WO2021119173A1 - Compositions d'accélérant thermique et procédés d'utilisation - Google Patents

Compositions d'accélérant thermique et procédés d'utilisation Download PDF

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Publication number
WO2021119173A1
WO2021119173A1 PCT/US2020/064082 US2020064082W WO2021119173A1 WO 2021119173 A1 WO2021119173 A1 WO 2021119173A1 US 2020064082 W US2020064082 W US 2020064082W WO 2021119173 A1 WO2021119173 A1 WO 2021119173A1
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WO
WIPO (PCT)
Prior art keywords
ablation
thermal accelerant
thermal
accelerant
tissue
Prior art date
Application number
PCT/US2020/064082
Other languages
English (en)
Other versions
WO2021119173A4 (fr
Inventor
William Keun Chan Park
Damian E. DUPUY
Original Assignee
Rhode Island Hospital
Brown University
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
Priority claimed from US16/708,416 external-priority patent/US11076916B2/en
Application filed by Rhode Island Hospital, Brown University filed Critical Rhode Island Hospital
Priority to EP20899590.2A priority Critical patent/EP4072457A4/fr
Priority to JP2022535545A priority patent/JP2023506466A/ja
Priority to KR1020227023594A priority patent/KR20220125252A/ko
Publication of WO2021119173A1 publication Critical patent/WO2021119173A1/fr
Publication of WO2021119173A4 publication Critical patent/WO2021119173A4/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/06—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating caused by chemical reaction, e.g. moxaburners
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/14—Probes or electrodes therefor
    • A61B18/1477—Needle-like probes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B18/1815—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using microwaves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/36—Image-producing devices or illumination devices not otherwise provided for
    • A61B90/37—Surgical systems with images on a monitor during operation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
    • 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
    • A61K49/0409—Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is not a halogenated organic compound
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
    • A61K49/1803—Semi-solid preparations, e.g. ointments, gels, hydrogels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
    • A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
    • A61K49/226—Solutes, emulsions, suspensions, dispersions, semi-solid forms, e.g. hydrogels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N7/02—Localised ultrasound hyperthermia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00315—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for treatment of particular body parts
    • A61B2018/00529—Liver
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00571—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for achieving a particular surgical effect
    • A61B2018/00577—Ablation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00571—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for achieving a particular surgical effect
    • A61B2018/00613—Irreversible electroporation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/36—Image-producing devices or illumination devices not otherwise provided for
    • A61B90/37—Surgical systems with images on a monitor during operation
    • A61B2090/374—NMR or MRI
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/36—Image-producing devices or illumination devices not otherwise provided for
    • A61B90/37—Surgical systems with images on a monitor during operation
    • A61B2090/376—Surgical systems with images on a monitor during operation using X-rays, e.g. fluoroscopy
    • A61B2090/3762—Surgical systems with images on a monitor during operation using X-rays, e.g. fluoroscopy using computed tomography systems [CT]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/36—Image-producing devices or illumination devices not otherwise provided for
    • A61B90/37—Surgical systems with images on a monitor during operation
    • A61B2090/378—Surgical systems with images on a monitor during operation using ultrasound
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2218/00—Details of surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2218/001—Details of surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body having means for irrigation and/or aspiration of substances to and/or from the surgical site
    • A61B2218/002—Irrigation

Definitions

  • the method can further apply the first thermal accelerant to a surface of a tissue at a target site to cauterize the target site.
  • positioning the first thermal accelerant can further include positioning the accelerant at an outer-boundary of the target site.
  • the method can further introduce a second applicator or a second thermal accelerant to the target site, the second applicator and the second thermal accelerant being positioned in a substantially rhombal shape with the first applicator and the first thermal accelerant.
  • the first applicator or the second applicator can include an electrode having one or more energy emitting devices thereon.
  • the method can further include passing one or more of the first applicator and the first thermal accelerant through the target site under image guidance.
  • FIG. IB shows a metastatic tumor in the liver of a patient and abutting the hepatic vein
  • FIG. 2B shows effective rates of temperature rise for untreated tissue and for different heat substrate formulations
  • FIG. 3B shows extension of ablation with the placement of FIG. 3 A;
  • FIG. 4 shows a liver section and placement of thermal accelerant between a tumor and a blood vessel;
  • FIG. 5 shows placement of two antennas and two sites of thermal accelerant for creating an enlarged ablation zone
  • the thermal accelerant can also be positioned to prevent the heat loss (also known as "heat sink” see FIG. 1C— that would otherwise occur due to the presence of a large blood vessel in or adjacent to the intended ablation zone, trapping an effective level of heating in the near field without ablating the blood vessel itself.
  • Modeling was performed for the use of multiple antennae, and for more than one localized body of thermal accelerant strategically placed to define a larger, or more uniform and expanded ablation zone, or to define an ablation zone while limiting the time that power is applied to other portions of the organ.
  • the thermal accelerant plays a cooperative and synergistic role in augmenting the effective microwave energy. The suitability for each of these interventions, however, will require that the actual level of increased heating be sufficient to overcome any countervailing conduction and absorption effects exerted by surrounding tissue.
  • FIG. 3 A and FIG. 3B This situation is illustrated schematically in FIG. 3 A and FIG. 3B wherein a small mass of the substrate located at the upper right distal region or surface of an irregular tumor (FIG. 3 A) and outside of a theoretical circular or symmetric effective ablation zone centered on the microwave antenna, produces a well-defined ablation region (thick band, as seen in FIG. 3B), extending the region of complete ablation to or beyond the tumor boundary.
  • the study was further designed to test the notion that the thermal accelerant can help avoid the heat loss (also known as "heat sink") caused by a blood vessel adjacent to the ablation zone, without ablating the blood vessel itself
  • FIG. 4 This situation is illustrated in FIG. 4, which identifies where to place the thermal accelerant to enhance tumor ablation while avoiding damage to the vessel.
  • FIG. 4 This situation is illustrated in FIG. 4, which identifies where to place the thermal accelerant to enhance tumor ablation while avoiding damage to the vessel.
  • FIGS. 3 A and 3B schematically diagram the microwave ablation, wherein a thermal accelerant is injected to an imaginary tumor target area.
  • a typical ablation zone is about 2.5 cm in diameter when a single antenna is used with the microwave ablation conditions: 915 MHz, 60 W for 10 minutes.
  • the thermal accelerant due to its viscous composition, remains relatively stationary at a target site once deposited since it turns to a gel at body temperature.
  • the track of the thermal accelerant gel is shown just outside of the nominal ablation zone, and runs through the outer-boundary of the imaginary tumor in the liver.
  • FIG. 3B shows the coagulative ablation zone extended by augmentation of the microwave energy.
  • CsCl cesium chloride
  • the polymer component possesses the unique property of being a liquid at ambient temperature, but a gel at typical body temperature (35-37° C.). Moreover, upon a further increase in temperature, the polymer precipitates by expelling water molecules from the polymeric lattice structure.
  • the Aim 1 is intended to examine heat augmentation efficiency of the thermal accelerant (TA) in percutaneous microwave ablation using a single antenna, while Aim 2 is intended to assess efficacy for overcoming heat sink effects, and Aim 3 investigate the TA being used for situations that may have been addressed previously by using an extra antenna.
  • TA thermal accelerant
  • the components of the TA may include three, non-toxic components: 1) a polymer (natural or artificial) as a carrier; 2) an ionic component for overall charge and viscosity balance; 3) an imaging component.
  • the coagulation temperature is pH-dependent, i.e., low pH shifts the coagulation (denaturation) temperature of albumin from 62 °C (at pH 7.4) to 46 °C (at pH 3.5).
  • Such ability to control the TA can allow for protection from collateral injury of important tissues or organs during ablation. While it will be appreciated that the temperature at which the TA switches off can be varied, though some non-limiting examples of such temperatures can be >60° C, >80° C, >100° C, and so forth in optimized formulations, in some embodiments, temperatures of up to 170° C can be observed under in vitro conditions during microwave ablations under the following conditions: 915 MHz, 60W for 10 minutes at 1.5 cm from the antenna.
  • TTC-treated kidney tissue images show a typical ablation zone using a single antenna with 60 W, 915 MHz, for 10 minutes, and the ablation is slightly off-centered as the connective tissues in the central renal sinus area are less affected.
  • the resultant ablation zone is about 1 cm in diameter.
  • TA was able to produce a drastic increase of the ablation zone (3 cm in diameter) where the central tissues were also shown to be completely ablated (60 W, 915 MHz, 10 minutes; the distance between antenna and TA was 1.3 cm).
  • the relative distances between the TA 140, the electrode 110, and the target site 130 can vary based on the desired ablation zone, patient anatomy, the size of the target site, and so forth, as discussed in detail above.
  • a second electrode or a second thermal accelerant can be added to the target site, as discussed above, to maximize the ablation zone.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Electromagnetism (AREA)
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  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Gynecology & Obstetrics (AREA)
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  • Acoustics & Sound (AREA)
  • Thermotherapy And Cooling Therapy Devices (AREA)
  • Surgical Instruments (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Lubricants (AREA)

Abstract

La présente invention concerne un accélérant thermique qui est administré à un site tissulaire et localisé pour moduler la forme, l'étendue ou toute autre caractéristique d'une ablation tissulaire hyperthermique induite par RF ou micro-ondes. L'accélérant peut être fourni par l'intermédiaire d'une pièce à main guidée par image ou par l'intermédiaire d'une lumière ajoutée à une antenne à micro-ondes, et favorise un chauffage plus rapide, une ablation plus complète et/ou une région de traitement plus étendue afin de réduire la récidive de cancers traités, surmonter les limitations naturelles, les variations de réponse tissulaire et la déperdition ou la perte de chaleur depuis l'antenne. L'accélérant est fourni sous la forme d'un fluide visqueux mais thermosensible, et est fixé en place pour former des régions d'absorption préférentielle ou de chauffage préférentiel. Des temps d'exposition plus courts pour chauffer le champ lointain peuvent permettre la survie de tissu vulnérable tel que les vaisseaux, et des antennes multiples peuvent être utilisées pour un traitement efficace de tumeurs irrégulières ou de grande taille.
PCT/US2020/064082 2019-12-09 2020-12-09 Compositions d'accélérant thermique et procédés d'utilisation WO2021119173A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP20899590.2A EP4072457A4 (fr) 2019-12-09 2020-12-09 Compositions d'accélérant thermique et procédés d'utilisation
JP2022535545A JP2023506466A (ja) 2019-12-09 2020-12-09 熱促進剤組成物および使用方法
KR1020227023594A KR20220125252A (ko) 2019-12-09 2020-12-09 열 촉진제 조성물 및 사용 방법

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US16/708,416 2019-12-09
US16/708,416 US11076916B2 (en) 2015-12-23 2019-12-09 Thermal accelerant compositions and methods of use

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WO2021119173A1 true WO2021119173A1 (fr) 2021-06-17
WO2021119173A4 WO2021119173A4 (fr) 2021-08-05

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WO (1) WO2021119173A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12016624B2 (en) 2015-12-23 2024-06-25 Rhode Island Hospital Thermal accelerant compositions and methods of use

Citations (6)

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Publication number Priority date Publication date Assignee Title
US20040210282A1 (en) * 2002-05-20 2004-10-21 Flock Stephen T. Electromagnetic treatment of tissues and cells
US20080171982A1 (en) * 2005-04-12 2008-07-17 Henri Mehier Implantable Tube For Injection Particularly Of Heat Transfer Fluid Into All Or Part Of A Human Or Animal Tissue
US20110152852A1 (en) * 2008-07-31 2011-06-23 Regents Of The University Of Minnesota Thermochemical ablation system using heat from delivery of electrophiles
US20130053932A1 (en) * 2009-01-28 2013-02-28 Clean Technology International Corporation Material for facilitating thermal treatments of biological tissues and method of energy targeting leading to thermal treatment of biological tissues
US20140094793A1 (en) * 2012-10-02 2014-04-03 Covidien Lp Device and method for heat-sensitive agent application
US20170182165A1 (en) * 2015-12-23 2017-06-29 Rhode Island Hospital Thermal accelerant compositions and methods of use

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Publication number Priority date Publication date Assignee Title
WO2016197093A1 (fr) * 2015-06-05 2016-12-08 Brown University Substrat thermique et/ou compositions d'amélioration d'image et procédés d'ablation de tissu améliorés
CN109464186B (zh) * 2017-09-08 2023-12-22 泽丹医疗股份有限公司 治疗肺部肿瘤的装置和方法

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040210282A1 (en) * 2002-05-20 2004-10-21 Flock Stephen T. Electromagnetic treatment of tissues and cells
US20080171982A1 (en) * 2005-04-12 2008-07-17 Henri Mehier Implantable Tube For Injection Particularly Of Heat Transfer Fluid Into All Or Part Of A Human Or Animal Tissue
US20110152852A1 (en) * 2008-07-31 2011-06-23 Regents Of The University Of Minnesota Thermochemical ablation system using heat from delivery of electrophiles
US20130053932A1 (en) * 2009-01-28 2013-02-28 Clean Technology International Corporation Material for facilitating thermal treatments of biological tissues and method of energy targeting leading to thermal treatment of biological tissues
US20140094793A1 (en) * 2012-10-02 2014-04-03 Covidien Lp Device and method for heat-sensitive agent application
US20170182165A1 (en) * 2015-12-23 2017-06-29 Rhode Island Hospital Thermal accelerant compositions and methods of use

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP4072457A4 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12016624B2 (en) 2015-12-23 2024-06-25 Rhode Island Hospital Thermal accelerant compositions and methods of use

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Publication number Publication date
EP4072457A1 (fr) 2022-10-19
EP4072457A4 (fr) 2024-01-03
WO2021119173A4 (fr) 2021-08-05
KR20220125252A (ko) 2022-09-14
JP2023506466A (ja) 2023-02-16

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