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WO2024129424A1 - Dispositif d'administration de médicament - Google Patents

Dispositif d'administration de médicament Download PDF

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Publication number
WO2024129424A1
WO2024129424A1 PCT/US2023/082372 US2023082372W WO2024129424A1 WO 2024129424 A1 WO2024129424 A1 WO 2024129424A1 US 2023082372 W US2023082372 W US 2023082372W WO 2024129424 A1 WO2024129424 A1 WO 2024129424A1
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WO
WIPO (PCT)
Prior art keywords
discrete
microneedles
substrate
disposed
arrays
Prior art date
Application number
PCT/US2023/082372
Other languages
English (en)
Inventor
Richard Brewer
Original Assignee
Kindeva Drug Delivery L.P.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kindeva Drug Delivery L.P. filed Critical Kindeva Drug Delivery L.P.
Publication of WO2024129424A1 publication Critical patent/WO2024129424A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0023—Drug applicators using microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/003—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles having a lumen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0038—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles having a channel at the side surface
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0046—Solid microneedles

Definitions

  • microneedles or micro-pins Devices including arrays of relatively small structures, sometimes referred to as microneedles or micro-pins, have been disclosed for use with the delivery of therapeutic agents and other substances through the skin and other surfaces.
  • the devices can be pressed against the skin to pierce the stratum corneum such that the therapeutic agents and other substances can sequentially or simultaneously pass through that layer and into the tissues below.
  • Microneedles of these devices pierce the stratum corneum upon contact, making a plurality of microscopic slits that serve as passageways through which molecules of active components can be delivered into the body.
  • the microneedle device can be provided with a reservoir for temporarily retaining an active component in liquid form prior to delivering the active component through the stratum corneum.
  • the method further includes disposing the plurality of discrete arrays on skin of a user.
  • FIG.5 is a schematic cross-section view of a portion of the discrete array of FIG.3.
  • FIG.6 is a schematic bottom perspective view of another embodiment of a drug delivery device.
  • FIG.7 is a schematic top plan view of another embodiment of a drug delivery device.
  • FIG.8 is a schematic side view of one embodiment of a microarray applicator that can be utilized to apply the drug delivery device of FIG.1 to skin of a user.
  • FIG.9 is a schematic partial cross-section view of the microarray applicator of FIG.8.
  • FIG.10 is a flowchart of one method of forming the drug delivery device of FIG.1. DETAILED DESCRIPTION
  • the present disclosure provides various embodiments of a drug delivery device.
  • the term “downward,” and variations thereof, is sometimes used to describe the direction in which microneedles are pressed into skin, and “upward” to describe the opposite direction.
  • the drug delivery device and applicator can be used where the microneedles are pressed into skin at an angle to the direction of the earth’s gravity, or even in a direction contrary to that of the earth’s gravity, and these terms are only used for simplicity and clarity to describe relative directions.
  • the term “transdermally,” and variations thereof, is generally used to refer to any type of delivery of an active ingredient that crosses any portion of skin.
  • transdermally can generally include systemic delivery (i.e., where the active ingredient is transported across, or substantially through, the dermis such that the active ingredient is delivered into the bloodstream), as well as intradermal delivery (i.e., where the active ingredient is transported partially through the dermis, e.g., across the outer layer (stratum corneum) of the skin, where the active ingredient is delivered into the skin, e.g., for treating psoriasis or for local anesthetic delivery).
  • transdermal delivery as used herein includes delivery of an active or placebo ingredient that is transported across at least a portion of skin (but not necessarily all of the layers of skin), rather than merely being topically applied to an outer layer of the skin.
  • the discrete arrays 16 can include only first discrete arrays 18. In one or more embodiments, the discrete arrays 16 can include one or more first discrete arrays 18 and one or more second discrete arrays 24. Further, in one or more embodiments, the discrete arrays 16 can include one or more first discrete arrays 18 and second discrete arrays 24, and one or more third discrete arrays 40.
  • the third discrete array 40 can include a third substrate 42 and third microneedles 44 disposed on the third substrate.
  • the device 10 can include any suitable number of types of discrete arrays, first, second, third, fourth, fifth or more discrete arrays.
  • the first discrete array 18 can include a first characteristic and the second discrete array 24 can include a second characteristic different from the first characteristic.
  • the third discrete array can include a third characteristic that can be different from at least one of the first characteristic of the first discrete array 18 or the second characteristic of the second discrete array 24.
  • the discrete arrays 16 can be disposed on the backing layer 12 (or directly onto the skin without a backing layer) such that individual arrays are not connected to one or more adjacent arrays. In one or more embodiments, one or more of the discrete arrays 16 can be connected using any suitable technique.
  • the first discrete array 18 includes one or more first alignment features 50 that extend from a perimeter 52 of the first discrete array.
  • the second discrete array 24 can include one or more second alignment features 58 that extend from a perimeter 60 of the second discrete array.
  • the alignment features 50, 58 can include any suitable features that are configured to align and connect adjacent discrete arrays.
  • the first alignment features 50 of the first discrete array 18 include one or more tabs 54 and one or more slots 56.
  • the tabs 54 can be configured to connect with one or more slots (not shown) of the second alignment features 58 of the second discrete arrays 24.
  • the tabs 54 can take any suitable shape and have any suitable dimensions.
  • the device 200 includes a plurality of discrete arrays 216 that each take hexagonal shape. Extending from a perimeter 252 of one or more of the discrete arrays 216 are alignment features 250. Such alignment features include one or more tabs 254 and one or more slots 256, where each tab extends from a substrate 220 of the discrete array 216, and each slot is disposed in the substrate. Each tab 254 has a thickness that is less than a thickness of the substrate 220, and each slot 256 has a thickness that is less than the thickness of the substrate 220.
  • the slots 256 are configured to connect to a tab 254 of an adjacent discrete array substrate 220 to provide cavities that are configured to receive the tabs, which have a depth that is no greater than a depth of the cavity.
  • the device 10 can include one or more openings 76 disposed through at least one of the discrete arrays 16. As shown in FIG.2, the opening 76 is disposed through the second substrate 26 of the second array 24. In one or more embodiments, the device 10 can include one or more openings disposed through one or more of the discrete arrays 16. Each of the openings 76 can include any suitable cross-sectional shape and have any suitable dimensions.
  • the discrete arrays 16 can be disposed in any suitable relationship or pattern on the backing layer 12 (or directly on the skin without a backing layer). For example, the discrete arrays 16 can form a tessellated pattern on the backing layer 12. Further, the discrete arrays 16 can be disposed such that two or more arrays are in contact. For example, in one or more embodiments, the first discrete array 18 can be in contact with the second discrete array 24. Further, two or more of the discrete arrays 16 can disposed such that there is a fluid channel 78 disposed between the arrays. For example, in the embodiment illustrated in FIG.2, the fluid channel 78 can be disposed between the first discrete array 18 and the second discrete array 24. The fluid channel 78 can take any suitable shape and have any suitable dimensions.
  • the device 10 can include any suitable number of fluid channels 78 disposed between adjacent discrete arrays 16.
  • discrete arrays useful for practicing the present disclosure can have a variety of characteristics, such as those described in the following patents and patent applications.
  • One embodiment for the microneedles of one or more of the discrete arrays 16 includes the structures disclosed in U.S. Patent Application Publication No.2005/0261631 (Clarke et al.), which describes microneedles having a truncated tapered shape and a controlled aspect ratio.
  • Another embodiment for the microneedles discrete arrays includes the structures disclosed in U.S. Patent No.6,091,975 (Daddona et al.), which describes blade-like microprotrusions for piercing the skin.
  • microneedles includes the structures disclosed in U.S. Patent No.6,312,612 (Sherman et al.), which describes tapered structures having a hollow central channel. Yet still another embodiment of microneedles includes the structures disclosed in U.S. Patent No.6,379,324 (Gartstein et al.), which describes hollow microneedles having at least one longitudinal blade at the top surface of the tip of the microneedle.
  • a further embodiment of microneedles includes the structures disclosed in U.S. Patent Application Publication Nos. US2012/0123387(Gonzalez et al.) and US2011/0213335 (Burton et al.), which both describe hollow microneedles.
  • a still further embodiment of microneedles includes the structures disclosed in U.S. Patent Nos.6,558,361 (Yeshurun) and 7,648,484 (Yeshurun et al.), which both describe hollow microneedle arrays and methods of manufacturing thereof.
  • Various embodiments of microneedles that can be employed in the discrete arrays of the present disclosure are also described in PCT Publication No. WO2012/074576 (Duan et al.), which describes liquid crystalline polymer (LCP) microneedles; and PCT Publication No. WO2012/122162 (Zhang et al.), which describes a variety of different types and compositions of microneedles.
  • the microneedle material can be (or include) silicon, glass, or a metal such as stainless steel, titanium, or nickel titanium alloy.
  • the microneedle material can be (or include) a polymeric material, e.g., a medical grade polymeric material.
  • exemplary types of medical grade polymeric materials include polycarbonate, liquid crystalline polymer (LCP), polyether ether ketone (PEEK), cyclic olefin copolymer (COC), polybutylene terephthalate (PBT).
  • the microneedle material can be (or include) a biodegradable polymeric material, e.g., a medical grade biodegradable polymeric material.
  • the microneedles can be prepared from a dissolvable, degradable, or disintegradable material referred to herein as “dissolvable microneedles.”
  • a dissolvable, degradable, or disintegradable material is any solid material that dissolves, degrades, or disintegrates during use.
  • a “dissolvable microneedle” dissolves, degrades, or disintegrates sufficiently in the tissue underlying the stratum corneum to allow a therapeutic agent to be released into the tissue.
  • the therapeutic agent may be coated on or incorporated into a dissolvable microneedle.
  • the dissolvable material is selected from a carbohydrate or a sugar.
  • the dissolvable material is polyvinyl pyrrolidone (PVP).
  • the dissolvable material is selected from the group consisting of hyaluronic acid, carboxymethylcellulose, hydroxypropylmethylcellulose, methylcellulose, polyvinyl alcohol, sucrose, glucose, dextran, trehalose, maltodextrin, and a combination thereof.
  • the microneedles can be made from (or include) a combination of two or more of any of the above-mentioned materials.
  • the tip of a microneedle may be a dissolvable material, while the remainder of the microneedle is a medical grade polymeric material.
  • a microneedle or the plurality of microneedles of a discrete array can have a variety of shapes that are capable of piercing the stratum corneum.
  • one or more of the microneedles e.g., first microneedles 22
  • one or more of the microneedles can have a square pyramidal shape.
  • one or more of the microneedles can have a triangular pyramidal shape. In one or more embodiments, one or more of the microneedles can have a stepped pyramidal shape. In one or more embodiments, one or more of the microneedles can have a conical shape. In one or more embodiments, one or more of the microneedles can have a microblade shape. In one or more embodiments, one or more of the microneedles can have the shape of a hypodermic needle. The shape can be symmetric or asymmetric. The shape can be truncated (for example, the microneedles can have a truncated pyramid shape or truncated cone shape).
  • one or more of the microneedles of a discrete array are solid microneedles (that is, the microneedles are solid throughout).
  • the solid microneedles can have a square pyramidal shape, triangular pyramidal shape, stepped pyramidal shape, conical shape, or microblade shape.
  • one or more of the microneedles are hollow microneedles (that is, the microneedles contain a hollow bore through the microneedle). The hollow bore can be from the base of the microneedle to the tip of the microneedle or the bore can be from the base of the microneedle to a position offset from the tip of the microneedle.
  • one or more of the hollow microneedles can have a conical shape, cylindrical shape, square pyramidal shape, triangular pyramidal shape, or the shape of a hypodermic needle.
  • FIG.5 is a schematic cross-section view of a portion of the first discrete array 18 that includes first microneedles 22 disposed on the first substrate 20.
  • Each microneedle 22 has a height h, which is the length from the tip of the microneedle to the microneedle base at the first substrate 20. Either the height of a single microneedle 22 or the average height of all microneedles of the first discrete array 18 can be referred to as the height of the microneedle, h.
  • each of the first microneedles 22 (or the average of all of the first microneedles) has a height of about 100 to about 3000 micrometers. In one or more embodiments, each of the first microneedles 22 (or the average of all of the first microneedles) has a height of less than about 3000 micrometers. In one or more embodiments, each of the first microneedles 22 (or the average of all of the first microneedles) has a height of at least about 100 micrometers. In one or more embodiments employing solid microneedles, each of the solid microneedles (or the average of all of the solid microneedles) has a height of about 100 to about 1500 micrometers.
  • each of the hollow microneedles (or the average of all of the hollow microneedles) has a height of about 100 to about 3000 micrometers.
  • a single microneedle or the microneedles of the discrete arrays 16 can also be characterized by their aspect ratio.
  • the aspect ratio of a microneedle is the ratio of the height of the microneedle, h to the width (at the base of the microneedle), w (as shown in FIG.5).
  • the aspect ratio can be presented as h:w.
  • Each microneedle of a discrete array can have any suitable aspect ratio.
  • each of the microneedles of a discrete array (or the average of all the microneedles of the discrete array) has an aspect ratio in a range of 2:1 to 5:1.
  • Each of the discrete arrays 16 can include any suitable number of microneedles.
  • a discrete array includes about 100 to about 1500 microneedles per cm 2 of the array.
  • a discrete array of solid microneedles can include about 100 to about 1500 solid microneedles per cm 2 of the array.
  • the discrete array of hollow microneedles contains about 3 to about 30 hollow microneedles per cm 2 of the array.
  • each of the microneedles (or the average of all of the microneedles) of a discrete array can penetrate into the skin to a depth of about 50 to about 1500 micrometers. It will be appreciated that the depth of penetration (DOP) of each of the microneedles (or the average of all of the microneedles) of a discrete array may not be the full length of the microneedles themselves. Further, any suitable area of the discrete array substrate can be covered with microneedles. In one or more embodiments, about 0.1 cm 2 to about 20 cm 2 of the surface area of the discrete array substrate is covered with microneedles. In one or more embodiments, the microneedles of the present disclosure can be disposed over substantially the entire surface of the discrete array.
  • a portion of the substrate of the discrete array may not be provided with microneedles (that is, a portion of the substrate is non-structured).
  • the first portion 80 of the substrate 20 of the first discrete array includes first microneedles 22 and the second portion 82 does not include first microneedles to provide a non-structured surface of the substrate.
  • the non-structured surface can have an area of more than about 1 percent and less than about 75 percent of the total area of the substrate surface that faces the skin surface.
  • the non-structured surface has an area of more than about 0.65 cm 2 (0.10 square inch) to less than about 6.5 cm 2 (1 square inch).
  • a hollow channel or bore extends through the substrate and microneedles.
  • the bore exits at a channel opening at or near the tip of the hollow microneedle.
  • the channel can exit at an opening near the tip of the hollow microneedle.
  • the channel or bore continues along a central axis of the microneedle but exits similar to a hypodermic needle on a sloping side-wall of the microneedle to help prevent blockage of the channel by tissue upon insertion.
  • the diameter of the channel bore is about 10 to about 200 micrometers. In one or more embodiments, the diameter of the channel bore is about 10 to about 150 micrometers.
  • the diameter of the channel bore is about 30 to about 60 micrometers. In one or more embodiments of hollow microneedles, the average cross- sectional area of the channel bore is about 75 to about 32,000 micrometers. In one or more embodiments of hollow microneedle discrete arrays, the average spacing between adjacent microneedles (as measured from microneedle tip to microneedle tip) is between about 0.7 mm and about 20 mm. In one or more embodiments of hollow microneedle arrays, the average spacing between adjacent microneedles (as measured from microneedle tip to microneedle tip) is greater than about 0.7 mm.
  • the average spacing between adjacent microneedles is less than about 20 mm. In one or more embodiments of solid microneedle discrete arrays, the average spacing between adjacent microneedles (as measured from microneedle tip to microneedle tip) is between about 200 micrometers and about 2000 micrometers. In one or more embodiments of solid microneedle discrete arrays, the average spacing between adjacent microneedles is greater than about 200 micrometers. In one or more embodiments of solid microneedle discrete arrays, the average spacing between adjacent microneedles is less than about 2000 micrometers.
  • the discrete arrays can be manufactured in any suitable way such as by injection molding, compression molding, metal injection molding, stamping, photolithography, or extrusion.
  • hollow microneedle discrete arrays can be made by injection molding of a polymer such as medical grade polycarbonate or LCP, followed by laser drilling to form the channels of the microneedles.
  • active ingredients or agents e.g., drugs
  • Examples of pharmaceutically active agents that can be incorporated into the discrete arrays of the present disclosure are those capable of local or systemic effect when administered to the skin.
  • Some examples include buprenorphine, clonidine, diclofenac, estradiol, granisetron, isosorbide dinitrate, levonorgestrel, lidocaine, methylphenidate, nicotine, nitroglycerine, oxybutynin, rivastigmine, rotigotine, scopolamine, selegiline, testosterone, tulobuterol, and fentanyl, which are commercially available in the form of transdermal devices.
  • antiinflammatory drugs both steroidal (e.g., hydrocortisone, prednisolone, triamcinolone) and nonsteroidal (e.g., naproxen, piroxicam); bacteriostatic agents (e.g., chlorhexidine, hexylresorcinol); antibacterials (e.g., penicillins such as penicillin V, cephalosporins such as cephalexin, erythromycin, tetracycline, gentamycin, sulfathiazole, nitrofurantoin, and quinolones such as norfloxacin, flumequine, and ibafloxacin); antiprotazoals (e.g., metronidazole); antifungals (e.g., nystatin); coronary vasodilators; calcium channel blockers (e.g., nifedipine, diltiazem); bronchodilators (e.g., the
  • peptide therapeutic agents can be delivered via the microneedles of the discrete arrays (e.g., via solid or hollow microneedles, as described below).
  • peptide therapeutic agents examples include parathyroid hormone (PTH), parathyroid hormone related protein (PTHrP), calcitonin, lysozyme, insulin, insulinotropic analogs, glatiramer acetate, goserelin acetate, somatostatin, octreotide, leuprolide, vasopressin, desmopressin, thymosin alpha-1, atrial natriuretic peptide (ANP), endorphin, vascular endothelial growth factor (VEGF), fibroblast-growth factor (FGF), erythropoietin (EPO), bone morphogenetic proteins (BMPs), epidermal growth factor (EFG), granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM- CSF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), growth hormone release hormone (
  • PTH parathyroid hormone
  • PTHrP par
  • drugs that are of a large molecular weight may be delivered transdermally. Increasing molecular weight of a drug typically can cause a decrease in unassisted transdermal delivery.
  • Such large molecules include proteins, peptides, nucleotide sequences, monoclonal antibodies, vaccines, polysaccharides, such as heparin, and antibiotics, such as ceftriaxone.
  • suitable vaccines include therapeutic cancer vaccine, anthrax vaccine, flu vaccine, Lyme disease vaccine, rabies vaccine, measles vaccine, mumps vaccine, chicken pox vaccine, small pox vaccine, hepatitis vaccine, hepatitis A vaccine, hepatitis B vaccine, hepatitis C vaccine, pertussis vaccine, rubella vaccine, diphtheria vaccine, encephalitis vaccine, Japanese encephalitis vaccine, respiratory syncytial virus vaccine, yellow fever vaccine, recombinant protein vaccine, DNA vaccines, polio vaccine, herpes vaccine, human papilloma virus vaccine, pneumococcal vaccine, meningitis vaccine, whooping cough vaccine, tetanus vaccine, typhoid fever vaccine, cholera vaccine, tubercul
  • vaccine thus includes, without limitation, antigens in the forms of proteins, polysaccharides, oligosaccharides, or weakened or killed viruses. Additional examples of suitable vaccines and vaccine adjuvants are described in U.S. Patent Application Publication No. 2004/0049150 (Dalton et al.).
  • small-molecule drugs that are otherwise difficult or impossible to deliver by passive transdermal delivery may be used. Examples of such molecules include salt forms; ionic molecules, such as bisphosphonates, including sodium alendronate or pamedronate; and molecules with physicochemical properties that are not conducive to passive transdermal delivery.
  • each discrete array of the plurality of discrete arrays 16 can include one or more characteristics that are the same as or different from one or more characteristics of one or more additional arrays of the device 10.
  • the first discrete array 18 of the device 10 can include a first characteristic and the second discrete array 24 can include a second characteristic.
  • the first characteristic can be the same as the second characteristic.
  • the first characteristic can be different from the second characteristic.
  • the device 10 includes one or more third discrete arrays 40
  • such third discrete arrays can include a third characteristic that is the same as or different from at least one of the first characteristic or second characteristic.
  • FIG.7 is a schematic plan view of a portion of another embodiment of a drug delivery device 300. All design considerations and possibilities described herein regarding the drug delivery device 10 of FIGS.1–5 apply equally to the drug delivery device 300 of FIG. 7.
  • the device 300 includes a backing layer 312 and a plurality of discrete arrays 316 disposed on a first major surface 314 of the backing layer.
  • the plurality of discrete arrays 316 includes a first discrete array 318 and a second discrete array 324.
  • the first discrete array 318 includes a first substrate 320 and first microneedles 322 disposed on the first substrate.
  • the second discrete array 324 includes a second substrate 326 and second microneedles 328 disposed on the second substrate.
  • the plurality of discrete arrays 316 also includes a third discrete array 340 that includes a third substrate 342 and third microneedles 344 disposed on the third substrate.
  • the device 300 can include any suitable number of each of the first, second, third discrete arrays disposed in any suitable arrangement on the first major surface 314 of the backing layer 312.
  • the device 300 can include one or more of fourth, fifth, sixth, or more discrete arrays.
  • the first discrete array 318 includes a first characteristic
  • the second discrete array 324 includes a second characteristic
  • the third discrete array 340 includes a third characteristic.
  • the first, second, and third characteristics can include any suitable properties of the discrete arrays 316.
  • the characteristics of each of the discrete arrays 316 can be any suitable property, e.g., an arrangement of microneedles, shape of at least one microneedle, cross-sectional shape of at least one microneedle, aspect ratio of at least one microneedle, medicament disposed on at least one microneedle, shape of the array substrate, number of microneedles, type of microneedle (e.g., solid, hollow, dissolvable), etc.
  • the first characteristic of the first discrete array 318 can include a first arrangement 384 of the first microneedles 322
  • the second characteristic can include a second arrangement 386 of the second microneedles 328
  • the third characteristic of the third discrete array 340 can include a third arrangement 388 of third microneedles.
  • the first arrangement 384 can be the same as or different from the second arrangement 386 and the third arrangement 388.
  • the first characteristic of the first discrete array 318 can include a shape of at least one first microneedle 322
  • the second characteristic of the second discrete array 324 can include a shape of at least one second microneedle 328
  • the third characteristic of the third discrete array 340 can include a shape of at least one third microneedle 344.
  • the first characteristic can include a first cross-sectional shape in a plane parallel to the backing layer 312 of at least one first microneedle 322
  • the second characteristic can include a second cross-sectional shape in the plane parallel to the backing layer of at least one second microneedle 328
  • the third characteristic can include a third cross-sectional shape in the plane parallel to the backing layer of at least one third microneedle 344.
  • the first characteristic can include an aspect ratio of at least one first microneedle 322
  • the second characteristic can include an aspect ratio of at least one second microneedle 328
  • the third characteristic can include an aspect ratio of at least one third microneedle 344.
  • the first characteristic can include a first medicament disposed on at least one first microneedle 322, the second characteristic can include a second medicament disposed on at least one second microneedle 328, and the third characteristic can include a third medicament disposed on at least one third microneedle 344.
  • the first characteristic can include a first quantity of a medicament disposed on at least one first microneedle 322, the second characteristic can include a second quantity of the medicament disposed on at least one second microneedle 328, and the third characteristic can include a third quantity of the medicament disposed on at least one third microneedle 344.
  • the first characteristic can include a first shape of the first substrate 320 in a plane parallel to the backing layer 312, the second characteristic can include a second shape of the second substrate 326 in the plane parallel to the backing layer, and the third characteristic can include a shape of the third substrate 342 in the plane parallel to the backing layer.
  • the first characteristic can include a first shape of the first substrate 320 in a plane orthogonal to the backing layer 312, the second characteristic can include a second shape of the second substrate 326 in the plane orthogonal to the backing layer, and the third characteristic can include a shape of the third substrate 342 in the plane orthogonal to the backing layer. Any suitable technique can be utilized to dispose the device 10 onto the skin of the user.
  • a microarray applicator can be configured to deliver the device 10.
  • Any suitable microarray applicator can be utilized, e.g., one or more embodiments of applicators described in U.S. Provisional Application No.63/422,965, filed November 5, 2022, and entitled MICRONEEDLE ARRAY APPLICATOR AND SYSTEM; U.S. Patent Application No. 16/956,222, filed June 19, 2020, and entitled MICROARRAY APPLICATION; and U.S. Patent No.11,458,289, issued October 4, 2022, and entitled APPLICATOR FOR APPLYING A MICRONEEDLE ARRAY TO SKIN.
  • One exemplary applicator 400 is illustrated in FIGS.8–9 and further described U.S.
  • the applicator 400 includes a body 402 having an upper housing 404 and a lower housing 406.
  • the lower housing 406 includes an upper portion 418, a middle portion 420, and a lower portion 422.
  • the upper portion 418 of the lower housing 406 includes an outer surface 424 that can have a smooth surface finish or other finish with low surface energy to enable sliding engagement with an inner surface of upper housing 404.
  • Middle portion 420 of the lower housing 406 can include a slot 430 or opening for insertion of a microneedle array carrier 440 (FIG.9).
  • Lower portion 422 includes a lower surface 438 on its underside.
  • the applicator 400 includes a plunger 474 that can include a plunger post 494, a first plunger disc 498, and a second plunger disc 500 proximate a lower end thereof.
  • the applicator 400 further includes a firing spring 510 disposed proximate the first plunger disc 498 presented on plunger 474.
  • biasing members other than compression springs such as leaf springs, rubber members, or structures, can be used in place of or alternative to compression springs.
  • the lower surface 438 of lower portion 422 of lower housing 406 is placed in contact with the skin or another surface, such as a sterile or sanitary surface “S.”
  • the upper housing 404 is pushed down axially along an axis 512 of applicator 400 such that the inner surface of the upper housing 404 slides over the outer surface 424 of lower housing 406 and firing spring 510 is compressed and, thus, energized.
  • This energized firing spring 510 is later used to drive the drug delivery device 10 from the applicator 400.
  • the drug delivery device 10 can be inserted into the slot 430 of the applicator 400 via a microneedle array carrier 440.
  • Such carrier 440 is further described, e.g., in U.S.
  • the second plunger disc 500 of spring-loaded plunger 474 can be positioned to rest directly against or very close to the second major surface 15 of the drug delivery device 10 once primed or come into direct contact of come very close to bottom surface second major surface of the drug delivery device when the upper housing 404 is again pressed axially down, but before the plunger 474 is released (i.e., the applicator 400 is fired).
  • a user can inhibit instability issues that might arise if a plunger were to accelerate and hit a microneedle array assembly to release it from the carrier while still in the applicator.
  • the plunger 474 pushes the drug delivery device 10 from microneedle array carrier 440 as it begins to accelerate and reaches the desired impact speed about a time, or substantially simultaneously with, the drug delivery device contacting the skin.
  • the applicator 400 can be configured to apply different impact and holding forces behind different discrete arrays to optimize depth of penetration.
  • the applicator 400 can be configured to apply a first impact force to a discrete array having a length h 1 of each microneedle and a second impact force to a discrete array having a length h2 of each microneedle, where h1 is greater than h2.
  • the applicator 400 can be configured such that a lower surface of the second plunger disc 500 that contacts the drug delivery device 10 can have one or more non-parallel or non-uniform shapes that can provide variations in penetration depth to the microneedles of the various discrete arrays 16.
  • FIG.10 is a flowchart of one embodiment of a method 600 of forming the drug delivery device 10. Although described regarding device 10 of FIGS.1–5, the method 600 can be utilized to form any suitable drug delivery device.
  • the plurality of discrete arrays 16 can be formed using any suitable technique.
  • the plurality of discrete arrays 16 includes the first discrete array 18 having the first substrate 20 and the first microneedles 22 disposed on the first substrate, and the second discrete array 24 having the second substrate 26 and the second microneedles 28 disposed on the second substrate 26.
  • the first discrete array 18 includes the first characteristic
  • the second discrete array 24 includes the second characteristic that is different from the first characteristic.
  • the plurality of discrete arrays 16 can include any suitable number and type of discrete arrays.
  • the plurality of discrete arrays 16 can include the third discrete array 40 that includes the third substrate 42 and third microneedles 44 disposed on the third substrate, where the third discrete array includes a third characteristic different from the first characteristic and second characteristic.
  • At least one of the first discrete array 18 or the second discrete array 24 can be formed by microreplication.
  • the adhesive layer 30 can optionally be disposed on the first major surface 14 of the backing layer 12 at 604 using any suitable technique for embodiments where the plurality of discrete arrays 16 are disposed on the backing layer prior to be disposed on the skin of the user.
  • the plurality of discrete arrays 16 can optionally be disposed on the first major surface 14 of the backing layer 12 when such backing layer is utilized. Any suitable technique can be utilized to dispose the discrete arrays 16 on the backing layer.
  • one or more of the discrete arrays 16 can be connected together prior to being disposed on the backing layer 12.
  • the discrete arrays 16 can be disposed on the skin of the user using any suitable technique.
  • an applicator e.g., applicator 400
  • One or more openings can be disposed through at least one discrete array of the plurality of discrete arrays 16 using any suitable technique prior to disposing such arrays on the skin of the user.
  • one or more fluid channels 78 can be disposed between adjacent arrays of the discrete arrays 16 using any suitable technique. Any suitable number of channels 78 can be disposed between two or more discrete arrays of the plurality of discrete arrays 16.
  • Example Ex1 A drug delivery device that includes a backing layer having a first major surface and a second major surface, and a plurality of discrete arrays disposed on the first major surface of the backing layer.
  • the plurality of discrete arrays includes a first discrete array that has a first substrate and first microneedles disposed on the first substrate, and a second discrete array that has a second substrate and second microneedles disposed on the second substrate.
  • Example Ex2. The device of Ex1, where the first discrete array includes a first characteristic and the second discrete array includes a second characteristic different from the first characteristic.
  • Example Ex2 where the first characteristic includes a first arrangement of the first microneedles and the second characteristic includes a second arrangement of the second microneedles, where the first arrangement is different from the second arrangement.
  • Example Ex4 The device of any of Ex2 to Ex3, where the first characteristic includes a shape of at least one first microneedle and the second characteristic includes a shape of at least one second microneedle.
  • Example Ex5. The device of Ex4, where the at least one first microneedle includes a first cross-sectional shape in a plane parallel to the backing layer and the at least one second microneedle includes a second cross-sectional shape in the plane parallel to the backing layer.
  • Example Ex6 Example Ex6.
  • Example Ex7 The device of any one of Ex2 to Ex5, where the first characteristic includes an aspect ratio of at least one first microneedle and the second characteristic includes an aspect ratio of at least one second microneedle.
  • Example Ex7 The device of any one of Ex2 to Ex6, where the first characteristic includes a first medicament disposed on at least one first microneedle and the second characteristic includes a second medicament disposed on at least one second microneedle.
  • Example Ex8 The device of any one of Ex2 to Ex7, where the first characteristic includes a first shape of the first substrate of the first discrete array in a plane parallel to the backing layer and the second characteristic includes a second shape of the second substrate of the second discrete array in the plane parallel to the backing layer.
  • Example Ex10. The device of Ex9, where the polygonal shape includes at least three sides.
  • Example Ex11. The device of any one of Ex9 to Ex10, where the polygonal shape includes no greater than seven sides.
  • Example Ex12. The device of any one of Ex9 to Ex11, where the polygonal shape includes a diamond shape.
  • Example Ex13 The device of Ex13, where a third characteristic of the third discrete array is different from the first characteristic and the second characteristic.
  • Example Ex15 The device of any one of Ex1 to Ex14, where the plurality of discrete arrays form a tessellated pattern on the backing layer.
  • Example Ex16 The device of any one of Ex1 to Ex15, where the first discrete array is in contact with the second discrete array.
  • Example Ex17 The device of any one of Ex1 to Ex15, further including a fluid channel disposed between the first and second discrete arrays.
  • Example Ex18 The device of any one of Ex1 to Ex17, where at least one microneedle of the first or second microneedles includes a dissolvable material.
  • Example Ex19 The device of any one of Ex1 to Ex17, where at least one microneedle of the first or second microneedles includes a dissolvable material.
  • Example Ex20 The device of any one of Ex1 to Ex18, further including an opening disposed through at least one of the first substrate of the first discrete array or the second substrate of the second array.
  • Example Ex20 The device of any one of Ex1 to Ex19, where a first portion of the first substrate of the first discrete array includes an arrangement of first microneedles and a second portion of the first substrate does not include first microneedles.
  • Example Ex21 The device of any one of Ex1 to Ex20, where the first discrete array further includes one or more alignment features that are configured to be connected to one or more alignment features of the second discrete array such that the first discrete array is connected to the second discrete array.
  • Example Ex22 Example Ex22.
  • Example Ex23 The device of any one of Ex1 to Ex21, further including an adhesive layer disposed on the first major surface of the backing layer such that the adhesive layer is between the first and plurality of discrete arrays and the first major surface of the backing layer.
  • Example Ex23 The device of Ex22, where a portion of the adhesive layer adjacent to a periphery of the backing layer is exposed such that the adhesive layer is configured to be adhered to skin of a user.
  • Example Ex24 The device of any one of Ex1 to Ex23, where the backing layer includes a polygonal shape in a plane parallel to the first major surface of the backing layer.
  • Example Ex26 A method of forming a drug delivery device. The method includes forming a plurality of discrete arrays, where the plurality of discrete arrays includes a first discrete array having a first substrate and first microneedles disposed on the first substrate, and a second discrete array having a second substrate and second microneedles disposed on the second substrate. The first discrete array includes a first characteristic and the second discrete array includes a second characteristic different from the first characteristic. The method further includes disposing the plurality of discrete arrays on skin of a user.
  • Example Ex27 A method of forming a drug delivery device. The method includes forming a plurality of discrete arrays, where the plurality of discrete arrays includes a first discrete array having a first substrate and first microneedles disposed on the first substrate, and a second discrete array having a second substrate and second microneedles disposed on the second substrate. The first discrete array includes a first characteristic and the second discrete array includes a second characteristic different from the first characteristic.
  • Example Ex26 further including disposing the plurality of discrete arrays on a first major surface of a backing layer prior to disposing the plurality of discrete arrays on the skin of the user, where the backing layer further includes a second major surface.
  • Example Ex28 The method of Ex27, further including disposing an adhesive layer on the first major surface of the backing layer such that the adhesive layer is between the plurality of discrete arrays and the first major surface of the backing layer.
  • Example Ex29 The method of any one of Ex26 to Ex28, where forming the plurality of discrete arrays includes microreplicating at least one of the first discrete array or second discrete array.
  • Example Ex31 The method of any one of Ex26 to Ex30, where forming the plurality of discrete arrays includes forming the first discrete array by disposing the first microneedles in a first arrangement on the first substrate and forming the second discrete array by disposing the second microneedles in a second arrangement on the second discrete array.
  • the first characteristic includes the first arrangement and the second characteristic includes the second arrangement.
  • Example Ex32 The method of any of Ex26 to Ex31, further including disposing a fluid channel between the first discrete array and the second discrete array.
  • Example Ex33 The method of any one of Ex26 to Ex32, further including disposing an opening through at least one of the first substrate of the first discrete array or the second substrate of the second array.
  • Example Ex34 The method of any one of Ex28 to Ex33, where forming the plurality of discrete arrays further includes forming a third discrete array having a third substrate and third microneedles disposed on the third substrate, where the third discrete array includes a third characteristic different from the first characteristic and second characteristic.
  • Example Ex35 A drug delivery system including the drug delivery device of any one of Ex1 to Ex25 and an applicator configured to apply the drug delivery device to skin of a patient.

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Medical Informatics (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Media Introduction/Drainage Providing Device (AREA)

Abstract

Divers modes de réalisation d'un dispositif d'administration de médicament (10, 200, 300) sont décrits. Le dispositif comprend une couche de support (12, 312) ayant une première surface principale (14, 314) et une seconde surface principale (15) et une pluralité de réseaux discrets (16, 216, 316) disposés sur la première surface principale de la couche de support. La pluralité de réseaux discrets comprend un premier réseau discret (18, 318) qui a un premier substrat (20, 220, 320) et des premières micro-aiguilles (22, 322) disposées sur le premier substrat, et un second réseau discret (24, 216, 324) qui a un second substrat (26, 220, 326) et des secondes micro-aiguilles (28, 328) disposées sur le second substrat.
PCT/US2023/082372 2022-12-16 2023-12-04 Dispositif d'administration de médicament WO2024129424A1 (fr)

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US63/433,257 2022-12-16

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