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WO1990011797A1 - Traitement photochimique de vaisseaux sanguins - Google Patents

Traitement photochimique de vaisseaux sanguins Download PDF

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Publication number
WO1990011797A1
WO1990011797A1 PCT/US1990/001647 US9001647W WO9011797A1 WO 1990011797 A1 WO1990011797 A1 WO 1990011797A1 US 9001647 W US9001647 W US 9001647W WO 9011797 A1 WO9011797 A1 WO 9011797A1
Authority
WO
WIPO (PCT)
Prior art keywords
blood vessel
photoreactive compound
compound
blood
photoreactive
Prior art date
Application number
PCT/US1990/001647
Other languages
English (en)
Inventor
Michael W. Berns
Original Assignee
The Regents Of The University Of California
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 The Regents Of The University Of California filed Critical The Regents Of The University Of California
Publication of WO1990011797A1 publication Critical patent/WO1990011797A1/fr

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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
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/062—Photodynamic therapy, i.e. excitation of 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
    • A61N5/067—Radiation therapy using light using laser light

Definitions

  • the present invention relates generally to the use of photoreactive dyes to treat vascular tissue. More particularly, the present invention involves using photoreactive dyes to selectively destroy unwanted blood vessels in normal tissue.
  • HPD hematoporphyrin derivative
  • Photofrin II hematoporphyrin II
  • HPD has been used to treat patients for many kinds of solid tumors, including those of the skin, lung, bladder, eye, neck, and esophagus.
  • the patient who is being treated will receive about two milligrams of Photofrin II per kilogram of body weight.
  • the Photofrin is typically injected into the bloodstream of the patient over a period of about five minutes.
  • the patient must be immediately protected from bright light to prevent undesirable non-selective photoactivation of the Photofrin II.
  • the physician then waits two to three days for the Photofrin II to congregate in the malignant tumor while the remainder of the Photofrin II is washed from normal tissues by the patient's system.
  • the physician generally then uses an argon-pumped dye laser to shine light on the patient's tumor and surrounding area.
  • the laser is focused directly on exterior tumors or those located within 3 to 10 mm of the skin surface.
  • the doctor utilizes an optical fiber to deliver the radiation to the tumor.
  • Hypervascular dermal lesions such as port-wine stains.
  • Hypervascular dermal lesions and other non-malignant tissue disorders are presently treated with lasers.
  • the treatment utilizes photothermal ablation whereby absorbed energies are converted to heat.
  • the lesion is destroyed either by direct thermal denaturization or by propagated shock waves due to near instantaneous heating provided by the laser.
  • a problem with this type of treatment is confining and localizing the thermal injury to a specific tissue location.
  • photosensitive dyes in combination with laser treatment would appear to be desirable in reducing the thermal damage to normal tissues surrounding the hypervascular dermal lesions.
  • photosensitive dyes have not been shown to selectively congregate at such non-malignant dermal lesions.
  • photodynamic therapy has not been suggested for use in treating such non-malignant dermal lesions. It would be desirable, however, to provide a process based on photodynamic therapy for treating such blood vessel disorders, even though the photosensitive dyes do not selectively migrate to such tissues. , c ⁇ ;
  • blood vessels can .be photochemically treated to provide selective destruction while, at the same time, limiting damage to surrounding tissues.
  • the present invention is based on a method wherein a therapeutic amount of a photoreactive compound is introduced into the blood flowing through the blood vessel. It was discovered that photoreactive compounds associate with the blood vessel wall. The photoreactive compound is allowed to accumulate in the blood vessel wall for a sufficient time to provide a sufficient amount of photoreactive compound within the blood vessel wall to destroy the blood vessel when the photoreactive compound is activated by radiation from a laser or other source.
  • the photoreactive compound associated with the blood vessel wall is activated prior to the time at which the photoreactive compound leaves the vessel and either enters the surrounding tissue or is washed away. It was dis ⁇ overed that sufficient photoreactive compound is present within blood vessel walls to allow photodynamic destruction of the blood vessel tissue without affecting surrounding tissue. As a result, the method of the present invention allows the destruction of undesirable blood vessels while limiting the amount of harm to surrounding tissues.
  • the method of the present invention is particularly well suited for treating hypervascular dermal lesions, such as port-wine stains.
  • the method eliminates many of the cosmetic problems associated with thermal destruction of surrounding tissue. Further, the method takes advantage of the selectivity of tissue destruction provided when using photoreactive compounds.
  • the drawing is a schematic representation of a preferred exemplary method in accordance with the present invention.
  • the present invention involves photochemical therapy which may be used to treat a wide variety of abnormal blood vessel conditions.
  • the method may be used for a wide variety of situations wherein it is desired to selectively destroy one or more blood vessels.
  • the invention is particularly well suited for treating hypervascular dermal lesions. Accordingly, the following description of a preferred embodiment will be limited to describing the treatment of hypervascular dermal lesions with it being understood that the method may be used for photoche ically treating other blood vessel abnormalities.
  • Hypervascular dermal lesions such as port-wine- stains or spider veins are abnormal assemblies of blood vessels located within the dermis.
  • the drawing depicts schematically the process in accordance with the present invention for treating such abnormal blood vessel assemblies.
  • a portion of the skin co be treated is shown at 10.
  • the skin is shown as an extremely simplified cross section showing the epidermis 12 and dermis or corium 14.
  • the dermis 14 includes blood vessels 16 which are shown in the simplified cross section.
  • the various structures present in the dermis, such as nerve endings, sweat glands, hair follicles and sebaceous glands are not depicted in order to simplify the- pictorial description of the method.
  • the blood vessels 16 include a blood vessel wall 18 which is made up of blood vessel tissue cells.
  • the blood vessels 16 have an interior surface 20 which defines a blood flow zone 22 through which blood flows.
  • the blood vessels 16 also include an exterior surface 24 which defines the outer perimeter of the blood vessel 16.
  • the first step in the method involves introducing a therapeutic amount of a photoreactive compound into the blood flowing through the blood flow zone 22.
  • the photoreactive compound is shown schematically as dots within the blood vessel 16.
  • the photoreactive compound can be any of the known photosensitive dyes which are suitable for use in photodynamic therapy. These compounds include hematoporphyrin derivative (HPD) and the purified form of HPD known as Photofrin II. These compounds are commercially available. These compounds and other porphyrin derivatives for use in photodynamic therapy are described in United States Patents Nos. 4,649,151; 4,699,903; 4,692,439; and 4,753,958. The contents of these United States Patents are hereby incorporated by reference. Although a variety of porphyrin based compounds are available, Photofrin II is a preferred photoreactive compound. Other suitable photoreactive compounds include chlorins, phthalocyanines and purpurin.
  • the photoreactive compound is injected intravenously into the patient.
  • the dosage level should be between about 1 milligram per kilogram of body weight to about 3 milligrams per kilogram of body weight.
  • the dosage level may vary depending upon the compound being administ-ered and the lesion being treated. The particular dosage levels which will, be most effective c ⁇ n be established by, routine experimentation. Such dosage levels may be as low as 0.1 milligram per kilogram of body weight or as high as 5 milligrams per kilogram of body weight.
  • the photoreactive compound is injected as a solution in which the photoreactive compound is dissolved in a suitable pharmaceutical carrier. Any of the pharmaceutical carriers which have been used in the past for injecting porphyrin dyes for photodynamic therapy may be used.
  • the top portion of the drawing at (1) depicts a portion of skin immediately after intravenous injection of the photoreactive compound. As can be seen, the dots representing the photoreactive compound are limited to the interior of the blood vessels 16. The photoreactive compound is then allowed to accumulate in the blood vessel wall 18 for a sufficient time to provide a sufficient amount of photoreactive compound within the blood vessel wall 18 to destroy the blood vessel when the photoreactive compound is activated by a laser in accordance with known techniques. This condition is shown in the middle of the drawing at (2) where the photoreactive compound, as represented * by the dots, has migrated from the interior of the blood vessel 22 out into the blood vessel walls 18.
  • the laser 30 is directed onto the blood vessel 16 to activate the photoreactive compound and destroy the blood vessel.
  • the irradiation of the vessels by laser 30 is represented by arrows 32.
  • the skin is irradiated within one to four hours after intravenous injection of the photoreactive compound. Shorter or longer waiting periods may be used depending upon the type of patient being treated and the particular compound being used. A waiting period of about two hours is preferred. The two-hour time period was found to optimize blood vessel destruction while limiting damage to surrounding tissues.
  • the wavelength and intensity of laser radiation directed at the blood vessels 16 can be varied within the range of intensities and wavelengths commonly used in photodynamic therapy. Wavelengths of between about 400 to 700 nanometers are acceptable. The preferred wavelength range for HPD is between 600 to 650 nanometers. Wavelengths in this range are preferred since they have sufficient energy to activate he ato porphyrin compounds to destroy the blood vessels while at the same time being able to penetrate through the skin to depths sufficient to reach the blood vessels. 630 nanometer laser light has been found to be particularly effective in treating blood vessels located in the skin. For blood vessels located at locations other than in the dermis, suitable means must be used for focusing laser ' light onto blood vessels. Various optical fiber devices commonly used to direct laser light onto tumors can be used for this purpose. The controlling consideration is to match the wavelength with the absorption by the dye and the location of the lesions. For example, shorter wavelengths which penetrate less deeply into the tissue, are more suitable for superficial lesions.
  • Photofrin II (DHE) was obtained and prepared by the method of Nelson et al. and injected without dilution intravenously at 10 g/kg. The Photofrin II was injected as a solution of 2.45 mg Photofrin per 1 ml of solu.
  • the laser used was a Krypton laser coherent Innova 90 of 405 nm wavelength.
  • Post-injection intervals prior to irradiation were compared by observing the chronological extent of persistent comb blanching. Blanching of the chicken comb is recognized as an effective measure of blood vessel destruction. The 2 hr. areas showed the most prominent blanching effects which persisted for 7, 9 and 14 days. All other post-injection intervals areas had less pronounced blanching and returned to baseline within 2 to 4 days.
  • Example 2 The same method as Example 1 was used to treat a number of chicken combs except that 630 mm red light from a dye laser was used instead of 405 nm light and all times between injections and irradiation were 2 hours. The results were similar except that permanent blanching of the chicken combs was achieved. As in Example 1, there was no damage found to the epidermis or other tissue of the comb surrounding the destroyed blood vessels. Having thus described exemplary embodiments of the present invention, it should be noted by those skilled in the art that the within disclosures are exemplary only and that various other alternatives, adaptations, and modifications may be made within the scope of the present invention. Accordingly, the present invention is not limited to the specific embodiments as illustrated herein, but is only limited by the following claims.

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  • Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pathology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Radiation-Therapy Devices (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Un procédé de traitement de vaisseaux sanguins, permet de détruire le vaisseau sanguin (16) sans endommager les tissus environnants (14). Le procédé consiste à introduire un composé photoréactif dans le sang qui circule dans le vaisseau sanguin (16) et à laisser le composé photoréactif s'accumuler dans la paroi (18) du vaisseau sanguin. Le composé photoréactif est activé par exposition à un rayonnement (32) avant accumulation du composé réactif dans les tissus environnants (14). L'activation du composé photoréactif avant d'entrer dans les tissus environnants (14) détruit sélectivement les vaisseaux sanguins (16) tout en limitant la destruction des tissus environnants (14).
PCT/US1990/001647 1989-03-31 1990-03-27 Traitement photochimique de vaisseaux sanguins WO1990011797A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US33201589A 1989-03-31 1989-03-31
US332,015 1989-03-31

Publications (1)

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WO1990011797A1 true WO1990011797A1 (fr) 1990-10-18

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AU (1) AU5413490A (fr)
CA (1) CA2012175A1 (fr)
WO (1) WO1990011797A1 (fr)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994012239A1 (fr) * 1992-11-20 1994-06-09 University Of British Columbia Procede d'activitation d'agents photosensibles
EP0712322A4 (fr) * 1994-06-08 1996-10-23 Thermolase Corp Procede de peeling de la peau en surface a l'aide d'un laser
US5752948A (en) * 1991-10-29 1998-05-19 Thermolase Corporation Hair removal method
US5752949A (en) * 1991-10-29 1998-05-19 Thermolase Corporation Hair removal method
US5817089A (en) * 1991-10-29 1998-10-06 Thermolase Corporation Skin treatment process using laser
US5925035A (en) * 1991-10-29 1999-07-20 Thermolase Corporation Hair removal method
US6152917A (en) * 1991-10-29 2000-11-28 Thermolase Corporation Hair removal device
US6267771B1 (en) 1991-10-29 2001-07-31 Thermotrex Corporation Hair removal device and method
WO2001019271A3 (fr) * 1999-09-15 2001-09-27 Neil David Glossop Procede et systeme destines a faciliter la chirurgie guidee par l'image
US7465312B2 (en) 2006-05-02 2008-12-16 Green Medical, Inc. Systems and methods for treating superficial venous malformations like spider veins
EP1872782A4 (fr) * 2005-04-14 2009-07-15 Takafumi Ohshiro Medicament pour le traitement ou le diagnostic d une lesion vasculaire dans la peau ou le tissu mou sous-cutane provoquee par une irradiation
US8470010B2 (en) 2006-05-02 2013-06-25 Green Medical, Inc. Systems and methods for treating superficial venous malformations like spider veins

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4541438A (en) * 1983-06-02 1985-09-17 The Johns Hopkins University Localization of cancerous tissue by monitoring infrared fluorescence emitted by intravenously injected porphyrin tumor-specific markers excited by long wavelength light
US4610241A (en) * 1984-07-03 1986-09-09 Gordon Robert T Atherosclerosis treatment method
US4612938A (en) * 1982-09-04 1986-09-23 Gesellschaft Fur Strahlen- Und Umweltforschung Mbh, Munchen Method for illuminating cavities
US4622952A (en) * 1983-01-13 1986-11-18 Gordon Robert T Cancer treatment method
US4622953A (en) * 1983-01-13 1986-11-18 Gordon Robert T Process for the treatment of atherosclerotic lesions
US4773899A (en) * 1982-11-23 1988-09-27 The Beth Israel Hospital Association Method of treatment of artherosclerosis and balloon catheter the same
US4815447A (en) * 1985-03-19 1989-03-28 Mills Randell L Mossbauer cancer therapy

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4612938A (en) * 1982-09-04 1986-09-23 Gesellschaft Fur Strahlen- Und Umweltforschung Mbh, Munchen Method for illuminating cavities
US4773899A (en) * 1982-11-23 1988-09-27 The Beth Israel Hospital Association Method of treatment of artherosclerosis and balloon catheter the same
US4622952A (en) * 1983-01-13 1986-11-18 Gordon Robert T Cancer treatment method
US4622953A (en) * 1983-01-13 1986-11-18 Gordon Robert T Process for the treatment of atherosclerotic lesions
US4541438A (en) * 1983-06-02 1985-09-17 The Johns Hopkins University Localization of cancerous tissue by monitoring infrared fluorescence emitted by intravenously injected porphyrin tumor-specific markers excited by long wavelength light
US4610241A (en) * 1984-07-03 1986-09-09 Gordon Robert T Atherosclerosis treatment method
US4815447A (en) * 1985-03-19 1989-03-28 Mills Randell L Mossbauer cancer therapy

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5817089A (en) * 1991-10-29 1998-10-06 Thermolase Corporation Skin treatment process using laser
US6267771B1 (en) 1991-10-29 2001-07-31 Thermotrex Corporation Hair removal device and method
US6152917A (en) * 1991-10-29 2000-11-28 Thermolase Corporation Hair removal device
US6036684A (en) * 1991-10-29 2000-03-14 Thermolase Corporation Skin treatment process using laser
US5752948A (en) * 1991-10-29 1998-05-19 Thermolase Corporation Hair removal method
US5752949A (en) * 1991-10-29 1998-05-19 Thermolase Corporation Hair removal method
US5925035A (en) * 1991-10-29 1999-07-20 Thermolase Corporation Hair removal method
EP0947222A3 (fr) * 1992-11-20 1999-10-27 The University Of British Columbia Procédé d'activation d'agents photosensibles
US5770619A (en) * 1992-11-20 1998-06-23 University Of British Columbia Method of activating photosensitive agents
WO1994012239A1 (fr) * 1992-11-20 1994-06-09 University Of British Columbia Procede d'activitation d'agents photosensibles
US5705518A (en) * 1992-11-20 1998-01-06 University Of British Columbia Method of activating photosensitive agents
AU679016B2 (en) * 1992-11-20 1997-06-19 University Of British Columbia, The Method of activating photosensitive agents
EP0925807A1 (fr) * 1994-06-08 1999-06-30 Thermolase Corporation Procédé de peeling de la peau en surface à l'aide d'un laser
EP0712322A4 (fr) * 1994-06-08 1996-10-23 Thermolase Corp Procede de peeling de la peau en surface a l'aide d'un laser
WO2001019271A3 (fr) * 1999-09-15 2001-09-27 Neil David Glossop Procede et systeme destines a faciliter la chirurgie guidee par l'image
US6317616B1 (en) 1999-09-15 2001-11-13 Neil David Glossop Method and system to facilitate image guided surgery
EP1872782A4 (fr) * 2005-04-14 2009-07-15 Takafumi Ohshiro Medicament pour le traitement ou le diagnostic d une lesion vasculaire dans la peau ou le tissu mou sous-cutane provoquee par une irradiation
JP5265186B2 (ja) * 2005-04-14 2013-08-14 貴史 大城 光照射による皮膚又は皮下軟部組織の血管性病変治療又は診断用薬剤
US7465312B2 (en) 2006-05-02 2008-12-16 Green Medical, Inc. Systems and methods for treating superficial venous malformations like spider veins
US8470010B2 (en) 2006-05-02 2013-06-25 Green Medical, Inc. Systems and methods for treating superficial venous malformations like spider veins
US8535360B2 (en) 2006-05-02 2013-09-17 Green Medical, Ltd. Systems and methods for treating superficial venous malformations like spider veins

Also Published As

Publication number Publication date
AU5413490A (en) 1990-11-05
CA2012175A1 (fr) 1990-09-30

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