CH713095B1 - Pharmaceutical composition for the treatment of inflammation. - Google Patents

Abstract

The invention relates to a pharmaceutical composition based on an aqueous solution of chlorine dioxide, for use in the local or systemic treatment of internal acute or chronic inflammation and thereby induced clinically relevant symptoms or conditions of the human or animal organism. It contains 5 to 1000 mg / l (ppm) of dissolved chlorine dioxide (CIO2) and, when ready for use, is essentially free of chlorate ions, hydrochloric acid and gaseous chlorine or contains these components in a maximum concentration of 1 mg / L (1 ppm ).

Description

Description Technical Field The present invention relates to a pharmaceutical composition in liquid form for the treatment of inflammation and inflammatory conditions in the human or animal body.

Background Art Chlorine dioxide has been used as an effective antimicrobial agent for almost a hundred years, with applications heretofore 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.

US 5,252,343 describes in 1993 the successful treatment of cattle mastitis with a chlorine dioxide solution (CDL) by rinsing the teats on the udder of the cow, whereas in contrast to conventional antibiotic therapy the milk of CDL-treated animals did not have to be discarded, but could continue to be used for consumption. 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 have to do with an incomplete understanding of the physiology of the immune system in humans and animals, which is widespread in the art, according to which many diseases are considered to be caused by free oxygen or nitric oxide radication and the therapy is therefore geared towards elimination of such free radicals The literature also referred to as "reactive oxidative species" (ROS) - aimed by the administration of antioxidants.

In his review "Oxidative Shielding or Oxidative Stress?" From 2012 (The Journal of Pharmacology and Experiments! Therapeutics, 2012, Voi. 342, No. 3, pp 608-618) Robert Naviaux tries to investigate this fact and shows that reactive oxidative species such as free oxygen radicals are not the cause but the result of diseases. 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 system 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, it can come in the course of disease or a weakened immune to overshooting, out of balance ongoing inflammatory reactions that cause not only diseased tissue, but also healthy tissue is attacked and damaged to a clinically relevant extent, for example the ROS from the 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 con sumption, whereby too slow degradation of the active ingredients and / or 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 counter this fact in order to restore the desired balance of destructive and regenerative processes of the immune system.

On the possible mechanism of action of CI02: Chlorine dioxide itself is a representative of such ROS, but has a different spectrum of activity than the ROS produced 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 shows that chlorodioxide, unlike chlorite and chlorate ions, does not indiscriminately attack any organic material, but especially 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. In general, the literature refers to "electron-rich" organic molecule regions (see, e.g., Lee et al., Water Research 44, (2010), 555-566), which are preferentially oxidized by chlorine dioxide in one or more sequential steps.

Investigations on model organisms in vitro also show that antiviral effects by the administration of CI02 solution probably come about by the fact that depending on the type of virus either spikes are changed so that an attachment to the host cell can no longer occur, or that the viral capsid is substantially altered so that immunogenicity is lost, or that certain steps in protein biosynthesis are adversely affected, so that either the transcription of the viral RNA or DNA no longer functions properly or the assembly of the virus particles is disturbed.

In the antibacterial and antifungal activity, the art seems to have recognized that this microbicidal effect is mainly caused by a disruption of the cell membranes or the lipid membranes of important organelles by CI02-action, such as by damage of Membrane proteins, eg Tunneling proteins, a non-specific permeability of the membranes is caused for certain ions, whereby the cells, organelles and / or bacterial spores can no longer maintain their membrane potential and perish.

There are also interesting reports on the signal function ("signaling") of small molecules such as e.g. CI02, especially in relation to apoptosis triggering, either directly or indirectly via the modulation of ATR ADP or GMP concentrations. However, apoptosis in the context of immune defense is by no means considered negative, but rather the limited, rapid elimination of individual, damaged, especially infected cells in order to impede 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" (Nosz-ticzius Z, Wittmann M, Kaly-Kullai K, Beregvari Z, Kiss I, et al., 2013, PLoS ONE 8 (11): e79 157. doi: 10.1371 / journal.pone. 0 079 157) describes in detail why the administration of CDL selectively kills small organisms such as bacteria and viruses and leaves body cells undisturbed. Among other things, they approach the topic from the kinetic side of the reaction and very plausibly suggest that 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 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 lacking viruses and bacteria.

Reservations in parts of the professional world regarding a therapeutic use of CI02 therefore seem to be based on an inadequate evaluation of existing specialist knowledge, perhaps also on certain prejudices, in the light of the relevant specialist literature.

It is an object of the present invention, the thoughts 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, is suitable. 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.

Description of the Invention Although the results of Noszticzius et al. refer only to the external treatment of inflammation and wounds of the skin, so these findings in the context of the present invention were nevertheless taken up and their transferability to the systemic use to combat internal, clinically relevant, acute and chronic inflammation and associated diseases by intestine and bladder rinses checked and tested. A special focus was 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. could be confirmed in the course of development of the present invention that contrary to the concerns of many parts of the professional therapeutic use of reactive oxidative species such as CI02, in this case mainly anorectal or intraurethral rinses and intravenous infusions, optionally in combination with oral use, 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 appear in the literature and no such effects have come to light in the course of experimental use in the context of the present invention.

By "internal" inflammations in this context are meant those inflammations and inflammatory conditions that are not or not exclusively on the outer surface of the body, i. E. 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.

In the context of therapeutic use in inflammation, the interaction with histamines, thiols and phenols might play a role. If CI02 is also administered concomitantly with DMSO or MSM (dimethylsulfone), this results in a weakened, more controllable oxidative intervention while simultaneously attenuating the oxidative stress prevalent in the patient's diseased organism and suppressing the formation of superoxides and hydrogen peroxide by the mitochondria. Furthermore, it should be remembered that the rinses of the intestinal tract or the urethra and bladder at the same time also the antiviral and anti-microbial effects of CI02 come into play and may possibly support the curative effect of this treatment method significantly. 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 part of CI02 are in physiological fluids, ultimately NaCl and water.

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

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 and chlorate ions. 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% based on 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, chlorine gas and hydrochloric acid are in the freshly prepared, concentrated CDL (1000-2000 ppm CI02) typically in a range of not more than 10-20 ppm and in the ready-to-use, diluted CDL at a maximum of 1-2 ppm or underneath.

The advantage of a high purity CDL is mainly that the possibility of any undesirable effects, which are described for Na-chlorite and especially for Na-chlorate in the literature, is further reduced, which is especially true for formulations and compositions 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, internal applications in the form of intestinal or bladder irrigation, may contain a tonicity regulator which allows the solution to be adjusted 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 polylols preferably from the group: glycerol, erythritol, mannitol, sorbitol, inositol, xylitol, threitol and maltitol.

An isotonic saline solution contains 9 g NaCl per liter of water (0.9%), the resulting osmolarity of 290-300 mosmol / l corresponds to the osmolarity of the blood, which also by means of KCl or a mixture of two or more of the mentioned ionic and non-ionic tonicity regulators can be adjusted.

Especially for injection and infusion solutions, it may be of crucial importance to adjust the pH of the CDL to those of the blood in a range of about pH 7.3-7.5 in order to avoid any undesirable effects. For this purpose, a pH regulator, in particular a buffer system, can be added to the CDL. As appropriate, a bicarbonate buffer or phosphate buffer (e.g., PBS) is considered. Although studies in vitro have shown that for some applications, a higher pH of the CDL would be beneficial, it is important to ensure compatibility with the blood pH in injection solutions. 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 novel compositions, in particular those which are intended for a longer, recurring application, the addition of further components from the group of preservatives, vitamins, mineral salts and trace elements may be advantageous.

The inventive CDL can be prepared as a concentrate with a CI02 content of typically 1000-2000 ppm, which is typically bottled under aseptic conditions in 25 ml glass ampoules of brown standard ampoule glass and stored until use at about 8 ° C. , 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 12 months with a loss of activity of available CI02 of max. 10%, The concentrate is added immediately before use with e.g. isotonic, pH neutral, or optionally bicarbonate buffered, NaCl solution diluted by a factor of 2-500 to adjust the noted CIO 2 levels, typically from 5 to 1000 ppm, of a ready to use solution.

For the preparation of a 50 ppm CDL immediately before the treatment, a 25 ml glass ampoule (1000 ppm) with pH neutral or preferably slightly alkaline saline (pH 7.3-7.5, adjusted 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 help of the inventive CDL can be treated not only the inflammation itself, but also often associated side effects or symptoms such as increased local body temperature, fever, small Ge-websläsionen, pain, redness, swelling, growths, thickening, hardening, knots , 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 pseudoobstruction, irritable bowel, lactose intolerance, leaky gut syndrome, lupus erythematosus, intestinal polyps, proctitis, rectal cancer, short bowel syndrome, ulcerative colitis, intestinal entanglement, Whipple's disease, nephritis, prostatitis, cystitis.

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 drugs positively affect and regenerate pathologically disturbed intestinal flora.

The following examples will make the invention even better understood and exemplify the effectiveness of the oxidative intervention using 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 2013. She takes a Micardis plus * tablet every morning. Twenty years ago she was operated on the thyroid, her leukocyte levels are consistently high, but tolerable in the view of the treating physician.

In addition, the woman takes Thymanax B as an antidepressant.

In July 2012, her first rheumatoid arthritis (RA) was diagnosed and confirmed in December 2012 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 tips of the feet; occasional nausea; Redness, pain and elevated temperature in the ankles, hands, wrists and right elbow; Difficulty in performing movements; Depressions; no detectable infections.

Some blood levels before starting treatment with CDL in May 2013:

Parameter current value reference value

Blood sedimentation 19; 25 2-14 mm

Leukocytes 12,300; 15 700 3800-10 500 / ul

Erythrocytes 4.88; 4.84 4.0-5.4 million / μl alkaline phosphatase 142; 127 130

Proteins 13.2; 14.2 8 mg / dl

Median platelet volume (MPV) 11.6 7.0-11.0 femtoliter

Glucose 111; 111 70-110mg / dl

Total cholesterol 204 200-220 mg / dl HDL 40> 40 mg / dl LDL 132 <160 mg / dl

Triglycerides 160 <150 mg / dl For the therapy, a high-purity chlorodixoid solution, prepared by electrolysis from a NaCl solution with a subsequent gas scrubbing method and without added acid, was administered as an infusion solution.

In order to largely avoid oxidative stress, 1% by weight of dimethyl sulfoxide 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.

Immediately prior to treatment, a 25 ml glass ampoule each with slightly alkaline, isotonic saline solution (pH 7.3-7.5, adjusted with bicarbonate buffer) was diluted to 500 ml, resulting in a CI02 concentration of about 50 ppm. The concentration of 50 ppm was checked photometrically by means of a photometer HI96 771C 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 such was not recognizable, the treatment was started in August 2013.

Therapy protocol: Altogether, 8 times 250 ml of CDL with a concentration of 50 ppm CI02 were administered intravenously in a 3-day rhythm 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 after that she did not feel that "stitch" in her liver.

The photographically documented improvement is dramatic. After the 20 days of treatment, she can walk on her tiptoes 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.

After 14 days of treatment, it was already possible to visually recognize that the swellings and redness on the wrists and in the elbow area had decreased significantly. Also at the ankles the swellings have decreased. After 20 days she can almost completely close her hands. She feels happy.

As an unexpected, positive side effect, a blood pressure lowering effect has been established. 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, with the difference that the isotonic CDL was pH neutral was set and: the CI02 concentration was 25 ppm.

Prior to treatment, the ATEC score (grade of severity of autism) was 56 for the first child and 86 for the other, which by definition corresponds to 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 were given CDL enemas of 1 to 2 liters of high purity, pH neutral CDL, rectally administered daily over a period of 6 and 14 months, respectively. The concentration of the solutions was about 25 ppm.

In addition to the daily enemas, both children were given a special diet without gluten, without dairy products and without sugar.

The ATEC score has fallen 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 autism was no longer 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.

The therapy was started with an 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. He also has severe prostatitis with a PSA level of 15.5 ng / ml.

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

Week 1 Monday 1 x 100 ml, 50 ppm Friday 1 x 150 ml, 50 ppm week 2 Monday 1 x 250 ml, 50 ppm Friday 1 x 250 ml, 50 ppm week 3 Monday 1 x 250 ml, 50 ppm Friday 1 x 250 ml, 100 ppm week 4 Monday 1 x 250 ml, 100 ppm Friday 1 x 250 ml, 100 ppm In addition, bladder irrigation is performed by urethral catheter after each treatment week. For this purpose, the high-purity, pFI-neutral chlorine dioxide solution with 100 ppm CI02 is used. The blister rinsing is done with 200ml CDL.

Result:

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.

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

Treatment: daily inlet of 1-2 liters of CI02 solution, pH neutral, with 150 ppm CI02, tempered to 34 ° C, over the period of 2 months.

Result:

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.

B) Patient female, 52 years Diagnosis:

Severe fibromyalgia for 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 two enemas daily of 1-2 liters of CLD, pH neutral, with 150 ppm, tempered to 34 ° C. Thereafter, 1 inflow daily of 1-2 liters of CLD, pH neutral, at 150 ppm, 34 ° C, during 3 months. In addition, oral intake of 4 x 150 ml CLD at 40 ppm daily (prepared from 6 ml CLD concentrate at 1000 ppm each, diluted to 150 ml water).

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 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 with 1-2 liter CDL at 100 ppm, 34 ° C.

Second week two enemas daily à 1-2 liter CDL with 150 ppm, 34 ° C.

Then 1 week break.

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

Claims (8)

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. Suffers from severe chronic cystitis, sometimes with mild hematuria and prostate problems. The PSA value is 15.5 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 200 ml of pH neutral CDL, 100 ppm, 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 15.5 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 Patient female, 23 years. Diagnosis: Leaky Gut syndrome, acne and gluten intolerance. The patient complains of a constantly swollen stomach, 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 gluten-free diet, largely without sugar and dairy products. In the 1st week, two enemas daily of 1-2 liters CDL with 100 ppm and 34 ° C are performed. In the 2nd week two enemas daily à 1-2 liter CDL with 150 ppm, 34 ° C. Then 1 week break. Then for 3 weeks an enema daily with 1-2 liters CDL with 200 ppm, 34 ° C. Again 1 week break. After that for 3 weeks an enema daily 1-2 liters CDL with 200 ppm, 34 ° C. It is additionally sprayed 2-4 times a day on the face a pH-neutral, 200 ppm CI02 solution. Result: The acne has decreased after treatment by about 80%. 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. claims A pharmaceutical composition based on an aqueous solution of chlorine dioxide, for use in the local or systemic treatment of internal acute or chronic inflammation of the human or animal organism, characterized in that the solution is sterile and pyrogen-free and 5 to 1000 mg / l contains dissolved chlorine dioxide, wherein the composition in the ready state is free of chlorate ions, hydrochloric acid and gaseous chlorine or contains these components in a concentration of not more than 1% of the Chiordi oxide concentration. 2. A pharmaceutical composition 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 Tonizitätsregulators from the group NaCl and KCl; or a nonionic Tonizi-tätsregulators from the group 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 or dimethyl sulfone. 3. Pharmaceutical composition 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 according to claim 3, as an agent for use in the treatment of symptoms or conditions associated with internal inflammation selected from the group: elevated local body temperature, fever, tissue lesions, pain, redness, swelling, growths, thickening , Hardening, nodules, tumors and ulcers. 5. A pharmaceutical composition according to claim 3, as an agent 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, Celiac disease, colon cancer, constipation, Crohn's disease, diarrhea, diverticulitis, fecal incontinence, anal fistulas, bloating, hemorrhoids, Hirschsprung's disease, inflammatory bowel disease, inflammatory bowel disease, intestinal adhesions, intestinal pseudoobstruction, irritable bowel, lactose intolerance, leaky gut syndrome, Lupus erythematosus, intestinal polyps, prostatitis, rectal cancer, short bowel syndrome, ulcerative colitis, intestinal entanglement, Whipple's disease, nephritis, prostatitis, cystitis. 6. A pharmaceutical composition according to claim 3, as an agent 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. A pharmaceutical composition according to claim 3, as an agent for use in the treatment of autism. A combination containing a pharmaceutical composition according to claim 3 and an oral chlorine dioxide solution of 5-1000 ppm.