Fluid-dynamically actuated preservative-free dispensing system

Abstract

Multi-dose preservative-free ocular fluid delivery devices are provided. The fluid delivery device includes a fluid dispensing system and a fluid package for storing a liquid in the fluid package and supplying the liquid to the dispensing system. The dispensing system includes an elongated chamber including a check valve defining an anterior closure of the chamber. The valve is normally closed and hermetically seals the chamber. The dispenser includes a vibrating motor that causes oscillation of the chamber and the fluid within the chamber. The oscillation of the chamber imparts momentum to the fluid stored in the chamber, which in turn imparts force to cyclically open the valve to dispense a stream or liquid droplets. Fluid is only dispensed when the motor is oscillating, otherwise the valve is hermetically closed.

Description

Technical Field

[0001] The present invention generally relates to devices for dispensing fluid medicines, and more particularly to such devices for storing and delivering preservative-free ophthalmic medicines, such devices being specifically configured to improve ease of use and enhance patient compliance with the drug administration instructions. Background Technology

[0002] Easy dispensing of fluid medications and adherence to dosing instructions are primary concerns for all patients. In particular, preservative-free dispensing bottles (such as ophthalmic squeeze dispensers) typically require greater actuation force due to the valve mechanism that seals the dispensing nozzle to prevent bacterial entry and contamination. Such systems require higher pressure to operate, thus necessitating greater squeezing force. Furthermore, existing dispensing bottles only dispense when inverted, requiring inconvenient head handling, which, along with the need for higher actuation force, further increases inconvenience.

[0003] The type of dispenser discussed is known from the prior art, for example from US 6,095,376, US 9,676,525, US 2014 / 0336596, US 2016 / 0107180, US 9,238,532, US 8,056,766, US 8,863,998, and US10,105,720. The dispenser shown in US 2014 / 0336596 includes an outlet channel that connects a liquid reservoir to an outlet opening via an outlet valve arranged in the outlet channel and opening when the bottle is squeezed and pressure is generated. Such preservative-free squeeze bottles typically require a squeezing force of about 25N-28N (Ophthalmic Squeeze Dispenser - Drug Development and Delivery, October 2017, Vol. 17, No. 7, p. 40). Elderly patients or other patients who lack sufficient strength and / or dexterity in their hands often encounter problems dispensing medication from such bottles.

[0004] This work provides a preservative-free ophthalmic dispensing device that can be held horizontally or in any convenient orientation, while being effortlessly actuated by an electric switch. This provides a cost-effective solution that conforms to standard pharmaceutical packaging processes. Summary of the Invention

[0005] A multi-dose, preservative-free ocular fluid delivery device is provided. The fluid delivery device includes a fluid dispensing system and a fluid reservoir for storing and supplying the fluid to the dispensing system. The dispensing system includes an elongated chamber containing a check valve defining a front closure of the chamber. The valve is typically closed and the chamber is hermetically sealed. In this work, the chamber includes a vibrating motor that causes oscillations in the chamber and the fluid within it. The oscillations impart momentum to the fluid stored in the chamber, which in turn imparts a force to cyclically open the valve to dispense the flow or liquid droplets. Fluid is dispensed only when the motor oscillates; otherwise, the valve is hermetically closed.

[0006] The check valve may include a flexible plate comprising a conical orifice extending through the thickness of the flexible plate. The valve may further include a stationary spherical member tangentially engaged with the inner wall of the conical orifice to form a hermetically sealed closure. The plate may be made of an elastomer with an elastic modulus in the range of 0.1 GPa to 1.2 GPa. The circumference of the plate may be attached to a chamber by a retaining ring, which engages with the chamber with an interference fit to form a hermetically sealed closure.

[0007] The conical orifice extends through the thickness of the plate, allowing droplets to be distributed through the smaller opening of the orifice, while the larger side of the orifice is in fluid communication with the chamber.

[0008] The spherical component may include an antimicrobial coating that covers the area of ​​the spherical component between the tangential joint line and the smaller opening of the hole.

[0009] A vibratory motor causes the chamber and the fluid within it to oscillate. This generates a cycle of hydrodynamic pulses, causing the valve to open cyclically and dispense fluid. Here, the characteristic of this phenomenon is the oscillating interaction between the valve and the surrounding fluid. The hydrodynamic force generated by the momentum of the fluid opens the valve and allows fluid to flow through the orifice.

[0010] Fluid is dispensed only when the hydrodynamic force is high enough to deform the orifice; otherwise, the orifice provides an airtight seal to the chamber. This system prevents microorganisms from entering the chamber, thus allowing the storage of preservative-free pharmaceuticals. This work provides a convenient and cost-effective electrically operated preservative-free dispensing system. Attached Figure Description

[0011] Figure 1A This is a cross-sectional view of an embodiment of the present invention.

[0012] Figure 1B yes Figure 1A Detailed cross-sectional view of an embodiment.

[0013] Figure 1Cyes Figures 1A to 1B A 3D view of an embodiment.

[0014] Figure 2A These are side views and partial cross-sectional views of embodiments of the invention in operation.

[0015] Figure 2B yes Figure 2A A detailed section view of the example.

[0016] Figure 3 A perspective view of a vibration motor, as used in an embodiment of the present invention, is shown.

[0017] Figure 4A This is a front view of an embodiment of the present invention.

[0018] Figure 4B yes Figure 4A A side view of an embodiment.

[0019] Figure 4C yes Figure 4A Detailed cross-sectional view of an embodiment.

[0020] Figure 5A This is a front view of an exemplary device enclosed in a housing.

[0021] Figure 5B yes Figure 5A A side view of an example.

[0022] Figures 6A to 6B It is a perspective view of a device having a housing including a rotating cover. Detailed Implementation

[0023] This work describes a dispensing device and method for delivering preservative-free solutions or suspensions for ophthalmic application of ophthalmic pharmaceuticals. The dispensing device includes a microdroplet ejection system fluidly connected to an ampoule containing the liquid to be dispensed. The microdroplet ejection system includes a chamber with a check valve defining a front closure of the chamber. The dispensing system further includes a vibration motor that oscillates the chamber and includes hydrodynamic pulses, which thus cause the valve to open cyclically and eject fluid microdroplets. The valve is normally closed and hermetically seals the chamber. The valve opens only in response to the hydrodynamic pulses caused by the oscillation of the chamber. In this way, fluid is dispensed only when the device is actuated, and otherwise the device is hermetically sealed and bacteria and microorganisms are prevented from entering, thereby allowing storage of preservative-free pharmaceutical preparations. The use of a vibration motor further enables convenient and cost-effective electronically controlled administration.

[0024] Figure 1A and Figure 1BA side view and an enlarged partial cross-sectional view of the fluid delivery device 100 are shown. The delivery device 100 includes a fluid reservoir 102 and a distribution system 104, which are connected to each other via a passage 106 in a fluid transfer relationship. The distribution system 104 includes a fluid chamber 108 and also includes a check valve, which includes an orifice plate 110 that provides a front closure to the chamber 108.

[0025] refer to Figure 1B As can be seen, the orifice plate 110 includes a conical or tapered orifice 116 (shown in the dashed circle for clarity) that extends through the center thickness of the orifice plate and has a larger inlet opening 116a and a smaller outlet opening 116b. The larger inlet opening is in fluid communication with the chamber 108, and fluid droplets will be dispensed through the smaller outlet opening.

[0026] The orifice plate 110 can be made of a flexible elastomer, such as VersaFlex silicone rubber manufactured by VersaFlex Inc., Kansas City, Kansas, USA. Other elastomers with a Young's modulus between 0.5 GPa and 2 GPa can also be used. The dispensing system 104 further includes a stationary spherical member 114 that tangentially engages with the inlet opening 116a of a conical orifice providing a hermetically sealed closure in a pressure transmission relationship. In a preferred embodiment, the spherical member 114 is made of high-density polyethylene (HDPE) with a hardness greater than silicone, thereby forming a tight closure when the spherical member engages with the softer orifice plate 110. Preferably, the spherical member 114 engages with the conical orifice 116a in a pressure transmission relationship with a preload force between 0.01 N and 0.05 N. The combination of the orifice 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. Because any shape capable of forming a good seal with the orifice plate 110 can be used, the component 114 can have a shape other than a sphere.

[0027] The orifice plate 110 can be held to the distribution system 104 by the retaining ring 130, thereby forming an airtight seal.

[0028] The dispensing system 100 includes a vent 126 configured to equalize the pressure inside container 102 when dispensing fluid from the device. An opening 134 of the vent 126 extends above the fluid level 132 in any orientation in which the device is held. The vent 126 may be connected via a 0.22-micron filter 128 to ensure that the air entering the device is sterile.

[0029] The distribution system 100 further includes a vibration motor configured to oscillate the chamber 108 and the fluid within it. Here, this motor is schematically shown as an eccentric mechanical load 118, which passes through the motor ( Figures 1A to 1B The motor is not shown, but it is mentioned below. Figure 3 (As described) and when rotated, the components vibrate as described.

[0030] Figure 1C yes Figures 1A to 1B A 3D view of an embodiment.

[0031] Figures 2A to 2B The response of the distribution system 104 to oscillations is illustrated. The vibration of the motor causes oscillations in the body of the distribution system 104, which in turn generates fluid momentum within the chamber due to the dynamic interaction between the fluid and the solid structure of the chamber 108. This phenomenon is commonly referred to as solid-fluid interaction (SFI). The force exerted by the momentum of the moving fluid causes the orifice plate 110 to flex outwards in the directions indicated by arrows 206a and 206b, thereby disengaging the orifice plate 110 from the spherical member 114, thereby opening the fluid flow path as indicated by arrows 208a and 208b and ejecting fluid droplets 210.

[0032] The dispensing device 100 is supported by a flexible beam 122 or other structural embodiments that allow the dispensing device to oscillate freely, as schematically shown by motion offsets 202 and 204. Preferably, the spring constant of the beam 122 is from 0.05 N / mm to 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 thickness of the resulting beam 122 is suitable for providing the spring constant as described above.

[0033] Figure 3 An exemplary vibration motor 302 is shown. This example DC motor 302 has a cylindrical body with a diameter of 4 mm and an overall length of 17 mm. An eccentric flywheel 118 is attached to the motor shaft. The flywheel has a mass of 1.7 grams and a center of mass distance of approximately 0.7 mm from the center of rotation. The motor receives 4.5VDC-12VDC and rotates at 6000RPM-12000RPM, generating a centrifugal force of 0.3N at a rotational speed of 8000RPM. Other DC motors that generate a centrifugal force of 0.1N-1N and a rotational speed of 1000RPM-50000RPM can be used. The motor can be controlled by a timer circuit that is set to provide an on-time as needed to deliver a dose of 8µL-12µL. The actuation on-time is 60ms-200ms, depending on the rheology of the fluid in use. A timer circuit can be used that combines a 555 timer IC or a microprocessor-based timer with a 12-volt battery (such as an A23 alkaline battery).

[0034] Figures 4A to 4C An alternative preferred embodiment of the distribution system 400 is shown. Figure 4A The front view of the distribution system 400 is shown, and Figure 4B A side view of the dispensing system is shown. The dispensing system 400 includes a concave mirror 402 that assists in aligning the device 400 and the fluid flow 210 towards 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 clearly in the center of the mirror for the user. At this time, the device is properly positioned in terms of the distance from the eye to the nozzle 404 and the angular orientation of the device relative to the eye. Upon actuation, the flow 210 will be precisely deposited on the corneal surface of the eye. Preferably, the device 400 includes a 0.22-micron air filter configured to filter the venting air flowing into the device 400, as in the previous example.

[0035] The device 400 includes a check valve having an orifice plate 406 with a conical orifice 116 extending through its thickness. The check valve further includes a spherical member 114 that tangentially engages with the inlet opening of the conical orifice 116. In this example, the check valve also includes a compression spring 408 configured to force the orifice plate 406 against the spherical member 114. In this way, a tight seal is formed along the engagement line 114a, thus forming a tight and airtight closure.

[0036] The spherical member 114 may be partially covered with an antimicrobial coating, specifically in the region of the spherical member 114 that is not in contact with the fluid in the chamber. Therefore, the coated region is between the joint line 114a and the outlet of the conical orifice (i.e., in...). Figure 4C Extending upwards to the left of 114a. Examples of antimicrobial coatings include metallic silver, silver alloys, or nonmetallic materials containing silver (including salts of silver chloride and silver sulfadiazine). Other alternative materials include biguanide derivatives, chlorhexidine diacetate, and chlorhexidine digluconate.

[0037] Figures 5A to 5B The front and side views of the dispensing device 400 encapsulated in the housing 502 are shown respectively. The housing 502 is... Figures 4A to 4C The dispensing system 400, described in connection with this, is provided with a convenient housing and is shown herein in dashed lines. The housing 502 includes circuitry (not shown) and a 12-volt battery (e.g., model A23) 506. The circuitry controls the dispensing time interval, such that a dose of 8-12 microliters is delivered to the ocular surface of the eye. A momentary switch 504 can be used to activate the device 400, causing a stream of microdroplets to be ejected from the orifice as described above. Figures 5A to 5BMirror 402 is also shown, which is visible on the front side of the device. Such a housing can also be used in the dispensing device 100 as described above.

[0038] Figures 6A to 6B Some preferred features of the housing are shown, which can be used with embodiments such as device 100 and device 400 as described above. In this example, the housing includes a rotating cap 602 that covers the dispensing nozzle 606 during non-use periods. The rotating cap 602 provides a means of preventing bacterial contamination on the external area that may be left with residual fluid after each use. Such residual fluid could contaminate subsequent flows when dispensing them through the nozzle. Preferably, the rotating cap 602 includes a flexible member 604 that includes a surface 604a covered with an antimicrobial coating. When the rotating cap 602 as Figure 6B When closed, surface 604a engages with the outlet opening of nozzle 606. This achieves antimicrobial activity. Alternatively, organic dyes with antiseptic properties can be used. Examples include toluidine blue, methylene blue, gentian violet, and acridine and related active substances (such as acridine orange and acridine yellow), as well as ethacridine lactate. Bactericidal polymers (such as polyhexylguanidine) are also possible. Materials containing additives, which include organometallic substances with ionizing effects, can also be used. Such additives are available from SteriOne GmbH in Berlin, Germany. Examples of antimicrobial coatings that can be used on surface 604a include metallic silver, silver alloys, or non-metallic materials containing silver (including salts of silver chloride and silver sulfadiazine). Other optional materials include biguanide derivatives, chlorhexidine diacetate, and chlorhexidine digluconate.

Claims

1. A device for delivering liquid to a patient's eye, the device comprising: a) A reservoir configured to contain the liquid; b) A liquid dispenser in fluid communication with the reservoir, wherein the liquid dispenser has (a) a flexible orifice through which the liquid can be dispensed, and (b) a pin member for sealingly engaging with the flexible orifice; c) An actuator that generates vibration within the liquid dispenser, thereby generating fluid momentum in the liquid, the liquid i) causing elastic deformation of the flexible orifice to disengage the pin member from the flexible orifice; and ii) ejecting the liquid through the flexible orifice; The pin component is stationary relative to the liquid dispenser.

2. The device as claimed in claim 1, wherein, The actuator includes a vibration motor having an eccentric mechanical load relative to the axis of rotation of the vibration motor.

3. The device as described in claim 2, wherein, The liquid dispenser is supported by a flexible member, thereby generating fluid momentum of the liquid by oscillating the liquid dispenser.

4. The device as described in claim 3, wherein, The spring constant of the flexible component is between 0.05 N / mm and 0.5 N / mm.

5. The device as claimed in claim 1, wherein, The Young's modulus of the pore is between 0.5 GPa and 2 GPa.

6. The device as claimed in claim 5, wherein, The mechanical hardness of the pin component is greater than that of the hole.

7. The device as claimed in claim 1, wherein, The hole is tapered, and the outlet of the hole is narrower than the inlet of the hole.

8. The device as claimed in claim 1, wherein, The end of the pin member engages with the hole, and the end of the pin member has a spherical shape.

9. The device as claimed in claim 8, wherein, The ends of the pin component are partially or completely coated with an antibacterial coating.

10. The device as claimed in claim 9, wherein, When the pin member engages with the flexible hole, the antibacterial coating covers at least a portion of the end of the pin member outside the liquid dispenser.

11. The device as claimed in claim 1, wherein, The preload force for the engagement of the pin member with the flexible hole is between 0.01 N and 0.05 N.

12. The device as claimed in claim 1, wherein, The reservoir includes a vent.

13. The device as claimed in claim 12, wherein, The vent includes a filter configured to ensure that the air entering the reservoir is sterile.

14. The device of claim 1, further comprising a concave mirror configured to provide the patient with a focused image of the patient's eye when the device is properly positioned to deliver the liquid to the patient's eye.

15. The device of claim 1, wherein the liquid dispenser further comprises: A fluid chamber in fluid communication with the reservoir and the flexible orifice, wherein the actuator generates vibration in the fluid chamber to generate fluid momentum within the fluid chamber, such that the liquid is distributed through the flexible orifice.

16. A fluid jetting device, the fluid jetting device comprising: A housing configured to receive the fluid to be ejected; A flexible hole is provided on the housing and a pin is fixed to the housing and stationary relative to the housing. The flexible hole is deformable to define i) a closed configuration such that the flexible hole receives at least a portion of the pin. ii) Open configuration in which the pin disengages from the flexible hole; and An actuator, connected to the housing and configured to vibrate the housing to generate fluid momentum in a fluid contained within the housing, such that the fluid elastically deforms the flexible orifice into the open configuration, causing the pin to disengage from the flexible orifice and fluid to flow through the flexible orifice.

17. The fluid jetting device of claim 16, further comprising a concave mirror configured to provide the patient with a focused image of the patient's eye when the fluid jetting device is properly positioned to deliver the fluid to the patient's eye.

18. The fluid jetting device according to claim 16, wherein, The end of the pin engages with the hole, and the end of the pin has a spherical shape.

19. The fluid jetting device according to claim 18, wherein, The end of the pin is partially or completely coated with an antibacterial coating.

20. A fluid jetting device, the fluid jetting device comprising: The casing that is in fluid communication with the fluid reservoir; The fluid can be injected to the intended location through the deformable orifice within the housing. and A pin fixed to the housing and stationary relative to the housing, the pin being configured to engage the deformable orifice to selectively close the deformable orifice to prevent fluid from being ejected from the housing; In response to vibrations generated by the fluid, the deformable orifice elastically deforms and disengages from the pin to allow fluid to be ejected from the fluid jetting device.

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