WO2022047544A1 - Traitement à effraction minimale de l'arthrose et d'autres affections - Google Patents

Traitement à effraction minimale de l'arthrose et d'autres affections Download PDF

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WO2022047544A1
WO2022047544A1 PCT/AU2021/051028 AU2021051028W WO2022047544A1 WO 2022047544 A1 WO2022047544 A1 WO 2022047544A1 AU 2021051028 W AU2021051028 W AU 2021051028W WO 2022047544 A1 WO2022047544 A1 WO 2022047544A1
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agent
blood vessel
target
bodily tissue
afferent
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PCT/AU2021/051028
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English (en)
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Steven Landers
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IP Cornerstone Pty Ltd
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Priority claimed from AU2020903180A external-priority patent/AU2020903180A0/en
Application filed by IP Cornerstone Pty Ltd filed Critical IP Cornerstone Pty Ltd
Publication of WO2022047544A1 publication Critical patent/WO2022047544A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/04—X-ray contrast preparations
    • A61K49/0433—X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
    • A61K49/0447—Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is a halogenated organic compound
    • A61K49/0452—Solutions, e.g. for injection
    • 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
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/48—Other medical applications
    • A61B5/4887—Locating particular structures in or on the body
    • A61B5/489—Blood vessels
    • 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
    • A61M25/00—Catheters; Hollow probes
    • A61M25/01—Introducing, guiding, advancing, emplacing or holding catheters
    • 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
    • A61M31/005—Devices for introducing or retaining media, e.g. remedies, in cavities of the body for contrast media

Definitions

  • the present invention relates generally to the treatment or prevention of osteoarthritis, and other conditions such as cancer in mammalian subjects.
  • methods utilising techniques of interventional radiology to administer therapeutic compounds in a highly targeted manner are particularly preferred.
  • Musculoskeletal conditions remain significant causes for long-term pain and disability in humans. Under the rubric of musculoskeletal conditions, osteoarthritis is a chronic and progressive joint disease typically affecting the hands, spine, hips, knees and ankles. It is the most common form of arthritis affecting well over 200 million individuals globally.
  • Osteoarthritis may arise from mechanical stress on joints, there being also an accompanied deficiency in the ability of joint tissues to repair damage.
  • the mechanical stress may arise from misalignment of bones, injury, forces placed on the joint by excessive body weight, a loss of strength in muscles supporting a joint, and impairment of peripheral nerves.
  • osteoarthritis include thickening of joint ligaments, wearing or detachment of menisci, formation of osteophytes about the joints, increase in subchondral bone volume and hypomineralization. Pain associated with osteoarthritis is thought to originate from the thickened synovium and subchondral bone lesions.
  • osteoarthritis There is no cure for osteoarthritis, with treatment options being chiefly directed to physical therapy to maintain joint mobility and flexibility as best as possible, and managing pain with oral analgesics and other pharmaceutical agents. It is a problem in the art that some pharmaceutical agents have low therapeutic indices, and therefore present issues of toxicity or side-effects when used at therapeutic levels.
  • destruction in the hostile environment of the gastrointestinal tract can be limiting.
  • first-pass degradation by the liver can limit therapeutic levels of the agent at a target site.
  • intra-articular administration of hyaluronic acid to supplement levels in the synovial fluid is helpful in regaining the natural lubricating effect of the fluid.
  • Administration of a therapeutic via the intra-articular route is painful, and can lead to infection of the joint.
  • the newly deposited hyaluronic acid eventually degrades and is not replaced by the body leading to a return of pain and dysfunction in the joint.
  • Intra-articular administration of a pharmacologically active agent may be ineffective where pain originates in intra-osseous or peri-articular tissues.
  • Arthroplasty is an option for severely degraded joints. This type of surgery is economically burdensome, and carries the risk of infection and the formation of blood clots. More over the artificial joint materials implanted in an arthroplasty can wear or loosen overtime and require later replacement.
  • the present invention provides a method of treating and/or preventing inflammation in a bodily tissue, the method comprising the step of introducing an anti-inflammatory agent and/or embolic agent into an afferent blood vessel of a target bodily tissue that is inflamed or is liable to become inflamed, and causing or allowing the anti-inflammatory agent and/or embolic agent to pass via the afferent blood vessel to the target bodily tissue.
  • the method comprising the steps of: identifying a target afferent blood vessel supplying blood to a target bodily tissue, introducing an anti-inflammatory agent and/or embolic agent into the target afferent blood vessel, and causing or allowing the anti-inflammatory agent and/or embolic agent to pass via the target afferent blood vessel to the target bodily tissue.
  • the step of identifying a target afferent blood vessel supplying blood to an inflamed bodily tissue comprises the steps of: identifying a candidate afferent blood vessel, introducing an imaging agent into the candidate afferent blood vessel, causing or allowing the imaging agent to pass via the candidate afferent blood vessel into surrounding tissue, generating an image of afferent blood vessels and/or a tissue region by way of detecting the presence or absence of the imaging agent, and assessing the image to determine whether or not the candidate afferent blood vessel supplies the target bodily tissue.
  • the candidate afferent blood vessel is considered or is more likely to be considered a target afferent blood vessel if it supplies the target bodily tissue, and/or a tissue region proximal thereto from which a blood vessel may be recruited to supply the target bodily tissue.
  • the method comprises the step of assessing the image to determine whether or not the candidate afferent blood vessel supplies nontarget bodily tissue.
  • the candidate afferent blood vessel is not considered or is less likely to be considered a target afferent blood vessel if it does not supply the target bodily tissue.
  • the method comprises the step of assessing the image to decide whether or not the candidate afferent blood vessel preferentially supplies the target bodily tissue over a non-target bodily tissue.
  • the candidate afferent blood vessel is considered or is more likely to be considered a target afferent blood vessel if it preferentially supplies the target bodily tissue over a non-target bodily tissue.
  • the candidate afferent blood vessel is considered or is more likely to be considered a target afferent blood vessel if it preferentially supplies the target bodily tissue over a non-target bodily tissue by a multiple of at least about 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 3, 4, 5, 6, 7, 8, 9 or 10.
  • the target afferent blood vessel supplies a network of abnormal neovessels which supplies the target bodily tissue.
  • the method comprises assessing the image to decide whether or not blood vessels supplied by the candidate afferent blood vessel forms a network of abnormal neovessels or a normal collateral vessel which supplies the target bodily tissue.
  • the candidate afferent blood vessel is considered or is more likely to be considered a target afferent blood vessel if blood vessels supplied by the candidate afferent blood vessel forms a network of abnormal neovessels which supplies the target bodily tissue.
  • the method comprises the step of occluding a non-target afferent blood vessel so as to prevent, inhibit or limit introduction of the antiinflammatory agent and/or embolic agent into the non-target afferent blood vessel.
  • the inflammation in a bodily tissue is inflammation in a musculoskeletal tissue.
  • the target bodily tissue is a component of a joint, or is functionally related to a joint.
  • the inflammation of the musculoskeletal target is at least partially causative of pain or malfunction.
  • the inflammation in a bodily tissue is inflammation in a tissue having a neoplasm, or a tissue associated with a neoplasm.
  • the neoplasm is malignant.
  • the anti-inflammatory agent lacks or substantially lacks any one or more of: vascularization activity, anti-angiogenic activity, vasodilator activity, vasoconstriction activity, embolization activity, blood vessel occlusion activity, thrombolytic activity, anti-neoplastic activity, inflammatory activity, anti-infective activity, or immunomodulatory activity.
  • the anti-inflammatory agent has one or more activities other than an anti-inflammatory activity, however anti-inflammatory activity is the primary activity.
  • the anti-inflammatory agent is a non-steroidal anti-inflammatory drug or a corticosteroidal drug.
  • the non-steroidal anti-inflammatory drug is selected form the group consisting of a COX-1 and/or COX-2 inhibitor, a salicylate, a proprionic acid derivative, an enolic acid derivative, an anthranilic derivative, a sulfon anilide, a cytokine, a cytokine inhibitor, or functional equivalent thereof.
  • the corticosteroidal drug is selected from the group consisting of hydrocortisone, methyl prednisolone, betamethasone, triamcinolone, or functional equivalent thereof.
  • the anti-inflammatory agent is a biologic agent or a gene therapy agent.
  • the biologic agent is a protein or a peptide or a polypeptide, or an antibody, or an antibody fragment, or a deoxyribonucleic acid or a ribonucleic acid.
  • the gene therapy agent is a coding nucleic acid in combination with a vector or transfection facilitating agent.
  • the anti-inflammatory agent and/or embolic agent is substantially solubilised in a solvent.
  • the anti-inflammatory agent and/or embolic agent is present in the form of an aqueous solution.
  • the anti-inflammatory agent and/or embolic agent is devoid or substantially devoid of a particle or other solid.
  • the present invention provides a composition comprising an anti-inflammatory agent and/or embolic agent, the composition formulated or presented so as to facilitate administration into an afferent blood vessel of a target bodily tissue.
  • the administration is via an image-guided method whereby the anti-inflammatory agent and/or embolic agent is introduced into an identified afferent target blood vessel by a minimally invasive method.
  • the present invention provides an anti-inflammatory and/or embolic composition comprising an anti-inflammatory agent and/or embolic agent when used in an image-guided method whereby the anti-inflammatory agent and/or embolic agent is introduced into an identified afferent target blood vessel of a target bodily tissue.
  • the identified target afferent blood vessel is identified by a minimally invasive method.
  • the anti-inflammatory and/or embolic composition comprises an imaging agent.
  • the composition is present in the form of a reservoir of anti-inflammatory agent and/or embolic agent configured to be locatable in an afferent blood vessel supplying a target bodily tissue by a minimally invasive visually- guided method, and configured to release the anti-inflammatory agent and/or embolic agent into blood passing through the afferent blood vessel over a time period so as to expose the target bodily tissue to the anti-inflammatory agent and/or embolic agent over the time period.
  • the reservoir is a drug-eluting depot, or port, such as used in hepatic arterial infusion, or a functional equivalent thereof.
  • FIG. 1 shows tabulated results from the trial described in Example 2.
  • FIG. 2 shows KOOS pain score results from the trial described in Example 2.
  • the present invention provides a method of treating and/or preventing inflammation in a bodily tissue, the method comprising the steps of: identifying a target afferent blood vessel supplying blood to a target bodily tissue, introducing an antiinflammatory agent and/or embolic agent into the target afferent blood vessel, and causing or allowing the anti-inflammatory agent and/or embolic agent to pass via the target afferent blood vessel to the target bodily tissue. It is proposed that inflammation is of clinical importance in the origin of pain and associated dysfunction of an arthritic joint.
  • the administration of an anti-inflammatory agent and/or embolic agent by image guided means into an afferent artery supplying inflamed tissue via interventional radiological means is useful in the symptomatic treatment of osteoarthritis.
  • the present invention is predicated at least in part on the recognition of the importance of inflammatory mechanisms in osteoarthritis, and furthermore the use of minimally invasive image-guided techniques to administer anti-inflammatory agent and/or embolic agents in a targeted manner to tissues involved in the pathophysiology of arthritis.
  • Interventional radiological methods allow for the highly targeted delivery of antiinflammatory agent and/or embolic agents at relatively high levels (and in some cases up to saturation or near saturation levels), without toxicities or other adverse effects that would normally be noted at such levels of the agent.
  • the present methods may allow for levels of anti-inflammatory to be provided at a target tissue that are simply not physically possible by way or oral, parenteral, topical, intra-articular, intramuscular or subcutaneous administration of an agent.
  • the use of a visually-guided method such as fluoroscopy using a contrast medium
  • identify an afferent blood vessel that supplies a suspected inflamed tissue allows for the anti-inflammatory agent and/or embolic agent to be delivered to a relatively small volume of tissue.
  • the antiinflammatory agent and/or embolic agent may be introduced via a catheter into the femoral artery.
  • the femoral artery supplies many tissues of the lower leg selective administration of the agent to the knee will not be achieved.
  • Injection of a contrast agent into the popliteal artery allows for visualisation of the descending genicular artery which specifically supplies blood to the knee.
  • the catheter may be further advanced (under fluoroscopic guidance) to branches and sub-branches of the genicular artery in order to provide for more highly targeted administration.
  • the catheter tip may be still further advanced into finer vessels to very precisely target an inflamed tissue. Indeed, even neovessels associated with an inflamed tissue may be identified and flooded with an anti-inflammatory agent and/or embolic agent via the catheter. [063]. Without wishing to be limited by theory in any way, it is contemplated that exposure of inflamed tissues to high levels of anti-inflammatory agent and/or embolic agent, even for only a short period of time, may significantly disrupt established inflammatory pathways leading to a therapeutic effect extending over weeks or even months. In addition, or alternatively, the anti-inflammatory agent and/or embolic agent may act to prevent escalation of the inflammatory response.
  • the tissue under treatment may be exposed for no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 minutes, however in that time period the pathological inflammatory response in osteoarthritis (and other inflammation-mediated conditions) may be sufficiently attenuated so as to give a therapeutic benefit well after exposure to the agent.
  • the level of anti-inflammatory agent and/or embolic agent is present about the inflamed tissue at a multiple of the level normally achievable where the agent is administered orally or parenterally.
  • the multiple may be about 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 3, 4, 5, 6, 7, 8, 9 or 10.
  • the absolute level will be dependent at least in part on the species of antiinflammatory agent and/or embolic agent used.
  • the level of anti-inflammatory agent and/or embolic agent achievable at the target tissue may be considered by reference to a saturation level of the agent (i.e. the level where no further agent can be added to the extracellular compartment before the agent starts to leave solution).
  • the level of antiinflammatory agent and/or embolic agent achievable at the target tissue may be at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of the saturation level for the agent concerned.
  • the concentration of the anti-inflammatory agent and/or embolic agent solution is preferably relatively high, and possibly even at or close to saturation with respect to the solvent concerned.
  • the agent when introduced at the target site the agent is at a very high concentration and therefore potentially capable of flooding the site with the agent.
  • the anti-inflammatory agent and/or embolic agent is ibuprofen
  • a saturated or even supersaturated solution may be prepared.
  • the molecule has a solubility of 21 mg/ml in water at 25 degrees Celsius, and so concentration about this value, or 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, or 10% that value may be introduced in the relevant afferent blood vessel.
  • the anti-inflammatory agent and/or embolic agent is introduced into the target afferent blood vessel in an extended release form, such as a depot form.
  • This form may allow for the slow release of agent over a period of hours, days, weeks or months.
  • the concentration of agent about the target tissue may not be unusually high, however the ongoing exposure of the tissue to the agent may be sufficient so as to disrupt the pathological inflammation of the tissue.
  • Extended release may be achieved by the use of a gel or similar comprising the anti-inflammatory agent and/or embolic agent within a matrix. Dissolution of the matrix over time at the target site may release agent in a controlled manner until exhausted.
  • a biodegradable stent which is coated with an anti-inflammatory agent and/or embolic agent (possibly in the form a slow-release matrix) may be introduced into the afferent blood vessel.
  • compositions of the present invention may be art-accepted or formulated for use with the present methods.
  • an organ or tissue is targeted for treatment, with a flexible catheter being introduced into a large vessel of the body via a small incision.
  • a small incision in the groin, wrist, arm, ankle or neck may be used to introduce an angiographic catheter via an introducer sheath into a large diameter blood vessel of the body.
  • the catheter is manually urged through the introducer sheath into the large blood vessel, the catheter tip being advanced toward the target site.
  • the catheter is manually steerable to assist in directing the tip into a desired branch blood vessel.
  • An imaging medium (typically a contrast agent being a solution of a radio-opaque material) is introduced into the blood vessel so as to allow the radiologist to visualize downstream vasculature and guide the catheter tip progressively through a series of blood vessel branches to arrive at or near the target site.
  • fluoroscopy is used to present an image of the vasculature on a screen to the medical specialist
  • the catheter tip will be guided by the radiologist according to known vascular landmarks as revealed by the contrast agent.
  • the operator may guide the vasculature tip not by any known landmark but instead by the presence of abnormal vessels (such as neovessels) or other anatomical feature as revealed by the contrast agent.
  • a target afferent blood vessel which supplies blood to a target tissue may be identified, such as a tissue of an osteoarthritic joint.
  • an antiinflammatory agent and/or embolic agent may be introduced into the identified target afferent blood vessel via a catheter and normal blood circulation used to carry the agent in the anterograde direction to the supplied inflamed tissue.
  • the target afferent blood vessel is known before commencement of the present method, in which case an image -guided method is implemented to guide the catheter to the known blood vessel.
  • the known vessel may be the genicular artery and the anti-inflammatory agent and/or embolic agent is introduced via a catheter into that artery.
  • the catheter tip will be guided to a branch, subbranch, sub-sub branch or further finer branch of the known artery to identify a blood vessel that more specifically supplies the target inflamed tissue. In this way, particularly high concentrations of anti-inflammatory agent and/or embolic agent may be delivered to the target tissue whilst sparing non-target tissue from exposure to the agent.
  • a candidate afferent blood vessel is identified as a potential vessel that supplies the target bodily tissue.
  • the candidate vessel may be identified by reference to a known vascular landmark.
  • the princips pollicis artery supplies the thumb and accordingly that artery may be selected as a candidate artery for delivery of an anti-inflammatory agent and/or embolic agent to a joint of the thumb.
  • a more highly targeted treatment may be given where the catheter is advanced to a branch or sub-branch of the princips pollicis artery.
  • the catheter tip may be advanced to a branch or a sub-branch as a candidate vessel (or even finer vessel), with contrast medium being introduced at that point in the vasculature.
  • the contrast medium enters the target tissue and/or shows neovessels then the vessel into which that contrast medium was introduced is considered to be the target vessel.
  • a candidate vessel that is shown to supply (and preferably specifically supply) a target tissue is in accordance with the present methods considered a target afferent blood vessel.
  • more than one candidate afferent blood vessel may exist for any given target tissue.
  • more than one target afferent blood vessel may exist for any given target tissue.
  • the some clinical judgement may be required to select a vessel that is most helpful (or least harmful) in the general aim of targeting delivery of an anti-inflammatory agent and/or embolic agent to an inflamed tissue.
  • little or no clinical judgement is required, for example where a main artery is indicated (such as the radial artery for delivery of anti-inflammatory agent and/or embolic agent to the hand).
  • the method will be most efficacious where most, substantially all, or all the afferent blood vessels that supply blood to the target tissue are used to introduce antiinflammatory agent and/or embolic agent. In this way, little or none of the target tissue is spared from exposure to the agent thereby ensuring maximal diminution of the inflammatory state of the tissue.
  • the target afferent blood vessel may be selected so as to limit exposure of a nontarget bodily tissue.
  • target vessel may be a part of the microvasculature that supplies the target tissue, or may be a vessel that selectively supplies the microvasculature that supplies the target tissue.
  • it may be necessary to implement microangiography to introduce contrast medium and antiinflammatory agent and/or embolic agent into vessels of diameter 200 pm and under.
  • the skilled person has familiarity with microangiographic techniques and having the benefit of the present specification is enabled practice the present methods in smaller diameter blood vessels.
  • the target afferent blood vessel is identified by determining that the vessel supplies, or is part of, pathological neovasculature.
  • Abnormal neovessels may appear as a tumor blush-type enhancement in the arterial phase of a digital subtraction angiogram.
  • a medical practitioner having a specialty in imaging (such as an interventional radiologist) will generally be capable of visually determining the presence of a neovessel, and having the benefit of the present specification may introduce anti-inflammatory into the neovessels according to the present methods.
  • the afferent blood vessel may be collateral blood vessel that may be normally present or may have formed to shunt blood around a blockage so as to supply the target inflamed bodily tissue.
  • any determination, judgement or decision executed in a method may be made by a human (typically an interventional radiologist).
  • the determination, judgement or decision may be made non-human means such as algorithmic means or by artificial intelligence means.
  • the non-human means may comprise software -based image analysis means whereby an electronic image of blood vessels highlighted by a contrast agent is analyzed to determine a particular image pattern.
  • the image analysis means may comprise software configured to identify a network of neovessels.
  • Neovessels may be treated by means of embolization or ablation to prevent the flow of blood therethrough.
  • the determination may be made according to the radiologist’s knowledge of the condition to be treated, the anatomy of the general target site and the tissues which are likely to be inflamed and require treatment.
  • the presence of neovessels having an abnormal radiological appearance may allow the radiologist to make a reasonable assumption as to the usefulness of those neovessels to deliver an antiinflammatory agent and/or embolic agent.
  • the radiologist may combine two or more of aspects of anatomical knowledge, knowledge of the pathophysiology of the relevant condition, the image of the vasculature provided by the present method, the kinetics of flow of contrast agent through the vasculature, images of other bodily structures of the subject available to the radiologist, and the like. In any event, the radiologist may conclude only a likelihood of a candidate vessel being a useful target vessel.
  • the anti-inflammatory agent and/or embolic agent used in the present method may be any agent presently known to have anti-inflammatory activity, or any agent that is synthesized or isolated or becomes known to have anti-inflammatory activity.
  • the agent may be an element, an ion, a compound, a polymer or a more complex species.
  • the agent is not necessarily homogenous, with a heterogeneous mixture of two or more species being considered to be an anti-inflammatory agent and/or embolic agent in the context of the present invention.
  • the anti-inflammatory agent and/or embolic agent is a non-steroidal anti-inflammatory drug (NSAID).
  • NSAID non-steroidal anti-inflammatory drug
  • NSAIDs include aspirin, celecoxib (CelebrexTM), diclofenac (VoltarenTM), diflunisal (DolobidTM), etodolac (LodineTM), ibuprofen (AdvilTM), indomethacin (IndocinTM), ketoprofen (OridisTM), ketorolac (ToradolTM), nabumetone (RelafenTM), naproxen (NaprosynTM), oxaprozin (DayproTM), piroicam (FeldeneTM), salsalate (AmgesicTM), sulindac (ClinorilTM) and tolmetin (TolectinTM).
  • the anti-inflammatory agent and/or embolic agent may be a corticosteroid.
  • This class of drug includes the glucocorticoids such as hydrocortisone (CortefTM), cortisone, ethamethasoneb (CelestoneTM), prednisone (IntensolTM), prednisolone (OrapredTM), triamcinolone (AristospanTM) Methylprednisolone (MedrolTM), and dexamethasone (IntensolTM).
  • the corticosteroid may be a mineralocorticoid such as Fludrocortisone (FlorinefTM).
  • the anti-inflammatory agent and/or embolic agent may be an antileukotriene, a class of drugs which typically function as leukotriene -related enzyme inhibitors (arachidonate 5 -lipoxygenase) or leukotriene receptor antagonists (cysteinyl leukotriene receptors) thereby disrupting the function of these inflammatory mediators.
  • antileukotriene a class of drugs which typically function as leukotriene -related enzyme inhibitors (arachidonate 5 -lipoxygenase) or leukotriene receptor antagonists (cysteinyl leukotriene receptors) thereby disrupting the function of these inflammatory mediators.
  • exemplary forms of this class of drug include zileuton and meclofenamate sodium.
  • the anti-inflammatory agent and/or embolic agent may be a disease modifying agent, as distinct from an agent that merely targets inflammatory pathways.
  • a disease modifying drug may act to indirectly act to reduce or prevent inflammation be altering the course of the disease underlying the inflammation.
  • the anti-inflammatory agent and/or embolic agent may be a biologic, such as a TNF- a inhibitor.
  • TNF-a inhibitors block tumor necrosis factor, a cytokine involved in inflammation.
  • Exemplary TNF-a inhibitors include: adalimumab (HumiraTM), certolizumab (CimziaTM), etanercept (EnbrelTM), golimumab (SimponiTM), and infliximab (RemicadeTM). These drugs may increase the risk of fungal infections and tuberculosis when administered systemically by infusion. However, targeted delivery to the biologic to a site of inflammation as provided by the present methods may lessen the occurrence or severity of adverse events.
  • Other potentially useful biologies include interleukin inhibitors, including inhibitors of IL-1, IL-6, IL-12, and IL-13 activity.
  • Drugs in this class include anakinra (KineretTM), tocilizumab (ActemraTM), canakinumab (HarisTM), secukinumab (CosentyxTM) and ustekinumab (StelaraTM).
  • Patients receiving interleukin inhibitors may suffer bowel perforation when systemically infused. The present method may avoid the need to flood the systemic circulation with agent causing gastrointestinal problems.
  • a useful biologic may be a peptide or polypeptide such as calcitonin, being a 32- amino acid polypeptide hormone of thyroid origin.
  • An exemplary calcitonin product is salmon calcitonin produced by recombinant DNA technology (MiacalcinTM), which is typically (in the prior art) administered parenterally.
  • MoacalcinTM recombinant DNA technology
  • cartilage and subchondral bone act as a functional unit, in both the normal and pathological state.
  • Vascular pathology and the loss of mineral density in subchondral bone have been found to be important in the initiation and progression of osteoarthritis.
  • Calcitonin acts to conserve or increase bone density, or improve fracture healing, and may therefore provide advantage in arthritis treatment and/or prevention.
  • a biologic used as an anti-inflammatory agent and/or embolic agent according to the present methods may function preventing excessive pro-inflammatory cytokine production, signaling, and downstream nuclear factor KB (NF-KB) activation.
  • NF-KB nuclear factor KB
  • small interfering RNA molecules (siRNAs), and other biological inhibitors are considered promising treatments.
  • the subject treated by the present invention is generally a mammal, preferably a human being, male or female, in whom a decrease of inflammatory activity is required in a discrete area of the body.
  • the anti-inflammatory agent and/or embolic agent is typically administered in a therapeutically effective amount, meaning an amount of the agent that will elicit the biological or medical response of a tissue, system, animal or human that is being sought by the researcher, veterinarian, physician or other clinician.
  • treatment means alleviating, inhibiting, slowing or arresting the development, reversing and/or relieving a condition related to inflammation including any disease, disorder, state, syndrome, symptom or aesthetic condition to which such term is associated. It is not intended that these terms are used to indicate a complete cure of any condition.
  • prevent means preventing of the development of, or alleviating to some extent, a condition related to inflammation including any disease, disorder, state, syndrome, symptom or aesthetic condition to which such term is associated. It is not intended that these terms are used to indicate a complete prevention of any condition.
  • compositions described in this section may be used any of the compositions described in this section below, and in that regard the contents of this section is imported into the description herein relating to methods.
  • the composition derives novelty in the context of the methods described herein, and in other embodiments the composition per se is novel.
  • composition is intended to encompass a product comprising an anti-inflammatory agent and/or embolic agent (optionally in a specified amount), or any product which results, directly or indirectly, from combination of an antiinflammatory agent and/or embolic agent with any other active or inert chemical species or solvent.
  • composition is intended to encompass a product comprising active agent(s), optionally inert ingredient(s), as well as any product which results, directly or indirectly, from combination, complexation or aggregation of any two or more of the agents/ingredients, or from dissociation of one or more of the agents/ingredients, or from other types of reactions or interactions of one or more of the agents/ingredients.
  • compositions of the present invention encompass any composition made by admixing an anti-inflammatory agent and/or embolic agent and a pharmaceutically acceptable carrier.
  • pharmaceutically acceptable it is meant the carrier, diluent or excipient must be compatible with the other agents/ingredients of the formulation and not deleterious to the subject recipient thereof.
  • the anti-inflammatory be administered in active form, or alternatively in non-active form as a pro-drug and converted to active form after administration.
  • an enzyme of the target tissue may convert a pro-drug to a drug.
  • the pro-drug is considered an anti-inflammatory agent and/or embolic agent in the context of the present invention.
  • the composition comprises a combination of antiinflammatory agent and/or embolic agent and a contrast agent.
  • a combination composition facilitates the concomitant introduction of therapeutic agent whilst allowing visualization of the vessels supplying the inflamed tissue.
  • the composition may be formulated so as to allow for the co-solution of the anti-inflammatory agent and/or embolic agent and the contrast agent concerned.
  • the skilled person is entirely familiar with various contrast agents useful in fluorography (such as iodinated agents) or MRI (such as magnetically active agents) and given the benefit of the present specification is enabled to produce useful combinations.
  • the concentration of anti-inflammatory agent and/or embolic agent in the present compositions may be higher compared with compositions used for parenteral administration or oral administration.
  • the present invention allows for more highly targeted administration of agent to target tissue.
  • a saturated or even supersaturated solution may be prepared from administration to a target tissue according to the present methods.
  • the agent may have a certain solubility value in water (or other solvent) at 25 degrees Celsius, and so the composition may be prepared by adding a saturating or supersaturating amount of the anti-inflammatory agent and/or embolic agent to a set volume of the desired solvent.
  • a lower concentration is required in which case an amount of about 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, or 10% of the saturating or supersaturating amount is added to the set volume.
  • the absolute amount of agent added to the set volume will of course vary depending on the agent itself, given the differences in solubility between agents and the difference in the ability of different solvents to solubilise a given agent.
  • compositions of the present invention contain at least one pharmaceutically acceptable anti-inflammatory agent and/or embolic agent and, where appropriate, one or more pharmaceutically acceptable excipients.
  • pharmaceutically acceptable excipients include, for example, physiologically harmless buffers (such as bicarbonate, phosphate, citrate), stabilizers (such as DTPA, sodium edetate, calcium disodium edetate), electrolytes (such as sodium chloride), antioxidants (such as ascorbic acid) or a substance to achieve a desired osmolality (such as mannitol, or glucose).
  • heparin may be added to inhibit blood clotting during or after performance of the method.
  • the compositions are of aqueous base.
  • solubilizers such as ethanol, dimethyl sulfoxide, propylene glycol, TweenTM 80, or TritonTM X-100 may be required in some cases.
  • compositions may be configured as a depot and may be in the form of a gel or present in some type of matrix causing the slow release of the agent to the target tissue.
  • the depot may be of low viscosity when passing through the catheter but then solidify or partially solidify once deposited.
  • a depot may be formed by the use of drug eluting beads, stents, coated stents, dissolving stents, cages or balloons.
  • Such compositions may use polyethylene glycol as a slow-release excipient.
  • the present methods may include the step of embolizing the vessels used to introduce the anti-inflammatory agent and/or embolic agent, or may include embolization alone.
  • the embolization may occur at the same time as the introduction, for example by the composition having an embolic agent (such as an embosphere) or an embolic solvent (such as an alcohol).
  • the depot may be deposited into a vessel by the present methods, and the vessel subsequently embolized.
  • the embolization may be temporary so as to allow for the introduction of further anti-inflammatory agent and/or embolic agent at a later date, or may be permanent.
  • anti-inflammatory agent and/or embolic agents to inflamed tissues in a highly targeted manner as provided by the present methods allows for the achievement of very high levels of the agent in the affected tissue.
  • oral or systemic administration of a therapeutic agent exposes the majority of bodily tissues to that agent.
  • delivery of anti-inflammatory agent and/or embolic agents to nontarget tissues can lead to adverse events (such as cardiac arrest or stroke where NSAIDS are used), especially when high dosages are utilized.
  • inflamed tissue to a high concentration of an anti-inflammatory agent and/or embolic agent (and even for just a single administration) can sufficiently interrupt the inflammatory response that is pathological in osteoarthritis so as to give protracted relief from swelling and pain in an affected joint.
  • methotrexate which is a potent anti-inflammatory but well known to cause cytotoxicity.
  • a further advantage of the highly targeted administration of anti-inflammatory agent and/or embolic agent is that lower amounts of agent may be used to achieve a desired clinical endpoint. While many NSAIDs and similar compounds are considered inexpensive drugs, more exotic agents such as biologies are typically very expensive and therefore used sparingly in a clinical environment. For example cytokines, peptides, antibodies and nucleic acids may be capable of achieving useful control of inflammation however large amounts (at a high cost) are required to be administered parenterally to achieve a desired concentration at a small target site.
  • a further advantage is that the anti-inflammatory agent and/or embolic agent may introduced to vessels that supply intra-osseous and periarticular tissues. This provides an advantage over intra-articular delivery whereby such tissues may not be exposed to an antiinflammatory agent and/or embolic agent.
  • a bonus effect of the present invention may be the treatment of conditions other than osteoarthritis according to the present methods.
  • Localized pathological inflammation may be involved in other conditions of the mammalian body, and may therefore be more effectively treatable by the present methods.
  • the present minimally invasive image-guided methods are useful in delivering anti-inflammatory agent and/or embolic agents to cancerous tissues.
  • Potentially treatable cancers include caner of the breast, colon, rectum, gallbladder, pancreas, lung, oesophagus and stomach, as well as melanoma and sarcoma.
  • the cancer may be a primary cancer or a metastatic cancer.
  • a cancer cell may express a cytokine or a cytokine receptor.
  • tumor microenvironment plays an important role in carcinogenesis.
  • An inflammatory component may be present and contributes to tumor proliferation, angiogenesis, metastasis and resistance to hormonal and chemotherapy.
  • Pro- inflammatory factors such as cytokines may be useful targets in that regard, particularly cytokines produced in the course of tumor metastasis.
  • An inflammatory environment comprising immune cells and their secreted cytokines, chemokines and growth factors cis contemplated to contribute significantly to the invasive and metastatic traits of cancer cells.
  • metastasis is a major cause of cancer mortality and accordingly inhibiting that process by disrupting inflammatory pathways using anti-inflammatory agent and/or embolic agents introduced in a highly targeted manner according to the present methods may lower mortality or otherwise extend lifespan.
  • the present methods may be used slow tumor progress and/or metastasis by flooding neoplastic cells with high levels of anti-inflammatory agent and/or embolic agent. Again, high levels of anti-inflammatory agent and/or embolic agent may be provided without concern for toxicity on other tissues of the body. Furthermore, the levels may be significantly higher than those achievable by another route of administration.
  • the anti-inflammatory agent and/or embolic agent may be provided in a combination composition with an antineoplastic agent, or an anti-angiogenesis agent, or an embolic agent.
  • additional agents may also be administered in a highly targeted manner according to the present methods. Synergistic effects between the actives may result to further improve the treatment of a solid tumor.
  • EXAMPLE 1 Transcatheter arterial delivery of anti-inflammatory agent and/or embolic agent to subject having moderate osteoarthritis of the knee. [120].
  • the subject for treatment has moderate knee pain, as determined by a visual analog scale (VAS).
  • VAS visual analog scale
  • the subject’s pain is not improved by conservative treatment such as oral pain medications, physiotherapy or intra-articular injection of hyaluronic acid.
  • radiography the patient is assessed as having osteoarthritis of less than grade 3 by Kellgren-Lawrence grading.
  • the subject is assessed by a physician, physiotherapist or other health professional. Assessment includes knee examination to determine range of motion and pain tenderness of the knee joint. Assessment further includes scoring by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) questionnaire which considers pain, stiffness, and physical function in the context of normal daily activities.
  • WOMAC Western Ontario and McMaster University Osteoarthritis Index
  • Transcatheter arterial delivery is performed under local anaesthesia.
  • a 3F introducer sheath was used to obtain percutaneous arterial access.
  • the subject’s femoral artery is accessed by puncturing in an ipsilateral anterograde fashion, and 2,000 IU heparin administered via the IV route.
  • a 3F angiographic catheter is passed through the introducer and advanced toward the popliteal artery.
  • the descending genicular artery, superior and inferior lateral genicular arteries, superior and inferior medial genicular arteries, and the median genicular artery are visualized.
  • Abnormal neovessels are visually identified, and accessed by way of a 2.4F microcatheter inserted coaxially via the 3F catheter and selectively located in the identified abnormal neovessels.
  • Antiinflammatory agent and/or embolic agent is introduced into the abnormal neovessels via the 2.4F microcatheter.
  • the anti-inflammatory agent and/or embolic agent is ToradolTM
  • a contrast agent is mixed with the anti-inflammatory composition.
  • an antiinflammatory agent and/or embolic agent may cause embolization, or may be mixed with an embolic agent in which case the contrast agent may assist in monitoring embolization.
  • the anti-inflammatory agent and/or embolic agent is co -administered with other biologically active agents such as a vasodilator, vasoconstrictor, embolic agent, immune modulator, or an analgesic.
  • Success of the treatment is determined by subsequent assessment by VAS (for pain) and WOMAC scoring (for pain stiffness and physical function).
  • EXAMPLE 2 Experimental trial of transcatheter arterial delivery of embolization composition to subjects having osteoarthritis of the knee demonstrating better efficacy using complete embolization.
  • the treatment group received angiography and embolization; the control group received a placebo embolization procedure.
  • One interventional radiologist trained in vascular embolization performed all procedures. The procedures, real or placebo, were performed within a 30-60 min duration.
  • embolic agents may be used, including liquid agents (such as glue, onyx, alcohol, ALGEL), particle-type agents (such as polyvinyl alcohol, and embospheres), and other agents useful in the occlusion of small vessels.
  • liquid agents such as glue, onyx, alcohol, ALGEL
  • particle-type agents such as polyvinyl alcohol, and embospheres
  • Participants in the control group received light sedation with midazolam and fentanyl and a local anaesthetic injection and incision into their groin.
  • the radiologist simulated the insertion of a guide wire and catheter into the femoral artery and completion of the embolization procedure. No wire or catheter was in fact introduced. No radiation was used. No contrast was administered.
  • the participant viewed pre-recorded video images of an angiogram and genicular artery vascular embolization. A dressing was applied to the incision site.
  • the results in FIG. 1 relate to participants that underwent complete intervention (i.e. complete occlusion of blood flow to the target tissue area).
  • positive differences (95% CI) are noted, indicating an improvement in the parameter concerned. Improvements were noted in all five parameters at 12 months post treatment. Particularly large improvements were seen for physical function and quality of life. Less favourable results overall were noted for the other two categories of treatment (i.e. single vessel intervention, or incomplete intervention (multi-vessel)).
  • EXAMPLE 3 Transcatheter arterial delivery of anti-inflammatory agent to subject having a solid malignant tumour.
  • a cancerous tissue requiring exposure to an anti-inflammatory agent may be accessed via central venous access device such as a port-a-catheter, Hickman catheter, pheresis catheter or a peripherally inserted central catheter (PICC) line.
  • central venous access device such as a port-a-catheter, Hickman catheter, pheresis catheter or a peripherally inserted central catheter (PICC) line.
  • PICC peripherally inserted central catheter
  • the anti-inflammatory agent is ToradolTM IV/IM (ketorolac tromethaminean, 15 mg in 1 mL (1.5%), or 30 mg in 1 mL (3%) in sterile solution or 60 mg in 2 mL (3%)).
  • a contrast agent is mixed with the anti-inflammatory composition.
  • an anti-inflammatory agent may cause embolization, or may be mixed with an embolization agent in which case the contrast agent may assist in monitoring embolization.
  • a chemotherapeutic agent may be mixed with the anti-inflammatory composition.
  • the two-dimensional anatomical information provided by fluoroscopy is insufficient or at least ambiguous. This may not allow the physician to properly resolve a target tissue, and the connection between any candidate blood vessel and a target tissue.
  • an interventional magnetic resonance system also termed XMR system
  • XMR systems allow for real-time interventional procedures to be performed in a clinical setting providing the ability to fully visualize the target tissue in three-dimensions and fully monitor any nontarget distribution.
  • Some XMR systems can also perform fluoroscopy. Accordingly catheter placement may be guided by fluoroscopy, and then the system switched to magnetic resonance mode to gain a more complete understanding of the target anatomy and the connection between various target tissues and afferent blood vessels in the region.
  • the anti-inflammatory agent and/or embolic agent is associated with a visualization agent so as to be radiopaque (to be detectable by fluoroscopy) or magnetically active (to be detectable by MRI).
  • a visualization agent so as to be radiopaque (to be detectable by fluoroscopy) or magnetically active (to be detectable by MRI).
  • the present invention is described by reference to osteoarthritis as an exemplary musculoskeletal disorder.
  • Other musculoskeletal disorders that may amenable to treatment or prevention by the present methods or treatable by the present compositions include rheumatoid arthritis, inflammation of the joint capsule (such as in adhesive capsulitis), tendonitis, tendinopathies, enthesopathies and the like.

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Abstract

La présente invention concerne, de manière générale, le traitement ou la prévention de l'arthrose, et d'autres affections telles que le cancer chez des sujets mammifères. Dans des modes de réalisation particuliers de l'invention, mais pas exclusivement, des procédés mettent en œuvre des techniques de radiologie interventionnelle pour administrer des composés thérapeutiques de manière hautement ciblée. Dans un mode de réalisation, l'invention se présente sous forme d'un procédé de traitement et/ou de prévention d'une inflammation dans un tissu corporel, le procédé comprenant l'étape consistant à introduire un agent anti-inflammatoire et/ou un agent embolique dans un vaisseau sanguin afférent d'un tissu corporel cible qui est enflammé ou est susceptible de s'enflammer, et à amener l'agent anti-inflammatoire et/ou à l'agent embolique à, ou à lui permettre de, passer par le vaisseau sanguin afférent pour atteindre le tissu corporel cible.
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Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004073688A1 (fr) * 2003-02-21 2004-09-02 Biocompatibles Uk Limited Administration d'un medicament a partir d'agents emboliques
WO2006013376A2 (fr) * 2004-08-04 2006-02-09 Biocompatibles Uk Limited Liberation de medicaments a partir d'agents emboliques
WO2009022190A1 (fr) * 2007-08-16 2009-02-19 Biocompatibles Uk Limited Administration de combinaisons de médicaments
WO2011029867A1 (fr) * 2009-09-10 2011-03-17 Occlugel Polymère bio-résorbable implantable
US20110104052A1 (en) * 2007-12-03 2011-05-05 The Johns Hopkins University Methods of synthesis and use of chemospheres
CA2732488A1 (fr) * 2010-01-27 2011-07-27 Biosphere Medical, Inc. Microspheres utiles pour l'embolisation vasculaire therapeutique
WO2020092815A1 (fr) * 2018-11-01 2020-05-07 Memorial Sloan Kettering Cancer Center Ciblage de tumeur intra-artériel amélioré pour un diagnostic et/ou un traitement
WO2020231842A1 (fr) * 2019-05-10 2020-11-19 Incept, Llc Embolisation avec des matériaux transitoires

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004073688A1 (fr) * 2003-02-21 2004-09-02 Biocompatibles Uk Limited Administration d'un medicament a partir d'agents emboliques
WO2006013376A2 (fr) * 2004-08-04 2006-02-09 Biocompatibles Uk Limited Liberation de medicaments a partir d'agents emboliques
WO2009022190A1 (fr) * 2007-08-16 2009-02-19 Biocompatibles Uk Limited Administration de combinaisons de médicaments
US20110104052A1 (en) * 2007-12-03 2011-05-05 The Johns Hopkins University Methods of synthesis and use of chemospheres
WO2011029867A1 (fr) * 2009-09-10 2011-03-17 Occlugel Polymère bio-résorbable implantable
CA2732488A1 (fr) * 2010-01-27 2011-07-27 Biosphere Medical, Inc. Microspheres utiles pour l'embolisation vasculaire therapeutique
WO2020092815A1 (fr) * 2018-11-01 2020-05-07 Memorial Sloan Kettering Cancer Center Ciblage de tumeur intra-artériel amélioré pour un diagnostic et/ou un traitement
WO2020231842A1 (fr) * 2019-05-10 2020-11-19 Incept, Llc Embolisation avec des matériaux transitoires

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
"Abstracts of the 31st Annual Meeting of the Society of Interventional Radiology", JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY, vol. 17, no. 2, 4 April 2006 (2006-04-04), Toronto, Ontario, Canada, pages 1 - 89 *
"CIRSE 2019 Abstracts", CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY, SPRINGER US, NEW YORK, vol. 42, no. Suppl 3, 1 August 2019 (2019-08-01), New York, pages 65 - 549, XP037076665, ISSN: 0174-1551, DOI: 10.1007/s00270-019-02282-x *
CIAMPI-DOPAZO J. J., MA MARQUINA-VALERO, C. LANCIEGO-PÉREZ , PUENTES-GUTIERREZ A, : "Combined transcatheter arterial embolization and rehabilitative treatment for adhesive capsulitis refractory to conservative treatment", INTERVENCIONISMO, 1 January 2020 (2020-01-01), pages 74 - 83, XP055911946, Retrieved from the Internet <URL:http://revistaintervencionismo.com/wp-content/uploads/In_junio_Original2.pdf> [retrieved on 20220412], DOI: 10.30454/2530-1209.2020.2.2 *
LANDERS, S. ET AL.: "Genicular Artery Embolization to Improve Pain and Function in Early-Stage Knee Osteoarthritis - 24-Month Pilot Study Results", JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY, vol. 31, no. 9, 2020, pages 1453 - 1458, [retrieved on 20200828] *
LEE, S. H. ET AL.: "Clinical Outcomes of Transcatheter Arterial Embolisation for Chronic Knee Pain: Mild-to-Moderate Versus Severe Knee Osteoarthritis", CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY, vol. 42, no. 11, 2019, pages 1530 - 1536, XP036897330, DOI: 10.1007/s00270-019-02289-4 *
OKUNO, Y. ET AL.: "Transcatheter Arterial Embolization as a Treatment for Medial Knee Pain in Patients with Mild to Moderate Osteoarthritis", CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY, vol. 38, no. 2, 2015, pages 336 - 343, XP035466046, DOI: 10.1007/s00270-014-0944-8 *
OWEN RICHARD J. T.: "Embolization of Musculoskeletal Bone Tumors", SEMINARS IN INTERVENTIONAL RADIOLOGY, THIEME, US, vol. 27, no. 02, 1 June 2010 (2010-06-01), US , pages 111 - 123, XP055911902, ISSN: 0739-9529, DOI: 10.1055/s-0030-1253510 *
YANG BIAO, LI CHUN-LIN, GUO WEN-HAO, QIN TIAN-QIANG, JIAO HE, FEI ZE-JUN, ZHOU XUAN, DUAN LIN-JIA, LIAO ZHENG-YIN: "Intra-arterial ethanol embolization augments response to TACE for treatment of HCC with portal venous tumor thrombus", BMC CANCER, vol. 18, no. 1, 1 December 2018 (2018-12-01), XP055911903, DOI: 10.1186/s12885-018-3989-2 *

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