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WO2007080108A1 - Composition d'acide ascorbique et d'un ion métallique pour l'élimination sélective de cellules mammaliennes pathologiques - Google Patents

Composition d'acide ascorbique et d'un ion métallique pour l'élimination sélective de cellules mammaliennes pathologiques Download PDF

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Publication number
WO2007080108A1
WO2007080108A1 PCT/EP2007/000164 EP2007000164W WO2007080108A1 WO 2007080108 A1 WO2007080108 A1 WO 2007080108A1 EP 2007000164 W EP2007000164 W EP 2007000164W WO 2007080108 A1 WO2007080108 A1 WO 2007080108A1
Authority
WO
WIPO (PCT)
Prior art keywords
metal ion
ascorbic acid
cells
mammalian cells
pathologically altered
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/EP2007/000164
Other languages
English (en)
Inventor
Thomas Lisowsky
Karlheinz Esser
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Multibind Biotec GmbH
Original Assignee
Multibind Biotec GmbH
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 Multibind Biotec GmbH filed Critical Multibind Biotec GmbH
Publication of WO2007080108A1 publication Critical patent/WO2007080108A1/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
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/26—Iron; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/34—Copper; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the invention concerns a composition for selective killing and destruction of pathological mammalian cells and uses of this composition.
  • composition comprising a synergistic mixture of a) ascorbic acid and b) at least one metal ion.
  • An additional enhancement of the effect of the two components, i.e. vitamin c or derivates thereof and at least one metal ion, can be achieved by the optional addition of factors that promote the up-take of metal ions into pathologically altered cells.
  • factors are for example natural transferrin receptors or the human growth factor Augmenter of Liver Regeneration protein (Alrp) [Lange et al.
  • One embodiment of the present invention comprises solutions containing a synergistic mixture of a) at least ascorbic acid or derivates thereof and b) at least one metal ion and c) optionally selected substances that support the up-take of metal ions.
  • Another purpose of the present invention is the use of the composition according to the invention for selective killing and destruction of pathologically altered mammalian cells.
  • ascorbic acid or derivates thereof with at least one metal ion results in a synergistic effect and in rapid, efficient and selective killing of pathologically altered mammalian cells.
  • the components are provided in appropriate concentrations.
  • composition according to the invention shows selective killing and destruction of pathological cells in the pH range of 1 to 6,5 with an essentially comparable efficiency.
  • Adjustment and consideration of correct pH values for the solutions according to the invention is therefore preferred.
  • ascorbic acid, their related salts or acidic derivates are used as well as at least one compound selected from the group of the water-soluble forms having the characteristics of an antioxidant.
  • the derivates of ascorbic acid or their respective salts or acidic derivates are one or several compounds and/or their related salts selected from the group of the highly water-soluble compounds. They are provided in concentrations of 0,1 mM to 50 mM in relation to the total volume of the solution, preferably, in concentrations of 0.1 mM to 5 mM.
  • the metal ions according to the invention are di- and/or tri- valent ions of metals found in the 4th period and/or subgroup I, II and VIII (IB, HB and VIIIB) of the periodic table of the elements. They are provided as salts in combination with their organic and/or inorganic acids and bases. According to the Invention, one or several compounds selected from sub-group VIII, especially iron, cobalt, nickel, copper or zinc are preferred. They are provided in concentrations of 0,01 itiM to 5 inM, in relation to the total volume of the solution, preferably in concentrations of 0.1 mM to 2 inM.
  • composition according to the invention can contain additional common inert adjuvants and additives like for example suitable buffer substances for defining a specific pH value, like Tris (Tris (hydroxymethyl) -aminomethan) , MES (2 (Morpholino)ethansulfonic acid), HEPES (2- [4- (2- Hydroxyethyl) -1-piperazinyl] -ethansulfonic acid, MOPS (3-(N- Morpholino) propansulfonic acid), carbonate and derivates of succinic acid.
  • suitable buffer substances for defining a specific pH value
  • suitable buffer substances like Tris (Tris (hydroxymethyl) -aminomethan) , MES (2 (Morpholino)ethansulfonic acid), HEPES (2- [4- (2- Hydroxyethyl) -1-piperazinyl] -ethansulfonic acid, MOPS (3-(N- Morpholino) propansulfonic acid), carbonate
  • the application in general takes place through intra-venous injection via the blood or by direct application into the pathologically altered cells.
  • Fig. 1 shows the principle for selective killing of pathologically altered cells by the composition according to the invention.
  • the up to thousand-fold accumulation of metal ions in pathologically altered cells results in sensitisation towards ascorbic acid and derivates thereof.
  • Combination of the application of ascorbic acid and derivates thereof with at least one additional metal ion and optionally with substances that support the up-take of metal ions results in selective killing of the pathologically altered cells.
  • Advantageous for this effect is the synergistic mixture of the components and preferably the compliance of well defined concentrations that have no deleterious effect on normal cells but that induce apoptosis for pathological cells .
  • Table 1 shows a preferred basic composition and a preferred mixture for a two component system made of ascorbic acid and/or derivates thereof and metal ions.
  • composition of the solutions pH range 1.0 to 6.5 ascorbic acid 0.1 mM to 5 mM metal ions: 0 01 mM to 2 mM proteins to enhance the up-take of metal ions: 1 mg to lOOmg per 1 kg body weight
  • Table 1 Preferred compositions of a solution comprising ascorbic acid and/or derivates thereof, metal ions and optionally different substances that support up-take of metal ions into pathologically altered mammalian cells. List with explanation of the abbreviations in the figures
  • Alrp Augmenter of Liver Regeneration protein
  • Apoptosis programmed cell death

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Inorganic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une composition comportant de la vitamine C et/ou ses dérivés et au moins un ion métallique pour l'élimination et/ou la destruction sélective et efficace de cellules mammaliennes ayant subi une altération pathologique. Les solutions selon l'invention sont appliquées par voie intraveineuse via le sang ou par injection directe dans une structure cellulaire unie ayant subi une altération pathologique, entraînant ainsi l'élimination et/ou la destruction efficace et sélective de ces cellules. Une amélioration additionnelle peut être obtenue par l'application éventuelle du substances qui supportent l'apport d'ions métalliques dans les cellules ayant subi une altération pathologique.
PCT/EP2007/000164 2006-01-10 2007-01-10 Composition d'acide ascorbique et d'un ion métallique pour l'élimination sélective de cellules mammaliennes pathologiques Ceased WO2007080108A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102006001213A DE102006001213A1 (de) 2006-01-10 2006-01-10 Synergistische Lösung aus Ascobinsäure oder deren Derivaten und Metallionen effizienten, selektiven Abtötung pathologischer Säugerzellen
DE102006001213.5 2006-01-10

Publications (1)

Publication Number Publication Date
WO2007080108A1 true WO2007080108A1 (fr) 2007-07-19

Family

ID=37946752

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2007/000164 Ceased WO2007080108A1 (fr) 2006-01-10 2007-01-10 Composition d'acide ascorbique et d'un ion métallique pour l'élimination sélective de cellules mammaliennes pathologiques

Country Status (2)

Country Link
DE (1) DE102006001213A1 (fr)
WO (1) WO2007080108A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9795133B2 (en) 2011-01-26 2017-10-24 Multibind Biotec Gmbh Synergistic disinfecting compositions with essential oils
US10980239B2 (en) 2005-04-30 2021-04-20 Multibind Biotec Gmbh Decontamination solution and its use for denaturation, modification, degradation, solubilisation and removal of proteins, nucleic acid molecules and microorganisms

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2041M (fr) * 1962-04-17 1963-09-30 Andre Anselme Marie Composition thérapeutique a propriétés cytotoxiques a base d'acide ascorbique et d'ions métalliques.
WO1999051585A1 (fr) * 1998-04-07 1999-10-14 Even Marstrand Composition de traitement du cancer et de la colite ulcereuse et utilisation d'un complexe de titane et d'un sel de zinc dans la preparation de la composition
WO2001024803A2 (fr) * 1999-10-04 2001-04-12 John Carter Compositions pharmaceutiques et leur utilisation
WO2001082938A2 (fr) * 2000-04-28 2001-11-08 Ocean Nutrition Canada Limited Compositions utiles pour le traitement de pathologies des tissus conjonctifs

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2041M (fr) * 1962-04-17 1963-09-30 Andre Anselme Marie Composition thérapeutique a propriétés cytotoxiques a base d'acide ascorbique et d'ions métalliques.
WO1999051585A1 (fr) * 1998-04-07 1999-10-14 Even Marstrand Composition de traitement du cancer et de la colite ulcereuse et utilisation d'un complexe de titane et d'un sel de zinc dans la preparation de la composition
WO2001024803A2 (fr) * 1999-10-04 2001-04-12 John Carter Compositions pharmaceutiques et leur utilisation
WO2001082938A2 (fr) * 2000-04-28 2001-11-08 Ocean Nutrition Canada Limited Compositions utiles pour le traitement de pathologies des tissus conjonctifs

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
BRAM S ET AL: "VITAMIN C PREFERENTIAL TOXICITY FOR MALIGNANT MELANOMA CELLS", NATURE, MACMILLAN JOURNALS, LONDON, GB, vol. 284, no. 5757, 1980, pages 629 - 631, XP008079336, ISSN: 0028-0836 *
GONZÁLEZ MICHAEL J ET AL: "Inhibition of human breast carcinoma cell proliferation by ascorbate and copper.", PUERTO RICO HEALTH SCIENCES JOURNAL MAR 2002, vol. 21, no. 1, March 2002 (2002-03-01), pages 21 - 23, XP008079367, ISSN: 0738-0658 *
LEUNG P Y ET AL: "ASCORBIC ACID WITH CUPRIC IONS AS A CHEMOTHERAPY FOR HUMAN LUNG TUMOR XENOGRAFTS IMPLANTED BENEATH THE RENAL CAPSULE OF IMMUNOCOMPETENT MICE", IN VIVO - INTERNATIONAL JOURNAL OF IN VIVO RESEARCH, XX, GB, vol. 6, no. 1, 1992, pages 33 - 40, XP008079419, ISSN: 0258-851X *
PEREZ YARITZA ET AL: "ASCORBIC ACID AND COPPER: EFFECTIVE CYTOTOXIC AGENTS AGAINST METASTATIC BREAST CARCINOMA (BRCA)CELLS", PROCEEDINGS OF THE ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH, NEW YORK, NY, US, vol. 42, March 2001 (2001-03-01), pages 215, XP001248648, ISSN: 0197-016X *
SATOH KAZUE ET AL: "EFFECT OF COPPER AND IRON IONS ON CYTOTOXICITY INDUCED BY ASCORBATE, GALLATE AND CAFFEATE", ANTICANCER RESEARCH, HELENIC ANTICANCER INSTITUTE, ATHENS,, GR, vol. 17, no. 3C, 1997, pages 2181 - 2184, XP008079363, ISSN: 0250-7005 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10980239B2 (en) 2005-04-30 2021-04-20 Multibind Biotec Gmbh Decontamination solution and its use for denaturation, modification, degradation, solubilisation and removal of proteins, nucleic acid molecules and microorganisms
US9795133B2 (en) 2011-01-26 2017-10-24 Multibind Biotec Gmbh Synergistic disinfecting compositions with essential oils

Also Published As

Publication number Publication date
DE102006001213A1 (de) 2007-07-12

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