WO2018185346A1 - Composition pharmaceutique pour le traitement de maladies infectieuses - Google Patents

Composition pharmaceutique pour le traitement de maladies infectieuses Download PDF

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Publication number
WO2018185346A1
WO2018185346A1 PCT/EP2018/059052 EP2018059052W WO2018185346A1 WO 2018185346 A1 WO2018185346 A1 WO 2018185346A1 EP 2018059052 W EP2018059052 W EP 2018059052W WO 2018185346 A1 WO2018185346 A1 WO 2018185346A1
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Prior art keywords
solution
chlorine dioxide
pharmaceutical composition
treatment
therapeutic
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PCT/EP2018/059052
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German (de)
English (en)
Inventor
Andreas Ludwig KALCKER
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Schweizer Zentrum für wissenschaftliche Forschung, Innovation und Entwicklung
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Publication of WO2018185346A1 publication Critical patent/WO2018185346A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • 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
    • A61K33/20—Elemental chlorine; Inorganic compounds releasing chlorine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A61P33/06—Antimalarials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention relates to a pharmaceutical composition, in particular an infusion or injection solution, based on an aqueous chlorine dioxide solution, for the treatment of infectious diseases and inflammation in humans and animals.
  • oxidizing substances such as chlorine gas, ozone, hydrogen peroxide, chlorite, chlorate or perchlorate solutions.
  • oxidizing substances such as chlorine gas, ozone, hydrogen peroxide, chlorite, chlorate or perchlorate solutions.
  • These chemicals react nonspecifically with organic material by oxidation of, in particular, amino groups, sulfhydryl groups, double bonds and aromatic systems. This effect is essentially based on their antibacterial and antiviral activity.
  • chlorine dioxide has also been used as an effective antimicrobial agent for almost one hundred years, with the applications so far being limited primarily to surface disinfection and water sanitation.
  • US5252343 describes 1,993 the successful treatment of cattle mastitis with a chlorine dioxide solution (CDL) by rinsing the teats on the udder of the cow, whereas unlike conventional antibiotic therapy the milk of the CDL treated animals did not have to be discarded, but continued to be consumed could be used. This is because the treatment with CDL evidently produced no pollutants of any kind and no potentially harmful decomposition products of CI02 were detectable in relevant concentrations.
  • CDL chlorine dioxide solution
  • ROS reactive oxidative species
  • Oxidative Shielding or Oxidative Stress attempts to investigate this fact in 201 2 [The Journal of Pharmacology and Experimental Therapist / cs, 2012, Vol.342, No.3, pp608-618] and points out that reactive oxidative species such as free oxygen radicals are not the cause but are the result of illnesses. Oxidative shielding is a protective mechanism and should not be a target for anti-oxidative therapy.
  • chlorodixoid in contrast to chlorite and chlorate ions, does not indiscriminately attack any organic material, but rather selectively proteins and amino acids with secondary and tertiary amines and / or sulfhydryl groups, especially cysteine, methionine and glutathione, and aromatic amino acids such as tyrosine and tryptophan.
  • Noszticzius et al. Describe in their paper "Chlorine Dioxide Is a Size Selective Antimicrobial Agent” (Noszticzius Z, Wittmann M, Kaly-Kullai K, Beregvari Z, Kiss I, et al., 201 3, PLoS ONE 8 (1 1): e791 57.
  • CDL selectively kills small organisms such as bacteria and viruses and leaves the cells unaffected, approaching the topic from, among other things, the kinetic side and side effects make it very plausible that on the one hand certain proteins and amino acids are primarily attacked (see above) and that on the other hand the flooding of small entities such as bacteria by CI02 in a germicidal amount is simply faster than in much larger cells such as blood cells or somatic cells.
  • eukaryotic cells have repair mechanisms against oxidative damage, especially those of sulfhydryl groups that cause viruses and bacteria choose.
  • This task is accomplished by a
  • the invention relates to a pharmaceutical composition containing high purity chlorine dioxide (CIO2) in an aqueous medium and suitable for systemic parenteral application.
  • CIO2 high purity chlorine dioxide
  • the composition contains dissolved CIO 2 in a concentration of typically 5 to 1000 ppm, corresponding to 5 to 1000 mg / l. For most applications, however, a concentration range of 10 - 500, especially 25 - 300 ppm is most suitable.
  • the composition is substantially free of chlorine gas, hydrochloric acid, chlorite and chlorate ions, i. typically contains these components only in concentrations of less than 1% of the CIO 2 concentration.
  • This is achieved by a manufacturing process, which does not follow the usual scheme of producing a chlorine dioxide solution (CDL) by acidification of a sodium chlorate solution, but CI02 by electrolysis of a pH-neutral NaCl solution, followed by gas scrubbing generated.
  • the gentle electrolysis carried out at a voltage of 6 V, leads directly to the formation of CIO 2, with NaClO 2 and NaClO 3 being formed as by-products only in very small amounts, typically in concentrations of less than 1% relative to the concentration of CIO 2.
  • Even free hydrochloric acid and gaseous chlorine are formed - if at all - only in the smallest amounts.
  • the concentrations of Na-chlorate, Na-chlorite, chlorine gas and hydrochloric acid in the freshly prepared, concentrated CDL which contains mostly 1000-2000 ppm (mg / L) of CI02, typically in a range of not more than 10-20 ppm (mg / L) and in the ready-to-use, diluted CDL at a maximum of 1 -2 ppm (mg / L) or below. If necessary, however, the CIO 2 solution can also be produced with higher contents of 3000 ppm and more of CIO 2.
  • CDL high-purity CDL
  • a composition according to the invention which, in addition to external, topical application, should be suitable above all for systemic, in particular parenteral, applications in the form of injection or infusion solutions may contain at least one tonicity regulator which allows the solution to be rendered isotonic.
  • Tonizticiansregulatoren ionic substances such as NaCl or KCl come into question, but also non-ionic substances and in particular representatives of the group of monosaccharides, disaccharides, oligosaccharides and low molecular weight polyols.
  • the mono- and disaccharides are preferably selected from the group: glucose, fructose, sucrose and mannose and the low molecular weight polyols preferably selected from the group: glycerol, erythritol, lactitol, mannitol, sorbitol, inositol, xylitol, threitol and maltitol.
  • An isotonic saline solution contains 9g NaCl per liter of water (0.9%), the resulting osmolarity of 290-300 mosmol / l corresponds essentially to the osmolarity of the blood, which can also be mixed with KCl or a mixture of two or more of the mentioned ionic and non-ionic ionic Tonizticiansregulatoren can be adjusted.
  • a pH regulator in particular a buffer system
  • Suitable is a bicarbonate buffer or a phosphate buffer, e.g. PBS, viewed.
  • compositions according to the invention in particular those intended for prolonged, repeated use, the addition of further components from the group of preservatives, flavors, vitamins, mineral salts and trace elements may be advantageous.
  • the CDL of the invention can be prepared as a concentrate having a CIO 2 content of typically 1000-2000 ppm, which is mixed with e.g. isotonic, pH-neutral or optionally pH-buffered, NaCl solution is diluted by a factor of 2 - 500 in order to set the above-mentioned therapeutic CIO 2 contents of about 5 to 1000 ppm of a ready-to-use solution.
  • the concentrated composition may further contain 1 to 5% by weight (10 to 50 g / L) of DMSO or methylsulfonylmethane (synonym: dimethylsulfone) MSM, or a mixture of both components. These components dampen and delay the action of chlorine dioxide, so that the administration of long-term treatments or by the administration of large amounts within a short time no unwanted oxidative stress is caused. In addition, these sulfur-containing components improve the storage stability of the concentrated CDL.
  • Noszticzius et al. primarily relate to the external treatment of inflammations and wounds of the skin, these findings are, for the purposes of the present invention, for the first time
  • the efficacy and safety for systemic applications of intravenous, subcutaneous, intramuscular or other forms of injections and infusions have been reviewed and tested.
  • reaction kinetic findings from the topical application of Noszticzius et al. could be confirmed in the course of development of the present invention that contrary to the concerns of other parts of the art parenteral therapeutic use, optionally in combination with oral use of reactive oxidative species such as CI02 by no means must be accompanied by undesirable or even damaging effects.
  • MRSA Methicillin-resistant Staphylococcus aureus
  • MDRS Multiple Drug Resistant Salmonella Typhimurium
  • Mycobacterium Mycobacterium
  • Mycobacterium tuberculosis Mycobacterium tuberculosis, Pediococcus acidilacti, Pseudomonas aeruginosa, Salmonella, Shigella, Staphylococcus aureus, Staphylococcus faecalis, Enterococcus faecalis (VRE), Vibrio spp., Yersinia.
  • spores of the following bacteria can be killed by CI02 in vitro and in vivo:
  • Alicyclobacillus acidoterrestris Bacillus anthracis, Bacillus atrophaeus, Bacillus coagulans, Bacillus megaterium, Bacillus polymyxa, Bacillus pumilus, Bacillus subtilis, Bacillus thuringiensis, Clostridium sporogenes, Geobacillus
  • viruses can be killed by the CDL according to the invention:
  • Adenovirus Type 40 Calicivirus, Canine Parvovirus, Coronavirus, Feiines
  • fungi can be killed by the CDL according to the invention:
  • Alternaria alternata Aspergillus, Botrytis species, Candida, Chaetomium globosum, Cladosporium cladosporioides, Debaromyces etchellsii, Eurotium spp., Fusarium solani, Lodderomyces elongisporus, Mucor, Penicillium, Phormidium boneri, Pichia pastoris, Poitrasia circinans, Rhizopus oryzae, Roridin A, Saccharomyces cerevisiae , Stachybotrys chartarum, T-mentag, Verrucarin A.
  • the following protozoa can be killed by the CDL according to the invention:
  • Lyme disease is caused by infection with the bacterium Borrelia burgdorferi, typically due to a tick bite. Borrelia belong to a category of spirochaetes.
  • the disease is a multi-system disease affecting the skin, the nervous system, the heart and the joints.
  • symptoms are similar to the onset of influenza, including severe headache, fatigue, joint and muscle pain, fever and possibly swollen lymph glands.
  • a second stage several weeks after the tick bite, more severe symptoms appear, including neurological complications such as facial paralysis, irritability, and poor motor coordination.
  • heart problems associated with irregular heartbeat and dizziness may occur.
  • a third stage of the disease may occur months or years after the first infection and may include chronic arthritis or chronic neurological effects. Only an immediate treatment with antibiotics in the first two
  • Lyme disease is also found in animals. For example, antibodies to Borrelia burgdorferi have been detected in cattle in Europe, Australia, the United Kingdom and the United States.
  • 1% by weight of dimethylsulfoxide was added to a concentrate of the aqueous, highly pure and pH-neutral chlorine dioxide solution (concentration 1000 ppm) as slightly retarding, oxidation-delaying agent.
  • concentration 1000 ppm concentration 1000 ppm
  • the DMSO-containing chlorine dioxide solution was filled under aseptic conditions in 25 ml glass ampoules made of brown standard ampoule glass and stored at about 8 ° C until use.
  • the storage stability of this concentrated solution is at least 1 2 months with a loss of activity of available CI02 of max. 10%
  • a 25 ml glass ampoule with pH-neutral or preferably slightly alkaline saline (pH 7.3-7.5, adjusted with bicarbonate buffer) is diluted to 500 ml, resulting in a CIO 2 concentration of about 50 ppm.
  • the concentration of 50 ppm is checked photometrically by means of a photometer HI96771 C from Hanna Instruments.
  • the erythrocytes are in the typical datura shape. After the 4 infusions according to the above scheme, all three patients were symptom-free and full of energy. No notable adverse effects were observed. The blood count was back to normal and there was no methaemoglobinaemia.
  • the infusion solution was prepared as in Example 1, but the dilution to the ready-to-use concentration was carried out with pH-neutral, isotonic saline, without pH buffer.
  • CDL pH-neutral chlorine dioxide solution
  • the animal is perfectly healthy after this treatment.
  • EXAMPLE 5 Treatment of Malaria A field study was conducted in the village of Iganga, near Kampala (Uganda). This field study was intended to show what effects and any undesirable side effects in the treatment of malaria with chlorine dioxide come to light or which treatment options open up.
  • Chlordixid also seems to have a positive effect on the physiological body fluids on a too low blood pH.
  • experiments have shown that a blood pH of about pH 7.25 increased to about pH 7.35, although in detail it has not yet been completely clarified to which mechanisms this pH increase can be attributed.

Abstract

L'invention concerne une composition pharmaceutique s'utilisant dans le traitement systémique, en particulier parentéral, de maladies infectieuses, à base d'une solution de dioxyde de chlore aqueuse, stérile et exempte d'agents pyrogènes, laquelle contient entre 5 et 1000 mg/l (ppm) de dioxyde de chlore dissous (CI02) ainsi que de préférence entre 3 et 10 g/l d'un régulateur de tonicité ionique, éventuellement en association avec un régulateur de tonicité non ionique. Ladite composition contient de préférence en outre un régulateur de pH, en particulier un système tampon de pH, ajusté à un pH compris entre 7,3 et 7,5, et peut par ailleurs contenir du diméthyl sulfoxyde ou de méthylsulfonylméthane. A l'état prêt à l'emploi, ladite composition est exempte d'ions chlorate, d'acide salique et de chlore gazeux ou contient ces constituants, chacun dans une concentration maximale de 1 mg/L (1 ppm).
PCT/EP2018/059052 2017-04-07 2018-04-09 Composition pharmaceutique pour le traitement de maladies infectieuses WO2018185346A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH00473/17A CH713711B1 (de) 2017-04-07 2017-04-07 Pharmazeutische Zusammensetzung zur Behandlung von Infektionskrankheiten.
CH473/17 2017-04-07

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2754881A1 (es) * 2018-10-19 2020-04-20 Medalab Res S L Procedimiento para el tratamiento de infecciones de Plasmodium resistentes a los medicamentos y producto utilizado
WO2021222291A1 (fr) 2020-04-29 2021-11-04 Radinor, Llc Composition pharmaceutique comprenant du dioxyde de chlore pour le traitement de la covid-19
WO2021255646A1 (fr) * 2020-06-15 2021-12-23 Margana Bio Technologies Ltd. Composition à base de cuivre pour la consommation animale
DE102021002129A1 (de) 2021-04-22 2022-10-27 Ulrich von der Heide Chlordioxid-Schaum-Lösung zur Desinfektion

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5252343A (en) 1992-03-20 1993-10-12 Alcide Corporation Method and composition for prevention and treatment of bacterial infections
US20040104127A1 (en) * 2002-12-02 2004-06-03 Rojas Juan Luis Araya Process and composition for obtaining an aqueous chlorine dioxide ready for its use, stabilized in a carbonate buffer, being a powerful disinfecting agent with ecological, non residual non toxic and non phytotoxic cataloging in the concentrations of usage
WO2011086579A1 (fr) * 2010-01-18 2011-07-21 Prophylaxis Procédé de production d'une forme liquide stable et pure de dioxyde de chlore
EP2926819A1 (fr) * 2012-11-29 2015-10-07 Xuewu Liu Méthode d'initiation de cellules souches de mammifère et utilisation du dioxyde de chlore dans la préparation d'un médicament pour l'initiation de cellules souches de mammifère

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5252343A (en) 1992-03-20 1993-10-12 Alcide Corporation Method and composition for prevention and treatment of bacterial infections
US20040104127A1 (en) * 2002-12-02 2004-06-03 Rojas Juan Luis Araya Process and composition for obtaining an aqueous chlorine dioxide ready for its use, stabilized in a carbonate buffer, being a powerful disinfecting agent with ecological, non residual non toxic and non phytotoxic cataloging in the concentrations of usage
WO2011086579A1 (fr) * 2010-01-18 2011-07-21 Prophylaxis Procédé de production d'une forme liquide stable et pure de dioxyde de chlore
EP2926819A1 (fr) * 2012-11-29 2015-10-07 Xuewu Liu Méthode d'initiation de cellules souches de mammifère et utilisation du dioxyde de chlore dans la préparation d'un médicament pour l'initiation de cellules souches de mammifère

Non-Patent Citations (8)

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Title
ANDREAS LUDWIG KALCKER: "Gesundheit verboten", March 2017, DAS NEUE LICHT / JIM HUMBLE VERLAG, Roermond, ISBN: 9789088791567, pages: 43-66,139-387,419,441 - 444, XP002782877 *
ANONYMOUS: "BfR rät von der Einnahme des Produkts "Miracle Mineral Supplement" ("MMS") ab", 2 July 2012 (2012-07-02), XP055486271, Retrieved from the Internet <URL:http://www.bfr.bund.de/cm/343/bfr-raet-von-der-einnahme-des-produkts-miracle-mineral-supplement-mms-ab.pdf> [retrieved on 20180620] *
ANONYMOUS: "Bundesinstitut für Arzneimittel und Medizinprodukte stuft zwei "Miracle Mineral Supplement"-Produkte als zulassungspflichtig und bedenklich ein", BFARM PRESSE, 26 February 2015 (2015-02-26), XP055489398, Retrieved from the Internet <URL:https://www.bfarm.de/SharedDocs/Pressemitteilungen/DE/2015/pm3-2015.html> [retrieved on 20180702] *
ANONYMOUS: "FDA Warns Consumers of Serious Harm from Drinking Miracle Mineral Solution (MMS)", 30 July 2010 (2010-07-30), XP055486143, Retrieved from the Internet <URL:https://www.pharmpro.com/news/2010/07/fda-warns-consumers-serious-harm-drinking-miracle-mineral-solution-mms> [retrieved on 20180620] *
ANONYMOUS: "Verordnung über Trinkwasser und über Wasser für Lebensmittelbetriebe (Trinkwasserverordnung - TrinkwV)", BGBL, 5 December 1990 (1990-12-05), XP055489433, Retrieved from the Internet <URL:https://www.ihph.de/publikationen/trinkwvero/Sonstige%20Dokumente/Alte%20TVO.pdf> [retrieved on 20180702] *
LEE ET AL., WATER RESEARCH, vol. 44, 2010, pages 555 - 566
NOSZTICZIUS Z; WITTMANN M; KÄLY-KULLAI K; BEREGVÄRI Z; KISS I ET AL., PLOS ONE, vol. 8, no. 11, 2013, pages e79157
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol. 342, no. 3, 2012, pages 608 - 618

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2754881A1 (es) * 2018-10-19 2020-04-20 Medalab Res S L Procedimiento para el tratamiento de infecciones de Plasmodium resistentes a los medicamentos y producto utilizado
WO2021222291A1 (fr) 2020-04-29 2021-11-04 Radinor, Llc Composition pharmaceutique comprenant du dioxyde de chlore pour le traitement de la covid-19
WO2021255646A1 (fr) * 2020-06-15 2021-12-23 Margana Bio Technologies Ltd. Composition à base de cuivre pour la consommation animale
DE102021002129A1 (de) 2021-04-22 2022-10-27 Ulrich von der Heide Chlordioxid-Schaum-Lösung zur Desinfektion

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CH713711A2 (de) 2018-10-15

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