Electrochemical pump for drug delivery and drug delivery device

Abstract

The present disclosure provides an electrochemical pump and a drug delivery device for drug delivery. The electrochemical pump includes a substrate including a first surface, a second surface, and a plurality of through holes, a plurality of electrodes, an electronic device, and an electrolyte-containing space. The second surface has a plurality of contacts, and the through holes have a conductive material therein and are electrically connected to the plurality of contacts. The plurality of electrodes are disposed on the first surface and are electrically connected to the plurality of contacts on the second surface via the conductive material inside the plurality of through holes. The electronic device is disposed on the second surface and is electrically connected to the contacts on the second surface. The electrolyte-containing space includes an electrolyte therein and is adjacent to the first surface such that the plurality of electrodes are in contact with the electrolyte. The present disclosure also provides a drug delivery device implementing the electrochemical pump.

Description

[Technical Field]

[0001] The present invention relates to electrochemical pumps and drug delivery devices used for the automated delivery of drugs. [Background technology]

[0002] Recently, the pharmaceutical industry has recognized that electrochemical pump technology for delivering therapeutic drugs has room for further development and improvement. However, the design of electrochemical pumps currently used for delivering therapeutic drugs has deficiencies that need to be addressed. For example, in electrochemical pumps using microelectrode structures, the electrolyte has high impedance and a low local electric field, which not only results in large power losses but also low solid free energy at the electrode surface. Both of these factors result in high power consumption for the entire pump system.

[0003] Furthermore, the electrodes and contact pads of conventional electrochemical pumps are usually located on the same side of the substrate, so the connection materials between the control circuit board and the electrodes are inevitably corroded by the electrochemical electrolyte during the electrochemical reaction, which seriously affects the operation and energy consumption of the entire electrochemical pump system. Summary of the Invention [Problem to be solved by the invention]

[0004] The operating mechanism of electrochemical drug delivery medical devices is primarily based on the generation of gas pressure as a driving force source. For example, the pressure difference between the interior of the drug delivery device and the device's ambient environment is utilized to deliver drugs. However, precise control of the amount of pressure generated within the device requires sophisticated device structure and electronic control device design. Without proper design, it can be difficult to accurately control the amount of gas generated to accurately control the amount of drug delivered and stabilize the drug delivery speed.

[0005] Furthermore, if a drug delivery device is required to drive a highly viscous drug at an ultra-high speed, the output of the electrochemical device must be increased accordingly, and it must be capable of outputting a very large driving force. Therefore, the circuit board and power supply must also be capable of outputting a very high output energy. If the contact pads and electrodes are designed on the same side, the lead parts between the contact pads and the electrodes will significantly increase the overall resistance impedance, which will seriously affect the loss of energy transmitted from the power supply to the electrodes and significantly reduce the pressure output performance of the entire electrochemical pump system.

[0006] Furthermore, when a high-concentration drug needs to be delivered in large quantities (e.g., several milliliters) via subcutaneous or intramuscular injection, a gentler injection speed and a slightly longer injection time are necessary to avoid the pain experienced by patients due to excessively fast injection. Manual injection delivery not only requires high labor costs, but also makes it difficult to accurately control the drug delivery speed to avoid the pain mentioned above. Currently, most commercially available automated drug delivery devices use mechanical force (e.g., a spring) or a micromotor as the delivery source. However, the unstable delivery force of a spring or micromotor can cause unexpected pain during injection, and it is difficult to achieve both high speed and stability in delivery.

[0007] Therefore, there is an urgent need to develop an electrochemical pump structure that can improve or solve the above problems in this field, avoid corrosion due to the electrodes and lead pads being located on the same side, reduce impedance to increase the efficiency of energy delivery, improve the control accuracy of energy delivery to reduce pain, and develop a miniaturized automated drug delivery device or method. [Means for solving the problem]

[0008] To achieve the objectives of the present invention, the present disclosure provides an electrochemical pump for drug delivery and a drug delivery device thereof. The electrochemical pump includes a substrate, a plurality of electrodes, an electronic device, and an electrolyte containing space. The substrate has a first surface, a second surface, and a plurality of through holes, the second surface having a plurality of contacts, the through holes containing conductive material therein and electrically connected to the plurality of contacts. The plurality of electrodes are disposed on the first surface and electrically connected to the plurality of contacts on the second surface via the conductive material in the plurality of through holes. The electronic device is disposed on the second surface and electrically connected to the contacts on the second surface. The electrolyte containing space contains an electrolyte therein and is adjacent to the first surface, allowing the plurality of electrodes to contact the electrolyte.

[0009] In one embodiment, the electrodes include at least an anode and a cathode. The electrodes may further include a reference electrode. The electrodes may further include a redundant electrode.

[0010] In one embodiment, any of the electrodes is electrically connected to multiple contacts through multiple through holes.

[0011] In one embodiment, the first surface is coated with a hydrophilic layer.

[0012] In one embodiment, the electrolyte-containing space is formed by attaching a high-absorbency material to the first surface.

[0013] In one embodiment, the highly absorbent material is a sponge.

[0014] In one embodiment, the superabsorbent material is polyvinyl alcohol (PVA), polyethylene oxide (PEO), polyacrylic acid, polylactic acid (PLA), polyglycolic acid (PGA), PLA / PGA copolymers, polycaprolactone (PCL), and polymeric fibers made from the aforementioned materials.

[0015] In one embodiment, the electrolyte-containing space is formed by attaching a breathable film to the first surface, the electrolyte-containing space being sealed with the breathable film.

[0016] In one embodiment, the electronic device includes a circuit board, an input terminal, and an output terminal.

[0017] In one embodiment, the circuit board is electrically connected to the electrochemical pump board by the output terminal, and one end of the input terminal is electrically connected to the circuit board and the other end is an input port of the power supply.

[0018] In one embodiment, the electronic device further includes drive circuitry.

[0019] In one embodiment, the electronic device includes a power source.

[0020] In one embodiment, the circuit board is electrically connected to the contacts by the output terminals, the power source is electrically connected to the circuit board via the input terminals, and the drive circuitry is electrically connected to the circuit board and electrically connected to the power source.

[0021] In one embodiment, the electronic device is removable.

[0022] Another aspect of the present disclosure provides a drug delivery device. The drug delivery device includes a container for containing a drug, having opposing first and second openings, an isolation member, and an electrochemical pump. The first opening is a drug delivery outlet. The isolation member is disposed within the container between the two openings and can slide freely along the wall of the container. The electrochemical pump is disposed at the second opening, and the electrochemical pump and the container are tightly coupled to seal the second opening.

[0023] In one embodiment, the container is a syringe, and the syringe can further include a needle disposed in the first opening.

[0024] In one embodiment, the container is transparent or translucent.

[0025] In one embodiment, the container is rigid or flexible.

[0026] In one embodiment, the isolation member comprises a rubber plug. [Brief explanation of the drawings]

[0027] [Figure 1] Schematic structural diagram of an electrochemical pump according to the present disclosure. [Figure 2] 1 is a cross-sectional view of a drug delivery device according to the present disclosure. [Figure 3] Figure showing the relationship between the flow rate of the electrochemical pump and the number of through-holes [Figure 4] Figure 1 shows the relationship between the total delivery volume of the electrochemical pump and the number of through-holes. DETAILED DESCRIPTION OF THE INVENTION

[0028] All technical and scientific terms used in the specification and claims have definitions known to those skilled in the art to which this invention belongs, unless otherwise defined. The singular forms "a," "an," "the," etc. include plural referents unless the context clearly dictates otherwise. As used herein, "or" or "and" means "and / or" unless specifically stated otherwise. Furthermore, the terms "comprising" and "including" are non-limiting open-ended conjunctions. The foregoing definitions are merely illustrative references to definitions of terms and should not be construed as limiting the present invention. Unless otherwise specified, materials used in the present invention are commercially available and readily available.

[0029] Ordinal numbers such as "first," "second," etc. used in the specification and claims are intended only to describe the elements described and do not imply or indicate an order of execution between the elements described, an order between one element and another, or an order between steps in a manufacturing process. These ordinal numbers are used merely to distinguish an element having a given name from another element having the same name.

[0030] Furthermore, as used herein, terms such as "on," "above," and "over" do not only refer to direct contact between an element and another element (e.g., a substrate), but also include indirect contact between an element and another element (e.g., a substrate).

[0031] (Example) 1, an electrochemical pump 10 is provided. The electrochemical pump 10 includes a substrate 101, an electrolyte containing space 102, a plurality of electrodes 103, and an electronic device 104.

[0032] The substrate 101 has a first surface 1011, a second surface 1012, a plurality of through holes 1013, a plurality of conductive materials 1014, and a plurality of contacts 1015. The contacts 1015 are disposed on the side of the through holes 1013 facing the second surface 1012, and the conductive materials 1014 are disposed within the through holes 1013. This allows electrical connection between components on the first surface 1011 and components on the second surface 1012. The electrolyte containing space 102 is disposed on the first surface 1011 and contains an electrolyte 1021. The electrode 103 is disposed on the first surface 1011 and is in direct contact with the electrolyte 1021 and electrically connected to the conductive materials 1014 in the through holes 1013. The electronic device 104 is disposed on the second surface 1012 and electrically connected to the contacts 1015.

[0033] According to the present disclosure, both sides of the through-hole 1013 can be electrically connected by, but not limited to, filling the through-hole 1013 with a conductive material, coating the wall of the through-hole 1013 with a conductive material layer, or inserting a conductive lead into the through-hole 1013. According to the present invention, the through-hole 1013 and the conductive material 1014 therein can be obtained using a feedthrough technique. The feedthrough technique is widely applied in the manufacturing of complementary metal-oxide semiconductor (CMOS) processes and integrated circuit (IC) packaging. This can completely isolate "wet" structures (i.e., various structures on a first surface that are directly connected to the electrolyte) from "dry" structures (i.e., various structures on a second surface that are directly connected to the surface, such as electronic devices), avoiding direct contact between the electrolyte and the electronic devices, and improving the reliability of the entire device.

[0034] In one embodiment, contacts 1015 are a plurality of contact pads.

[0035] According to the present disclosure, the electrolyte-containing space 102 for containing the electrolyte is constructed by attaching a superabsorbent material to the first surface or by attaching a breathable film to the first surface. In one embodiment, the electrolyte-containing space 102 is a superabsorbent material coated on the first surface 1011, which forms the electrolyte 1021 into a gel state, maintaining contact between the electrode 103 and the electrolyte 1021, preventing electrolyte leakage, and allowing generated gas to leave the electrolyte-containing space 102. The electrolyte 1021 can be a solution capable of generating gas through the electrodes, such as, but not limited to, water or an electrolyte solution.

[0036] In a preferred embodiment, the highly absorbent material is a sponge. In another embodiment, the highly absorbent material is attached to the surface of the electrode 103. The highly absorbent material is made of a material selected from the group consisting of polyvinyl alcohol (PVA), polyethylene oxide (PEO), polyacrylic acid, polylactic acid (PLA), polyglycolic acid (PGA), PLA / PGA copolymer, and polycaprolactone (PCL).

[0037] In a preferred embodiment, the number of electrodes 103 is at least three. More specifically, two electrodes 103 function as anodes and cathodes, respectively. To achieve better electrochemical performance, the anodes and cathodes are alternately arranged to form an interdigitated electrode structure. The remaining electrode serves as a reference electrode to avoid voltage drops, such as those caused by ohmic voltages generated by current flow in dilute acid solutions or saltwater plasma electrolytes. Voltage drops can affect the accuracy of drug delivery, so it is necessary to avoid voltage drops to obtain accurate voltage level measurements. When there are four or more electrodes, the remaining electrodes are redundant. Providing these redundant electrodes avoids the inconvenience of repairing suddenly failed electrodes.

[0038] To improve electrochemical efficiency, any electrode 103 can be electrically connected to the electronic device 104 through multiple through-holes 1013. In a preferred embodiment, the anode and cathode each contain 20 through-holes. Figures 3 and 4 show a comparison of the electrochemical efficiency of this configuration with other electrode designs. The design with 20 through-holes (40 through-holes, with the electrode and contact pads on opposite sides) increased the flow rate and total delivery volume by approximately 30% compared to a design with no through-holes (the electrode and contact pads on the same side). The design with one through-hole (2 through-holes, with the electrode and contact pads on opposite sides) also increased the flow rate and total delivery volume by approximately 20%.

[0039] To improve electrochemical efficiency, a hydrophilic layer can be coated on the first surface 1011 and the electrode 103. Coating materials can include, but are not limited to, polyvinylphenol (PVP), polyacrylic acid (PAA), poly(vinylphenol), ethylene oxide (PEO), polysaccharides, proton exchange membranes (e.g., sulfonated tetrafluoroethylene, also known as Nafion), nanostructured metals, epoxy resins, and polymer fibers made from the aforementioned materials.

[0040] The coated hydrophilic layer is used to ensure that the first surface 1011 of the electrochemical pump 10 is hydrophilic and capable of continuously producing gas during the electrochemical reaction. The coated electrode can provide higher gas solubility compared to conventional untreated electrodes.

[0041] To further enhance this electrochemical efficiency, it is effective to change the electrode geometry. In some embodiments, an inverted trapezoidal electrode is fabricated by an improved standard electron beam lithography program or an improved photolithography program with an improved oxygen plasma treatment, an improved reactive ion etching (RIE), an improved deep reactive ion etching (DRIE), or an improved inductively coupled plasma (ICP). Alternatively, the electrochemical efficiency can be enhanced by changing the electrode geometry. In one embodiment, the electrode 103 is fabricated in an inverted trapezoidal shape to generate a stronger electric field and generate a larger amount of gas. In another embodiment, the hydrophilicity of the electrochemical pump 10 can be achieved by hydrophilic treatments, such as an oxygen plasma process, chemical etching, and mechanical friction.

[0042] Electronic device 104 is electrically connected to contacts 1015 and is used to power electrodes 103 and control the time and power of the electrochemical reaction. In a preferred embodiment, electronic device 104 is removable and can be assembled with or separated from other components of electrochemical pump 10.

[0043] In one embodiment, the electronic device 104 comprises a circuit board 1041 , an input terminal 1042 , and an output terminal 1043 .

[0044] The output terminal 1043 electrically connects the circuit board 1041 to the contacts 1015 to control the electrodes 103 and, in turn, control the electrochemical pump 10 to produce gas. The input terminal 1042 is electrically connected at one end to the circuit board 1041 and at the other end to a power source to provide power to the electrochemical pump 10. The power source may be an external power source or may be contained within the electronic device 104.

[0045] In one embodiment, the electronic device 104 further includes a power supply 1044 that is electrically connected to the input terminal 1042 .

[0046] In a preferred embodiment, the electronic device 104 further comprises drive circuitry to control the activation and deactivation of the electronic device 104 .

[0047] Thus, the output terminal 1043 serves as an electrical bridge between the electronic device 104 and other components of the electrochemical pump 10. The output terminal 1043 may be a microconnector, such as a pogo pin.

[0048] As shown in FIG. 2, the present disclosure provides a drug delivery device 200, which includes a container, for example a syringe 20, and an electrochemical pump 10.

[0049] The syringe 20 includes a first opening 21, a second opening 22, and an isolation member 23. The first opening 21 and the second opening 22 face each other.

[0050] In a preferred embodiment, the syringe 20 further includes an injection needle 24 disposed in the first opening 21 .

[0051] In one embodiment, the drug delivery device 100 is small enough to deliver minute amounts of drug, with the syringe 10 preferably having a volume in the microliter (μL) range (0.1 to 500 microliters).

[0052] In another embodiment, the drug delivery device 100 is capable of delivering high-concentration, large-volume drug, and the volume of the syringe 20 is preferably in the milliliter (mL) range (0.1 to 500 mL).

[0053] According to one embodiment of the present invention, the isolation member 23 is disposed inside the syringe 20 and separates the syringe 20 into a first chamber 201 and a second chamber 202. The first chamber 201 is used to contain a drug, and the second chamber 202 is used to contain the electrolyte-containing space 102 of the electrochemical pump and the electrolyte 1021 therein.

[0054] According to one embodiment of the present invention, the container may be a syringe 20 and may be made of a transparent or translucent material. The container, such as a syringe, may be rigid or flexible. Preferably, the syringe 20 is made of a rigid material, which may include, but is not limited to, glass (e.g., quartz, fused silica, alkali lime, silicate, borosilicate, etc.), polymers / plastics (e.g., polycarbonate (PC), polymethyl methacrylate (PMMA), polypropylene (PP), polyethylene (PE), ethylene terephthalate (PET), polylactic acid (PLA), thermoplastic elastomers (TPE), and parylene, COP or COC cyclic olefin polymers, etc.), rubbers (natural rubber and rubber), colloids (epoxy resins, silicones, and acrylic resins), and conductive polymers (polyfluorene, polybiphenyl compounds, propylene, polyazulene, polynaphthalene, polypyrrole (PPY), polyaniline (PANI), polythiophene (PT), poly(3,4-ethylenedioxythiophene) (PEDOT), polyparaphenylene sulfide (PPS), polyacetylene (PAC), and polyphenylene vinylene (PPV)).

[0055] In this embodiment, the isolation member 23 is a diaphragm. The isolation member 23 may be made of, but is not limited to, a thermoplastic elastomer (TPE), a styrene-ethylene-butylene-styrene block copolymer (SEBS), a styrene-ethylene-propylene-styrene block copolymer (SEPS), and polyparaethylene. However, in another embodiment, the isolation member 23 may be a blocking member made of a rubber stopper, which may be made of a material such as rubber, polytetrafluoroethylene (Teflon®), silicone, a thermoplastic elastomer (TPE), a styrene-ethylene-butylene-styrene block copolymer (SEBS), a styrene-ethylene-propylene-styrene block copolymer (SEPS), and parylene.

[0056] According to the present disclosure, the electrochemical pump 10 is disposed at the second opening 22 of the syringe 20, and the electrochemical pump 10 and the syringe 20 are tightly coupled to seal the second opening 22. This prevents leakage of the electrolyte 1021 contained therein and gas generated by the electrochemical pump 10. Therefore, when the electrolyte 1021 undergoes an electrochemical reaction to generate gas, the pressure in the second chamber 202 becomes higher than the pressure in the first chamber 201, causing the isolation member 23 to move toward the first opening 21 and delivering the drug. The isolation member 23 is disposed to isolate the first chamber 201 and the second chamber 202 from each other to prevent mixing of the electrolyte and the drug. Sealing methods include, but are not limited to, the use of a gasket (e.g., an O-ring), an adhesive seal, or welding (e.g., ultrasonic, heat, or laser welding).

[0057] In one embodiment, after the second opening 22 is sealed, the electrochemical pump 10 is removable.

[0058] In another embodiment, the electrochemical pump 10 is not removable after the second opening 22 is sealed.

[0059] It will be apparent to those skilled in the art that the embodiments disclosed herein are illustrative and not restrictive. Those skilled in the art can implement the present invention through numerous modifications or substitutions without departing from the technical characteristics of the present invention. It should be noted that, according to the embodiments described herein, the present invention can be modified in various ways without interfering with its implementation. The following claims define the scope of the present invention and cover the above-described methods and structures, as well as their equivalents. [Explanation of symbols]

[0060] 10 Electrochemical Pump 101 Substrate 1011 First Surface 1012 Second Surface 1013 through hole 1014 Conductive materials 1015 Contact 102 Electrolyte storage space 1021 Electrolyte 103 Electrode 104 Electronic Devices 1041 Circuit Board 1042 input terminal 1043 output terminal 1044 Power supply 200 Drug delivery device 20 syringes 201 Chamber 1 202 Second Chamber 21 First opening 22 Second opening 23 Isolation member 24 Syringe needle

Claims

1. 1. An electrochemical pump comprising: a substrate including a first surface, a second surface, and a plurality of through holes; a plurality of contact pads disposed on the second surface; a plurality of electrodes disposed on the first surface and electrically connected to the contact pads via a conductive material; an electronic device disposed on the second surface and electrically connected to the contact pads; an electrolyte-containing space containing an electrolyte therein and adjacent to the first surface such that the plurality of electrodes are in contact with the electrolyte; Equipped with each of the through holes includes the conductive material therein, the conductive material being electrically connected to at least one of the contact pads; The conductive material is filled in each of the through holes or coated on the wall surface of each of the through holes, the electrodes are made of a corrosion-resistant material for electrochemical reactions and are made of a material different from the conductive material; Electrochemical pump.

2. The electrodes include at least an anode and a cathode.

10. The electrochemical pump of claim 1.

3. The electrodes further include a reference electrode or a redundant electrode.

3. The electrochemical pump of claim 2.

4. Each of the electrodes is electrically connected to one of the contact pads via one of the through holes.

10. The electrochemical pump of claim 1.

5. The substrate has up to 20 through-holes as anodes and up to 20 through-holes as cathodes.

3. The electrochemical pump of claim 2.

6. The electrolyte-containing space is configured by attaching a highly absorbent material to a first surface.

10. The electrochemical pump of claim 1.

7. The highly absorbent material is a sponge.

7. The electrochemical pump of claim 6.

8. The highly absorbent material is made of a material selected from the group consisting of polyvinyl alcohol (PVA), polyethylene oxide (PEO), polyacrylic acid, polylactic acid (PLA), polyglycolic acid (PGA), PLA / PGA copolymer, polycaprolactone (PCL), and polymeric textiles made from these materials; 7. The electrochemical pump of claim 6.

9. the electrolyte-containing space is formed by attaching a breathable film to the first surface; The electrolyte storage space is sealed with the breathable film.

10. The electrochemical pump of claim 1.

10. The electronic device includes a circuit board, an input terminal, and an output terminal.

10. The electrochemical pump of claim 1.

11. The electronic device further includes a driving circuit component.

11. The electrochemical pump of claim 10.

12. the electronic device includes a power source; 12. The electrochemical pump of claim 11.

13. the circuit board is electrically connected to at least one of the contact pads by the output terminal; the power supply is electrically connected to the circuit board via the input terminal; the drive circuit component is electrically connected to the circuit board and to the power supply; 13. The electrochemical pump of claim 12.

14. The electronic device is removable.

10. The electrochemical pump of claim 1.

15. 1. A drug delivery device comprising: a container for containing a drug, the container having a first opening and a second opening opposite to each other, the first opening being a drug delivery outlet; an isolation member disposed within the container between the first opening and the second opening, the isolation member being freely slidable along a wall of the container; the electrochemical pump of claim 1 , disposed at the second opening and tightly coupled to the container to seal the second opening; Equipped with Drug delivery devices.

16. 16. The drug delivery device of claim 15, wherein the container is a syringe.

17. The syringe includes a needle disposed in the first opening.

17. The drug delivery device of claim 16.

18. 16. The drug delivery device of claim 15, wherein the container is transparent or translucent.

19. 16. The drug delivery device of claim 15, wherein the reservoir is rigid or flexible.

20. The isolation member is made of a rubber plug.

16. The drug delivery device of claim 15.

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