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WO2006078770A2 - Creation d'espace provisoire entre les tissus corporels - Google Patents

Creation d'espace provisoire entre les tissus corporels Download PDF

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Publication number
WO2006078770A2
WO2006078770A2 PCT/US2006/001826 US2006001826W WO2006078770A2 WO 2006078770 A2 WO2006078770 A2 WO 2006078770A2 US 2006001826 W US2006001826 W US 2006001826W WO 2006078770 A2 WO2006078770 A2 WO 2006078770A2
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WO
WIPO (PCT)
Prior art keywords
prostate
bioresorbable
rectum
spacing
fluid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2006/001826
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English (en)
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WO2006078770A3 (fr
Inventor
Winston E. Barzell
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Civco Medical Instruments Co Inc
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Civco Medical Instruments Co Inc
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 Civco Medical Instruments Co Inc filed Critical Civco Medical Instruments Co Inc
Publication of WO2006078770A2 publication Critical patent/WO2006078770A2/fr
Anticipated expiration legal-status Critical
Publication of WO2006078770A3 publication Critical patent/WO2006078770A3/fr
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • 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
    • A61B90/08—Accessories or related features not otherwise provided for
    • A61B2090/0815—Implantable devices for insertion in between organs or other soft tissues
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N2005/1092—Details
    • A61N2005/1094—Shielding, protecting against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1001—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
    • A61N5/1027—Interstitial radiation therapy

Definitions

  • This invention relates generally to the creation of temporary space between body tissues.
  • the present invention also relates, for example, to the use of a biodegradable spacer between the rectum and prostate prior to delivering external radiation therapy in the treatment of prostatic cancer.
  • Prostate cancer is a relatively radioresistant malignancy, but can be effectively treated with radiation if a high dose can be delivered.
  • the major risk to the delivery of high doses of radiation to the prostate is collateral radiation damage to surrounding structures, the rectum being the most vulnerable.
  • the rectum is susceptible because of the very close natural anatomic proximity of the posterior surface of the prostate and the anterior rectal wall and the comparative radiation sensitivity of the bowel. Radiation proctitis is the major limiting factor for the radiation therapist using this modality.
  • This type of proctitis may occur acutely during treatment and/or develop later as chronic and progressive radiation induced inflammatory reaction of the rectal wall that can cause diarrhea, rectal pain, tenesmus, bleeding and in the worst case, a recto-urethral fistula.
  • external beam radiation therapy either as monotherapy or in combination with implanted radioactive seeds (brachytherapy).
  • brachytherapy implanted radioactive seeds
  • the natural anatomic tissues that exist between the posterior surface of the prostate and the anterior rectal wall include two very thin but consistent fibrous layers or planes that define a potential space. These layers were discovered by anatomic dissection over 100 years ago and routinely are taken advantage of surgically to separate the prostate from the rectum in many operations.
  • transient filling of the potential space between these two separable layers has been exploited using saline or a temporary balloon to separate the rectal wall from the prostate for acute one-time therapies such as cryotherapy or microwave thermotherapy.
  • cryotherapy for example, in one technique a long needle may be inserted through the perineum while the patient is in the lithotomy position.
  • the needle tip may be placed into this potential space between the layers of Denonvillier's fascia and fluid instilled. The fluid then hydraulically dissects and fills this potential space to create a pillow shaped "balloon" of liquid separating the prostate and rectum.
  • the filled space between the two fascial layers can achieve one or a few centimeters of additional separation of the rectal wall and prostate when compared to normal anatomic proximity. This transient separation improves the safety margin for avoiding rectal injury during treatment.
  • One potential consequence of this dissection is scarring and adhesion making subsequent attempts to repeat this process more difficult.
  • U.S. Patent No. 6,210,314 Bl to Ein-Gal is directed to a prostate radiotherapy apparatus for spatially fixing a target volume in a prostate which is to be irradiated.
  • this patent describes the injection of water in the area of Denonvilliers' fascia for reflecting the rectal wall away from the prostate and provision of cooling in the area of the prostate to reduce the adverse effects of radiation on healthy tissue, e.g., the rectal wall or urethra.
  • This patent also is incorporated herein by reference.
  • the use of biodegradable materials has been known, for example, in the marking of biopsy sites, as exemplified in U.S. Patent No. 6,567,689 B2, which is incorporated herein in its entirety.
  • this patent falls short of the present inventions which relate to the treatment of the prostate.
  • the present invention provides for a more convenient and efficient method of creating a temporary biodegradable spacer between the rectum and the prostate. After the spacer is inserted, the prostate can be treated, for example, by radiation therapy with minimal or negligible harm to the rectum.
  • the invention relates to a method for treating a prostate with radiation comprising: introducing a fluid into a potential space defined between two layers of fascia to contact the two layers; forming a bioresorbable spacer from the fluid to provide an increased spacing of the prostate and a rectum from one another beyond natural spacing thereof; applying radiation therapy to the prostate after introducing the fluid into the potential space; maintaining a minimum spacing between the prostate and the rectum with the bioresorbable spacer for a time period of at least one month, wherein the minimum spacing is greater than the natural spacing.
  • the method may further include at least one of: allowing the prostate and the rectum to return to natural spacing thereof as the bioresorbable spacer is broken down in vivo; piercing at least one of the two layers of fascia to introduce the fluid into the potential space; obtaining an ultrasound image to determine whether the fluid is disposed in the potential space; obtaining an ultrasound image to determine whether the bioresorbable spacer is maintaining the minimum spacing; conducting x-ray fluoroscopy to determine whether the fluid is disposed in the potential space; conducting x-ray fluoroscopy to determine whether the bioresorbable spacer is maintaining the minimum spacing; obtaining imaging to determine whether the fluid is disposed in the potential space; obtaining imaging to determine whether the bioresorbable spacer is maintaining the minimum spacing.
  • the rectum has a rectal wall and in some embodiments when radiation therapy is applied to the prostate less than 50% of the rectal wall receives a dose of radiation no more than 55 Gy when the minimum spacing is maintained. In some embodiments, when radiation therapy is applied to the prostate less than 20% of the rectum receives a dose of radiation no more than 65 Gy when the minimum spacing is maintained.
  • the radiation therapy may deliver a dose of radiation to the prostate of at least 80 Gy, and the radiation therapy may be external beam radiation therapy and/or brachytherapy.
  • the fluid may include a liquid or a gel.
  • the minimum spacing may be maintained for a time period of at least two months or at least three months.
  • the minimum spacing for example, may be at least 0.5 cm, at least 1.0 cm, at least 1.5 cm, or at least 2.0 cm.
  • the fluid may be introduced into the potential space by injection.
  • the fluid may include a beneficial agent.
  • the fluid may include a therapeutic agent such as an anti-inflammatory agent.
  • the fluid may include a plurality of components that interact to form the spacer.
  • the spacer is sponge-like.
  • the spacer is at least partially solid.
  • the invention also relates to a method for providing temporarily increased spacing between a prostate and a rectum during radiation therapy including: introducing a volume of bioresorbable composition into a region between two layers comprising the fascia intestinal of the rectum and the Denonvilliers' fascia to directly contact the layers and exert pressure thereon, the volume selected to provide spacing of the prostate and the rectum from one another by at least 5.0 mm; applying radiation therapy to the prostate after introducing the volume of bioresorbable composition into the region; maintaining the at least 5.0 mm of spacing between the prostate and the rectum as a result of introduction of the bioresorbable composition for a time period of at least one week.
  • the method may further include one or more of: allowing the prostate and the rectum to return to natural spacing thereof as the bioresorbable composition is broken down in vivo; piercing at least one of the two layers to introduce the bioresorbable composition into the region; obtaining an image to determine whether the bioresorbable composition is maintaining the at least 5.0 mm of spacing between the prostate and the rectum.
  • the rectum may have a rectal wall and when radiation therapy is applied to the prostate less than 50% of the rectal wall receives a dose of radiation no more than 55 Gy when the spacing is maintained. Also, when radiation therapy is applied to the prostate less than 20% of the rectum may receive a dose of radiation no more than 65 Gy when the spacing is maintained.
  • the radiation therapy may deliver a dose of radiation to the prostate of at least 80 Gy and the radiation therapy may be external beam radiation therapy and/or brachytherapy.
  • the composition may include a fluid. In some embodiments, the composition may include a liquid or a gel.
  • the present invention also relates to a rectal spacing implant including an injectable volume of fluid for providing a bioresorbable mass adapted to directly contact anatomical layers defining recto-prostatic space while providing and maintaining a mass thickness of at least 5.0 mm between portions of a prostate and a rectum for at least one week before break down thereof.
  • the bioresorbable mass may be sponge-like.
  • the bioresorbable mass may be at least partially solid.
  • the present invention relates to a rectal spacing implant including an injectable volume of fluid for providing a bioresorbable mass adapted to directly contact anatomical layers defining recto-prostatic space while providing and maintaining a mass thickness of at least 5.0 mm between portions of a prostate and a rectum for at least forty-eight hours.
  • the bioresorbable mass may be sponge-like.
  • the bioresorbable mass may be at least partially solid.
  • the present invention relates to a radiation treatment system including: a radiation seed; and a rectal spacing implant including an injectable volume of fluid for providing a bioresorbable mass adapted to directly contact two layers of fascia defining recto-prostatic space, the bioresorbable mass capable of providing and maintaining a separation of at least 5.0 mm between portions of the two layers of fascia for at least forty-eight hours.
  • the bioresorbable mass may be sponge-like.
  • the bioresorbable mass may be at least partially solid.
  • the bioresorbable mass may be capable of providing and maintaining a separation of at least 5.0 mm between portions of the two layers of fascia for at least one week.
  • the present invention relates to a process for treating the prostate with radiation which process comprises the creation of a temporary space between the rectum and the prostate by preparing a biodegradable member having a predetermined lifetime and injecting said biodegradable member between the two layers of fascia separating the prostate and the rectum so as to develop a space between the prostate and the rectum, and applying radiation therapy after the creation of the temporary space with the biodegradable member.
  • the biodegradable member may help to protect the rectum from damage that may result from the radiation.
  • FIG. 1 illustrates a side view of a prostate and a rectum
  • FIG. 2 illustrates a front view of the prostate and rectum physically separated by fluid according to the prior art
  • FIG. 3 is a schematic illustration in cross-sectional side view of fluid disposed between two layers of fascia according to the present invention (not shown to particular scale of desired spacing necessarily provided by the fluid).
  • any reference to direction or orientation is intended primarily and solely for purposes of illustration and is not intended in any way as a limitation to the scope of the present inventions. Also, the particular embodiments described herein, although being preferred, are not to be considered as limiting of the present inventions.
  • two layers of fascia means the two macroscopically and generally readily separable layers that are disposed between and separate the prostate and the rectum, described in an anatomical sense as (1) the fascia intestinal of the rectum, containing the mesorectum, and (2) the true Denonvarria covering the prostate and seminal vesicles.
  • the term "potential space” means a region of adjustable size defined between the two layers of fascia. The size may be adjusted by insertion of fluid between the two layers of fascia to increase the spacing therebetween.
  • fluid means a composition that may be in the form of a liquid, gel, slurry, or combination thereof and which optionally may have bubbles therein containing gas such as air. Fluids also include pastes and viscous suspensions. The fluid is flowable so that it may be dispensed from a delivery device such as a needle.
  • the terms “drug” and “therapeutic agent” are used interchangeably to mean any therapeutically active substance that is delivered to an anatomical region of a living being to produce a desired, usually beneficial, effect.
  • the therapeutic agent may be an anti-inflammatory agent or another agent for addressing common side effects of radiation treatment for prostate cancer including irritation of the skin around the rectum, bowel irritability including mild diarrhea, gas, bowel urgency, and tenderness, increased urinary frequency, and mild burning with urination.
  • the therapeutic agent also may be an anti-infection agent such as an antimicrobial agent.
  • bioresorbable and “biodegradable” are used interchangeably to refer to a composition that can be broken down by either chemical or physical process, such as a biological process, upon interaction with a physiological environment.
  • a bioresorbable fluid, bioresorbable mass, or bioresorbable spacer of the present invention may be broken into components that are metabolizable or excretable, over a period of time from minutes to years, while maintaining any requisite anatomical spacing in that same time period.
  • the term "spacer” refers to a mass, formed of solid, semisolid, fluid, or combinations thereof, that provides spacing between anatomical portions.
  • the present invention is directed to a method of injecting a biodegradable spacer in place of the fluid separator 10 in the recto-prostatic space between the rectum 12 and prostate 14, as shown in FIGS. 1 and 2, prior to delivering external radiation therapy in the treatment of prostatic cancer.
  • the spacer aids in protecting the rectum from the harmful effects of radiation while allowing for maximizing the dose of radiation to the prostate.
  • the toxic dose to the rectum is approximately 65 Gy and, as long as less than 20% of the rectum gets less than 65 Gy, rectal complications are reduced to less than 5%.
  • the complications to the rectum are thought to be negligible if less than 50% of the rectal wall gets no more than 55 Gy. It is estimated that a 1 centimeter (cm) separation between the rectal wall and the prostate results in about a 10% reduction of the dose to the rectum; a 1.5 cm separation results in about 15-20% reduction of the dose; and a 2 cm separation in about 30-35% reduction in the dose to the rectum.
  • a biodegradable tissue spacer can be injected into the potential space between the two layers of fascia to develop the space between the prostate and rectum and thus separate the rectal wall from the prostate capsule.
  • the biodegradable tissue spacer can be injected in place of the fluid separator shown in FIG. 1 between the prostate 14 and the rectum 12.
  • Biodegradable materials are currently in wide use in medicine and, by varying the chemical composition, one can provide for a precise "lifetime" in tissue.
  • fluid 20 may be injected or otherwise delivered, such as by needle 22, to provide increased separation between rectal wall 12a of the rectum and the prostate/seminal vesicles 14a.
  • fluid 20 may be delivered to the potential space between the fascia intestinal of the rectum 12b, containing the mesorectum 12c, and the true Denonvilliers' fascia 15.
  • a biodegradable agent with a 3-4 month expected duration is used so that the amount of spacer remains generally constant during the approximate 6-8 weeks that it takes to complete a course of external radiation therapy. In this fashion, larger doses of radiation to the prostate can be achieved with improved overall cure rates, but diminished side effects on the rectum.
  • the fluid used in creating the expanded potential space may comprise or be derived from collagen collected from any number of mammalian sources and maybe an injectable, aqueous suspension of cross-linked, quenched collagen.
  • One such preferred biodegradable material includes a sterile, cross-linked, bovine-derived collagen marketed as Contigen® Bard® Collagen Implant available from C. R. Bard, Inc.
  • the fluid dispensed to the potential space is reabsorbed over time.
  • a variety of other fluids are contemplated such as a biodegradable gels of hyaluronic acid or hyaluronic acid derivatives, or hydrogels.
  • the fluid may, for example, be catabolized.
  • the fluid may include one or more components selected from the group consisting of collagen, gelatin, albumin, chondroitin sulfate, hyaluronic acid, heparin, oxidized cellulose, dextran, polyglycolic acid, polylactic acid, and polyanhydride.
  • what is proposed by this invention is to inject a biodegradable spacer with a predetermined known half-life in tissue preferably into the potential space between the two layers of fascia — the fascia intestinal of the rectum, containing the mesorectum, and the true Denonvilliers' fascia covering the prostate and seminal vesicles — and thus to separate the rectum from the prostate capsule by about 1 -2 cm or more.
  • the present invention includes the application of a method for separating the rectal wall 12a from the prostate 14a during external beam radiation therapy.
  • the method demands that greater than normal anatomic separation between the posterior aspect of the prostate and the rectal wall be maintained over a period of weeks rather than the transient period using currently available methods which typically provide some separation for less than about 24 hours.
  • the present inventions instead of saline or other quickly absorbed or dispersed liquids, involve the use of a more viscous or more slowly absorbed or dispersed substance.
  • there are numerous compounds in several classes of approved biocompatible materials that can serve as a fluid for injection into the potential space between the two layers of fascia and that would achieve a generally sufficiently long lasting filling of the space.
  • the substance chosen for the fluid may dissolve or be metabolized over time, so that the normal anatomic positions of the two layers of fascia may be restored eventually.
  • bioresorbable spacer may be formed when the fluid is transformed, e.g. through chemical reaction, to sponge-like or other at least partially solid compositions in vivo.
  • a bioresorbable spacer may provide a matrix that optionally may be porous and that may separate the two layers of fascia from each other by a desired distance, e.g. at least 0.5 mm, for a desired time period, e.g. at least forty-eight hours, before gradually losing the ability to maintain such a separation.
  • the substance chosen for the fluid could be radiolucent and relatively pliable for anatomic conformance.
  • the substance chosen for the fluid may be delivered, for example, using a needle positionable between the two layers of fascia using a template grid as described in United States Patent Application Publication No. US 2004/0143150 Al to Barzell et al. directed to a template grid system, which is incorporated herein in its entirety.
  • External beam radiation therapy is delivered in once or twice a day fractional doses over a period of about 4 to 6 weeks or more.
  • the typical saline induced separation of the two layers of fascia is very transient lasting less than one hour unless additional fluid is instilled.
  • the balloon method which is described for example in U.S. Patent No. 6,064,914 is also transient with a placement duration of several hours.
  • the present inventions propose using an injectable substance that will function as a spacer in this anatomic compartment between the prostate and rectum for a finite residence time therein for a period of weeks or months.
  • the injected fluid preferably is bioresorbable and is broken into components that are metabolizable or excretable, over a period of time of at least one week such as between one week and one year, and more preferably between one month and three months, while maintaining any requisite anatomical spacing in that same time period.
  • the injected fluid maintains the desired anatomical spacing for the entire multi-week period during radiation therapy.
  • the placement or injection of this substance preferably can be performed using real time imaging such as ultrasound or x-ray fluoroscopy. Confirmation of the persistence of this artificial spacer may be done using ultrasound, CT, MRI or other modality. Because of the inverse square relationship of radiation dose with distance from the target, the modest degree of separation achieved by this exemplary method will greatly reduce the risks of rectal morbidity from prostate irradiation and allow higher, potentially more effective doses to be delivered. The present inventions will be very well accepted by radiation oncologists because of the potential for improving radiation therapy outcomes in patients with prostate cancer.
  • the two layers of fascia may not themselves create a completely enclosed region that would limit migration of fluid delivered to the potential space
  • surrounding anatomy combined with the two layers of fascia acts to limit such migration so that the fluid maintains desired spacing between the two layers of fascia prior to bioresorption causing loss of an ability of the fluid to otherwise maintain such desired spacing.
  • Delivery of the fluid expands the potential space to provide a desired spacing between the prostate and rectum. Once the fluid is delivered, it is generally static in the potential space, e.g., it is not continuously recirculated as is the case with some balloon catheters of the prior art inserted between the two layers of fascia and employing saline as the fluid.
  • At least one of the two layers of fascia may be pierced by the delivery device such as a needle.
  • the delivery device such as a needle.
  • LDR low dose rate
  • HDR high dose rate
  • radiation may be delivered interstitially using radioactive seeds.
  • a radioactive seed has a radioactive material with a half-life defined as the amount of time it takes for half of the radioactive material to decay.
  • Iodine- 125 for example, has a half life of about sixty days, while Palladium- 103 has a half-life of about 17 days and Iridium- 195 has a half-life of about 72 days.
  • the two layers of fascia preferably are spaced apart as described above for at least the half-life of the radioactive material of the seed. More preferably, the two layers of fascia are spaced apart as described above for at least two times the half-life of the radioactive material of the seed, and in some embodiment, for between two and six times the half-life.
  • the two layers of fascia are spaced apart for at least the time period during which the seed is disposed in or proximate the prostate. While various descriptions of the present invention are described above, it should be understood that the various features can be used singly or in any combination thereof. Therefore, this invention is not to be limited to only the specifically preferred embodiments depicted herein.
  • the fluid(s) delivered to the potential space remain in fluid form for the desired period of time before no longer no longer being able to maintain desired spacing between the two layers of fascia.
  • some fluid(s) delivered to the potential space may transform to sponge-like or other at least partially solid compositions in vivo while being bioresorbable and losing an ability to maintain desired spacing between the two layers of fascia after a finite time therein of at least one week, and in some embodiments of at least one month.
  • Injectable and bioerodible polymers may be used in accordance with the present invention to provide a body of solid gel polymer to undergo degradation, erosion and solubilization as a result of hydrolysis of labile linkages at the physiologic conditions of use, after providing the desired spacing for the desired period of time when disposed in the potential space as described above.
  • the present invention is described for use in the potential space between two layers of fascia in connection with radiation therapy of the prostate, the present invention may be applied in connection with separating other anatomical regions during radiation therapy and thus may be applied to therapies other than prostate cancer treatment.

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Pathology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Veterinary Medicine (AREA)
  • Radiation-Therapy Devices (AREA)
  • Surgical Instruments (AREA)

Abstract

L'invention concerne une technique de radiothérapie de la prostate qui consiste à: injecter un liquide dans un espace potentiel délimité par deux couches de fascia de manière à les toucher; former un espaceur biorésorbable à partir du fluide pour élargir l'espacement entre la prostate et le rectum au-delà de leur espacement naturel; soumettre la prostate à la radiothérapie après injection du fluide dans l'espace potentiel; et enfin, maintenir un espacement minimum entre la prostate et le rectum à l'aide de l'espaceur biorésorbable pendant au moins 48 heures, l'espacement minimum étant supérieur à l'espacement naturel.
PCT/US2006/001826 2005-01-21 2006-01-20 Creation d'espace provisoire entre les tissus corporels Ceased WO2006078770A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US64607005P 2005-01-21 2005-01-21
US60/646,070 2005-01-21

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WO2006078770A2 true WO2006078770A2 (fr) 2006-07-27
WO2006078770A3 WO2006078770A3 (fr) 2007-10-18

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Cited By (6)

* Cited by examiner, † Cited by third party
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US7872068B2 (en) 2006-05-30 2011-01-18 Incept Llc Materials formable in situ within a medical device
US8383161B2 (en) 2009-12-15 2013-02-26 Incept, Llc Radioopaque covalently crosslinked hydrogel particle implants
EP2497534A4 (fr) * 2009-11-05 2013-04-17 Nat Univ Corp Kobe Univ Intercalaire pour thérapie par rayonnements ionisants
US10188876B2 (en) 2014-02-18 2019-01-29 Dosevue Nv Locally injectable dosimetric organ spacer
CN109963619A (zh) * 2016-09-15 2019-07-02 国立大学法人神户大学 放射线治疗用间隔物
US11298444B2 (en) 2005-04-01 2022-04-12 Trivascular, Inc. Non-degradable, low swelling, water soluble radiopaque hydrogel polymer

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US5733316A (en) * 1995-10-27 1998-03-31 Dornier Medical Systems, Inc. Organ separation for thermal therapy
US6064914A (en) * 1998-04-01 2000-05-16 Trachtenberg; John R. Thermotherapy method
WO2003005889A2 (fr) * 2001-07-10 2003-01-23 Ams Research Corporation Kit chirurgical pour le traitement de tissus prostatiques

Cited By (17)

* Cited by examiner, † Cited by third party
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US11298444B2 (en) 2005-04-01 2022-04-12 Trivascular, Inc. Non-degradable, low swelling, water soluble radiopaque hydrogel polymer
US7872068B2 (en) 2006-05-30 2011-01-18 Incept Llc Materials formable in situ within a medical device
US8044137B2 (en) 2006-05-30 2011-10-25 Incept Llc Materials formable in situ within a medical device
EP2497534A4 (fr) * 2009-11-05 2013-04-17 Nat Univ Corp Kobe Univ Intercalaire pour thérapie par rayonnements ionisants
JP5432281B2 (ja) * 2009-11-05 2014-03-05 国立大学法人神戸大学 電離放射線治療用スペーサー及びこれを作製するための、繊維集合体を含むシート
KR102070986B1 (ko) * 2009-11-05 2020-01-29 고쿠리츠다이가쿠호진 고베다이가쿠 전리방사선 치료용 스페이서
KR20180012346A (ko) * 2009-11-05 2018-02-05 고쿠리츠다이가쿠호진 고베다이가쿠 전리방사선 치료용 스페이서
US10272164B2 (en) 2009-12-15 2019-04-30 Incept, Llc Implants and biodegradable tissue markers
US9669117B2 (en) 2009-12-15 2017-06-06 Incept, Llc Implants and biodegradable tissue markers
US10786581B2 (en) 2009-12-15 2020-09-29 Incept, Llc Implants and biodegradable tissue markers
US11083802B2 (en) 2009-12-15 2021-08-10 Incept, Llc Echolucent implant compositions and methods
US11154624B2 (en) 2009-12-15 2021-10-26 Incept, Llc Echolucent implant compositions and methods
US11160883B2 (en) 2009-12-15 2021-11-02 Incept, Llc Echolucent implant composition and methods
US8383161B2 (en) 2009-12-15 2013-02-26 Incept, Llc Radioopaque covalently crosslinked hydrogel particle implants
US11786612B2 (en) 2009-12-15 2023-10-17 Incept, Llc Implant and biodegradable tissue marker compositions and methods
US10188876B2 (en) 2014-02-18 2019-01-29 Dosevue Nv Locally injectable dosimetric organ spacer
CN109963619A (zh) * 2016-09-15 2019-07-02 国立大学法人神户大学 放射线治疗用间隔物

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