Drug liquid transport device

Abstract

A drug liquid transport device (1) according to the present invention comprises: a drive liquid accommodation unit (11) that accommodates a drive liquid (13); a transport liquid accommodation unit (12) that accommodates a drug liquid (18); an electroosmotic flow pump (14) that transports the drive liquid between the drive liquid accommodation unit and the transport liquid accommodation unit; and a needle for injecting the drug liquid supplied from the transport liquid accommodation unit (12) into the skin. The transport liquid accommodation unit (12) comprises: a first chamber that accommodates the drug liquid and that is connected to a needle hole of the needle; and a second chamber that accommodates the drive liquid and is separated from the first chamber by a diaphragm. The drug liquid transport device is configured such that the electroosmotic flow pump transports the drive liquid from the drive liquid accommodation unit to the second chamber to change the capacity of the first chamber, whereby the drug liquid (18) is injected into the skin.

Description

Drug Delivery Device

[0001] The present invention relates to a drug solution transport device for transdermal administration of a drug solution.

[0002] The main methods of drug administration currently used in medical settings are oral administration and injection. Furthermore, because oral administration requires absorption of drug solutions through the digestive tract, it is not possible to use medium- to high-molecular-weight drug solutions that are easily degraded in the digestive tract. Injection administration has drawbacks such as the risk of pain from the injection needle and hardening of the injection site, the need for a long needle that can incite fear in users, and the need for a doctor's intervention for administration. For these reasons, transdermal administration has attracted attention as a third administration method. Transdermal administration has the advantage that drugs are less likely to be degraded because they do not pass through the digestive tract, and it avoids the risk of injury and fear caused by injection needles.

[0003] However, when administered transdermally, the body's inherent skin barrier function (the ability to prevent the entry of foreign substances from the body) makes it difficult for drug solutions to penetrate, and there are currently few transdermal absorption formulations in practical use around the world. The skin is composed of the epidermis and dermis, and the epidermis contains a stratum corneum that is approximately 10 to 20 μm thick. This stratum corneum is the largest barrier preventing the entry of foreign substances from the outside, making transdermal absorption of medium to large molecular weight drugs difficult.

[0004] Various approaches have been adopted commercially to penetrate the stratum corneum and promote the absorption of medicinal solutions. For example, Patent Document 1 (Patent Document 1) focuses on a method called iontophoresis, which uses an electric field to promote transdermal absorption by utilizing the electrical repulsion and attraction of electrodes. In iontophoresis, the amount of medicinal solution permeation is proportional to the value of the current. On the other hand, if the current amount is greater than 400 μA, burns may occur due to heat caused by skin resistance. Furthermore, in general, in iontophoresis, the amount of permeation is affected by the pH and ionic strength of the solution, the concentration of the medicinal solution, the positive and negative charges upon ionization, and the presence of competing ions, which limits the medicinal solutions that can be administered.

[0005] Patent Document 2 discloses a device that uses a driving means such as a spring to move a piston and inject a drug solution from a cartridge. Devices that inject drug solutions into the body in a short period of time can rapidly increase the drug concentration in the blood, making them susceptible to side effects. Therefore, devices that continuously inject drug solutions over a long period of time have attracted attention. Furthermore, in recent years, technology has been gaining attention for acquiring biological information using wearable devices and administering the optimal amount of medication at the optimal time based on the results. This has created a demand for drug solution delivery devices that can precisely control the delivery speed and turn the delivery on and off.

[0006] JP 2009-34118, JP 2016-523115, JP 2019-170690

[0007] Patent Document 3 proposes a microneedle continuous injection device that uses a microneedle that pierces the stratum corneum using a very short needle of 200 μm to 800 μm that penetrates the stratum corneum of the skin and a drug solution transport pump that transports a drug solution using the elastic biasing force of a coil spring, etc. Such a device enables continuous injection of a drug solution over a long period of time, but does not achieve precise control of the liquid delivery rate or ON / OFF control during drug delivery. Patent Document 3 also suggests using an electroosmotic flow pump as the pump, but electroosmotic flow pumps typically apply a voltage of 10 V or more, and applying a high voltage to the drug solution may cause decomposition of the drug solution.

[0008] The present invention aims to provide a drug solution transport device that allows for the transport of drug solutions without any restrictions on the drug solutions that can be administered, without the risk of burns or other injuries, and that allows for precise speed control and ON / OFF control of drug solution transport.

[0009] In order to solve the above problems, the drug solution transport device of the present invention comprises a driving solution containing unit that contains a driving solution, a transport solution containing unit that contains a drug solution or subcutaneous interstitial fluid, an electroosmotic flow pump that transports the driving solution between the driving solution containing unit and the transport solution containing unit, a needle for injecting the drug solution supplied from the transport solution containing unit into the skin or for storing the subcutaneous interstitial fluid collected from the skin in the transport solution containing unit, a power source that supplies voltage to the electroosmotic flow pump, a switch installed between the power source and the electroosmotic flow pump, and a control circuit that controls the switch. and a control unit that controls the transport of the driving liquid by the electroosmotic flow pump, wherein the transport liquid storage unit includes a first chamber that stores the drug solution or subcutaneous interstitial fluid and is in communication with the needle hole of the needle, and a second chamber that stores the driving liquid and is separated from the first chamber by a diaphragm, and the electroosmotic flow pump is configured to change the volume of the first chamber by transporting the driving liquid from the driving liquid storage unit to the second chamber or by transporting the driving liquid from the second chamber to the driving liquid storage unit.

[0010] In order to achieve the above object, the drug solution transport device of the present invention comprises a driving liquid storage unit that stores a driving liquid, a plurality of transport liquid storage units that store a drug solution or subcutaneous interstitial fluid, a first electroosmotic flow pump connected between a first transport liquid storage unit of the plurality of transport liquid storage units and the driving liquid storage unit, a second electroosmotic flow pump connected between a second transport liquid storage unit of the plurality of transport liquid storage units and the driving liquid storage unit, a needle for injecting the drug solution supplied from the first transport liquid storage unit into the skin or for storing the subcutaneous interstitial fluid collected from the skin in the second transport liquid storage unit, a power source that supplies voltage to the first electroosmotic flow pump and the second electroosmotic flow pump, and a power supply that supplies voltage to the first electroosmotic flow pump and the second electroosmotic flow pump. The device further comprises a switch disposed between the first and second electroosmotic pumps, and a control unit that controls the switch to control the transport of the drive liquid by the first and second electroosmotic pumps, wherein the first transport liquid storage unit and the second transport liquid storage unit each include a first chamber that stores the drug solution or subcutaneous interstitial fluid and is in communication with the needle hole of the needle, and a second chamber that stores the drive liquid and is separated from the first chamber by a diaphragm, and the first and second electroosmotic pumps are configured to change the volume of the first chamber by transporting the drive liquid from the drive liquid storage unit to the second chamber or by transporting the drive liquid from the second chamber to the drive liquid storage unit.

[0011] In order to solve the above problems, the drug solution transport device of the present invention comprises a plurality of transport solution storage units that store a drug solution or subcutaneous interstitial fluid and a driving solution; an electroosmotic flow pump connected between a first transport solution storage unit and a second transport solution storage unit of the plurality of transport solution storage units; a first needle for injecting the drug solution supplied from the first transport solution storage unit into the skin; a second needle for storing the subcutaneous interstitial fluid collected from the skin in the second transport solution storage unit; a power source that supplies voltage to the electroosmotic flow pump; a switch installed between the power source and the electroosmotic flow pump; and a device that controls the switch to control the transport of the driving solution by the electroosmotic flow pump. the first transport liquid containing unit includes a first chamber containing the drug solution and communicating with the needle hole of the needle, and a second chamber containing the driving liquid separated from the first chamber by a diaphragm; the second transport liquid containing unit includes a third chamber containing the subcutaneous interstitial fluid and communicating with the needle hole of the needle, and a fourth chamber containing the driving liquid separated from the third chamber by a diaphragm; and the electroosmotic pump is configured to transport the driving liquid from the fourth chamber to the second chamber, thereby changing the volumes of the first chamber and the second chamber.

[0012] According to the present invention, it is possible to provide a drug solution transport device that enables drug solution transport without any restrictions on the drug solution that can be administered, without the risk of injury such as burns, and that allows precise speed control of drug solution transport and ON / OFF control.

[0013] Fig. 1 is a side view showing a configuration example of a liquid drug transport device according to a first embodiment of the present invention. Fig. 2 is a side view showing a configuration example of a liquid drug transport device according to a second embodiment of the present invention. Fig. 3 is a side view showing a configuration example of a liquid drug transport device according to a third embodiment of the present invention. Fig. 4 is a side view showing a configuration example of a liquid drug transport device according to a fourth embodiment of the present invention. Fig. 5 is a side view showing a configuration example of a liquid drug transport device according to a fifth embodiment of the present invention. Fig. 6 is a configuration example of a computer constituting a control unit that controls liquid drug transport according to the embodiments of the present invention.

[0014] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described in detail below with reference to the accompanying drawings. The present invention can be implemented in various embodiments and is not limited to the embodiments described below.

[0015] 1 is a side view showing an example of the configuration of a drug solution transport device according to Embodiment 1. The drug solution transport device 1 includes a transport solution storage unit 12 that stores a transport solution such as a drug solution 18, a driving solution storage unit 11 that stores a driving solution 13, an electroosmotic flow pump 14 that uses an electroosmotic flow generated in the driving solution 13 to pump the driving solution 13, a drug solution transport device main body 10 that includes at least one microneedle (15-1 to 15-4), a power supply 20 that supplies a voltage to the electroosmotic flow pump 14, and a switch 30 that is disposed between the power supply 20 and the electroosmotic flow pump 14 and switches the voltage supplied from the power supply 20 to the electroosmotic flow pump 14 between ON and OFF.

[0016] The drug solution transport device 1 includes a control unit 40 that controls the operation of the switch 30. The control unit 40 controls the value of the voltage supplied from the power supply 20 to the electroosmotic flow pump 14, and controls the ON / OFF state of the switch 30 disposed between the power supply 20 and the electroosmotic flow pump 14, thereby switching the drug solution transport ON / OFF. In FIG. 1 , the power supply 20, the switch 30, and the control unit 40 are installed outside the main body 10 of the drug solution transport device 1, but they may also be configured to be provided inside the main body 10 of the drug solution transport device 1.

[0017] The transport liquid containing unit 12 is filled with a medicinal liquid 18. An isolation diaphragm 16 is installed inside the transport liquid containing unit 12 to isolate the medicinal liquid 18 from the driving liquid 13. The isolation diaphragm 16 provides a chamber (first chamber) that contains the medicinal liquid 18 and a chamber (second chamber) that contains the driving liquid 13 inside the transport liquid containing unit 12. The chamber that contains the medicinal liquid 18 is connected to the needle holes (17-1 to 17-4) of the microneedles (15-1 to 15-4).

[0018] In this embodiment, the electroosmotic pump 14 moves the driving liquid 13 between the driving liquid storage unit 11 and the transport liquid storage unit 12, thereby changing the volume of the chamber that stores the drug solution 18 and the chamber that stores the driving liquid 13, and thereby injecting the drug solution 18 supplied from the transport liquid storage unit 12 into the skin.

[0019] (1-2) Operation of Drug Transport Device When a drug solution is injected into the skin using drug solution transport device 1, microneedles (15-1 to 15-4) are inserted into the skin. When power supply 20 applies a voltage to electroosmotic flow pump 14 with a polarity such that driving liquid accommodating unit 11 has a positive potential relative to transport liquid accommodating unit 12, electroosmotic flow pump 14 begins to pump driving liquid 13 from driving liquid accommodating unit 11 to transport liquid accommodating unit 12.

[0020] When the driving liquid is transferred from the driving liquid storage unit 11 to the transport liquid storage unit 12, the internal pressure of the chamber storing the driving liquid 13 of the transport liquid storage unit 12 increases, the isolation diaphragm 16 is crushed, and the medicinal liquid 18 filled in the chamber storing the medicinal liquid 18 of the transport liquid storage unit 12 is transported into the skin through the needle holes (17-1 to 17-4) of the microneedles (15-1 to 15-4).

[0021] (1-3) Advantages of the First Embodiment According to the first embodiment, by using an electroosmotic flow pump 14 that applies a voltage only to the driving liquid 13, no voltage is applied directly to the skin, thereby enabling drug solution transport without the risk of burns or other injuries. Furthermore, by controlling the voltage supplied to the electroosmotic flow pump 14 and switching the drug solution transport ON / OFF with the switch 30, precise control of the liquid transport speed and ON / OFF control of the drug solution transport are possible. Furthermore, by applying a voltage to the driving liquid 13 without applying a voltage directly to the drug solution 18 and transporting the drug solution using the electroosmotic flow generated in the driving liquid 13, drug solution transport with no limitations on the drug solution that can be administered is possible.

[0022] (1-4) Microneedles The drug solution 18 is delivered into the skin through the needle holes (17-1 to 17-4) of the microneedles (15-1 to 15-4). Hollow or porous microneedles can be used as the microneedles (15-1 to 15-4). Any material usable in the medical field can be used as the material for the microneedles (15-1 to 15-4). Materials that are highly biosafe are preferred as the material for the microneedles (15-1 to 15-4), and materials that are prone to break when pierced and remain in the skin are not preferred. For example, hydrogel materials, resins, oxides, metals, biodegradable materials, etc. can be used.

[0023] Here, the hydrogel material refers to a material that forms a hydrogel when dispersed in water (dispersion medium). Examples of hydrogel materials include agarose, acrylamide crosslinkers, gum arabic, alkyl-modified carboxyvinyl polymers, curdlan, casein, carrageenan, galactan, karaya gum, carboxyvinyl polymers, agar, xanthan gum, chitosan, guar gum, quince seed, glucomannan, collagen, chondroitin sulfates such as sodium chondroitin sulfate, gellan gum, silicone, sclerotium gum, gelatin, cellulose gum, tamarind gum, dextrin, starch, tragacanth gum, hyaluronic acid (mucopolysaccharides) and hyaluronates such as sodium hyaluronate, fibrin, pectin, peptides, poly(N-isopropylacrylamide), crosslinkers of poly(methyl vinyl ether-alt-maleic anhydride) and polyethylene glycol, poly 2-acrylamido-2-methylpropanesulfonic acid, Examples of suitable polymers include poly(2-hydroxyethyl methacrylate), polyacrylamide, polyalkylene oxide resins, polyethylene glycol, polyethylene glycol crosslinkers, polystyrene sulfonic acid, polyhydroxyethyl methacrylate, polyvinyl alcohol, polyvinylpyrrolidone, mannan, maleic anhydride copolymers, locust bean gum, and crosslinked starch-acrylate graft copolymers; interpenetrating network hydrogels and semi-interpenetrating network hydrogels; and N-vinylacetamide crosslinkers. Examples of suitable metals include aluminum, gold, silver, brass, tin, iron, copper, nickel, magnesium, and alloys thereof. Examples of suitable resins include acrylic resins, acrylonitrile-butadiene-styrene (ABS) resins, phenolic resins, polyalkylene oxide resins, and methacrylic resins (such as polyglycidyl methacrylate resins). Examples of oxides include zinc oxide, aluminum oxide, silicon oxide, zirconia oxide, tin oxide, tungsten oxide, tantalum oxide, titanium oxide, niobium oxide, hafnium oxide, and derivatives thereof.Examples of biodegradable materials include β-tricalcium phosphate, hydroxyapatite, polyethylene glycol, polycaprolactone, polydioxanone, polylactic acid-glycol copolymer (PLGA), and mixed materials mainly containing PLGA. The microneedles (15-1 to 15-4) may be made of a mixture of two or more of the above-mentioned materials.

[0024] The microneedles (15-1 to 15-4) are erected on the main body 10, and it is sufficient that at least one is installed. The length of the microneedles (15-1 to 15-4) is preferably, for example, 0.2 mm to 3.0 mm. When multiple microneedles (15-1 to 15-4) are installed, they may be installed at uniform intervals or may be arranged sparsely and densely. Furthermore, there may be areas where no microneedles (15-1 to 15-4) are present.

[0025] (1-4) Electroosmotic Flow Pump The electroosmotic flow pump 14 is a pump that pumps a chemical solution using an electroosmotic flow generated in the driving liquid 13. The electroosmotic flow pump 14 can be made of any solid material. Porous ceramics are preferred as the material for the electroosmotic flow pump 14. Examples include alumina, silica, zirconia, BaTiO3, TiO2, or mixtures thereof.

[0026] The operating principle of the electroosmotic pump 14 will now be explained. In an electrolyte, solid surfaces are generally negatively charged. Cations in the electrolyte solution are attracted to the negatively charged solid surfaces inside the electroosmotic pump 14, forming an electric double layer at the interface between the inner wall surface of the electroosmotic pump 14 and the electrolyte solution.

[0027] In this state, when a voltage is applied across the electroosmotic pump 14, the cations that were attracted to the solid surface inside the electroosmotic pump 14 are attracted to the side with the lower voltage. This flow of cations causes an osmotic flow in which the entire electrolyte flows toward the cathode. The speed of the osmotic flow can be increased by increasing the applied voltage. The direction of the osmotic flow can be changed by changing the polarity of the applied voltage.

[0028] (1-5) Driving Liquid The driving liquid 13 is used as an electrolyte for the electroosmotic pump 14. Any electrically conductive liquid can be used as the driving liquid 13. For example, water, methanol, or ethanol can be used.

[0029] (1-6) Drug The drug to be dissolved in the drug solution 18 may be any drug that can be effectively administered by subcutaneous injection. For example, therapeutic agents include agalsidase-β, adalimumab, adenosine deaminase, adrenaline, anakinra, anistreplase, abatacept, abciximab, aripiprazole, alglucosidase-α, aldesleukin, alteplase, alefacept, alemtuzumab, angiotensin II diuretic hormone agonist, antithrombin III, idursulfase, ibritumomab tiuxetan, insulin, insultropin, interleukin-1, and the like. -feron α, interferon β, interferon Y, interleukin, interleukin-10 (IL-10), urokinase, exenatide, estrogen, etanercept, ethinyl estradiol, etonogestrel, epinephrine, efalisman, epoprostenol, erythropoietin, enkephalin, ondansetron hydrochloride, methadone hydrochloride, endorphin, enfluvirtide, luteinizing hormone-releasing hormone, oxytocin, octreotide Tide, oprelvekin, omacetaxine mepesuxinate, omalizumab, olanzapine, pituitary hormones (HGH, HMG, desmopressin acetate, etc.), granular macrukagon, calcitonin, glucagon-like peptide-1 (GLP-1), granular macrukagon, calcitonin, calcitonin gene-related peptide (CGRP), galsulfase, estradiol valerate, chymopapain, recombinant human bone morphogenetic protein 7, glycopyrrolate, glucagon-like peptide-1 (GLP-1), GLP-1), platelet-derived growth factor-releasing factor, gemtuzumab ozogamicin, antithymocyte globulin, collagenase, corticotropin, cholecystokinin, colony-stimulating factors, thyrotropin alpha, histrelin acetate, pramlintide acetate, salmon calcitonin, sargramostim, digoxin immune serum Fab (sheep), divotermin-α, methylnaltrexone bromide, chorionic gonadotropin, pancreatic enzymes, streptokinase, sumatoplitan, growth factors (FGF,EGF, PDGF, etc.), growth factor-releasing factor (GFRF), growth hormone-releasing factor (GHRF), growth hormone-releasing hormone (GHRH), cetuximab, ceredase, tissue plasminogen activator, somatostatin, somatotropin, somanostatin, factor IX, factor VIIIa, factor VIII, daclizumab, darbepoetin-α, temocin α-1, deamino[Val4,D-Arg8]arginine vasopressin, tecteplase, testosterone , desmopressin, teduglutide, denileukin diftitox, tositumomab, trastuzumab, triamcinolone hexacetonide, trypsin, triptorelin pamoate, drotrecogin-α, droperidol, natalizumab, nicotine, nesiritide, nesterone, basiliximab, pasireotide, vasopressin, vasopressin antagonist analogues, panitumumab, papain, palivizumab, palifermin, hyaluronidase, bisphosphonate, human Albumin, human chorionic gonadotropin, human deoxyribonuclease I, human follicle-stimulating hormone, hydrophorone, bivalirudin, filgrastim, pooled immunoglobulin, fentanyl, fondaparinux, parathyroid hormone, bradykinin, bradykinin antagonist, progesterone, prostaglandin, protein C, protein S, becaplermin, pegsomant, pegfilgrastim, bevacizumab, heparin, pentigetide, botulinum toxins (types A and B), bortezomib, muromonab-CD3, mecasermin, dihydroergotamine mesylate, benztropine methanesulfonate, methotrexate, lactase, rasburicase, ranibizumab, laronidase, follicular luteoid, lypressin, rituximab, lidocaine, lypressin, bleomycin sulfate, morphine sulfate, liraglutide, lutropin-α, reteplase, renin inhibitors, lepirudin, levonorgestrel, levonorgestrel,Prostaglandin antagonists, thrombolytic agents, anti-rhesus (rh) immunoglobulin G, neurotrophic factors, parathyroid hormone and agonists, l-asparaginase, aANF, ACTH analogs such as ACTH(1-24), ANP, bMSH, crotalidene multivalent Fab (sheep), CSI, Fab fragments, GH, IgE peptide inhibitors, IGF-1, LHRH analogs (e.g., leupropid, buserelin, triptorelin, gonadorelin, nafarelin, menotropins), T-36 (N-[[(s)-4-oxo-2-azetidinyl]carbonyl]-L-histidyl-L-prolinamide), TRN, α1-antitrypsin, α-1 protease inhibitors, and β-glucocerebrosidase.

[0030] Vaccines include therapeutic vaccines for infectious diseases, cancer, neurological disorders, allergies, smoking cessation or other addictions, as well as current and future vaccines for the prevention of influenza (seasonal and novel), Ebola, yellow fever, rabies, tuberculosis, Vibrio cholerae, cytomegalovirus, monkeypox, diphtheria, chickenpox, meningitis, shingles, anthrax, typhoid, dengue fever, smallpox, West Nile, Japanese encephalitis, pneumococcus, syphilis, tetanus, cervical cancer, whooping cough, rubella, herpes, polio, measles, malaria, Lyme disease, mumps, Pseudomonas aeruginosa, Legionella pneumophila, and rotavirus.

[0031] Vitamins, herbs, and nutritional supplements include, for example, zinc, red koji, slippery elm, acai berry, angelica tree, ashwagandha, astaxanthin, acetyl-L-carnitine, apple cider vinegar, American witch hazel, arginine, alpha-lipoic acid, aloe vera, ginkgo biloba, inulin, nettle, oolong tea, echinacea, emu oil, elderberry, milk thistle, barley, krill oil, omega-3 fatty acids, olive, oregano, activated charcoal, valerian, chamomile, potassium, Calcium, xanthan gum, xylitol, chitosan, conjugated linoleic acid, cranberry, glycine, glucosamine, glucosamine sulfate, glutathione, creatine, chromium, chlorella, chlorophyll, quercetin, black tea, coenzyme Q10, bitter melon, coconut juice, choline, fenugreek, chondroitin, saffron, sea buckthorn, citicoline, cinnamon, ginger, camphor, St. John's wort, gelatin, selenium, senna, turmeric, damiana, chasteberry, chosen Ginseng, tyrosine, theanine, deer velvet, tea tree oil, iron, passionflower, feverfew, nicotinic acid, whey protein, saw palmetto, hibiscus, terrestris, bee pollen, biotin, vitamin A, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, phenylalanine, forskolin, cordyceps, blackcurrant, black cohosh, black cherry, progesterone, probiotics, bromelain, branched amino acids, beta-carotene Alanine, beta-carotene, beta-glucan, pectin, horny goat weed, holy basil, phosphatidylserine, magnesium, ginseng, evening primrose oil, magnolia, folic acid, yohimbe, lactobacillus, ribose, reishi mushroom, resveratrol, rose hips, 5-HTP, DHEA, DMSO, D-mannose, EDTA, GABA, L-carnitine, L-citrulline, L-trypothophan, MSM (methylsulfonylmethane), SAM-e.

[0032] (1-5) Isolation Diaphragm The isolation diaphragm 16 is installed inside the transport liquid storage unit 12 and isolates the chemical solution 18 from the drive liquid 13. The isolation diaphragm 16 can be made of any material that can isolate the chemical solution 18.

[0033] Second Embodiment (2-1) Configuration of Drug Solution Transport Device Fig. 2 is a side view showing an example of the configuration of a drug solution transport device according to a second embodiment. In Fig. 2, drug solution transport device 1 has a configuration similar to that of drug solution transport device 1 of the first embodiment, but differs in the configuration of switch 30 installed between power supply 20 and electroosmotic flow pump 14. Switch 30 in Fig. 2 is configured to switch ON / OFF the voltage supplied from power supply 20 to electroosmotic flow pump 14 and to control the direction of delivery of drive liquid 13 by controlling the polarity of the voltage supplied to electroosmotic flow pump 14. Transport liquid storage unit 12 is capable of storing drug solution 18 and subcutaneous interstitial fluid 19 collected from the subcutaneous tissue.

[0034] (2-2) Operation of Drug Transport Device When using the drug solution transport device 1, the microneedles (15-1 to 15-4) are inserted into the skin. When a voltage of such polarity that the driving liquid accommodating unit 11 side is at a positive potential relative to the transport liquid accommodating unit 12 side is applied from the power source 20 to the electroosmotic flow pump 14, the electroosmotic flow pump 14 starts to pump the driving liquid 13 from the driving liquid accommodating unit 11 to the transport liquid accommodating unit 12.

[0035] When the driving liquid is sent from the driving liquid storage unit 11 to the transport liquid storage unit 12, the internal pressure of the chamber storing the driving liquid 13 of the transport liquid storage unit 12 increases, crushing the isolation diaphragm 16, and the medicinal liquid 18 filled in the chamber storing the medicinal liquid 18 of the transport liquid storage unit 12 is transported into the skin through the needle holes (17-1 to 17-4) of the microneedles (15-1 to 15-4). The operation up to this point is the same as in the first embodiment.

[0036] The switch 30 in the second embodiment is configured to control the liquid transfer direction of the electroosmotic pump 14. When a voltage of opposite polarity to the above-described voltage polarity is applied, that is, a voltage of such polarity that the driving liquid accommodating unit 11 side is at a negative potential with respect to the transport liquid accommodating unit 12 side, the driving liquid 13 is transferred from the chamber containing the medicinal liquid 18 in the transport liquid accommodating unit 12 to the driving liquid accommodating unit 11, the chamber containing the medicinal liquid 18 in the transport liquid accommodating unit 12 is depressurized, and the subcutaneous interstitial fluid 19 is sucked into the transport liquid accommodating unit 12 through the needle holes (17-1 to 17-4) of the microneedles (15-1 to 15-4). This allows the collection of subcutaneous interstitial fluid 19.

[0037] (2-2) Advantages of the Second Embodiment According to the second embodiment, it is possible to realize a single drug solution transport device that can be used for two purposes: transdermal drug solution transport and subcutaneous interstitial fluid collection. This allows for cost reduction compared to when separate devices are provided for transdermal drug solution transport and subcutaneous interstitial fluid collection.

[0038] 3 is a side view showing an example of the configuration of a drug solution transport device according to a third embodiment. The drug solution transport device 1 includes a drug solution transport device main body 10 including transport solution storage units (12-1, 12-2) that store a transport solution such as a drug solution 18, a driving solution storage unit 11 that stores a driving solution 13, electroosmotic flow pumps (14-1, 14-2) that use electroosmotic flow generated in the driving solution 13 to transport the drug solution, microneedles (15-1 to 15-6), a power supply 20 that supplies voltage to the electroosmotic flow pumps (14-1, 14-2), a switch 30 that is disposed between the power supply 20 and the electroosmotic flow pump 14 and switches ON / OFF the voltage supplied from the power supply 20 to the electroosmotic flow pump 14, and a control unit 40 that controls the operation of the switch 30.

[0039] The drug solution transport device 1 in Fig. 3 has a configuration similar to that of the drug solution transport device 1 of the second embodiment, but differs from the configuration of the second embodiment in Fig. 2 in that it has two systems of transport solution storage units (12-1, 12-2) and electroosmotic flow pumps (14-1, 14-2) and in the configuration of a switch 30 installed between the power source 20 and the electroosmotic flow pumps (14-1, 14-2). The transport solution storage units (12-1, 12-2) are capable of storing drug solution 18 and collected subcutaneous interstitial fluid 19.

[0040] 3 is configured to independently control the ON / OFF, value, and polarity of the voltage supplied to each of the two electroosmotic flow pumps (14-1, 14-2) from the power supply 20. With this configuration, in the third embodiment, the ON / OFF control of the delivery of the drive liquid 13, the delivery speed, and the delivery direction can be independently controlled for each of the two electroosmotic flow pumps (14-1, 14-2).

[0041] (3-2) Operation of the Drug Solution Transport Device In the third embodiment, as described above, the ON / OFF control of the drive solution 13, the delivery speed, and the delivery direction can be independently controlled for each of the two electroosmotic flow pumps (14-1, 14-2). Therefore, it is possible to control the first electroosmotic flow pump (14-1) to deliver the drug solution 18 and the second electroosmotic flow pump (14-2) to collect subcutaneous interstitial fluid, or to control both the first electroosmotic flow pump (14-1) and the second electroosmotic flow pump (14-2) to deliver the drug solution 18. Furthermore, it is also possible to control both the first electroosmotic flow pump (14-1) and the second electroosmotic flow pump (14-2) to collect subcutaneous interstitial fluid after delivering the drug solution 18. The operation of the drug solution transport device 1 when transporting the drug solution 18 and the operation of the drug solution transport device 1 when collecting the subcutaneous interstitial fluid 19 are the same as those described in the first and second embodiments, and therefore will not be described here.

[0042] (3-3) Advantages of the Third Embodiment According to the third embodiment, it is possible to transport medicinal liquids and collect subcutaneous interstitial fluid independently for each of the multiple transport liquid storage units. This makes it possible to transport multiple types of medicinal liquids, and simultaneously transport medicinal liquids transdermally and collect subcutaneous interstitial fluid, which is expected to reduce costs and improve the efficiency of medical care.

[0043] <Fourth Embodiment> (4-1) Configuration of Drug Solution Transport Device Fig. 4 is a side view showing an example of the configuration of a drug solution transport device according to a fourth embodiment. In Fig. 4, the drug solution transport device 1 includes transport solution storage units (12-1, 12-3) that store a transport solution such as a drug solution 18, an electroosmotic flow pump 14 that uses an electroosmotic flow generated in the drive solution 13 to pump the drive solution 13, a drug solution transport device main body 10 that includes at least one microneedle (15-1 to 15-6), a power supply 20 that supplies voltage to the electroosmotic flow pump 14, and a switch 30 that is disposed between the power supply 20 and the electroosmotic flow pump 14 and switches ON / OFF the voltage supplied from the power supply 20 to the electroosmotic flow pump 14. The configuration of the switch 30 is the same as that of the first embodiment. The transport liquid storage units (12-1, 12-3) are provided with isolation diaphragms (16-1, 16-3) for isolating the drug liquid 18 and the subcutaneous interstitial fluid 19 from the driving liquid 13.

[0044] In the first embodiment, the driving liquid 13 is accommodated in the driving liquid accommodation unit 11, and the electroosmotic flow pump 14 is installed between the driving liquid accommodation unit 11 and the transport liquid accommodation unit 12. In the fourth embodiment, the driving liquid accommodation unit 11 is not necessary, and the driving liquid 13 is accommodated in a chamber (fourth chamber) that is isolated by an isolation diaphragm (16-3) in the transport liquid accommodation unit (12-3). The electroosmotic flow pump 14 is installed between the two transport liquid accommodation units (12-1, 12-3), and the driving liquid 13 accommodated in the transport liquid accommodation unit (12-3) is transported to a chamber (second chamber) that is isolated by an isolation diaphragm (16-1) in the transport liquid accommodation unit (12-1).

[0045] (4-2) Operation of the Drug Solution Transport Device When using the drug solution transport device 1, the microneedles (15-1 to 15-6) are inserted into the skin. When a voltage is applied from the power source 20 to the electroosmotic flow pump 14 so that the transport liquid storage unit (12-3) side is at a positive potential relative to the transport liquid storage unit (12-1) side, the electroosmotic flow pump 14 starts to pump the drive liquid 13 from the transport liquid storage unit (12-3) toward the transport liquid storage unit (12-1).

[0046] When the driving liquid 13 is transferred from the transport liquid storage unit (12-3) to the transport liquid storage unit (12-1), the internal pressure of the chamber (second chamber) in which the driving liquid 13 of the transport liquid storage unit (12-1) is stored increases, the isolation diaphragm (16-1) is crushed, and the medicinal liquid 18 filled in the chamber (first chamber) in which the medicinal liquid 18 of the transport liquid storage unit (12-1) is stored is transported into the skin through the needle holes of the microneedles (15-4 to 15-6).

[0047] On the other hand, when the driving liquid 13 is sent from the transport liquid storage unit (12-3) to the transport liquid storage unit (12-1), the chamber (fourth chamber) storing the driving liquid 13 in the transport liquid storage unit (12-3) is depressurized, and the subcutaneous interstitial fluid 19 in the skin is sucked into the transport liquid storage unit (12-3) through the needle holes of the microneedles (15-1 to 15-3) and stored in the chamber (third chamber) storing the subcutaneous interstitial fluid 19. This makes it possible to collect the subcutaneous interstitial fluid 19.

[0048] (4-3) Effects of the Fourth Embodiment According to the fourth embodiment, it is possible to simultaneously transport drug solution and collect subcutaneous interstitial fluid using a single drug solution device, and to simultaneously control the ON / OFF of drug solution transport and subcutaneous interstitial fluid collection, which is expected to reduce costs and improve the efficiency of medical treatment.

[0049] <Fifth Embodiment> (5-1) Configuration of Drug Solution Transport Device Fig. 5 is a side view showing a configuration example of a drug solution transport device according to a fifth embodiment. The drug solution transport device 1 in Fig. 5 is provided with a sensor 50 in an area of ​​the transport solution storage unit 12 where collected subcutaneous interstitial fluid 19 is stored. The configuration of the drug solution transport device 1 other than the transport solution storage unit 12 is the same as that of the second embodiment, and therefore description thereof will be omitted. The configuration of the transport solution storage unit 12 provided with the sensor 50 can be applied to the third and fourth embodiments.

[0050] The sensor 50 is composed of a stimulus-responsive substance. The stimulus-responsive substance is a substance that reacts selectively with the collected analyte and changes its physical properties, such as swelling, water content, color, and dielectric constant, depending on the degree of reaction. By measuring the change in the physical properties of the sensor 50, it is possible to measure the type and amount of the subcutaneous interstitial fluid 19, which is the analyte. By constructing the outer walls of the transport liquid storage unit 12 and the main body 10 of the drug solution transport device 1 from a transparent material, the change in the physical properties of the sensor 50 can be measured from the outside of the drug solution transport device 1 using an imaging device or a reflection-type measuring device.

[0051] (5-2) Operation of the drug solution transport device In the fifth embodiment, the sensor 50 is fixed to a surface in contact with the outer wall inside the transport liquid accommodation unit 12 of the drug solution transport device 1, and changes in the physical properties of the substance constituting the sensor 50, such as volume, color, and dielectric constant, are measured from the outside of the drug solution transport device 1 using a reflection-type measurement system or the like. By measuring the changes in the physical properties of the sensor 50, the type and amount of the subcutaneous interstitial fluid 19, which is the analyte, can be determined.

[0052] (5-3) Effects of the Fifth Embodiment According to the fifth embodiment, a single device can not only transport the drug solution 18 and collect the subcutaneous interstitial fluid 19, but also detect the concentration of the analyte in the collected subcutaneous interstitial fluid 19.

[0053] (5-4) Sensor The stimuli-responsive substance used in the sensor 50 may be any substance that reacts with an analyte in subcutaneous interstitial fluid to change its physical properties. For example, a stimuli-responsive hydrogel can be used. To produce the hydrogel, a solution containing a monomer, a crosslinker, and a polymerization initiator is cured by thermal polymerization, photopolymerization, or the like. Examples of the monomer include uncharged acrylamide-based monomers such as acrylamide, N-isopropylacrylamide, and dimethylacrylamide; vinyl-based monomers such as vinyl acetate, vinylpyridine, and styrene; alkyl acrylate-based monomers such as methyl methacrylate; hydroxyalkyl acrylate-based monomers such as hydroxyethyl acrylate; and fluorine-containing unsaturated monomers such as trifluoroethyl acrylate. Examples of the charged monomer include 2-acrylamido-2-methylpropanesulfonic acid, acrylic acid, and methacrylic acid.

[0054] When preparing functionalized gels such as stimuli-responsive gels, in addition to the aforementioned monomers, substances appropriate for the application are used. For example, in the case of glucose-responsive hydrogels, acrylic phenylboronic acids such as 3-acrylamidophenylboronic acid (3-APBA), which are monomers with chemical probes in their side chains, the enzyme glucose oxidase, and the protein concanavalin A may be included. The crosslinking monomers are selected according to the monomer, such as acrylic crosslinkers such as N,N'-methylenebisacrylamide (Bis) and polyethylene glycol diacrylate.

[0055] As for the polymerization initiator, examples of the initiator include water-soluble thermal catalysts such as persulfates and redox initiators such as thiosulfates for thermal polymerization, and examples of the initiator for photopolymerization include 2-oxoglutaric acid. The type of polymerization initiator can be selected depending on the polymerization method and the monomer to be polymerized, for example, azobisisobutyronitrile, benzoyl peroxide, or other thermal catalysts soluble in organic solvents are used for thermal polymerization of styrene, which is an organic monomer, and benzophenone is used for photopolymerization.

[0056] The control unit 40 that controls the transport of the drive liquid by the electroosmotic pump described in the embodiment of the present invention can be realized by a computer equipped with a CPU (Central Processing Unit), a storage device, and an interface, and a program that controls these hardware resources. Figure 6 shows an example of the configuration of a computer that constitutes the control unit that controls the transport of the drug solution according to the embodiment of the present invention.

[0057] 6, computer 100 includes a CPU 101, a storage device 102, and an interface device (I / F) 103. A power supply 20 and a switch 30 that controls the transport of drive liquid by electroosmotic pump 14 are connected to I / F 103. In such a computer, a program for realizing the control of the present invention is stored in storage device 102. CPU 101 executes the control described in the embodiment of the present invention in accordance with the program stored in storage device 102.

[0058] <Effects of the embodiment of the invention> According to the present embodiment, a drug solution transport device is provided that does not pose a risk of burns or other injuries by using an electroosmotic flow pump that applies voltage only to the driving liquid, rather than directly to the skin. A drug solution transport device is provided that allows precise control of the liquid transport speed by changing the voltage applied to the electroosmotic flow pump. Furthermore, a drug solution transport device is provided that does not apply a voltage directly to the drug solution, but instead applies a voltage to the driving liquid, and transports the drug solution using the electroosmotic flow generated in the driving liquid, thereby allowing for the administration of any drug solution. A device is provided that can transport drug solutions and collect subcutaneous interstitial fluid in a single device, improving the efficiency of medical treatment and reducing costs.

[0059] In the drug solution transport device of the first embodiment, when water was selected as the driving liquid and a voltage of 10 V was applied to the electroosmotic pump, a liquid delivery rate of approximately 9 μL / min was achieved. When the amount of drug solution was 0.5 mL, continuous administration was possible for 78 hours. Furthermore, the above measurements did not confirm decomposition of the drug solution due to the voltage.

[0060] Although the present invention has been described above with reference to the embodiments, the present invention is not limited to the above-described embodiments. Various modifications that can be understood by those skilled in the art can be made to the configuration of the present invention within the scope of the present invention.

[0061] Some or all of the above-described embodiments can be described as, but are not limited to, the following supplementary notes.

[0062] [Supplementary Note 1] A device comprising: a driving liquid containing unit containing a driving liquid; a transport liquid containing unit containing a drug solution or subcutaneous interstitial fluid; an electroosmotic flow pump which transports the driving liquid between the driving liquid containing unit and the transport liquid containing unit; a needle for injecting the drug solution supplied from the transport liquid containing unit into the skin or for storing the subcutaneous interstitial fluid collected from the skin in the transport liquid containing unit; a power source which supplies a voltage to the electroosmotic flow pump; a switch installed between the power source and the electroosmotic flow pump; and a control unit which controls the switch to control the transport of the driving liquid by the electroosmotic flow pump, wherein the transport liquid containing unit comprises a first chamber which contains the drug solution or subcutaneous interstitial fluid and which is in communication with a needle hole of the needle, and a second chamber which contains the driving liquid and is separated from the first chamber by a diaphragm, The electroosmotic pump is configured to change the volume of the first chamber by transporting the drive liquid from the drive liquid unit to the second chamber or by transporting the drive liquid from the second chamber to the drive liquid unit. [Supplementary Note 2] The drug transport device according to Supplementary Note 1, wherein the switch is configured to switch the polarity of a voltage supplied to the electroosmotic pump, and the control unit is configured to control the switch to switch the direction of transport of the drive liquid by the electroosmotic pump.[Supplementary Note 3] A device comprising: a driving liquid containing unit containing a driving liquid; a plurality of transport liquid containing units containing a drug solution or subcutaneous interstitial fluid; a first electroosmotic flow pump connected between a first transport liquid containing unit of the plurality of transport liquid containing units and the driving liquid containing unit; a second electroosmotic flow pump connected between a second transport liquid containing unit of the plurality of transport liquid containing units and the driving liquid containing unit; a needle for injecting the drug solution supplied from the first transport liquid containing unit into the skin or for storing the subcutaneous interstitial fluid collected from the skin in the second transport liquid containing unit; a power supply for supplying a voltage to the first electroosmotic flow pump and the second electroosmotic flow pump; a switch installed between the power supply and the first electroosmotic flow pump and the second electroosmotic flow pump; and a control unit for controlling the switch to control transport of the driving liquid by the first electroosmotic flow pump and the second electroosmotic flow pump, The first transport liquid storage unit and the second transport liquid storage unit each include a first chamber that stores the drug liquid or subcutaneous interstitial fluid and is in communication with the needle hole of the needle, and a second chamber that stores the driving liquid and is separated from the first chamber by a diaphragm, and the first electroosmotic flow pump and the second electroosmotic flow pump are configured to change the volume of the first chamber by transporting the driving liquid from the driving liquid unit to the second chamber or by transporting the driving liquid from the second chamber to the driving liquid unit.[Supplementary Note 4] A device comprising: a plurality of transport liquid accommodating units accommodating a drug solution or subcutaneous interstitial fluid and a driving liquid; an electroosmotic flow pump connected between a first transport liquid accommodating unit and a second transport liquid accommodating unit of the plurality of transport liquid accommodating units; a first needle for injecting the drug solution supplied from the first transport liquid accommodating unit into the skin; and a second needle for storing the subcutaneous interstitial fluid collected from the skin in the second transport liquid accommodating unit; a power source for supplying a voltage to the electroosmotic flow pump; a switch installed between the power source and the electroosmotic flow pump; and a control unit for controlling the switch to control transport of the driving liquid by the electroosmotic flow pump, wherein the first transport liquid accommodating unit comprises a first chamber for accommodating the drug solution and communicating with a needle hole of the needle, and a second chamber for accommodating the driving liquid and separated from the first chamber by a diaphragm, The drug solution transport device according to any one of Supplementary Notes 1 to 4, further comprising a sensor made of a stimulus-responsive substance in the first chamber of the transport solution storage unit, the sensor comprising a third chamber configured to store the subcutaneous interstitial fluid and communicate with the needle hole of the needle, and a fourth chamber configured to store the driving solution and separated from the third chamber by a diaphragm, the electroosmotic pump configured to transport the driving solution from the fourth chamber to the second chamber, thereby changing the volumes of the first chamber and the second chamber.

[0063] 1...drug solution transport device, 10...drug solution transport device main body, 11...driving solution storage unit, 12, 12-1, 12-2, 12-3...transported solution storage unit, 13...driving solution, 14, 14-1, 14-2...electroosmotic flow pump, 15-1 to 15-6...microneedles, 16, 16-1, 16-2, 16-3...isolation diaphragms, 17-1 to 17-6...needle holes, 18...drug solution, 19...subcutaneous interstitial fluid, 20...power source, 30...switch, 40...control unit, 50...sensor

Claims

1. A device comprising: a driving fluid storage unit that stores a driving fluid; a transport fluid storage unit that stores a drug solution or subcutaneous interstitial fluid; an electroosmotic pump that transports the driving fluid between the driving fluid storage unit and the transport fluid storage unit; a needle for injecting the drug solution supplied from the transport fluid storage unit into the skin or for storing the subcutaneous interstitial fluid collected from the skin in the transport fluid storage unit; a power source that supplies voltage to the electroosmotic flow pump; a switch installed between the power source and the electroosmotic flow pump; and a control unit that controls the switch to control the transport of the driving fluid by the electroosmotic flow pump, wherein the transport fluid storage unit comprises a first chamber that stores the drug solution or subcutaneous interstitial fluid and is in communication with the needle hole of the needle, and a second chamber that stores the driving fluid and is separated from the first chamber by a diaphragm, a drug solution transport device, wherein the electroosmotic pump is configured to change the volume of the first chamber by transporting the drive solution from the drive solution storage unit to the second chamber or by transporting the drive solution from the second chamber to the drive solution storage unit.

2. The drug transport device according to claim 1, wherein the switch is configured to be able to switch the polarity of the voltage supplied to the electroosmotic flow pump, and the control unit is configured to control the switch to switch the direction of transport of the drive liquid by the electroosmotic flow pump.

3. A driving fluid storage unit that stores a driving fluid, and a plurality of transport fluid storage units that store a drug solution or subcutaneous interstitial fluid, a first electroosmotic flow pump connected between a first transport fluid storage unit of the plurality of transport fluid storage units and the driving fluid storage unit, and a second electroosmotic flow pump connected between a second transport fluid storage unit of the plurality of transport fluid storage units and the driving fluid storage unit, a needle for injecting the drug solution supplied from the first transport fluid storage unit into the skin or for storing the subcutaneous interstitial fluid collected from the skin in the second transport fluid storage unit, a power source that supplies voltage to the first electroosmotic flow pump and the second electroosmotic flow pump, a switch installed between the power source and the first electroosmotic flow pump and the second electroosmotic flow pump, and a control unit that controls the switch to control the transport of the driving fluid by the first electroosmotic flow pump and the second electroosmotic flow pump, a first chamber that contains the drug solution or subcutaneous interstitial fluid and that communicates with the needle hole of the needle; and a second chamber that contains the driving solution and is separated from the first chamber by a diaphragm; and the first electroosmotic flow pump and the second electroosmotic flow pump are configured to change the volume of the first chamber by transporting the driving solution from the driving solution storage unit to the second chamber or by transporting the driving solution from the second chamber to the driving solution storage unit.

4. A device comprising: a plurality of transport liquid storage units for storing a drug solution or subcutaneous interstitial fluid and a driving liquid; an electroosmotic flow pump connected between a first transport liquid storage unit and a second transport liquid storage unit of the plurality of transport liquid storage units; a first needle for injecting the drug solution supplied from the first transport liquid storage unit into the skin; a second needle for storing the subcutaneous interstitial fluid collected from the skin in the second transport liquid storage unit; a power source for supplying voltage to the electroosmotic flow pump; a switch installed between the power source and the electroosmotic flow pump; and a control unit for controlling the switch to control the transport of the driving liquid by the electroosmotic flow pump, wherein the first transport liquid storage unit comprises a first chamber for storing the drug solution and communicating with the needle hole of the needle, and a second chamber for storing the driving liquid separated from the first chamber by a diaphragm, The second transport liquid storage unit includes a third chamber that stores the subcutaneous interstitial fluid and is in communication with the needle hole of the needle, and a fourth chamber that stores the driving liquid and is separated from the third chamber by a diaphragm, and the electroosmotic pump is configured to transport the driving liquid from the fourth chamber to the second chamber, thereby changing the volumes of the first chamber and the second chamber.

5. The drug transport device according to claim 1, further comprising a sensor made of a stimulus-responsive substance in the first chamber of the transport liquid containing unit.

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