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WO2007115291A2 - Marquages tissulaires à l'aide de particules d'absorption discrètes - Google Patents

Marquages tissulaires à l'aide de particules d'absorption discrètes Download PDF

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Publication number
WO2007115291A2
WO2007115291A2 PCT/US2007/065928 US2007065928W WO2007115291A2 WO 2007115291 A2 WO2007115291 A2 WO 2007115291A2 US 2007065928 W US2007065928 W US 2007065928W WO 2007115291 A2 WO2007115291 A2 WO 2007115291A2
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WIPO (PCT)
Prior art keywords
discrete absorption
ink according
particles
ink
aggregate
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/US2007/065928
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English (en)
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WO2007115291A3 (fr
Inventor
Ljiljana Kundakovic
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Freedom 2 LLC
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Freedom 2 LLC
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Publication of WO2007115291A2 publication Critical patent/WO2007115291A2/fr
Publication of WO2007115291A3 publication Critical patent/WO2007115291A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
    • A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
    • A61K49/0089—Particulate, powder, adsorbate, bead, sphere
    • A61K49/0091—Microparticle, microcapsule, microbubble, microsphere, microbead, i.e. having a size or diameter higher or equal to 1 micrometer
    • A61K49/0093—Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0017—Fluorescence in vivo
    • A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
    • A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
    • A61K49/0032—Methine dyes, e.g. cyanine dyes
    • A61K49/0034—Indocyanine green, i.e. ICG, cardiogreen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/006—Biological staining of tissues in vivo, e.g. methylene blue or toluidine blue O administered in the buccal area to detect epithelial cancer cells, dyes used for delineating tissues during surgery
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
    • A61K49/0065—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the luminescent/fluorescent agent having itself a special physical form, e.g. gold nanoparticle

Definitions

  • the present invention relates to tissue markings with discrete absorption particles. Also, it relates to methods for preparing and removing such tissue markings.
  • Tissue markings e.g., tattoos
  • tattoos have been used in almost every culture throughout history. They have been found on a five thousand year old human mummy, and decorated figurines suggest their use at least fifteen thousand years ago.
  • Tattoos have been used for many purposes including identity, beauty, artistic and spiritual expression, medicine, and magic.
  • tattoo uses include not only the familiar artistic tattoo, but also permanent makeup (for example, permanent eyebrows, eyeliner, lip liner, and lip color); corrective or reconstructive pigmentation (for example, re- pigmentation of scar tissue or areola reconstruction on mastectomy patients); medical markings (for example, marking gastrointestinal surgery sites for future monitoring or marking locations for radiation treatment); and identification markings on animals (for example, pedigree "tags" on purebred pets).
  • permanent makeup for example, permanent eyebrows, eyeliner, lip liner, and lip color
  • corrective or reconstructive pigmentation for example, re- pigmentation of scar tissue or areola reconstruction on mastectomy patients
  • medical markings for example, marking gastrointestinal surgery sites for future monitoring or marking locations for radiation treatment
  • identification markings on animals for example, pedigree "tags" on purebred pets.
  • the tissue marking procedure traditionally consists of piercing the skin with needles or similar instruments to introduce ink that typically includes inert and insoluble pigment particles having a wide distribution of sizes, which are suspended in a liquid carrier.
  • machines typically used to apply a tattoo include an electromagnetic coil tattooing machine (such as that disclosed in U.S. Patent No. 4,159,659 to Nightingale); a rotary permanent cosmetics application machine (such as that disclosed in U.S. Patent No. 5,472,449 to Chou); or any manual tattooing device (such as the sterile single-use device marketed by Softap Inc., San Leandro, CA).
  • pigment particles can be affected in a variety of ways, many of which are detrimental to the appearance of the tissue marking. In particular, some small particles may readily diffuse and make the tissue marking blur. Other small particles may be taken up by the macrophages and phagocytes. Large particles may be removed from the implantation area directly through, for example, transdermal elimination, or sequestered in the extracellular matrix. Also, particles may be moved away from the implantation area to the lymphatic system.
  • tissue marking the remaining particles of pigment located where they typically are engulfed by phagocytic skin cells (such as macrophages, phagocytes and fibroblasts) or are sequestered in the extracellular matrix. Transdermal elimination, diffusion and removal via the immune system tend to reduce the intensity and clarity of the tissue marking.
  • phagocytic skin cells such as macrophages, phagocytes and fibroblasts
  • a widely recognized problem with tattoos is that they cannot be easily removed.
  • tattoo removal was an issue as early as the first century A.D. in Rome, when soldiers returned from barbaric regions with tattoos that were unacceptable to society.
  • Tattoo "removal” methods include overtattooing without ink, dermabrasion, and surgical excision, all of which may leave an unacceptable appearance and/or scarring.
  • There currently does not publicly available efficacious, cost-effective method for tattoo removal [0013]
  • One current tattoo removal method is treatment with Q-switched laser pulses, perhaps in the nanosecond domain, which method has been shown to remove and lighten tattoos with a low risk of scarring and skin pigment changes.
  • a series of typically six to ten Q-switched laser treatments, which are expensive and usually cause discomfort, are administered at approximately one-month intervals.
  • this method is generally inefficient and ineffective - only about 50% of tattoos are successfully removed in less than ten Q-switched laser treatments, and various wavelength lasers may be necessary to remove all of the types of ink used in a tattoo.
  • Q-switched laser treatment of tattoos is based on the concept of selective photo thermolysis, in which a selectively-absorbed pulse of light is used to locally heat and destroy dermal cells containing the tattoo ink. After a laser treatment, some ink particles are naturally eliminated, for example, by the lymphatic system. Other ink particles, however, are re-phagocytosed by dermal cells, or otherwise remain in the skin as a residual tattoo, requiring re-treatment.
  • fixed wavelength lasers are used for Q-switched laser treatment of tattoos. Because some tattoo inks absorb only weakly or, like yellow, orange, sky blue and some green colored inks, do not absorb laser energy at the fixed wavelengths used for the laser treatment, several treatments employing different lasers may be necessary in order to remove multi-colored tattoos. These multiple treatments may also have to be combined with other types of treatment, such as dermabrasion, in order to remove the resistant inks. On average, multi-colored tattoos require the use of at least three different fixed wavelength lasers. Since the number of fixed wavelength lasers available for treatment of tattoos is limited and since such lasers may still be ineffective to remove a variety of different colored tissue markings, a new approach to tattoo removal is clearly needed.
  • the encapsulated pigment or dye may be selected such that it safely interacts with living tissue, and allows the use of pigments or dyes that otherwise could not be used in a traditional tissue marking.
  • Such encapsulated, complexed or aggregated pigments or dyes may include, in addition to those conventionally used in the art, pigments or dyes that are dispersible or biodegradable in living tissue, or pigments that could cause an adverse reaction if placed directly into a living organism.
  • Such improved tissue markings can be designed in advance to be susceptible to a specific type and amount of energy, which, when applied, ruptures or breaks apart the vehicle associated with the pigment or dye.
  • a design may, but not necessarily, include the use of a wavelength-specific discrete absorption particles to assist in the rupturing or breaking apart of the vehicle.
  • a single fixed wavelength laser can be used to remove inks of different colors, permitting accurate and efficient removal. If the pigment or dye carried by the vehicle is readily dissolvable, digestible or dispersible in living tissue, rupturing or breaking apart the vehicle results in the substantial or entire removal of an otherwise permanent tissue marking.
  • the present invention provides an improved tissue marking ink, and methods for implanting and removing tissue markings made from this ink.
  • the markings can be applied to tissue (whether human or animal) such as, but not limited to, skin, iris, sclera, muscles, tendons, organs, brain, small and large intestines, uterus, tumors and other cellular masses, legions, tissue beneath fingernails, tissue beneath toenails, tissue inside the mouth including the tongue, or tissue lining internal body passages. Most likely, the tissue is skin.
  • the improved tissue marking ink includes at least one discrete absorption particle, which is designed to absorb a specific, exogenous energy.
  • the tissue marking ink, and in particular the pigment or dye and the discrete absorption particles are phagocytosed or otherwise internalized by cells and/or their cytoplasm or organelles, forming a tissue marking.
  • the tissue marking will be permanent until it is desired to remove it.
  • exogenous energy is applied to the tissue. Once a sufficient amount of such exogenous energy has been applied, the discrete absorption particles can act like an "egg tooth” that rupture, or otherwise disrupt, the cells and/or their cytoplasm or organelles, releasing the pigment or dye into the extracellular space.
  • the pigment or dye may then be removed from the original tissue marking location by natural biological processes, such as via the lymphatic system or through expulsion through the skin.
  • the discrete absorption particles are, preferably, in particulate form, and are, preferably, of a size and shape and have physical and chemical properties that allow them to be used with tissue marking inks without affecting the desired color of the ink or the tissue.
  • the discrete absorption particles are added to the tissue marking ink at a desired concentration, so that they can be efficiently and effectively used to release the pigment or dye from the tissue cells when exogenous energy is applied to the tissue marking.
  • the discrete absorption particles may be designed to absorb electromagnetic radiation or heat.
  • electromagnetic radiation include visible radiation, near- IR, IR, near UV, high intensity visible radiation and visible radiation.
  • the discrete absorption particles may be designed from materials that exhibit magnetic properties, such as iron oxides.
  • the discrete absorption particles preferably have a size, shape and physical and chemical properties to be eliminated by natural biological processes as discussed above.
  • the present invention provides an improved tissue marking ink, which includes discrete absorption particles, which are mixed, or otherwise combined, with the pigment or dye particles prior to implantation in tissue.
  • the discrete absorption particles are preferably suspended or dispersed in the tissue marking ink, which, in addition to the pigment or dye, includes a carrier.
  • the discrete absorption particles can be used with conventional tissue marking inks, as well as with a variety of modified tissue marking inks as discussed herein.
  • the cells may be ruptured, or otherwise made to release pigment or dye particles. This may be accomplished by applying a specific form of exogenous energy, which targets the discrete absorption particles, thereby generating heat and rupturing, or otherwise disrupting, the cell to release the pigment or dye and the discrete absorption particles. If, for example, a discrete absorption particle that absorbs visible, high intensity visible, near- IR, IR, near UV, or UV radiation, exposing it to such radiation should lead to heat generation that is sufficient to rupture, or otherwise disrupt, the cell to release the pigment or dye internalized by the cell.
  • an external magnetic field generator producing focused alternating magnetic energy can be applied to force the magnetic poles of the discrete absorption particles to reverse with each alternation, resulting in a small discharge of heat.
  • the cumulative heat generated in the cells that phagocytosed the pigment or dye along with the discrete absorption particles should be sufficient to rupture, or otherwise disrupt, the cell and release the pigment or dye into the extracellular space. The heating effect is very local and does not harm nearby tissue cells.
  • a permanent, but removable on demand, tissue marking ink can be made by combining the tissue marking pigment or dye with at least one discrete absorption particle in a carrier.
  • This carrier is preferably, but not limited to, a liquid, such as water or ethanol.
  • the carrier may also be, for example, in a form of a gel.
  • At least one discrete absorption particle is included in the sphere, capsule or aggregate as disclosed in Provisional Application Nos. 60/709,619 and 60/710,614.
  • the discrete absorption particle(s), once the sphere, capsule or aggregate is phagocytosed by the tissue cell, can be used to efficiently rupture, or otherwise disrupt, the cell more to release the pigment or dye particles from the cell into the extracellular space.
  • tissue marking is any mark created by the introduction of the pigment into tissue, typically living tissue, with the intention of permanent or long-term endurance. Markings may be invisible or any visible color, and should be detectable, for example, by the naked eye or by using a detection device.
  • a tissue marking "pigment” or “dye” is broadly defined as a substance, which, upon implantation into tissue, can provide a tissue marking having diverse colors or appearance properties.
  • the pigment or dye can be comprised of graphite and other carbon substances, as well as any other conventional pigment or dye material.
  • the pigment can include inorganic metal salts and brightly colored organometallic complexes, etc.
  • the pigment or dye may be that disclosed in, for example, U.S. Patent Nos. 6,013,122; 6,800,122 (chromophores); 6,814,760; and 6,881,249; Provisional U.S. Patent Application Nos. 60/709,619 and 60/710,614; or U.S. Patent Application Publication No. 2005/0172852 Al.
  • a "tattoo” is a type of tissue marking wherein the tissue is usually, but not limited to, skin.
  • tissue marking ink is a form, which is different from the encapsulation or complex of the discrete absorption particles in U.S. Patent Nos. 6,800,122; 6,814,760; and 6,881,249.
  • the discrete absorption particle(s) in accordance with the present invention may be dispersed or suspended in a carrier as individual particles, a group of particles, as a sphere, capsule or aggregate, as disclosed in Provisional U.S. Patent Application Nos. 60/709,619 and 60/710,614, or in addition to the pigment or dye particles in the sphere, capsule or aggregate disclosed in these provisional patent applications.
  • diameter refers to a diameter of a spherical body and the largest linear dimension of a non- spherical body.
  • nanoparticle with a diameter is a particle or a structure in the nanometer (nm) range, typically from about 1 to about 100 nm in diameter.
  • nanometer- sized structure in accordance with the present invention include, but are not limited to, nanoshells and nanometer- sized encapsulations (nanocapsules) of nanometer-sized materials.
  • a material is "invisible" when essentially no color can be detected apart from the normal coloration of the its surroundings by the naked eye under normal lighting conditions, for example, diffuse sunlight or standard artificial lighting.
  • FIG. 1 is a schematic representation of a tissue marking ink containing conventional tissue marking pigment or dye particles and discrete absorption particles dispersed in a carrier.
  • FIG. 2 is a schematic representation of a tissue marking ink containing discrete absorption particles in a sphere, capsule or aggregate with pigment or dye particles.
  • FIG. 3 is a schematic representation of a tissue marking containing discrete absorption particles, both as individual particles and a sphere, capsule or aggregate of discrete absorption particles, dispersed in a carrier with spheres, capsules or aggregates of pigment or dye particles.
  • the concept of a removable on demand tissue markings such as a tattoo, according to the present invention includes a pigment or dye and at least one discrete absorption particle, which may be combined in a carrier to form tissue marking ink. Once the pigment or dye and the discrete absorption particle(s) are phagocytosed by a tissue cell, the discrete absorption particle(s) may be used to lyse, or otherwise disrupt, the cell to release the pigment or dye from the cell.
  • the energy necessary for the disruption would depend on the specific properties of the discrete absorption particles, such as absorption and/or polarization, and not on the type or color of the pigment, it is possible to use one type of exogenous energy, such as one frequency of laser light or an alternating magnetic field, to remove tissue markings of different colors if the same discrete absorption particles are used with the pigments or dyes of these colors.
  • one type of exogenous energy such as one frequency of laser light or an alternating magnetic field
  • the discrete absorption particle(s) 1 having a desired size, structure and chemical, physical and energy absorption properties, are mixed with pigment or dye particles 2 at a suitable or desired concentration in a carrier 3 to form tissue marking ink.
  • the ink is then implanted in tissue, for example, by conventional tattoo application methods.
  • the size of the discrete absorption particles can be adjusted to be in the same size range as that of conventional pigment or dye particles used to mark tissue. While the pigment or dye particle size distribution in conventional tissue marking or tattoo inks varies greatly, the pigment or dye ink particles are generally smaller than about 10 microns.
  • the most commonly used tissue marking inks such as India Ink or a suspension of amorphous carbon, contain particles smaller than 1 micron and, in some cases, smaller than 0.2 micron. Therefore, the size of the discrete absorption particles may be adjusted to be generally smaller than about 10 microns, and preferably smaller than about 1 micron. For some pigment or dye particles, it may be necessary to introduce the discrete absorption particles with the particle size smaller than about 0.2 micron.
  • discrete absorption particles For incorporation with certain types of pigments or dyes, it is desirable to prepare discrete absorption particles on a nanometer scale. It is preferable that these particles are smaller than about 100 nm or that they have a specific nanostructure, so that the particle properties, such as absorption of specific energy, are better controlled. Also, it may be desirable to introduce nanosized discrete absorption particles to facilitate particle elimination from the tissue by natural biological processes after the pigment or dye-containing cells are ruptured, or otherwise disrupted, during a removal treatment.
  • the discrete absorption particles may, preferably, be nanoparticles that are smaller than about 100 nm, and more preferably smaller than about 20 nm.
  • the discrete absorption particles of such a size can be introduced into the tissue marking ink either as individual particles or as aggregates, capsules or spheres to prevent their rapid elimination during introduction into tissue and to facilitate phagocytosis, as discussed in Provisional Application Nos. 60/709,619 and 60/710,614.
  • the discrete absorption particles absorb in the visible, near IR and/or IR region, they are preferably introduced at a concentration that does not affect the desired color of the tissue marking. Generally, this concentration should be not more than about 10% (v/v), and is preferably about 2% (v/v) or less, to ensure efficient removal.
  • tissue marking or tattoo that includes at least one discrete absorption particle that is susceptible to laser light
  • light from only a single fixed wavelength laser need be applied. Since each phagocytic tissue cell that engulfed the tissue marking ink contains a certain number of discrete absorption particles, along with what is typically, but not necessarily, a larger number of pigment or dye particles, a laser is selected to specifically target the absorption of the discrete absorption particles, not the absorption of the pigment or dye particles as it is currently done in conventional tattoo removal.
  • the discrete absorption particles absorb the light and generate heat to rupture, or otherwise disrupt, the cells and release the pigment or dye particles, as well as the discrete absorption particles, into the extracellular space, where the released particles are partly or completely eliminated by the lymphatic system.
  • the released discrete absorption particles that were not removed by the lymphatic system may potentially be re-phagocytosed by other, undamaged tissue cells.
  • the discrete absorption particles are preferably dispersible in tissue.
  • the discrete absorption particles are thus substantially or completely invisible when in tissue.
  • discrete absorption particles may be introduced into tissue marking inks disclosed in Provisional U.S. Patent Application Nos. 60/709,619 and 60/710,614, as shown in FIGs. 2 and 3.
  • the discrete absorption particles particle(s) 1 may be included in (e.g., FIG. 2) or with (e.g., FIG. 3) the sphere, capsule or aggregate at a concentration, which would be sufficient to rupture, or otherwise disrupt, the cell after phagocytosis, releasing the pigment or dye particles into the extracellular space.
  • the discrete absorption particles may themselves form a sphere, capsule or aggregate 5 akin to that formed by pigment or dye particles.
  • the discrete absorption particles can be designed to absorb near- IR, IR, UV, near UV and/or visible radiation.
  • the discrete absorption particles exhibiting magnetic properties may also be used.
  • the cells may be disrupted by using only one fixed wavelength laser selected based on the absorption properties of the discrete absorption particles and/or by alternating an external magnetic field, releasing the pigment or dye particles, as well as the discrete absorption particles, into the extracellular space.
  • Non-limiting examples of materials that can be used to form discrete absorption particles include metals, such as gold, silver and platinum. Particles formed from such metals, particularly those on a nanometer scale and their derived nanostructures, exhibit specific absorption features associated with the plasmon resonance of conduction electrons confined in the nanoparticle.
  • the absorption frequency, such as absorption maxima or color, and other absorption features, such as the shape and the width of the absorption peaks, of these nanoparticles and other metallic nanostructures, such as nanoshells are determined by the type of material, size and shape of nanoparticles and nanostructures, size distribution and the environment that surrounds these particles (Flutter and Fendler, Advanced Materials, 2004, 16(19), p. 1685).
  • gold nanoparticles have a strong plasmon resonance absorption at 520 nm.
  • Silver nanoparticles have a plasmon resonance absorption at 390 nm.
  • the absorption cross-section of metallic nanoparticles and nanostructures, such as nanoshells, is a million times larger than that of typical molecular pigments or dyes, resulting in an efficient light to heat conversion (Brongersma, Nature Materials, 2002, 2, p. 296), which is sufficient to efficiently rupture tissue, particularly dermal tissue, cells that contain pigment or dye particles.
  • Metallic and composite metallic discrete absorption nanoparticles and nano structures that exhibit plasmon resonance can be prepared as nanospheres, nanoshells, rods, rings, disks and cubes.
  • preparation techniques such as colloidal metallic preparation methods, microemulsions, surfactant stabilized micelles, reverse micelles, surfactant vesicles, as well as laser ablation methods, vacuum deposition and electron beam lithography may be used to form these structures (Advanced Materials, 2004, 16(19), p. 1685 and its references).
  • Nanoshells are optically tunable nanoparticles composed of a dielectric (for example, silica) core coated with an ultra-thin metallic layer.
  • Gold nanoshells for example, those developed by Nanospectra Biosciences, Inc., Houston, TX, have physical properties, particularly a strong plasmon resonance, similar to a gold colloid.
  • the maximum absorption (plasmon resonance) of nanoshells can be varied over a wide range by varying the ratio of inner to outer diameter of the shell, yielding plasmon resonance tunable from about 600 nm to greater than about 1000 nm (Halas, Nano Letters, 2003, 3(10), p. 1411).
  • gold silica nanoshells with a 100 nm core and a 5 nm shell thickness show a maximum absorption at about 1000 nm, while those having the shell thickness of 20 nm have a maximum absorption at about 700 nm.
  • Nanoshells ranging in size from a few nanometers to a few hundred nanometers may be prepared and used as discrete absorption particles in tissue markings. Such nanoshells may be, for example, about 800 nm in diameter (Halas et al. Science, 2003, 302, p. 419).
  • the metallic nanoparticles and nanostructures can be stabilized by covalently bound thiol and disulfide functionalized monolayers. If desired, the surface of metallic nanoparticles can be functionalized to induce a specifically desired immune response or to target specific surface receptors of antigen- presenting tissue cells to induce surface receptor mediated endocytosis, as discussed in Provisional Application No. 60/587,864 and International Application No. PCT/US2005/024865, which are incorporated herein by reference.
  • Other materials that may be used as discrete absorption particles with IR and near IR absorption include those disclosed in U.S. Patents No. 6,800,122 to Anderson.
  • these materials include, but are not limited to, graphite and other forms of carbon and metal oxides, such as iron oxide (red/brown or black), glasses (BG-7 and KG-3 filter glass made by Schott, Inc.), cyanine dyes (including indocyanine green and other colors), phthalocyanine dyes (green-blue), and pyrylium dyes (multiple colors).
  • Visible-colored materials that can be targeted by visible radiation include, but are limited to, dispersible colorants approved by Food and Drug Administration (FDA) for use in foods, pharmaceutical preparations, medical devices, or cosmetics, such as the non-soluble salts and lakes of FD&C and D&C dyes, as disclosed in U.S. Patents No. 6,800,122. Additional FDA approved dyes and colored drugs that can be used to form discrete absorption particles are listed in the Code of Federal Regulations (CFR) for Food and Drugs (see Title 21 of CFR chapter 1, parts 1-99).
  • FDA Food and Drug Administration
  • CFR Code of Federal Regulations
  • materials with magnetic properties can also be used to form discrete absorption particles.
  • black iron oxide particles such as superparamagnetic iron oxide (SPIO, particle size greater than about 50 nm), ultrasmall superparamagnetic iron oxide (USPIO, particle size smaller than about 50 nm) and monodisperse iron oxide nanoparticles (MION, particle size smaller than about 20 nm) may be used.
  • SPIO superparamagnetic iron oxide
  • USPIO ultrasmall superparamagnetic iron oxide
  • MION monodisperse iron oxide nanoparticles
  • Superparamagnetic iron oxide consists of nonstoichiometric microcrystalline magnetite cores, which are coated with dextrans (in ferumoxides) or siloxanes (in ferumoxsils).
  • iron oxide The most common form of iron oxide that may be used is magnetite, which is a mixture of Fe 2 O 3 and FeO. Fe 3 O 4 may be used in lieu of FeO. These materials are available as tissue specific MRI contrast agents (Feridex®, EndoremTM, GastroMARK®, Lumirem®, Sinerem®, Resovist®). USPIO particles are also available as MRI contrast agents (Sinerem®, Combidex®, ClariscanTM ). [0062] If desired, magnetic iron oxide nanoparticles can be functionalized to induce a specifically desired immune response or to target specific surface receptors of antigen presenting cells in the tissue to induce surface receptor mediated endocytosis, as disclosed in Provisional Application No. 60/587,864 and International Application No. PCT/US2005/024865.
  • the iron oxide nanoparticles described above are particularly advantageous, because they may be successfully targeted using different methods.
  • the iron-oxide nanoparticles may be targeted by a conventional laser, such as Q-switched Nd: YAG (1064 nm), frequency doubled Nd: YAG (532 nm), Alexandrite (755 nm) or Ruby (694 nm) laser.
  • a conventional laser such as Q-switched Nd: YAG (1064 nm), frequency doubled Nd: YAG (532 nm), Alexandrite (755 nm) or Ruby (694 nm) laser.
  • iron oxide nanoparticles phagocytosed by tissue cells can be targeted by an external magnetic field generator, such as the one being developed by Triton Biosciences for treatment of cancer, which generator produces focused, alternating magnetic energy.
  • a magnetic field may be applied to the tissue to force the magnetic poles of each nanoparticle or aggregate of nanoparticles to reverse with each alternation, which results in a small discharge of heat. Because the magnetic field alternates thousands of times per second, the cumulative heat generation in the pigment or dye-containing cells is sufficient to rupture the cell and release the pigment or dye into the extracellular space. The nanoparticles or their aggregates are so small that the heating effect is very local and does not harm nearby tissue cells.
  • Tissue markings in accordance with the present invention may be implanted using conventional tattooing methods. However, any method that would deliver the ink so that a tissue marking is formed can be used.

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Abstract

La présente invention concerne une encre de marquage tissulaire qui comprend au moins une particule d'absorption discrète.
PCT/US2007/065928 2006-04-04 2007-04-04 Marquages tissulaires à l'aide de particules d'absorption discrètes Ceased WO2007115291A2 (fr)

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US74422406P 2006-04-04 2006-04-04
US60/744,224 2006-04-04

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WO2007115291A3 WO2007115291A3 (fr) 2008-06-26

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Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2474671A (en) * 2009-10-22 2011-04-27 Angela Maria Hirtreiter Tattoo removal using magnetic properties of the ink
EP2274386A4 (fr) * 2007-09-13 2011-10-26 Performance Indicator Llc Marquages de tissu et procédés pour marquer de manière réversible un tissu à l'aide de ceux-ci
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