Sustainable hydrophobic coating for medical products

Abstract

The invention relates to a sprayable formulation based on natural raw materials for protecting against microorganisms and for the hydrophobisation of surfaces of medical products, in particular skin coverings.

Description

[0001] Sustainable hydrophobic coating for medical products

[0002] The present invention relates to a sprayable formulation based on natural raw materials for protection against microorganisms and for hydrophobizing surfaces of medical products, in particular skin coverings.

[0003] The functionalization of surfaces is a very common method for endowing materials with additional properties. Functionalizing surfaces and layers, i.e., aligning them with specific functions, helps traditional materials achieve new and improved properties.

[0004] Functionalization can be achieved by various processes, such as coating, chemical vapor deposition (CVD), electrochemically, whereby a covalent bonding of polymers, the adsorption of molecules / polymers to surfaces or film formation takes place.

[0005] In particular, the hydrophilization and hydrophobization of surfaces are of great interest. These can, for example, increase the tolerability of medications (hydrophilization to enable solubility of a drug) or prevent water penetration (hydrophobization), for example in rainwear.

[0006] Hydrophobic treatment is of great importance for medical devices. Hydrophobicized textiles can be given water-repellent properties, thus protecting a wound from water penetration, which can cause swelling of the cells and thus lead to scarring or a poor cosmetic outcome, as well as any germs that may be present within them. However, in the world of medical devices, the regulations for hydrophobic treatments are very strict; for example, the most common technologies, such as fluorine-based systems, are not permitted. Other technologies, such as the use of oils or waxes, also have some disadvantages, as these oils and waxes can either be of animal origin, have a high allergenic potential, adhere poorly to the textile surface, or impair the textile properties (for example, the material can become stiffer or change color).A recurring problem is the migration of germs, especially bacteria, viruses and fungi, through a skin covering into the underlying skin.

[0007] This immigration, i.e. the contamination of the covered skin area with germs, results from the type of skin covering, which is only in very few cases a closed, pore-free "film", but usually consists of a textile, which must also have a high level of breathability in order to avoid skin maceration.

[0008] Experts are familiar with adhesive bandages called “Bacteria Shield Plasters” from Beiersdorf AG in Hamburg, which achieve 99% blocking through a purely mechanical process, i.e., solely through a suitable selection of the woven backing material (see https: / / www.hansaplast.de / ratqeber / wundversorgung / bacteria-shield-pflaster). A clear disadvantage here is the limitation to the material of the adhesive bandage, in particular the backing material of the adhesive bandage, which must be more valuable, thicker and / or more tightly woven than non-protective materials and is therefore generally more expensive and / or less flexible. They are therefore less comfortable to wear than simple adhesive bandages.

[0009] In the context of the invention, textiles are understood to mean fabrics made of woven, knitted, nonwoven or nonwoven materials, as well as nets, permeable / holey / perforated films, foams and laminates as well as papers.

[0010] In particular, textile fabrics within the scope of the invention are understood to mean woven, knitted, warp-knitted fabrics and nonwovens made of interwoven fibers or spinnable material, wherein the fibers may be of natural (natural fibers) or synthetic (chemical fibers) origin.

[0011] Skin coverings in connection with the inventive method include, in particular, wound dressings, plasters, or self-adhesive bandages applied over wounds or scars / skin sutures to promote healing. For the purposes of the invention, however, skin coverings also include self-adhesive films or fabric / nonwoven sections applied to uninjured skin, for example, to protect against external influences. Good examples of this class of skin coverings are tapes, kinesiology tapes, or scar, wart, and blister plasters.

[0012] It is therefore advantageous if the infiltration of germs and water can be prevented or at least reduced. The object of the invention is to counteract the aforementioned disadvantages and to provide a preparation for the hydrophobization of textile fabrics that is also capable of preventing the infiltration of germs and water, regardless of the material, in particular regardless of the material's physical and spatial properties.

[0013] The invention addresses this problem with a specifically composed preparation. A first and general subject matter of the invention is a preparation for application to textile fabrics, comprising ethylcellulose, glycerin, castor oil, and a microbicidal active ingredient as essential components.

[0014] According to the invention, cellulose is preferably used as the natural polymer. Celluloses with a molar mass of 100,000 to 500,000 g / mol are advantageous according to the invention. Celluloses with a molar mass of 150,000 to 250,000 g / mol are particularly advantageous.

[0015] Antibacterial agents are preferred as microbicidal agents because the penetration of bacteria can cause the greatest damage.

[0016] The cellulose or cellulose derivative surprisingly absorbs wound secretions, allowing the film to be hydrated (“hydration” of the wound closure film). This allows water to “diffuse” through the wound closure film. The hydrated film can thus keep the wound moist, but not wet, thereby supporting wound healing.

[0017] With this invention, the germ permeability of any textile-based wound dressing can be increased and thus better protection of the wound can be ensured.

[0018] Glycerin, as used herein, refers to technical-grade glycerin for the pharmaceutical industry and cosmetic applications. It may therefore contain the usual traces of water (maximum 0.5% by weight) that are inherent in the manufacturing process. Tests have shown that no differences in performance are achieved with the purest glycerin (analytical grade).

[0019] The castor oil content increases the hydrophobic content of the film formed, which leads to increased adhesion of the film to the skin surface. Castor oil, as defined in the invention, is purified castor oil as approved for cosmetic and / or medicinal purposes (density: 0.95-0.97 g / cm³). 3 ; viscosity: approx. 1000 mPas).

[0020] According to the invention, it is advantageous if the preparation, in addition to the castor oil content, also contains a smaller content of a second vegetable oil, in particular sunflower oil. This additional vegetable oil ensures even greater water resistance of the film formed from the preparation on the skin.

[0021] The total oil content is advantageously not higher than 20% by weight.

[0022] The preparation according to the invention also contains antimicrobial active ingredients.

[0023] According to the invention, microbicidal active ingredients from the group of biodegradable active ingredients are chlorhexidine, AMP systems (antimicrobial peptide), proteins, enzymes and biguanide systems, but classic non-biodegradable active ingredients such as octenidine can also be used.

[0024] This is particularly interesting because such active ingredients normally require aqueous systems such as hydrogels to function as antiseptic agents. Thanks to the cellulose scaffold, they can also be used in the non-aqueous systems of the invention.

[0025] These antimicrobial agents can then kill bacteria, viruses, and fungi penetrating the surface of the coated skin cover. At the same time, they also ensure the preservation of the preparation according to the invention.

[0026] Antimicrobial agents are usually characterized by their positive charges. These can interact with the membranes of microorganisms through various mechanisms and often "destroy" these microorganisms. The length of the agents and their flexibility play an important role. AMPs are particularly interesting. These are sometimes more stable than proteins and enzymes with respect to solvents and the pH of the medium. AMPs are also characterized by their rapid action. Research has shown that combinations of positively charged amino acids, such as lysine or arginine, with long lipophilic amino acids, such as phenylalanine or tryptophan, are very effective. In addition, there are a large number of different AMPs, consisting of either short peptide sequences (2-8 amino acids) or long peptide sequences (10 to 40), and exhibit varying levels of effectiveness.

[0027] The shorter the AMP, the more important it is that it has a cationic and sterically demanding structure. Tripeptides that have demonstrated antimicrobial activity preferably consist of a combination of arginine, tryptophan, and / or phenylalanine and preferably have a structure with the following sequence: positively charged amino acid - hydrophobic and sterically demanding amino acid - positively charged amino acid. It is also known that modifications, for example, by attaching protecting groups, even at unusual sites, such as multiple tert-butylations on the aromatic ring of tryptophan, positively influence the antimicrobial properties of such AMPs.

[0028] According to the invention, it is also conceivable to use longer peptides as AMPs for this invention. One example could be palmitoyl tripeptide de-3 / 5, which, in addition to a slight antimicrobial effect, also simulates the naturally occurring thrombospondin-1 (TSP-1 sequence: Pal-Lys-Val-Lys; SYNO-COLL), which in turn promotes collagen formation and thus supports wound healing. Longer peptides such as RRP9W4N from Red Dead Discovery AB have also shown good antimicrobial properties and can also be used for this invention, as can AMPs from the LL-37, defensin peptide, and bacterial permeabilizing protein (BPI) families. Longer peptides composed of the same amino acid can also be used for this invention, such as e-poly-L-lysine.

[0029] Biodegradable active ingredients, AMP systems (antimicrobial peptides), proteins or enzymes are preferably used as antiseptic agents.

[0030] Conventional antiseptic agents with long-lasting activity are also of interest. Octenidine, chlorhexidine, and similar agents, in particular, demonstrate very good properties (see Figure 3).

[0031] By adding a slightly volatile solvent, the formulation consistency (especially viscosity, sprayability) can be adjusted so that the formulation can be spread or sprayed more easily.

[0032] According to the invention, it is also possible to apply the preparation as an aerosol, in which case the propellant gas can also function as a solvent. According to the invention, different solvents are suitable depending on the application method. For application as a solution, solvents boiling above room temperature up to 80°C, such as lower alcohols (such as ethanol and isopropyl alcohol), are advantageous. For application as an aerosol, common propellant gases such as propane, butane, mixtures of propane and butane, dimethyl ether, or nitrous oxide are advantageous.

[0033] The preparation advantageously has a viscosity in the range of up to 1500 mPas.

[0034] After application or spraying onto the textile fabric, the preparation forms a thin, transparent, breathable and extremely flexible film, if necessary as soon as the solvent has evaporated.

[0035] The film formed by the preparation according to the invention adheres excellently to various surfaces (textile, paper, skin) and imparts a very good hydrophobic effect to the carrier material.

[0036] The effect of the preparation according to the invention is illustrated by the following examples.

[0037] Figure 1 shows schematically in sample 10 the effect that develops when a textile carrier material (1) was impregnated with the preparation according to the invention so that the concentration was 0.001 g / cm 2 Figure 4 shows a photograph of the situation depicted in Figure 1.

[0038] The carrier material (1) in this example is a standard coffee filter, which is technically a paper fleece. Sample 10, located on the left in Figure 1, is treated with the preparation according to the invention, while sample 20, located to the right, is not.

[0039] Sprayed water forms small beads / droplets 3 on the treated surface of sample 10, which clearly stand out from the carrier material 1. If the carrier material were moved, these drops 3 would run down or be shaken off. In the untreated sample 20, however, the sprayed water seeped into the carrier material and did not form beads / droplets sitting on the surface, but only a wet spot 4. Samples 11 and 21 schematically show the condition after wetting in a side view of samples 10 and 20. The sprayable preparation used for the comparison test had the following components:

[0040] - Ethylcellulose (1.9%),

[0041] - Castor oil (2.6%),

[0042] - Glycerin (0.5%),

[0043] - Ethanol (45%) and

[0044] - Propellant gas propane / butane (50%)

[0045] What happens to a coating after the evaporation of the ethanol and the propellant gas from

[0046] - Ethylcellulose (38%),

[0047] - Castor oil (52%) and

[0048] - Glycerin (10%).

[0049] Figure 2 shows, in sample 10, schematically the effect that develops when a textile carrier material (1) was impregnated with the preparation according to the invention, so that the concentration was 0.001 g / cm 2 Figure 5 shows a photograph of the situation depicted in Figure 2.

[0050] The carrier material (1) in this example is a standard wound dressing, which is technically a fabric. Sample 10, located on the left in Figure 1, is treated with the preparation according to the invention, while sample 20, located to the right, is not.

[0051] Sprayed water forms small beads / droplets 3 on the treated surface of sample 10, which clearly stand out from the carrier material 1. If the carrier material were moved, these drops 3 would run down or be shaken off. In the untreated sample 20, however, the sprayed water has seeped into the carrier material and does not form beads / droplets sitting on the surface, but only a wet spot 4. Samples 11 and 21 schematically show the state after wetting in the side view of samples 10 and 20.

[0052] The sprayable preparation used for the comparison test contained the following components:

[0053] - Ethylcellulose (1.9%),

[0054] - Castor oil (2.6%),

[0055] - Glycerin (0.5%), - Ethanol (45%) and

[0056] - Propellant gas propane / butane (50%)

[0057] What happens to a coating after the evaporation of the ethanol and the propellant gas from

[0058] - Ethylcellulose (38%),

[0059] - Castor oil (52%) and

[0060] - Glycerin (10%).

[0061] Figure 3 shows the antimicrobial properties against Staphylococcus aureus of a coffee filter paper impregnated with a preparation from comparative experiments 1 and 2, whereby the preparation contains 0.1 wt.% octenidine (based on the preparation with solvent and propellant gas) in addition to the preparation according to comparative experiments 1 and 2.

[0062] Column A (Control Plate) shows bacterial growth on an untreated agar plate (corresponding to uncovered skin). This demonstrates that the bacteria thrive there and can proliferate rapidly.

[0063] Column B (Ctrl Filter) shows the bacterial growth after an untreated filter paper was placed on the agar plate, corresponding to the adhesive bandages known on the market with a low, purely “mechanical” protective effect, analogous to the Bacteria Shield technology.

[0064] Column C (Formula with 0.1% Octenidine) shows bacterial growth after a filter paper treated with the inventive preparation was applied to the agar plate. The filter paper was sprayed with the inventive preparation before application and then dried. The coating before application is intended to prevent the inventive preparation from being absorbed through the filter paper and contaminating the agar plate. If the inventive preparation were to directly wet the agar plate, the bacteriostatic agent contained therein would directly prevent bacterial growth. Therefore, it would not be possible to determine the extent of contamination by bacteria migrating through the sample material.

[0065] The sample materials (with and without the preparation of coated filters according to the invention) were stored at room temperature for 10 days and then measured according to an abbreviated DIN EN 58953-6 test to determine the effectiveness of the coating. The prepared sample materials were placed on the agar plate, and a total of 5 drops (each containing 100 μl) of an aqueous suspension containing Staphylococcus aureus (concentration: 10 7 ) given.

[0066] The incubation time was three hours. This was intended to demonstrate the permeability of the sample material—which can also be applied to films and membranes—when they come into contact with bacteria, as well as the lasting effect of the coating over many days.

[0067] The unabsorbed bacterial suspension is then carefully pipetted away, and the sample material is removed. The agar plate is then incubated for 24 hours to allow the bacteria to grow. Finally, the number of bacteria that have passed through the filter onto the agar and have multiplied is counted.

[0068] As can be seen in Figure 3, the bacteria incubated on the film pretreated with the preparation (Sample C) were significantly reduced. Compared to the uncovered agar plate (Sample A), the reduction was approximately 10g4, corresponding to a reduction of 99.99% (ten-thousandths) of the bacteria. Compared to Sample B, which corresponds to the Bacteria Shield technology, a reduction of approximately 10g3, or one-thousandth fewer bacteria, was achieved.

[0069] This comparative experiment thus shows that untreated filter paper (Sample B - Ctrl Filter) cannot effectively prevent the permeability of S. aureus. Filter paper coated with a preparation according to the invention (Sample C), treated with the preparation from Comparative Experiments 1 and 2 and subsequently stored for 10 days at room temperature and with normal sunlight exposure, showed a significant reduction in the incubated bacteria.

[0070] The experiment shows that even very simple materials (filter paper is thin and relatively coarse-pored compared to this) achieve extremely satisfactory protection. The preparation according to the invention and its coating also have the advantage of being very suitable for use both in doctor's offices and outside, in private settings or in emergency care. Sterilized skin coverings are certainly essential in the clinical setting; for the majority of necessary wound care procedures that are performed using non-sterilized skin coverings, spraying / coating with the preparation according to the invention represents a major advance in wound hygiene and contributes to faster healing.In addition, the preparation according to the invention is absolutely skin-compatible and, when sprayed / coated, only leads to a brief feeling of cold due to the evaporating solvent, even if it comes into contact with uncovered skin areas around the skin covering.

[0071] As has been shown, the protective effect does not depend solely on the microbicidal active ingredient in the preparation according to the invention and its use; the impregnating effect produced by the applied preparation also plays a decisive role. The most common way for microorganisms to penetrate a skin covering / wound dressing onto the covered skin or into the covered wound is by wetting the skin covering. It does not matter whether there are already germs on the surface of the skin covering, e.g. from dry soiling, or whether the wetting liquid itself is contaminated. The liquid acts as a transport medium, which, due to the impregnation, can no longer penetrate the skin covering, or can only penetrate it very slowly. As a result, even small amounts of a microbicidal substance in the "coating" are sufficient to very effectively prevent the microbes from multiplying or to kill them off.

[0072] The inventive preparation and its use exhibits a synergistic and inventive effect of impregnation and inhibition of microorganisms that is unforeseeable for the person skilled in the art.

Claims

Patent claims 1. Hydrophobic preparation containing - 28 to 42% by weight (dry weight) cellulose and / or cellulose derivative, - 42 to 56% by weight castor oil, - 14 to 16% by weight glycerol, - 0.01 to 0.5% by weight of at least one microbicidal active ingredient, wherein the preparation components are dissolved in a biocompatible solvent so that the solution is sufficiently low-viscosity to be sprayed.

2. Preparation according to claim 1, characterized in that the preparation has a viscosity in the range of 10 to 1500 mPas.

3. Preparation according to claim 1, characterized in that the cellulose and / or cellulose derivative is exclusively ethylcellulose.

4. Preparation according to at least one of the preceding claims, characterized in that the body-compatible solvent is selected from the group of alcohols.

5. Preparation according to claim 15, characterized in that the biocompatible solvent is ethanol.

6. Preparation according to at least one of the preceding claims, characterized in that the cellulose and / or cellulose derivative has a molar mass of 150,000 to 250,000 g / mol.

7. Preparation according to at least one of the preceding claims, characterized in that it contains an antiseptic active ingredient as the microbicidal active ingredient.

8. Preparation according to at least one of the preceding claims, characterized in that the antiseptic active ingredient is selected from the group of bisguanidines or from the group of polyamides.

9. Preparation according to at least one of the preceding claims, characterized in that the antiseptic active ingredient is at least one polyhexanide.

10. Preparation according to at least one of the preceding claims, characterized in that the antiseptic active ingredient is at least one AMP.

11. Preparation according to claim 10, characterized in that the AMP comprises at least one of the amino acids from the group arginine, tryptophan and phenylalanine. Preparation according to at least one of the preceding claims, characterized in that the antiseptic active ingredient is selected from the group of bacteria-permeabilizing proteins (BPI). Preparation according to at least one of the preceding claims, characterized in that the antiseptic active ingredient is a peptide. Preparation according to claim 13, characterized in that the antiseptic active ingredient comes, for example, from the family of LL-37 or the defensin peptides. Preparation according to claim 13, characterized in that the peptide consists of arginine, lysine, or histidine as the cationic amino acid and phenylalanine and / or tryptophan as the demanding amino acid. Preparation according to claims 13 to 15, characterized in that the peptide is composed of three to thirty amino acid units, in particular three to five amino acid units.Preparation according to at least one of the preceding claims, characterized in that the antiseptic active ingredient is chlorhexidine and / or octenidine. Use of a preparation according to at least one of the preceding claims for the hydrophobization of textile fabrics. Use according to claim 18, characterized in that the textile fabric is intended as a carrier material for wound care articles, in particular wound dressings, plasters, and bandages. Pump spray comprising a preparation according to at least one of the preceding claims, characterized in that it has the following contents: 2.3% ethylcellulose, 3.2% castor oil, 0.7% glycerol, 93.8% ethanol, and a microbicidal active ingredient.Aerosol spray comprising a preparation according to at least one of the preceding claims, characterized in that it has the following contents: 1.9% ethylcellulose, 2.6% castor oil, 0.5% glycerin, 45% ethanol, and a microbicidal active ingredient dissolved in propane / butane 40 / 60. A method for hydrophobizing textile fabrics, characterized in that a preparation according to at least one of claims 1 to 18 is applied to the textile fabric in a first step, and in a second step, any solvent present is evaporated. A method for hydrophobizing textile fabrics, characterized in that a textile fabric is placed on a body and secured thereto, and then the textile fabric resting on the body is wetted on the outside with a preparation according to at least one of claims 1 to 18, wherein the textile fabric is part of a wound covering, a plaster, a dressing material, an orthosis, a rigid bandage (plaster cast, plastic cast), a tubular bandage, or a wrap bandage. 4.Method for protecting skin areas covered with textile fabrics against microbial contamination, characterized in that a textile fabric is placed on a body and fastened thereto, then the textile fabric lying on the body is wetted on the outside with a preparation according to at least one of claims 1 to 18, wherein the textile fabric is part of a wound covering, a plaster, a dressing material, an orthosis, a hard dressing (plaster cast, plastic cast), tubular dressing, wrap dressing.

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