WO2018185346A1

WO2018185346A1 - Pharmaceutical composition for treating infectious diseases

Info

Publication number: WO2018185346A1
Application number: PCT/EP2018/059052
Authority: WO
Inventors: Andreas Ludwig KALCKER
Original assignee: Schweizer Zentrum für wissenschaftliche Forschung, Innovation und Entwicklung
Priority date: 2017-04-07
Filing date: 2018-04-09
Publication date: 2018-10-11
Also published as: CH713711B1; CH713711A2

Abstract

The invention relates to a pharmaceutical composition for systemic, particularly parenteral treatment of infectious diseases, based on an aqueous, sterile and pyrogen-free solution of chlorine dioxide, which contains 5 to 1000 mg/l (ppm) dissolved chlorine dioxide (CI02) and preferably 3 to 10 g/l of an ionic tonicity regulator, optionally in combination with a non-ionic tonicity regulator. The composition additionally preferably contains a pH regulator, particularly a pH buffer system, adjusted to pH 7.3-7.5, and can furthermore contain DMSO or MSM. In the ready-to-use state, the composition is free of chlorate ions, hydrochloric acid and gaseous chlorine, or contains said components in a concentration of 1 mg/L (1 ppm) at maximum each.

Description

PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF INFECTION DISEASES

TECHNICAL AREA

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.

STATE OF THE ART

For surface disinfection a variety of chemicals are used, mostly 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.

In addition, 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.

However, medical-therapeutic applications are also known, albeit to a surprisingly small extent, for example for external skin and wound disinfection, root canal treatments in dentistry, bad breath mouth or candidiasis, and similar topical applications to humans and animals.

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.

There is ample literature on the possible mechanisms of action of CI02 with respect to proteins, amino acids, nucleic acids, polysaccharides, lipids, lipid membranes, bacteria, spores, viruses, fungi, protozoa, and higher parasites. It is all the more astonishing that this simple oxidant CI02 is still not widely used in the medical and veterinary treatment of inflammation and inflammation

Infectious diseases listed. This may be with one in the professional world widespread, incomplete understanding of the physiology of the immune system in humans and animals have to do, as a result of which many diseases are considered to be caused by free oxygen or nitric oxide radicals and the

Therapy, therefore, for elimination of such free radicals - also referred to in the literature as "reactive oxidative species" (ROS) - by the administration of

Targets antioxidants.

In his review, "Oxidative Shielding or Oxidative Stress?" Robert Naviaux 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.

The possible mechanism of action of CI02:

Although the mechanism of action may not always be clarified in detail, the pertinent literature nevertheless shows that 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. In general, the literature refers to "electron-rich" organic molecule regions (see, eg, Lee et al., Water Research 44, (2010), 555-566), which are preferentially oxidized by chlorine dioxide in one or more sequential steps On the CI02 side, chloride ions are finally, in physiological solutions, NaCl, and water.

Reservations in parts of the professional world about a therapeutic use of CI02 therefore seem to rest on the basis of the relevant literature rather on an insufficient evaluation of existing expertise, perhaps also on certain prejudices. For example, recent studies on model organisms in vitro indicate that antiviral effects are likely to result from spike changes depending on the type of virus so that attachment to the host cell can no longer be achieved, or that the viral capsid is significantly altered so immunogenicity lost, or that certain steps in the protein biosynthesis are adversely affected, so that, for example, the transcription of the viral RNA or DNA is no longer functioning properly or the assembly of the virus particles is disturbed.

In the case of the effect on living unicellular organisms, for example in the case of the antibacterial and antifungal activity, it seems that experts have recognized that this microbicidal effect is primarily due to a disruption of the cell membranes or the lipid membranes of important organelles due to the action of CIO 2 is caused by about Damage to membrane proteins, such as tunneling proteins, a non-specific permeability of the membranes is caused for certain ions, whereby the cells, organelles, or, for example, bacterial or fungal spores, their membrane potential can not maintain and perish. There are also interesting reports on signal signaling ("signaling") of small molecules such as CI02, especially with respect to apoptosis induction, either directly or indirectly via the modulation of ATP, ADP or GMP levels Immune defenses is by no means considered negative, but rather as the limited, targeted elimination of individual, infected cells, to hinder or prevent a rapid multiplication and spread of the pathogens, for the benefit of the whole organism.

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. doi: 10.1 371 /journal.pone.00791 57), explains why the administration of 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. In addition, eukaryotic cells have repair mechanisms against oxidative damage, especially those of sulfhydryl groups that cause viruses and bacteria choose.

Reservations in parts of the professional world about a therapeutic use of CI02 therefore seem to rest on the basis of the relevant literature rather on an insufficient evaluation of existing expertise, perhaps also on certain prejudices.

It is an object of the present invention to provide these thoughts of Naviaux on the one hand and Noszticzius et al. on the other hand, to provide a water - based composition containing high purity chlorine dioxide as an oxidative agent and for systemic, particularly oral or parenteral, topical treatment, or a combination of systemic and topical treatment, numerous pathological conditions and human and Animal is suitable and usable. This task is accomplished by a

Composition solved as described in the independent claim.

Further advantageous features of the invention are set forth in the dependent claims. DESCRIPTION OF THE INVENTION

In one embodiment, the invention relates to a pharmaceutical composition containing high purity chlorine dioxide (CIO2) in an aqueous medium and suitable for systemic parenteral application.

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.

By "high purity" in this context is meant that 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.

Above all, the advantage of a high-purity CDL is that it reduces as far as possible the likelihood of any undesirable effects described for Na-chlorite and, above all, Na-chlorate in the specialist literature, which is especially true for formulations and compositions of is of particular importance, which should be used as infusion solutions or injection solutions.

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. As Tonizitätsregulatoren 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 Tonizitätsregulatoren can be adjusted.

Especially for injection and infusion solutions, it may be crucial to adjust the pH of the CDL to that of the blood within a range of approximately pH 7.3 - 7.5 to avoid any undesirable effects. For this purpose, a pH regulator, in particular a buffer system, can be added to the CDL. Suitable is a bicarbonate buffer or a phosphate buffer, e.g. PBS, viewed. Although studies in vitro have shown that for some applications a higher or lower pH of the CDL would be beneficial, injection and infusion solutions should focus on compatibility with blood pH. For other applications, for example rectal enemas or intestinal irrigation, higher or possibly lower pH values can also be set.

For the 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.

While the results of 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. In accordance with the 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.

In fact, to date no such reports of serious side effects or even deaths have been found in the literature and no such effects have been encountered in the course of experimental use in the context of the present invention.

By means of the methods according to the invention for systemic parenteral treatment of viral or microbial infections, optionally in combination with an oral therapy based on an aqueous chlorine dioxide solution, the following bacterial species, for example, can be successfully controlled:

Blakeslea trispora, Bordetella bronchiseptica, Brucella, Burkholderia, Campylobacter jejuni, Clostridium botulinum, Corynebacterium bovis, Coxiella burneti, Escherichia coli, Franscicella tularensis, Helicobacter pylori, Helminthosporium solani, Klebsiella pneumonia, Lactobacillus, Legionella, Leuconostoc citreum, Leuconostoc

Mesenteroides, Listeria, Methicillin-resistant Staphylococcus aureus (MRSA), Multiple Drug Resistant Salmonella Typhimurium (MDRS), Mycobacterium,

Mycobacterium tuberculosis, Pediococcus acidilacti, Pseudomonas aeruginosa, Salmonella, Shigella, Staphylococcus aureus, Staphylococcus faecalis, Enterococcus faecalis (VRE), Vibrio spp., Yersinia.

Furthermore, in physiological body fluids, 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

stearothermophilus.

The following viruses can be killed by the CDL according to the invention:

Adenovirus Type 40, Calicivirus, Canine Parvovirus, Coronavirus, Feiines

Calicivirus, Foot and Mouth Disease Virus, Hantavirus, Hepatitis A Virus, Hepatitis B Virus, Hepatitis C Virus, Human Coronavirus, Human Immunodeficiency Virus, Human Rotavirus Type 2 (HRV), Influenza A Virus, Newcastle Disease Virus, Norwalk Virus, Parvovirus, Poliovirus, rotavirus, SARS virus, coronavirus, Sendai virus, vaccinia virus. The following 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:

Amoeba, Chironomid larvae, Cryptosporidium, Cryptosporidium parvum, Oocyst spp., Cyclospora cayetanensis oocysts, Giardia lamblia.

The following examples are intended to further illustrate the invention and to underpin the therapeutic utility of the oxidative intervention using chlorine dioxide solution. It should also be noted at this point that the treatments described in the following patient examples were performed either by doctors or under medical supervision.

EXAMPLE 1: Lyme borreliosis

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. In the first stage of the disease, symptoms are similar to the onset of influenza, including severe headache, fatigue, joint and muscle pain, fever and possibly swollen lymph glands. In 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. Furthermore, 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

Stages of the disease according to conventional medicine allows - often unfortunately not complete - recovery.

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.

In the context of the present invention, a new treatment method has been used. This was a high purity Chlordixoidlösung prepared by Electrolysis from a NaCl solution followed by gas scrubbing and without addition of acid, administered as an infusion solution. However, a comparable, high purity chlorine dioxide solution prepared by another method would also be usable provided it meets the criteria for a high purity solution mentioned herein.

In order to largely avoid oxidative stress and to avoid any phlebitis at the puncture site of the infusion cannula, 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. 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%

Immediately prior to treatment, 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.

Each 500 ml of this solution is administered intravenously at a rate of 3 drops per second for 2 weeks at 4-day intervals:

Infusion 1, day 01: 500ml;

Infusion 2, day 05: 500 ml;

Infusion 3, day 09: 500 ml;

Infusion 4, day 1 3: 500 ml.

According to this scheme, two male and one female patient are treated between the ages of 30 and 50 years. Patients complain of exhaustion, headache, joint pain, limb weakness and impaired muscle movement. Blood analyzes carried out in Germany and Spain confirm the presence of Borrelia. It is not known exactly how long the patients are already suffering from these symptoms, according to subjective data for several weeks to several months. Immunohistochemical analyzes show in the female patient also a significant compromise of the immune system and IgM antibodies to Epstein-Barr virus and Mycoplasma pneumoniae.

Under the microscope, 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.

All three patients were discharged as healthy.

EXAMPLE 2: Lyme Disease

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.

Two patients, female, 30-35 years, with clinically diagnosed Lyme disease for several years, received CI02 infusions of 50-70ppm CI02 administered intravenously, three drops per second, according to the following schedule:

Day 01: 1 x 100 ml

Day 05 1 x 400ml

Day 09 1 x 500ml

Day 1 3 1 x 500ml

Day 1 7 1 x 500ml

The result was very pleasing and positive in both patients and no significant, undesirable side effects were observed. While Borrelia was clearly detectable under the microscope before treatment, it was no longer detectable after treatment.

EXAMPLE 3 Tetanus treatment in a dog

A 4-month-old Old English Bulldog weighing 1 7.5 kg injured himself with a cane in the under tongue area and developed tetanus symptoms within three days, which the veterinarian said were final and untreatable, including jaw clamp, cramping, seizure noises and under the influence of light.

The treatment with chlorine dioxide solution took place over 8 days after the following

scheme: For the first four days, 4 ml of a high-dose, pH-neutral chlorine dioxide solution (CDL) of 500 ppm, 4 times a day, was administered orally to the animal. From the 5th day, 100 ml of a low-dose, bicarbonate-buffered (pH 7.4) CDL of 50 ppm were administered intravenously 4 times per day.

The animal is perfectly healthy after this treatment.

EXAMPLE 4 Treatment of foaling of a foal A foal suffering from foal disease (foal septemia), a serious infectious disease caused by various bacteria (blood poisoning), was already terminally ill and which had been classified by the local veterinarians as unfortunately untreatable , as a last resort the following treatment was done by CDL:

For 10 days, 200 ml of CDL at a concentration of 50 ppm were administered per day twice per day. Subsequently, 500 ml of a 100 ppm CDL were administered intravenously for a further 4 days. Result: after 14 treatment days, the foal was completely healthy and well again.

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.

For this purpose, the patients were divided into different groups. In each case two blood tests were carried out, namely once chemically and once

microscopic to definitively detect malaria.

Thereafter, all patients tested positive for malaria received a first intravenous infusion dose of 200 ml of an aqueous chlorine dioxide solution with a concentration of 400 ppm CI02. After one hour, all patients were given the same dose a second time.

After 24 hours, a further blood test per patient was performed to detect any remaining malaria parasite (plasmodium). The results were checked by a doctor and confirmed: Results: 1 of 54 tested malaria patients were malignant 1 to 24 after 24 hours, the remaining 1 1 patients were also malaria free after another dose (as described above) after 48 hours, which was quite surprising for the doctors and medical staff present was. Ultimately, the efficiency of treatment with chlorine dioxide was 100% successful.

Based on the above-presented and innumerable other infection cases not disclosed herein, it can be concluded that the systemic treatment - whether intravenous, oral or rectal or a combination of these treatments - with high purity, preferably pH neutral chlorine dioxide for therapeutic intervention in infectious diseases and thus associated pathological conditions and concomitants, is extremely promising and more than recommended for regular clinical use.

It should also be noted that in addition to the effects mentioned at the beginning of the chlorine dioxide administration may be even more, less well studied

Effects can play a role. In particular, more and more findings indicate that the administration of the CI02 solution according to the invention leads to an increase in the oxygen partial pressure in the blood capillaries and generally in tissues poorly supplied with blood and thus in particular also provides the mitochondria with urgently needed oxygen can. This could u.U. play a crucial role in immunocompromised patients as well as in the successful treatment of sepsis (blood poisoning).

Chlordixid also seems to have a positive effect on the physiological body fluids on a too low blood pH. In any case, 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.

Claims

1 . Chlorine dioxide in aqueous solution, which solution is sterile and pyrogen-free and contains 5 to 1000 mg / l (ppm) of dissolved chlorine dioxide (CI02) and is free of chlorate ions, hydrochloric acid and gaseous chlorine or these components in a ready to use state Each containing at most 1% of the chlorine dioxide concentration, for use as a therapeutic in the systemic treatment of viral or microbial infections of the human or animal body.

2. Chlorine dioxide solution according to claim 1, characterized in that it contains one or more of the following components:

a) 3 to 10 g / l of an ionic tonicity regulator from the group NaCl and KCl; or a nonionic tonicity regulator from the group of monosaccharides, disaccharides, oligosaccharides, and low molecular weight polyols; or a mixture of the aforementioned components;

b) a pH regulator in the form of a pH buffer system, adjusted to a value in the range of pH 5.0 - 7.5;

c) 0.1 to 20 g / l dimethyl sulfoxide (DMSO) or dimethyl sulfone (MSM).

3. Chlordixoidlösung according to claim 1 or 2, adapted as isotonic

Injection or infusion solution.

A pharmaceutical composition based on the chlorodixoid solution according to claim 3, for use as a therapeutic in the systemic treatment of viral or microbial infections of the human or animal body.

5. Pharmaceutical composition according to claim 4, characterized in that as non-ionic Tonizitätsregulator at least one mono- or

Disaccharide from the group: glucose, fructose, sucrose, mannose, and / or at least one low molecular weight polylol from the group: glycerol, erythritol, lactitol, mannitol, sorbitol, inositol, xylitol, threitol and maltitol is included.

6. A pharmaceutical composition according to claim 4, for use as a therapeutic agent in the systemic parenteral treatment of viral, bacterial or fungal, plasmodium or protozoan-induced infectious diseases of the human or animal body.

A pharmaceutical composition according to claim 4, for use as a therapeutic in the treatment of Lyme disease, tetanus or septicemia.

8. Pharmaceutical composition according to claim 4, for use as a therapeutic agent in the form of an orally administered solution, or in the form of a

Injection solution for subcutaneous, intramuscular or intravenous administration, or in the form of a solution for intravenous infusion.

9. Combination of the pharmaceutical composition according to claim 4 with an orally and / or topically applicable, containing 5-1000 ppm CI02

Chlorine dioxide solution, for use as a therapeutic in the systemic

Treatment of viral or microbial infections of the human or animal body.