Vent-type multi-dose ophthalmic solution delivery system

Abstract

A device for delivering a precise amount of medicinal fluid to an eye is provided. The device includes an ampoule for holding the liquid and an opening for discharging the liquid. The device further includes a vibrating membrane with a needle protruding from the membrane and extending to the opening to form a needle valve. The needle valve seals the opening, allowing the medicinal fluid to be stored without the use of preservatives. The system further includes an electromagnetic transducer that moves the membrane back and forth to discharge the liquid through the nozzle. Finally, the system further includes a vent that allows air to enter the ampoule as the fluid is discharged from the ampoule. The vent preferably includes a filter to prevent microorganisms or other contaminants from entering the ampoule.

Description

Technical Field

[0001] The present invention relates to the topical delivery of ophthalmic agents to the eye.

Background Art

[0002] Currently, eye drops are usually delivered to the surface of the eye by using a dropper bottle. This method has several drawbacks, including: (1) the patient cannot accurately aim the drops at the eye, and often the drops miss the eye; (2) the amount of the liquid drop from the dropper bottle (in units of 50 μL) is not clearly defined and is excessive for absorption by the tear film of the cornea (the amount that the tear film can hold is 7 μL); and (3) since the patient often blinks during the delivery of the drop, part of the drop adheres to the eyelid and the rest overflows from the cornea.

Summary of the Invention

Means for Solving the Problems

[0003] We have developed a device to address these problems by enabling: (1) the delivery of an accurate amount of liquid; (2) the delivery of a small amount (10 μL or less) that can be held by the tear film; (3) the delivery within the blink time (~100 ms); and (4) accurate self-administration using optical aiming at the cornea.

[0004] To aim, a fluid ejector needs to be placed near the eye, but it should not touch the eyelashes or eyebrows. Therefore, as shown in FIG. 1, the device 102 is preferably placed in the range of L = about 1 to 10 cm, more preferably 2 to 6 cm, from the eye. In this figure, reference numeral 102 indicates the fluid ejector, reference numeral 104 indicates the flow of the ejected fluid, and reference numeral 106 indicates the patient's eye.

[0005] The diameter D of the cornea is about 12 mm, i.e., it has a radius of 6 mm. To reliably deliver the fluid to approximately the center of the cornea, the jet 104, under gravity, must not be deflected by more than about half of the radius of the cornea from the center of the cornea, i.e., h > about 3 mm. As shown in Figure 1, the vertical deflection h of a projectile released horizontally with a velocity v at a distance L is given by h = g*L / (2v 2 ). To ensure that the vertical deflection does not exceed h, the horizontal jet velocity should be v = L*(g / 2h) 0.5 . For L = 5 cm, g = 9.8 m / s 2 , and h = 3 mm, v = 2 m / s is obtained. For L = 5 cm and h = 1 mm, the velocity is v = about 3.6 m / s, and for L = 10 cm and h = 1 mm, the velocity is v = 7.2 m / s. Thus, overall, the jet velocity is preferably about 1 - 10 m / s, more preferably 2 - 4 m / s. Velocities much greater than these can cause discomfort to the patient and may damage the cornea.

[0006] The liquid flow reaches the eye within a few milliseconds from the moment of ejection (t = L / v, in the range of 1 - 100 milliseconds). As soon as the fluid contacts the cornea, a blink reflex is triggered, which typically takes about T = 100 milliseconds. To prevent the drug from being blocked by the eyelid, it is advisable to deliver the fluid before the patient closes their eye. To deliver the required volume V at a jet velocity v within a time T, the cross-sectional area of the jet should be S = V / (T*v). Since the opening is circular, S = π*d 2 / 4, and its diameter is d = (4V / (πT*v)) 0.5 . For example, for v = 2 m / s, T = 100 milliseconds, and V = 10 μL, d = 250 μm is obtained. For v = 1 m / s, d = 350 μm, and for v = 7 m / s, d = 130 μm. Thus, the ejection aperture diameter is preferably about 200 - 600 μm, more preferably 400 - 550 μm. Alternatively, to deliver at a higher speed, multiple openings can be used to generate multiple parallel flows.

[0007] It can also be said that an important feature of this system is that it can prevent the intrusion of microorganisms into the stored or used storage liquid. Similar to other closed systems, when the liquid is discharged, air can be introduced to make up for the discharged volume to balance the pressure (venting). In order to prevent the intrusion of microorganisms, preferably, air is introduced through a special inlet equipped with a 0.2 μm filter. Ideally, by operating the device so that the liquid is discharged from the opening when the opening is opened, it is possible to prevent air from entering through the opening.

[0008] An exemplary embodiment relates to a configuration for storing and discharging droplets, and has a housing including a chamber for holding a liquid therein, and an intake port connected to an ampoule for holding a pharmaceutical fluid to be discharged. The chamber includes a discharge opening plate that defines a front closure for the chamber, and therein includes an opening for discharging the liquid forward of the housing. The chamber further includes a diaphragm fixed to the housing, and the diaphragm is in a pressure transmission relationship with the liquid in the chamber. The diaphragm is formed together with a needle protruding from its center and extending to an opening on the opposite side of the chamber. By the needle closing the opening, the outflow of the liquid from the chamber and the intrusion of bacteria are prevented.

[0009] An electromagnetic transducer is attached to the housing, and when energized, it pulls the membrane backward against a spring in the chamber. When the electromagnetic transducer is turned off, the spring returns the membrane to its original position and the valve closes. When a pulsating current or an alternating current flows through the electromagnetic transducer, the membrane vibrates and pressure is generated in the liquid. At an appropriate frequency, sufficient pressure can be obtained to discharge the flow of the liquid from the opening.

[0010] Typical frequencies are from 10 Hz to 500 Hz, more preferably from 50 Hz to 200 Hz. The diameter of the nozzle, the discharge velocity of the fluid, and the duration of the electromagnetic burst are preferably optimized to deliver the required amount of fluid within the required time as described above. The actuation pulse duration is preferably 250 milliseconds or less, more preferably 100 milliseconds or less. Here, the "actuation pulse duration" refers to the length of time that the electromagnetic transducer is energized to withdraw the needle from the opening using a single actuation pulse.

[0011] In this configuration, other types of transducers such as coin-type vibrating motors may be used to drive fluid discharge.

Brief Description of the Drawings

[0012]

Figure 1

Figure 2

Figure 3A

Figure 3B

Figure 3C

Figure 4A

Figure 4B

Figure 5

Figure 6

Modes for Carrying Out the Invention

[0013] Figure 2 shows a perspective view of a first embodiment of the liquid discharge unit. The fluid discharge unit (device) 200 is specifically suitable for use when delivering a pharmaceutical liquid without preservatives to the surface of the eye, but is not limited thereto. The liquid discharge device 200 includes a plastic body 206 that forms a liquid chamber and is connected to a fluid supply ampoule 202. The discharge unit includes a nozzle 208 for discharging the liquid 210, as will be described in more detail below.

[0014] Figure 3A shows a cross-sectional view of the fluid discharge device. As described above, the fluid discharge device includes a plastic body 206 that defines a chamber 316 connected to a fluid supply ampoule 202 that houses a fluid 302. The fluid discharge device includes a nozzle 208 for discharging the liquid. The device further includes a membrane 308 at the end of the chamber facing the nozzle. The membrane 308 includes an integrated needle 306, and they form one component. The needle 306 and the membrane 308 are connected to an electromagnetic transducer 310 via a link member 318. When an electrical pulse is applied to the electromagnetic transducer 310, the magnetic force generated by the current flowing through the coil 312 pulls the plunger 314 backward against the spring 320.

[0015] In Figure 3A, the reference numeral 304 indicates the direction in which the fluid flows from the ampoule 202 to the chamber 316. The vent tube 404 will be described in more detail below.

[0016] Figure 3B shows the device of Figure 3A after the application of an electrical pulse to the electromagnetic transducer 310. It can be seen that the plunger 314 is pulled toward the electromagnetic transducer in the direction indicated by the arrow by the magnetic force. The membrane 308 is connected to the plunger 314 by a link member 318 and is pulled by the plunger 314. Figure 3C shows the situation when the electromagnetic transducer 310 is turned off. Here, the spring 320 pushes the membrane 308 back to its original position, so that the valve closes and the chamber is sealed, preventing the intrusion of microorganisms.

[0017] When the electromagnetic transducer 310 is energized with a pulsating or alternating current (AC), the diaphragm generates pressure in the liquid, and as a result, flow is discharged from the opening. The operating frequency is typically from 1 to 500 Hz, more specifically, from 50 to 200 Hz. In one embodiment, the membrane 308 is formed from silicon having a durometer hardness of 50 to 70 (Shore A), and the displacement of the plunger 314 is about 200 μm. Since the flow occurs only outward, even when the valve is open, the intrusion of microorganisms is prevented.

[0018] As shown in FIGS. 4A - B, the liquid discharge device includes a venting device for making the pressure inside the ampule 202 equal to the ambient atmospheric pressure. Here, FIG. 4A is a cross-sectional view taken along the line E - E of FIG. 4B.

[0019] The venting system of this embodiment includes an air injection vent tube 404 that extends beyond the liquid level of the fluid 302 inside the ampule 202. It should be noted that the vent tube 404 is above the liquid level in any orientation of the device shown in FIGS. 4A and 4B. The vent tube 404 is connected to a vent hole 406 that is open to the atmosphere. In one embodiment, a filter 408 is disposed at the vent hole 406 so as to filter the vented air flowing into the ampule and prevent the intrusion of potential airborne contaminants such as microorganisms. The filter 408 filters particles having a size larger than 1 μm (preferably larger than 0.5 μm, more preferably larger than 0.2 μm). In this way, even when air 402 enters the ampule 202 during fluid discharge, the system can be isolated from contamination by microorganisms.

[0020] In the foregoing example, the diaphragm 308 is driven by a solenoid. As shown in FIG. 5, the diaphragm is driven using a coin-type vibrating motor. More specifically, reference numeral 306 indicates a needle connected to the diaphragm 308 as described above. This assembly is integrally formed with a magnetic steel pin 510. Reference numeral 502 indicates a coin-type vibrating motor (e.g., model number C1026B002F of JINLONG MACHINERY&ELECTRONICS CO.,LTD). Reference numeral 504 indicates a plastic molded part (i.e., a motor holder) that holds the motor 502 so that the motor 502 can slide along the rail. Reference numeral 506 indicates a plastic molded part that provides the above-described rail guide for the motor holder 504 to slide therein. Reference numeral 510 indicates a magnetic steel pin formed in the shape of the membrane / needle assembly (308 / 306). Reference numeral 512 indicates a housing that holds all the parts together.

[0021] As described in more detail above, the needle 306 normally seals the opening (i.e., seals the opening except when fluid is discharged). The coin-type vibrating motor has a weight eccentric from the rotation axis (the rotation axis is perpendicular to the plane of FIG. 5). Since the weight is offset from the axis, when the motor rotates, due to the unbalanced weight, the motor mainly vibrates in the plane of FIG. 5. By disposing the coin-type vibrating motor 502 in a plastic motor holder 504 that fits into the corresponding rail (within member 506), the coin-type vibrating motor is restricted to move only linearly (e.g., from left to right in FIG. 5). As a result of this physical constraint, when the motor rotates, instead of vibrating in the plane, the motor can vibrate only from left to right. Since the coin-type vibrating motor is coupled to the diaphragm 308, when the motor vibrates from left to right, the diaphragm also vibrates from left to right. The flow of the discharged fluid is generated in the same manner as described above. That is, the needle 306 moves back and forth within the opening to discharge the liquid.

[0022] In other embodiments, the coin-type vibrating motor 502 may be coupled to the diaphragm via an optional magnet 508. The magnet 508 is fixed to a motor holder 504 that is also attached to the coin-type vibrating motor 502. When the magnet 508 approaches the magnetic steel pin 510, the magnet 508 and the magnetic steel pin 510 latch onto each other, thereby coupling the motor to the diaphragm. The motor may be easily added to the system without requiring tight tolerances, and since the motor can be added at multiple different steps during the assembly process, this can be considered an advantageous assembly feature.

[0023] The example of FIG. 5 includes a disc spring 320. The spring is in a slightly deformed state from its planar state during assembly and serves to transmit force to the needle 306. Due to this force or load, the needle 306 is pressed against the orifice, so that the flow path is in a closed state. Without the spring, even a very small force will push the needle and open the aperture, and the device will easily cause liquid leakage. Furthermore, the spring has an important spring constant to ensure the proper frequency and amplitude of the vibration of the needle when the motor is energized. Also, in the case of not having a spring, it is also critical that the load to maintain the needle 306 in the closed position depends only on the rigidity of the diaphragm 308. The diaphragm may be made of an elastomer. Many elastomers have significantly different mechanical properties even with a slight temperature change. By using the spring 320, a significant portion of the load applied to the needle 306 is provided by the spring 320 rather than the diaphragm 308. Since the mechanical properties of spring steel (such as the material of the spring 320, etc.) remain constant even with the same temperature change, adding a spring can make the performance of the system more stable.

[0024] In other embodiments, the disc spring 320 of FIG. 5 is replaced with a conical spring. The conical spring resembles a conventional wire compression spring, but instead of being wound with a constant diameter, the diameter gradually decreases, so that the spring is conical rather than cylindrical. Here, refer to FIG. 6. When the conical spring is fully compressed, the coils become nested with each other, the spring becomes flat, and it has only the thickness of the diameter of the wound wire. Therefore, the fully compressed conical spring can fit into a shape factor similar to that of the disc spring 320 of FIG. 5 and can perform the same function. The conical spring is less expensive than the disc spring and can easily ensure a wide range of spring constants and operating deflection amounts, so it can be said to be a characteristic of a currently preferred form.

[0025] The tip of the needle 306 and / or the opening with which it engages may contain an antibacterial material. It should be noted that the following aspects are disclosed in this specification. [Aspect 1] An apparatus for delivering a fluid to a patient's eye, a reservoir configured to hold the fluid, an opening, and a needle configured to seal the opening when the fluid is not discharged from the opening, and a fluid package having an elastic diaphragm connected to the needle and configured to provide a mechanical force for engaging and holding the tip of the needle with the opening when the fluid is not discharged from the opening; an actuator configured to discharge the fluid through the opening by providing mechanical vibration to at least the needle; and a vent configured to allow air to enter the reservoir when the fluid is discharged from the reservoir. [Aspect 2] The apparatus according to Aspect 1, further comprising a particle filter configured to remove particles larger than 0.2 μm from the air entering the reservoir through the vent. [Aspect 3] The apparatus according to Aspect 1, wherein the actuator comprises an electromagnetic solenoid. [Aspect 4] The apparatus according to Aspect 1, wherein the actuator comprises a coin-type vibration motor. [Aspect 5] The apparatus according to Aspect 1, wherein the fluid package comprises an elastic spring configured to provide an additional mechanical force for engaging and holding the tip of the needle with the opening when the fluid is not discharged from the opening. [Aspect 6] The apparatus according to Aspect 1, configured to deliver a dosage of 10 μL or less. [Aspect 7] The apparatus according to Aspect 1, wherein the diameter of the opening is configured to be 200 μm to 600 μm. [Aspect 8] The apparatus according to Aspect 1, wherein the velocity of the fluid discharged from the opening is configured to be 1 m / s to 10 m / s. [Aspect 9] The apparatus according to Aspect 1, wherein the operating pulse duration is configured to be 250 milliseconds or less. [Aspect 10] The apparatus according to Aspect 1, wherein the repetition frequency of the operating pulse is configured to be 10 Hz to 500 Hz. [Aspect 11] The apparatus according to Aspect 1, wherein the needle has a tip that engages with the opening, and the tip contains an antibacterial material. [Aspect 12] The apparatus according to Aspect 1, wherein the opening contains an antibacterial material. [Aspect 13] The apparatus according to aspect 1, wherein the opening is arranged on the front wall of the reservoir, and the elastic diaphragm is arranged on the rear wall of the reservoir.

Claims

**Claim 1** An apparatus for delivering a fluid to a patient's eye, comprising: a reservoir configured to hold the fluid, an opening, and a needle configured to seal the opening when the fluid is not discharged from the opening, and a fluid package having an elastic diaphragm configured to provide a mechanical force for engaging and holding the tip of the needle with the opening when the fluid is not discharged from the opening, and an actuator configured to discharge the fluid through the opening by providing mechanical vibration to at least the needle, and a vent configured to allow air to enter the reservoir when the fluid is discharged from the reservoir, the vent being configured to equalize the pressure in the reservoir with the ambient atmospheric pressure, the vent including an air injection vent tube extending above the liquid level in the reservoir during use. **Claim 2** The apparatus according to claim 1, wherein the air injection vent tube is connected to a vent hole open to the atmosphere. **Claim 3** The apparatus according to claim 1, further comprising a particle filter configured to remove particles larger than 0.2 μm from the air entering the reservoir through the vent. **Claim 4** The apparatus according to claim 1, wherein the actuator comprises an electromagnetic solenoid. **Claim 5** The apparatus according to claim 1, wherein the actuator comprises a coin-type vibrating motor. **Claim 6** The apparatus according to claim 1, wherein the fluid package comprises an elastic spring configured to provide an additional mechanical force for engaging and holding the tip of the needle with the opening when the fluid is not discharged from the opening. **Claim 7** The apparatus according to claim 1, configured to deliver a dosage of 10 μL or less. **Claim 8** The apparatus according to claim 1, wherein the diameter of the opening is configured to be 200 μm to 600 μm. **Claim 9** The apparatus according to claim 1, wherein the velocity of the fluid discharged from the opening is configured to be 1 m / s to 10 m / s. **Claim 10** The apparatus according to claim 1, wherein the actuation pulse duration is configured to be 250 milliseconds or less. **Claim 11** The apparatus according to claim 1, wherein the repetition frequency of the actuation pulse is configured to be 10 Hz to 500 Hz. **Claim 12** The device according to claim 1, having the tip portion where the needle engages with the opening, the tip portion containing an antibacterial material.

13. The device according to claim 1, the opening containing an antibacterial material.

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