A fluid-dynamically actuated preservative-free dispensing system

Abstract

A multi-dose, preservative-free ophthalmic fluid delivery device is provided. The fluid delivery device includes a fluid dispensing system and a fluid package for storing and supplying a liquid to the dispensing system. The dispensing system includes an elongated chamber including a check valve providing a closure on the front of the chamber. The valve is normally closed to hermetically seal the chamber. The dispenser includes a vibration motor that induces vibrations in the chamber and the fluid therein. The vibration of the chamber imparts momentum to the fluid stored within the chamber, which in turn exerts a force that periodically opens the valve to dispense a stream or droplets. Fluid is dispensed only while the motor is vibrating; the valve is otherwise hermetically sealed.

Description

Technical Field

[0001] The present invention generally relates to an apparatus for dispensing a liquid agent, and more particularly to an apparatus configured to store and deliver a preservative-free ophthalmic agent that is particularly user-friendly and allows patients to appropriately follow the instructions for taking the medicine.

Background Art

[0002] The ease of dispensing a liquid agent and compliance with the dosing instructions are major concerns for all patients. In particular, preservative-free dispensing bottles such as ophthalmic squeeze dispensers typically require a stronger starting force due to the valve mechanism that seals the discharge nozzle to prevent the entry and contamination of bacteria. Such a system requires extremely high pressure for operation and thus extremely high squeezing force. In addition, conventional dispensing bottles can only be dispensed upside down, which is troublesome because the patient has to move their head, and the higher the starting force, the more inconvenient it becomes.

[0003] The dispensing devices in question are known from the prior art, for example, U.S. Patent Nos. 6,095,376, 9,676,525, U.S. Patent Application Publication Nos. 2014 / 0336596, 2016 / 0107180, U.S. Patent Nos. 9,238,532, 8,056,766, 8,863,998, and 10,105,720. The dispenser shown in U.S. Patent Application Publication No. 2014 / 0336596 includes an outlet channel that connects a reservoir to an outlet opening that passes through an outlet valve disposed in the outlet channel and that opens when the bottle is squeezed to generate pressure. Such preservative-free squeeze bottles typically require a squeezing force of about 25-28 N (Ophthalmic Squeeze Dispenser - Drug Development and Delivery October 2017, Vol. 17 No. 7 page 40). Elderly patients, or other patients lacking sufficient hand strength and / or dexterity, often have difficulty with the medicine dispensed from such bottles.

Summary of the Invention

Means for Solving the Problem

[0004] This application provides a preservative - free ophthalmic dispenser that can be easily activated by an electric switch and can be held in a horizontal or any convenient orientation. This application provides a cost - effective solution that is compatible with standard drug packaging processes.

[0005] Provide a preservative - free eye drop delivery device for multiple administrations. The fluid delivery device includes a fluid dispensing system and a fluid package that stores liquid internally and supplies the liquid to the dispensing system. The dispensing system includes an elongated chamber that includes a check valve with a closure provided on the front of the chamber. The valve is normally closed and hermetically seals the chamber. In this application, the chamber includes a vibration motor that induces vibration in the chamber and the internal fluid. The vibration of the chamber imparts momentum to the fluid stored in the chamber, and then the liquid applies a force that periodically opens the valve to dispense a liquid stream or droplets. The fluid is dispensed only while the motor is vibrating, and otherwise the valve is hermetically sealed.

[0006] The check valve may include a flexible plate. The flexible plate includes a conical aperture that penetrates its thickness. The valve may further include a fixed spherical member that engages with the inner wall of the conical aperture to form a hermetically sealed closure. The plate may be made of an elastomer with a modulus of elasticity of 0.1 - 1.2 GPa. The periphery of the plate can be attached to the chamber by a retaining ring that engages with the chamber in an interference - fit state to form a hermetically sealed closure.

[0007] The conical aperture extends across the thickness of the plate such that droplets are dispensed from the smaller opening of the aperture with the larger side of the aperture in fluid communication with the chamber.

[0008] The spherical member may include an antibacterial coating that covers the region of the spherical member between the tangential engagement line and the smaller opening of the aperture.

[0009] The vibration motor vibrates the chamber and the fluid within the chamber. As a result, a period of a hydrodynamic pulse is generated that periodically opens the valve to dispense the fluid. Here, this phenomenon is characterized by the vibratory interaction between the valve and the surrounding fluid. The hydrodynamic force generated by the momentum of the fluid causes the valve to open so that the fluid flows through the aperture.

[0010] The fluid is dispensed when the hydrodynamic force is high enough to deform the aperture, otherwise the aperture hermetically seals the chamber. The system enables the storage of preservative-free agents by preventing the entry of microorganisms into the chamber. This application provides a convenient and cost-effective electric preservative-free dispensing system.

Brief Description of the Drawings

[0011]

Fig. 1A

Fig. 1B

Fig. 1C

Fig. 2

Fig. 3

Fig. 4

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Fig. 6

Modes for Carrying Out the Invention

[0012] This application describes a dispensing device and method for delivering a preservative-free solution or suspension for instilling eye drops. The dispensing device includes a droplet discharge system fluidly connected to an ampoule package containing the liquid to be dispensed. The droplet discharge system includes a chamber having a check valve that provides a closure at the front of the chamber. The droplet discharge system further includes a vibration motor that vibrates the chamber, thereby inducing a hydrodynamic pulse that periodically opens the valve to discharge fluid droplets. The valve is normally closed and provides an airtight seal for the chamber. The valve opens in response only to the hydrodynamic pulses induced by the vibration of the chamber. Fluid is dispensed in this manner only when the device is activated, and otherwise the aperture seals the device to prevent the ingress of bacteria and microorganisms, thereby enabling the storage of preservative-free formulations. The use of a vibration motor is further convenient, cost-effective, and enables electronically controlled management.

[0013] Figures 1A and 1B each show a side view and an enlarged partial cross-sectional view of a fluid delivery device 100. The delivery device 100 includes a dispensing system 104 fluidly connected to each other via a reservoir 102 and a passage 106. The dispensing system 104 includes a fluid chamber 108 and a check valve including an aperture plate 110 that provides a front closure for the chamber 108.

[0014] Referring to FIG. 1B, it can be seen that the aperture plate 110 includes a conical or tapered opening 116 (shown within the dashed circle for clarity) having a large inlet opening 116a that extends across its central thickness and is in fluid communication with the chamber 108 and a small outlet opening 116b for dispensing fluid droplets.

[0015] The aperture plate 110 may be made of a flexible elastomer such as silicone rubber manufactured by VersaFlex Incorporated, Kansas City, Kansas, USA. Other elastomers with a Young's modulus value in the range of 0.5 GPa to 2 GPa may also be used. The dispensing system 104 further includes a stationary spherical member 114 that engages in a pressure transmission relationship so as to contact an inlet opening 116a of a conical aperture that provides an airtight seal. In a preferred embodiment, the spherical member 114 is made of high-density polyethylene (HDPE) which forms a rigid closure when engaging with the softer aperture plate 110 because it is harder than silicone. The spherical member 114 preferably engages in a pressure transmission relationship with the conical aperture 116a with a preload force in the range of 0.01 N to 0.05 N applied. The combination of the aperture plate 110 and the spherical member 114 provides a check valve as described above. The spherical member 114 is supported by a pin member 112. Since any shape that can form a good seal with the aperture plate 110 may be used, the member 114 may have a shape other than spherical.

[0016] The aperture plate 110 can be held in the dispensing system 104 by a retaining ring 130 to form an airtight seal.

[0017] The dispensing system 100 includes a vent tube 126 configured to equalize the pressure in the container 102 as fluid is dispensed from the device. The opening 134 of the vent tube 126 extends above the fluid level 132 in any direction in which the device is held. The vent tube 126 may be connected via a 0.22 micron filter 128 to ensure that the air input to the device is sterile.

[0018] The dispensing system 100 further includes a chamber 108 and a vibration motor configured to vibrate the fluid within the chamber. Here, the motor is schematically shown as a mechanical eccentric load 118 that vibrates the assembly as described above when rotated by a motor (not shown in FIGS. 1A - B but described below in relation to FIG. 3).

[0019] FIG. 1C is a 3D view of the embodiment of FIGS. 1A - B.

[0020] FIGS. 2A - B show the response of the dispensing system 104 to vibration. The vibration of the motor induces vibration in the body of the dispensing system 104, which then generates a fluid momentum within the chamber due to the dynamic interaction of the fluid with the solid structure of the chamber 108. This phenomenon is often referred to as solid - fluid interaction (SFI). The momentum of the moving fluid exerts a force that deflects the aperture plate 110 outward in the directions indicated by arrows 206a, 206b, separating the aperture plate 110 from the spherical member 114, thereby opening the fluid flow path and discharging the droplets 210 as shown by arrows 208a, 208b.

[0021] The dispensing device 100 is supported by a flexible beam 122 or other structural embodiments so as to be able to vibrate freely, as schematically shown by the movement regions 202, 204. Preferably, the spring constant of the beam 122 is between 0.05 N / mm and 0.5 N / mm. For example, the beam 122 can be formed by creating a groove 124 in the support structure 120 such that the resulting beam 122 has a thickness suitable for providing a spring constant as described above.

[0022] FIG. 3 shows an exemplary vibration motor 302. The DC motor 302 in this example has a cylindrical body with a diameter of 4 mm and an overall length of 17 mm. An eccentric cam 118 is attached to the motor shaft. The cam has a mass of 1.7 grams and a center of mass 0.7 mm from the center of rotation. The motor receives a voltage of 4.5 - 12 VDC and rotates at 6000 - 12000 RPM, generating a centrifugal force of 0.3 N at a rotational speed of 8000 RPM. Other DC motors that generate a centrifugal force of 0.1 - 1 N and a rotational speed of 1000 - 50000 RPM may be used. The motor can be controlled by a timer circuit set to provide the ON time required to deliver a volume of 8 - 12 microliters. The startup ON time is 60 - 200 ms depending on the rheology of the fluid used. A timer circuit incorporating a 555 timer IC or a microprocessor-based timer with a 12-volt battery such as an A23 alkaline battery may be used.

[0023] FIGS. 4A - C show a preferred alternative embodiment of the dispensing system 400. FIG. 4A shows a front view of the dispensing system 400 and FIG. 4B shows a side view. The dispensing system 400 includes a concave mirror 402 that aids in aligning the device 400 and the fluid stream 210 with the user's eye. In use, the dispensing device 400 is positioned in front of the eye such that the image of the eye appears sharp and centered in the mirror as seen by the user. At this point, the device is properly positioned in terms of the distance between the nozzle 404 and the eye and the angular orientation with respect to the eye. When activated, the fluid stream 210 is accurately dispensed onto the corneal surface of the eye. The device 400 preferably includes a 0.22 micron air filter configured to filter the ventilation air flowing into the device 400 as in the previous example.

[0024] The device 400 includes a check valve having an aperture plate 406 with a conical aperture 116 that passes through its thickness. The check valve further includes a spherical member 114 that engages to contact the inlet opening of the conical aperture 116. In this example, the check valve also includes a compression spring 408 configured to press the aperture plate 406 against the spherical member 114. In this way, a robust seal is formed along the engagement line 114a, thus forming a robust airtight closure.

[0025] The spherical member 114 may be partially covered with an antibacterial coating in regions of the spherical member 114 that do not come into contact with the fluid in the chamber, in particular. The coated region thus extends between the engagement line 114a of the conical aperture (i.e., to the left of 114a in FIG. 4C) and the outlet. Examples of antibacterial coatings include silver in a metallic state, silver alloys, or non-metallic materials containing silver in the form of salts of silver chloride and silver sulfadiazine. Other optional materials include biguanide derivatives, chlorhexidine diacetate, and chlorhexidine digluconate.

[0026] Figures 5A - B show a front and a side view, respectively, of the dispensing device 400 housed in a housing 502. The housing 502 conveniently houses the dispensing system 400, described with respect to FIGS. 4A - C and shown in dashed lines in this figure. The housing 502 includes an electrical circuit (not shown) and a 12 - volt (e.g., A23 type) battery 506. The circuit controls the dispensing cycle such that, for example, 8 - 12 microliters of the drug are dispensed onto the surface of the eye. The momentary switch 504 can be used to activate the device 400 so that the droplet stream is released from the opening as described above. Figures 5A - B also show a mirror 402 visible on the front of the device. Such a housing can also be used for the dispensing device 100 as described above.

[0027] Figures 6A - B show some suitable features of the housing that can be used in some embodiments of devices 100, 400, etc. as described above. In this example, the housing includes a swivel cover 602 that covers the dispensing nozzle 606 when not in use. The swivel cover 602 provides a means to prevent bacterial contamination of the external area where fluid can remain after each use. Such residual fluid can contaminate subsequent fluid flows dispensed through the nozzle. The swivel cover 602 preferably includes a flexible member 604 that includes a surface 604a covered with an antibacterial coating. The surface 604a engages the outlet opening of the nozzle 606 when the swivel cover 602 is closed as shown in Figure 6B. In this way, anti - pathogen measures are realized. Alternatively, an organic dye with preservative properties may be used. For example, there are toluidine blue, methylene blue, gentian violet and acridine and related active substances, such as acridine orange and acridine yellow, and further ethylacridine lactate. A bactericidal polymer such as polyhexanide may be used. A material containing an additive that includes an organometallic substance with an ionization effect may be used. Such additives are sold by SteriOne GmbH (Berlin, Germany). Examples of antibacterial coatings that can be used on the surface 604a include silver in a metallic state, silver alloys, or non - metallic materials containing silver in the form of salts of silver chloride and silver sulfadiazine. Other optional materials include biguanide derivatives, chlorhexidine diacetate and chlorhexidine digluconate.

Claims

1. An apparatus for delivering a liquid to a patient's eye, comprising: a) a liquid reservoir configured to store the liquid; b) a liquid dispenser in liquid communication with the liquid reservoir, the liquid dispenser including a check valve and an actuator; c) the check valve including an aperture capable of dispensing the liquid and a pin member engaging with the aperture to achieve a normally closed configuration of the check valve; d) the actuator being configured to apply a mechanical stimulus to the liquid dispenser to vibrate the liquid; e) a device for discharging the liquid through the aperture by elastically deforming the aperture to open the check valve by the vibration of the liquid.

2. The apparatus according to claim 1, wherein the actuator includes a vibration motor having a mechanical eccentric load with respect to the rotation axis of the vibration motor.

3. The apparatus according to claim 2, wherein the liquid dispenser is supported by a flexible member, and the operation of the vibration motor vibrates the liquid by vibrating the liquid dispenser.

4. The apparatus according to claim 3, wherein the spring constant of the flexible member is in the range of 0.05 N / mm to 0.5 N / mm.

5. The apparatus according to claim 1, wherein the aperture is formed in an aperture plate having a Young's modulus in the range of 0.5 GPa to 2 GPa.

6. The apparatus according to claim 5, wherein the mechanical hardness of the pin member is higher than the mechanical hardness of the aperture plate.

7. The apparatus according to claim 1, wherein the aperture is tapered such that the outlet of the aperture is narrower than the inlet of the aperture.

8. The apparatus according to claim 1, wherein the pin member is stationary with respect to the liquid dispenser.

9. The apparatus according to claim 1, wherein the tip of the pin member engages with the aperture and the tip of the pin member is spherical.

10. The apparatus according to claim 9, wherein the tip of the pin member is partially or completely covered by an antibacterial coating.

11. The apparatus according to claim 10, wherein the antibacterial coating covers at least a part of the tip of the pin member that is outside the liquid dispenser in the normally closed configuration of the check valve.

12. The apparatus according to claim 1, wherein the preload force for engaging the pin member with the aperture in the normally closed configuration of the check valve is between 0.01 N and 0.05 N.

13. The apparatus according to claim 1, wherein the liquid reservoir includes a vent.

14. The device according to claim 13, wherein the vent includes a filter configured to ensure that the air flowing into the liquid storage tank is sterile.

15. The device according to claim 1, further comprising a concave mirror configured to present a focused image of the patient's eye to the patient when the device is positioned to appropriately deliver liquid to the patient's eye.

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