WO2006117640A1 - Apparatus and method for administering ophthalmic solutions - Google Patents

Apparatus and method for administering ophthalmic solutions Download PDF

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Publication number
WO2006117640A1
WO2006117640A1 PCT/IB2006/001085 IB2006001085W WO2006117640A1 WO 2006117640 A1 WO2006117640 A1 WO 2006117640A1 IB 2006001085 W IB2006001085 W IB 2006001085W WO 2006117640 A1 WO2006117640 A1 WO 2006117640A1
Authority
WO
WIPO (PCT)
Prior art keywords
orifice
liquid
housing
frame
feed nozzle
Prior art date
Application number
PCT/IB2006/001085
Other languages
French (fr)
Inventor
Joel Fontannaz
Emmanuel Gremion
Hans Himbert
Robert Forrest Landeryou
Bohdan Pavlu
Christian Peclat
Alain Saurer
Daniel Eliot Siegfried
Original Assignee
Pfizer Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pfizer Inc. filed Critical Pfizer Inc.
Priority to CA002606469A priority Critical patent/CA2606469A1/en
Priority to EP06744612A priority patent/EP1877194A1/en
Publication of WO2006117640A1 publication Critical patent/WO2006117640A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
    • A61M11/06—Sprayers or atomisers specially adapted for therapeutic purposes of the injector type
    • A61M11/08—Pocket atomisers of the injector type
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
    • A61M11/006—Sprayers or atomisers specially adapted for therapeutic purposes operated by applying mechanical pressure to the liquid to be sprayed or atomised
    • A61M11/007—Syringe-type or piston-type sprayers or atomisers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B11/00—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use
    • B05B11/01—Single-unit hand-held apparatus in which flow of contents is produced by the muscular force of the operator at the moment of use characterised by the means producing the flow
    • B05B11/10—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle
    • B05B11/109—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle the dispensing stroke being affected by the stored energy of a spring
    • B05B11/1092—Pump arrangements for transferring the contents from the container to a pump chamber by a sucking effect and forcing the contents out through the dispensing nozzle the dispensing stroke being affected by the stored energy of a spring automatically released from a loaded state at the end of the loading stroke
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/0008—Introducing ophthalmic products into the ocular cavity or retaining products therein
    • A61F9/0026—Ophthalmic product dispenser attachments to facilitate positioning near the eye
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2210/00—Anatomical parts of the body
    • A61M2210/06—Head
    • A61M2210/0612—Eyes

Definitions

  • the present invention concerns a dispensing apparatus for liquid products, particularly medicinal products, such as an ophthalmic solution.
  • This design allows no ullage to be left in the apparatus during ejection of the liquid, and thus will not result in quality loss of residual solution within the apparatus between dosing sessions. This is particularly important for medicinal products, and particularly ophthalmic solutions. Also, dosing is more accurate, and the patient is less likely to overdose and experience ocular irritation.
  • prostaglandins beta- blockers or other expensive active ingredients, all having other than the desired pressure relieving action when absorbed by other body tissues than the eye.
  • Small volume dosing is negatively affected by even small uncontrolled or dead spaces in delivery equipments used.
  • medical preparation components may be sensitive to degradation or absorption at prolonged exposure to materials and extended surfaces present in delivery devices. Similar considerations apply for sterility preservation. With regard to stream quality, proper administration of small amounts is complicated by the fact that the active ingredients cannot enter the eye but through the limited area of the cornea. It is also necessary that the entire dose be delivered before the triggered blink reflex closes the eyelid.
  • a large number of devices are already known for applying a specified quantity of a liquid medicinal product onto a part of the body, such as an ophthalmic solution, on the surface of the eye. These devices generally rely on the principle of a syringe which can be either pre-filled with a specified quantity of liquid, or graduated to suck up said quantity of liquid contained in a separate bottle, or connected to a fixed receptacle in permanent communication with the dosing chamber of the syringe, as is described for example in one of the embodiments of US Patent No. 4,623,337. It will be observed that permanently feeding the dosing chamber from the receptacle via gravity means that neither the precision of the quantity of liquid to be ejected, nor the sterility thereof, can be guaranteed. In these devices, the pressure exerted on the plunger, manually or automatically, is generally exerted in the same direction as that of the liquid jet, as is described for example in Patent Cooperation Treaty Publication WO 92/20455.
  • the direction of the jet can sometimes be deviated by bent conduits, but it is then difficult to control the force with which the jet reaches its target.
  • a device of this kind similar to, for example, that disclosed in French Patent No. FR 2 647 757 for food products or cosmetics in liquid or paste-like form, for which respecting a given ejection pressure is of no importance.
  • the present design allows no ullage to be left after a precise quantity of liquid has been ejected, eliminating an important risk associated with traditional technology: quality loss of residual solution in the apparatus between dosing sessions. Both the ejection of a precise quantity of liquid and maintenance of solution quality are particularly important for medicinal products, and particularly ophthalmic solutions.
  • This design also provides accurate horizontal delivery of liquid to a target surface (like an eye) with minimal effort and with minimal dependence on a patient's dexterity. The design minimizes dosing failures associated with traditional technology, ensuring that only 1 dosing session is required.
  • the design ensures more efficient use by the patient, and reduces the medical safety risks associated with multiple attempts to dose medication (like overexposure to active drug, increased ocular irritation due to increase volume of irritants in the formulation, higher risk of infection due to increased frequency of eye contact).
  • the design also allows for horizontal delivery of liquid to facilitate those who have difficulties angling their head, which is required for successfully administrating eye drops using traditional technology.
  • the invention relates to an apparatus for dispensing a liquid product comprising: a) housing or frame having an opening, b) a receptacle for the liquid with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of liquid through the second orifice, and e) a through passage arranged to allow the ejected liquid to pass in a direction different from the feed nozzle and out of the opening, wherein i) the mechanism comprises a mobile element movable with respect to the housing or frame between at least a first position in which the first orifice of the dosing chamber and the feed nozzle are in flow communication and a second position in which the second orifice and the through passage are in flow communication, and ii) the mechanism is arranged to allow aspiration of liquid through the first orifice when the mobile element is in the first position and
  • Another embodiment of the invention relates to the apparatus, wherein the eyepiece optionally comprises an eyepiece ring.
  • Another embodiment of the invention relates to the apparatus, wherein the eyepiece ring is comprised of thermoplastic elastomer or silicone.
  • the invention relates to the apparatus, wherein at least one actuator is included and is adapted to operate the mechanism.
  • An embodiment of the invention relates to the apparatus, wherein the actuator is arranged to be maneuvered by application of manual force.
  • Another embodiment of the invention relates to the apparatus, wherein the actuator is adapted to move or carry the mobile element between a filling position, when the mobile element is in the first position, and an ejection position, when the mobile element is in the second position.
  • the invention relates to the apparatus, wherein the actuator is adapted to perform a substantially continuous movement during which the mechanism performs at least the aspiration step and the movement of the mobile element between the first position and the second position.
  • the invention relates to the apparatus, wherein the actuator mobilizes the mobile element in substantially continuous movement between the first position and the second position.
  • An embodiment of the invention relates to the apparatus, wherein the actuator mobilizes the mobile element in substantially continuous movement to fill the dosing chamber with the liquid product at the first position.
  • An embodiment of the invention relates to the apparatus, wherein the actuator is arranged to mobilize the mobile element in a substantially continuous movement to eject the liquid product from the dosing chamber at the second position.
  • Another embodiment of the invention relates to the apparatus, wherein the actuator is adapted to give a tactile feedback immediately before the ejection step in the continuous movement.
  • Another embodiment of the invention relates to the apparatus, wherein the mobile element is adapted to move in a substantially vertical direction.
  • the invention relates to the apparatus, wherein the mobile element is adapted to move or carry the dosing chamber in a substantially horizontal direction.
  • the invention relates to the apparatus, wherein the dosing chamber comprises a substantially cylindrical barrel, defining a concentric barrel axis.
  • An embodiment of the invention relates to the apparatus, wherein the first orifice is adapted to connect to the aspiration element.
  • Another embodiment of the invention relates to the apparatus, wherein the mobile element comprises an aperture, that when the mobile element is in first position, the aperture is adapted to be blocked, and when the mobile element is in the second position, the aperture is aligned with the second orifice and the opening to eject fluid.
  • the invention relates to an apparatus, wherein the mechanism is adapted to perform in sequence the aspiration of liquid in the first position, the movement of the mobile element to the second position, and the ejection of liquid in the second position.
  • the invention relates to the apparatus, wherein the mechanism is adapted to perform the aspiration by retraction of a pump member against a return spring and to perform the ejection by protraction of a pump member by return spring.
  • An embodiment of the invention relates to the apparatus, wherein the mechanism is adapted to return to the start or rest position also after liquid ejection.
  • Another embodiment of the invention relates to the apparatus, wherein the mechanism is adapted to return to the start or rest position before liquid ejection.
  • the invention relates to the apparatus, wherein the feed nozzle is disposed at a proximal end of the receptacle.
  • the invention relates to the apparatus, wherein the dosing chamber is in operative communication with the feed nozzle.
  • An embodiment of the invention relates to the apparatus, wherein the mobile element is linear cam face shaped.
  • An embodiment of the invention relates to the apparatus, wherein the mobile element has a cam surface.
  • Another embodiment of the invention relates to the apparatus, wherein the dosing chamber comprises an aspiration element therein.
  • Another embodiment of the invention relates to the apparatus, wherein the aspiration element has a cylindrical shape.
  • the invention relates to the apparatus, wherein the aspiration element is a cannula.
  • the invention relates to the apparatus, wherein the aspiration element is formed of a hard plastic material.
  • the invention relates to the apparatus, wherein the aspiration element is formed of polycarbonate (PC). In yet another embodiment, the invention relates to the apparatus, wherein the aspiration element is formed of metal.
  • An embodiment of the invention relates to the apparatus, wherein the aspiration element is formed of acrylonitrile butadiene styrene (ABS).
  • ABS acrylonitrile butadiene styrene
  • Another embodiment of the invention relates to the apparatus, wherein the second orifice is adapted to create a liquid spray.
  • the invention relates to the apparatus, wherein the second orifice is adapted to create a substantially coherent stream.
  • the invention relates to the apparatus, wherein the second orifice is adapted to eject liquid substantially directly into the air. In yet another embodiment, the invention relates to the apparatus, wherein the second orifice is adapted to create a steam of droplets.
  • the invention relates to the apparatus, wherein the stream of droplets is a horizontal stream.
  • the invention relates to a method of operating an apparatus for dispensing a liquid product, comprising: a) housing or frame having an opening, b) a receptacle for the liquid with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of liquid through the second orifice, and e) a through passage arranged to allow the ejected liquid to pass in a direction different from the feed nozzle and out of the opening, the method comprising i) connecting the first orifice and the nozzle in flow communication, ii) filling liquid into the dosing chamber through the first orifice, and iii) ejecting liquid from the dosing chamber through a second orifice onto an ophthalmic target.
  • the invention relates to a kit for operating an apparatus for dispensing a liquid product, the kit comprising an apparatus for dispensing a liquid product, a liquid product, and directions for use; the apparatus comprising: a) housing or frame having an opening, b) a receptacle for the liquid with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of liquid through the second orifice, and e) a through passage arranged to allow the ejected liquid to pass in a direction different from the feed nozzle and out of the opening.
  • An embodiment of the invention relates to the kit, wherein the liquid product is an ophthalmic solution.
  • An embodiment of the invention relates to the kit, wherein the ophthalmic solution is a composition comprising latanoprost or a pharmaceutically acceptable salt or solvate thereof.
  • the invention relates to a method of treating an ophthalmic condition, the method comprising an apparatus for dispensing a liquid product, the apparatus comprising: a) housing or frame having an opening, b) a receptacle for the liquid with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of liquid through the second orifice, and e) a through passage arranged to allow the ejected liquid to pass in a direction different from the feed nozzle and out of the opening, wherein the liquid product comprises a pharmaceutically effective amount of an ophthalmic solution.
  • the ophthalmic solution is a composition comprising latanoprost or a pharmaceutically acceptable salt or solvate thereof.
  • Another embodiment of the invention relates to the use of a pharmaceutically effective amount of an ophthalmic solution for the treatment of an ophthalmic condition wherein the ophthalmic solution is provided to the patient via an apparatus comprising: a) a housing or frame having an opening, b) a receptacle for the ophthalmic solution with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of the ophthalmic solution through the second orifice, and e) a through passage arranged to allow the ejected ophthalmic solution to pass in a direction different from the feed nozzle and out of the opening.
  • the ophthalmic solution contains an active ingredient latanoprost.
  • the invention relates to the use wherein the ophthalmic solution contains a combination of active ingredients latanoprost and timolol maleate.
  • An embodiment of the invention relates to a kit for use in the treatment of ophthalmic conditions, the kit comprising an ophthalmic solution, an apparatus for administering the ophthalmic solution and directions for use; the apparatus comprising: a) a housing or frame having an opening, b) a receptacle for the ophthalmic solution with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of the ophthalmic solution through the second orifice, and e) a through passage arranged to allow the ejected ophthalmic solution to pass in a direction different from the feed nozzle and out of the opening.
  • the invention relates to a kit wherein the ophthalmic solution contains latanoprost. In another embodiment, the invention relates to a kit wherein the ophthalmic solution contains latanoprost and timolol maleate.
  • An embodiment of the invention relates to an ophthalmic composition
  • an ophthalmic composition comprising: a pharmaceutically effective amount of latanoprost solution and an apparatus for holding the latanoprost solution, the apparatus comprising: a) a housing or frame having an opening, b) a receptacle for the latanoprost solution with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of the latanoprost solution through the second orifice, and e) a through passage arranged to allow the ejected latanoprost solution to pass in a direction different from the feed nozzle and out of the opening.
  • An embodiment of the invention relates to a use of a composition for providing an ophthalmic solution wherein said composition comprises: a pharmaceutically effective amount of a ophthalmic solution and an apparatus for holding the ophthalmic solution, the apparatus comprising: a) a housing or frame having an opening, b) a receptacle for the ophthalmic solution with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of the ophthalmic solution through the second orifice, and e) a through passage arranged to allow the ejected ophthalmic solution to pass in a direction different from the feed nozzle and out of the opening.
  • the invention relates to the use wherein the ophthalmic solution contains latanoprost.
  • the invention relates to the use wherein the ophthalmic solution contains latanoprost and timolol maleate.
  • Figure 1 shows a perspective view of a dispensing apparatus according to the invention with the housing attached.
  • Figure 2 shows a frontal perspective view of a dispensing apparatus according to the invention with the housing attached.
  • Figure 3 is an exploded perspective view of the apparatus shown in Figure 1.
  • Figure 4 shows a cross-section along the line V-V of Figure 1, of the mechanism assembly in the rest position.
  • Figure 5 shows an exploded perspective view of the eyepiece shown in Figure 1.
  • Figure 6 shows perspective views of the mobile element as shown in Figure 3.
  • Figure 7 shows perspective view of the mobile element in the ejection position.
  • Figure 8 shows perspective view of the front face of dosing chamber.
  • a perspective view is shown of an embodiment depicting a disposable multi-dose dispensing apparatus according to the invention.
  • Figure 1 externally depicts the apparatus, which includes a housing formed of two shells, housing right 1 and housing left 2, assembled by any suitable means.
  • the liquid product which will be ejected from the apparatus through the air in the direction of the ophthalmic target, the cornea of the eye for example, is contained in a receptacle 18 which is substantially stationary with respect to the housing and support.
  • the liquid product contained in the receptacle 18 comes in fluid communication with the dosing chamber 7, via aspiration, after the dosing chamber 7 is pressurized by the retraction of plunger sealing 11. Once the dosing chamber 7 has been pressurized and is filled with liquid product, the plunger sealing 11 and plunger 12 protract to eject fluid onto the ophthalmic target.
  • FIG 1 it can be seen that actuation by a vertical force is effected in a substantially perpendicular direction to the direction of the ejected liquid product.
  • the actuation mechanism takes the form of an actuator 4.
  • the actuator 4 is configured to receive mobile element 5 and actuator spring 17.
  • the mobile element 5 forms the mobile component, which drives the plunger 12, attached to piston 10, either toward or away from the ophthalmic target.
  • Mobile element 5 has a linear cam face shape and is operatively connected to actuator 4 at an elongated portion 5c and at arms 5b and 5a.
  • Mobile element 5 also has a cam surface 5d, which operates to engage piston 10 to cause plunger 12 to retract and protract.
  • Mobile element 5 also includes at its center an orifice 5e, Figure 6, corresponding to a through passage, that when aligned with dosing orifice 7d, liquid product will be ejected through and onto the ophthalmic target.
  • actuator 4 being in operative communication with mobile element 5 and actuator spring 17, contributes to the precision of the quantity of liquid ejected and to the non-contamination of the dosing chamber 7 by external polluting agents.
  • mobile element 5 is a linear cam face shaped component, which forms the mobile element of the invention.
  • a user may manually exert an external vertical force onto the actuator 4. This force moves the mobile element 5 in a plane perpendicular to the ejection plane.
  • Piston 10 extends horizontally over the dosing chamber 7 and the valve assembly 19.
  • the cam surface 5d is in operative communication sliding along, and pushing the exposed outer surface of the piston 10. This operative communication results in a retraction of the piston assembly 10a, simultaneously causing plunger 12 to retract.
  • plunger sealing 11 When plunger sealing 11 retracts, pressure is then created and aspiration occurs causing liquid to flow from the receptacle 18 into the dosing chamber 7 by valve seal 9.
  • the plunger sealing 11 acts to seal and guide the plunger 12, and the combination of the piston 10, plunger sealing 11 , and plunger 12 combine to form piston assembly 10a.
  • the driving spring 15, housed in plunger spring guide 13, is situated behind the piston 10 and is provided to store potential energy resulting from the retraction of the piston assembly 10a.
  • the cam surface 5d acts as the dosing mechanism causing retraction of the plunger 12 at a distance that is directly proportional to the angle of protrusion of the cam surface 5d.
  • piston assembly 10a Once piston assembly 10a has retracted to a point directly proportional to the greatest angle of protrusion, position 5f, the mobile element 5 then continues moving along the plane.
  • the potential energy stored within the driving spring 15 is released, causing the plunger 12 to protract, simultaneously ejecting fluid from the dosing chamber 7 through orifice 5e onto the ophthalmic target in the form of a spray or stream.
  • the amount or dose of liquid product entering the dosing chamber 7 from receptacle 18 is defined by the tipping angle of mobile element 5.
  • the actuator spring 17 is housed in cylinder 6a of support 6, which abuts the bottom surface of actuator 4. Return valve springs 16 are disposed between valve 8 and valve spring guide 14. When in the rest phase, no force is exerted onto the actuator 4. When a user a exerts manual vertical force onto actuator 4, actuator spring 17 and valve spring 1 16 then become compressed. The vertical compression of actuator spring 17 and valve spring 16 stores potential energy in this active phase, and upon release, expends this energy and restores the actuator 4 to the original rest phase.
  • mobile element 5 includes an orifice 5e, for ejection of the liquid product onto the ophthalmic target.
  • the mobile element 5 is configured to have a cam surface 5d, which abuts a piston assembly 10 at a certain point when mobile element 5 moves in a plane perpendicular to the ejection plane.
  • Valve assembly 19 is comprised of a valve 8 and a valve seal 9 which abut front face dosing chamber 7a. Valve 8 and valve seal 9 work in concert to contain the pressure in the dosing chamber 7.
  • the dosing chamber 7 is comprised of a substantially cylindrical barrel that defines a concentric barrel axis and having a substantially constant cross-section area perpendicular to the barrel axis, and having an aspiration element 7f and a plunger 12 inserted in the barrel, the plunger 12 being movable along the barrel axis. Additionally, orifice 5e has a substantially smaller cross-sectional area than the barrel.
  • Front face dosing chamber 7a includes two apertures, a dosing orifice 7d and an ejection orifice 7e.
  • the mobile element 5 acts to retract the plunger 12 in a direction opposite the ophthalmic target to fill the dosing chamber 7.
  • the pressure created in the dosing chamber 7 fills dosing orifice 7d.
  • the mobile element 5 then continues moving along the plane, and at a second position 5g, the liquid product in the dosing orifice 7d moves to the ejection orifice 7e and the liquid product is ejected through the eyepiece orifice 3b onto the ophthalmic target through orifice 5e.
  • the ejection orifice 7e is substantially narrower than eyepiece orifice 3b or orifice 5e and, the eyepiece orifice 3b is substantially wider than the orifice 5e and the ejection orifice 7e.
  • Housing right 1 and housing left 2 are each formed of hard plastic material, such as bisphenol A, also known as polycarbonate (PC) Lexan ® manufactured by General Electric company or acrylonitrile butadiene styrene (ABS), both plastics are commercially available from Modern Plastics located in Bridgeport, Connecticut, USA, or any suitable hard plastic material available to one of ordinary skill in the art.
  • hard plastic material such as bisphenol A, also known as polycarbonate (PC) Lexan ® manufactured by General Electric company or acrylonitrile butadiene styrene (ABS)
  • the actuator 4 is formed of hard plastic material, such as polycarbonate (PC) Lexan ® or acrylonitrile butadiene styrene (ABS), or any suitable hard plastic material commercially available to one of ordinary skill in the art.
  • PC polycarbonate
  • ABS acrylonitrile butadiene styrene
  • the mobile element 5 is formed of hard plastic material, such as such as polycarbonate (PC) Lexan ® or acrylonitrile butadiene styrene (ABS), or any suitable hard plastic material commercially available to one of skill in the art.
  • PC polycarbonate
  • ABS acrylonitrile butadiene styrene
  • Dosing chamber 7 is formed of hard plastic material, such as polycarbonate (PC) Lexan ® or acrylonitrile butadiene styrene (ABS), or any suitable hard plastic material commercially available to one of ordinary skill in the art.
  • PC polycarbonate
  • ABS acrylonitrile butadiene styrene
  • the receptacle 18 interfaces with the dosing chamber 7 at feed nozzle 18a. This interface may be achieved by a lock and groove mechanism.
  • Receptacle 18 is formed of a plastic material, such as high-density polyethylene (HDPE) commercially available from Equistar, located in Houston, Texas, USA, or polypropylene (PP), or any suitable hard plastic material commercially available to one of ordinary skill in the art.
  • HDPE high-density polyethylene
  • PP polypropylene
  • the aspiration element 7f has substantially cylindrical shaped, such as that of a spike, and is formed of a metal, such as steel, or hard plastic material such as polycarbonate (PC) Lexan ® or acrylonitrile butadiene styrene (ABS), (PE), (HDPE), or any suitable hard plastic material commercially available to one of ordinary skill in the art.
  • the aspiration element 7f may also have a securing means, such as a barb or knob, to help secure to the receptacle 18.
  • Piston 10 is affixed to support 6 and chamber 7 of the apparatus and is formed of a hard plastic material, such as Celanex ® polybutylene terephthalate copolymer (PBT) commercially available from Ticona North America located in Florence, Kentucky, USA, or any suitable hard plastic material commercially available to one of ordinary skill in the art.
  • a hard plastic material such as Celanex ® polybutylene terephthalate copolymer (PBT) commercially available from Ticona North America located in Florence, Kentucky, USA, or any suitable hard plastic material commercially available to one of ordinary skill in the art.
  • PBT polybutylene terephthalate copolymer
  • Plunger 12 is formed of a hard plastic material, such as high-density polyethylene (HDPE), linear low-density polyethylene (LLDPE), or polypropylene (PP), or any suitable hard plastic material commercially available to one of ordinary skill in the art.
  • the plunger may be formed of the same material as the receptacle 18.
  • the plunger 12 constitutes an embodiment of the invention allowing the objectives of precision and sterility to be achieved for the dispensing apparatus, but other types of plunger may be used without departing from the scope of the invention.
  • Plunger sealing 11 is formed of a flexible plastic material, such as Huntsman ® polyethylene or Huntsman ® polypropylene (PP) commercially available from Huntsman ® The Woodlands Texas, USA, or any suitable flexible plastic material commercially available to one of ordinary skill in the art.
  • the valve 8 is formed of a hard plastic material, such as Celanex ® polybutylene terephthalate copolymer (PBT), or any suitable hard plastic material commercially available to one of ordinary skill in the art.
  • the valve seal 9 is formed of a soft elastomeric, such as DanFlex ® commercially available from to one of ordinary skill in the art or Santoprene ® TPE commercially available from Advanced Elastomer Systems located in Akron, Ohio, USA, or any suitable soft thermoplastic elastomer commercially available to one of ordinary skill in the art.
  • a soft elastomeric such as DanFlex ® commercially available from to one of ordinary skill in the art or Santoprene ® TPE commercially available from Advanced Elastomer Systems located in Akron, Ohio, USA, or any suitable soft thermoplastic elastomer commercially available to one of ordinary skill in the art.
  • the plunger spring guide 13 and valve spring guide 14 are both formed of a harder plastic material, such as (HDPE) or (PP), or any suitable hard plastic material commercially available to one of skill in the art.
  • the actuator spring 17, the valve spring 16, (valve spring right 16b and valve spring left 16a) and driver spring 15 are each formed of steel, such as stainless steel, commercially available to one of ordinary skill in the art.
  • Eyepiece assembly 3 is housed onto both housing right 1 and housing left 2.
  • Eyepiece assembly 3 is immobile, but may optionally be mobile, for example retractable for ease of storing the apparatus. Eyepiece assembly 3 is provided to guide the administration of ophthalmic liquid product into the eye.
  • the eyepiece 3a is formed of a soft flexible material, such as Santoprene ® TPE, VersaFlex ® , or silicone commercially available to one of skill in the art and is provided for comfort.
  • the eyepiece 3 is formed of hard plastic material, such as polycarbonate (PC) Lexan ® or acrylonitrile butadiene styrene (ABS), or any suitable hard plastic material commercially available to one of ordinary skill in the art.
  • PC polycarbonate
  • ABS acrylonitrile butadiene styrene
  • Support 6 is operatively connected to actuator 4, the mobile element 5, the dosing chamber 7, the piston assembly 10a, the valve assembly 19, and the valve spring guide 14.
  • Support 6 is formed of a hard plastic material, such as Celanex ® polybutylene terephthalate copolymer (PBT), or any suitable hard plastic material commercially available to one of skill in the art.
  • Support 6 is itself housed onto the interior of both housing right 1 and housing left 2 of the apparatus.
  • the liquid product envisioned by the invention concerns ophthalmic solutions, such as for example Xalatan ® and Xalacom ® , or any latanoprost containing solution, timolil compositions, dry eye solutions, topical eye solutions, topical antibiotics, such as Visine ® , or any product containing active ingredients such as tetrahydrozoline HCL or zinc sulfate, or any suitable ophthalmic solution known to one of ordinary skill in the art.
  • the apparatus may optionally be adapted to include a dose counter, a switch to display the date and time, etc.
  • a suitable kit would include the ophthalmic solution, for example Xalatan ® , the apparatus, and directions for use.
  • All apparatus components work in concert to facilitate ophthalmic dosing, and subsequent delivery.
  • all apparatus components are formed of medium-weight cost effective components, which lend to the disposable nature of the device.
  • a typical single dose volume for delivery to the eye can be less than 100 ⁇ L, suitably less than 50 ⁇ L, and suitably less than 30 ⁇ L.
  • the volume in the standby position is at least 1 ⁇ L, suitably at least 2 ⁇ L and suitably at least 3 ⁇ L.
  • the receptacle 18 suitably has the capacity to deliver a plurality of such doses.
  • a suitable distance from the outlet of the apparatus to the eye is about 24 mm.
  • a suitable jet time is from about 40 to about 60 ms.
  • a suitable speed for the stream of drops or jet ejected is a balance between having enough linear momentum to traverse an air gap between apparatus opening and target, without gravity assistance, traveling fast enough not be obstructed by blinking, and not causing an inconvenient, harmful impact on the eye.
  • the ideal speed is to some extent dependent on the drop size used but as a general rule the drops should be able to traverse at least 1 cm, suitably at least 3 cm and most suitably at least 5 cm through air by its own momentum, incorporating reasonable distances between opening and target.
  • a suitable lower speed limit when leaving the apparatus opening is 0.1 , m/s, suitably 0.5 m/s, suitably at least 5 m/s and most suitably at least 10 m/s.
  • the upper speed is lower than 200 m/s and suitably lower than 100 m/s.
  • a suitable drop size so defined should be sufficient not to be retarded too quickly and not to be easily redirected, e.g. to be inhaled, and suitably has a minimum diameter of 20 ⁇ m, suitably not less than 50 ⁇ m and most suitably at least 100 ⁇ m. Normally the size is less than 200 ⁇ m and suitably less than 150 ⁇ m.
  • the stream may take the form of a horizontal shower or spray of atomized liquid droplets but suitably the stream is narrow and fairly coherent although even such a stream tends to break up into individual droplets after a certain time and distance.
  • the above given values are intended to relate to spherical droplets and for multiple droplets to the weight average of particle diameters.
  • a coherent stream tends to break up into droplets of a diameter of roughly double the diameter of the stream.
  • suitable opening diameters for the dosing orifice are about half the above given drop diameters or roughly between 10 and 1000 ⁇ m, suitably between 20 and 800 ⁇ m.
  • the above considerations are fairly independent of liquid viscosity and tend to apply both for liquid products and ointments. It is desirable that the whole dose can be delivered in a time shorter than the blink reflex time, i.e. in a time shorter than about 150 m/s, suitably shorter than 100 m/s and most suitably shorter than 75 m/s.

Abstract

An apparatus for dispensing a liquid product having: a) housing or frame having an opening (3a) , b) a receptacle for the liquid with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber (7) having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of liquid through the second orifice, and e) a through passage arranged to allow the ejected liquid to pass in a direction different from the feed nozzle and out of the opening (3a) , wherein i) the mechanism comprises a mobile element movable with respect to the housing or frame between at least a first position in which the first orifice of the dosing chamber and the feed nozzle are in flow communication and a second position in which the second orifice and the through passage are in flow communication, and N) the mechanism is arranged to allow aspiration of liquid through the first orifice when the mobile element is in the first position and ejection of liquid through the second orifice when the mobile element is in the second position.

Description

APPARATUS AND METHOD FOR ADMINISTERING OPHTHALMIC SOLUTIONS
Field of the Invention The present invention concerns a dispensing apparatus for liquid products, particularly medicinal products, such as an ophthalmic solution. This design allows no ullage to be left in the apparatus during ejection of the liquid, and thus will not result in quality loss of residual solution within the apparatus between dosing sessions. This is particularly important for medicinal products, and particularly ophthalmic solutions. Also, dosing is more accurate, and the patient is less likely to overdose and experience ocular irritation.
Background of the Invention
Although the principles of the present invention may have utility in many areas, for convenience it will be described mainly in connection with a liquid treatment for eyes. Weinreb RN and Khaw PT, Lancet, 2004; 363: 1711-1720 discuss various eye conditions, such as primary open-angle glaucoma, and is incorporated herein by reference. Typically the medical preparation must be delivered in a fairly well defined volume to assure a specified dose is delivered or absorbed. A large surplus cannot be allowed due to improper systemic physiological effects from absorbency in non-target tissue or drainage of excess amounts through the tear channel into the throat cavity, or the inconveniences caused by overflow on face and clothes. Also price considerations apply to expensive medications. As an example, the treatment of glaucoma requires frequent daily administrations of e.g. prostaglandins, beta- blockers or other expensive active ingredients, all having other than the desired pressure relieving action when absorbed by other body tissues than the eye. Small volume dosing is negatively affected by even small uncontrolled or dead spaces in delivery equipments used. Moreover, medical preparation components may be sensitive to degradation or absorption at prolonged exposure to materials and extended surfaces present in delivery devices. Similar considerations apply for sterility preservation. With regard to stream quality, proper administration of small amounts is complicated by the fact that the active ingredients cannot enter the eye but through the limited area of the cornea. It is also necessary that the entire dose be delivered before the triggered blink reflex closes the eyelid.
A large number of devices are already known for applying a specified quantity of a liquid medicinal product onto a part of the body, such as an ophthalmic solution, on the surface of the eye. These devices generally rely on the principle of a syringe which can be either pre-filled with a specified quantity of liquid, or graduated to suck up said quantity of liquid contained in a separate bottle, or connected to a fixed receptacle in permanent communication with the dosing chamber of the syringe, as is described for example in one of the embodiments of US Patent No. 4,623,337. It will be observed that permanently feeding the dosing chamber from the receptacle via gravity means that neither the precision of the quantity of liquid to be ejected, nor the sterility thereof, can be guaranteed. In these devices, the pressure exerted on the plunger, manually or automatically, is generally exerted in the same direction as that of the liquid jet, as is described for example in Patent Cooperation Treaty Publication WO 92/20455.
The direction of the jet can sometimes be deviated by bent conduits, but it is then difficult to control the force with which the jet reaches its target. A device of this kind similar to, for example, that disclosed in French Patent No. FR 2 647 757 for food products or cosmetics in liquid or paste-like form, for which respecting a given ejection pressure is of no importance.
In the case of a an ophthalmic solution, it is, however, very important not only to control very precisely the dose to be ejected for obvious reasons of safety and efficacy of the treatment, but also in order to be able to control the impact pressure of the liquid jet on the eye, which certain devices attempt to achieve by using an eyepiece or a spacing member applied to find the periphery of the target to impose a fixed distance with respect to the liquid ejection orifice, as is disclosed for example in US Patent Nos. 4,623,337 and 5,836,911. It will be observed however that these devices do not always allow the impact force of the liquid jet to be reproduced when the pressure is exerted directly on the plunger manually.
The present design allows no ullage to be left after a precise quantity of liquid has been ejected, eliminating an important risk associated with traditional technology: quality loss of residual solution in the apparatus between dosing sessions. Both the ejection of a precise quantity of liquid and maintenance of solution quality are particularly important for medicinal products, and particularly ophthalmic solutions. This design also provides accurate horizontal delivery of liquid to a target surface (like an eye) with minimal effort and with minimal dependence on a patient's dexterity. The design minimizes dosing failures associated with traditional technology, ensuring that only 1 dosing session is required. The design ensures more efficient use by the patient, and reduces the medical safety risks associated with multiple attempts to dose medication (like overexposure to active drug, increased ocular irritation due to increase volume of irritants in the formulation, higher risk of infection due to increased frequency of eye contact).
The design also allows for horizontal delivery of liquid to facilitate those who have difficulties angling their head, which is required for successfully administrating eye drops using traditional technology.
Thus, the dispensing apparatuses of the prior art provide individual solutions to particular problems, but none of them allows all of the aforementioned problems to be simultaneously resolved. Summary of the Invention
The invention relates to an apparatus for dispensing a liquid product comprising: a) housing or frame having an opening, b) a receptacle for the liquid with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of liquid through the second orifice, and e) a through passage arranged to allow the ejected liquid to pass in a direction different from the feed nozzle and out of the opening, wherein i) the mechanism comprises a mobile element movable with respect to the housing or frame between at least a first position in which the first orifice of the dosing chamber and the feed nozzle are in flow communication and a second position in which the second orifice and the through passage are in flow communication, and ii) the mechanism is arranged to allow aspiration of liquid through the first orifice when the mobile element is in the first position and ejection of liquid through the second orifice when the mobile element is in the second position. An embodiment of the invention relates to the apparatus, wherein the housing optionally comprises an eyepiece.
Another embodiment of the invention relates to the apparatus, wherein the eyepiece optionally comprises an eyepiece ring.
Another embodiment of the invention relates to the apparatus, wherein the eyepiece ring is comprised of thermoplastic elastomer or silicone.
In yet another embodiment, the invention relates to the apparatus, wherein at least one actuator is included and is adapted to operate the mechanism.
An embodiment of the invention relates to the apparatus, wherein the actuator is arranged to be maneuvered by application of manual force. Another embodiment of the invention relates to the apparatus, wherein the actuator is adapted to move or carry the mobile element between a filling position, when the mobile element is in the first position, and an ejection position, when the mobile element is in the second position.
In yet another embodiment, the invention relates to the apparatus, wherein the actuator is adapted to perform a substantially continuous movement during which the mechanism performs at least the aspiration step and the movement of the mobile element between the first position and the second position.
In yet another embodiment, the invention relates to the apparatus, wherein the actuator mobilizes the mobile element in substantially continuous movement between the first position and the second position.
An embodiment of the invention relates to the apparatus, wherein the actuator mobilizes the mobile element in substantially continuous movement to fill the dosing chamber with the liquid product at the first position.
An embodiment of the invention relates to the apparatus, wherein the actuator is arranged to mobilize the mobile element in a substantially continuous movement to eject the liquid product from the dosing chamber at the second position.
Another embodiment of the invention relates to the apparatus, wherein the actuator is adapted to give a tactile feedback immediately before the ejection step in the continuous movement. Another embodiment of the invention relates to the apparatus, wherein the mobile element is adapted to move in a substantially vertical direction.
In yet another embodiment, the invention relates to the apparatus, wherein the mobile element is adapted to move or carry the dosing chamber in a substantially horizontal direction.
In yet another embodiment, the invention relates to the apparatus, wherein the dosing chamber comprises a substantially cylindrical barrel, defining a concentric barrel axis.
An embodiment of the invention relates to the apparatus, wherein the first orifice is adapted to connect to the aspiration element. Another embodiment of the invention relates to the apparatus, wherein the mobile element comprises an aperture, that when the mobile element is in first position, the aperture is adapted to be blocked, and when the mobile element is in the second position, the aperture is aligned with the second orifice and the opening to eject fluid.
In yet another embodiment, the invention relates to an apparatus, wherein the mechanism is adapted to perform in sequence the aspiration of liquid in the first position, the movement of the mobile element to the second position, and the ejection of liquid in the second position.
In yet another embodiment, the invention relates to the apparatus, wherein the mechanism is adapted to perform the aspiration by retraction of a pump member against a return spring and to perform the ejection by protraction of a pump member by return spring.
An embodiment of the invention relates to the apparatus, wherein the mechanism is adapted to return to the start or rest position also after liquid ejection.
Another embodiment of the invention relates to the apparatus, wherein the mechanism is adapted to return to the start or rest position before liquid ejection. In yet another embodiment, the invention relates to the apparatus, wherein the feed nozzle is disposed at a proximal end of the receptacle.
In yet another embodiment, the invention relates to the apparatus, wherein the dosing chamber is in operative communication with the feed nozzle.
An embodiment of the invention relates to the apparatus, wherein the mobile element is linear cam face shaped.
An embodiment of the invention relates to the apparatus, wherein the mobile element has a cam surface.
Another embodiment of the invention relates to the apparatus, wherein the dosing chamber comprises an aspiration element therein. Another embodiment of the invention relates to the apparatus, wherein the aspiration element has a cylindrical shape.
Another embodiment of the invention relates to the apparatus, wherein the aspiration element is a cannula. In yet another embodiment, the invention relates to the apparatus, wherein the aspiration element is formed of a hard plastic material.
In yet another embodiment, the invention relates to the apparatus, wherein the aspiration element is formed of polycarbonate (PC). In yet another embodiment, the invention relates to the apparatus, wherein the aspiration element is formed of metal.
An embodiment of the invention relates to the apparatus, wherein the aspiration element is formed of acrylonitrile butadiene styrene (ABS).
Another embodiment of the invention relates to the apparatus, wherein the second orifice is adapted to create a liquid spray.
In yet another embodiment, the invention relates to the apparatus, wherein the second orifice is adapted to create a substantially coherent stream.
In yet another embodiment, the invention relates to the apparatus, wherein the second orifice is adapted to eject liquid substantially directly into the air. In yet another embodiment, the invention relates to the apparatus, wherein the second orifice is adapted to create a steam of droplets.
In yet another embodiment, the invention relates to the apparatus, wherein the stream of droplets is a horizontal stream.
The invention relates to a method of operating an apparatus for dispensing a liquid product, comprising: a) housing or frame having an opening, b) a receptacle for the liquid with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of liquid through the second orifice, and e) a through passage arranged to allow the ejected liquid to pass in a direction different from the feed nozzle and out of the opening, the method comprising i) connecting the first orifice and the nozzle in flow communication, ii) filling liquid into the dosing chamber through the first orifice, and iii) ejecting liquid from the dosing chamber through a second orifice onto an ophthalmic target.
The invention relates to a kit for operating an apparatus for dispensing a liquid product, the kit comprising an apparatus for dispensing a liquid product, a liquid product, and directions for use; the apparatus comprising: a) housing or frame having an opening, b) a receptacle for the liquid with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of liquid through the second orifice, and e) a through passage arranged to allow the ejected liquid to pass in a direction different from the feed nozzle and out of the opening.
An embodiment of the invention relates to the kit, wherein the liquid product is an ophthalmic solution. An embodiment of the invention relates to the kit, wherein the ophthalmic solution is a composition comprising latanoprost or a pharmaceutically acceptable salt or solvate thereof.
The invention relates to a method of treating an ophthalmic condition, the method comprising an apparatus for dispensing a liquid product, the apparatus comprising: a) housing or frame having an opening, b) a receptacle for the liquid with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of liquid through the second orifice, and e) a through passage arranged to allow the ejected liquid to pass in a direction different from the feed nozzle and out of the opening, wherein the liquid product comprises a pharmaceutically effective amount of an ophthalmic solution.
Another embodiment of the invention relates to the method, wherein the ophthalmic solution is a composition comprising latanoprost or a pharmaceutically acceptable salt or solvate thereof. Another embodiment of the invention relates to the use of a pharmaceutically effective amount of an ophthalmic solution for the treatment of an ophthalmic condition wherein the ophthalmic solution is provided to the patient via an apparatus comprising: a) a housing or frame having an opening, b) a receptacle for the ophthalmic solution with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of the ophthalmic solution through the second orifice, and e) a through passage arranged to allow the ejected ophthalmic solution to pass in a direction different from the feed nozzle and out of the opening.
In yet another embodiment of the invention relates to the use wherein the ophthalmic solution contains an active ingredient latanoprost.
In still yet another embodiment, the invention relates to the use wherein the ophthalmic solution contains a combination of active ingredients latanoprost and timolol maleate.
An embodiment of the invention relates to a kit for use in the treatment of ophthalmic conditions, the kit comprising an ophthalmic solution, an apparatus for administering the ophthalmic solution and directions for use; the apparatus comprising: a) a housing or frame having an opening, b) a receptacle for the ophthalmic solution with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of the ophthalmic solution through the second orifice, and e) a through passage arranged to allow the ejected ophthalmic solution to pass in a direction different from the feed nozzle and out of the opening.
An yet another embodiment, the invention relates to a kit wherein the ophthalmic solution contains latanoprost. In another embodiment, the invention relates to a kit wherein the ophthalmic solution contains latanoprost and timolol maleate.
An embodiment of the invention relates to an ophthalmic composition comprising: a pharmaceutically effective amount of latanoprost solution and an apparatus for holding the latanoprost solution, the apparatus comprising: a) a housing or frame having an opening, b) a receptacle for the latanoprost solution with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of the latanoprost solution through the second orifice, and e) a through passage arranged to allow the ejected latanoprost solution to pass in a direction different from the feed nozzle and out of the opening.
An embodiment of the invention relates to a use of a composition for providing an ophthalmic solution wherein said composition comprises: a pharmaceutically effective amount of a ophthalmic solution and an apparatus for holding the ophthalmic solution, the apparatus comprising: a) a housing or frame having an opening, b) a receptacle for the ophthalmic solution with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of the ophthalmic solution through the second orifice, and e) a through passage arranged to allow the ejected ophthalmic solution to pass in a direction different from the feed nozzle and out of the opening.
In yet another embodiment, the invention relates to the use wherein the ophthalmic solution contains latanoprost.
In still another embodiment, the invention relates to the use wherein the ophthalmic solution contains latanoprost and timolol maleate. Other features and advantages of the present invention will appear more clearly upon reading embodiment examples, given purely by way of non-limiting illustration, with reference to the annexed drawings, in which:
Figure 1 shows a perspective view of a dispensing apparatus according to the invention with the housing attached. Figure 2 shows a frontal perspective view of a dispensing apparatus according to the invention with the housing attached.
Figure 3 is an exploded perspective view of the apparatus shown in Figure 1. Figure 4 shows a cross-section along the line V-V of Figure 1, of the mechanism assembly in the rest position. Figure 5 shows an exploded perspective view of the eyepiece shown in Figure 1.
Figure 6 shows perspective views of the mobile element as shown in Figure 3. Figure 7 shows perspective view of the mobile element in the ejection position. Figure 8 shows perspective view of the front face of dosing chamber. In Figure 1 , a perspective view is shown of an embodiment depicting a disposable multi-dose dispensing apparatus according to the invention. Figure 1 externally depicts the apparatus, which includes a housing formed of two shells, housing right 1 and housing left 2, assembled by any suitable means. The liquid product, which will be ejected from the apparatus through the air in the direction of the ophthalmic target, the cornea of the eye for example, is contained in a receptacle 18 which is substantially stationary with respect to the housing and support. The liquid product contained in the receptacle 18 comes in fluid communication with the dosing chamber 7, via aspiration, after the dosing chamber 7 is pressurized by the retraction of plunger sealing 11. Once the dosing chamber 7 has been pressurized and is filled with liquid product, the plunger sealing 11 and plunger 12 protract to eject fluid onto the ophthalmic target.
In Figure 1 , it can be seen that actuation by a vertical force is effected in a substantially perpendicular direction to the direction of the ejected liquid product. The actuation mechanism takes the form of an actuator 4. Reference will now be made to Figure 3, in which housing right 1 and housing left 2 have been removed. The actuator 4 is configured to receive mobile element 5 and actuator spring 17. The mobile element 5 forms the mobile component, which drives the plunger 12, attached to piston 10, either toward or away from the ophthalmic target. Mobile element 5 has a linear cam face shape and is operatively connected to actuator 4 at an elongated portion 5c and at arms 5b and 5a. Mobile element 5 also has a cam surface 5d, which operates to engage piston 10 to cause plunger 12 to retract and protract. Mobile element 5 also includes at its center an orifice 5e, Figure 6, corresponding to a through passage, that when aligned with dosing orifice 7d, liquid product will be ejected through and onto the ophthalmic target. The particular structure of actuator 4, being in operative communication with mobile element 5 and actuator spring 17, contributes to the precision of the quantity of liquid ejected and to the non-contamination of the dosing chamber 7 by external polluting agents.
As shown in Figure 6, mobile element 5 is a linear cam face shaped component, which forms the mobile element of the invention. At the rest phase, a user may manually exert an external vertical force onto the actuator 4. This force moves the mobile element 5 in a plane perpendicular to the ejection plane. Piston 10 extends horizontally over the dosing chamber 7 and the valve assembly 19. At a certain point in the movement of the mobile element 5 along the plane, the cam surface 5d is in operative communication sliding along, and pushing the exposed outer surface of the piston 10. This operative communication results in a retraction of the piston assembly 10a, simultaneously causing plunger 12 to retract.
When plunger sealing 11 retracts, pressure is then created and aspiration occurs causing liquid to flow from the receptacle 18 into the dosing chamber 7 by valve seal 9. For stability, the plunger sealing 11 acts to seal and guide the plunger 12, and the combination of the piston 10, plunger sealing 11 , and plunger 12 combine to form piston assembly 10a. The driving spring 15, housed in plunger spring guide 13, is situated behind the piston 10 and is provided to store potential energy resulting from the retraction of the piston assembly 10a. The cam surface 5d acts as the dosing mechanism causing retraction of the plunger 12 at a distance that is directly proportional to the angle of protrusion of the cam surface 5d. Once piston assembly 10a has retracted to a point directly proportional to the greatest angle of protrusion, position 5f, the mobile element 5 then continues moving along the plane. At a protrusion angle of about 0°, position 5g, the potential energy stored within the driving spring 15 is released, causing the plunger 12 to protract, simultaneously ejecting fluid from the dosing chamber 7 through orifice 5e onto the ophthalmic target in the form of a spray or stream. The amount or dose of liquid product entering the dosing chamber 7 from receptacle 18 is defined by the tipping angle of mobile element 5. Once the liquid product is ejected from the apparatus, the external force exerted onto the actuator 4 by the user may be removed, and the actuator spring 17 acts to return the actuator 4 to its original position.
The actuator spring 17 is housed in cylinder 6a of support 6, which abuts the bottom surface of actuator 4. Return valve springs 16 are disposed between valve 8 and valve spring guide 14. When in the rest phase, no force is exerted onto the actuator 4. When a user a exerts manual vertical force onto actuator 4, actuator spring 17 and valve spring1 16 then become compressed. The vertical compression of actuator spring 17 and valve spring 16 stores potential energy in this active phase, and upon release, expends this energy and restores the actuator 4 to the original rest phase.
As can be seen more clearly in enlarged Figure 6, mobile element 5 includes an orifice 5e, for ejection of the liquid product onto the ophthalmic target. The mobile element 5 is configured to have a cam surface 5d, which abuts a piston assembly 10 at a certain point when mobile element 5 moves in a plane perpendicular to the ejection plane. Valve assembly 19 is comprised of a valve 8 and a valve seal 9 which abut front face dosing chamber 7a. Valve 8 and valve seal 9 work in concert to contain the pressure in the dosing chamber 7.
As shown in Figure 3, the dosing chamber 7 is comprised of a substantially cylindrical barrel that defines a concentric barrel axis and having a substantially constant cross-section area perpendicular to the barrel axis, and having an aspiration element 7f and a plunger 12 inserted in the barrel, the plunger 12 being movable along the barrel axis. Additionally, orifice 5e has a substantially smaller cross-sectional area than the barrel.
Front face dosing chamber 7a includes two apertures, a dosing orifice 7d and an ejection orifice 7e. When in the active phase, at a first position 5d, the mobile element 5 acts to retract the plunger 12 in a direction opposite the ophthalmic target to fill the dosing chamber 7. The pressure created in the dosing chamber 7 fills dosing orifice 7d. The mobile element 5 then continues moving along the plane, and at a second position 5g, the liquid product in the dosing orifice 7d moves to the ejection orifice 7e and the liquid product is ejected through the eyepiece orifice 3b onto the ophthalmic target through orifice 5e. The ejection orifice 7e is substantially narrower than eyepiece orifice 3b or orifice 5e and, the eyepiece orifice 3b is substantially wider than the orifice 5e and the ejection orifice 7e.
Housing right 1 and housing left 2 are each formed of hard plastic material, such as bisphenol A, also known as polycarbonate (PC) Lexan® manufactured by General Electric company or acrylonitrile butadiene styrene (ABS), both plastics are commercially available from Modern Plastics located in Bridgeport, Connecticut, USA, or any suitable hard plastic material available to one of ordinary skill in the art.
The actuator 4 is formed of hard plastic material, such as polycarbonate (PC) Lexan® or acrylonitrile butadiene styrene (ABS), or any suitable hard plastic material commercially available to one of ordinary skill in the art.
The mobile element 5 is formed of hard plastic material, such as such as polycarbonate (PC) Lexan® or acrylonitrile butadiene styrene (ABS), or any suitable hard plastic material commercially available to one of skill in the art.
Dosing chamber 7 is formed of hard plastic material, such as polycarbonate (PC) Lexan® or acrylonitrile butadiene styrene (ABS), or any suitable hard plastic material commercially available to one of ordinary skill in the art.
The receptacle 18 interfaces with the dosing chamber 7 at feed nozzle 18a. This interface may be achieved by a lock and groove mechanism. Receptacle 18 is formed of a plastic material, such as high-density polyethylene (HDPE) commercially available from Equistar, located in Houston, Texas, USA, or polypropylene (PP), or any suitable hard plastic material commercially available to one of ordinary skill in the art.
The aspiration element 7f has substantially cylindrical shaped, such as that of a spike, and is formed of a metal, such as steel, or hard plastic material such as polycarbonate (PC) Lexan® or acrylonitrile butadiene styrene (ABS), (PE), (HDPE), or any suitable hard plastic material commercially available to one of ordinary skill in the art. The aspiration element 7f may also have a securing means, such as a barb or knob, to help secure to the receptacle 18.
Piston 10, is affixed to support 6 and chamber 7 of the apparatus and is formed of a hard plastic material, such as Celanex® polybutylene terephthalate copolymer (PBT) commercially available from Ticona North America located in Florence, Kentucky, USA, or any suitable hard plastic material commercially available to one of ordinary skill in the art.
Plunger 12 is formed of a hard plastic material, such as high-density polyethylene (HDPE), linear low-density polyethylene (LLDPE), or polypropylene (PP), or any suitable hard plastic material commercially available to one of ordinary skill in the art. Optionally, the plunger may be formed of the same material as the receptacle 18.The plunger 12 constitutes an embodiment of the invention allowing the objectives of precision and sterility to be achieved for the dispensing apparatus, but other types of plunger may be used without departing from the scope of the invention. Plunger sealing 11 is formed of a flexible plastic material, such as Huntsman® polyethylene or Huntsman® polypropylene (PP) commercially available from Huntsman® The Woodlands Texas, USA, or any suitable flexible plastic material commercially available to one of ordinary skill in the art. The valve 8 is formed of a hard plastic material, such as Celanex® polybutylene terephthalate copolymer (PBT), or any suitable hard plastic material commercially available to one of ordinary skill in the art.
The valve seal 9 is formed of a soft elastomeric, such as DanFlex® commercially available from to one of ordinary skill in the art or Santoprene® TPE commercially available from Advanced Elastomer Systems located in Akron, Ohio, USA, or any suitable soft thermoplastic elastomer commercially available to one of ordinary skill in the art.
The plunger spring guide 13 and valve spring guide 14 are both formed of a harder plastic material, such as (HDPE) or (PP), or any suitable hard plastic material commercially available to one of skill in the art. The actuator spring 17, the valve spring 16, (valve spring right 16b and valve spring left 16a) and driver spring 15 are each formed of steel, such as stainless steel, commercially available to one of ordinary skill in the art.
Eyepiece assembly 3 is housed onto both housing right 1 and housing left 2.
Referring to Figure 1 , Eyepiece assembly 3 is immobile, but may optionally be mobile, for example retractable for ease of storing the apparatus. Eyepiece assembly 3 is provided to guide the administration of ophthalmic liquid product into the eye. The outer ring of eyepiece
3a is formed of a soft flexible material, such as Santoprene® TPE, VersaFlex®, or silicone commercially available to one of skill in the art and is provided for comfort. The eyepiece 3 is formed of hard plastic material, such as polycarbonate (PC) Lexan® or acrylonitrile butadiene styrene (ABS), or any suitable hard plastic material commercially available to one of ordinary skill in the art.
Support 6 is operatively connected to actuator 4, the mobile element 5, the dosing chamber 7, the piston assembly 10a, the valve assembly 19, and the valve spring guide 14. Support 6 is formed of a hard plastic material, such as Celanex® polybutylene terephthalate copolymer (PBT), or any suitable hard plastic material commercially available to one of skill in the art. Support 6 is itself housed onto the interior of both housing right 1 and housing left 2 of the apparatus.
The liquid product envisioned by the invention concerns ophthalmic solutions, such as for example Xalatan® and Xalacom®, or any latanoprost containing solution, timolil compositions, dry eye solutions, topical eye solutions, topical antibiotics, such as Visine®, or any product containing active ingredients such as tetrahydrozoline HCL or zinc sulfate, or any suitable ophthalmic solution known to one of ordinary skill in the art.
The apparatus may optionally be adapted to include a dose counter, a switch to display the date and time, etc. A suitable kit would include the ophthalmic solution, for example Xalatan®, the apparatus, and directions for use.
All apparatus components work in concert to facilitate ophthalmic dosing, and subsequent delivery. In addition, all apparatus components are formed of medium-weight cost effective components, which lend to the disposable nature of the device.
Filling position
From the filling position shown in Figure 4, by exerting a vertical force on actuator 4, the cam surface 5d causes piston assembly 10a to move in a direction opposite the ophthalmic target, thereby retracting plunger 12, subsequently compressing valve spring 16. In this position the receptacle 18 is in liquid communication with dosing chamber 7, via the aspiration element 7f, which enables the dosing chamber 7 to fill with liquid product. By exerting a vertical force on actuator 4, at position 5f, chamber 7 fills with the fully dosed liquid product.
Ejection position By continuing to exert vertical pressure, on the actuator 4, mobile element 5 releases piston assembly 10a as shown in Figure 7. Liquid product then fills ejection orifice 7e, and orifice 5e is aligned therewith. The liquid to be ejected is ejected through both ejection orifice 7e and orifice 5e by virtue of the return action of the driving spring 15. By releasing the vertical external force on actuator 4, mobile element 5 pivots upward just inside piston 10 sliding upward in the opposite the direction of the vertical force by return action of button spring 17 and valve spring 16.
It is clear that the devices described are arranged for multi-dose applications, i.e. applications in which doses are repeatedly drawn from a supply and repeatedly ejected. It is also clear that the devices are exemplified with features suitable for eye treatment applications. Typical parameters for this application will be given below although the invention shall not be regarded as limited to this application or any such exemplified parameter. A typical single dose volume for delivery to the eye can be less than 100 μL, suitably less than 50 μL, and suitably less than 30 μL. Generally the volume in the standby position is at least 1 μL, suitably at least 2 μL and suitably at least 3 μL. The receptacle 18 suitably has the capacity to deliver a plurality of such doses.
A suitable distance from the outlet of the apparatus to the eye is about 24 mm. A suitable jet time is from about 40 to about 60 ms. A suitable speed for the stream of drops or jet ejected is a balance between having enough linear momentum to traverse an air gap between apparatus opening and target, without gravity assistance, traveling fast enough not be obstructed by blinking, and not causing an inconvenient, harmful impact on the eye. The ideal speed is to some extent dependent on the drop size used but as a general rule the drops should be able to traverse at least 1 cm, suitably at least 3 cm and most suitably at least 5 cm through air by its own momentum, incorporating reasonable distances between opening and target. A suitable lower speed limit when leaving the apparatus opening is 0.1 , m/s, suitably 0.5 m/s, suitably at least 5 m/s and most suitably at least 10 m/s. Generally the upper speed is lower than 200 m/s and suitably lower than 100 m/s. A suitable drop size so defined should be sufficient not to be retarded too quickly and not to be easily redirected, e.g. to be inhaled, and suitably has a minimum diameter of 20 μm, suitably not less than 50 μm and most suitably at least 100 μm. Normally the size is less than 200 μm and suitably less than 150 μm.
The stream may take the form of a horizontal shower or spray of atomized liquid droplets but suitably the stream is narrow and fairly coherent although even such a stream tends to break up into individual droplets after a certain time and distance. The above given values are intended to relate to spherical droplets and for multiple droplets to the weight average of particle diameters. A coherent stream tends to break up into droplets of a diameter of roughly double the diameter of the stream. Accordingly suitable opening diameters for the dosing orifice are about half the above given drop diameters or roughly between 10 and 1000 μm, suitably between 20 and 800 μm. The above considerations are fairly independent of liquid viscosity and tend to apply both for liquid products and ointments. It is desirable that the whole dose can be delivered in a time shorter than the blink reflex time, i.e. in a time shorter than about 150 m/s, suitably shorter than 100 m/s and most suitably shorter than 75 m/s.

Claims

We claim:
1. An apparatus for dispensing a liquid product comprising: a) housing or frame having an opening, b) a receptacle for the liquid with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of liquid through the second orifice, and e) a through passage arranged to allow the ejected liquid to pass in a direction different from the feed nozzle and out of the opening, wherein i) the mechanism comprises a mobile element movable with respect to the housing or frame between at least a first position in which the first orifice of the dosing chamber and the feed nozzle are in flow communication and a second position in which the second orifice and the through passage are in flow communication, and ii) the mechanism is arranged to allow aspiration of liquid through the first orifice when the mobile element is in the first position and ejection of liquid through the second orifice when the mobile element is in the second position.
2. The apparatus of claim 1 , wherein the housing optionally comprises an eyepiece.
3. The apparatus of claim 1, wherein at least one actuator is included and is adapted to operate the mechanism.
4. The apparatus of claim 1, wherein the mobile element is adapted to move in a substantially vertical direction.
5. The apparatus of claim 1 , wherein the dosing chamber comprises a substantially cylindrical barrel, defining a concentric barrel axis.
6. The apparatus of claim 1 , wherein the first orifice is adapted to connect to the aspiration element.
7. The apparatus of claim 1 , wherein the mechanism is adapted to perform in sequence the aspiration of liquid in the first position, the movement of the mobile element to the second position, and the ejection of liquid in the second position.
8. The apparatus of claim 1 , wherein the feed nozzle is disposed at a proximal end of the receptacle.
9. A method of operating an apparatus for dispensing a liquid product, comprising: a) housing or frame having an opening, b) a receptacle for the liquid with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of liquid through the second orifice, and e) a through passage arranged to allow the ejected liquid to pass in a direction different from the feed nozzle and out of the opening, the method comprising i) connecting the first orifice and the nozzle in flow communication, ii) filling liquid into the dosing chamber through the first orifice, and iii) ejecting liquid from the dosing chamber through a second orifice onto an ophthalmic target.
10. A kit for operating an apparatus for dispensing a liquid product, the kit comprising an apparatus for dispensing a liquid product, a liquid product, and directions for use; the apparatus comprising: a) housing or frame having an opening, b) a receptacle for the liquid with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of liquid through the second orifice, and e) a through passage arranged to allow the ejected liquid to pass in a direction different from the feed nozzle and out of the opening.
11. A method of treating an ophthalmic condition, the method comprising an apparatus for dispensing a liquid product, the apparatus comprising: a) housing or frame having an opening, b) a receptacle for the liquid with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of liquid through the second orifice, and e) a through passage arranged to allow the ejected liquid to pass in a direction different from the feed nozzle and out of the opening, wherein the liquid product comprises a pharmaceutically effective amount of an ophthalmic solution.
12. The use of a pharmaceutically effective amount of an ophthalmic solution for the treatment of an ophthalmic condition wherein the ophthalmic solution is provided to the patient via an apparatus comprising: a) a housing or frame having an opening, b) a receptacle for the ophthalmic solution with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of the ophthalmic solution through the second orifice, and e) a through passage arranged to allow the ejected ophthalmic solution to pass in a direction different from the feed nozzle and out of the opening.
13. A kit for use in the treatment of ophthalmic conditions, the kit comprising an ophthalmic solution, an apparatus for administering the ophthalmic solution and directions for use; the apparatus comprising: a) a housing or frame having an opening, b) a receptacle for the ophthalmic solution with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of the ophthalmic solution through the second orifice, and e) a through passage arranged to allow the ejected ophthalmic solution to pass in a direction different from the feed nozzle and out of the opening.
14. An ophthalmic composition comprising: a pharmaceutically effective amount of latanoprost solution and an apparatus for holding the latanoprost solution, the apparatus comprising: a) a housing or frame having an opening, b) a receptacle for the latanoprost solution with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of the latanoprost solution through the second orifice, and e) a through passage arranged to allow the ejected latanoprost solution to pass in a direction different from the feed nozzle and out of the opening.
15. A use of a composition for providing an ophthalmic solution wherein said composition comprises: a pharmaceutically effective amount of a ophthalmic solution and an apparatus for holding the ophthalmic solution, the apparatus comprising: a) a housing or frame having an opening, b) a receptacle for the ophthalmic solution with a feed nozzle arranged substantially stationary with respect to the housing or frame, c) a dosing chamber having a valve containing at least a first orifice and a second orifice, d) a mechanism arranged to allow ejection of the ophthalmic solution through the second orifice, and e) a through passage arranged to allow the ejected ophthalmic solution to pass in a direction different from the feed nozzle and out of the opening.
PCT/IB2006/001085 2005-04-29 2006-04-18 Apparatus and method for administering ophthalmic solutions WO2006117640A1 (en)

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CN110575393A (en) * 2019-09-18 2019-12-17 北京中国科学院老专家技术中心 Disconnect-type eyeshield liquid ration mixes out liquid eye drop bottle and disconnect-type eyeshield liquid

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JP2017006656A (en) * 2015-06-18 2017-01-12 参天製薬株式会社 Instillation auxiliary tool
CN109201754B (en) * 2018-09-01 2024-03-22 江苏宏宝优特管业制造有限公司 Lubricating equipment and lubricating method for outer wall of steel pipe

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CN110575393A (en) * 2019-09-18 2019-12-17 北京中国科学院老专家技术中心 Disconnect-type eyeshield liquid ration mixes out liquid eye drop bottle and disconnect-type eyeshield liquid
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JP2006305347A (en) 2006-11-09
CA2606469A1 (en) 2006-11-09
TW200714274A (en) 2007-04-16
EP1877194A1 (en) 2008-01-16

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