DK201300152Y3 - Antimicrobial blend and a cover to support wound healing and having an antimicrobial activity - Google Patents

Abstract

The invention relates to an antimicrobial composition for healing of superficial wounds based on a physiologically acceptable hyaluronic acid salt, optionally with one or more other polysaccharides, and a compound having an antimicrobial activity which can be used to cure superficial wounds, especially chronic ulcers, e.g. varicose ulcers. , and a cover containing said mixture.

Description

in DK 2013 00152 Y3

Antimicrobial blend and a wound-supporting cover with antimicrobial activity.

FIELD OF THE INVENTION

The invention relates to a composition for healing of superficial wounds based on a physiologically acceptable hyaluronic acid salt, optionally with one or more other polysaccharides, and a compound having an antimicrobial activity which can be used to cure superficial wounds, especially chronic wounds, for example varicose ulcers, and a cover containing said mixture.

BACKGROUND OF THE INVENTION Wound healing, especially abnormal wound healing, is a complicated process supported by a cover which provides adequate healing conditions and / or contains active compounds. Abnormal wound healing includes conditions of excessive wound healing (such as fibrosis, adhesion, and contractures), or, more commonly, inadequate wound healing (such as chronic varicose ulcers or diabetic wounds). Despite many new, significant advances in the field, abnormal wound healing still represents the cause of high costs, disease rates and mortality. All of this highlights the importance of providing an optimal environment for wound healing, which can positively impact the healing process (Stephanie R. Goldberg, Robert F. Diegelmann: Wound Healing Primer, Surgical Clinics of North America, Volume 90, Issue 6, December 2010, p. 1133 to 1146).

A brief overview of the literature dealing with the topic of wound healing is e.g. presented in the publication of James R. Hanna, Joseph A. Giacopelli: A Review of Would Healing and Wound Dressing Products, The Journal of Foot and Ankle Surgery, Volume 36, Issue 1, January-February 1997, pp. 2-14. In particular, the authors discuss the importance of a suitable wound covering, which ensures the optimal environment for wound healing. It is described that modern 2 DK 2013 00152 Y3 covers usually consist of more than one layer and that the contact layer has the greatest effect on healing.

There are many commercial products on the market today, however, which do not adequately meet the important requirements imposed on wounds or the production costs are high and therefore large-scale use is limited. As a rule, various gel-forming natural or synthetic substances are used which are capable of controlling humidity. However, these substances essentially only regulate moisture within the wound and do not support the body's self-regeneration ability. In addition, the use of such substances reduces gas permeability and therefore the wound respiration is blocked. Infections are eliminated by using disinfectants before the dressing is applied, which means the disinfection effect is only short-lived. These wounds cannot be used for chronic wounds because there is a risk that the humid environment may promote infection multiplication and thereby significantly aggravate the patient's condition.

Many patents and publications describe the use of hyaluronan as the main component of wound covers, but due to the high cost, these formulations are not used very commercially. Therefore, the practical use of hyaluronan remains directed only to intra-somatic (intra-articular injections), optional for special applications (ophthalmology, eye drops for eye contact moisturization for contact lens patients).

Commercial use of hyaluronan is illustrated with the preparation described in US Patent 4736024 based on hyaluronan combined with another active substance. In particular, the product is intended for ophthalmology, and the pharmacologically active substances used include e.g. kanamycin, neomycin, tetracycline, chloramphenicol and combinations thereof.

US Patent 5,128,136 discloses a composition used to prevent wound dehydration and infection, i.e. for a similar purpose as the preparation presented. However, unlike the composition of the invention, it contains soluble collagen as the main component, which does not affect wound healing, and it does not contain hyaluronic acid or salts thereof. The disadvantage of US Patent 5128136 is that collagen can cause undesirable reactions such as inflammation. Another disadvantage is that after use, the liquid transforms its phase into a solid gel, which blocks the gas permeability.

Content of the invention

The above mentioned disadvantages of the existing compositions which support wound healing are eliminated by the composition of the invention, the mixture comprises a physiologically acceptable hyaluronic acid salt and an antimicrobial substance selected from the group consisting of octenide dihydrochloride, cetrimide, benzalconium chloride, benzalconide chloride, benzalconide chloride, benzalconide chloride carbethopenedecinium bromide, cetyltrimethylammonium bromide, and a mixture thereof in any ratio. The mixture may further contain one or more polysaccharides selected from the group comprising the naturally occurring or modified polysaccharides hyaluronan, xanthan, schizophyllan, chitosan, glucan, alginate, cellulose, β-1-3-glucan and a mixture thereof; and optionally also an adjuvant which increases the antimicrobial effect, for example a chelating agent such as EDTA, betaine and 2-phenoxyethanol. The mixture may optionally also include a saccharide selected from the group consisting of glucose, fructose and sucrose, and / or an electrolyte selected from the group comprising sodium chloride, potassium chloride, potassium iodide, magnesium chloride, sodium hydrogen phosphate, sodium dihydrogen phosphate, zinc sulfate, and / or a plant extract or other natural product. selected from the group consisting of bipropolis, olive oil, tea tree oil, oak extract, marigold, mint or citrus fruit, or a mixture of any combination of said substances.

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The composition of the invention preferably comprises hyaluronan and octenide dihydrochloride as the antimicrobial substance, preferably in a weight ratio of 500: 1.

The term modified polysaccharide means a polysaccharide having a covalently bonded molecule or functional group wherein this molecule may be the same polysaccharide or another polysaccharide, synthetic polymer or polymerized or cross-linked polysaccharide consisting of identical or different molecules.

The mixture may take the form of a chemical or physical blend, wherein the chemical blend is preferably an aqueous solution containing alcohol and the physical blend is preferably a layer of polysaccharide fibers containing an antimicrobial substance in its structure.

The invention further relates to the tire to support the wound healing, which is in the form of a single layer or multi layer formation. The multilayer formation comprises layers arranged in the following direction from the wound: the contact layer (K) which, on a side to be in contact with the wound, is provided with the coating (P) made of polysaccharides with an antimicrobial substance, i.e. prepared from the above-mentioned mixture according to the invention (the chemical or physical mixture), then one or more absorption layers (A) and the surface layer (R). Therefore, the lower contact layer (K) contains at one (lower) side, intended to contact the wound, the coating (P) made from the mixture of polysaccharides with an antimicrobial substance, and the other (upper) side abuts one or the other. several layers of absorption (A, or Al, A-2, etc.). The upper side of the last upper absorption layer, which is the furthest from the wound, abuts the surface layer (R). All layers can be welded together at the edges, forming the so-called tea bag with dimensions of e.g. 10 x 10 cm. In the case of the one-layer tire, the formation consists only of the contact layer (K) with the coating (P) made from the mixture of polysaccharides with an antimicrobial substance, wherein the contact layer (K) may be composed of textile with a high absorption capacity (K). it can also be a super absorbent).

The contact layer is preferably made of woven or knitted fabric made of polyamide (PAD) monofilaments, optionally of staple fibers; of nonwoven textile or a porous membrane, polyurethane, polyester, viscose, blends of said fibers or other materials, for example synthetic fibers such as polypropylene. The coating (P) may preferably be in the form of a freeze-dried product or a dried coating, more specifically in the form of a freeze-dried or dried layer of the chemical mixture or a layer of the physical mixture. The absorption layer (s) are preferably made from materials selected from the group comprising polyester, viscose, polyamide, polyethylene, polypropylene, polysaccharide, for example xanthan or cellulose derivative, superabsorbent, a combination of woven or nonwoven textile fibers and superabsorbents, or a mixing said materials. In the case of multiple absorption layers (A), it is preferred to arrange them in such a way that the absorption capacity gradient is increased in the direction of the wound, e.g. the absorption layer (A-1) is close to the wound made of 100% polyester, and the absorption layer (A-2) further away from the wound is made of 1: 1 polyester and viscous mixture. The surface layer (R), preferably made of nonwoven polyester fabric, may optionally have an antimicrobial modification by impregnating with a suitable antimicrobial substance or by using antimicrobial fibers, for example obtained from bamboo, or by silver content. microparticles.

The coating (P) may be composed of a layer of precipitated polysaccharide fibers coated with a layer of an antimicrobial solution of substance wherein the amount of the polysaccharide coating is at least 0.1 mg / m2 and the amount of coating of the antimicrobial substance is at least 0.0001 mg / m2. If hyaluronan is used as the polysaccharide and octenide dihydrochloride is used as the antimicrobial substance, then the amount of hyaluronan coating is in the range of 1 to 50 g / m2 and the amount of octenide dihydrochloride coating is in the range of 0, 0001 to 0.5 g / m2. The most preferred amount of the hyaluronone coating is in the range of 5 to 20 g / m2 and the amount of the octenide dihydrochloride coating is in the range of 10 to 40 mg / m2.

The contact layer (K) and the surface layer (R) may be secured to each other at their edges to close the absorption layer (s) (A) between the contact layer (K) and the surface layer (R), e.g. For example, the edges of the contact layer (K) and the surface layer (R) can be welded together.

Brief description of the figures

Figure 1 represents a cross-section of the tire, the lower side being the contact layer K composed of 100% polyamide with the coating P of the mixture of polysaccharides and the antimicrobial substance, then the first absorption layer A1 composed of 100% polyester, the second absorption layer A-2 composed of a mixture of 50% polyester and 50% viscose, and over this surface layer R composed of 100% polyester. Layers K and R are welded together as a "tea bag" where there are absorption layers inside instead of tea.

Figure 2 represents a section of the coverage area from the direction of the polysaccharide coating. The edge S is formed by a weld (the layers marked as K and R in Figure 1 are welded), part N is the coating composed of the mixture of the polysaccharides and the antimicrobial substance.

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Figure 3 represents a graph showing the wound healing efficiency of a fast rat model where the healing wound area was measured versus the healing time, using the cover of Example 1 and using a gauze bandage without any preparation (i.e., without polysaccharides and without antimicrobial substance).

Figure 4 represents a graph showing the wound healing efficiency of a fast miniature pig model where the healing wound area was measured versus the healing time, using the cover of Example 1 and using a control dressing with the same structure made of the same textile materials, with no preparation coating (i.e. without polysaccharides and without antimicrobial substance).

Figure 5 represents a graph showing the effectiveness of the overall antimicrobial effect of the preparation of Example 1 and the control dressing (see description related to Figure 4) on a miniature pig model.

Figure 6 represents a graph showing the antimicrobial effect of the composition of Example 1 and the control dressing (see description related to Figure 4) on "G" rods on a miniature pig model.

examples

Example 1 Cover with hyaluronan, octenide dihydrochloride and two different absorbent layers, lyophilized

Dissolve octenide dihydrochloride (10 mg) in 1 ml of absolute ethanol, then take 30 μΐ of this solution to 10 ml of sterile water for injections. Sodium hyaluronan (150 mg) of molecular weight 1650000 g / mol is gradually added to this solution with stirring and stirred for 12 hours. The resulting viscous solution is evenly applied using a 8 mm 2013 Y3 template with a width of 1 mm and the hole 10 x 10 cm on the supporting fabric (contact layer) with the dimension 13 x 13 cm, the supporting textile is a 40 g / m2 knitted trimming cloth made of monofilaments of 22 dtex-polyamide "M". The contact layer with the applied coating attached to a suitable support is immediately frozen to -70 ° C and then transferred to the freeze dryer (the coating must remain frozen) and freeze dried. The resulting sponge-like, porous, elastic freeze-dried product with white color adheres to the contact layer, it is partially inside the textile material, but most of the deposited material is on one side of the textile. The contact layer is positioned in such a way that the freeze-dried product is in contact with the base on which it resides, for example, with the table or frame on which the fabric is stretched (i.e., most of the coating is directed to the base), and a square of 10 x 10 cm of a 140 g / m2 nonwoven fabric made of polyester (the first absorbent layer) is placed thereon. On the first absorbent layer is placed the second absorption layer (a 10 x 10 cm square of a 140 g / m2 nonwoven fabric made of polyester and 1: 1 viscose). On the second absorbent layer is placed the surface layer made of 30 g / m2 nonwoven polyester with the dimensions 13 x 13 cm. The tire is completed by welding the contact and surface layers at a suitable distance from the absorption layers to prevent them from being damaged by heat. The final product (a square of about 11 x 11 cm) is then produced by cutting off the excess edges of the contact and contact layers.

The resulting square tire is applied to the wound with the contact layer against the wound and then secured by a secondary tire. On a very exuding wound, a dry cover is applied. On slightly exuding wounds, the contact layer is moistened with 5 to 10 ml of physiological solution, sterile water or drinking water before application. On dry wounds, it is always necessary to moisten the cover with 10 ml of a suitable liquid (examples mentioned above). This cover can be left on the wound for up to 3 or 4 days, and then reconnected. In cases of massive exudate, only the secondary tire is changed as often as necessary, the primary tire is not changed. The absorption capacity of the secondary tire can be increased by using any commercially available superabsorbent or other suitable system.

Example 2 Cover with hyaluronan, octenide dihydrochloride and two different absorption layers, dried

Dissolve octenide dihydrochloride (10 mg) in 1 ml of absolute ethanol and take 30 μΐ of this solution into 10 ml of sterile water for injections and isopropanol 1: 1 (ie 50% solution of isopropanol). Sodium hyaluronan (150 mg) of molecular weight 1650000 g / mol is gradually added to this solution with stirring and stirred for 30 minutes. The resulting viscous solution is evenly applied using a template of 1 mm width and the hole of 10 x 10 cm on the supporting fabric (contact layer) with the dimension 13 x 13 cm, the supporting textile is a 40 g / m2 knitted trimming cloth made of monofilaments of 22 dtex-polyamide "M". The contact layer with the deposited solution attached to a suitable support is oven dried at 40 ° C for 2.5 hours or a suitable drying profile is used (eg drying at 40 ° C for 60 minutes, heating to 70 ° C for 30 minutes, delay at 70 ° C for 15 minutes, then cooling to 40 ° C). The resulting glassy, elastic, clear (colorless) film adheres to the contact layer, it is partially within the textile material, but the majority of the deposited material is on one side of the textile and has the same structure as the support surface to which the fabric was attached; if the support is smooth, the film is also smooth; a more preferred is a relief with small recesses. The contact layer is positioned in such a way that the coating is in contact with the base (ie the majority of the coating is directed towards the base) and a square of 10 x 10 cm of a 140 g / m2 nonwoven is made of fabric. of polyester (the first absorption layer) is placed thereon. On the first absorbent layer is placed the second absorbent layer, which is a 10 x 10 cm square of a 140 g / m2 nonwoven fabric made of polyester and 1: 1 viscose. On the second absorption layer is placed the surface layer, made of 30 g / m2 nonwoven polyester with the dimensions 13 x 13 cm. The tire is completed by welding the contact and surface layers at a suitable distance from the absorption layers to prevent damage from heat. The final product (a square of about 11 x 11 cm) is then produced by cutting off the excess edges of the surface and contact layers.

The resulting cover is applied to the wound with the contact layer facing the body in the same manner as in Example 1. The difference between the film and the freeze-dried product is that the film is less porous to gases and dissolves more quickly. Therefore, it is preferred to use the film especially in the first phase of the healing process when the chronic wound is to be converted to the standard healing process. When the second phase begins, ie. when the solid granulation tissue begins to form, it is possible to use the freeze-dried or other cover instead, in the event of the granulation tissue being entangled into the tire.

Example 3 Cover with hyaluronan, octenide dihydrochloride and two different absorbent layers, fibrous

Sodium hydroxide (6 g) is dissolved in 100 ml of sterile water and then 8 g of molecular weight sodium hyaluronan is added 1650000 g / mol gradually with stirring and the solution is stirred for 12 hours. The resulting viscous solution is filled into a syringe and extruded into the settling bath composed of 400 ml of concentrated acetic acid (about 98%) and 100 ml of isopropanol (about 99%). The resulting fibers are left in the bath and their length can be modified, for example, by means of rapidly rotating knives (for example, in a machine similar to the normal mixer). The solution of shorter fibers is then filtered through the contact fabric and a suitable porous membrane (e.g., a fixed panel with drilled holes on which the fabric is placed) to form a layer of fibers having the capacity of about 15 g / m2. Optionally, the coating of fibers can be prepared on a porous membrane and then transferred (for example, by "reprint" on the contact layer). The fiber layer of the contact fabric is washed with a suitable liquid, e.g. a mixture of isopropanol and water (the concentration of isopropanol must be higher than 60% to ensure that the fibers do not dissolve). The washed layer is then pressed in a defined manner to attach the fibers to the base and to each other without damaging the porous structure. As a result, the size of the support or contact fabric and the layer of fibers is modified in such a way that a 13 x 13 cm square of the contact layer with the 10 x 10 cm fiber coating is obtained. Dissolve octenide dihydrochloride (10 mg) in 1 ml of absolute ethanol, after which 30 μΐ of this solution is taken up to 2 ml of a mixture of sterile water for injections and isopropanol 1: 1 (ie 50% isopropanol). Octenide dihydrochloride solution is then applied homogeneously over the entire fiber coating area, e.g. by spray coating, and optionally, the fibers are pressed (a small solution of the fiber surface occurs, which improves the attachment of the fibers to each other and the attachment of the fibers to the contact fabric). In this way, octenide dihydrochloride, i.e. the antimicrobial substance, into the polysaccharide fiber structure, and a physical mixture of polysaccharide (s) and antimicrobial substance is formed. The fiber-coated contact layer attached to a suitable support is oven-dried at 40 ° C for 2.5 hours or a suitable drying profile is used (e.g., drying at 40 ° C for 60 minutes, heating to 70 ° C for 30 minutes, delay at 70 ° C). For 15 minutes, then cooling to 40 ° C). Further treatment to obtain the wound cover and its use is the same as in Example 1. The fiber coating is more porous than the film made in Example 2, but at the same time the structure of the pores is different from that of the freeze-dried product described in 12 DK 2013 00152 Y3

Example 1. The properties of the fiber-coated coating are more similar to those for the freeze-dried product than those for the film.

Example 4

Substitution of part of hyaluronan with another substance or mixture of substances

A similar process is used as in Example 1, 2 or 3, but 0.1 to 99.9% of hyaluronan is replaced with another polysaccharide, for example, with cellulose derivatives, xanthan, alginate, schizophyllan, chitosan, glucan, or with a saccharide, for for example glucose, fructose, sucrose or with an electrolyte, for example, with sodium chloride, potassium chloride, potassium iodide, magnesium chloride, sodium hydrogen phosphate, sodium dihydrogen phosphate, zinc sulfate, or a plant extract, or a suitable natural product, for example, propolis, olive oil, extract oil oak, marigold, mint or citrus fruit, or any combination of said substances. The formulation can be easily modified by using 0.1 to 99.9% of the starting amount of hyaluronan and a higher amount of a different substance or mixture of substances than the original amount of hyaluronan. For example, only 10 mg of hyaluronan is used instead of 150 mg of hyaluronan in the formulation of Example 1, and 150 mg of xanthan is added so that the total amount of polysaccharides is higher than the original amount of hyaluronan (160 mg of the mixture compared to the original 150 mg ). Other substances or mixture of substances may be used up to the concentrations corresponding to their saturated solutions. The purpose of this modification is to obtain a hypertonic environment which is advantageous for some stages of wound healing in particular, most of chronic wounds (especially necrosis resolution).

Example 5

Substitution of octenide dihydrochloride with another substance or mixture of substances 13 DK 2013 00152 Y3

A similar process is used in Examples 1, 2, 3 or 4, but octenide dihydrochloride is replaced with another suitable antimicrobial substance at a suitable concentration (calculated here per area of 10 x 10 cm). For example, 1.5 mg of benzalconium chloride may be used; 3.5 mg of chlorhexidine; 0.5 mg PHMB; or a mixture of any combination of different amounts of said substances with octenide dihydrochloride, optionally without octenidine hydrochloride.

Example 6

Evaluation of the efficacy of the preparation (antimicrobial efficacy tests, preclinical assessment)

Models used, brief description

The antimicrobial efficacy was tested in vitro. The samples were tested batchwise for several days. The samples were transferred with sterile tweezers to sterile glass tubes (in the case of solid covers), liquid mixtures were transferred to tubes with a pipette. 15 ml of culture medium BHI (Brain Heart Infusion Broth; Hi-Media) was added to each tube and the samples were seeded with the following microorganisms: Staphylococcus areus subsp. aureus CCM 4516 (gram-positive cook), Escherichia coli CCM 4517 (gram-negative rod), Pseudomonas aeruginosa CCM 1969 (gram-negative non-fermenting rod), Bacillus subtilis subsp. spizizenii CCM 1999 (spore-forming gram-positive rod), Aspergillus niger CCM 8222 (fungus). The growth characteristics of the culture medium were tested. The tubes were closed with a metal cover and transferred to culture in a constant temperature chamber. Liquid samples were grown for 24 to 48 hours, solid cover samples were grown for one week at the temperature within the range of 30 to 35 ° C, and the following week at 20 to 25 ° C. After the said period, the presence or absence of obscurity was investigated. Unclear samples were plated with sterile inoculation loop in Petri dishes with blood agar KA (Merck) for culture verification of the present microorganisms. Their incubation continued for 5 days at 30 to 35 ° C.

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The healing effect was assessed by using the excisional wound model in healthy rats (ZDF male rats). Wounds 2 x 2 cm were prepared and healing was measured twice a week based on the wound concentration using computer evaluation of photographic recording of the wound.

In addition, the healing effect was assessed with the Minnesota-type miniature pig model, with 5 deep full-profile excisions of 25 x 25 mm on each side, prepared under stunning with the procedure described by Van Dorp Verhoeven MC, Koerten HK, Van Der Nat-Van Der Meij TH, Van Blitterswijk CA, Ponec M. Dermal regeneration in full-thickness wounds in Yucatan miniature pigs using a biodegradable copolymer, Wound Repair Regen, 1998, 6 (6): 556-68. The wounds were then covered with a control and an experimental cover until healing was complete. Regular re-application of bandages, photo documentation and scrap for microbiological examination was performed twice weekly. Based on the image analysis, the wound closure rate (concentration, epithelialization) was measured and, based on the culture tests, the effect of the tire on the microbiological colonization of the wound was also measured.

Microbial efficiency of the active mixture (liquid of Example 1)

A sample of the liquid mixture (viscous solution) used to coat according to Example 1 showed the total (i.e. 100%) inhibition of E. coli strain growth (starting suspension 20000 CFU / ml), S. aureus (20000 CFU / ml ), P. aeruginosa (40000 CFU / ml) and B. Subtilis (1000 CFU / ml) when the octenide dihydrochloride content was 4 mg. When 1 mg of octenide dihydrochloride was used, the inhibition was only 100% for B. subtilis and S. aureus strains, the inhibition for E. coli strain was 99.95% and for P. aeruginosa strain 90%.

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A sample of the finished tire showed an inhibition zone around the contact layer, however, microorganism growth was not inhibited at a greater distance from the tire. On the other hand, this fact provides evidence that the antimicrobial substance is not released from the tire into the surrounding environment and therefore the patient will not be adversely affected.

Microbial efficiency of the active mixture (liquid of Example 5)

A sample of the liquid mixture (viscous solution) used for the tire of Example 5 showed total (i.e. 100%) inhibition of E. coli strain growth (starting suspension 1800 CFU / ml), S. aureus (600 CFU / ml) and A. niger (65 CFU / ml) containing 16 mg of benzalconium chloride (BAC); or 40 mg of chlorhexidine or 40 mg of PHMB. When 1.6 mg of BAC was used, the inhibition was only 100% for S. aureus strains, the inhibition of E. coli strain was 16% and inhibition of A. niger strain was 89%. When 4 mg of chlorhexidine was used, the inhibition of growth of E. coli was 61%, S. aureus 95% and A. niger 32%. When 4 mg of polyhexamethylene biguamide (PHMB) was used, the inhibition of E. coli growth was 44% and of A. niger 57%.

Samples of the finished tires exhibited zones of inhibition in a similar manner as described for the composition of Example 1. Therefore, when a suitable amount of a suitable antimicrobial substance is used, the tires have similar microbiological inhibition properties based on the overall design and production process of the tire, only on the particular antimicrobial substance.

Tire according to Example 1, healing effect, fast rat model When the tire in Example 1 was used, a significant acceleration of wound contraction was observed, which in the model used represents the scale of healing or healing efficiency. Compared to the untreated control wound (see Figure 3), it is clear that the use of the tire according to Example 1 shortens the wound healing time, especially thanks to the fact that the wound healing process starts immediately after the injury. In the situation of the non-treated wound, the healing process starts about three days after the injury. Thus, the intensity of subsequent wound healing is similar to each other in both cases, as can be seen in the similar slope of both features in Figure 3. Since healthy rats were used, the effectiveness of chronic wounds cannot be assessed.

Cover according to Example 1, healing effect, fast miniature pig model

It was discovered that the tire of Example 1 had a positive effect on the wound closure rate (Figure 4) and also that the total bacterial content of the wounds decreased (Figure 5), where the gram-negative bacteria in particular were monitored (Figure 6).

Claims (11)

17 DK 2013 00152 Y3 A composition for supporting wound healing comprising a physiologically acceptable hyaluronic acid salt, characterized in that it comprises a physiologically acceptable hyaluronic acid salt and octenide dihydrochloride in a weight ratio of 500: 1. Cover for supporting wound healing with an antimicrobial effect, characterized in that it is in the form of a multilayer formation and further comprises one or more absorption layers (A) and a surface layer (R), wherein all layers are arranged in the following order in the direction. from the wound: contact layer (K) which, on the side to be in contact with the wound or on both sides, contains a coating (P) made from the mixture according to claim 1; one or more absorption layers (A) and a surface layer (R). Cover according to claim 2, characterized in that the contact layer is preferably made of a woven or knitted fabric made of polyamide (PAD) monofilaments, optionally of staple fibers; of nonwoven fabrics or porous membrane, polyurethane, polyester, viscose, mixtures of said fibers or of other materials, for example of synthetic fibers such as polypropylene. Cover according to claim 2 or 3, characterized in that the coating (P) made from the mixture according to claim 1 can be in the form of a freeze-dried product or a dried coating. Cover according to any one of claims 2 to 4, characterized in that it comprises one or more absorption layers (A) made from materials selected from the group comprising polyester, viscose, polyamide, polyethylene, polypropylene, polysaccharide such as xanthan or cellulose derivative, superabsorbent material, a combination of woven or non-woven textile fibers and superabsorbents, or a mixture of said materials. Cover according to any one of claims 2 to 4, characterized in that it comprises several absorption layers (A) arranged in a manner in which the absorption capacity gradient increases in the direction from the wound. Cover according to claim 6, characterized in that it comprises absorption layers (A1) and (A-2), wherein said absorption layer (A1) is closer to the wound and is made of 100% polyester and the absorption layer (A-2) is further away. from the wound and is made from a 1: 1 mixture of polyester and viscose. Cover according to any one of claims 2 to 7, characterized in that the coating (P) is composed of precipitated hyaluronan fiber layer, on which is applied a layer of octenide dihydrochloride, wherein the amount of the hyaluronene coating is at least 0.1 mg / m2 and the amount of coating of octenide dihydrochloride substance is at least 0.0001 mg / m2. Cover according to claim 8, characterized in that the amount of hyaluronan coating is in the range of 1 to 50 g / m2 and the amount of octenide dihydrochloride coating is in the range of 0.0001 to 0.5 g / m2. Cover according to claim 9, characterized in that the amount of hyaluronan coating is in the range of 5 to 20 g / m2 and the amount of octenide dihydrochloride coating is in the range of 10 to 40 mg / m2. Cover according to any one of claims 2 to 10, characterized in that the contact layer (K) and the surface layer (R) are fixed to each other at their edges to close the absorption layer 19 or the absorption layers (A) between the contact layer (K) and the surface layer (R).