EP4294469A1 - Procédés et dispositifs pour implants médicaux - Google Patents

Procédés et dispositifs pour implants médicaux

Info

Publication number
EP4294469A1
EP4294469A1 EP22709167.5A EP22709167A EP4294469A1 EP 4294469 A1 EP4294469 A1 EP 4294469A1 EP 22709167 A EP22709167 A EP 22709167A EP 4294469 A1 EP4294469 A1 EP 4294469A1
Authority
EP
European Patent Office
Prior art keywords
wall
esophagus
ring
prp
patient
Prior art date
Legal status (The legal status 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 status listed.)
Pending
Application number
EP22709167.5A
Other languages
German (de)
English (en)
Inventor
Norman Godin
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Biomedix SA Switzerland
Original Assignee
Biomedix SA Switzerland
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 Biomedix SA Switzerland filed Critical Biomedix SA Switzerland
Priority claimed from PCT/US2022/070759 external-priority patent/WO2022178555A1/fr
Publication of EP4294469A1 publication Critical patent/EP4294469A1/fr
Pending legal-status Critical Current

Links

Classifications

    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/02—Inorganic materials
    • A61L31/022—Metals or alloys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • 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
    • A61F5/00—Orthopaedic methods or devices for non-surgical treatment of bones or joints; Nursing devices; Anti-rape devices
    • 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
    • A61F5/00—Orthopaedic methods or devices for non-surgical treatment of bones or joints; Nursing devices; Anti-rape devices
    • A61F5/0003—Apparatus for the treatment of obesity; Anti-eating devices
    • A61F5/0013—Implantable devices or invasive measures
    • A61F5/0076—Implantable devices or invasive measures preventing normal digestion, e.g. Bariatric or gastric sleeves
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/005—Ingredients of undetermined constitution or reaction products thereof
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/30—Compounds of undetermined constitution extracted from natural sources, e.g. Aloe Vera
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/64—Animal cells
    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/22—Materials or treatment for tissue regeneration for reconstruction of hollow organs, e.g. bladder, esophagus, urether, uterus

Definitions

  • the presently disclosed technology relates generally to medical devices, prosthesis, and methods of using and/or implanting same. More particularly, one embodiment of the presently disclosed technology relates to methods and devices to place long-term implants in the wall and/or lumen of the esophagus of a patient to treat any of a variety of ailments, including but not limited to gastro-esophageal reflux disease and/or obesity, often without surgery.
  • Obesity affects up to 40% of the world population. Removal of portions of the stomach and gastric by-pass are known treatments that are invasive and challenging procedures. Developing safe and relatively non- invasive methods of treatment could have an important impact on large segments of the population.
  • reflux is an ailment that also affects a large portion of the world population. It is known to use a prosthesis to treat Gastro-Esophageal Reflux Disease (GERD) and/or to help a patient reduce their weight. Examples of such prior art devices are disclosed in WO 2019/155284, WO 2018/222819, and WO 2013/050381, which are hereby incorporated by reference.
  • GSD Gastro-Esophageal Reflux Disease
  • the presently disclosed technology provides a method of allowing integration of the mesh ring using platelet rich plasma (PRP) obtained from the patient's own blood and the mesh ring is integrated within the wall of the esophagus between the PRP added to the biopsy sites of the wall of the esophagus, which helps coagulation and "grips” the mesh on the external side of the mesh and esophageal cell wall stem cells that are obtained from the biopsies and are "recycled” and reinjected on the "internal” or luminal side of the mesh ring.
  • PRP platelet rich plasma
  • PRP and esophageal adult stem cells will help obtain a better integration of the mesh in the wall of the esophagus and the third and last ring (after the first ring compressing the wall of the esophagus or DM-1 (Diagnosis and Management 1) and the DM-2 (Therapeutic mesh ring), the DM-3 ring puts pressure on the area to help integrate the mesh supporting the tubular devices treating GERD and obesity in the wall of the esophagus.
  • the presently disclosed technology is directed to a device and method used to implant a variety of Gastro-intestinal Anti-Reflux Devices (GARDTM) placed minimally-invasively or non-invasively through the mouth of the patient to treat gastro-esophageal reflux disease and obesity with autologous biological compounds.
  • GARDTM Gastro-intestinal Anti-Reflux Devices
  • FIG 1 illustrates a Diagnosis and Management (DM) GARDTM according to one embodiment of the presently disclosed technology
  • FIG 2A illustrates a tubular-type GARDTM for GERD
  • FIG 2B illustrates a lamellar-type GARDTMfor GERD
  • FIG 2C illustrates another lamellar-type GARDTMfor GERD
  • FIG 3A illustrates one type of Obesity GARDTM according to one embodiment of the presently disclosed technology
  • FIG 3B illustrates another type of Obesity GARDTM according to one embodiment of the presently disclosed technology
  • FIG 3C illustrates yet another type of Obesity GARDTM according to one embodiment of the presently disclosed technology
  • FIG 4A illustrates normal layers of the esophageal wall of a human being
  • FIG 4B illustrates adult stem cells at the level of the basal membrane of the esophageal epithelium
  • FIG 5 shows a niche created by the ring of the DM-1 GARDTM compressing the different layers of the esophageal wall.
  • FIG 6 illustrates different layers of the esophageal wall with the depth of penetration (level) of different methods of endoscopic resection of the esophageal wall
  • FIG 7 illustrates that after mucosal resection (X), Platelet Rich Plasma (PRP) with calcium gluconate are sprayed on the bottom of the bleeding niche. Resected mucosa (X) including stems cells is kept for later reinjection (not shown);
  • PRP Platelet Rich Plasma
  • FIG 8A illustrates one embodiment of the presently disclosed technology where a delivery catheter with a balloon that is used to deploy the mesh ring held on the delivery catheter with a stretchable magnetic bead ring;
  • FIG 8B shows the inflated balloon pressing the mesh ring on the bleeding niche where PRP and calcium gluconate were sprayed to integrate the mesh ring in the coagulating blood;
  • FIG 9A illustrates one embodiment of the presently disclosed technology, wherein instead of a balloon, a helical spring ring is placed inside the mesh ring and folded on the delivery, similarly to the introduction of the DM GARDTM. Knots are holding the mesh ring on the helical spring to avoid any displacement of the mesh ring when the slip knots are pulled out and the helical spring is deployed;
  • FIG 9B illustrates that the surgical threads holding the mesh ring will be cut or pulled endoscopically once the helical spring is deployed and the mesh ring is in contact with the patient's blood, PRP and calcium gluconate in the bottom of the niche;
  • FIG 9D illustrates that the mesh ring is free in the bleeding niche with PRP and gluconate calcium.
  • the slip knot holding the tubular part of the GARDTM for GERD is still in position to maintain device in place;
  • FIG 10A illustrates that fragments of the biopsies of the epithelium cells obtained in the beginning of the procedure with or without cultured epithelial cells obtained when the DM GARDTM was placed originally are sprayed in a PRP/calcium gluconate solution on the "luminal" side of the mesh to reconstitute the esophageal epithelium;
  • FIG 10B illustrates that the mesh ring is now "sandwiched" between the bottom of the coagulating niche and the reconstituted autologous epithelium of the esophageal wall
  • FIG 11A shows the different layers of the normal esophageal wall
  • FIG 11B illustrates the different depths of placement of the mesh ring depending how deep the mucosal resections are according to one embodiment of the present disclosed technology
  • FIG 12 illustrated a ring of one embodiment of the presently disclosed technology that is used at the end of the procedure to compress the area once the mesh has been covered with epithelial cells and the ring is left in position for a period of time before possible removal. All other remaining devices have been removed from the esophagus.
  • the slip knot is removed on the tube and the tube opens;
  • FIG 13A is a top perspective view of a stent or ring of one embodiment of the presently disclosed technology
  • FIG 13B is a side perspective view of the device shown in FIG 13A.
  • FIGS 13C is a perspective view of the device shown in FIG 13A attached to a tubular part.
  • the method according to one embodiment of the presently disclosed technology includes GARDsTM placed through the mouth of a patient after calibration of the diameter of the patient's esophagus to select appropriately sized devices with a new Therapeutic Endoscopy technique to which autologous biological compounds are added, called a Therapeutic BIO- Endoscopy (TBE) procedure.
  • GARDsTM placed through the mouth of a patient after calibration of the diameter of the patient's esophagus to select appropriately sized devices with a new Therapeutic Endoscopy technique to which autologous biological compounds are added, called a Therapeutic BIO- Endoscopy (TBE) procedure.
  • TBE Therapeutic BIO- Endoscopy
  • Therapeutic GARDsTM are optionally made of 2 parts: a ring made out of a circular soft mesh in one embodiment or a stent, made out of metal or an alloy material like nitinol in another embodiment, and a tubular part. Collectively, the two parts comprise a structure sometimes referred to herein as a "prosthesis.”
  • the mesh ring is placed within the wall of the esophagus after localized resection of the esophageal wall using a series of biopsies or deeper resection with Endoscopic Mucosal Resection (EMR) or Endoscopic Submucosal Dissection (ESD).
  • EMR Endoscopic Mucosal Resection
  • ESD Endoscopic Submucosal Dissection
  • the resection causes bleeding and plasma or PRP prepared from the patient's blood is injected or sprayed (e.g., through a catheter) to speed up coagulation and healing.
  • Gluconate calcium can optionally be added to the PRP so that the solution is more viscous and helps adhere better to the bleeding niche.
  • the mesh ring of the Therapeutic GARDTM is then pressed mechanically with either a balloon mounted on the introduction delivery system that presses the mesh ring on the coagulating mix of blood and PRP/calcium gluconate or a self deploying helical spring ring on which the mesh ring supporting the tube is mounted.
  • the balloon is then slowly deflated and removed or the knots holding the mesh ring to the helical spring are cut or pulled out if slip knots have been used and the ring is delicately pulled back in the esophagus or out of the body through the mouth leaving the mesh ring in place.
  • the patient's epithelial stems cells and possibly fibroblasts are optionally removed with the biopsies taken during placement of the DM GARDTM and put in culture in a laboratory.
  • the stem cells can be obtained when the biopsies (or EMR/ESD) are taken from the niche at the beginning of the therapeutic procedure are then placed in a PRP/calcium gluconate solution and are sprayed on the mesh ring on the luminal side of the mesh that supports the tubular devices. This is done to help reconstitute the epithelial layers of cells removed previously at resection.
  • a balloon on the delivery catheter is inflated and presses the epithelial stem cells in PRP on the mesh and/or a third ring is placed at the end of the procedure to exert pressure for a longer period of time than an inflated balloon place through the mouth can.
  • the mesh ring is integrated in the wall of the esophagus between the esophageal wall side (external) where the bottom of the niche and the coagulating blood with PRP/calcium gluconate mix is located and the luminal side (internal) that is reconstituted with the patient's own epithelial stems cells from the biopsies added to the PRP/calcium gluconate solution.
  • the surgical mesh is "sandwiched" in the reconstituted wall.
  • the surgical mesh can be made of several different non-resorbable compounds, such as but not limited to polypropylene, polyester, polyethylene terephthalate (PET), polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF) among others that are all used safely for many years in surgery as well as some mesh that include animal collagen, and mixtures thereof.
  • a ring is added in the lumen of the esophagus at the end of the procedure to help put pressure and help heal the esophageal wall now holding the mesh ring supporting the Therapeutic GARDTM in the gastro-intestinal lumen.
  • TBE Therapeutic Bio- Endoscopy
  • PRP platelet rich plasma
  • Table 1 shows a summary of the GARDTM family of devices with the temporary DM-GARDTM placed first then removed and the Therapeutic- GARDTM separated in 2 families, the GARDTM device for GERD models and the Obesity GARDTM models for obesity. Table 1:
  • the GARD tubes reaches the stomach.
  • the GARD tube reaches the duodenum
  • the GARD tube reaches the jejunum
  • the patient's adult stem cells can be "cultured" in vivo in the patient's own PRP obtained from the patient's blood.
  • Another technique is to culture biopsies from the esophagus in an existing device made for cell culture/sorters in a lab.
  • a fibrin glue or fibrin sealant can seal the passage of the surgical thread through the wall of the esophagus as well as the knot tied by the healthcare professional on the "external" or peritoneal/mediastinal side) of the esophagus.
  • a double approach can be employed, from inside the esophagus with endoscopy and outside the esophagus with laparoscopic surgery, preferably with a robot.
  • FIG 1 illustrates the DM GARDTM placed in the esophagus (1) and the tubular (e.g., cylindrical and/or conical) part (10) reaching or extending into the stomach (2).
  • the tubular part (10) is optionally flexible.
  • a hiatus hernia (4) often associated with moderate to severe GERD is shown.
  • the diaphragm (3) separates the abdominal cavity underneath from the thorax above.
  • FIG 1 also shows the lumen (40) of the esophagus.
  • FIGS 2A-2C illustrate the 2 main models used to treat GERD, namely in FIG 2A, the GARDTM GERD device that blocks reflux and can also help patients who are overweight lose a few pounds.
  • the GARDTM for GERD device blocks vomiting as surgery for reflux with its most common operation called the Nissen fundoplication also does.
  • the lamellar model (12) will also block reflux and allow vomiting when the lamellae under vomiting pressure turn back on themselves (FIG 2C), but will have less effect on weight loss.
  • An important feature is the radio-opaque zone (18) placed or located between the thinner mesh ring (9) and the tube (10) or the lamellae (12).
  • FIGS 3A-3C illustrate 3 models of the Obesity GARDTM.
  • FIG 3A shows the OB1- GARDTM.
  • FIG 3B show the OB2-GARDTM.
  • FIG 3C show the OB3-GARDTM.
  • the tube (10) of OB1-GARDTM device ends in, terminates in, and/or extends into the stomach and can be used for people having class 1 obesity, which is a Body Mass Index (BMI) of 30 to 34.9.
  • BMI Body Mass Index
  • the effect is mainly restriction to help lose weight, which means that people will have to eat smaller quantities and chew their food longer.
  • the tube (10) of the device reaches the duodenum (5) so the device will cross or pass the whole stomach entering the stomach (2) where the lower esophagus (1) meets the stomach (2) and ending in the duodenum (5).
  • This device mimics the effect of the "sleeve gastrectomy" where the healthcare professional cuts 3 ⁇ 4 of the stomach on the greater curvature side leaving a narrow band along the lesser curvature now occupied by the tube (10).
  • the OB2-GARDTM can be used for patients who have class 2 obesity with a BMI of 35 to 39.9.
  • the mesh ring supporting the tube will have to be implanted over a higher surface of the esophageal mucosa and certainly deeper than for the GARDTM for GERD devices or the OBI devices.
  • the OB3-GARDTM (FIG 3C) can be placed with the tube ending in the jejunum (6).
  • the OB3-GARDTM will help lose weight both by restriction as for the OB2-GARDTM but also by creating malabsorption as food will stay in the tube and will not be in contact with enzymes from the pancreas, or duodenum nor with bile before reaching the duodenum, in many ways similarly to the effect of gastric by-pass but again without surgery and surgical risk as the mortality of gastric by-pass is estimated to be about 1% because these patients are obviously high risk patients because of their morbid obesity.
  • FIGS 3A-3C also show the lumen (40) of the esophagus.
  • Table 2 describes one method to obtain PRP from the patient's venous blood by centrifuging the blood twice.
  • Other commercial centrifuges exist that allow for a single centrifugation, but usually the platelet concentration is lower than in this method and is therefore not recommended unless proven equivalent in platelet concentration.
  • FIG 4A illustrates schematically the different layers of the normal human esophageal wall. If one considers that the esophagus is a tube, the innermost layer in contact with food ingested through the mouth and passing through the esophagus into the stomach is the esophageal epithelium (13) and the outer most layer is a muscular layer that will "push" the food down into the stomach from the mouth using a progressive wave of contraction called the peristaltic wave (20).
  • the esophageal epithelium (13) is at the top of FIG 4A.
  • the bottom of the esophageal epithelium is similar to a wave called the basal membrane (14) that carries cells called adult stem cells (see element 15 of FIG 4B) that play an essential role in repairing the esophageal epithelium if the wall is injured by disease or in our case by esophageal resection as in biopsies of the esophagus or deeper resections such as endoscopic mucosal resection (EMR) or endoscopic submucosal resection (ESD).
  • EMR endoscopic mucosal resection
  • ESD endoscopic submucosal resection
  • FIG 5 illustrates the compression niche (8) left after removal of the DM GARDTM and its thick ring that presses on the esophageal wall as shown in FIG 1. This niche will facilitate the positioning of the much softer mesh ring of the Therapeutic GARDTM.
  • Elements 13, 14, 16, 17, 19, and 20 of FIG 5 show the different layers of the esophageal wall that have been compressed by the ring of the DM GARDTM.
  • FIG 6 illustrates the different depths of esophageal resection that can be used.
  • Level A reaching the basal membrane with standard biopsies or level B reaching the lamina intestinal with endoscopic mucosal resection (EMR) should be sufficient to place the mesh of the Therapeutic GARDTM in position.
  • Level C (submucosa) using Endoscopic submucosal dissection should only be used if longer, heavier tubes such as the OB2-GARD and OB3-GARD are needed to treat obesity since complications of using ESD are not unusual.
  • Fibroblasts (22) from the lamina intestinal and the submucosa can also be cultured with the epithelial cells and reinjected once the mesh ring has been positioned in place. Blood vessels in the submucosa (21) are also shown.
  • Level A and Level B can be combined by doing EMR and biopsies as well as Level B and Level C by doing EMR and ESD and some standard biopsies can be added.
  • FIG 7 symbolizes the partial resection of the wall of the esophagus with biopsies and/or EMR (24) and the bleeding (PRP) prepared at the beginning of the procedure with Calcium gluconate to make the PRP more viscous is sprayed (25) with a spray catheter (26) passed through the gastroscope (not shown)
  • the mesh ring (28) of the Therapeutic GARDTM here the GARDTM for GERD in its tubular form, is passed folded on the balloon (31) of a delivery catheter (27) through the mouth and into the esophagus and kept in place with a stretchable ring of magnetic beads (29).
  • the tube of the GARDTM for GERD is also folded on the delivery catheter with a slip knot (33).
  • the mesh is placed facing the bleeding niche (8) under endoscopic vision.
  • Element 24 in FIG 7 is the sites of the biopsies where viscous PRP has been sprayed.
  • FIG 8A shows the lumen (40) of the esophagus.
  • FIG 8B illustrates the balloon (31) that is inflated and the mesh ring is held in position with the stretched ring of magnetic beads (29) that presses the mesh ring on the niche (8), where the mucosal biopsies have been made and the PRP with calcium gluconate have been added (see FIG 7).
  • the 2 strings holding the magnetic bead ring (30) are loose.
  • the tubular part of the GARD for GERD device (32) is held folded on the delivery (27) with the slip knot.
  • FIG 8C shows the magnetic bead ring (29) having been pulled from the mesh ring (9) by pulling on the other end of the threads (30) at the head of the delivery catheter (not shown).
  • This allows the inflated balloon (31) on the delivery catheter (27) to compress the mesh ring (9) on the niche with the coagulating blood and the added PRP with gluconate calcium (see FIG 7).
  • FIG 8C shows the lumen (40) of the esophagus.
  • FIG 9A illustrates a method of placement of the GARDTM for GERD on the niche (8) using a free helical pressure ring (34) similar to the ring of the DM-GARD (7) in FIG 1 placed inside the mesh ring (9) that is folded and held In position on the delivery catheter (27) with a slip knot (33). When in position facing the bleeding niche (8), the slip knot is pulled.
  • FIG 9B shows the lumen (40) of the esophagus.
  • the delivery catheter also has a balloon (31) placed on the delivery catheter.
  • FIG 9C illustrates that the knots (35) have been removed and the helical spring is gently pulled out with a forceps (36) leaving the mesh ring (9) positioned on the niche (8) where biopsies have been taken (x) and the coagulating blood with viscous PRP and calcium gluconate have been added (see FIG 7).
  • the slip knot (33) holding the tubular part of the GARDTM for GERD is still in position to exert a counterforce to the traction on the helical spring.
  • FIG 9C shows the lumen (40) of the esophagus.
  • FIG 9D illustrates the mesh ring (9) is in position and the delivery catheter (27) is still kept in place holding the tubular valve with the slip knot.
  • FIG 9D shows the lumen (40) of the esophagus.
  • the removable helical spring (34) has been pulled back towards the top of the esophagus to free access to the "inner” or luminal side of the mesh ring (9).
  • the balloon (31) is not inflated and the slip knot (33) on the tubular part of the delivery is still in position.
  • FIG 10A illustrates that the mesh ring (9) is sprayed through the endoscope (38) with epithelial cells that have been placed in culture when the DM-GARD was first positioned in the esophagus and/or fragments of the biopsies of the esophageal wall containing adult stem cells of the epithelium of the esophageal wall cut up after biopsies were taken in the bottom of the niche (see FIG 9) at the beginning of the procedure placing the Therapeutic GARD devices in the esophagus.
  • a balloon (31) that is fixed or otherwise secured on the delivery catheter is shown as not yet inflated.
  • the slip knot (33) of the tube is still in place and the delivery catheter (27) is in position.
  • the helical spring (34) has been pulled upwards and the endoscope (38) passes through the helical spring to spray the luminal side of the mesh ring (9) with epithelial cells in PRP with calcium gluconate (37) to make the mixture more viscous and adhering to the mesh ring (9) so as to reconstitute the epithelial layer of the esophageal wall.
  • FIG 10B illustrates the inflated balloon (31) on the delivery catheter pressing outwardly on the epithelial cells that were just sprayed on the mesh ring (9) so that the mesh ring (9) is “sandwiched” between the "external” niche containing coagulating blood and PRP/calcium gluconate and the "internal" reconstitution of the epithelial layer after spraying the adult stem cells in PRP to regenerate the epithelial layer in vivo.
  • FIG 11A illustrates a transverse view of the esophagus as shown in a longitudinal view in FIG 6A. Visible in FIG 11A is the esophageal epithelium (13), the basal epithelium (14), the lamina basement (16), the muscularis mucosae (19) separating the mucosal part (13, 14, 16) from the submucosa (17) and the muscularis propria (20).
  • FIG 11A shows the lumen (40) of the esophagus.
  • FIG 11B illustrates various options for the depth of placement of the mesh ring in the esophageal wall at the end of the procedure.
  • Location (39A) is the most superficial placement of the mesh ring at the level of the basal epithelium (Level A of FIG 6).
  • Location (39B) is the mid-level placement of the mesh ring in the lamina intestinal (16) of the mucosal wall (Level B of FIG 6).
  • Location (39C) is the deepest placement of the mesh ring in the submucosa (17) (Level C of FIG 6).
  • FIG 12 illustrates a final compression ring (41) that is introduced to put pressure on the "reconstituted” esophageal wall after placement of the mesh ring (9) shown integrated in the esophageal wall (39) supporting the tubular or conical valve (10) of the Therapeutic GARDsTM within the esophageal lumen (40).
  • FIG 12 shows the esophagus (1) and the radio-opaque zone (18) of the Therapeutic GARD that allows location of the Therapeutic GARD after the compression ring with its nitinol radio-opaque springs is removed.
  • nitinol ring 42 An advantage of using the nitinol ring 42 is that when the healthcare professional pulls on the strings of the delivery catheter, the ring 42 springs into place. As a result, the ring 42 is placed on the bleeding site caused by the biopsies made just previously. This helps direct the adult stem cells of the esophagus that are injected in the Platelet rich plasma (PRP) solution on the lumenal side of the esophagus, thereby covering the nitinol ring 42 with cells that should reconstitute the normal internal wall (mucosa) of the esophagus. Other materials that have the same desirable properties as nitinol could be used to form the ring 42.
  • PRP Platelet rich plasma
  • the presently disclosed technology can include putting the esophageal adult stem cells from the patient obtained by the biopsies in PRP was found to be a good milieu to put cells in culture or repair tissues (but not described to hold a foreign device like the Therapeutic GARDTM in position) and is used to reconstitute and/or repair) the internal mucosa of the esophagus in vivo after damaging it with the biopsies.
  • the above allows for the integration of the stent in the esophageal wall at the mucosal-submucosal level of the esophageal wall and allows holding the anti-reflux and/or the anti-obesity devices in the lumen opening. This creates a completely new era of endoscopic treatment (without surgery) of these very common diseases on an ambulatory basis.
  • the nitinol ring is thin, such as in the order of 0.3 mm think. When combined with the muscular layer, the two are about 3 mm thick, at most.
  • a method of the presently disclosed technology can include first calibrating the diameter of the esophagus at the level of the esophagus (e.g., lower third) where the healthcare professional intends to put the Therapeutic GARD.
  • the healthcare professional can place the DM-1 GARDTM in and/or at the level identified above for approximately 1-2 weeks to create a niche (e.g., see Fig. 5).
  • an experienced healthcare professional could optionally skip this stage to avoid an additional endoscopy.
  • the method can include preparing the PRP from the patient's blood by spinning the blood twice.
  • the DM GARDTM is removed from the esophagus.
  • biopsies can be taken from the bottom of the niche.
  • ten biopsies can be used for their stem cells and two biopsies can be used to have regular pathology to make sure the basal membrane is present as the adult esophageal stem cells are known to be right at the level of the basal membrane. This can be done for the control of the quality of the biopsies so they include stem cells.
  • the sixth step of the above-identified embodiment can include placing the biopsies (e.g., possibly cut-up in 2-3 pieces) in the PRP solution.
  • the nitinol stent of the Therapeutic GARDTM can be placed on the bleeding niche.
  • the PRP with esophageal adult stem cells can be injected on the internal (lumenal) side of the nitinol stent.
  • the PRP and stem cells can be compressed on the nitinol stent, such as with a balloon.
  • An optional tenth step can include injecting botulinum toxin above the ring of the Therapeutic GARDTM.
  • An optional eleventh step can include positioning an additional helical spring ring on the nitinol stent for additional compression, such as for 1- 2 weeks.
  • a method of the presently disclosed technology can include, first, balloon calibration.
  • the DM-1 device can be placed at the desired site for a predetermined period of time (e.g., 1 week), thereby creating a niche.
  • the DM-1 device can be removed, and biopsies can be made at the bottom of the niche to obtain adult stem cells.
  • the biopsies can be kept in the PRP obtained from the host (e.g., minipigs or patients).
  • the nitinol stent (DM-2 or Therapeutic GARD) can be placed on the bleeding site with the ring part in the bleeding niche.
  • lamellar devices can be used.
  • the PRP with the biopsies that include adult stem cells can be injected or sprayed on the luminal side of the ring to reconstitute the esophageal wall and incorporate the nitinol ring in the esophageal wall.
  • the DM-3 compression ring can be placed on the site for a predetermined amount of time (e.g., a week).
  • the DM-3 ring can be removed after a predetermined amount of time (e.g., a week).
  • some PRP can be added and compressed with a balloon for a predetermined amount of time (e.g., 5-10 minutes). Once the balloon is removed, the procedure is finished.
  • 1A A method for maintaining a medical device in place in a lumen of a hollow organ of a patient for a period of months or years without using a metal or bioresorbable stent.
  • IB A method for placement of a medical device in a lumen of the gastrointestinal tract of a patient using a flexible endoscope having at least one 2.8 mm working channel for placement of a guidewire, biopsy forceps, endoscopic mucosal resection or endoscopic submucosal dissection devices as well as injection and spraying devices and aspiration of fluids and aspiration of air or blood or secretions.
  • IC IC.
  • ID A temporary device using essentially pressure on a wall of a lumen of an esophagus after calibration of a size of the esophagus that can be easily removed through the mouth after a period of one day to 1 month, usually 2 to 3 weeks.
  • EMR endoscopic mucosal resection
  • ESD endoscopic submucosal dissection
  • IG A method of isolating a portion of the esophagus to place temporary or permanent medical devices in a wall of the esophagus using biopsies to make the wall of the esophagus bleed adding platelet rich plasma to help adhesion and incorporation of medical devices in the esophageal wall made with an incorporated upper mesh ring and tubular devices placed in the luminal wall to treat at least one of Gastroesophageal reflux disease (GERD) or obesity.
  • GFD Gastroesophageal reflux disease
  • IH A method of isolating a portion of an esophagus of a patient to place temporary or permanent medical devices in a wall of an esophagus using local injection of botulinum toxin to decrease peristaltic contraction of the esophagus for a few weeks or months to keep the device in place to help a permanent device stay in position.
  • GFD Gastroesophageal Reflux Disease
  • IJ A method of using a combination of biopsies of an esophageal epithelium to obtain esophageal cells for culture and reinjection at a later endoscopy or immediately for repairing the esophageal epithelium resected to place a net or mesh ring within a wall of esophagus.
  • IK A method of using culture of esophageal cells for reinjection at a later endoscopy or immediate reinjection of esophageal cells in platelet rich plasma (PRP) with calcium gluconate as a culture medium in vivo for repairing esophageal epithelium resected to contain a net or mesh ring in a wall of an esophagus of a patient that supports medical devices in a lumen of the esophagus.
  • PRP platelet rich plasma
  • IL A method of using bleeding and injection of autologous platelet rich plasma (PRP) solution in an esophagus of a patient to help heal lesions caused by mucosal resection to obtain epithelial cells for culture or incorporation of a mesh net ring in a esophageal wall.
  • PRP platelet rich plasma
  • IM A method of using platelet rich plasma with small fragments of about 1 mm of epithelial mucosa to culture an epithelium on a luminal side of a mesh ring so as to repair the epithelium and help incorporate safely the mesh ring at a flexible endoscopy to support luminal devices.
  • IO A method of using platelet rich plasma with small fragments of epithelial mucosa to culture an epithelium on an external side (submucosal and muscular side of the esophagus) of a mesh ring so as to repair a wall and help incorporate safely the mesh ring using cultures of epithelial cells or culture of fibroblasts from a lamina basement obtained at flexible endoscopy to support luminal devices.
  • IP IP.
  • IQ A method of using platelet rich plasma with small fragments of epithelial mucosa to culture an epithelium on a luminal side of a mesh ring so as to repair a epithelium and help incorporate safely the mesh ring at flexible endoscopy to support luminal devices to treat obesity.
  • IR A method of culturing esophageal cells in vitro obtained from biopsies at a time of placement of the temporary device to supplement the endogenous culture of epithelial cells if needed at the time of the second definitive device for treatment of gastroesophageal reflux or obesity.
  • a helical ring used to deploy a soft mesh ring of a definitive device help place the mesh ring in position and exert pressure on the mesh ring so as to pressure the mesh in position on the bleeding, coagulating mix of blood, PRP and calcium gluconate.
  • a soft mesh ring comprising or consisting of polypropylene, polyester, polyethylene terephthalate (PET), polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF), synthetic compounds integrating animal collagen components, and mixtures thereof, among others.
  • IW The use of a balloon to introduce a definitive device, the use comprising inflating the mesh net ring in position and exert pressure on the mesh before removing the balloon to allow cultured endogenous or exogenous autologous epithelial cells to be injected to repair and restore original esophageal epithelium.
  • IX A mesh ring that is radio-opaque to localize the mesh ring with fluoroscopy without repeating a gastroscopy.
  • IZ A glue inducing adhesion of a mesh of a ring to a tubular part of a Gastro-intestinal Anti-Reflux Device that is radio-opaque by mixing silicon glue with a radio-opaque substance such as barium sulfate.
  • IAA tubular or lamellar GARD made of a medical grade plastic.
  • IAB tubular or lamellar GARD made of a medical grade implantable silicone.
  • IAC IAC.
  • PRP platelet rich plasma
  • a mesh ring is integrated within a wall of the patient's esophagus between the PRP added to the biopsy sites of the wall of the esophagus that helps coagulation and grips the mesh on an external side of the mesh ring, wherein esophageal cell wall stem cells that are obtained from biopsies and are reinjected on an internal or luminal side of the mesh ring.
  • PRP platelet rich plasma
  • a method of preventing displacement of a prosthesis, optionally a stent and optionally formed of nitinol comprising: inserting the prosthesis into a preexisting passageway of a living organism, the prosthesis contacting an interior wall of the passageway; and applying plasma, optionally platelet rich plasma (PRP), to at least one of the wall and the prosthesis so that the prosthesis becomes integrated into the wall of the passageway.
  • plasma optionally platelet rich plasma (PRP)
  • IAE A system comprising: a prosthesis, optionally a stent and optionally formed of nitinol, configured to contact or engage an interior wall of a preexisting passageway of a living organism, and plasma, optionally platelet rich plasma (PRP), for applying to at least one of the wall and the prosthesis so that the prosthesis becomes integrated into the wall of the passageway.
  • PRP platelet rich plasma
  • 3AE The system of embodiment 1AE or 2AE, wherein the plasma is sprayed or injected.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Vascular Medicine (AREA)
  • Surgery (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Nursing (AREA)
  • Inorganic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Child & Adolescent Psychology (AREA)
  • Obesity (AREA)
  • Medical Informatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Prostheses (AREA)

Abstract

L'invention concerne un procédé permettant de maintenir un dispositif médical en place dans une lumière d'un organe creux d'un patient pendant une période de plusieurs mois ou années comprenant la non-utilisation d'une endoprothèse métallique ou biorésorbable auto-expansible. Facultativement, une solution de plasma riche en plaquettes (PRP) peut être appliquée à une endoprothèse pour intégrer l'endoprothèse dans un passage intérieur d'un patient. L'endoprothèse peut facultativement être formée d'un nitinol et insérée à travers la bouche du patient. Des sutures peuvent être utilisées pour fixer l'endoprothèse au passage intérieur du patient.
EP22709167.5A 2021-02-22 2022-02-22 Procédés et dispositifs pour implants médicaux Pending EP4294469A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202163200212P 2021-02-22 2021-02-22
PCT/US2022/070759 WO2022178555A1 (fr) 2021-02-22 2022-02-22 Procédés et dispositifs pour implants médicaux

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EP4294469A1 true EP4294469A1 (fr) 2023-12-27

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US (1) US20240024541A1 (fr)
EP (1) EP4294469A1 (fr)
IL (1) IL304446A (fr)

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US20240024541A1 (en) 2024-01-25
IL304446A (en) 2023-09-01

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