Patent Description:
Disposable devices, including syringes, pipettes and other such applicators, are currently used to deliver fluids to the mouths and noses of animals. Unfortunately, existing devices are not well-designed to provide safe and effective vaccination. Applicants thus sought to develop an improved, ergonomic, liquid applicator, which contains an angled or flexible stem, which can deliver fluids, including vaccines, safely and effectively to animals in need thereof. Examples of existing devices include the following prior art documents. <CIT> discloses treatment of migrainous headaches and associated symptoms; it further discloses compositions, unit dose applicators, treatment regimens and compositions comprising parthenolide and/or feverfew. <CIT> discloses mainly single-use applicator devices comprising reservoir and applicator components, for convenient storage and dispensing of various compositions to surfaces. <CIT> discloses a mixing and dispensing device with a dual compartment, for packaging and premixing pharmaceutical preparations immediately before direct administration. <CIT> discloses a method of treating canine diseases comprising administering to dogs therapeutically effective amounts of a vaccine, where the vaccine comprises viral antigens, a bacterin, or both, and is administered subcutaneously or orally according to defined schedules.

The present invention is described in the appended claims and based upon the successful engineering of a liquid applicator for delivering liquid formulations to animals. In an aspect, the disclosure provides an improved device for the rapid oral administration of vaccines or other pharmaceutical agents to animals, including canine and feline animals, including puppies and kittens. The applicator may be pre- filled with sterile carrier liquid, which may include but not be limited to water, surfactants, adjuvants, preservatives, and other non-immunogen, and/or pharmaceutically and/or veterinarily acceptable excipients. In other embodiments, the applicator is not pre-filled and may be used to dispense vaccines or other pharmaceutical active agents that are in the form of a liquid solution, emulsion or suspension. In one embodiment, to use the applicator, a user opens the applicators and dispenses or pours carrier liquid into a vial containing lyophilized immunogens. The user then blends the liquid with the immunogens, and draws the resulting liquid formulation back into the applicator by compressing and releasing the applicator's resilient reservoir. Finally, the user inserts the formulation-loaded applicator into the mouth of an animal to be vaccinated, compresses the resilient reservoir, thereby administering the liquid formulation to the animal. In other embodiments, the liquid applicator may be used to administer a liquid medicament to animals via other routes of administration (e.g. topical, nasal, ocular, otic, among others).

The disclosure includes a method of vaccinating an animal in need there of comprising administering a liquid vaccine to the animal; e.g., using a kit. Such a kit is found to increase the safety of the animal and the person administering the vaccine to the anima. Such a method, applicator and/ or kit is found to reduce the anxiety of an animal in need of vaccination while receiving the vaccination.

With reference to the figures, embodiments are described with regard for the best mode and preferred embodiment. In a general sense, the description includes a pipette-type liquid applicator <NUM>/<NUM>/<NUM> for administering liquid formulations, including vaccine formulations, to animals, e.g., per os. The applicator <NUM>/<NUM>/<NUM> includes at least one resilient reservoir 10a/10b/10c and stem 20a/20b/20c for drawing a liquid into the applicator and expelling a liquid, e.g., a blended vaccine formulation <NUM> from the applicator. In an embodiment, the blended vaccine formulation may comprise one or more lyophilized immunogens. Once the applicator is opened via removal of a seal, e.g., seal 25a/25b or seal <NUM>, a carrier liquid <NUM> may be poured or dispensed into vial <NUM>/<NUM> containing one or more lyophilized immunogens <NUM>, e.g., a vaccine component. Once the carrier liquid <NUM> is sufficiently blended with the lyophilized immunogen <NUM>, e.g., the vaccine component, to form a blended vaccine formulation <NUM>, the resilient reservoir 10a/10b/10c is compressed by squeezing (e.g., <NUM>) to generate suction to draw up the blended vaccine formulation, re-inserted into the vial, and the reservoir released. Due to the resulting vacuum, the formulation is thereby urged through the distal opening <NUM> of the stem 20a/20b/20c and into the reservoir 10a/10b/10c. In an embodiment, the combined volume of the reservoir 10a/10b/10c and stem 20a/20b/20c is large enough to accommodate and/ or deliver at least one dose of blended vaccine formulation <NUM> to an animal per os. After the blended vaccine formulation <NUM> is loaded into the applicator <NUM>/<NUM>/<NUM>, the distal end e.g., <NUM> is inserted into the mouth of an animal to be vaccinated, and the reservoir 10a/10b/10c is compressed to deliver the formulation into the mouth of the animal, e.g., a buccal surface, or buccal cavity thereof.

As described herein, with reference to <FIG>, applicator <NUM> comprises hollow stem 20a in fluid communication with reservoir 10a. Stem 20a is bounded at a distal end by frangible seal 25a. Tab 9a bounds the reservoir end of the applicator. Stem 20a further comprises a bend and two linear stem regions <NUM> and <NUM>. In an embodiment, the stem regions <NUM>, <NUM>, defining axes A and B respectively may intersect to form angle theta (θ). In an embodiment the stem regions <NUM>, <NUM> may have a length ratio of from <NUM>:<NUM> to <NUM>:<NUM>; or from <NUM>:<NUM> to <NUM>:<NUM> or from <NUM>:<NUM> to <NUM>:<NUM>; or from <NUM>:<NUM> to <NUM>:<NUM>.

In an embodiment of the present invention, with reference to <FIG>, applicator <NUM> comprises hollow stem 20b in fluid communication with reservoir 10b. Stem 20b is bounded at a distal end by frangible seal 25b. Graspable tab 9b bounds the reservoir 10b end of applicator <NUM>. Stem 20b further comprises a bend and two linear stem regions <NUM> and <NUM>. In an embodiment the stem regions <NUM>, <NUM>, defining axes A' and B' respectively may intersect to form angle theta (θ). Stem regions <NUM>, <NUM> may have a length ratio of from <NUM>:<NUM> to <NUM>:<NUM>; or from <NUM>:<NUM> to <NUM>:<NUM> or from <NUM>:<NUM> to <NUM>:<NUM>; or from <NUM>:<NUM> to <NUM>:<NUM>. In an embodiment, stem region <NUM> may further comprise one or more longitudinal stiffeners <NUM>, <NUM>. Longitudinal stiffeners <NUM> and <NUM>, that in part join stem 20b to reservoir 10b, may be adapted to allow stem 20b to resist deformation during applicator <NUM> use. According to the invention, diametrically disposed tabs 28a and 28b provide a support surface for a user to grasp while removing seal 25b. Tabs 28a, 28b allow distal end <NUM> to remain fully opened and resist deformation during use. Tab <NUM> (e.g., formed by thermosealing of the reservoir) may be grasped by a user, for example, to avoid prematurely dispensing vaccine (i.e. prior to achieving optimal placement in the animal's mouth).

As described herein, with respect to <FIG>, applicator <NUM> comprises hollow stem 20c in fluid communication with reservoir 10c. Stem 20c is bounded at a distal end 27c. Applicator <NUM> may comprise separate, e.g., separated reservoirs <NUM>, wherein reservoir <NUM> contains a liquid carrier. Reservoir 10c is resilient, and functions as an elastic suction bulb. In this embodiment, a seal at the distal end <NUM> of stem 20c may be omitted, since the first reservoir <NUM> has its own frangible seal <NUM>. In other words, only one seal is required for retaining the carrier liquid within the applicator as provided to the user. As is visible in <FIG>, sealing region <NUM> defines a barrier between reservoirs 10c and <NUM>.

In both the single and multi-reservoir embodiments, application of mechanical force (e.g. a user squeezing thumb and finger around the reservoir) expels liquid contents, and release of mechanical force (e.g. user releasing thumb and finger from around the reservoir) generates the suction required to draw up the liquid.

In some embodiments of the present invention, the applicator may comprise fused dual or double stems <NUM>, e.g., to provide a stiffer stem <NUM> while, e.g., concomitantly decreasing residual volume of liquid formulation.

The description may include one or more of the following items.

Item <NUM> may be an applicator <NUM>/<NUM>/<NUM>, e.g., for containing, e. g, sealably containing, a carrier liquid <NUM> and for delivering a veterinarily acceptable nutraceutical, pharmaceutical or biological formulation <NUM> to an animal in need thereof, the applicator comprising:
a resilient and/or elongated reservoir 10a/10b/10c, defining a longitudinal axis A/A'. An elongate, angled, hollow stem 20a/20b/20c, adapted to be inserted into the animal's mouth, the stem 20a/20b/20c comprising proximal (102a/106a) and distal ends (e.g., <NUM>/<NUM>/<NUM>), the proximal end 102a/106a operably connected to and in fluid communication with the reservoir 10a/10b/10c, and distal end (e.g.,<NUM>/<NUM>/<NUM>) serving as a conduit through which a liquid exits and enters the applicator;.

Item <NUM> may also comprise a frangible seal 25a/25b wherein exit and entry of fluid from the applicator is blocked until the frangible seal is broken.

Item <NUM> may also comprise an applicator <NUM>/<NUM>/<NUM> adapted to deliver a liquid composition to an animal per os, comprising a resilient and/ or elongated reservoir defining a longitudinal axis, an elongate, angled, hollow stem adapted to be inserted into the animal's mouth, the stem comprising proximal and distal ends, the proximal end operably connected to and in fluid communication with the reservoir and the distal end adaptable to allow liquid to exit and enter the applicator; and wherein the applicator is adapted to sealably contain a carrier liquid of the liquid composition to be dispensed to the animal.

Item <NUM> may comprise an applicator <NUM> for sealably containing a carrier liquid and for delivering a veterinarily acceptable nutraceutical, pharmaceutical or biological formulation to an animal in need thereof, the applicator comprising at least a first reservoir defining an axis A", adapted to contain a carrier liquid to be dispensed; at least a second reservoir 10c, the second reservoir 10c optionally coaxial with the first reservoir, resilient and elongated, and adapted to draw liquid into the second reservoir 10c when mechanical pressure is first applied to the second reservoir 10c and then released while the second reservoir is in fluid communication with the liquid;
an elongated, optionally angled, hollow stem 20c, adapted to be inserted into the animal's mouth, the stem 20c comprising proximal 106b and distal 27c ends, the proximal end 106c operably connected to and capable of fluid communication with the second reservoir 10c and not the first reservoir, and the distal end 27c defining a conduit through which the liquid exits and enters the applicator.

Item <NUM> may comprise a first frangible seal <NUM> wherein fluid exit of the liquid from the first reservoir is blocked until a first frangible seal <NUM> is broken.

Item <NUM> may comprise the applicator of item <NUM>, wherein a portion of the stem defines an axis B/B' and the axis is angled to an angle theta (θ) wherein theta is from about <NUM> to about <NUM> degrees, with respect to the longitudinal axis A/ A'.

Item <NUM> may comprise the applicator of item <NUM>, wherein the stem is angled to an angle theta (θ) wherein theta is from about <NUM> to about <NUM> degrees, with respect to the longitudinal axis A/ A'.

Item <NUM> may comprise the applicator of item <NUM> or <NUM>, wherein theta is from about <NUM> to about <NUM>, or from about <NUM> to about <NUM>, about <NUM> to about <NUM> degrees, or about <NUM> degrees.

Item <NUM> may comprise the applicator of item <NUM>, wherein the distal end of the stem sealed by a frangible seal 25a/25b.

Item <NUM> may further comprise the frangible seal 25a/25b breakable by a twisting or torqued force.

Item <NUM> may comprise the applicator of item <NUM>, wherein the distal end of the first reservoir <NUM> is sealed by a frangible sealing means <NUM> configured to be broken, e.g., by a twisting motion or torque, thereby permitting the liquid to be poured out of the applicator.

Item <NUM> may comprise the applicator of item <NUM>, wherein the stem is for suction of liquids by vacuum created by compressing the resilient reservoir and thereafter gradually releasing the compression of the resilient reservoir.

Item <NUM> may further comprise the stem in fluid communication with, and is substantially in airtight connection with, the reservoir, once the sealing means is broken.

Item <NUM> may comprise the applicator of item <NUM>, wherein an inside surface of the resilient reservoir and stem are smooth and without projections or depressions.

Item <NUM> may comprise the applicator of item <NUM>, wherein a transition between an inside surface of the resilient reservoir and an inside surface of the stem is smooth and without edges.

Item <NUM> may comprise the applicator of item <NUM>, wherein the stem angle optimized to reduce the amount of residual blended vaccine formulation after a single compression of the resilient reservoir.

Item <NUM> may comprise the applicator of item <NUM>, wherein less than about <NUM>% to about <NUM>% (v/v) of the blended vaccine formulation remains in the resilient reservoir after a single compression of the resilient reservoir.

Item <NUM> may comprise the applicator of item <NUM> less than about <NUM>% (v/v) of the formulation remains in the resilient reservoir after two compressions of the resilient reservoir.

Item <NUM> may comprise the applicator of item <NUM>, wherein the first reservoir and second reservoir are not in fluid communication with one another, and are blow-molded from a single piece of polymeric material.

Item <NUM> may comprise the applicator of item <NUM>, wherein the first reservoir is resilient enough to be compressed, but not so resilient that when the frangible sealing means is broken, the mere holding force causes the liquid contained within the first reservoir to be expelled.

With respect, for example, to <FIG>, item <NUM> may comprise a method of vaccinating an animal in need thereof comprising the steps of:.

The applicator as described herein also encompasses any of the items <NUM>-<NUM> described above wherein the applicator of the disclosure is used administering a liquid solution, suspension or emulsion containing a vaccine or pharmaceutical agent that does not require reconstitution with water or another liquid to an animal in need thereof. In this alternate embodiment, the applicator is not pre-filled with a reconstituting liquid and the liquid, suspension or emulsion containing the vaccine or pharmaceutical agent in a vial or other container is directly drawn into the empty applicator for subsequently administering the solution to the animal.

It will also be appreciated that the present disclosure encompasses administration of a vaccine or other pharmaceutical agent in the form of a liquid solution, suspension or emulsion to an animal via other routes of administration including, but not limited to, topical administration (to the skin), ocular administration, otic administration (via ear), nasal administration, rectal or vaginal administration, or by inhalation.

With respect, for example, to <FIG>, an alternative item <NUM> may comprise a method of vaccinating an animal in need thereof comprising the steps of:.

Item <NUM> may comprise the method of item <NUM>, wherein the applicator has only one reservoir, which serves the multiple purposes of: containing the carrier liquid, dispensing the earner liquid into the vial, drawing up the vaccine formulation into the applicator, and finally, delivering the vaccine formulation to the animal.

Item <NUM> may comprise the method of item <NUM>, wherein there are only two reservoirs:.

Item <NUM> may comprise the method of any one of items <NUM> to <NUM>, wherein the animal is a canine and the vaccine comprises a protective immunogen capable of providing the canine with protective immunity against a rabies virus or a Bordetella virus; or alternatively, a pathogen selected from the group consisting of an influenza virus, a parainfluenza virus, a canine influenza virus, a bordatella virus, a rabies virus a parvovirus, an adenovirus, and a distempter virus.

Item <NUM> may comprise the method of item <NUM>, wherein one vaccination is protective in the canine for at least <NUM> year, or at least <NUM> years, or from <NUM> years to about <NUM> year, or from about <NUM> years to about <NUM> years, or from about <NUM> years to about <NUM> years.

In one embodiment the present invention may comprise a kit <NUM> comprising an applicator <NUM>/<NUM>/<NUM> and a sealed vial <NUM>/<NUM> comprising a lyophilized immunogen.

Applicator Production. The applicator may generally be produced according to the following steps: <NUM>) Blow Fill Seal; <NUM>) printing or labelling; and <NUM>) packaging (e.g. bags of <NUM>). The sealed reservoir may be pre-filled with water and suitable, e.g., veterinarily acceptable, excipients. In some embodiments, a <NUM> dose is recoverable from the applicator, taking in account: residual volume in <NUM> cc vial and tube, any loss while opening the tip (splashing), any water loss/intake through the tube walls and through the entire shelf-life of liquid carrier (e.g. diluent; <NUM> months). In some embodiments, the estimated filling volume of the applicator may be from about <NUM> to about <NUM>, or from about <NUM> to about <NUM>, or from about <NUM> to about <NUM>, or from about <NUM> to about <NUM>, or from about <NUM> to about <NUM>.

In other embodiments for delivering larger volumes, the filling volume of the applicator may be from about <NUM> to about <NUM>, from about <NUM> to about <NUM> or from about <NUM> to about <NUM>. In other embodiments, the filling volume of the applicator may be larger than about <NUM> including from about <NUM> to about <NUM>, from about <NUM> to about <NUM> or from about <NUM> to about <NUM>. In yet other embodiments, the fill volume of the applicator may be from about <NUM> to about <NUM>, from about <NUM> to about <NUM> or from about <NUM> to about <NUM>. The applicator may be made of any suitable material, including but not limited to LDPE, MDPE and HDPE.

The amount of dry material to be reconstituted with liquid will depend on the dose to be administered. Accordingly, various dosages may be administered with applicators having different fill volumes. In some embodiments, the amount of dry material (e.g. lyophilized material) in the vial or other container which is reconstituted with liquid prior to dispensing may be from about <NUM> grams to about <NUM> grams or more. More typically, the weight of the material to be reconstituted may be from about <NUM> grams to about <NUM> gram or from about <NUM> grams to about <NUM> grams. In other embodiments, the weight of dry material that will be reconstituted will be from about <NUM> grams to about <NUM> grams or from about <NUM> grams to about <NUM> grams. In yet another embodiment, the amount of dry material that is reconstituted with liquid is about <NUM> grams.

In some embodiments, the applicator is intuitive and easy to open for adults, including veterinarians. In some embodiments, no sharp edges are created during removal of the tip/seal.

In some embodiments, the applicator is adapted to allow the user to dispense into and then withdraw from a <NUM> cc vial. As indicated in <FIG>, the applicator should be able to be inserted into a vial having the following dimensions (in inches, <NUM> inch = <NUM>):.

In some embodiments, the applicator may deliver a dose of the blended vaccine formulation <NUM> with one (<NUM>) squeeze or at most two (<NUM>) squeezes. Residual volumes, e.g., the volume of formulation 6oo remaining after application to the animal's mouth, are kept to a minimum, for example, less than about <NUM>% of the original volume of formulation <NUM>, or less than about <NUM>%, or less than about <NUM>%, or less than about <NUM>%, or less than about <NUM>%, or less than about <NUM>%, or less than about <NUM>%, or less than about <NUM>%, or less than about <NUM>%, or less than about <NUM>%, or less than about <NUM>%, or less than about <NUM>%, or less than about <NUM>%, or less than about <NUM>% or less than about <NUM>% residual volume. In some embodiments, two squeezes leave less than about <NUM>% residual volume and <NUM> squeeze leaves less than about <NUM>%.

In some embodiments, the applicator stem is designed to complement the shape of the mouth of the animal to be vaccinated. For example, a long stem can improve ergonomics and facilitate administration. In some embodiments, a long stem with appropriate flexibility, or a long gently angled stem may be employed.

In some embodiments, the applicator, particularly once the seal has been broken, may be used to administer vaccines to animals using only one hand. This applicator feature allows the user to hold and coax the animal with one hand/ arm, while administering vaccine with the other hand. In particular embodiments, the applicator allows for one-hand, one-motion administration. Moreover, the applicator eliminates the need to inject the animal, thereby increasing safety for both the animal and the person administering the vaccine.

Claim 1:
An applicator (<NUM>/<NUM>) adapted to deliver a liquid vaccine composition (<NUM>) to a canine or feline animal by oral administration;
wherein the applicator is adapted to the canine or feline mouth, comprising a resilient and/or elongated reservoir (10b, 10c) defining a longitudinal axis (A'), an elongate, angled, hollow stem (<NUM>) adapted to be inserted into the canine or feline animal's mouth, the stem (<NUM>) comprising proximal and distal ends, the proximal end operably connected to and in fluid communication with the reservoir (10b, 10c) and the distal end adaptable to allow liquid to exit and enter the applicator (<NUM>/<NUM>);
and wherein the applicator is adapted to sealably contain a carrier liquid (<NUM>) of the liquid vaccine composition (<NUM>) to be dispensed to the canine or feline animal;
further wherein a portion of the stem (<NUM>) is angled with respect to the longitudinal axis (A') and wherein the portion of the stem defines a second axis (B'), wherein the longitudinal axis (A') and the second axis (B') define an angle theta (θ) with respect to the longitudinal axis (A'), wherein theta is from about <NUM> to about <NUM> degrees, or from about <NUM> to about <NUM> degrees, or about <NUM> degrees; and
further wherein the distal end (<NUM>/<NUM>) of the stem (<NUM>) comprises two diametrically opposed tabs (28a, 28b), which allow the distal end to remain fully opened and resist deformation during use.