WO2000007515A1 - Methode amelioree de traitement local cible de maladie - Google Patents

Methode amelioree de traitement local cible de maladie Download PDF

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Publication number
WO2000007515A1
WO2000007515A1 PCT/US1999/017515 US9917515W WO0007515A1 WO 2000007515 A1 WO2000007515 A1 WO 2000007515A1 US 9917515 W US9917515 W US 9917515W WO 0007515 A1 WO0007515 A1 WO 0007515A1
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WIPO (PCT)
Prior art keywords
agent
light
pdt
diseased tissue
treatment zone
Prior art date
Application number
PCT/US1999/017515
Other languages
English (en)
Inventor
H. Craig Dees
Timothy Scott
John Smolik
Eric A. Wachter
Walter Fisher
Original Assignee
Photogen, 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.)
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Publication date
Application filed by Photogen, Inc. filed Critical Photogen, Inc.
Priority to KR1020017001602A priority Critical patent/KR20010072307A/ko
Priority to JP2000563202A priority patent/JP2002522111A/ja
Priority to CA002339384A priority patent/CA2339384C/fr
Priority to BR9912773-3A priority patent/BR9912773A/pt
Priority to IL14127399A priority patent/IL141273A0/xx
Priority to EP99939669A priority patent/EP1109506A4/fr
Priority to AU53917/99A priority patent/AU750633B2/en
Priority to MXPA01001336A priority patent/MXPA01001336A/es
Publication of WO2000007515A1 publication Critical patent/WO2000007515A1/fr
Priority to HK02101267.2A priority patent/HK1039555B/zh

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    • 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
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0601—Apparatus for use inside the body
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B2017/22051—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for with an inflatable part, e.g. balloon, for positioning, blocking, or immobilisation
    • A61B2017/22062—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for with an inflatable part, e.g. balloon, for positioning, blocking, or immobilisation to be filled with liquid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B2017/22051—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for with an inflatable part, e.g. balloon, for positioning, blocking, or immobilisation
    • A61B2017/22065—Functions of balloons
    • A61B2017/22069—Immobilising; Stabilising
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B2017/22082—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for after introduction of a substance
    • A61B2017/22087—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for after introduction of a substance photodynamic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
    • 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
    • A61M25/10—Balloon catheters
    • A61M25/104—Balloon catheters used for angioplasty

Definitions

  • the present invention is related to a method and apparatus for topical treatment of tissue, particularly diseased tissue, using photodynamic therapy (PDT) and a PDT agent More specifically, the present invention is directed to a method and apparatus for topical or systemic application of the PDT agent to the diseased tissue and then topical application of light to the diseased tissue.
  • PDT photodynamic therapy
  • PDT was developed to treat cancer and other diseases with the promise of limiting the invasiveness of the therapeutic intervention and lessening potential collateral damage to normal, non-diseased tissue
  • Key elements of PDT include either selective application or selective uptake of a photosensitive agent into the diseased tissue and site-directable application of an activating light
  • PDT agents are typically applied systemically (for example, via intravenous injection or oral administration) or via localized topical application directly to diseased tissues (for example, via topical creams, ointments, or sprays)
  • an activating light is applied to the disease site, locally activating the agent, and destroying the diseased tissue
  • Light is typically applied by direct illumination of the site, or by delivery of light energy to internal locations using a fiberoptic catheter or similar means
  • porphyrin-based agents include porfimer sodium (PHOTOFRJN®), hematoporphyrin- derivative (HPD), or SnET 2 PHOTOFRJN® is one of the few agents currently licensed by the FDA
  • Porphyrin-based agents generally are derived from complex mixtures of natural or synthetically prepared materials
  • Many components of porphyrin-based agents are lipophilic As a result of this lipophilicity, porphyrin-based agents have shown a slight tendency to preferentially accumulate in some tumors
  • the targeting of such agents to diseased tissue is still unacceptably low when compared to uptake in normal tissue, (i e , 2-10x greater uptake in diseased tissue relative to normal tissue)
  • porphyrin-based agents were developed primarily as a result of a desire to have agents that are compatible with highly-penetrating activating light so as to enable treatment of deep-seated cancerous tumors.
  • porphyrin-based agents are typically activated using light at wavelengths from 600-750 nm, which may penetrate tissue to a depth of 1 cm or more. In contrast, light at wavelengths below 600 nm will penetrate tissue only to a depth much less than 1 cm.
  • the dark toxicity of most porphyrin-based agents is high. Dark toxicity is the cellular toxicity in the absence of activating light. Only a small increase in cytotoxicity is achieved upon illumination which necessitates high dosages of agent in order to effect treatment in specific tissues.
  • the systemic clearance time which is the duration subsequent to agent administration wherein significant agent concentrations are present in skin and other external tissues, can extend from weeks to months, forcing patients to avoid exposure to bright light or sunlight for extensive periods in order to avoid serious skin irritation and other complications. Systemic administration also necessitates a delay of between 30 min to 72 hours between agent administration and light activation, essentially precluding the possibility of immediate treatment of diseased tissue upon detection of such diseased tissue.
  • detection and treatment of gastrointestinal diseases, such as Barrett's esophagus requires at least two endoscopic procedures: one procedure to diagnose, and a subsequent procedure to treat the diseased tissue with light following administration of a PDT agent.
  • porphyrin-based PDT agents achieve light-activated cytotoxicity via type-II mechanisms, typically the conversion of cellular O 2 into cytotoxic singlet oxygen. Because cellular O 2 levels can be readily depleted during activation of a type-II PDT agent, use of such agents mandates relatively low intensity illumination and thus relatively long illumination durations in order to allow O 2 levels to remain sufficient throughout the duration of light activation. For example, in the treatment of Barrett's esophagus with PHOTOFRJN®, light intensities typically must be held well below 100-150 mW/cm 2 during treatment, necessitating illumination periods of 10-20 minutes or more.
  • type-II agents that it is equally important to avoid any tissue manipulation that might compromise blood circulation at the treatment site during illumination, again in order to avoid potential depletion of available O 2 .
  • careful control of the illumination apparatus and procedure is critical in order to assure that proper light intensities are delivered without affecting tissue in a manner that might affect blood circulation.
  • Barrett's esophagus is a perfect example of a superficial disease that is an attractive candidate for PDT as it occurs in a location that is difficult to access via conventional surgical means but is readily accessible using endoscopic catheters It is a condition in which chronic acid reflux from the stomach irritates the esophagus at the gastro- esophageal junction, causing epithelial tissue in the esophagus to proliferate. Patients with Barrett's esophagus have a significantly increased risk of developing esophageal cancer.
  • the FDA has approved PDT (PHOTOFRJN® with light at 630 nm) to destroy the proliferating tissue in Barrett's patients. Similar regimens can also be used to remove esophageal stricture caused by esophageal cancer.
  • FIG. 1(a) A common method for treatment of Barrett's esophagus using PDT is shown in cross-sectional form in Fig. 1(a).
  • the esophagus 10 has a proximal tissue surface 12 and a distal tissue surface 14.
  • a portion of esophagus 10 is healthy tissue 16 while another portion is diseased tissue 18.
  • a non-compliant balloon 20 inserted into the esophagus 10 is used to stabilize the tissue to be treated.
  • the balloon is filled with gas or liquid so that it will expand to a known radius (nearly filling the esophagus) while avoiding dilation of the esophagus.
  • An optical fiber inserted into the center of the balloon 20 serves as a light source 22 to provide a uniform light intensity at the surface of the balloon.
  • the outer structure of this balloon 20 may be composed of a material that scatters activating light 24 or may be transparent to the activating light.
  • PDT agent present in tissue located proximal to the balloon is thereby activated by light emitted from the surface of the balloon 20 Because the balloon 20 is non-compliant, it is possible to estimate the light intensity at the surface of the balloon based on geometrical properties of the balloon and knowledge of the light emitting properties of the light source 22.
  • a fiberoptic diffuser tip is an example of such a light source.
  • the external surface of the balloon 20 generally will not conform exactly to the shape of the esophagus, it is not possible to accurately estimate light intensity at all points along the circumference of the proximal tissue surface 12.
  • the light field present at the proximal tissue surface 12 be uneven, for example due to non-uniform light emitting properties of the light source 22 or incorrect location of the light source 22 in the esophagus 10, uneven treatment may result. In extreme cases, such uneven treatment can compromise tissue sufficiently to result in tissue perforation and patient death.
  • a treatment zone 26 which will generally include the entire zone of diseased tissue 18 in Fig.1 (a) and may extend radially and circumferentially a significant distance beyond the margins of the zone of diseased tissue 18
  • use of NIR light for agent activation can result in formation of a treatment zone that extends a significant distance from the proximal tissue surface 12 to the distal tissue surface 14 of the esophagus 10 This is a consequence of the large penetration depths characteristic of NIR light and the presence of a significant systemic concentration of agent in healthy tissue In extreme cases, this enlargement of the treatment zone can compromise healthy tissue sufficiently enough to result in tissue perforation and patient death
  • Systemic agent application requires significant delay between disease diagnosis and disease treatment in order for the agent to reach the diseased tissue while clearing out of the surrounding healthy tissue, (5) Systemic agent application provides PDT practitioners with limited control over the site of agent delivery and concentration;
  • the present invention is directed to a method and apparatus for topical treatment of diseased tissue, including topical or systemic application of a PDT agent to diseased tissue, followed by topical application of light.
  • the method involves the steps of applying a PDT agent to diseased tissue to form a treatment zone; purging excess agent; and applying light to the treatment zone to activate agent associated with the diseased tissue. The light penetrates the treatment zone while minimizing activation of the agent outside the treatment zone.
  • Rose Bengal is the PDT agent.
  • the PDT agent is directly applied only to the treatment zone.
  • the PDT agent can be applied systemically.
  • the depth of activation of the PDT agent is controlled by proper selection of wavelength of activating light so as to avoid activation of agent that may be present in underlying healthy tissues.
  • the diseased tissue is diagnosed before applying the PDT agent.
  • detection and treatment of a lesion may be effected in a short time period using a single procedure (such as endoscopy) instead of by separate diagnostic and therapeutic procedures.
  • treatment rate is not limited by oxygen-dependent mechanisms.
  • heat is also applied to the treatment zone to increase efficacy of activation of the agent.
  • activating light is delivered through a "balloon" or other delivery apparatus located at the disease site.
  • the method of the present invention can be used for treatment of disease in the gastrointestinal tract.
  • the method of the present invention can also be used for treatment of disease in vessels of the circulatory system.
  • the present invention is also directed to an apparatus for topical treatment of diseased tissue.
  • the present invention is directed to a method and apparatus to improve the evenness of light delivery, and to improve the safety and efficacy and reduce the cost of PDT, for treatment of Barrett's esophagus and other conditions.
  • FIGURE 1(a) shows a cross-sectional view of an esophagus illustrating a common method for treatment of Barrett's esophagus using PDT;
  • FIGURE 1(b) illustrates the treatment zone of the method of Figure 1(a);
  • FIGURE 2(a) illustrates an example of an embodiment of the present invention for treatment of diseased esophageal tissue
  • FIGURE 2(b) illustrates an alternate example of the embodiment of Figure 2(a);
  • FIGURE 2(c) illustrates an additional alternate example of the embodiment of Figure 2(a);
  • FIGURE 3(a) illustrates an example of another embodiment for the treatment of disease in vessels of the circulatory system.
  • FIGURE 3(b) illustrates an alternate example of the embodiment of Figure 3(a) wherein the PDT agent is directly applied to the diseased tissue.
  • the method and apparatus of the present invention is applicable to improved treatment of various dermatologic afflictions, such as psoriasis or skin cancer, and to diseased tissues at sites within the body, such as disease of the digestive or respiratory tracts.
  • the present invention can also be used for the treatment of other anatomical sites, including intra-abdominal, intra-thoracic, intra-cardial, intra-circulatory, intra-cranial, and the reproductive tract.
  • the method of the present invention involves one or more of the following steps. Initially, disease is diagnosed using, for example, histologic examination, or by measurement of the autofluorescence properties of diseased tissue or by detecting selective uptake of an indicator agent, such as a fluorescent dye or a PDT agent, into such diseased tissue. Thereafter, a sufficient quantity of a topical or systemic formulation of a desired PDT agent is applied to the disease site so as to cover, perfuse, or saturate the diseased tissue.
  • an indicator agent such as a fluorescent dye or a PDT agent
  • the wavelength of the light is preferably chosen so as to allow optical penetration into the diseased tissue but to minimize further optical penetration beyond the diseased tissue into underlying healthy tissue.
  • visible light in the spectral region between 400-600 nm may be used to afford shallow penetration depths on the order of several millimeters or less. Use of such light affords efficacy in agent activation in superficial diseased tissues while simultaneously minimizing potential for deleterious photosensitization of underlying tissue.
  • laser light is used. It can be delivered by fiberoptic catheters. Alternatively, light can be delivered by direct illumination. Other alternate light source configurations and delivery apparatus include fiberoptic bundles, hollow-core optical waveguides, and liquid-filled waveguides.
  • Alternate light sources including light emitting diodes, micro-lasers, monochromatic or continuum lasers or lamps for production of activating light, and continuous wave or pulsed lasers or lamps.
  • Either single-photon or two-photon excitation methods can be used for agent activation. A more detailed explanation of such excitation methods is given in commonly assigned application serial no 08/739,801 filed October 30, 1996 which is incorporated herein by reference
  • the time and order of the applications of the agent and light can also be varied. For example, application of the agent and the light treatment regimen can be repeated one or more times to eliminate residual diseased tissue Further, for some applications, an increased delay between agent application and light treatment can be beneficial. Additionally, the step of diagnosing can almost immediately be followed by the steps of applying a PDT agent, purging excess agent and applying light so that said method of diagnosis and treatment is done in a single procedure If PDT agent uptake is used to diagnose or detect diseased tissue, the step of diagnosing can be immediately followed by the step of applying activating light Alternatively, there may be an indefinite delay between diagnosis and PDT treatment
  • Rose Bengal is used as the PDT or photosensitizing agent as it is inexpensive, non-toxic, has a proven safety record in human use, has significant intrinsic lipophilic properties, exhibits both type-I and type-II PDT response and therefore can be activated by type-I, oxygen-independent mechanism and is strongly phototoxic upon activation with light between 500 nm and 600 nm Because of its O 2 -independent response, Rose Bengal is compatible with high intensity light activation, which reduces treatment time relative to porphyrin-based agents More specifically, Rose Bengal is optimally activated using light between 500 nm and 600 nm, which is sufficient for activation of superficial diseased tissue and substantially avoids the potential for activation of underlying healthy tissues
  • a PDT agent is a solution of Rose Bengal formulated with a suitable lipophilic delivery vehicle, such as 1-octanol or liposomes
  • PDT agents including type-I or type-II agents
  • standard PDT agents include psoralen derivatives, porphyrin and hematoporphyrin derivatives, chlorin derivatives, phthalocyanine derivatives, rhodamine derivatives; coumarin derivatives, benzophenoxazine derivatives, chlorpromazine and chlorpromazine derivatives, chlorophyll and bacteriochlorophyll derivatives, pheophorbide a (Pheo a), merocyanine 540 (MC 540), Vitamin D, 5-amino-laevulinic acid (ALA), photosan, pheophorbide-a (Ph-a), phenoxazine Nile blue derivatives including various phenoxazine dyes, PHOTOFRJN, benzoporphyrin derivative mono-acid, SnET 2 , and Lutex.
  • psoralen derivatives porphyrin and hematoporphyrin derivatives
  • the present invention is not limited to the use of one PDT agent. Instead, more than one PDT agent can be used during a treatment regimen.
  • the PDT agent used in the present invention can include at least one targeting moiety.
  • targeting moieties include DNA, RNA, amino acids, proteins, antibodies, ligands, haptens, carbohydrate receptors or complexing agents, lipid receptors or complexing agents, protein receptors or complexing agents, chelators, and encapsulating vehicles.
  • targeting moieties may be used to improve the selectivity of agent delivery to diseased tissue, and can function either by association with the photosensitizing PDT agent (for example where the PDT agent is encapsulated in a vehicle composed of the targeting moiety) or by attachment to the photosensitizing PDT agent (for example where the PDT agent is covalently attached to the targeting moiety).
  • the PDT agent is applied directly to the diseased tissue.
  • Employment of direct topical application provides a number of advantages. In particular, it affords improved targeting of the agent specifically to the diseased tissue, reduces the required latency period between agent administration and light activation and thereby shortens the treatment cycle, substantially eliminates the potential for systemic photosensitization, reduces agent consumption, and reduces the overall potential for side effects from exposure to the agent.
  • the agent is applied as a topical spray or wash. After a brief accumulation period (generally not to exceed 30 minutes), the excess agent is removed from the tissue surface by flushing with liquid, such as with water or saline. Following this flushing, it is preferred that the residual agent associated with the diseased tissue be activated by illumination of the diseased site with visible light between 400 nm and 600 nm. Optically, the light can be applied as discussed supra.
  • the PDT agent can be applied systemically.
  • this application may be via intravenous injection or parenteral administration (such as by consumption of a tablet or liquid formulation of the PDT agent).
  • heat can be applied to the treatment zone to increase PDT effectiveness via hyperthermia.
  • Heat can be applied, for example, through the use of a heated liquid in an illumination balloon, a transparent heating pad positioned between the illumination source and the tissue, or simultaneous illumination of the treatment site with infrared energy.
  • Fig. 2(a) illustrates an example of a treatment of diseased esophageal tissue using a non-compliant balloon 20 illumination apparatus.
  • a treatment zone 30 is identified. This can be done for example via endoscopic examination of the esophagus and visual or spectroscopic identification of zones of diseased tissue. Such identification can include detection of histologic changes or other visual indicators of disease, detection of changes in autofluorescence, or detection of uptake of PDT or other agents into diseased tissue.
  • PDT agent is applied to the identified diseased tissue. This agent can be applied, for example, via systemic application or more preferably, by direct spray application using a nozzle or other means provided at the distal end of an endoscope. Excess agent is subsequently purged from the site by, for example, natural systemic clearance or by flushing with liquid.
  • a transparent, non-compliant balloon apparatus 20 is then inserted into the esophagus so as to span the treatment zone 30.
  • the non-compliant balloon 20 is filled with gas or liquid to a pre-determined pressure so as to establish a desired pre-determined radius.
  • Visible light 24 is then uniformly delivered radially to the treatment site through the walls of the balloon 20 using a light source 22, such as for example a fiberoptic diffuser, located along the central axis of the balloon.
  • the balloon 20 can be filled with a scattering medium, such as a dilute solution of intralipid, so as to improve the uniformity of light intensity delivered at the surface of the balloon.
  • a scattering medium such as a dilute solution of intralipid
  • the balloon 20 can be composed of or include a material that scatters the light 24 delivered at the surface of the balloon so as to further improve the uniformity of light intensity delivered at the surface of the balloon. Examples of such a material include a material that is naturally translucent, such as latex; a polymer that includes particulate scattering materials; or a polymer with a roughened surface.
  • the intensity of the light source 22 is operated at a pre-determined level for a pre-determined duration based on the filled radius of the non-compliant balloon 20 and the desired light intensity and light dose at the surface of the balloon.
  • An alternate example of this embodiment is shown in cross-sectional form in Fig 2(b), where diseased esophageal tissue is treated using an enlarged non-compliant balloon 40.
  • PDT agent is applied to the identified diseased tissue Excess agent is subsequently purged from the site
  • a transparent, non-compliant balloon apparatus 40 is then inserted into the esophagus so as to span the treatment zone 30
  • the non-compliant balloon 40 is filled with gas or liquid so as to substantially distend or slightly dilate the esophagus, eliminating folding of the esophageal surface and thereby presenting a more uniform tissue surface 12 for illumination
  • Fill pressure is measured to establish the radius of the filled balloon Visible light 24 is then uniformly delivered radially to the treatment site through the walls of the balloon using a light source 22, such as for example a fiberoptic diffuser, located along the central axis of the balloon
  • the balloon 40 can be filled with a scattering medium, such as a dilute solution of intralipid, so as to improve the uniformity of light intensity delivered at the surface of the balloon
  • a scattering medium such as a dilute solution of intralipid
  • the balloon 40 can be composed of or include a material that scatters the light 24 delivered at the surface of the balloon Examples of such materials include material that is naturally translucent, such as latex, a polymer that includes particulate scattering materials; or a polymer with a roughened surface
  • the pressure used to fill the balloon is measured and used to establish the operational radius of the filled balloon, and the intensity of the light source 22 is operated at a level that is selected based on the operational radius of the filled non-compliant balloon 40 so as to deliver a desired light intensity and light dose at the surface of the balloon It is preferred in this alternate embodiment that sufficient pressure be used so as to minimize folding of the treated esophageal region without significantly dilating the esophagus so as to avoid potential stenosis or other non-specific irritation of esophageal tissue.
  • FIG. 2(c) An additional alternate example of this embodiment is shown in cross-sectional form in Fig. 2(c), where diseased esophageal tissue is treated using a compliant balloon 50.
  • PDT agent is applied to the identified diseased tissue Excess agent is subsequently purged from the site
  • a transparent, compliant balloon apparatus 50 is then inserted into the esophagus so as to span the treatment zone 30
  • the compliant balloon 50 is filled with gas or liquid so as to fill, distend or slightly dilate the esophagus, substantially eliminating non-uniform contact between the esophageal surface and the balloon and thereby presenting a uniform tissue surface for illumination
  • Fill pressure is measured to establish the approximate radius of the filled balloon.
  • Visible light 24 is then uniformly delivered radially to the treatment site through the walls of the balloon 50 using a light source 22, such as for example a fiberoptic diffuser, located along the central axis of the balloon
  • the balloon 50 can be filled with a scattering medium, such as a dilute solution of intralipid, so as to improve uniformity of light intensity delivered at the surface of the balloon.
  • a scattering medium such as a dilute solution of intralipid
  • the balloon 50 can be composed of or include a material that scatters the light 24 delivered at the surface of the balloon. Examples of such materials include material that is naturally translucent, such as latex; a polymer that includes particulate scattering materials; or a polymer with a roughened surface
  • the pressure used to fill the balloon is measured to establish the operational radius of the filled balloon
  • the intensity of the light source 22 is operated at a level that is selected based on the operational radius of the filled compliant balloon 50 so as to deliver a desired light intensity and light dose at the surface of the balloon.
  • sufficient pressure is used so as to minimize folding of the treated esophageal region without significantly dilating the esophagus (to avoid potential stenosis or other non-specific irritation of esophageal tissue)
  • FIGs. 3(a) and 3(b) illustrate an alternate preferred embodiment of the present invention
  • a photosensitive agent is applied parenterally or via intravenous injection.
  • the agent accumulates in diseased tissue of the vessel wall 60 to form a treatment zone 62.
  • This agent is chosen based on preferential concentration in diseased material present at the desired treatment zone
  • a light 64 is applied to the disease site in order to activate the agent associated with the diseased material
  • This application may be effected by using a fiberoptic catheter 66 or similar means having a focusing, collimating, or diffusing terminus for spatial control of light delivery
  • the fiberoptic catheter 66 is able to deliver the light 64 directly to the treatment zone 62 so that the light can be applied topically
  • visible light in the spectral region between 400-600 nm be used so as to effect shallow penetration depths on the order of several millimeters or less Use of such light affords efficacy in agent activation in superficial diseased material while simultaneously minimizing potential for deleterious photosensitization
  • the photosensitive agent administration can be effected via localized, direct application of an agent to diseased material in the treatment zone 62, as illustrated in Fig. 3(b).
  • Agent administration may be readily effected via an agent delivery device 68, such as a capillary tube, attached to and terminating near the end of the fiberoptic catheter 66, that is used to deliver a small quantity of agent, as a stream 70 or other flow, directly to or in the vicinity of the treatment zone 62.
  • this delivery device 68 may be separate from the fiberoptic catheter 66, thereby facilitating independent position of the respective termini of the light delivery fiberoptic catheter 66 and the agent delivery device 68.
  • delivery of a small quantity of photosensitive agent to diseased material in the treatment zone 62 is followed, after a short accumulation period, with application of light 64 to the disease site in order to activate agent associated with diseased material.
  • Rose Bengal is used as the photosensitizing agent.
  • Rose Bengal is optimally activated using light between 500 nm and 600 nm, which is sufficient for activation of superficial diseased material and substantially avoids potential for activation of underlying healthy tissues.
  • this agent is compatible with high intensity activating light, which may thereby be used to substantially reduce treatment times over that required with other agents, such as Type-II PDT agents.

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  • Radiology & Medical Imaging (AREA)
  • Biochemistry (AREA)
  • Pathology (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Hematology (AREA)
  • Anesthesiology (AREA)
  • Pulmonology (AREA)
  • Biophysics (AREA)
  • Child & Adolescent Psychology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Surgery (AREA)
  • Radiation-Therapy Devices (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Laser Surgery Devices (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

L'invention concerne une méthode et un dispositif de traitement local d'un tissu malade, notamment l'application par voie locale ou générale d'un agent thérapeutique photodynamique, sur le tissu malade, suivie d'une application locale de lumière (24).
PCT/US1999/017515 1998-08-06 1999-08-02 Methode amelioree de traitement local cible de maladie WO2000007515A1 (fr)

Priority Applications (9)

Application Number Priority Date Filing Date Title
KR1020017001602A KR20010072307A (ko) 1998-08-06 1999-08-02 질병의 표적화 국소치료를 위한 개선된 방법
JP2000563202A JP2002522111A (ja) 1998-08-06 1999-08-02 疾患の標的局所治療の改善された方法
CA002339384A CA2339384C (fr) 1998-08-06 1999-08-02 Methode amelioree de traitement local cible de maladie
BR9912773-3A BR9912773A (pt) 1998-08-06 1999-08-02 Processo e aparelho para o tratamento tópico de tecido doente e processo para o tratamento de doenças em vasos do sistema circulatório
IL14127399A IL141273A0 (en) 1998-08-06 1999-08-02 Improved method for targeted topical treatment of disease
EP99939669A EP1109506A4 (fr) 1998-08-06 1999-08-02 Methode amelioree de traitement local cible de maladie
AU53917/99A AU750633B2 (en) 1998-08-06 1999-08-02 Improved method for targeted topical treatment of disease
MXPA01001336A MXPA01001336A (es) 1998-08-06 1999-08-02 Metodo mejorado para tratamiento topico selectivo de enfermedad.
HK02101267.2A HK1039555B (zh) 1998-08-06 2002-02-21 靶向局部治療疾病的裝置

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US13004198A 1998-08-06 1998-08-06
US09/130,041 1998-08-06

Publications (1)

Publication Number Publication Date
WO2000007515A1 true WO2000007515A1 (fr) 2000-02-17

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ID=22442778

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PCT/US1999/017515 WO2000007515A1 (fr) 1998-08-06 1999-08-02 Methode amelioree de traitement local cible de maladie

Country Status (13)

Country Link
EP (1) EP1109506A4 (fr)
JP (1) JP2002522111A (fr)
KR (1) KR20010072307A (fr)
CN (1) CN1132557C (fr)
AR (1) AR021750A1 (fr)
AU (1) AU750633B2 (fr)
BR (1) BR9912773A (fr)
CA (1) CA2339384C (fr)
HK (1) HK1039555B (fr)
IL (1) IL141273A0 (fr)
MX (1) MXPA01001336A (fr)
TW (1) TW396030B (fr)
WO (1) WO2000007515A1 (fr)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1126782A1 (fr) * 1998-11-02 2001-08-29 Photogen, Inc. Procede de visualisation et de therapie photodynamique ameliorees
EP1210078A1 (fr) * 1999-08-13 2002-06-05 Photogen, Inc. Medicaments topiques ameliores et methodes permettant de traiter des maladies de maniere photodynamique
JP2003528143A (ja) * 2000-03-24 2003-09-24 フォトゲン インク 疾病を光力学的に治療するための体内薬剤
EP1496994A2 (fr) * 2002-04-02 2005-01-19 Lumerx, Inc. Dispositifs et procedes utilisant la lumiere visible pour affaiblir et/ou tuer des micro-organismes dans le corps
WO2008024290A2 (fr) * 2006-08-19 2008-02-28 Fritsch Michael H Dispositifs et procédés de diagnostic de pathologie in vivo
WO2008085215A1 (fr) * 2007-01-09 2008-07-17 Health Research, Inc. Traitement de l'œsophage de barrett à l'aide d'une thérapie photodynamique
US7845039B2 (en) 2003-09-09 2010-12-07 The Procter & Gamble Company Toothbrush with severable electrical connections
EP1691707B1 (fr) * 2003-12-10 2015-06-17 EL.EN. S.p.A. Dispositif pour traiter des tumeurs par thermotherapie au laser
JP2016513567A (ja) * 2013-03-15 2016-05-16 ザ ジェネラル ホスピタル コーポレイション 組織照射装置、ならびにそれを用いた方法およびキット
US9889041B2 (en) 2012-10-08 2018-02-13 Universitat Leipzig Device for a medical treatment of a sclera
US10292381B2 (en) 2012-07-20 2019-05-21 The General Hospital Corporation Vessel treatment systems, methods, and kits
US10478284B2 (en) 2012-07-20 2019-11-19 The General Hospital Corporation Methods for tissue passivation
US10549112B2 (en) 2012-07-20 2020-02-04 The General Hospital Corporation Apparatus for tissue irradiation and methods and kits utilizing the same
US11350625B2 (en) 2013-07-18 2022-06-07 The General Hospital Corporation Vessel treatment systems, methods, and kits

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Publication number Priority date Publication date Assignee Title
DE102008047640B4 (de) * 2008-09-17 2012-10-25 Anton Kasenbacher Verwendung eines Laserbearbeitungsgeräts zur Ablation von Zahnmaterial
WO2011097458A2 (fr) * 2010-02-04 2011-08-11 University Of Rochester Dispositifs et procédés d'adaptation d'une thérapie photodynamique à des emplacements anatomiques spécifiques
DE102015225400A1 (de) * 2015-12-16 2017-06-22 Vimecon Gmbh Schwenkbarer Ablationskatheter
CN107213554B (zh) * 2017-07-17 2019-11-19 尚华 一种介入用的液态光传导装置
CN107376132B (zh) * 2017-07-17 2020-02-04 尚华 一种新型光纤导管及其制备方法

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US5829448A (en) 1996-10-30 1998-11-03 Photogen, Inc. Method for improved selectivity in photo-activation of molecular agents

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US5034613A (en) * 1989-11-14 1991-07-23 Cornell Research Foundation, Inc. Two-photon laser microscopy
US5829448A (en) 1996-10-30 1998-11-03 Photogen, Inc. Method for improved selectivity in photo-activation of molecular agents

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KATSUMI ET AL: "Photodynamic Therapy with a Diode Laser for Implanted Fibrosarcome in Mice Employing Mono(L-Aspartyl Chlorn E6, Research Note", PHOTOCHEMISTRY, vol. 64(4), 1996, pages 671 - 675, XP002922321 *
See also references of EP1109506A4
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Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1126782A4 (fr) * 1998-11-02 2003-06-04 Photogen Inc Procede de visualisation et de therapie photodynamique ameliorees
EP1126782A1 (fr) * 1998-11-02 2001-08-29 Photogen, Inc. Procede de visualisation et de therapie photodynamique ameliorees
EP2020242A2 (fr) 1999-08-13 2009-02-04 Provectus Pharmatech, Inc. Médicaments topiques améliorés et procédés de traitement photodynamique de maladies
EP1210078A1 (fr) * 1999-08-13 2002-06-05 Photogen, Inc. Medicaments topiques ameliores et methodes permettant de traiter des maladies de maniere photodynamique
EP1210078A4 (fr) * 1999-08-13 2004-06-09 Photogen Inc Medicaments topiques ameliores et methodes permettant de traiter des maladies de maniere photodynamique
EP2020242A3 (fr) * 1999-08-13 2009-02-11 Provectus Pharmatech, Inc. Médicaments topiques améliorés et procédés de traitement photodynamique de maladies
JP2003528143A (ja) * 2000-03-24 2003-09-24 フォトゲン インク 疾病を光力学的に治療するための体内薬剤
EP1496994A2 (fr) * 2002-04-02 2005-01-19 Lumerx, Inc. Dispositifs et procedes utilisant la lumiere visible pour affaiblir et/ou tuer des micro-organismes dans le corps
EP1496994A4 (fr) * 2002-04-02 2008-04-16 Lumerx Inc Dispositifs et procedes utilisant la lumiere visible pour affaiblir et/ou tuer des micro-organismes dans le corps
US7845039B2 (en) 2003-09-09 2010-12-07 The Procter & Gamble Company Toothbrush with severable electrical connections
EP1691707B1 (fr) * 2003-12-10 2015-06-17 EL.EN. S.p.A. Dispositif pour traiter des tumeurs par thermotherapie au laser
WO2008024290A3 (fr) * 2006-08-19 2008-05-22 Michael H Fritsch Dispositifs et procédés de diagnostic de pathologie in vivo
WO2008024290A2 (fr) * 2006-08-19 2008-02-28 Fritsch Michael H Dispositifs et procédés de diagnostic de pathologie in vivo
WO2008085215A1 (fr) * 2007-01-09 2008-07-17 Health Research, Inc. Traitement de l'œsophage de barrett à l'aide d'une thérapie photodynamique
US10292381B2 (en) 2012-07-20 2019-05-21 The General Hospital Corporation Vessel treatment systems, methods, and kits
US10478284B2 (en) 2012-07-20 2019-11-19 The General Hospital Corporation Methods for tissue passivation
US10549112B2 (en) 2012-07-20 2020-02-04 The General Hospital Corporation Apparatus for tissue irradiation and methods and kits utilizing the same
US9889041B2 (en) 2012-10-08 2018-02-13 Universitat Leipzig Device for a medical treatment of a sclera
JP2016513567A (ja) * 2013-03-15 2016-05-16 ザ ジェネラル ホスピタル コーポレイション 組織照射装置、ならびにそれを用いた方法およびキット
US11350625B2 (en) 2013-07-18 2022-06-07 The General Hospital Corporation Vessel treatment systems, methods, and kits

Also Published As

Publication number Publication date
CN1317952A (zh) 2001-10-17
KR20010072307A (ko) 2001-07-31
IL141273A0 (en) 2002-03-10
CN1132557C (zh) 2003-12-31
CA2339384C (fr) 2008-07-08
AU5391799A (en) 2000-02-28
BR9912773A (pt) 2001-10-16
AR021750A1 (es) 2002-08-07
JP2002522111A (ja) 2002-07-23
AU750633B2 (en) 2002-07-25
MXPA01001336A (es) 2002-04-24
CA2339384A1 (fr) 2000-02-17
HK1039555A1 (en) 2002-05-03
HK1039555B (zh) 2004-05-07
EP1109506A1 (fr) 2001-06-27
EP1109506A4 (fr) 2009-09-09
TW396030B (en) 2000-07-01

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