CZ37951U1 - An antimicrobial polysaccharide transparent film for the treatment of early infections - Google Patents

Description

Antimicrobial polysaccharide transparent film for the treatment of early infections

Field of technology

The subject of the technical solution is a hydrogel cover intended for the treatment of infected skin defects with the possibility of monitoring the condition of the wound, prepared from biocompatible and biodegradable polymers, which is enriched with antimicrobial substances.

Current state of the art

Skin wound healing is a complex process that involves the interaction of a large number of cells and enzyme systems. Healing itself under physiological and pathophysiological conditions consists of four overlapping phases: hemocoagulation, inflammation, proliferation and remodeling. This process can be complicated by a number of external or internal influences. The most common cause of disruption of the healing process is the presence of microorganisms in the wound, which lead to the slowing down or complete stoppage of the wound closure phase, i.e. the persistence of the inflammatory phase. This leads to the risk of developing difficult-to-heal or non-healing chronic wounds. In order to prevent these adverse effects already at an early stage of healing, it is advisable to use antimicrobial wound covers, which suppress and eliminate the number of microorganisms and the risk of the development and persistence of infection from the moment of application to the wound.

The use of tailor-made hydrogel wound covers significantly increases the effectiveness of healing, as the material very well imitates the behavior of the skin (strength and elasticity), isolates the wound area from external influences and prevents disruption of the healing process, for example by the emergence of infection. Biomaterials represent a suitable choice for the production of skin coverings due to their natural properties, which include biocompatibility, biodegradability, suitable mechanical properties, gas permeability, sorption and water retention, which make them an ideal material for the production of wound coverings and substitutes in tissue engineering. Polysaccharides are a suitable material for the production of skin coverings not only in terms of their physico-chemical and biological properties, but also in terms of availability, renewability and financial simplicity.

An ideal skin covering mimicking skin in case of loss of its continuum should be fully biocompatible, non-toxic and partially or fully biodegradable. New tissue is formed under the skin cover, which should not adhere to the cover, and it should be possible to monitor the healing status of the wound through the cover material. In addition to the appropriate composition, the cover should have mechanical and elastic properties similar to the original skin, as well as sufficient absorption and retention properties. An equally important factor is the ability of the material to release the bioactive substance. The release of these compounds and the physical properties of the cover are significantly influenced by the internal and external structure of the material. Currently, similar active molecules are mainly used separately, in the form of solutions, which include, for example, Septoderm, Octenisept, Septonex, or iodine-containing solutions such as Betadine and Inadine®, but there is a risk of an allergic reaction when applying them. The hydrogel covers used today contain added antimicrobial components, but mainly these are silver ions, which, although they prevent the potential development of infection, can nevertheless cause allergic reactions. Antiseptic medical devices containing silver include Atrauman® Ag or Aquacel®, but the use of these materials has started to be withdrawn in recent years, precisely because of the increasingly frequent occurrence of allergic reactions. Among the transparent hydrogel coverings that are currently available on the market, we include Tegaderm® or Mepore®, which only provide mechanical protection of the wound against external contamination and bacteria.

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The essence of the technical solution

The subject of this technical solution is a transparent hydrogel cover intended for superficial wounds, which contains the natural polymer karaya resin, which is fully deacetylated, and the synthetic polymer polyvinyl alcohol and/or polyethylene glycol, as well as the plasticizer glycerol. The mass ratio of natural and synthetic polymer is in the range of 1:1 to 1:8. The mass ratio of polymers (karaya resin with polyvinyl alcohol and/or polyethylene glycol) to glycerol is in the range of 1:1 to 1:6. The hydrogel cover is further enriched with chemical or biological antimicrobial substances, i.e. antiseptics or bacteriophages.

Karaya resin is biocompatible, biodegradable and has mild antimicrobial properties. Karaya resin, optionally deacetylated, is used in the food industry under code E416.

Karaya resin is a natural high-molecular polysaccharide obtained in the form of resin from the Sterculia urens tree, so it is an affordable and renewable source of material with natural antimicrobial properties. Karaya resin is a biodegradable, non-toxic to the human body, biocompatible, partially degradable and resorbable biopolymer, which is insoluble in its native state, but swells in the presence of water. The full potential of karayi resin can be used after its chemical treatment by deacetylation, which promotes the solubility of the polymer, i.e. its affinity to water (deacetylation can be verified using infrared spectroscopy). Complete deacetylation yields a water-soluble biopolymer. The molar mass of deacetylated karaya resin is usually in the range of 2000 to 16000 kg/mol. The molar mass of deacetylated karaya resin can be determined using the SEC-MALS method.

Polyvinyl alcohol and polyethylene glycol are synthetic water-soluble polymers that form a strong and elastic three-dimensional polymer network that improves mechanical properties.

Polyvinyl alcohol is a water-soluble synthetic polymer produced by alkaline hydrolysis of polyvinyl acetate. Polyvinyl alcohol in the molar mass range of 10 to 130 kg/mol is preferably used. In biomedical applications, it is used for its suitable mechanical properties (high elastic modulus and mechanical strength), chemical stability, biocompatibility, non-toxicity for the human organism and the ability to form a cross-linked polymer network capable of holding a large amount of water without losing its mechanical properties. In biomedical applications, it is used as a drug carrier, scaffold, biosensor, or wound cover.

Polyethylene glycol is a synthetic water-soluble polymer used for its non-toxicity and biocompatibility in the biomedical industry as a drug delivery system, in tissue engineering and for surface modification. It is advantageous to use low molecular weight polyethylene glycol in the molar mass range of 200 to 600 g/mol, which is liquid in anhydrous form. Polyethylene glycol has an active hydroxyl group at both ends of the polymer chain and is widely used because it has the ability to form functional hydrogels in combination with other polymers. Mechanical properties and swelling are influenced by the molecular weight of the polymer, low molecular weight PEG increases the swelling and compressive strength of hydrogels.

The plasticizer glycerol contributes to the elasticity and transparency of the material. It is a water-soluble and biocompatible chemical molecule. Glycerol is a low-molecular compound that is widely used as a plasticizer, humectant, or for its antifreeze properties as a cryoprotectant. In higher concentrations, glycerol exhibits bactericidal and virucidal activity.

Antiseptics selected from the group of benzalkonium chloride, povidone iodine, carbethopendecinium chloride, hydrogen peroxide, octenidine dihydrochloride, and chlorhexidine can be contained in the hydrogel cover.

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In a preferred embodiment, the antiseptic contained in the hydrogel cover is octenidine dihydrochloride, which is an antiseptic with a non-specific effect that effectively eliminates microbial infection without the possibility of resistance. It is effective against gram-positive and gram-negative bacteria, but also against yeasts and fungi.

Improving the antibacterial properties of the hydrogel cover can also be achieved by using biological agents that are able to eliminate even resistant types of microorganisms. Bacteriophages, or phages, are viruses that attack bacteria, which are used as part of biological treatment for so-called phage therapy. The use of phage therapy is an option to effectively suppress and prevent infection with a minimal risk of developing resistance. The main essence of phage therapy is the elimination of a specific species, or strains of bacteria by lytic action. During this process, phages are able to multiply and eradicate even severe infections without the negative side effects common with antibiotics. Some types of phages are able to target specific strains of the Staphylococcus aureus species, gram-positive bacteria resistant to a wide range of antibiotics and responsible for serious diseases including, for example, skin abscesses or wound infections. In order to treat these wounds, it is necessary to find a suitable phage strain, its optimal concentration and a suitable carrier, which phage strain or phage cocktail (mixture of different phage strains) will suitably complement and act together in the wound. For example, 812K1/420 is a dsDNA phage suitable for the treatment of staphylococcal infections, it is biocompatible and non-toxic to the organism. The hydrogel according to the technical solution is therefore particularly advantageously enriched with one or more strains of phage eliminating strains of bacteria of the genus Staphylococcus, which includes, for example, strains of phage K, phage Twort, phage JK2(=812K1/420), phage philPLA-RODI, phage 187 or phage SA97 .

The hydrogel cover according to the technical solution is mechanically strong and elastic, but at the same time hydrophilic and able to absorb and retain a large amount of liquid in its structure.

The hydrogel cover can be prepared by drying in air or under reduced pressure, for example by lyophilization.

Antiseptic or bacteriophages can be added to the hydrogel during its preparation or can be adsorbed on the surface of the hydrogel cover after it has dried. They are preferably adsorbed on the surface.

In a large animal model (deep infection of the skin and soft tissues of a pig, duration of the experiment for 14 days), the antimicrobial effectiveness of the wound dressing according to the presented technical solution was confirmed, which suppressed the bacterial infection in the entire area and depth of the skin and soft tissue defect, but also accelerated healing and wound regeneration.

To verify and evaluate the antimicrobial effect of the presented technical solution, two methods were chosen, namely impressions from the surface of wounds and biopsy sampling of wound tissues. Both of these methods showed a 2- to 3-order reduction of the pathogen in wounds (from the original more than 6 to 7 log CFU/g of tissue and more than 1000 CFU/25 cm ² of wound surface) over the course of two-week experiments. Specifically, the cover with the phage preparation showed a reduction in the amount of pathogen in the tissue by 2.5 ± 0.7 log CFU/g tissue, which corresponds to successful treatment of the infection (reduction below 5 log CFU/g tissue).

Examples of implementing a technical solution

Chemicals:

Deacetylated karaya resin was obtained from commercial sources. Its molar mass was verified by the SEC (size separation chromatography) method with a MALS (multi-angle light scattering) detector HELEOS-II and RI (refractive index) detector Optilab T-rEX - both instruments from Wyatt Technology. Ultrapure water with the addition of 200 ppm sodium azide was used as the mobile phase. The specific refractive index increment dn/dc = 0.145 ml/g was

- 3 CZ 37951 U1 used to evaluate the results. Two Waters Ultrahydrogel Linear 300 x 8 mm columns were used for separation, the flow rate of the mobile phase was 0.6 ml/min. The weight average molar mass Mw = 3800 kg/mol was determined.

Polyvinyl alcohol was obtained from commercial sources, with a molar mass declared by the manufacturer of 90 kg/mol.

Polyethylene glycol was obtained from commercial sources, with a molar mass declared by the manufacturer of 400 g/mol (PEG400).

Example A

Freeze-dried hydrogel cover based on karaya resin and polyvinyl alcohol 1:1

The hydrogel cover is based on a lyophilized polymer solution of deacetylated karaya resin, polyvinyl alcohol, polyethylene glycol and glycerol in a weight ratio of 8:8:1:50. Aqueous solutions of karaya resin, polyvinyl alcohol with a weight ratio of 1:1, polyethylene glycol and glycerol were homogenized for 24 hours at 23 °C and then centrifuged to remove air bubbles. The homogeneous solution was then poured into 5 x 5 cm plastic dishes, frozen at -30 °C and then lyophilized at -35 °C at 1 mBar pressure for 15 hours. This was followed by secondary drying at 25°C under a pressure of 0.01 mBar (1 mBar = 100 Pa).

Example B

Lyophilized hydrogel cover based on karaya resin and polyvinyl alcohol 1:2

The hydrogel cover is based on a lyophilized polymer solution of deacetylated karaya resin, polyvinyl alcohol, polyethylene glycol and glycerol in a weight ratio of 5:10:1:50. Aqueous solutions of karaya resin, polyvinyl alcohol with a weight ratio of 1:2, polyethylene glycol and glycerol were homogenized for 24 hours at 23 °C and then centrifuged to remove air bubbles. The homogeneous solution was then poured into 5 x 5 cm plastic dishes, frozen at -30 °C and then lyophilized at -35 °C at 1 mBar pressure for 15 hours. This was followed by secondary drying at 25 °C under a pressure of 0.01 mBar.

Example 1

Hydrogel lyophilized cover with the addition of the antiseptic octenidine dihydrochloride

The hydrogel cover is based on a lyophilized polymer solution of deacetylated karaya resin, polyvinyl alcohol, polyethylene glycol and glycerol. The preparation of the material was the same as in example A. Subsequently, the antiseptic octenidine dihydrochloride in final concentrations of 0.05% by weight/cm ² dissolved in absolute ethanol was sorbed onto the lyophilized hydrogel covers of a given area. The samples were then dried at 60°C for 2 days.

Example 2

Hydrogel lyophilized cover with the addition of the antiseptic octenidine dihydrochloride

The hydrogel cover is based on a lyophilized polymer solution of deacetylated karaya resin, polyvinyl alcohol, polyethylene glycol and glycerol. The preparation of the material was the same as in example B. Subsequently, the antiseptic octenidine dihydrochloride in final concentrations of 0.1% by weight/cm ² dissolved in absolute ethanol was sorbed onto the lyophilized hydrogel covers of a given area. The samples were then dried at 60°C for 2 days.

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Example 3

Hydrogel lyophilized cover with the addition of the antiseptic octenidine dihydrochloride

The hydrogel cover is based on a lyophilized polymer solution of deacetylated karaya resin, polyvinyl alcohol, polyethylene glycol and glycerol. The preparation of the material was the same as in example B. Subsequently, the antiseptic octenidine dihydrochloride in final concentrations of 0.05% by weight/cm ² dissolved in absolute ethanol was sorbed onto the lyophilized hydrogel covers of a given area. The samples were then dried at 60°C for 2 days.

Example 4

Hydrogel lyophilized cover with the addition of the antiseptic octenidine dihydrochloride

The hydrogel cover is based on a lyophilized polymer solution of deacetylated karaya resin, polyvinyl alcohol, polyethylene glycol and glycerol. The preparation of the material was the same as in example A. Subsequently, the antiseptic octenidine dihydrochloride in final concentrations of 0.1% by weight/cm ² dissolved in absolute ethanol was sorbed onto the lyophilized hydrogel covers of a given area. The samples were then dried at 60°C for 2 days.

Example 5

Hydrogel lyophilized cover with addition of phage preparation

The hydrogel cover is based on a lyophilized polymer solution of deacetylated karaya resin, polyvinyl alcohol, polyethylene glycol and glycerol. The preparation of the material was the same as in Example A. Then, 1 ml of the phage preparation (strain 812K1/420) at a concentration of 108 PFU/ml was adsorbed onto a 5 x 5 cm lyophilized hydrogel cover and the cover was prepared for direct application to the wound.

Example 6

Hydrogel lyophilized cover with addition of phage preparation

The hydrogel cover is based on a lyophilized polymer solution of deacetylated karaya resin, polyvinyl alcohol, polyethylene glycol and glycerol. The preparation of the material was the same as for Example A. Then, 1 ml of the phage preparation (strain 812K1/420) at a concentration of 109 PFU/ml was adsorbed onto a lyophilized hydrogel cover measuring 5 x 5 cm, and the cover was prepared for direct application to the wound.

Example 7

Hydrogel lyophilized cover with addition of phage preparation

The hydrogel cover is based on a lyophilized polymer solution of deacetylated karaya resin, polyvinyl alcohol, polyethylene glycol and glycerol. The preparation of the material was the same as in Example B. Then, 1 ml of the phage preparation (strain 812K1/420) at a concentration of 108 PFU/ml was adsorbed onto a 5 x 5 cm lyophilized hydrogel cover and the cover was prepared for direct application to the wound.

Example 8

The hydrogel covers prepared in Examples A and B were subjected to dynamic mechanical analysis to test the material's maximum strength and elongation in the hydrated state. The measurement was carried out by a deformation test in which the samples were cut to a size of 0.5 x 3 cm and before

- 5 CZ 37951 UI each test also measured the thickness of the sample (0.50 to 1.00 mm). The base position of the holder was set at 0.5 cm and all measurements were taken from this distance. The samples were hydrated for 5 to 10 minutes at a temperature of 37 °C directly in the device in a special built-in chamber. All measurements were plotted with strain curves showing the relationship of stress to elongation. Measurements were performed on an RSA-G2 device from TA Instruments lne. (USA).

Table 1: Comparison of results of mechanical properties of hydrogel covers: effect of composition.

Labeling the example Karaya/PVA composition Maximum strength Maximum extension kPa 0/ /0 Example A 1/1 25.1 139.1 Example B 1/2 128.7 148.1

It follows from Table 1 that the effect of composition significantly affects the mechanical properties of hydrogel covers. A higher content of polyvinyl alcohol, especially in the hydrated state, when the hydrogel network expands, significantly increases the strength of the material and thus its resistance to breaking or tearing. Glycerol in the hydrogel acts as a plasticizer, in combination with polyvinyl alcohol it forms a synergy that increases not only the tensile strength, but also the maximum elongation (Example B). The hydrogel of Example A contains a lower amount of polyvinyl alcohol, which significantly affected the maximum strength, which was reduced compared to the other examples, however, the maximum elongation is comparable to Example B.

Example 9

The hydrogel covers prepared in Examples A, B and Examples 1 to 4 were subjected to an analysis that determines the sorption capacity of the hydrogel and its ability to retain liquid in the structure. The measurement was carried out by the gravimetric method, where a sample measuring 1x1 cm was immersed in a physiological solution (0.9 wt.% NaCl) and measured at certain intervals for 90 minutes at 37 °C, the temperature of the human body. The sorption capacity was calculated by the formula:

w _s sorption capacity (%) =--100 w _d where Wd corresponds to the weight of the dry sample and w _{s to} the weight of the hydrated sample. The results compare the original weight of a dry sample against a hydrated one, which retains more than 100% of its original weight as sorbed liquid.

Table 2: Comparison of the results of the sorption capacity of individual samples: influence of composition and additives.

Labeling the example Time (min) 1 10 40 60 90 Sorptive capacity i %) Example A 102.13 194.3 231.5 225.6 204.6 Example B 61.0 148.3 175.6 172.3 163.7 Example 1 100.3 171.3 163.9 153.7 131.5 Example 2 111.98 147.2 140.77 136.3 123.4 Example 3 55.5 129.6 154.3 153.5 149.1 Example 4 71.1 129.7 153.7 158.3 157.2

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It can be seen from Table 2 that Examples A, B have a different ability to absorb and retain liquid in their structure. This ability is influenced by the chemical composition of the hydrogels as well as the morphology of the final material. Absorption of liquid by the material without degradation is one of the main properties required for wet wound healing. In this state, the material retains its 3D structure for a long time, which ensures a moist environment for long-term healing of skin wounds. For Examples A and B, it can be observed that the material reached maximum absorption after only 40 minutes of measurement, and although its weight gradually decreases over time, the sample retains its structure and loses weight very slowly. Examples 1 to 4 have a lower sorption capacity compared to Examples A and B due to the presence of an adsorbed antiseptic, which does not affect the stability of the hydrogels in any way.

Example 10

The hydrogel covers prepared in Examples A, B and Examples 1 to 5 and 7 were subjected to testing for antimicrobial activity against strains of S', aureus (CCM 4750) and E. coli (CCM 3954) obtained from the Czech Collection of Microorganisms for susceptibility testing antimicrobial substances. Susceptibility testing was performed according to standards by the broth microdilution method according to EUCAST standards with some modifications. Test materials were tested in triplicate in a 24-well microtiter plate (JET BIOFIL, Guangzhou, China). Bacterial strains were cultured overnight in 10 ml Mueller Hinton broth (Merck, UK) at 37°C. These cultures were then centrifuged twice and resuspended in fresh MHB. Bacterial cultures were then diluted with fresh MHB to a final concentration of 5 χ 10 ^Λ 5 CFU/ml. 1 mL of the respective bacterial suspension was added to the test materials and sealed with sterile ThermalSeal® foils (Sigma-Aldrich, St. Louis, MO, USA). The plates were incubated at 37°C with shaking in a Tecan Infinite M200 PRO reader (Tecan Trading AG, Trasadingen, Switzerland) and the optical density (A = 600 nm) was measured every 5 minutes for 20 hours. The optical density in this measurement corresponds to the amount of bacteria in the culture. As the amount of bacteria in the culture increases, so does the optical density. If the optical density of the sample does not increase over time, it can therefore be concluded that the tested bioactive material has an antimicrobial effect against the tested strains.

Table 3: Comparison of antimicrobial susceptibility results of individual samples and additives.

Labeling the example Microbial strain time (hours) at 1 2 4 | 8 12 20 Optical Density (-) Example A aureus -0.0022 | 0.0367 0.2659 | 0.6421 0.7539 0.7864

E. coli -0.0003 0.1245 0.4212 0.4940 0.5668 0.628 Example B S. aureus 0.0005 0.0441 0.291 0.7230 0.89767 1.0508 E. coli -0.0080 0.1259 0.445 0.6420 0.7592 0.8595 Example 1 S. aureus 0.0009 -0.0017 -0.0013 -0.0023 -0.0031 -0.0034 E. coli -0.0016 0.0073 0.0082 0.0154 0.0155 0.0211 Example 2 S. aureus 0.0021 0.0058 0.0059 0.0066 0.0060 0.0049 E. coli 0.0043 -0.0029 -0.001 -0.0009 -0.0023 -0.0083 Example 3 S. aureus 0.0009 -0.0009 -0.001 -0.0028 -0.0034 -0.0049 E. coli 0.0022 0.0082 0.0067 0.0098 0.0095 -0.0007 Example 4 S. aureus 0.0012 0.0023 0.0025 0.0037 0.0029 0.0014 E. coli 0.0033 0.0015 0.0007 0.0005 -0.0063 -0.0093 Example 5 S. aureus 0.0923 0.0866 0.0876 0.0883 0.0893 0.0933 Example 7 S. aureus 0.0866 0.0857 0.0850 0.0846 0.0894 0.1020

From Table 3, it can be deduced that the materials of Example A and B do not have much antibacterial activity against bacteria by themselves, which is indicated by the increasing optical density, which means an increased number of bacterial cells, i.e. the materials themselves are not suitable for the treatment of infected wounds. In Examples 1 to 4, it can be observed that the optical density does not increase for both tested bacterial strains, which confirms the antibacterial effectiveness of both materials with different concentrations of antiseptic and thus supports its usefulness in the treatment of early infections caused by

CZ 37951 UI by both gram-positive (S. aureus) and gram-negative (E. coli) bacteria. Antibacterial tests in Examples 5 and 7 on the S. aureus strain confirm the antibacterial activity of the phage preparation, which is able to effectively suppress or even eliminate the bacterial infection (optical density does not increase again). This result indicates the applicability of bacteriophages in combination with GK hydrogel films for the treatment of wounds infected with staphylococcal strains.

Example 11

The hydrogel covers prepared in Examples 5 and 6 were tested on surgically reshaped full-thickness skin defects of a large animal model (Sus scrofa f. domesiicď) for antimicrobial activity against a .S', aureus strain (NRL/Atb 5921) obtained from the National Collection of Microorganisms reference laboratories for staphylococci. The bacterial strain was cultured overnight in 50 ml Mueller Hinton broth (Merck, UK) at 37°C. These cultures were then centrifuged twice and resuspended in fresh PBS. Bacterial cultures were then diluted with fresh PBS to a final concentration of 2 χ 10 ^Λ 9 CFU/ml.

A total of 4 representatives (Sus scrofa f. domesiicď) were included in the tested sample of animals. in which a total of 80 5x5 cm skin defects (20 defects per animal) were created in the back region simulating full thickness skin loss and muscle fascia damage. A staphylococcal inoculum was introduced into these defects, simulating a complicated infection of the skin and soft tissues by this pathogen.

After the successful induction of infection, hydrogel covers containing the phages described in Comparative Examples 5 and 6 were applied to these defects. The duration of the entire experiment was 14 days, during which period identical hydrogel covers (Examples 5 and 6) were re-applied on the 4th, 7th and 11th . the day after the induction of an infectious complication in the wound area. During these days, microbiological surveillance took place at the same time, and the obtained samples (quantitative biopsies) from the wounds were further processed by standard microbiological methods and the bacterial load in specific samples was determined.

Table 4 documents the therapeutic effect of the applied hydrogel covers containing the phages described in comparative examples 5 and 6 leading to the reduction of the bacterial population in specific samples. A statistically significant treatment effect was noted on days 11 and 14 of the experiment (p <0.001).

Table 4: Comparison of antimicrobial activity results (determined in CFU/ml ± SD) of applied hydrogel covers with phages under in vivo conditions.

The day of the experiment Day 4 Day 7 Day 11 Day 14 Control shots 6.1 ±0.37 6.4 ± 1.08 6.8 ± 0.64 7.2 ± 0.38 Example 5 6.9 ± 0.64 6.1 ±0.32 3.8 ± 0.28 4.4 ± 0.82 p-value (control vs. example 5) 0.020 0.612 <0.001 <0.001 Example 6 6.8 ±0.68 6.0 ±0.15 4.0 ± 0.82 4.4 ± 0.06 p-value (control vs. example 6) 0.039 0.510 <0.001 <0.001

Industrial applicability

The technical solution relates to a transparent, porous, non-absorbable hydrogel cover applicable to skin wounds to promote healing by providing an appropriate environment together with clearly defined antimicrobial properties. According to the technical solution, this cover is intended for clinical application in skin wounds of various etiologies and duration (acute and chronic non-healing wounds) with a risk of developing infectious complications or potential therapy of an already developed infection in the wound area (preventive or therapeutic indication).

Claims (3)

1. A hydrogel cover for covering superficial wounds, characterized by the fact that it contains the natural polymer karaya resin, which is fully deacetylated, and the synthetic polymer polyvinyl alcohol and/or polyethylene glycol, and also the plasticizer glycerol, and an antimicrobial substance selected from antiseptics and bacteriophages, while the mass the ratio of natural to synthetic polymer is in the range of 1:1 to 1:8, and the mass ratio of polymers to glycerol is in the range of 1:1 to 1:6. 2. A hydrogel cover for covering superficial wounds, characterized in that it contains the natural polymer karaya resin, which is fully deacetylated, and the synthetic polymer polyvinyl alcohol and/or polyethylene glycol, as well as the plasticizer glycerol, and an antimicrobial agent selected from octenidine dihydrochloride and phage K bacteriophages , phage Twort, phage 812K1/420, phage philPLA-RODI, phage 187 and phage SA97, wherein the weight ratio of natural to synthetic polymer is in the range of 1:1 to 1:8, and the weight ratio of polymers to glycerol is in the range of 1:1 up to 1:6. 3. A hydrogel cover for covering superficial wounds, characterized in that it contains the natural polymer karaya resin, which is fully deacetylated, and the synthetic polymer polyvinyl alcohol and/or polyethylene glycol, as well as the plasticizer glycerol, and an antimicrobial agent selected from octenidine dihydrochloride and phage K bacteriophages , phage Twort, phage 812K1/420, phage philPLA-RODI, phage 187 and phage SA97, while the mass ratio of natural and synthetic polymer is in the range of 1:1 to 1:8, the mass ratio of polymers to glycerol is in the range of 1:1 to 1:6, the molar mass of polyvinyl alcohol is in the range of 10 to 130 kg/mol and the molar mass of polyethylene glycol is 200 to 600 g/mol.