Patent Application
20240374881
The present invention relates to a hand-held underarm spray delivery device for topically delivering a medicinal spray to a person's armpit, wherein the delivery device comprises a shroud for preventing the spray from reaching areas other than the person's armpit. Typically, medicinal spray, which may for instance comprise an aqueous formulation comprising buffered tiotropium bromide, or ipratropium, for topical treatment of hyperhidrosis, should only be applied to the person's armpit, and contact of the spray with any other part of the person, e.g. his or her fingers, and/or inhalation of the spray is to be avoided.
From US 2004/050964 A a hand-held dispensing device is known for dispensing and applying a substance, such as a medicinal spray, to the skin of a host. The known device includes a hollow body, a capsule mounted within the hollow body for containing the substance, a nozzle mounted within the hollow body communicating with the substance in the capsule, an actuator to cause metered quantities of the substance to be dispensed from the capsule through the nozzle, a shroud defining an exit space for receiving the substance emerging from the nozzle, and a cap detachably mounted on the shroud to selectively open and close the nozzle and thereby control escape of the substance from the capsule.
However, the known device is somewhat unwieldy to use and carry around. It is an object of the invention to provide an underarm spray delivery device which at least partially overcomes this drawback.
According to this end, the present invention provides a hand-held underarm spray delivery device, comprising: a container for containing medically active ingredient; an actuatable pump connected to the container and comprising a spray dispensing orifice with a spray axis, wherein the pump is adapted for, upon actuation, releasing a spray comprising the medically active ingredient through said orifice along the spray axis; a housing comprising a first part, a second part, and a flexible shroud attached to the first and the second part, wherein the pump is arranged within the housing, and wherein the first part and/or the second part is provided with an opening aligned with the spray dispensing orifice for allowing spray released through the dispensing orifice to pass through, wherein the second part is rotatable about an axis of rotation relative to the first part between an open position in which spray can pass out of the housing, and a closed position in which spray is prevented from passing out of the housing. When the second part is in the closed position, the device takes up relatively little space, in this manner providing a device that can easily be carried in a purse or pocket.
Typically, the first and second housing part are preferably substantially rigid, e.g. made from, or comprising, a hard plastic material such as polypropylene, polyethylene, an acetal copolymer, and the shroud is typically elastic, e.g. made from, or comprising, an elastic material such as silicone or rubber. The substantially rigid first and second part provide a protective shell for the pump and part or all of the container against deformation and damage. When the second part is in the open position, inner sides of the flexible shroud and of the first and second part together substantially prevent passage of spray from said inner side to an outer side of the shroud other than beyond the edge of the shroud. When the second part is in the closed position, interior surfaces of the device that may come in contact with the spray are completely covered, and the device can be picked up and held without risk of coming into contact with the spray.
In an embodiment the housing, when the second part is in the closed position, seals off an interior volume delimited by the flexible shroud and facing inner surfaces of the first and second housing part, in a substantially liquid tight manner. Liquid containing the medically active ingredient is thus prevented from passing out of the interior volume when the device is closed.
In an embodiment the first and/or second part of the housing is provided with one or more locking mechanisms, adapted for locking the first and second part in the closed position. A user will thus actively have to open the device before the device is ready to dispense spray. Additionally, when the shroud, or at least the circumferential distal edge of the shroud, comprises an elastic material, the locking mechanisms help to press the first part and the second part together such that the shroud can form a liquid-tight seal. The one or more locking mechanisms, which may be spring loaded locking mechanisms, are preferably arranged to be operated by a user from the outer side of the housing when the housing is in the closed position.
In an embodiment the device further comprises a biasing element for biasing the second part to the open position. In this manner, in order to open the device, a user does not have to touch the distal edge of the shroud with his or her fingers. This further helps the user to avoid contact between the user's fingers and any spray that may be present along the distal edge of the shroud. In case the device is provided with one or more locking mechanisms, releasing the locking mechanism(s) will typically result in the second part moving to the open position.
In an embodiment, the pump is adapted for providing a metal-contact free fluid path for the spray through the pump upon actuation of the pump. A suitable pump is offered by Aptar Pharma under the name “Advanced Preservative Free plus”.
In an embodiment the first part and the second part each have an inner surface, wherein a layer of liquid absorbing material is provided on the inner surface of the first and/or second part, for preventing liquid containing medically active ingredient from running along the inner surface of the first and/or second part out of the device. An example of absorbing material is tissue. When some of the spray, rather than reaching its intended target, is directed onto the absorbing material, it may be thus substantially prevented that the medically active ingredient will leak out of the device.
In an embodiment the pump is adapted to be actuated by pressing the container relative to the first and second housing part towards the spray dispensing orifice, preferably by pressing the container towards said orifice along the axis of rotation. Thus, when the pump is actuated, the position of the orifice relative to the first and second part of the housing remains the same.
In an embodiment the container comprises a circumferential portion arranged within the housing, and an end surface spaced distally from the dispensing orifice and arranged to be pressed towards the spray dispensing orifice by a user for actuating the pump. In this manner, the pump can be operated by pressing the end surface of the container towards the orifice. Preferably the end surface of the container is arranged outside of the first and housing parts at least when the pump is not actuated and preferably also when the pump is actuated. The end surface of the container may in this manner function as a button, or part of such a button, for actuating the pump.
In an embodiment the circumferential portion of the container comprises a transparent material, and the first and/or second part of the housing comprises a see-through portion for allowing visual inspection, through the see-through portion and the transparent material, of a level of liquid in the container when the second part of the housing is in the closed position. Though the see-through portion may simply be formed as an opening in the first or second part of the housing, it is preferred that the see-through portion comprises a transparent piece of plastic material.
In an embodiment the flexible shroud comprises a circumferential distal edge shaped and adapted for lying against an armpit along said entire edge when the second part is in the open position. As the edge is adapted for lying against a user's armpit, escape of liquid through gaps between the user's skin and the shroud may be substantially avoided. The distal edge is preferably adapted for folding onto itself when the second part of the housing is in the closed position, for sealing an interior space defined by the housing. This may be achieved for instance when the distal edge of the flexible shroud comprises an elastic material that is adapted to be compressed between the first part and the second part of the housing when the second part is in the closed position.
In an embodiment, when seen in projection onto a plane normal to the spray axis and parallel to the axis of rotation, and when the second part is in the open position, each part of the circumferential distal edge is spaced apart from the spray axis by at least 3 cm. In this manner a spray cone is possible which substantially does not contact the first or second housing parts.
In an embodiment the device further comprises a blocking mechanism adapted for preventing actuation of the pump when the second part is in the closed position. In this manner, accidental spraying of the medically active ingredient is substantially avoided, allowing the device to be safely carried in a user's purse or pocket. The blocking mechanism preferably is arranged within the first and/or second part, to prevent a user from accidentally unblocking the mechanism.
In an embodiment the pump is releasably arranged within the housing, to allow the pump and/or the pump and container connected thereto to be replaced. In this embodiment the device is provided with a latch which is moveable between a first position in which the latch block movement of the pump out of the housing, and a second position in which the pump can be removed from the housing in a direction parallel to the axis of rotation, wherein the latch is adapted to be moveable from the first to the second position only when the second part of the housing is in the closed position. The latch is preferably arranged to be operated by a user from the outer side of the housing.
In an embodiment the axis of rotation is substantially parallel to the longitudinal axis of the container, preferably wherein the axis of rotation and the longitudinal axis of the container substantially coincide.
In an embodiment the spray axis is substantially perpendicular to the longitudinal axis of the container.
In an embodiment, when the second part of the housing is in the closed position the device has a substantially wedge-like shape, e.g. similar to the shape of a closed cockle, providing a particularly compact device.
In an embodiment the first and second housing part each comprise a distal edge, wherein when the second part is in the closed position the distal edges of the first and second part are spaced apart by a first distance, and when the second part is in the open position the distal edges of the first and second part are spaced apart by a second distance greater than the first distance. The first distance may correspond substantially to twice the thickness of the circumferential edge of the shroud when the second part is in the closed position, in which case the second distance is at least 3 times greater than the first distance.
Preferably, when seen in projection onto a plane normal to the axis of rotation, the container has an outer diameter which is greater than the first distance and smaller than the second distance. In an embodiment the second part is adapted for rotating between the closed and the open position relative to the first part, and preferably also relative to the spray axis over an angle of between 65 and 80 degrees around the axis or rotation.
In an embodiment, when the second part is in the closed position, the entire device fits within a rectangular box of dimensions 12 cm×12 cm×3.3 cm.
In an embodiment the container is releasably attached to the pump by means of a liquid tight connection, e.g. a liquid-tight screw connection. By replacing an empty container with a container that contains a medically active component, the device can be reused many times.
In an embodiment the container contains an aqueous formulation comprising an anticholinergic agent as the active ingredient, such as tiotropium bromide, ipratropium, glycopyrronium, and/or oxybutynin. Besides affecting the sweat glands, some anticholinergic agents have the capability of influencing the gastrointestinal tract, urinary tract, lungs or other parts of the body. The dispensing device according to the invention helps prevent that the anticholinergic agent comes into contact with other parts of the user's body than the user's armpits, and in particular prevents the spray from being ingested or inhaled.
The formulation may further comprise an aqueous phase, and a dermatologically acceptable pH adjustment agent to provide the formulation with a pH in the range of 3.0 to 6.0 at 21° C. These compounds are highly suitable for topical treatment of hyperhidrosis. The pH of the aqueous formulation according to the invention is measured at 21° C. using conventional techniques known to the skilled person.
The term “dermatologically acceptable pH adjustment agent” as used herein refers to buffering agents. The pH of the formulation is suitably adjusted by adding a dermatologically acceptable pH adjustment agent selected from buffering systems or salts of weak organic or inorganic acids, such as carbonate buffers, citrate buffers, phosphate buffers, acetate buffers, hydrochloric acid, lactic acid, tartric acid, diethylamine, triethylamine, diisopropylamine, aminomethylamine, or the like. Preferably, the buffer is citrate buffer. Typical citrate buffers are comprised of citric and sodium or potassium citrate, or citric acid and Na2HPO4.
The aqueous formulation may comprise dermatologically acceptable excipients. Typically, the excipients are selected from bactericides, preservatives, antioxidants, humectants, sequestering agents, moisturizers, emollients, surfactant, drying agents, fragrances and the like.
In an embodiment the aqueous formulation comprises 70-99.9 wt. % aqueous phase, by weight of the total formulation, preferably 80-99.7 wt. %, even more preferably 85-99.5, most preferably 90-99.25 wt. % aqueous phase by weight of the total formulation. According to a preferred embodiment, the aqueous phase comprises, based on the weight of the aqueous phase, at least 50 wt. % water, preferably at least 60 wt. % water, more preferably at least 75 wt. % water, even more preferably at least 80 wt. % water, most preferably at least 90 wt. % water. The term “aqueous phase” as used herein refers to an aqueous phase comprising water or pharmaceutically acceptable water-soluble components, such as ethanol, propylene glycol, glycerol, and conventional water-soluble components. The “aqueous phase” is in the liquid state or in the semi-solid state at 20° C., preferably the liquid state. All “wt. %” referred to herein are based on weight of total aqueous formulation, unless otherwise indicated.
In an embodiment the anticholinergic agent is “oxybutynin”. “Oxybutynin equivalent” as used herein refers to oxybutynin free base or a dermatologically acceptable salt of oxybutynin, such as oxybutynin hydrochloride (C22H31NO3·HCl; 4-diethylaminobut-2-ynylalpha-cyclohexylmandelate hydrochloride), or mixtures thereof. Oxybutynin as used herein refers to the (R) and(S) tereoisomers of oxybutynin, and mixtures of the stereoisomers. Preferably, oxybutynin equivalent is present in an aqueous formulation in an amount of 1.0-8 wt. % oxybutynin equivalent, more preferably 1.5-6.0 wt. %, more preferably in an amount of 2.0-5.0 wt. %, even more preferably 2.5 to 4.5 wt. %, based on total weight of the aqueous formulation. Suitable oxybutynin salts are selected from the group consisting of, but not limited to, acetate, bitartrate, citrate, edetate, edisylate, estolate, esylate, fumarate, gluceptate, gluconate, glutamate, hydrobromide, hydrochloride, lactate, malate, maleate, mandelate, mesylate, methylnitrate, mucate, napsylate, nitrate, pamoate, pantothenate, phosphate, salicylate, stearate, succinate, sulfate, tarmate, tartrate, xinafoate, palmitate, pamoic salt, a resonate salt, a laurate salt and others. Pharmaceutical derivatives of oxybutynin which are closely related to oxybutynin are also understood to fall within the scope of the present invention. Preferably, oxybutynin is oxybutynin hydrochloride or used in equivalent amount thereof.
In an embodiment the anticholinergic agent is “glycopyrronium”. “Glycopyrronium equivalent” as used herein refers to glycopyrronium free base or a dermatologically acceptable salt of glycopyrronium, such as glycopyrronium bromide (C19H28BrNO3; [(3S)-1,1-dimethylpyrrolidin-1-ium-3-yl] (2R)-2-cyclopentyl-2-hydroxy-2-phenylacetate;bromide), or mixtures thereof. Preferably, glycopyrronium equivalent is present in an aqueous formulation in an amount of 0.25-6 wt. % glycopyrronium equivalent, more preferably 0.25-3.0 wt. %, even more preferably in an amount of 0.5-3.0 wt. %, yet more preferably 1.0 to 2.0 wt. %, based on total weight of the aqueous formulation. Suitable glycopyrronium salts are selected from the group consisting of, but not limited to, such as iodide, acetate, sulphate, chloride, fluoride, iodide, nitrate, sulfonate, phosphate, propionate, glycolate, pyruvate, oxalate, succinate, fumarate, tartrate, citrate, benzoate, methanesulfonate, 4-methylbenzenesulfonate (tosylate), salicylate and others. Pharmaceutical derivatives of glycopyrronium which are closely related to glycopyrronium are also understood to fall within the scope of the present invention. Preferably, glycopyrronium is glycopyrronium bromide or used in equivalent amount thereof.
In a preferred embodiment, the aqueous formulation comprises, by weight of the total formulation: 1.0-2.0 wt. % glycopyrronium equivalent; 70-98 wt. % aqueous phase; dermatologically acceptable pH adjustment agent to provide the formulation with a pH in the range of 3.0 to 6.0 at 21° C.
In an embodiment, the container contains an aqueous formulation for use in the treatment of a skin disease, said treatment comprising topically administering to a human patient an aqueous formulation comprising, by weight of the total formulation: 1.0-2.0 wt. % glycopyrronium equivalent; 70-98 wt. % aqueous phase; dermatologically acceptable pH adjustment agent comprising citrate, wherein the formulation has a pH in the range of 3.0 to 6.0, preferably 3.0 to 4.0 at 21° C. The skin disease may for instance be primary or secondary hyperhidrosis.
In an embodiment the anticholinergic agent is “ipratropium”. “Ipratropium equivalent” as used herein refers to the substance (8-methyl-8-propan-2-yl-8-azoniabicyclo [3.2.1] octan-3-yl) 3-hydroxy-2-phenylpropanoate. Typically, ipratropium is present in the aqueous formulation in the form of a pharmaceutically acceptable salt. The pharmaceutically acceptable salt is suitably selected from ipratropium bromide anhydrous or monohydrate, or ipratropium chloride. Preferably, ipratropium is ipratropium bromide, more preferably ipratropium bromide monohydrate. Preferably, ipratropium as used herein refers to anhydrous or monohydrate ipratropium bromide. Typically, monohydrate ipratropium bromide is freely soluble in water (10 mg/mL) at 20° C. Preferably, ipratropium equivalent is present in the aqueous formulation in an amount of 0.01-2 wt. %, more preferably 0.3-1.5 wt. %, even more preferably in an amount of 0.5 to 1.0 wt. %.
In a preferred embodiment, the aqueous formulation comprises, by weight of the total formulation: 0.01-2 wt. % ipratropium equivalent; 70-98 wt. % aqueous phase; dermatologically acceptable pH adjustment agent to provide the formulation with a pH in the range of 3.0 to 6.0 at 21° C. The skin disease may for instance be primary or secondary hyperhidrosis.
In an embodiment the anticholinergic agent is “tiotropium”. “Tiotropium equivalent” as used herein refers to the substance (1α, 2β, 4β, 5α, 7β)-7-[(hydroxydi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo [3.3.1.02,4] nonane and salts thereof. Suitable salts are fluoride, chloride, bromide, iodide, C1-C4alkyl sulfate, sulfate, hydrogen sulfate, phosphate, hydrogen phosphate, dihydrogen phosphate, nitrate, maleate, acetate, trifluoroacetate, citrate, fumarate, tartrate, oxalate, succinate and benzoate. Preferably, tiotropium as used herein refers to anhydrous or monohydrate tiotropium bromide. Tiotropium equivalent, preferably tiotropium bromide is present in the aqueous formulation in an amount of 0.0001-1.5 wt. %, preferably in an amount of 0.001-1.0 wt. %, more preferably 0.01-1.0 wt. %, even more preferably 0.025-1.0 wt. %, yet more preferably 0.05 to 0.5 wt. %. Preferably, the aqueous formulation comprises 0.001-1.0 wt. % tiotropium equivalent, more preferably 0.01-1.0 wt. %, even more preferably 0.025 to 0.05 wt. % tiotropium equivalent, preferably tiotropium bromide. Typically, tiotropium equivalent is present in the aqueous formulation in the form of a pharmaceutically acceptable salt. The pharmaceutically acceptable salt is selected from the group consisting of fluoride, chloride, bromide, iodide, C1-C4alkyl sulfate, sulfate, hydrogen sulfate, phosphate, hydrogen phosphate, dihydrogen phosphate, nitrate, maleate, acetate, trifluoroacetate, citrate, fumarate, tartrate, oxalate, succinate and benzoate. The tiotropium equivalent may be anhydrous or a monohydrate. Preferably, the tiotropium equivalent is a monohydrate. More preferably, the tiotropium equivalent is tiotropium bromide monohydrate, or tiotropium chloride monohydrate, most preferably tiotropium bromide monohydrate.
In a preferred embodiment, the container contains an aqueous formulation for use in the treatment of a skin disease, said treatment comprising topically administering to a human patient an aqueous formulation comprising, by weight of the total formulation: 0.0001-1.5 wt. % tiotropium equivalent; 70-99.9 wt. % aqueous phase; dermatologically acceptable pH adjustment agent comprising citrate, wherein the formulation has a pH in the range of 3.0 to 6.0, preferably 3.0 to 5.5 at 21° C. The skin disease may for instance be primary or secondary hyperhidrosis.
The present invention will be discussed in more detail below, with reference to the attached drawings, in which
The first housing part 110 and second housing part 120 each comprise a distal edge 113, 123 in contact with the circumferential distal edge of the shroud 130 is
The device 1 can be folded such that the second part 120 is rotated relative to the first part 110 around the axis of rotation R from the closed position to the open position or vice versa, by a person touching only the exterior surfaces of the housing. During regular use, a person's fingers do not have to come into contact with inner surfaces 111, 121 and 131 of the first and second part and the shroud, which face a side of the device where spray may adhere, i.e. a “wet side” of the device.
When assembled, the container 10 is translatable relative to the first and second housing portion 110, 120 along the axis of rotation R, so that pressing end surface 12 of the container towards the pump 20 causes actuation of the pump so that the active ingredient is sprayed out of dispensing orifice 21.
In order to prevent the device, when closed, from inadvertently opening, the first and second housing portion 110 and 120 are provided with a locking mechanism 141, 142. When the device is in the closed position shown in
As shown in
The pump and container are releasably arranged within the housing, allowing these to be replaced, e.g. to refill the container or replace an empty container with another container that is filled with medically active ingredient. During general use, though the container can slide within the housing, both the container and pump are prevented from sliding completely out of the housing.
The present invention has been described above with reference to a number of exemplary embodiments as shown in the drawings. Modifications and alternative implementations of some parts or elements are possible, and are included in the scope of protection as defined in the appended claims.
| Number | Date | Country | Kind |
|---|---|---|---|
| 21168582.1 | Apr 2021 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2022/060164 | 4/15/2022 | WO |
