WO2009118002A2

WO2009118002A2 - Killing germs using carbon dioxide and concurrent adjuvant cavitation treatment

Info

Publication number: WO2009118002A2
Application number: PCT/DE2009/000444
Authority: WO
Inventors: Hans-Werner Bender
Original assignee: Hans-Werner Bender
Priority date: 2008-03-27
Filing date: 2009-03-27
Publication date: 2009-10-01
Also published as: DE102009015933A1; WO2009118002A3

Abstract

The invention relates to a method for killing germs by way of at least one suitable, potentially germicidal substance in conjunction with at least one additional complementary treatment with physical and/or chemical effect in the treatment of germs and/or their biological structures. Due to the development of resistances of the germs, protective layers of the germs (for example by biofilms etc.) and/or for other reasons it is difficult or sometimes even impossible to treat germs/problematic germs and/or to medically treat infections/problematic infections, for example wounds. To solve this problem, the invention devises a treatment with concentrated carbon dioxide in conjunction with a complementary sonication treatment with cavitation effect at low to medium sound energy, the cavitation having a boosting effect but not being sufficiently germicidal, and the germicidal effect being due to a chemical reaction of carbon dioxide. The method according to the invention is used in the medical treatment of infections, especially of infections caused by problematic germs. It can also be used in the non-medical treatment of germs/problematic germs for cleaning, hygiene etc., but also in the technical field.

Description

Germ killed by carbon dioxide with adjuvant cavitation treatment

description

Germ kill by treatment of the germs with at least one potentially germicidal substance and at least one complementary treatment with adjuvant effect. Using the example of carbon dioxide as a potential germicidal substance and a complementary sound treatment with sound-induced supporting (adjuvant) cavitation.

Germs and infections caused by germs, especially problematic germs and infections due to problematic germs, are not only common problems in medicine, but also in other areas of life science as well as in the technical / industrial field. Methicillin infections can often not be solved Resistant Staphylococcus aureus (MRSA) and / or vancomycin-resistant enterococci (VRE) are a serious challenge in treating infections. Also, seed colonies protected by "protective coatings" such as biofilms, small colony variants (SCV) and / or other protective coatings are often difficult to treat.

The following description provides a simple, effective and tissue-sparing solution for the purpose of germ killing in the medical and / or non-medical

Germ treatment, especially if problematic germs / problem infections are to be treated, other forms of treatment / methods for killing germs and / or treatment of infections fail and / or are not applicable for different reasons and / or should not be used. The offered treatment is simple and safe to perform, for example, in the medical treatment of infected wounds, skin infections, bone infections and more.

It is a treatment with at least one suitable non-germicidal substance which, in combination with at least one other appropriate complementary treatment (a treatment with mechanical and / or other physical and / or chemical and / or bioactive / biological / Physiological adjuvant effect) can be germicidal effect. The interaction of the appropriate substance and the complementary treatment leads to a synergistic effect, which makes the germ-killing substance per se a germicidal substance. The germicidal effect of the substance is based on properties of the substance itself, for example on its chemical properties, but not on the direct / immediate effect of the complementary treatment and / or its adjuvant effect.

The potentially germicidal substance can be germicidal under certain conditions, the prerequisites for this are created by the complementary treatment and / or by one of its adjuvant effects. This complementary treatment and / or its effect (at least one of its effects) has an auxiliary function, a supporting function, a preparatory function, a promoting function, an activating function (ie an adjuvant function / effect) without itself - under the given treatment conditions - in sufficient amount / in sufficient numbers germicidal to act.

This is shown with carbon dioxide as a potential germicidal substance and a complementary sound treatment with sound-induced cavitation treatment (also adjuvant cavitation treatment), wherein the germ killing is caused by properties of carbon dioxide, but not by the effect of cavitation treatment under the given conditions as adjuvant treatment / effect not capable of destroying germs in sufficient numbers / sufficient extent (therapeutically relevant, therapeutically effective, hygienically relevant).

Carbon dioxide is normally per se a little or no germicidal gas acting on germs / microorganisms, especially by protective layers protected germs, no / hardly germicidal activity to it as suitable for killing germs, in particular problematic germs and / or for the treatment of infections / Problem infections appear to be particularly suitable. At most as part of a Kavitationsmediums with germicidal effect by a Kavitationswirkung, for example in a cavitation treatment with high sound energy (power sound). But that is not meant here. What is meant is the effect of carbon dioxide as a germicidal substance in the interaction of carbon dioxide with adjuvant cavitation treatment as described later.

The suitable, potentially germicidal substance is usually referred to in the description below as "substance." Carbon dioxide is always "substance". "Substance" may be replaced by carbon dioxide in the description, but "Substance" may be another suitable substance. Another suitable treatment with at least one mechanical and / or other physical and / or chemical and / or bioactive effect is hereinafter also referred to in the description as "complementary treatment", the effect also being "adjuvant". Sound = complementary treatment, sound-induced cavitation = adjuvant effect / cavitation.

Summary

Carbon dioxide, as a relatively small molecule, can easily penetrate tissue (eg, skin), biological structures of germs / microorganisms (eg, through normal diffusion), which is normally harmless to germs. However, if under special conditions an enrichment of carbon dioxide (for example an enrichment of carbon dioxide in the cell interior of germs) that goes beyond the normal level and is no longer regulated by the germ takes place, then under certain circumstances carbon dioxide can become germicidal and therefore "potentially" This is part of the description, especially when contemporaneous with and / or with the use of carbon dioxide, which is preferably contained / dissolved in high concentration in a medium (eg water) complementary to the use of carbon dioxide promptly a sound treatment With adjuvant cavitation treatment of germs and / or their biological structures, cavitation effect creates conditions that make carbon dioxide germicidal, namely as a substance with its properties and not (causally, directly) through the cavitation effect itself is only indirectly supportive involved. Especially when the cavitation is induced by sound with low to medium intensity / energy and the cavitation energy is insufficient to kill germs in sufficient numbers.

Carbon dioxide as a potentially germicidal gas interacting with cavitation generated by sound, preferably by low-frequency ultrasound, is called "cavitation-based potential germicidal effect of carbon dioxide." Cavitation has the task / function of biological structures of germs change, for example, that carbon dioxide is enriched in the cell interior of germs / and can cause in the cytoplasm / cytosol by a dissociation reaction (according to DE 102 33 293, Figure Figure 1) no longer regulated by the germ lowering of the pH The "change" of biological structures of the germs by an adjuvant cavitation effect and the penetration of carbon dioxide into these structures, the penetration of carbon dioxide into the cell interior of the germs is an example of the interaction of cavitation and carbon dioxide. Cavitation creates the conditions for carbon dioxide to penetrate these structures into the cell interior of the germs. Another example of the interaction is that carbon dioxide, as a cavitation-effective component of the cavitation medium, participates in the cavitation and at the same time (at the same time) can act as a potentially germicidal substance.

The cavitation-based potential germicidal effect of carbon dioxide in the treatment of problematic germs and / or problematic infections with a carbon dioxide strongly enriched medium (which may preferably serve as a cavitation medium, not must) is characterized in that as a result, in a Kavitationsmedium (z B. the said medium), complementarily successful sound treatment of the germs with Kavitationswirkung on the germs, the carbon dioxide can accumulate in a sufficient for a germicidal effect high concentration in the cell interior of the germs to trigger a reaction in the aqueous environment of the cytoplasm (cytosol) , which leads to a strong, no longer controllable by the germ hyperacidity of the cytosol and thus to cell death.

If a cavitation medium is used as described in detail in the documents DE 10 233 293, DE 10 2004 004 415 ("Carbonic acid water", then carbon dioxide is a cavitation-effective component of the cavitation medium and cavitation (as "oscillating / oscillating gas bubbles") At the same time, carbon dioxide is a potentially germicidal gas as a constituent of the cavitation medium, which results in new features, properties and applications for the cavitation medium.

Carbon dioxide as a potentially germicidal gas and carbon dioxide as a cavitation effective component of the cavitation medium in a sound-induced cavitation by the interaction of Kavitationswirkung and the effect of potentially germicidal acting gas synergy effect, which can not be achieved with carbon dioxide alone and / or by cavitation alone would.

The cavitation treatment can be carried out simultaneously with the use of carbon dioxide, as shown schematically in Figure 1. The cavitation treatment can be carried out promptly with the use of carbon dioxide, as shown schematically in Figure 2.

Comments and definitions

Interaction in the sense of interaction, combination and vice versa.

Function in terms of property, feature, task, purpose and vice versa.

Circumstances in terms of conditions, conditions, conditions and vice versa. Treatment in terms of treatment, treatment method and vice versa.

Effect in the sense of reaction, consequence, effect, effect, influence, power, energy and vice versa.

Properties in the sense of characteristics, characteristics and vice versa.

Adjuvant in the sense of supportive, helpful, complementary.

Adjuvant in the sense of aids, auxiliary ...

Complementary in the sense of supplementary, supplementary.

A complementary treatment of the description is for example a sound treatment. This induces / produces an adjuvant / supportive cavitation / cavitation effect.

A cavitation treatment / cavitation / cavitation effect of the description has an adjuvant / supporting effect, for example for carbon dioxide, for example in such a way that cavitation creates conditions for carbon dioxide to be germicidal, and not due to cavitation.

Physiology of the germs in terms of "the life processes" concerning the functional level of, for example, cells, cell assemblies, these are, for example, control mechanisms, the

Regulate and / or control metabolic processes, cell division, etc.

Physiology = Physiological reactions, for example, are all life-regulating processes.

In sufficient numbers and / or to a sufficient extent and / or sufficiently germ-killing is meant in the sense of therapeutically relevant, therapeutically effective, hygienically relevant.

An active substance is a substance that triggers a certain effect in a small dose in an organism of humans and / or animals, eg. B. a physiological reaction. For example, a pharmaceutical (pharmacologically active) active ingredient such as a drug, a drug (in the broader sense

Drugs). Also substances for killing germs are among the active ingredients, such as

Drugs (drugs, medicines) but also other substances such as disinfectants, some anti-infective agents, etc., but active substances are also such substances that serve for example for cleaning / hygiene, certain ingredients in cosmetics and others. Also in the field of crop protection.

Pharmaceutical agent = drug, drug, drug, e.g. As antibiotics, anti-infective agents,

Polyhexanide, rinsing solutions etc. per se in the sense of itself, on its own, in itself, of itself, in itself

The description is based on the gas carbon dioxide. Carbon dioxide explicitly as carbon dioxide. Carbon dioxide is a particularly preferred gas of this description. Furthermore, carbon dioxide be exemplified for another suitable gas and / or other suitable substance. Potentially germicidal according to the previous and / or later description. Cavitation explicitly means cavitation. However, cavitation may also be an example of another suitable complementary treatment with physical and / or chemical and / or bioactive action (without expressly mentioning this). In the description cavitation preferably means a cavitation induced by a complementary sound treatment, an effect of the sound is thus that of a cavitation effect.

Problem germs are, for example, germs which have formed a resistance to pharmaceutical active substances and / or to another germicidal substance / active substance, for example MRSA, VRE and / or by a protective layer (eg biofilm, SCV, pus, fibrin, etc.). But also when other conventional treatments / methods for germ treatment fail / are ineffective and / or difficult to perform and / or can not be used / performed. Other equally important examples of application and / or problem infections by problem germs are listed later. Problem infections are infections (for example of wounds) by problem germs. Problem infections are those infections that are not and / or not sufficient and / or very difficult to treat with conventional, conventional methods and / or devices and / or devices, for example, not by an ultrasound application at high sound energy (power sound) such as ultrasonic debridement.

Sound in the description initially means sound of any sound frequency, preferably sound in the specification means ultrasound with at least one sound frequency between 20 kHz and 20 MHz, more preferably sound in the specification means low frequency ultrasound with at least one sound frequency between 20 kHz and 800 kHz More preferably, sound in the specification means low frequency ultrasound with at least one sound frequency between 20 kHz and 150 kHz.

Germs (microorganisms) represent a biological system. Germs can all germs, preferably pathogen / facultative pathogens acting germs / microorganisms (eg anaerobic / aerobic bacteria, gram-negative / gram-positive bacteria, dermatophytes, yeasts, molds, dimorphic fungi and other microorganisms , possibly also viruses). Common infections / problem infections for example by Pseudomonas aeruginosa, Staphylococcus. aureus, Staphylococcus epidermidis, Escheria coli, Candida albicans and the like. a ..

Structures of biological systems (biological structures) can be, for example, cell walls / membranes and other components of germs. Structures of biological systems (biologic structures) may be biofilm, other protective layers, etc. Biological structures as protective layer / biological, mechanical barrier can be for example Biofiime. Biofilms (covering, mucous layer) can Germs in multiple layers contained as a solid phase, embedded in a slimy matrix of extracellular polymeric substances / EPS / exopolysaccharides and water as hydrogel, containing besides polysaccharides also polypeptides, proteins, lipids and other substances. Further, coatings may also consist of mixed forms of different organic and / or inorganic substances / materials / materials, for example fibrin coatings, pus, mucus, necrotic material, bacteria, germs, cell debris, liquids, blood, other biological material and / or other compounds / materials , mostly of organic material. Also difficult to treat are small colony variants (CSV) of germs.

Germicidal (germicidal) is a (generic) term that includes, for example, terms such as biocidal, antibacterial, disinfecting, antiseptic, bactericidal / bacteriostatic, fungicidal / fungistatic, virucidal / virustatic, toxic, antiseptic, cytotoxic / cytostatic, denaturing, etc.

Cavitation, of which preference is the milder form of cavitation, the gas cavitation, which at lower to medium sound intensity / sound energy to stimulate and with a suitable Kavitationsmedium (for example, "carbonic acid") is better controlled and shows a better biocompatibility compared to the transient cavitation. The milder gas bubble cavitation (gas cavitation, pseudo cavitation, stable cavitation) is preferred in humans and animals, and is easy to handle even by laymen. The strength of this cavitation should not be sufficient to kill germs in sufficient numbers (sufficient number means medically sufficient, therapeutically effective / necessary, hygienically necessary, etc.).

In principle, all possibilities for generating cavitation should be possible. Preferably, however, the sound-induced cavitation, of which in particular by low-frequency ultrasound in the lower frequency range (20 kHz - 150 kHz) induced cavitation.

A cavitation-effective [cavitation-active, cavitation-involved, cavitation-capable, cavitation-effecting] component of a cavitation medium is, for example, a gas which contains cavitation medium (eg a liquid such as water, etc.) in the form of gas bubbles and / or cavitation medium molecular form (molecular) and / or dissolved in another form. Sound effects on the cavitation medium (eg, as in FIG. 1) stimulate gas bubbles to oscillate (oscillating gas bubbles) and / or gas bubbles are newly formed, which are then excited to cavitation oscillations. Excitation of gas bubbles to a sound-induced cavitation. A gas which is contained in a cavitation medium as gas bubbles and / or molecularly (as a molecule) and / or in another form and (as a gas bubble supplier) can contribute to cavitation and / or contribute, for example by oscillating gas bubbles, is a cavitation-effective component a cavitation medium. It is part of the cavitation medium and is directly involved in cavitation processes.

Potentially germicidal substances are those that are normally not germicidal and not originally intended for germ killing, and are generally not used for this purpose. Carbon dioxide per se is a non-germicidal gas.

In the context of the description, however, carbon dioxide is a potentially germicidal gas because, under certain conditions, it can have a germicidal effect on germs.

But not meant is the germ killing as a direct effect of a cavitation effect on germs at, for example, high sound energy / high-energy cavitation, z. B. by power sound (sound of very high intensity to over 300 W / cm ² ) induced high-energy cavitation. Not meant are other effects of cavitation and / or other sound effects that are germicidal. Not meant germicidal effects of pharmaceutical agents and / or other active substances that are germicidal per se, eg. As antibiotics, anti-infective agents, antiseptics, disinfectants (including ethanol, methanol and other, higher-value alcohols, formaldehyde / formalin and other aldehydes, phenols, other disinfectants, denaturants / denaturing methods) etc .. Potentially germicidal in the sense of the description also means not in that at least one per se acting germicidal substance (eg an antibiotic) is contained in the cavitation medium and / or this substance is subsequently applied to a cavitation treatment and the germicidal effect is completely and / or predominantly due to this substance.

Medical treatment of wounds / infected wounds, for example diabetic foot, leg ulcers, bedsores, burn wounds, traumatic wounds, surgical wounds, osteomyelitis (wound including bone infection, also referred to as osteitis), stoma wounds and other wounds. Also for infection prophylaxis.

Medical treatment of germs, eg. Treatment of germs, for example for disinfecting, hygiene, cleaning, etc .. Treatment of germs in the technical / industrial area.

Additional comments or terminology later in the description elsewhere.

cavitation medium

Carbon dioxide in any concentration in water and / or in aqueous solution and / or in any other suitable liquid therein as gas bubbles and / or in other form contained therein. Carbon dioxide dissolves very well in water, in aqueous solutions, and in some other (polar) liquids (eg, alcohol, alcoholic solutions, acetone, serum, etc.) in which carbon dioxide, similar to water, can dissociate.

Highly preferred is water as a cavitation medium in which carbon dioxide in high to very high concentration (up to 1500 mg CO ₂ /! Even to over 1500 mg CO ₂ / I at about 40 ° C and atmospheric pressure, and is partially supersaturated) is enriched and because of the dissociation of carbon dioxide in water (corresponding to DE 102 33 293, Fig. 1) may also be called "carbonic acid water." The carbon dioxide is partly contained therein as gas bubbles, but predominantly dissolved therein in molecular form (molecular) and / or in in another form, for example in (fine) disperse form, in the form of associated molecules (cluster, aggregation, micelle form, others associated Shapes, etc.). The cavitation medium is stable to handle.

Sound effects on the cavitation medium cause gas bubbles to be excited into cavitation oscillations (up to resonance vibrations) and / or cavitation-capable / resonant gas bubbles can be newly formed in situ by sound and excited by the sound to oscillating vibrations. Said medium is a gas bubble source, in which potentially viable (namely, when they are formed by the sound effect in Kavitationsmedium) vibrating gas bubbles are available in large numbers. Potentially because gas bubbles in the medium, for example under sound effect, can only arise. Due to the high concentration of carbon dioxide in the medium, new gas bubbles can always arise. The advantage of such a cavitation medium is also that the carbon dioxide through the molecular and / or finely dispersed distribution in the cavitation medium in small hairline cracks, crevices, pores, caverns, courses of mechanical / biological structures (eg skin, biofilms and other protective layers of Germs, etc.) can penetrate, which gas bubbles can not to this extent in order to be effective (wherever the water comes also carbon dioxide and everywhere there is a cavitation possible).

Such a cavitation medium ("carbonic acid water") is described in detail in the documents DE 102 33 293, DE 10 2004 004 415. The production and / or production of such a cavitation medium are mentioned in the cited documents, where further applications, uses, treatment of called biological systems

Carbon dioxide concentration in "carbon dioxide" is equivalent to "high density"?

State of the art

The treatment of wounds, skin, superficial infections of the skin / wounds, etc., with

Ultrasound, in particular with low frequency ultrasound, preferably as cavitation treatment in one

Cavitation medium, such as subaqual and contactless in a water bath, has been publicly publicized at international congresses since about 1990. These treatments were performed at low sound intensity up to 100mW / cm ² . Schematic representation of a subaqual treatment in FIG.

1. Literature selection: Peschen M. et. Low-frequency Ultrasound Treatment of Chronic Leg Ulcers in Outpatient Therapy, Acta Derm Venereol 1997; 77: 311-314 Weichenthal et al., Low-frequency ultrasound treatment of chronic venous ulcers, Wound Rep Reg 1997; 5: 18-22 Ottstadt et al., "Subaqually applied low frequency ultrasound heals arterial venous leg ulcers", Vasomed 1998; 10: 24-32.

The successful treatment of severely infected ulcers of low frequency ultrasound in tap water in combination with antiseptics has been known since at least 1990 and has been presented at several international congresses since 1991. Among them a very successful treatment of a patient with leg ulcers and strong bacterial plaque, micro- / macroangiopathy, diabetes mellitus, Werner syndrome. Tap water was used as cavitation medium to which either an antibacterial active ingredient (PVP-iodine) was added and / or the active ingredient following the Ultrasound treatment was applied. The effect of low-frequency ultrasound treatment in conjunction with the topically applied active ingredient (eg PVP-iodine) was attributed to the effect of cavitation and brought the ulcer for healing.

The low-frequency ultrasound device used for the abovementioned treatments, in particular the ultrasound device, corresponded in technically essential points to the description in EP 0335851, EP 0595783.

The contactless application of low-frequency ultrasound in the form of power sound with the aid of a liquid aerosol for the treatment of diabetic gangrene has been described by Lindner et al. "Results and experience with performance sound in the context of the complex treatment of diabetic gangrene", Z. Klin. Med. 42 (1987); Issue 6: 503-506 described.

Wound debridement with low frequency ultrasound followed later. Ultrasonic debridement takes place at high to very high sound intensity (power sound) and at the same time has a germicidal effect. A special cavitation medium is not necessary. This particular treatment of wound debridement is in the hands of trained professionals and, unlike low frequency / midrange low intensity ultrasound, is not available to anyone, nor anywhere, and involves some risks.

Various scientific publications describe that a cavitation induced by cavitation (especially by low-frequency ultrasound in a cavitation medium), the structure of biological systems and / or biological structures (for example, cell walls, biofilm, etc. but also skin, stratum corneum, etc.), sometimes reversible, Some of them are permanently changed in this way and openings, channels, holes, pores, caverns, passages (a type of perforation) are created in the biological structures due to substances / substances to be supplied externally due to improved / increased permeability (permeability, increasing the diffusion length [path length / Distance that a substance can cover in a biological structure by diffusion / migration]) can penetrate the structures that can penetrate (pass / diffuse and / or be transported through) structures, examples being transdermal drug delivery (also known as Sonophor ese), the improved efficacy of antibiotics and other germicidal agents in the treatment of wound infections.

The transdermal application of carbon dioxide (used, for example, as a gas or as a carbonic acid bath) for therapeutic and / or cosmetic treatment with an advantageous physiological action (for example in circulatory disorders for vasodilation) has been known for many years. Carbon dioxide diffuses through the skin - probably on a molecular basis - into the tissue. That would not work with gas bubbles. For example, arterial and / or venous circulatory disorders, arterial and / or venous leg ulcers (ulcera cruris), etc. are treated. Therapeutically applied also for many years, the treatment of leg ulcers in the combination of a subaqual low-frequency ultrasound treatment and the subaqualen treatment in a carbonic acid bath. Both treatments were subaqual, so it was natural to combine the different effects of low frequency sonication and carbonation in one subaqual treatment.

In this combination of subaqual low-frequency ultrasound treatment and subaqual carbonic acid treatment, not only the effects of both individual treatments come into play, but the medium "carbonic acid water" carbonic acid bath is at the same time a highly effective cavitation medium. "Carbonic acid water" in the sense of carbon dioxide dissolved in water and partially dissociated.

The basis is also the documents DE 102 33 293, DE 10 2004 004 415 which, in addition to the description of a cavitation medium, also contain definitions of terms and definitions which can / should be valid for this description.

The germ killing with carbon dioxide is used industrially, for example in the food industry. For example, by the action of highly concentrated, high-density carbon dioxide under high pressure on microorganisms, an accumulation of carbon dioxide in the germs (inside the cell) can be achieved, which then - allegedly by a no longer regulated by the microorganism pH change - lowering the pH - leads to the death of germs. Selection of Literature: "Killing Microorganisms by Compressed Carbon Dioxide" Dissertation (2005) to obtain a Doctor of Engineering degree from the Faculty of Mechanical Engineering of the Ruhr University Bochum presented by Reiner Daiminger from Burghausen.

The treatment of germs / problem germs, preferably the medical treatment of infections / problem infections, for the purpose of killing germs by a carbon dioxide application in conjunction with an adjuvant sound-induced cavitation treatment of the germs, has not been described, the effect of cavitation being insufficient to prevent germs from cavitation kill in sufficient numbers. The germicidal effect is mainly based on the effect of carbon dioxide as a potentially germicidal gas.

Symptoms / Problem

The treatment of germs / problem germs and / or the medical treatment of infections, especially infections by problematic germs are often a problem for the reasons exemplified below.

^■ Reduced efficacy of drugs / pharmaceutical agents or even resistance of germs to these drugs, for example, MRSA, VRE and others.

^■ Protective layers, for example biofilms, which shield the germs from external influences and therefore, for example, render topically and / or systemically applied / administered active substances ineffective. ■ Undesirable side effects, for example of active substances, for example allergy formation, intolerance, stress on the organs, interaction with other drugs, cell damage, disruption of cell growth (eg of granulation tissue) etc.

■ Certain treatments (eg, ultrasound debridement) can not be used and / or should not be used. For example, because of the location / location of the infection, because of adverse reactions in / by the treatment and / or for other reasons.

■ Treatment should only be performed by trained personnel, but not at home by the patient, etc ...

■ The treatment is linked to certain (expensive) treatment devices / treatment methods that are not available everywhere, can not be used by anyone, etc.

In the above-mentioned industrial application of carbon dioxide for germ treatment several difficulties have to be overcome. The high / very high concentration of carbon dioxide in a medium. The overcoming of mechanical barriers / protective layers of germs by carbon dioxide, the penetration of carbon dioxide into barriers (eg protective layers) and their penetration, the accumulation of carbon dioxide in the cell interior of germs. These problems should also be solved.

Problem solving in the treatment of germs / problem germs and / or in the medical treatment of infections / problem infections for the purpose of killing the germs ..

The germ killing by treatment of the germs with a potentially germicidal substance and a complementary treatment with a supporting effect is based on carbon dioxide as a potentially germicidal substance and a complementary sound treatment with sound-induced cavitation (adjuvant) as a "cavitation-based, potentially germicidal effect of carbon dioxide" described.

The cavitation-based potential germicidal effect of carbon dioxide, that is the germicidal effect of carbon dioxide on germs, preferably by a (mostly in the cell interior (cytoplasm) of the germs) caused by carbon dioxide effect / reaction of physical and / or chemical and / or bioactive / physiological nature / Way that leads to cell death. A sound-induced cavitation (adjuvant) contributes / creates the conditions for the carbon dioxide to penetrate, pass through, and penetrate biological structures of germs into the cell interior of the germs. The cavitation-based potential germicidal effect of carbon dioxide treats / affects the killing effect of carbon dioxide on germs and further when, how and under what circumstances (prerequisites, conditions) carbon dioxide can be germicidal on germs.

The cavitation-based potential germicidal effect of carbon dioxide in the treatment of

Problem germs and / or problematic infections with a carbon dioxide strongly enriched medium. The medium can also serve as a cavitation medium. One for carbon dioxide treatment Completely complementary sonic treatment with cavitation effect on the germs and / or on their biological structures lead to changes (for example increased permeability to external substances) of the biological structures (for example cell walls, biofilms, other protective layers) such that carbon dioxide is in for a germicidal effect sufficiently high concentration in the cell interior of the germs can accumulate in order to trigger a reaction in the aqueous environment of the cytoplasm (cytosol), which leads to a strong, no longer controllable by the germ hyperacidity of the cytosol and thus to cell death.

Carbon dioxide can under certain conditions have a germicidal effect, namely, for example, if it is possible to bring carbon dioxide to the surface of the germs and especially in the germs / in the cell interior of the germs in a sufficiently large amount / in a sufficiently high concentration. The carbon dioxide then dissolves in the aqueous environment of the cytoplasm (in the cytosol), dissociates (corresponding to the Figure 1 Fig. Document DE 102 33 293) and thereby causes hyperacidity of the cytosol by lowering the pH. Due to the sufficiently high concentration of carbon dioxide (sufficiently high concentration to achieve this effect) in the cell interior of the germs / cytoplasm, the germ can no longer regulate the hyperacidity and dies off. That is, carbon dioxide interferes with the normal physiological life processes / regulatory mechanisms (in the physiology) of the germs and leads to changes in / on the germ and / or in the cytoplasm / cytosol what the germ attempts to repair / correct / regulate, but what because of the massive interference caused by the sufficiently high concentration of carbon dioxide is not possible (regulates to death) and this leads to cell death [current state of knowledge]. The germicidal effect is based in this case on a chemical reaction / action of carbon dioxide and water, but not on a Kavitationswirkung, z. B. in contrast to the power sound (ultrasonic debridement, ultrasonic disintegrator) not on a mechanical destruction of the germs by cavitation.

Accompanying adjuvant sound-induced cavitation treatment creates the prerequisites for carbon dioxide to be enriched in the germs and / or to be introduced in a sufficiently high concentration into the cell interior of the germs. For example, by the action of the cavitation treatment, biological structures (in the simplest case, the cell walls, otherwise biofilms and other protective layers) are altered, for example mechanically altered, so that carbon dioxide can penetrate these structures, pass through these structures, if these structures can penetrate For example, cell walls / membranes are to enter from outside (from the surface of the germs) into the cell interior of the germs. If these structures are, for example, biofilms, coverings and / or other protective layers, carbon dioxide can penetrate from the surrounding medium into these protective layers, penetrate them and initially accumulate / concentrate in the environment / surface of the germs, in order then to reach the cell interior of the germs / to be introduced. Additional effects / effects of sound and / or cavitation may promote / accelerate these processes (eg microflow, including micromassage, compression / traction, mass transfer, flow phenomena, injection of matter into matter, etc., also effects biological / physiological, mechanical / physical, chemical type. Accumulation of carbon dioxide on and / or in the germs can be due to high Carbon dioxide concentration in the medium, by high partial pressure, by diffusion, etc. take place. In particular, however, by the effect / effects of sound and / or cavitation, for example by the sound pressure, by flow effects, local compression of carbon dioxide, driving carbon dioxide into biological structures, etc.). Carbon dioxide can thus be actively transported. A cavitation in the cell interior of the germs in enriched carbon dioxide in the germs may play a role. etc.).

Preference will therefore be given, for example, when carbon dioxide is a cavitation-active constituent of a cavitation medium, preferably the carbon dioxide called "carbonic acid." In "carbonic acid", carbon dioxide is also present in high concentration in molecularly dissolved form.

The sound-induced cavitation (preferably a gas cavitation) should be excited by sound of low to medium energy / intensity. Sufficient to produce useful cavitation, but not sufficient to kill germs in sufficient numbers by the effect of cavitation. Sufficient to produce a usable cavitation means that the effect of cavitation on the biological structures of the germs, for example, causes a mechanical change of the structures. That is, the structures (eg, protective layers) become more permeable to at least one externally supplied substance, such as carbon dioxide. If a cavitation medium is used in the treatment, as described above, for example, as "carbonic acid water", the carbon dioxide can penetrate further and further into the biological structures during the treatment, and by cavitation loosen up the structures and modify them so that more carbon dioxide enters these structures penetrate, penetrate and possibly destroy, with the aim that carbon dioxide can reach the germs, is enriched to the germs to penetrate into the germs (inside the cell) / to be introduced. The effect of cavitation and the effect of carbon dioxide as a potentially germicidal substance have a synergistic effect. The cavitation medium with carbon dioxide as a cavitation-active ingredient itself, by the carbon dioxide, has a potential germicidal effect and is synergistically effective.

If a cavitation medium is used in the treatment, as described above, for example, as "carbonic acid water", then carbon dioxide is a cavitation-effective component of the cavitation medium (eg involved as "oscillating gas bubbles" in the cavitation processes) and at the same time a potentially germicidal substance. Carbon dioxide acts as a cavitation-effective component of the cavitation medium as Kavitationswirkung and carbon dioxide is also effective as a germicidal substance and has the interaction of these effects a synergy effect (by the same gas.) Carbon dioxide cavitation effective component of Kavitationsmediums has by cavitation effect on the germs and / or on their biological structures, which cause changes in the germs and / or biological structures of the germs, which are prerequisites for carbon dioxide to have a germicidal effect The effect of carbon dioxide as a cavitation-effective component with a cavitation effect and as a potentially germicidal substance is an effect that would not be possible without the interaction. This is not to be confused with a cavitation treatment, at the cavitation itself germicides.

The simultaneous (simultaneous) application of carbon dioxide as a cavitation-effective component of a cavitation medium and as a potentially germicidal gas / active substance is shown by way of example in the arrangement in FIG. 1. FIG. 1 shows one of the possible arrangements of a treatment with a potentially germicidal substance and at least a complementary treatment (in the example carbon dioxide and sound / cavitation). Arrangement of object, in the example a leg / foot immersed in a cavitation medium for a subaquale ("underwater") treatment and a (in this example) also immersed in the Kavitationsmedium sound applicator by sound / sound on / generates cavitation in the cavitation medium, for example by the sound effect in the cavitation medium gas bubbles are excited to cavitation oscillations (oscillating gas bubbles) and / or gas bubbles are formed by the sound effect, which are then excited to vibrate, in this example, the cavitation predominantly ( Preferably, in the layer between the object / the object surface and the sound-emitting surface of the sound applicator.To allow the cavitation to take place close to and / or on the object surface, the layer (distance sound-emitting surface to the object surface) should be as small as possible.

The cavitation itself should not / only slightly germicidal effect / can be, for. B. because of too low a sound intensity and thus insufficient energy-rich cavitation. That is, the germicidal effect of such a treatment should not be based / only to a small extent on mechanical forces that lead to the destruction of the germs, but completely / predominantly on the potential germicidal effect of carbon dioxide. In this example, carbon dioxide is a cavitation-effective component of the cavitation medium and at the same time a potentially germ-destroying gas. The cavitation medium (containing carbon dioxide) is a potentially germicidal cavitation medium.

Case study of a treatment of a bacterially infected wound, e.g. B. in the region of the Achilles tendon as shown in Fig. 1. This wound is covered with a protective layer, so that drugs (antibiotics, drugs, drugs and / or other drugs) in topical and / or systemic application of the drugs neither the wound nor the germs can reach and thus remain ineffective. Sharp wound debridement (eg due to ultrasound debridement) should / must be avoided. Thus, the infected wound can not be treated effectively enough and the germs can not be killed. An easily performed sound-induced cavitation treatment in a carbon dioxide-containing cavitation medium can bring the solution. Due to the cavitation effect on the protective layers (biological structures) and / or on the germs, these protective layers are initially mechanically modified superficially in their structure (eg by crack formation, hair / capillary cracks, etc.), biofilms already show a corresponding topography with aisles , Pores, caverns, etc. into which carbon dioxide can penetrate), so that the cavitation medium can penetrate into these protective layers. Since the cavitation medium contains molecularly and / or finely dispersed carbon dioxide in a high concentration, cavitation can also be produced in the hair / capillary cracks, and the destruction of the hair Protective layer can be continued (gas bubbles could penetrate because of their size, or only in small numbers in the fine cracks, capillary cracks). As a result, the structure of the protective layer is further loosened, more cavitation medium, more carbon dioxide penetrates into the protective layer, this loosens further by cavitation and reaches the germs around them in a similar manner (eg, their protective covers, membranes, cell walls) attack. Carbon dioxide can accumulate on and / or in the germs and unfold with this / by the enrichment a germicidal effect. Possibly the penetration of the protective layers with the cavitation medium / carbon dioxide and / or the accumulation of carbon dioxide in the germs is promoted by further effects / effects by / of low-frequency ultrasound and / or cavitation, eg. B. by microflows.

As one of the other possible arrangements, FIG. 2 schematically shows the timely, non-simultaneous application of a cavitation treatment and a carbon dioxide treatment. The use of carbon dioxide as a germicidal active ingredient is not carried out simultaneously with the cavitation treatment, but the application of (highly concentrated) carbon dioxide (as gas, gas mixture, water / gas mixture / mist, aerosol, etc.) takes place, for example, promptly following a cavitation treatment. First, a cavitation treatment (eg subaqual with a cavitation medium containing no or insufficient carbon dioxide) is followed by treatment with carbon dioxide, for example in a pressure chamber containing carbon dioxide.

The cavitation-based, potentially germicidal effect of carbon dioxide is:

Characterized in that the treatment of germs and / or their biological structures with at least one potentially germicidal substance - the substance per se is not germicidal - in interaction with at least one complementary treatment - a treatment with mechanical and / or other physical and / or chemical and / or other action (adjuvant effect) - can be germicidal effect, the complementary treatment and / or at least one of its effects creates conditions that the substance can be germicidal effect, without the complementary treatment and / or at least one of its effects is itself sufficiently germicidal. The substance is preferably carbon dioxide, the complementary treatment preferably a sonication, at least one effect of the sonication is that of a sound-induced cavitation.

■ The cavitation-based potential germicidal effect of carbon dioxide in the treatment of problematic germs and / or problematic infections with a medium strongly enriched with carbon dioxide is characterized in that due to a complementary in a cavitation medium sound treatment of the germs with Kavitationswirkung on the germs, the carbon dioxide in a concentration sufficient for a germicidal effect in the cell interior of the germs can accumulate to trigger a reaction in the aqueous environment of the cytoplasm (cytosol), which leads to a strong, no longer regulated by the germ hyperacidity of the cytoplasm / cytosol and thus cell death. The cavitation medium is preferably identical to the carbon dioxide-rich medium which is used to treat the germs / infections. ■ Characterized by a treatment / application of carbon dioxide in / with a medium that Contains carbon dioxide in high / very high concentration, for example, the described cavitation medium also called "carbonic acid", wherein the medium is a carbon dioxide source, which preferably provides carbon dioxide as a cavitation effective ingredient for cavitation available as well as carbon dioxide, which accumulate in the germs and Thus, carbon dioxide preferably has at least bi-functional activity.

■ characterized by a complementary to the application of carbon dioxide treatment with at least one mechanical and / or other physical and / or chemical and / or bioactive effect. For example, a complementary sound treatment with a cavitation effect.

■ Characterized by a complementary sound treatment with adjuvant sound-induced cavitation effect.

Characterized in that the killing of germs is based on a physical and / or chemical and / or bioactive action / reaction and / or properties of carbon dioxide, but not causally / directly / directly on the effect of the adjuvant cavitation treatment, that is not (predominantly not) by a mechanical destruction of the germs by mechanical forces. Characterized by the fact that carbon dioxide in the physiology of the germ [affecting the life processes at the functional level of, for example, cells, cell associations, which are, for example, regulatory mechanisms that regulate the metabolic processes, cell division, etc., and / or control] such that this leads to cell death, the complementary treatment (eg sound) and / or its adjuvant effect (eg cavitation) but is not directly / directly involved in cell death. - The cavitation-based potential germicidal effect of carbon dioxide in the treatment of germs and / or infections is characterized by the fact that carbon dioxide, which is used in the treatment in a carbon dioxide-containing medium, then germicidal effect, if by means of a supporting acting cavitation effect on the Germs and / or on their biological structures such as cell walls, biofilms, other protective layers carbon dioxide in the cytoplasm / in the aqueous cytosol of germs accumulate in sufficient for a germicidal effect amount and the enriched carbon dioxide in the physiology of the germs can intervene such that this by a Acidification of the cytosol leads to cell death, but the cavitation is not directly involved in cell death, the germ killing is thus not by a Kavitationswirkung but by an effect of carbon dioxide. ■ The cavitation-based potential germicidal effect of carbon dioxide in the treatment of germs and / or infections is characterized by the fact that carbon dioxide, if a supportive, adjuvant Kavitationswirkung on the germs and / or their biological structures such as cell walls, biofilms, other protective layers for the conditions that carbon dioxide accumulates in the cytoplasm of the germs and the enriched carbon dioxide in the physiology of the germs [the life processes concerning the functional level of, for example, cells, cell assemblies, such as regulating mechanisms that regulate and / or control the metabolic processes, cell division, etc.) can intervene that this leads to cell death, but the cavitation is not directly involved in cell death, the germ killing is thus not done by a Kavitationswirkung but by an effect of carbon dioxide. ■ Characterized by the fact that carbon dioxide can have a germicidal effect if carbon dioxide in sufficiently large amount / in sufficiently high concentration at / in germs / in the cell interior of germs is introduced.

■ Characterized by the fact that carbon dioxide can have a germicidal effect if the carbon dioxide introduced into the cell interior dissolves in the cytosol, dissociates and thus causes hyperacidity of the cytosol by lowering the pH value. This hyperacidity through the physiological regulatory mechanisms of the germ - because of the high concentration can not be corrected and this then leads to cell death.

■ Characterized by the fact that the effect of a cavitation treatment on germs and / or on their biological structures creates the conditions for carbon dioxide to reach the germs.

Characterized by the fact that these prerequisites are changes, preferably mechanical changes, to biological structures that allow an external substance to penetrate, penetrate and pass / overcome these structures.

■ Characterized by the fact that the supporting effect of an adjuvant cavitation treatment, the carbon dioxide accumulate on germs, cell walls happen and is accumulated in a sufficiently large amount in the cell interior / cytoplasm of the germs.

■ Characterized by the fact that the supporting and / or preparatory effects of adjuvant cavitation treatment allow carbon dioxide to pass through biological structures, even if the germs are originally protected from carbon dioxide by protective layers (biofilm, SCV and / or other coverings).

■ Characterized by the fact that carbon dioxide when used in a sufficiently high concentration in the medium (cavitation medium, mist, aerosol, etc.) is available, preferably as a cavitation effective component of a Kavitationsmediums, for example, as "carbonic acid".

Characterized by the fact that an originally not / only slightly germicidal active substance, such as the preferred carbon dioxide, under certain conditions (as described) can be germicidal effect, therefore potentially germicidal effective called.

Characterized by the fact that by at least one complementary treatment with physical and / or chemical and / or biological / physiological (bioactive) and / or other effect, for example, preferably by sound and sound-induced cavitation / cavitation effect conditions are created which include a suitable substance such as preferred carbon dioxide germicidal effect.

■ Characterized by a substance that can potentially kill germs and at the same time, by a completely different effect, creates the conditions for the substance to be germicidal, for example by the effect that the substance mechanically alters biologic structures of germs and thus the Conditions creates that the same substance can penetrate into the germs and germicidal effect there by at least one further reaction / effect, preferably the substance is carbon dioxide .. As is the case with carbon dioxide, which creates as a cavitation effective component of a cavitation by cavitation the conditions for it in that the carbon dioxide, as a constituent of the cavitation medium, can become germicidal by being able to penetrate into the germs in order to unfold its germicidal effect there. ■ Characterized by a synergistic effect between carbon dioxide as a potentially germicidal substance and carbon dioxide as a cavitation-effective gas. Synergy effect between cavitation-effective carbon dioxide and potentially germicidal carbon dioxide. These are two different effects of the same gas, which can / have synergistic effects on simultaneous and / or timely application / effect.

■ Characterized by a substance, preferably carbon dioxide, which has at least two different effects of the same substance, for example the effect of cavitation and the germicidal effect, the substance itself has a synergistic effect. The substance, preferably carbon dioxide, is synergistically effective, especially if the substance, preferably carbon dioxide, is a cavitation-effective and potentially germicidal component of a cavitation medium. This is especially true in a cavitation treatment in the presence of this substance, preferably carbon dioxide.

■ Characterized by a Kavitationsmedium that by the same substance (preferably this carbon dioxide) as part of the Kavitationsmediums at least two different functions and / or effects, which are due to different effects of this one substance and these modes of action complement each other and together to a synergistic effect through the same substance. With carbon dioxide as the cavitation-effective component of a cavitation medium cavitation can be induced by sound in the cavitation medium (this is a mode of action of carbon dioxide), this cavitation has involved carbon dioxide in the treatment of germs and / or their biological structures and the like. a. a mechanical effect on the structures and leads to changes in the structures through which the carbon dioxide can get into and into the germs to be enriched there. In the cell interior of the germs, carbon dioxide dissolves in the cell fluid and dissociates when the pH is lowered (second mode of action). The pH reduction has germicidal effect (mode of action of carbon dioxide) and leads to cell death of the germs. The accumulation of carbon dioxide and the killing of germs would not be possible without the effect of cavitation, in which carbon dioxide plays a decisive role. The interaction of different modes of action of carbon dioxide has led to a synergistic effect / acts synergistically.

■ Characterized by a synergistic effect of a cavitation treatment with a carbon dioxide-containing cavitation medium.

■ Characterized by a Kavitationsmedium containing at least one synergistically active substance as a component, preferably the substance is carbon dioxide. Synergistically effective because the substance has at least two different effects, and in that these effects interact, it also has a synergistic effect.

■ Characterized by a cavitation medium with internal, own synergy effect, in that a substance is a cavitation-effective component of the cavitation medium and at the same time has a potential germicidal effect and neither cavitation nor substance is germicidal on its own.

«Characterized by a cavitation medium with new properties, features, applications. For example, with potentially germicidal effect. For example, with synergy effect.

■ Characterized by an application of carbon dioxide, which takes place at the same time and / or in time for cavitation treatment. ■ characterized preferably by the use of a Kavitationsmediums, in which Carbon dioxide is a cavitation-effective component and is a potentially germicidal and / or additionally therapeutically physiologically acting substance.

Characterized in that the treatment may be subaqual, as shown in FIG. 1 and / or in the description associated with FIG. 1 and / or relating thereto. And / or in a based on the subaqualen treatment and the arrangement described thereby underlying, but modified form, can be done.

■ The cavitation medium is characterized by further possible therapeutic effects, for example physiological effects of the gas dissolved therein (eg carbon dioxide).

■ characterized in that the carbon dioxide strongly enriched medium for the treatment of problematic germs and problematic infections is preferably identical to the Kavitationsmedium and preferably consists of water and / or an aqueous solution in which carbon dioxide is dissolved in high to very high concentration, preferably in one Concentration 1500mg / l, even over 1500mg / l.

■ Characterized that the cavitation effect on the problem germs / problem infections by treatment in the cavitation medium and the treatment of germs with potentially germicidal carbon dioxide occur simultaneously, simultaneously in the same medium.

■ characterized in that the cavitation medium is a medium in which the dissolved carbon dioxide in cavitation, as a cavitation effective component, is involved and at the same time contained as a germicidal substance in cavitation medium, the carbon dioxide in the cavitation medium has at least two different effects, the cavitation effect and that of the germicidal substance and both effects complement each other synergistically.

■ Characterized that the cavitation medium has at least two different effects due to the carbon dioxide dissolved therein, which together have a synergistic effect.

■ characterized in that the sonication from the cavitation medium induces a supporting cavitation in such a way that the cavitation / cavitation effect acts on the biological structures of the germs, preferably on cell walls, biofilms and other protective layers, preferably mechanically, to make them externally supplied substances How to make the carbon dioxide permeable with the aim of enriching carbon dioxide inside the cell, thereby causing cell death.

Advantages Important advantages were mentioned in / by the solution of the problem (for example with regard to resistance formation of the germs, protective layers, side effects, etc.).

Other important benefits are safe, safe use. The treatment can be combined with other treatments. A gentle / tissue-sparing treatment, for example in contrast to a risky ultrasound debridement. Carbon dioxide can have multiple effects that can be used therapeutically at the same time. Carbon dioxide can penetrate into the smallest cracks, pores, etc., in order to be effective there. The treatment is easy to perform, inexpensive, safe to handle, without side effects.

Pictures Fig. 1. Subaquale arrangement for a treatment of the object in a "water bath", the object is in Submerged and covered by cavitation medium. Arrangement of a subaquional cavitation treatment of a leg (biological system) in a water bath at the same time as carbon dioxide treatment. The leg is covered / enveloped by the cavitation medium. Carbon dioxide is part of the cavitation medium. In this presentation, both the leg and the sound applicator dive into the cavitation medium. The cavitation is preferably / predominantly in the liquid layer between the leg and the sound-emitting surface of the sound applicator. A subaquale treatment would also be possible if the sound applicator did not dive into the cavitation medium, but would touch it, for example, only at one contact surface. Fig. 2. Represents a possible arrangement in which the cavitation treatment and the application of carbon dioxide take place in a timely manner. The cavitation treatment of the biological system can also take place in the chamber and / or outside the chamber. Subsequently, the thus treated biological system is subjected to an application with carbon dioxide. In the example, inside the chamber under pressure in a concentrated carbon dioxide atmosphere.

In a sound and / or cavitation treatment of biological systems, as well as in germs and / or their biological structures, the sound characteristic has an effect on the cavitation and / or on depth / surface effect, including the transport of substances, the absorption of substances / of biological systems, etc. Besides the frequency and the sound intensity, further sound characteristics also play a role. For example, whether the sound is emitted in continuous or in pulsed form. The burst of sound (eg, sinusoidal, triangular, rectangular, or other shape), the way in which bursts of sound are delivered, the signal / waveform (eg, symmetric, asymmetrical), etc., which amplifies, for example, the compression or tension phases / can be reduced. A multitude of possibilities for influencing, controlling and optimizing the cavitation and / or the effect of sound on the sound characteristic are known and described. Design options of Schallapplikators, the sound generator and the sound characteristic according to the state of the art, for example, inter alia, in EP 0 330 636 B1, EP 0 442 278 B1, EP 0 595 783, EP 0335851, WO 98/07470 and many others described and can also be applied here. Additional / extended description of sound applicator, sound characteristics, etc. also in DE 10 2004 060 071, DE 10 2006 027 789, DE 10 2004 004 415.

3 shows an example for understanding a different sound output by the sound applicator. A = continuous sound. B = delivery in rectangular shaped sound packets (sound bursts) with temporal

Distance between two sound packets.

Example for understanding the schematic representation of a sinusoidal sound packet (sound burst) in Fig. 3 of DE 102 33 293.

Example for the understanding of a single sawtooth-shaped sound pulse (single sound burst) with asymmetrical signal ΛΛ / ellenform. Unsymmetrical, sawtooth waveform / waveform of a single sonic pulse (single sonic burst). In the schematic diagram is the negative

Pressure component greater than the positive pressure component in FIG. 2 of DE 102 33 293. Treatment, application, method, method, manufacture, use

■ Use and / or use of carbon dioxide as a potentially germicidal agent in the treatment of germs, preferably in the treatment of problematic germs, more preferably in the medical treatment of infections, even more preferably in the medical treatment of human and / or animal problematic infections ,

Use and / or use of a cavitation medium with carbon dioxide as a cavitation-active ingredient and as a potentially germicidal substance in the treatment of germs, preferably in the treatment of problematic germs, more preferably in the medical treatment of infections, even more preferably in the medical treatment of Problem infections in humans and / or animals. The described "carbonic acid water" is preferred as the cavitation medium.

Use and / or use of carbon dioxide and / or a carbon dioxide-containing medium, preferably a cavitation medium, for example the "carbonic acid water", for the treatment of germs / problem germs and / or of infections / problem infections in conjunction with a complementary sound treatment with cavitation effect.

■ Use of a potentially germicidal cavitation medium in the treatment of germs for the purpose of killing them.

■ Method / method for killing germs / microorganisms with a potentially germicidal cavitation medium and / or a potentially germicidal substance. ■ Method / method for killing germs / microorganisms with carbon dioxide and a complementary sound treatment, preferably with Kavitationswirkung.

Method and / or method for killing germs with a potentially germicidal substance, preferably of carbon dioxide, in the case of by (with the help of) physical and / or chemical forces / energy / effect, preferably by sound-induced cavitation at low to Moderate sound intensity, by the action of these forces / effects / energies on germs and / or on their biological structures (for example protective layers) Prerequisites (for example and / or preferably by structural alteration of biological structures of the germs, eg loosening, destruction, increase of Permeability, etc.) are created (therefore potentially), so that the substance can reach the germs to be killed, penetrate them, accumulate in the cell interior of the germs, and lead to cell death, for example by a physiological and / or chemical and / or physical reaction / mechanism / effect. The germicidal effect of the method and / or the method is not / not predominantly based on the Kavitationswirkung, so not / mostly not by mechanical destruction of the germs as would be the case for example in transient cavitation.

Treatment and / or method of killing germs / microorganisms with a potentially germicidal substance, preferably of carbon dioxide, by (by means of) physical and / or chemical forces / energy / action, preferably by sound-induced cavitation at low to medium levels Sound intensity, by the action of these forces / effects / energies on germs and / or on their biological structures (for example protective layers) Requirements (for example and / or preferably by structural alteration of biological structures of the germs, eg loosening, destruction, increase in permeability etc.) so that the substance is to be killed Enter germs, penetrate into these, can accumulate in the cell interior of the germs, thereby leading to cell death, for example, by a physiological and / or chemical and / or physical reaction / mechanism / effect. The germicidal effect of the method and / or the method is not / not predominantly based on the cavitation effect, ie not / predominantly not by mechanical destruction of the germs as would be the case for example in transient cavitation (eg ultrasonic debridement).

■ Manufacture and / or use / application of a cavitation medium, preferably the "carbonic acid" water to kill germs in conjunction with a complementary sound treatment with Kavitationswirkung ■ Use / application of a suitable material, preferably carbon dioxide for the production of a potentially germicidal cavitation medium (as described above ), preferably with carbon dioxide as the cavitation-active ingredient and / or as a germicidal substance.

Use / application of a suitable substance, preferably of carbon dioxide, as potentially germicidal substance in conjunction with at least one further complementary treatment, preferably sound, with physical and / or chemical and / or bioactive action, preferably with cavitation effect, for the treatment of germs, especially of problem germs and / or their biological structures.

■ cavitation medium and / or use / application of a cavitation medium with potential germicidal effect (as described above) to kill germs, better problem germs, for example preferably in the treatment of infections in humans and / or animals, more preferably for the treatment of problematic infections.

Cavitation medium and / or use of a cavitation medium, preferably a cavitation medium / cavitation medium with potentially germicidal action (as described above) for enrichment of at least one potentially germicidal substance, preferably of carbon dioxide, in the cell interior of germs / microorganisms.

^■ Cavitation medium and / or use / application of a cavitation medium, preferably a cavitation medium with potentially germicidal effect (as described above) for acting on germs and / or their biological structures, for example by cavitation, to their permeability / permeability for externally supplied substances / substances increase. ■ Use / application / use of the cavitation effect and / or its (mechanical) effect in order to make a germ-killing substance from a per se not or only slightly toxic substance (preferably carbon dioxide) by the cavitation and / or their effect of Substance can accumulate on / in the germ and cause an effect that has a germicidal effect, not germicidal / only slightly effective by the Kavitationswirkung.

■ Use / application / use of cavitation and / or its effect for introducing / introducing / enriching at least one potentially germ-killing substance, preferably of carbon dioxide, into the cell interior of germs and / or into their biological structures.

^■ Simultaneous and / or timely use / application of carbon dioxide (as a potentially germicidal gas) and / or cavitation treatment in the treatment of germs, preferably infections in humans and / or animals and / or biological structures of the germs. Cavitation medium and / or use / application / use thereof, which in addition to its action / function / use as Kavitationsmedium simultaneously (by at least one suitable and / or cavitation effective gas / suitable material, preferably carbon dioxide) at least one bioactive, for example, a physiological and / or has a germicidal effect, especially when this cavitation medium is used in combination with sound for a cavitation treatment and / or the sound is coupled to the biological system by means of the cavitation medium. Application / Use of carbon dioxide as potentially germicidal gas and / or of a potentially germicidal cavitation medium in an arrangement for the treatment of biological systems and / or germs and / or their biological structures, as exemplified in FIG. 1 and FIG / or Fig. 2 shown and / or described.

additions

The combination of at least two potentially germicidal substances may be possible, for example carbon dioxide with oligodynamically active substances / compounds, eg. Metals / metal ions / alloys / metal compounds. For example, silver / silver ions / nanocrystalline silver, other metals / metal ions / metal compounds e.g. As platinum, gold, copper, manganese, etc. Also other substances / active ingredients / pharmaceutical agents can be added to the Kavitationsmittel and / or applied before, after a Kavitationsbehandlung. Of course, substances other than carbon dioxide can penetrate into the protective layers made permeable by the cavitation effect, for example substances added to the cavitation medium.

Described are "open" infections, ie infections that are accessible from the outside The treatment of germs, cells, cell aggregates, etc. with potentially germicidal substances, such as carbon dioxide, can in principle also in not openly accessible places (eg. As organs) may be possible, for example, if they can be enriched / filled with a potentially germicidal substance, for example, in a cavity.

The formation of the gas bubbles and the cavitation preferably take place on and / or near the object surface (eg of the biological system). The cavitation medium is used for coupling the sound to the biological system, wherein the germs / microorganisms, for example as a germ / bacteria suspension, can be located directly in the cavitation medium. More commonly, the cavitation medium will contact the germs / microorganisms and / or their biological structures at an interface, for example, in subaqually treating a skin infection similar to that shown in FIG. 1.

The effectiveness of carbon dioxide as a germicidal substance requires the effect of cavitation on the biological structures of germs. In the simple case these barriers / biological structures are cell walls / membranes, in more difficult cases biofilms and / or other protective layers. The effects of cavitation on biological systems of germs are, for example, increasing the permeability of membranes, cell walls, etc., but also increasing the permeability to Substances / substances of protective layers / barriers (as described elsewhere), so that, for example, carbon dioxide can better overcome biological structures, ie rapidly and in a sufficiently high amount / concentration. DE 10 2004 004 415 describes some effects of cavitation and / or sound in the form of depth / surface effects.

Additional comments or definitions

Sound in the description may mean monofrequent sound (one frequency) and / or duo-frequency (two different frequencies) and / or multifrequency sound (with at least two different sound frequencies). In duo and / or multifrequent sound, the different frequencies simultaneously and / or not simultaneously (for example, temporally intermittent and / or in another form) to the medium, for. B. to the Kavitationsmedium, by at least one sound source (for example, at least one sound applicator) are delivered.

The sound characteristics (for example with regard to frequency, intensity etc., for example also pulsed sound, continuous sound etc., for example also the signal intensity) can have a special influence on the cavitation as well as on the effect (depth / surface effect) of the sound / cavitation. / Waveform, etc.). Sound emission according to the technical state and according to the optimization of a certain effect, for example optimization with regard to cavitation. Sound in the description initially means sound of any sound intensity [in accordance with conventional terms such as SATA, etc.] (eg, from 0.001 watts / cm ² to 500 watts / cm ² , 0.001 watts / cm ² to 20 watts / cm ² , preferably 0.001 watt / cm ² to 10 watt / cm ^2, more preferably 0.001 watt / cm ² to 5 watt / cm ² , more preferably 0.001 watt / cm ² to 2 watt / cm ² ), any sound pressure (eg from 0, 05 Pa to over 500000 kPa range, preferably 0.5 Pa to 500 kPa, further preferred sound pressure ranges 0, 5 Pa to 50 kPa, 50 kPa to 2100 kPa, 100 kPa to 300 kPa, 300 kPa to 500 kPa), any sound amplitude. Preferably low to medium intensity sound (1 mW / cm ² - 10W / cm ² ) and / or above, more preferably from 0.001 watt / cm ² to 5 watt / cm ^2, even more preferably from 0.001 watt / cm ² to 2 watt / cm ² . The distance of the sound-emitting surface to the object (surface of the biological system may initially be arbitrary (0.0001 mm - 100 m) Preferably below 1mm to 100cm, more preferably below 1mm to 20cm, even more preferably from below 1mm to 5cm, most preferably from less than 1 mm (for example) 0.01 mm to 2 cm.

The coupling of the sound to the biological system should preferably take place through the cavitation medium, preferably subaqual as in FIG. 1 and / or in that the cavitation medium contacts the biological system and / or the object surface. Between the sound-emitting surface of the sound applicator and the cavitation medium, at least one further sound-conducting layer can be located and / or attached, wherein for example the sound is transmitted from the sound applicator to the further sound-conducting layer and from there to the cavitation medium.

Any suitable sound applicator adapted to meet the requirements of a sound applicator which are applied to a sound applicator by the treatment described above under "cavitation-based potentially germicidal action of carbon dioxide" [sound intensity, Schailcharakteristik etc.].

Any suitable gas that can potentially kill germs under the conditions described. Advantageous if the gas dissolves in water, in aqueous solutions and / or in another suitable liquid, other suitable medium in a sufficiently high concentration, for example, polar gases in polar liquids. Other examples of gases are mentioned in DE 102004004415, which, however, need not be suitable gases.

The cavitation is preferably carried out in a liquid cavitation medium, but other conventional well-known cavitation media (for example, steam, fog, aerosol, etc.) are possible. In the gas cavitation cavitation occurs by excitation of, for. B. located in Kavitationsmedium, gas bubbles to (oscillating) gas bubble oscillations up to resonant vibrations of the gas bubbles. Furthermore, the formation of gas bubbles from the cavitation medium may be possible by a sound effect on the cavitation medium during the treatment (by the passage of dissolved, eg molecularly dissolved gas into the gas bubble state), and these gas bubbles are excited to vibrate. Formation of gas bubbles in situ: the gas bubbles do not have to be present from the beginning in the cavitation medium, but they can also be formed during the treatment, the cavitation medium serves as a gas bubble source. Gas dissolved in the cavitation medium is converted to the bubbling state (gas bubble formation) by the sound pressure when sound is applied to the cavitation medium.

Cavitation has almost only an effect on a biological system and / or its surface, if the cavitation occurs near the surface and / or on the surface. This can be achieved, for example, if the distance of the sound-emitting surface to the object surface can be kept low. The gas concentration in the medium should be high and it should be possible to repeatedly form new gas bubbles (in situ) during the treatment.

Cavitation, preferably sound-induced cavitation, more preferably ultrasound-induced cavitation, even more preferably cavitation induced by low-frequency ultrasound. Surface and / or depth effect caused by cavitation and / or by sound, preferably low-frequency ultrasound causes / causes.

A cavitation / cavitation reaction can also take place without an actual cavitation medium, for example if an object surface (eg skin as the surface of a biological system) is enriched with gas bubbles which adhere to the surface / in pores etc.

Cavitation can also take place without actual cavitation medium. For example, if sufficient gas bubbles are available for cavitation in the boundary layer between the coupling medium and the object surface and these can also be excited to oscillate. For example, in an enrichment of an object surface (surface of a biological system, eg skin, wound, etc.) with at least one gas, e.g. With carbon dioxide. By coupling the sound to the surface with a coupling medium (eg liquid), in which the gas is only slightly / not soluble, the gas can be held on the object surface, without entering the Migrate coupling medium. One possibility for enriching the surface of the object (eg skin) with gas / gas bubbles may be that the retention / adhesion (eg by adhesion) of the gas at the surface is improved, for example by using the polarity in the case of polar Gases like carbon dioxide. Another possibility may be that the object surface is first wetted with a polar liquid layer and then exposed to a gas atmosphere (eg carbon dioxide), preferably under pressure (analogous to FIG. Another possibility may be that, for example by using at least one further substance / active substance (eg urea, containing urea as an example), which is applied to the surface, moisture (eg water) is supplied to the surface and this leads to a chemical reaction / decomposition in which at least one gas is released, for example the hydrolysis of urea. In aqueous environment urea decomposes by hydrolysis into carbon dioxide and ammonia. Gases that are cavitation-active and potentially capable of destroying germs.

Cavitation such as sonication have on the object to be treated / biological system depth as well as surface effect (DE 10 2004 004 415).

Further areas of application and / or use

Area of application / field of application / field of application of the potentially germ-killing action of carbon dioxide supported by cavitation can be any areas in which germs are to be killed, in particular also where problem germs occur and / or other methods / methods for germ treatment fail and / or are not used can. This also applies in areas with biofilm problems.

Field of application / field of application / field of application of a cavitation medium which contains carbon dioxide as a cavitation-effective constituent and / or as a potentially germicidal gas as constituent, can be any areas in which germs are to be killed, this also applies where problem germs occur and / or other processes / Methods for germ treatment fail and / or can not be applied. This also applies in areas with biofilm problems.

In the therapeutic / medical treatment of infections with problematic germs in humans and / or animals, for example, if the germs have formed a resistance to active substances (eg against antibiotics and / or against other active substances) and / or the germs by protective coatings against Active ingredients are protected, etc., and the active ingredients fail (almost ineffective / ineffective).

In the therapeutic / medical treatment of infections with germs in humans and / or animals, for example, even if other treatment methods and / or products / devices fail and / or can not be used (eg because of strong side effects, etc.) and / or should not be used. This also applies to applications in which a high energy, eg. B. a high sound energy (eg., Performance sound) can lead to unwanted damage to biological systems, and / or treatment (eg, an ultrasonic debridement, surgical debridement, etc.) because of high risk potential for patients and / or for users only from trained personnel. Therefore a treatment with low / medium

Sound energy / sound intensity is to be preferred. A treatment that can also be handled by an extended group of people. This also applies to applications / treatments that can not be performed everywhere (eg ultrasound debridement) because, for example, the required

Devices are missing because, for example, the treatment should be carried out at the patient's home, etc.

In the therapeutic / medical treatment for the prophylaxis of infections with germs

Humans and / or animals.

In the non-therapeutic / non-medical treatment of humans and / or animals for disinfecting, for example in the areas of hygiene, cosmetics, etc., in biofilm problems

To avoid and / or combat germ colonization in the technical field, water technology, etc., even with biofilm problems.

Applications / Use of the described potentially germicidal gas and / or the Kavitationsmediums for the therapeutic / medical treatment of external (external) infections / problem infections by germs / problem germs in humans and / or animals. For example, in infections of wounds, skin, bones

(Osteitis / osteomyelitis), nail bed infections and other medical uses

Treatment and / or infection prophylaxis.

Therapeutic / medical treatment of infections that can not be treated externally, for example, organs, for example, organs that form a cavity and could be filled with a cavitation medium and / or a suitable gas. Ultrasonic application from the outside and / or from the inside possible.

Therapeutic / medical and / or scientific treatment of cells, cell aggregates, tissue.

Use / non-therapeutic / non-medical use in the treatment of humans / animals, e.g. In the field of hygiene / body culture (eg athlete's foot, surgical hand disinfection, decontamination, cleaning, etc.) and / or in the field of cosmetics, other areas of application. Also for prophylaxis. General application in the field of "Life Science" Cleaning, disinfection Application / Use in technical / industrial / scientific fields in which contamination with germs is to be prevented and / or eliminated, for example in the case of problems with biofilms, bio-corrosion, bio-fouling etc. For example, medical / medical technology, medical devices / appliances, etc., food industry, water management, general industry, etc. where cleanliness, production of germ-free / germ-free conditions is necessary, etc. Household appliances, cleaning equipment / devices, etc. Application / Use as material- / gentle process in areas where (transient) cavitation is normally used for cleaning / disinfection.

Claims

protection claims

1. The cavitation-based potential germicidal effect of carbon dioxide in the treatment of problematic germs and / or problematic infections with a carbon dioxide strongly enriched medium is characterized in that due to a complementary in a cavitation medium sound treatment of the germs with Kavitationswirkung on the germs, the carbon dioxide itself in a sufficiently high concentration for germicidal effect in the cell interior of the germs can accumulate to trigger a reaction in the aqueous environment of the cytoplasm (cytosol), which leads to a strong, no longer controllable by the germ hyperacidity of the cytosol and thus cell death.

2. Characterized in that the carbon dioxide strongly enriched medium of claim 1 for the treatment of problematic germs and problematic infections is preferably identical to the cavitation medium of claim 1 and preferably consists of water and / or an aqueous solution in the carbon dioxide in high to very high concentration is dissolved, preferably in a concentration 1500mg / l, even over 1500mg / l.

3. Characterized in that it is clear from claim 1 and 2, that the cavitation effect on the problem germs / problem infections by the treatment in the cavitation medium and the treatment of germs with potentially germicidal carbon dioxide simultaneously, simultaneously in the same medium.

4. characterized in that the cavitation medium of claim 1 together with the

Claims 2 and 3 results in a Kavitationsmedium in which the dissolved carbon dioxide in the cavitation, as a cavitation effective component, is involved and simultaneously contained as a germicidal substance in cavitation medium, the carbon dioxide in the cavitation medium has at least two different effects, the cavitation effect and the of the germicidal substance and both effects complement each other synergistically. Carbon dioxide as a synergistically effective component of a cavitation medium.

5. Characterized in that the cavitation medium of claim 4, 5 by the carbon dioxide dissolved therein has at least two different effects, which together have a synergistic effect. Cavitation medium with internal, own synergy effect, in that carbon dioxide is a cavitation-effective component of the cavitation medium and at the same time has a potential germicidal effect and neither cavitation nor carbon dioxide alone is germicidal / would be effective.

Characterized in that the sonication of claim 1 in the cavitation medium of claims 1-5 induces a supporting cavitation such that the cavitation / Kavitationswirkung on the biological structures of the germs, preferably on cell walls, biofilms and other protective layers, acts preferred mechanically acting to make them permeable to externally supplied substances such as carbon dioxide with the aim of enriching carbon dioxide inside the cell, thereby causing cell death.

Characterized in that according to claim 1 and 6, the carbon dioxide by the Kavitationswirkung sufficient for a germicidal effect in the cell interior is enriched and dissolves in the aqueous environment of the cytosol, dissociates and causes hyperacidity of the cytosol by lowering the pH and leads to the death of the germs, because they can no longer regulate / correct the hyperacidity. The killing of germs is due to the properties and reactions of carbon dioxide, which thereby interferes with the physiology of the germs, but not as a direct, immediate consequence of a cavitation effect.

8. The cavitation-based potential germicidal effect of carbon dioxide on germs of claim 1 is further characterized in that these processes and also the germicidal effect of carbon dioxide at low to medium sound intensity occur and / or that the treatment can be carried out at low to medium sound intensity. The

Cavitation effect is not sufficient to kill germs in medically relevant extent.

9. Arrangement for the subaqual treatment of infections / problem infections with a cavitation medium containing carbon dioxide as a potentially germicidal substance.

Characterized in that the germs in the claims are problematic germs which are protected against the action of active ingredients and / or pharmaceutical agents, preferably by resistance formation, more preferably by protective layers, preferably biofilms, small colony variants, other protective layers predominantly consisting of organic material, wherein an external substance can not reach the germs sufficiently to germicidal effect, not carbon dioxide.

11. Characterized in that the germs in the claims are problematic germs that can not be treated by drugs because of side effects and / or other reasons.

12. Characterized in that by the supporting and / or preparatory effect of an adjuvant cavitation treatment according to claim 1, 6, the carbon dioxide can pass through biological structures, even if the germs by protective layers (biofilm, SCV and / or other deposits) originally protected from carbon dioxide are.

13. According to claim 1, the cavitation-based potential germicidal effect of carbon dioxide is characterized in that by at least one complementary treatment with physical and / or chemical and / or biological / physiological (bioactive) and / or other action, for example, preferably by sound and sound-induced cavitation / Cavitation effect conditions are created that make a suitable substance such as the preferred carbon dioxide germicidal effect.

14. Application and / or use of carbon dioxide as a potentially germicidal substance in the treatment of germs, preferably in the treatment of problematic germs, more preferably in the medical treatment of infections, even more preferably in the medical treatment of human problematic and / or Animal.

15. Application and / or use of a cavitation medium with carbon dioxide as a cavitation-active ingredient and as a potentially germicidal substance in the treatment of germs, preferably in the treatment of problematic germs. The described "carbonic acid water" is preferred as the cavitation medium.

16. Application and / or use of carbon dioxide and / or a carbon dioxide-containing Medium, preferably a Kavitationsmediums, for example, the said "carbon dioxide", for the treatment of germs / problem germs and / or infections / problem infections in conjunction with a complementary sound treatment with Kavitationswirkung.

17. Use of a potentially germicidal cavitation medium in the treatment of germs for the purpose of killing them.

18. Method / method for killing germs / microorganisms with a potentially germicidal cavitation medium and / or a potentially germicidal substance.

19. Method / method for killing germs / microorganisms with carbon dioxide and a complementary sonic treatment, preferably with Kavitationswirkung.