Clinoptilolite or clinoptilolite-containing mineral mixture for use as a mineral wound covering

Abstract

The invention relates to clinoptilolite or a clinoptilolite-containing mineral mixture for use as a mineral wound covering for treating secondary-healing wounds of the skin and / or of underlying tissue, in particular chronic, poorly healing or non-healing wounds, wherein the clinoptilolite / the clinoptilolite-containing mineral mixture is comminuted in powder form or comminuted within a suspension.

Description

[0001] Patent application for clinoptilolite or a clinoptilolite-containing mineral mixture for use as a mineral wound dressing. The invention relates to clinoptilolite or a clinoptilolite-containing mineral mixture for use as a mineral wound dressing for the treatment of secondarily healing wounds of the skin and / or underlying tissue. The topic of wound care is gaining increasing importance. The 2015 report by the Primary Care Research Group (PMV) at the University of Cologne on the "Epidemiology and Care of Patients with Chronic Wounds" shows that at that time there were approximately 2.7 million wound patients in Germany, of whom approximately 890,000 suffered from chronic wounds, the remainder from acute wounds resulting from accidents or in the aftercare of medical procedures.These figures, and especially the number of wounds healing by secondary intention, which include chronic wounds such as pressure ulcers, diabetic foot ulcers, and leg ulcers, will continue to rise as a consequence of demographic change with the increasing number of elderly people. Innovative and effective wound care makes life easier for patients and can reduce treatment times, thereby lowering care costs and staffing requirements. From WO 2023 / 152241 A1, a substance from the group of anion exchange resins, such as cholestyramine, is known for the treatment and prophylaxis of wounds and injuries, particularly in the presence of local bacterial infections or critical colonization, with the aim of biologically neutralizing healing-impairing bacterial toxins during wound healing. Application can be by direct application of the product or in combination with conventional wound care materials and procedures.The object underlying the invention is to improve and simultaneously simplify the treatment of secondarily healing wounds, particularly chronic wounds. The solution to this problem lies in clinoptilolite or a mineral mixture containing clinoptilolite according to claim 1 for use as a mineral wound dressing for the treatment of secondarily healing wounds of the skin and / or underlying tissue, especially chronic, poorly healing, or non-healing wounds (for example, pressure ulcers, medical foot syndrome, and leg ulcers). The clinoptilolite / the mineral mixture containing clinoptilolite is present in pulverized form or pulverized within a suspension and is applied to the wounds in powder or suspension form to promote wound healing. Embodiments and further developments are specified in the dependent claims. According to the invention, the naturally occurring zeolite clinoptilolite is used.Clinoptilolite is a crystalline, microporous rock of volcanic origin belonging to the zeolite group. It is gray-green in color and odorless. The basic skeleton of the clinoptilolite crystal lattice consists of SiO₂ tetrahedra and Al₂O₃. The ratio of silicon to aluminum in the tetrahedra is typically 4:1 to 8:1. The silicon oxide content in clinoptilolite is 60 to 80% by weight, while the aluminum oxide content is 10 to 14%. The crystal structures, formed via oxygen bridges, create pores and channels. The exchange of tetravalent silicon atoms for trivalent aluminum atoms results in a cation exchange capacity. This exchange causes a negative charge surplus. The negative charges of the silicon / aluminum tetrahedra are compensated internally by positive ions of alkali and alkaline earth elements (Ca, K, Na, Mg) as well as by water.Due to its large specific crystal surface area, clinoptilolite possesses interesting properties. Applications are based on its ability for selective ion exchange and its high absorption and adsorption capacity. Its microporous structure allows it to bind irritants and pollutants, particularly mercury, lead, cadmium, radionuclides, ammonium, histamine, and other biogenic amines. This property allows clinoptilolite to be applied to wounds, for example, in the case of injured skin, acting as a protective shield where it can accelerate hemostasis and prevent further penetration by microorganisms. Powdered clinoptilolite is already used as a material for medical devices in various fields, including dermatology.It is already known from WO 2010 / 057849 A1 that clinoptilolite or clinoptilolite-containing mixtures can be used for the absorption or elimination of amines and / or their salts that occur in aqueous suspension in the digestive tract or on the skin of humans and animals. The clinoptilolite is not absorbed through the intestine or skin and therefore has no pharmacokinetic activity. In the case of minor skin injuries, such as insect bites and abrasions, but also deeper wounds, histamine released by microorganisms can be absorbed and eliminated by clinoptilolite. For this purpose, the cleaned wound is repeatedly treated with clinoptilolite or a mixture of clinoptilolite and water and then bandaged with a sterile dressing. Finally, the clinoptilolite can dry and fall off along with a scab.Surprisingly, mineral wound dressings made of clinoptilolite or a mineral mixture containing clinoptilolite are suitable for treating wounds that heal by secondary intention, such as those caused by vascular circulatory disorders and wound healing disorders of various origins. Secondarily healing wounds include, in particular, chronic wounds such as diabetic foot ulcers resulting from diabetic foot syndrome and leg ulcers. Diabetic foot is a complication of diabetes mellitus characterized by poorly healing chronic foot wounds. Leg ulcers are also commonly known as "open leg." Furthermore, clinoptilolite or the mineral mixture containing clinoptilolite is also suitable for treating wounds that heal by secondary intention resulting from burns and injuries involving dermal damage.This application is also advantageous if the wound(s) are one or more infected and / or acute, malodorous wounds. The clinoptilolite / clinoptilolite-containing mineral mixture can be applied directly to the wound and, if necessary, the surrounding area. The following effects have been observed compared to conventional wound treatment: ➢ the formation of smooth wound edges, ➢ enhanced epithelialization, ➢ improved wound environment, ➢ a reduction in fibrin deposits, ➢ a significant reduction in wound area, ➢ a reduction in pain / itching, ➢ a reduction in redness, ➢ the elimination of wound odor, and ➢ enhanced granulation and thus improved hemostasis. These effects are based on studies and current knowledge gained through in vivo and in vitro investigations.A particular advantage was that the mineral mixture containing clinoptilolite, despite its hygroscopic properties, did not function as a dry wound dressing like other wound powders. This is because the mineral wound dressing formed by the clinoptilolite creates a moist environment due to exposure to moisture beneath the wound, thus becoming a moist wound dressing. This dressing can then remain on the wound for more than a day, similar to a mineral plaster, but can also be easily removed if necessary without damaging the granulation or epithelial tissue, thereby reducing wound pain.However, it has proven particularly advantageous and effective to leave the mineral wound dressing on the wound for several days, preferably 3 to 5 days, and only to dust the remaining moist areas with the mineral mixture containing clinoptilolite as needed. The mineral wound dressing visibly promotes the development of granulation tissue. As a result of granulation, the mineral wound dressing is pushed upwards from the inside of the wound and therefore does not initially need to be removed. Such a mineral wound dressing, in powder or suspension form, can conform to the irregular anatomical contours of a wound better than wound dressings used in conventional wound treatment methods, acting like a "mineral plaster." Furthermore, the use of a mineral wound dressing can eliminate the need for various other wound dressings.The clinoptilolite or the clinoptilolite-containing mineral mixture is preferably subjected to a special processing method before use, whereby the clinoptilolite material is comminuted and thereby activated and modified. According to a particularly preferred embodiment of the invention, a clinoptilolite / a clinoptilolite-containing mineral mixture is used which has been comminuted by a micronization process. As a result of such a micronization process, the particles of the powder consisting of the clinoptilolite / the clinoptilolite can have particle sizes that result in a mean diameter in the range of 8.0 µm to 12 µm.An advantageous particle size distribution has: ➢ a 10th percentile value, below which 10% of all particles are found, in the range of 1.1 µm to 3.0 µm; ➢ a 50th percentile value, below which 50% of all particles are found, in the range of 5.0 µm to 10 µm; and ➢ a 90th percentile value, below which 90% of all particles are found, in the range of 20 µm to 26 µm. According to a further embodiment, the particles of a comminuted clinoptilolite / clinoptilolite-containing mineral mixture, intended for use within a suspension, can have particle sizes that result in a mean diameter in the range of 1.5 µm to 2.5 µm.In this case, a particle size distribution is preferably characterized by: ➢ a percentile value X10, below which 10% of all particles are found, in the range of 0.5 µm to 1.0 µm; ➢ a percentile value X50, below which 50% of all particles are found, in the range of 1.5 µm to 2.5 µm; and ➢ a percentile value X90, below which 90% of all particles are found, in the range of 3.0 µm to 4 µm. The particle size is determined in each case by laser diffractometry. Further details, features, and advantages of embodiments of the invention will become apparent from the following description of exemplary embodiments and study results with reference to the accompanying figures. Figures show:Figure 1: A bar chart comparing the total wound area of ​​patient group B receiving standard wound treatment to the total wound area of ​​patient group A treated with clinoptilolite at specific monitoring days within an observation period, with the total area values ​​expressed as percentages relative to a baseline of 100%. Figure 2A: A photograph of a patient's chronic leg ulcer (ulcus cruris) on the left lower leg at the time of admission for treatment. Figure 2B: A photograph of the same patient's wound after four weeks of treatment with micronized clinoptilolite. Figure 3A: A photograph of a patient's chronic leg ulcer (ulcus cruris) on the right leg as a result of varicose vein disease (ulcus cruris varicosum) at the time of admission for treatment.Fig. 3B: a photographic image of the same patient's wound after four weeks of treatment with micronized clinoptilolite, Fig. 4A: a photographic image of a chronic wound of a patient with a leg ulcer on the left lower leg at the time of admission for treatment, Fig. 4B: a photographic image of the patient's wound after four weeks of treatment with micronized clinoptilolite, Fig. 5A: a photographic image of a chronic wound of a patient with a leg ulcer at the time of admission for treatment, Fig. 5B: a photographic image of the patient's wound after four weeks of standard wound treatment, Fig. 6A: a photographic image of a chronic wound of a patient with a leg ulcer on the left calf at the time of admission for treatment, Fig. 6B: a photographic image of the patient's wound after four weeks of standard wound treatment, Fig.7A: A photographic image of a chronic wound of a patient with a leg ulcer on the right lower leg at the time of the photograph for standard wound care, and Fig. 7B: A photographic image of the patient's wound after four weeks of standard wound care. The following presents parts of a study that demonstrates the effects of applying a powder or skin powder based on clinoptilolite, hereinafter referred to as clinoptilolite powder, compared to any clinically and standardly recommended wound care.This study was designed to provide patients with chronic inflammatory wounds resulting from diabetes mellitus (DM) or other causes of chronic circulatory disorders of the lower extremities with controlled therapy over four weeks. This included multidimensional monitoring according to the ABCDE approach, encompassing medical history, bacterial profiling via microbiological swab, clinical examinations such as photographic documentation, circulatory status assessment, and additional services like wound odor analysis for volatile organic compounds (VOCs). Wound healing findings, such as size and environmental reaction, were to be documented photographically and examined using bacterial cultures from the wound swab. The randomized, controlled trial was conducted with 50 patients, 19 female and 31 male.According to predefined inclusion criteria, the patients presented with chronic wounds, some of which had been present for many months or years, for example, in connection with diabetic foot syndrome and other vascular circulatory disorders of various origins. In an observation period of only four weeks, a significantly faster reduction in wound area was observed under treatment with clinoptilolite powder, regardless of the underlying disease. This was accompanied by a significant reduction in inflammation / redness of the wound and surrounding tissue, and was also reflected in faster granulation of the wounds. A reduction in fibrin deposits and an increase in epithelialization were observed with the application of clinoptilolite powder compared to conventional treatment.Furthermore, the clinoptilolite powder, used as a wound powder, had a positive effect on the wound's moisture environment, thus supporting exudate management during wound care. No adverse side effects occurred during treatment with the clinoptilolite powder, and its tolerability as a skin powder was very good. In addition, patients treated with the clinoptilolite powder no longer experienced an unpleasant wound odor, and the therapy was perceived as painless. For the study, an activated, natural clinoptilolite modified by a comminution or micronization process described below was used. Such micronized clinoptilolite is also known under the name MANCà as a material for natural medical products.Clinoptilolite is a natural zeolite, which, like most minerals in the zeolite group, belongs to the class of framework silicates or tectosilicates. The micronization of the clinoptilolite material is carried out according to a manufacturer-specific, validated, and qualified manufacturing process by FROXIMUN AG. For this purpose, FROXIMUN AG maintains a complete quality management system and is certified according to EN ISO 13485:2016 for the development, manufacture, and distribution of dermal and oral medical devices made from zeolite. The clinoptilolite material appears as a light gray, odorless solid powder that is insoluble in water. The pH of the aqueous supernatant in a suspension of clinoptilolite in water is approximately pH 7. The solid clinoptilolite is hygroscopic. Different clinoptilolite products vary in terms of the particle size distribution achieved through micronization.Particle size is determined by laser diffractometry and serves as a product control measure to ensure that the respective products meet the required specifications. Table 1 shows the particle size distribution of a clinoptilolite powder for use as a wound powder for secondarily healing wounds. Table 1 Cumulative Values ​​[%] X. 10 X 50 X 90Mean diameter Particle size [µm] 1.1-3.0 5.0-10.0 20.0-26.0 8.0-12.0 Table 2 shows the particle size distribution of a comminuted clinoptilolite material intended for use in a suspension for the treatment of secondarily healing wounds. Table 2 Cumulative values ​​[%] X10 X50 X90 Mean diameter Particle size [µm] 0.5-1.0 1.5-2.5 3.0-4.0 1.5-2.5 The clinoptilolite used, regardless of the degree of comminution or micronization, is a dry, non-greasy, mineral substance that is not subject to any material changes through degradation or natural, chemical, or biological degradation processes. Furthermore, the clinoptilolite material is not subject to degradation in the form of a loss of material properties, such as material fatigue or chemical decomposition.The crushed or micronized clinoptilolite material contains no organic components and therefore no proteins, fats, carbohydrates, or fiber. Likewise, the clinoptilolite material contains no enzymes. Consequently, the clinoptilolite material is not subject to biological degradation, which could affect the product and its stability. Details of the Study: The study aimed to investigate the extent to which various characteristics or symptoms of chronic inflammation of wounds of different origins could be influenced by a clinoptilolite powder obtained through the described crushing process. Wound healing was to be compared between the local application of the clinoptilolite powder and established wound management in a clinical setting. During the study, the clinoptilolite powder was used on 25 of 50 patients with open wounds and impaired wound healing.All other 25 individuals received standard wound care (SoC). Treatment group A thus consisted of 25 patients with open wounds and impaired wound healing who were treated exclusively with clinoptilolite powder. Control group B consisted of 25 patients with open wounds and impaired wound healing who received standard wound care (SoC) without clinoptilolite powder. The study included at least four observational visits per patient to assess wound healing and tolerability. Visit 1 (T1) took place between day 1 and day 6 of initial inpatient admission, visit 2 (T2) on day 6 or 7, visit 3 (T3) on day 15 (+ / - 2 days), and visit 4 (T4) around day 32 (+ / - 2 days).The starting point for documentation was Visit 1 (T1), during which patients were assigned to their respective groups, where treatment was then carried out either with or without clinoptilolite powder. The study procedure was conducted according to a Clinical Trial Protocol (CIP). Dressing changes were performed at least at Visit 2 (T2), Visit 3 (T3), and Visit 4 (T4). At each visit, swabs were taken to determine bacteriology and assess for potential wound infection, and standard sterile wound irrigation with Octenisept and isotonic saline solution was performed. In addition, photographic documentation of the lesions, including measurement of the wound area, was performed. In Group A, the treatment group, the wound was completely covered with clinoptilolite powder at each dressing change, while Group B, the control group, received a new dressing without clinoptilolite powder.Final documentation of recorded data and photos was completed for each patient after visit 4, which generally took place around day 32 (+ / - 2 days). Conventional therapy, or standard wound care (SoC), was based on the MOIST concept and considered the following wound management parameters: M – Moisture balance (exudate management): Active intervention was implemented to create an optimal moisture environment. For example, hydrogels were used for dry wounds, while alginates or superabsorbents were used for moist wounds. O – Oxygen balance management: Oxygen-permeable wound dressings were used. I – Infection control: In addition to routine laboratory diagnostics, antiseptic cleansing and irrigation solutions were used.S – “Support”: Supportive measures for wound treatment, such as compression, were administered as needed. T – Tissue Management: Depending on the situation, debridement, i.e., deep cleaning of the wound, was performed as a standard procedure. The aim of the clinical trial was, on the one hand, to demonstrate the clinical efficacy and biosafety of clinoptilolite powder during the treatment of impaired wound healing in patients with chronic wounds, including patients suffering from diabetic foot syndrome, and on the other hand, to investigate a possible influence of clinoptilolite powder on the bacterial environment and the wound healing process.Regarding the population of study participants for the clinical trial, particularly concerning inclusion and exclusion criteria as well as sample size, the following was determined: As already mentioned, the sample size was set at two groups of 25 patients each. The total of four measurement points per patient over time allowed for both the evaluation of continuous values ​​over time and the assessment of discrete data, such as swab findings. The following inclusion criteria applied: ➢ Age from 18 to 90 years inclusive, ➢ Individuals of both biological sexes, ➢ Indication according to the objective, ➢ Healthy skin areas had to be present as a control area, ➢ Patients with diabetic neuropathy (neuropathic foot) or diabetic angiopathy (gangrene).The following exclusion criteria applied: ➢ severe cardiovascular disease, ➢ other primary chronic skin diseases, ➢ severe liver and / or kidney failure, ➢ severe dementia / delirium, ➢ septic condition, ➢ lack of compliance, and ➢ lack of informed consent. In the study, regardless of whether clinoptilolite powder was used or not, conservative wound care was performed, including daily dressing changes and sterile irrigation of the wound with Octenisept® and isotonic saline solution. The clinoptilolite powder was dosed to ensure uniform wound coverage, regardless of the thickness of the dressing. Administration involved sprinkling the clinoptilolite powder onto the wound after dressing changes and / or wound cleaning, distributing it according to the specified dosage.Group A, the treatment group of 25 patients with chronic wounds and impaired wound healing, particularly patients with diabetic foot syndrome, was treated with clinoptilolite powder. Group B, the control group of 25 patients with chronic wounds and impaired wound healing, particularly patients with diabetic foot syndrome, received only standard wound treatment without clinoptilolite powder. Participants were available at all times. All 50 patients were able to undergo outpatient monitoring and the corresponding group-specific treatment at each scheduled appointment (T1 to T4). All patients in Group A were treated with the same batch of clinoptilolite powder.The study's objective was to demonstrate the clinical efficacy and biosafety of clinoptilolite powder during the treatment of impaired wound healing in patients with chronic wounds, including wounds resulting from diabetic foot syndrome. The study aimed to determine whether clinoptilolite powder had a positive effect on the wound healing process in this condition. The data presented below demonstrate that the primary endpoint was met and the interventions were successful. The primary endpoints were defined as measurable, assessable, and clearly defined parameters: wound area size, inflammatory status, and the visual development of the wound and surrounding tissue.The clinical verbal assessment of the wounds treated in the study for all included patients is shown in Table 3, which reports on the wound characteristics at each examination time point T1 to T4 based on the listed assessment parameters. Table 3 Assessment Parameter SoC Clinoptilolite Powder Formation of smooth wound edges - + Improvement of the wound environment - + Reduction of wound area - / + + + Reduction of redness - / + + Increase in granulation - / + + + Reduction of fibrin deposits - / + + Increase in epithelialization - / + + + Drying of the wound - + No pain - + Elimination of wound odor - + - not observed - / + partially observed + observed + + frequently observed The verbal assessment of both groups showed the clear benefit of clinoptilolite powder for the wound healing of critical chronic wounds.While the descriptive parameters were only observed very sporadically in group B with standard wound care (SoC), only positive effects were observed with the application of clinoptilolite powder, which were found in almost every patient. Furthermore, photographic documentation of the wound area was recorded for each patient on monitoring days T1 to T4. The location and size of the wound area were noted, as well as whether it was treated with standard wound care (SoC) or with clinoptilolite powder. Table 4 below lists the change in the respective total wound area in group A and group B for all monitoring days T1, T2, T3, and T4. The wound areas were recorded both as absolute values ​​in mm. 2 as well as in percent of the initial value, shown in a table. Table 4 Total area T1 T2 T3 T4 in mm 2Area 68805 38962 32443 17728 Group A Area 26986 20075 21033 17952 Group B Total area T1 T2 T3 T4 in mm 2Percent 100 67 60 33 Area Group A Percent 100 73 65 55 Area Group B Figure 1 shows the values, expressed as percentages, of the total wound areas of Group B (treated with standard wound care) and Group A (treated with clinoptilolite) at monitoring days T1, T2, T3, and T4 of the observation period, as presented in a bar chart. The standard deviation around the mean is also shown, with a corresponding 95% confidence interval. Figure 1 shows that after one or two weeks of wound treatment, there was no significant difference in wound area reduction between wounds treated with standard wound care (SoC) and those treated with clinoptilolite powder.After 4 weeks of treatment, i.e., at time point T4, the total wound area had decreased to a smaller percentage (i.e., with a significant probability of p = 0.02) when using clinoptilolite compared to standard wound care (SoC). While the total wound area was approximately halved under standard wound care, it was reduced to one-third of the original total area under treatment with clinoptilolite powder. This is all the more remarkable because the initial total area of ​​the wounds treated with clinoptilolite was considerably larger than the initial total area of ​​the wounds treated with standard wound care (SoC), as shown in the upper part of Table 4. Thus, significantly larger absolute wound areas healed under treatment with clinoptilolite powder. Figures 2A to 3A illustrate this.Figure 7B shows an excerpt from the photographic documentation of treatment with and without clinoptilolite powder (MANC). This provides visual support for the results above. Three patients each from treatment group A and treatment group B are shown at the time of admission for treatment (T0) and after four weeks of treatment (T4). The photographs in Figures 2A and 2B are assigned to a patient in group A who, at the time of admission for treatment, was 74 years old, weighed 77 kg, and had a BMI of 27.61 (Battery Mass Index, which relates body weight to height in meters squared). Underlying conditions listed are hypothyroidism (overactive thyroid), protein V deficiency, and acute lumbar spine syndrome.The initial findings included diabetes mellitus and hypertension, while neither chronic kidney disease nor liver disease could be detected. The patient was a non-smoker. She presented with bilateral mixed leg ulcers on her right lower leg. A leg ulcer is a chronic wound. Colloquially, it is also known as an "open leg" or "leg ulcer." Older people with underlying conditions such as varicose veins or arteriosclerosis are particularly at risk. A mixed leg ulcer is defined as a leg ulcer in which both chronic venous insufficiency and peripheral arterial disease are contributing factors. It is therefore a mixed form of venous and arterial leg ulcer. According to the initial findings, these wounds occurred in the patient's condition following a pulmonary embolism and deep vein thrombosis (DVT).The photographic image in Fig. 2A shows the ulcus cruris on the left lower leg during the admission for treatment, with the wound area at that time being 4311 mm. 2 The figure in Fig. 2B shows the wound at time point (T4) after the fourth week of treatment with clinoptilolite powder, with a significantly reduced wound area, now only 2466 mm². 2The amount of redness recorded was also reduced. In addition, the wound and surrounding area appear lighter in the black and white image, and smooth wound edges have formed. The photographic images in Figures 3A and 3B are assigned to a patient in group A who, at the time of admission for treatment, was 36 years old, weighed 109 kg, and had a BMI of 28.67. Underlying conditions included varicose leg ulcer (ulcus cruris varicosum), i.e., an "open leg" resulting from varicose vein disease, and asthma. Initial findings for this patient regarding diabetes mellitus, hypertension, liver disease, and chronic kidney disease (CKD) were all negative. The patient was a smoker. The photographic image in Fig.3A shows the ulcus cruris on the right leg in the area of ​​the medial maleolus, also known as the inner malleolus or tibial malleolus, at the time of admission for treatment, with the wound area measuring 3090 mm at that time. 2 The image in Fig. 3B shows the wound at the time after week 4 (T4) of treatment with clinoptilolite powder, in this case where the wound area has even decreased by about four-fifths to only 578 mm². 2The photographic images in Figures 4A and 4B are assigned to a patient in group A who, at the time of admission for treatment, was 76 years old, weighed 75 kg, and had a BMI of 29.30. Underlying medical conditions included diabetes, hypertension, and chronic kidney disease (CKD). Accordingly, the initial findings were positive for diabetes mellitus, hypertension, and CKD, whereas no liver disease was detected. The patient was a smoker. The photographic image in Figure 4A shows a leg ulcer on the patient's left lower leg at the time of admission for treatment, with the wound area measuring 11,585 mm² at that time. 2 The image in Fig. 4B shows the wound at the time after week 4 (T4) of treatment with clinoptilolite powder, where in this case the wound area is only 16.0 mm². 2The wound could be reduced, meaning that it has almost completely disappeared, except for a small remnant. Figures 5A to 7B show a portion of the photographic documentation illustrating the results of standard wound care (SoC) for group B, i.e., without clinoptilolite powder (MANC). The photographs in Figures 5A and 5B are of a group B patient who, at the time of admission for treatment, was 90 years old, weighed 69 kg, and had a BMI of 26.95. Underlying conditions from which the patient suffered, and which may be causally related to the chronic wound, include hypertension, chronic kidney disease, and diabetes mellitus. Accordingly, the initial findings regarding diabetes mellitus, high blood pressure (hypertension) and chronic renal insufficiency (cNI) were positive, whereas no liver diseases could be detected.The patient was a smoker. The photographic image in Fig. 5A shows a leg ulcer on the patient's left lower leg at the time of the photograph being taken for treatment, with the wound area measuring 4125 mm² at that time. 2 The figure in Fig. 5B shows the wound at the time after week 4 (T4) of a standard wound care (SoC) treatment, where hardly any improvement occurred and in this case the wound area even increased to 4375 mm². 2The photographic images in Figures 6A and 6B are assigned to a patient in group B who, at the time of admission for treatment, was 73 years old, weighed 58 kg, and had a BMI of 21.56. Her underlying medical conditions included stage IV peripheral arterial disease (PAD) on the left side, coronary artery disease (CAD), and aortic ectasia. The patient suffered from hypertension and stage II chronic kidney disease (CKD). Initial examinations were negative for diabetes mellitus and liver disease. The patient was a non-smoker. The photographic image in Figure 6A shows a massive, multi-part leg ulcer on the patient's left calf at the time of admission for treatment, with a wound area of ​​4213 mm². 2The illustration in Fig. 6B shows the multi-part wound at the time point after week 4 (T4) of a standard wound care (SoC) treatment, with a total wound area of ​​4885 mm². 2The photographic images in Figures 7A and 7B are assigned to a patient in group B who, at the time of admission for treatment, was 78 years old, weighed 97 kg, and had a BMI of 39.35. Underlying conditions included stage IV peripheral arterial disease (PAD) on the right side, hypothyroidism (overactive thyroid), and hypercholesterolemia. Initial findings were positive for diabetes mellitus and hypertension, but negative for chronic kidney disease (CKD) and liver disease. The patient was a non-smoker. The photographic image in Figure 7A shows a leg ulcer on the patient's right lower leg at the time of admission for treatment, with a wound area of ​​4390 mm² at that time. 2The figure in Fig. 7B shows the wound at the time point after week 4 (T4) of a standard wound care (SoC) treatment, with the wound area having increased by about a quarter to a total of 3262 mm². 2The wound area was reduced. However, there appeared to be little improvement in terms of redness reduction and smoothing of the wound edges. The results regarding wound area development show that the wounds treated with clinoptilolite powder exhibited a faster and overall greater reduction in wound area. The wound area decreased significantly more with clinoptilolite powder than with standard wound care (SoC). Clinoptilolite powder demonstrates a significantly greater benefit for the healing of critical chronic wounds than conventional wound care. Over the observation period, the wounds transformed from a chronic wound state to a physiologically healing wound.III. Further Observations and Conclusion Based on the verbal evaluation of both groups, the clinoptilolite powder demonstrated a significantly greater benefit in promoting the healing of critical, open wounds compared to standard wound care (SoC). The clinoptilolite powder better supported the formation of smooth wound edges, led to an improvement in the wound environment, resulted in a noticeable reduction in wound area, a decrease in redness, increased granulation, a reduction in fibrin deposits, and enhanced epithelialization. Furthermore, as a mineral wound dressing, the clinoptilolite powder supported wound drying, caused no pain, and also eliminated unpleasant wound odor. In all patients in treatment group A, the clinoptilolite powder achieved a faster and greater wound healing effect within the same treatment period than the standard wound care of control group B.In the clinoptilolite treatment, every patient experienced improved wound healing. The reduction in wound area after four weeks was significantly greater (p=0.02) with clinoptilolite than with conventional standard wound care (SoC). Clinoptilolite powder demonstrated a significantly greater benefit for the healing of critical chronic wounds than conventional wound care. Wound depth also decreased significantly with clinoptilolite powder, paralleling the reduction in wound area. During the observation period, the wound transitioned from a chronic to a physiological state. Outside of the study period, complete wound healing with closure was observed with continued treatment using clinoptilolite powder.During the visits, it was observed that wound maceration in treatment group A (clinoptilolite powder) differed from that in control group B (standard wound care). Maceration did not occur with clinoptilolite powder, yet the wound was neither dry nor cracked. Despite its hygroscopic properties, clinoptilolite powder did not function as a dry wound dressing like other wound powders. The mineral wound dressing formed by the clinoptilolite powder, due to the presence of moisture in the wound, created a moist environment beneath the wound. Particularly in patients where it was not possible to remove the clinoptilolite powder from the wound over several days, the interaction of the moist environment and the clinoptilolite powder on the wound resulted in the formation of a plaster-like layer, a "mineral plaster."As a result of granulation, the mineral wound dressing is shifted upwards and therefore did not initially need to be removed. Any remaining moist areas of the wound surface could easily be dusted with powder. Such a mineral wound dressing, acting like a "mineral plaster," conforms better to anatomical contours than a textile dressing used in standard wound care (SoC). Furthermore, the mineral wound dressing can eliminate the need for various other dressings. The clinoptilolite powder absorbs excess exudate and toxic substances more effectively than a conventional dressing used in standard wound care, as it can absorb both, even under compression bandages.The mineral wound dressing formed by clinoptilolite powder also helps maintain a moist environment and protects against drying out. The advantage over conventional wound dressings is that the mineral dressing adheres to the wound like a "second skin" (scab), thus creating an optimal environment for wound healing. This "second skin" also prevents bacterial penetration and helps protect against secondary infections. The mineral dressing visibly promotes the development of granulation tissue and apparently also encourages the formation of new blood vessels. Furthermore, the mineral dressing is easily removed without damaging the granulation or epithelial tissue, which reduces wound pain. Therefore, clinoptilolite powder is suitable as a mineral dressing for the treatment of chronic wounds.

[0002] Abbreviations: BMI Body Mass Index (body weight in relation to height in meters squared) Diabetes mellitus PAD Peripheral arterial disease Uc / UC Leg ulcer CNI Chronic kidney disease SoC Conventional wound care, standard wound care DVT Deep vein thrombosis

Claims

1. Claims 1. A mineral mixture containing clinoptilolite or clinoptilolite for use as a mineral wound dressing for the treatment of secondarily healing wounds of the skin and / or underlying tissue, in particular chronic, poorly healing, or non-healing wounds, wherein the clinoptilolite / clinoptilolite-containing mineral mixture is present in comminuted form as a powder or in comminuted form within a suspension.

2. A mineral mixture containing clinoptilolite or clinoptilolite for use according to claim 1, characterized in that the wound(s) is one or more chronic wounds in the form of a leg ulcer.

3. A mineral mixture containing clinoptilolite or clinoptilolite for use according to claim 1, characterized in that the wound(s) is one or more chronic wounds resulting from diabetic foot syndrome. 4.A mineral mixture containing clinoptilolite or clinoptilolite for use according to any one of claims 1 to 3, characterized in that the wound(s) is / are one or more infected and / or acute, malodorous wounds.

5. A mineral mixture containing clinoptilolite or clinoptilolite for use according to any one of claims 1 to 4, characterized in that the clinoptilolite / clinoptilolite-containing mineral mixture is applied directly to the wound and optionally to its surroundings.

6. A mineral mixture containing clinoptilolite or clinoptilolite for use according to any one of claims 1 to 5, characterized in that the clinoptilolite / clinoptilolite-containing...

2. Mineral mixture is comminuted by a micronization process.

7. Clinoptilolite or clinoptilolite-containing mineral mixture for use according to claim 6, characterized in that the particles of the powder consisting of the clinoptilolite / the clinoptilolite-containing mineral mixture have, after micronization, particle sizes that result in a mean diameter in the range of 8.0 µm to 12 µm.

8. A mineral mixture containing clinoptilolite or clinoptilolite for use according to claim 7, characterized in that a particle size distribution is present with a percentile value X10, below which 10% of all particles are found, in the range from 1.1 µm to 3.0 µm, with a percentile value X50, below which 50% of all particles are found, in the range from 5.0 µm to 10 µm, and with a percentile value X90, below which 90% of all particles are found, in the range from 20 µm to 26 µm. 9.A mineral mixture containing clinoptilolite or clinoptilolite for use according to claim 6, characterized in that the particles of the comminuted clinoptilolite / clinoptilolite-containing mineral mixture, which is present in a suspension, have particle sizes that result in a mean diameter in the range of 1.5 µm to 2.5 µm.

10. Clinoptilolite or a mineral mixture containing clinoptilolite for use according to claim 9, characterized in that a particle size distribution is present with a percentile value X10, below which 10% of all particles are found, in the range from 0.5 µm to 1.0 µm, with a percentile value X50, below which 50% of all particles are found, in the range from 1.5 µm to 2.5 µm, and with a percentile value X90, below which 90% of all particles are found, in the range from 3.0 µm to 4 µm.

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