture that includes packaging material and an amount of a cosmetic agent, for example a dermal filler such as hyaluronic acid (HA), and devices as disclosed herein. These articles of manufacture can comprise kits, for example comprising a dermal filler or fillers, disclosed systems and devices, and instructions for use.

Further embodiments can comprise a topical agent, for example a cream comprising an attractive EMF, to apply to a treatment area following a treatment. For example, a cream that produces an attractive field can be applied over an injected material treatment site, such as the lips or the glabellar line area.

The instant disclosure relates to devices and systems for localizing injected botulinum neurotoxin through use of energy applied to or about the injection site. Such energy can include, for example, electromagnetic energy such as electric energy, electric charge, electric fields, magnetic energy, electric currents, combinations thereof, or the like.

For example, BoNT/A has an isoelectric point of roughly <NUM>. Thus, at physiological pH values, BoNT/A carries a net positive charge. In embodiments, by applying a negative source charge to a location, for example a desired treatment or injection location, the toxin can be "fixed" in or attracted to that location. Similarly, by applying a positive source charge to a location, for example around part or all of the perimeter of a treatment site, the toxin can be excluded from that location. Type E (BoNT/E) has an isoelectric point of about <NUM>; therefore, at physiological pH values the toxin carries a net negative charge. This electromotive effect of an electric field on the toxin can be seen in SDS/PAGE images.

Botulinum neurotoxins suitable for use with disclosed methods and systems include, for BoNT/A, BoNT/B, BoNT/C, BoNT/D, BoNT/E, BoNT/F, BoNT/G, BoNT/H, and combinations thereof. Further suitable neurotoxins can comprise the "light chain" of a botulinum toxin. Embodiments can comprise a combination of neurotoxins, for example BoNT/A and BoNT/E. Embodiments can comprise the dissociation of the heavy chain and the light chain, either prior to or following administration. Disclosed embodiments can comprise use of an electric charge, field, or current to dissociate a neurotoxin from accessory proteins or formulation components, for example HSA, either prior to or following an administration, for example an injection.

Embodiments comprise aligning the dipole of a botulinum toxin to provide the correct orientation for binding.

Similarly, dermal fillers can be localized via the disclosed devices. For example, in embodiments, at physiological pH values, hyaluronic acid carries a net negative charge. In embodiments, by applying a positive source charge to a location, the dermal filler can be "fixed" in that location. Similarly, by applying a negative source charge, for example p part or all of the perimeter of a treatment site, the dermal filler can be excluded or repelled from a location.

As seen from electrophoresis gels, the dermal filler's movement can be controlled through use of an electric field, current, or combination thereof. Dermal fillers suitable for use with disclosed methods and systems include, for example, those containing Hyaluronic Acid (HA), Calcium Hydroxylapatite (CaHA), Poly-L-lactic Acid, Polymethylmethacrylate (PMMA), Autologous fat injections (facial fat grafting), and combinations thereof.

Embodiments can also comprise adjusting the pH of an injected material to, for example, the material's isoelectric point, then applying an electric field "perimeter" to localize the material through use of a repellant field.

In embodiments, the electric field can be supplied by a substrate, for example a flexible substrate comprising an electrode of an appropriate charge; for example a positive electrode can comprise silver. A negative electrode can comprise zinc. Embodiments comprise self-contained localization devices that do not require a power supply. Embodiments comprise devices that require a power supply, for example a power supply connected to electrodes such that one or more electrodes produces a negative electric field, and one or more electrodes produces a positive electric field. Substrates suitable for use with disclosed embodiments can comprise resorbable materials. Substrates suitable for use with disclosed embodiments can comprise clear or opaque materials.

Disclosed embodiments comprise the use of magnetic field to localize injected materials based upon the materials' electrical or magnetic properties. For example, a magnetic field can be used to affect and manipulate the dipole of a molecule, for example a neurotoxin molecule such as BoNT/A, to orient the molecule in a position that increases or decreases the molecule's binding efficiency.

Embodiments comprise modified neurotoxins, said modification comprising increasing the inherent "charge" of the molecule or conductivity of the formulation to increase the effect of disclosed embodiments.

"Administration," or "to administer" means the step of giving (i.e. administering) an injected material such as a pharmaceutical composition or active ingredient or dermal filler to a subject. The materials disclosed herein can be administered via a number of appropriate routes, however as described in the disclosed methods, in embodiments the compositions are locally administered by e.g. intramuscular, intradermal, or subcutaneous routes of administration, such as by injection or use of an implant.

"Attractive electromagnetic field" means a charge, field, or current that attracts the injected material, for example an electric field and/or charge.

"Botulinum toxin" or "botulinum neurotoxin" means a wild type neurotoxin derived from Clostridium botulinum, as well as modified, recombinant, hybrid and chimeric botulinum toxins. A recombinant botulinum toxin can have the light chain and/or the heavy chain thereof made recombinantly by a non-Clostridial species. "Botulinum toxin," as used herein, encompasses the botulinum toxin serotypes A, B, C, D, E, F, G and H. "Botulinum toxin," as used herein, also encompasses both a botulinum toxin complex (i.e. the <NUM>, <NUM> and <NUM> kDa complexes) as well as pure botulinum toxin (i.e. the about <NUM> kDa neurotoxic molecule), all of which are useful in the practice of the present invention. "Purified botulinum toxin" means a pure botulinum toxin or a botulinum toxin complex that is isolated, or substantially isolated, from other proteins and impurities which can accompany the botulinum toxin as it is obtained from a culture or fermentation process. Thus, a purified botulinum toxin can have at least <NUM>%, and more preferably at least <NUM>% of the non-botulinum toxin proteins and impurities removed.

"Clostridial neurotoxin" means a neurotoxin produced from, or native to, a Clostridial bacterium, such as Clostridium botulinum, Clostridium butyricum or Clostridium beratti, as well as a Clostridial neurotoxin made recombinantly by a non-Clostridial species.

"Dermal filler" means compositions used for aesthetic treatments that are injected into or below the skin. Typically, they are designed to effectively reduce the appearance of unwanted wrinkles, contour and create volume, and to revitalize the skin. Suitable fillers can include hyaluronic acid, polyalkylimide, polylactic acid, Polymethyl-methacrylate microspheres (PMMA), and the like.

"Limiting" the dissipation of an administered material means that the total area affected by the administered material is less than the total area would be in the absence of the limiting action.

"Intermediate-acting" as used herein refers to a botulinum toxin that produces effects more slowly that a fast-acting toxin.

"Neurotoxin" means a biologically active molecule with a specific affinity for a neuronal cell surface receptor. Neurotoxin includes Clostridial toxins both as pure toxin and as complexed with one or more non-toxin, toxin-associated proteins.

"Patient" means a human or non-human subject receiving medical or veterinary care.

"Pharmaceutical composition" means a formulation in which an active ingredient can be a neurotoxin, a dermal filler, or the like. The word "formulation" means that there is at least one additional ingredient (such as, for example and not limited to, an albumin [such as a human serum albumin or a recombinant human albumin] and/or sodium chloride) in the pharmaceutical composition in addition to a botulinum neurotoxin active ingredient. A pharmaceutical composition is therefore a formulation which is suitable for diagnostic, therapeutic or cosmetic administration to a subject, such as a human patient. The pharmaceutical composition can be: in a lyophilized or vacuum dried condition, a solution formed after reconstitution of the lyophilized or vacuum dried pharmaceutical composition with saline or water, for example, or; as a solution that does not require reconstitution. As stated, a pharmaceutical composition can be liquid or solid. A pharmaceutical composition can be animal-protein free.

"Repellant electromagnetic field" means a charge, field, or current that repels the injected material, for example a magnetic or electric field or charge.

"Substantially free" means present at a level of less than one percent by weight of a culture medium, fermentation medium, pharmaceutical composition or other material in which the weight percent of a substance is assessed.

"Therapeutic formulation" means a formulation that can be used to treat and thereby alleviate a disorder or a disease and/or symptom associated thereof, such as a disorder or a disease characterized by an activity of a peripheral muscle.

"Therapeutically effective amount" means the level, amount or concentration of an agent (e.g. such as a botulinum toxin or pharmaceutical composition comprising botulinum toxin) needed to treat a disease, disorder or condition without causing significant negative or adverse side effects.

"Toxin-naive" means a patient who has not been administered a neurotoxin, for example a clostridial toxin, for example BoNT/A.

"Treat," "treating," or "treatment" means an alleviation or a reduction (which includes some reduction, a significant reduction a near total reduction, and a total reduction), resolution or prevention (temporarily or permanently) of an disease, disorder or condition, so as to achieve a desired therapeutic or cosmetic result, such as by healing of injured or damaged tissue, or by altering, changing, enhancing, improving, ameliorating and/or beautifying an existing or perceived disease, disorder or condition.

"Unit" or "U" means an amount of active BoNT standardized to have equivalent neuromuscular blocking effect as a Unit of commercially available BoNT/A.

In embodiments, the devices can be used for localizing injected materials by applying an energy field, for example an electric charge, field or current, or combinations thereof, to at least one injection site, or applying an energy field, for example an energy field, for example an electric charge, field or current, or combinations thereof, surrounding at least one injection site, and combinations thereof. For example, an energy field, for example an attractive electric charge, field or current, or combinations thereof, can be applied directly on top of the injection site. In embodiments, an energy field, for example a repellant electric charge, field or current, or combinations thereof, can be applied around the perimeter of one or multiple injection sites. These methods can be combined such that attractive and repellant forces are applied.

In embodiments, methods of minimizing an immune response caused by injected materials can comprise applying an energy field, for example an electric charge, field or current, or combinations thereof, to at least one injection site, or surrounding at least one injection site. For example, an attractive energy field, for example an electric charge, field or current, or combinations thereof, can be applied directly on top of the injection site. In embodiments, a repellant energy field, for example an electric charge, field or current, or combinations thereof, can be applied around the perimeter or a part thereof of one or multiple injection sites. These methods can be combined such that attractive and repellant fields are applied.

In embodiments the energy field can comprise, for example, an electric field, electric charge, electric current, a magnetic field, a combination thereof, or the like. For example, an electric field can be applied to an injection site through the use of an electrode supplying a suitable voltage to produce an attractive field to "attract" the materials. In embodiments, an electric field can be applied to surround (either partially or completely) an injection site through the use of an electrode supplying a suitable voltage to produce a repellant field to "repel" the materials. In embodiments, both attractive and repellant field are applied. In this manner, the spread or dissipation of the injected materials can be reduced or eliminated.

In embodiments, an electric field can comprise voltages suitable for application to the mammal. For example, a suitable electric field can comprise voltages appropriate to application to the body of a mammal, for example a human.

In various embodiments the difference of the standard potentials of the electrodes providing attractant and repellant fields can be in a range from about <NUM> V to approximately about <NUM> V. For example, the standard potential can be about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, about <NUM> V, or the like.

In embodiments, the electric field between the attractant and repellant electrodes can be, for example, <NUM> volt/cm, <NUM> volt/cm, <NUM> volt/cm, <NUM> volt/cm, <NUM> volt/cm, <NUM> volt/cm, <NUM> volt/cm, <NUM> volt/cm, <NUM> volt/cm, <NUM> volt/cm, <NUM> volt/cm, <NUM> volt/cm, <NUM> volt/cm, <NUM> volt/cm, <NUM> volt/cm, <NUM> volt/cm, <NUM> volt/cm, <NUM> volt/cm, <NUM> volt/cm, <NUM> volt/cm, or the like.

In embodiments, the electric field between the attractant and repellant electrodes can be, for example, between <NUM> volt/cm and <NUM> v/cm, between <NUM> volt/cm and <NUM> v/cm, between <NUM> volt/cm and <NUM> v/cm, between <NUM> volt/cm and <NUM> v/cm, between <NUM> volt/cm and <NUM> v/cm, between <NUM> volt/cm and <NUM> v/cm, between <NUM> volt/cm and <NUM> v/cm, between <NUM> volt/cm and <NUM> v/cm, between <NUM> volt/cm and <NUM> v/cm, between <NUM> volt/cm and <NUM> v/cm, or the like.

In embodiments, the electric field between the attractant and repellant electrodes can be, for example, no more than <NUM> volt/cm, no more than <NUM> volt/cm, no more than <NUM> volt/cm, no more than <NUM> volt/cm, no more than <NUM> volt/cm, no more than <NUM> volt/cm, no more than <NUM> volt/cm, no more than <NUM> volt/cm, no more than <NUM> volt/cm, no more than <NUM> volt/cm, no more than <NUM> volt/cm, no more than <NUM> volt/cm, no more than <NUM> volt/cm, no more than <NUM> volt/cm, no more than <NUM> volt/cm, no more than <NUM> volt/cm, no more than <NUM> volt/cm, no more than <NUM> volt/cm, no more than <NUM> volt/cm, no more than <NUM> volt/cm, or the like.

In embodiments, the electric field between the attractant and repellant electrodes can be, for example, no less than <NUM> volt/cm, no less than <NUM> volt/cm, no less than <NUM> volt/cm, no less than <NUM> volt/cm, no less than <NUM> volt/cm, no less than <NUM> volt/cm, no less than <NUM> volt/cm, no less than <NUM> volt/cm, no less than <NUM> volt/cm, no less than <NUM> volt/cm, no less than <NUM> volt/cm, no less than <NUM> volt/cm, no less than <NUM> volt/cm, no less than <NUM> volt/cm, no less than <NUM> volt/cm, no less than <NUM> volt/cm, no less than <NUM> volt/cm, no less than <NUM> volt/cm, no less than <NUM> volt/cm, no less than <NUM> volt/cm, or the like.

Embodiments can comprise an electric current between the attractant and repellant electrodes. In embodiments, systems and devices disclosed herein can produce a low level electric current between the attractant and repellant electrodes of between for example about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> micro-amperes (<NUM> milli-amp [mA]), between about <NUM> and about <NUM> mA, between about <NUM> and about <NUM>. 2mA, between about <NUM> and about <NUM>. 3mA, between about <NUM> and about <NUM>. 4mA, between about1. <NUM> and about <NUM>. 5mA, between about <NUM> and about <NUM>. 6mA, between about <NUM> and about <NUM>. 7mA, between about <NUM> and about <NUM>. 8mA, between about <NUM> and about <NUM>. 9mA, between about <NUM> and about <NUM>. 0mA, between about <NUM> and about <NUM> mA, between about <NUM> and about <NUM>. 2mA, between about <NUM> and about <NUM>. 3mA, between about <NUM> and about <NUM>. 4mA, between about <NUM> and about <NUM>. 5mA, between about <NUM> and about <NUM>. 6mA, between about <NUM> and about <NUM>. 7mA, between about <NUM> and about <NUM>. 8mA, between about <NUM> and about <NUM>. 9mA, between about <NUM> and about <NUM>. 0mA, between about <NUM> and about <NUM> mA, between about <NUM> and about <NUM>. 2mA, between about <NUM> and about <NUM>. 3mA, between about <NUM> and about <NUM>. 4mA, between about <NUM> and about <NUM>. 5mA, between about <NUM> and about <NUM>. 6mA, between about <NUM> and about <NUM>. 7mA, between about <NUM> and about <NUM>. 8mA, between about <NUM> and about <NUM>. 9mA, between about <NUM> and about <NUM>. 0mA, between about <NUM> and about <NUM> mA, between about <NUM> and about <NUM>. 2mA, between about <NUM> and about <NUM>. 3mA, between about <NUM> and about <NUM>. 4mA, between about <NUM> and about <NUM>. 5mA, between about <NUM> and about <NUM>. 0mA, between about <NUM> and about <NUM>. 5mA, between about <NUM> and about <NUM>. 0mA, between about <NUM> and about <NUM>. 5mA, between about <NUM> and about <NUM>. 0mA, between about <NUM> and about <NUM>. 0mA, between about <NUM> and about <NUM>. 5mA, between about <NUM> and about <NUM>. 0mA, between about <NUM> and about <NUM>. 5mA, between about <NUM> and about <NUM>. 0mA, between about <NUM> and about <NUM>. 5mA, between about <NUM> and about <NUM><NUM>. 0mA, between about <NUM><NUM> and about <NUM><NUM>. 5mA, between about <NUM><NUM> and about <NUM>. 0mA, between about <NUM> and about <NUM>. 5mA, between about <NUM> and about <NUM>. 0mA, between about <NUM> and about <NUM>. 5mA, between about <NUM> and about <NUM>. 0mA, between about <NUM> and about <NUM>. 5mA, between about <NUM> and about <NUM>. 0mA, or the like.

In embodiments, systems and devices disclosed herein can produce a low level electric current of between for example about <NUM> micro-ampere and about <NUM> milli-ampere, between about <NUM> and about <NUM> micro-amperes, between about <NUM> and about <NUM> microamperes, between about <NUM> and about <NUM> micro-amperes, or the like.

In embodiments, systems and devices disclosed herein can produce a low level electric current of about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> microamperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM><NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> microamperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> microamperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> microamperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> micro-amperes, about <NUM> milli-ampere (mA), about <NUM> mA, about <NUM>. 2mA, about <NUM>. 3mA, about <NUM>. 4mA, about <NUM>. 5mA, about <NUM>. 6mA, about <NUM>. 7mA, about <NUM>. 8mA, about <NUM>. 9mA, about <NUM>. 0mA, about <NUM> mA, about <NUM>. 2mA, about <NUM>. 3mA, about <NUM>. 4mA, about <NUM>. 5mA, about <NUM>. 6mA, about <NUM>. 7mA, about <NUM>. 8mA, about <NUM>. 9mA, about <NUM>. 0mA, about <NUM> mA, about <NUM>. 2mA, about <NUM>. 3mA, about <NUM>. 4mA, about <NUM>. 5mA, about <NUM>. 6mA, about <NUM>. 7mA, about <NUM>. 8mA, about <NUM>. 9mA, about <NUM>. 0mA, about <NUM> mA, about <NUM>. 2mA, about <NUM>. 3mA, about <NUM>. 4mA, about <NUM>. 5mA, about <NUM>. 6mA, about <NUM>. 7mA, about <NUM>. 8mA, about <NUM>. 9mA, about <NUM>. 0mA, about <NUM> mA, about <NUM>. 2mA, about <NUM>. 3mA, about <NUM>. 4mA, about <NUM>. 5mA, about <NUM>. 6mA, about <NUM>. 7mA, about <NUM>. 8mA, about <NUM>. 9mA, about <NUM>. 0mA, about <NUM> mA, about <NUM>. 2mA, about <NUM>. 3mA, about <NUM>. 4mA, about <NUM>. 5mA, about <NUM>. 6mA, about <NUM>. 7mA, about <NUM>. 8mA, about <NUM>. 9mA, about <NUM>. 0mA, about <NUM> mA, about <NUM>. 2mA, about <NUM>. 3mA, about <NUM>. 4mA, about <NUM>. 5mA, about <NUM>. 6mA, about <NUM>. 7mA, about <NUM>. 8mA, about <NUM>. 9mA, about <NUM>. 0mA, about <NUM> mA, about <NUM>. 2mA, about <NUM>. 3mA, about <NUM>. 4mA, about <NUM>. 5mA, about <NUM>. 6mA, about <NUM>. 7mA, about <NUM>. 8mA, about <NUM>. 9mA, about <NUM>. 0mA, about <NUM> mA, about <NUM>. 2mA, about <NUM>. 3mA, about <NUM>. 4mA, about <NUM>. 5mA, about <NUM>. 6mA, about <NUM>. 7mA, about <NUM>. 8mA, about <NUM>. 9mA, about <NUM>. 0mA, about <NUM> mA, about <NUM>. 2mA, about <NUM>. 3mA, about <NUM>. 4mA, about <NUM>. 5mA, about <NUM>. 6mA, about <NUM>. 7mA, about <NUM>. 8mA, about <NUM>. 9mA, about <NUM><NUM>. 0mA, about <NUM> mA, about <NUM>. 2mA, about <NUM>. 3mA, about <NUM>. 4mA, about <NUM><NUM>. 5mA, about <NUM><NUM>. 6mA, about <NUM>. 7mA, about <NUM>. 8mA, about <NUM>. 9mA, about <NUM>. 0mA, about <NUM>. 1mA, about <NUM>. 2mA, about <NUM>. 3mA, about <NUM>. 4mA, about <NUM>. 5mA, about <NUM>. 6mA, about <NUM>. 7mA, about <NUM>. 8mA, about <NUM>. 9mA, about <NUM>. 0mA, about <NUM> mA, about <NUM>. 2mA, about <NUM>. 3mA, about <NUM>. 4mA, about <NUM>. 5mA, about <NUM>. 6mA, about <NUM>. 7mA, about <NUM>. 8mA, about <NUM>. 9mA, about <NUM>. 0mA, about <NUM> mA, about <NUM>. 2mA, about <NUM>. 3mA, about <NUM>. 4mA, about <NUM>. 5mA, about <NUM>. 6mA, about <NUM>. 7mA, about <NUM>. 8mA, about <NUM>. 9mA, about <NUM>. 0mA, about <NUM> mA, about <NUM>. 2mA, about <NUM>. 3mA, about <NUM>. 4mA, about <NUM>. 5mA, about <NUM>. 6mA, about <NUM>. 7mA, about <NUM>. 8mA, or the like.

In embodiments, the disclosed systems and devices can produce a low level electric current of not more than <NUM> micro-amperes, or not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM><NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> micro-amperes, not more than about <NUM> milli-ampere (mA), not more than about <NUM> mA, not more than about <NUM>. 2mA, not more than about <NUM>. 3mA, not more than about <NUM>. 4mA, not more than about <NUM>. 5mA, not more than about <NUM>. not more than about <NUM>. not more than about <NUM>. not more than about <NUM>. 9mA, not more than about <NUM>. 0mA, not more than about <NUM> mA, not more than about <NUM>. 2mA, not more than about <NUM>. 3mA, not more than about <NUM>. 4mA, not more than about <NUM>. 5mA, not more than about <NUM>. 6mA, not more than about <NUM>. 7mA, not more than about <NUM>. 8mA, not more than about <NUM>. 9mA, not more than about <NUM>. 0mA, not more than about <NUM> mA, not more than about <NUM>. 2mA, not more than about <NUM>. 3mA, not more than about <NUM>. 4mA, not more than about <NUM>. 5mA, not more than about <NUM>. 6mA, not more than about <NUM>. 7mA, not more than about <NUM>. 8mA, not more than about <NUM>. 9mA, not more than about <NUM>. 0mA, not more than about <NUM> mA, not more than about <NUM>. 2mA, not more than about <NUM>. 3mA, not more than about <NUM>. 4mA, not more than about <NUM>. 5mA, not more than about <NUM>. 6mA, not more than about <NUM>. 7mA, not more than about <NUM>. 8mA, not more than about <NUM>. 9mA, not more than about <NUM>. 0mA, not more than about <NUM> mA, not more than about <NUM>. 2mA, not more than about <NUM>. 3mA, not more than about <NUM>. 4mA, not more than about <NUM>. 5mA, not more than about <NUM>. 6mA, not more than about <NUM>. 7mA, not more than about <NUM>. 8mA, not more than about <NUM>. 9mA, not more than about <NUM>. 0mA, not more than about <NUM> mA, not more than about <NUM>. 2mA, not more than about <NUM>. 3mA, not more than about <NUM>. 4mA, not more than about <NUM>. 5mA, not more than about <NUM>. 6mA, not more than about <NUM>. 7mA, not more than about <NUM>. 8mA, not more than about <NUM>. 9mA, not more than about <NUM>. 0mA, not more than about <NUM> mA, not more than about <NUM>. 2mA, not more than about <NUM>. 3mA, not more than about <NUM>. 4mA, not more than about <NUM>. 5mA, not more than about <NUM>. 6mA, not more than about <NUM>. 7mA, not more than about <NUM>. 8mA, not more than about <NUM>. 9mA, not more than about <NUM>. 0mA, not more than about <NUM> mA, not more than about <NUM>. 2mA, not more than about <NUM>. 3mA, not more than about <NUM>. 4mA, not more than about <NUM>. 5mA, not more than about <NUM>. 6mA, not more than about <NUM>. 7mA, not more than about <NUM>. 8mA, not more than about <NUM>. 9mA, not more than about <NUM>. 0mA, not more than about <NUM> mA, not more than about <NUM>. 2mA, not more than about <NUM>. 3mA, not more than about <NUM>. 4mA, not more than about <NUM>. 5mA, not more than about <NUM>. 6mA, not more than about <NUM>. 7mA, not more than about <NUM>. 8mA, not more than about <NUM>. 9mA, not more than about <NUM>. 0mA, not more than about <NUM> mA, not more than about <NUM>. 2mA, not more than about10.3mA, not more than about <NUM>. 4mA, not more than about <NUM>. 5mA, not more than about <NUM>. 6mA, not more than about <NUM>. 7mA, not more than about <NUM>. 8mA, not more than about <NUM>. 9mA, not more than about <NUM>. 0mA, not more than about <NUM>. 1mA, not more than about <NUM>. 2mA, not more than about <NUM>. 3mA, not more than about <NUM>. 4mA, not more than about <NUM>. 5mA, not more than about <NUM>. 6mA, not more than about <NUM><NUM>. 7mA, not more than about <NUM>. 8mA, not more than about <NUM>. 9mA, not more than about <NUM>. 0mA, not more than about12. <NUM> mA, not more than about <NUM>. 2mA, not more than about <NUM>. 3mA, not more than about <NUM>. 4mA, not more than about <NUM>. 5mA, not more than about <NUM>. 6mA, not more than about <NUM>. 7mA, not more than about <NUM>. 8mA, not more than about <NUM>. 9mA, not more than about <NUM>. 0mA, not more than about <NUM> mA, not more than about <NUM>. 2mA, not more than about <NUM>. 3mA, not more than about <NUM>. 4mA, not more than about <NUM>. 5mA, not more than about <NUM>. 6mA, not more than about <NUM>. 7mA, not more than about <NUM>. 8mA, not more than about <NUM>. 9mA, not more than about <NUM>. 0mA, not more than about <NUM> mA, not more than about <NUM>. 2mA, not more than about <NUM>. 3mA, not more than about <NUM>. 4mA, not more than about <NUM>. 5mA, not more than about <NUM>. 6mA, not more than about <NUM>. 7mA, not more than about <NUM>. 8mA, not more than about <NUM>. 9mA, not more than about <NUM>. 0mA, not more than about <NUM> mA, not more than about <NUM>. 2mA, not more than about <NUM>. 3mA, not more than about <NUM>. 4mA, not more than about <NUM>. 5mA, not more than about <NUM>. 6mA, not more than about <NUM>. 7mA, not more than about <NUM>. 8mA, and the like.

In embodiments, systems and devices disclosed herein can produce a low level electric current of not less than about <NUM>. 8mA, not less than about <NUM>. 9mA, not less than about <NUM>. 0mA, not less than about <NUM> mA, not less than about <NUM>. 2mA, not less than about <NUM>. 3mA, not less than about <NUM>. 4mA, not less than about <NUM>. 5mA, not less than about <NUM>. 6mA, not less than about <NUM>. 7mA, not less than about <NUM>. 8mA, not less than about <NUM>. 9mA, not less than about <NUM>. 0mA, not less than about <NUM> mA, not less than about <NUM>. 2mA, not less than about <NUM>. 3mA, not less than about <NUM>. 4mA, not less than about <NUM>. 5mA, not less than about <NUM>. 6mA, not less than about <NUM>. 7mA, not less than about <NUM>. 8mA, not less than about <NUM>. 9mA, not less than about <NUM>. 0mA, not less than about <NUM> mA, not less than about <NUM>. 2mA, not less than about <NUM>. 3mA, not less than about <NUM>. 4mA, not less than about <NUM>. 5mA, not less than about <NUM>. 6mA, not less than about <NUM>. 7mA, not less than about <NUM>. 8mA, not less than about <NUM>. 9mA, not less than about <NUM>. 0mA, not less than about <NUM> mA, not less than about <NUM>. 2mA, not less than about <NUM>. 3mA, not less than about <NUM>. 4mA, not less than about <NUM>. 5mA, not less than about <NUM>. 6mA, not less than about <NUM>. 7mA, not less than about <NUM>. 8mA, and the like.

In embodiments, disclosed devices can provide an electric field of greater than physiological strength to a depth (as measured from the surface of the device) of, at least <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM><NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or more.

In embodiments, disclosed devices can provide an electric field of greater than physiological strength to a depth (as measured from the surface of the device) of, not more than <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM><NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or more.

In active embodiments, for example utilizing a TENS device, TENS is applied at high frequency (><NUM>) with an intensity below motor contraction (sensory intensity) or low frequency (<<NUM>) with an intensity that produces motor contraction. Disclosed embodiments typically utilize an intensity below that required to cause motor contraction. In embodiments, the attractant electrode is placed atop the treatment area.

In embodiments, an electric charge, field, current, or combinations thereof is applied using a system comprising devices comprising electrodes. For example, a disclosed device can comprise conductive electrodes. In embodiments, the device comprises attractive and repellant electrodes, said attractive and repellant electrodes comprising opposing charges. For example, in powered devices, electrodes can comprise platinum, with one of the attractive/repellant electrodes comprising a positive charge, and the other comprising negative charge.

Disclosed embodiments can be used to limit the amount of non-therapeutic materials to be injected into a patient. For example, in embodiments, the vessel containing the material to be injected is subjected to an electromagnetic field that attracts the therapeutic material, and the injection material is withdrawn from the vessel in the vicinity of the attractant electromagnetic field.

In embodiments, the injected materials can comprise pharmaceutical compositions. For example, suitable pharmaceutical compositions can comprise any materials typically administered via injection (to include needle-less injection). Such compositions can comprise neurotoxins, for example botulinum toxins.

For example, in disclosed embodiments, the neurotoxin is formulated in unit dosage form; for example, it can be provided as a sterile solution in a vial or as a vial or sachet containing a lyophilized powder for reconstituting in a suitable vehicle such as saline for injection. Although examples of routes of administration and dosages are provided, the appropriate route of administration and dosage are generally determined on a case by case basis by the attending physician. Such determinations are routine to one of ordinary skill in the art. For example, the route and dosage for administration of a Clostridial neurotoxin according to the present disclosure can be selected based upon criteria such as the solubility characteristics of the neurotoxin chosen as well as the intensity and scope of the condition being treated.

The neurotoxin can be administered in an amount of between about <NUM>"<NUM> U/kg and about <NUM> U/kg. In an embodiment, the neurotoxin is administered in an amount of between about <NUM>"<NUM> U/kg and about <NUM> U/kg. In another embodiment, the neurotoxin is administered in an amount of between about <NUM>_1 U/kg and about <NUM> U/kg. In another embodiment, the neurotoxin is administered in an amount of between about <NUM> U/kg and about <NUM> U/kg. In many instances, an administration of from about <NUM> unit to about <NUM> units of a neurotoxin, such as a botulinum type E, provides effective therapeutic relief. In an embodiment, from about <NUM> units to about <NUM> units of a neurotoxin, such as a botulinum type E, can be used and in another embodiment, from about <NUM> units to about <NUM> units of a neurotoxin, such as a botulinum type E, can be locally administered into a target tissue such as a muscle.

In embodiments, administration can comprise a dose of about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM><NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or the like.

In embodiments, administration can comprise a dose of not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, or about <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, not less than <NUM> units of a neurotoxin, or the like.

In embodiments, administration can comprise a dose of not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, not more than <NUM> units of a neurotoxin, or the like.

In embodiments, the dose of the neurotoxin is expressed in protein amount or concentration. For example, in embodiments the neurotoxin can be administered in an amount of between about. 2ng and <NUM> ng. In an embodiment, the neurotoxin is administered in an amount of between about. <NUM> ng and <NUM> ng, about. <NUM> ng and <NUM> ng, about. <NUM> ng and <NUM> ng, about. <NUM> ng and <NUM> ng, about. <NUM> ng and <NUM> ng, about. <NUM> ng and <NUM> ng, about. <NUM> ng and <NUM> ng, about <NUM> ng and <NUM> ng, about <NUM> ng and <NUM><NUM> ng, about <NUM> ng and <NUM> ng, about <NUM> ng and <NUM> ng, and the like, into a target tissue such as a muscle.

In embodiments, neurotoxin administration can comprise a total dose of between <NUM> and <NUM> ng, between <NUM> and <NUM> ng, between <NUM> and <NUM> ng, between <NUM> and <NUM> ng, between <NUM> and <NUM> ng, between <NUM> and <NUM> ng, between <NUM> and <NUM> ng, or the like.

In embodiments, administration can comprise a total dose of not more than <NUM> ng, not more than <NUM> ng, not more than <NUM> ng, not more than <NUM> ng, not more than <NUM> ng, not more than <NUM> ng, not more than <NUM> ng, not more than <NUM> ng, not more than <NUM> ng, not more than <NUM> ng, not more than <NUM> ng, not more than <NUM> ng, not more than <NUM> ng, not more than <NUM> ng, not more than <NUM> ng, not more than <NUM> ng, or the like.

In embodiments, neurotoxin administration can comprise a total dose of not less than <NUM> ng, not less than <NUM> ng, not less than <NUM> ng, not less than <NUM> ng, not less than <NUM> ng, not less than <NUM> ng, not less than <NUM> ng, not less than <NUM> ng, not less than <NUM> ng, not less than <NUM> ng, not less than <NUM> ng, not less than <NUM> ng, not less than <NUM> ng, not less than <NUM> ng, not less than <NUM> ng, not less than <NUM> ng, or the like.

In embodiments, administration can comprise a total dose of about <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> n of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> n of a neurotoxin, <NUM> n of a neurotoxin, <NUM> n of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, or the like.

In embodiments, administration can comprise a dose per administration of about <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> n of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> n of a neurotoxin, <NUM> n of a neurotoxin, <NUM> n of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, <NUM> ng of a neurotoxin, or the like.

Ultimately, however, both the quantity of toxin administered and the frequency of its administration will be at the discretion of the physician responsible for the treatment and will be commensurate with questions of safety and the effects produced by the toxin.

Embodiments comprise injection of a volume of dermal filler, for example hyaluronic acid. In embodiments, the volume of hyaluronic acid composition comprises, for example,. <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or the like.

In embodiments, the volume of dermal filler composition comprises, for example, not more than. <NUM>, not more than. <NUM>, not more than. <NUM>, not more than. <NUM>, not more than. <NUM>, not more than. <NUM>, not more than. <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, not more than <NUM>, or the like.

In embodiments, the volume of dermal filler composition comprises, for example, not less than. <NUM>, not less than. <NUM>, not less than. <NUM>, not less than. <NUM>, not less than. <NUM>, not more than. <NUM>, not more than. <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not more than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not more than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, not less than <NUM>, or the like.

In embodiments, the treatment device or devices applying the electric charge, field, or current is applied surrounding or to the treatment area for, for example, <NUM> seconds, <NUM> seconds, <NUM> seconds, <NUM> minute, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, <NUM> minutes, or more, or the like.

In embodiments, the treatment device or devices applying the electric charge, field, or current is applied surrounding or to the treatment area for, for example, not less than <NUM> seconds, not less than <NUM> seconds, not less than not less than <NUM> seconds, not less than <NUM> minute, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, <NUM> minutes, <NUM> not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, not less than <NUM> minutes, or more, or the like.

In embodiments, the treatment device or devices applying the electric charge, field, or current is applied surrounding or to the treatment area for, for example, not more than <NUM> seconds, not more than <NUM> seconds, not more than not more than <NUM> seconds, not more than <NUM> minute, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, not more than <NUM> minutes, or more, or the like.

In embodiments, the attractive/repellant electric charge, fired, or current are applied to and about the treatment site. For example, in embodiments, electrodes are powered by, for example between <NUM> and 10V and applied about <NUM> apart, with the attractive electrode applied upon the treatment site and the repellant electrode applied to form a partial or complete perimeter around the treatment site. The distance between the attractive and repellant electrodes can be determined based on the voltage applied to affect the most beneficial treatment. For example, the attractive and repellant electrodes can be applied <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, <NUM> apart, or more, or the like.

In embodiments, the distance between the attractive and repellant electrodes can be, for example, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, at least <NUM> apart, or more, or the like.

In embodiments, the distance between the attractive and repellant electrodes can be, for example, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, at not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, not more than <NUM> apart, or more, or the like.

In embodiments, the distance between the attractive and repellant electrodes can be, for example, between <NUM> and <NUM>, <NUM> and <NUM>, <NUM> and <NUM>, <NUM> and <NUM>, <NUM> and <NUM>, or the like. In embodiments, the distance between the attractive and repellant electrodes can be, for example, between <NUM> and <NUM>, <NUM> and <NUM>, <NUM> and <NUM>, <NUM> and <NUM>, <NUM> and <NUM>, <NUM> and <NUM>, <NUM> and <NUM>, <NUM> and <NUM>, <NUM> and <NUM>, or the like. In embodiments, the distance between the attractive and repellant electrodes can be, for example, between <NUM> and <NUM>, <NUM> and <NUM>, <NUM> and <NUM>, <NUM> and <NUM>, <NUM> and <NUM> <NUM> and <NUM>, <NUM> and <NUM>, <NUM> and <NUM>, or the like.

In embodiments, the distance between the attractive and repellant electrodes can be, for example, between at least <NUM> and <NUM>, at least <NUM> and <NUM>, at least <NUM> and <NUM>, at least <NUM> and <NUM>, at least <NUM> and <NUM>, or the like. In embodiments, the distance between the attractive and repellant electrodes can be, for example, between at least <NUM> and <NUM>, at least <NUM> and <NUM>, at least <NUM> and <NUM>, at least <NUM> and <NUM>, at least <NUM> and <NUM>, at least <NUM> and <NUM>, at least <NUM> and <NUM>, at least <NUM> and <NUM>, at least <NUM> and <NUM>, or the like. In embodiments, the distance between the attractive and repellant electrodes can be, for example, between at least <NUM> and <NUM>, at least <NUM> and <NUM>, at least <NUM> and <NUM>, at least <NUM> and <NUM>, at least <NUM> and <NUM>, at least <NUM> and <NUM>, at least <NUM> and <NUM>, at least <NUM> and <NUM>, or the like.

In embodiments, the distance between the attractive and repellant electrodes can be, for example, between not more than <NUM> and <NUM>, not more than <NUM> and <NUM>, not more than <NUM> and <NUM>, not more than <NUM> and <NUM>, not more than <NUM> and <NUM>, or the like. In embodiments, the distance between the attractive and repellant electrodes can be, for example, between not more than <NUM> and <NUM>, not more than <NUM> and <NUM>, not more than <NUM> and <NUM>, not more than <NUM> and <NUM>, not more than <NUM> and <NUM>, not more than <NUM> and <NUM>, not more than <NUM> and <NUM>, not more than <NUM> and <NUM>, not more than <NUM> and <NUM>, or the like. In embodiments, the distance between the attractive and repellant electrodes can be, for example, between not more than <NUM> and <NUM>, not more than <NUM> and <NUM>, not more than <NUM> and <NUM>, not more than <NUM> and <NUM>, not more than <NUM> and <NUM>, not more than <NUM> and <NUM>, not more than <NUM> and <NUM>, not more than <NUM> and <NUM>, or the like.

In embodiments, disclosed devices can comprise a circular or "donut" shaped device (including a void in the center) comprising an electrode producing a repellant field, for example an electric field. For example, disclosed devices can comprise an electrode producing a repellant electric field that can be applied with the void directly over the treatment site and the body of the device surrounding the treatment site. This type of embodiment can be particularly suitable for use with treatments where no spread of the injected material is desired. For example, in methods comprising administration of a neurotoxin to the patient's head, for example for treatment of migraine or depression or pain, disclosed devices can be applied prior to the injections, then the injection is made through the void region.

Disclosed compositions suitable for use with disclosed devices can comprise cosmetic pharmaceutical compositions, such as dermal fillers.

A <NUM> year old male patient is going to be treated to minimize glabellar lines with BoNT/A. Prior to administering the toxin via needle injection, the doctor applies a disclosed embodiment that generates a positive electric field in a perimeter within <NUM> surrounding the intended injection sites. Then, the doctor injects <NUM> sites with <NUM> U of the BoNT/A to the typical glabellar lines treatment sites. The patient wears the embodiment producing the positive electric field for three hours. The patient experiences no ptosis.

A <NUM> year old male patient is going to be treated to minimize glabellar lines with BoNT/E. Prior to administering the toxin via needle injection, the doctor applies a disclosed embodiment that generates a positive electric field in a perimeter within <NUM> surrounding the intended injection sites. Then, the doctor injects <NUM> sites with <NUM> U of the BoNT/E to the typical glabellar lines treatment sites. The patient wears the embodiment producing the positive electric field for three hours. The patient experiences no ptosis.

A <NUM> year old female patient is going to be treated to minimize glabellar lines with BoNT/B. Prior to administering the toxin via needle injection, the doctor applies a disclosed embodiment that generates a positive electric field in a perimeter within <NUM> surrounding the intended injection sites. Then, the doctor injects <NUM> sites with <NUM> U of the BoNT/B to the typical glabellar lines treatment sites. The patient wears the embodiment producing the positive electric field for three hours. The patient experiences no ptosis.

A <NUM> year old male patient is going to be treated to minimize glabellar lines with BoNT/A. Prior to administering the toxin via needle injection, the doctor applies a disclosed embodiment comprising a platinum electrode powered by a 5V power source that generates a positive electric field in a perimeter within <NUM> surrounding the intended injection sites. Then, the doctor injects <NUM> sites with <NUM> U of the BoNT/A to the typical glabellar lines treatment sites. The patient wears the embodiment producing the positive electric field for three hours. The patient experiences no ptosis.

A <NUM> year old male patient is going to be treated to minimize glabellar lines with BoNT/A. Prior to administering the toxin via needle injection, the doctor applies a disclosed embodiment comprising a platinum electrode powered by a 3V power source that generates a positive electric field in a perimeter within <NUM> surrounding the intended injection sites. Then, the doctor injects <NUM> sites with <NUM> U of the BoNT/A to the typical glabellar lines treatment sites. The patient wears the embodiment producing the positive electric field for three hours. The patient experiences no ptosis.

A <NUM> year old female patient is going to be treated to minimize crows feet with BoNT/A. Prior to administering the toxin via needle injection, the doctor applies a disclosed embodiment comprising a zinc electrode that generates a positive electric field in a perimeter surrounding the intended injection sites. Then, the doctor injects <NUM> sites with <NUM> U of the BoNT/A to the typical crows feet treatment sites. Following the injections, the doctor applies a disclosed embodiment comprising a silver electrode that generates a negative electric field directly on top of the injection sites. The patient wears the embodiments producing the positive and negative electric fields for <NUM> minutes. The patient experiences no ptosis.

A <NUM> year old female patient is going to be treated to minimize crows feet with BoNT/A. Prior to administering the toxin via needle injection, the doctor applies a disclosed embodiment comprising a zinc electrode that generates a positive electric field in a perimeter surrounding the intended injection sites. Then, the doctor injects <NUM> sites with <NUM> U of the BoNT/E to the typical crows feet treatment sites. Following the injections, the doctor applies a disclosed embodiment comprising a silver electrode that generates a negative electric field directly on top of the injection sites. The patient wears the embodiments producing the positive and negative electric fields for <NUM> minutes. The patient experiences no ptosis.

A <NUM> year old female patient is going to be treated to minimize crows feet with BoNT/B. Prior to administering the toxin via needle injection, the doctor applies a disclosed embodiment that generates a positive electric field in a perimeter surrounding the intended injection sites. Then, the doctor injects <NUM> sites with <NUM> U of the BoNT/B to the typical crows feet treatment sites. Following the injections, the doctor applies a disclosed embodiment that generates a negative electric field directly on top of the <NUM> injection sites.

The patient wears the embodiments producing the positive and negative electric fields for three <NUM> minutes. The patient experiences no spread of the toxin from the treatment site.

A <NUM> year old male patient is going to be treated with hyaluronic acid. Prior to administering the filler via needle injection, the doctor applies a disclosed embodiment that generates a negative electric field in a perimeter surrounding the intended injection sites. The patient wears the embodiment producing the positive electric field for three hours. The patient experiences no diffusion of the filler.

A <NUM> year old female patient is going to be treated with hyaluronic acid. Prior to administering the filler via needle injection, the doctor applies a disclosed embodiment that generates a negative electric field in a perimeter surrounding the intended injection sites. Following the injections, the doctor applies a disclosed embodiment that generates a positive electric field directly on top of the injection sites. The patient wears the embodiments producing the positive and negative electric fields for <NUM> minutes. The patient experiences no diffusion of the filler.

A <NUM> year old female patient is going to be treated to minimize crows feet with BoNT/A. Prior to administering the toxin via needle injection, the doctor applies a TENS device to minimize spread of the neurotoxin. Prior to injection, positive electrodes of the TENS is applied to repel the toxin from beyond the treatment area, while the negative electrode is placed directly on top of the injection sites. The intensity of the TENS is increased until the patient reports a tingling sensation.

Claim 1:
A device for localizing an injected botulinum toxin at a glabellar line treatment site, the device comprising an electrode that produces a negative charge if the injected botulinum toxin has an isoelectric point less than <NUM> and produces a positive charge if the injected botulinum toxin has an isoelectric point greater than <NUM>, characterized in that the electrode is provided on a flexible substrate that overlays the skin and is configured to repel the injected botulinum toxin.