WO2022061430A1 - Dispositif prothétique tubulaire cylindrique non polymère - Google Patents

Dispositif prothétique tubulaire cylindrique non polymère Download PDF

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Publication number
WO2022061430A1
WO2022061430A1 PCT/BR2021/050361 BR2021050361W WO2022061430A1 WO 2022061430 A1 WO2022061430 A1 WO 2022061430A1 BR 2021050361 W BR2021050361 W BR 2021050361W WO 2022061430 A1 WO2022061430 A1 WO 2022061430A1
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release
stent
prosthetic device
cells
vascular
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PCT/BR2021/050361
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English (en)
Portuguese (pt)
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Christiane Dias MAUÉS
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Maues Christiane Dias
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
    • A61B5/6862—Stents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0002—Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network
    • A61B5/0015—Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network characterised by features of the telemetry system
    • A61B5/0024—Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network characterised by features of the telemetry system for multiple sensor units attached to the patient, e.g. using a body or personal area network
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0002—Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network
    • A61B5/0031—Implanted circuitry
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06—Blood vessels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment

Definitions

  • the present invention refers to medical devices implantable in the human body, and, more precisely, to intravascular prosthetic devices, called “stents", expandable, of usual shape, of metallic constitution, or biocompatible organic resin, with anatomical properties , physiological (pharmacological) and favorable mechanics, used in the correction of stenosis or narrowing of the vascular wall or body ducts, aiming to maintain their support for a longer period of time, in addition to promoting an ideal remodeling process due to balanced healing activity of the affected vascular wall.
  • Such a device required a cooling technique prior to its insertion, and the subsequent administration of local heat (electrical heating) until its complete expansion, with recovery of its initial configuration, unlike the current balloon catheters that are widely used for its insufflation; this process was reflected in a great disadvantage, causing serious injury to the surrounding vascular tissues and increasing blood thrombogenic potential.
  • the release balloon catheters have a smaller profile, which allows the use of smaller guide catheters, being able to reach higher pressures, in addition to the conventional guide ropes for coronary angioplasty, with 0.014 inches. Radiopaque gold markings have been added to the ends of this latest generation of Gianturco prostheses for safer and more accurate positioning.
  • stents by themselves, can prevent the phenomenon of post-intervention vascular elastic recoil and seem to also act in adverse remodeling, but in preventing in-stent restenosis, the additional use of an agent release strategy antiproliferative drugs of the stent itself, acting to synergistically reduce the restenotic lesion, was necessary.
  • endoprostheses have current applicability both in acute ischemic syndromes (unstable angina and myocardial infarction) and in stable chronic coronary artery disease.
  • acute myocardial infarction its use has ranged from the primary interventional condition, such as rescue circumstances after failure of fibrinolytic treatment, and still the elective indication, when the presence of severe residual stenosis is verified.
  • the first stents were developed with the aim of increasing short and long-term results in coronary angioplasty procedures, but with the introduction of the first drug-eluting stents, the immediate results showed a significant reduction in restenosis rates, but these concomitantly caused a chemical sweep of the subendothelial and neointimal layers of the vascular wall, rather than preventing a balanced tissue neoformation. Later effects related to polymeric biodegradation, involving the phenomenon of late thrombosis, inevitably emerged.
  • the ideal stent is the one that offers a biocompatible platform of polymeric material or, when absent, provides effective and safe rates and concentrations of drug release at the affected site, in addition to electrochemical properties and biomolecular, and high absorption capacity of the vascular wall.
  • PI 0317150-7 A Publication Date: 11/01/2005
  • PI0213279-6 A Publication Date: 10/26/2004
  • PI 0503201-6 A Publication Date: 03/13/2007
  • US 20100191323 A1 Publication Date: 07/29/2010
  • US 20090182404 Al Publication Date: 07/16/2009.
  • the primary objective of the invention is the development of a biocompatible, non-polymeric intracoronary device for the release of multiple drugs, in a gradual and controlled manner, through extrinsic factors, such as precursor drugs released via implants organic - intradermal microchips (which would have the function of releasing in a controlled, gradual and pre- programmed, via remote central, by a software, device or cell phone, the precursor drugs, responsible for, through the bloodstream, reaching the prosthesis and acting in the mechanism of release of specific medications in the target site of the stent), or via matrices slow drug release organics, of polymeric constitution, or biological films, or even subdermal resins (release systems); and when that is the case, these microchips still contain nanochips and biosensors in their own structure, in order to optimize the control and the in-stent drug release pulse, in addition to providing real-time measurements of hemodynamic, chemical and homeostatic variables, aiming at this type of prosthesis to fill the gap of biases and clinical complications, through the
  • the objective through the control of vascular proliferative response or intimal hyperplasia, is to significantly reduce the rates of late restenosis and complications emerging from the post-drug stent era, whether thromboses intra- or peri-stent acute episodes.
  • this privilege has a non-polymeric biological matrix constituting a release coating on its inner part, and which has the function of elution of biomolecules of chemical substances, with anti-atherogenic, antiproliferative, antithrombotic, antichemotactic and vascular wall restructuring agents, providing the storage and multi-release function of drugs, stored and grouped in microcapsules or microspheres (liposomes), involved in a network (matrix) of macromolecular protein composition, or a biological film that has chemical compatibility reaction with the various types of medication to be delivered extrinsically (such as a subdermal implanted precursor medication delivery biochip).
  • Such a mechanism would be responsible for minimizing the late effects resulting from the degradation of polymers, since the first stents were introduced in 2001, with monotherapy-type delivery platforms (a single drug), eventually generating the fearsome long-term complications related to the necessary and massive oral antithrombotic prophylaxis (anticoagulation), as well as acute late in-stent thrombosis.
  • the skeleton of the prosthetic drug delivery system with a non-polymeric matrix say cylindrical tubular prosthetic device or stenter-type prosthetic device itself, consists of a fenestrated tubular diagram, with a regular cylindrical shape, multifilament, without presenting, however, median joint; characterized by having an initial diameter, which allows its release intravascular or in any organic duct containing a lumen, and a final diameter, expanded, through the application of radial and centrifugal force, via balloon catheter, or simply being self-expanding.
  • Nitinol is composed of a nickel-titanium metal alloy, with thermal memory properties, often used in medical prostheses and orthotics; shows good biocompatibility: minimal inflammatory response in adjacent tissues, without corrosion of the material.
  • the first intravascular stents described by Dotter and subsequent authors were nitinol stents.
  • the objective is the elaboration of prostheses in diameters of 4.0 mm and 5.0 mm, with lengths ranging from 12 mm, 18 mm and 24 mm, not discarding a posteriori a smaller diameter and/or longer length molding.
  • the thickness of the stem cells can range from 0.08 to 0.12 mm, an important fact to reduce the tendency to thrombosis and trauma to the vascular wall, which is also a consequence of the prosthesis finishing process, which includes the chemical polishing of the rods and laser cutting for the configuration of the material and its spatial structure.
  • the internal matrix of release is represented by an artificial biological membrane, biocompatible, and may consist of phospholipids and/or macroproteins, or similar substrate, and may or may not be microporous, as long as it allows good capacity for diffusion and release of drugs.
  • the spatial geometric design is arranged in hexagonal cells that come from the extension of the supporting prosthesis, that is, from the cells that compose the spatial conformation of the "stent" itself, open, on the entire internal surface of the stent, that is, in towards the vascular lumen.
  • This inner layer will also follow the format compatible with the "design" of the mesh of the stent to be chosen, whether with pure hexagonal cells, hexagonal cells coapted at the lower and upper ends by diamond cells, or intercepted by hexagonal cells in a more cylindrical shape, largest longitudinal diameter, interposed between standard hexagonal cells.
  • microcapsules or groups of liposomes contained within the hexagonal cells that form the supporting biological membrane, are arranged in aggregate and sustained, immersed in a matrix that forms chains or networks of protein macromolecules, or these conjugated to other molecules organic compounds such as phospholipids, in the form of a biological film or gel, so that they provide sufficient sustainability and an ideal fixation rate.
  • the microcapsules/liposomes (which in this space would be grouped into morulae) will be gradually and selectively released through a combination action and pharmacological reaction (from precursor drugs released in a controlled and programmed way by an implanted intradermal microchip, subject to the control of any modality of external central, or even from electrical stimuli or release of the same types of pharmacological precursors from nanochips on the internal surface of the stent, arranged in the proper intervals, corridors separating the hexagonal cells of the "coating" internal), responsible for the rupture of connection bridges and stabilization of macromolecular protein chains, a process that occurs via enzymatic degradation.
  • a biologically compatible resin contained in porous or non-porous surface, such as the use of albumin, with the objective of increasing the matrix porosity coefficient.
  • the drugs released from the encapsulated structure or from the liposomal group will be gradually and protocolarily submitted to an investigation process in an experimental model, computational analysis, pre-clinical and clinical studies, in order to evaluate with effectiveness and certainty the compatible pharmacological type to be used, the ideal concentration to be reached in the vessel lumen, the best diffusion coefficient, the speed and intervals of release, half-life at the vascular locus, metabolism and toxicity, among other aspects; emphasizing that, during all phases of the elaboration, evaluation, production, "in vitro” and "in vivo” scientific feasibility tests, it will be possible to modify, eliminate, add or merge whatever types of drugs, according to the necessary formalities, as well as obliterating or reconstructing pertinent elements, provided that there are no profound changes in the previously idealized global set.
  • the present invention is objectively established to attenuate or eliminate the occurrence of restenosis (recurrent atheromatous plaque growth), later on, and still prevent late acute thrombosis, even after balloon angioplasty and/or prosthesis placement stenting type of the vascular wall, which arise from a variety of factors, namely:
  • Myointimal hyperplasia or proliferation of neointimal tissue, is one of the main mechanisms responsible for in-stent restenosis.
  • micro or nanochips in conjunction with intravascular or organic devices: much has been reported about the innovative possibility of incorporating drugs into medical implants, thus using multiple reservoirs containing small doses of these drugs.
  • microchips represent a new type of technology capable of releasing different drugs for long periods of time.
  • IDDS Industrial Drug Delivery Systems
  • biodegradable and non-biodegradable physiological pump systems of microfluids
  • micromanufacturing of controlled release systems endowed with an intelligent and programmable microelectronic capacity, which microchips consist of.
  • Implantable microchips solved the need for a controlled release system, being mostly made of silicone, containing multiple drug reservoirs, in a possibility of different forms and presentations, usually hermetically sealed, and covered by a metallic membrane, to be dissolved by electrical stimulation, allowing the release of its constituents (drugs) to the environment.
  • Microchips are manufactured using the same technology developed in microelectronic integrated circuits and systems of microelectromechanical origin, a process used for the manufacture of microdevices, such as flow and pressure sensors, ink printer heads, etc. Still, it is noteworthy that the manufacture of this technology involves the use of surface substrate, ceramic, and more often silicone, combining photolithography techniques, aiming at the creation of desired geometric shapes to be applied to the reservoirs. Then, anode-cationic dipoles are created, and, after that, complementation with the drugs of choice.
  • FIGURE 1 is a perspective illustration of a cylindrical tubular prosthetic device, standardized stent type, intraluminally expandable, balloon-catheter or self-expanding, in metallic support or in biocompatible resin, isolated from its internal matrix of release, "coating" as described (FIGURE IA and FIGURE 1B), where the conformational pattern of its mesh, support or support of the internal biological coating can be observed, and in the complete presentation showing its internal "coating” (FIGURE 1C), and also a peripheral intradermal microchip, working together with the stent; the one with its spatial structure arranged in hexagonal cells, coapted together, in a regular polyhedral geometric conformation (FIGURE 1B), or in the pattern of hexagonal cells coapted by lozenge cells, arranged in the longitudinal direction of the prosthesis (FIGURE IA), emphasizing the direction of arrangement of the hexagonal mesh can be alternative, if in a transverse arrangement (sides of the hexagon make up the edges of the prosthesis), FIGURE 2
  • Such a prosthetic device will be responsible for the gradual, regulated and continuous release of different drugs, in order to prevent coronary restenosis and induce early regeneration of the previously affected vascular wall, from the release of precursor drugs, coming from this peripheral intradermal biochip, which at released into the bloodstream, after a certain period of time, reach the vascular prosthetic device, drug-eluting stent, in its inner layer, and through a conjugation with the internal matrix of the hexagonal cells (combination and pharmacological reaction, mainly by enzymatic hydrolysis, or other alternative types of chemical reaction compatible with the medium), are responsible for carrying out the release of in-stent medications, whether microcapsules, or unified groups of liposomes, contained and housed in specific superimposed layers in which constitute the hexagonal cells of the internal coating of the stent.
  • precursor drugs released in a controlled and programmed manner by this intradermal microchip, present their pulse of release into the bloodstream, as well as intervals, concentration, and other potentially measurable pharmacological variables, subject to control over this microchip implant from any external central modality. , software or mobile communication device. Presence of supporting nanosensors in the structure of the releasing biochip is possible to introduce, with the function of measuring the volume of release pulses, hemodynamic and serum biochemical variables, control of intervals, concentrations, etc.
  • FIGURE 2 indicates a perspective illustration of the same standardized stent-type cylindrical tubular prosthetic device, intraluminally expandable, by balloon-catheter or self-expanding, in metallic support or in biocompatible resin (FIGURE 2A), stripped of its internal matrix of release, internal coating as described, revealing that the incorporation of nanosensors/nanochips is feasible not only in this implantable biochip in the skin, but can even be represented and located on the internal surface of the stent (FIGURE 2B), or arranged in the proper intervals between cells, separating corridors of the hexagonal cells of the internal coating of the prosthesis, able to regulate and compulsorily measure the concentration rates of intra-stent drugs, serum medication half-life, sequential metabolism rate, and drug elimination time , among several other pharmacological and metabolic variables, as well as biochemical markers.
  • FIGURE 3 is a different perspective illustration of a cylindrical tubular prosthetic device, standardized stent type, intraluminally expandable, balloon-catheter or self-expanding, in metallic support or in biocompatible resin, isolated from its internal matrix of release ( FIGURE 3A), internal coating as described, where the conformational pattern of its mesh can be observed, different from the the former, as a support or support of the internal biological coating, and the global prototype with the aforementioned "coating" (FIGURE 3B), and a peripheral intradermal microchip, in joint action; the one with its spatial structure arranged in hexagonal cells, coapted laterally to each other, in a regular polyhedral geometric conformation, and intercepted at their upper and lower ends, that is, sides that make up the acute internal angle of the hexagonal cells, by cells in the shape of a diamond, in complete contiguity, arranged in the longitudinal direction of the prosthesis.
  • Such a prosthetic device will also be responsible for the gradual, regulated and continuous release of several drugs, in order to prevent coronary restenosis and induce early regeneration of the previously affected vascular wall, from the release by precursor drugs, coming from this peripheral intradermal biochip, which when released into the bloodstream, after a certain period of time, they reach the vascular prosthetic device, drug-eluting stent, in its inner layer, and through a conjugation with the internal matrix contained in both hexagonal and diamond cells (combination and pharmacological reaction, primarily by enzymatic hydrolysis, or other alternative types of chemical reaction compatible with the medium), are responsible for executing the release of in-stent medications, whether microcapsules, or unified groups of liposomes, contained and housed in specific layers superimposed on that make up the hexagonal and rhombus cells es of the internal stent coating.
  • Nanosensors/nanochips can also be present in this implantable biochip in association, which constitutes the delivery system in its complexity, or even be represented by nanochips or nanosensors, located on the inner surface of the stent, or arranged in the very intervals between cells, corridors for separating hexagonal and diamond cells from the internal coating of the prosthesis, capable of regulating and compulsorily measuring the concentration rates of in-stent drugs, drug serum half-life, sequential metabolism rate, and drug elimination time , among several other pharmacological, metabolic, and biochemical markers.
  • FIGURE 4 and FIGURE 5 represent a perspective illustration of the same prosthetic device of FIGURES 1 and 2, now together with its internal release matrix, described internal "coating”, which is represented by artificial biological membrane, biocompatible, It can be produced by tissue engineering techniques and consist of phospholipids and proteins, or similar substrate of organic constitution or synthesized in tissue engineering, and can be microporous or not, as long as it allows good diffusion and drug release capacity.
  • internal "coating” which is represented by artificial biological membrane, biocompatible, It can be produced by tissue engineering techniques and consist of phospholipids and proteins, or similar substrate of organic constitution or synthesized in tissue engineering, and can be microporous or not, as long as it allows good diffusion and drug release capacity.
  • the spatial geometric design of the internal coating is arranged in hexagonal cells, as shown in FIGURE 1B and FIGURE 1C, which come from the extension of the support prosthesis, that is, from the cells that make up the spatial conformation of the stent itself, open , on the entire internal surface of the stentor, that is, towards the vascular lumen (FIGURE 4A, 4B and 4C), or it is arranged in alternating hexagonal cells with lozenge cells intercepted to the last ones, according to the "design" shown of the metallic mesh in FIGURE IA, which also come from the extension of the supporting prosthesis, that is, from the cells that make up the spatial conformation of the stent itself, open, on the entire internal surface of the stent, that is, towards the vascular lumen (FIGURE 5A and 5B ).
  • FIGURE 6 shows, from an approximate focus, the microcapsules or group of liposomes, contained within the hexagonal cells, since referenced specifically, the first type of stent, with a conformational pattern of its "design" of mesh continued between hexagonal cells, as already highlighted in the epigraph, these then form the biological support membrane, and which are arranged in aggregates and sustained, in specific layers , immersed in a matrix that forms chains or networks of protein macromolecules, or these conjugated to other organic molecules such as phospholipids, in the form of a biological film or gel, in a way that provides sufficient sustainability and an ideal fixation rate.
  • FIGURES 6 and 7 are perspective illustrations of said cylindrical tubular prosthetic device, standardized stent type, intraluminally expandable, with its internal drug delivery matrix, in an approximate section that shows how this matrix is arranged, whether in cells also hexagonal, in a universal conformational pattern (FIGURE 6), or according to the diverse model with hexagonal cells coapted laterally, intercepted superiorly and inferiorly by lozenge cells, thus forming a conformational pattern of its mesh "design” alternating between hexagonal cells and lozenge, as already mentioned in the title (FIGURE 7); that come from the extension of the supporting prosthesis, that is, from the cells that compose the spatial conformation of the prosthesis, according to its reference "design-model", properly speaking, open, on the entire internal surface of the stent, that is, towards the to vascular light.
  • microcapsules or groups of liposomes contained within the hexagonal cells, or hexagonal cells + diamond cells, which form the biological support membrane, are arranged in aggregates and supported, in homogeneous layers, one on top of the other (in the figures , represented by different colors, that is, each layer shown in a certain color, representing a modality of liposome/microcapsule group, containing a different type of drug), immersed in a matrix that forms chains or networks of protein macromolecules, or others types of biomolecules, in a way that provides sufficient sustainability and an ideal fixation rate.
  • Each layer will be formed by a support matrix of different chemical composition, one from the other, aiming to provide the specificity and selectivity of release of a certain in-stent drug, contained in liposomes/microcapsules, according to the type of medication. released by the intradermal microchip implant, this release being fully optimized by a remote control center, regarding the release pulse interval, concentration, doses, pharmacological specificity, etc.
  • This precursor drug released via intradermal microchip implantation, when falling into the bloodstream, reaching the internal surface of the stent, will be responsible for interacting with the specific support matrix of a certain layer, for which it is programmed, dissolving and releasing it, selectively and specifically, a particular type of drug, aiming not only to control vascular restenosis, but also to modulate the inflammatory and proliferative response of the myointimal wall, adversity that frequently occurred in the implantation of polymeric drug-eluting stents, in general.
  • FIGURES 8 and 9 are perspective illustrations of said cylindrical tubular prosthetic device, standardized stent type, intraluminally expandable, with its internal drug delivery matrix, and the schematic representation of the substance released via intradermal implant of any constitution (precursor drugs ), represented by polymeric matrices for remote release, microfluids, but mainly by a biochip for releasing pharmacological substances, remotely programmed and controlled, among others.
  • Biochip that may have an inorganic or organic constitution, polymer or silicone, or any other compatible resin.
  • FIGURES 10 and 11 are a new perspective illustration of the same prosthetic device as FIGURES 1, 2, 3 and 4 in which they portray the arrival of substances/medications released by subdermal implants, those with a different biochemical constitution from the previous one, mainly in the with regard to the application of a subdermal implanted biochip, whose release of these precursor drugs must be controlled, quantified and monitored by a remote external central, reaching the light of the vessel in which the prosthetic device is located, and interact with the support matrix of the layers that form and fill the internal cavity of each hexagonal cell, or hexagonal and diamond-shaped, of the delivery platform.
  • these substances will interact with the first layers of the support matrix located towards the vessel light, that is, only and specifically with those layers whose chemical constituents are reactive to the action of these substances, thus providing the release of microcapsules/groups of liposomes stored and supported by this matrix.
  • the possibility of effecting a selectivity and diversity in the release mechanism of drugs applied intra-stent or intra-prosthetic device In schematic color presentations, the different representations of each type of medication administered are differentiated by each color, and this is also applied to the microcapsules/groups of liposomes programmed to be released, from the specific layer (hexagonal or lozenge cell support matrix) .
  • FIGURES 12 to 16 sequentially represent the perspective illustration of the mechanism of interaction of the precursor substance/medication, released by the intradermal biochip, which reaches the stent, with its internal surface where it combines the support layers of the liposomes/microcapsules, and these are progressively released to act on the vascular wall.
  • FIGURES 17 to 24 also represent, in perspective view through the vascular prosthetic device, a new process of arrival of a different administered substance released by any other route, whether it is an intradermal implant of chemical or electronic constitution (biochip with reservoir drug release, controlled by an external central), that is, an intradermal biochip, reaching the inner surface of the stent, culminating, in the same way as described in the last paragraph, with the release of other types of in-stent drugs, compatible and programmed for release according to the action of the substance released by the intradermal implant.
  • an intradermal implant of chemical or electronic constitution biochip with reservoir drug release, controlled by an external central
  • FIGURE 25 demonstrates, in essence or scope, the novelty and pioneering spirit on which this privilege is based, with the introduction of a new modality of drug release in vascular stent, through the remote action of a biochip implantable, containing one or more activation-reception boards, operated by any modality of central/external command, be it automated control, telephony devices, PC unit, etc. support of the precursor drugs, these will then be released via the bloodstream, reaching the vascular stent, and acting locally in the specific pharmacological release, arranged in its internal cover, under temporal control pulses, concentration and specific type of in-stent medication.
  • a biochip implantable containing one or more activation-reception boards, operated by any modality of central/external command, be it automated control, telephony devices, PC unit, etc. support of the precursor drugs, these will then be released via the bloodstream, reaching the vascular stent, and acting locally in the specific pharmacological release, arranged in its internal cover, under temporal control
  • FIGURE 26 emphasizes that it is feasible and opportune to consider the alternative production of this organic or vascular prosthetic device in a variant of this second model, with hexagonal cells, coapted at their lower and upper ends by diamond cells, and these, in turn, are fenestrated. , not coated internally in their area by the drug release coating, which is an advantage and an indication property for the introduction of vascular prosthesis in situations of lesions in collateral branches.
  • FIGURES 27 to 30 demonstrate in perspective view the same intraluminal drug delivery system of the previous figures, in which, in a next step of new administration of another type of substance, it already reaches, interacts and releases another type of intraluminal medication - stent, contained in aggregated microcapsules/liposomes and supported in a different layer, consisting of a compatible support matrix.
  • FIGURES 1, 2, 3 and 4 illustrate a first and second embodiment of an expandable intraluminal cylindrical tubular prosthetic device, or stent type prosthetic device, or simply a prosthesis, or even a stent, built in accordance with the standards of the present invention.
  • the aforementioned terms "expandable intraluminal cylindrical tubular prosthetic device”, “stent type prosthetic device”, “stent” or simply “prosthesis” are applied simultaneously to name the present invention, as the latter may have its use attributed to vascular segments in a general, as well as to organic ducts, with the aim of correcting stenosis or narrowing and sustaining their tonus.
  • FIGURE 1 presents the prosthetic device type stenter 41 (FIGURE IA), in metallic support or in biocompatible resin, with its spatial structure arranged in hexagonal cells, coapted laterally to each other, in regular polyhedral geometric conformation, and intercepted in its upper and lower ends, that is, sides that make up the internal acute angle of the hexagonal cells, by diamond-shaped cells, in complete contiguity, arranged in the longitudinal direction of the prosthesis.
  • FIGURE 1B shows the same stent type prosthetic device 31, in metallic support or biocompatible resin, whose spatial structure configures the conformational alternative modality of hexagonal cells, coapted together, arranged in the longitudinal direction of the prosthesis, isolated from its internal matrix of release , internal "coating" as described above 32, where the conformational pattern of its mesh, support or support of the internal biological coating can be observed, this increased to FIGURE 1C, which defines the global structure of the stent (intravascular prosthetic device) 50 , already associated or together with its internal release matrix, described internal “coating", which is represented by an artificial biological membrane, biocompatible, which may consist of phospholipids and proteins, or similar substrate, and may or may not be microporous, as long as allow good diffusion capacity and drug release 32.
  • FIGURE 1 a microc peripheral intradermal implanted hip 43, acting together with the stent, causing the release of precursor drugs 36, contained in plate(s) 44 that are located inside, arranged in groups of micro-reservoirs, surrounded by peculiar circuits 45, each which contains a specific type of precursor drug 36, which will be released into the bloodstream, which, after a certain time interval, reaches the vascular prosthetic device 50, drug-eluting stent, in its inner layer, and through a conjugation with the matrix of the cells that constitute their "coating" (internal coating) 32, stratified in layers with specific intra-stent medications 33, will be responsible for carrying out the release of these, either the microcapsules 33 or unified groups of liposomes, contained and housed in specific superimposed layers that constitute the hexagonal or diamond-shaped cells of the stent's internal coating 32.
  • precursor drugs 36 contained in plate(s) 44 that are located inside, arranged in groups of micro-reservoirs, surrounded by peculiar circuits 45
  • these precursor drugs 36 released in a controlled and programmed manner by this intradermal microchip 43, present their release pulse in the bloodstream, as well as ranges, concentration, and other potentially measurable pharmacological variables, subject to control over this microchip implant from any form of external switch, software, or mobile communication device.
  • nanosensor(s) 46 adjunct(s) in the structure of the releasing biochip is subject to introduction, as also shown in FIGURE 1, with the function of measuring the volume of release pulses, hemodynamic and serum biochemical variables , control of intervals, concentrations, etc.
  • FIGURE 2 is a different perspective illustration of a cylindrical tubular prosthetic device, standardized stenter type 41, intraluminally expandable, by balloon-catheter or self-expanding, in metallic support or in biocompatible resin (FIGURE 2A), proving to be feasible the incorporation of nanosensors/nanochips 49 not only in this skin implantable biochip 43, but they can even be represented and located on the inner surface of the "stent" (FIGURE 2A and FIGURE 2B), whose functions are described above.
  • the cylindrical tubular prosthetic device standardized stenter type 41
  • the cylindrical tubular prosthetic device is accompanied by its internal release matrix, internal "coating" as described 42, see FIGURE 3A and FIGURE 3C, whose spatial conformation ("design") follows the geometric spatial pattern of the metallic support stent 41, detailed in this one, where the conformational pattern of its mesh, different from the previous one, as support or support of the internal biological coating 42, and a peripheral intradermal implanted microchip 43, in joint action; the one with its spatial structure arranged in hexagonal cells 47, coapted laterally to each other, in polyhedral regular geometric conformation, and intercepted at their upper and lower ends, that is, sides that make up the internal acute angle of the hexagonal cells, by rhombus-shaped cells 48, in complete contiguity, arranged in the longitudinal direction of the prosthesis.
  • design follows the geometric spatial pattern of the metallic support stent 41, detailed in this one, where the conformational pattern of its mesh, different from the previous one, as support or
  • Such a prosthetic device will also be responsible for the gradual, regulated and continuous release of different drugs via microcapsules or a group of liposomes 33, in the sense of preventing coronary restenosis and inducing early regeneration of the previously affected vascular wall, from the release by precursor drugs, coming from this peripheral intradermal biochip 43, which, when released into the bloodstream, after a certain time interval, reach the vascular prosthetic device, drug-eluting stent 51, in this example of a different modality from the precursor 50, in its inner layer, and through a conjugation with the internal matrix 35 contained in both hexagonal and lozenge cells (combination and pharmacological reaction, mainly by enzymatic hydrolysis, or other alternative types of chemical reaction compatible with the medium), are responsible for executing the in-stent medication release, either namely, microcapsules, or unified groups of liposomes 33 , contained and housed in specific superimposed layers that make up the hexagonal 47 and lozenge 48 cells of the stent's internal coating 42
  • These precursor drugs 36 released in a controlled and programmed manner by this intradermal microchip 43 present their release pulse in the current blood, as well as ranges, concentration, and other potentially measurable pharmacological variables, subject to control over this microchip implant from any form of external central, software or mobile communication device, through the use of radiofrequency waves or any other transmission/ compatible energy transformation.
  • Nanosensors/nanochips 46 can also be present in this implantable biochip in association, which constitutes the delivery system in its complexity, or even be represented by nanochips or nanosensors 49, located on the inner surface of the stent 51, see letters (B) and (C), in any of their modalities, or arranged in the intervals between cells, separating corridors of hexagonal 47 and lozenge 48 cells of the internal coating of the prosthesis 42, as explicit in FIGURE 2, capable of regulating and compulsorily measuring the concentration rates of in-stent drugs , serum medication half-life, sequential metabolism rate, and drug elimination time, among several other pharmacological, metabolic, and biochemical markers.
  • the stenter-type prosthetic devices 50 and 51 are constituted on their surface by a fenestrated tubular diagram 31 and 41, without presenting median articulation, with a regular cylindrical shape, multifilament, associated with internal coating for drug delivery, which can be a self-expanding or balloon-expandable device.
  • FIGURE 4 illustrates the stent-type prosthetic device 50, showing, from an approximate focus, the microcapsules or liposomes 33, contained within the hexagonal cells 34 that form the biological support membrane , and which are arranged in aggregate and sustained, immersed in a matrix that forms chains or networks of protein macromolecules 35, or these conjugated to other organic molecules such as phospholipids, in the form of a biological film or gel, in a way that provides sufficient sustainability and a ideal fixation rate.
  • FIGURE 3 refers to a different perspective illustration of a cylindrical tubular prosthetic device, standardized stenter type 41, as shown in FIGURE 3A, intraluminally expandable, by balloon-catheter or self-expandable, in metallic support or in resin biocompatible, unaccompanied by its internal release matrix, and in FIGURE 3B, this matrix in question is already accompanied, internal "coating" as described 42, whose spatial conformation ("design") follows the geometric spatial pattern of the metallic support stent 41, where the conformational pattern of its mesh can be observed, different from the previous one, as support or support of this internal biological coating 42, and a microchip implanted peripheral intradermal 43, working together; the one with its spatial structure arranged in hexagonal cells 47, coapted laterally to each other, in regular polyhedral geometric conformation, and intercepted at their upper and lower ends, that is, sides that make up the acute internal angle of the hexagonal cells, by cells in the form of of diamond 48, in complete contiguity, arranged in the longitudinal
  • Such a prosthetic device will also be responsible for the gradual, regulated and continuous release of different drugs via microcapsules or a group of liposomes 33, in the sense of preventing coronary restenosis and inducing early regeneration of the previously affected vascular wall, from the release by precursor drugs 36 , arising from this peripheral intradermal biochip 43, which reach the vascular prosthetic device, drug-eluting stent 51, in its inner layer, and through a conjugation with the internal matrix 35 contained in both hexagonal and lozenge cells, these being precursor drugs 36 responsible for perform the release of in-stent medications, whether microcapsules or unified groups of liposomes 33, contained and housed in specific superimposed layers in which the hexagonal 47 and lozenge 48 cells of the stent's internal coating 42 are constituted.
  • Nanosensors/nanochips 46 can also be present in this implantable biochip in association, which constitutes the delivery system in its complexity, or even be represented by nanochips or nanosensors 49, located on the inner surface of the stent 51, in any of its modalities , or arranged in the intervals between cells, separating corridors of the hexagonal 47 and lozenge 48 cells of the internal coating of the prosthesis 42, as explicit in FIGURE 2, capable of regulating and compulsorily measuring the concentration rates of in-stent drugs, drug serum half-life, sequential metabolism rate, and drug elimination time, among several other pharmacological, metabolic, and biochemical markers.
  • FIGURES 5 and 6 are perspective illustrations of said cylindrical tubular prosthetic device, standardized stent type, intraluminally expandable 51, as seen in FIGURE 5A, in an alternative geometric pattern, with its internal drug delivery matrix 42, in a section approximation that shows how this matrix is arranged, either in hexagonal cells 47 and lozenge 48, which come from the extension of the supporting prosthesis 41, that is, from the cells that make up the spatial conformation of the prosthesis, properly speaking, open, on the entire internal surface of the stentor 51, that is, towards the vascular lumen.
  • microcapsules or liposomes 33 contained within the hexagonal cells 47 and adjacent and coapted rhombus cells 48, which form the biological support membrane 42, are arranged aggregated and supported, in homogeneous layers, one on top of the other (in the figures, represented by different colors, that is, each layer shown in a certain color, representing a modality of liposome/microcapsule 33, containing a different type of drug), immersed in a matrix that forms chains or networks of protein macromolecules 35 (matrix support), or other types of biomolecules, in a way that provides sufficient sustainability and an ideal rate of fixation.
  • Each layer will be formed by a support matrix of different chemical composition, one from the other, aiming to provide the specificity and selectivity of release of a given drug, contained in the groups of liposomes/microcapsules 33, according to the type of medication remotely selected and released 36 by the implanted biochip 43, which, when it falls into the bloodstream, reaching the surface of the stent, will be responsible for interacting with the specific support matrix of a certain layer 35, for which it is programmed, dissolving and releasing it, selectively and specific type of drug 33, aiming not only to control vascular restenosis, but also to modulate the inflammatory and proliferative response of the myointimal wall, an adversity that frequently occurred in the implantation of first and second-generation drug-eluting stents, polymers in general.
  • FIGURE 5B shows the microcapsules or group of liposomes 33, contained within the hexagonal 47 and lozenge 48 cells (specifically in the second conformational modality of the stent) that form the biological support membrane 42, and which are arranged aggregated and sustained, in specific layers, immersed in a matrix that forms chains or networks of protein macromolecules, or these conjugated to other organic molecules such as phospholipids, in the form of a biological film or gel, in a way that provides sufficient sustainability and an ideal rate. of fixation.
  • FIGURE 6 shows a perspective illustration in section/section of a certain area of the internal intra-stent drug delivery matrix 32 of said cylindrical tubular prosthetic device, standardized stent type, intraluminally expandable 50, showing how this matrix is arranged , that is, in hexagonal cells 34, which come from the extension of the support prosthesis 31, that is, from the cells that make up the spatial conformation of the prosthesis, itself, open, on the entire internal surface of the stent 50, that is, towards the vascular lumen.
  • microcapsules or liposomes 33 contained within the hexagonal cells 34, which form the biological support membrane 32, are arranged in aggregate and supported, in homogeneous layers, one on top of the other, ditto immersed in a matrix that forms chains or networks of protein macromolecules 35, or other types of biomolecules, in such a way that they provide sufficient sustainability and an ideal fixation rate.
  • Each layer will be formed by a matrix of support of different chemical composition, one from the other, aiming to provide the specificity and selectivity of release of a certain drug, contained in liposomes/microcapsules 33, according to the type of medication released 36 by the intradermal implant - biochip 43, which, when falling in the bloodstream, gradually reaching the surface of the stent 50, will be responsible for interacting at specific sites with the given support matrix 35 of a given layer, for which it is programmed, dissolving it and releasing, selectively and specifically, a given type of drug, a process that occurs from the highest (external) to the lowest (deep) layers, encompassing the same therapeutic efficacy objectives of the aforementioned alternative standard.
  • FIGURES 7, 8, 9, 10, 11 are a perspective illustration of the same prosthetic device as FIGURES 1, 2, 3, 4 and 5 with its internal drug delivery matrix 32 (of the stent in hexagon geometry only ) and 42 (of the stent in geometry of intercepted hexagons and diamonds), in an approximate section that shows how this matrix is arranged, either in hexagonal cells 34 or hexagonal/lozenge 47 and 48, which come from the extension of the prosthesis of support 31 (model with hexagonal geometric pattern only) and 41 (model with hexagonal and diamond geometric pattern), that is, of the metallic base cells or biological resin material as previously described, which make up the spatial conformation of the prosthesis itself , open, on the entire internal surface of the stentor, that is, towards the vascular lumen, with microcapsules or groups of liposomes 33, contained within the hexagonal cells that form the biological support membrane 32 and 42, and are arranged aggregated and supported, in homogeneous layers, one on top of the other; so that FIGURE 7A shows a perspective view of
  • these substances will interact with the first layers of the support matrix 35 located towards the light of the vessel, that is, only and specifically with those layers whose chemical constituents are reactive to the action of these substances, thus providing the release of microcapsules/ liposomes stored and supported by this matrix.
  • the possibility of effecting a selectivity and diversity in the release mechanism of drugs applied intra-stent or intra-prosthetic device In schematic color presentations, the different representations of each type of medication administered are differentiated by each color used, and this is also applied to the microcapsules/liposomes programmed to be released, from the specific layer (support matrix of each hexagonal or lozenge cell) 35.
  • FIGURE 8A defines a standard initial stent 50, obeying a metallic geometric conformation 41, in a blood vessel 60, and the arrival of a precursor medication 36, eliminated from a subdermal intra-chip plate 44 43, as well as FIGURE 8B defines this stent in close-up focus, with the sectional view of the drug delivery system 32, the parent drug 36, and the in-stent medication 33 (microcapsules/liposomes).
  • FIGURE 8C shows an approximate 3D section of the biological coverage of medication release 32, constituting the in-stent cells 34, and the effect produced by the precursor drug 36 when it reaches the interior of the prosthesis, precipitating the release of in-stent medications 33 , represented by microcapsules.
  • FIGURE 9A demonstrates, in approximate focus, the process of releasing the precursor medication from the microcapsule/liposomal groups 36, coming from the plate 44, from the implanted microchip 43, through its microreservoirs.
  • FIGURE 9B shows a sequential moment of release of in-stent medications, contained in the microcapsules/liposomes 33, in a sense that can occur both for the vessel lumen and for the face of the vascular wall, if it is delimited or indicated that the immersion of the microcapsules 33 is carried out in a single type or pharmacological species, in all layers, and with only one type of support matrix, of a single biochemical nature.
  • FIGURE 9C indicates a later moment of release of these intra-capsulated medications 33 in the vessel lumen, in a standard stentor 50.
  • FIGURES 12 to 16 represent in perspective view the same drug delivery system 33, intraluminal, of the previous figures, as a new process of arrival of a different substance released by the organic implant (precursor drug) 36, said implantable biochip intradermally 43, to the inner surface of the stent, which reaches, interacts and releases another type of in-stent medication 33, compatible and programmed for release according to the action of the substance released 36 by the implanted biochip, culminating, in the same way as described in last paragraph, with the release of other types of in-stent drugs, contained in aggregated microcapsules/liposomes 33 and supported in different layers, consisting of a compatible support matrix 35.
  • FIGURE 12A relates to a new 3D view perspective of a standard stent 50, and its internal drug delivery system 32, with the arrival of a new precursor drug 36, in the vessel lumen 60, and its moment of release of its drug content responsible for releasing the in-stent medications 33, either represented by microcapsules.
  • FIGURE 12B Sequentially, in approximate focus, in FIGURE 12B, this precursor drug 36, coming from the microreservoirs of the plate 44, contained in the microchip 43, dissolving and acting on the intracellular matrix of support 35 of the microcapsules 33, releasing them to the vessel lumen and , according to the single-drug method, to the affected vascular wall.
  • FIGURE 12C shows a further moment of release of the in-stent medications, represented and encapsulated in structure 33.
  • FIGURE 13A shows a schematic 3D section of the hexagonal cells 34, delimiting the various superimposed layers in which the microcapsules 33 are constituted, housing the in-stent medications, and the arrival of precursor drugs 36, coming from plate 44, attached to the microchip implanted in the organism 43, in a continuous process of controlled, pulsatile, and intelligent release.
  • An external switch which can be represented by a cell phone, an application or any other type of software 55 sends the signal to the microchip, aiming to trigger this process.
  • FIGURE 13B depicts a later moment of release of these microcapsules 33, with the in situ action of the precursor drug 36.
  • FIGURE 13C confirms the dissolution of the internal matrix 35, intracellular of the stent, through these precursor drugs 36, releasing in-stent medications 33, in microcapsule content.
  • FIGURES 17 to 24 represent in perspective view the same drug delivery system 33, intraluminal, of the previous figures, as a new process of arrival of a different substance released by the organic implant (precursor drug) 36, said implantable biochip intradermally 43, up to the internal surface of the stent, which reaches, interacts and releases another type of in-stent medication 33, compatible and programmed for release according to the action of the substance released 36 by the implanted biochip, culminating, in the same way as described in last paragraph, with the release of other types of in-stent drugs 33.
  • FIGURE 25 refers to the perspective demonstration of the structure of the plate 44, inside the implanted biochip 43, containing reservoirs that differ according to the type of medication remotely selected and released 36 by it, which when falling into the current blood, reaching the inner surface of the stent 50 or 51, will be responsible for interacting with the certain support matrix of a certain layer 35, for which it is programmed, dissolving it and releasing, in a selective and specific way, the certain type of drug 33, aiming not only to control vascular restenosis, but also to modulate the inflammatory and proliferative response of the myointimal wall, an adversity that frequently occurred in the implantation of first and second-generation, drug-eluting, polymeric stents of a generally.
  • FIGURES 1, 2 and 3 in perspective illustration shown together with its internal release matrix, internal coating described 32 and 42, according to the prosthesis modality, which is represented by an artificial, biocompatible biological membrane, arranged in hexagonal cells or hexagonal + lozenge cells, which come from the extension of the supporting prosthesis, that is, from the cells that make up the spatial conformation of the stent itself, containing the microcapsules or liposomes 33, and these aggregates are sustained, immersed in a matrix that forms chains or networks of protein macromolecules 35, in such a way that they provide sufficient sustainability and an ideal fixation rate.
  • the prosthesis modality which is represented by an artificial, biocompatible biological membrane, arranged in hexagonal cells or hexagonal + lozenge cells, which come from the extension of the supporting prosthesis, that is, from the cells that make up the spatial conformation of the stent itself, containing the microcapsules or liposomes 33, and these aggregates are sustained, immersed in a matrix that forms chains or networks of protein macromolecules 35, in such
  • FIGURE 26 in an exceptional way, shows the possibility of the mesh design of the intravascular prosthetic device 51 to be fenestrated, since the alternative production of this organic or vascular prosthetic device in derivation of the second model, of cells hexagonal 47, coapted at their lower and upper ends by diamond cells 48, and these, in turn, remain fenestrated, not coated internally in their area by the drug release coating 42, consisting of an advantage and indication property for the introduction of vascular prosthesis in situations of lesions in bifurcations/trifurcations, collateral vessels emerging from the lesion site, among other indications.
  • FIGURE 26A composes the metallic geometric pattern 41 of the stent 51, in axial spatial arrangement along the cut of a patterned organic vessel 60, in a "design" of hexagonal cells 47 alternating with diamond cells 48.
  • the fenestrated mesh as already described, is a favorable factor in certain types of coronary angioplasty procedure indication.
  • FIGURE 26B shows, in close focus, the fenestrated mesh of the stent 51, with emphasis on the release system - biocompatible coating 42, and the in-stent cells 47 and 48.
  • Bio coating has its acceptable application as a coating for artificial and natural aac valves, intravascular filters, and intraorganic devices;
  • Interventional Cardiology has developed greatly, and the application of percutaneous transluminal coronary angioplasty has become increasingly routine.
  • the first drug-eluting, drug-eluting stents were primarily designed to reduce in-stent neointimal proliferation, thereby preventing the early or late occurrence of vascular restenosis.
  • implantable devices consisting of controlled drug delivery systems
  • implantable microchips programmable microelectronic function and intelligent, called implantable microchips
  • the scope of this invention privilege resides in the application of these intelligent microelectronic implantable devices, able to be programmed by any command source or remote central, and may contain hundreds of micro-reservoirs that bring together different modalities of drugs (in this case , called precursor drugs), which, when released in the body, will reach the inner surface of the vascular stent and, acting directly on the constituents of its organic matrix, which make up the internal biological cover of the stent, will be responsible for the dissolution and release of a certain in-stent drug.
  • precursor drugs drugs
  • these implantable microchips are capable of exhibiting highly complex release patterns, simultaneously at constant intervals and controlled pulses, demonstrating greater accuracy, as well as maintaining drug isolation from the external environment.

Abstract

L'invention concerne un dispositif prothétique intravasculaire ou organique (50, 51), extensible, biocompatible, non polymère, pour la libération de multiples agents pharmaceutiques (33) par des facteurs extrinsèques, notamment de médicaments précurseurs (36), libérés via des implants organiques - micropuces intradermiques (43) (pour libération contrôlée, graduelle et pré-programmée, via une centrale distante, par un logiciel, un dispositif ou un appareil mobile, de ces agents pharmaceutiques précurseurs, qui atteignent la prothèse et agissent sur le mécanisme de libération des substance médicamenteuses spécifiques au niveau du site cible du stent). Ces micropuces peuvent contenir des nanopuces et des biocapteurs (46) dans leur structure, de manière à optimiser le contrôle et l'impulsion de libération des agents pharmaceutiques intra-stent, et permettre des mesures de variables hémodynamiques, chimiques et homéostatiques, en vue de résoudre les problèmes de biais et de complications cliniques. Le dispositif vient s'accoupler avec sa matrice interne de libération, représentée par une membrane biologique artificielle, dont la disposition spatiale géométrique provient des propres cellules qui composent l'extenseur à proprement parler, ouvertes sur toute la surface intérieure.
PCT/BR2021/050361 2020-09-27 2021-08-25 Dispositif prothétique tubulaire cylindrique non polymère WO2022061430A1 (fr)

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BR102021015189A2 (pt) * 2021-08-01 2023-02-14 Christiane Dias Maués Dispositivo protético tubular cilíndrico; e dispositivo protético com sistema de liberação local de medicações através de nanopartículas funcionalizadas, mais precisamente lipossomas, de liberação passiva ou ativa controlada

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US5797898A (en) * 1996-07-02 1998-08-25 Massachusetts Institute Of Technology Microchip drug delivery devices
WO2004096176A2 (fr) * 2003-04-25 2004-11-11 Boston Scientific Scimed Inc. Formulation de medicament solide, et dispositif de stockage et de distribution controlee de ce medicament
US20080140172A1 (en) * 2004-12-13 2008-06-12 Robert Hunt Carpenter Multi-Wall Expandable Device Capable Of Drug Delivery Related Applications
BR102016012105A2 (pt) * 2016-05-27 2017-12-12 Dias Maués Christiane Cylindrical tubular protective device; and protetic device with biological support matrix for drug release; with or without polymers
US10485968B2 (en) * 2015-10-20 2019-11-26 The University Of Melbourne Medical device for sensing and or stimulating tissue

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Publication number Priority date Publication date Assignee Title
US5797898A (en) * 1996-07-02 1998-08-25 Massachusetts Institute Of Technology Microchip drug delivery devices
WO2004096176A2 (fr) * 2003-04-25 2004-11-11 Boston Scientific Scimed Inc. Formulation de medicament solide, et dispositif de stockage et de distribution controlee de ce medicament
US20080140172A1 (en) * 2004-12-13 2008-06-12 Robert Hunt Carpenter Multi-Wall Expandable Device Capable Of Drug Delivery Related Applications
US10485968B2 (en) * 2015-10-20 2019-11-26 The University Of Melbourne Medical device for sensing and or stimulating tissue
BR102016012105A2 (pt) * 2016-05-27 2017-12-12 Dias Maués Christiane Cylindrical tubular protective device; and protetic device with biological support matrix for drug release; with or without polymers

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