TWI840716B - Electrochemical pump and its drug-delivery device - Google Patents

Abstract

The present disclosure is to provide an electrochemical pump and its drug-delivery device. The electrochemical pump comprises: a substrate having a first surface, a second surface, and a plurality of vias, wherein the second surface comprises a plurality of contacts, the plurality of vias comprises conducting materials which electrically in contact with the plurality of contacts; a plurality of electrodes disposed on the first surface and electrically in contact with the plurality of contacts on the second surface through the conducting materials in the plurality of vias; an electronic device disposed on the second surface and electrically in contact with the plurality of contacts on the second surface; and a space for containing electrolyte having electrolyte solution therein, which is adjacent to the first surface so that the plurality of electrodes are in contact with the electrolyte solution. The present disclosure is also to provide a drug-delivery device implementing the electrochemical pump, comprises: a container containing a medication, having a first opening and a second opening opposite to each other, wherein the first opening is the output port of the medication; a spacer arranged in the container between the two openings which can slide freely along the wall of the container; and the electrochemical pump disposed on the second opening, and the electrochemical pump and the container are tightly combined to seal the second opening.

Description

Electrochemical pump for drug delivery and drug delivery device thereof

The present disclosure relates to an electrochemical pump and a drug delivery device thereof, which are used for automatically delivering drugs.

Recently, in the pharmaceutical industry, the use of electrochemical pumps for the delivery of therapeutic drugs has been considered an area that can be further developed and improved. However, the design of electrochemical pumps used for the delivery of therapeutic drugs has defects that need to be improved. For example, the high impedance and low local electric field of the electrolyte in electrochemical pumps using microelectrode structures cause high power loss; and the lower solid free energy of the electrode surface, both of which cause high power consumption of the overall pump system.

In addition, the electrodes and contact plates of traditional electrochemical pumps are usually located on the same side of the substrate, which causes the connection structure materials between the control circuit board and the electrode to be inevitably corroded by the electrochemical electrolyte during the electrochemical reaction, seriously affecting the operation and energy consumption performance of the entire electrochemical pump system.

The actuation mechanism of electrochemical drug delivery medical devices mainly uses the pressure of generated gas as the driving power source, for example: using the pressure difference between the inside of the drug delivery device and the surrounding environment of the device to deliver the drug. However, accurate control of the pressure amplitude generated in the device requires advanced device structure (mechanical) design and electronic control device design. The incorrect design of the above structure and electronic control system may make it difficult to accurately control the amount of gas generated to achieve the purpose of accurately controlling a small amount of drugs and stabilizing the drug delivery speed.

In addition, when the drug delivery device is required to output an ultra-high flow rate to drive high-viscosity drugs, the power output of the electrochemical device needs to be increased accordingly so that it has the ability to output ultra-large driving force. Therefore, the circuit board and power supply must also have the ability to output ultra-high output energy. For the same-side structural design between the contact plate and the electrode, the lead part (Lead) between the contact plate and the electrode greatly increases the overall resistance impedance, which seriously affects the energy loss from the power supply to the electrodes, thereby greatly reducing the pressure power output performance of the overall electrochemical pump system.

In addition, when a large volume (such as several milliliters) of high-concentration drugs need to be delivered by subcutaneous or intramuscular injection, in order to avoid the problem of pain caused by too fast injection speed, a gentler injection speed and a slightly longer injection time are required. If manual injection delivery is used, it will not only consume manpower, but also be difficult to accurately control the drug delivery rate to avoid the above-mentioned pain problem. Currently, the automatic delivery devices on the market mostly use mechanical force (such as springs) or micro motors as the source of driving power, but the unstable driving force caused by springs or micro motors may cause unexpected pain during the injection process, and it is difficult to achieve a fast and stable delivery speed at the same time.

Therefore, there is an urgent need to improve and solve the above problems in this field, and to develop an electrochemical pump structure that will not cause corrosion due to the electrodes and the conductor plate being located on the same side, while reducing impedance to increase the efficiency of large energy transmission, increasing the control accuracy of energy transmission to reduce pain, and having a small-sized actuation drug delivery device or method.

To achieve the purpose of the invention, the present disclosure provides an electrochemical pump for drug delivery and a drug delivery device thereof. The electrochemical pump includes: a substrate having a first surface, a second surface, and a plurality of through holes, wherein the second surface has a plurality of contacts, the through holes have conductive materials and are electrically connected to the plurality of contacts; a plurality of electrodes are disposed on the first surface and are electrically connected to the plurality of contacts on the second surface through the conductive materials in the plurality of through holes; an electronic device is disposed on the second surface and is electrically connected to the contacts on the second surface; and a space for containing electrolyte, wherein the electrolyte is contained and adjacent to the first surface, so that the plurality of electrodes are in contact with the electrolyte.

In one embodiment, the electrodes at least include an anode and a cathode, wherein the electrodes further include a reference electrode, and wherein the electrodes further include a redundant electrode.

In one embodiment, any one of the electrodes is electrically connected to a plurality of contacts through a plurality of through holes.

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

In one embodiment, the space for accommodating the electrolyte is formed by attaching a superabsorbent material to the first surface.

In one embodiment, the superabsorbent material is a sponge.

In one embodiment, the superabsorbent 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 polymer fiber products made from the aforementioned materials.

In one embodiment, the space for containing electrolyte is formed by attaching a breathable membrane to the first surface, wherein the space for containing electrolyte is sealed by the breathable membrane.

In one embodiment, the electronic device includes: a circuit board; an input port; and an output port.

In one embodiment, the output port electrically connects the circuit board to the electrochemical pump substrate, and one end of the input port is electrically connected to the circuit board, and the other end is an input port for power.

In one embodiment, the electronic device further includes a driving circuit component.

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

In one embodiment, the output port electrically connects the circuit board to the contacts, the power source is electrically connected to the circuit board via the input port, and the drive circuit component is electrically connected to the circuit board and on the other hand electrically connected to the power source.

In one embodiment, the electronic device is detachable.

On the other hand, the present disclosure provides a drug delivery device, comprising: a container for accommodating a drug, having a first opening and a second opening opposite to each other, wherein the first opening is an outlet for the drug; a spacer disposed inside the container between the two openings and capable of sliding freely along the container wall; and an electrochemical pump disposed at the second opening, so that the electrochemical pump is tightly combined with the container to seal the second opening.

In one embodiment, the container is a syringe, which may further include an injection needle disposed at the first opening.

In one embodiment, the container is transparent or translucent.

In one embodiment, the container is rigid or flexible.

In one embodiment, the spacer is formed by a rubber plug.

All technical and scientific terms described in this specification and the scope of patent application, unless otherwise defined, are definitions that can be known to those with ordinary knowledge in the technical field to which the present invention belongs. The singular terms "one", "an", "the", or similar terms, unless otherwise specified, can refer to more than one object. "Or", "and", "and" used in this specification, unless otherwise specified, all refer to "or/and". In addition, the terms "include" and "include" are open conjunctions without restrictions. The above definitions only illustrate the references of the term definitions and should not be interpreted as limitations on the subject matter of the invention. Unless otherwise specified, the materials used in the present invention are all commercially available and easily available.

The ordinal numbers mentioned in the specification and claims, such as "first", "second", etc., are only used to describe the disclosed elements, and do not refer to or indicate any execution order between the elements, nor do they refer to or indicate the order between one element and another element, or the order of steps in a process. These ordinal numbers are only used to make a component with a certain name clearly distinguishable from another component with the same name.

In addition, the terms “on”, “above”, “above”, or similar terms used in this specification refer to a component being in direct contact with another component (such as a substrate), but also refer to a component being in non-direct contact with another component (such as a substrate).

Embodiment

As shown in FIG. 1 , the present disclosure provides an electrochemical pump 10 , which includes: a substrate 101 ; a space 102 for containing an electrolyte; a plurality of electrodes 103 ; and an electronic device 104 .

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 arranged on one side of the through holes 1013 located on the second surface 1012, and the conductive materials 1014 are arranged in the through holes 1013, so that the components on the first surface 1011 and the components on the second surface 1012 can be electrically connected. The space 102 for accommodating electrolyte is arranged on the first surface 1011, and contains electrolyte 1021. The electrodes 103 are arranged on the first surface 1011, and are in direct contact with the electrolyte 1021, and are electrically connected to the conductive material 1014 in the through holes 1013. The electronic device 104 is disposed on the second surface 1012 and is electrically connected to the contacts 1015 .

In the present disclosure, the two sides of the through hole 1013 can be electrically connected by filling the through hole 1013 with a conductive material, coating the through hole wall with a conductive material layer, or inserting a wire, but the technical means should not be limited to this. In the present disclosure, the through holes 1013 and the conductive material 1014 therein can be completed by using the feedthrough technology widely used in the complementary metal oxide semiconductor (CMOS) process and integrated circuit (IC) packaging technology, thereby achieving a complete separation of the "wet" structure (i.e., various structures on the first surface, which are in direct contact with the electrolyte) and the "dry" structure (i.e., various structures on the second surface that are in direct contact with the surface, such as electronic devices), avoiding direct contact between the electrolyte and the electronic device, so as to enhance the reliability of the overall device.

In one embodiment, the contacts 1015 are a plurality of contact pads.

In the present disclosure, the electrolyte space 102 is formed by attaching a superabsorbent material to the first surface, or attaching a breathable film to the first surface. In a specific embodiment, the electrolyte space 102 is a superabsorbent material coated on the first surface 1011, and the electrolyte 1021 is made into a gel state to keep the electrodes 103 in contact with the electrolyte 1021, and to prevent the electrolyte from leaking, and to allow the generated gas to leave the electrolyte space 102; the electrolyte 1021 is a solution that can generate gas through the electrode, such as water or an electrolyte solution, but should not be limited thereto.

In a preferred embodiment, the superabsorbent material is a sponge. In another specific embodiment, the superabsorbent material is attached to the surface of the electrodes 103, and the superabsorbent 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).

In a preferred embodiment, the number of the electrodes 103 is not less than 3. More specifically, two of the electrodes 103 are used as anodes and cathodes. For better electrochemical performance, the anodes and cathodes are arranged in a staggered comb electrode structure, and the other electrode is a reference electrode to avoid voltage decay, such as the ohmic voltage generated by the flow of current in dilute acid, saline plasma electrolyte. Voltage decay may affect the accuracy of drug delivery, so it must be avoided to obtain accurate potential measurement. If a fourth electrode or more electrodes are provided, the remaining electrodes are redundant electrodes. The redundant electrodes can avoid the inconvenience of repairing an electrode when it fails suddenly.

To improve electrochemical efficiency, any electrode 103 can be electrically connected to the electronic device 104 through a plurality of through holes 1013. In a preferred embodiment, the anode and the cathode each have 20 through holes. Figures 3 and 4 show the comparison of the electrochemical efficiency of the electrode with other designs, where the design with 20 through holes in the anode and cathode (the electrode and the contact pad are on opposite sides, with 40 through holes) increases the flow rate and the total delivery volume by about 30% compared to the electrode without through holes (the electrode and the contact pad are on the same side); compared to the design with only one through hole in the cathode and anode (the electrode and the contact pad are on opposite sides, with 2 through holes), the flow rate and the total delivery volume also increase by about 20%.

The first surface 1011 and the electrodes 103 may be coated with a hydrophilic layer to improve electrochemical efficiency. The coating materials include but are not limited to: polyvinyl phenol (PVP), polyacrylic acid (PAA), polyethylene oxide (PEO), polysaccharides, proton exchange membranes (such as sulfonated tetrafluoroethylene (Nafion)), nanostructured metals, epoxy resins, and polymer fiber products made from the aforementioned materials.

The coated hydrophilic layer is used to ensure that the first surface 1011 of the electrochemical pump 10 has hydrophilicity, and can continuously generate gas during the electrochemical reaction. Compared with the conventional untreated electrode, the coated electrode can provide better gas solubility.

In order to further enhance the electrochemical efficiency, it is effective to change the geometry of the electrode. In some specific embodiments, the inverted trapezoidal electrode is made by a modified standard electron beam lithography or modified photolithography process with modified oxygen plasma treatment, modified reactive ion etching (RIE), modified deep reactive ion etching (DRIE) or modified inductively coupled plasma (ICP). On the other hand, the electrochemical efficiency can be enhanced by changing the shape of the electrode. In one specific embodiment, the electrode 103 is made into an inverted trapezoidal shape to generate a strong electric field and cause a larger amount of gas to be generated. In another specific embodiment, the hydrophilicity of the electrochemical pump 10 can be achieved by hydrophilic treatment, such as oxygen plasma treatment, chemical etching and mechanical friction.

The electronic device 104 is electrically connected to the contacts 1015 to provide power to the electrodes 103 and control the time and power of the electrochemical reaction. In a preferred embodiment, the electronic device 104 is configured to be detachable and can be assembled and separated from the other components of the electrochemical pump 10.

In a specific embodiment, the electronic device 104 includes: a circuit board 1041; an input port 1042; and an output port 1043.

The output port 1043 electrically connects the circuit board 1041 to the contact 1015 to control the electrodes 103 and further control the electrochemical pump 10 to generate gas. One end of the input port 1042 is electrically connected to the circuit board 1041, and the other end is the input port of the power source, which can be electrically connected to a power source to provide power to the electrochemical pump 10. The power source can be an external power source or included in the electronic device 104.

In one embodiment, the electronic device 104 further includes a power source 1044 , which is electrically connected to the input port 1042 .

In a preferred embodiment, the electronic device 104 further includes a driving circuit component to control the switch of the electronic device 104.

Accordingly, the output port 1043 serves as a bridge between the electronic devices 104 and the remaining components of the electrochemical pump 10. The output port 1043 may be a micro connector, such as a pogo pin.

As shown in FIG. 2 , the present disclosure provides a drug delivery device 200, comprising: a container, which is a syringe 20; and the electrochemical pump 10.

The syringe 20 has a first opening 21, a second opening 22, and a spacer 23. The first opening 21 and the second opening 22 are opposite to each other.

In a preferred embodiment, the syringe 20 further has an injection needle 24, which is disposed at the first opening 21.

In one embodiment, the drug delivery device 200 is small enough to deliver trace amounts of drugs, wherein the volume of the syringe 20 is preferably in the microliter range (0.1-500 microliter).

In another embodiment, the drug delivery device 200 can deliver high-concentration, large-volume drugs, wherein the volume of the syringe 20 is preferably in the milliliter (mL) range (0.1-500mL).

According to the embodiment disclosed herein, the partition 23 is disposed in the syringe 20 and divides the syringe 20 into a first chamber 201 and a second chamber 202. The first chamber 201 is used to contain the drug, and the second chamber 202 is used to contain the electrolyte space 102 of the electrochemical pump and the electrolyte 1021 therein.

According to an embodiment of the present disclosure, the container may be a syringe 20, made of a transparent or translucent material, and the container, such as a syringe, may be rigid or flexible. Preferably, the syringe 20 is made of a rigid material, including but not limited to: glass (such as quartz, fused silica, alkali lime, silicate and borosilicate), polymer/plastic (such as polycarbonate (PC), polymethyl methacrylate (PMMA), polypropylene (PP), polyethylene (PE), ethylene terephthalate (PET), polylactic acid (PLA), thermoplastic elastomer (TPE) and polyparaxylene, C Cyclic olefin polymers of OP or COC), rubbers (natural rubber and rubber), colloids (epoxy resins, silicones and acrylic resins) and conductive polymers (polyfluorene, polybiphenyl compounds, polypyrene, polyazulene, polynaphthalene, polypyrrole (PPY), polyaniline (PANI), polythiophene (PT), poly(3,4-ethylenedioxythiophene) (PEDOT), polyp-phenylene sulfide (PPS), polyacetylene (PAC) and polystyrene (PPV)).

In this embodiment, the spacer 23 is a diaphragm. The diaphragm can be made of materials such as thermoplastic elastomer (TPE), styrene-ethylene-butylene-styrene block copolymer (SEBS), styrene-ethylene-propylene-styrene block copolymer (SEPS), and polyparaxylene, but the present disclosure is not limited thereto. However, in another embodiment, the spacer 23 can also be a blocking member, which is made of a rubber plug. The rubber plug can be made of materials such as rubber, polytetrafluoroethylene (Teflon), silicone, thermoplastic elastomer (TPE), styrene-ethylene-butylene-styrene block copolymer (SEBS), styrene-ethylene-propylene-styrene block copolymer (SEPS), and polyparaxylene.

In the present disclosure, the electrochemical pump 10 is disposed at the second opening 22 of the syringe, and the electrochemical pump 10 is tightly combined with the syringe 20 to seal the second opening 22, so as to prevent the electrolyte 1021 contained therein and the gas generated by the operation of the electrochemical pump 10 from leaking out. Therefore, if the electrolyte 1021 is subjected to an electrochemical reaction and generates gas, the pressure of the second chamber 202 will be higher than the pressure of the first chamber 201, and the partition 23 will be pushed toward the first opening 21, thereby outputting the agent. Therefore, the partition 23 must be disposed to isolate the first chamber 201 and the second chamber 202 from each other to prevent the electrolyte and the agent from mixing. The sealing method includes, but is not limited to, using a gasket (such as an O-ring), sealing using an adhesive, or sealing using welding (such as ultrasonic, heat, or laser welding).

In one embodiment, after the second opening 22 is sealed, the electrochemical pump 10 is detachable.

In another embodiment, after the second opening 22 is sealed, the electrochemical pump 10 is non-detachable.

In the contents disclosed in the embodiments of this specification, it is obvious to those with ordinary knowledge in the field to which the present invention belongs that the aforementioned embodiments are only illustrative and not restrictive; those with ordinary knowledge in the technical field to which the present invention belongs can implement the present invention through many changes and substitutions, which do not differ from the technical features of the present invention. According to the embodiments of the specification, the present invention can be implemented in many ways without hindering its implementation. The claims provided in this specification define the scope of the present invention, which covers the aforementioned methods and structures and inventions equivalent thereto.

10: electrochemical pump 101: substrate 1011: first surface 1012: second surface 1013: through hole 1014: conductive material 1015: contact 102: space for electrolyte 1021: electrolyte 103: electrode 104: electronic device 1041: circuit board 1042: input port 1043: output port 1044: power supply 200: drug delivery device 20: syringe 201: first chamber 202: second chamber 21: first opening 22: second opening 23: spacer 24: injection needle

FIG. 1 is a schematic diagram of the electrochemical pump structure of the present disclosure.

FIG. 2 is a cross-sectional view of the drug delivery device disclosed herein.

FIG. 3 is a graph showing the relationship between the electrochemical pump flow rate and the number of through holes.

FIG. 4 is a graph showing the relationship between the total electrochemical pump delivery volume and the number of through holes.

without

10:Electrochemical pump

101: Substrate

1011: First surface

1012: Second surface

1013:Through hole

1014: Conductive materials

1015: Contact

102: Space for electrolyte

1021:Electrolyte

103:Electrode

104: Electronic devices

1041: Circuit board

1042: Input port

1043: output port

1044: Power supply

Claims (21)

An electrochemical pump includes: a substrate having a first surface, a second surface and a plurality of through holes, wherein the second surface has a plurality of contacts, and the through holes have a conductive material and are electrically connected to the plurality of contacts; a plurality of electrodes, disposed on the first surface and electrically connected to the plurality of contacts on the second surface through the conductive material in the plurality of through holes; an electronic device, disposed on the second surface and electrically connected to the contacts on the second surface; and a space for containing electrolyte, wherein the electrolyte is contained and adjacent to the first surface, so that the plurality of electrodes are in contact with the electrolyte. An electrochemical pump as described in claim 1, wherein the electrodes include at least an anode and a cathode. An electrochemical pump as described in claim 2, wherein the electrodes further include a reference electrode. An electrochemical pump as described in claim 2, wherein the electrodes further include a redundant electrode. An electrochemical pump as described in claim 1, wherein any of the electrodes is electrically connected to a plurality of contacts through a plurality of through holes. An electrochemical pump as described in claim 1, wherein the first surface is coated with a hydrophilic layer. An electrochemical pump as described in claim 1, wherein the space for containing the electrolyte is formed by attaching a superabsorbent material to the first surface. An electrochemical pump as described in claim 7, wherein the superabsorbent material is a sponge. An electrochemical pump as described in claim 7, wherein the superabsorbent 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 polymer fiber products made from the aforementioned materials. An electrochemical pump as described in claim 1, wherein the space for containing electrolyte is formed by attaching a breathable membrane to the first surface, wherein the space for containing electrolyte is sealed by the breathable membrane. An electrochemical pump as described in claim 1, wherein the electronic device includes: a circuit board; an input port; and an output port. An electrochemical pump as described in claim 11, wherein the electronic device further includes a driving circuit component. An electrochemical pump as described in claim 12, wherein the electronic device includes a power source. An electrochemical pump as described in claim 13, wherein the output port electrically connects the circuit board to the contacts, the power source is electrically connected to the circuit board via the input port, and the drive circuit component is electrically connected to the circuit board and on the other hand electrically connected to the power source. An electrochemical pump as described in claim 1, wherein the electronic device is detachable. A drug delivery device, comprising: a container for containing a drug, having a first opening and a second opening opposite to each other, wherein the first opening is an outlet for the drug; a spacer, disposed inside the container between the two openings, and capable of sliding freely along the container wall; and an electrochemical pump as described in claim 1, disposed at the second opening, so that the electrochemical pump is tightly combined with the container to seal the second opening. A device as described in claim 16, wherein the container is a syringe. As described in claim 17, the syringe includes a needle disposed in the first opening. A device as described in claim 16, wherein the container is transparent or translucent. A device as described in claim 16, wherein the container is rigid or flexible. A device as described in claim 16, wherein the spacer is formed by a rubber plug.