WO2019211832A1 - Administration localisée d'un agent actif - Google Patents

Administration localisée d'un agent actif Download PDF

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Publication number
WO2019211832A1
WO2019211832A1 PCT/IL2019/050466 IL2019050466W WO2019211832A1 WO 2019211832 A1 WO2019211832 A1 WO 2019211832A1 IL 2019050466 W IL2019050466 W IL 2019050466W WO 2019211832 A1 WO2019211832 A1 WO 2019211832A1
Authority
WO
WIPO (PCT)
Prior art keywords
strand
agent
delivery
body cavity
dimensional anchor
Prior art date
Application number
PCT/IL2019/050466
Other languages
English (en)
Inventor
Ilan Bar-Am
Ariel Weinstein
Original Assignee
Ocon Medical Ltd.
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 Ocon Medical Ltd. filed Critical Ocon Medical Ltd.
Publication of WO2019211832A1 publication Critical patent/WO2019211832A1/fr

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Classifications

    • 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
    • A61F6/00—Contraceptive devices; Pessaries; Applicators therefor
    • A61F6/06—Contraceptive devices; Pessaries; Applicators therefor for use by females
    • A61F6/14—Contraceptive devices; Pessaries; Applicators therefor for use by females intra-uterine type
    • 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
    • A61F6/00—Contraceptive devices; Pessaries; Applicators therefor
    • A61F6/06—Contraceptive devices; Pessaries; Applicators therefor for use by females
    • A61F6/14—Contraceptive devices; Pessaries; Applicators therefor for use by females intra-uterine type
    • A61F6/18—Inserters or removers ; Apparatus for loading an intra-uterine device into an insertion tube
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
    • A61K9/0039—Devices retained in the uterus for a prolonged period, e.g. intrauterine devices for contraception
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
    • A61M31/002—Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time

Definitions

  • the present invention relates to a device for delivering an agent to a body cavity or tissues adjacent thereto.
  • Embodiments of the present invention relate to an intrauterine device for delivering an agent to the uterus and/or surrounding tissues such as the vaginal canal.
  • Drugs have long been used to treat diseases and extend lives. Drugs can be delivered locally or systemically with the efficacy of the drug being directly related to the way its formulated and delivered.
  • Systemic delivery methods such as oral, intravenous, intramuscular, and transdermal are effective but can produce undesirable side effects due to systemic exposure and may result in a less than optimal quantity of a drug at the desired treatment site.
  • Local drug delivery via, for example a local injection addresses this limitation of systemic delivery but can be difficult to carry out especially in cases where the targeted tissue is deep within the body and/or the treatment regimen requires more than a single administration.
  • a device for delivering an agent into a body cavity comprising a strand capable of self-forming a three dimensional anchor having a first loop approximately perpendicular to, and positioned through, a second loop; and a delivery conduit attached to, or forming a part of, the strand, the delivery conduit being for delivering the agent into the body cavity from outside the body when the three dimensional anchor is in the body cavity.
  • the body cavity is the uterus and the strand is selected such that the three dimensional anchor is capable of elastically compressing in response to contraction of the uterus.
  • the strand is composed of Nitinol wire having a diameter of 0.3-0.5 mm.
  • a distal end portion of the delivery tube is positioned over at least a portion of the strand.
  • a distal end portion of the delivery tube is molded over at least a portion of the strand.
  • a distal end portion of the delivery tube includes at least one opening for delivering the agent.
  • the strand is at least partially hollow and the delivery conduit forms a part of the strand.
  • the strand is composed of an elastic polymer.
  • the at least one opening is positioned within or adjacent to the three dimensional anchor.
  • the device further comprises a reservoir filled with the agent in fluid communication with the delivery conduit.
  • the agent is selected from the group consisting of at least one hormone, an antineoplastic, an analgesic, an antibiotic, a stimulant, an ablative agent and a contraceptive.
  • the at least one hormone is selected from the group consisting of estrogen, progesterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH), Human chorionic gonadotropin (HCG).
  • the strand is formed from Nitinol and the delivery tube is formed from a polymer.
  • a proximal portion of the strand is positioned outside the body cavity when the three dimensional anchor is in the body cavity.
  • the proximal portion of the strand is attached to an outer surface of the delivery tube.
  • the three dimensional anchor is 12- 20 mm in diameter.
  • a device for delivering an agent to a tissue region adjacent a body cavity comprising a strand capable of self forming a three dimensional anchor having a first loop approximately perpendicular to, and positioned through, a second loop; and a delivery element attached to, or forming a part of, the strand, the delivery element including the agent and being in contact with the tissue region when the three dimensional anchor is in the body cavity.
  • the body cavity is the uterus and the adjacent tissue region is the cervix or vaginal canal.
  • the agent is selected from the group consisting of a chemotherapeutic agent, at least one hormone, an analgesic and an antibiotic.
  • FIG. 1 illustrates an embodiment of the present device having a delivery tube covering the entire length of the strand.
  • FIG. 2 illustrates an embodiment of the present device having a delivery tube covering a three dimensional anchor portion of the strand.
  • FIG. 3 illustrates another embodiment of the present device having a delivery tube covering a linear portion (tail) of the strand.
  • FIG. 4 illustrates an embodiment of the present device connected to an automated drug pump.
  • FIG. 5 illustrates an embodiment of the present device connected to a syringe.
  • FIG. 6 illustrates an embodiment of the present device having drug release openings in a single loop of the three dimensional anchor.
  • FIG. 7 illustrates an embodiment of the present device having drug release openings along the entire three dimensional anchor.
  • FIGs. 8A-D illustrate delivery of an embodiment of the present device into a uterus.
  • FIG. 9 illustrates an embodiment of the present device having a drug release reservoir portion connected to an anchor portion.
  • the present invention is of a device for delivering an active agent to a body cavity to or to tissues adjacent the body cavity.
  • the present invention can be used to deliver an active agent such as a hormone or an anti-neoplastic drug to the uterus or adjacent tissues.
  • Localized delivery of drugs can be effected via a local injection or via implanted drug depots.
  • the latter approach is advantageous in that it enables sustained delivery of a drug in a localized manner thereby traversing the need for repeated injections while minimizing side effects typically associated with systemic delivery.
  • the present inventors have devised a drug delivery device that enables localized delivery of an active agent such as a drug in a sustained or pulsatile manner.
  • an active agent such as a drug in a sustained or pulsatile manner.
  • Such a device is particularly advantageous when configured for pulsatile delivery of gonadotropins to the uterus for the purpose of inducing ovulation for IVF treatment.
  • IVF treatment is typically effected using one of three main approaches: (i) Luteal suppression (or long luteal or simply just long) - involves suppression of the ovaries using a GnRH analog such as LupronTM) during the luteal phase of the menstrual cycle preceding the planned IVF treatment cycle.
  • Luteal suppression or long luteal or simply just long
  • ovarian stimulation is accomplished with daily sub cutaneous or intra muscular injections of gonadotropins (e.g., Gonal-FTM, FollistimTM). Lupron is usually continued until the day of the HCG trigger shot (to trigger ovulation).
  • gonadotropins e.g., Gonal-FTM, FollistimTM
  • Lupron is usually continued until the day of the HCG trigger shot (to trigger ovulation).
  • a common variation of this protocol is to stop Lupron at the time of starting stimulation with the gonadotropins.
  • Flare stimulation in which no medications are taken until the second day of the menstrual cycle. At that time, a micro-dose (most commonly) of Lupron is used to stimulate the pituitary gland and induce it to release its store of FSH and LH. Simultaneously, gonadotropins are administered producing an accumulated effect of ovarian stimulation.
  • GnRH-antagonist stimulation in which GnRH antagonists are added later in the stimulation cycle in order to prevent premature ovulation.
  • the gonadotropins are started on cycle day 2 of a normal menstrual period. Once the follicles have reached a specific size (usually 12 to 14 mm), the woman begins the GnRH-antagonist medication, which almost instantaneously prevents the pituitary gland from generating an LH surge.
  • SC subcutaneous
  • IM intra muscular
  • a device for delivering an agent into a body cavity there is provided a device for delivering an agent into a body cavity.
  • body cavity refers to any hollow tissue structure. Examples of body cavities include, but are not limited to, the anal canal, the rectum, the GI tract, the urinary tract, the uterus, the vaginal canal, the nasal tract and the respiratory tract.
  • Embodiments of the device of the present invention include a strand capable of self forming a three dimensional anchor having a first loop about perpendicular to a second loop.
  • the first loop can be positioned the second loop (intersecting a plane thereof), or it can be positioned outside the second loop.
  • the term "strand" denotes an elongated member having two free ends.
  • the strand can be a wire (e.g. single filament, multi-filament or braided metal or polymer wire), a string, a strip or a tube.
  • the strand can be solid or hollow.
  • Embodiments of the present device further include a delivery conduit attached to, or forming a part of, the strand.
  • the delivery conduit can be configured for delivering the agent into the body cavity from outside the body when the three dimensional anchor is in the body cavity.
  • the delivery tube includes two openings fluidly connected via a conduit (the lumen of the delivery tube). A first (proximal) opening is positionable outside the body and a second (distal) opening is positionable within the cavity.
  • the first opening can be connected to a reservoir/source (e.g. syringe) of an active agent provided in liquid/gel form.
  • a reservoir/source e.g. syringe
  • the delivery tube can be 100-2000 mm in length with an inner lumen/s diameter/s of 0.3- 6 mm and a wall thickness of 0.1-1 mm.
  • the delivery tube can be made from a polymer such as silicone, polyethylene and the like.
  • the proximal opening of the delivery tube can be fitted with a port (e.g. a Luer lock port or a sterilizable injection port) for connecting to a source of the delivered agent.
  • the delivery conduit can be a tube attached to the strand by gluing or welding a wall portion of the delivery tube to a wall of the strand or by molding the delivery tube over a (proximal) portion of the strand.
  • the delivery tube and strand can also be a unitary structure, e.g., the strand and tube can be fabricated from a single elastic hollow tube (metallic or polymeric).
  • the strand portion of embodiments of the present device is capable of forming an elastically deformable three dimensional anchor.
  • the strand can be composed of an elastic material selected capable of being pre-shaped into the three dimensional anchor and being linearized by a pulling force on the ends of the strand. Such a transition between three dimensional and linear configurations can be effected repeatedly due to the elastic nature of the material and its ability to maintain the three dimensional shape in the absence of any pulling force on the ends of the wire (e.g. shape memory).
  • materials suitable for such purposes include alloys such as stainless steel, nickel-titanium, copper- aluminum-nickel and other copper containing alloys or polymers such as polyurethanes, polyols, polyethylene terephthalates and acrylates.
  • the strand can be 50-200 mm long with the portion forming the three dimensional anchor being 50-100% of the overall length (50-80 mm).
  • the three dimensional anchor of embodiments of the present device is formed by two or more contiguous loops of the strand which are angled with respect to each other.
  • the loops can be 10-20 mm in diameter and can be arranged (in a two loop configuration) such that one loop is positioned within the plane of the second loop and is angled 60-120, preferably 80-100 degrees with respect thereto (the angle is measured at the wire portion interconnecting the loops).
  • the loops form a loop-in-loop structure that 'traps' a roughly spherical volume of 0.5-4.2 cm 3 (1.15-3.0 cm 3 preferred) with a surface area of 3.1-12.6 cm 2 (5.3-10.2 cm 2 preferred). Further description of the three dimensional anchor and formation of the loops from the linear/linearized wire is provided hereinbelow.
  • the present device was designed in order to enable localized delivery of an active agent such as a drug with the three dimensional anchor configured for anchoring an opening of a delivery tube within the cavity in which delivery of the drug is desired.
  • the three dimensional anchor In the case of delivery into a uterus, the three dimensional anchor must provide stable anchoring of the delivery tube throughout the delivery regimen and must resist migration during uterine contractions and possible unintentional pull out forces applied to the proximal end of the delivery tube.
  • embodiments of the present device apply a counter force to both the relaxed and contracted states of the uterus.
  • Such a counterforce ensures that the three dimensional anchor portion of embodiments of the present device does not substantially migrate within the uterus and more importantly, is not accidentally pulled out from the uterus.
  • the agent deliverable through embodiments of the present device can be a hormone (e.g., a gonadotropin), an antineoplastic (e.g., paclitaxel), an analgesic (e.g., ibuprofen), an antibiotic (e.g., doxycycline), a stimulant (e.g., methylphenidate), an anesthetic (e.g., lidocaine), an immunotherapy agent (e.g., bevacizumab), an antidepressant agent (e.g., sertraline), an ablative agent (e.g., silver nitrate) or a contraceptive (e.g., levonorgestrel).
  • a hormone e.g., a gonadotropin
  • an antineoplastic e.g., paclitaxel
  • an analgesic e.g., ibuprofen
  • an antibiotic e.g., doxycycline
  • a stimulant
  • Figures 1-8D illustrates embodiments of the present device configured for uterine drug delivery and referred to herein as device 10.
  • device 10 includes a strand 12 forming a three dimensional anchor 14 having a first loop 16 contiguous with a second loop 18.
  • the distal end of strand 12 (indicated by E) is turned inward in the direction of the volume defined by loops 16 and 18 of device 10 and can include a protective thickening or bead 15.
  • Proximal end E can be pulled into a delivery sleeve 100 for strand 12 linearization.
  • Loops 16 and 18 are connected via a contiguous segment 20 which forms an angle ⁇ ' between loops 16 and 18; angle ⁇ ' can be 60-100 degrees.
  • Three dimensional anchor 14 is attached to or contiguous with proximal portion 38 (also referred to herein as tail 38) of strand 12.
  • the overall diameter of three dimensional anchor 14 (D) can be 15-20 mm. Loops 16 and 18 are substantially of equal diameter (d) of 15-20 mm.
  • the diameter of strand 12 can be 0.2 - 0.6 mm.
  • three dimensional anchor 14 is configured to partially compress under the forces applied by the walls of a relaxed uterine cavity.
  • a three dimensional anchor 14 having an overall diameter of 20 mm constructed from a Nitinol wire (0.2 mm in diameter) formed into two contiguous loops (each 20 mm in diameter) angled at 90 degrees with respect to each other would partially compress under a gram force (grL) of 25-190 grams per cm 2 . Near flattening of this configuration of device 10 would require about 120-380 grams per cm 2 . Device 10 can be compressed between the loops with (25-120 grL - partial to near flat), or through a loop (190-380 grL - partial to near flat).
  • three dimensional anchor 14 When partially compressed, three dimensional anchor 14 applies an elastic counterforce to the walls of the uterine cavity thus firmly securing three dimensional anchor 14 in position.
  • Compression of three dimensional anchor 14 under such forces is influenced by two separate or combined mechanisms, change in angle A (elastic bending at segment 20) and shape change (round to oval) in each of loops 16 and 18 (elastic bending of the loops).
  • Compression along one axis of three dimensional anchor 14 is primarily mediated by segment 20 which can bend under relatively lower forces (exerted by relaxed uterine walls). Such compression of device enables three dimensional anchor 14 to assume the oval-shaped configuration described above. Collapse along the other axis requires a larger force (uterine contractions) since it necessitates a shape-change (round to oval) in loops 16 and 18 (as well as further bending of segment 20). Collapse through a combination of axis is also possible and will depend on the orientation of three dimensional anchor 14 in the uterine cavity and type of contractions.
  • Device 10 further includes a delivery tube 30 attached to (co-axially), or forming a part of strand 12.
  • Delivery tube includes proximal opening 32 and at least one distal opening 34 (Ligures 2, 3, 6 and 7) fluidly connected via lumen 36.
  • Figure 1 illustrates a configuration of device 10 in which delivery tube 30 covers the entire length of strand 12 (anchor 14 and tail 38).
  • Figures 2 and 3 illustrate configurations of device 10 in which delivery tube 30 is attached to a proximal portion 38 (tail) of strand 12. Such attachment can be effected by gluing, welding or otherwise mechanically securing a distal portion 40 of delivery tube 30 to proximal portion 38 of strand 12 (e.g., outer wall to outer wall).
  • distal portion 40 of delivery tube 30 can be positioned over (joined to) a proximal portion 38 of strand 12 in a manner which enables delivery of an agent from opening 34.
  • distal portion 40 can be molded over proximal portion 38 of strand 12 or it can simply be threaded over strand 12.
  • opening(s) 34 of delivery tube can be positioned proximally to the region of joining or opening 34 can be formed between delivery tube 30 and strand 14 (as is shown in Figures 2 and 3).
  • Figures 2 and 3 illustrate two slightly different configuration of device 10. While both configurations include two loops roughly perpendicular to each other, differences in segment 20 connecting loops 16 and 18 and region of intersection between the loops result in a slightly different overall shape of three dimensional anchor 14.
  • the loops of device 10 are oriented such that when the device is pulled out of the cavity by linearizing anchor 14, loops 16 18 freely slide with respect to each other without entangling.
  • Strand 12 can alternatively be formed from a hollow polymeric or metallic wire with a first portion capable of self forming three dimensional anchor 14 and a second and contiguous portion forming delivery tube 30.
  • One or more openings 34 can be positioned along strand 12 at the first and/or second portions.
  • Figures 6 and 7 illustrate a device 10 configuration in which delivery tube 30 includes openings 34 along a portion of a single loop ( Figure 6) or the entire three dimensional anchor ( Figure 7).
  • Such openings can be 0.1-0.5 mm in diameter and can be shaped as simple cylindrical holes or, for example, as outward cones for aerosolizing a delivered fluid.
  • Figures 4 and 5 illustrate the present device connected to an automated drug delivery pump 70 ( Figure 4) or a syringe 80 ( Figure 5).
  • a proximal opening 32 of delivery tube 30 can include a fitting (e.g. Luer lock) to enable connection to pump 70 or syringe 80.
  • Device 10 of the present invention can be used to deliver an agent such as a hormone, an antineoplastic, an analgesic, an antibiotic, a stimulant, an ablative agent or a contraceptive to the walls of the uterus and/or fallopian tube openings in a pulsatile or continuous manner over a period of hours, days, weeks or months.
  • Figures 8A-D illustrate delivery of device 10 into the uterus (U) of an IVF patient.
  • Device 10 is first linearized within a delivery sleeve 70 by pulling the distal end of strand 12 into a lumen of delivery sleeve 100 until the region of strand 12 forming three dimensional anchor 14 is completely linearized with delivery tube 30 positioned outside delivery sleeve 100 ( Figure 8A).
  • a distal opening of delivery sleeve 100 is then positioned inside the uterus and three dimensional anchor 14 is deployed therein (Figure 8B) by pulling on an end of delivery tube 30 while holding delivery sleeve 100 in position.
  • three dimensional anchor 14 is deployed ( Figure 8C)
  • delivery sleeve 100 is removed ( Figure 8D)
  • a proximal opening 32 of delivery tube 30 is connected to a pump 70/syringe 80 containing gonadotropins at IVF concentrations and a delivery dose suitable for IVF treatment (as described hereinabove) is provided to the patient in a bolus or pulsatile manner.
  • the present device allows a more localized delivery and thus a more efficacious uptake of gonadotropins, lower doses can be used in IVF treatment.
  • the present device can enable a dose regimen including half or less of the gonadotropin dose typically administered in IVF treatment.
  • the device also enables to abrade (scratch) the endometrium (Pippelle) prior to its removal by producing suction in the delivery tube via a syringe. Such abrasion can increase the embryo implantation success rate.
  • device 10 is pulled out of the uterus by simply pulling on the proximal end of delivery tube 30.
  • embodiments of the present device can also be configured for delivery of an agent to tissues adjacent the body cavity.
  • FIG. 9 One configuration of such a device is illustrated in Figure 9 and is referred to herein as device 200.
  • Device 200 includes strand 202 (which is similar to strand 12 described above) capable of self forming a three dimensional anchor 204 and a reservoir 206 attached thereto.
  • the reservoir can take the form of a strip, tube and the like and includes (or can be filled with) and agent in liquid, gel or solid form.
  • the agent can be configured for bulk or continuous release.
  • An example of reservoir 206 can be a strip or a perforated tube that can include an antineoplastic (e.g., paclitaxel), an analgesic (e.g., ibuprofen) or an antibiotic (e.g., doxycycline) in liquid/gel or dry form.
  • antineoplastic e.g., paclitaxel
  • an analgesic e.g., ibuprofen
  • an antibiotic e.g., doxycycline
  • Device 200 can be used by positioning three dimensional anchor 204 within cavity (as is described above for device 10) such that attached reservoir 206 is positioned adjacent to, and optionally in contact with, the walls of the cervix (C) and/or vagina to enable delivery of an agent contained therein to these tissues.
  • Device 200 can be used to treat cervical cancer by delivering chemotherapy to cervical tissues.

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  • Health & Medical Sciences (AREA)
  • Reproductive Health (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medicinal Chemistry (AREA)
  • Vascular Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Anesthesiology (AREA)
  • Hematology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Urology & Nephrology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des dispositifs d'administration d'un agent dans une cavité corporelle ou sur des tissus adjacents à celle-ci. Des modes de réalisation du dispositif comprennent un fil susceptible d'auto-former un ancrage tridimensionnel ayant une première boucle approximativement perpendiculaire à une seconde boucle, et positionnée à travers celle-ci, et un conduit ou élément d'administration fixé au fil, ou formant une partie de celui-ci.
PCT/IL2019/050466 2018-04-30 2019-04-25 Administration localisée d'un agent actif WO2019211832A1 (fr)

Applications Claiming Priority (2)

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US201862664300P 2018-04-30 2018-04-30
US62/664,300 2018-04-30

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WO2019211832A1 true WO2019211832A1 (fr) 2019-11-07

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024005634A1 (fr) * 2022-06-28 2024-01-04 Stichting Vumc Thérapie anti-angiogénique utilisée en tant que traitement de troubles utérins bénins

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3200815A (en) * 1962-04-24 1965-08-17 Mount Sinai Hospital Res Found Coil spring intra-uterine contraceptive device and method of using
US3256878A (en) * 1964-05-28 1966-06-21 Schwartz Jerome Intra-uterine contraceptive appliance
US5846219A (en) * 1994-05-26 1998-12-08 Vancaillie; Thierry G. Variable backflow suction-hydraulic curet
US6679266B2 (en) * 1995-06-07 2004-01-20 Conceptus, Inc. Contraceptive transcervical fallopian tube occlusion devices and their delivery
US7320325B2 (en) * 2000-04-25 2008-01-22 Impres Medical, Inc. Method and apparatus for creating intrauterine adhesions
US20140180067A1 (en) * 2012-12-20 2014-06-26 Volcano Corporation Implant delivery system and implants
US9259233B2 (en) * 2007-04-06 2016-02-16 Hologic, Inc. Method and device for distending a gynecological cavity
US20170246027A1 (en) * 2014-12-11 2017-08-31 Ocon Medical Ltd. Device positionable in the uterine cavity

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3200815A (en) * 1962-04-24 1965-08-17 Mount Sinai Hospital Res Found Coil spring intra-uterine contraceptive device and method of using
US3256878A (en) * 1964-05-28 1966-06-21 Schwartz Jerome Intra-uterine contraceptive appliance
US5846219A (en) * 1994-05-26 1998-12-08 Vancaillie; Thierry G. Variable backflow suction-hydraulic curet
US6679266B2 (en) * 1995-06-07 2004-01-20 Conceptus, Inc. Contraceptive transcervical fallopian tube occlusion devices and their delivery
US7320325B2 (en) * 2000-04-25 2008-01-22 Impres Medical, Inc. Method and apparatus for creating intrauterine adhesions
US9259233B2 (en) * 2007-04-06 2016-02-16 Hologic, Inc. Method and device for distending a gynecological cavity
US20140180067A1 (en) * 2012-12-20 2014-06-26 Volcano Corporation Implant delivery system and implants
US20170246027A1 (en) * 2014-12-11 2017-08-31 Ocon Medical Ltd. Device positionable in the uterine cavity

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024005634A1 (fr) * 2022-06-28 2024-01-04 Stichting Vumc Thérapie anti-angiogénique utilisée en tant que traitement de troubles utérins bénins

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