Ventilated multi-dose ocular fluid delivery system

Abstract

An apparatus for delivering a precise amount of a pharmaceutical fluid to an eye is provided. The apparatus includes an ampoule for storing a liquid and an orifice through which the liquid is expelled. The apparatus also includes a diaphragm that includes a needle that protrudes from the diaphragm and extends to the orifice to form a needle valve. The needle valve provides an air-tight closure of the orifice to allow the pharmaceutical fluid to be stored in the apparatus without a preservative. The system also includes an electromagnetic transducer to move the diaphragm back and forth to expel the liquid through the nozzle. Finally, the system also includes a vent to allow air to enter the ampoule as the fluid is expelled from the ampoule. Preferably, the vent includes a filter to prevent microorganisms or other contaminants from entering the ampoule.

Description

Technical Field

[0001] This invention relates to the topical ocular delivery of ophthalmic drugs. Background Technology

[0002] Currently, medication fluids are typically delivered to the surface of the eye using dropper bottles. This method has several drawbacks: (1) patients cannot aim well and often miss the eye; (2) the volume of the droplets from the bottle cannot be well controlled and is too large (approximately 50 μL) for the tear film on the cornea to be absorbed - the tear film cannot hold more than 7 μL; (3) patients blink very frequently during droplet delivery, so that some droplets fall onto the eyelids while the rest are wiped away from the cornea. Summary of the Invention

[0003] We have developed a device that addresses these problems by: (1) delivering precise amounts of fluid; (2) using micro-dose (<10 μL) that can be maintained with a tear film; (3) delivering within a blink time (~100 ms); and (4) using optics aimed at the cornea for precise self-management.

[0004] For easy aiming, the liquid discharge device should be placed close to the eye, but should not touch the eyelashes or eyebrows. Therefore, refer to... Figure 1 The device 102 should be located within a range of approximately L = 1-10 cm from the eye, or more ideally within a range of 2-6 cm. In this figure, 102 is the liquid discharge device, 104 is the discharged fluid flow, and 106 is the patient's eye.

[0005] The diameter of the cornea is approximately D = 12 mm, or approximately 6 mm in radius. To ensure that the fluid is delivered approximately to the center of the cornea, the jet 104 should not deflect beyond approximately half the corneal radius under gravity, i.e., no more than approximately h = 3 mm. Figure 1 As shown, the vertical deflection h of a projectile ejected horizontally at a distance L with velocity v is: h = g * L / (2v) 2 To ensure that the vertical deflection does not exceed h, the velocity of the horizontal jet should exceed v = L*(g / 2h). 0.5 For L = 5cm and g = 9.8m / s² 2 With h = 3 mm, we get v = 2 m / s. For L = 5 cm and h = 1 mm, the velocity should be approximately v = 3.6 m / s, while for L = 10 cm and h = 1 mm, the velocity v = 7.2 m / s. Therefore, in general, the jet velocity should be in the range of approximately 1-10 m / s, and ideally in the range of approximately 2-4 m / s. Velocities much higher than these may cause patient discomfort or even damage to the cornea.

[0006] The fluid will reach the eye within milliseconds after dispensing (t = L / v, in the range of 1-100 ms). Once the fluid touches the cornea, it will trigger a blink reflex that typically takes about T = 100 ms. To prevent the medication from being blocked by the eyelids, the fluid should be delivered before the eye closes. For the required volume V delivered at a jet velocity v over time T, the jet cross-sectional area should be S = V / (T*v). Because for a circular orifice, S = π*d 2 / 4, its diameter d=(4V / (πT*v)) 0.5 For example, for v = 2 m / s, T = 100 ms, and V = 10 μL, we obtain d = 250 μm. For v = 1 m / s, d = 350 μm, and for v = 7 m / s, d = 130 μm. Therefore, the diameter of the orifice of the discharge part should be in the range of approximately 200-600 μm, and more ideally in the range of approximately 400-550 μm. Alternatively, several orifices can be used to generate several parallel fluid flows for faster delivery.

[0007] Another key property of the system is preventing microorganisms from entering the contained liquid during storage or use. As with any closed system, air should be introduced to replace the discharged volume as liquid is drained, thus balancing the pressure (venting). To prevent microbial entry, air is introduced through a special inlet, preferably with a 0.2µm filter. Ideally, the device should operate such that liquid is drained through the orifice at any time it is open, thus preventing air from entering through the orifice.

[0008] An exemplary embodiment is an arrangement having a housing for storing and dispensing droplets, the housing including a chamber for holding liquid therein, and the housing having an inlet connected to an ampoule containing a pharmaceutical fluid to be dispensed. The chamber includes a dispensing orifice plate defining a front closure of the chamber and including an orifice opening through which liquid is dispensed forward from the housing. The chamber also includes a vibrating diaphragm fixed to the housing, the vibrating diaphragm being in a pressure-transmitting relationship with the liquid in the chamber. The vibrating diaphragm is formed together with a needle that protrudes from the center of the vibrating diaphragm and extends to an orifice on the opposite side of the chamber, the needle closing the orifice to prevent liquid from flowing out of the chamber and to prevent bacteria from entering.

[0009] The electromagnetic transducer is attached to the housing and, when powered, pulls the diaphragm back against a spring in the chamber. When the electromagnetic transducer is turned off, the spring returns the diaphragm to its initial position, and the valve closes. When the electromagnetic transducer is powered by a pulsating or alternating current, the diaphragm oscillates, which in turn generates pressure on the liquid. At the correct frequency, the pressure is sufficient to force the liquid to flow out of the orifice.

[0010] Typical frequency ranges are from 10 Hz to 500 Hz, more ideally from 50 to 200 Hz. The nozzle diameter, fluid discharge rate, and duration of the electromagnetic pulse are preferably optimized to deliver the desired amount of fluid within the required time, as described above. Preferably, the actuation pulse duration is 250 ms or less, more preferably 100 ms or less. "Actuation pulse duration" as used herein refers to the length of time the electromagnetic transducer is energized to pull the needle out of the orifice in a single actuation pulse.

[0011] In this configuration, other types of transducers can also be used to drive fluid discharge, such as coin vibration motors. Attached Figure Description

[0012] Figure 1 The diagram shows the geometry used to deliver fluid to a patient's eye.

[0013] Figure 2 This is an external view of an exemplary embodiment of the present invention.

[0014] Figure 3A This is a cross-sectional view of the first embodiment of the present invention.

[0015] Figure 3B-3C It shows Figure 3A The operation of the embodiment.

[0016] Figures 4A-4B An example of ventilation is shown.

[0017] Figure 5 This is a cross-sectional view of the second embodiment of the present invention.

[0018] Figure 6 A conical spring is shown. Detailed Implementation

[0019] Figure 2 A perspective view of a first embodiment of the liquid dispensing unit is shown. Specifically, but not exclusively, the fluid dispensing unit 200 is suitable for use in delivering preservative-free pharmaceutical liquids to the surface of the eye. The liquid dispensing unit 200 includes a thermoplastic body 206 formed with a liquid chamber and connected to a fluid supply ampoule 202. The dispensing unit includes a nozzle 208 through which liquid 210 is dispensed, as will be explained in more detail below.

[0020] Figure 3AA cross-sectional view of the fluid discharge device is shown. As previously mentioned, the fluid discharge device includes a thermoplastic body 206 defining a chamber 316 connected to a fluid supply ampoule 202 containing fluid 302. The fluid discharge device includes a nozzle 208 through which liquid is discharged. The device also includes a membrane 308 at the end of the chamber opposite the nozzle. The membrane 308 includes an integrated needle 306, making them a single component. The needle 306 and the membrane 308 are connected to an electromagnetic transducer 310 via a linking member 318. When an electrical pulse is applied to the electromagnetic transducer 310, current flows through a coil 312 and generates a magnetic force that pulls a plunger 314 back against a spring 320.

[0021] exist Figure 3A In Figure 304, the direction of fluid flow from ampoule 202 to chamber 316 is shown. Vent tube 404 is described in more detail below.

[0022] Figure 3B This shows the effect after an electrical pulse is applied to the electromagnetic transducer 310. Figure 3A The device. As can be seen, as a result of the magnetic force, the plunger 314 is pulled into the electromagnetic transducer in the direction indicated by the arrow. The diaphragm 308 is connected to the plunger 314 via the connecting rod member 318 and is also pulled back. Figure 3C The diagram illustrates the situation when the electromagnetic transducer 310 is not powered. Here, the spring 320 pushes the membrane 308 back to its initial position, thus closing the valve and sealing the chamber airtight to prevent microorganisms from entering.

[0023] When the electromagnetic transducer 310 is powered by a pulsating or alternating (AC) current, the oscillating membrane generates pressure in the liquid, thereby producing a flow of liquid exiting from the orifice. Typically, the operating frequency is 10 to 500 Hz, and more particularly 50 to 200 Hz. In this embodiment, the membrane 308 is made of silicon with a hardness between 50 and 70 (Shore A), and the displacement of the plunger 314 is approximately 200 μm. Because the flow is generated only in the outward direction, it prevents microbial entry even when the valve is open.

[0024] exist Figures 4A to 4B In the example, the liquid discharge device includes a venting arrangement to ensure that the pressure inside ampoule 202 is equal to the ambient atmospheric pressure. Here, Figure 4A It is along Figure 4B The sectional view obtained by cutting along the EE line.

[0025] The ventilation system in this example includes an inlet vent pipe 404 that extends within the ampoule 202 beyond the liquid level of the fluid 302. It should be noted that the vent pipe 404... Figures 4A-4BThe device is positioned above the liquid level in any orientation. A vent 404 connects to a vent outlet 406, which opens to the atmosphere. In one embodiment, a filter 408 is placed in the vent outlet 406 such that the venting air flowing to the ampoule is filtered to prevent the infiltration of potentially airborne contaminants such as microorganisms. The filter 408 filters out particles larger than 1 μm (more preferably >0.5 μm, even more preferably >0.2 μm). Thus, even if air 402 enters the ampoule 202 with the discharge fluid, the system is able to isolate it from microbial contamination.

[0026] In the previous example, membrane 308 was driven by a solenoid. Figure 5 In this example, the membrane is driven using a coin-type vibrating motor. More specifically, 306 is the needle attached to the membrane 308 as described above. This assembly is overmolded together with a magnetic steel pin 510. 502 is a coin-type vibrating motor (e.g., Jinlong Machinery & Electronics Co., Ltd., model #C1026B002F). 504 is a plastic molded part that holds the motor 502 so that it can slide along a guide rail (i.e., it is a motor retainer). 506 is a plastic molded part that provides the aforementioned guide rail for the motor retainer 504 to slide internally. 510 is a magnetic steel pin molded into the membrane / needle assembly (308 / 306). 512 is a housing that holds all the components together.

[0027] Needle 306 typically seals the orifice (i.e., the orifice is sealed except when discharging fluid), as described in more detail above. Coin-type vibratory motors have an offset from their axis of rotation (the axis of rotation is perpendicular to...). Figure 5 The eccentric weight (on the plane). Because the weight is off-axis, as the motor rotates, the unbalanced weight causes the motor to primarily rotate on the plane. Figure 5 Vibration occurs in the plane of the object. By placing the coin-type vibrating motor 502 in a plastic motor holder 504 that fits into a corresponding guide rail (in component 506), the coin-type vibrating motor is constrained, so it can only move linearly (e.g., in...). Figure 5 (From left to right). As a result of this physical constraint, when the motor rotates, it is only allowed to oscillate from left to right, rather than vibrating in a plane. A coin-type vibrating motor is connected to the membrane 308, so that as the motor oscillates from left to right, the membrane also vibrates from left to right. The discharged fluid flow is generated in the same manner as described above—that is, the needle 306 moves back and forth in the orifice to discharge the liquid.

[0028] In an alternative embodiment, the coin-type vibrating motor 502 can be coupled to the membrane via an optional magnet 508. The magnet 508 is fixed to the motor holder 504, which is also attached to the coin-type vibrating motor 502. When the magnet 508 approaches the magnetic steel pin 510, the two latch together, and the motor is thereby coupled to the membrane. This is an advantageous assembly feature because the motor can be easily added to the system without requiring tight tolerances, and the motor can be added at several different steps in the assembly process.

[0029] Figure 5 Examples include a disc spring 320. The spring deforms slightly during assembly to transfer force to the needle 306. The force or load holds the needle 306 against the orifice to close the flow path. Without the spring, the force required to push the needle open is very low, and the device would easily leak. Additionally, the spring has a spring constant, which is important for ensuring the correct oscillation frequency and amplitude of the needle when the motor is energized. Also importantly, without the spring, only the stiffness of the load-bearing diaphragm 308 holds the needle 306 in the closed position. The diaphragm can be made of an elastomer. For most elastomers, the mechanical properties can vary considerably even with small temperature changes. With the spring 320, a large portion of the load applied to the needle 306 comes from the spring 320, not the diaphragm 308. Because the mechanical properties of spring steel (e.g., the material of spring 320) are much more constant over the same temperature changes, adding the spring makes the system performance more consistent.

[0030] In an alternative embodiment, Figure 5 The disc spring 320 is replaced by a conical spring. A conical spring is similar to a traditional compression spring made of metal wire, but instead of being wound with a constant diameter, its diameter gradually decreases, giving the spring a conical shape rather than a cylindrical one. See also Figure 6 When a conical spring is fully compressed, the coils nest together, allowing the spring to become flat, only the same thickness as the diameter of the metal wire wound around it. Therefore, a fully compressed conical spring can fit into... Figure 5 The conical spring has a similar shape to the disc spring 320 and can perform the same function. Conical springs are cheaper and easier to obtain a wide range of spring constants and operating deflections compared to disc springs, so they are a feature of the current preferred embodiment.

[0031] The tip of needle 306 and / or its associated orifice may include antimicrobial material.

Claims

1. A device for delivering fluid to a patient's eye, the device comprising: A fluid package, the fluid package including a reservoir (202) configured to hold fluid, an orifice and a needle (306) configured to seal the orifice when fluid is not discharged through the orifice; The fluid package includes an elastic membrane configured to provide mechanical force to keep the tip of the needle engaged with the orifice when the fluid is not discharged through the orifice. The elastic membrane is connected to the needle; An actuator configured to discharge the fluid through the orifice by providing mechanical vibration to at least the needle; characterized in that the device includes a venting arrangement configured to allow air to enter the reservoir as the fluid is discharged from the reservoir, wherein the venting arrangement is configured to balance the pressure inside the reservoir (202) with the ambient atmospheric pressure.

2. The device as described in claim 1, characterized in that, It also includes a particle filter configured to remove particles larger than 0.2 μm from the air entering the storage unit via an air inlet.

3. The device as described in claim 1, characterized in that, The actuator includes an electromagnetic solenoid.

4. The device as described in claim 1, characterized in that, The actuator includes a coin-type vibrating motor.

5. The device as described in claim 1, characterized in that, The fluid package includes an elastic spring configured to provide additional mechanical force to keep the tip of the needle engaged with the orifice when fluid is not discharged through the orifice.

6. The device as described in claim 1, characterized in that, The device is configured to deliver a dose volume of 10 μl or less.

7. The device as described in claim 1, characterized in that, The diameter of the orifice is in the range of 200 μm to 600 μm.

8. The device as described in claim 1, characterized in that, The velocity of the fluid discharged from the orifice is in the range of 1 m / s to 10 m / s.

9. The device as described in claim 1, characterized in that, The duration of the actuation pulse is 250 ms or less.

10. The device as claimed in claim 1, characterized in that, The repetition rate of the actuation pulse is in the range of 10Hz to 500Hz.

11. The device as claimed in claim 1, characterized in that, The needle has an end that engages with the orifice, and wherein the end comprises an antimicrobial material.

12. The device as claimed in claim 1, characterized in that, The orifice contains antimicrobial material.

13. The device as claimed in claim 1, characterized in that, The orifice is in the front wall of the storage unit, and the membrane is in the rear wall of the storage unit.

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