WO2018185347A1

WO2018185347A1 - Pharmaceutical composition for the treatment of internal inflammations

Info

Publication number: WO2018185347A1
Application number: PCT/EP2018/059056
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: CH713095B1

Abstract

The invention relates to a pharmaceutical composition based on an aqueous solution of chlorine dioxide adapted as a solution for rectal intestinal lavage, as a solution for ureteral and bladder lavage or as an isotonic injection or infusion solution for use in the systemic treatment of acute or chronic internal inflammations and clinically relevant symptoms or states of the human or animal organism brought about thereby. The composition contains 5 to 1000 mg/l (ppm) of dissolved chlorine dioxide (ClO2) and is in a ready-to-use state substantially free from chlorate ions, hydrochloric acid and gaseous chlorine or contains these components in a concentration of not more than 1 mg/L (1 ppm) in each case.

Description

PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF INTERIORS

INFLAMMATION

TECHNICAL AREA

The present invention relates to a pharmaceutical composition based on an aqueous solution of chlorine dioxide, for the therapeutic treatment of internal inflammations, inflammatory conditions and / or related, clinically relevant pathological symptoms or conditions in the human or animal body.

STATE OF THE ART

For almost a century, chlorine dioxide has been used as an effective antimicrobial agent, with applications that have so far been 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 rinses 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 infectious diseases. This may be related to an incomplete understanding of the physiology of the immune system in humans and animals that is widespread in the art, as a result of which many diseases are considered to be caused by free radicals of oxygen or nitric oxide, and the therapy therefore aims at the elimination of such free radicals - in the literature also known as "reactive oxidative species" (ROS) - by the gift of

Targets antioxidants.

In his review, "Oxidative Shielding or Oxidative Stress?" from the year 201 2 {The Journal of Pharmacology and Experimental Therapeutics, 2012, Vol.342, No.3, pp608-618) Robert Naviaux tries to investigate this fact and shows that reactive oxidative species such as free oxygen radicals are not the cause but the Are the result of illnesses. Oxidative shielding is a protective mechanism and should not be a target for anti-oxidative therapy.

Inflammations are an essential part of the highly complex immune defense of the human and animal organism and serve - very simply said - especially the detection and removal of damaged or infected cells of the human or animal body and the removal of cellular debris of dead cells. In particular, mitochondria, both as energy suppliers and producers of reactive oxidative species (ROS) and important signal molecules on the one hand, and macrophages as scavenger cells and modulators of the immune defense on the other, are of paramount importance.

However, in the course of illness or a weakened immune defense, excessive inflammatory reactions may occur which result in not only diseased tissue but also healthy tissue being attacked and damaged to a clinically relevant extent, for example by the ROS Mitochondria, which can subsequently lead to a variety of diseases including cancer. A disturbed or weakened immune defense may also be the direct or indirect consequence of drug use, with too slow a degradation of the active ingredients and / or their concomitant substances by accumulations of such substances in and outside of tissues may have additional undesirable effects. It is therefore one of the most urgent goals of modern immunology to counteract this fact in order to restore the desired balance of destructive and regenerative processes of the immune system.

The possible mechanism of action of CI02:

Chlorine dioxide is itself a representative of such ROS, but has a different spectrum of activity than the ROS generated by the mitochondria. How the systemic or topical administration of therapeutic doses of CI02 interferes in detail with the immune defense process is not fully understood at present.

However, the pertinent literature indicates that chlorodixoid, unlike chlorite and chlorate ions, does not indiscriminately attack any organic material, but primarily proteins and amino acids with secondary and tertiary amines and / or sulfhydryl groups, especially cysteine, methionine and glutathione , as well as aromatic amino acids such as tyrosine and tryptophan. Generally, in the See, for example, Lee et al., Water Research 44, (2010), 555-566), which are preferably oxidized by chlorine dioxide in one or more successive stages.

Studies on model organisms in vitro also show that antiviral effects of the administration of CI02 solution are probably due to the fact that, depending on the type of virus either spikes are changed so that attachment to the host cell can no longer occur, or that the virus capsid substantially is changed, so that the immunogenicity is 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 live unicellular organisms, in particular with regard to their 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, for example by damage of membrane proteins, eg of tunnel proteins, a non-specific permeability of the membranes is caused for certain ions, whereby the cells, organelles or even fungal and bacterial spores can no longer maintain their membrane potential and perish.

There are also interesting reports on the signaling function ("signaling") smaller

Molecules such as e.g. CI02, especially in relation to apoptosis triggering, either directly or indirectly via the modulation of ATP, ADP or GMP concentrations.

Apoptosis is by no means considered negative in the context of immune defense, but rather as the limited, rapid elimination of individual, damaged, especially infected cells in order to hinder or prevent a rapid multiplication 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 the ideas of Naviaux on the one hand and Noszticzius et al. on the other hand, and to provide a water-based composition containing high-purity chlorine dioxide as an oxidative agent and for the systemic and topical treatment of clinically relevant acute or chronic inflammation, especially in the area of the urogenital tract and the anorectal region, in humans and animals, suitable and usable is. This object is solved by a composition as described in the independent claim. Further advantageous features of the invention are set forth in the dependent claims. PICTURES

Fig. 1 a and 1 b: show treatment progress in the foot in diabetes mellitus

Figs. 2a and 2b show treatment progress on the open leg in diabetes

mellitus.

DESCRIPTION OF THE INVENTION

While the results of Noszticzius et al. For the first time in the context of the present invention, these findings are only applicable to the external treatment of inflammations and wounds of the skin for their transferability to systemic use for combating internal, clinically relevant, acute and chronic inflammations and associated diseases by means of the intestine and bladder rinses checked and tested. A special focus is placed on the treatment of such inflammations, which are difficult or even untreatable with conventional drug therapy.

In accordance with the reaction kinetic findings from the topical application of Noszticzius et al. In the course of the development of the present invention, it has been possible to confirm that, contrary to the fears of other parts of the art, a therapeutic use of reactive oxidative species such as CI02, in the present case mainly anorectal or intraurethral irrigation and intravenous infusions, optionally in combination with oral use, must by no means be accompanied by unwanted or even damaging effects. In fact, no such reports of serious side effects or even deaths appear to be found in the literature to date and are also in the course of Applications in the context of the present invention did not have such effects.

Under "internal" inflammations and inflammatory states are intended in this

Context are understood to be those clinically relevant inflammatory and inflammatory conditions that are not or not exclusively at the external

Body surface, i. on the skin or in the outer skin layers, but the underlying tissues, internal organs, mucous membranes, joints, body fluids, blood vessels, nerves, bones, etc. are active. For this purpose, for the purposes of the present invention, also those clinically relevant, pathological symptoms or conditions are to be included, which are directly related to inflammatory processes in the human or animal body, either as a cause or as a consequence, as described e.g. autism, fibromyalgia syndrome, Leaky-Gut syndrome, hypoxia, ALS, diabetes mellitus, and venous thrombosis.

The interaction with histamines, thiols and phenols may play a role in the context of therapeutic use in internal inflammation. If CI02 is administered concomitantly with DMSO or MSM (dimethylsulfone), this results in a weakened, more controllable oxidative intervention while simultaneously attenuating the oxidative stress present in the diseased organism of a patient and suppressing the formation of superoxides and hydrogen peroxide by the mitochondria , It should also be borne in mind that flushing of the intestinal tract or urethra and urinary bladder may at the same time also affect the antiviral and anti-microbial effects of CI02 and may, if appropriate, significantly support the curative effect of this treatment method. It is also possible to specifically influence the microbiome of the intestinal tract with a colonic irrigation according to the invention and to prepare it in a favorable manner for the regeneration of a healthy intestinal flora.

The reaction products on the side of CI02 are ultimately NaCl and water in physiological fluids.

In one embodiment, the invention therefore relates to a pharmaceutical composition which preferably contains high purity chlorine dioxide (CIO 2) in an aqueous medium and is suitable for therapeutic use in the form of solutions for single or multiple irrigation of the intestine, ureter and / or urinary bladder and can be used.

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. "High purity" in this context means that the composition is substantially free of chlorine gas, hydrochloric acid, chlorite and chlorate ions, ie typically containing 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-chlorite, Na-chlorate, chlorine gas and hydrochloric acid are typically in the freshly prepared, concentrated CDL, which contains mostly 1000-2000 ppm (mg / L) CIO 2, but if necessary also up to 3000 ppm CIO 2 and more within a maximum range of 10-20 ppm and in the ready-to-use, diluted CDL at a maximum of 1 -2 ppm (mg / L) or below. 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 set forth herein.

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 special importance is to 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, internal applications in the form of intestinal or bladder irrigation, may contain a 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 are 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 determined by means of KCl or a mixture of two or more several of the mentioned ionic and nonionic 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, such as rectal enemas, intestinal irrigation, bladder and / or urethral irrigation, higher or possibly lower pH values may also be adjusted.

For the compositions according to the invention, in particular those intended for prolonged, repeated use, the addition of further components, for example from the group of preservatives, vitamins, mineral salts and trace elements, may be advantageous.

The CDL according to the invention can be produced as a concentrate with a CIO 2 content of typically 1000-2000 ppm, if necessary but also with higher contents of 3000 ppm and more of CIO 2, which is filled under aseptic conditions into 25 ml glass ampoules made of brown standard ampoule glass and stored at about 8 ° C until use. The concentrate may further contain 1 - 5 wt.% (10 - 50 g / L) of DMSO or MSM (methylsulfonylmethane, dimethylsulfone), 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, the addition of these sulfur-containing components improves the storage stability of the concentrated solution.

The storage stability of a concentrated CI02 solution with 1% DMSO addition is at least 1 2 months with a loss of activity of available CI02 of max. 10%. The concentrate is mixed immediately before use with e.g. isotonic, pH neutral or optionally bicarbonate buffered, NaCl solution by a factor of 2 - 500 diluted to adjust the mentioned CI02 contents of typically 5 - 1000 ppm of a ready to use solution.

For preparation of a 50ppm CDL, immediately before treatment, a 25 ml glass ampoule (CI02 concentration 1000 ppm) is diluted with pH neutral or preferably slightly alkaline saline (pH 7.3-7.5, with bicarbonate buffer) and diluted to 500 ml resulting in a CI02 Concentration of about 50 ppm results. To prepare a 25 ppm CDL, a 25 ml vial (1000 ppm) can be diluted to one liter.

With the aid of the CDL according to the invention, not only the inflammations themselves can be treated but also often associated side effects or symptoms such as increased local body temperature, fever, small tissue lesions, pain, redness, swelling, growths, thickening, hardening, nodules, tumors and ulcers , Examples of such inflammatory associated symptoms and symptoms include anal and genital warts, anal cancer, anal fissures, anorectal abscesses, appendicitis, autism, celiac disease, colon cancer, constipation, Crohn's disease, diarrhea, diverticulitis, fecal incontinence, anal fistulas, flatulence, hemorrhoids, Hirschsprung's disease, inflammatory Inflammatory bowel disease, intestinal adhesions, intestinal pseudo-obstruction, irritable bowel, lactose intolerance, leaky gut syndrome, lupus erythematosus, intestinal polyps, proctitis, rectal cancer, short bowel syndrome, ulcerative colitis, bowel obstruction, Whipple's disease, nephritis, Prostatitis, cystitis, diabetes mellitus, venous thrombosis, fibromyalgia syndrome, ALS.

Likewise, with the CDL according to the invention it is possible to reduce damage to the intestinal mucosa, for example caused by chemotherapy or radiation therapy, and also to reduce damage caused by e.g. Antibiotics or other medicines positively affect and regenerate pathologically impaired intestinal flora.

The following examples are intended to make the invention even better understandable and exemplify the effectiveness of the oxidative intervention by means of chlorine dioxide solution. It should also be noted at this point that the treatments in the following patient examples were performed either by physicians or under medical supervision.

EXAMPLE 1: Treatment of Rheumatoid Arthritis

A 48-year-old woman has been treated for hypertension since May 201 3. She takes a Micardis plus ^® tablet every morning. It was operated on the thyroid gland 20 years ago and its leukocyte counts are consistently high, but in the opinion of the treating physician they are tolerable.

In addition, the woman takes Thymanax ^® as an antidepressant.

In July 201 2, she was first diagnosed with rheumatoid arthritis (RA) and confirmed in December 201 2 by bone scintigraphy. The intensities of elbows, hands and wrists, ankles, shoulders and both knees are different.

General condition: pain and stiffness in the morning; Inability to close hands; Inability to walk on the toes; occasional nausea; Redness, pain and elevated temperature in the ankles, hands, wrists and right elbow; Difficulty in performing movements; Depressions; no detectable infections.

Table 1 shows some blood levels before starting treatment with CDL in May 201 3:

For therapy, a high purity Chlordixoidlösung prepared by electrolysis from a NaCl solution followed by gas scrubbing and without added 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 high purity solution set forth herein.

In order to largely avoid oxidative stress, 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-retarding 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.

Immediately prior to treatment, a 25 ml glass ampoule each containing slightly alkaline, isotonic saline (pH 7.3-7.5, adjusted with bicarbonate buffer) was diluted to 500 ml, resulting in a CIO 2 concentration of about 50 ppm. The concentration of 50 ppm was checked photometrically using a HI96771 C photometer from Hanna Instruments. In the two days prior to treatment, the CDL was repeatedly topically applied to the patient's skin to test for any allergic reaction. Since one was not recognizable, the treatment was started.

Regimen:

A total of 8 times 250 ml of CDL with a concentration of 50 ppm CI02 were intravenously administered in a 3-day cycle within 20 days. At the beginning of the treatment, an infusion rate of 2 to 3 drops per second was set, which was increased to 5 drops per second after the consumption of approximately half of the liquid volume.

From the first day of treatment, there was a gradual improvement. The patient initially complained of a "stitch" in the liver three to four times, after which the infusion was discontinued for that day and continued the next day, but afterward she no longer felt this "prick" in the liver.

The photographically documented improvement is dramatic. After the 20 days of treatment, she can walk on tiptoe again, she can perform without pain movements that were previously impossible because of the pain. She is happy and in a good mood. To suppress the residual pain, she continues to take painkillers as needed, but she is more likely to be all day without analgesics.

Already after 1 days of the treatment one could visually recognize that the

Swelling and redness on the wrists and elbow area have decreased significantly. Also on the ankles, the puffiness has gone back. After 20 days she can close her hands almost completely. She feels happy.

As an unexpected, positive side effect, a hypotensive effect has set in. After each infusion, blood pressure dropped to normal levels.

It may therefore be possible to use CDL for the targeted treatment of hypertension. EXAMPLE 2: Treatment of Autism

Two children, male, 4 and 5 years with clinically diagnosed autism for one year, were treated with a chlorine dioxide solution (CDL) similar to that of Example 1, except that the isotonic CDL was adjusted to pH neutral and the CIO 2 concentration was 25 ppm amounted to.

Prior to treatment, the ATEC Score (severity rating of autism) was 56 for the first child and 86 for the other, which is defined as severe autism. Both children could not or did not want to speak and were in their world without social or emotional attachment to the parents. The second child was always prone to self-harm and had to be treated several times in the emergency room.

Both children received CDL enemas of 1 to 2 liters of the high-purity, pH-neutral CDL rectally administered daily for a period of 6 and 1, respectively

Months. The concentration of the solutions was about 25ppm. In addition to the daily enemas, both children were given a special diet without gluten, without dairy products and without sugar.

The ATEC Score fell to 5 for the first child and 7 for the second child. Both started talking again. Up to an ATEC score of 10, a child is still considered normal.

After another 4 months only with diet, no autism was recognizable and the two children have fully integrated socially.

EXAMPLE 3: Renal insufficiency and prostatitis

A male patient, 68 years old, has been suffering from hematuria and renal insufficiency for 5 years and regularly receives dialysis for one year. The condition of his bladder causes him additional problems.

Therapy was started with oral treatment of 250 ml CDL daily, pH neutral, 50 ppm CI02 for one week. The patient responded well to the treatment, but initially complained about the extra burden and pain of his bladder. On top of that, he has severe prostatitis with a PSA level of 1.55 ng / ml.

Thereafter, it is decided to intravenous treatment with highly pure, isotonic CDL, buffered to about pH 7.4, on 2 days (Tuesday and Friday) during the week, according to the following scheme:

Week 1 Monday 1 x 100ml, 50ppm

Friday 1 X 1 50ml, 50 ppm

Week 2 Monday 1 x 250ml, 50ppm

Friday 1 x 250ml, 50ppm

Week 3 Monday 1 X 250ml, 50 ppm

Friday 1 x 250ml, 100ppm

Week 4 Monday 1 x 250ml, 100ppm

Friday 1 x 250ml, 100ppm In addition, bladder irrigation is performed by urethral catheter after each treatment week. For this purpose, the high-purity, pH-neutral chlorine dioxide solution with 100 ppm CI02 is used. The blister rinsing is done with 200ml CDL.

Result:

5 Already after the first week of treatment, the patient can leave almost painless water again. After 4 weeks, most blood values have largely normalized, the PSA value is 1, the patient no longer has hematuria and no longer needs dialysis.

10 EXAMPLE 4: Fibromyalgia syndrome

a) female patient, age 49 years, clinical diagnosis: fibromyalgia syndrome with 14 points, since 4 years.

Treatment:

Daily inlet of 1 - 2 liters of CI02 solution, pH neutral, with 1 50 ppm CI02, tempered to 1 5 34 ° C, over the period of 2 months.

Result: Already after 5 days the patient feels subjectively better. After 2 months of treatment, a clear improvement in the condition is noticeable and the patient is largely symptom-free. No conspicuous side effects were observed.

0 b) patient female, 52 years

Diagnosis: severe fibromyalgia syndrome since 5 years, patient is mostly bedridden and incapacitated, has severe pain and depression; In addition, she suffers from hypertension, osteoarthritis and insulin resistance.

Treatment:

For 1 week, warm two enemas daily from 1 to 2 liters of CLD, pH neutral, with 1 50 ppm, to 34 ° C. Then 1 enema daily a 1 -2 liter CLD, pH neutral, with 1 50 ppm, 34 ° C, during 3 months. Additional oral intake of 4 x 1 50ml CLD daily at 40 ppm (prepared from 6ml CLD concentrate at 1000ppm, diluted to 1 50ml water).

0 Result: After only 3 days the patient has no more pain and is

overjoyed. It is decided after 1 week to extend the treatment nevertheless over the period of 3 months. The treatment is extremely successful. Subsequent examinations revealed that both high blood pressure had normalized and insulin resistance had disappeared. The 5 body aches of osteoarthrosis were also gone and the patient was discharged from the treatment. No negative side effects were observed. EXAMPLE 5: Ulcerative colitis

Female patient diagnosed with ulcerative colitis for 20 years.

Condition before treatment: Very severe pain, patient is depressed and suicidal, has difficulty in feeding, severe food intolerances, severe sleep disorders, is unable to work.

Treatment:

First week two enemas daily a 1 -2 liter CDL at 100 ppm, 34 ° C.

Second week two enemas daily a 1 -2 liter CDL with 1 50 ppm, 34 ° C

Then 1 week break.

Then, for 3 weeks, a daily intake of 1 to 2 liters of CDL at 200 ppm, 34 ° C.

Result: Clear improvement after the first two weeks of treatment and symptom-free after completion of the treatment. No adverse effects were observed. In the subsequent colonoscopy no colitis was seen and the intestinal mucosa was normal.

EXAMPLE 6: Chronic cystitis

Patient male, 67 years.

Suffer from severe chronic bladder infection, sometimes with mild hematoma and prostate problems. The PSA value is 1 5.5 ng / ml. The patient could not hold water and was depressed because of this fact. A catheter was placed.

Treatment:

1 intraurethral irrigation daily, with 200ml pH neutral CDL, 100ppm, over a period of 30 days.

Result:

After the treatment, the patient was painless and had no more blood in the urine. Surprisingly, his previously elevated renal values of urea and creatinine have also returned to normal. The PSA value dropped from 1 5.5 to 3.5. The result was rated as very satisfactory by the accompanying doctor. No conspicuous side effects were observed.

EXAMPLE 7: Leaky Gut Syndrome

Female patient, 23 years. Diagnosis: Leaky Gut syndrome, acne and gluten intolerance. The patient complains about a constantly swollen belly, with alternating diarrhea or constipation, the allergy test shows gluten intolerance. The severe acne on the face puts a heavy burden on the young patient. She feels constantly tired and exhausted and has difficulty concentrating.

Treatment:

It is switched to a gluten-free diet, largely without sugar and dairy products.

In the 1. Week two enemas daily a 1 -2 liter CDL with 100 ppm and 34 ° C is performed.

In the 2nd week two enemas daily a 1 -2 liter CDL with 1 50 ppm, 34 ° C.

Then 1 week break.

Then a daily intake of 1 -2 liters of CDL at 200 ppm, 34 ° C for 3 weeks.

Again 1 week break.

Thereafter, a daily intake of 1 -2 liters of CDL at 200 ppm, 34 ° C for 3 weeks

In addition, a pH-neutral, 200ppm CI02 solution is sprayed 2 to 4 times a day on the face.

Result:

The acne has decreased by about 80% after treatment. The patient has more energy and concentration and is very happy with the result. The bowel movement has normalized. The diet continues to be used. No adverse effects were observed.

EXAMPLE 8: Hypoxia

This is clinical hypoxia, caused for example by drug use. The two cases described below are acute hypoxia in the blood or in the cells of the patient's organs.

To be able to accurately determine the effect of chlorine dioxide in the blood, an analysis of the venous blood gases in real time was made. For the blood gas analysis, 250 ml saline solution with a concentration of 100 ppm of highly pure chlorine dioxide, which was prepared electrolytically, with the addition of 1%

Dimethyl sulfoxide as oxidation retarder, prepared.

As a result, the two volunteers who were diagnosed with hypoxia received this solution intravenously. 30 minutes later, the following could be found: a) Patient 1 male 54 years

In patient 1, the blood pH increased from 7,279 to 7,377, while lactate levels decreased from 3.26 to 1 .20 mmol per liter.

Oxygen saturation increased from 31 .9% to 55.2% and C02 partial blood pressure dropped from 65.3 to 46.0 mmHg.

The following table 2 shows the corresponding expression of the blood analysis:

Patient 2 male 56 years

b) In patient 2, the pH increased from 7,329 to 7,404 and the lactate levels dropped from 2.49 to 0.79 mmol per liter.

Oxygen saturation increased from 62.5% to 75.0% and CO 2 levels dropped from 56.7 to 42.0 mmHg (see Table 3). Table 3: Blood analysis 6:51

fl l / L l / l l / L

Both patients consistently report that they experienced more energy and increased physical well-being after infusion treatment with the CI02 solution. Objectively it could be determined that the symptoms of hypoxia had disappeared. No conspicuous side effects related to the dose administered were observed. It should also be pointed out in this connection that in addition to the effects of a chlorine dioxide administration mentioned at the outset, other, less well-studied effects may also play a role. In particular, the observed increase in the partial pressure of oxygen in the blood after administration of the CI02 solution according to the invention could also be of benefit to other tissues poorly supplied with blood and possibly also the mitochondria urgently needed both for immune defense and for the regeneration of body cells Provide oxygen directly and in increased concentration.

If this is the case, then it could be the immunocompromised patients as well as patients with excessive infection reactions as well as patients with sepsis (blood poisoning) that could provide a decisive aid for the recovery.

EXAMPLE 9: Amyotrophic Lateral Sclerosis

In modern medicine there is apparently no efficient therapeutic treatment of amyotrophic lateral sclerosis, abbreviated ALS ("Lou Gehrig

Syndrome ") It is a neuromuscular, degenerative disease that arises when the so-called motor neurons gradually stop functioning and die which causes progressive muscle paralysis with fatal consequences.

The subject, an ALS suffering surgeon, was already at an advanced stage with nocturnal artificial respiration, artificial nutrition,

Spasticity and hyper-reflexes. The experimental treatment was as follows:

One dose of 2L water containing 200 ppm chlorine dioxide was orally administered daily for one month daily. Thereafter, the first intravenous administration was carried out with 5 ml of 0.3% chlorine dioxide solution in 250 ml of isotonic saline, in three rows daily, over a period of 7 days.

Thereafter, the dose was gradually increased up to 25 ml of 0.3% chlorine dioxide solution in 500 ml of isotonic saline, about pH 3.5, and administered for another 7 days. Care was taken to extend the duration of infusion as long as possible in order to maintain a constant oxygen supply.

Result: the progress of the disease has come to a complete standstill in the patient and even a certain remission could be observed, because the patient no longer needed any artificial nocturnal ventilation and was able to sleep lying down again. He was able to consume any kind of food again and even managed to get up at short notice. The patient is relatively stable at the moment, has no more spasticity and no hyper-reflexes. EXAMPLE 10: Diabetes Mellitus

One of the major problems with diabetes mellitus is ulceration, typically at the distal and medial areas of the legs and feet. These are due to lack of oxygen supply to the microcirculation and the associated necrosis of the non-supplied or underserved cells and tissues. a) Subject 1

The subject was a 57 year old male who was diagnosed with type 2 diabetes mellitus. Application log:

After 21 days daily oral intake of 1 -2 liters of a chlorine dioxide solution according to the invention with 200-400 ppm CI02 (daily dose: 400 mg CI02), the person received daily for 4 days a high purity isotonic solution of 500 ml with a concentration of 100 ppm CI02 , administered over a period of 3 hours, administered intravenously.

The glycemic index dropped from 21 9 mg per deciliter to 100 mg per deciliter, while other blood levels also improved. The corresponding documents are available. b) Subject 2

It was a 59-year-old female female with a severe case of diabetes, leg and foot gangrene. At the request of the patients, a CI02 treatment was carried out in order to avert an imminent amputation.

Application protocol:

For 21 days daily, the patient was given 1 -2 liters of a chlorine dioxide solution according to the invention with a concentration of 200-400 ppm CI02 (daily dose: 400 mg CI02) for drinking. Thereafter, 500 ml of an isotonic, pH-adjusted CIO 2 infusion solution containing

Concentration of 100 ppm, distributed over 3 hours each, administered intravenously.

At the same time the open wounds were cleaned and daily with a 0.3%

Chlorine dioxide solution treated directly.

Thereafter, the oral treatment protocol was maintained for a further six months, as was the local treatment of the ulcerations.

Result of the treatment:

The amputation could be successfully averted and the open wounds could heal, which was previously not possible for years. It could Surprisingly enough, even necrosis receded and new healthy tissue developed in previously dead areas.

Figures 1 a and 1 b show the progress of treatment on the foot, the figures 2a and 2b those on the open leg.

EXAMPLE 1 1: Venous thrombosis

Venous thrombosis is a vascular disease in which a blood clot (thrombus) forms in a blood vessel. This has the consequence that the blood circulation within the blood vessel stops due to the blood clot.

Subject:

Male, 59 years, central venous thrombosis in the right eye with a venous retinal vascular occlusion. The subject was completely and irreversibly blinded on the eye in 2008 due to this cause on the eye, according to the attending physicians.

Application:

The subject took 2L of a chlorine dioxide solution of this invention at 400 ppm per day, over the period of one month, throughout the day.

Result:

Surprisingly, after this month of treatment, the person could see a white spot on the eye and the blood clot started to dissolve slowly. After another month of the same treatment, the ophthalmologist confirmed that he had regained about 20% of his vision.

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 For use as a therapeutic in the systemic treatment of internal acute or chronic inflammation of the human or animal organism and / or directly related, clinically relevant symptoms or conditions.

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 pH 7.3 - 7.5;

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

3. Chlorine dioxide solution according to claim 1 or 2, adapted as a solution for rectal intestinal lavage, as a solution for ureteral and bladder irrigation or as an isotonic solution for injection or infusion.

A pharmaceutical composition based on the chlorodixoid solution of claim 3, for use in the systemic treatment of internal acute or chronic inflammation of the human or animal organism and / or directly related, clinically relevant symptoms or conditions.

5. A pharmaceutical composition according to claim 4, for use in the treatment of symptoms or conditions associated with internal inflammation selected from the group:

increased local body temperature, fever, tissue lesions, pain, redness, swelling, growths, thickening, hardening, lumps, tumors and ulcers.

A pharmaceutical composition according to claim 4, for use in the treatment of clinically relevant symptoms or conditions associated with internal inflammation selected from the group:

Anal and genital warts, anal cancer, anal fissures, anorectal abscesses,

Appendicitis, autism, celiac disease, colon cancer, constipation, Crohn's disease, diarrhea, diverticulitis, fecal incontinence, anal fistulas, bloating, hemorrhoids, Hirschsprung's disease, inflammatory bowel disease, intestinal adhesions, intestinal pseudoobstruction, irritable bowel, lactose intolerance, "leaky syndrome, lupus erythematosus, intestinal polyps, proctitis, rectal cancer, short bowel syndrome, ulcerative colitis, intestinal entanglement, Whipple's disease,

Nephritis, prostatitis, cystitis, diabetes mellitus, venous thrombosis, fibromyalgia syndrome, ALS.

7. A pharmaceutical composition according to claim 4, for use in the treatment of damage to the intestinal mucosa, caused by chemo- or radiotherapy and / or for the regeneration of a pathologically disturbed intestinal flora.

8. A pharmaceutical composition according to claim 4, for use as a therapeutic in the form of a rectal intestinal lavage, a ureteral and

Bladder irrigation, or an intravenous injection or infusion application.

A combination of the pharmaceutical composition of claim 4 with an orally and / or topically applicable chlorine dioxide solution of 5-1000 ppm, for use as a therapeutic in the therapeutic treatment of internal acute or chronic inflammation of the human or animal

Organism.